MSCCH-507

MSCCH
M
M. Sc. II Semester
ORGANIC CHEMISTRY-II

SCHOOL OF SCIENCES
DEPARTMENT OF CHEMISTRY
UTTARAKHAND OPEN UNIVERSITY
 MSCCH-507

ORGANIC CHEMISTRY-II

SCHOOL OF SCIENCES
DEPARTMENT OF CHEMISTRY
UTTARAKHAND OPEN UNIVERSITY

Phone No. 05946-261122, 261123

Toll free No. 18001804025
Fax No. 05946-264232, E. mail [email protected]
htpp://uou.ac.in
 Expert Committee

Prof. B.S.Saraswat Prof. A.K. Pant

Department of Chemistry Department of Chemistry
Indira Gandhi National Open University G.B. Pant Agriculture, University
Maidan Garhi, New Delhi Pantnagar

Prof. A. B. Melkani Prof. Diwan S Rawat

Department of Chemistry Department of Chemistry
DSB Campus, Kumaun University, Nainital Delhi University, Delhi

Dr. Hemant Kandpal Dr. Charu C. Pant

Assistant Professor Department of Chemistry
School of Health Science Uttarakhand Open University,
Uttarakhand Open University, Haldwani Haldwani

Board of Studies
Prof. P.D. Pant Prof. B. S. Saraswat
Director, School of Sciences Professor Chemistry
Uttarakhand Open University Department of Chemistry
Haldwani, Nainital School of Sciences, IGNOU, New Delhi

Prof S.P. S. Mehta Prof. Viveka Nand

Professor Chemistry Professor Chemistry
Department of Chemistry Department of Chemistry
DSB Campus, Kumaun University College of Basic Science & Humanities
Nainital GB Pant University, Pantnager

Dr. Shalini Singh Dr. Charu C. Pant

Department of Chemistry Department of Chemistry
School of Sciences, School of Sciences,
Uttarakhand Open University Uttarakhand Open University
Haldwani, Nainital Haldwani, Nainital
 Programme Coordinator
Dr. Shalini Singh
Department of Chemistry
School of Sciences,
Uttarakhand Open University
Haldwani, Nainital

Unit Written By Unit No.

1. Dr. Raveendra Kumar 01, 02 06, 08
Assistant Professor
Department of Chemistry
GBPUA &T, Pantnager

2. Dr. Ameeta Tewari 03

Assistant Professor
Department of Chemistry
MBPG College, Haldwani

3. Dr. Om Prakash 04, 05, 07, 09 & 10

Professor,
Department of Chemistry
GBPUA &T, Pantnager

Course Editor
Prof. Sanjay Kumar
Principal
Govt. PG College, Haldwani

Course Co-Editor
Dr. Charu C. Pant
Assistant Professor
Department of Chemistry
Uttarakhand Open University, Haldwani

Title : : Organic Chemistry-II

ISBN No.: :
Copyright : Uttarakhand Open University
Edition : 2022
Published by : Uttarakhand Open University, Haldwani, Nainital- 263139
 CONTENTS

Block I: Nucleophilic Substitution

Unit 1 Aliphatic Nucleophilic Substitution 1-60

Unit 2 Aromatic Nucleophilic Substitution 61-86

Block II: Electrophilic Substitution

Unit 3 Aliphatic Electrophilic Substitution 87-112

Unit 4 Aromatic Electrophilic Substitution 113-135

Unit 5 Elimination Reactions 136- 156

Block III: Addition and free Radical Reactions

Unit 6 Addition to Carbon-Carbon Multiple Bonds 157- 200

Unit 7 Addition to Carbon-Hetero Atom Multiple Bonds 201-236

Unit 8 Free Radical Reactions 237-261

Block IV Pericyclic Reactions

Unit 9 Electrocyclic Reactions 262-294

Unit 10 Cycloadditions and Sigmatropic Reaction 295-344

ORGANIC CHEMISTRY-II MSCCH-507

UNIT-1 ALIPHATIC NUCLEOPHILIC SUBSTITUTION

CONTENTS:
1. Objectives
1.1 Introductions
1.1.1 Leaving groups as (or leaving) nucleophiles or nucleofuge
1.1.2 Incoming nucleophile
1.2 Mechanism SN2 reactions
1.2.1 Evidence for the SN2 mechanism
1.3. The SN1 mechanism (carbocation process)
1.3.1 Evidence for the SN1 mechanism
1.4. Mixed SN1 and SN2 mechanism
1.5. SNi mechanism
1.6. SET mechanism
1.6.1 Evidence for SET mechanism:
1.7. Neighbouring Group Participation (Intramolecular Nucleophilic Displacement)
1.8. Classical and Non- Cassical Carbocation (bridged carbocations)
1.9. Carbocation Rearrangements
1.10: Norbornyl systems
1.11: Norbornyl cation
1.12. Nucleophilic substitution at an allylic carbon
1.13. Nucleophilic substitution at an aliphatic trigonal carbon
1.14. Nucleophilic substitution at vinylic carbon
1.15. Structure & Reactivity Analysis of Nucleophilic Substitution Reactions
1.16. HSAB principle
1.16.1 HSAB Principle
1.16.2. HSAB & FMO Analysis
1.16.3 Characteristics of Hard, Soft & Borderline Acids & Bases
1.16.4 Applications of HSAB Principle
1.17. Ambident Nucleophiles
1.18. Summary
1.19 Terminal questions
1.20. Answer to terminal questions
1.21. References

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1. OBJECTIVES

Objective of this unit is to make students aware about the SN2, SN1, mixed SN1 and SN2,
SNi and SET mechanism. This chapter will also provide knowledge of neighboring group
participation by π and σ bonds, anchimeric assistance, classical and non-classical
carbocations, arenium ions, norbornyl systems and common carbocation rearrangements.
This chapter will also provide useful information about the SNi mechanism, nucleophilic
substitution at an allylic, aliphatic trigonal and a vinylic carbon. The other objectives of this
chapter are reactivity effects of substrate structure, attacking nucleophile, leaving group,
reaction medium, HSAB principle and ambident nucleophiles.

1.1 INTRODUCTION

Replacement of an atom or group by any other atom or group is known as substitution

reaction. Attack of nucleophile at saturated carbon atom bearing a substituent, known as
leaving group, result in substitution reaction. The group that is displaced (leaving group)
carries it’s bonded pair of electrons. The new bond is formed between nucleophile and the
carbon using the electron supplied by the nucleophilic reactant. In general, an aliphatic
substitution reaction may be depicted as follows:
Substrate + Nucleophile Product + Leaving Group
2 2
R R
_ 1 1
:Nu + R C L R +
Nu C L-

R R

Nucleophile may be neutral or negatively charged, whereas substrate undergoing nucleophilic

substitution may be neutral or positively charged. Four possibilities in nucleophilic
substitution reaction may thus be visualised as below:

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_ _
(i) OH + CH3Br CH3OH + Br
+ _
(ii) NH3 + CH3Br CH3NH3 + Br
_ +
(iii) Cl + CH3OH2 CH3Cl + H2 O
+ +
(iv) H2S + RN(CH3)3 RSH2 + N(CH3)3

1.1.1 Leaving groups as nucleophiles or nucleofuge

The leaving group is the part of the substrate that is missing at the end of the reaction. The
leaving group must have following characteristics:

(i) A leaving group is electron-withdrawing so that it creates a partial positive on the

carbon atom.

R δ+----Lδ−

(ii) The leaving group should be stable after leaving with the bonding pair of electrons. In
general good leaving group should be weak bases, and therefore, they are
conjugate bases of the strong acids. Thus
Leaving power of the group ∝ 1/ Basicity of the group
For example:

Acid Conjugate base

HF F
HCl Cl
HBr Br
HI I

Acidity in increasing order Basicity in decreasing order

(leaving group nucleophilicity in
increasing order)
Thus, the stronger the conjugate acid of the leaving group, the better is its ability
(iii)The ability of a species to act as a good leaving depends on its polarisability.
Decreasing order of leaving ability of some group is as follows:

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O O
1
R N N > R O R >R O S C4H9 > R O S CF3 >
O O
O O O
R O S Br > R O S CH3 > R O S C6H5 >
O O O

O O
R O S CH3 > R I >R Br > R O C CF3 > R O H>
O H
O
R Cl > R F> R O C CH3 >R O H>R O R > R H

1.1.2 Incoming nucleophile:

An incoming nucleophile may either be negatively charged or it may be an uncharged species
with lone pair of electrons. Examples of some incoming nucleophiles given as followes:

NO2, N3, RCOO, CN, I, Br , Cl, OH , RO, HOH, ROH, NH3, RNH2, SH, RSH

The reactivity of nucleiophile is known its nucleophilicity. The nucleophilicity increases with
increasing polarisability. Nucleophilicity can be explained as given below:

(i) A negative charge species is a stronger nucleophile than a smilar species without a
negative charge (a base is a stronger nucleophile than its conjugated acid). For
example- OH- is a stronger nucleophile than HOH.
(ii) Nucleophilicity decreases on going from left to right in the periodic table. Therefore-

CH3 > NH2 > OH > F

Similarly, NH3 is more nucleophilic than HOH.

(iii)Nucleophilicity increases on going down in the group of the periodic table. Therefore:

SeH > SH > OH and R3P > R3N

I- > Br- > Cl- > F- , Similarly
(iv) Bulky group present on nucleophile centre decreases nucleophilicity and increase
basicity of the negatively charged species.
CH3
HO CH3 O CH3 CH O CH3 C O
CH3 CH3
nucleophilicity in decreasing order, basicity in increasing order

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Depending on nuleophile, substrate, leaving group and reaction conditions, several

mechanism are possible for aliphatic nucleophilic substitution reaction but most proceed
either by a direct displacement mechanism in which bond making and bond breaking
simultaneous, or by a two-step mechanism in which C-L bond is broken first, followed by a
reaction between the resultant carbocation and nucleophile.

Direct Displacement Process

_ _ _
Nu + R L [Nu ---- R ---- L] Nu R+ L
transition state
Carbocation Process
+
_
R L R + :L
_ +
Nu + R Nu R

1.2 THE SN2 MECHANISM (DIRECT DISPLACEMENT PROCESS)

The designation SN2 stands for substitution nucleophilic bimolecular. The IUPAC
designation is ANDN. The letter A represents formation of a bond (association), D the
breaking of a bond (dissociation). In any process, the subscript is N if a core atom is forming
a bond to a nucleophile (AN) or breaking a bond to a nucleofuge (DN). The direct
displacement mechanism is concerted (single step), without an intermediate and with a single
rate determining transition step. In SN2 reaction, the substrate is attacked by the nucleophile
from the side opposite the nucleofase (1800).
The direct displacement reaction generally occurs at an aliphatic sp3 carbon center
with an electronegative, stable leaving group attached to it (X), which is frequently a halide
atom. The breaking of the C–X bond and the formation of the new bond (C–Y or C–Nu)
occur simultaneously through a transition state in which a carbon under nucleophilic attack is
penta coordinate, and approximately sp2 hybridised. The nucleophile attacks the carbon at
180° to the leaving group, since this provides the best overlap between the nucleophile's lone
pair and the C–X σ* antibonding orbital. The leaving group is then pushed off the opposite
side and the product is formed with inversion of the tetrahedral geometry at the central atom.

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Antibonding orbital

Nu C L Nu C + L

Bonding orbital

Let us consider an example: the attack of Br− (the nucleophile) on an ethyl chloride (the
electrophile) results in ethyl bromide, with chloride ejected as the leaving group.

H 3C
H 3C - Cl CH3
rear side attack Br Br C Cl
C Cl Br C
Br H H H
H H
H
Nucleofuse

Nucleophile Transition Stage

SN2 reaction of chloroethane with bromide ion

SN2 attack occurs if the backside route of attack is not satirically hindered by substituents on
the substrate. Therefore, this mechanism usually occurs at unhindered primary and secondary
carbon centres. If there is steric crowding on the substrate near the leaving group, such as at a
tertiary carbon centre, the substitution will involve an SN1 rather than an SN2 mechanism.
Figure represents the free energy vs reaction coordinate diagram for SN2 reaction.

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H H

H O C Br
H

H
H
H O + C Br
H
H
H
H O C + Br
H

Reaction coordinate

Fig:1 Potential energy diagram for the reaction of methyl bromide with
hydroxide ion by the SN2 mechanism
1.2.1 Evidence for the SN2 Mechanism
1. Kinetics: Both the substrate and the nucleophile take part in the rate determining step
(the only step), the reaction should be first order in each component, second order
overall and satisfy the below mentioned rate expression. Thus the reaction follows
second order kinetics. Hence, the rate equation is:
Rate = k [substrate] [nucleophile]
This law was found to apply for many reactions in chemistry. But for reactions
involving excess of nucleophile (solvent), even though the mechanism is bimolecular,
experimentally determined rate will be first order. This is because the rate is
dependent on the concentration of the substrate molecule, the kinetics involved in this
reaction is referred as pseudo first order:
Rate = k [substrate]
The unfortunate part is that the reaction mechanism can’t be operated for the substrate
containing the leaving group at bridgehead carbon atom of any polycyclic systems.

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The reason is that the back side of this carbon can’t be free to allow the nucleophile
from that side during the formation of transition state. For example: The reaction
between [2.2.2] system with ethoxide ion and [3.3.1] system with NaI, where acetone
is used as a solvent does not result in product formation. But their open chain
analogues underwent the reactions gradually.

C 2H 5O
N o re a c tio n
Br
2 .2 .2

O
C
N o re a c tio n
N aI
Br
3 .3 .1

2. Stereochemistry: The SN2 reaction proceeds with inversion of configuration at the

carbon at which the substitution has taken place. The SN2 reaction is a stereospecific
reaction. When a substitution takes place in a chiral carbon, inversion of configuration
occurs and this is known as Walden inversion (Paul Walden 1863-1957) and was
observed long before the SN2 mechanism was formulated by Hughes and Ingold. In
SN2 reaction an ethyl chloride converted into ethyl bromide in presence of strong base
results inversion of configuration. The change of configuration can be established by
observing the directions of optical rotation. Examples for Walden inversion:
1. Chlorination of (+)-malic acid: When (+)-malic acid is treated with SOCl2, it
results in (+) - chlorosuccinic acid, where retention in configuration is there. On
the other hand, when (+)-malic acid is treated with PCl5, it results in (-)-
chlorosuccinic acid, i.e inversion in configuration is there.
COOH COOH
COOH
SOCl2 H OH PCl5 Cl H
H Cl
H COOH H COOH
H COOH
H H
H
chlorosuccinic acid malic acid chlorosuccinic acid

2. Hydrolysis of (+)-chlorosuccinic acid: When (+)-chlorosuccinic acid is

hydrolyzed with silver hydroxide or aqueous silver oxide, it results in (+)-malic

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acid, where retention in configuration is there. On the other hand, when (+)-
chlorosuccinic acid is hydrolysed with KOH, it results in (-) malic acid, i.e
inversion in configuration is there.
COOH COOH COOH
Ag2O KOH
H OH H Cl HO H
H COOH H2O H COOH H COOH
H H H
malic acid chlorosuccinic acid malic acid
Philips & co-workers (1923) reported about the prediction of exact position of
inversion by using (+)-1-phenyl-2-propanol as a starting material. In this reaction,
two routes are possible, first (step 1 and 2) and second- (step 3 and 4). In the step
1, 3 and 4, C-O bond is not broken at all, which creates no possibility of inversion.
Thus there is high probability of retention of configuration. But in step 2 the C-O
bond is broken and the new C-O bond is formed which must come from the
reagent ethanol in presence of base, thus the step 2 should follow the inversion of
configuration.

TsCl C2H5OH
step 1 K2CO3
H3C OH H3C OTs step 2
H3C OC2H5
(+)-1-phenyl-2-propanol 0 0
0 31.0 α= 19.9
α=
α= 33.0
K step 3

C2H5Br
step 4
H3C OC2H5
H3 C OK 0
α= 23.5

Hughes & Ingold did fabulous work to establish the inversion of configuration in SN2
reaction. For example, reaction of (+)-2-iodooctane with KI* (radioactive iodide) results in (-
)-iodooctane. The rate of this reaction is as follows:
Rate α [C6H13CHICH3] [I-]*

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Thus the exchange of actual iodide with the radioactive iodide results the loss of optical
activity, which indicates the formation of (-) isomer from (+) isomer. Thus, inversion of
configuration indicates the SN2 reaction.

C6H13 C6H13

C I C I
I H3C H
radioactive iodine H3 C I
H
2 iodidoocatne transition state

C6H16
I
C
I CH3
H
2 iodidoocatne

3. Linearity of Transition State: Eschenmoser and co-workers postulated that the

transition state in SN2 reactions should be linear. The base treatment of methyl-α-
tosyl-o-toluene sulfonate (1) results in o-(1-tosylethyl) benzene sulphonate (2). In
this reaction base is used to remove α-proton which results in the formation of an
anion. Thus this reaction may undergo an internal nucleophilic substitution
reaction.

O O
O O O
O S
S S O
O base O
CH3 CH3 CH3
H Ts Ts
Ts
2
1

The carbanion produced was believed to act as an internal nucleophile and attacks
the methyl carbon of sulfonate ester by intramolecular mechanism. If it is linear
the transition state cannot be achieved. But later, the cross over experiments of
this reaction showed that the negatively charged carbon attacks the methyl group
of another molecule rather than the nearby one in the same molecule i.e. this is an

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intermolecular reaction and not intramolecular reaction which confirms the linear
transition state. In intra molecular reactions linearity of transition state can be very
difficult.

1.3 THE SN1 MECHANISM (CARBOCATION PROCESS)

The ionization mechanism for nucleophilic substitution proceeds by rate determining

heterolytic dissociation of the reactant to a tricoordinate carbocation and the leaving group.
This dissociation is followed by rapid combination of the electrophilic carbocation with a
Lewis base (nucleophile) present in the medium. A potential energy diagram representing this
process for a neutral reactant and anionic nucleophile is shown in Fig. 2 The ionization
mechanism has several distinguishing features. The ionization step is rate determining and
the reaction exhibits first-order kinetics, with the rate of decomposition of the reactant being
independent of the concentration and identity of the nucleophile. The symbol assigned to this
mechanism is SN1, for substitution, nucleophilic, unimolecular (IUPAC: DN+AN).

H3 C CH3
C

activation energy CH3

carbocation
E

(CH3)3C Br + HO

(CH3)3C OH + Br

Reaction coordinate

Fig: 2 Energy diagram for SN1 mechanism

Let us take the example of of a reaction taking place with an SN1 reaction mechanism is the
hydrolysis of tert-butyl bromide with water forming tert-butanol.

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This SN1 reaction takes place in three steps:

Step 1 (Formation of a tert-butyl carbocation by separation of a leaving group (a

bromide anion) from the carbon atom): This step is slow and reversible.

CH3
H3 C slow
H3C C Br
H3 C C Br
H3C CH3

Step 2 (Nucleophilic attack): The carbocation reacts with the nucleophile. If the
nucleophile is a neutral molecule (i.e. a solvent) a third step is required to complete the
reaction. When the solvent is water, the intermediate is an oxonium ion. This reaction step is
fast.

H H3C H
CH3
O H3C C O
H3 C C
H H3C H
CH3

Step 3 (Deprotonation): Removal of a proton on the protonated nucleophile by water acting

as a base forming the alcohol and a hydronium ion. This reaction step is fast.

H3C H H H3C
fast H3C C OH + H3 O
H3C C O + O
H3 C H H H3C

1.3.1 Evidence for the SN1 mechanism

1. Kinetics: The SN1 reaction is initiated by the dissociation of the leaving group and
formation of the carbocation intermediate in the first step. After formation of the
carbocation intermediate, the nucleophile takes part in the second step. Increasing or
decreasing the concentration of the nucleophile has no measurable effect on the rate.

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The nucleophile is not involved in the initial step of rate-determination, thus the
concentration does not affect the overall reaction rate. This reaction follows first order
kinetics. The reaction is first order with respect to alkyl halide while zero order with
respect to the nucleophile.
Rate = k [Substrate]
2. Stereochemistry: If the SN1 reaction proceeds via a carbenium ion, the
stereochemical outcome must quite different from that the SN2 reaction because the
central carbon of the intermediate is sp2 hybridised and planar. The lobes of the
vacant 2p orbital (LUMO) are perpendicular to the plane of the carbenium ion and the
HOMO of the nucleophile may interact with either of the lobes. If the reaction site of
substrate (RY) is a chiral centre, and the nucleophilic attack at the carbenium ion is
equally possible from both sides, the outcome must be the formation of the racemic
product regardless of the enantiomeric purity of the substrate (RY).
Racemization is usually only partial (experimentally) because the leaving group is still
present as counter-ion on the side of the carbenium ion from which it departed. In
another way we can say that the carbenium ion initially exists as an ion pair and its
counter ion Y- (leaving group) inhibits nucleophilic capture from the side leading to
product with retention of the configuration. The result is partial inversion of the
configuration, the degree of which depends on the stability (lifetime) of the ion pair
and the nature of the solvent.
vacant 2p orbital
Nu Nu
R1 R1 R1
R1
Y
C Y C Nu C + C Nu
R2 Y R2
R2 R2
H H H
H
an enantiomer (chiral) carbenium ion intermediate
(achiral) a mixture of enantiomer
(a recimic or partial inversion)

1.4 MIXED SN1 AND SN2 MECHANISM

In a Nucleophilic substitution reaction a nucleophile (electron rich species) bonds

with a positive/partially positively charged centre in a substrate expelling the leaving group.
The two factors i.e. molecularity and reaction kinetics, classifies nucleophilic substitution
mechanisms as substitution nucleophilic unimolecular (SN1) and substitution nucleophilic
bimolecular (SN2). Where the SN1 mechanism is a two step mechanism, involving carbocation

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intermediate whereby the product of the reaction is a racemic mixture and the SN2
mechanisms proceed in a single step through a transition state whereby the reaction leads to
inversion of configuration.
There is only difference in the timing of the steps between SN1 and SN2 mechanisms.
On one hand in the SN1 mechanism, first the leaving group leaves followed by the nucleophile
attack whereas, in the SN2 mechanism, the two things happen simultaneously. But sometimes
under a given set of conditions there are reactions that are known to proceed with a
mechanistic ‘‘borderline’’ region i.e. mixed SN1 and SN2. At least two broad theories have
been devised to explain mixed SN1 and SN2 mechanism.
1. One theory explain that One theory holds that intermediate behavior is caused by a
mechanism that is neither ‘‘pure’’ SN1 nor ‘‘pure’’ SN2, but some ‘‘in-between’’
type (given by Sneen et al, 1973).
2. According to second theory, there is no intermediate mechanism at all and
borderline behavior is caused by simultaneous operation, in the same flask, of both
the SN1 and SN2 mechanisms; that is, some molecules react by the SN1, while
others react by the SN2 mechanism.

According to Seen, all SN1 and SN2 reactions can be accommodated by the ion-pair
mechanism. Firstly, the substrate ionizes in to an intermediate ion pair then an intermediate
ion pair converted in to products:

k1 k2
RX R X Product
substrate intermediate
ion pair

The difference between the SN1 and SN2 mechanisms is that in the former case the formation
of the ion pair (k1) is rate determining, while in the SN2 mechanism its destruction (k2) is rate
determining. Borderline behavior is found where the rates of formation and destruction of the
ion pair are of the same order of magnitude.

The Experimental evidence suggests that the borderline mechanism or mixed SN1/SN2
mechanism were shown by benzyl chloride hydrolyses in aqueous solvents. The substitution
proceeds with a clear SN2 mechanism. However, upon p-substitution, p-methoxybenzyl
chloride solvolysis takes place by the SN1 route. As the para substituent changes from the
order of electron withdrawing to electron donating functional groups (NO2, Cl, H, CH3,

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OCH3), a progressive change from the bimolecular mechanism to the unimolecular pathway
is observed. The intermediate situation for p-methylbenzyl chlorides was found to be border
line where it was argued that SN1 and SN2 processes occur side by side. With the addition of
azide ions (good nucleophile) to the reaction, the alcohol is still there as a product, but 4-
methoxybenzyl azide comes out to be another product. The role of additional nucleophile
azide ions is thus to increase in the rate of ionization (by the salt effect) but decreases the rate
of hydrolysis. Thus, both SN1 and SN2 mechanisms were shown to be operative
simultaneously.

Example of mixed SN1 and SN2 mechanism:

Cl CH3ONa/CH3OH O

1.5 SNi MECHANISM

The label SNi stands for substitution, nucleophilic internal. The IUPAC designation is
DN + ANDe. A typical representative organic reaction displaying this mechanism is the
chlorination of alcohols with thionyl chloride, or the decomposition of alkyl chloroformates,
the main feature is retention of stereochemical configuration. Thionyl chloride first reacts
with the alcohol to form an alkyl chloro sulfite, actually forming an intimate ion pair. The
second step is the concerted loss of a sulfur dioxide molecule and its replacement by the
chloride, which was attached to the sulphite group. In SNi reaction both the reactants are the
crucial component and both are playing crucial role in completion of reaction. Thus the rate
will be directly proportional to the reactant and catalyst therefore; we can say the reaction
follows a second order rate equation.

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C 6H 5 Cl C 6H 5
H s te p 1 H
C O + S O C O S O
H 3C Cl H 3C Cl

s te p 2

C 6H 5
H
C Cl + SO 2

CH3
R e te n tio n
R a te = k [ R O H ] [ S O C l 2 ]

In the SNi reaction the sulphite reacts with a chlorine ion in a standard SN2 reaction with
inversion of configuration. When the solvent is also a nucleophile such as dioxane two
successive SN2 reactions take place and the stereochemistry is again retention. With standard
SN1 reaction conditions the reaction outcome is retention via a competing SNi mechanism
and not racemization and with pyridine added the result is again inversion.

1.6 SET MECHANISM

Involvement of free radicals has been shown in many aliphatic substitution reactions.
Following steps are involved in SET mechanism.

Step 1: Transfer of an electron from the nucleophile to the substrate to form a radical anion.

R X Y R X Y
substrate nucleophile a radical anion

Mechanisms that begin this way are called single electron transfer mechanisms.

Step 2: The radical ion cleaves.

R X R X

The radicals formed in this way can go on to product by reacting with the Y• produced in
Step 1 or with the original nucleophilic ion Y−.

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Step 3: The radicals formed in step 2 can go on to product by reacting with the Y• produced
in Step 1.

R Y R Y

Or

Step 3: The radicals formed in step 2, reacting with the the original nucleophilic ion Y− and
formed a radical anion.

R Y R Y

Step 4: A radical ion coming from step 3 react with substrate and formed a radical ion like in
step 1 (chain reaction).

R Y R X R Y R X

1.6.1 Evidence for SET Mechanism: Above reactions show inversion of configuration, but
in many reactions some racemization has also been determined. In case of racemization,
involves intermediacy of a simple free radical and a completely racemized product (R-Y)
would have been formed. Explanation- it has been suggested that nucleophile approaches
substrate from the backside and the radical is tied up in solvent cage having the nucleophile
on the back side.

R X Y Y R X Y R X
substrate nucleophile solvent cage

R Y X

Another example of substitution reaction in which SN1 mechanism is highly probable and
free radicals involved in the reaction (intermediates detected by ESR). In such cases, a
carbocation is a good electron acceptor and the nucleophile is an electron donor. The reaction

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between the triphenylmethyl cation and tert-butoxide ion can be explained by SET
mechanism.

SET
Ph3C tert BuO Ph3C t BuO t BuO CPh3
electron electron free radicals product
acceptor donor

1.7 NEIGHBOURING GROUP PARTICIPATION

(INTRAMOLECULAR NUCLEOPHILIC DISPLACEMENT)

Neighbouring Group Participation (NGP) is observed in nucleophilic substitution reactions,

where a neighbouring group helps in the removal of the leaving group to form a reactive
intermediate that leads to the formation of the product. Increase in the reaction rate
(anchimeric assistance) and unexpected stereo chemical outcomes (retention of
configuration) are associated in reactions involving NGP.

An atom having an unshared pair of electrons and also present at least β to the leaving group
can act as a neighbouring group. Also, NGP is mostly observed on solvolysis reactions where
the solvent acts as the nucleophile.

A typical reaction involving NGP is shown below.

slow intramolecular fast intramolecular

Z S N 2 (inversion) S N 2 (inversion) Z
Z
step 1 step 2
C C C C C C

L Nu Nu
L
net result is
Z= neighbouring group retention of
L= leaving group configuration
Nu= nucleophile
During NGP, the neighbouring group (G) attacks the electrophilic centre to eliminate the
leaving group (L). This leads to the formation of a cyclic intermediate which is very reactive.
This is called anchimeric assistance from the neighbouring group. The nucleophile (Nu-) then
attacks this intermediate to form the product. If the attack happens of the carbon that was
having the leaving group the configuration will be retained because the configuration at that
carbon will be inverted twice.

The neighbouring group mechanism follows the first order rate law shown below:

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Rate = K [substrate]

That is, the external nucleophile does not take part in the rate determining step.

Groups like halides, hydroxides, ethers, thio ethers, amino groups, carboxylates, phenyl
group, pi-bonds etc. have been indentified to act as neighbouring groups in many reactions.

Some more examples of reaction involving NGP are shown below.

1. Lone pair as Neighboring group

Example 1: alkaline hydrolysis of 2-bromopropanoate anion to lactate anion in which
the carboxylate anion participates as a neighbouring group. When 2-bromopropanoic
acid is treated with dilute alkali, it gives lactate anion with complete retention of
configuration. However, with concentrated sodium hydroxide (R)-2-bromopropanoic
acid gives (L)-lactic anion. This reaction proceeds with inversion of configuration and
is a typical SN2 reaction.
H H
OH H O
CH3 O
C C OH CH3
C C Br C C
O H2O first inversion CH3
Br O O
Br intramolecular
SN2
(R) 2 bromopropanoic acid OH
second inversion
intramolecular
SN2
H
O
CH3
C C
O OH
net result is retention
(R) Lactic acid

Example 2: The base catalysed hydrolysis of mustard gas is an example of

neighbouring group participation by sulphur. The toxicity of mustard gas is because
of neighbouring group participation by sulphur, which accelerates its alkylation
reactions.

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slow Cl HOH Cl OH
Cl Cl S S
S Cl H
three membered ring
Mustured gas (sulphonium ion)

Example 3: A very good example of neighbouring group participation by iodo group

is the acetolysis of trans-2-iodocyclohexyl brosylate which is 1.7 × 106 times faster
than the acetolysis of the cis isomer in which the iodo group cannot attack from the
backside, thus, there is no neighbouring group participation.

I
I
OBs AcOH
I
NGP H
OAc
OBS

trans isomer

I
×NGP
BsO

cis isomer

2. Double bond as Neighbouring group

Example 1: The acetolysis of 7-norbornenyl tosylate (1) is 1011 times faster than that
of the saturated analogue, 7-norbornyl tosylate (2) and process with retention of
configuration, which gives a very strong evidence that C=C π bond can act as a
neighbouring group. In the case (2) of the saturated analogue, no such anchimeric
assistance is available, thus, its acetolysis proceeds through simple SN2 reaction with
inversion of configuration and at a normal rate which is very low (1011 times) as
compared to that in the (1).

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TsO
AcO

AcOH
OTs H
1 nonclassical retention of
carbocation configuration

TsO OAc

OAc

OTs
2
Inversion of configuration
Example 2: The acetolysis of cholesteryl chloride (1) to give cholesteryl acetate (2) with
retention of configuration, while its dihydro derivative cholestanyl chloride (3) undergoes
normal SN2 reaction with inversion of configuration (4).

1 9
2 Cl
10 8 AcOH
3 7
Cl 4
5 AcO
6
1 2
(retention)

AcOH
SN2
Cl AcO
3 4

(inversion)
3. Phenyl group as Neighbouring group
The neighbouring group participation by an aryl group is indicated by retention of
configuration and occurs through the formation of resonance stabilized phenonium
ion.

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X
phenonium ion
As shown in the following example, the substitution takes place with retention of
configuration (path I) and is accompanied by a rearranged product (path II).

Br

CH3 CH CH C2H5 H3 C CH CH C2H5

Br II I
H2O
II I

H3C CH CH C2H5 CH
H3C CH C2H5

OH OH
rearrangement
retention
Evidence for the existence of the phenonium ion was provided by Olah in 1970s, who
prepared many phenonium ions and investigated their structures using NMR spectroscopy.
Treatment of β-phenylethyl chloride, for instance, with SbF5-SO2 at low temperature
generated the corresponding phenonium ion, which has been adequately characterized by
NMR spectroscopy.

SbF5 SO2
SbF5Cl
low temp
CH2CH2Cl

Resonance in the phenyl ring has been demonstrated by a combined application of 1H and 13C
NMR spectroscopy. Overlapping of the cyclopropyl orbitals with π-orbitals of the phenyl ring
helps in the delocalization of the electron-deficiency and the resultant positive charge in to
the cycloprapane ring.

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3. Sigma bond (σ) as Neighbouring group

(1) Participation by C-C single (σ) bond (the cyclopropylmethyl system): In
solvolysis of primary cyclopropylmethyl systems the rate is high because of the
participation by sigma (σ) bond of the ring. The ion which forms initially is an
unrearranged cyclopropylmethyl cation which is symmetrically stabilized i.e.
sigma (σ) bond at the position 2,3 and the 2,4 help to stabilized the positive charge
(The evidence for cyclopropylmethyl cation is symmetrical is that substitutation of
one or more methyl groups in the 3 and 4 positions increases the rate of solvolysis
of cyclopropylcarbinyl 3,5-dinitrobenzoates by approximately a factor of 10 for
each methyl group). The cation may be represented as follows:
4

2 CH2
1
3

Unrearranged cyclopropylmethyl cation

(2) Participation by C-C single (σ) bond (the 2-norbornyl system): The acetolysis
of optically active exo-2-norbornyl brosylate (1) which gave a racemic mixture of
two exo acetates (2, 3), no endo imomer was formed. Furthermore (1) solvolysed
about 350 times faster than its endo isomer (4). These two results (A) that
solvolyis of an exo isomer gave only racemic exo isomers and (B) the high
exo/endo rate ratio, were interpreted by Winstein and Trifan (1952) as indication
that the 1,6 bond assists in the departure of the leaving group and that a
nonclassical intermediate (5) is involved.

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AcOH
1 OBs OAc OAc
H
6
H
H H 3 H
2 4 OBs
1
Racemic mixture

Solvolysis of the endo isomer (4) is not assisted by the 1,6 bond because it is not in a
favourable position for the backside attack. Consequently, solvolysis of (4) takes place at a
normal rate. Therefore, much faster rate for the solvolysis of (1) must be caused by
anchimeric assistance. The stereochemistry of the product is also explained by the
intermediacy of the nonclassical carbocation (5), since in (5) the 1,2 positions are equivalent
and would be attaked by the nucleophile with equal facility but from the exo direction in
either case.

AcO OAc
H
H
2

HOAc

1
1 OBs HOAc
6 2
H
H 5
1
OAc

3 H

Acetolysis of (4) also leads exclusively to the exo acetetes (2) and (3). In this case it has been
postulated that a classical ion (6) is first formed and then converted to more stable (5).
Evidence for this interpretation is that the product from solvolysis of (4) is not racemic but
contains somewhat more (3) than (2), suggesting that when (6) is formed; some of it goes to
give (3) before it is converted to (5).

OBs
H
4 6 5
OBs
(3) Methyl as a neighbouring group: Neopentyl tosylate (1) undergoes almost
exclusive rearrangement on solvolysis and (2) lie in the reaction path. Evidence

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has been presented that under some conditions the methyl group in the neopentyl
system does indeed participate. Evidence that (2) is an intermediate is that small
amounts of cyclopropanes (10-15%) can be isolated in these reactions. (2) is
protonated cyclopropane and would give a cyclopropane on loss of a proton.

CH3 CH3
H3C H3C
CH3 C OTs
CH2 OTs C CH2 C CH2CH3
2
H3C H3C
CH3
1
H H H2O

H3C H3C
C CH2CH3
H3C
H3C
OH
Rearranged product

1.8 CLASSICAL AND NON CLASSICAL CARBOCATION

(BRIDGED CARBOCATIONS)

The carbocations so far studied are called classical carbocations in which the positive charge
is localized on one carbon atom or delocalized by resonance involving an unshared pair of
electrons or a double or triple bond in the allylic positions (resonance in phenols or aniline).
R
R
R C O C2H5 R C O C2H5

CH2 CH2 CH2 CH2

CH2 CH CH2 CH2 CH CH2

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In a non-classical carbocation the positive charged is delocalized by double or triple bond that
is not in the allylic position or by a single bond. These carbocations are cyclic, bridged ions
and possess a three centre bond in which three atoms share two electrons. The examples are
7-norbornenyl cation, norbornyl cation and cyclopropylmethyl cation.

1 L
6
H

2 CH2
1
3

1.9 COMMON CARBOCATION REARRANGEMENTS

In a rearrangement a group moves from one atom to another in the same molecule. Most are
migrations between adjacent atoms and are called 1,2-shifts. Carbocation rearrangements
occur more frequently on secondary carbocations to form tertiary which are more stable and
energetically more favourable. Simple alkyl primary carbocations are too high in energy to
form so you don’t tend to see a primary carbocation. There are some exceptions to this
general rule for primary carbocations. Certain structural conditions such as being benzylic or
allylic, due to resonance, allows for the formation of primary carbocations. Tertiary
carbocations do not need to rearrange as they are already the most stable. In general, the
bonding electrons of a carbocation may shift between adjacent atoms to form a more stable
carbocation.

If a secondary carbocation is vicinal to a tertiary carbon bearing a hydrogen, a 1,2- hydride

shift should occur.

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Vicinal H
tertiary
carbon

0
2 carbocation

If a secondary carbocation is vicinal to a quaternary carbon, a 1,2-alkyl shift should occur.

The general rule in alkyl shifts is: the smaller alkyl substituent tends to be the substituent that
shifts. Therefore, the most common 1,2-alkyl shift is a 1,2-methyl shift.

quaternary
carbon

0
2 carbocation

The mechanism of a 1,2-hydride shift and 1,2-alkyl shift: The mechanism for a 1,2-
hydride and a 1,2-alkyl shift are the same. The arrow (electron movement) starts at the bond
of the substituent moving and point’s right at the carbocation. This shows that the atom/atoms
in the substituent with the electrons moved to the carbocation. The shift (moving the
electrons) results in a new carbocation where the substituent moved from.

H hydride shift
1,2
1
2
H

1,2 alkyl shift

1
2

The following “rules” hold for carbocation rearrangements:

i. Carbocation rearrangements are equilibrium processes.

ii. Usually lead to more stable carbocations.
iii. Sometimes lead to carbocations of equal stability (not so common).
iv. Sometimes lead to less stable carbocations (very unusual but does happen).

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v. Hydride shift is more common, favorable, than alkyl shift.

vi. The least bulky alkyl substituent shifts (usually CH3).
vii. Only groups adjacent to C+ can migrate.
viii. Only carbon groups and H atoms can shift (1, 2-OH shift is forbidden)

1, 2-Hydride Shift: If a carbocation is vicinal to a tertiary carbon bearing a H atom, a 1,2-

Hydride shift should occur. Hydride shift leads to a 3o carbocation which is more stable than a
2o.
H H H
H3C H H3C
Hydride shift
H3C H H3C H
CH3 H CH3 H

Secondary carbocation Primary carbocation

(less stable)

The hydride shift would occur more readily than the alkyl shift. For nucleophilic substitution,
the pattern of bonds that form and break is pretty straightforward. You break C-(leaving
group) and you form C-(nucleophile), a straight swap. But you might see a “weird”
substitution reaction. If you look closely at the pattern of bonds formed and bonds broken in
the second reaction below, there’s an extra set.

Br Br
2 H2O 2
3 3
1
HBr
1

A normal Substitution Reaction

H H
H Br HO H
2 H2O 2
3 3
1
HBr
1

Substitution with Rearrangement

In other words it’s a substitution reaction where the hydrogen has moved or rearranged. As it
turns out, reactions that go through carbocations can sometimes undergo rearrangements.
And looking back at substitution reactions, recall that the SN1 reaction goes through a
carbocation intermediate. Carbocations contains six electrons bearing a positive charge. In

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other words, they are electron deficient (–2 electrons short of a full octet). So, it would make
sense that carbocations become more stable as you increase the number of electron donating
groups attached to them. Alkyl groups are a perfect example. That’s why carbocation stability
increases as you go from primary to secondary to tertiary. Carbocation with the same
substitution pattern can rearrange if it result in a resonance stabilized carbocation.

4
H H CH3
2
3 1 H 3 1 H 2
2 3 1 H
H 3C H 3C H 3C
H H
H H H

prim ary carbocation Secondary carbocation T ertiary carbocation

(least stable) (m ost stable)

Secondary Secondary
(resonance stabilized)

Carbocations are also stabilized by resonance, which allows the positive charge to be
delocalized or “spread out” over a greater area on the molecule. One rearrangement pathway
where an unstable carbocation can be transformed into a more stable carbocation is called a
hydride shift.

H3 C H CH3
H H3C H H
H3C
3
2 H
3 2 3
4 H3C 2
H
1 CH
3 H3C CH3 4
4 1 1 CH
3
Secondary
carbocation Transition state Tertiary carbocation

Hydride shift pathway

In this rearrangement reaction, the pair of electrons in the C-H bond is transferred to the
empty p orbital on the carbocation. In the transition state (or called non classical carbocation)
of this reaction, there’s a partial C-H bond on C3 and a partial C-H bond on C2. The
transition state here is kind of like that split second in a relay race where one sprinter is
passing the baton to another sprinter and they both have their hands on it. Then, as the C2-H

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bond shortens and the C3-H bond weakens, we end up with a carbocation on C3 (3o
carbocation) in the product which is more stable. Here are some examples of “allowed”
rearrangement reactions. Notice how we are always going from a less substituted carbocation
to a more substituted carbocation. One exception is at the very bottom; the rearrangement is
favorable because the new carbocation has increased stabilization. Some example of
“allowed” H rearrangements to make more stable carbocation:

H
Primary Secondary

H
Primary Tertiary

H
Secondary Tertiary

Example: Br
H Br
H2O H H
H Br H
H 2 Secondary
3 2
2 1 carbocation 3 1
3 1

Tertiary
carbocation
1. Loss of leaving group
2. Rearrangement
3. Addition of nucleophile
to carbocation

H 2O H
H H Br
H H H O
HO 2
3
H3O Br 1

4. Deprotonation
Final product
1
SN reaction Hydride shift

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1, 2-Alkyl Shifts

If a carbocation is vicinal to a 3o carbon, a 1,2-alkyl shift should occur. You might note
something with this example, however: There is only possibility to form more stable 3o
carbocation if an alkyl group migrates. The most common situation where alkyl shifts can
occur is when a quaternary carbon is adjacent to a 2o carbocation.

Secondary
H carbocation
H3 C H H3C H
Alkyl shift H3C H
H3C H
CH3 H H
CH3 H
Quaternary
carbon Tertiary carbocation
(more stable)

The pair of electrons from the C-C bond can be donated into the empty p-orbital on the
carbocation (this means they have to be aligned in the same plane). In the transition state,
there are partial bonds between the carbon being transferred and each of the two adjacent C-
atoms. Then, as one bond shortens and the other lengthens, we end up with a (more stable) 3o
carbocation.

H H
H
C CH3
H3C H H3C H H3 C

H3C CH3 H
CH3 H3 C CH3 H3 C CH3
Transition state
Secondary tertiary
carbocation carbocation

Alkyl shift pathway

Once a carbocation is formed, rearrangements can potentially occur at any time. That
includes SN1 reactions. Here’s an example of an SN1 with an alkyl shift.

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Cl
H2O Cl
Cl
6
H2O
2
5 3 1
4
secondary tertiary
carbocation carbocation
1. Loss of leaving group
2. Alkyl shift
3.Nucleophilic attack
on carbocation

6
H
H3O Cl O H2 O H
3 2 1 H O
5
4

SN 1 reaction Alkyl shift

It doesn’t always have to be a methyl group that moves. One interesting example is when a
carbocation is formed adjacent to a strained ring, such as a cyclobutane. Even though the CH3
could potentially migrate in this case, it’s favorable to shift one of the alkyl groups in the
ring, which leads to ring expansion and the formation of a less strained, 5-membered ring.

H 2O
Cl
7 Cl 7
1
6 2 6 2 6 3
3 1 3 1 2

5 4 5 4 5 4

1. lo ss o f le a v in g 3. N u c le o p h ilic a tta c k
2. A lk y l sh ift
g ro u p

H
OH H
O
H 3O Cl
OH2

4. D e p ro to n a tio n
1
SN re a c tio n a lk y l sh ift le a d s to rin g e x p a n sio n

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1.10 NORBORNYL SYSTEMS

Norbornane is an organic compound and its chemical formula C7H12. Its IUPAC name is
[2.2.1] heptane. It is a 1, 4 bridged bicyclohydrocarbon. The norbornane molecule possesses a
rigid structure with uncommon steric characteristics. Carbon atoms 1-6 constitute a
cyclohexane structure in the higher-energy boat conformation. Moreover, the 7-methylene
group not only locks this ring system into a rigid boat conformation, but the constraint so
produced accentuates the steric crowding within the boat structure. Much of the chemistry of
norbornane is dominated by the far greater steric accessibility of the exo as compared to the
endo position. For example, in many free radical substitution reactions the exo product is
produced preferentially.

7
4

5 3
1
H exo bond
6 2
H
endo bond
Norbornane

1.11 NORBORNYL CATION

Many naturally occurring terpenes are derivatives of Norbornane. Molecular rearrangements
are common among these bicyclic terpenes. Winstein and roberts (1950) actively pursued the
mechanism of the rearrangemts and the associated stereochemical problems using the basic
norbornyl system.

Acetolysis of 2-norbornyl brosylates: Each of the isomeric brosylates (1 and 2) is prepared

and subjected to acetolysis. (Solvolysis using acetic acid as solvent and nucleophile).

Observations regarding following reactions: (i) Rate of solvolysis of 1 to 2 is about 400 (ii)
Both 1 and 2 give 3, the exo-acetate (iii) Optically active exo-brosylate (1) gives 3 which is
racemic (±) (iv) The recovered brosylate (1) is also racemic (v) The rate of racemisation
(measured from specific Rotation) is greater than solvolysis in the case of the exo-isomer (vi)
The rate of racemization is equal to the rate of solvolysis in the case of endoisomer.

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Following are for comparison: (i) Solvolysis rate of endo-brosylate is nearly equal to
cyclohexyl brosylate (ii) Relative rate of 1 to cyclopentyl brosylate is 13.

HOAc, KOAc
1 OBs OAc
3

Exo 95%
5%

OAc
2 BsO 3
87% 13%
Endo

OBs = OSO2 Br

Satisfactory explanation for these observations is needed and also identifies the nature of the
intermediate norbornyl carbocation and its reactivity. Beginning 1950 and till 1980, the topic
became one of the very important area in theoretical organic chemistry. A new concept has
been evolved, namely non-classical carbocation, nonclassical resonance, the sigma (σ)
bridged norbornyl cation. The researches have raised healthy debates and also great
controversies.

Acetolysis of 2-exo and 2-endo-norbornyl brosylate: (i) A → B → C → D is acetolysis

with retention of configuration. The norbornyl cation C is attached by actetate ion from the
exo face (preferred) (ii) B→E is ion pair rearranging to another (C1 – C6 bond migration to
C2) (ii) A → B →E →G (H) is acetolysis of A with rearrangement. D and I are (+),(-) forms
of the acetate (mirror images) (iv) J → B is a slow ionization of endo–brosylate (the C1- H
and C1 – C6 bonds hinder ionisation) No such hindrance exist with A. B→A is ion pair return
and E→F is the rearranged ion pair (E) return. A and F are enantiomers and hence racemic.

