Addition, Substitution and

Elimination Reactions
 Preliminary Concepts
Carbocation
 A carbocation is an ion with a positively charged carbon atom.
 Carbanion
 Carbanion is an anion in which carbon is trivalent (forms three bonds) and bears a
formal negative charge
 an anion in which carbon has an unshared pair of electrons and bears a negative
charge usually with three substituents for a total of eight valence electrons.
 Carbanions are nucleophiles and react efficiently with a variety of electrophiles
 Hyperconjugation
 Hyperconjugation is a general stabilising interaction. It involves delocalisation
of σ electrons of C—H bond of an alkyl group directly attached to an atom of
unsaturated system or to an atom with an unshared p orbital. The σ electrons
of C—H bond of the alkyl group enter into partial conjugation with the
attached unsaturated system or with the unshared p orbital. Hyperconjugation
is a permanent effect.

hyperconjugation in ethyl cation hyperconjugation in propene

 Nucleophiles and Electrophiles
 A nucleophile is a reactant that provides a pair of electrons to form a new covalent
bond. Nucleophiles are Lewis bases.
 “nucleophiles” means “nucleus loving”, or “positive-charge loving”)

 An electrophile is a reactant that accepts a pair of electrons to form a new covalent

bond. Electrophiles are Lewis acids.
 “electrophilicity” means “electron-loving”, or “negative-charge loving”
Reactions between Electrophile and Nucleophile -
Examples
 Addition and Elimination Reactions

 Addition and elimination are equilibrating reactions: – Which side is favoured depends on
temperature

 The higher the temperature, the more important entropy becomes.

 Higher temp means a bigger entropy term

 Addition reactions are favoured by enthalpy.

 Sigma bonds are stronger (more stable) than π-bonds.
 Addition vs. Elimination Reactions

TWO ONE
Reactants Product

ΔH = Bonds broken – bonds formed

ΔH = 166 kcal/mol – 185 kcal/mol
ΔH = –19 kcal/mol

 Addition reactions are NOT favoured by Entropy.

 Two molecules combine to form one product; entropy decreases.
 Addition vs. Elimination Reactions

 At lower temps, enthalpy dominates, and addition reactions are favoured.

 At higher temps, entropy dominates, and elimination reactions are favoured.

 So, we use lower temperatures when doing an addition reaction

 Addition Reactions
 In addition reactions the substrate gains atoms (or groups) from the reactant
but doesn’t lose any.
• Substrate is unsaturated (has multiple bond(s))
• Occur easily & quickly because σ-bonds are more stable than the π-bonds
they replace

Nucleophilic
addition

Electrophilic
additions
 Nucleophilic Addition

Nucleophilic addition: a Nu:- attacks the electrophilic carbonyl carbon of the

substrate and adds to the substrate.

counter-ion

E+ Nu:-

final product
Hydrohalogenation
Hydrohalogenation - Regioselectivity
Hydrohalogenation - Regioselectivity
 Hydrohalogenation - Regioselectivity
 The regioselectivity of HBr addition can be controlled:

What product do you expect?

 Hydrohalogenation - Mechanism

 The mechanism is a two step process

Electrophilic attack
Hydrohalogenation - Mechanism
 Hydrohalogenation - Stereochemistry
 Hydrohalogenation may often result in the formation of a chirality center.

 There are actually TWO Markovnikov products formed in this reaction:

Two enantiomers are formed in equal

amounts – Racemic mixture

The carbocation intermediate can be attacked from

either side of the empty π-orbital, with equal
probability.
 Electrophilic Addition
 Electrophilic addition: an alkene or alkyne serves as the Nu: and donates :
to the electropositive atom of a molecule, typically an acid
• Substrate is unsaturated
• Reactant is often an acid
• The two halves (electropositive & electronegative) are both added
“across” the double bond

Nu:-

final products
E+ carbocation

Nu:-

E+ Nu:-
Nu:-
carbocation
 Hydrohalogenation - Rearrangements
 Carbocations can rearrange (hydride or methide shift) if they can become more
stable.
What product do you expect?

