Types of organic reactions

Objectives
The main objectives of the topic are
 to provide a basic foundation of the general organic reactions.
 to place the different mechanisms associated with the different
reaction types.
 to impart the stereochemistry associated with the different types of
reactions.
 to encourage enterprising research in organic chemistry.

Summary
The study of reactions and relevant synthetic applications of organic compounds
concernswith the development of powerful and useful reactions, inventionof
strategies for the construction of defined target molecules.To pursue the
objectives general organic reactions are grouped together into some categories
based on their kinetic and dynamic characters. The general groups are
substitution, addition, elimination and rearrangement reaction. Further each
group may be subdivided on the basis of the reactive intermediates involved or
the nature of the reaction center. Different types of the reactions are
accompanied by different stereochemical outcome also.

TEXT
Introduction:

There are millions of reactions involving naturally occurring as well as synthetic

organic molecules. It is very difficult to learn and understand each and every
reaction if they are treated and analyzed as unique and isolated process.Using
certain generalized basic principles such vast organic reactions can be woven
together and fitted neatly into general patterns. Based mainly on the functional
groups, electron rich sites, electron deficient sites and weak polar bonds of the
molecules, organic reactions may be categorized into four general types:
Substitution reaction, Addition reaction, Elimination reaction and rearrangement
reaction. In substitution reactions an atom or group bonded to a carbon atom of
the reactant molecule is replaced by a new atom or group. In an elimination
reaction two atoms or groups are removed from the reactant molecule to form
the product. Substitution and elimination take place side by side in a
competitive pattern. Addition reactions two reactant molecules or reactant
molecule and reagent add together to form a single product without leaving out
any other part.In rearrangement reactions there is reorganization of bonds along
with atoms and groups of the reactant molecule to give a new compound.

Organic reactions:
Enterprises in chemical synthesis concernwith the development of powerful and
useful reactions, inventionof strategies for the construction of defined target
molecules.So as to pursue the objectives general nature of the reactions
encountered with organic molecules should be thoroughly understood. Here one
must be familiar with two aspects:first the structure and representation of
organic molecules and secondly the descriptionof the reaction mechanism. From
static and dynamic aspects organic reactions may be classified into four general
categories mentioned below:
1. Substitution reactions
2. Addition reactions
3. Elimination reactions and
4. Rearrangement reactions
1. Substitution reactions
Substitution reactions involve the replacement of an atom or group of the
reactant molecule by a new atom or group.
For example,in the presence of diffused sunlight chlorine substitutes
hydrogen from methane to form chloromethane as product

On the basis of the mechanism involved or nature of the leaving and the
incomingatom / group, substitution reactions may be classified into the
following types:
(i) Nucleophilic substitution reactions
(ii)Electrophilic substitution reactions
(iii) Free radical substitution reactions
1.1Nucleophilic substitution reactions
Innucleophilic substitution reactions both the attacking atom/group and the
leaving atom/group are nucleophiles (ei. electron rich species). The attacking
atom or group comes with an electron pair and uses it to form a new sigma
bond while the leaving group moves away along with the bonding electron
pair.
This type of reactions occurs mainly in compounds with an electronegative
atom or group bonded to a sp3-hybridized carbon atom.Haloalkanes are a
good family of compounds that undergo nucleophilic substitution reactions
 with many different nucleophilic reagents. The halogen atom can easily go
away with the bonding electrons to be stable halide ions and are thus said to
be good leaving groups.

For example,
Hydrolysis of bromomethane with aqueous sodium hydroxideto
givemethanol is a nucleophilic substitution reaction. Here the leaving
group bromide ion at the sp3-hybridized carbon is substituted by the
attacking nucleophile, hydroxide ion of sodium hydroxide.

Based on the timing of bond formation and bond cleavage at such sp3
hybridized carbon atom, two main reaction types of nucleophilic substitution,
are available:
(i) 2reaction
(ii)1 reaction

2 reaction
The abbreviation2 stands for substitution nucleophilic bimolecular. The reaction
is characterized by
- a second order kinetics ei. its rate depends on the first power of the
concentration of both the substrate and reagent,

- a concerted single step mechanism passing through a transition state

without intermediate species formation. Partial bond formation and
partial bond cleavage take place in the transition state.

