Organic reactions and mechanisms
Substrate: In a chemical reaction, the reactant molecule undergoing attack is referred to as the
substrate.
Reagent: general term used to describe the attacking species is the reagent.
The substrate and the reagent interact to yield the products of the reactions.
Substrate + Reagent → Product(s)
The carbon bonds in the substrate molecule are broken (or cleaved) to give fragments which are
very reactive and constitute transitory intermediates. The steps of an organic reactions showing the
breaking and making of new bonds of carbon atoms in the substrate and leading to the formation
of the final products through transitory intermediates, are often referred to as its mechanism.
Organic reactions and mechanisms
Factors which influence a reaction
A reaction may occur or may not occur depending upon density of electrons at the site of reaction
in the substrate.
1. Inductive effect (I effect)
2. Mesomeric/resonance effect (M effect)
Organic reactions and mechanisms
Factors which influence a reaction
Inductive effect (I effect)
It is the polarity produced in a molecule as a result of higher electronegativity of one atom
compared to another.
It involves σ bonds. The σ bond electrons which form a covalent bond are seldom shared equally
between two atoms. This is because different atoms have different electronegativity values (i.e.
different powers of attracting the electrons in the bond).
Electrons are displaced towards the more electronegative atom. This introduces a certain degree of
polarity in the bond. The more electronegative atom acquires a small negative charge (δ -). The less
electronegative atom acquires a small positive charge (δ +).
http://www.chem.sc.edu/faculty/shimizu/333/Chem_333/1a.ii.htm
Organic reactions and mechanisms
Factors which influence a reaction
Inductive effect (I effect)
The carbon-hydrogen bond is used as a standard. Zero effect is assumed in this case.
+I effect: Atoms or groups which lose electrons toward a carbon atom (electronreleasing/donating). Example: CH3, CH2R, CHR2 etc.
-I effect: Atoms or groups which draw electrons away from a carbon atom (electron-withdrawing).
Example: -X, -NH2, -NO2, -CN, -OH, -SH, -C6H5, -CHO etc.
An inductive effect is transmitted along a chain of carbon atoms, although it tends to be
insignificant beyond the second bond.
Organic reactions and mechanisms
Factors which influence a reaction
Mesomeric/resonance effect (M effect)
It is the polarity produced in a molecule as a result of interaction between two π bonds or a π bond
and lone pair of electrons. This effect is transmitted along a chain in a similar way as are inductive
effects.
It involves π electrons of double or triple bonds. The mesomeric effect is of great importance in
conjugated compounds (compounds in which the carbon atoms are linked alternatively by single
and double bonds). In such systems, the π electrons get delocalized as a consequence of mesomeric
effect, giving the number of resonance structure of the molecule.
H3C
C
H
C
H
C
H
O
H3C
+
C
H
C
H
C
H
-
O
Organic reactions and mechanisms
Factors which influence a reaction
Mesomeric/resonance effect (M effect)
In carbonyl group, the oxygen atom is more electronegative than the carbon atoms. As a result, the
π electrons of the carbon-oxygen double bond get displaced toward the oxygen atom.
C
O
+
C
-
O
Organic reactions and mechanisms
Factors which influence a reaction
Mesomeric/resonance effect (M effect)
+M effect: atoms which lose electrons toward a carbon atom. Example: -X, -NH 2, -OH, -SH etc.
(Activating groups or ortho/para directors). Exception: halogens are weak ortho-para director and
also ring deactivator.
+
NH2
NH2
+
NH2
-
+
NH2
-
Organic reactions and mechanisms
Factors which influence a reaction
Mesomeric/resonance effect (M effect)
-M effect: atoms or groups which draw electrons away from a carbon atom. Example: -NO 2, -CN,
-CHO, -COOH, -SO3H etc. (Deactivating group or meta directors).
O
O
-
O
N
O
N
-
O
O
N
+
-
O
O
N
+
+
Organic reactions and mechanisms
Bond fission
A covalent bond (σ bond) can undergo fission in two ways:
1. Homolytic fission: In this process each of the atoms acquires one of the bonding electrons.
A
B
or A B
A
+
B
The products A• and B• are called free radicals. They areElectrically neutral
Have one unpaired electron
Extremely reactive (tendency to become paired at the earliest opportunity)
Reactions which proceed via free radical formation, take place very rapidly
Homolytic fission is the most common mode of fission in the vapour phase. They are usually initiated by
heat, light or organic peroxide.
