UNIT 4

MAJOR ORGANIC REACTIONS

Kind of organic reaction

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 Curved arrows indicate breaking and forming of bonds
Arrowheads with a “half” head (“fish-hook”) indicate
homolytic and homogenic steps

Arrowheads with a complete head indicate heterolytic and

heterogenic steps

Bond breaking Symmetrical

Unsymmetrical

Bond making
Symmetrical

Unsymmetrical

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Nucleophile (Nu): - is a substance that is nucleus-loving.
- has a negatively polarized, electron reach atom and can form a bond by
donating electrons.
Characteristics: Nucleophilic atoms have either lone pairs or pi bonds that can be
used to form new bonds to electrophiles

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Electrophile (E): - is a substance that is electron-loving.
- has a positively charge, electron poor atom and can form a bond by
accepting a pair of electrons from nucleophiles.
Characteristics: Electrophilic atoms have positive charge, a partial positive
charge, or be very polarizable

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Electrons move from a nucleophilic source (Nu) to an electrophilic sink (E)

The octet rule must be followed during electron movement. 5

 4.1 Substitution reactions

Nucleophilic Substitution
Nucleophiles attack electrophilic centers
+ -
Nu + R X R Nu + X
Nucleophile Leaving group

The carbon –halogen bond in an alkyl halide is polar and is cleaved on

attack by a nucleophile so that the two electrons in the bond are
retained by the halogen

The most frequently encountered nucleophiles are anions of

metal salts
RO RCOO SH CN

CH3CH2O + CH3CH2CH2 Br CH3CH2CH2 O CH2CH2 + Br

There are two mechanisms of substitution: SN1 & SN2 6

 SN2 Mechanism
 substitution nucleophilic bimolecular

second order overall

 It is a single-step process (concerted reaction) in which both the alkyl

halide and the nucleophile are involved at the transition state.
 It is a concerted reaction

Carbon is partially bonded to both the incoming nucleophile and

the departing halide at the transition state.
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  SN2 occurs with inversion of configuration with back side attack.

- C X Y- C + x-
Y
back-side attack

transition state

Ex. The Fischer projection formula for (+)-2-bromooctane is shown.

Write the Fischer projection of the (-)-2-octanol formed from it by
nucleophilic substitution with inversion of configuration.

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SN1 Mechanism
is Substitution nucleophilic unimolecular

(CH3)3C-Br + 2H2O (CH3)3C OH + H3O+ + Br

tert-Butyl bromide tert-Butyl alcohol

First order overall

The rate depends on only the alkyl halide

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 Carbocations are involved in SN1 reaction. Thus, the rate depends on the
stability of carbocations.

Carbocation is a carbon cation

• The order of carbocation stability is: 3o > 2o > 1o > methyl

• Alkyl group stabilize carbocations by inductive effect.

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The more stable the carbocation, the rapid the reaction by SN1

Reaction (a) takes place more rapidly than (b) since passes through more
stable 3o carbocation.

Carbocation stability

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 Stereochemistry of SN1 Reactions
 SN1 is not stereospecific
 Since carbocation has a trigonal planar structure, the Nucleophile can attack
from front side or back side

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 A mixture of (R) and (S) products are possible= Racemization

The Structure of Substrate

 SN1 depends on the nature of carbocations. The more stable the carbocation,

the faster the reaction.

 In general, more highly substituted alkyl halides are more reactive toward

SN1reaction than less substituted ones.

SN1 reactivity rates follow the trend: 3 > 2 > 1 > methyl

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E.g reaction of alkyl halides with acetic acid

Ex. Rank the following substances in order of their expected SN1 reactivity:

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SN2 is a single step reaction.

Large groups prevent the approach of a nucleophile in S N2 reaction. The

nucleophile must approach the alkyl halide from the side opposite the bond to the
leaving group.

Easy approach of the

approach of the nucleophile is
nucleophile.
difficult
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SN2 reactivity rates follow the trend: methyl > 1 > 2 > 3

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 Applications of Substitution Reactions

1. Alkyl halides
 Williamson ether synthesis

• preparation of primary amine

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• Preparation of alkynes

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2. Alcohols
-OH is too basic to be displaced by a nucleophile

• Acid protonation change –OH to –OH2+ (good leaving group)

Preparation of alkyl halide from alcohol

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• Thionyl chloride (SOCl2) and phosphorus halide (PX3) are also used for this
purpose

3. Ether

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4. Epoxides

Acid catalysed cleavage of epoxides

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 4.2 ELIMINATION REACTIONS
An elimination reaction is a type of organic reaction in which two
substituents (two atoms or groups) are removed from a molecule

• base removes H+ as X- leaves

• base attacks H (nucleophile attacks C)

There are two mechanisms of elimination: E1 and E2

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 E2 and E1 Mechanism

E2 Elimination Mechanism
 concerted (single step)
 all bond-breaking and bond-forming steps are concerted
 the H and X eliminated must be aligned anti to one
another

H CH3
OH H3C
Br
CH3
CH3

H CH3
H3 C CH3
CH3
Br
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 E1 Elimination Mechanism
 two-step mechanism

Step 1: ionization of C-X gives a carbocation intermediate

CH3 slow, rate CH3
determining –
CH2 -C-CH3 CH3 -C-CH3 + Br
+
Br (A carbocation
intermediate)