- stereospecificoutcome in the sense that different stereoisomers

undergoing the reaction give different stereoisomericforms of the
product. The incoming nucleophile attacks from a side opposite to the
leaving group and attaches to a position opposite to that the leaving
group was present. The backside attack turns the tetrahedral
configuration around the carbon centre inside out and it is said to
undergo inversion of configuration (often called Walden inversion).
When the reaction centre is a chiral carbon inversion of configuration
 around it in the product results in enantiomeric form. For example the
substitution of the bromine atom by hydroxide ion at the chiral carbon
with S-configuration of 2-bromobutane by 2 mechanism results in 2-
butanol with R- configuration at the chiral carbon.

Factors which favour2 reactions are

(a) strong nucleophiles
(b) good leaving group with polarizableand electronegative nature
(c) small groups with less steric hindrance around the reaction centre
(d) Polar aprotic solvents

1reactions
The abbreviation 1stands for substitution nucleophilicunimolecular. These
reactions are characterized by:
- a first order kinetics with respect to the substrate ei. its rate depends
on the first power of the concentration of only the substrate and
independent of the reagent. For example for hydrolysis of 2-bromo-2-
methylpropane with aqueous alkali is expressed as

- atwo-step mechanism in which the leaving group is releasedfirst in a

reversible slow process followed by a fast second step in which the
attacking nucleophile attaches to the carbocation intermediate.

- non-stereospecific in nature in the sense that a mixture of inversion

and retention in configuration around the reaction centre in the product
is achieved. In the case of substrates with chiral reaction centre,
 racemization (ei. formation of enantiomers in equal amounts) occurs.
Here the cationic carbon in the carbocation intermediate is sp2
hybridized and is planar in shape. The attacking nucleophile can attach
to the carbon from either side with equal chances. When the attack
takes place from the side in which the leaving group left the product
has retention in configuration and attack from the other side results in
inversion of configuration.

Here hydrolysis of 2-bromobutane with alkali by SN1 process gives a racemic

mixture of the product butan-2-ol.
Factors which favour1 reactions are
(a) good leaving group with polarizable and electronegative nature
(b) groups that stabilize carbocation like alkyl groups, conjugated
multiple bonds
(c) Polar protic solvents

Nucleophilic substitution can take place at sp2-hybridized carbon also. There are
two main cases- nucleophilic substitution at aromatic carbon and nucleophilic
substitution at acyl carbon. In these cases the mechanism follows different
processes.
Aromatic nucleophilic substitution reactions

A nucleophilic leaving group from an aromatic can also be substituted by

another nucleophile.Here nucleophilic substitution can take place in two
different mechanisms:
(i) Elimination-Addition mechanism (also known as Benzyne
mechanism) and
(ii)Addition-Elimination mechanism
Elimination-Addition mechanism
In the first step of this mechanism,with the elimination of the leaving group a
strong base removes a proton from an adjacent position and generates a reactive
Benzyne intermediatecontaining a highly strained triple bond in the ring. In the
second step the nucleophilicattack at either end of the strained triple bond
followed by protonation gives the product. Here the substitution at the position
adjacent to that of the leaving group is called cine-substitution. This
mechanism operates when there is no activating group in the aromatic ring. For
example the substitution reaction of bromobenzene with sodamide goes by this
mechanism.

Addition-Elimination mechanism
When strongly electron withdrawing groups are present at o,p-positions with
respect to the leaving group, the substitution mechanism goes by Addition-
Elimination mechanism(also known as SNArmechanism). Here the attacking
nucleophile adds to the carbon atom bearing the leaving group and generates a
resonance stabilized anionic sigma complex. In a fast second step the sigma
complex eliminates the leaving group to give the product.
For example,2,4-dinitrochlorobenzene on heating with aqueous sodium
hydroxide solution the chlorine atom is substituted by hydroxide ion by
addition-elimination mechanism.

