Organic Chemistry

Dr. S. Sakthivel
Assistant Professor
Department of Chemistry
NIT Jamshedpur
 Chemical Reaction and Bond Cleavage
 A chemical reaction is a process by which one or more reactants are converted into one or more products.
 In this process, chemical bonds are either broken or formed.
 Reactants are the substances that participate (or consumed) in the reaction and products are the
substances formed.

Symmetrical Bond Making/Breaking (homolytic process)

Unsymmetrical Bond Making/Breaking (heterolytic process) - Polar Reactions
Classification of Organic Reactions

1. Addition Reactions
2. Elimination Reactions
3. Substitution Reactions
4. Rearrangements Reactions

Addition Reaction

Elimination Reaction
Substitution Reaction

Rearrangement Reaction
 Nucleophiles (nucleus-loving)
o Nucleophiles are molecule/group/atom that are electron rich .
o Nucleophiles have lone pair/extra electrons.
o Nucleophiles can be neutral or negatively charged, but tend to have partial or full negative charges, or if
neutral will have a lone pair. (Nu- or :Nu)

Decreasing order of nucleophilicity

Less stable anion > more stable anion > lone pair on less electronegative atom > lone pair on more
electronegative > atom C=C

CH3O- > -OH > NH3 > H2O > C=C

 Electrophiles (electron-loving)
o Electrophiles are molecule/group/atoms that are electron deficient.
o Electrophiles can have vacant orbital to accommodate the incoming electrons pair from a nucleophile.
o Electrophiles can be neutral or positively charged. (E+).

Decreasing order of Electrophilicity

Less stable cation > more stable cation > neutral atom with incomplete octet > large partial positive atom > small
partial positive atom
Addition Reactions: Electrophilic Addition
The π bond is localized above and below the C-C  bond. The π electrons are relatively far away from the nuclei
and are therefore loosely bound.
Double bonds is converted to  bond. Since  bonds are stronger than π bonds, addition reactions are typically
exothermic.
o The double bond acts as a
nucleophile (attacks the electrophile).
An electrophile will attract those
electrons and can pull them away to
form a new bond. This leaves one
carbon with only three bonds and a
+ive charge (vacant orbital,
carbocation).
o In most cases, the cation produced will
react with another nucleophile to
produce the final electrophilic addition
product.
Addition Reactions: Electrophilic Addition

o Markovnikov’s Rule: The addition of a proton/

electrophile to the alkene double bond results in a
product with the proton/electrophile bound to the
carbon atom that has the greater number of
hydrogens attached. (More generally: In an
electrophilic addition to an alkene, the electrophile
adds in such a way that it generates the most stable
intermediate).
o Reactions that give such products are said to have
Markovnikov orientation and are Markovnikov
products.
o The electrophilic addition of HBr is said to be
regiospecific, since it only gives one orientation of
addition
Addition Reactions: Free radical addition
It is possible to obtain anti-Markovnikov products when HBr is added to alkenes in the presence of free radical
initiators. The free radical initiator changes the electrophilic addition of HBr to free radical addition. This change
of mechanism gives rise to the opposite regiochemistry.

The free radical initiator has the weak the oxygen-oxygen bond, which can be easily homolytically cleaved to
generate two alkoxy radicals. These radicals abstract the hydrogen from HBr and thus produces the bromine
radicals.
 Addition Reactions: Free radical addition

The bromine radical is electron deficient and electrophilic in nature. It adds to the double bond and generates a
carbon centered radical. This radical then abstracts hydrogen from a molecule of H-Br, giving the product, and
another bromine radical. (Chain process)
The orientation of this reaction is anti Markovnikov. The
reversal of regiochemistry through the use of peroxides (free
radical initiator) is called the peroxide effect. As usual, the
electrophile adds to the least substituted end, but here the
electrophile is a bromine radical (not a proton). This generates
an intermediate radical (carbon centered - Tertiary radicals are
more stable than secondary radicals). The reaction goes
through the most stable intermediate. (It still follows the
expanded Markovnikov rules, but the orientation is anti
Markovnikov). Radical additions do not proceed with HCl or HI,
only HBr
Substitution Reactions : Nucleophilic Substitution Reactions - SN2 Reaction

The notation SN2 represents Substitution

Nucleophilic Bimolecular. This mechanism is a
concerted process in which the bond forming and
bond breaking occur simultaneously (but the
extend may differ). Energy required to break the
bond is compensated by bond formation.