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7
4

5 3 BsO
1
A OBs
6 OBs F
fast
7

4
slow
5
OBs 1 OBs
BsO B ion pair 6 ion pair
E 2
J

C G

AcO

OAc
D AcO H
AcO
I

There are two proposals to represent the intermediate carbocation (1) Two rapidly
equilibrating carbocations (C) and (G). (2) Sigma bridged non –classical norbornyl cation.

7
5
4
4

7 6 3
1
6
1 2
G
C
a. classical carbocations b. non classical carbocations

The carbocation (b) is unconventional and unusual therefore called non–classical as against
(a) which is localized carbocation. The cation (b) is also spoken as split – sigma bond (C1 –
C6), bridged cation. Some call these delocalized structures as non – classical resonance. We
will not enter into any discussion at this stage but sum-up the main points.

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There appears to be small anchimeric assistance to solvolyis of A – from C1 – C6

bond at the T.S. This bond is just located at the back of the 2 – exo position. The intermediate
derived from this Transition State is stabilized in comparison with localized carbonium ion
by about 3kcal / mole (calculated from rates of acetolysis of A and J) this energy difference is
too small to think of major reorganization of bonds. The non–classical norbornyl carbocation
has a plane of symmetry (passing through C4, C5 and C6 and the midpoint of C1 - C2 and
therefore achiral. The achiral carbocation is expected to give racemic acetate (product).

1.12 NUCLEOPHILIC SUBSTITUTION AT AN ALLYLIC

CARBON

Generally nucleophilic substitution reactions are involved in direct displacement at a

carbon center: the carbon that is bonded directly to the leaving group is the target for the
attacking nucleophile. This process also known as SN2 substitution. Generally primary alkyl
halides undergo substitution by the SN2 mechanism and do not undergo SN1 reaction.
However, a primary allyl halide is very reactive in an SN1 reaction, for example allyl halides
are more than 30 times reactive than an ethyl halide. Allylic substrates are usually
accompanied by a rearrangement known as allylic rearrangement. In an SN1 mechanism, the
carbocation intermediate would have two possible resonance forms. This is likely in cases
when the allyl compound is unhindered, and a strong nucleophile is used and the products
will be similar to those seen with SN1 substitution. Thus reaction of 1-halo-2-butene system
with nucleophile (viz. NaOH) gives a mixture of 2- buten-1-ol and 1-buten-3-ol, as:

4 2 4 2
Nu
R X R R Nu
3 1 3 A A

Nu
4 2 Nu
R R
B
3 B

The incoming nucleophile, therefore, could attack either C2 (the carbon originally bonded to
the leaving group), or alternatively at C4. These two events would lead to two different
substitution products B and A, respectively:

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Nu
Nu
2 2
4
R X R
3 1 3

Nu

4 4 2
2 R Nu
R X 3
3 1
B

The mechanisms leading to product A are referred to as nucleophilic allylic substitution.

They are also sometimes referred to as 1,4 substitutions, according to a numbering system
where the leaving group is designated atom. If the conjugated π-orbital system extends
further, more allylic substitution products can result: in the following example, 1,6 as well as
1,4 and 1,2 substitutions are possible.

electro p h ilic carb o n

6 4 2

R 5
X
3 1

For example: Hydrolysis of 1-Chloro-2-butene

Cl
4 3 2
1
CH 3 CH C H C H 2C l C H 3C H C H CH 2 CH 3C H CH CH 2
3 C h lo ro 1 b u te n e Cl C l
3 C h lo ro 1 b u te n e

CH 3C H CH CH 2
4 3 2 1

A lly lic c a tio n

(re s o n a n a c e s tru c tu re )

H 2O

O H
C H 3C H CH C H 2C l C H 3C H CH CH 2 H
2 B u te n e 1 ol 2 B u te n e 1 ol

Two distinct mechanisms for aliphatic nucleophilic substitution (SN) are SN1 and SN2. In
terms of stereochemistry, the SN2 process is attended with inversion of configuration where
substitution occurs at a chiral carbon. The SN1 mechanism involves inversion and retention of
configuration (racemization). The question is that arise is whether there are cases where is

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retention of configuration in SN reactions. The answer is yes. Besides NGP in SN reactions,

there is another important mechanism labelled SNi.

Allylic System: The positions adjacent to C=C often show enhanced reactivity compared to
simple alkanes due to the proximity of the adjacent p system. Such positions are referred as
"allylic". Recall that the term "vinylic" is used to described the atoms directly associated with
the C=C unit.

1 1
2 2
resonance hybrid

Thus in allylic systems C1 and C3, each carry a partial positive charge and both were
attacked by a nucleophile which lead to the formation of two products.

The resonance stabilization of the allylic carbocation is presented as above in the orbital
picture. The positive charge is delocalized over two C-atoms by overlap of the filled p-orbital
of the π bond with the vacant p-orbital of the carbocation. Nucleophilic substitution at an
allylic carbon can also take place by an SN2 mechanism in which no allylic rearrangement
usually takes place. However, allylic rearrangements can also take place under SN2
conditions through the following mechanism in which the nucleophile attacks at the γ carbon
rather than the usual position. This mechanism is called SN2’ mechanism. The SN2’
rearrangement normally occurs exclusively when the SN2 process is sterically hindered.

3 3
R R R R

R C C C X R C C C X
1 2 1 2
R R Y R R

Thus, the p orbital system of a double bond can stabilize an adjacent carbocation by donating
electron density through resonance. Due to the stability of these allylic cations, they are
readily formed as intermediates during chemical reactions, for example SN1 reactions of
allylic halides.

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1. Allyl chlorides, bromides and iodides are good substrates for substitution reactions.

2. A variety of nucleophiles can be used to generate a range of new functional groups.

3. The process can be complicated by the allylic rearrangement where the nucleophile
can attack either of the deficient sites.

1.13 NUCLEOPHILIC SUBSTITUTION AT AN ALIPHATIC

TRIGONAL CARBON

Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is
double bonded to oxygen, sulphur or nitrogen. The nucleophilic substitution occurs through
tetrahedral mechanism, often called as addition-elimination. Although this mechanism
displays second order kinetics, it is not the same as the SN2 mechanism.

O O O
slow fast
R C X Y R C X R C Y
X
Y

In tetrahedral mechanism first the nucleophile (Y) attacks to give a tetrahedral intermediate
containing both X (leaving group) and Y and then the leaving group (X) departs. The
tetrahedral mechanism is supported by the second order kinetics and isotopic labelling. In
some cases, tetrahedral intermediates have been isolated or detected spectrally. When the
reaction is carried out in acid solution the hydrogen ion acts as a catalyst. The reaction rate is
increased as it is easier for the nucleophile to attack the carbon when the electron density of it
has decreased.

O H OH
O
R C X H R C X R C X

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Mechanism:

OH OH

step 1: R C X Y R C X

OH OH OH

step 2: R C X C R C X
R

Y Y Y

OH
O
step 3: R C R C X H

1.14 NUCLEOPHILIC SUBSTITUTION AT VINYLIC CARBON

The subject matter under the title is concerned with nucleophilic substitution at unsaturated
carbon such as vinylchloride (CH2=CHCl).

C C Y C C X C C
X Y

Under normal conditions, nucleophilic substitution at vinylic carbon is extremely slow

compared to substitution at saturated carbon. Vinyl substrates are essentially inert towards
nucleophiles. There are two reasons for this lack of reactivity. The first one is vinyl C-X bond
(X- halogens). This is clearly depicted in the above reaction.

In fact most of contexts, vinyl halides and related compounds can be considered essentially
inert towards nucleophiles. There are two reasons for this, first, a vinyl C–X bond (X =
halogen, oxygen, or nitrogen) is stronger than and alkyl C–X bond because of a resonance
interaction between the double bond and an unshared pair on X. This interaction also
weakens and polarizes the π-bond, which is why such compounds are reactive towards
electrophilic addition.

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C C C C C C
X X X

The second reason for low reactivity of vinyl substrate towards nucleophilic substitution is
that the SN2 transition state as well as the SN1 intermediate (a vinyl cation), are too high in
energy to be readily accessible

1/ 2
Nu
A A Nu
SN2 like C C
C C

B B
A X1/ 2
C C

B A A Nu A
SN1 like Nu
C C C C C C
Nu
B B B

Example: The heterolytic bond dissociation energy for vinyl chloride is 207 kcal as
compared with 191 kcal for EtCl and 227 kcal for MeCl. Values for the fluorides, bromides
and iodides show the similar differences. It takes 16-18 kcal more energy to break the C–X
bond in a vinyl halide than in the corresponding EtCl. Except for the bond in methyl halides,
this is the strongest C–X bond we have so far encountered. The bond length for vinylic C-Cl
is 1.73 Ǻ compared with 1.78 Ǻ for the saturated C-Cl bond. A shorter bond is, in general, a
stronger bond. Thus the rate determining step involves breaking of the C–X bond. The bond
in vinyl halides is harder to break, and reaction is slower.

Not surprisingly, the difficulty of generating vinylic cations by heterolysis has been taken as
a challenge by the organic chemist, and, in work done mostly since about 1970’s, vinylic
cations have emerged as accessible intermediates with fascinating properties. Many people
from many countries have been involved in this research. The vinylic cations can readily be
made through solvolysis of the SN1 kind if two conditions are met:

a) The leaving group is extremely good one, and

b) The vinylic group contains electron releasing substituents.

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Most commonly used for this purpose is the super leaving group, viz. trifluoro
methanesulfonate, (–OSO2CF3) which is also known as triflate. The powerful electron
withdrawing F-atom (through dispersal of the negative charge) help to stabilize the triflate
anion, and make the parent acid CF3SO2OH one of the strongest Lowry Bronsted acids
known, much stronger than the familiar H2SO4 or HClO4. The triflate anion is
correspondingly an extremely weak base, and one of the best leaving group in organic
chemistry.

OTf
OTf
Triflate anion
vinylic triflate vinylic cation

1.15 STRUCTURE REACTIVITY ANALYSIS OF ATTACKING

NUCLEOPHILE, LEAVING GROUP AND REACTION
MEDIUM

1.15.1 Factors Influencing SN2 Reaction:

a. Solvent: Nucleophiles are more stabilized than the transition state in polar protic solvents
due to solvation where the ground state energy of nucleophile is reduced in comparison to the
transition state's energy. Due to this, reaction progress leads to a higher activation energy and
thus to a lower reaction rate. The nucleophiles are less solvated in polar aprotic solvents
(DMSO, DMF and HMPT) which results in the less stabilized ground state when compared
to the polar protic solvents. Thus, the nucleophile is more reactive which leads to the
lowering of activation energy, and a higher rate of the reaction. Thus, for SN2 mechanism,
increasing solvent polarity usually decreases the rate of reaction.

b. Nucleophile: In SN2 reaction, the nucleophile is involved in the rate determining step, so
the nature and concentration of nucleophile affect the rate of SN2 reaction. The stronger the
nucleophile, the faster is the SN2 reaction. In SN2 reaction the high energy transition is
required. Therefore, a high concentration of strong nucleophile is required for SN2 reaction.
Good nucleophiles having higher energy in the ground state, and are less stable than the poor
nucleophiles. Thus, the activation energy in SN2 reaction is lower and the reaction rate is

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consequently higher than in SN1 reaction with a comparatively stable nucleophile. The
reactivity of small nucleophiles is rapid than the sterically demanding nucleophiles. Basic and
negatively charged nucleophiles are more reactive as compared to uncharged nucleophiles.

c. Substrate: Activation energy of the transition state in SN2 reaction increases as the steric
hindrance in the substrate increases, while at the same time reaction rate is decreased. The
reaction rate of SN2 reactions will be in the order of 1o > 2o > 3o alkyl halide (CH3–X >
RCH2–X >> R2CH–X >>> R3C–X). In the cases of secondary and tertiary alkyl compounds,
SN2 reaction is largely superseded by an SN1 reaction or elimination. Rates of SN2 reactions
for allylic and benzylic systems are also increased because of resonance in the transition
state.

d. Leaving Group: A leaving group which becomes a more stable species after it departs is a
better leaving group. The best leaving groups are the weakest bases. Stable anions are good
leaving groups which results in the lowering of activation energy while reaction rate is
higher. For example, iodide anions are better leaving groups than chloride anions. Hydroxide
anions, alkoxides, fluoride anions, and amide anions are poor leaving groups thus SN2
reactions with fluoroalkanes, alcohols, ethers, or amines virtually never occur. However,
acid-catalysed SN2 reactions with alcohols or amines can take place, as the leaving group
does not consist of the hydroxide anion. Thus the leaving groups can be arranged in the order:

MsO‒, TsO‒ > I‒ > Br‒ > Cl‒ > F‒ > (‒OH, ‒NH2)

Where, MsO‒ and TsO‒ are extremely good leaving groups due to resonance stabilization.
Thus, the nature of leaving group not only affects the rate of reaction but may also change the
reaction mechanism.

1.16.2 Factors Influencing SN1 Reaction:

a. Solvent: The rate of the reaction can be affected by the energy level of the reagents.
Solvation of the carbocation allows the carbocation to be surrounded by more electron
density, making the positive charge more stable (see below). The solvent can be protic or
aprotic, but it must be polar solvent. Polar protic solvents have a H-atom attached to an
electronegative atom so the hydrogen is highly polarized. Polar aprotic solvents have a dipole
moment, but their hydrogen is not highly polarized. Polar aprotic solvents are not used in
SN1 reactions because some of them can react with the carbocation intermediate and lead to
unwanted product. Thus, polar protic solvents are preferred in SN1 reaction which helps to

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speed up the rate of reaction due to large dipole moment of the solvent which helps to
stabilize the transition state. The highly positive and highly negative parts interact with the
substrate to lower the energy of the transition state. Since the carbocation is unstable,
anything that can stabilize this even a little will speed up the reaction.

Sometimes in an SN1 reaction the solvent acts as the nucleophile known as solvolysis
reaction. The polarity and the ability of the solvent to stabilize the intermediate carbocation,
is very important as shown by the relative rate data for the solvolysis (in table). The dielectric
constant of a solvent provides a measure of the solvent's polarity. A dielectric constant below
15 is usually considered non-polar. Thus, higher the dielectric constant more polar will be
substance and in the case of SN1 reactions the faster the rate.

Table

Solvent Dielectric Constant Relative rate

Acetic acid 6 1
Methanol 33 4
Water 78 150000
The example given here illustrates this concept.

b. Nucleophile: Nucleophiles involved in the SN1 mechanism are mostly weak and neutral
molecules (viz. H2O, ROH). The strength of the nucleophile does not affect the reaction rate
of SN1 because; the nucleophile is involved in the rate-determining step. However, if you

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have more than one nucleophile competing to bond to the carbocation, the strengths and
concentrations of those nucleophiles affect the distribution of products. For example, if you
have (CH3)3CCl reacting in water and formic acid where the water and formic acid are
competing nucleophiles, you will get two different products: (CH3)3COH and
(CH3)3COCOH. The relative yields of these products depend on the concentrations and
relative reactivities of the nucleophiles.

c. Substrate: The hyperconjugation and the inductive effect allow alkyl groups to stabilize
carbocations. The more stable carbocation intermediate has a lower activation barrier, so the
SN1 reaction occurs faster. In general, the SN1 reaction is favored in the order is-

Benzylic > Allylic > 3° > 2° > 1° >> Me+

Substrates wherein the leaving group (LG) is on a 3° carbon will lead to a reaction in the
presence of a good nucleophile (Nu). Since, 1° carbocations are highly energetically
unfavorable, as a rule of thumb they generally do not form. The rate for hydrolysis of alkyl
halide is in the order of halides, 3o > 2o > 1o > MeX. Thus, we can say the electronic factor is
more important than the steric factor. The Eact for the carbocation intermediate will be
highest for MeX (1o), while least for the 3o. The molecules in which carbon next to the site of
substitution contains a double bond, the SN1 reaction is possible. The reason is that the
positive charge on the carbocation can be delocalized among multiple possible resonance
structures (resonance and delocalization) making the carbocation dramatically stable. This
effect can occur when the carbon atom of interest is next to one double bond (allylic) or a
benzene ring (benzylic). In allylic case the delocalization of the positive charge, the
nucleophile can attack at multiple sites while this effect is absent in the benzylic system due
to the need to preserve aromaticity. For example, the allylic carbocation can form two
different resonance structure, both are available for reaction (see below). In the first example
we end up with similar carbocation intermediate but we have different situation in the second
example where we have 2o and 3o carbocation intermediates. Thus, second reaction will lead
to 3o product through stable 3o carbocation intermediate.

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Br

Br

Delocalized and resonance

If there is a benzylic carbocation, it is also resonance stabilized but only the carbocation on
the benzylic position is reactive (retains the aromatic ring) as follows:

d. Leaving Group: The leaving group is almost always expelled with a full negative charge.
The best leaving groups are those that can best stabilize an anion (i.e. a weak base). SN1
reaction speeds up with a good leaving group. This is because the leaving group is involved
in the rate-determining step. A good leaving group wants to leave so it breaks the C-leaving
group bond faster. Examples of LG:

(Good…….) -OMs, -OTos, Triflate ion, NH3 > H2O ≈ I- , Br- > Cl- > F- (-OH, -NH2)
(…….poor)

As you go from left to right on the periodic table, electron donating ability decreases and thus
ability to be a good leaving group increases. Halides are an example of a good leaving group
whose leaving-group ability increases as you go down the column. Other examples of good
leaving group viz. methyl sulfate ion and other sulfonate ions.

(Good)….. I- > Br- > Cl- > F- …..(poor)

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For example: The two reactions below is the same reaction done with two different leaving
groups. One is significantly faster than the other. This is because the better leaving group
leaves faster and thus the reaction can proceed faster.

Br NaOH OH

faster

NH3 NaOH OH

slower

1.16 HSAB PRINCIPLE

Hard and Soft Acids and Bases (HSAB) Theory is a qualitative concept introduced by Ralph
Pearson to explain the stability of metal complexes and the mechanisms of their reactions.
However it is possible to quantify this concept based on Klopman's FMO analysis using
interactions between HOMO and LUMO. According to this theory, the Lewis acids and bases
can be further divided into hard or soft or border line types. Hard Lewis acids are
characterized by small ionic radii, high positive charge, strongly solvated, and empty orbital’s
in the valence shell and with high energy LUMOs. Soft Lewis acids are characterized by
large ionic radii, low positive charge, and completely filled atomic orbital’s and with low
energy LUMOs. Hard Lewis bases are characterized by small ionic radii, strongly solvated,
highly electronegative, weakly polarizable and with high energy HOMOs. Soft Lewis bases
are characterized by large ionic radii, intermediate electro negativity, highly polarizable and
with low energy HOMOs. The Border line Lewis acids and bases have intermediate
properties. Remember that it is not necessary for Lewis acid or base to possess all the
properties to be classified as hard or soft or borderline. In short, hard acids and bases are
small and non-polarisable, whereas soft acids and bases are larger and more polarisable.
1.16.1 HSAB Principle: According to HSAB concept, hard acids prefer binding to the hard
bases to give ionic complexes, whereas the soft acids prefer binding to soft bases to give
covalent complexes. It is sometimes referred to as Hard-Soft Interaction Principle (HSIP).
The large electro negativity differences between hard acids and hard bases give rise to strong
ionic interactions. The electro negativities of soft acids and soft bases are almost same and
hence have less ionic interactions. i.e., the interactions between them are more covalent. The

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interactions between hard acid - soft base or soft acid - hard base are mostly polar covalent
and tend to be more reactive or less stable. The polar covalent compounds readily form either
more ionic or more covalent compounds if they are allowed to react.

1.16.2. HSAB & FMO Analysis: According to FMO analysis, the interactions between
acids and bases are controlled by the relative energies of the participating frontier molecular
orbitals (FMO) i.e., HOMO and LUMO. Greater the energy gap between the HOMO &
LUMO, harder is the species. Quantitatively the absolute hardness of a species is determined
by following equations.

or

Here, it’s better to conclude with the Soft Bases as good nucleophile and a comprehensive
comparison between Basicity & Nucleophilicity ….

Section 1.16.3 and 1.16.4 are academic overflows can be avoided to have a space in Organic
Chemistry domains.

1.16.3: Characteristics of Hard, Soft & Borderline Acids & Bases

Type of Acid/Base Characteristics Examples

a. Atomic centres of small
H+, Li+, Na+, K+, Be2+, Mg2+,
ionic radii (<90 pm).
Ca2+, Sr2+, Sn2+
b. High positive charge.
c. Empty orbitals in their
Al3+, Ga3+, In3+, Cr3+, Co3+,
valence shells.
Hard acids Fe3+, Ir3+, La3+, Si4+, Ti4+, Zr4+,
d. Low electronegativity (0.7-
Th4+,U4+, VO2+ , UO22+
1.6) and low electron affinity.
e. Likely to be strongly
BeMe2, BF3, BCl3, B(OR)3,
solvated.
AlMe3
f. High energy LUMO.

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a. Large radii (>90 pm).

b. Low or partial positive
Cu+, Ag+, Au+, Hg+ , Cs+ , Tl+
charge.
, Hg2+ , Pd2+, Cd2+ , Pt2+
c. Completely filled orbitals in
their valence shells.
Soft acids Metal atoms in zero oxidation
d. Intermediate
states
electronegativities (1.9-2.5)
e. Low energy LUMO's with
BH3
large magnitude of LUMO
coefficients.
Fe2+ , Co2+ , Ni2+ , Cu2+ , Zn2+ ,
Border line acids
Pb2+ , B(CH3)3, SO2, NO+
a. Small radii (around 120pm)
& highly solvated.
H2O, OH-, F-, Cl-, CH3CO2-,
b. electronegative atomic
PO43-, SO42-, CO32-, NO3-,
Hard bases centres (3.0-4.0).
ClO4-, ROH, RO-, R2O, NH3,
c. Weakly polarizable.
RNH2, N2H4
d. Difficult to be oxidized.
e. High energy HOMO.
a. Large atoms (>170 pm)
with intermediate
electronegativity (2.5-3.0). S2-, RSH, RS-, R2S, I-, CN-,
b. High polarizability SCN-, S2O3-, R3P, R3As,
Soft bases
c. Easily undergoes oxidation. (RO)3P, RNC, CO, C2H4,
d. Low energy HOMO's but C6H6, R-, H-
large magnitude HOMO
coefficients.
Aniline, pyridine, N3-, Br-,
Border line bases
NO2-, SO32-, N2

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1.16.4 Applications of HSAB Principle

a. In hydrogen bonding: The strong hydrogen bond is possible in cases of H2O, NH3 and
HF, since the donor atoms (F, O & N) are hard Lewis bases and their interactions with
partially positively charged H, which is a hard acid, are stronger.

b. Linkage of ambidentate ligands to metal atoms:

The SCN- ligand is an ambidentate ligand and can be S-bound to metal (M-SCN) and referred
to as thiocyanate or can be N-bound to metal (M-NCS) and is referred to as isothiocyanate.
The choice among S-bound or N-bound is decided by soft or hard acid base behaviour. S is
comparatively soft base than N atom. Hence soft metal ions are S-bound while hard metal
ions are N-bound.

1) SCN- bonds through sulfur atom (soft base) when bonded to Pt2+, a soft acid.

2) It bonds through nitrogen atom (a hard base) when linked to Cr3+, a hard acid.

3) When Fe2+ reacts with SCN- a bright red [Fe(SCN)]+ ion is formed, whereas Cr3+ forms
[Cr(NCS)]2+. Fe2+ is a border line acid and is S-bound. Whereas Cr3+ is hard acid and prefers
to be N-bound.

4) The molecule (CH3)2NCH2PF2 would bond to BF3 through N whereas it would bond to
BH3 through P. BF3 is a hard acid and prefers to bind with N atom - a hard base. Whereas,
BH3 is a soft acid and preferentially bonded to soft base, P atom.

Symbiotic effect: The hard-soft character of the metal ion is altered by the other groups
attached. It is referred to as a symbiotic effect. For example, the isolated Co3+ is a hard acid
and is expected to make bond with SCN- ion through N atom as observed in
[Co(NH3)5(NCS)]3-. However, when bound to five soft base ligands like CN- ions, the
hardness of cobalt ion (Co3+) is reduced. Thus [Co(CN)5]2- behaves as a soft acid and prefers
to bind with SCN- ion through S atom to form [Co(CN)5(SCN)]3-.

c. HSAB to predict direction of Inorganic reactions:

HSAB principle is used to predict the outcome of few of the reactions. We can predict
whether a reaction proceeds to the right or left based on soft or hard acid/base interactions.

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1) The following reaction is possible and proceeds to the right since As3+ is softer than P3+
and I- is softer than F-. Remember that both As3+ and P3+ are soft but relatively As3+ is softer
due to larger size.

AsF3 PI3 Asl3 PF3

2) The following reaction is possible since Mg2+ is harder acid than Ba2+ and O2- is harder
base than S2-.

MgS BaO MgO BaS

3) P2F4 is prepared by treating PF2I with mercury as shown below.

2PF2I + 2Hg ------> Hg2I2 + P2F4

In this reaction, it is iodine rather than fluorine that is removed from PF2I. Hg22+ ion is a soft
acid that prefers soft base I- rather than hard base F-.

d. Hard Soft interactions - Types of ores:

We know that the hard metals prefer to bind with hard anions and thus they are available as
oxides or fluorides or carbonates or silicates in the nature. Whereas, the soft metals prefer to
bind with soft anions and hence are found in the nature as sulfides or phosphides or selenides.
E.g. Aluminium is mostly found in nature as alumina, Al2O3 - an oxide ore, since Al3+ is a
hard metal which prefers to combine with hard oxide anion rather than the soft sulfide ion.
Silver & copper metals exist as sulfide ores since both Ag+ and Cu2+ are soft metals. The f-
block elements are found in nature as silicate minerals since the trivalent lanthanides are
actinides are hard acids and tend to bind with hard oxygen bases as in silicates.

e. Precipitation reactions & Qualitative analysis:

The softer acids like Ag+, Hg+, Hg2+ etc., and border line acids like Fe2+, Ni2+, Cu2+, Zn2+,
Pb2+ etc., can be precipitated as sulfides from their aqueous solutions since S2- ion is a softer
base. Following table illustrates the separation of cations based on their hardness or softness.

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1.17. AMBIDENT NUCLEOPHILES

Many nucleophiles may be represented by two or more resonance forms in which the
unshared pair of electrons may residue on two or more atoms. In these cases, the nucleophiles
may attack in two or more different ways to give different products. E.g. removal of a proton
from ethyl acetoacetate (i), for instance, gives an ion which is a resonance hybrid of ii
(Carbanion) and iii (Enolate).

i ii iii

Such ions are called ambident anions, since they have two possible attacking atoms leading to
the formation of two compounds. Similar types of anions are derived from compounds such
as diethyl malonate DEM (a) and acetylacetone (b).

a.

b.

On treatment with alkyl halides, these ions attack the carbon (leading to C-alkylation) or
oxygen (leading to O-alkylation).

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O R O
C alkylation
O O C CH C

C CH C

R X

O OR
O O
O alkylation
C CH C
C CH C

Mention Chemoselectivity Reaction conditions ?????

Similarly, phenoxide ions, generated by the treatment of phenols with base, may undergo C-
alkylation (a) or O- alkylation (b) on treatment with alkyl halides.

O O
OH
R R R
base etc.

O O CH3
O
R R R
CH3Br
CH3 Br

C alkylation O alkylation

The positive counter ion plays an important role in deciding the atom which act as a
nucleophile. For example, in case of NaCN, the attack of cyanide ion takes place from the
carbon atom, whereas in AgCN, attack takes place from the nitrogen atom.

NaCN- Kinetically controlled product and the more nucleophilic C-atom is approached

AgCN- Thermodynamically controlled and more electronegative N-atom is approached as

Ksp of AgX is quite large in organic medium

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C N C N

NaCN
R C N NaX
R X
R NC AgX
AgCN

In many cases, it has been observed that the nature of solvent influence the course of reaction.
When a nucleophile is relatively free, it normally attacks with its more electronegative atom.
However, when the atom is solvated or located close to the positive counterion, attack takes
place through the less electronegative atom. An illustrative example is that of sodium
naphthoxide which gives the product of O-alkylation, on treatment with benzoyl bromide in
DMSO, in 95% yield. However, when the same reaction is performed in 2,2,2-
trifluoroethanol, the major product is obtained by C-alkylation.

OCH2Ph
DMSO

ONa O alkylation

CH2Ph
Ph CH2Cl
OH
CF3CH2OH
C alkylation

Ambident dianions can be generated by treating compounds such as ethyl acetoacetate with
two moles of a strong base.

O O O O
base
CH3 C CH2 C OEt CH2 C CH C OEt
2 moles
ambident dianion

Hydrogen atom attached to the middle carbon atom of compound such as ethyl acetoacetate,
being flanked by two carbonyl group, would be more acidic than those on the end carbon
being attached to a single group.

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O O

CH2 C CH C OEt

ambident dianion

RX 1 mole

O O

RCH2 C CH C OEt

O O

RCH2 C CH2 C OEt

In case one mole of base is used, the alkylation at methylene can be carried out as methine
Carbanion is more stabilized through delocalization.

O O

CH3 C CH2 C OEt

base 1 mole

O O

CH3 C CH C OEt

RX

O R O

CH3 C CH C OEt

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1.18. SUMMARY
In this unit we have provided a brief knowledge about the SN2, SN1, mixed SN1 and SN2, SNi
and SET mechanism. This chapter will also provide knowledge of neighboring group
participation by and bonds, anchimeric assistance, classical and non-classical
carbocations, arenium ions, norbornyl systems and common carbocation rearrangements. We
also learned about the the SNi mechanism, nucleophilic substitution at an allylic, aliphatic
trigonal and a vinylic carbon. We learned reactivity effects of substrate structure, attacking
nucleophile, leaving group, reaction medium, HSAB principle and ambident nucleophiles.

1.19. TERMINAL QUESTIONS

1. Using the given codes, arrange the following compounds in decreasing order the rate of
solvolysis by SN1 mechanism:

Cl
Cl
Cl
A B C

Codes:

A. A ˃ C ˃ B
B. C ˃ B ˃ A
C. A ˃ B ˃ C
D. B ˃ A ˃ C

2. Which one of the following statements is correct for the reactivity in SN2 reaction?

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A. Cl is more reactive than CH2Cl

B. is more reactive than I

I

C. is more reactive than Cl

Cl

D. is more reactive than I

Cl

3. Which of the following statements are correct?

A. Vinyl chloride does not give SN reaction but allyl chloride gives.
B. CH3CH=CHCH2Cl react with KCN to give a mixture of isomeric products.
C. Displacement of H- is easier than that of Cl-.
D. CH3CH2-O-CH2Cl is much more reactive in SN1 reaction than CH3CHClCH3
4. Using the following codes, arrange the given halides in order of decreasing reactivity
towards NaI in acetone:
MeCl Me2CHCl Me2CHF
1 2 3

A. 1 ˃ 2 ˃ 3
B. 2 ˃ 3 ˃ 1
C. 2 ˃ 1 ˃ 3
D. 3 ˃ 2 ˃ 1
5. Which among the following anions is the best nucleofuse?
A. AcO-
B. –OH
C. TsO-
D. EtO-
6. Predict the products of the following SN2 reactions?

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1. EtI
N

I EtO
2.

3. Br
I

7. Complete the following reaction:

1. CH3CH CHCH2Cl H2O

2. CH3CH CHCH2Cl aq. NaOH

Cl

3. CH3OH

8. Most nucleophiles are anions but some anions are not nucleophiles. A particular example
is BF4-. Explain the inertness of BF4- as a nucleophile.
9. Thiocynate (SCN-) and cynate (OCN-) each give two products when allowed to react with
allyl bromide. In the former case, one product predominates highly. Show the products in
each reaction and account for this predominance.
10. 3-Bromo-3-methyl-1-butene forms two substitution products when it is added to a
solution of sidium acetate in acetic acid.
a. Give the structures of the substitution products.
b. Which are the kinetically controlled products?
c. Which is the thermodynamically controlled product?

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1.20. ANSWER TO TERMINAL QUESTIONS

1. C
2. B
3. A, B & D
4. A
5. C

6.

1.

N
I
Et

OEt
2.

3. I

OH
1. CH3CH CHCH2OH and CH3 CH CH CH2

2. CH3CH CHCH2OH and CH3 CH CH CH2

OH
OMe

3.
and

OMe

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1.21. REFERENCES

1. Singh, J and Yadav, L.D.S, 2004, advanced organic chemistry, Pragati Prakashan,
Meerut. 329-383.

2. Jerry March. 2007. Advanced Organic Chemistry-Reactions, Mechanism and

Structure, John Wiley. 4th edition. 293-500.

3. Mukherji S. M. and Singh S. P. 2015. Reactions Mechanism in Organic Chemistry.

Trinity Press. 280-327.

4. Singh M.S. 2005. Advanced Organic Chemistry. Reaction and Mechanisms. Pearson
Education. 74-122.

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UNIT-2 AROMATIC NUCLEOPHILIC

SUBSTITUTION REACTION

CONTENTS:
2. 0. Objectives
2.1 Introductions
2.2 The SNAr mechanism
2.2.1 Evidence for Nucleophilic Aromatic Substitution (SNAr) mechanism:
2.3 The SN1 mechanism
2.3.1 Evidence for a unimolecular sN1 mechanism
2.4 The benzyne (arynes) mechanism
2.4.1 Benzyme (aryne) mechanism:
2.5 The SRN1 mechanism
2.5.1 Evidence for the SRN1 mechanism:
2.6 Effects of Reactivity & Structure, leaving group and attacking nucleophile
2.6.1 The effect of substrate structure:
2.6.2 The effect of the leaving group:
2.6.3 The effect of the attacking nucleophile:
2.7 Von Richter rearrangements
2.8 Sommelet-Hauser rearrangement
2.9 Smiles rearrangement
2.10 Summary
2.11 Terminal questions
2.12 Answers to terminal questions
2.13 References

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2.0 OBJECTIVES

Objective of this unit, Aromatic Nucleophilic Substitution reaction is to make students

aware about the SNAr, SN1, benzyne and SNR1 mechanism. This chapter will also provide
knowledge of reactivity effect of substrate structure, leaving group and attacking nucleophile.
Besides important name reactions of synthetic utility alongwith the von Richter, Sommelet-
Hauser and Smiles rearrangements.

2.1 INTRODUCTION

A Nucleophilic Aromatic Substitution reaction is a reaction in which one of the substituent’s

in an aromatic ring is replaced by a nucleophile (Ipso Substitution).

X Nu

Nu

X
R R
X= halogen etc.
Nu= nucleophile

Unlike aliphatic compounds having a nucleophilic group as a leaving group, aromatic

compound having the same group bonded directly to the aromatic rings, which do not
undergo nucleophilic substitution under ordinary conditions. This unusual reactivity of
aromatic compounds arises due to the presence of a lone pair of electrons/π-bond on the
leaving group/key atom. As a result result of delocalization of this lone pair of e- / π-bond
through conjugation with the π e- of the ring, there is partial double bond character between
the carbon of the ring and the key atom. Thus, the key atom/leaving group become soundly
bonded to the aromatic ring and cannot be replaced by easily.

L L L L

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Another reason for the low reactivity is the aromatic rings behave like a nucleophile due to
the presence of electron cloud above and below the plane of aromatic rings. This shields the
ring carbon from the attack of a nucleophile.

Aromatic nucleophilic substitution may take place in extreme conditions like high pressure or
high temperature or both, catalyst etc. Aromatic nucleophilic substitution reactions undergoes
with less difficulties by proper substitution of aromatic rings with –R or –I group at ortho or
para or both the positions and aromatic nucleus having electronegative heteroatom (O, N, S
etc.) because –R or –I group are the activating groups for aromatic nucleophilic substitution.
These groups decrease electron density on the aromatic ring and activate it for nucleophilic
substitution. There are four principal mechanisms for aromatic nucleophilic substitution.
Each of the four is similar to one of the aliphatic nucleophilic substitution mechanisms.

1. The SNAr Mechanism

2. The SN1 Mechanism
3. The Benzyne Mechanism
4. The SRN1 Mechanism

2.2 THE SNAr MECHANISM

The IUPAC designation is AN+DN (the same as for the tetrahedral mechanism). This
mechanism is generally found where activating groups are present on the ring. Nucleophilic
aromatic substitution (SNAr) mechanism consists of following two main steps:

Step 1: Attack of the nucleophilic species at the ipso carbon (the carbon bearing the leaving
group) of the aromatic ring. It is a rate determining step (not always).

Y Y
Y
X
slow X X X
Y
ipso
addition
Meisenheimer complex

Step 2: Elimination of the leaving group and regeneration of the aromatic ring.

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Y Y
fast X
X elimination

It resembles the arenium ion mechanism of aromatic electrophilic substitution. In both the
cases (aromatic nucleophilic substitution & aromatic electrophilic substitution), the attacking
species form a bond with the substrate, giving an intermediate and then the leaving group
depart, i.e., both involve an addition elimination process.

2.2.1 Evidence for Nucleophilic aromatic substitution (SNAr) mechanism:

1. Probably the most convincing evidence for nucleophilic aromatic substitution

mechanism was the isolation of Meisenheimer or Meisenheimer–Jackson salts
intermediate, prepapred by the reaction between 2,4,6-trinitrophenetole and
methoxide ion. The structures have been proved by NMR and by X-ray
crystallography.

OEt EtO OMe

O2N NO2
O2 N NO2
etc.
OMe

N
NO2 O O
Meisenheimer-Jackson salts intermediate

2. Studies of the effect of the leaving group on the nucleophilic aromatic substitution
reaction. If the nucleophilic aromatic substitution mechanism were similar to either
the SN1 or SN2 mechanisms, the Ar–X bond would be broken in the rate-determining
step. In the nucleophilic aromatic substitution mechanism, this bond is not broken
until after the rate-determining step (i.e. if step 1 is rate determining). There is some
evidence that electron transfer may be operative during this process. We would
predict from this that if the SNAr mechanism is operating, a change in leaving group
should not have much effect on the reaction rate. In the reaction of dinitro compound
with piperidine, when X was Cl, Br, I, SOPh, SO2Ph, or p-nitrophenoxy, the rates
differed only by a factor of 5.

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X
NO2
O2N N X
N
NO2
NO2 H

This behavior would not be expected in a reaction in which the Ar–X bond is broken
in the rate-determining step. We do not expect the rates to be identical, because the
nature of X affects the rate at which Y attacks. An increase in the electronegativity of
X causes a decrease in the electron density at the site of attack, resulting in a faster
attack by a nucleophile. The very fact that fluoro is the best leaving group among the
halogens in most aromatic nucleophilic substitutions is good evidence that the
mechanism is different from the SN1and the SN2 mechanisms, where fluoro is by far
the poorest leaving group of the halogens.

Some examples of nucleophilic aromatic substitution (SNAr) reaction:

a. With substrate having no activating group.

Cl

o
300 C o CuCN/ o
Aq. NaOH Aq. NH3/ 200 C 200 C
200 atm Pyridine
Cu2O

OH NH2 CN

b. With substrates having activating group (s)

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Cl
1.

NO2

o o
NH3/EtOH 150 C NaOH 200 C

NH2 OH

NO2 NO2

2.
OMe OH

NaOH
Temp.

NO2 NO2

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NH2

NO2
NH3
o
170 C

NO2
3.
OH
Cl
NO2
NO2 aq Na2CO3

NO2
NO2
NHNH2

NO2
NH2NH2
o
130 C

NO2

2.3 THE SN1 MECHANISM

A unimolecular SN1 mechanism (IUPAC: DN+AN) is very rare; it has only been observed for
aryl triflates in which both ortho positions contain bulky groups (tert-butyl or SiR3). A
unimolecular SN1 mechanism are mainly given by aromatic diazonium salts.

ArN N Nu Ar Nu N2
Mechanism:

Step 1:

N N
N2

Step2:

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Y
Y

Aryl cation is highly unstable but nitrogen is highly stable. Hence nitrogen is very good
leaving group, this makes the generation of aryl cation extremely easy.

2.3.1 Evidence for a unimolecular SN1 mechanism

1. The reaction rate is first order in diazonium salt and independent of the concentration of
nucleophile.

2. When high concentrations of halide salts are added, the product is an aryl halide but the
rate is independent of the concentration of the added salts.

3. The effects of ring substituents on the rate are consistent with a unimolecular rate-
determining cleavage e.g., electron releasing m substituents (OH, OMe, Me, etc.) increase the
rate and electron withdrawing m substituents (COOH, NO2, Cl, etc.) decrease the rate of
reaction.

4. When reactions were run with substrate deuterated in the ortho position, isotope effects of
1.22 were obtained. It is difficult to account for such high secondary isotope effects in any
other way except that an incipient phenyl cation is stabilized by hyperconjugation, which is
reduced when hydrogen is replaced by deuterium.

H
H

Some examples of unimolecular SN1 reactions of aromatic diazonium cation are given
below:

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N N

H2O N2 X N2 N3 N2 CH3OH N2

X N3 OCH3
OH

H
H

2.4 THE BENZYNE (ARYNES) MECHANISM

Some aromatic nucleophilic substitutions are clearly different in character from those that
occur by the SNAr mechanism or the SN1 mechanism. Unactivated aryl halides having at lest
one hydrogen in ortho position undergo nucleophile substitution with a very strong base like
potassium amide or sodium amide in liquid ammonia. The reaction also occurs with bases
such as PhLi and BuLi. This reaction proceeds through benzyne (aryne) intermediate and the
mechanism is called benzyne (aryne) mechanism.
Some important facts involve in the benzyne (arynes) mechanism are:
i. Substitutions occur on aryl halides that have no activating groups.
ii. Bases are required that are stronger than those normally used.
iii. The incoming group does not always take the position vacated by the leaving
group (Cine substitution).
Example of aromatic nucleophilic substation via benzyne:

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CPh3
Ph3C

Cl
KNH2

chlorobenzene benzyne
NH2
NH3

2.4.1 Benzyme (Aryne) Mechanism: This mechanism involves elimination followed by

addition. Hence, it is called elimination-addition mechanism of aromatic nucleophilic
substitution.
Step 1: a suitable base removes the ortho hydrogen, with subsequent (or concomitant)
loss of the chlorine (leaving group) to generate symmetrical intermediate is called
benzyne.

Cl
NH2 NH3 Cl

H
Step 2: benzyne is attacked by the NH3

NH3 NH2
NH3

Evidence in support of the benzyne (aryne) mechanism:

i. 1-14C-chlorobenzene reacts with potassium or sodium amide in liquid ammonia
gives almost equal amounts of 1-14C-aniline and 2-14c-aniline, due to the
formation of symmetrical intermediate benzyne.
14 NH2
NH3

14 Cl 14
KNH2/NH3

14
H
NH3
NH2

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ii. Aryl halides having no hydrogen, ortho to the halogen do not react under the
same conditions.

Br
H3C CH3
KNH2 No Reaction
NH3

CH3

iii. Benzynes are usually detected by spectroscopy or by their participation in

dimerisation and trapping through cycloaddition.

dimerisation
2

cycloaddition

cycloaddition

2.5 THE SRN1 MECHANISM

When 5-iodo-1,2,4-trimethylbenzene treated with KNH2 in NH3, gives A and B in the ratio
0.63:1. The presence of an unactivated substrate and a strong base, the cine substitution occur
along with normal substitution product indicate that the reaction proceeds through the
benzyne mechanism. However the 6-iodo isomer of 5-iodo-1,2,4-trimethylbenzene should
have given A and B in the same ratio (because the same aryne intermediate would be formed
in both cases), but in this case the ratio of A–B was 5.9:1 (the chloro and bromo analogs did
give the same ratio, 1.46:1, showing that the benzyne mechanism may be taking place there).

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CH3 CH3
CH3
CH3 H2N CH3
CH3
NH2

I H2 N
CH3 CH3
CH3
5 1,2,4 A B
Iodo trimethylbenzene

To explain the result of iodo analogue of 5-iodo-1,2,4-trimethylbenzene, it has been proposed

that besides the benzyne mechanism, this free-radical mechanism is also operating here:

electron
ArI ArI Ar I
donor

ArI
Ar NH2 ArNH2 ArNH2 ArI

This is called the SRN1 mechanism (The IUPAC designation is T+DN+AN). The above
reaction involves a chain mechanism. An electron donor is required to initiate the reaction
and solvated electrons from KNH2 in NH3.

2.5.1 Evidence for the SRN1 mechanism:

1. The addition of potassium metal (a good producer of solvated electrons in

ammonia) completely suppressed the cine substitution.
2. Addition of radical scavengers (which would suppress a freeradical mechanism)
led to A:B ratios much closer to 1.46:1.
3. Some 1,2,4-trimethylbenzene was found among the products. This could be easily
formed by abstraction of H by Ar from the solvent NH3.
4. Besides initiation by solvated electrons, SRN1 reactions have been initiated
photochemically, electrochemically, and even thermally.
The SRN1 reactions have a fairly wide scope. The efficiency of the reaction has been traced to
the energy level of the radical anion of the substitution product. There is no requirement for

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activating groups or strong bases, but in DMSO haloarenes are less reactive as the stability of
the anion increases. The reaction has also been done in liquid ammonia, promoted by
ultrasound and ferrous ion has been used as a catalyst. Alkyl, alkoxy, aryl, and COO- groups
do not interfere, although Me2N, O-, and NO2 groups do not interfere.

2.6 EFFECTS OF REACTIVITY & STRUCTURE, LEAVING

GROUP AND ATTACKING NUCLEOPHILE

2.6.1 The Effect of Substrate Structure:

Generally, ArSN2 reactions are accelerated by electron withdrawing groups, especially in the
ortho and para positions to the leaving group and retarded by electron donating groups.
Heteroatoms of the ring are also strongly activating e.g., nitrogen which is more activating
when quaternized. The decreasing order of activating power of some groups in ArSN2
reaction is given below:
NH3˃NO2˃CF3˃CN˃SO3H˃CHO˃CO˃COOH˃COOR˃CONH2˃F˃Cl˃Br˃I
2.6.2 The Effect of the Leaving Group:
The common leaving groups in aliphatic nucleophilic substitution (halide, sulfate, sulfonate,
NR3+, etc.) are also common leaving groups in aromatic nucleophilic substitutions, but the
groups NO2, OR, OAr, SO2R and SR, which are not generally lost in aliphatic systems, are
leaving groups when attached to aromatic rings. Surprisingly, NO2 is a particularly good
leaving group. An approximate order of leaving-group ability is F > NO2 > OTs > SOPh >
Cl, Br, I > N3 > NR3+> OAr, OR, SR, NH2. However, this depends greatly on the nature of
the nucleophile, as illustrated by the fact that C6Cl5OCH3 treated with NH2- gives mostly
C6Cl5NH2; that is, one methoxy group is replaced in preference to five chlorines. As usual,
OH can be a leaving group if it is converted to an inorganic ester. Among the halogens, fluoro
is generally a much better leaving group than the other halogens, which have reactivities
fairly close together. The order is usually Cl > Br > I, but not always. The leaving-group
order is quite different from that for the SN1 or SN2 mechanisms. The most likely explanation
is that the first step of the SNAr mechanism is usually rate determining, and this step is
promoted by groups with strong –I effects. This would explain why fluoro and nitro are such
good leaving groups when this mechanism is operating. Fluoro is the poorest leaving group
of the halogens when the second step of the SNAr mechanism is rate determining or when the

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benzyne mechanism is operating. The four halogens, as well as SPh, NMe3-, and OPO(OEt)2,
have been shown to be leaving groups in the SRN1 mechanism. The only important leaving
group in the SN1 mechanism is N2+.