In the case of diazonium group as the leaving group, the elimination however
goes by the general SN1 mechanism.
Nucleophilic acyl substitution reactions

Nucleophilic substitution at acyl carbon of carboxylic acid derivatives goes in

two steps. In the first step the attacking nucleophile adds to the trigonalreaction
centreand forms a tetrahedral intermediate. In the second step the leaving group
is eliminated to form the product. For example Propanoyl chloride on hydrolysis
with alkali solution undergoes nucleophilic substitution at the acyl carbon atom.
1.2Electrophilic Substitution reactions

Substitution reactions in which both the attacking group and the leaving group
are electrophiles (ei. electron deficient species) are called electrophilic
substitution reaction.The leaving group is eliminated without the bonding
electron pair and the same is used to form a new sigma bond with the attacking
electrophile. This type of substitution is generally encountered at aromatic ring
with a hydrogen atom as the leaving group.
All aromatic electrophilic substitution reactions proceed through two
basic steps. In the rate determining first step the attacking electrophile is
generated and it adds to the aromatic ring to produce a resonance stabilized
cationic sigma complex (also known as arenium ion). In the second step the
sigma complex regains the aromatic stability by eliminating a proton from the
tetrahedral carbon atom. For example in nitration of benzene with a mixture of
concentrated nitric acid and concentrated sulphuric acid the electrophile
nitronium ion substitutes a proton from the aromatic ring.

Halogenation, sulphonation, Friedel Craft’s alkylation, Friedel Craft’s acylation

are the other important electrophilic substitution reactions at aromatic rings.

1.3Free radical substitution

Free radicals are highly reactive species with an odd number of electrons. They
can abstract an atom with one bonding electron from a molecule leaving behind
another radical resulting in radical substitution reaction.This type of reaction is
not so common as the cases of electrophilic and nucleophilic substitutions but is
important as it shows many effects in biological systems.

A simple free radical substitution reaction may be cited by the chlorination of

methane.

A general free radical substitution reaction occurring at saturated sp3-hybridized

carbon atom proceeds through a chain mechanism. The Basic steps in the chain
mechanism may be represented as follows:
(a) Chain initiation: Chain initiation involves the absorption of energy
form radiation or heat and breaking the covalent bond between the
chlorine atoms homolytically to generate chlorine free radicals.

(b) Chain propagation: The chlorine free radical abstracts a hydrogen

atom from the substrate molecule thereby leaving the carbon as
another radical. The carbon free radical then reacts with a chlorine
molecule to form product and leave behind a chlorine free radical.

(c) Chain termination: Chain termination involves combination of free

radicals to form neutral molecules. As no free radical is generated the
chain process stops once such a step occurs.

In aromatic systems however the mechanism simply does not operate. Here the
reaction goes just like electrophilic substitution. The aryl radical formed adds to
another aromatic ring thereby generating a resonance stabilized radical
intermediate.

2. Addition reaction
In addition reaction two molecules combine to form a product molecule. This
type of reaction is encountered in substrate molecules containing multiple
bonds. In principle many reagents can add to a multiple bond to form stable
products usually in two steps. Based on the nature of the species added in the
primary stage of the mechanism, the reaction may be classified into the
following classes:
(i) Electrophilic addition reaction
(ii)Free radical addition reaction and
(iii) Anionic addition reaction
2.1 Electrophilic addition reaction
The pi- electrons of multiple bonds are loosely held by the carbon nuclei
and hence addition of electrophilic part of the reagent is highly encouraged. For
example addition of hydrogen bromide to ethene takes place by electrophilic
addition mechanism.

In the first step of the reaction the electrophile is added to the multiple bond and
generates a carbocation intermediate. In the second stage of the reaction a
nucleophile adds to the cationic intermediate.

When the substrate and the reagent are unsymmetrical, the addition
reaction shows regioselectivity. In such systems the outcome of the addition
reaction follows an empirical rule called Markovnikov’s rule. According to the
rule the positive end of the reagent attaches to the multiple bonded carbon
having more hydrogen atoms. Of all possible addition products that one formed
according to the rule will be major product.
For example the addition of HBr to propene gives 2-bromopropane as the
major product.