During SN2 reaction nucleophile first

approaches the anti-bonding molecular
orbital of the C-L bond

The attractive interaction between the donor orbital (filled electrons) and the acceptor orbital (unfilled) results
in a new bonding between incoming group and the carbon atom. Simultaneously the leaving group begin to
depart away from the carbon center.
 Substitution Reactions : Nucleophilic Substitution Reactions - SN2 Reaction

Kinetics
The rate of the reaction is found to vary linearly with non-zero slope with respect to electrophile as well as
nucleophile. In the presence of large excess of nucleophile, the kinetics tends to follow first order even though
the mechanism is bimolecular. Nucleophile affects the rate even being in large excess but the change in
concentration is not significant. So, the determined rate depends on the electrophile concentration. Such a
situation is known as “Pseudo first order reaction.

Complete inversion in stereochemistry is

observed during aliphatic nucleophilic
substitution via SN2 pathway. This confirms
the backside attack of nucleophile is
preferred over the front side attack.
Stereochemical outcome of the SN2 reaction
is termed as Walden inversion in honor of
his discovery.
 Substitution Reactions : Nucleophilic Substitution Reactions – SN1 Reaction

SN1 corresponds to Substitution Nucleophilic Unimolecular. The rate depends on the concentration of the
substrate (i.e. only one reactant), and not the nucleophile. Highly substituted reactants undergo SN1 reactions.
Increase in substitution at carbon favors SN1 pathway.
In this example, heterolytic bond cleavage of
C-Br bond leads to a tertiary carbocation,
which is subsequently attacked by the
nucleophile (hydroxide). The rate of the
reaction is decided by how fast the
carbocation can be generated.

The first step of the reaction involves the formation of a carbocation. This is a slow process due to higher
activation energy for bond breaking. Carbocation can be stabilized by the substituents through two important
effects (i) hyperconjugation if the carbon is highly substituted or (i) by resonance. The second step proceeds
fast as it involves combination of two ionic substrate and the incoming nucleophile.
 Substitution Reactions : Nucleophilic Substitution Reactions – SN1 Reaction

Kinetics
The kinetics of SN1 follow first
order kinetics. The rate constant
is dependent on how fast the
leaving group can depart. It is
independent of the incoming
nucleophile.
The rate depends on
1. The nature of the substrate.
2. The rate of leaving group The nucleophile can approach the planar carbocation intermediate from
departure. either of the faces (as shown above), resulting in a racemic mixture with equal
3. The nature of the solvent. quantity of both enantiomers (provided the R groups on the central carbon are
not identical).
 Substitution Reactions : Nucleophilic Substitution Reactions – SN1 Reaction

The starting compound has a chiral centre. The attack of incoming nucleophile (water in the present case) on
the top and bottom plane of the planar carbocationic intermediate is equally probable. Hence, it leads to
racemization.
Substitution Reactions : Nucleophilic Substitution Reactions – SN2` Reaction

Allylic rearrangement under SN2

conditions are known as SN2`reaction
The attack of the nucleophile is not on
the same carbon atom as that of the
leaving group.
Attack at γ-carbon under SN2 reaction condition is termed as
SN2`. Simultaneous movement of three electron pair in the
transition state. The final product resembles that of an SN2
product.
Increasing the size of the nucleophile as well as steric
hindrance at the α-carbonincreases the extent of SN2product.
Leaving group also an affect in deciding the extent of
reaction in certain cases. Stereochemistry depends on the
nature of the incoming and leaving groups in SN2reaction,
still syn-substitution is preferred over anti.
Elimination Reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a
molecule(substrate) in either a one or two step mechanism, resulting in the formation of a molecule(product)
with increase in unsaturation or a decrease in an atom by two. (This process is usually called as reductive
elimination). The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as
the E1 reaction.

In these reactions, the substituents are lost from

adjacent carbon atoms, one of them being a proton
and the other is a good leaving group. A general
scheme of elimination reactions is