Organic reactions and mechanisms
Bond fission
2. Heterolytic fission: In this process one of the atoms acquires both of the bonding electrons,
when the bond is broken. The products of heterolytic fissions are ions.
A
B
+
A
+
B
Organic reactions and mechanisms
Reaction intermediates
Heterolytic and homolytic bond fissions result in the formation of short-lived fragments called
reaction intermediates.
i) Carbonium ions (Carbocations)
Organic ions which contain a positively charged carbon atom are called carbonium ions. They are
formed by heterolytic bond fission.
C Z
where, Z is more elctronegative than carbon.
C+
+
Z
Organic reactions and mechanisms
Reaction intermediates
Carbonium ions are named after the parent alkyl groups and adding the word ‘carbonium ion’. The
stability of carbonium ions is influenced by:
a. Resonance effect: allyl and benzyl carbonium ions are much more stable than propyl carbonium
ions. Resonance forms of allyl carbonium ion:
H2C
+
C
H
CH2
+
H2C
C
H
CH2
Resonance forms of benzyl carbonium ion:
+
CH2
CH2
CH2
+
CH2
+
+
Organic reactions and mechanisms
Reaction intermediates
b. Inductive effect: electron releasing groups (+I groups) stabilize carbonium ions by partial
neutralization of the positive charge on carbon. Thus, a tertiary carbonium ion is more stable than a
secondary.
Organic reactions and mechanisms
Reaction intermediates
ii) Carbanions
Organic ions which contain a negatively charged carbon atom are called carbanions. They are also
formed by heterolytic bond fission.
C Z
where, Z is less elctronegative than carbon.
C
-
+
+
Z
Organic reactions and mechanisms
Reaction intermediates
ii) Carbanions
Carbanions are named after the parent alkyl groups and adding the word ‘carbanion’. The stability
of carbanions is also influenced by:
a. Resonance effect: the benzyl carbanion is much more stable than propyl carbanion.
-
CH2
CH2
CH2
-
CH2
-
Organic reactions and mechanisms
Reaction intermediates
ii) Carbanions
b. Inductive effect: Electron releasing groups (+I groups) make the carbanions less stable. Thus a
primary carbanion is more stable than a secondary.
Organic reactions and mechanisms
Reaction intermediates
iii) Carbon free radicals
They have no charge. They are formed by homolytic fission.
C Z
C
+
Z
Here, Z and carbon atom have similar electronegativity.
Free radicals combine with other free radicals or with other molecules to produce larger free
radicals.
Organic reactions and mechanisms
Reaction intermediates
iii) Carbon free radicals
Carbon free radicals are named after the parent alkyl groups and adding the word ‘free radical’.
Free radicals are also stabilized by resonance.
Organic reactions and mechanisms
Reaction intermediates
iv) Carbenes
Carbenes are neutral species having a carbon atom with two bonds and two electrons.
C
For example: Methylene (H2C )
Carbenes are highly reactive. They act as strong electrophiles, because they can accept a pair of
electrons to complete their outer shell.
Organic reactions and mechanisms
Classification of reagents
Organic reagents fall into two main groups:
a) Electrophiles (E+): a reagent which can accept an electron pair in a reaction.
Electrophile means ‘electron-loving’, they are electron deficient.
Attacks the regions of high electron density (negative centres) in the
substrate molecule.
They may be Positive ions or
Neutral molecule (AlCl3, BF3 etc.)
b) Nucleophiles (Nu-): a reagent which can donate an electron pair in a reaction.
Nucleophile means ‘nucleus-loving’, hey are electron rich.
Attacks the regions of low electron density (positive centres)
in the substrate molecule.
They may be Negative ions or
Neutral molecule (H2O, NH3 etc.)
http://www.chem.ucla.edu/~harding/tutorials/elec_nuc/elec_nuc.html
Energy requirements of organic reactions
Activation energy (Ea): Molecules of the reactants are in a state of rapid motion and possess kinetic
energy. The reaction occurs when the reacting molecules approach in proper alignment and collide. On
such collision, the kinetic energy possessed by the molecules is transformed into potential energy of the
system. Thus to start a reaction, the required energy is supplied by the collisions of the reacting
molecules.