Depending on the substrate and reaction conditions the addition of the

electrophile and nucleophile shows stereochemical preferences. When they are
added from the same side of the multiple bond the addition is said to be syn-
addition and addition from opposite sides is called anti-addition. For example
addition of bromine to but-2-ene is stereospecifically anti-addition and hence
the trans-but-2-ene specifically gives the meso-isomer of the product.
.
2.2 Free radical addition reaction

Free radical addition reactions occur either in the gas phase or in an inert non-
polar solvent in the presence of UV-light or diffused sunlight, heat or other
radical sources like peroxides. The radical addition takes place through the
usual chain reaction steps- initiation, propagation and termination. An
interesting case of free radical addition is the addition of HBr to unsymmetrical
multiple bond with a regioselectivity anti- to Markovnikov’s rule. Thus addition
of HBr to propene in the presence of a peroxide gives 1-bromopropane as the
major product.

In general radical addition reactions are a little less controllable as

compared to the other ionic addition reactions. However in biological systems in
the presence of enzymes the reactions are more controllable.

2.3 Nucleophilicaddition reaction

Nucleophilic addition reaction operates when electron withdrawing groups and

atoms are present around the multiple bonds.The electron withdrawing groups
reducethe pi-electron density around the multiple bonded carbon atoms and the
attack by electron rich nuleophile is facilitated.The most important reactions of
this category are the Michael addition reactions.
For example, the addition of diethyl malonate to cyclohex-2-enone in the
presence of a base takes place by the initial addition of the carbanion formed by
removal of the acidic methylene hydrogen.

The addition reaction of all the types takes place not only at carbon-carbon
multiple bonds but also at multiple bonds involving heteroatom.Further the
addition may take place not only at adjacent positions but also at 1,4-positions.

3. Elimination reaction

An elimination reaction involves the removal of two atoms or groups from the
substrate molecule. Often it accompanies and competes with substitution
reaction.
Depending on the relative positions of the atoms from which the two
atoms or groups are removed, elimination reactions may be classified into two
main types:
1. α- Elimination 2. β- Elimination

3.1α- Elimination
When the two atoms or groups are removed from the same centre of the
substrate molecule theelimination is α-elimination or 1,1-elimination. The
reaction gives an unstable carbene or nitrene as product.
For example removal of hydrogen and chlorine from the same carbon of
chloroform by the action of alkali to form dichlorocarbene is α- elimination
reaction.

3.2β- Elimination
Elimination reaction in whichthe two atoms or groups are removed from
adjacent centres is called β- elimination or 1,2-elimination reaction. This
type of elimination is the most common elimination reaction and results in
the formation of a new π-bond ei. a double bond or triple bond. Here one of
the atom or group is eliminated with the bonding electron pair while the
other atom or group is removed without bonding electron (often hydrogen
atom).
Depending on the conditions involved and timing of removal of the two
atoms or groups, elimination reactions are classified into three types:
(i) El reaction
(ii) E2 reaction
(iii) E1cB reaction
3.2.1El reaction

The abbreviation E1 stands for elimination unimolecular. The reaction obeys

a first order kinetics with a mechanism of two basic steps. In the first slow rate
determining step the leaving group is eliminated along with the bonding electron
pair to generate a carbocation intermediate. In thefast second step, abase
abstracts a proton from the carbon atom adjacent to the cationic carbon(referred
to as β-hydrogen)anda new pi bond is formed in between the two carbon atoms.

Like other reactions involving carbocation intermediate, the E1 may be

accompanied by rearrangement to give mixtures of products.In a pure E1
reaction(without ion pairs, etc.), the product should be completely non-
stereospecific.

3.2.2 E2 reaction
The abbreviation E2 stands for elimination bimolecular. It obeys asecond order
kinetics ( firstorder in substrate and first order in base).The mechanism takes
place in one step in whichthe two groups depart simultaneously,with the proton
being pulled off by a base.