2.6.3 The effect of the attacking nucleophile:

It is not possible to construct an invariant nucleophilicity order because different substrates

and different conditions lead to different orders of nucleophilicity, but an overall approximate
order is -NH2 > Ph3C- > PhNH- (aryne mechanism) > ArS- > RO- > R2NH > ArO->-OH >
ArNH2 > NH3 > I- > Br- > Cl- > H2O > ROH. As with aliphatic nucleophilic substitution,
nucleophilicity is generally dependent on base strength and nucleophilicity increases as the
attacking atom moves down a column of the periodic table, but there are some surprising
exceptions, for example, -OH, a stronger base than ArO-, is a poorer nucleophile. In a series
of similar nucleophiles, such as substituted anilines, nucleophilicity is correlated with base
strength. Oddly, the cyanide ion is not a nucleophile for aromatic systems, except for sulfonic
acid salts and in the von Richter and Rosenmund-von Braun reactions, which are special
cases.

2.7 VON RICHTER REARRANGEMENT

The Von-Richter reaction, also named Von-Richter rearrangement & it is named after Victor
von Richter, who discovered this reaction in year 1871. In this reaction, aromatic nitro
compounds with potassium cyanide giving carboxylation ortho to the position of the former
nitro group. As with other aromatic nucleophilic substitutions, the reaction gives best results
when an electron-withdrawing group (Z) is present in ortho and/or para positions. For
example-conversion of bromonitrobenzene into bromobenzoic acid in the presence of cyanide
ion.

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NO2

COOH
CN

Z (Br) Z (Br)

Mechanism:
O O
O O O O N
O O N
N
N C N
C N C N
H

C N H

Z
Z Z
Z
2H

O
NH2
N
N N
N N OH C

C OH C OH C O
N2 H2O

O O O
Z
B Z A
Z Z

COOH

First, the cyanide attacks the carbon-atom in ortho-position to the nitro-group. After this the
compound is aromatic again. In the next step, the negative charged oxygen-atom attacks the
neighbor carbon-atom and a five-membered ring is build. It opens under building a
carconlylic-grou. Next, another five-membered ring is built. After a condensation, a double
bond is build between the two nitrogen-atoms. Elemental nitrogen is cut off for opening the
ring. In the last step, the compound is protonated and the 3-halogenbenzoic acid is built.

Evidence support of the Von-Richter rearrangement:

1. N2 is a major product of the reaction. This indicates that nitrogen-nitrogen bond

must be formed during the course of the reaction.
2. A is stable compound which has been prepared independently, and gives the
product of Von-Richter rearrangement when subjected to the condition of this
reaction.

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3. When the reaction was performed in H218O with CN-, the half oxygen in the
product was labeled, showing that one of the oxygen of the carbonyl group came
from the NO2 group and one from the solvent as required by the above
mechanism.
4. When the reaction is carried out in the presence of D2O/C2H5OD, the carboxylic
acid formed contains the deuterium at the position originally occupied by the NO2
group. This confirms the formation of the species B.

2.8 SOMMELET-HAUSER REARRANGEMENT

The Sommelet–Hauser rearrangement (named after M. Sommeletand Charles R.

Hauser) is a rearrangement reaction of certain benzyl quaternary ammonium salts. The
reagent is sodium amide or another alkali metal amide and the reaction product a N, N-
dialkylbenzylamine with a new alkyl group in the aromatic ortho position.

For example, benzyl trimethyl ammonium iodide, [(C6H5CH2) N(CH3)3]I, rearranges in the
presence of sodium amide to yield the o-methyl derivative of N,N-dimethylbenzylamin.

Mechanism:

The benzylic methylene proton is acidic and deprotonation takes place to produce the
benzylic ylide (1). This ylide is in equilibrium with a second ylide that is formed by
deprotonation of one of the ammonium methyl groups (2). Though the second ylide is present
in much smaller amounts, it undergoes a 2,3-sigmatropic rearrangement and subsequent
aromatization to form the final product (3).

The Sommelet–Hauser rearrangement is most often carried out with three methyl
groups on nitrogen, but other groups can also be used. However, if beta-hyhydrogen is

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present, Hofmann elimination often competes. This mechanism is an example of [2,3]

sigmatropic rearrangement.

CH3 CH3 CH2

I
NaNH2
N NaI/NH3 N N CH3
CH3 CH3

H CH3 CH3 CH3

1 2

CH3
H3C CH3 H3C
N N
H
CH2 CH2

CH3 CH2
3

The main drawback of Sommelet rearrangement is that it is accoupanied by Stevens

rearrangement.

CH2Ph CH2Ph
CH N Sommelet CH3
CH2 N NaNH2
CH3 CH3
CH3 NH3 (l) CH3 rearrangements
CH3 CH N
CH3
Stevens Ph
rearrangements

CH3
CH2 CH N
CH3
Ph

2.9 SMILES REARRANGEMENT

Smiles rearrangements are simply intramolecular nucleophilic substitution as shown in the

following reaction.

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Z Z Z

X X X
C Base C C
1 1
1 Z
C Z Z C
C Y
YH Y
cyclohexadienylide anion

Z Z

Y Y
C C
H
1 1
Z C Z
C
XH X

Z and Z1 are the activating groups for a nucleophilic aromatic substitution reaction,
which are electron-withdrawing substituent’s, to stabilize the cyclohexadienlide anion
generated in the reaction. In this rearrangement, X in the arene compound can be a
sulfone, a sulfide, an ether or any substituent capable of dislodging from the arene
carrying a negative charge. The terminal functional group in the chain end Y is able to
act as a strong nucleophile for instance an alcohol, amine or thiol.

For example, o-(o-nitrosulphonyl) phenol undergoes Smiles rearrangement to o-

(o-nitrophenoxy) sulphinic acid in the presence of hydroxide ions.

NO2 NO2 SO2

SO2 SO2 NO2

OH
O
OH O

In this case, SO2Ar is the leaving group, and ArO- the nucleophile. The nitro group serves to
activate the ortho position of the ring. In this rearrangement the chain linking X and Y can be
aromatic as well as aliphatic. The rearrangement also takes place in heterocyclic aromatic
systems. Examples of Smiles rearrangement:

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CH3 CH3
SO2 SO2H
CH3ONa
a. NO2
H3O
OH SO2CH3 O

NO2

NO2
OH
O
b. BuLi NO2
H2O/H H3 C NH
H3C NH2 NO2

NO2

c. N S N N SH
BuLi

NH2 H3O NH N
NO2

NO2

2.10 SUMMARY

This unit provided us concise knowledge about the SNAr, SN1, benzyne and SNR1 mechanism.
This chapter also provides the knowledge of reactivity effect of substrate structure, leaving
group and attacking nucleophile. We learned also about the von Richter, Sommelet-Hauser
and Smiles rearrangements.

2.11 TERMINAL QUESTIONS

1. Which among the following compounds will undergo ArSN2 reaction?

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Cl Br
NO2 B. NO2
A.

NO2

Br

C. NO2 D. All of these

NO2

2. Which of the following compounds will undergo aromatic nucleophilic substitution

through benzyne intermediate?

NO2 Cl

A. B.

OCH3

Cl Cl
CH3 CH3 D. O2N NO2
C.

NO2

3. Consider the following reaction:

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CH3

NaNO2
(X)
H3O
Cl

(X) Will be:

CH3 CH3
NH2 B.
A.

NH2

CH3 CH3
D.
C.
NH2

4. Complete the following reactions:

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a.

b.
HN

OMe
NO2 KOH/EtOH
c.

NO2

NO2
NH3/EtOH
d.
NO2

5. The reaction of o-bromoanisole with NaNH2 in liquid NH3 gives only m-

aminoanisole. Explain the regioselectivity in this reaction.
6. Both m-bromoanisole and o-bromoanisole tield the same product m-anisidine.
Explain why?
7. Complete the following reaction with mechanism.
OMe
F
PhLi
then H2O

8. After the reaction of fluorobenzene with deuterated amide ion (ND2-) in

deuterated ammonia (ND3). The unreacted starting material contains deuterium.
Explain.
9. Complete the following sequences of reactions:

SO2 OH reduction OH H2O2

A B C D
H3O SO2H SH H3O
OH SO2CH3

10. Predict the product in the following reactions:

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NO2

a. CN

Cl

Me
CH2NMe3I
b. NaNH2

Me

Cl
c.
Cl CH3ONa/CH3OH

NO2

2.12 ANSWER TO TERMINAL QUESTIONS

1. D

2. B

3. D

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a.

b.
N

OH
NO2
c.

NO2

NH2
d.
NO2

5. The attack of nucleophile at the carbon shown by star in the benzyne intermediate will
lead to more stable carbanion where the negative charge is closer to the –I group.

OCH3 OCH3 OCH3

Br NaNH2 NH2
NH3 NH3
NH2

NH3 NH2

OCH3

NH2

6. The yield the same product because they form the same benzyne intermediate.

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OMe OMe
F
PhLi
then H2O
Ph

Mechanism:
OMe OMe OMe
F F
PhLi PhH PhLi
Li
Stronger
base

H2O

OMe
OMe
Li
LiOH Ph
H2O
Ph

7. The reaction indicates that the hydrogen ortho to florine is replaced in a rapid
reversible reaction. These data also support that the rate-determining step in benzyne
formation from flourobenzene is loss of fluoride ion.

F
F
H
ND2 Rate determing
F
step

ND3

F
D
ND2

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2.13 REFERENCES

1. Singh, J and Yadav, L.D.S, 2004, advanced organic chemistry, Pragati Prakashan,
Meerut. 441-449.

2. Jerry March. 2007. Advanced Organic Chemistry-Reactions, Mechanism and

Structure, John Wiley. 4th edition. 641-676.

3. Mukherji S. M. and Singh S. P. 2015. Reactions Mechanism in Organic Chemistry.

Trinity Press. 498-515.

4. Singh M.S. 2005. Advanced Organic Chemistry. Reaction and Mechanisms. Pearson
Education. 304-344.

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UNIT-3 ALIPHATIC ELECTROPHILIC SUBSTITUTION

CONTENTS:
3.1 Objectives
3.2 Introduction
3.3 Unimolecular Substitution Reactions (SE1)
3.3.1 Evidence for the SE1 mechanism
3.3.2 Stereochemistry of SE1 reaction
3.4 Bimolecular Substitution Reaction (SE2)
3.4.1 SE2 (Front) and SE2 (Back): Evidence and Stereochemistry
3.4.2 SEi mechanism: Evidence and Stereochemistry
3.5 Electrophilic substitution accompanied by double bond shift
3.6 Effect of various factors on aliphatic electrophilic substitution
3.6.1 Effect of substrate
3.6.2 Effect of leaving group
3.6.3 Effect of solvent
3.7 Migration of double bond
3.7.1 Base catalysed double bond migration
3.7.2 Acid catalysed double bond migration
3.8 Some examples of aliphatic electrophilic substitution reactions
3.8.1 Halogenations of aldehydes and ketones
3.8.1a Mechanism of base catalysed halogenations
3.8.1b Mechanism of acid- catalysed halogenations
3.8.2 Halogenations of carboxylic acids and acyl halides
3.8.3 Halogenation of sulphoxide and sulphones
3.8.4 Aliphatic Diazonium coupling
3.8.5 Diazo transfer reaction
3.8.6 Nitrosation at Carbon (C-Nitrosation)
3.8.7 Nitrosation at Nitrogen (N-Nitrosation)
3.8.8 Addition – Elimination mechanism
3.8.8.1 Acylation at an aliphatic carbon

3.9 Some Naming Reaction of Aliphatic Substitution

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3.9.1 Hell-Volhard-Zelinskii reaction

3.9.2 The Stork- Enamine reaction
3.9.3 Haloform reaction
3.10 Summary
3.11 Terminal questions with answers.
3.12 References

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3.1 OBJECTIVES

In this unit learner will be able to

► Learn various types of aliphatic electrophilic substitution reactions like unimolecular SE1
and bimolecular SE2 (front), SE2 (back) and SEi.
► Learn comparative mechanism and stereochemistry of SE1, SE2 (front), SE2 (back) and
SEi reactions.
► Learn Effect of various factors on aliphatic electrophilic substitution like effect of
substrate,effect of leaving group and effect of solvent.
► Learn Migration of double bond as base catalysed double bond migration and acid
catalysed double bond migration
► Learn about Some aliphatic electrophilic substitution reactions like Halogenations of
carboxylic acids and acyl halides, halogenation of sulphoxide and sulphones, aliphatic
diazonium coupling, diazo transfer reaction, nitrosation at carbon (C- Nitrosation), nitrosation
at Nitrogen (N-Nitrosation), addition-elimination reaction.
► Learn about Mechanisms of some naming Reaction of Aliphatic Substitution Hell-
Volhard-Zelinskii reaction, Stork- Enamine reaction and haloform reaction

3.2 INTRODUCTION

Aliphatic electrophilic substitution reactions are related to carbanions. The

mechanism of electrophilic substitution is less clear than the aliphatic nucleophilic
substitution and aromatic electrophilic substitution reactions. In electrophilic substitution
reactions, the entering and the leaving group (electrofuse) are the electrophiles, i.e. Lewis
acid. Aliphatic substitution reactions also proceed through unimolecular or bimolecular
(direct displacement) mechanism. The four possible electrophilic aliphatic reaction
mechanisms are SE1, SE2 (front), SE2 (back) and SEi types. In the SE1 mechanism, the
substrate first ionizes into the carbanion or a positively charged organic residue then quickly
recombines with the electrophile. The SE2 reaction mechanism has a single transition state in
which the old bond and the newly formed bond are both present.

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3.3 UNIMOLECULAR ELECTROPHILIC SUBSTITUTION

(SE1) MECHANISM

SE1 reaction involves two steps, i.e. a slow heterolysis following carbanion formation and
fast combination of the resulting carbanion with electrophile.

Step 1. R X R + X

Step 2. R + Y R Y

Electrophilic substitution can occur when the leaving group is more electro positive with
respect to carbon i.e. metal atom and hydrogen.

Example of SE1 reaction

• Hydrogen-deuterium or hydrogen-tritium exchanges

B R D + B H
R H +B D

B = base

Such exchange occurs with relatively acidic protons, e.g. alpha position to a carbonyl group.
However, even weakly acidic protons can exchange bases which are strong enough.

• Decarboxylation

X CH2 C O X CH2 ROH X CH3 + RO

-CO2

• Anionic fragmentation

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O O

X CH2 C R' X CH2 + R' C R''

R'' ROH

X CH3 + RO

X= X3C , Ar , O2 N ,N C , R C

3.3.1 Evidence for the SE1 mechanism

• The reaction follows first order kinetics.

• In the following base catalysed tautomerisation

Me O Me O

C Ph + D2O OD Et C C Ph
Et C

H D
optically active racemisation

The rate of deuterium exchange was found to be the same as the rate of racemisation and
there was an isotope effect. SN1 reaction do not occur at bridgehead carbons in [2, 2, 1]
bicyclic systems because planer carbocations cannot form at these carbons. Carbanions not
stabilised by resonance need not be planar, hence SE1 reaction should readily occur at
bridgeheads and this is found to be the case also.

3.3.2 Stereochemistry of SE1 reaction

The carbanion formed as an intermediate in SE1 reactions retains its tetrahedral

configuration and hence will be attack only from one side retaining the original configuration.
For ex. Replacement of the metal in an organometallic compound by hydrogen proceeds with
retention of configuration.

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MgBr H
slow .. H
C -MgBr C fast C
R' R R' R R' R
CH3 CH3 CH3

3.4 BIMOLECULAR ELECTROPHILIC SUBSTITUTION

REACTION

SE2 reactions occur with organometallics that have a considerable degree of covalent
character or with C—H bonds under conditions not sufficiently basic for proton removal.
They have been extensively studied with organomercury compounds, but have been observed
with a number of other metals as leaving group, e.g., Li, Cr, Sn, Fe, and Co. Aliphatic
bimolecular substitution reactions are of two types: SE2 and SEi.

3.4.1 SE2 and SEi Mechanisms

Both SE2 and SEi mechanisms are bimolecular and are analogous to SN2 mechanism.
i.e. the new bond forms and at the same time, the old bond breaks. In the SN2 mechanism,
the attacking group brings with it a pair of electrons and the leaving group takes away its
electrons. These things are happening simultaneously. Therefore the incoming attacking
group attacks backside at a position 1800 away from the leaving group, resulting in inversion
of configuration.

But in SE2 mechanism the attacking group is an electrophile. This brings to the
substrate only a vacant orbital. Therefore we cannot predict from which direction the attack
must come. We can imagine two main possibilities. They are attack from the front, i.e. SE2
(front) and attack from rear, i.e., SE2 (back). These can be represented as follows.

Y Y
SE2 (front)
C C + X
X
Retention
of configuration

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SE2 (back)
Y C X Y C + X

Inversion
of configuration

3.4.2 The SEi Mechanism

When an electrophile attacks from the front, there is a possibility for a portion of the
electrophile to assist in the removal of leaving group, forming a bond with it at the same time
a new C-Y bond is formed.

Y Y Z
SEi
C Z C +
X
X

This mechanism also results in retention of configuration, where a second order

kinetics involves internal assistance that prevents the backside attack of an electrophile.

The SE2 (front), SE2 (back) and SEi mechanism are not easy to distinguish. All these
three types of mechanisms give second order kinetics in which SE2 (front) and SEi result in
retention of configuration. The study of stereochemistry can distinguish between SE2 (front),
SE2 (back) and SEi in such a way that SE2 (back) results in inversion of configuration on the
one hand and SE2 (front) and SEi on the other. In the majority of second order electrophilic
substitution reaction, the results have been retention of configuration due to the front side of
electrophile following either SE2 (front) or SEi mechanism.

R"

R' Hg R" R' Hg

R' Hg X + X Hg R"
X Hg X
Hg X Retention of configuration
(R=EtCHMeHgBr) estabilishes SE2 (front) mechanism
X

This indicate the bonds between the Hg atom and the ring on the one side, and the
carbon (Hg-C) on the other side have be broken , electrophile which facilitate the front side
attack of the electrophile on the substrate carbon to produce the cis isomer. Another

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indication of front side attack is that the second order electrophilic substitutions proceed very
easily at bridgehead carbons, where back side attack is impossible.
However, inversion of configuration has been found in certain case indicating that
SE2(back ) mechanism can also takes place for example, the reaction of optically active sec-
butyl tri-neopentyl tin with bromine gives inverted sec-butyl bromide.

R
R Sn R R
CH3 CH CH2 CH3
CH3 CH CH2 CH3 + Br2 + R Sn R
sec- butyl tri neopentyltin Br
Br
(R = neopentyl) sec- butylbromide
(inverted)

3.5 ELECTROPHILIC SUBSTITUTION ACCOMPANIED BY

DOUBLE BOND SHIFTS

When electropilic substitution is carried out at an allylic substrate, the product may be
rearranged:

Y + C C C X C C C + X

This type of process is analogous to the the nucleophilic allylic rearrangements. There
are two principal pathways. The first of these is analogous to the SE1 mechanism in that the
leaving group is first removed, giving a resonance stabilised allylic carbanion and then the
electrophile attacks.

C C C X C C C C C C Y Y C C C
-X

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In the other pathway the Y group first attacks, giving a carbocation, which then loses X.

Y + C C C X C C C X C C C+ X

Y Y
Most electrophilic allylic rearrangements involve hydrogen as the leaving group, but
they have also been observed with metallic leaving groups. The crotyl mercuric bromide
reacted with HCl about 107 times faster than n-butyl mercuric bromide and the product was
more than 99% 1-butene. These facts point to a SEi mechanism.

3.6 EFFECT OF FACTORS ON ALIPHATIC ELECTROPHILIC

SUBSTITUTION

3.6.1 Effect of substrate:

For SE1 reaction, electron–donating group decreases while electron withdrawing
group increases the rate of reaction. This is as would be expected from a reaction in which the
rate determining step is analogous to the cleavage of a proton from an acid.
For the SE2 (back) reaction, it is shown that the reactivity of the alkyl group is similar
to that for the SN2 reaction (i.e. Me.> Et > Pr > iso-Pr > t-Bu> Neo pentyl), as would be
expected, since both involve backside attack and both are equally affected by steric
hindrance. In fact, this pattern of reactivity can be regarded as evidence for the occurrence of
the SE2 (back) reaction in cases where stereo chemical investigation is not feasible. For SE2
reactions that proceed with retention. α- branching of alkyl group increases, while the β-
branching decreased the rate of reaction. The decreased rates to steric hindrance, through
attack here was definitely front side, and the increased rates to the electron-donating effect of
the alkyl groups, which stabilized the electron-deficient transitions state. Of course, steric
hindrance should also be present with the branched groups.

3.6.2 Effect of leaving group:

For both SE1 and second order mechanisms, the more polar the C-X bond, the easier
it is for the electrofuge to cleave. For metallic leaving groups in which the metal has a
valence greater than 1, the nature of the other groups attached to the metal thus has an effect

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on the reaction. For example, consider a series of organo mercurials RHgW. Because a more
electronegative decreases the polarity of the C-Hg bond and furthermore results in a less
stable HgW+, the electrofugal ability of HgW decreases with increasing electronegativity of
W. Thus, HgR’(from RHgR’) is a better leaving group than HgC (from RHgCl). Also in
accord with this is the leaving group order Hg-tert-Bu>Hg-Iso-Pr >HgEt >HgMe, reported
for acetolysis of R2Hg, since the more highly branched alkyl groups better help to spread the
positive charge. It might be expected that, when metals are the leaving group, SE1 mechanism
would be favoured, while with the carbon leaving groups, second order mechanism would be
found. However the results so far reported have been just about the reverse of this. For carbon
leaving groups the mechanism is usually SE1, while for metallic leaving groups the
mechanism is almost always SE2 or SEi.

3.6.3 Effect of solvent:

In addition to the solvent effects on certain SE1 reactions, solvent can influence the
mechanism that is preferred. As with nucleophilic substitution, an increase in solvent polarity
increases the possibility of an ionising mechanism, in this case SE1, in comparison with the
second order mechanisms, which do not involve ions. The solvent can exert an influence
between the SE2 (front or back) and SEi mechanism in that the rates of SE2 mechanisms
should be increased by an increase in solvent polarity, while SEi mechanisms is much less
affected.

3.7 MIGRATION OF DOUBLE BOND

The double bonds of many unsaturated compounds are shifted on treatment with
strong bases. In many cases equilibrium mixtures are obtained and the thermodynamically
most stable isomer predominates. Thus if the new double bond can be in conjugation or with
an aromatic ring, it goes that way. If the choice is between an exocyclic and an endocyclic
double bond (in a six membered ring), it chooses the latter. In the absence of consideration
like Zaitsev rule* applies and the double bond goes to the carbon with the fewest hydrogens.
All these considerations lead us to predict that terminal olefins can be isomerized to internal
ones, non conjugated olefins to conjugated, exo six membered-ring olefins to endo etc., and
not the other way around. This is usually indeed the case.

This reaction, for which the term prototropic rearrangement is sometimes used, is an example
of electrophilic substitution with accompanying allylic rearrangement. The mechanism

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involves abstraction by the base to give a resonance – stabilized carbanion, which then
combines with a proton at the position that will give the more stable olefins.

*Zaitsev rule (also known as Saytzeff rule): This rule implies that an elimination reaction will
predominantly to lead to the highly substituted olefin formation.

3.7.1 Base catalysed double bond migration:

The double bonds of many unsaturated compounds are shifted (rearranged) on treatment with
strong bases. Usually this results in equilibrium mixtures in which the thermodynamically
most stable isomer predominates, thus terminal olefins can be isomerised to internal olefins;
as the double bond has a tendency to become internal, non-conjugated olefins to conjugated,
exo six member-ring olefins to endo, etc. This reaction is an example of electrophilic
substitution accompanied by allylic rearrangement and sometimes it is also called prototropic
rearrangement. The mechanism is as follows:

R CH -BH R CH CH2 R
CH CH2 + B CH CH CH CH2

H
BH

R CH CH CH3 + B

In the first step the base abstract a proton to give a resonance-stabilised carbanion, which then
combines with a proton (electrophile) to give the more stable product. The mechanism is
exactly analogous to the allylic rearrangement mechanism for nucleophilic substitution.

3.7.2 Acid catalysed double bond migration:

Both proton and Lewis acids can also bring about double bond rearrangement. As in the base
catalysed .as in the case of base-catalysed double bond migration, thermodynamically most
stable olefin is predominantly formed. The mechanism is as follows:

R CH2 CH CH2 + H R CH CH CH3 -H R CH CH CH3

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3.8 Some Electrophilic substitution reactions:

3.8.1 Halogenation of aldehydes and ketones
Aldehydes and ketones undergo α-helogenation with chlorine, bromine or iodine.
Aldehyde or Ketone itself is not halogenated but the corresponding enol or enolate ion is
halogenated. A base is used acid is used as a catalyst to generate a small amount of enol or
enolate ion. When basic catalyst are used, one α position of a ketone is completely
halogenated before the other is attacked, and the reaction cannot be stopped until all the
hydrogens of the first carbon has been replaced. If one of the groups is methyl group them
Haloform reaction takes place. In the case of acid catalyst it is easy to stop the reaction at
mono substitution stage, though the second halogen can be introduced by using excess
reagents.

O O O
slow
Step 1. R2CH C R' + OH R 2C C R' R 2C C R'

O O

R2 C C Fast
Step 2. R' R2C C C R' + Br
Br

Br

3.8.1a. Mechanism of base catalysed halogenations:

The above mechanism is supported by the kinetics

Rate = K [ ketone ] [base]

The rate of the reaction depends on the concentration of the ketone and that of base but is
independent of the concentration of the halogen. Another evidence for the carbanion
mechanism is provided by the base catalysed racemisation of (+)-phenyl sec- butyl ketone.
The rate of racemisation and the rate of bromination are found to be the same. The rate of
racemisation is also found to be the same as the rate of deuteriation when the reaction is
carried out in the presence of a base in D2O.

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The electron–withdrawing effect of the first halogen increases the acidity of the
remaining hydrogen’s on the same carbon, e.g. a CHX group is more acidic than a CH2
group, and the more acidic hydrogen is replaced by halogen more easily because the greater
the acidity of the -hydrogen, the more rapid is the enolization of the carbonyl compound.
Thus base catalysed halogenation of an unsymmetrical ketone preferably takes place on that α
carbon which bears fewer alkyl groups because the +I effect of alkyl group decreases the
acidity of α-hydrogen, and so the rate of enolization.
Base catalysed halogenation of a carbonyl compound cannot be stopped until all
the α-hydrogens are replaced. For example, a methyl ketone thus results in the formation of a
trihaloketone through the mechanism (shown in 3.8.1). Because of the combined –I effect of
the three halogen atoms, the carbonyl carbon of the trihaloketone is highly positive, hence it
is attacked by a base with cleavage of the C C bond to give a haloform and salt of a
carboxylic acid. This reaction is known as haloform reaction. Methyl ketones, acetaldehyde,
the primary and secondary methyl alcohols (which are first oxidised to the carbonyl
compounds and then produce haloform under the reaction conditions) give haloform
reaction* with Cl2, Br2 or I2 in the presence of a base.

O O

R C CH3 + 3Br2 OH C
R CBr3 Br3C + RCOOH
OH

Br3CH + RCOO

3.8.1b Mechanism of acid- catalysed halogenations:

O O H OH
+ H, fast - H, slow
R2CH C CH3 R2CH C CH3 R2 C C CH3 + Br Br
- H, slow + H, fast
-Br

O OH

R2C C CH3 + H R2C C CH3

Br Br

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*
Haloform reaction is given by those compounds which have R C O CH3 or
RCH(OH)CH3 group.
3.8.2 Halogenations of carboxylic acids and acyl halides:
Carboxylic acid undergoes α-halogenations with bromine or chlorine in the presence
of phosphorus halide as catalyst. The reaction is known as Hell-Volhard-Zelinskii reaction
(HVZ reaction). The reaction actually takes place on the acyl halide formed from the
carboxylic acid and phosphorus halide, as it has higher enol content than the acid itself.
For example, the use of Cl2 and PBr3 gives α-chlorination but not α-bromination. The halogen
from the catalyst does not enter the α-position. It can be explained by the following
mechanism:

PBr3 R CH COOH
(i) R CH2 COOH + Cl2

. Cl

PBr3 CH COOH
(ii) R CH2 COOH + Br2 R

Br

3.8.3 Halogenation of sulphoxide and sulphones:

Sulphoxide can be chlorinated in the α position by treatment with NOCl, Cl2, TsCl*, or
N- Chlorosuccinimide, all in the presence of pyridine,

O O
NOCl S R'
RCH2 S R' pyridine
RCH

Cl

The chlorination can also be brought about in the absence of base, e.g., with SO2Cl2 in
CH2Cl2. The bromination of sulphoxide can be brought about with Br2 with N-
bromosuccinimide-bromine. Sulphones have been chlorinated by treatment of their conjugate
base RSO2CHR’ with SO2Cl2, CCl4, N- Chloro succinimide, and hexachloroethane.

*
TsCl is 4- Toluene Sulphonyl Chloride having molecular formula C7H7ClO2S

3.8.4 Aliphatic Diazonium coupling:

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Compounds containing active hydrogen (acidic C-H bond) couple with diazonium salts in the
presence of a base, usually aqueous sodium acetate, e.g.

Z'
AcO
Z CH2 Z' + ArN2 Z C NNHAr

(Z, Z’= electron –withdrawing groups such as NO2, CN, COOR, SO2R, COR, etc.)
The reaction proceeds through simple SE1 mechanism as follows:

Z' Z'
-BH ArN2
Z CH2 Z' + B Z CH Z CH N N Ar
Azo compound

Tautomerisation

Z'

Z C N NH Ar
Hydrazone

If the carbon containing the azo group has hydrogen then it tautomerises to more stable
hydrazone. When the azo compound does not have a tautomerisable group, and at least one
Z is acyl or carboxyl, this group cleaves to give a hydrazone, e.g.

O R

C C N N Ar B C N NAr R C N NHAr
CH3 R
CH2 C B
Z' Z' Z'
O

If there no acyl or carboxyl group present then the aliphatic azo compound is stable.

3.8.5 Diazo transfer reaction:

Compound containing a CH2 group bonded to two electron –withdrawing groups (Z, Z’) can
be directly converted into diazo compounds on treatment with tosyl azide in the presence of a
base. This reaction is called diazo transfer reaction. It can also be applied to other reactive
positions, e.g., 5-position of cyclopentadiene.

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TsN3 CN2 + TsNH2

Z CH2 Z
OH
Z' Z'
diazo compound

3.8.6 Nitrosation at carbon (C- nitrosation):

Carbons containing an active hydrogen can be nitrosated with HNO2 or alkyl nitrites to give
the C-nitroso compounds which tautomerises to more stable oximes if a tautomerisable
hydrogen is available, e.g.,

O OH OH NO
H ,slow NOX
R C CH2 R' R C CH R' R C CH R'

-H

O O NO
Tautomerisation
R C C R' R C CH R'

N OH
Oxime

The attacking species is NO or a carrier of it which is formed as follows, e.g. when NaNO2
and HCl are used.

NaNO 2 + HCl H O N O + NaCl

H O N Cl
O + H O N O H2O + NO NOCl
H

In dilute acids the actual attacking species is N2O3 formed as:

2HNO2 N2O3 + H2O

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3.8.7 Nitrosation at Nitrogen (N-Nitrosation):

Secondary amines and mono-N-substituted amides (RCONHR’) undergo N-nitrosation when

treated with nitrous acid.

R2NH + HONO R 2N NO
N-nitroso compound
(nitrosamine)

Tertiary amines have also been N-nitrosated but in this case one group cleaves to give the
nitroso derivative of a secondary amine and an aldehyde or ketone. The mechanism

is as follows and the attacking species is N2O3, NOCl, NO, H2NO2 Nucleophiles Cl-, SCN-

and thiourea catalyse the reaction by converting HNO2 to a better nucleophile, e.g.

HNO2 + Cl + H NOCl + H2O

2HNO2 N2O3 + H2O

R2NH + N2O3 R2N N O + NO2

sec.amine
H
R2N N O R2N N O
-H nitrosamine
H

The following is the mechanism for the reaction with tertiary amines:

H
H H / HCl
O N O H O N O N O
-H2O

H
R2N CH R2' NO R2N CR2' R 2N
- HNO CR2'
tert-amine
N O H2O

HNO2
R 2N N O R2NH2 + R2'C O
N-nitrosoamine
(yellow oily liquid)

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3.8.8 Carbon Electrophiles (Addition–Elimination Mechanism):

Addition- Elimination mechanism is also known. Less work has been done on aliphatic
substitution mechanisms than nucleophilic substitution mechanisms, so the exact mechanisms
of many of the reactions are in doubt.

3.8.8.1 Acylation at an aliphatic carbon

H COR
AlCl3
C C + RCOCl C C

Olefins can be acetylated with an acyl halide and Lewis-acid catalyst in what is essentially a
Friedal-Crafts reaction at an aliphatic carbon. The product can arise by two paths (path A and
path B). The initial attack is by the acyl cation RCO+ at the double bonded carbon atom to
give a carbocation.

Cl COR
C C H (path A)
-
Cl
H COR (beta-chloro ketone)
C C + RCO+ C C H
-H+ -HCl
COR
(Olefin) (carbocation) C C (path B)

(unsaturated ketone)

Carbocation can either lose a proton or combine with chloride ion. If it loses a
proton, the product is an unsaturated ketone. If it combines with chloride ion, the product is a
β- halo-ketone, which can be isolated. On the other hand, the β- halo-ketone may under the
condition of the reaction, lose HCl to give the unsaturated ketone, this time by an addition–
elimination mechanism. In the case of unsymmetrical olefins, the attacking ion prefers the
position at which there are more hydrogens, following Markovnikov’s rule. Anhydrides and
carboxylic acids are sometimes used instead of acyl halides. With some substrates and
catalysts double-bond migrations are occasionally encountered so that, for example, when

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1-methylcyclohexene was acetylated with acetic anhydride and zinc chloride, the major
product was 6-acetyl-1-methylcyclohexene. Conjugated dienes can be acetylated by treatment
with acyl-or alkylcobalt tetracarbonyls, followed by base-catalysed cleavage of the resulting
π- allyl carbonyl derivatives.

CH2COR
CH
-CO Co(CO)3
RCOCo(CO)4 + CH2 CH CH CH2 H C
CH2

base

CH2 CH CH CH C R + HCo(CO)3

The reaction is very general with unsymmetrical dienes, the acyl group generally
substitutes most readily at a cis double bond, next at a terminal olefinic group, the least
readily at a trans double bond. The most useful bases are strongly basic, hindered amines
such as dicylohexylethylamine. The use of an alkyl cobalt tetracarbonyl RCo(CO)4 gives the
same product as that shown above. Acylation of vinylic ethers has been accomplished with
aromatic acyl chloride, a base, and a palladium catalyst.

ArCOCl
ROCH CH2 ROCH CHCOAr
Pd

Formylation of olefins can be accomplished with N di-substituted formamides and

POCl3. This is a Vilsmeier reaction. Vilsmeier formylation can also be performed on the α-
position of the acetals and ketals, so that hydrolysis of the products gives keto aldehydes or
dialdehydes.

OR" OR"
POCl3 Hydrolysis
R CH2 C R' + Ph N CHO R CH C R' R CH COR'

OR" Me CHO OR" CHO

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Acetylation of acetal or ketals can be accomplished with acetic anhydride and BF3-
etherate. The mechanism with acetals or ketals also involves attack at an olefinic carbon,
since enol ethers are intermediates. Ketones can be formylated in the α- position by
treatment with CO and a strong base.

3.9 SOME NAMING REACTION OF ELECTROPHILIC

ALIPHATIC SUBSTITUTION

3.9.1 Hell-Volhard-Zelinskii Reaction:

The α-hydrogen atoms of carboxylic acids can be replaced by bromine or chlorine
with a phosphorus halide as catalyst. This reaction is known as Hell–Volhard-Zelinskii
(HVZ) reaction. This is not applicable to iodine or fluorine*.

R CH2 COOH + Br2 PBr3 R CH COOH

Br

The reaction actually takes place on the acyl halide formed from the acid and the catalyst.

*Iodine is large; therefore, it cannot undergo substitution in presence of COOH group due
to steric hindrance while Fluorine is reactive enough to replace all hydrogen atoms.

PBr3 R CH COOH
(i) R CH2 COOH + Cl2

I Cl

O O OH
P,Br2 enolisation
RCH2 C OH RCH2 C Br R CH C Br
PBr3
-HBr Br2

O O
RCH2COOH
R CH2 C Br + R CH COOH R CH C Br

Br Br
II

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Enolisation of the acyl bromide is far more rapid than the bromine exchange between
II) and the parent acid (I), thus the equilibrium is shifted in the forward direction. Since HVZ
reaction with bromine is specific for α-hydrogen, it can be used to detect the presence of α-
hydrogen in a carboxylic acid. When there is more than one α-hydrogen, all may be replaced;
it is often difficult to stop the reaction at the mono substitution stage.

3.9.2 The Stork-Enamine reaction:

This reaction involves the addition of an enamine to an α, β – unsaturated carbonyl acceptor.
The product is then hydrolysed by an aqueous acid to produce a 1, 5- dicarbonyl compound.
While if the electrophile is an acylhalide, a 1, 3- diketones is formed (Stork acylation)
The process follows the following steps:
Step I - Formation of an enamine from a ketone.
Step II - Addition of the enamine to α, β – unsaturated aldehyde or ketone.
Step III – Hydrolysis of an enamine results in the formation of a ketone.

O N N N
H
H
+
Cyclohexanone O O

O
N
H2O

O
!,5 diketone O
enamine

When enamine is treated with acyl halides, an alkylation occurs. This is analogous to the first
step of Freidel Craft acylation at an aliphatic carbon and the hydrolysis of the resultant imine
salt gives a ketone.

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CH2R + X
N-alkylated product

N
+ R CH2 X heat

halide

enamine
N
CH2R + X
CH2 CH
Where R= or
C6H5 C-acylated product

H2O

O
CH2R
+ N

H
pyrrolidine

The net result is the alkylation of ketone at the α-position since the enamine is formed from a
ketone. This method is known as Stork Enamine reaction. This method is alternative to the
alkylation of ketone by the aliphatic nucleophilic substitution method. The stork method has
an advantage that the reaction can be brought to an end with the introduction of just one alkyl
group. Alkylation usually takes place on the less substituted side of original ketone.
The most commonly used amines are the cyclic amines such as piperidine, morpholine and
pyrrolidine. This method is quite useful for active alkyl halides such as allyl, benzyl and
propargyl halides and also for alpha–halo ether and esters. This is not applicable for ordinary
primary, secondry and tertiary halides.
3.9.3 Haloform reaction:

Br2
CH3 C R
OH-
HCBr3 + RCOO-
O

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In the Haloform reaction, methyl ketones (and the only methyl aldehyde, acetaldehyde) are
cleaved with halogen and a base. The halogen can be bromine, chlorine or iodine. It takes
place is actually a combination of two reactions. The first is an example in which, under the
basic conditions employed, the methyl group is tri-halogenated. Then the resulting tri halo
ketone is attacked by hydroxide ion.

OH
Br3C C R + OH Br3C Br3CH + RCOO-
C R Br3C + RCOOH
O O

Primary or secondary methyl carbinols also give the reaction, because they are oxidised to the
carbonyl compounds under the conditions employed. A side reaction is α-halogenation of the
non methyl R group. Sometimes these groups are also cleaved. The reaction cannot be
applied to F2, but ketones of RCOCF3(R=alkyl or aryl) give fluoroform and RCOO- when
treated with base. The haloform reaction is often used as a test for methyl carbinols and
methyl ketones. Iodine is most often used as the reagent, since idoform is an easily
identifiable yellow solid. The reaction is also frequently used for synthetic purposes. Methyl
ketones RCOCH3 can be converted directly to methyl esters RCOOCH3 by an
electrochemical reaction.

3.10 SUMMARY

In electrophilic substitution in aliphatic compounds, an electrophile displaces a functional

group. This reaction is similar to nucleophilic aliphatic substitution.

In electrophilic substitution reactions, the entering and the leaving group are the
electrophile, i.e. Lewis acid. The electron pair of the breaking bond remains with the
substrate and is used to form the new bond to the entering electrophile.
Aliphatic substitution reactions proceed through unimolecular or bimolecular (direct
displacement) mechanism. The four possible electrophilic aliphatic reaction mechanisms are
SE1, SE2 (front), SE2 (back) and SEi.
In the SE1 reaction the substrate first to ionizes into carbanion and a positively
charged organic residue. The carbanion then quickly recombines with the electrophile.
The SE2 reaction mechanism has a single transition state in which the old bond and
the newly formed bond are both present. In SE2 mechanism the attacking group is an

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electrophile. It attacks to the substrate only a vacant orbital. Therefore we cannot predict from
which direction the attack must come. We can imagine two main possibilities. This can attack
from the front, i.e. SE2 (front) and attack from rear, i.e., SE2 (back).
In SEi reaction an electrophile attacks from the front, there is a possibility for a portion
of the electrophile to assist in the removal of leaving group, forming a bond with it at the
same time a new bond is formed. All these three types of mechanisms give second order
kinetics in which SE2 (front) and SEi result in retention of configuration but SE2 (back) results
in inversion of configuration.
For both SE1 and SE2, the more polar the C-X bond, the easier it is for the
electrofuge to cleave. For metallic leaving groups in which the metal has a valence greater
than 1, the nature of the other groups attached to the metal thus has an effect on the reaction.
An increase in solvent polarity increases the possibility of an ionising mechanism of SE1
reaction. The solvent can exert an influence between the SE2 (front or back) and SEi
mechanism in that the rates of SE2 mechanisms should be increased by an increase in solvent
polarity, while SEi mechanisms are much less affected.

3.11 TERMINAL QUESTIONS

Ques.1. what do you mean by electrophilic substitution reaction?

Answer: Electrophilic substitution reaction is chemical reaction in which an electrophile

displaces a functional group in a compound which is typically, but not always, a hydrogen
atom.

Ques.2. Complete the following reaction:

CH3Cl
C C + CS2 + NaOH A B
250oC
OH

Answer :
A: C C B: C C + COS + MeSH

O C S Na

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Ques.3. Complete the following reaction:

RCOOH A
C C
300-350oC
OH

Answer : A: C C + H2O

Ques.4. Can you explain Haloform test.

O O
Answer : R OH
C CH3 + X2 R C O + CHX3

X2 = Cl2, Br2 or I2

Ques.5. Which of the following does not give HVZ reaction:

(a) CH3CH2COOH

(b) CH3COOH

(c) HCOOH

(d) (CH3)2CHOH

Answer: C

Ques.6. SE1 results in inversion in configuration. (True/False)

Answer: False

Ques.7. Increase in polarity in solvent can increase the rate of reaction of SE2. (True/False)

Answer: True

Ques.8. Compare the mechanism between SE1 and SE2 reaction.

Ques.9. Write a short note on SEi reaction and its mechanism.

Ques.10. Discuss the stereochemistry of aliphatic electrophilic substitution reaction with

reference to SE1 and SEi reaction.

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Ques11. What is an aliphatic electrophilic substitution reaction. Discuss various types of

aliphatic electrophilic substitution?

Ques.12. Write a short note of the following reaction.

(A) Haloform reaction
(B) Stork- Enamine reaction
(C) Hell-Volhard-Zelinskii reaction

Ques.13. Explain the effect of substrate in aliphatic substitution reaction.

3.12 REFERENCES

1. Jerry March Advanced Organic Chemistry. Reaction Mechanisms and Structure.

Fourth Edition, 1999, John Wiley & Sons, New York.
2. Peter Sykes, A guide book to mechanism in Organic Chemistry, Fifth Edition, 1980,
Longmann, UK.
3. S. M. Mukherji & S.P. Singh, Reaction Mechanism in Organic Chemistry, 1976,
Macmillan India Limited, India.
4. Jonathan Clayden, Nick Greeves and Stuart Warren, Organic Chemistry, Second Edition,
2001, Oxford University Press, New York.
5. Jagdamba Singh & L.D.S. Yadav Advanced Organic Chemistry, Fifth Edition, 2009,
Pragati Prakashan, Meerut, India.
6. P.S. Kalsi, Organic Reaction and their Mechanisms, Second edition, 2000, New Age
International Publishers, India.

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UNIT-4 AROMATIC ELECTROPHILIC

SUBSTITUTION

CONTENTS:
4. Objectives
4.0 Introduction
4.1 The arenium ion mechanism
4.1.1 Energy profile diagrams of Aromatic Electrophilic Substitution eaction:
4.1.2 Nitration
4.1.3 Sulphonation
4.1.4 Halogenation
4.1.5 Alkylation
4.1.6 Acylation
4.2 Orientation and reactivity
4.2.1 Electrophilic substitution in other poly-substituted benzene rings:
4.3 Some name reactions involving aromatic electrophilic substitution mechanism:
4.3.1 Vilsmeir reaction
4.3.2 Gatterman –Koch Reaction
4.3.3 Diazonium compounds coupling
4.3.3 .1 Diazonium coupling
4.4 Summary
4.5 Terminal questions
4.6 Answers to terminal questions
4.7 References

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4. OBJECTIVES

The Objective of this chapter is to aware students about the electrophilic substitution
reactions in aromatic compounds. The nature of the electrophile, its attack on electron rich
aromatic ring, formation of σ and π complexes, formation of arenium ion and its stability, the
energy profile diagram of electrophilic substitution reactions. How electron rich aromatic ring
direct the attacking electrophile in presence of substituents or without substituents.
Mechanism of some important name reactions involving electrophilic substitution reactions

4. 0 INTRODUCTION

The marked reactivity of aromatic compounds towards the electron deficient species,
electrophiles arises mainly from two factors: the presence of π electron cloud above and
below the plane of the ring, which shield it from the attack on electron rich nucleophiles, at
the same time the electron cloud of π electrons are loosely held as compared to σ electrons.
These loosely bound π electrons are available for easy attack of electrophiles. In contrast the
olefinic compound with π electrons cloud undergo addition reactions because of their
localized nature

4.1 THE ARENIUM ION MECHANISM

A arenium ion in organic chemistry is a non-classical cyclohexadienyl cation and

formed as a reactive intermediate during aromatic electrophilic substitution reaction. So far
the mechanism is concerned, it is a bimolecular reaction and also designated as SE2
(electrophilic substitution bimolecular) reaction. It is a two-step reaction;
Step 1. The electrophile attack to the substrate in this step and produce a resonance establized
reactive intermediate known as benzonium ion or cyclohexadienyl cation or σ-complex. This
step is rate determining step.
Step 2.The leaving group from benzene ring (H or substituent) depart in this step. The
attacking electrophile may be positive ion or a dipole. Fig. 1

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Fig.1 Mechanism of aromatic electrophilic substitution reaction

4.1.1 Energy profile diagrams of E+ substitution reaction:

As discussed in above reactions the attacking reagent produce a reactive arenium ion (Wheland
Intermediate) through transition state I followed by the removal of departing group through
transition state II, which ultimately gives the thermodynamically stable product. The entire
mechanism can be presented through energy profile diagram as in fig.2. Similar energy profile
diagram can be drawn for substituted aromatic rings. However the rate of substitution and the
regioselectivity of the reaction at ipso, ortho, para or meta positions depends on the height of
+
the energy barrier E (∆G+) between the reactant and the T.S.

+ H E

+ H+
T.S. I
T.S.II

+
G H
Energy + E

+ E+ E
+ H+

Progress of the reaction

Some common electrophilic substitution reactions are:

Electrophilic Aromatic Substitution (Aromatic compounds)

H
Ar H

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1. Nitration

Ar-H + HNO3, H2SO4 Ar-NO2 + H2O

2. Sulfonation

Ar-H + H2SO4, SO3 Ar-SO3H + H2O

3. Halogenation

Ar-H + X2, Fe Ar-X + HX

4. Friedel-Crafts alkylation and acylation

Ar-H + R-X, AlCl3 Ar-R + HX

4.1.2 Nitration: H is substituted by NO2 group while the aromatic compound is treatied with
nitrating mixture at elevated temperature.