In the elimination reactions, the carbon atom which carries the leaving group is generally designated as α
carbon and the adjacent carbon which carries the hydrogen is called as β carbon. So, these type of
eliminations are known as the 1,2- (or α,β-) elimination or simple the β-elimination.
Elimination Reaction: E1 Reaction
E1 stands for unimolecular elimination and has the following reaction pathway:
1) It is a two-step process of elimination: ionization and deprotonation.
Ionization: The leaving group leaves the α–carbon to give a carbocation intermediate.
Deprotonation: Deprotonation of the carbocation gives the alkene.
2) E1 reaction typically takes place with tertiary alkyl halides (R3CX), but is possible with some secondary alkyl
halides under suitable conditions.
3) The reaction rate is influenced only by the concentration of the alkyl halide because carbocation formation is
the slowest step, known as the rate-determining step. Therefore, first-order kinetics apply (unimolecular).
4) The reaction usually occurs in the complete absence of a base or the presence of only a weak base (acidic
conditions and high temperature).
5) E1 reactions are in competition with SN1 reactions because they share a common carbocationic intermediate.
6) There is no antiperiplanar requirement.
H H CH3
H Br RDS H CH3 Weak Ethanol solvent is not sufficiently polar to
C C H 2C
C C Base
H EtOH facilitate an SN1 reaction. CN- is a good
H3C CH3 H CH3 KCN CH3
nucleophile and a decent base.
t-Butyl bromide t-Butyl carbocation Isobutene
Elimination Reaction: E2 Reaction

The E2 stands for bimolecular elimination and

involves a one-step mechanism in which carbon-
hydrogen and carbon-leaving group bonds break
to form a carbon-carbon double bond.
E2 is a single step elimination and hence it involves with a single transition state. It is typically shown by
primary substituted alkyl halides. But it is possible with some secondary alkyl halides and other compounds
under suitable conditions. Since, it is influenced by both the alkyl halide and the base (bimolecular), the reaction
rate is second order. The E2 mechanism leads to the formation of a π-bond, So, the two leaving groups need to
be antiperiplanar. An anti-periplanar transition state has staggered conformation with lower energy than a
syn-periplanar transition state which is in eclipsed conformation with higher energy. The reaction mechanism
involving staggered conformation is more favorable for E2 reactions (unlike E1 reactions).
E2 requires a strong base enough to remove a weakly acidic hydrogen. In order for the π-bond to be created, the
hybridization of carbons needs to be lowered from sp3 to sp2. The C-H bond is weakened in the rate
determining step. E2 competes with the SN2 reaction mechanism if the base can also act as a nucleophile (true
for many common bases).
Elimination Reaction: E2 Reaction – Orientation of double bond
Substrates having alternate β-hydrogen atoms will give more than one alkene on elimination. Here, there will be
two possibilities:
Saytzeff (on R-Br compounds) states that the hydrogen H H
H H

will be eliminated preferentially from that β-carbon CH CH2 NaOEt

CH CH2 H
H + C CH2
H3C C
atom having least number of hydrogens. Therefore, EtOH H 3C C
H
H 3C C
H
Br 1-Butene 2-Butene
according to Saytzeff rule, highly substituted alkene 2-Bromobutane 19% 81%
will predominate on elimination. (more substituted
double bond carbons)

Hofmann (working on RNMe3+ compounds) states that

the hydrogen will be eliminated preferentially from that
β-carbon atom having more number of hydrogen atoms.
Therefore, according to Hofmann rule least substituted
alkene will predominate on elimination. (less
substituted double bond carbons).
Rearrangement Reaction

A rearrangement reaction is a broad class of organic reactions in which an atom, ion, group of atoms, or
chemical unit migrates from one atom to another atom in the same or different species, resulting in a structural
isomer of the original molecule. Rearrangement reactions mostly involve breaking and/or making C—C, C—O,
or C—N bonds. The migration origin is the atom from which the group moves, and the migration terminus
is the atom to which it migrates.

Hofmann Rearrangement

The Hofmann rearrangement is a conversion

reaction of primary amide to primary amine
with one carbon atom less (via the intermediate
isocyanate formation) using alkali (NaOH) and
halogen (chlorine or bromine) or hypohalite
(NaOCl or NaOBr). This reaction is also referred
to as the Hofmann degradation of amide.
Hofmann Rearrangement mechanism
Hydroxide abstracts an acidic N–H proton.

The anion reacts with bromine to form an N-bromoamide.

Hydroxide abstracts another acidic H

atom from N–H of N-bromoamide.

Elimination of bromide and migration of

R1 group to nitrogen atom occur
simultaneously to form an isocyanate.

Water or hydroxide reacts with

isocyanate.

Proton transfer produces a carbamic acid.

Abstraction of proton with hydroxide.