Stereochemically, E2 reaction is stereospecific in nature.The five

atomsinvolved (including the base) in the transition state must be in one plane.
There aretwo ways for this to happen. The two atoms or groups may be trans to
one another with a dihedral angle of 180° (called anti-periplanar) or they may be
cis with a dihedral angle of 0°(called syn-periplanar). Elimination from anti-
periplanar conformation is called anti-elimination and elimination from the
syn-periplanar conformation is called syn-elimination.
In the absence of special effects ( such as ring strain) anti-elimination is usually
greatlyfavored over syn-elimination, probablybecause anti-periplanar is a
staggered conformation and the molecule requires lessenergy to reach this
transition state than it does to reach the eclipsed transition state of syn-
periplanar form.
3.2.3E1cB reaction
E1cB stands for elimination unimolecular from conjugate base. The reaction
mechanism goes in two steps. In the reversible first step the β-hydrogen is
removed by the base to generate a carbanion intermediate (conjugate base of the
substrate). The second step involves the elimination of the leaving group as a
new pi-bond is formed using the electron pair of the anionic carbon.
For example, the elimination of hydrogen bromide from 1-bromo-2-
phenylethane to form styrene goes by this mechanism.

This type of reaction is most likely to take place with substrate having acidic β-
hydrogen and poor leaving groups.
Irrespective of the types of reaction mechanism involved, in elimination
reactions with substrates having two or more different β-hydrogen atoms, the
multiple bond is formed regioselectively. The regioselectivity of the new
multiple bond and predominant product formation is governed by certain rules.
(a) The multiple bond is not formed at bridgehead carbon.
(b) In the absence of specific conditions the multiple bond is formed
according to Zaitsev’s rule. According to the rule the elimination
takes place in such a way that most substituted multiple bond(ei.
having least number of hydrogen atoms) is formed.
(c) If multiple bond or aromatic ring is already present in the substrate,
the new multiple bond is formed conjugated to them.
(d) In E2 reaction with charged leaving group like , etc. the elimination
forms the least substituted multiple bond as predominant product
(Hofmann’s rule) if the substrate is acyclic.
4. Rearrangement reaction

In rearrangement reactions an atom or group migrates from a center to another

center in the same molecule. The original center is called migration origin and
the final center is called migration terminus.
For example in the Hofmann-Martiusrearrangement of N-alkylanilines the alkyl
group migrates from nitrogen atom to the o- and p-carbon atom of the aromatic
ring.

Rearrangement reactions are classified into three main categories on the basis of
the nature of the group transferred.
(a) Nucleophilic or anionic rearrangement
(b) Electrophilic or cationic rearrangement and
(c) Free radical rearrangement

4.1Nucleophilic rearrangement

In nucleophilic rearrangement an atom or group is transferred along with the

bonding electron pair. Here the migration terminus should be a center of
electron deficient nature so as to accept the incoming group along with the
electron pair.
For example in Pinacol-Pinacolone rearrangement the 1,2-methyl shift of
carbocation intermediate is anucleophilic rearrangement.

4.2Cationic rearrangement

In electrophilic rearrangement the migrating group is transferred without

bonding electron to an electron rich migration terminus.For example
Ph3CCH2Br on treatment with sodium undergoes rearrangement by the cationic
migration of the phenyl group towards the anionic carbon.
 This type of rearrangement is very rare.
4.3Free radical rearrangement

In free radical rearrangement the migrating group is transferred with a single

bonding electron to the migration terminus which must be already a radical
center. The new radical then stabilizes by further reactions.For example the
rearrangement of 3-phenylbutanal on treatment with ditertiarybutyl peroxide to
2,5-diphenylhexane involves the phenyl radical migration.

Conclusion
To carry out enterprising research and development, a basic foundation for
organic reactions is framed by classifying them into some different categories.
The general groups are substitution, addition, elimination and rearrangement
reaction. Further each group are subdivided on the basis of the reactive
intermediates involved, mechanism and the nature of the reaction center. A
particular type of reaction may involve different mechanisms with aliphatic and
aromatic reaction centres. The stereochemical nature of the different types of
reaction is also different.