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4.1.3 Sulphonation:

Sulphonation is done usually in presence of fuming sulphuric acid or con. H2SO4. The
reaction takes place as under:

SO3H
F. H2SO4

Mechanism:
Generation of electrophile
+ _
2 H2SO4 SO3 + H3O + HSO4
Electrophile _
_ _
H SO3 + SO3 SO3
_ H
+ SO3 SO3 H +
H
+ +

Finally deprotonation by base lead the formation of final product

_
SO3 _
SO3
H
+ H2SO4
+
_
SO3
SO3H
+ H2O

Sulphonation is a reversible reaction at higher temperature

4.1.4 Halogenation:

Aromatic compounds can be halogenated through chlorination or bromination particularly in

presence of Lewis acids viz; BF3, AlCl3, FeCl3, FeBr3, AlBr3 etc. The electrophile in such
reactions is either halogen-Lewis acid complex or positive halogen. As per the mechanism
predicted in fig. 1 the halogenated product is/are formed as under:

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Cl

AlCl3
+ Cl2

+ + + _
Cl Cl + AlCl3 Cl Cl AlCl3 + Cl + AlCl4

Cl
+ + _
+ AlCl4
+ Cl Cl AlCl3 + H

Finally the conjugate base of Lewis acid depronate the arenium ion to give halogenated product

Cl _
AlCl4 Cl
+
+ H + HCl + AlCl3

A similar mechanism is operated with HOCl and HOBr in presence of strong acid. The
electrophile in that case is H2O+- X or positive halogen where X= Cl or Br

4.1.5 Alkylation:

Introduction of alkyl group on benzene ring is known as alkylation. The most common
method for alylation is Friedel-Craft alkylation. The reaction is carried out in presence of
Lewis acids Viz; BF3, AlCl3, FeCl3, FeBr3, AlBr3 etc. Since alkyl substituents activate the
arene substrate, polyalkylation may occur. The active E+ in Friedel – Craft alkylation is either
an alkyl halide- Lewis acid complex or an alkyl carbocation.

E+ from alkyl halides:

RCl + AlCl3 R + AlCl4

E+ from alcohol and Lewis acid:

ROH + AlCl3 ROAlCl2 R + OAlCl2

_ HCl
E+ from alcohol and proton acid:

ROH + H ROH2 R + H2O

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E+ from olefins: (proton is always required)

+ H H

The active E+ generated as above attack the aromatic molecule and lead to the formation of

product:

Limitations of Friedel –Craft alkylation:

1. Generally it is not possible to introduce a 10 alkyl group (except –CH3 and –CH2CH3)
into an aromatic ring as the alkyl substituent obtained undergo rearrangement viz;
alkylation of benzene by n-propyl chloride gives a mixture of n and isopropylbenzene
2. The entering group in alkylation is ring activation hence di and polyalkylation occur
frequently
3. Aromatic molecules containing m-directing groups do not undergo Fridel-Craft
alkylation.
4. Aryl halids cannot be used in place of alkylhalides,
5. Rearrangement can also occur after the formation of product through isomerization
4.1.6 Acylation:
Introduction of acyl group into an aromatic ring is called acylation. This reaction can also be
frequently Carried out through Fridel-Craft reaction using Lewis acid catalysts.
O O

Cl
Lewis acid

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Mechanism:

O O

+ AlCl3 Cl AlCl3
+ AlCl4
Cl
E

O O
H
C

-H

4.2 ORIENTATION AND REACTIVITY

What do we mean by these terms? If we have mono substituted benzene instead of

benzene itself then attack by the electrophile can occur in four possible positions (ipso, ortho,
meta and para): Which of these possible sites will be attacked by a reactive E+ is called
orientation effect.
(Note: The electron density calculations based on partial rate factor can be included from
Bruckner’s book)

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The rate of the reaction of mono-substituted benzene may be slower or faster than benzene.
This is the Reactivity of the reaction. If the reaction is slower the substituent is said to
deactivate the ring; if faster than it is said to be activating the ring.
NO2

H2SO4
I
HNO3

CH3 CH3 CH3

NO2
H2SO4
II +
HNO3

NO2
NO2 NO2

H2SO4
III
HNO3
NO2

In above reactions toluene II react faster and produce ortho and para product than benzene I,
while nitrobenzene III is very much less reactive and give only meta product. In ipso attack a
position already occupied by a non-hydrogen substituent in aromatic is replaced by attacking
substituent is called ipso attack, while the position is called ipso position ipso (Latin: ipso, on
itself)

CH3 CH3
H3C CH3 H3C
H3C H
H+ CH3
+ + CH3
ipso attack
CH3

In above ipso attack the tertiary alkyl group is most easily removed, because it departs as
stable 30 carbocation. The t-butyl group is generally used to protect the most reactive position
in a compound to effect reaction at other position.

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Rearrangement of alkylbenzenes leading to their isomerism also involve ipso attack viz
isomerization of o-xylene to m-xylene

CH3 CH3 CH3 CH3

CH3 H H
+ Rearrangement H+
H + CH3 +
H
ipso attack
H CH3
CH3

Other examples of ipso attack are bromodesilylation and protodesylylation as under:

COOH COOH

bromodesilylation
+ Br2 + CH3SiBr

SiCH3 Br

SiCH3 H
SiCH3
ipso addition -H
+
+ H3O+ + + H2O + CH3SiOH

In electrophilic substitution reactions of benzene derivatives, a substituent directs the

incoming group either to the ortho and para positions or the meta positions. The otho para
directing group increase electron density at o and p positions and decrease activation energy
between T.S and substrate while the energy gap is more in meta position viz; electrophilic
substitution reaction of toluene (Fig.3). The o,p director group activate the aromatic ring for
further substitution(X=Cl, Br,I are exception, because in case of them -I effect of halogen
atoms). The directions of uncoming electrophile in benzene ring generally depend upon the
nature of key atom (the atom directly attached with benzene ring). If the key atom has loan
pair of electron, it will direct the incoming electrophile to attack at ortho or para positions (-
CH3 is exception. –CH3 is o,p director in spite of having no loan pair of electron. The reason
is hyperconjugation as a result it increases electron density at otho and para positions). The
orientation of attacking electrophile is also influenced by inductive and steric effect. These

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effects lead to the positional and reactivity preferences as summarized in table 1-2. The
activating and diacticating effect of groups have been presented in fig.4
CH3

meta product
+ E

H
+ CH3
+
G + E
+
G
+ H ortho product

CH3

+ para product
Energy
H E

Reaction coordinate

Fig 3. Energy profile activity for electrophilic substitution reaction of toluene

Table 1: Orientation (ortho and para) effect of groups attached in aromatic system

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Table 2: Orientation (ortho and para) effect of groups attached in aromatic system

(A) (B)

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(C)
Fig.4 Energy profile diagram: (A) ortho, para director, activator (B): Meta director, deactivator:
(C): Ortho, para director, deactivator

4.2.1 Electrophilic substitution in other poly-substituted benzene rings:

If two or more groups are attached to a ring, electrophilic substitution is influenced by
a combination three factors

1. He position to which the attacking E+ will be oriented by each substituent (o/p vs

m)
2. He relative activating and deactivating strength of each substituent teric effect
The general orientation and activating properties of various substituents have been
summarized above in tables1-2. With regard to activation and deactivation, substituents can
be more precisely classified according to their relative strengths, as in table 3.
A. Whent two meta directing substituents are attached to a ring, E+ substitution occurs with
difficulty because the ring is too deactivated.
B. Feiedel-Craft alkylation and acylation do not occur if ring has only m-directing
substituent.

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Table 3 Relative effect of activation on benzene ring by o, p-directing substituents and of

deactivation by m- directing substituents

4.3 SOME NAME REACTIONS INVOLVING AROMATIC

ELECTROPHILIC SUBSTITUTION MECHANISM

4.3.1 Vilsmeir reaction:

The chemical reaction of asubstituted amide with POCl3 and an electron rich arene to
produce an aryl aldehyde or ketone is known as Vilsmeir reaction.

The reaction follows following mechanism:

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N-phenyl N- methylformamide is the most common reagent in this reaction, however

substituted amides are also used. In place of POCl3, other halides like SOCl2, and COCl2
have also been used.In all the case the reacting electrophile is always chloroiminium ion.

4.3.2 Gatterman –Koch Reaction:

The formylation of aromatic compound with CO and HCI in presence of Lewis acid is
known as Gatterman-Koch reaction.The reaction require out either under pressure or using
copper(I) chloride whose role may be to aid the reaction between CO and HCl via the
complex which it forms with CO

Though the mechanism of this reaction is uncertain, however probably the formyl cation is
the active electrophile. The reaction takes place as follow:

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4.3.3 Diazonium compounds coupling:

Diazonium compounds are nitrogencontaining organic compounds with following
functionality. Where R can be any organic group such as alkyl or aryl, while X is an
inorganic or organic anion like halogen.

Diazonium salts especially where R is aryl group have synthetic utility as they play
important role as reaction intermediate in organic synthesis.
Molecular nitrogen is the vest possible leaving group that exists, so it is dissociated as N2
and a reactive phenyl cation is formed.

Some of the compounds synthesized by using diazonium compounds are summerised as

under.

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4.3.3.1 Diazonium coupling:

The diazonium ion has two resonance forms, one of which place the positive charge on the
terminal nitrogen atom

If activated aromatic compounds are added to the solution of diazonium salt, then
electrophilic substitution can occur. Only the most activated substrates derivatives of aniline
and phenol can be employed in this reaction, because the diazonium ion is a weak
electrophile.

The mechanism of coupling reaction takes place as follow:

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Besides these reactions the diazo coupling reactions are used for the synthesis of organic
dyes in textile industry.

4.4 SUMMARY

This chapter provides us concise knowledge about electrophile, electrophilic reactions

in arene system. We studied about formation of arenium ion as aresult of attack of
electrophile. We learned about how thermodynamically different orientation are possible in
substituted and unsubstituted arenes. We also studied about the mechanism of important
name reactions with possible products.

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4.5 TERMINAL QUESTIONS

Q.1. which of the following can act as electrophile

A. AlCl3
B. NH3
C. H2O
D. All are electrophile

Q.2. Which one of the following cannot easily undergo Friedel-Craft reaction?
A. Anisol
B. Nitro benzene
C. Toluene
D. Xylene

Q.3.Which among the following undergoes nitration readly?

A. Benzene
B.Acetamide
C. Acetophenone
D. Chlorobenzene

Q.4. Which among the following will undergo Gatterman-Koch formylation?

Q.5.Which in the following product is formed due to ipso substitution?

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Q.6. Increasing amount of ortho isomers is obtained on nitration in the series:

Q.7. Why nitration of anisol with fuming HNO3 in Ac2O gives mainly ortho product, while
with mixed acid para isomer is chief product?

Q.8. what are the major products in following reactions?

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Q.9. Predict the product (s) and indicate the active electrophile in each of the following
reactions:

CH3

D2SO4
A. H2SO4
B. + (CH3)2C=CH2

AlCl3 H2SO4
C. + (CH3)2CHCH2Cl D. + (CH3)2COH

AlCl3
E. + (CH3)2CCl

Q. 10. Explain why aniline is more reactive than actanilide in electrophilic substitution
reaction?

4.6 ANSWERS TO THE TERMINAL QUESTIONS

1. A

2. B

3. B

4. C

5. D

Q.6 this is because the deactivation effect at the ortho position decreases with the decreasing
electro negativity from F to I.

Q.7 In the case of fuming HNO3 in Ac2O the nitrating agent is acetyl nitrate which intrects
with the methoxy group resulting in predominant formation of the ortho isomer as shown in
the reaction. On the other hand, in the case of mixed acid the nitrating agent as NO2 this is
free to attack at the less hindered para position to give para isomer predominantly. See
following reactions

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Q.8 Ans.

CH=CHCOOH CH=CHCOOH
CH=CHCOOH
HNO3/H2SO4 NO2
A

Minor
(Due to steric hinderance) NO2
Minor product
CH2CH2OCH3
CH2CH2OCH3 CH2CH2OCH3
N2 O5 NO2
B

Major
NO2
Minor product
N2O5 NO2 O NO2 NO3 + NO2
Intrect with methoxy group
Q.9. The product for A is:

CH3 CH3
D
and The Electrophile is D

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For B. C D and E the product and electrophile is:

CH3
H3C C CH3
CH3
The active electrophile is C CH3
CH3

Q.10 In case of aniline the nitrogen contains loan pair of electron and participate in resonance
with benzene ring as a result increase electron density at ortho and para position hence more
reactive for electrophilic substitution. In acetanilide the electrons on nitrogen are involved in
resonance with adjacent carobyl group and are less available for donation towards benzene
ring at the same due to resonance with carbonyl group the nitrogen acquire partial positive
charge which further exert great electron withdrawl from benzene than aniline.

CH3 CH3
NH C NH C

O O

4.7 REFERENCES

1. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan, Meerut.
336-379.

2. Sorrell, T.N,Organic chemistry,2006 University Science Books USA, 562-603

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UNIT-5 ELIMINATION REACTIONS

CONTENTS:
5.0 Objectives
5.1 Introduction
5.2 E2 Elimination Reaction
5.3 E1 Elimination Reaction
5.4 E1CB Elimination reaction
5.5 E2C Elimination reaction
5.6 Orientation of the double bond
5.7 Reactivity effects of substrate, attacking base, leaving group and solvent medium

5.7.1 Factors effecting E2 Elimination

5.8 Mechanism of pyrolytic elimination reaction:

5.9 Cope elimination

5.11 Saytzeff elimination

5.12 Hofmann Elimination

5.12 Summary

5.13 Terminal Question

5.14 Answers (MCQ) terminal questions

5.15 References

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5.0 OBJECTIVES

Objective of this chapter is to provide students with a concise detail on the elimination
reactions. The topics covered in this chapter will be types of elimination reactions like E1,
E2, E1CB etc. Mechanism of elimination reaction and direction of double bond formed as
aresult of elimination. Discussions of Pyrolitic elimination and Satyzeffs elimination besides
Hoffman and Cope eliminations. The chapter is developed to stimulate interest of the reader
into the elimination reactions and to build the deep understanding of the fundamental
mechanisms. To offer students an easy and interesting learning experience, each of the topics
is covered with struct

5.1 INTRODUCTION

The elimination reactions are the organic reaction in with two substituents from a molecule
are eliminated in asingle or two steps. These reactions are carried out inpresence of acid or
base or some time throufg pyrolysis. During elimination reactions two sigma bonds are
broken and a pi bond is formed. In most organic elimination reactions, at least one hydrogen
is lost to form the double bond. An important class of elimination reactions is those involving
alkyl halides, and alcohols. The halogens are considered to be good leaving group.The
elimination reactions are reverse of addition reactions.When the substrate molecule is
asymmetric; the regioselective products are formed in elimination reaction. The elimination
reactions occur via three distinct mechanisms, viz; E1, E2, E1CB

5.2 E2 ELIMINATION REACTION

E2 elimination reaction is a single step reaction and facilitated through a transtition

state. 10 alky halides generally undergo E2 elimination but some time are possible in 20
halides and other compounds.Since it is a biomolecular reaction and rate of reaction depends
upon the concentration of both substrate and reagent (base) hence follow second order
kinetics. The E2 mechanism results in the formation of a π bond, the two leaving groups
(often a hydrogen / halogen) should be in antiperiplanar (staggered) orientation. Because this
orientation has minium energy and are thermodynamically stable than syn- periplanar
(eclipsed) therefore the reaction mechanism involving staggered conformation is more
favorable for E2 reactions (unlike E1 reactions). The elimination reaction to occur E2

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typically uses a strong base which can remove the weakly acidic hydrogen.The hybridization
stae of carbon should be lowered from sp3 to sp2 in order to form π- bond. E2 elimination
reactions compete with the mechanism, if the base can also act as a nucleophile.

Fig1 Enerrgy profile diagram of E2 reaction

5.3 E1 ELIMINATION REACTION

It is a two step reaction. The first step is a unimolecular ionization of the

substrate to form carbocation. It is a slow and rate determing step.

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In second steps the base abstract proton on the adjacent carbon atom to form a
double bond. It is fast step
In first step ionization is favourd by electron releasing group
The composition of product (alkene) in E1 elimination generally follow the
Saytzeff orientation
During E1 elimination the carbocation intermediate is expected to two
competeting reactions: SN1 or proton removal E1. A strong base favor E1 path
over SN1.
E1 Mechanism:
The hydrolysis of t-butyl bromide in presence of NaOH is an example of E1 elimination

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Fig.2 Enerrgy profile diagram of E2 reaction

Fig: 3 Orientation of double in E1 elimation follow Saytzeff’s orientation

There is always a competetive reaction between Elimination and Substitution reactions.

Depending upon the availability of a strong nuleophile or a strong base the common
carbocation undergo substitution or elimination reaction as follow.

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5.4 E1cB ELIMINAYION REACTION

This reaction stands for elimination, unimolecular of the conjugate base. It is a two step
reaction and occur via carbanions in first step.E1cB mechanism is limited to substrates with
substituents which can stabilize the carbanion intermediate i. e. the leaving group is β to a
carbonyl, nitro, cyano,sulphonyl or other carbanion stabilizing group.

The reaction is second order in kinetics like E2 reaction

Rate=K[alkyl halide(substrate)][Base]

The leaving group in E1cB reaction is generally poor, while the β-hydrogen should be highly
acidic so that carbanion mau form eaisy.since the reaction takes place through conjugate base
of the starting material hence designated as E1cB reaction. The E1cB reactions generally
compete with E2 elimination, however E1cB are less common than E2 reactions. Indeed very
small percentage of elimination follow this path.The mechanism of E1cB is as follow.

X X
C C C C + H B Step I
H

B A carbanion

Strong
base

X
C C X +
Step II

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Example: reaction of t-butylbromide with ethanol:

CH3 CH3 CH3

CH3CH2OH
H3C C Br H3 C C O CH2 CH3 H2 C
CH3
CH3 CH3
periods
ethyl t - butyl ether 2 _ methylpropene

nucleophilic product elimination product

5.6 ORIENTATION OF THE DOUBLE BOND

During elimination reactions when two β-hudrogen atoms can be eliminated, an

alkene mixture is formed. The formation of an alkene with more substituted alkene us
considered to be most stable and called Saytzeff’s orientation while in the formation of less
substituted alkene product is said ti be Hoffmann’s orientation.

The preferred direction of double bond in E2- elimination may be because of

intermediate transition state.The two T.S. in the case of E2 elimination resemble E1 and E1cB
mechanism in their orientational effect.

The leaving group also also effects the orientation of double bond. Poorer is the leacing
group the more E1cB like is the transition state (Hoffmann orientation). The positively charged
leaving group may also favor E1cB reactionsince their field and inductive effect increase the
acidity of the β-proton. Besids this direction of elimination is also determined by stearic
hinderance. The orientation of double bond in detail is being described in following sections;

5.7 REACTIVITY EFFECTS OF SUBSTRATE, ATTACKING

BASE, LEAVING GROUP AND SOLVENT MEDIUM

As discussed above in section 5.6 the orientation of double dependes upon various factors
like substrate, reagent, leaving group, medium etc.

5.7.1 Factors effecting E2 Elimination:

1. Substrate: It has been found that branchin at α and β- carbon increases the rate of E2
reaction. The reason is as the number of substituents increases on carbon atoms of the
developing double bond, the stabilitu of T.S. increases. The presence of electron withdrawing

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group at β-carbon enhances E2 elimination because of –I effect, which increase the acidity of
β-hydrogens and stablise the carbanion chacter of the T.S.

The rate of SN2 reaction is slowed down because of steric strain at α and β carbon, while it is
branching at α and β carbon increase the rate of elimination reaction.

The table-1 as follow show the rate and yield of elimination reactions because os substrate in
E2 elimination

Table 1: Structure of substrate and E2 reactions

Substrate Yield (%) Rate of reaction at 250C

H3C CH2 Br 0.9 1.0×105

CH3 80.3 2.3 ×105

H3C CH Br
branching at alpha

CH3 97 4.7 ×105

H3C C Br
CH3
branching at alpha

H3C CH2 CH2 Br 8.9 5.3×105

branching at beta

H3C CH CH2 Br 59.5 4.5×105

CH3
branching at beta

The table also predicts that the order of reaction in alkyl halides is: 30 > 20 > 10

E1 reactions takes place by the formation of carbocation as reaction intermediate.The rate of

E1 reaction thus depends upon stability of carbocation. Because +I effect and
hyperconjugation effect stabilize the carbocation in following order

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Further steric strain around leaving group also favours the formation of carbocation. Thus the
alkyl or aryl group on α and β –carbons with respect to leaving group increase E1 reactions.

2. Strength of base:

With the increasing basicity of the base being used in elimination reaction, the rate of E2
reactions have been found to increase for eample the basic strength and order of rate of E2
elimination among three bases is as under

However, when the base is weak and stron nucleophilic towards carbon then the ratio E2/SN2
decreases while if it is strong then the ratio is increased.

In E1 elimination the reactions generally do not require any base because of first order
reaction kinetics and the purpose is also served by solvent in rate determining step which
themselves hehave as base. The con and strength has nothing to do with E1 reactions.

3. The nature of leaving group:

Better the leaving group, the higher the rate of the E2 elimination. Thus when β-phenyl halids
are treated with NaOC2H5 in C2H5OH the rate of E2 reaction increasese with leaving power
off halogenatoms as under

It has also been found that increasing size of halogen atom increases the ratio of E2/SN2 but to
a minimum extent.

In E1 reactions the reactivity of the substrate depends mainly on the nature of the departing
group. The best leaving groups are those which are least basic and more polarizable. Thus
the decreasing oreder of leaving group reactivity is:

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I Br Cl F
4. Nature of solvent:

The E2 elimination reactions are favoured in less polar or aprotic solvents.Because the less
polarsolvents favour the formation of the transition state of the reaction.The ratio of E2/SN2
increase as the solvent polarity decreases

Comparasion between E2 and SN2 reactions is as under in table-2

Table 2: comparasion between E2 and SN2 reactions

S.N. Reaction parameters SN2 E2

1 Step Single Single

2 Reagent Strong bucleophile Stron base

3. Solvent Aprotic solvent Aprotic solvent

favour this reaction favour this reaction

4. Phse transfer catalyst Favour Favour

5. Substrate 10 > 20 > 30 30 >20 >10

6. Kinetics IInd order IInd order

7. Stereochemistry Inversion of Anti elimination (in

configuration pyrolytic reactions
syn-elimination)

Since E1 elimination reactions involve ionic reaction intermediate, the carbocation. Thus the
rate of reaction increases with increasing polarity of the solvent .i.e. E1 elimination reactions
are favoured in protic solvents. Since E1 reactions enerally competye with SN1 reaction ,then
the comparasion between with respect to various reaction parameters becomes essential. The
comparasion is as follow in table 3.

Table 3: comparasion between E2 and SN2 reactions

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S.N. Reaction parameters SN1 E1

1 Step Two Two

2 Reagent Favoured by weakly basic reagent of Favoured by weak

low con. base

3. Solvent Polar protic Polar protic solvents

5. Substrate 30 >20 >10 30 >20 >10

6. Kinetics Ist order Ist order

7. Stereochemistry Racemeic mixture Non streospecific

5.8 MECHANISM OF PYROLYTIC ELIMINATION REACTION

The elimination reactions which do not require any reagent like base for elimination
but are facilitated through acyclic transition by involving one molecule of the substrate in
presence of heat is known as pyrolytic elimination.Esters and amine oxides are the examples
of two substrate which do not require base to promote elimination. In these compounds
heating provides sufficient energy for the leaving group to function as a nitermolecular
base.The thermal cleavage of molecules are termed pyrolysis (Ei –elimination internal). The
organoselenium analoge of amine –oxide and sulfoxides provide good alkene precursors,
which require room temperature conditions and give good yield of alkenes.

Mechanism:

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5.9 COPE ELIMINATION

The cope elimination involves the cleavage of amine oxide, sulfoxide or selenoxide to give
alkene through five membered cyclic T.S. when heated. In this reaction the elimination takes
place on the same face i.e. syn elimination. And the substrate must be planar in geometry.
During this elimination reaction The amine oxiode sulfoxide and or selenoxide act as its own
base and facilitate the elimination of neural molecules like hydroxylamine, sulfenic acid and
selenic acid and result the formation of an alkene as follow.

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5.10 SAYTZEFF’S ELIMINATION

Elimination reactions which decides regeoslectivity i.e. orientation of double bond is called
Saytzeff’s rule and the orientation is called Saytzeff’s orientation. According to this rule the
in mixture of eliminated product the major product is that which contain maximum no of
alkyl substituted double bonded carbon atom because of thermodynamic stbility as shown in
fig 2.

The mechanism of Saytzeff’s elimination is as follow:

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So far stability order of the product is concerned as in above case it is I>II>III because as the
number of substituent α to the double bonded carbon will increase, the number of
hyperconjugative structures will increase that provides stability to the molecule.

The alcohols also undergo Saytzeff’s reactions when dehydrated in presence of con H2SO4
and than heated.

5.11 HOFMANN ELIMINATION

When the least substituted alkene is favoured product in elimination, than it is called
Hofmann’s orientation and the elimination is called Hofmann’s elimination.

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Similarly debromination of 2-bromo pentane gives 2-pantene and 1-pantene

respectively upon elimination of HBr from 2-bromo pentane. In this reaction regioslecetively
the double bond is oriented either to give Saytzeff’s elimination or Hofmann’s elimination to
give less substituted alkene. Conformationally it can be explained that the steric effect is the
important factor to give two different products. The anti elimination of 2-bromopentane could
occur via two most stable conformations (staggered) I and II as follow (L= leaving group, -
Br). Bothe the conformation are present in solution and the major elimination occurs through
conformation I to give the thermodynamically more stable product, which is the more highly
substituted alkene i.e. 2.pentene.

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CH3CH2CH2CHCH3
Br
E2

+
CH3CH2CH=CHCH3 CH3CH2CH2CH=CH2

Saytzeff's product Hofmann product

(major)

C2 C3 C1 C2

H
H3C H H
CH3CH2CH2 H

H CH2CH3
L H H
the leaving group L
L= Br the leaving group

I II
Saytzeff's product Hofmann product
(major)

CH3CH2CH=CHCH3 CH3CH2CH2CH=CH2

(Note: Discussion of E1 reactions are not proportionate further SN/Elimination reaction

competition needs more space).

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5.12 SUMMARY

This chapter was aimed to enhance the knowledge of students about elimination
reactions. In this unit the mechanism of various types of elimination reactions was discussed
alongwith their energy profile diagrams. The orientation of double bond in product which is
resulted by the loss of two sigma bond was discussed. The factors like nature of substrate
undergoing elimination reaction, base, and solvent medium has been discussed with suitable
example. Most of the organic reactions undergo elimination without external base generally
by heating known as pyrolytic eliminations have also been discussed. The unit is also
helpful to understanding the Cope, Saytzeff’s and Hofmann’s elimination processes. Last
but not least the there is a competition between nucleophilic substitution and elimination
reactions.This chapter provide the feasibility and possibility of nucleophilic or elimination
reactions.

5.13 TERMINAL QUESTIONS:

Q.1 Tick the correct options.

i Which of vthe following compounds undergo thermal elimination reaction

A. Acetate

B. Chlorides

C. Bromides

D. Alcohols

ii Reaction intermediate in E1cB reaction is:

A. Carbocation

B. Carbanion

C. Cyclic T.S.

D. Carbene

iii Reaction intermediate in E1 reaction is

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A.Carbocation

B.Carbene

C. Cyclic T.S.

D. Carbanion

iv Which one of the following is correctly matched

A. Saytzeff’s rule, least substituted alkene

B. Hofmann rule, most substituted alkene

C. E1cB reaction, Hofmann elimination

D. E1 reaction, Hofmann product

v Which one of the following alcohol will give E1 elimination reaction ?

A. CH3CH2OH

B. CH3CH2CH2OH

C. C(CH3)3CH2CH2CH2OH

D. C(CH3)3CH2OH

vi. In which reaction product formation takes place by Hofmann rule?

(CH 3 ) 3 COK
A. CH 3 CH 2 CHBrCH 3
heat
OAc
heat
B. CH 3 CH 2 CHCH 3

heat
C. CH 3 CH 2 CHCH 3
N(CH 3 ) 3
CH 3 ONa
D. CH 3 CH 2 CHCH 3
heat vii. Pyrolytic elimination is
Br
A. Carried out at elevated temperature in amine oxides

B. Carried out in presence of strong base and temperature

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C. Carried by using acid and catalyst

D. Carried out in alkanes by using strong base and elevated temperature

viii. In the following reaction [A] will be:

CH3
Alc. KOH
H3C CH CH2Br [A]

A. 3-methyl-1- butane

B. 2-methyl-2-butene

C. 2-butene

D. 2-butene

ix. In the following proposed reaction how many alkene molecules will be formed?

CH3
Conc. H2SO4
H3C CH CH CH3 alkenes
heat
OH

A.One

B. Two

C.Three

D. Four

x. Cope elimination is related to

A. Six membered cyclic T.S.

B. Five membered cyclic T.S.

C. T.S. not involved

D. None of them

Q.2. What are eliminationreactions?

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Q.3. How will you define elimination reaction? Discuss various types of elimination
reactions

Q.4. What is pyrolytic elimination? Discuss your answer with example. Why the reactions
undergoing pyrolytic elimination does not require base?

Q.5. Write note on

a. Saytzeff,s orientation

b. Regeoselectivity

c. Hofmann orientation

d. Cope rearrangement

Q.6. Sketch out mechanism of following reaction with justification.

?
CH3CH2CH2CHCH3 CH3CH2CH=CHCH3 + CH3CH2CH2CH=CH2
N(CH3)3

5.14 ANSWER (MCQ) TERMINAL QUESTIONS

iA

ii C

iii A

iv C

vD

vi A

vii A

viii B

ix C

x. B

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5.14 ANSWER (MCQ) TERMINAL QUESTIONS

1. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 336-379.
2. Sorrell, T.N, Organic chemistry, 2006 University Science Books USA, 562-603.
3. P.S. Kalsi Stereochemistry and mechanism through solved problems IIIrd Ed.1999.New
Age International (p) Ltd. Publisher New Delhi.

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UNIT-6 ADDITION TO CARBON-CARBON

MULTIPLE BOND

CONTENTS:
6. 0. Objective
6.1. Introduction
6.2. Electrophilic addition
6.2.1 Halogen addition reaction
6.2.2 Hydrohalogenation
6.2.2.1 Anti-Markovnikov addition
6.2.3 Oxymercuration reaction
6.2.3.1 Regioselectivity and stereochemistry of oxymercuration
6.3 Nucleophilic addition
6.3.1 Cyanoethylation
6.3.2 Hydro-cyano-addition
6.3.4. Epoxidation of α,β-unsaturated carbonyls
6.4 Free radical addition
6.4.1 Stereochemistry of Free radical addition of HBr
6.4.2 Free Radical Addition of Halomethanes
6.4.3 Other Free Radical Additions of Alkenes

6.5 Addition to cyclopropane ring

6.5.1 Structure and bonding in the cyclopropane ring
6.5.2 Addition reactions of cyclopropane ring
6.5.3 Mechanism of electrophilic addition to cyclopropane
6.5.4 Nucleophilic addition to cyclopropane
6.5.5 Addition of Free radicals to cyclopropane
6.6 Hydrogenation of double and triple bonds
6.7 Hydrogenation of aromatic rings
6.8 Hydroboration and related reactions
6.8.1 Properties of Borane
6.8.2 Concerted mechanism of hydroboration
6.8.3 Steric-effects also explain regiochemistry and stereochemistry of hydroboration

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6.9 Michael addition

6.10 The Sharpless asymmetric epoxidation
6.10.1 Selectivity of Sharpless epoxidation
6.10.2. Mechanism of Sharpless epoxidation
6.10.3 Application of Sharpless epoxidation
6.11 Summary
6.12 Terminal questions
6.13 Answers to terminal questions
6.14 References

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6.0. OBJECTIVES

Objective of this chapter is to make students aware about electrophilic addition, nucleophilic
addition and free radical addition reaction. This unit will also provide knowledge of addition
to cyclopropane ring hydroboration and Michael addition. Besides this many important name
reactions of synthetic utility alongwith the Sharpless asymmetric epoxidation, selectivity of
Sharpless epoxidation, mechanism of Sharpless epoxidation and their applications have been
provided.

6.1 INTRODUCTION

There are four basic ways in which addition to carbon-carbon multiple bond can take place.
Three of these are two-step processes, with initial attack by a nucleophile, or attack upon an
electrophile or a free radical. The second step consists of combination of the resulting
intermediate with, respectively, a positive species, a negative species, or a neutral entity (a
free radical). In the fourth type of mechanism, attack at the two carbon atoms of the double or
triple bond is simultaneous (concerted). Which of the four mechanisms is operating in any
given case is determined by the nature of the substrate, the reagent, and the reaction
conditions.

6.2 ELECTROPHILIC ADDITION

In this mechanism, a positive species approaches the double or triple bond and in the first step
forms a bond by donation of the p pair of (extending π) electrons to the electrophilic species
to form a s pair (Carbocation):

Better first discuss the π-complex formation

In step 2 of an electrophilic addition, the positively charged intermediate combines with (W)
that is electron-rich and usually an anion to form the second covalent bond. Step 2 is the same

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nucleophilic attack process found in an SN1 reaction. The exact nature of the electrophile and
the nature of the positively charged intermediate are not always clear and depend on reactants
and reaction conditions. In all asymmetric addition reactions to carbon, regioselectivity is
important and often determined by Markovnikov's rule. Organoborane compounds give anti-
Markovnikov additions. Electrophilic attack to an aromatic system results in electrophilic
aromatic substitution rather than an addition reaction.

Typical electrophilic additions to alkenes with reagents are:

6.2.1 Halogen addition reaction

A halogen addition reaction is a simple organic reaction where a halogen molecule is added
to the carbon–carbon double bond of an alkene functional group. The general chemical
formula of the halogen addition reaction is:

C=C + X2 → X−C−C−X

(X represents the halogens bromine or chlorine, and in this case, a solvent could be CH2Cl2 or
CCl4). The product is a vicinal dihalide. This type of reaction is a halogenation and an
electrophilic addition. The reaction mechanism for an alkene bromination can be described as
follows-

In the first step of the reaction, a bromine molecule approaches the electron-rich alkene
carbon–carbon double bond. The bromine atom closer to the bond takes on a partial positive
charge as its electrons are repelled by the electrons of the double bond.

Br

Br
Br Br

Br

Br

The atom is electrophilic at this time and is attacked by the pi electrons of the alkene
(carbon–carbon double bond). It forms for an instant a single sigma bond to both of the
carbon atoms involved. The bonding of bromine is special in this intermediate, due to its
relatively large size compared to carbon, the bromide ion is capable of interacting with both
carbons which once shared the π-bond, making a three-membered ring. The bromide ion

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acquires a positive formal charge. At this moment the halogen ion is called a "bromonium
ion" or "chloronium ion", respectively.

When the first bromine atom attacks the carbon–carbon π-bond, it leaves behind one of its
electrons with the other bromine that it was bonded to in Br2. That other atom is now a
negative bromide anion and is attracted to the slight positive charge on the carbon atoms. It is
blocked from nucleophilic attack on one side of the carbon chain by the first bromine atom
and can only attack from the other side. As it attacks and forms a bond with one of the
carbons, the bond between the first bromine atom and the other carbon atoms breaks, leaving
each carbon atom with a halogen substituent.

In this way the two halogens add in an anti addition fashion, and when the alkene is part of a
cycle the dibromide adopts the trans configuration. For maximum overlap of the C–Br σ*
antibonding molecular orbital (the LUMO, shown to the right in red) and the nucleophile
(X−) lone pair (the HOMO, shown to the right below in green), X− must attack the
bromonium ion from behind, at carbon.

This reaction mechanism was proposed by Roberts and Kimball in 1937. With it they
explained the observed stereospecific trans-additions in brominations of maleic acid and
fumaric acid. Maleic acid with a cis-double bond forms the dibromide as a mixture of
enantiomers:

While the trans-isomer fumaric acid forms a single meso compound:

The reaction is even stereospecific in alkenes with two bulky tert-butyl groups in a cis
position as in the compound cis-di-tert-butylethylene. Despite the steric repulsion present in
the chloronium ion, the only product formed is the anti-adduct.

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6.2.2 Hydrohalogenation

A hydrohalogenation reaction is the electrophilic addition of hydrohalic acids like hydrogen

chloride or hydrogen bromide to alkenes to yield the corresponding haloalkanes.

If the two carbon atoms at the double bond are linked to a different number of hydrogen
atoms, the halogen is found preferentially at the carbon with fewer hydrogen substituents, an
observation known as Markovnikov's rule. This is due to the abstraction of a hydrogen atom
by the alkene from the acid (HX) to form the most stable carbocation (relative stability:
3°>2°>1°>methyl), as well as generating a halogen anion.

A simple example of a hydrochlorination is that of indene with hydrochloric acid gas (no
solvent):

6.2.2.1 Anti-Markovnikov addition

In the presence of peroxides, HBr adds to a given alkene in an anti-Markovnikov addition

fashion. This regiochemistry follows from the reaction mechanism, which favors formation
of the most stable carbon radical intermediate (relative stability: 3° > 2° > 1°> methyl). The
mechanism for this reaction is similar to a chain reaction such as free radical halogenation in
which the peroxide promotes the formation of the bromide radical. Therefore, in the presence
of peroxides, HBr adds so that the bromine atom is added to the carbon bearing the most
numerous hydrogen substituents and hydrogen atoms will add to carbons bearing fewest
hydrogen substituents. However, this process is restricted to addition of HBr.

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Other hydrogen halide (HF, HCl, HI) do not behaves in the manner described above. The
resulting 1-bromoalkanes are versatile alkylating agents. By reaction with dimethyl amine,
they are precursors to fatty tertiary amines. By reaction with tertiary amines, long-chain alkyl
bromides such as 1-bromododecane, give quaternary ammonium salts, which are used as
phase transfer catalysts.

With Michael acceptors the addition is also anti-Markovnikov because now a nucleophilic X−
reacts in a nucleophilic conjugate addition for example in the reaction of HCl with acrolein.

6.2.3 Oxymercuration reaction

The oxymercuration reaction is an electrophilic addition organic reaction that transforms an

alkene into a neutral alcohol. In oxymercuration, the alkene reacts with mercuric acetate
(AcO–Hg–OAc) in aqueous solution to yield the addition of an acetoxymercury (HgOAc)
group and a hydroxy (OH) group across the double bond. Carbocations are not formed in this
process and thus rearrangements are not observed. The reaction follows Markovnikov's rule
(the hydroxy group will always be added to the more substituted carbon) and it is an anti
addition (the two groups will be trans to each other). Oxymercuration followed by reductive
demercuration is called an oxymercuration–reduction reaction or oxymercuration–
demercuration reaction.

Oxymercuration can be fully described in three steps (the whole process is sometimes called
deoxymercuration), which is illustrated in stepwise fashion to the right. In the first step, the
nucleophilic double bond attacks the mercury ion, ejecting an acetoxy group. The electron
pair on the mercury ion in turn attacks a carbon on the double bond, forming a mercuronium
ion in which the mercury atom bears a positive charge. The electrons in the highest occupied

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molecular orbital of the double bond are donated to mercury's empty dz2 orbital and the
electrons in mercury's dxz orbital are donated in the lowest unoccupied molecular orbital of
the double bond.

In the second step, the nucleophilic water molecule attacks the more substituted carbon,
liberating the electrons participating in its bond with mercury. The electrons collapse to the
mercury ion and neutralize it. The oxygen in the water molecule now bears a positive charge.

In the third step, the negatively charged acetoxy ion that was expelled in the first step attacks
hydrogen of the water group, forming the waste product HOAc. The two electrons
participating in the bond between oxygen and the attacked hydrogen collapse into the oxygen,
neutralizing its charge and creating the final alcohol product.

Step1:

Step2:

Step3:

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6.2.3.1 Regioselectivity and stereochemistry of Oxymercuration

Oxymercuration is very regioselective and is a textbook Markovnikov reaction; ruling out

extreme cases, the water nucleophile will always preferentially attack the more substituted
carbon, depositing the resultant hydroxy group there. This phenomenon is explained by
examining the three resonance structures of the mercuronium ion formed at the end of the
step one.

By inspection of these structures, it is seen that the positive charge of the mercury atom will
sometimes reside on the more substituted carbon (approximately 4% of the time). This forms
a temporary tertiary carbocation, which is a very reactive electrophile. The nucleophile will
attack the mercuronium ion at this time. Therefore, the nucleophile attacks the more
substituted carbon because it retains a more positive character than the lesser substituted
carbon.

Stereochemically, oxymercuration is an anti addition. As illustrated by the second step, the

nucleophile cannot attack the carbon from the same face as the mercury ion because of steric
hindrance. There is simply insufficient room on that face of the molecule to accommodate
both a mercury ion and the attacking nucleophile. Therefore, when free rotation is impossible,
the hydroxy and acetoxymercuri groups will always be trans to each other.

Shown below is an example of regioselectivity and stereospecificity of the oxymercuration

reaction with substituted cyclohexenes. A bulky group like t-butyl locks the ring in a chair
conformation and prevents ring flips. With 4-t-butylcyclohexene, oxymercuration yields two
products – where addition across the double bond is always anti – with slight preference
towards acetoxymercury group trans to the t-butyl group, resulting in slightly more cis
product. With 1-methyl-4-t-butylcyclohexene, oxymercuration yields only one product – still

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anti addition across the double bond – where water only attacks the more substituted carbon.
The reason for anti addition across the double bond is to maximize orbital overlap of the lone
pair of water and the empty orbital of the mercuronium ion on the opposite side of the
acetoxymercury group. Regioselectivity is observed to favor water attacking the more
substituted carbon, but water does not add syn across the double bond which implies that the
transition state favors water attacking from the opposite side of the acetomercury group.

Oxymercuration stereospecificity

Oxymercuration regioselectivity

6.3 NUCLEOPHILIC ADDITION

The steps of nucleophilic addition to alkenes are just the reverse of electrophilic addition.
Thus, the nucleophile first attacks the alkene double bond and adds up to form a carbanion. In
the second step, the carbanion combines with the electropositive species.

This is illustrated in the following figure.

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Because of the conjugation, the α, β-unsaturated carbonyls have two electrophilic sites: the
carbonyl carbon and the β-carbon. Thus, the nucleophile may possibly attack both sites
leading to either a 1,2-addition or a 1,4-addition respectively. The latter is also known as
conjugate addition as addition occurs to the double bond conjugated with the carbonyl
functionality. The conjugate addition results initially to an enol which tautomerizes to the
keto form. The addition to the 3- position never occurs since the resulting carbanion would
have no resonance stabilization. These scenarios are illustrated in the following figure.

The regiochemistry of nucleophilic addtions is dependent upon the type of nucleophile

employed. Stronger the nucleophile, the more chance is for 1,2-addition. Thus strong
nucleophiles such as Grignard reagents (RMgX) or RLi or hydride ion favour 1,2-addition.
Whereas weaker nucleophiles such as enolate ions favour 1,4-addition. Actually, a 1,2-
addition occurs first (kinetically favoured) and it may be reversible or irreversible (again
depending upon the nature of nucleophile; stronger nucleophiles are poor leaving groups and
hence difficult to eliminate from a 1,2-addition product). If irreversible, then 1,2-addition
predominates. If reversible and allowed to run for more time, then 1,4-addition product will
predominate as it is more stable and thermodynamically favoured. Also if perfomed at lower
temperatures, kinetic product i.e. 1, 2-addition product predominates while at higher
temperatures thermodynamic product i.e. 1,4-addirion product prevails. Important
nucleophilic addition reactions of alkenes are discussed as follows:

6.3.1 Cyanoethylation

With alkenes containing a -CN substituent, the most common being acrylonitrile, a variety of
nucleophiles such as phenols, alcohols, amines or sulfides may easily add to the unsubstituted
carbon of the double bond. Thus, on abstraction of a proton from the solvent, the original
nucleophile now has an attached 2-cyanoethyl group and this process is termed as
cyanoethylation.

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Thus, incorporation of a 3-carbon unit takes place in which the terminal cyano group can be
transformed via reduction, hydrolysis etc. for further synthetic manipulations. The
cyanoethylation procedure is performed in presence of a base which can convert the HNu to
the more powerful nucleophile Nu¯.

6.3.2 Hydro-cyano-addition

Alkenes having electron-withdrawing groups and also poly haloalkenes undergo base
catalysed addition with HCN to give nitriles.

HCN in presence of base gives –CN which is a good nucleophile and adds to the activated
alkene. Proton abstraction then results in the formation of the nitrile product. When the
reaction is performed with α,β-unstaurated carbonyls, then the 1,2-addition may be the
competing reaction an sometimes is the major reaction.

6.3.4. Epoxidation of α,β-unsaturated Carbonyls

The epoxidation of α,β-unsaturated ketones with hydrogen peroxide under basic conditions is
essentially a nucleophilic addition reaction. These conjugated alkenes usually do not give
epoxides when treated with peroxyacids. But this method is quite good for prepartaion of
epoxides from α,β-unsaturated ketones, aldehydes and even sulfones. The reaction involves
1,4addition of the nucleophile HOO– (generated by reaction of H2O2 and NaOH) to the
conjugated alkene and subsequent internal attack of the carbanion to the O—O bond to form
an epoxide ring via liberation of an OH– ion as depicted below

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6.4 FREE RADICAL ADDITION

It was observed that in presence of peroxide, the addition of HBr to alkenes takes place in an
anti-Markovnikov manner. This was discovered by famous chemist Kharasch and this effect
came to be known as peroxide effect or Kharasch effect. Thus, 1-butene gave 1-bromobutane
(anti Markovnikov product) with HBr/H2O2, while 2-bromobutane was formed when no
peroxide was used.

H2C CHCH2CH3 Peroxides

HBr BrCH2CH2CH2CH3

no Peroxides
H2C CHCH2CH3 HBr CH3CHCH2CH3

Br

This anomaly was explained by the involvement of a free radical mechanism in the addition
reaction of HBr in presence of peroxide. Subsequently it was also demonstrated that the
reaction could occur even if peroxides were not deliberately added to the reaction mixture.
Alkenes can be oxidised by atmospheric oxygen and become contaminated with small
amounts of alkyl hydroperoxides (ROOH) which can cause the same effect.

For examples-

R1 R3 R1 H
H Br Peroxides R3
R2
R2 R4
R4
Br

The steps involved in the mechanism are:

1. Initiation

Peroxides contain a weak oxygen-oxygen bond (bond energy~35 kcal/mol). Homolytic

dissociation of the peroxide into two hydroxyl (or alkoxy) radicals by heat or light occurs and
the subsequent abstraction of Hydrogen atom from hydrogen bromide by this radical results
in a Bromine radical.

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1
R O O R R O O R

R O H Br R O H Br

2. Propagation

The bromine radical is electron deficient and adds to the double bond, generating a carbon
centered radical. This radical, in turn, abstracts hydrogen from a molecule of H-Br, giving the
desired product, and another bromine radical which may gain add up to the alkene leading to
a chain process.

R1 R3 R1

Br R3
R2
R2 R4 R4
Br

R1 R1 H
R3 R3
R2 H Br R2 Br
R4 R4
Br Br

3. Termination

The termination of the reaction can occur via 3-ways:

i. Two bromine radicals may combine

Br Br Br Br
ii. An alkyl free radical may combine with a bromine free radical

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R1 R1 Br
R3 R3
Br R2
R2
R4 R4
Br Br

iii. Two alkyl radicals may combine with each other to terminate the reaction.
R1 R1 R1 R2 Br R4
R3 R3
R3
R2 R3
R4
R4 R2
R4 Br R2 R1
Br Br
Under free-radical conditions the regioselectivity is governed by addition of the bromine
radical to give the more stable alkyl radical. Also, addition of bromine radical to the alkene
is governed by steric factors. Thus, bromine radical adds to the less substituted carbon of
the double bond (resulting in lesser steric strain) which in turn leads to a more stable alkyl
radical and hence the observed orientation is anti-Markovnikov. The stability order for alkyl
radicals is

R R H H

R C R C R C H C

R H H H
tertiary secondary primary methyl
radical radical radical radical

Decreasing order of radicals

It must be noted that while HBr in presence of peroxides can undergo free radical addition
with alkenes, no such mechanism has been observed ever with HF or HI or rarely with HCl
owing to the greater bond energies of these hydrogen halides. HI has lower bond energy than
HBr, but the alkyl radical that forms by addition of iodine radical to the alkene is unstable
and quickly loses the iodine radical to regenerate the alkene.