The minimum amount of potential energy that must be provided by collisions of the reacting molecules
for the reaction to occur is known as the activation energy.
Consider the energy change during the course of the reaction.
C
+
A
B
C
A
+
B
In the beginning both C and A-B possess certain potential energy. These reacting molecules also possess
kinetic energy which on collisions is transformed into potential energy. This results in the increase of
potential energy and the system moves up along the curve till the cliff is reached. The energy of cliff
state is a sort of temporary phase and leads to products C-A + B, when the potential energy of the
system is again changed into kinetic energy and then heat or any other form of energy.
Energy requirements of organic reactions
Energy requirements of organic reactions
Transition state (activated complex): an extremely transitory specific arrangement of atoms and
groups through which a reaction system must pass on its way to the products.
The transition state is •Imaginary molecule and cannot be isolated
•Bonds are being partial
•System possesses maximum energy and is most unstable.
B
C + A
Reactants
C
A
B
Transition state
Reaction intermediate: An intermediate is a stable entity and
can be isolated under appropriate condition. A reaction which
proceeds through an intermediate has to surmount two energy
barriers.
conversion of the reactants to the intermediate (E a) and
 conversion of the intermediate into products (E a’).
C
A + B
Products
Types of organic reactions
The reactions of organic compounds can be classified into four main types.
1.Substitution reactions
2.Addition reactions
3.Elimination reactions
4.Rearrangement reactions
Substitution reactions
Substitution reactions are those reactions in which an atom or group of atoms directly attached to a
carbon in the substrate molecule is replaced by another atom or group of atoms. For example, The
chlorination of methane in the presence of ultraviolet light, as follows:
CH4 +
Methane
Cl2
UV light
CH3Cl + HCl
Methyl chloride
Mechanism of substitution reaction
a) Free radical substitution reactions: These reactions, as above, are initiated by free radicals and take
place in 3 consecutive steps involving •Initiation
•Propagation and
•Termination.
Substitution reactions
Mechanism of substitution reaction
a) Free radical substitution reactions: contd.
i) Initiation steps: A chlorine molecule undergoes homolytic fission in the presence of ultraviolet light to
give chlorine free radicals.
Cl
Cl
UV
2Cl
ii) Propagation steps: A chlorine free radical attacks the methane molecule to give methyl free radical
and hydrogen chloride. The methyl free radical attacks a chlorine molecule to yield methyl chloride and
chlorine free radical. These propagation steps are repeated again and again.
Cl
Cl
H
Cl
CH3
CH3
HCl
+
CH3
Cl
+
CH3Cl
Substitution reactions
Mechanism of substitution reaction
a) Free radical substitution reactions: contd.
iii) Termination steps: These involve the formation of stable molecules by combination of free radicals.
2Cl
CH3 + Cl
2 CH3
Cl2
H3C
H3C
Cl
CH3
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions: When a substitution reaction involves the attack by an
electrophile, the reaction is referred to as electrophilic substitution.
e.g. bromination of benzene in the presence of FeBr 3.
Br
+
Br2
FeBr3
+
Bromo benzene
Benzene
The mechanism of the above reaction involves the following steps:
Step 1: Formation of the electrophile.
Br
Br +
FeBr3
Br+ + FeBr4Electrophile
HBr
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions: contd.
Step 2: The electrophile (Br+) attacks the π electron system of the benzene ring to form a resonance
stabilized carbonium ion.
Br+
H
Br
H
Br
H
+
Br
H
+
+
Resonance hybrid
+
Benzene
Step 3: Elimination of proton to give the substituted product.