Glossary
1. Walden Inversion- Inversion in configuration around a chiral
center.
2. Syn-addition- Addition of the reagent from the same side of the
double bond.
3. Anti-additIon- Addition of the reagent from opposite sides of the
double bond.
4. α-Elimination- Elimination of the two groups from the same atom
 of the molecule.
5. β-Elimination -Elimination of the two groups from adjacent atoms
of the molecule.
6. Stereospecific reaction- Reaction in which a particular
stereoisomer of the reactant gives a particular stereoisomer of the
product.
7. Racemic modification- A mixture of equimolar amounts of the
enantiomers.
8. Rate equation- An equation that shows the relationship between
rate of reaction and concentration of the reactants.
9. Reactive intermediate- A high energy unstable species formed in
the course of a reaction.
10.Polar protic solvent- A solvent containing polar hydrogen atom
that can be involved in hydrogen bonding.

FAQ
1. What are nucleophiles? Give example.
Ans: Nucleophiles are chemical reagents that come with an electron pair
for bond formation during the reaction. They may be anionic nucleophile
like , etc. or neutral neucleophile like, H2O, NH3 etc.
2. What is a nucleofuge?
Ans: An atom or group which is eliminated along with the bonding
electron pair during the reaction is called nucleofuge.
3. What is an electrofuge?
Ans: An atom or group which is eliminated without the bonding electron
pair during the reaction is called electrofuge.
4. What are electrophiles? Give example.
Ans: Electron deficient chemical reagents that accept electron pair from
other to form chemical bond during the reaction are called electrophile.
They may be cationic electrophile like , etc. or they may be neutral
electrophile like , etc.
5. Explain heterolytic and homolytic bond cleavages.
Ans: Covalent bond cleavages in organic raections take place in two
ways. When a covalent bond is broken in such a way that both the
bonding electrons are taken away by one of the departed atom/group
leaving behind the other part without electron it is called heterolytic bond
cleavage. This type of cleavage results in formation of ions. For example
 the ionization of HCl involves heterolytic bond cleavage.

When a covalent bond is broken in such a way that the departed

atoms/groups depart with one of the bonding electrons it is called
hemolytic cleavage. Here free radicals are formed. For example under
thermal or radiation initiation chlorine molecule undergoes hemolytic
bond cleavage.

6. Explain the difference between a base and a nucleophile.

Ans: Both base and nucleophile are electron donors in chemical
reactions. When an electron rich species uses its electron pair to form a
covalent bond with a proton it is referred to as base. When the species
uses its electron pair to form covalent bond with other atoms (specially
carbon atom) it is referred to as nucleophile.
For example ethoxideion canfuction as base as well as nucleophile under
suitable conditions.

7. What are carbenes?

Ans: Reactive intermediates containing a divalent carbon with a
nonbonding electron pair are called carbenes. When the two electrons
occupy the orbital the species is said to be singlet carbine and when the
two nonbonding electrons occupy different orbitals the species is called
triplet carbine.

Example: Dichlorocarbene
8. Explain active methylene group.
Ans: Methylene group (-CH2-) linked to electron withdrawing atoms or
groups can release the hydrogen atom as proton and the carbanion is
 stabilized by the electron withdrawing atoms/groups. Such methylene
groups are said to be active methylene group.
For example the methylene group in diethylmalonate is active because of
the two ester groups.

9. Arrange the following species in increasing order of nucleophilicity

and give reason:
,,
Ans: The increasing order of nucleophilicity of the species is <<. Here
the presence of the lone pair electrons on the adjacent oxygen linked to
the nitrogen increases the nucleophilicity of hydroxylamine. The presence
of the negative charge makes the amide ion highly nucleophilic.
10.Identify the attacking electrophile in Reimer-Tiemann reaction.

Ans: Reimer-Tiemann reaction is the formylation reaction of phenols at o,p-

positions by reaction with chloroform in the presence of an alkali. Here the
attacking electrophile is dichlorocarbene generated by the reaction of
chloroform and alkali.