6.4.1 Stereochemistry of Free radical addition of HBr: The free radical addition of HBr to
alkenes favours anti addition. This is contrary to the concept that the alkyl free radical
generated can also rotate about the C-C bond having the radical sp2 carbon to give a mixture
of both syn and anti-products. At very low temperatures (–80 0C), HBr adds by overall anti

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addition but at higher temperatures the reaction is not stereospecific. This was attributed to
the involvement of a bridged intermediate.

R Br R
H H Br
R H
Br H
H R H H
R R

For example, HBr addition to cylohexenes is strictly trans-diaxial at lower temperatures

owing to the formation of a bridged intermediate.

Br
Br
H
HBr HBr
o Cl
78 C
Cl Cl
H

At higher temperatures, however, rotation at C—C* bond can take place resulting in loss in
stereo-specificity of the reaction.

6.4.2 Free Radical Addition of Halomethanes

Various polyhalomethanes such as CCl4, CBr4, and CHBr3 etc. have been found to add to
alkenes via a free radical mechanism. The reactivity order of the halomethanes is CBr4 >
CBrCl3 > CCl4 > CH2Cl2 >CHCl3.

Addition of CBr4 to an alkene via use of an initiator (In) is shown as an example:

In CBr4 InBr CBr3

CBr3 H2C CHR Br3CCH2CHR

Br3CCH2CHR CBr4 Br3CCH2CHR

Br

Chain polymerization can compete with the halogen atom abstraction step. For substituted
terminal alkenes having phenyl or ester substituents, the polymerization reaction is more
rapid.

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The stereo-chemistry of this free radical addition is governed by the steric bulk of the
substituents present in the alkene. This effect is more pronounced in sterically congestedused
skeletons such as in decalin or in norbornene where the addition is anti due to blocking of one
side by the trihalomethyl group as shown for addition of BrCCl3 to norbornene.

6.4.3 Other Free Radical Additions of Alkenes

Acyl radicals can be formed by abstraction of the aldehydic hydrogen by a free radical
initiator and can add to the alkenes.

In RCH RC O InH

RC O H2C CHR RCCH2CHR

O O O

RCCH2CHR RCH RCCH2CH2R RC O

An example is shown below:

hv
CH3CH O H2C CCO2(CH3)3 CH3CCH2CH2CO2C(CH3)3

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Also, free radical addition of thiols and thiocarboxylic acids also occurs efficiently and the
mechanism is similar to the peroxide initiated HBr addition to alkenes. The stereo-chemistry
is anti but the reactions have less stereoselectivity than HBr addition. An example is
illustrated below:

6.5 ADDITION TO CYCLOPROPANE RING

6.5.1 Structure and bonding in the cyclopropane ring:

Cyclopropane has a triangular planar structure due to which, the bond angles between
C-C bonds are expected to be 60°. This is far less than the thermodynamically stable angle of
109.5° as per the sp3 hybridisation of the carbon atoms. Due to this there is a considerable
amount of ring strain in the cyclopropane molecule. In addition to this angular strain,
cyclopropane also suffers additional torsional-strain. The torsional strain is due to the
coplanar arrangement of the carbon atoms wherein leading to the eclipsed arrangement of the
C-H bonds. Important characteristics of cyclopropane ring are as given below:

i. C—C bonds are shorter than in alkanes (1.51 Å vs. 1.54 Å).
ii. H—C—H angle opened up (115 Å vs. 106 Å in propane)
iii. C—H bonds are more acidic (pKa=46, vs. 51 in propane
iv. Strain energy = 27.5 kcal/mol.
v. The C-C bond strength in cyclopropane is considerably weaker (65 kcal/mol) than for a
typical C-C bond (80-85 kcal/mol).

It has been suggested that significant re-hybridization occurs in cyclopropane and bonding
between the carbon centres occurs in terms of ‘bent’ bonds (Coulson-Moffitt model) wherein
the carbon-carbon bonds are bent outwards so that the inter-orbital angle is 104° which
consequently reduces the level of bond strain. So it is intermediate between σ and π bonding.
These bonds are also sometimes called "banana bonds" (Fig). Thus, the C—C bonds have
more p-character than normal while C—H bonds have more s character. Thus, it can be seen
that ring strain substantially weakens the C-C bonds of the cyclopropane ring. Hence,
cyclopropane is much more reactive than alkanes or other higher ring systems. Another

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model viz. Walsh model based on M.O. considerations, envisions cyclopropane as being
constructed from three sp2-hybridized methylenes (CH2), (Fig 1). Two of these sp2 orbitals
are used for C−H-bonds (not shown) and one forms an inner two-electron-three-centre σ
bond, leaving p-orbitals to form some kind of degenerate π-like orbitals. Thus, Walsh
cyclopropane has considerable sp2 character and should react in analogy to olefins. Fig 1
shows the Molecular Orbital diagram for cyclopropane as formed up of 3 methylenes, in
inceasing order of energy.

Fig. 1 : Models for bonding in cyclopropane

6.5.2 Addition Reactions of Cyclopropane Ring:

Cyclopropane ring system suffers from a large ring strain (which is a combination of angle
strain and torsional strain) which leads to a significant weakening of the C—C bond. Thus,
C—C bonds show a greater p-character, while C—H bonds have more s character. Thus, in
effect, the cyclopropane ring undergoes any such reaction which can subsequently help in
relieving the ring strain. Most of these reactions are similar to those of alkenes and most
common of these are addition reactions (electrophilic nucleophilic or free-radical) which lead
to opening of the ring. For example:

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Ni/H2
0
CH3CH2CH3
80 C

Cl2/FeCl3
ClCH2CH2CH2Cl

conc.H2SO4
CH3CH2CH2OH
H2O

HBr
CH3CH2CH2Br

In each of these reactions, a C—C bond is broken leading to ring fission and the atoms of the
reagent attach at two terminals of the resulting propane chain. Depending upon the
substitution of cyclopropane ring, which can be electron donors or acceptors, any of its three
bonds are likely to undergo cleavage. The reagent must be able to polarize itself into
nucleophilic and electrophilic centres for the subsequent addition to occur. Thus, propylene
reacts more readily with Br2 or Cl2 while for reaction with cyclopropane a Lewis acid is
required (FeCl3 or FeBr3) to effect sufficient polarization of the Cl2 or Br2 molecule.

6.5.3 Mechanism of Electrophilic Addition to Cyclopropane:

Before discussing the mechanism, there are two important points to be noted for addition
reaction of cyclopropane:

1. The mechanism must be stepwise as reaction of D2SO4 with cyclopropane yields along
with the expected product (I), minor amounts of 2 more products (II and III) as shown below:

2. The electrophilic addition in substituted cyclopropanes generally follows Markovnikov's

rule wherein hydrogen adds to the carbon which already contains more hydrogens.

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This suggests that the mechanism comprises of an initial attack by the electrophile (e.g. H+)
on the ring carbon with the most hydrogens, generating a positive charge on the carbon
(carbocation). This positive charge may be transferred on to the other carbons of the ring and
the most favourable intermediate would be the one in which the positive charge is on the
most substituted carbon (most stable carbocation). This cation is subsequently trapped by its
reaction with the nucleophile as shown below.

Another type of mechanism has been suggested which depicts an edge-protonated

cyclopropane:

6.5.4 Nucleophilic Addition to Cyclopropane:

Ring-fission of cyclopropane by nucleophiles is possible only when an electron-withdrawing

group (W) is present on the ring.

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W
W W
H
R Nu Nu
Nu R R
H

This reaction has been used widely in organic synthesis and can be used as a homologous
variant to a Michael-type addition to generate a 5-membered ring as shown.

CO2Et
EtO2C CO2Et CO2Et

EtO2C EtO2C
EtO EtO
O O
CO2Et CO2Et
EtO2C CO2Et

CO2Et
EtO2C CO2Et
EtO2C CO2Et
CO2Et
EtO

O CO2Et O
O CO2Et CO2Et

EtO2C CO2Et

O CO2Et

Similarly, secondary amines or alcohols can also effect the opening of the cyclopropane ring
as shown below.

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6.5.5. Addition of Free radicals to Cyclopropane

Free radicals also add to the cyclopropane ring system. Thus, Br2 can add to a cyclopropane
ring in presence of UV light via a free radical mechanism. Initially, Br● attacks the least
hindered carbon, to yield the most stable radical, and the second one goes to the most
substituted carbon.

6.6 HYDROGENATION OF DOUBLE AND TRIPLE BONDS

In the incidence of a metal catalyst such as Pt, Pd, or Ni, H2 adds to the double and
triple bonds of alkenes and alkynes, respectively to form an alkene. Hydrogen adds to an
alkyne in the same manner that it adds to an alkene. It is complicated to stop the reaction at
the alkene stage because hydrogen readily adds to alkene in the presence of these catalysts.
Ultimately, the product of the hydrogenation reaction of alkynes is an alkane. For example-

CH3CH CHCH3 Pt/C CH3CH2CH2CH3

H2

CH3 CH3

Pt/C
H3CC CH2 H2 CH3CH CH3

Pt/C Pt/C
CH3CH2 CH CH3CH2CH CH2 CH3CH2CH2CH3
H2 H2

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Withuot catalyst the energy barrier to the reaction would be massive because of the
strength of the H-H bond. The catalyst decreases the energy of the activation by breaking the
H-H bond. Platinum and palladium are used in a finely divide state adsorbed on charcoal
(Pt/C, Pd/C). The platinum catalyst is commonly used in the form of PtO2, which is known as
Adam’s catalyst. Due to existence of a catalyst in these reactions, the process is called
catalytic hydrogenation. The metal catalysts are insoluble in the reaction mixture, and are
consequently, classified as heterogenous catalysts. A heterogenous catalyst can easily be
separated from the reaction mixture by filteration. It can then be recycled, which is an
important property, since metal catalysts are expensive. The reaction can be stopped at the
alkene stage if partially deactivated metal catalyst is used.the most commonly used partially
deactivated metal catalyst is Lindler catalyst, which is prepared by precipitating palladium on
calcium carbonate and treating it with lead (II) acetate and quinoline. This modifies the
surface of palladium, making it much more effective at catalyzing the addition of hydrogen to
a triple bond than to a double bond.

6.6.1 Heat of hydrogenation and relative stability of alkene:

The stability of an alkene depends on its structure. The heat released in a

hydrogenation reaction is called the heat of hydrogenation. When an alkene is treated with
hydrogen in the presence of a platinum catalyst, hydrogen adds to the double bond, reducing
the alkene to an alkane. Hydrogenation is exothermic, evolving about 20 to 30 kcal of heat
per mole of hydrogen consumed.

The difference in the stabilities of alkenes is the difference in their heats of

hydrogenation. While considering the hydrogenation of 1-butene (a monosubstituted alkene),
2-butene (a disubstituted alkene) and 2-methyl-2-butene (a trisubstituted alkene), 2-methyl-2-
butene is more stable by 3.4 kcal/mol and 2-butene is stable by 2.7 kcal/mol (Scheme 1).
More substituted double bonds are usually more stable. In other words, the alkyl groups
attached to the double bonded carbons stabilize the alkene.

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Alkene, which releases the most heat, must be the least stable. In contrast, the alkene,
whichreleases the least heat, must be the most stable.

The heats of hydrogenation show that trans- isomers are generally more stable than the
corresponding cis- isomers. Because the alkyl substituents are separated farther in trans-
isomers than they are in cis- isomers. The greater stability of the trans- isomer is evident in
the following example, which shows that the trans -isomer is stable by 1.0 kcal/mol (Scheme
2).

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6.7 HYDROGENATION OF AROMATIC RINGS

Aromatic rings are among the hardest to be hydrogenated and even with precious metal
catalysts, require higher temperatures and pressures. But, once a benzene ring starts to
hydrogenate, there is nothing like partial hydrogenation, and it hydrogenates to cyclohexane.
This is because when benzene has been converted to cyclohexadiene (the first hydrogenation
and the hardest, endothermic step), it is associated with the loss of resonance energy and the
subsequent hydrogenations are exothermic and faster than the first one.

OH OH

H2, Raney Ni
200 atm, room temp

HO OH HO OH
phloroglucinol

Pt and Rh catalysts are common and used at ordinary temperatures whereas Raney-Nickel or
Ru catalysts require higher temperatures and pressures and Raney-Nickel is used for large
scale hydrogenations involving heating at 150ᴼC at high pressures (100-200 atm). Rh over
Alumina is another prominent catalyst used and requires milder conditions than others. Also,
it does not cause hydrogenolysis of the sensitive C—O bonds present in the molecule.

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OH
OH
H2, Rh/Al2O3
6 atm, 60oC

OH
OH

OH
OH
H2 COOH
COOH Rh Al2O3

Hydrogenation of polycyclic aromatic rings such as naphthalenes and phenanthrenes are also
performed and by varying the reaction conditions, partially hydrogenated or fully
hydrogenated products may be obtained. For example, Raney-Nickel may be used to obtain
tetrahydro or decahydro-naphthalene by varying the reaction conditions. Similarly, 9, 10-
dihydro phenathrenes or anthracenes can be obtained by reduction over copper-chromite and
to fully reduce them, more active catalysts are required.

H2
catalyst

When aromatic rings are reduced by Li/K/Na in liquid ammonia (such reductions are known
as dissolving metal reductions), usually in the prersence of an alcohol (eg. EtOH, 2-propanol,
or t-BuOH), 1,4-addition takes place and nonconjugated cyclohexadienes are produced. This
reaction is known as Birch reduction. According to this reaction an aromatic ring is more
readily reduced than an alkene.

When lithium (or potassium or sodium) dissolved in ammonia an intense blue solution is
obtained. Blue is colour of the solvent electrons: e-(NH3)n. In Birch reductions there blue
solutions with solvated electrons. Are used as reducing agent. The reaction NH3 to NH2 and
H2 is quite slow and a better electron-acceptor is preferentially gets reduced.

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Li fast Li e (NH3)n slow NH2 1/2 H2

nNH3
blue solution NH3 colourless
solution

The mechanism begins with a single electron transfer (SET) from the metal to the aromatic
ring, forming a radical anion. The anion then picks up a proton from the alcohol which results
in a neutral radical intermediate. Another SET, and abstraction of a proton from the alcohol
results in the final cyclohexadiene product and two equivalents of metal alkoxide salt as a
byproduct. In the case of substituted aromatic rings, the regiochemistry can be predicted
using Birch's empirical rules.

R1
product if R1
R1 is an EDG

M, NH3 (l)
R1
ROH
product if R1
aromatic rings is an EWG
where, M= Li, Na
EDG= electron
donating group unconjugated
EWG= electron cyclohexadienes
withdrawing group

Electron-withdrawing groups stabilize electron density at the ipso and para positions through
conjugation and so the negative charge will mainly be found in these positions; subsequent
protonation occurs para.

Electron-donating groups destabilize a negative charge (when compared to simple benzene)

through conjugation and this effect would be strongest at the ipso and para positions.

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Thus the negative charge will mainly be found at the ortho and meta position.

6.8 HYDROBORATION AND RELATED REACTIONS

Hydroboration refers to the addition of a hydrogen-boron bond to an unsaturated system such

as alkene or alkyne resulting in the formation of organoboranes which can be converted to
other products via subsequent transformations. This reaction was first explored by H. C.
Brown and coworkers during 1950s. Alkenes react with borane, BH3, and a number of its
derivatives to give synthetically useful alkylboranes. The reaction is an electrophilic addition
to alkene, but unlike others, this addition is a concerted one. The initially formed
monoalkylborane product may undergo addition with another molecule of alkene to produce
a dialkyl borane which in turn may undergo further reaction to produce a trialkyl borane.

H
H
hydroboration BH2 hydroboration B
R BH3 slow R R
fast R
Borane
hydroboration very slow

B
R R

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Thus, ethylene will yield triethyl borane on hydroboration.

CH2 CH2 BH3 CH3CH2BH2

H
ethylborane
CH2 CH2 CH3CH2BH2 (CH3CH2)2BH

H
diethylborane
CH2 CH2 (CH3CH2)2BH (CH3CH2)3
triethylborane

However, trisubstituted alkenes usually yield a dialkylborane and tetrasubstituted alkenes

form only the monoalkylboranes. The extent of hydroboration may also be controlled by the
stoichiometry of alkene and borane. This reaction is often combined with subsequent
oxidation reaction to produce an alcohol and is commonly known as hydroboration-oxidation
reaction.

6.8.1 Properties of Borane

Borane (BH3) is a very reactive electrophile since it has only a sextet of electrons Borane
(BH3) exists primarily as a colourless gas called diborane (B2H6) which is actually its dimeric
form. This is because, Boron is a highly electron-deficient element and thus, two B-atoms
share the electrons in the two B-H bonds in an unusual manner. Diborane gas may be
generated in situ by the reaction of NaBH4 with BF3 in laboratory. But, the diborane gas is
highly toxic, flammable and explosive gas and is more conveniently handled by making it’s
adduct with an electron-donor such as tetrahydrofuran (THF), dimethylsulfide (DMS) etc.
and are available in solution form in an ethereal solvent, commonly THF. The
dimethylsulfide complex (BH3.Me2S) is more stable than BH3·THF and is soluble in a variety
of organic solvents, such as diethyl ether and hexane. Borane is very reactive and is also used
for reduction of a host of carbonyl compounds including aldehydes, ketones, carboxylic acids
and other functional groups such as epoxides, lactones and nitriles. Thus, on treatment with
borane of alkene substrates which contain these functionalities may also cause their reduction
in addition with the hydroboration reaction. Thus, easily reducablefunctional groups like
aldehydes must be protected as their acetal. Carboxylic esters are usually tolerated.
Sometimes mono- or di-alkyl borane reagents are used for hydroboration which are less

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reactive and more selective than diborane and can be used for hydroboration of less-hindered
alkenes. Common examples of such alkylborane reagents include disiamylborane,
thexylborane and 9-borabicyclo [3.3.1] nonane (9-BBN).

6.8.2 Concerted Mechanism of Hydroboration

The boron atom is highly electrophilic because of its empty p orbital and the π-electrons of
the alkene act as a nucleophile to attack the electrophilic B-atom. However, the reaction is a
concerted process and no carbocation-type intermediate has ever been isolated. A four-
membered transition state is thought to involve in which breaking of B—H bonds and making
of C—H bonds all take place simultaneously as shown below for the hydroboration of
methylcyclohexene.

The reaction results in anti-Markovnikov product i.e. the hydrogen adds to the more
substituted carbon of the double bond. This regio-chemistry is reverse of a typical HX
addition to the alkene which is a result of the polarity of the B—H bonds. The B—H bond in
diborane is polarized (Bδ+—Hδ-) due to electronegativity difference between the B and H-
atoms. As the addition of the empty p orbital to the less substituted end of the alkene gets
under way, a hydrogen atom from the boron adds, with its pair of electrons, to the carbon
atom, which is becoming positively charged. Thus, the addition is a syn addition. The
formation of the C–B bond is slightly faster than that of the C–H bond (but still concerted) so
that boron and carbon are partially charged in the fourcentred transition state. The developing
positive charge is present on the more substituted carbon (analogous to a stable carbocation)
and hence the reaction proceeds via anti-Markovnikov regiochemistry.

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H H
H B H B
H H
H BH2
H H H
H
BH3

syn addition occurs

most favoured T.S.

H B H

H H H BH2
H

Due to the syn-addition of the boron and hydrogen atom, the reaction can also be
stereoselective, with hydroboration taking place preferentially on the less hindered side of the
double bond as shown for 1-methylcyclopentene.

BH3 H H3C

BR2 H
H CH3 (syn addition of BH3)
1 Methylcyclopentene (R= 2 methylcyclopentyl)

6.8.3 Steric-effects also explain regiochemistry and stereochemistry of hydroboration

Another explanation for the anti-Markovnikov regiochemistry of hydroboration is the steric

effect of Boron containing group which is much bulkier than H-atom and hence boron gets
attached to the less hindered end of the double bond. The selectivity of the first addition of
borane is relatively low but the steric effect is more pronounced in the second or third
successive hydroboration and anti-Markovnikov selectivity may predominate in the end.

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With most substituted alkenes, the reaction stops at second hydroboration as third
hydroboration becomes quite difficult due to increased steric strain.

BH B
BH3

BH2

However, it must be noted that borane itself may not give good regioselectivity as it is highly
reactive and does not have enough steric bulk. The steric effect is more pronounced in
sterically-congested alkylborane reagents like 9-BBN, which are also less reactive than
borane and lead to enhanced regioselectivity. This is exemplified by the case of
hydroboration of 4methylpent-2-ene by various boron reagents.

B B R

BH3 57 : 43
disamylborane 97 : 3
9 BBN 99.8 : 0.2

The sterically-congested alkyl boranes (9-BBN etc.) show extremely good stereoselectivities
in bicyclic systems where the attack of 9-BBN occurs from the less hindered side as
exemplified by the norbornyl systems as shown below.

Haloboranes like BH2Cl, BH2Br, BHCl2, and BHBr2 are also useful hydroborating reagents.
These compounds show similar reactivity as borane but are somewhat more regioselective
than borane. Also, after hydroboration, the halogen-atom can be replaced by hydride and
subsequent hydroboration can be carried out and thereby preparation of unsymmetrical alkyl
boranes can be carried out.

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6.9 MICHAEL ADDITION

The Michael addition is an organic reaction used to convert an activated methylene and a
conjugated olefin to the corresponding addition product using a base catalyst followed by an
acid work-up. The activated methylene is essentially a methylene bonded to electron
withdrawing groups that would stabilize the negative change that forms after deprotonation
by the base. This deprotonation results in an enolate which in turn does a 1, 4 additions to the
conjugated olefin. An acid work-up then provides the final Michael addition product

The substrates of the Michael reaction are compounds, esters, cyanides, quinines, α, β-
unsaturated nitro compounds. Reagents of the reaction are those compounds which have at
least one acidic hydrogen and convert into nucleophile in the presence of a base. Such
compounds are compouns having active methylene group, nitroalkanes, sulphones, indene,
fluoenes, alcohols, and thioalcohols and terminal alkynes. For example

O O
O
C 1. base
C
1 1
R CR2 H O R CR2 CH2 CH2 C R

2. H2 C CH C R

Mechanism:

Step 1: First, an acid-base reaction. Hydroxide functions as a base and removes the acidic α-
hydrogen giving the reactive enolate.

Step 2: The nucleophilic enolate attacks the conjugated ketone at the electrophilic alkene C
in a nucleophilic addition type process with the electrons being pushed through to the
electronegative O, giving an intermediate enolate.

Step 3: An acid-base reaction. The enolate deprotonates a water molecule recreating

hydroxide and the more favourable carbonyl group.

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CH3 CH2 H

HO
S tep 1

HOH
CH3 CH2

H 2C CH
O
S tep 2 H 3C

O
O

CH3 CH2 CH2 CH C CH3

H H
S tep O
3

O
O

CH3 CH2 CH2 CH C CH3

HO

Thus the net reaction can be written as followes

O O
1 2 1 2
Base
Nu H CH2 CH C R Nu CH CH2 C R

addition addition of
of Nu on H on
carbon 1 carbon 2

Michael addition is conjugate addition, i.e., 1,4-addition reaction but overall product of the
reaction is 1,2-addition product which takes place on carbon-carbon double bond due to the
tautomerisation.

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6.10 THE SHARPLESS ASYMMETRIC EPOXIDATION

The Sharpless and co-workers reported a method that has since become one of the most
valuable tools for chiral synthesis. The Sharpless epoxidation is an organic reaction used to
steroselectively (with preference for one enatiomer rather than formation of a racemic
mixture) convert an allylic alcohol to an epoxy alcohol using a titanium isopropoxide
catalyst, t-butyl hydroperoxide (TBHP), and a chiral diethyl tartrate (DET). The esters most
commonly used are (+) or (-) diethyl or diisopropyl tartrate (DET and DIPT). The tartrate
stereisomer that is chosen depends on the specific enantiomer of the epoxide desired. The
main attraction of the Sharpless epoxidation procedure is that it effords a single enantiomer of
the epoxide in high enantiomeric excess and in a predictable manner. For example

1.
O
DET
OH
Ti(OPri)4
TBHP (S) Methylglycidol

OH

DET O

Ti(OPri)4 OH
TBHP
(R) Methylglycidol

R1
2.
O
DET 2
R
Ti(OPri)4
t R3
R1 BuOOH
(S)
2
R

R3 R1
DET O
allyl alcohol
2
R
Ti(OPri)4
t
BuOOH R3
(R)

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6.10.1 Selectivity of Sharpless epoxidation

The chirality of the product of a Sharpless epoxidation is sometimes predicted with the
following mnemonic. A rectangle is drawn around the double bond in the same plane as the
carbons of the double bond (the xy-plane), with the allylic alcohol in the bottom right corner
and the other substituents in their appropriate corners. In this orientation, the (−) diester
tartrate preferentially interacts with the top half of the molecule, and the (+) diester tartrate
preferentially interacts with the bottom half of the molecule. This model seems to be valid
despite substitution on the olefin. Selectivity decreases with larger R1, but increases with
larger R2 and R3.

6.10.2. Mechanism of Sharpless epoxidation

As discussed, there are four main elements required for Sharpless epoxidation: the allyl
alcohol, t-butylhydroperoxide (TBHP), the transition metal catalyst Ti(OiPr)4 and the chiral
ligand (dialkyltartrate). Initially, the reaction involved use of stoichiometric amounts of the
Ti(OiPr)4 catalyst but use of molecular sieves improved the scope of the reaction requiring
only about 5-10 mol% Ti(IV) catalyst. However, no reaction takes place in the absence of the
Ti-catalyst. Ti(OiPr)4 is added so that the oxidizing agent, the chiral ligand, and the substrate
can assemble to form an enantiomerically pure chiral complex. The actual mechanism is not

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known, but DFT and kinetic studies along with experimental results have led to a most
plausible mechanism for this reaction (Fig.):

1. The coordination of the tartrate ligand to the Titanium catalyst occurs with displacement of
two isopropoxide ligands (attributed to higher binding constant of the bidentate
tartrateligand).

2. Then, the tert-butyl peroxide displaces one more isopropoxide followed by another
isopropoxide displacement by the allyl alcohol to coordinate with the metal.

3. This Titanium complex is the active catalyst species and is believed to exist as a dimer. It
has many features conducive for the successful epoxidation to occur:

(a) Instead of a planar arrangement, the peroxide-titanium interaction has a spiro

arrangement in the TS for oxygen transfer.

(b) The O—O bond of peroxide is approximately perpendicular to the plane of the¬ alkene
bond, facilitating the latter’s attack.

(c) The steric effects of the bulky peroxide and the chiral tartrate ligand lead to such a¬
conformation of the TS that blocks one side of attack by the alkene and play an important
role in deciding the enantioselectivity of the reaction.

4. Oxidation of the olefin with TBHP then occurs. The alkene acts as a nucleophile to attack
the equatorial oxygen atom of the peroxide. Studies have shown that the dimeric complex has
ester groups of the tartrate in axial positions which blocks one mode of approach. Thus, the
chiral diiethyltartrate dictates the face of attack and leads to a steroselective epoxide alcohol.

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Fig.: 2 Catalytic cycle showing the Sharpless Asymmetric epoxidation

6.10.3 Application of Sharpless epoxidation

1. Synthesis of the β-blocker (S)-propranolol

ONa

OH TBHP O OH
( ) DET
OH

O OH

TsCl/Py
CH3
CH NH2
OH CH3
CH3
O NH CH
CH3 O
O

2. Synthesis of gypsy moth pheromone (7R, 8S)-disparlure

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CH3 (CH2)9 CH2 Br

CH3
i. (C6H5)3P
iii. CH (CH2)4 CHO
ii. BuLi CH3

TBHP
i
Ti(OPr)4
( ) DET

H
O
H

(7 R, 8S) Disparlure

2. Synthesis the anti-depressant drug fluoxetine

OH
O
TBHP Al [H]
C6H5 OH C6H5 OH C6H5 OH
( ) DET
MsCl/Et3N

OH

C6H5 OMs

CH3NH2

OH

O CF3 NaH/
C6H5 NHCH3

C6H5 NHCH3 CF3 Cl

Fluoxetine

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6.11 SYMMARY

In this chapter provided us concise knowledge about electrophile, nucleophilic and free
radical addition reaction to carbon-carbon multiple bond. We also studied about addition to
cyclopropane ring, hydrogenation of double, triple bonds and aromatic rings. We learned
about hydroboration, Michael addition and the Sharpless asymmetric epoxidation reactions.
We also studied about the stereoselectivity, mechanism of important name reactions with
possible products.

6.12 TERMINAL QUESTIONS

1. Which one of the following alkenes will give optically active product with Br2/CCl4?
A. 1-Butene
B. Propene
C. trans-2-butene
D. cis-2-butene
2. Which one of the following alkenes will give optically active product with Bayer’s
reagent?
A. 1-Butene
B. Propene
C. trans-2-butene
D. cis-2-butene

3. In which compound electrophilic addition takes place according to anti-Markovnikov rule?

1. CH2=CH-NO2
2. CH2=CH-CHO
3. CH2=CH-CN
4. CH3-CH=CH2
Select the answer on the basis of given code:
Code:
A. 1, 2 and 3
B. 1, 2, 3 and 4
C. Only 4
D. Only 1

4. Consider the following statements:

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1. Alkene is more reactive than alkyne for electrophilic addition

2. Alkyne is more reactive than alkene for nucleophilic addition
3. Alkyne is more reactive than alkene for electrophilic addition
4. Alkene having CF3 at vinylic carbon is more reactive than alkene having CH3
Of these, correct statements are:
A. 3 and 4
B. 1, 2 and 3
C. 1, 2 and 4
D. 1 and 2

5. Which among the following reagents gives syn-addition with alkenes.

1. Br2
2. Dil KMnO4/OH-
3. OsO4 | NaSO3H | HOH
4. H2 | Ni | ∆
Select the answer on the basis of given code:
Code:
A. Only 1
B. 2 and 3
C. 2, 3 and 4
D. Only 4

6. Give the mechanism of and application of Sharpless asymmetric epoxidation.

7. Addition of HX on alkenes is regioselective. Why?

8. What is meant by iodolactonisation? Give mechanism of this reaction.

9. Propose the mechanism for the following reaction.

CH3
Br CH3 CH3 CH3
C CH2
CH3 Br
HBr

10. Predict the product of the following reactions:

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HBr
1. CH3CH=CH2

KMnO4
2. RCH=CHR
OH

3.
3 CH
3CH=CH2 BH3

4. CH2=C=CH2 HCl

5. CH2=CH CH=CH2 Br2

6.13 ANSWERS TO TERMINAL QUESTIONS

1. D
2. C
3. A
4. D
5. C
8. 4- Pentanoic acids from iodonium ion with iodine in the presence of NaHCO3. This
reaction is an example of electrophilic addition reaction in which electrophile is I-. In the
presence of NaHCO3, carboxylic group convert in to carboxylate ion. Thus thus nucleophile
of the reaction is carboxylate ion. The carboxylate ion attacks intramolecularly to form
iodolactone. This type of reaction: the cyclization of 4-pentenoic acids in to lactone is known
as iodolactonisation. This reaction is also given by bromine and in this case reaction is known
as bromolactonisation. Intermolecular attack on the bromonium ion by bromide ion (or by I-)
does not complete with the intramolecular cyclization step.

OH
I2
O I O
O NaHCO3 I O
O

OH Br2
O Br O
NaHCO3 Br O
O
O

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6.14 REFERENCES

1. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 471-536.

2. Jerry March. 2007. Advanced Organic Chemistry-Reactions, Mechanism and

Structure, John Wiley. 4th edition. 734-878.

3. Mukherji S. M. and Singh S. P. 2015. Reactions Mechanism in Organic Chemistry.

Trinity Press. 328-364.

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UNIT-7 ADDITION TO CARBON-HETERO ATOM

MULTIPLE BONDS

CONTENTS:
7.0 Objectives
7.1 Introduction
7.2 Mechanism of metal hydride reductions in saturated and unsaturated carbonyl compounds
7.3 Addition of Grignard reagent with carbonyl groups
7.4 Reformatsky and related reactions.
7.5 Wittig reaction and its mechanism
7.5.1 Modified Wittig Reaction (Horner-Wadsworth-Emmons reaction)
7.5Knoevenagel reaction
7.6 Claisen condensation
7.7 Mannich reaction
7.8 Stobbe reactions
7.9 Stork enamine reaction
7.10. Concept and applications of Reaction Umpolung
7.11 Sulfur ylides
7.12 Summary
7.13 Terminal questions
7.14 Answers(MCQ) terminal questions
7.15 References

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7. OBJECTIVES
Objective of this chapter is to make students aware about metal hydrides, their
synthetic application particularly to remove the funcationality and introduction of
stereocenters by gaining protons. This unit will also provide knowledge of addition of
reagents to pi-bonds in a carbon-hetero atom multible bonds.Besides many important name
reactions of synthetic utility alongwith the concepts of umpouling and sulfur yelides and their
applications.

7.1 INTRODUCTION
The carbon carbon hetero atom containing multiple bonds is very indespensible group of
compounds for synthesis point of view. One of the important processes for carbon-caron
bond formation is reaction between nucleophilic carbons with an electrophile. A very crusial
mean to generate a carbon nucleophile is to remove proton from a carbon which generate
carbanion. The rate of deprotonation for the generation of nucleophilic carbon and its stability
are enhanced by the substituent groups attached.The negatively charged carbon attached with
carbonyl or multiply bonded hetero atom gets stabilized by resonance through delocaiztion of
electrons.The carbanions formed by deprotonation of α-hydrogen bear negative charge on
hetero atom like oxygen and are termed as enolates.The enolates are highly reactive and
resonance stabilized, react with electron deficient carbonyl compound and form carbon-
carbon bond.

R R R
Deprotonation
R C C O R C C O R C C O
H
resonance stablized enolate
B
O R O R
Formation of carbon - carbon bond
R C C R R C C R
H C H C
O O

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7.2 MECHANISM OF METAL HYDRIDE REDUCTIONS IN

SATURATED AND UNSATURATED CARBONYL
COMPOUNDS
Metal hydrides play very important role in the reduction of carbonyl groups. They play a
versatile method for introducing stereocentres. Formally reduction is the gain of electrons but
it is more easy to visualise it as the gain of hydrogen (although this far from mechanistically
correct).The most common metal hydrides are lithium aluminium hydride (LiAlH4) and
sodium borohydride (NaBH4) There are differences mechanistically In many cases the
lithium cation is vital for reaction.

Reduction of ketone to alcohol

Reduction of amide to amine:-

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In NaBH4 reactions cation is not important but solvent can be not concentrated

Lithium aluminium hydride LiAlH4

This metal hydride reduce all types of carbonyl groups.It also reduce other functional
groups.Reaction of LiAlH4 with acidic protons generate H2

3LiAlH4 + 4RCO2H = LiAl (OCH2R)4 + 2 LiAlO2 + 4H2

During carbonyl group reduction by LiAlH4 there is a initial transfer of hydride to the
carbonyl generates 2, possibly via direct coordination of aluminum to oxygen and transfer of
hydride to the carbonyl carbon. Complex 1 has also been proposed as an
intermediate.Alkoxide 2contains three additional active hydrides, so a second equivalent of
carbonyl can react to give bis(alkoxide) 3. Similarly, a third equivalent gives 4 and a fourth
gives 5.

O R
LiAlH4 [H]
+ 4 HO C R
4
R R Reduction
H
Metal hydride Carbonyl group Alcohol reduced product

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Mechanism:

LiAlH4 H H
H Al H Al
H Li H O Li H O Li
H Al
O H C R H C R
H H
R R
R R
Carbonyl group
1 2
O

R R

O O
R Li H R H R Li
Li
Al O C R R R R R
Al O C R Al O C R
H H H 2
4 H 3
5 4 3
H3O

R
4 HO C R Alcohol reduced product
H
Mechanism of carbonyl group reduction by metal hydride like LiAlH4

Reduction of amides to amine:

Which path is followed is a result of electronics around the amine

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Similarly it reduces the unsaturated carbonyl group as in case of enones (α,β- unsaturated
ketone The metal hydride react with unsaturated carbonyl compounds with same mechanism
and yield a mixture of saturated and unsaturated alcohols as discussed follow.The metal
hydride react with different way through 1,4-addition or 1,2 addition. Addition via normal 1,2
additon gives a saturated alcohol while via 1,4- addition gives allylic alcohol(unsaturated
alcohol).

H OH
Li
H Al 1, 2 addition
CH3
H H
O1 Saturated alcohol
1. LiAlH4 THF +
2
R 4
3 CH3 2. H O
3 OH
Unsaturated carbonyl compound 1, 4 addition
CH3
allyl alcohol

Mechanism: 1, 2 addition

CH3 Li R Li
H 3C
O H R O
Al Al
R O O
H
CH3 R CH3

LiAlH4 unsaturated carbonyl complex

H3O

OH

Reduction of esters: CH3

The reaction mechanism of esters by metal hydride like LiAlH4 is based on nucleophilic
addition of hydride to the carbonyl carbon. In some cases, the alkali metal cation, especially
Li+, activates the carbonyl group by coordinating to the carbonyl oxygen, thereby enhancing
the electrophilicity of the carbonyl.

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O
O
LiAlH4
R C O R R OH + R C H
[H]

Mechanism

Li H
H Al H Li
O
O O
H H
R C O R R C O R R OH + R C H
H

Reduction of acids:

Reduction of nitriles gives an amine via two successive hydride additions

C N CH2
LiAlH4 NH2

Benzonitrile Benzylamine

Mechanism:

C N H H AlH3
H
LiAlH4 LiAlH4 2
N N
ether AlH3 ether AlH3

H2O

CH2 NH2

Benzylamine

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7.3 ADDITION OF GRIGNARD REAGENT WITH CARBONYL

GROUPS
The Grignard reagent is an organometallic reagent like alkyl/aryl magnesium halide.
Grignard reagents are prepared by the reaction of an alkyl or aryl halide with magnesium
metal. The reaction is conducted by adding the organic halide to a suspension of magnesium
in an etherial solvent, which provides ligands, required to stabilize the organomagnesium
compound. The reaction of an organic halide with magnesium is not a Grignard reaction, but
provides a Grignard reagent. This reagent is an important tool for the formation of carbon–
carbon bonds. Some of the reactions of Grignard reagents with carbonyl groups are being
explained herewith:

The carbonyl compound react with Grignard reagent to form halomagnesium

alkoxide, which in susquent step react with water in presence of mineral acid (HX) to give
alcohol. If the product is 30 alcohol than a solution of NH4Cl in H2O is preferred because 30
alcohols are pron to acid catalysed dehydration. Hence to avoid dehydration the ammonium
chloride solution in water is used which convert the halomagnesium alkoxide to ROH(30
alcohol) without causing dehydration.
O OMgX
C " R Mg X C
R' R R' R"
R
halomagnesium alkoxide

R= alkyl, or X= halide, Cl,Br I etc

OMgX
H O HX OH X
C
R'
+
R" +
H C HOH + Mg
R R' R" X
R
halomagnesium alkoxide

The oveeall reaction is:

O
OH X
C i RMgX +
R' R" C HOH + Mg
ii HOH/HX R' R" X
R

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The addition of Grignadrd reagent is influenced by steric hinderance by the presence of

groups around the carbonyl funcationality or in itself in Grignard reagent both. In such cases
either the reaction does not take place or takeplace in reduced extent or sometime some
abnormal different products have been reported.

CH3 O

CH3 i C H 3M gB r
N o re a c tio n , B e c a u s e o f s te r ic h in d e r a n c e
+ in c a rb o n y l g ro u p
H 3C CH3 ii H O H /H

CH3
i H 3C C M gX
O
CH3 B e c a u s e o f s te r ic h in d e r a n c e in
H 3C CH C CH3 N o r e a c tio n ,
G r ig n a rd r e a g e n t a n f c a r b o n y l
CH3 +
ii H O H /H g ro u p

If bulky group of Grignard reagent has β- hydrogen which is abstractable then reduction of
carbonyl group via hydride ion transfer is observed

O B rM g CH3 R H 3C
C CH3 R C O M gX + CH2
+
R R CH2 H 3C
H
H

b e ta c arb o n tran sfe r a s H - io n

Grignard reagent adds to α, β –unsaturated aldehyde and ketones. In these reactions 1, 2 and
1, 4 addition products are formed. Generally α, β –unsaturated aldehyde gives dominantly 1,
2- addition product while ketones give 1, 4- addition product as the major one.

O
i CH3MgBr
CH=CH C H CH=CH CH2OH
ii HOH/H+
100 %

1, 2 _ addition

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O

CH2CH2 CH3

1, 4 _ adduct
O Major
i CH3MgBr
CH=CH CH3 +
ii HOH/H+

OH

CH=CH CH3

1, 2 _ adduct
Minor

In presence of Cu2Br2 during addition of Grignard reagent in α, β –unsaturated ketones only

1, 4 –addition adduct is formed

CH3
O O
i CH3MgBr/Cu2Br2

ii HOH/H+

O
O
i CH3MgBr/Cu2Br2

ii HOH/H+

Orientation of group in cyclic system like cyclohexanone depends upon bulky nature of ra
group in Grignard reagent. If bulkier the group ,-OH orient in axial position, while in less
bulkier group the position lies in equatorial side, because the reagent always attack to the keto
group from less hindered side due to steric repulsion.

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OH
CH3
R= C CH
O 3
O CH3
equatorial orientation
i RMgBr
CH3
ii HOH/H+

OH R= CH3
Cyclohexanone
axial orientation

Similarly R-Li, the organolithium compound react with carbonyl and yields hydroxyl
compound as a result of hydrolysis of RCOLi (lithium alkoxide). But in some case
elimination as result of deprotonation because of strong basic nature of RLi has been
observed.

OLi OH
O HOH/H+
+ R Li R' C R" R' C R"
R' C R"
R R
There are few advantages of RLi compound over RMgX.-

1. RLi react with hindered side and gives normal product, while RMgX fails to react
with highly hindered side.

2. RLi compounds do not give conjugate addition products, they only give 1, 2 –addition
reactions
O OH
i RLi
1. C C R= t - butyl
ii HOH/H+

O OH
i RLi
2. CH3CH=CH C CH3 CH3CH=CH C CH3
ii HOH/H+
CH3
1, 2 addition only product

7.5 WITTIG REACTION AND ITS MECHANISM

The reaction of aldehyde with phosphorane or phosphonium ylide (tre Wittig’s reagent) to
produce an olefinic compound is dessignated as Wittig reaction. The Wittig reaction was
discovered in 1954 by Georg Wittig, for which he was awarded the Nobel Prize in Chemistry
in 1979. It is widely used in organic synthesis for the preparation of alkenes

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The Wittig reagent in this reaction is prepared from triphenylphosphine and alkyl halides
with at least one α- hydrogen.( 10 or 20 alkyl halides) in presence of astrong base usually
alkyllithium, sodium hydride or sodamide which abstract hydrogen from carbon which is
attached with phosphorus to give oppositely charged adjacent group known as yelide.

R' R'
R' SN2 strong base
R3P CH X R3P CH X R3P C
sodamide or R"
R" R"
sod. hydride or + R H
Alkyltriphenyl RLi etc
R= C6H5 phosphonium halide
R'
R3P C
R"
R'
R3P C H + R Li
R"
Mechanism:

The carbon of ylide with negative charge is a nucleophile and attack to carbonyl group to
give addition product BETAINE [1]. Betaine further leads the formation of four membered
ring oxaphosphetane [2].The four membered oxaphospetane intermediate is formed because
of strong phosphorus oxygen bond. The ring is strained and unstable, which ultimately gives
an alkene (olifine) [3] and triphenylphosphene oxide [4]. The complete mechanism is as
under:-

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7.5.1 Modified Wittig Reaction (Horner-Wadsworth-Emmons reaction:

A variation in Wittig reaction was done by Horner-Wadsworth-Emmons and known as

Horner- Wadsworth-Emmons modification. In this modification a phosphanate ester instead
of triphenyl phosphonium salt was used. Formation of phosphonate in this reaction is known
as Arbuzov reaction.The base used in this reaction were NaH, potassium tert-butoxide and
phenyllithium.The entire reaction sequence can be understand as follow:-

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Application of Wittig reaction:

This reaction is widely applicable for the synthesis of alkenes from aldehydes and ketones.A
Wittig reaction gives advantage over most other alkene synthesis in that no ambiguity exists
as to the location of double bond in the product. This is incontrast to β- elimination reaction
of alkyl halides which gives multiple alkene products either by rearrangement or by β- carbon
as under.

One of the applications of Wittig reaction is synthesis of pheromone known bombukol in two
consecutive steps

Polyzonimine a natural insect repellent produced by millipedes having E- geometry can also
be synthesized by Wittig reaction.

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7.5 Knoevenagel reaction

It is a modified aldol condensation. In is simply a nucleophilic addition of active hydrogen to

the carbonyl group which finally undero dehydration with the formation of α, β- unsaturated
product.This reaction is catalysed by amines generally piperidine/buffer system containing an
amine and acid. A base is required to generate carbanion while acid is for activation carbonyl
group.

Mechanism of the reaction:

The sequencewise mechanism of Knoevenagel reaction is as follow:-
Step-I The weak base RCOO- abstract the hydrogen from active methylene group and
provide aresonance stabilized enolate/ crabanion.

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Step II. This step involve the formation of reactive electrophile from pyridine by reaction
with aldehyde viz; benzaldehyde to form iminium ion. This intermediate is more reactive
than carbonyl group.

Step III In this step the electron-deficient carbon of iminium ion is attacked by carbanion

Step IV The weak base depronates acidic hydrogen followed by elimination of NR2 group to
give α, β- unsaturated derivative of the adduct

With malonic acid or cynoacetic acid as reactant, the products usually undergo
decarboxylation, which occurs as a concerted decomposition.

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Decarboxylation is also carried out in presence of pyridine.

O
O O
H COOH
N
+
O O

benzaldehyde

7.6 CLAISEN CONDENSATION

The Claisen condensation is a reaction between two esters or one ester and another carbonyl
compound in the presence of a strong base like alkosixd to form carbon–carbon bond. As
aresult of Claisen reaction a β-keto ester or a β-diketone is formrd.

Mechanism:

The ester in first step reacts with alkoxide to form enolate or cabanion by the removal of
hydrogen due to base. The enolate/carbanion so formed is resonance stabilized and reacts
nucleophilically with another molecule of ester which finally gives β-keto ester as end
product. The entire mechanism is as follow

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As ethoxide ion is anucleophile, it can attack the carbonyl group of the ester to give usual
carbonyl substitution reaction but the product are same as the reactant.This is the reason why
ethoxide ion is used as a base in the Claisen condensation.