Br
H
Br
+
FeBr4-
Br
+ HBr + FeBr3
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions:
Nitration
Step 1: Formation of the electrophile
Step 2: The electrophile (NO2+)
attacks the π electron system
Step 3: Elimination of proton to give
the substituted product
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions:
Sulfonation
Step 1: Formation of the electrophile
Step 2: The electrophile (SO3) attacks
the π electron system
Step 3: Elimination of proton to give
the substituted product
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions:
Friedel-Craft Alkylation
Step 1: Formation of the electrophile
Step 2: The electrophile (R+) attacks
the π electron system
Step 3: Elimination of proton to give
the substituted product
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions:
Friedel-Craft Alkylation
Step 1: Formation of the
electrophile
Step 2: The electrophile [(CH3)3C+]
attacks the π electron system
Step 3: Elimination of proton to give
the substituted product
Substitution reactions
Mechanism of substitution reaction
b) Electrophilic substitution reactions:
Friedel-Craft Acylation
Step 1: Formation of the electrophile
Step 2: The electrophile (RCO+)
attacks the π electron system
Step 3: Elimination of proton to give
the substituted product
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
When a substitution reaction involves the attack by a nucleophile, the raction is referred to as S N. The
hydrolysis of alkyl halides by aqueous NaOH is an example of nucleophilic substitution.
R
OHNucleophile
X +
R
OH + X-
Leaving group
The nucleophilic reactions are divided into two classes:
•SN2 mechanism
The terminology SN2 stands for “substitution nucleophilic bimolecular”.
rate of SN2 reaction depends on the concentration of both the substrate and the nucleophile, the
reaction is of second-order
Rate ∝ [Substrate] [Nucleophile]
two reactants take part in the transition state of the slow or rate-determining step of a reaction and is
therefore bimolecular
The reaction consists of single step
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN2 mechanism
For example: hydrolysis of methyl bromide by aqueous NaOH. The reaction and transition state are
represented in the following figure.
H
-
HO
C
H
Br
δ
HO
-
H
H
C
δ
Br
H
HO
-
C
H
H
Methyl bromide
H
Transition state
+ Br
H
Methyl alcohol
The alkyl halide substrate contains a polarized carbon halogen bond. The S N2 mechanism begins when
hydroxide ion approaches the substrate carbon from the opposite side of the bromine ion. This is
because both hydroxide ion and bromine atom are electron rich. In transition state, both OH and Br are
partially bonded to the substrate carbon. Carbon in the resulting complex is trigonal bipyramidal in
shape. With the loss of the leaving group, the carbon atom again assumes a pyramidal shape and its
configuration is inverted.
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN2 mechanism
Walden inversion: The inversion of stereochemical configuration at a chiral center during a chemical
reaction. A molecule can form two enantiomers around a chiral center. Walden inversion converts the
configuration of the molecule from one enantiomeric form to the other.
CH2CH3
H3CH2C
I
H
H3C
C
Cl
I
C
H
CH3
+ Cl
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN2 mechanism
Factors affecting SN2 reactions
1. Steric hindrance: SN2 reactions require a rearward attack on the carbon bonded to the leaving group.
The larger and bulkier the group(s), the greater the steric hindrance and the slower the rate of reaction.
In general, the order of reactivity of alkyl halides in S N2 reactions is: methyl > 1° > 2°. The 3° alkyl halides
are so crowded that they do not generally react by an S N2 mechanism.
H3C
H
-
HO
C
H
H
Easy attack
(Primary halide)
X
-
HO
C
H3C
H3C
Difficult attack
(Tertiary halide)
X
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN2 mechanism
Factors affecting SN2 reactions
2. Nucleophilicity: Because the nucleophile is involved in the rate-determining step of S N2 reactions,
stronger nucleophiles react faster.
3. Solvent effects: For protic solvents (solvents capable of forming hydrogen bonds in solution), an
increase in the solvent's polarity results in a decrease in the rate of S N2 reactions. This decrease occurs
because protic solvents solvate the nucleophile, thus lowering its ground state energy. Because the
energy of the activated complex is a fixed value, the energy of activation becomes greater and
therefore, the rate of reaction decreases.
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN1 mechanism
The terminology SN1 stands for “substitution nucleophilic unimolecular”.
rate of SN1 reaction depends only on the concentration of the alkyl halide, the reaction is of firstorder
Rate ∝ [Substrate]
Activated complex contains only one species, alkyl carbocation and is therefore unimolecular
The reaction consists of two steps
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN1 mechanism
This mechanism proceeds via two steps.
i) The first step (the slow step) involves the breakdown of the alkyl halide into an alkyl carbocation and
a leaving group anion. This is the rate determining step.
ii) The second step (the fast step), the nucleophile can attack the planar carbonium ion from either side
to give the product.