Step 2: proton transfer from the carbocation intermediate to a base

(in this case, the solvent) gives the alkene

CH3 CH3
H fast H +
O + H-CH2 -C-CH3 O H + CH2 =C-CH3
+
H3 C H3 C

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 Zaitsev’s Rule
 Elimination reactions almost always give mixtures of alkene products.
 Zaitsev's rule states that if more than one alkene can be formed by an
elimination reaction, the more stable alkene is the major product.
H H H H H R R H R R
Stability of alkenes: C C < C C
< C C < C C < C C
H H R H R H R R R R
Mono-substituted Di-substituted Tri-substituted Tetra-substituted

more highly substituted C=C double bond is more stable due to the
electron donating properties of the alkyl group
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 Elimination versus Substitution
Nucleophilic substitution and elimination reactions often compete.
Since bases are nucleophilic, they can undergo substitution

• to favor elimination: use a strong, hindered base

e.g., KOtBu (Potassium tert-butoxide)

• to favor substitution: use a small, unhindered nucleophile

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• Reactivity Patterns

With 1o halide substitution is highly favoured

With 2o halide elimination favoured

steric effect makes substitution difficult

With 3o halide elimination highly favoured

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 Applications of Elimination Reactions
1. Dehydration of alcohol

2. Dehydrohalogination

3. Elimination of vicinal dihalides - Simmon' Smith reaction

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 4.3 ADDITION REACTIONS

Rules for Addition Reactions

Markovnikov's Rule: addition reaction pass through the formation
of more stable carbocation as an intermediate.

The reaction tends to pass through more stable carbocation.

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Carbocation stability: 3° > 2° > 1°
Examples

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 Anti-Markovnikov’s (Radical) addition

Addition of HX on double bond in the presence of peroxides follow

anti-Markovnikov’s rule
+ no peroxide
CH3CH2CH CH2 HBr CH3CH2CH CH3 Markovnikov
Br
90%

+ ROOR
CH3CH2CH CH2 HBr CH3CH2CH2 CH2 anti-Markovnikov
Br
95%

The overall reaction

+ ROOR
CH3CH2CH CH2 HBr CH3CH2CH2 CH2
heat or light Br

Mechanism
a) Initiation
Step 1 : dissociation of a peroxide in to two radicals
light or + OR
RO OR heat
RO
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 Step 2: Hydrogen atom abstraction from hydrogen bromide by an alkoxy radical:
RO H Br RO H + Br

(b) Chain propagation

Step 3: Addition of a bromine atom to the alkene:

CH3CH2CH CH2 Br CH3CH2CHCH2 + CH3CH2CHCH2
Br Br
2o 1o
A secondary alkyl radical
is more stable than a primary radical.

Step 4: Abstraction of a hydrogen atom from hydrogen bromide by the free radical
formed in step 3:

CH3CH2CHCH2 H Br CH3CH2CH2CH2 + Br
Br
Br
2o

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 Application of Addition Reactions

1. Hydrogenation

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Partial hydrogenation of an alkyne to produce alkene could be
achieved using Lindlar catalyst.

Lindlar catalyst = palladium on CaCO3combination to which lead

acetate and quinoline have been added.
Hydrogenation of alkynes with internal triple bonds gives cis
alkenes

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2. Addition of Halogens X

CH3 CH CH2 + X2 CH3 CH CH2

X
vicinal dihalide

• anti-stereochemistry-two new groups are added to opposite sides of

the original pi bond
Br
+ Br2
Br
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The reaction intermediate is not a carbocation but is instead a bromonium ion, R 2Br+.
Formed by addition of Br+ to the alkene.

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3. Addition of Hydrogen Halide (HX)

The major product is determined by Markovnikov's rule

4. Addition of water (Hydration)

The reaction follows Markovnikov's rule.

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 The reaction follows Markovnikov's rule.

5. Hydroboration-Oxidation of Alkenes
• A two steps reaction

• borane-tetrahydrofuran complex (H3B-THF)-common hydroborating agent

anti-Markovnikov's
addition 42
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6. Conversion of Alkenes to Vicinal Halohydrins

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7. Ozonolysis of Alkenes
Ozone is a powerful electrophile and undergoes a remarkable reaction
with alkenes in which both the σ and π components of the carbon-carbon
double bond are cleaved to give a product referred to as an ozonide.

Ozonides undergo hydrolysis in water, giving carbonyl compounds.

The two-stage reaction sequence is called ozonolysis 45

ozonolysis

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8. Ozonolysis of Alkynes
Ozonolysis of an internal alkyne produces two carboxylic acids
O O
1. O3
R C C R' R C OH + HO C R'
2. H2O

O O
H3C C C CH2CH2CH3 1. O3
CH3 C OH + HO C CH2CH2CH3
2. H2O

• Ozonolysis of a terminal alkyne yields a carboxylic acid and

carbon dioxide.

CH3CH2CH2CH2C CH 1. O3 CH3CH2CH2CH2COOH + CO2

2. H2O

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8. Hydroxylation
• addition of two OH groups to each of the two double bonded carbon

CH3 CH3
CH3 O O OH
OsO4 Os NaHSO3
O H2O
CH3 O OH
CH3 CH3

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9. Oxidative cleavage of an alkene using hot alkaline KMnO4
Acidic KMnO4 also causes double bond cleavage like ozone.

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