O
CH2CH3 O O
H3C O
CH3CH2O C OCH2CH3 CH2CH3 + CH3CH2O
H3C O
CH3CH2O CH3

Base

Crossed Claisen Condensation:

In crossed Claisen condensation two reactin esters are of different types.The reactions are
synthetically not so useful if both the ester contain α- hydrogens with comparable acidity.
Such esters give mixiture of all of the four possible products. However successful crossed
Claisen condensation makes use of one ester which lacks any α- hydrogens. Such esters are
known as reactive esters and do not undergo enolization.such esters serve as a carbanion
acceptor
O
CH3 COOCH2CH3 i C2H5O
+ CH3 CH2 COOCH2CH3 CH3 C CH2COOC2H5
ii HOH/HCl
(I)

O CH3 O CH3 O
CH3 CH2 C CH COOC2H5 CH3 C CH COOC2H5 CH3 CH2 C CH2 COOC2H5
(II) (IV)
(III)

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R O O R O O
R C C OC2H5 + i C2H5O
CH3 C OC2H5 R C C CH2 C OC2H5
R ii HOH/HCl
R
As the only cross product

Reactive esters that cannot enolise are diethyl oxalate, ethyl formate, diethyl carbonate and
ethyl benzoate
O

O O O O OC2H5
C 2H 5O C C OC2H5 H C OC2H5 C 2H 5O C OC2H5

Eletrophilic character of carbonyl carbon in decreasing order

Some examples of crossed Claisen condensation are as follow:-

O
O O
O
OC2H5 + i C2H5O
CH3 CH2 C OC2H5 CH C OC2H5
ii HCl
CH3

O O O O
C2H5O C OC2H5 +
i C2H5O
CH3 C OC2H5 C2H5O C CH2 C OC2H5
ii HCl
diethyl malonate

O O O O O
i C2H5O
C2H5O C C OC2H5 + CH3 C OC2H5 C2H5 C C CH2 COOC2H5
ii HCl
diethyl oxaloacetate

O
CH2 O i C2H5O
C O + CH3 CH2 COOC2H5 HO CH2 CH2 O C CH COOC2H5
CH2 O ii HCl
CH3

7.7. MANNICH REACTION

A Mannich Reaction is a formation of a β - amino carbonyl compound. The Mannich base is

an endproduct in the Mannich reaction, which is formed through nucleophilic addition
reaction of a non-enolizable aldehyde (formaldehyde) and any primary or secondary amine to
produce resonance stabilized imine salt. Finally the addition of a carbanion from compound

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(any enolizable carbonyl compound, amide, carbamate etc.) to the imine gives the Mannich
base.

O
O
O CH2 R1
R1 N
+ H C H +
i HCl
H N
ii HO R2
R2
enolizable non enolizable
carbonyl compound carbonyl compound amine beta amino carbonyl compound
Mannnich base

Mechanism:

The mechanism involve the formation of imine salt first from formaldehyde and amine. In
this reaction being nucleophilic nature of amine it attacks the carbonyl group of
formaldehyde. No acid is required for that, however the acid-catalysed dehydration of the
addition product reveals the imine salt as follow.

O R1 O R1 R1
H C H + H N CH2 N R2 HO CH2 N R2
R2
H
amine i HCl

R1
R1 H
O CH2 N R2
H2O + CH2 N R2 Cl
H
imine salt

The imine salt is a just intermediate but quite stable. The iodide salt is solid in nature and
known as Ecchenmoser salt.

R1
CH2 N R2 I

The electrophile imine salt now add to the enol form of carbonyl compound to give the
product of the reaction, β- amino carbonyl compound or Mannich base

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O OH OH
_ H+
H+ H

enol
H
O O H O
R1 _ H+ CH2 R1
CH2 R1
CH2 N R2 N N
+
imine R2 R2
beta amino carbonyl compound
or Mannich base

The reaction can further react by there different way provided that:

1. The Mannich base is 10 or 20 amine, in such cases it condense further with two or one
additional HCHO and enolizable carbonyl compound.
O
O
H
CH3 +
H
+ HCHO + RNH2 CH2 CH2 N R

O O O
O R
H
+
H CH2 CH2 N CH2 CH2
CH3 + CH2 CH2 N R
HCHO +

2. The enolizable carbonyl compound has active methylene group, stepwise condensation of
two or more molecules of HCHO and amine with one molecule of the compound with active
methylene group will take place.

COOC2H5 H COOC2H5
HCHO + R NH2 H+
+ CH2 R N CH2 CH
COOC2H5 COOC2H5

H COOC2H5 H
H+ COOC2H5
HCHO + R NH2 + R N CH2 CH R N CH2 C
COOC2H5 COOC2H5
R N CH2
H
3. The Mannich base obtained may condense with excess HCHO

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O O

CH2 NH2 + HCHO CH2 N=CH2

Mannich reaction is very important reaction for the synthesis of reaction intermediate imine
salt. The mannich product can be converted to enones which can be used in Mannich
addition.

Phenols, furan, pyrrole, indole also give this reaction because intermediate of the reaction is
iminium salt which is a strong electrophile and these compounds give aromatic electrophilic
substitution (ArSE) reaction.

OH
OH
+ CH2 N
H
+ HCHO + N H

R
N R
CH2
OH
OH
+ HCHO +
H+
R2NH

R
CH2 N R

+ HCHO +
H+
R2NH
N
N
H
H

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7.8 STOBBE REACTIONS

The reaction of aldehydes or ketones with an ester of succinic acid to form alkylidenesuceinic
acids (substituted itaconic acids), or isomers formed by a tautomeric shift of hydrogen, is
known as the Stobbe condensation.

O
O O
CH2 C OCH2CH3 NaH
R C R' + R C C CH2 C ONa
CH2 C OCH2CH3 + CH3CH2OH
R' C O CH2CH3
O O

Mechanism:

The mechanism of Stobbe condensation follows the following consecutive steps.

Step I formation of enolate of succinic acid ester in the presence of base

O O O
CH2 C OCH2CH3 CH3CH2O CH C OCH2CH3 CH C OCH2CH3
CH2 C OCH2CH3 CH3CH2OH CH2 C OCH2CH3 CH2 C OCH2CH3
O O O
enolate ion of
succinic acid ester
Step II Enolate ion as generated in step I give nucleophilic addition reaction with aldehyde or
ketone reversibly.

O O O O
O
CH C OCH2CH3 CH C OCH2CH3 R C CH C OCH2CH3
R C
+ R' CH
R' CH2 C OCH2CH3 CH2 C OCH2CH3 2 C OCH2CH3

O O O
enolate ion of adduct
succinic acid ester

Step III The resulting adducts as in step II cyclise to γ-lactone. This process is also reversible

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O O O
COCH2CH3 OCH2CH3
O O C
CH2 _ CH CH O O
CH2 2 3
R C CH R C CH R
R' C OCH CH R' C OCH CH
2 3 2 3 R' C OCH2CH3
O O O
adduct gama lactone

Step IV Irreversible ring –opening of the conjugate base of the lactone –ester to give the
anion of the unsaturated ester- acid

O O

O CH2CH3O O O O
H3O R C C CH C OH
R R R C C CH2 C O 2
H R' C OCH2CH3 R' C OCH2CH3
R' C OCH2CH3 R' C OCH2CH3
O O
O O
gama lactone conjugate base of the lactone

The prime synthetic application of the Stobb condensation arises from the fact that the final
condensation product, the unsaturated acid ester, may be decarboxylated with
HBr/CH3COOH. The product obtained is β, γ- unsaturated acid.
R
HBr/CH3COOH R
C C CH2 COOH
R' C CH CH2 COOH
C OCH2CH3 H2O, reflux R'
O beta gama unsaturated acid

The β, γ- unsaturated acid can be hydrogenated to saturated acid as follow

R R
H2/Cr2O3 CuO
C CH CH2 COOH CH CH2 CH2 COOH
R' R'

O O
O
CH2 C OCH2CH3 i NaH/C2H5OH/C6H6
CH3 + C C C OCH2CH3
I ii CH3COOH/HOH
CH2 C OCH2CH3
H3C CH2COOH
O

O O
O C OCH2CH3
II CH2 C OCH2CH3 i (CH3)3COK/(CH3)COH/
n C11H23 C H + n_ C11H23 CH C
CH2 C OCH2CH3 ii HCl/C2H5OH C OCH2CH3
O O

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7.9 STORK ENAMINE REACTION

The Stork enamine reacton is a addition of an enamine to α, β- unsaturated carbonyl

compound. The process is similar to the Michael reaction. The product of the reaction upon
hydrolysis by an aqueous acid to produce a 1, 5-dicarbonyl compound.

The mechanism involve the

1. formation of an enamine from a ketone

2. addition of the enamine to an alpha, beta-unsaturated aldehyde or ketone

3. hydrolysis of the enamine back to a ketone

The entire sequence of the reaction can be mentioned as follow.

O
N R'
N H N
2. R R'
+ R
1.
O O

O N R
H2 O R'

3.
O O

7.10 CONCEPT AND APPLICATIONS OF UMPOLUNG

Majority of organic molecules containing heteroatoms, polarize carbon skeletons by virtue of

their electronegativity. Therefore, in reactions, the new bonds are formed between atoms of
opposite polarity, which we call the "normal" mode of organic reactions. In umpolung means
reversal of polarity/pole inversion in organic reactions is the modification of functionality in

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order to reverse the polarity in synthones. The umpolung allows the secondary type of
reactions in the functional groups which otherwise difficult or not possible.

Example:
The carbonyl group is electrophilic at the carbon atom and hence is susceptible to
attack by nucleophilic reagents. Thus, the carbonyl group reacts as a formyl cation or as an
acyl cation. A reversal of the positive polarity of the carbonyl group so it acts as a formyl or
acyl anion would be synthetically very attractive. Umpolung in a synthesis usually requires
extra steps. Thus, one should strive to take maximum advantage of the functionality already
present in a molecule

Reversal of carbonyl group polarity (Umpolung) :-

O
O O -
normal mode of reactivity Nu (nucleophilic attack)
R
R R traditional Nu
approach

(electrophilic carbon)
formyl/acyl cation
reversal of polarity
(Umpolung)
[R= H formyl, R= alkyl = acyl]

O
O
E+ (electrophilic attack)
R +
R
(nucleophilic carbon Umpolung approach E
(formyl/acyl anion)

Cyanide type Umpolung:

In this umpolung reaction CN- play key role as catalyst the well known example is Benzoin
condensation in which the net result is that a bond is formed between two carbons that are
normally electrophiles, because of umpolung.

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acidic H due to O- and CN group

O O
OH
H
H C C N
CN
CN

electophilic carbon
OH
C C N
nucleophilic carbon

OH
O
C +
C
CN OH O
H
C C
OH
CN H
C
cynohydrin benzoin
C N

Rapid transfer of H+

In this O OH O OH reaction CN-

act C C rapid loss of CN C C as
H CN H
benzoin
catalyst which is due to its good nucleophilicity, stablizing
nature to carbanion and good leaving group.

Carbonyl umpolung
The polarity can be reversed when the carbonyl group is converted into a dithiane or a
thioacetal. In synthon terminology the ordinary carbonyl group is an acyl cation and the
dithiane from carbonyl group reversed to acyl anion by treating with n-butyllithium in THF
at low temperatures, which then reacts as a nucleophile in nucleophilic displacement with
alkyl halides such as benzyl bromide, with other carbonyl compounds such as cyclohexanone
or oxiranes such as phenyl-epoxyethane. After hydrolysis of the dithiane group the final
reaction products are α-alkyl-ketones or α-hydroxy-ketones. A common reagent for dithiane
hydrolysis is (bis (trifluoroacetoxy) iodo) benzene

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. O
SH SH
Li
R H CHCl3 S S 0
S S
THF - 40
HCl(g) R H R
nucleophilic carbon
electrophilic carbon
( 1, 3 dithane)

Br
O O

oxirane
phenylepoxyethane cyclohaxanone benzyl bromide

S S S S S S
OH
R R R

OH

HOH [bis9trifluoroacetoxy)iodo] benzene HOH [bis9trifluoroacetoxy)iodo] benzene HOH

O
The O
O
R
R R OH
OH

umpolung reactions are veru useful for synthetic and biological point of view. Viz; The
human body can employ cyanide-like umpolung reactivity without having to rely on the toxic
cyanide ion. Thiamine (which itself is a N-heterocyclic carbenes) pyrophosphate (TPP)
serves a functionally identical role. The thiazolium ring in TPP is deprotonated within the
hydrophobic core of the enzyme, resulting in a carbene which is capable of umpolung.

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H
R _ H+
N R R
S N N
H + S S

R
R R

O
OH OH
CO2- O
C C
R C H+
R O - R
N N N
S S S

R R R

OH
O
R C H
N R
+ S N
+
S
R
R
Enzymes which use TPP as a cofactor can catalyze umpolung reactivity, such as
the decarboxylation of pyruvate. In the absence of TPP, the decarboxylation of pyruvate
would result in the placement of a negative charge on the carbonyl carbon, which would run
counter to the normal polarization of the carbon-oxygen double bond.

7.11 SULFUR YLIDES

Sulfur ylides are oppositely charged sulpher and carbon with positive charge on sulfur and
negative on adjacent carbon. The most important sulphur ylides are dimethylsulfonium
methylide and dimethylsulfoxonium methylide (Corey -Chaykovskyreagent).

O
CH3 S CH2
CH3 S CH2
CH3
CH3
dimethylsulphonium methylide dimethylsulfoxonium methylide
sulphonium ylide sulphoxonium ylide

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These ylides are prepared by deprotonation of the corresponding sulfonium salts, which can
be Prepared from the reaction of either dimethylsulphide or dimethylsulphoxide with methyl
iodide/methyl bromide.

I
CH3 S CH3 + CH3 I CH3 S CH3
dimethyl sulphide methyl iodide CH3
trimethylsulphonium iodide
I
O O O
CH3 S CH3 CH3 S CH3 + CH3 I CH3 S CH3
CH3
dimethyl sulphide trimethylsulphoxonium iodide
Br
O
O O
CH3 S CH3 CH3 S CH3
+ CH3 Br CH3 S CH3
CH3
dimethyl sulphide trimethylsulphoxonium bromide
Synthetic utility of sulfur ylides

To synthesise epoxides from carbonyl compounds

O
O

+ CH3 S CH2 + CH3 S CH3

CH3

O O
O O
+ CH3 S CH2 + CH3 S
CH3 CH3

H O H O
O O
+ CH3 S CH2 + CH3 S
CH3 CH3
H H

Aldehydes and ketone form epoxide with sulfur ylides while phosphorus ylide gives alkenes

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O O
O
R C H + CH2 S CH3 R C CH2 S CH3 +
R CH3 S CH3
CH3 H CH3
H

a good leaving group

O O O O O
O
R C H + CH2 S CH3 R C CH2 S CH3 + CH3 S CH3
R
CH3 H CH3
H

a good leaving group

Reaction of Sulphur Ylides with α,β-unsaturated Aldehydes and Ketones

O hard carbon
O O O O

, soft carbon
cyclohexanone
cyclohexenone

Whereas the harder nucleophile dimethylsulfonium methylide reacts with α,β-unsaturated

carbonyl compounds to provide epoxides, the softer reagent dimethylsulfoxonium methylide

reacts by conjugate addition to give cyclopropanes.

CH3 CH3
O O
+ CH2 S CH3 + CH3 S CH3
CH3

CH3 CH3
O O O
O
+ CH2 S CH3 + S CH3
CH3 CH3

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epoxide
CH3 CH3
O CH3 O
O
H 2C S CH3 slow
+ CH3 S
CH3 fast
O O CH3
O
CH3 S CH2 +
CH3 cyclopropane
O CH3 CH3
sulphur ylide O
CH3 S CH2 O O
+ CH3 S
CH3 fast
CH3

epoxide Vs cylopropane from sulphur ylide

7.12 SUMMARY

This unit reveals the knowledge about the mechanism of reduction of carbonyl groups and
unsaturated molecules by metal hydrides to form many beneficial products which otherwise
are difficult to synthesise from carbonyl functionalities. The important reactive reagent,
named Grignard reagent with wide synthetic ultility has been incorporated with
mechanism.In this unit we also learn about the transformation of carbonyl functionalities to
other many beneficial synthetic compounds by using different mechanistic pathways along
with specific reagent and reaction conditions. These transformations include Reformatsky
reaction, Wittig reaction, Knoevenagel, Claisen, Mannich, Stobbe reactions and enamine
reactions. The carbonyl compounds generally contain electrophilic carbon because of
polarization by hetero atoms, hence only nucleophile can attack to this carbon in traditional
mode, however this unit gives an idea how the electrophilic nature of carbonyl carbon is
reversed by using the concept of umpolung. This process of polarity reversal has much
synthetic application in synthesis and biological system. The formation and applications of
sulphur ylides along with their comparision with phosphorus ylide has also been given in this
unit.

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7.13 TERMINAL QUESTION

Q1. Tick the correct option (MCQ):

i. Which of the following compound givs epoxide while reacting with aldehydes?

A Ph3P CH B ArMgI
R
O

C LiAlH4 D CH3 S CH2

CH3

ii The catalyst in Benzoin condensation is:

A. K+ B. CN-
C. KCN D. C2H5/OH

iii Stobbe reaction is given by

COOC2H5
COOC2H5
A. CH2 B. (CH )
2 2
COOC2H5 COOC2H5

COOC2H5 CH2COOC2H5
C. D.
COOC2H5 CH2COOC2H5

iv Which of the following compounds will form enolate anoin ?

1. CH3COCH3 2. CH3COCH2COCH3 3. CH3COCH2COOC2H5 4. CH3COOC2H5

A. Onle A B. 2 and 3

C. Only 4 D. All 1, 2, 3 and 4

v. Reformatsky reagent is
OZnBr
A. BrZnCH2COOC2H5 B. CH2=C COOC2H5

OZn
C. CH2=C COOC2H5 D. CH3COOZnBr vi. Which of the following reactions vi.

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can be used for the formation of C-C bond in organic synthesis?

1. Reformatsky reaction 2. Claisen condensation

3. Wittig reaction 4. Knoevenagel reaction

A. Only 4 B. 1,2 and 3

C. 2,3 and 4 D. All 1,2,3 and 4

vii Which of the following represent umpolung?

O O O O
A. B.

O OH
O
C. D.

viii Which gives epoxide with sulphur ylide?

A. Aldehyde B. cyclohexene

C. Ester D. Amide

ix. In the given reaction sequence what will be the final product A ?
O
i NaH/C2H5OH/C6H6
CH2COOC2H5 ii CH3COOH/HOH
+ [A]
CH2COOC2H5 iii HBr/CH3COOH/H2O/heat

C CCOOC2H5 C CCOOH
A. B.
CH3CH2COOC2H5 CH3CH2COOC2H5

C CHCH2COOH C CHCH2COOCH2CH5
C. D.
CH3 CH3

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x. Consider the following compound [X] and tick the correct answer which can be best used
for its synthesis
O

C CH2 CH3
O
[X]
A. Crossed-claisen- ester condensation B. Wittig reaction

C. Benzoin condensation D. All A, B and C

Q.2 Discuss the mechanism of:

1. Wittig reaction

2. Stobbe reaction

3. Mannich reaction

4. Benzoin condensation

Q.3Complete the following reaction with mechanismand give name of the product

O
CH2CHO Base
+ CH3 NH2 + CH3 C CH3
CH2CHO

Q.4.What is sulphur ylides? Discuss their importance

Q.5 what do you understand by umpolung? Discuss mechanism of carbonyl group

umpolung. Write applications of umpolung

7.14 ANSWERS (MCQ) TERMINAL QUESTIONS

iD

ii B

iii D

iv D

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v. B

vi. D

vii A

viii A

ix. C

x. A

7.15 REFERENCES

1. For reagents used to reduce acid derivatives, see Reference 17, pp 1263-1273 1999, p
1077.18.
2. Gröbel, B. T.; Seebach, D. (1977). "Umpolung of the Reactivity of Carbonyl
Compounds Through Sulfur-Containing Reagents". Synthesis. 1977 (6): 357.
doi:10.1055/s-1977-24412.
3. March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and
Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7.
4. McMurry, John (21 March 2003). Organic Chemistry (Hardcover) (6th ed.). Belmont,
CA: Thomson- Brooks/Cole. ISBN 0-534-38999-6.
5. Reformatsky, S. "Neue Synthese zweiatomiger einbasischer Säuren aus den Ketonen".
Berichte der Deutschen Chemischen Gesellschaft. 20 (1): (1887). 1210–1211.
doi:10.1002/cber.188702001268.
6. Seebach, D. (1979). "Methods of Reactivity Umpolung". Angewandte Chemie
International Edition in English. 18 (4): 239. doi:10.1002/anie.197902393.
7. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 336-379.
8. Sorrell, T.N,Organic chemistry,2006 University Science Books USA, 562-603

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UNIT-8 FREE RADICAL REACTIONS

CONTENTS:
8.0 Objectives
8.1 Introduction
8.2 Mechanism of free radical substitution
8.2.1 Free-radical substitution of alkanes
8.2.2 Free-radical halogenation is most commonly applied to allylic or benzylic
halogenations
8.3 Neighbouring group assistance in free radical reactions
8.4 Reactivity
8.4.1 Reactivity for aliphatic substrates:
8.4.2 Reactivity in aromatic substrate:
8.4.3 Reactivity in the attacking radicals:
8.4.4 The effect of solvent on reactivity:
8.4.5 Reactivity at a bridgehead:
8.5 Oxidation of aldehydes to carboxylic acids
8.6 Autooxidation
8.7 Coupling of alkynes
8.7.1 Modifications: Eglinton Reaction
8.8 Arylation of aromatic compounds by diazonium salts
8.8.1 Gomberg or Gomberg-Bachmann reaction
8.8.2 Sandmeyer reaction:
8.9 Hunsdiecker reaction
8.10 Sandmeyer reaction
8.11 Free radical rearrangement
8.12 Summary
8.13 Terminal questions
8.14 Answers to terminal questions
8.15 References

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8. OBJECTIVES

Objective of this chapter is to let students aware about types of free radical reactions,
mechanism of free radical substitution, reactions on aromatic substrates and neighboring
group assistance. This unit will also provide knowledge of reactivity for aliphatic and
aromatic substrates at a bridgehead carbon, reactivity of the attacking radicals, the effect of
solvents on reactivity and allelic halogenations (NBS). This chapter also aware about
oxidation of aldehydes to carboxylic acids, auto-oxidation, coupling of alkynes and arylation
of aromatic compounds by diazonium salts. Besides many important name reactions of
synthetic utility alongwith Sandmeyer reaction, free radical rearrangement and Hunsdiecker
reaction.

8.1 INTRODUCTION

A free radical is a species containing one or more unpaired electrons. Free radicals are
electron-deficient species, but they are usually uncharged, so their chemistry is very different
from the chemistry of even-electron electron-deficient species such as carbocations and
carbenes. The alkyl radical (·CR3) is a seven-electron, electron-deficient species. The
geometry of the alkyl radical is considered to be a shallow pyramid, somewhere between sp2
and sp3 hybridization, and the energy required to invert the pyramid is very small. In
practice, one can usually think of alkyl radicals as if they were sp2-hybridized.

Both alkyl radicals and carbocations are electron-deficient species, and structural features that
stabilize carbocations also stabilize radicals. Alkyl radicals are stabilized by adjacent lone-
pair-bearing heteroatoms and by π bonds, just as carbocations are, and the order of stability of
alkyl radicals is 3° > 2° > 1°. However, there are two major differences between the energy
trends in carbocations and alkyl radicals.

1. A C atom surrounded by seven electrons is not as electron-deficient as a C atom

surrounded by six electrons, so alkyl radicals are generally not as high in energy as

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the corresponding carbocations. Thus, the very unstable aryl and 1° alkyl carbocations
are almost never seen, whereas aryl and 1° alkyl radicals are reasonably common.
2. The amount of extra stabilization that adjacent lone pairs, π bonds, and σ bonds
provide to radicals is not as great as that which they provide to carbocations. The
reason is that the interaction of a filled AO or MO with an empty AO (as in
carbocations) puts two electrons in an MO of reduced energy, whereas the interaction
of a filled AO or MO with a half-filled AO (free radicals) puts two electrons in an
MO of reduced energy and one electron in an MO of increased energy.

Even though adjacent lone pairs, π bonds, and σ bonds do not stabilize radicals as much as
they stabilize carbocations, the cumulative stabilizing effect of several such groups on a
radical can be considerable. Benzylic radicals (those with the radical on a C atom next to a
benzene ring, but not in a benzene ring) are particularly low in energy, as the radical center
is stabilized by resonance with three π bonds.

The most important reaction types involving free radicals are:

i. Free-radical substitution, for instance free-radical halogenation and autoxidation.
ii. Free-radical addition reactions
iii. Intramolecular free radical reactions (substitution or addition) such as the Hofmann–
Löffler reaction or the Barton reaction
iv. Free radical rearrangement reactions are rare compared to rearrangements involving
carbocations and restricted to aryl migrations.
v. Fragmentation reactions or homolysis, for instance the Norrish reaction, the
Hunsdiecker reaction and certain decarboxylations. For fragmentations taking place in
mass spectrometry see mass spectrum analysis.

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vi. Electron transfer. An example is the decomposition of certain peresters by Cu(I)

which is a one-electron reduction reaction forming Cu(II), an alkoxy oxygen radical
and a carboxylate. Another example is Kolbe electrolysis.
vii. Radical-nucleophilic aromatic substitution is a special case of nucleophilic aromatic
substitution.
viii. Carbon–carbon coupling reactions, for example manganese-mediated coupling
reactions.
ix. Elimination reactions

8.2 MECHANISM OF FREE RADICAL SUBSTITUTION

8.2.1 Free-Radical Substitution of Alkanes

Probably the best-known example of a free-radical reaction is the halogenation of alkanes
with Br2 or NBS (N-Bromosuccinimide). This chain reaction is initiated by homolytic
cleavage of Br2 induced by light or heat. The propagation step consists of two atom
abstraction reactions.

When more than one kind of H atom is present, the H atom that is removed is usually the
one that will leave behind the lowest energy radical. H atoms are never removed from C(sp)
or C(sp2), only from C(sp3). Among C(sp3)–H bonds, it is easiest to remove a H if a
heteroatom such as N or O is attached to the C. If no such H atom is present, then the H

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atom that is removed is best allylic or benzylic (the C is attached to a C=C π bond or to a
benzene ring). If there are no allylic or benzylic H atoms, then the order of reactivity of H
atoms is 3° > 2° > 1°.

8.2.2 Free-radical halogenation is most commonly applied to allylic or benzylic

halogenation because the radicals formed at these positions are most stable. Note that
alkenes can react with Br2 by either an electrophilic addition reaction, to give 1,2-
dibromoalkanes, or by a free-radical substitution reaction, giving 3-bromoalkenes. The
former pathway predominates in the dark, whereas the latter pathway predominates in the
presence of strong light.

NBS (N-bromosuccinimide) is often used as the Br source in freeradical brominations. This

is to keep the concentration of bromine low and hence reduce competition by electrophilic
addition of Br2 to give 1,2-dibromoalkane. In these reactions using NBS in CCl4, it is
thought that Br2 is the actual halogenating agent.

Br2 is generated as follows:

i. Homolytic cleavage of the N-Br bond of NBS generates a Br atom, which abstracts an
allylic hydrogen from the alkene (cyclopentene).

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ii. The HBr thus formed reacts with NBS to produce a Br2 molecule.

iii. This Br2 molecule reacts with the allylic radical formed earlier and a new bromine atom is
produced that can begin the cycle a new.

Of course, in allylic halogenation, transposition of the double bond can easily occur. For
example, in 4,4-dimethylcyclopentene:

Elemental chlorine can be used in free-radical halogenation reactions, too, but these reactions
are less easily controlled, because the Cl· radical is more reactive than the Br· radical and
hence less selective. The reagents t-BuOCl and SO2Cl2 are used as alternative chlorinating
agents. The F· radical is so reactive, and the reaction F–F + C–H → H–F + C–F is so
exothermic, that free-radical fluorinations result in violent and uncontrollable exotherms

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(explosions). At the other extreme, free-radical iodinations of alkanes do not work well at all,
as the H· abstraction step is too endothermic.

8.3 NEIGHBOURING GROUP ASSISTANCE IN FREE

RADICAL REACTIONS

In a few cases it has been shown that the free radical reactions are accelerated by the presence
of neighbouring groups. Bromination of carbon chains containing a bromine atom occurs
with high regioselectivity. Bromination of alkyl bromides gave 84 to 94% substitution at the
carbon adjacent to the bromine already in the molecule. This is especially as positions close
to a –I group such as bromine should actually be deactivated by the electron-withdrawing
effect of bromine. The unusual regioselectivity is explained by a mechanism in which
abstraction of hydrogen is assisted by a neighbouring bromine atom as shown below:

In the normal mechanism, Br• abstracts a hydrogen from RH, leaving R•. When bromine is
present in the proper position, it assists this process, giving a cyclic intermediate (a bridged
free radical, III). In the final step, this bridgehead free radical is attacked by another Br• to
give the dibromoalkane. The above mechanism is supported by the fact that it proceeds with
retention of configuration. Photolytic bromination of optically active 1-bromo-2-
methylbutane gave 1, 2-dibromo-2-methylbutane with the retention of configuration. You
already know that an aromatic ring can assist in the formation of a carbocationic intermediate
called a phenonium ion by delocalising the positive charge.

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Let us now study about the NGP by aromatic rings involving free radicals.
NGP by an aromatic ring involving free radicals:
Taking an example of free radical NGP, Ruchardt has successfully distinguished between
these pathways in the given reaction by showing that the optically active aldehyde undergoes
decarbonylation to from the product (5) with at least 98% racemization.

If the reaction involved attack by a bridged radical intermediate on a second molecule of

aldehyde, then retention of configuration would have been observed, as with the analogous
carbonium ion rearrangement (Route A). Racemization indicates that the bridged radical (3)
rearranges to the acyclic radical (4) before reaction with a second molecule of aldehyde.

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8.4 REACTIVITY

8.4.1 Reactivity for aliphatic substrates:

It is the abstraction step that determines which product will be formed in a chain reaction. A
free radical almost always abstracts a univalent (hydrogen or halogen) and never a tetra- or
tercovalent atom, and seldom a divalent one. For example, a reaction between a chloride free
radical and ethane gives an ethyl radical, not a hydrogen free radical:

H Cl CH3CH2 H= 3 kcal/mole

CH3 CH3 Cl

CH3CH2 Cl H H= 18 kcal/mole

The main reason for this is steric. A univalent atom is much more exposed to attack by the
incoming radical than an atom with a higher valency. Another reason is that in many cases
abstraction of a univalent atom is energetically more favoured.
In the case of alkanes, the following is the decreasing order of the ease of abstraction of
different kinds of hydrogens:
Tertiary H ˃ secondary H ˃ primary H ˃ methane
This is according to the relative stabilities of the free radicals formed after the abstraction of
hydrogen.
In the case of alkyl chains of aromatic rings the preferential position of attack on a side chain
is usually the position alpha to the ring. Aromatic hydrogens are seldom abstracted if there
are aliphatic hydrogen present.
In the case of compounds containing electron withdrawing substituents e.g., Z-CH2CH3
(Z=COOH, COCl, COOR, SO2Cl or CX3) the β-position is attacked predominantly or
exclusively in free radical halogenations. This is because electron-withdrawing group highly
deactivate adjacent alpha position. Compounds like acetic acid and acetyl chloride are not
attacked at all. This is because halogen atoms are electrophilic radical and look for positions
of high electron density. Hydrogens on carbon atom next to the electron-withdrawing groups
have low electron densities; therefore, the attack is avoided at this position. The radicals that
are not electrophilic do not show this behavior e.g., the methyl radical does not avoid the
attack at the alpha position. Some radicals, e.g., t-butyl, benzyl, cyclopropyl and phenyl are
nucleophilic and tend to abstract electron poor hydrogens.

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8.4.2 Reactivity in aromatic substrate:

Free radical substitution at an aromatic carbon seldom takes place by a mechanism in which
ring hydrogen is abstracted to give an aryl radical. Usually, the mechanism is similar to that
of aromatic electrophilic and nucleophilic substitution.

H Y

Z Y

The following generalizations have been made regarding the reactivity in aromatic
substitution:
1. All substituents increase reactivity at ortho and para positions as compared to that of
benzene. There is no great difference between electron-donating and electron
withdrawing group. This is because radicals are neutral species and are not influenced
by the polar properties of the substrate to any significant extent. Furthermore, it has
been shown that both electron donating and electron withdrawing group stabilize a
free radical.
2. Reactivity at meta positions almost equal to that of benzene. This fact, coupled with
preceding one, means that all substituents are activating and ortho-para directing,
none are deactivating or mainly meta directing.
3. Reactivity at ortho positions is greater than at para positions, except where a large
group decreases ortho reactivity due to steric reasons.
4. Electron withdrawing group exert a greater ortho-para directing and activating effect
than electron donating groups.
5. Substituents have a much smaller effect than in electrophilic and nucleophilic
substitution.
6. Although hydrogen is the leaving group in most free radical aromatic substitutions,
ipso attack and ipso substitution (e.g., with Br, NO2, or CH3CHO as the leaving
group) have been found in certain cases.
8.4.3 Reactivity in the attacking radicals: The greater the reactivity of a species the less is
the selectivity. The bromine atom is so selective that when only primary hydrogen are
available, as in neopentane or t-butylbenzene, the reaction is slow or nonexistent. Isobutene

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can be selectively brominatede to give t-bromide and toluene reacts with bromine instantly.
Other alkylbenzenes e.g., ethylbenzene and cumine are brominated exclusively at the alpha
position emphasizing the selectivity of bromine free radical.
Some radicals e.g., triphenylmethyl are so unreactive that they abstract hydrogen very slowly.
As mentioned earlier, some free radicals e.g., chloro are electrophilic and some eg., t-butyl
are nucleophilic. However, the predominant character of a free radical is neutral, whether it
has slight electrophilic or nucleophilic tendency.

8.4.4 The effect of solvent on reactivity: Unlike ionic substitutions, the solvent usually has
little effect on free radical substitutions. Free radical reactions in solution are quite similar in
character to those in the gas phase, where there is no solvent. However, in certain cases the
solvent can make an appreciable difference.
For example, chlorination of 2, 3-dimethylbutane in aliphatic solvents gave about 60%
(CH3)2CHCH(CH3)CH2Cl and 40% (CH3)2CHCCl(CH3)2, while in aromatic solvents the ratio
become 10:90. This is due to complex formation between the aromatic solvent and the
chlorine free radical which makes the chlorine less reactive and thus more selective.

Cl

8.4.5 Reactivity at a Bridgehead: Many free radical reactions have been observed at
bridgehead carbons. For example, in the following reaction a free radical is formed at the
bridgehead carbon.

COOAg Br

Br2

This demonstrates that the free radical need not be planner. Although bridgehead free radical
substitution is possible, it is not preferred because of the straine involved.

8.5 OXIDATION OF ALDEHYDES TO CARBOXYLIC ACIDS

Oxidation of aldehyde to carboxylic acids has been carried out with various oxidizing agents,
the most well-liked of which is acidic, basic or neutral solution of permanganate, chromic
acid, silver oxide, bromine, Benedict’s solution and Fehling’s solution. The mechanism of

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aldehyde oxidation may be free radical or ionic. Both the mechanism may take place
simultaneously. In the free radical mechanism, the aldehyde hydrogen is abstracted to give an
acyl radical, which obtains OH from the oxidizing agent. For example-

R C O H2CrO4 R C O Cr(V)
H

R C O H2CrO4 R C OH Cr(V)

The above mechanism is also similar with KMnO4

For alkaline permanganate, the ionic mechanism is as follows:

O O
OH MnO4 3
R C H R C H RCOOH HMnO42 RCOO MnO3 H2O
slow
OH

For neutral and acidic permanganate, the following ionic mechanism has been proposed:

O O MnO3 O

R C H B MnO3 BH
R C H HMnO4 R C
Mn(VII) Mn(V)
OH OH

Similarly, with H2CrO4 the ionic mechanism is as follows:

O O CrO3H O

R C H B HCrO 3 BH
R C H H2CrO4 R C
Cr(IV)
Cr(VI) OH OH

8.6 AUTOOXIDATION

Oxidation reaction takes place by atmoshpheric oxygen without combustion is called

autooxidation. This type of reaction occurs when compounds are stand in air. Autoxidation
catalysed by light and and initiators and inhibited by antioxidants (like hydoquinone).

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According to observation it is suggested that a free radical mechanism is involved. By the

autooxidation process foods, rubber, paint, lubricating oils etc. deteriorate on exposure to the
atmoshphere for a long time. A important application of autooxidation is the drying of paints
and varnishes in atmospheric conditions.
Oxygen itself (a diradical) is not reactive enough to abstract the hydrogen. But if a
trace of free radical (R’.) is produced by some initiating step, it reacts with oxygen to give R-
O-O. Which abstract hydrogen. The following reraction is the reaction chain-

R H
R' O2 R' O O R R' O O H

R H R R
R O2 R' O O O O H
hydroperoxide
As with other free radical reaction, resonance stabilization of tertiary, benzylic, and allylic
free radicals, the abstraction of these hydrogens is greatly facilitated. Example-

O O H

O2

O O H
O2

O O H

O2

The alpha positions of ethers are also easily attacked by oxygen. This reaction is responsible
for a hazard in the storage of ethers because solutions of these hydroperoxides and their
rearrangement products in ethers are potential spontaneous explosive. Hydroperoxides
decompose further to generate radicals which start new chain reaction.

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RO O2 RO O H
C H C O

R O O H R O O H

R O R H R OH R

The autooxidation of organic compouns is usually inhibited by the addition of antioxidants.

These compounds, which are usually phenols or secondary amines, destroy the chain carrying
radicals.
ROO HA ROOH A (HA= an antioxidant)

The radical A. is resonance stabilisd and relatively unreactive thus, it is not capable of
initiating a fresh chain. It is destroyed either by combination with a peroxy radical or with a
similar radical species.
ROO A ROOA

A A A A

8.7 COUPLING OF ALKYNES

The Glaser coupling is a type of coupling reaction. It is by far the oldest acetylenic coupling
and is based on cuprous salts like copper (I) chloride or copper (I) bromide and an additional
oxidant like oxygen. The base in its original scope is ammonia. The solvent is water or an
alcohol. The reaction was first reported by Carl Andreas Glaser in 1869.

8.7.1 Modifications: Eglinton reaction

In the related Eglinton reaction two terminal alkynes are coupled directly by a copper (II) salt
such as cupric acetate.

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The Eglinton Reaction has been used to synthesize a number of fungal antibiotics and is
important for carbon-carbon bond formation via the oxidative coupling of alkynes.

This procedure was used in the synthesis of cyclooctadecanonaene. Another example is the
synthesis of diphenyldiacetylene from phenylacetylene.

8.8 ARYLATION OF AROMATIC COMPOUNDS BY

DIAZONIUM SALTS

8.8.1 Gomberg or Gomberg-Bachmann reaction

Ar'H OH
ArN2X Ar Ar'

When diazonium salt solution is made alkaline, the aryl portion of the diazonium salts can
couple with aromatic ring. This reaction is known as the Gomberg or Gomberg-Bachmann
reaction and has been permormed on several types of aromatic rings and on quinines. When
the Gomberg-Bachmann reaction is performed intramolecularly, either by alkaline solution
by the alkaline solution or by the copper ion procedure, it is called Pschorr ring closer.

Z Z

N2

[ Z= CH CH, CH2CH2, NH, C O, CH2 ]

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Mechanism

OH HO N N Ar
ArN2X Ar N N OH Ar N N O N N Ar
H2O
Anhydride

Ar N N O N N Ar Ar O N N Ar
Anhydride A

H Ar Ar
O N N Ar
A
Ar R HO N N Ar
R R
B

The aryl radical thus formed attacks the substrate to give the intermediate B, from which the
radical A abstracts hydrogen to give the product. It has been shown that whatever is the
nature of substituents (R) in substrate, ortho or para substitution always predominents but
small amount of meta product is also formed.

8.8.2 Sandmeyer reaction:

CuX
ArN2X ArX N2

[X=Cl or Br]
Treatment of diazonium salts with cuprous chloride or bromide gives aryl or bromide gives
aryl chlorides or bromides respectively. This reaction is called the Sandmeyer reaction. The
reaction can also be carried out with copper and HBr or HCl, in this case it called the
Gattermann reaction. The Sandmayer reaction is not useful for the preparation of fluorides
and iodides but it is probably the best way of introducing brominr or chlorine in to an
aromatic ring.
Mechanism:
Step 1: The reduction of diazonium ion by cuprous ion to give an aryl radical:

ArN2X CuX Ar N2 CuX2

Step 2: The aryl radical abstract halogen from cupric chloride, reducing it. CuX is
regenerated and is thus a true catalyst.

Ar CuX2 Ar X CuX

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Mention must be made about Radical Redox Reacions of all Sandmeyer type reactions

8.9 HUNSDIECKER REACTION

The Hunsdiecker reaction (also called the Borodin reaction or the Hunsdiecker–Borodin
reaction) is a name reaction in organic chemistry whereby silver salts of carboxylic
acids react with a halogen to produce an organic halide. It is an example of both
a decarboxylation and a halogenation reaction as the product has one fewer carbon atoms
than the starting material (lost as carbon dioxide) and a halogen atom is introduced its place.
The reaction was first demonstrated by Alexander Borodin in his 1861 reports of the
preparation of methyl bromide from silver acetate. Shortly after, the approach was applied to
the degradation of fatty acids in the laboratory of Adolf Lieben. However, it is named
for Cläre Hunsdiecker and her husband Heinz Hunsdiecker, whose work in the
1930s developed it into a general method.

The reaction mechanism of the Hunsdiecker reaction is believed to involve organic

radical intermediates. The silver salt of the carboxylic acid 1 will quickly react with bromine
to form acyl hypohalite intermediate 2. Formation of the diradical pair 3 allows for
radical decarboxylation to form the diradical pair 4, which will quickly recombine to form the
desired organic halide 5. The trend in the yield of the resulting halide is
primary > secondary > tertiary.

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8.10 SANDMEYER REACTION

The Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from
aryl diazonium salts. It is an example of a radical-nucleophilic aromatic substitution. The
Sandmeyer reaction provides a method through which one can perform unique
transformations on benzene, such as halogenation, cyanation, trifluoromethylation,
and hydroxylation. The reaction was discovered in 1884 by Swiss chemist Traugott
Sandmeyer, when he synthesized phenylacetylene from benzenediazonium chloride and
cuprous acetylide. The reaction is a method for substitution of an aromatic amino group via
preparation of its diazonium salt followed by its displacement with a nucleophile, often
catalyzed by copper(I) salts. The nucleophile can include halide anions, cyanide, thiols,
water, and others. The reaction does not proceed well with the fluoride anion, but fluorination
can be carried out using tetrafluoroborate anions (Balz–Schiemann reaction).

The substitution of an aromatic amino group is possible via preparation of its diazonium salt
and subsequent displacement with a nucleophile (Cl-, I-, CN-, RS-, HO-). Many Sandmeyer
Reactions proceed under copper (I) catalysis, while the Sandmeyer-type reactions with thiols,
water and potassium iodide don't require catalysis.

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Reaction mechanism
The nitrous acid is typically prepared in situ from sodium nitrite and acid. Following
two protonation steps, one equivalent of water is lost to form the nitrosonium ion. The
nitrosonium ion then acts as an electrophile in a reaction with an aromatic (or heterocyclic)
amine, such as aniline, to form a diazonium salt, proceeding through
a nitrosamine intermediate. The substitution of the aromatic diazo group with a halogen
or pseudohalogen is initiated by a one-electron transfer mechanism catalyzed by copper (I) to
form an aryl radical with loss of nitrogen gas. The substituted arene is formed through a
radical mechanism with regeneration of the copper (I) catalyst. This reaction is known as the
Sandmeyer reaction and is an example of a radical-nucleophilic aromatic substitution. The
radical mechanism of the Sandmeyer reaction was resolved through the detection
of biaryl byproducts. It proceeds through the following mechanism.

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8.11 FREE RADICAL REARRANGEMENT

Allylic rearrangements are very common in free radical reactions on allylic substrates, for
examples:

R CH2 CH CH2 X R CH CH CH2

HX

R CH CH CH2

X2
X
R CH CH CH2 R CH CH CH2 X

A primary radical may sometimes produce a tertiary radical by migration by migration of a

substituents from the neighbouring carbon atom. However, such radical rearrangements are
less common than carbocation rearrangements because the stability differencesbetween a
primary and a tertiary radical is not as much as that between a primary and a tertiary radical is
not as much as that between a primary and tertiary carbocation. Most of the published
rearrangement involves the shift of an aryl group from one atom to the adjacent atom. For
example the rearrangement of beta-phenylisovaleraldehyde A accompanying
decarbonylation. The reaction is initiated by t-butyl peroxide and yields a mixture of almost
equal amounts of isobutyl benzene B and t-butylbenzene C.

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CH3 O CH3 O CH3

Initiator
Ph C CH2 C H Ph C CH2 C Ph C CH2
CO
CH3 CH3 CH3
D
A
Rearrangements

CH3 CH3 O CH3

A
H C CH2Ph Ph C CH2 C C CH2 Ph

CH3 CH3 CH3

B

CH3 CH3 O
D A Ph C CH2 Ph C CH2 C

CH3 CH3

The yield of the rearranged product B increases with dilution of the reaction mixture. This
supports the above mechanism because a decrease in concentration of a hydrogen donor A
would increase rearrangement at the expense of the hydrogen abstraction by the radical D.
Additional; the rate of the rearrangement is inhibited by addition of an effective hydrogen
donor such as thiophenol. The above rearrangement proceeds through the intermediate
bridged radical.

8.12 SYMMARY

In this chapter provided us concise knowledge about about free radical reactions, mechanism
of free radical substitution, reactions on aromatic substrates and neighboring group
assistance. We also studied about reactivity for aliphatic and aromatic substrates at a
bridgehead carbon, reactivity of the attacking radicals, the effect of solvents on reactivity and
allelic halogenations (NBS). We learned about oxidation of aldehydes to carboxylic acids,
auto-oxidation, coupling of alkynes and arylation of aromatic compounds by diazonium salts.
Besides many important name reactions of synthetic utility alongwith Sandmeyer reaction,
free radical rearrangement and Hunsdiecker reaction.

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8.13 TERMINAL QUESTIONS

1. Which one of the following alkenes will undergo free radical bromination most readily?
A. CH3COOH
B. CH3COCl
C. CH3CH2COOH
D. HOOCCH2CH2COOH
2. Free radical monobromination of n-butane gives:
A. (+)-2-bromobutane
B. (-)-2-bromobutane
C. (±)-2-bromobutane
D. achiral 2-bromobutane
3. Using the given codes, arrange the following compounds in decreasing order of reactivity
with NBS/CCl4/hv:

1. PhCH3

2. PhCH2CH2CH3
.
3 PhCH2CH=CH2

4. Ph CH CH CH2
CH3

Codes:
A. 4, 3, 1, 2
B. 4, 3, 2, 1
C. 1, 2, 3, 4
D. 1, 3, 2, 4

H Y

R
4. Z Y Z RH
Z
(I)
In the above reaction I will be least reactive if Z is:
A. H
B. NO2
C. Cl

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D. OH
5. How will you account for the formation of the following products on treatment of labeled
(* = 14C) cyclohexene with NBS?

Br Br Br

NBS
hv

6. Give major products expected for each of the following reactions. Pay attention to
regiochemistry and stereochemistry where appropriate.
CH3
HBr
1.
ROOR

H3 C
CCl4/hv
2. CH2
H3 C

C CH
3. HBr
ROOR

7.Give the structures of all the free radical monochlorination products of 1,2-dichloropropane
and indicate them as chiral or achiral.
8. Give the mechanism of photobromination of 1-bromo-2-methylbutane and indicate the
stereochemistry of the reaction, if any.
9. Complete the following reaction and indicate the configuration(s) (R or S) of the product(s)
formed.
NBS/CCl4
CH3 CH2 C CH
hv
10. Predict the product (s) in the following reactions:

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NBS/hv
1.