X
Nu
X
C
Y
L
Slow
Y
Fast
+
C
Z
C
Z
X
Y
Z
Nu
-
X
+
L
C
Y
Z
Nu
Substitution reactions
Mechanism of substitution reaction
c) Nucleophilic substitution reactions:
•SN1 mechanism
•SN1 mechanisms proceed via a carbocation intermediate, so a nucleophile attack is equally possible
from either side of the plane. Therefore, a pure, optically active alkyl halide undergoing an S N1
substitution reaction will generate a racemic mixture as a product.
[Racemic mixture: one that has equal amounts of left- and right-handed enantiomers of a chiral
molecule.]
Stability: Primary and methyl carbocations do not proceed through the S N1 pathway.
Addition reactions
Addition reactions are those in which atoms or groups of atoms are simply added to a double or triple
bond without the elimination of any atom or other molecules. In these reactions, at least one π bond is
lost while two new σ bonds are formed. Double bonds become saturated and triple bonds are
converted into double bonds or may become saturated by further addition. For example:
H
H
H
C
C
H + Br2
H
Ethylene
H
H
C
C
Br
Br
H
1,2-dibromo methane
Mechanisms of addition reactions
These reactions may be initiated by electrophiles, nucleophiles or free radicals.
a) Electrophilic addition reactions:
When an addition reaction involves the initial attack by an electrophile, the reaction is referred to as
electrophilic addition. The addition of HBr to ethylene is an example of electrophilic addition.
H
H2C
CH2 + HBr
Ethylene
H2C
Br
CH2
Ethyl bromide
Addition reactions
Mechanisms of addition reactions
H
H2C
CH2 + HBr
Ethylene
a) Electrophilic addition reactions: contd.
The mechanism of the above reaction involves the following steps:
Step 1: Hydrogen bromide gives a proton and bromide ion.
H
+
+
H
Electrophile
Br
-
Br
Nucleophile
Step 2: The electrophile attacks the π bond of ethylene to give a carbonium ion.
H
+
+
H2C
+
H3C
CH2
CH2
Carbonium ion
Step 3: The nucleophile attacks the carbonium ion to give the addition product.
H3C
+
CH2
Carbonium ion
+
-
Br
H3C
H2
C
Br
Ethyl bromide
H2C
Br
CH2
Ethyl bromide
Addition reactions
When an alkene is symmetrical about the double bond, the produce formed in addition reaction is the
same no matter which way the reagent becomes attached to the alkene.
H2C
CH2
+ HBr
H3C
H2
C
Br
Identical
H2C
+ HBr
CH2
Br
H2
C
CH3
Markovnikov's rule
When an unsymmetrical reagent adds to an unsymmetrical double bond, the positive part of the
reagent becomes attached to the double bonded carbon atom which bears the greatest number of
hydrogen atoms.
Br
A
A
H3C
C
H
CH2
B
H3C
C
H
CH3
H2
C
H2
C
Isopropyl bromide (major)
+ HBr
B
H3C
Br
n-propyl bromide (minor)
Addition reactions
Br
A
A
Markovnikov's rule
The mechanism of this reaction involves the following steps:
Step 1: Hydrogen bromide gives a proton and bromide ion.
H
+
+
Electrophile
Br
H
H3C
C
H
CH2
B
H3C
C
H
CH3
H2
C
H2
C
Isopropyl bromide (major)
+ HBr
B
-
H3C
n-propyl bromide (minor)
Br
Nucleophile
Step 2: The electrophile attacks the π bond of propene to give a more stable carbonium ion.
H3C
H3C
C
H
CH2 + H
+
H
C
CH
3
+
2°Carbonium ion
(more stable)
H2
C
H3C
+
CH2
1°Carbonium ion
(less stable)
Step 3: The nucleophile combines with the more stable 2° carbonium ion to give the major product.
H3C
H
C
+
CH3 +
2°Carbonium ion
Br
-
Br
H3C
C
H
CH3
Isopropyl bromide
Br
Addition reactions
b) Free-radical addition (Anti-Markovnikov Addition)
In the presence of a peroxide initiator, hydrogen halide adds to alkene via free-radical mechanism. Such
reactions are said to be anti-Markovnikov, since the positive part adds to the less substituted carbon,
exactly the opposite of Markovnikov reaction. This process was first explained by Kharasch.