Carbamic acid loses CO2 and after protonation gives the amine
product.
Wolff Rearrangement

The Wolff rearrangement is a conversion of an

α-diazoketone to a ketene with the loss of
molecular nitrogen accompanying 1,2-
rearrangement using a silver oxide catalyst or
thermal or photochemical conditions.
Generally, these ketenes are not stable to
isolate. These can undergo a nucleophilic
attack by water or alcohol or amine to form one
carbon homologation of acid or ester or amide
(having one carbon more from starting
material). The German chemist Ludwig Wolff
discovered this reaction in 1902.
Wolff Rearrangement - mechanism

Elimination of nitrogen molecule as gas, R group migration, and formation of ketene intermediate.
Water attacks as a nucleophile to the ketene.
Proton transfer.
Tautomerization gives the desired product.
Pinacol–Pinacolone rearrangement

The pinacol–pinacolone rearrangement is an acid-catalyzed conversion of a 1,2-diol to a carbonyl compound.

The name of this reaction comes as pinacol rearranges to pinacolone.
If both the –OH groups are not similar, then the one that gives a more stable carbocation participates in the
reaction. Subsequently, an alkyl group from the adjacent carbon migrates to the carbocation center.

Protonation of one hydroxyl group.

Elimination of water and formation of a carbocation.
Migration of one methyl group.
The loss of proton and formation of final product.
Carbocation:

An organic species which has a carbon atom bearing only six electrons in its outermost shell and has a
positive charge is called carbocation. The positively charged carbon of the carbocation is sp2 hybridized.
The unhybridized p-orbital remains vacant. They are highly reactive intermediate.

Carbocation: Structure

The positively charged carbon of the carbocation is sp2 hybridized. This

carbon used the three sp2 hybridized orbitals for single bonding to three
substituents. The unhybridized p-orbital remains vacant. Due to sp2
hybridization carbocation possesses planar structure with the bond angle of
120° between them.
Carbocation - Formation of carbocations
1). Ionization
Unimolecular ionization results in a carbocation and a leaving group. If the carbocation leads to a substitution
product = SN1reaction. If the carbocation leads to an elimination product = E1reaction. In both cases the
ionization is the rate determining step.
Acid catalysed dehydration (loss of water) The protonation (and
deprotonation) occur faster
than the loss of water from the
protonated alcohol.

Spontaneous ionization of a triflate

Ionization is encouraged here by several factors:

i) benzylic cation is resonance stabilized ii) para MeO-group further
stabilizes the cation iii) excellent leaving group iv) Polar solvent stabilizes
the ionic species.
Carbocation - Formation of carbocations
2) Addition of an Electrophile to a π-bond
A common way to generate cations is an addition of a Lewis acid (often a H+) to a π-bond.
E.g. protonation of an alkene: E.g. protonation of a carbonyl group:

In acid, carbonyl compounds become protonated on the O, although there is significant +ve charge on the
carbon (activated carbonyl complex towards nuc attack).

3) Reaction of a carbonyl compound with a Lewis acid.

The basicity of the carbonyl oxygen allows reaction with Lewis acids such as AlCl3, BF3 and SnCl4, leading to
complexes which are usually reactive intermediates.
Carbocation - Stability

Cation stability is influenced by FOUR factors:

a) Hyperconjugation: Increasing the number of alkyl substituents increases the stability of the carbocation.
This is due to orbital overlap between the σ-bond and the empty p orbital on the sp2carbon.
b) Inductive Effects: Neighbouring alkyl groups contain electrons that are polarizable, and these can shift
towards the positive charge. (Small Hydrogen substituents cannot do this as well).
c) Resonance Effects: Conjugation with a multiple bond or lone pairs of electrons increase the stability of a
carbocation.
d) Hybridization: It also influences cation stability. The more s character in an orbital, the less stable the cation.
Therefore, sp hybrid cations are very unstable.

The stability order of carbocations bearing only alkyl groups is 3o > 2o > 1o > CH3
Carbocation - Reactions
1. SN1 reactions
2. E1 Reactions
3. Rearrangement reactions
Carbocation – Rearrangement Reactions
Rearrangement reactions usually occur to increase the stability of a carbocation. So, less stable cation might
undergo a rearrangement reaction to form more stable cation. The most come rearrangements are 1,2-
hydride and 1,2-alkyl shifts.

The term hydride describes an electron-rich hydrogen atom. In a 1,2-hydride shift, the moving
hydrogen atom takes both electrons in the carbon-hydrogen bond along with it. A 1,2-hydride shift is a
rearrangement reaction that can occur if there is a hydrogen atom on the carbon adjacent to the positively-
charged carbon of a carbocation. In this reaction, the hydrogen atom (on carbon 1) shifts to the positively-
charged carbon (carbon 2); hence, it is a 1,2-shift. As carbon 1 now only has three bonds, it has gained a
positive charge.
Carbocation – Rearrangement Reactions

A 1,2-alkyl shift is a rearrangement reaction that can occur if there is an alkyl group (methyl, ethyl, etc) on
the carbon next to the positively-charged carbon of a carbocation. In this reaction, the alkyl group (on
carbon 1) shifts to the positively-charged carbon (carbon 2), taking the electrons from the carbon-carbon
bond with it, and leaving a positive charge on carbon 1.