NBS/hv
2. PhCH2CH2CH3

3.
Ph
O2

4. Br2/hv

N CH3

8.14 ANSWERS TO TERMINAL QUESTIONS

1. C
2. C
3. B
4. A
5. Hint: write all the resonating structures of the radicals generated at both the allylic
positions. The addition bromine to the radical carbon gives the observed products.
7. ClCH2CHClCH2Cl (Achiral),
CH3C*HClCHCl2 (Chiral),
CH3CCl2CH2Cl (Achiral)
10.

1.

Br

2. P h C H B rC H 2C H 3

OOH

3.

4.

N C H 2B r

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8.15 REFERENCES

1. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 450-470.

2. Jerry March. 2007. Advanced Organic Chemistry-Reactions, Mechanism and

Structure, John Wiley. 4th edition. 677-733.

3. Mukherji S. M. and Singh S. P. 2015. Reactions Mechanism in Organic Chemistry.

Trinity Press. 564-604.

4. Singh M.S. 2005. Advanced Organic Chemistry. Reaction and Mechanisms. Pearson
Education. 214-247.

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UNIT 9- ElLECTROCYCLIC REACTIONS

CONTENTS:
9. Objectives
9.1 Introduction
9.2 Molecular orbital symmetry
9.3 Frontier orbitals of ethylene, 1,3-butadiene, 1,3,5-hexatriene and allyl system.
9.4 Classification of pericyclic reactions.
9.5 Woodward-Hoffmann correlation diagrams
9.5.1 Correlation diagram Electrocyclic reaction
9.5.2 Frontier Molecular Orbital (FMO) aproach for electrocyclic reactions
9.5.3 Perturbation Molecular orbital (PMO) Aproach for electrocyclic reactions(H-M)
Huckel-Mobius system
9.6 Summary
9.7 Terminal questions
9.8 Answers (MCQ) terminal questions
9.9 References

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9.0 OBJECTIVES
Objectives of this unit are to make aware students about concerted reactions, Concept
of molecular orbital symmetry conservation Principle given by Woodward-Hoffmann,
correlation diagrams, different methods for the explanation of electrocyclic reactions,
conrotatory and disrotatory mode of ring opening and ring closer reactions and Feasibility of
thermally or photochemically induced reaction, reactions of 4nπ and 4n +2π systems
interconversion through thermal or photochemical induction.

9.1 INTRODUCTION
Electrocyclic reaction is a type of pericyclic reaction.Pericyclic reactions are also known as
concered reactions in which bond breakin in reactant and bond formation in product takes
place simultaneously in a single step. These reactions are:

1. Characteristic reactions of olefinic cimpounds

2. Cyclic Transition State

3. Stereospecific in nature

4. Initiated by heat or electromagnetic radiation

5. No reaction intermediates are formed

Pericyclic reactions have been classified in different category (electrocyclic reactions,

cycloaddition reaction, sigmatropic reaction and group transfer reactions) electrocyclic
reactions is one of them. In these reactions a concerted shift of electron takes place which
ivolve conversion of two pie bonds to a pie bond and sigma bond if a reactant is open chain.
A pie bond and a sigma bond are converted to two pie pie bond if the reactant is close chain
in nature. In brief

If open chain partner contain Kπ electrons, its cyclic partner will contain K-2 π e- + a
σ bond

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K 4

open chain close chain open chain K=6 close chain

CH3
H
CH3

CH3 H
H3 C cis trans
hv CH3
H
H H H

CH3
trans trans

9.2 MOLECULAR ORBITAL SYMMETRY

According to Woordword and Hoffmann 1965 the symmetry of molecular orbitals are
conversed during interconvertion of open to cyclic parterner and vice-versa.K. Fukuii
proposed another explanation based upon the frontier molecular orbitals.The theory proposed
is known as FMO method. The Woodward- Hoffmann rule and Huckel-Mobius(H-M)
method or perturbation of molecular orbitals (PMO) are also used for the explanation of
pericyclic reactions.These foure theories predict the same explanation of pericyclic reactions.

To understand the theories of pericyclic reactions, we must first understand the molecular
orbitals and their symmetry of compounds containing π-bonds.

The two molecular orbitals are important in understanding pericyclic reactions. One is the
occupied molecular orbital of highest energy known as highest occupied molecular orbital
(HOMO). The other is unoccupied molecular orbital of lowest energy known as lowest
unoccupied molecular orbital (LUMO). Both HOMO and LUMO orbitals are referred to as
frontier molecular orbitals (Fig 1)

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3 LUMO
E
2 HOMO

Electronic state S0 of
1= ᴪ1, 2= ᴪ2, 3= ᴪ3, 4= ᴪ4

Fig 1. HOMO, LUMO orbitals of 1,3-butadiene

The molecular orbitals π and σ have two types of symmetry.

1. Mirror plane of symmetry: in this symmetry the molecular orbitals have two halves
having mirror image of each other fig 2

2. C2 or two fold axis of symmetry: in this type of symmetry the molecular orbitals
posses center of symmetry or mirror image of each other if rotated by 1800 or 3600/2

M
M

Miror plane of symmetry a pi molecular orbital Mirror plane of symmetry a sigma bonding MO
Fig.2 Mirror plane of symmetry in π and σ bonding molecular orbitals

In C2 symmetry keeping one orbital in position rotate second by two fold first by 900
then again by 900 which makes two rotations (or simply 1800 or 3600/2 in total).
After doing this if the molecular orbital posses mirror plane bisecting the orbitals in
to mirror image, then it is called C2 symmetry of two fold axis of symmetry Fig 3.
On the other hand if the molecular orbitals (MO) have centre of symmetry, then it is
simply called C2 symmetry.

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0 0 0
Rotation 90 then again 90 180 = C2
0
360
2

M
Centre of the MO
Both the orbitals are not mirror image There is a centre of symmetry (i.e. C2 symmetry)
hence there is no M symmetry

0 0 0
Rotation 90 then again 90 180 = C2
0
360
2

Nomirror plane of symmetry No centre of symmetry i.e. no C2 symmetry

Fig.3 Two fold axis or C2 of symmetry in π and σ bonding molecular orbitals

Mrror Plane
3600 360 0
2 2
LUMO 2 2'

M=A
M=S M=A M=A
C2 = A C2 = A
C2 = A C2 = S

360 0 360 0
2 2
HOMO 1 1'

M=A M=S M=S M=S

C2 = S C2 = A C2 = S C2 = S

1=π1 2=π2, 1’=σ and 2’=σ*

Fig.4 Molecular orbital symmetry in π and σ molecular orbitals of ethylene molecule

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9.3 FRONTIER ORBITALS OF ETHYLENE, 1,3-BUTADIENE,

1,3,5-HEXATRIENE AND ALLYL SYSTEM

2 LUMO

M=S
C2 = A CH2=CH2
ethylene

1 HOMO

M=A
C2 = S
Molecular orbital symmetry of ethylene with HOLO, LUMO orbitals
1=π1 / ᴪ1 2=π2/ ᴪ2

Fig 5. Moleculer orbitals symmetry in ethylene

When no of nodes (n-1) is zero or even, ᴪn will be symmetric with M and symmetric with C2
while if (n-1) is an odd, ᴪn will have the symmetric exactly opposite

Nodes M C2

0 or even S A

ᴪ1, ᴪ3, ᴪ5, ᴪ7,------- Odd A S

Table: 1 Moleculer orbital symmetry properties and Frontier orbitals of ethylene

(n-1) Orbital Symmetry

With respect to mirror C2 Frontier MO
Plane (M)

1 ᴪ1/π1 S A HOMO

2 ᴪ2/π2 A S LUMO

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M=A
6 C2 = S

M=A
C2 = S M=S
4
5 C2 =A

M=S
LUMO 3 C2 = A
M=A
LUMO 4 C2 = S

M=A
HOMO C2 = S
2

M=S
HOMO 3 C2 = A
M=S
1 C2 = A

Molecular orbital symmetry in

M=A
2 C2 = S
Molecular orbital symmetry in
_
1, 3 butadiene

A M =S
1 C2 = A
1 ,3 ,5 _ hexatriene

A = 1= ᴪ1/π1, 2= ᴪ2/π2, 3= ᴪ3/π3, 4 = ᴪ4/π4 B

B= ᴪ1/π1, 2= ᴪ2/π2, 3= ᴪ3/π3, 4 = ᴪ4/π4, 5= = ᴪ5/π5, 6 = = ᴪ6/π6

Fig 6. Molecular orbitals of A 1,3-butadiene and B 1,3 5- hexatriene

Table 2 Moleculer orbital symmetry properties and Frontier orbitals of 1,3-butadiene

(n-1) Orbital Symmetry property

With respect to mirror C2 Frontier

MO
Plane (M)

1 ᴪ1/π1 S A HOMO

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2 ᴪ2/π2 A S LUMO

3 ᴪ3/π3 S A

4 ᴪ4/π4 A S

Table 3 Moleculer orbital symmetry properties and Frontier orbitals of 1,3 5- hexatriene

(n-1) Orbital Symmetry property

With respect to mirror C2 Frontier

MO
Plane (M)

1 ᴪ1/π1 S A

2 ᴪ2/π2 A S

3 ᴪ3/π3 S A HOMO

4 ᴪ4/π4 A S LUMO

5 ᴪ5/π5 S A

6 ᴪ6/π6 A S

Ther are two p-orbitals in the molecule of ethylene (ignoring σ-skeleton). Their combinations
give us two π-MO designated as 1= ᴪ1/π1 and 2= ᴪ2/π2, thermodynamically with different
energy. The energy of 1 = ᴪ1/π1 is lowest and it acoomodate both the electrons. This MO is
also designated as bonding MO. Since both the electrons are acccomdated in it hence also
known as HOMO in ground state (highest occupied molecular orbitals i.e. the orbital which
occupy the last electron/s). 2= ᴪ2/π2 is vacant and higher in energy is known as LUMO
(lowest unoccupied molecukar irbital i.e. the orbital which lowest in energy and vacat) in
ground state (fig.5). So far the symmetry properties of these MOs are concerned the ᴪ1/π1
orbital is symmetric ( zero node) with respect to mirror plane and asymmetric with respect to
C2 similary ᴪ2/π2 is asymmetric (one node, odd no) with respect to mirror plane ans
symmetric with respect to C2 plane(fig.5, table 1).

There are four p- orbitals in the molecule of 1,2-butadiene (ignore σ-skeleton in this
treatment) and their possible combinations provide us an approximation set of four
molecular π- orbitals designated as ᴪ1/π1, ᴪ2/π2, ᴪ3/π3 and ᴪ4/π4 have different energies.The
energy of 1= ᴪ1/π1 is considerably lower than any of the other approximations and it is

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therefore reasonable that two out of four electrons in the ground state are accomomodated by
this orbital. The enery of next higher orbital 2= ᴪ2/π2 is also lower than other two molecular
orbitalshence remaining two electrons out of four are accommodated in it. These two MO are
designated as bonding MO while remainin two (3= ᴪ3/π3, 4 = ᴪ4/π4) vacant MO are higher in
energy and are anti bonding in nature (fig 6A). Six p- electrons of 1,3,5-hexatriene are
similarly accommodated in the first three MOs viz; 1 = ᴪ1/π1, 2= ᴪ2/π2 ,3 = ᴪ3/π3 (bonding
MOs), while remaining three MOs viz; 4= ᴪ4/π4, 5= ᴪ5/π5, 6 = ᴪ6/π6 (anti-bonding MOs) are
unoccupied in ground (S0) state(fig.6B). As per the description 2= ᴪ2/π2 is HOMO and 3 =
ᴪ3/π3 is LUMO in 1, 3-butadiene in S0 (fig. 6A table 2). Similarly 3 = ᴪ3/π3 is HOMO and 4 =
ᴪ4/π4 is LUMO in ground state of 1, 3, 5-hexatriene respectively.( fig. 6B table 3)

Conjugated unbranched ions (cations and anions) and radicals have an odd number of
carbons. First member of these classes are allyl carbocations, allyl carbanions and allyl
free radoicals.

CH2=CH CH2 allyl carbocation

sp2 sp2 sp2

This system has three isolated p- orbitals and has only one π- bond (two π electrons)

CH2=CH CH2 allyl carbanion

This system has three isolated p- orbitals and has only one π- bond and one lone pair
of electrons.

Similarly in following system there are three p-orbitals and has one π-bond and one
electron in unhybrid p-orbital. The electron occupiency in these systems can be
represented as follow

CH2=CH CH2 allyl free radical

The MOs of allyl shows two important differences between these MOs and those of
conjugated polyenes.

A. One MO in allylic system is neither bonding MO nor anti-bonding MO but has the similar
energy as the isolated p-orbitals This MO is called nonbonding MO.The nonbonding MO in
allylic system is 2= ᴪ2. The remaining MOs are bonding and anti-bonding ( half are bonding
and half are anti-bonding)( fig7

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nodes

LUMO
3 anti bonding S

E node

HOMO
LUMO
2 non bonding A

HOMO
Isolated p orbitals 1
bonding S
cation radical anion
Molecular orbitals symmetry
electron occupancy

1= ᴪ1, 2 =ᴪ2, 3 = ᴪ3

Fig. 7 π- molecular orbitals with HOLMO- LUMO designation and symmetry properties of
allyl system

B. In some of the MO’s nodes pass through carbon atom viz; in allyl free radical there is
node on the central carbon atom of 2= ᴪ2. The cation anion and free radicals involving the
same π- system have the same MOs because all three species contain similar number of p-
orbitals (fig 7). Similarly the the π- MOs of 2,4- pentadienyl system are shown in fig 8.

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nodes

5 S

anti bonding

HOMO HOMO
4 A

HOMO HOMO
3 LUMO
S non bonding

HOMO
Isolated p orbitals
2 A
cation radical anion

bonding

S
1

cation radical anion symmetry

Molecular orbitals
electron occupancy

pentadienyl cation pentadienyl free radical pentadienyl anion

1= ᴪ1, 2 = ᴪ2, 3 = ᴪ3, 4 = ᴪ4, 5 = ᴪ5

Fig. 8 π- molecular orbitals with HOLMO- LUMO designation and symmetry properties of 2,4-
pentadienyl system

9.4 CLASSIFICATION OF PERICYCLIC REACTIONS

As also mentioned earlier pericyclic reactions are of four types. The first type is the
electrocyclic reaction: A reaction in which a ring is closed (or opened) through a cyclic shift
of electrons at the expense of conjugated double bond or a pi bond. If open chain partner
contain Kπ electrons, its cyclic partner will contain K-2 π e- + a σ bond.

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new sigma bond close aring

loss of one pi bondand gain
of one sigma bond

1,3 _ butadiene cyclobutene

open chain closed chain
K= 4 ( 4 _ 2 ) = 2 pi electron + a sigma bond

new sigma bond close aring.

loss of one pi bond and gain
of one sigma bond
1, 3, 5 _ hexatriene cyclohexadiene

K= 6 ( 6 _ 2 ) = 4 pi electron + a sigma bond

open chain closed chain

The second type of pericyclic reaction is cycloaddition reaction: a reaction in which two or
more π-electron system reacts to form aring at the expense of one π-bond in each of the
reacting parterns

new sigma bond new sigma bond

hv heat
+ +
;

new sigma bond new sigma bond

The third type of reaction is the sigmatropic rearrangement (or reaction): a reaction in which
a σ-bond formally migrates from one end to the other end of π-electron system and net
number of π- bonds remains the same. The reactions are often classified with two numbers,i
and j set in brackets [i, j ] and the system is numbered by starting at the atoms forming the
migrating σ-bond. These (i and j) indicates the new positios of the σ-bond whose termini are
i-1 and j- 1 atoms removed from the original loci.

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5 H sigma bond moves from one end to H

D
4 H1 the other end of the pi electron system H
D1
3
D hv/heat [ 1, 5 ] shift D
2 D D

1R R
2 [1, 3] shift
CH2 CH CH CH CH2 CH2 CH CH CH CH2
1 3 sigma bond moves from one end to
the other end of the pi electron system
2
2
1 3
1 3 X= C or O
X 3
X 1
1 3 [ 3, 3] shift 2
2

The fourth type of reaction is group transfer: a reaction in which one or more groups or
atoms transfer from one molecule to another molecule. In this reaction both the molecules
are joined by a sigma bond.

H H
+ heat

9.5 WOODWARD-HOFFMANN CORRELATION DIAGRAMS

According to Woodward –Hoffmann rule the pericyclic reactions can be interpreted by
correclation diagram methods. In correclation diagram method if the MOs of reactant (open
chain/ close chain) correlate with the MOs of product (open/close chain) molecule in ground
state, the reaction is considered to be feasible in through thermal induction and if theexcited
state molecular symmetry of reactant species correlate with excited stae molecular symmetry
of the product, the the reaction is possible by phytochemical induction.

9.5.1 Correlation diagram of electrocyclic reaction:

As also mentioned earlier an electrocyclic reaction is interconversion of cyclic to close chain
molecules containing double bonds. The reaction is initiated by heat of EMR. The reactions
are stereospecific in nature.

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Let us consider the simplest example in which a cyclobutene system opens to a 1, 3-

butadiene. This reaction can be performed thermally or photochemically and under either
condition the reaction is completely stereospecific.

CH3
H
heat CH3
CH3
CH3 H
cis, trans
H hv
CH3
H
H
H

CH3
trans, trans
For above conversion of close chain of cyclobutene to open chain 1,3 –butadiene a σ-bond
of cyclobutene must break break to yield open chain butadiene. In reverse reaction ring
closer also involve σ- bond. The ring opening and ring closer takes place by two different
methods as discussed follow.

A. conrotatory motions: In conrotatory motion the orbitals rotate in same directions either
clockwise or anticlockwise direction. During corotation C2 symmetry is maintained.

Conrotation

anticlockwise rotation C2 = S

Conrotation

clockwise rotation C2 = S

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B. disrotatory motions: In disrotatory motion the orbitals rotate in opposite directions, one
clockwise and the other anticlockwise mirror plane (M) symmetry is maintained in
disrotation

disrotatory

anticlockwise rotation clockwise rotation M=S

disrotatory

M=S
clockwise rotation anticlockwise rotation

The stereochemical significance of these two modes of ring – opening /closing becomes
apparent when we consider substituted reactants.

An electrocyclic reaction is a concerted reaction. The transition state of electrocyclic

reaction should be intermediate between electronic ground stats of starting material and
product. The most stable transition state will be the one which conserve the symmetry of
reactant MOs in passing to MOs of products. In other words the the symmetry(S) MOs in
the reactant must transform into symmetry (S) MOs in the product and asymmetric (A) MOs
of reactant must transform into asymmetry (A) MOs of the product. In case the symmetry
properties of MOs are not sustained during the reaction, the reaction will not take place in a
concerted manner.

Let us analyse the cyclobutene-1, 3-butadiene interconversion. The ring opening/closing in

such transformation may take place by disrotation or conrotation. To analyse this
transformation construct symmetry properties of MOs of cyclobutene and 1,3 – butadiene as
follow (fig.9,10)

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M=A M= A
?4 s*
C2 = S C2 = A

?3 M=S M= A
C2 = A ? C2 = S
2

?2 M =A M= S
C2 = S ?1
C2 = A
?1
M= S s M=S
C2 = A C2 = S

Fig. 9 Symmetry properties of molecular orbitals (MOs) of cyclobuten and 1,3- butadiene

Analysis through coorelation diagram can be done either presuming the disrotation or
conrotation. In disrotation M symmetry in suctained while in corotation C2 symmetry is
maintained.
Dis.

M , Symmetry maintained
cyclobutene 1, 3 butadiene

Fig 10. Correlation for disrotatory interconversion of cyclobutene- butadiene system M symmetry
mainitained

σ* A A ᴪ4

π* A S ᴪ3

π S A ᴪ2

σ S S ᴪ1

Disrotation mode for ring closing/opening

1. σ2π2 ᴪ12 ᴪ22 or ᴪ12 ᴪ22 σ2π2

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2. σ2π2 σ2 π π* ᴪ12 ᴪ2 ᴪ3 ᴪ12 ᴪ22

S0 S1 S1 S0

Ground state first excited state first excited state ground state
Two conclusions can be drawn from above correlation diagram
1. We expect a thermal transformation to take place only if the S0 i.e ground state
orebital symmetry of reactant correlates with the S0 state of the products. While
considering condition 1 as above although the cyclobutene ground state orbital
symmetry of σ-orbital correlate with S0 state of 1,3- butadiene ᴪ1, the π-orbital symmetry
of former does not correlate with ᴪ2 of the latter. It correlate with ᴪ3 which is an excited
state and antibonding orbital.Thermal transformation of cyclobuten to 1,3-butadiene by
dirotatory process through concerted manner is thus symmetry-forbidden and or not
allowed.

2. Irrediation of cyclobutene produce the first excited state (S1) as point 2 above in which an
electron is promoted from π* orbital and in this case σ, π and π* orbitals of cyclobutene
correlate with ᴪ1, ᴪ2, and ᴪ3 orbitals of 1, 3- butadiene. In other words the first excited
state (S1= σ2 π π*) of cyclobuten correlate with first excited state (S1= ᴪ12 ᴪ2 ᴪ3) of 1, 3-
butadiene hence disrotatory ring opening (and ring cosing) is allowed process by
concerted manner (fig.11)
Con.

C2, symmetry maintained

cyclobutene 1, 3 butadiene

Fig.11 Correlation diagram for conrotatory interconversion of cyclobutadiene- butadiene system C2

symmetry mainitained

σ* A S ᴪ4

π* S A ᴪ3

π A S ᴪ2

σ S A ᴪ1

Conrotation mode for ring closing/opening

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1. σ2π2 ᴪ12 ᴪ22 or ᴪ12 ᴪ22 σ2π2

2. σ2π2 σ2 π π* ᴪ12 ᴪ2 ᴪ3 ᴪ12 ᴪ22

S0 S1 S1 S0

Ground state first excited state first excited state ground state
Two conclusions can again be drawn from above correlation diagram.
1. Since there is correlation between the ground state (S0) orbital symmetry of cyclobutene
(σ2π2) and 1, 3 –butadiene (ᴪ12 ᴪ22 ). Hence the cyclobetene – butadiene interconversion
by conrotation mode is symmetry allowed by thermal induction and will take place by
concerted manner.

2. The first excited state (S1= σ2 π π*) correlate with the upper excited state (S1= ᴪ12 ᴪ2 ᴪ3) of
1, 3- butadiene thus making it a high energy symmetry forbidden process. Similarly, the
first excited state of butadiene (S1= ᴪ12 ᴪ2 ᴪ3) correlate with a high energy upper excited
state (S1 = σ2 π π*) of cyclobutene.In other words, a photochemical conrotatory process in
either direction is symmetry- forbidden and will not proceed by concerted manner.

From above statements it becomes clear that thermal opening of cyclobutene proceeds in a
conrotatory process while photochemical involvs adisrotatory mode. These generalizations
are true for all the systems containing 4nπ electrons where n= 0, 1, 2 etc.However, for system
containing (4n + 2)π electrons theoretical prediction is entirely differentand is in conformity
with actual observations. A typical system of this type is interconversion of cycloheadiene
and 1, 3, 5-hexatriene as follow.

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Fig. 12 Symmetry properties of molecular orbitals (MOs) cyclohexadiene to 1,3,5-hexatriene

In above transformation of cycloheadiene and 1, 3, 5-hexatriene MOs (ᴪ1 to ᴪ6) of

hexatriene and six MOs (four π = ᴪ1, ᴪ2, ᴪ3 and ᴪ4 and two σ and σ*) of cyclohexadiene
system are actually involved and need to be considered for explation. Symmetry properties
of six MOs of hexatriene and cyclohexadiene have been constructed (fig 12, 13).

Analysis through coorelation diagram can be done either presuming the disrotation or
conrotation.

Dis.

M symmetry maintained
cyclohexadiene 1, 3, 5 - hexatriene

Conrotation mode for ring closing/opening

Fig 13 Correlation diagram for disrotatory interconversion of cyclohexadiene- hexatriene system M

symmetry mainitained

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σ* A A ᴪ6

ᴪ4 A S ᴪ5

ᴪ3 S A ᴪ4

ᴪ2 A S ᴪ3

ᴪ1 S A ᴪ2

σ S S ᴪ1

The correlation diagram as above (fig 13) for disrotatory pathways is constructed in the
similar way as in the case of cyclobutene-butadiene system.

The following inferences may be drawn from the above correclation diagrams

1. In the disrottory mode (M symmetry) S0 bonding MOs of cyclohexadiene correlate with

the S0 bonding MOs of hexatriene and and is thus the interconersion of cyclohexadiene to
hextriene and vice-versa is a thermally allowed process.

σ 2 ᴪ12 ᴪ22 ᴪ12 ᴪ22 ᴪ32 Or σ 2 ᴪ12 ᴪ22 ᴪ12 ᴪ22 ᴪ32

2. In conrotatory mode (C2- symmetry), ground state(S0) bonding MOs of cyclohexatriene

do not correlate with S0 bonding MOs of hexatriene Since the presence of two electrons in
ᴪ4 is a very high energy process, a conrotatory mode for the interconersion of
cyclohexadiene to hextriene and vice-versa is prohibited under thermal condition(fig13).

σ 2 ᴪ12 ᴪ22 ᴪ12 ᴪ22 ᴪ32 ᴪ12 ᴪ22 ᴪ32 σ 2 ᴪ12 ᴪ22

S0 S1 S1 S0

Con.

C2 symmetry maintained
cyclohexadiene 1, 3, 5 - hexatriene

Conrotation mode for ring closing/opening

Fig 14 Correlation diagram for conrotatory interconversion of cyclohexadiene- hexatriene system C2

symmetry mainitained

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σ* A S ᴪ6

ᴪ4 S A ᴪ5

ᴪ3 A S ᴪ4

ᴪ2 S A ᴪ3

ᴪ1 A S ᴪ2

σ S A ᴪ1

3. If we promote an electron from ᴪ2 to ᴪ3 in cyclodiene or ᴪ3 to ᴪ4 in hexatriene by

irradiation then the MOs of cyclohexadiene correlate with the MOs of hexatriene with first
excited (S1) states of each other. ᴪ3 is S1 state of cyclohexadiene while ᴪ4 is S1 for
hexatriene (fig.12 & 14).

σ 2 ᴪ12 ᴪ22 σ 2 ᴪ12 ᴪ2 ᴪ3 ᴪ12 ᴪ22 ᴪ3 ᴪ3 ᴪ12 ᴪ22 ᴪ32

S0 S1 S1 S0

In is inferred therefore, that photochemical interconversion is symmetry allowed in

conrotatory pathways.These generalizations are true for all the systems containing (4n + 2)π
electrons, where n= 0,1, 2,---etc. The Woodward- Hoffmann rules for electrocyclic reactions
may be summed upin the form of table 4.

Table 4. Selection rules for electrocyclic reactions.

Number of π electrons Thermal mode (∆) Photochemical mode(hv)

5 nπ electrons Con. Dis.

(4n +2)π electrons Dis. Con.

Woodward- Hoffmann have explained that under severe thermal conditions, symmetry-
forbidden reactions may also take place but they follow a non-concerted pathway and their
energy of activation is 10-15 kcl/mole higher than those of symmetry allowed processes.

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9.5.2 Frontier Molecular Orbital (FMO) aproach for electrocyclic reactions

FMO approach is quick method for the interpretation of electrocyclic reactions. In this
approach our guide for explanation is HOMO orbitals of open chain parterner.In this
approach if the MO of open chain has C2 symmetry then the reaction follow conrotatory
mode of cyclization and if it has M symmetry, it will follow disrotatory mode. It has already
been mentioned above in section 9.3 that the the MOs with zero or even number of nodes (n-
1) posses M symmetry while with odd numer of nodes (n-1) exhibit symmetry with respect
to C2. So far the 1,3- butadiene - cyclobutene is concerned. In ground state (S0) of
butadiene ᴪ2 is HOMO and since it has one node and display C2 symmetry. Hence according
to FMO approach the ring closere/ ring opening in the intercoversion will follow conrotatory
mode. Irradiation of butadiene by EMR promote electrone from ᴪ2 (HOMO in S0) to ᴪ3
(LUMO in S0) which becomes now HOMO (because possing last electron in it). Since this
orbital has two nodes and it display M symmetry, hence as per FMO approach the ring
closere/ ring opening in the intercoversion will follow disrotatory mode. The explanation
based on the fact that overlapping of wave function of same sign is essential for bond
formation (fig.15)
I n te r c o n v e r s io n

1 , 3 b u ta d ie n e c y c lo b u te n e

Fig 14. FMO approach for electrocyclic interconversion of butadiene- cyclobutene system.

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Similarly, in hexatriene – cyclohexadiene interconversion ᴪ3 is HOMO in ground state. It displays M

symmetry which is maintained in disrotation hene the hexatriene-cyclohexadiene interconversion
will follow disrotatory path in concerted reaction as shown in fig 16.

Fig 15. FMO approach for electrocyclic interconversion of hexatriene –cyclohexadiene system.
Disrotatory process

Similarly when hexatriene, the open chain parterner in the above conversion is irradiated,
electron is promoted to ᴪ4 orbital which now is a photochemically HOMO orbital and posses
three nodes. Based on number of nodes, this orbital display C2 symmetry which in maintained
in conrotatory mode of ring cycling or closing. Hence based on FMO approach the ring
closing of hexatriene to cyclohexadien will follow photochemical mode of activation through
conrotatory mode fig.16. It is clear from above approach that conrotatory or disrotatory mode
of ring opening (or the reverse process) takes plae in two directions each. The preferred
direction will depend on its stereochemical factor involving the end groups in transtition state
fig 16.

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Fig 16. FMO approach for electrocyclic interconversion of hexatriene –cyclohexadiene system.
conrotatory process

CH3 dis. CH3 H

CH3 H hv and/or
H CH3
H H CH3
H 3C H
favoured
heat
H H
HH and/or CH3
CH3 CH3 dis.
H 3C H H 3C H
favouredC H 3

hv HH
H 3C
CH3 H C on. and/or
H CH3 H
H CH3 CH3 CH3
favoured

Fig 17 prefrred directions of ring opening

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9.4.3. Perturbation Molecular Orbital (PMO) aproach for electrocyclic reactions (H-M)
Huckel-Mobius System:

Another method for quickly assessing whether a given pericyclic process is allowed is to
examine the cyclic array of orbitals at the transition state of the preicyclic reaction. This
method was popularized by H. Zimmerman and M.J.S. Dewar.

According to Huckel- Mobius system (developed by Zimmerman & Dewar ), monocyclic,

conjugated, planar system with 4n + 2πe are aromatic and stable in S0 and the monocyclic,
conjugated, planar system with (4n)2πe are antiaromatic and unstable in S0

Calculation shows that these rules are reversed by the presence of a NODE in the array of
atomic orbital thus:

If system has no NODE

4n + 2πe = Aromatic and stable in S0
(4n)2πe = Antiaromatic and unstable in S0

If system has NODE

4n + 2πe = Antiromatic and unstable in S0
(4n)2πe = Aromatic and stable in S0
If system has no node, it is called Huckel system & array is called Huckel array.
If system has node, it is called Mobius system & array is called Mobius array
Application of these rules to pericyclic reactions led to the generalization that thermal
reactions take place via aromatic transition state [i.e.(4n + 2)π electrons having no node or
4nπ electrons having one node]where as photochemical reaction proceed via antiaromatic
transition state [i.e. (4nπ) electrons having no node or (4n + 2)π electrons having one node].

A cyclic transition state is said to be aromatic with corresponding aromatic system if the
number of the conjugated atoms and that of the π-electrons involved are the same as in the
corresponding aromatic system. Similarly, a cyclic transition atate is said to be antiaromatic
with the corresponding antiaromatic syatem if the number of conjugated atoms and that of
the π-electrons involved are the same as in the corresponding antiaromatic system. We have
only to consider a cyclic array of atomic orbitals representing those orbitals which undergo
change in the transition state and assign signs to the wave function in the best mannar for
overlap. Then the number of nodes in the array and number of electrons involved are

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counted (fig.18 &19). For convenience the selection rule by PMO or Huckel- Mobius
approach to electrocyclic reactions are given in table 5.

Table 5: Selection rule for electrocyclic reactions by H-M Method/PMO approach

Array of πelectrons involved No. of nodes Aromaticity ∆ allowed hv allowed

4nπ zero antiaromatic - disrotatory

4nπ one aromatic conrotatory -

(4n + 2) π zero aromatic conrotatory -

(4n + 2) π one antiaromatic - disrotatory

pericyclic
interconversion

1, 3 butadiene cyclobutene
open chain partner

(+Ve) lobe interact with (+Ve ) (-Ve) lobe interact with (+Ve )
or Con. or
Dis. (- Ve) lobe interact with ( -Ve ) (+Ve) lobe interact with (-Ve )

No NODE 4- pi, zero bode, antiaromatic, NODE 4 - pi, one node, aromatic
Huckel system, hv allowed Mobius system, thermally allowed

Fig 18. Array diagram for 4nπ system

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pericyclic interconversion

hexatriene, open chain partner cyclohexadiene, close chain partner

(+Ve) lobe interact with ( -Ve )

Con. or (+Ve) lobe interact with (+Ve )
( -Ve) lobe interact with (+Ve ) Dis. or
( -Ve) lobe interact with (-Ve)

NODE 6 -pi
electron, one node
No NODE 6 - pielectron, zero node
antiaromatic, Mobius system
aromatic, Huckel system
hv allowed
thermally allowed

Fig 19. Array diagram for (4n +2) π system

9.6. SUMMARY
In present unit we discussed about pericyclic reactions, how these reactions are different from
other reactions. We discussed the types of pericyclic reactions. Electrocyclic reactions which
one of the type of pericyclic reactions has been discussed in details The correlation diagram
of different olefinic system viz; ethylene, 1,3-butadiene, 1,3,5-hexatriene alongwith the
description of their HOMO , LUMO orbital has been described. The allylic system with
cationic form, free radical form and anionic form has been interpreted with their MOs
alongwith description of HOMO, LUMO orbitals. The bond braking/making during ring
closere/opening through conrotatory and disrotatory mode has been described. The
interconversion of 4nπ and (4π + 2) π system by correlation diagram, FMO approach and
PMO (Huckel-Mobius system) have been well described alongwith selectin rules. Finally it
can be inferred that this unit educates us how concerted reactions in olefinic system takes
place by electrocyclic (cyclic array of electrons) mode.

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9.6 TERMINAL QUESTIONS

Q1. Tick the correct answer (MCQ)

i The HOMO orbital in 1,3,5-hexatriene is:

A. ᴪ1

B. ᴪ2

C. ᴪ3

D. ᴪ4

ii Pericyclic reaction are:

A. Concerted and stereospecific

B. Concerted and non stereospecific

C. Reactions of olefinic compounds

D. Both A and C

iii Pericyclic reaction are activated by

A. Heat and EMR

B. Polar solvent

C. Catalyst

D. None of them

iii M- symmetry is maintained in

A. Conrotatory mode

B. Disrotatory mode

C. Both A and B

D. None of them

iv Interconversion of butadiene-cyclobutene in S0 is feasible by:

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A. Thermally by disrotation

B. Thermally by conrotation

C. Photochemically by disrotation

D. Photochemically by conrotation

v. Which is the quickest mode for the explanation of electrocyclic reactions?

A. Correlation diagram

B. PMO and FMO mode

C. Only PMO

D .All of them

vi What will be the mode of ring opening and structure of the product in following reaction?

heat
CH3 CH3
H H

A. Conrotatory, H3 C H
H H3C

B. Disrotatory, H3C H
H H3C

C. Disrotatory, H CH3
CH3 H

D. Conrotatory, H CH3
H H3C

vii LUMO orbital in 1,3,5 hexatriene under photochemical condition is:

A. ᴪ1

B. ᴪ2

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C. ᴪ3

D. .ᴪ4

viii. Predict the product of the following reaction.

hv
[A]

A. Conrotatory, B. Disrotatory,

H H H H

C. Disrotatory, D. Conrotatory ,

H H H H
ix Give product with its stereochemistry in the following reaction.
heat
[A]
CH3 H3C H
H
2 E,3Z
HC CH3
A. Conrotatory, 3
H H

H3C CH3
B. Disrotatory,
H H

H3C H
C. Disrotatory,
H CH3

H3 C CH3
D. Conrotatory
H H

x. Who popularized correlation diagram and molecular orbital symmetries for pericyclic
reactions?

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A. Woodwar- Hoffmann

B. Huckel Mobius

C. Dewar

D. Zeimermann

9.7 ANSWERS (MCQ) TERMINAL QUESTIONS

iC

ii D

iii A

iv B

vB

vi A

vii D

viii C

ix A

x. A

Q.2. What are pericyclic reactions? Discuss classification of pericyclic reactions

Q.3. Draw and discuss the symmetry properties of molecular orbitals of 1,3 –butadiene and
1,3,5-hexatriene

Q.4 What do you understandand by conrotation and disrotation? Discuss with example

Q.5. Find out the selection rules for following interconversion using FMO and PMO
meyhod

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A.

B.

Q.6. Predict the product in the following reactions.

hv
1. [A]

heat
2. H [A]

hv
[A]
3. CH3
H3 c H H

hv
4. [A]

CH3 CH3

Q.7. What is meant by “conservation of molecular orbital symmetry”? What are the
symmetry elements which control the course of a reaction?

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9.8 REFERENCES

1. Singh, J and Singh,J. Phptochemistry and pericyclic reactions 2004, 1-26, New Age
International (P) Limited, Publisher, New Delhi, India

2. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 336-379.

3. Mukherji, S.M., Singh, S.P. and Kapoor, R.P. 1998, 978-1006, New Age International
(P) Limited, Publisher, New Delhi, India

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UNIT-10 CYCLOADDITIONS AND SIGMATROPIC

REACTIONS
CONTENTS:
10. Objectives
10.1 Introduction
10.2 Antarafacial and suprafacial additions

10.3 Cycloaddition in 4n π and [4n +2] π system

10.4 2+2 Cycloaddition Reaction
10.5 cheleotropic reactions
10.5.1 [2 + 2] Chelotropic cycloaddition
10.6: [1, 3]-dipolar cycloadditions
10.7. Sigmatropic reactions/rearrangement
10.7.1 Explanation of [1, 3] and [1, 5] sigmatropic shift
10.8 Sigmatropic shifts of alkyl group
10.9 Huckel- Mobius approach in sigmatropic rearrangemant
10.10 [3,3] sigmatropic rearrangements Cope rearrangements
10.11 Claisen rearrangement
10.12 [5, 5] rearrangement reactions.
10.13 Aza-Cope rearrangements:
10.14. Fluxional tautomerism
10.15 Ene reaction
10.16 Summary
10.17 Terminal questions
10.18 Answers (MCQ) terminal questions
10.19 References

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10. OBJECTIVES
Objective of this unit are to make aware students about cyclodiition and sigmatropic
concerted reactions. Introduction, antarafacial and suprafacial additions, 4n and 4n+2
systems, 2+2 addition of ketenes, 1,3-dipolar cycloadditions and cheleotropic reactions.
Sigmatropic rearrangements- suprafacial and antarafacial shifts of H, Sigmatropic shifts
involving carbon moieties, 3,3- and 5,5 sigmatropic rearrangements. Claisen, Cope and Aza-
Cope rearrangements. Fluxional tautomerism, Ene reaction.

10.1 INTRODUCTION
As also discussed in unit 9 electrocyclic reactions, that cycloaddition, sigmatropic and
chaelotropic reactions are also type of pericyclic reactions, i.e. these reactions are concerted
and given by olefinic compounds. Incyloaddition reactions two or more unsaturated
molecules undergo an addition reaction to yield a cyclic product. Formation of cyclic product
takes place at the expense of one π- bond in each of the reacting partener and gain of two σ-
bonds at the end of the both components having π-bonds. Thus there is aloss of two π-bonds
of the reactants and gain of two σ-bonds in the product.

hv 2 + 2 cycloaddition
+

loss of two pi bond and gain of two sigma bonds

heat
+ 4+ 2 cycloaddition

loss of two pi bond and gain of two sigma bonds

Similarly sigmatropic reactions are another class of concerted reactionsgoverned by orbital
symmetry. This rearrangement involves aconcerted reorganization of electrons during which
a group attached by σ-bond migrates to the terminus of an adjacent π- electron system. The
reactions are called sigmatropic because a σ-bind move from one place to another during
reactionThere is simultaneous shift of π-bond, The number of π and σ-bonds remains
separately unchanged.

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1 2
1, 3 shift
CH2 CH2 R
CH2 CH CH2
CH2 CH CH2
1 2 3 CH2 CH2 R

migration of sigma bond from one position to other position

net number of sigma and pi bonds remains the same

In chelotropic reactions two σ-bonds are formed or broken on the same atom

N N + N N

two sigma bonds are broken on nitrogen

+ SO2
SO2

two sigma bonds are formen on sulphur

In this unit we will discuss various types of cycloaddition and sigmatropic reactions, their
explanations by different methods alonwith their selection rules. The chelotropic and dipolar
reactions will be discussed in this unit.

10.2 ANTARAFACIAL AND SUPRAFACIAL ADDITIONS

The cycloaddition reactions are caterogised with respect to three facts of the reactions:

1. The number of electrons of each unit participating in cycloaddition

2. The nature of orbitals undergoing change (π or σ ) and

3. The sytereochemical mode of addition [ supra (s)/syn or antara(a), anti ]

The stereochemical mode is generally given by subscript s or a, which reavels whether the
addition occurs in supra or antara mode on each unit. A cycloaddition may occur either
across the similar face or across the opposite faces of the planes in each reacting
component.If the reaction takes place across the same face of a π-system, the reaction is said
to be suprafacial with respect to that π- system. It is nothing than a syn addition.

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4s

2s

both the lobes are above the plane of the molecule

or both the lobs are in same plane, hence
suprafacial (a) 4 s + 2 s cycloaddition reaction

This reactioncan also be represented as follow

attack on the
same face of
the molecule
+
supra

If the reaction takes place across the opposite face of a π- system, it is said to be antarafacial
(a)

4s

2s

suprafacial hence 2 s
antarafacial
hence 4 a 4a + 2s cycloaddition reaction

This reaction can also be represented as:

antara
+

4a + 2 s

supra

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antara

antara
or +
antara
4 a + 2a

4a + 2 a cycloaddition
antara

In antarafacial, attack takes place with one bond forming to one surface but other bond
forming to other surface. It is rare, it dose not occur in any reaction. Almost all cycloaddition
reactions are suprafacial on both components.

R R

R R + R R
+

H H R1 R1 R1 R1

R1 R1

10.3 CYCLOADDITION IN 4n AND [4n + 2 ]π SYSTEM

In 4π electron system there are [2 + 2] cycloaddition of two ethylene molecules.Like
electrocyclic reactions the cycloaddition reactions viz; [2 + 2] and [4 + 2] cycloaddition
reactions can be interpreted by different merhods like correlation diagram, FMO and PMO
methods.

1. Orbital symmetry in cycloaddition reaction: correlation diagram: To illustrate the contrl

of orbital symmetry on cycloaddition reactions, we choose the example [2 + 2] cycloaddition
in which two ethylene molecules approach each other vertically to form a molecule of
cyclobutane. Such a system has vertical and horizontal plane of symmetry which is referred
to as 1 and 2 respectively.

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Fig. 1 Symmetry properties of interacting ethylene π-orbitals and cyclobutane σ-orbitals.

In above transformation we are concerned with the four π orbitals of two ethylene molecules
and four orbitals of cyclobutane. Since the symmetry properties of the remaining orbitals
remain unchanged during the reaction hence are not to be considered. The symmetry
classification mentioned are with respect to plane of symmetry 1 and then 2. Based on the
above information as in fig.1 a correlation diagram for ethylene [2 + 2 ] cycloaddition can be
constructed,
1 1

2 + 2 2 2

1 1
ethylene cyclobutane

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Table 1. Correlation diagram for cycloaddition and of ethylene-cyclobutane system

Symmetry properties of ethylenes Symmetry properties of cyclobutane

AA π4 AA σ4

AS π3 SA σ3

SA π2 AS σ2

SS π1 SS σ1

The examination of the diagram leads the following conclusions:

A. The S0 prbitals of ethylene correlate with an excited state (S1) of cyclobutane, π12 π12
σ12σ3* i.e. the combination of two ground state ethylene molecules cannot result in the
formation of ground state cyclobutane while conserving the orbital symmetry.Hence
thermal process is symmetry forbidden.

B. There is correlation between the first excited state of the ethylene system and
cyclobutane, π12 π1 π1* σ12σ2σ3* the photochemical process is symmetry allowed in
aconcerted manner.

Similarly correlation diagram may be constructed for [4 + 2] π cycloaddition (fig.2) viz; for
Diels – Alder reaction which is 4s + 2s cycloaddition.In this case there is only asingle
vertical plane of symmetry

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Fig. 2 correlation diagram for 4s + 2s cycloaddition (Diels-Alder reaction) and the reverse process

It is clear from above correlation diagram (fig. 2) that there is smooth transformation of the
reactant orbitals into the product orbitals. Again following conclusions can be drawn.

A. ψ12π12ψ22 = σ12σ22π22 i.e. the molecular orbital symmetries of ground states (S0) of
reactants (ethylene and 1,3-butadiene) correlate to the ground states(S0) of products
(cyclobutene). Hence the transformation of ethylene and butadiene 4s + 2s, (Deils-Alder
reaction) is thermally allowed process and takes place in a concerted manner.

B. ψ12π12ψ2ψ3 ≠ σ12σ22π1π2 i.e. the MOs symmetries of excited state ( S1) of reactant do not
correlate with S1 of product and there is symmetry imposed barrier to photochemical
reaction, Hence the 4s + 2s transformation is photochemically not allowed. The reaction
under irradiation will not take place by concerted manner.

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2. Frontier molecular orbital (FMO) method: The cycloaddition reactions can also be
explained by using FMO approach like in electrocyclic reaction. In this approach symmetry
properties of HOMO orbital of one reactant and LUMO of other reactant are to be
considered. A favourable interaction is possible only if the sign of the coefficient of HOMO
and LUMO are similar. In [2 +2] cycloaddition of CH2=CH2 to form cyclobutane, lobes of
HOMO in one molecule and LUMO of other molecules are not same, hence the conversion
of ethylene to cyclobutane under thermal activation is symmetry forbidden. However when
ethylene is irradiated, electron promotes to the antibonding π* orbital, which now becomes
HOMO orbital This orbital now interact with LUMO of the second unexcited ethylene
molecule. Since now the sign of coefficient of HOMO and LUMO orbital are similar. Hence
the interconversion of ethylene to cyclobutane system proceeds smoothly i.e. the reaction is
photochemically allowed (fig 2).

Fig.3 [2 + 2] cycloaddition of CH2=CH2 under thermal and hv condition by FMO method.

Similarly the Diels-Alder reaction may also be analysed of the molecular orbitals of ethylene and
butadiene [4n + 2] system.

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Fig. 4 [4 + 2] cycloaddition of CH2=CH2 and butadiene by thermal induction ( FMO method).

In above transformation the HOMO of one reactant butadiene when intreact with the LUMO
of other reactant ethylene or vise-versa, the sign of coefficient of HOMO-LUMO are same.
Hence this transformation is symmetry allowed in ground state and is thermally allowed
(fig.4).

However when butadiene is irradiated then ᴪ3 orbitals becomes HOMO because of the
promotion of electron from ᴪ2 orbital or if ethylene is irradiated, π*/ ᴪ2 becomes HOMO.
Now according to FMO approach HOMO of one (butadiene/ethylene) intract with LUMO of
other (ethylene/butadiene), the sign of coefficient of HOMO-LUMO do not intract through
bonding intraction. The process is thus photochemically symmetry forbidden and can not
take place by concerted manner (fig5).