H3C
C
H
CH2
+ HBr
Peroxide
H3C
H2
C
H2
C
Br
i) Chain initiation: The chain is initiated by free radicals produced by an oxygen-oxygen bond in the
organic peroxide breaking. These free radicals extract a hydrogen atom from a hydrogen bromide
molecule to produce bromine radicals.
RO
OR
Heat
2RO
HBr
ROH
+ Br
ii) Chain propagation: When the bromine radical joins to the propene, a secondary radical is formed.
This is more stable than the primary radical which would be formed if it attached to the other carbon
H2
atom.
H
H C
Br
C
C
3
H3C
C
H
CH2
+
Br
2° free radical
(more stable)
H3C
H
C
Br
CH2
1° free radical
(less stable)
Addition reactions
b) Free-radical addition (Anti-Markovnikov Addition)
The more stable secondary radical reacts with another HBr molecule to produce 1-bromopropane and
another bromine radical to continue the process.
H3C
H2
C
H
C
Br
+ HBr
H3C
H2
C
H2
C
Br
+
Br
iii) Chain termination: In termination step, two free radicals hit each other and produce a neutral
molecule.
Br +
Br
Br2
Why don't the other hydrogen halides behave in the same way?
Hydrogen fluoride: The hydrogen-fluorine bond is so strong that fluorine radicals aren't formed in the
initiation step.
Hydrogen chloride: With hydrogen chloride, the second half of the propagation stage is very slow
(endothermic reaction). This is due to the relatively high hydrogen-chlorine bond strength.
Addition reactions
Why don't the other hydrogen halides behave in the same way? Contd.
Hydrogen iodide: In the first step of the propagation stage turns out to be endothermic and this
slows the reaction down. Not enough energy is released when the weak carbon-iodine bond is formed.
Hydrogen bromide: In the case of hydrogen bromide, both steps of the propagation stage are
exothermic.
Addition reactions
c) Nucleophilic addition reactions
When an addition reaction involves the initial attack by a nucleophile, the reaction is referred to as
nucleophilic addition. Aldehydes and ketones which contain carbon-oxygen double bonds undergo such
reactions.
The carbonyl group is highly polar in character. This is because of higher electronegativity of oxygen as
compared to carbon. The carbonyl group may be represented as shown below:
C
+
O
C
δ+
-
O
C
δ
O
The addition of HCN to acetone is an example of nucleophilic addition.
CH3
C
O
+
HCN
H3C
C
CN
OH
Addition reactions
c) Nucleophilic addition reactions
CH3
C
O
+
The mechanism of the above reaction involves the following steps:
HCN
H3C
C
CN
Step 1: Hydrogen cyanide gives a proton and a cyanide ion.
H
+
+
Electrophile
CN
H
-
CN
Nucleophile
Step 2: The nucleophile attacks the positively charged carbonyl carbon to give the corresponding anion.
CH3
δ
δ+
C
H3 C
O
-
CN
C
-
O
CN
Step 3: The electrophile combines with the anion to form the addition product.
CH3
CH3
H3C
C
CN
-
O
+
H
H3C
C
CN
OH
OH
Addition reactions
c) Nucleophilic addition reactions
All aldehydes and unsymmetrical ketones will form a racemic mixture by this reaction.
They are planar molecule, and attack by a cyanide ion will either be from above the plane of the
molecule, or from below. There is an equal chance of either happening.
-
CN
Attack can be from here
O
H3C
-
CN
C
H
or from here
Attack from one side will lead to one of the two isomers, and attack from the other side will lead to the
other.
Elimination reactions
Elimination reactions are those which involve the removal of atoms or groups of atoms from two
adjacent atoms in the substrate molecule to form a multiple bond.
Elimination reactions may be regarded as reverse of addition reactions.
In these reactions, two σ bonds are lost and a new π bond is formed. Saturated compound become
unsaturated.
For example:
H
H
H
C
C
Br
Br
H
1,2-dibromo methane
+ Zn
∆
H
H
H
C
C
Ethylene
H
+
ZnBr2
Elimination reactions
Mechanisms of elimination reactions
These reactions are also divided into two classes:
a) E2 Reaction
E2 stands for elimination bimolecular. The reaction rate, influenced by both the alkyl halide and the
base and of second order.
 E2 typically uses a strong base, it needs a chemical strong enough to pull off a weakly acidic hydrogen.