The mechanism for a 1,2-alkyl shift is shown by

drawing a curved arrow from the carbon-carbon bond
(of the migrating alkyl group) to the positively-charged
carbon:

This example shows a shifting methyl group, note

that other alkyl groups can also shift.
Carbanion
Carbanions can be considered as species containing trivalent carbon with lone pair of electrons and the
carbon is negatively charged. This carbon is electron rich and has good nucleophilic properties. Carbanions
thus act as nucleophiles in substitution reactions, in carbonyl addition and substitution reactions, and in 1,4-
addition (Michael) reactions.

Carbanion: Structure
The central carbon atom of carbanions is sp3 hybridized. One of the sp3 orbitals is occupied C
by the lone pair of electrons. The geometry is thus pyramidal. However, when the carbanion
is stabilized by delocalization, it assumes sp2 hybridization for effective resonance. Carbanion

The carbanion can undergo inversion or retain its

stereochemistry depending on the attached substituents. A
methyl carbanion has a barrier to inversion of about 2
kcal.mol-1. The trifluoromethyl carbanion has a barrier of 120
kcal.mol-1. A fluorine atom is however more stabilizing than a
hydrogen atom because of the fluorine electronegativity.
Carbanion: Formation CH3 CH2
base
Abstraction of H by base
O2N
An appropriate organic substrate having acidic C-H bond on O2N

treatment with a suitable base (NaOH/ether, aqueous NaOH, t- base

BuO/t-BuOH, Rli/DMF, HMPA, N-methylpyrrolidine/ether)

results in abstraction of hydrogen to generate a carbanion. H H H

Ph3C-H + NaNH3 Ph3C Na + NH3

From unsaturated compound
Addition of a nucleophile to an unsaturated C-C bond
generates a carbanion.

Reaction of alkyl halide

Reaction of alkyl halide with Mg turning in presence
of anhydrous ether as solvent generates Grignard
reagent. The Grignard reagent behaves like a
carbanion
Carbanion - Stability

A carbanion possesses an unshared pair of electrons and acts as a base to accept a proton to form corresponding
conjugate acid. The stability of the carbanion depends on the stability of this conjugate acid. Like carbocation,
carbanion also stabilized by resonance.

The decreasing stability of carbanion

Benzyl > vinyl > phenyl > methyl > ethyl > isopropyl > t-Butyl

The stability of carbanion when a functional group is present in the α-position

-NO2 > -COR > -COOR > -SO2 > -CN = -CONH2 > halogen > H > R

Resonance stabilized carbanion

Carbanion - Reactions
1. Aldol Condensation
2. Claisen condensation
3. Reformatsky reaction

Carbanion – Aldol Reactions

An aldehyde or ketone that has an α-hydrogen (a hydrogen atom on the carbon next to the carbonyl group), can
form an enolate in basic solution. The enolate can act as nucleophile and added to the carbonyl group of
another molecule. This process is a very important synthetic procedure and is known as the Aldol
Condensation. The final product from aliphatic aldehydes or ketones contains both a carbonyl and an alcohol
group. The product is called an aldol.
Carbanion – Claisen condensation Reactions
Esters, like aldehydes and ketones, give an aldol-type reaction. The α-hydrogen of the ester is removed by
base to give the enolate. The enolate reacts with another molecule of the ester in an addition-elimination
reaction which is characteristic of esters, it would appear as displacement of the alkoxide. The resulting
product is a β-ketoester. The reaction is known as the Claisen condensation.
The α-hydrogens in the product β-ketoester are more acidic than the α-hydrogens in the starting
ester. Thus, a new enolate is formed that is more stable than the first enolate, thus helping the reaction go to
completion.
Carbanion - Reformatsky Reaction
Instead of forming the enolate from an α-hydrogen, an α-bromine atom can also be used. Zinc reacts with ethyl
α-bromoacetate to form a zinc enolate that reacts at the carbonyl function of aldehydes and ketones to
produce β-hydroxyester. The method is made easier by addition of the bromoester to a mixture of zinc and the
carbonyl compound.