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ii Photochemical(hv) induction
hv excited C2 symmetry

4 hv excited C symmetry
LUMO 2
M symmetry C2 symmetry
M symmetry
pi* LUMO
3 HOMO
LUMO
HOMO
hv
hv

2 HOMO pi HOMO
C2 symmetry
hv excited
Dienophile
1

Dienophile
Diene hv excited
Diene

Photochemically excited Diene

Diene non excited state

HOMO M symmetry
non bonding LUMO M symmetry
LUMO C2 symmetry Or
non bonding Bonding interaction

Dienophile non excited state HOMO C2 symmetry

Photochemically excited Dienophile

Phase wrong for overlap Diels Alder reaction hence the reaction is photochemically forbidden

1= ᴪ1, 2= ᴪ2, 3= ᴪ3, 4= ᴪ4 and pi* = π*/ ᴪ1, pi = π/ ᴪ

Fig. 5[4 + 2] cycloaddition of CH2=CH2 and butadiene by hv(photochemical) induction ( FMO

method).

An intresting example of the role of FMO is determining the product is the Diels-Alder
reaction of cyclopentdiene forming dicyclopentadiene. In this reaction endo product is
formed rather than exo because of the favourable secondary forces which lowers the energy
of the transition state. In exo product the secondary interactions are absent. Thus the endo
transition state for the reaction is stabilized vis-à-vis the exo and therefore the endo attack
should be favoured. However in some cases the steric factors may be of greater magnitude
than this effect (fig.6).

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HOMO
secondary interactions

LUMO
endo dicyclopentadiene dimer

HOMO

LUMO
exo dicyclopentadiene dimer

Fig.6. Orbital interaction in Diels-Alder reaction of cyclopentadiene by FMO approach.

The cycloaddition reactions can be summarized in tabular for their selection rules table 2

Table 2: Selection rules for cycloaddition reactions

m + n electrons Mode ofactivation Allowed stereochemistry

4n Photochemical supra-supra

4n Thermal supra- antara

4n + 2 Thermal supra- supra

4n + 2 Photochemical supra- antara

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3. Perturbation of molecular orbital (PMO) approach: The alternative mode for the
explanation of cycloaddition reaction is PMO method which is based on the concept of
aromaticity as discussed in electrocyclic reaction in unit 9. This system is also known as
Huckel- Mobius (H-M) system. According to this system if system has no node then it is
called Huckel system and array is called Huckel array. Similarly if system has node it is
called Mobius system and array is called Mobius array. Use of above concepts to
cycloaddition reactions led to the generalization that thermal reactions take place via
aromatic transition state whereas photochemical reactions proceed via antiaromatic
transition state (fig. 7)
i 2+ 2 Cycloaddition reaction

2s
2a + 2 a 2 s + 2a
2 s+ 2s or

2s

4 n electrons,zero nodes; Huckel system zero nodes; Huckel system 4 n electrons, one nodes; Mobius system
4 n electrons,
antiaromatic; hv allowed aromatic; thermally allowed
antiaromatic; hv allowed

ii 4+ 2 Cycloaddition reaction

4 s
4 s
4 s+ 2a
4 s+ 2s
Node
2 a
2s

6 n electrons, zero nodes; Huckel system 6 n electrons,one nodes; Mobius system

aromatic; thermally allowed antiaromatic; hv allowed

Fig 7 PMO approach for cycloaddition reactions

The PMO approach can also be summed up in table for cycloaddition reactions Table 3)

Table.3: Selection rules for cycloaddition by PMO approach

m+n Number of Aromaticity Thermally Photochemically

electrons nodes allowed allowed

4n Zero Antiaromatic - supra-supra

antara-antara

4n One Aromatic supra-antara -

antara-supra

4n + 2 Zero Aromatic supra-supra -

antara-antara

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4n + 2 One Antiaromatic - supra-antara

antara-supra

10.4 2+2 CYCLOADDITION OF KETENES

The reaction of ketene with olefinic compound (alkene) shows some characteristics of pericyclic
cycloaddition. The reaction is syn addition and geometry of reactant is maintained in the product.
H
H O O
+ C 0
25 C
H Cl
Cl Cl
H Cl
cis k eten e b o th h y d ro g en s are cis
O H
H C 0 O
+ 25
Cl
H Cl Cl
tran s k eten e
H Cl
b o th h y d ro g en s are tran s

In above reactions stereochemistry of the reactant is sustained in the product.These two reactions
are pericyclic [ 2 +2 ] cycloaddition and thermally allowed reactions. It is known to us that [
2+ 2] cycloaddition is photochemical reaction and suprafacial- suprafacial. If reaction is
thermally allowed then reaction should be suprafacial-antarafacial reaction i. e. [ π 2s + π
2a]cycloaddition (table 3)

Two molecules approach each other at right angle for overlapping in an antarafacial sense of
the ketene. Making the reaction the allowed [π 2s + 2πa] cycloaddition that we have
dismissed as being unreasonable. This is the simplest explanation. The [2 + 2]
cycloadditions of ketenes being concerted is more likely to be a consequence of the fact that
ketenes have two sets of π orbitals at right angle to each other and overlap can developed to
orthogonal orbitals (dashed lines) and in addition there is transmission of information from
one orbital to its orthogonal neighbor (heavy line) (fig.8)

Fig. 8 overlapping orbitals of ketene and alkene

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The vision identifies the reaction as an allowed [ π 2s +π 2a +π 2S] cycloaddition reaction.

The FMO approach exhibit that the bond formation between C-1 and C-1’ develops mainly
from the interaction of the LUMO of ketene (π* of C=O) and HOMO of alkene and that the
bond between C-2 and C-2’ develops mainly from the interaction of HOMO ketene [ᴪ2 ] the
three atom linear set of orbitals analogous to the allyl anion] and LUMO of the alkene
(fig.9).
- + 2 - +
1 1
C ketene ketene
O C O C C2
+ -
+
- antarafacial
LUMO suprafacial
- - HOMO + -
1' 2' 1' 2'
+ + alkene - + alkene
HOMO LUMO
Fig .9 Bond formation between C-1 of keten and C-1’ of alkene and between C-2 of ketene and C-2’
of alkene

The reaction can br represented as follow:

H H R
H H H H
C C C H
H H H
C C O C C O C C O
CH3CH2O CH3CH2O CH3CH2O H O
C C
H R C CH3CH2O
H R H R

10.5 CHELOTROPIC REACTIONS:

As also discussed in section 10.1 introduction part of this unit the,chelotropic reactions are
those reactions in which either two σ-bonds are formed or broken on same atom, viz trapping
reactions of carbenes with alkenes.
alkene
H3C CH3 CH3
H3C
C C
H + H H H
C
CH2 H H
carbene
two sigma bonds are formed on the carbon of carbene in product

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10.5.1 [2 + 2] Chelotropic cycloaddition:

Chelotropic reaction of alkenes with singlet carbine can be considered here for [2 + 2]
chelotropic cycloaddition reaction. In this reaction alkene reacts with carbine to form
cyclopropane or substituted cyclopropane. The reaction is highly stereospecific in nature
while reacting with singlet carbenes. The reaction is thermally allowed.
cis alkene
trans alkene
H3C CH3 H3C CH3
H3C H H
C C H3C
+ H H C C
H H +
H CH3 H CH3
C
H H C
CH2 CH2 H
H
singlet carbene cis product singlet carbene trans product
The above reaction is pericyclic type and is concerted in nature. Examination of MOs
properties of carbine shows that a bonding interaction between HOMO of a carbine and
LUMO of an alkene or vise-versa is possible.

Carbon in signlet carbine is sp2 hybridised and having three sp2 hybrid orbitals and one
empty p-orbital which is perpendicular to the plane defined by the carbon atom and the two
substituents on it. Among three sp2 hybrid orbitals two are bonding and one is non- bonding
having two electrons in it (fig.10).
empty orbital, LUMO of carbene

R +
_ 2
C + sp hybrid orbitail accomodating both electrons
with opposit spin, it is HOMO of carbene
_
R
Fig. 10. Molecular orbital diagram of singlet carbene

The cycloaddition of carbine carbine and alkene is [ 2 + 2 ] cycloaddition reaction. This

reaction is possible only if the carbine approaches the alkene sideways so that the plane
defined by the carbon atom and its two substituents parallels the plane of the alkene. In this
orientation, the empty p- orbital of the carbine pointing towards the electrons of the π-bond
of alkene (fig 11).
H + + H
HOMO of an alkene
_ _
H3C CH3
R _ bonding interaction

_
C +
empty orbital, LUMO of carbene
R +

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H +
_ H
LUMO of alkene (suprafacial)
_
H3 C + CH3
bonding interaction bonding interaction
R _
_
_C + HOMO of carbene (antarafacial)

R +

Fig 11 interaction beween HOMO of alkene and LUMO carbine and vise-versa

Chelotropic reaction of carbine with alkene (trapping reaction) is [2 + 2] cycloaddition. As

per the explanation in fig 11 above chelotropic reaction of carbine with alkene is symmetry
forbidden if both the reactant interact suprafacially Antarafacial reaction of alkene is very
unlike thus the reaction is likely to involved the CH2 antarafacial.

Chelotropic reaction of alkene with SO2 can also be explained in similar fashion as above
for carben and alkene.

LUMO of SO2 O

O
HOMO of SO2
Molecular orbital diagram of SO2

LUMO of alkene (suprafacial)

bonding interaction O
bonding interaction
S HOMO of SO2 (antarafacial)

O
Interaction of MOs of alkene and SO2 (HOMO LUMO interaction)

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10.6 1,3-DIPOLAR CYCLOADDITIONS

The 1,3 –dipolar cycloaddition reactions are analogous to Diels-Alder reaction in which a
1,3-dipole react with a dipolarophile to form a five membered ring. The 1,3-dipolar
cycloadditions were described in the late 19th century to the early 20th century, following
the discovery of 1,3-dipoles. Mechanism and synthetic application of these reactions were ,
primarily established by Rolf Huisgen in 1960 . Thus, the reaction is also designated as
Huisgen cycloaddition.

There were two proposals that describe the mechanism of the 1,3-dipolar cycloaddition:
first, the concerted pericyclic cycloaddition as developed by Rolf Huisgen in 1963 and the
second, was stepwise mechanism which involved diradical intermediate. This mechanism
was, proposed by Firestone in 1968. The former proposal is generally accepted. The 1,3-
dipole reacts with the dipolarophile in a concerted and symmetry-allowed π4s + π2s fashion
through a thermal six-electron Huckel aromatic transition state. Although, there are few
examples of stepwise mechanism of the catalyst free 1,3-dipolar cycloaddition reactions for
thiocarbonyl ylides and nitrile oxides.

1, 3 dipole

pi 4 s
b b b
a c a a
c c
+
e e
d d
d e pi 2 s

dipolarophile pericyclic concerted step

six electron Huckel aromatic transition state

symmetry allowed under thermal condition
The 1,3–dipolar molecule are isoelectronic and with the allylcarbanion and have four
electrons in a π system. All 1,3- dipoles contain 4π(pi) electrons in three parallel p-orbitals of
a, b and c. Stereochemically the reaction are syn addition analogous to Diels-Alder
cycloaddition reaction.
b
a c
1, 3 dipole

a. a has six electrons in its orbit. b has its complete octet having at least one lone pair of
electron. c has its complete octect having negative charge.

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b. a may be C, O or N b may be N or O and c may be C, O or N

c. If b is N then it has single or double bond. If b is o then it has single bond only.

Few 1, 3 –dipolar species are given here in table 4.

Table 4 Name and structures of some 1, 3 –dipoles

Name of dipolar compounds structures Name of dipolar compounds structures

azoxy compounds N N O N N O nitrones C N O C N O

azomethyne imines C N N C N N
nitrosoxides N O O N O O

nitrous oxide N N O N N O azomethane ylides C N C C N C

carbonyl oxides O O O O O O
azimines N N N N N N

ozone O O O O O O
nitro compounds O N O O N O
nitrile oxide C N O C N O
carbonyl imines C O N C O N
nitrile imine C N N C N N

N N C carbonyl imides C O C C O C
diazoalkenes N N C

nitrosimines N O N N O N nitrile ylide C N C C N C

azides N N N N N N carbonyl ylides C O C C O C

The dipolarophile are alkenes, alkynes, imines, nitriles and carbonyl compounds. The steric
and electronic factors play a role in determining the regioselectivity of the addition. The
justified explanation is based on FMO concept. The HOMO- LUMO interaction of 1, 3-
dipole and dipolarophile take place. In most of the dipolar addition LUMO of the
dipolarophile intracts with the HOMO of the 1, 3 –dipole. However in certain cases the
condition is reversed. 1, 3- dipolar species has three p- orbitals with four electrons hence
HOMO will be π2 or ᴪ2 which has C2-symmetry. For example say the dipole is
diazomethane. Its HOMO will be π2 or ᴪ2 and suppose the dipolarophile is ethylene, its
LUMO will be π* or ᴪ2 . The cycloaddition between these two species by concerted manner
well be as follow (fig. 12).

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3 antibonding

pi*

E
2 nonbonding HOMO of dipole
LUMO of dipolarophile

1 bonding

N N
CH2 N CH2 N
+

CH2=CH2
N
HOMO of dipole 2

+
N
H2C N
pi*
LUMO of dipolarophile CH2 CH2

CH2=CH2
1 = ᴪ1 , 2 = ᴪ2 , 3 = ᴪ3, pi* = π*

Fig. 12. Concerted cycloaddition reactions of 1,3-dipoar and dipolarophile.

Some of the dipoles are stablecompounds like O3, diazomethane and suitably substituted
azides, nitrones and nitrile oxides. Others like ylides, imines and carbonyl oxides are
reactive intermediates. In most reactions the 1, 3 –dipole is not isolated but generated in situ
in the presence of the dipolarophile.viz;:

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H 3C CH 3 CH 3
O H 3C O
C C
O O
C +
O C
H 3C CH 3 O
H 3C CH 3

O ozonoid of alkene [ 4 + 2 ]
O cycloaddition product
H O H
N N
+ N N
H N N
H

CH 2 trazoline
CH CH 2
N tautomierzation N H
+
N
N N
N

CHO

CH 3 NHOH / C 6 H 5 CH=CH 2
N CH 3
heat O

mechanism product [A]

CHO
CH N O CH N O

+ CH 3 NHOH CH 3 CH 3
_H O
2

_
CH N O N _ methyl C phenyl nitrone
CH 3 + C 6 H 5 CH=CH 2 product [A]

All the reactions explained above have six electrons in the T.S. In some reactions more than
six electrons take part in cyclic T.S. during concerted reaction of cycloaddition The common
example are [ 8+ 2 ] and [ 6 + 4 ] cycloadditions.

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5 10
6 5 6
7
4 9
4 8
+
3 8
3 9
2 1 7 2 10
1

[6 + 4 ] cycloaddition O

0
+ O 25 C

[6 + 4 ] cycloaddition

O O
N C OCH3 N C OCH3
+
N C OCH3
N C OCH3
O
O
[8 + 2 ] cycloaddition

COOCl
COOCl 0
+ 4 C
COOCl
COOCl

[ 8 + 2 ] cycloaddition

10.7 SIGMATROPIC REACTIONS/REARRANGEMENT

As discussed in 10.1 many thermal or photochemical reactions of olefinic compounds
involve shift of a σ- bond from one position to the other position of π-electron system. Such
reactions take place by concerted manner and known as sigmatropic reactions. The
sigmatropic reactions are caterogised bya double numbering system termed as i, j or m, n
which refers to the relative positions of theatom or group involved in the migration or shift.
This classification is different from cycloaddition where it is bases on the number of π-
electrons involved in the T.S. This classification in sigmatropic reactions can be well
understood by following example.

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1 2
CH 2 CH 2 CH 2 CH 3 CH 2 CH CH 2
1, 3 shift
CH 2 CH CH CH 2 CH 2 CH 2 CH 3
1 2 3 2

For easy understanding in sigmatropic rearrangement reaction the substrate can be divided in
two parts. The alkenyl or polyalkenyl chain and, the migrating atom/group. The alkenyl chain
should have at least one allylic group for concerted sigmatropic rearrangement as follow.

1 2
CH2 CH2 CH2 CH3 migrating group

CH2 CH CH2 alkenyl chain

1 2 3

allylic carbon of alkenyl chain

The numbering in both migrating group and alkenyl chain is done separately. In alkenyl
chain numbering is started from the allylic carbon which is numbered as 1. In migrating
group the atom (H, C or hetero atom) directly bonded with allylic carbon by σ-bond is
always numbered as 1 viz;

1
1 2 allylic carbon
migrating group CH CH2 CH2 CH3 1 CH2 2
2 migrating group O CH
CH2 CH CH
3 2
1 2 CH2
2
allylic carbon 3

As discussed above the sigmatropic reactions are named as i, j or m, n as in case of the

following example atom -1 of the migrating group shift on the atom-3 of the alkenyle chain.
Hence theclassification is mentioned as [1, 3] sigmatropic rearrangement.

Where 1, 3 (i. e. i, j) i or m = 1 and j or n = 3 similarly in second example i or m= 1 and j or

n=7

1 2
CH2 CH2 CH2 CH3 CH2 CH CH2
1, 3 shift
CH2 CH CH CH2 CH2 CH2 CH3
1 2 3 2

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migrating group
1
H H
1, 7
CH2 CH CH CH CH CH CD2 CH2 CH CH CH CH CH CD2
1 2 3 4 5 6 7 shift
alkenyle chain
allylic carbon

It is not always the first atom of the migrating group shift to the alkenyl chain in the
rearrangement viz;
2 2
3 CD3 migrating group 3 CD3 CD3
1 1 4
3, 3

shift
1 3 alkenyle chain 1 3
2 2
allylic carbon

In this rearrangement atom m=3 of the migrating group shift to atom n= 3 of the alkenyl
chain hence this rearrangement is an example of [3, 3] sigmatropic shift. Based on this fact.
The sigmatropic rearrangement can be categorized in two different classes.

1. The rearrangements in which the migrating atom or group is attached via the same atom
in both reactant and product

2. Those reactions in which the migrating atom or group is bonded through different atoms
in reactant and in product

3
3 2 4
1, 3 1, 5
2
D
1 D
1 1 5
R R
1
D is bonded to carbon both in R is bonded to carbon both in
reactant and product reactant and product
a lly lic c a rb o n a tta c h e d w ith O a lly lic c a rb o n a tta c h e d w ith O

a lly lic c a rb o n a tta c h e d w ith C a lly lic c a rb o n a tta c h e d w ith C

1
2
1O
O 2
H 1 3
2
3 3, 3 O 3, 3
O
sh ift 1 3 s h ift
2

c a rb o n o f a lly lic g ro u p is b o n d e d to o x y g e n in th e re a c ta n t a n d c a rb o n in th e p ro d u c t

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10.7.1 Explanation of [1, 3] and [1, 5] sigmatropic shift:

It is generally argued that the [1, 3] sigmatropic shift requires short path than the [1,5] shift.
It is also assumed that [1, 3] shift are induced photochemically while [1, 5] are by thermally.
FMO approach can be used to explain and analyse these reactions.Let us start with the
following thermally induced [1, 3] sigmatropic rearrangement.
1 H
heat
CH2 CH CH R CH2 CH CH2 R
1 2 3 1, 3 shift

In order to analyse the orbitals, it is presumed that the σ-bond connecting the migrating group
undergo hemolytic fission to produce free radicals.
1 H H
homolytic cleavage
CH2 CH CH R CH2 CH CH R
1 2 3
allyl free radical

The product of the hypothetical fission is hydrogen atom and an allyl free radical, which
contain three p-orbitals. The symmetry oroporties of these orbitals are following (fig.13)

H = Migrate from the same face or opposite face i.e. migration may suprafacial or antarafacial

E Overlapping bonding Overlapping antibonding

3
H H

2 T.S.
In C H bond overlapping Symmetry forbidden
HOM O
lobes are of the same sign (phase incorrect for overlapping)

MOs of allyl free radical

large distance Similar faces

H
H
B

Overlapping is bonding symmetry allowed process

but geometrically forbidden because of large distance
between two similar lobes and small size of H atom

1= ᴪ1, 2= ᴪ2, 3= ᴪ3

Fig 13. Aanlysis of [1,3] sigmatropic rearrangement A suprafacial B antarafacial migration

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In case A the migrating group remains on the same side of the π-orbital system. It is called
suprafacial migration. In thermal [1,3] sigmatropic shift a suprafacial migration is
geometrically feasible but symmetry forbidden. In case B (fig.12) a symmetry allowed [1,3]
sigmatropic shift to occur. The migrating group must shift by antarafacial process.However
the symmetry allowed [1,3] antarafacial sigmatropic rearrangement of hydrogen is not
geometrically favourable because the 1s orbital is smallest and cannot effectively span the
distance required for antarafacial shift. Alternatively the size of 1s orbital of H is smallest and
distance between two lobes of interacting p-orbitals of carbon is maximum hence 1s-orbital
cannot intrect effectively with p-orbitals at same time in the formation of T.S.

[1, 3]-sigmatropic shift take place in presence of UV-light but examples are rare. Let us
obserb again wht happen when a molecule absorb photon. The electron from ᴪ2 promot to ᴪ3
which now becomes HOMO of excited state known as photochemical HOMO. In this
reaction the suprafacial migration in ᴪ3, the HOMO and reaction is feasible (fig.14)

E p h o to c h e m ic a l
E
3 LUM O 3 HOMO
hv

2 2
HOMO

1 1

M O s o f a lly l f r e e r a d ic a l M O s o f a lly l fre e ra d ic a l

3
3

p h o to c h e m ic a l H O M O
p h o to c h e m ic a l H O M O
e a s y s u p r a f a c ia l m ig r a tio n
(p h o to c h e m ic a l re a c tio n )

2 H O M O g ro u n d s t a te

2
H O M O g ro u n d s t a te

a n ta ra fa c i a l m o d e is r e q u ir e d fo r t h e rm a l re a c t io n

1= ᴪ1, 2= ᴪ2, 3= ᴪ3

Fig. 14.[1,3] suprafacial migration is possible in 3= ᴪ3 and antrafacial in 2= ᴪ2 under

photochemical and thermal inductions

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In similar fashion [1,5] sigmatropic rearrangement can be explained. This reactionis feasible
thermally and forbidden photochemically through concerted manner (fig. 15).

5 5

4 4 HOMO
hv

3 HOMO 3

2 2

1 1

Pie MO of pentadienyl radical Thermally induced Photochemically excited state Photochemically induced

HOMO
HOMO
H
H
Thermal
hv

Suprafacial migration Antarafacial migration

symmetry allowed and symmetry allowed but
geomatrically feasible geometrically difficult
H H
T.S.
T.S.
1= ᴪ1, 2= ᴪ2, 3= ᴪ3, 4 = ᴪ4, 5= ᴪ5,

Fig. 15. MO symmetries of pentadienyl radical with thermal and photochemical [1, 5] migration.

10.8 SIGMATROPIC SHIFTS OF ALKYL GROUP

The shift of alkyl group during sigmatropic migration can also occur. If an alkyl group shifts
there is additional stereochemical feature to be taken into account. The shift can occur with

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retention(r) or inversion (i ) at the migrating centre. The allowed process includes the
suprafacial 1,3- shift with inversion and the suprafacial 1,5-shift with retention.

In comparasion to hydrogen atom which has its electron in 1s orbital has only one lobe while
carbon free radical has its odd electron in ap-orbutal having two lobes of opposite saign. The
imaginary T.S. show that if in place of H one has C then during athermal suprafacial [1,5]
process, symmetry can be conserved only provided the shift carbon in amanner that the lobe
which was origionally attached to the π-system remains attached to it(fig 15 A). The only
way for this happen is the retention of configuration within the migrating group. However, a
related [1, 3] thermal suprafacial would involve opposite lobes. Thus if the migrating carbon
was origionally bonded via its positive lobe, it must now use its negative lobe to form the
new C-C bond. The stereochemical outcome of such a process is the inversion of
configuration in the migrating group (fig 15 B)

1, 3

shift
R
1, 3 alkyl shift

A B

a thermal suprafacial [ 1 , 5 ] migration. a thermal suprafacial [ 1, 3 ] migration.

configuration is retained within the configuration in the migrating group will
migrating group be inverted

Fig 16. A [1, 5] and B [1, 3] thermal suprafacial migration of carbon (alkyl shift)
2
3
1
heat
C D
H 1,3 shift
AcO H
H H C H AcO
both H are trans D AcO H
cis

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In above reaction there is a [1,3] shift with inversion of configuration at the migratin
centre.This can be explained by orbital symmetry. The hemolytic cleavage takes place in
this reaction to as also discussed earlier. The bond between the alkyl system and the
migrating carbon stretches during T. S., the phase relationship between two bonded lobes is
mentioned as follow.The explanationcan be understand from following MOs representation
through FMO approach (fig 16)

stretch carbon carbon bond

developing two p orbital (H.F)

(homolytical fission) 3 1
bonding overlap
C D T.S
AcO D
AcO
3 1 3 1
A

D D
AcO
AcO
T.S symmetry forbidden, phase incorrect, geometrically feasible

3 1
B 1
3
further rotation
D
D and OAc are cis
AcO
D
T.S D AcO
AcO
Fig 16 B.Explanation for [1, 3 ] allylic shift with stereochemistry of the reaction.

The suprafacial/antarafacial shift in sigmatropic rearrangement can be summed in selection

rule for thermal and photochemical mode of activation (table 5).

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Table:5 Selection rule for [1 +n] in which migrating group is hydrogen

m+n Thermally allowed Photochemically allowed

Photochemically forbidden Thermally forbidden

4n antara supra

4n +2 supra antara

Table:5 Selection rule for [1 +n] in which migrating group is carbon

m + n Thermally allowed Photochemically allowed

4n ar sr

4n sr ai

4n +2 sr ar

4n +2 ai si

s= supra, a = antara, r= retention, i = inversion

10.9 HUCKEL-MOBIUS APPROACH IN SIGMATROPIC

REARRANGEMANT
PMO method or H-M methods as also discussed for electrocyclic and cycloaddition reaction
can be applied for sigmatropic rearrangements. According to this system, which is based on
the concept of aromaticity and antiaromaticity point no 3 section 10.3, the thermal
sigmatropic rearrangement take place through aromatic transition state whereas
photochemical sigmatropic rearrangement take place through antiaromatic transition state.
The moleculat orbital symmetries alongwith thermal and photochemical feasibility through
suprafacial and antarafacial under aromatic and antiraomatic system has been depicted in
fig.17 as under.

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PMO METHOD, HUCKEL MOBIUS SYSTEM

R
1 2 2
C CH CH2
R
1H H
Suprafacial 1,3, 4 electron
Zero node, Huckel system
Antiaromatic, hv allowed
[1, 3]Sigmatropic rearrangment

R
1 2
C CH CH2
3
R H
1H
Antrafacial 1,3 , 4 electron Node
One node, Mobius system
Aromatic, thermally allowed

R [ 1,5 ]
C CH CH CH CH2
R Suprafacial
H
H
Six electrons, zero node; aromatic
Huckel system; thermally allowed
[ 1,5] Sigmatropic rearrangment

R [ 1,5 ]
C CH CH CH CH2
R Antarafacial
H
H
Node
Six electrons, one zero node; antiaromatic
Mobius system; hv allowed

Fig.17. The Huckel-Mobius (PMO) approach for sigmatropic rearrangements

Finally based on above explanation the selection rules for sigmatropic rearrangement are summerised
in table 6.

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Table: 6 Selection ruls for sigmatropic rearrangement by H-M (PMO) method

No. of electrons involved No. of nodes Aromaticity Shift mode Mode of activation

4n zero aniaromatic supra photochemical

4n one aromatic antara thermal

4n + 2 zero aromatic supra thernal

4n + 2 one antiaromatic antara photochemical

10.10 [3, 3] SIGMATROPIC REARRANGEMENTS (COPE

REARRANGEMENT
The [3, 3] sigmatropic rearrangements are very important rearrangements, which involve
carbon-carbon bond. The thermal rearrangement of 1, 5 –diene by [3, 3] sigmatropic shift is
known as Cope rearrangement. The reaction takes place in thermodynamically favoured
direction as:-

(old) sigma bond both the end

2
numbered 1 2
3
1
1 3, 3 3

rearrangement
1 1
3
3 2
2
(fresh) sigma bond both the end
numbered 1
In above rearrangement the new sigma bond formed has 3, 3 relationship hence
thisrearrangement is called [3, 3 ] sigmatropic rearrangement or [3, 3 ] sigmatropic shift or
Cope rearrangement. Donor substituents at C-2, C-3, C-4 or C-5 accelerate the
rearrangement. Donor group at C-2 and C-3 have accelerating effect, which can be
rationalized in term of stabilization of T>S. by depecting their different effect on two
niteractiong system (fig. 18).

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X X X
Y 2 1 Y
3 Y
4
5
1, 4 diradical T.S.

X X
Y
Y

T.S.
two independent allyl radical
Fig.18. Rationalisation of [3,3] shift in 1,5- pentadiene system via concerted mechanism

The T.S. as above involve six electrons being converted from one 1,5-diene system to
another. The T.S. range from 1, 4-diradical to two nearly independent allyl radical depending
upon whether the bond making or bond breaking is more advanced. The general framework
for understanding the effect of substituents is that the the reaction are concerted with
relatively late T.S. with well developed C-1-C-6 bond (fig 18).

In case of Cope rearrangement the migrating group is allylic radical. An alalysis of symmetry
of MOs involved shows why this reaction is facile thermally but not observed commonly by
photochemical induction. As we break the C-(1) - C-(1) bond the phase of the overlapping
lobes must be the same. The HOMO of the allyl radical ᴪ2 and that information allows us to
fill the symmetries of the two allyl radicals making up of T.S. (fig 19).

2 2
1 3 1 3 3

1 3 1 3 3
2 2
T.S. migration of allyl radical

Fig 19. Bond breaking at C-(1)-C(1) and making at C-(3)-C(3) in allylic transformation during T.S.

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Reattachment the two C (3) position is allowed because the interation of the two lobes on
C(3) in bonding. If interaction is carried out in the presence of UV-light than one electron is
excited from HOMO to the LUMO which now become photochemically HOMO (fig. 20)

3
bonding interaction bonding interaction
symmetry allowed symmetry allowed
3

shi2 HOMO
3
hv symmetry forbidden
non bonding interaction
3

Photochemical HOMO shi3

shi2 = ᴪ2, shi3 = ᴪ3

Fig. 20 [3, 3] Cope rearrangement of allyl radical under thermal ahnd photochemical conditions

Stereochemically the Cope rearrangement procceds via the chair like T.S. gives the
following stereospecific product.This reaction has made [3, 3] shift valuable in
enantiospecific synthesis.

CH3 CH3 CH3

H H
CH3 H
heat CH3
CH3

meso form T.S. H

H H cis trans
H H H
CH3 CH3
CH3 CH3
heat CH3
CH3
trans trans H
T.S. H
H

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Unsaturated carbonyl compounds can be synthesized with the lelp of Cope rearrangement
viz; heating of 1,5-pentadiene-3-ol under go Cope rearrangement with the formation of
unsaturated carbonyl compounds.. The reaction is asselerated in presence of strong bas as
follow.

H O O
HO
heat

unsaturated carbonyl compound

enol
HO O O
heat 3, 3
KH

O
HO
O H2O/H+ tautomerism

product

10.11 CLAISEN RERRANGEMENT

The Claisen rearrangement was the first sigmatropic rearrangement which was discovered
by Rainer Ludwig Claisen in 1912. This reaction should not be confused with the Claisen
condensation. The Claisen rearrangement is a powerful carbon–carbon bond-forming
chemical reaction. The heating of an allyl vinyl ether without solvent rearrange to a product

called O-allylphenol. The formation of product is atwo step reaction. The first step is [3, 3]
sigmatropic rearrangement.
OH
O CH2 CH CH2
heat
CH2 CH CH2
3, 3

Mechanism: In order to conveniently understand the mechanism, the Claisen Rearrangement

can be explained in two steps.

The I-step is [3, 3] sigmatropic rearrangement as follow:

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migrating group

1 1 2 3 O CH2
O CH2 CH CH2 alkenyle chain CH
2
CH2
3
allyic carbon H

1
O 1
2 CH2 O CH2
[ 3, 3 ] sigmatropic shift
3 CH CH
2 CH2
H2C
3 H

In step II, the product simply undergo ionic proton transfer to regenerate aromaticity of the
phenyl ring.

O CH2 OH CH
hydrogen transfer 2
CH
CH
CH2
CH2
H

Claisen rearrangement is also given by allyl vinyl ether but in this reaction the
rearrangement is called aliphatic Claisen rearrangement or ClaiseniCope rearrangement.
These [3, 3] sigmatropic rearrangements take place by chair-like six membered T.S. as in
thecase of Cope rearrangement (section 10.10). The chair like T.S. to predict the
stereochemistry if any of the new double bond in the product.

1
O O
2 1 [ 3, 3] shift
3 2 heat
3

[ 3, 3] O O
O
shift
product

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10.12 [5 5] RARRANGEMENTS REACTION

Like [3,3] sigmatropicrearrangements, the Woodward-Hoffman rules predicted that [5,5]
sigmatropic shifts would proceed suprafacially, Huckel topology transition state. These
reactions are rarer than [3, 3] sigmatropic shifts, but this is mainly a function of the fact that
molecules that can undergo [5, 5] shifts are rarer than molecules that can undergo [3,3] shifts.

1
1 OH
2
O
2 3
3 4

4 5
5

1
1 2
OH
O O
2 3
[ 5, 5 ] shift
3 4

4 5
H
5

Similarly examples of [4.5] sigmatropic shift anf [9, 9] sigmatropic shift are available as
follow.

4 2 1 CH3
3 CH3
CH3 Ph N
Ph N NaOCH3 Ph N [4, 5 ] CH3
CH3 CH3
5 1 shift
3
4 2

CH3 CH3 CH3

sigmatropic rearrangement
quaternary ammonium ion
product

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1 NH NH
2 1 2 NH2 NH2
2 3
2
3
4
4
5 5 9, 9 shift
6
6 7
7
8
8
9 H
9

H2N NH2

product
Benzidine rearrangement is an example of [ 9, 9 ] sigmatropic rearrangement

10.13 AZA-COPE REARRANGEMENTS:

Like Cope rearrangement the aza-Cope rearrangement reactions are an examples of [3, 3]
rearrangement reactions. The only difference between Cope and aza Cope reaction is that the
aza cope reaction is a heteroatom version of the Cope rearrangement. In this reaction [3, 3]-
sigmatropic rearrangement shifts single and double bonds between two allylic components.
According to Woordward and Hoffmann the aza cope reactions takes place in concerted
manner via suprafacial mode. The first example of an aza-Cope rearrangement was the
cationic 2-aza-Cope Rearrangement, which takes place at temperatures 100-200 °C lower
than the Cope rearrangement due to the facile nature of the rearrangement. The facile nature
of this rearrangement is attributed both to the fact that the cationic 2-aza-Cope is inherently
thermoneutral, meaning there's no bias for the starting material or product, as well as to the
presence of the charged heteroatom in the molecule, which lowers the activation barrier(fig
21).

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2 2
3
1 3
1
[3 , 3 ] shift
1
3 1 3
2N 2N

cationic 2 aza com pound

2
2
1 3 1 aza cpoe 3
1
3 aza cpoe
1 NH NH
3 1 3
2 2
Fig. 21 [3, 3] aza-cope sigmatropic rearrangement

The aza-Cope rearrangements wer predicted by the Woodward-Hoffman rules to proceed

suprafacially. However, while never explicitly studied, Overman and coworkers have
hypothesized that, as with the base-catalyzed oxy-Cope rearrangement, the charged atom
distorts the sigmatropic rearrangement from a purely concerted reaction mechanism (as
expected in the Cope rearrangement), to one with partial diradical/dipolar character, due to
delocalization of the positive charge onto the allylic fragment, which weakens the allylic
bond. This results in a lowered activation barrier for bond breaking. Thus the cationic-aza-
Cope rearrangement proceeds more quickly than more concerted processes such as the Cope
rearrangement.

2
3
1

Vs
Vs
1 -
N 3 N
N
2

concerted T .S . dipolar T .S . diradical T .S .

10.14 FLUXIONAL TAUTOMERISM

Molecules that undergo rapid bond shift are called fluxional molecules. In fluxional
molecules their atoms are in a continual state of motion associated with rapid changes in
bonding. The rearrangement may involve either bond reorganization or atm/group migration,
In general fluxional molecules are a unique class of molecules with no permanent structure

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Almost all molecules are fluxional in certain respects, for example:bond rotations in many of
the organic compounds. A molecule is considered to be fluxional if it shows line broadening
in spectroscopic signature due to chemical exchange (which is beyond Heisenberg’s
uncertainity principle).

A few common features of fluxional molecules are;

Fluxional molecules behave differently at different temperatures
While interchanging between different conformations many intermediates and meta-
stable forms are reached
Fluxionality provides diversity in structure of a molecule.
The [3, 3] sigmatropic rearrangement in bullvalene interconvert identical forms of the
molecule is an example of fluxional molecule. Bullvalene may undergo 1209600 Cope
rearrangements and still maintain the same structure due to its fluxional nature.

many others

bullvalene: tricyclo [ 3, 3, 2, 0 ] deca 2,7 tricyclo

hv hv
+

C16H16 C10H10

The cycloocttetraene molecule undego dimerization to give a product which is afluxional molecule
(fig 22). The fluxional molecules behaves differently at different temperature,

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heat

3
1 2 dimer
O O

O
O

O
7 O
O O
6
4
5

Fig.22. Dimerization of cyclooctatetraene and further Diels Alder reaction with unsaturated ketones

Ladderane are an interesting class of compounds containing two or more fused cyclobutane
Rings. The name arises from the resemblance of a series of fused cyclobutane rings to a
ladder.A useful mechanism for synthesis for ladderanes involves[2 + 2]
photocycloadditions,which is a useful reaction for creating strained 4 membered rings.The
molecule 1 shown below belongs to ladderane polymer class. In a study it was shown that
shiftamer 2 is fluxional at room temperature and undergoes degenerate Cope rearrangement
to give rise to 2’, which is equivalent to 2. Continued indefinitely, the Cope rearrangement
process leads to a pair of double bonds running down the polymer chain running back and
forth along the polycyclo butane framework (Fig 23).

1 2

Fig. 23 Fluxional tautomerism in ladderaness

The phenomena of fluxionality appear to be rather more common in organic cations and
organometallic compounds. The fluxionality of the σ-bonded metal cyclopentadienide
involves migration.

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M
H
M H

H H M
M
H M

Fluxionality is most readly ascertained by means of NMR. Conversion of one structure into
other in fluxional molecule is known as valence tautomerism and isomers are known as
valence tautomers.

10.15 ENE REACTION

In pericyclic reaction groups or atoms transfer from one molecule to another. Such reactions
are called group transfer reactions. Ene reaction is one of the common group transfer
reaction. The ene reaction also known as the Alder-ene reaction), is a chemical reaction
which takes place between ene and enophile. An alkene with an allylic hydrogen is generally
called ene while a molecule with multiple bond is known as enophile.In ene reaction there is
a formation of new σ-bond with migration of the ene double bond and 1,5 hydrogen shift.

ene
ene: alkene, alkyne, arene , allene, C heteroatom bond
+
H H enophile: C=C, C=O, C=S,C=N,C C, O=O,N=N,C N etc
adduct
enophile

Ene component: Enes are π-bonded molecules containin at least one active hydrogen atom
at the allylic, α-position. Possible ene components include olefinic, acetylenic, allenic,
aromatic, cyclopropyl, and carbon-hetero bonds. Usually, the allylic hydrogen of allenic
components participates in ene reactions, but in the case of allenyl silanes, the allenic
hydrogen atom α to the silicon substituent is the one transferred, affording a silylalkyne.
Phenol can act as an ene component, for example in the reaction with dihydropyran, but high
temperatures are required (150–170 °C). Nonetheless, strained enes and fused small ring
systems undergo ene reactions at much lower temperatures. In addition, ene components
containing C=O, C=N and C=S bonds have been reported, but such cases are rare.

Enophile components: Enophiles are π-bonded molecules which have electron-withdrawing

substituents that lower significantly the LUMO of the π-bond. Possible enophiles contain
carbon-carbon multiple bonds (olefins, acetylenes, benzynes), carbon-hetero multiple bonds

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(C=O in the case of carbonyl-ene reactions, C=N, C=S, C≡P), hetero-hetero multiple bonds
(N=N, O=O, Si=Si, N=O, S=O), cumulene systems (N=S=O, N=S=N, C=C=O, C=C=S, SO2)
and charged π systems (C=N+, C=S+, C≡O+, C≡N+).

Mechanism: According toFMO approach the interaction takes place between HOMO of ene
and LUMO of enophile (fig 24).

HOMO of ene
ene bonding component
interaction allyl free radical
+
H H
bonding interaction
H
enophile LUMO of enophile
component

H
adduct

Fig.24 Concerted mechanism for the ene reaction

The energy of activation for ene reaction is greater than that of Diels-Alder reaction due to
this reason the ene reactions take place at higher temperature than Diels-Alser reaction

O O
0
200 C
+ O O
H H
O O
ene enophile adduct

O O
0
25 C
+ O O

O O
diene adduct
dienophile
Many ene reactions can be catalysed by Lewis acids like AlCl3 under mild conditions

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+ 2000 C
OCH3
OCH3
O H
O
0
25 C HC3CH2AlCl2 (Lewis acid)

OCH3
H
O
The ene reaction is reversible like Diels-Alder reaction

0
400 C
+
H
H
The enophile as also mentioned above can alo be heteroenophiles

CH COOC4H9 SnCl4 CH2Cl2 COOC4H9

+
N Ts 0
CH3CH2 H 0 C NHTs
CH3CH2
H CH2 OH

O
(CH3)2AlCl
CH2 + C H 0
CH2Cl2 25 C
H3C CH3

CH3 CH3

+
O
O
H singlet oxygen
O O H

Intramolecular ene reactions has great importance for the synthesis ofcyclic compounds
particularly five membered ring compounds from 1, 6- diene and 1,8 and 7,10- dienes etc.

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4
5

3
8 6 heat H
2
H 7 H
1 CH3
1, 6 diene
1 CH3
H
O O
2 O
0
3 6 7 300 C
4 5
8 enolization

1, 8 alkadiene

O O H O O H
CH3
1
C O
2
3 0
8 10 350C
4 7
11 enolisation
5 9
6

7, 9 alkadiene

10.16 SUMMARY
In continuation to electrocyclic reaction in unit 9 this unit describes cycloaddition in 4n and
4n +2 systems, their explanation by using correlation diagram, FMO and PMO approach.
Sigmatropic rearrangements in various systems like [1, 3], [1, 5], [1, 7], [3, 3], [5, 5] system
have been described with their mechanism. Chelotropic reaction in which two σ-bonds are
either formed or broken at the same atom has been narrated with mechanism. This unit also
explains sigmatropic shift of alkyl group, mechanism of Cope rearrangement, Claisen
rearrangement, Aza-Cope rearrangement, fluxional tautomerism with example, mechanism
and applications. Ene reactions, the important class of reactions for synthesis point of view
has been explained in detail.

10.17 TERMINAL QUESTIONS

Q.1 Tick the correct opetion (MCQ):-

i Which one an example of chelotropic reaction?

A. Alkene + carbine

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B. Alkene + phenol

C. Alkene + ketone

D. Ene + diene

ii What [A] in the following reaction?

O
hv
+ C6H5 C C6H5 [A]
O

Ph Ph Ph
Ph
O O
A. B.
O O
Ph
Ph Ph
O O
C. D.
Ph
O O

iii. The process followed by following reaction is:

COOEt
C COOEt hv
+ COOEt
N C COOEt
N
H
H

A. [2 + 2] cycloaddition followed by sigmatropic rearrangement

B. [2 + 2] cycloaddition followed by another [2 + 2] cycloaddition
C. [2 +2] cycloaddition followed by electrocyclic reaction
D. [2 +2] cycloaddition reaction only
iv Aza-Cope rearrangement follow
A. sigmatropic rearrangement followed by elimination
B. [5, 5] group transfer reaction
C. [1,7] sigmatropic shift
D. [3, 3] sigmatropic rearrangement

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v . The chief product in the following thermal product will be ?

C COOEt heat
O + Product
C COOEt

O COOEt
COOEt O COOEt
A. B.

COOEt

COOEt
O
C. COOEt
D.
COOEt
COOEt

vi. Which condition favour the sigmatropic shift of 4n +2 system via suprafacial shift under
thermal condition?

A. 4n + 2, number of electrons, with zero node and antiaromatic character

B. 4n +2, number of electrons with one node and aromatic character

C. 4n +2, number of electrons with zero node and aromatic character

D. None of them

vii The following reaction is an example of:

O O

hv

A. [ [3, 3] shift

B. [2 + 2] cycloaddition

C. [3, 4] sigmatropic shift

D. Electrocyclic ring closing

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viii. Trapping reaction of alkene with carbine gives.

A. Chelotropic reaction

B. Sigmatropic reaction

C. 1,3-dipolar reaction

D. It is simply fluxional change

ix. The following reaction takes place through:

CH3

C6H5CH CH2 heat

CH3CHO + C6H5NHOH +
N C6H5
H5C6 O
A. Elimination of CO2 followed by addition of C6H5=CH2 with the generated 1,3-dipole

B. Elimination of H2O followed by addition of C6H5=CH2 with the generated 1,3-dipole

C. Elimination of H2O followed cycloaddition reaction.

D. Elimination of CO2 chelotropic addition

x. In sigmatropic reartrangement

A. A sigma bond migrate from one place to the other place of compound containing pi-bond

B. Transfer of pi-bond

C. Formation of pi-bond and sigma bond durin cyclization

D. Addition of functional group to pi-system

Q.2. What do you understand by cycloaddition reaction ? Discuss various approaches to

exaplain cycloaddition reactions

Q.3. What are chelotropic reaction? Discuss maechanism of chelotropic reaction following
FMO approach

Q.4. What are dipolar reactions? Discuss their importance in organic chemistry

Q.5. Write short notes on:

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1. Fluxional tautomerism

2. Ene reaction

3. Aza-Cope reaction

4. Claisen rearrangement

5. Cope rearrangement

Q.6. Complete the following reaction and discuss the type of reaction and mechanism.

heat
A. + C C O

hv
B

heat
+ CHCOOCH3
C.
CH2

H C6H5 CH2 CH CH2OH

D. C N
O heat
H5C6

10.18. ANSWERS (MCQ) TERMINAL QUESTIONS

iA

ii B

iii C

iv D

vD

vi C

vii B

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viii A

ix B

x. A

10.19. REFERENCES
1. Singh, J and Singh,J. Phptochemistry and pericyclic reactions 2004, 1-26, New Age
International (P) Limited, Publisher, New Delhi, India
2. Singh, J and Yadav, L.D.S, Advanced organic chemistry 2004, Pragati Prakashan,
Meerut. 336-379.
3. Mukherji, S.M., Singh, S.P. and Kapoor, R.P. 1998, 978-1006, New Age International
(P) Limited, Publisher, New Delhi, India
4. Huisgen, Rolf (1963). "1.3-Dipolare Cycloadditionen Ruckschau und Ausblick"
(abstract). Angewandte Chemie. 75: 604–637. doi:10.1002/ange.19630751304
5. Huisgen, Rolf (November 1963). "Kinetics and Mechanism of 1,3-Dipolar
Cycloadditions". Angewandte Chemie International Edition. 2 (11): 633–645.
doi:10.1002/anie.196306331.
6. Fireston, R (1968). "Mechanism of 1,3-dipolar cycloadditions". Journal of Organic
Chemistry. 33: 2285–2290. doi:10.1021/jo01270a023
7. Miller, Bernard. Advanced Organic Chemistry. 2nd Ed. Upper Saddle River: Pearson
Prentice Hall. 2004. ISBN 0-13-065588-0
8. Paderes, G. D.; Jorgensen, W. L. (1992). "Computer-assisted mechanistic evaluation
of organic reactions. 20. Ene and retro-ene chemistry". J. Org. Chem. 57 (6): 1904.
doi:10.1021/jo00032a054. and references therein.

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