 A good leaving group is required because it is involved in the rate determining step.
E2 is the one step process with a transition state.
Typically undergone by primary substituted alkyl halides, but is possible with some secondary alkyl
halides.
Because E2 mechanism results in formation of a pi bond, the two leaving groups (often a hydrogen
and a halogen) need to be anti-periplanar (or 180o). That’s why eliminations often favor the transproduct over the cis-product (stereoselectivity).
Elimination reactions
Mechanisms of elimination reactions
a) E2 Reaction contd.
In the E2 mechanism, a base abstracts a proton from the β-carbon and the expulsion of the halide ion
from the α-carbon occurs simultaneously. A double bond is formed between α and β carbon.
-
H
HO
C2H5
β
C
H
H
α
C
Br
C2H5
H
CH3
H
CH3
Elimination reactions
Mechanisms of elimination reactions
b) E1 Reaction
E1 stands for elimination unimolecular. The reaction rate is influenced only by the concentration of
the alkyl halide and is of first-order.
 A strong base not required, since it is not involved in the rate-determining step.
 A good leaving group is required, since it is involved in the rate-determining step.
E1 typically takes place with tertiary alkyl halides, but is possible with some secondary alkyl halides.
Elimination reactions
Mechanisms of elimination reactions
b) E1 Reaction contd.
E1 reactions are two step processes.
Step 1: The alkyl halide ionizes to give the carbonium ion.
H3C
C
H3C
CH3
+
C
Br
H3C
H3C
+
-
Br
CH3
Tert-butyl bromide
Carbonium ion
Step 2: A proton is abstracted by the base from the adjacent β-carbon atom to give the alkene.
-
HO
H3C
+
C
H2
C
CH3
Carbonium ion
H
CH2 + H2O
H3C
C
CH3
2-methyl propene
Unlike E2, which requires the
proton to be anti to the leaving
group, E1 reactions simply require
a neighboring hydrogen. This is due
to the fact that the leaving group
has already left the molecule.
Elimination reactions
Zaitsev's or Saytzeff's rule
It states that although more than one product can be formed during alkene synthesis, the more
substituted alkene is the major product. This infers that the hydrogen on the most substituted carbon is
the most probable to be deprotonated, thus allowing for the most substituted alkene to be formed.
-
-
HO
OH
H
H3C
H
C
H2
C
Br
2-bromo butane
H
H2C
H
C
H
H2
C
CH3
1-butene (20%)
CH3
HC
Br-
H
C
+
C
H
CH3
H2O
H3C
C
H
C
H
2-butene (80%)
CH3
Rearrangement reactions
Rearrangement reactions involve the migration of an atom or group of atoms from one site to another
within the same molecule. The product is always the structural isomer of the original compound.
For example:
H
H
OH
C
C
H
H
H
C
H
Vinyl alcohol (ethenol)
O
C
H
Acetaldehyde (ethanal)
Fries Rearrangement
The reaction of an aryl ester with a Lewis acid (AlCl 3) catalyst followed by an aqueous acid to give
phenols is known as Fries rearrangement.
OH
O
O
CH3
OH
O
Catalyst AlCl3
Aqueous HCl
CH3
+
H3C
O
Rearrangement reactions
Fries Rearrangement contd.
O
OH
O
CH3
OH
O
Catalyst AlCl3
CH3
Aqueous HCl
+
H3C
O
Mechanism: The mechanism begins with coordination of the ester to the Lewis acid, followed by a
rearrangement which generates an electrophilic acylium ion.
O
AlCl3
-
Cl3Al
O
+
-
O
CH3
O
CH3
Cl3Al
O
+
+
O
C
CH3
Acylium ion
Rearrangement reactions
Fries Rearrangement contd.
Mechanism:
Free acylium ion which reacts in a classical electrophilic aromatic substitution with the aromatic ring.
Deprotonation to regenerate aromaticity and Bronsted acid work-up to regenerate the Lewis acid
catalyst provide the product. A low reaction temperature
favors para substitution and with high
+
H
temperatures the- ortho product prevails.
Cl3Al
O
O
O
+
O
+
C
H
O
OH
CH3
CH3
CH3
+
H
-
Cl3Al
O
O
OH
Or,
+
+
O
C
CH3
H
O
H C
H3C
O