1,2-hydride shift

 When this alkene undergoes hydrohalogenation, the 2˚ carbocation could rearrange to a

more stable, 3˚ carbocation.
 Acid-Catalyzed Hydration
 The components of water (H and OH) are added across the π-bond
Acid-catalyzed hydration follows Markovnikov regioselectivity

 Sulfuric acid is typically the acid catalyst used

 The OH is added to the more substituted carbon of the alkene

The more substituted the carbon atom is, the faster the reaction
 Acid-Catalyzed Hydration- Mechanism
 The mechanism for acid-catalyzed hydration is essentially the same as
hydrohalogenation:

 But with hydration, nucleophilic attack produces an oxonium ion, which is deprotonated
to afford the alcohol product:
 Hydration - Thermodynamics
 The reactants and products of hydration are in equilibrium.
 We can exploit La Chatelier’s principle to control the equilibrium.

 If we are synthesizing an alcohol from an alkene, we would use excess water

 If we are synthesizing an alkene from an alcohol, we would only use acid, and
not add water to the reaction
 Hydration - Stereochemistry
 The stereochemistry of hydration is analogous to hydration, for the same reason(s).
 If a new chirality center is formed, a mixture of R and S is obtained.

 As always, if enantiomers are formed in a reaction, then a racemic mixture is

obtained.

Find out which one is R and which is S in the above two

products!
 Nucleophilic
Substitution Reaction
(SN1 and SN2)
 Nucleophilic Substitution Reaction
 A substitution reaction is a chemical reaction during which an atom or one
functional group in a chemical compound is replaced by another atom or
functional group. In organic chemistry, nucleophilic substitution is a class of
reactions in which a leaving group (LG) is replaced by an electron rich species
(nucleophile). The whole molecular entity of which the electrophile and the
leaving group are part is usually called the substrate.
 The most general form of substitution reaction may be given as the
following:

 The electron pair from the nucleophile (Nu:) attacks the substrate (R-LG) forming
a new bond, while the leaving group (LG:) departs with an electron pair. The
principal product in this case is R-Nu.
 Nucleophilic Substitution Reaction – General Features
 The nucleophile may be electrically neutral or negatively charged, whereas the
substrate is typically neutral or positively charged.

 Three components are necessary in any nucleophilic substitution reactions as

abbreviated in its general form:
1. R- in R-X: An alkyl group R containing an sp3 hybridized carbon atom
bonded to X in the substrate, R-X.
2. X- in R-X: An atom (or group of atoms) called a leaving group, which is
capable of accepting the electron density in the C-X bond.
3. Nu: or Nu-: A nucleophile is an electron rich (a neutral or an anion) species
that tends to attack the substrate at a position of low electron density
 Nucleophilic Substitution Reaction – General Features
 As these substitution reactions involve electron rich species, i.e., nucleophiles,
they are called nucleophilic substitution reactions. Nucleophilic substitutions are
Lewis acid-base reactions. The nucleophile (Lewis base) donates its electron pair,
the alkyl halide
(Lewis acid) accepts it, and the C-X bond is heterolytically cleaved.

 Nucleophilic substitution reactions can be broadly categorised as taking place at a

saturated aliphatic carbon or at (less often) an aromatic or other unsaturated
carbon centre.

 Nucleophilic substitution reactions occur when an electron rich species, the

nucleophile, reacts at an electrophilic saturated carbon atom attached to an
electronegative group, the leaving group, that can be displaced.
 Nucleophilic Substitution Reaction
 A common example of nucleophilic substitution reaction is the alkaline hydrolysis
of an alkyl halide, e.g., R-Br to the corresponding alcohol (R-OH), where the
attacking nucleophile is the OH- and the leaving group is Br-.

 Kinetic measurement on reactions in which alkyl halides (R-X) react with a variety
of different nucleophiles, Nu:, have revealed two essentially extreme types: one
in which, rate of the reaction is dependent of [Nu:],

and another in which, the rate is independent of [Nu:],

 Mechanism of Nucleophilic Substitution Reactions
 Overall a nucleophilic substitution can be represented as follows:

 There are two fundamental events in a nucleophilic substitution reaction:

1. breaking of the σ bond to the leaving group

2. formation of the new σ bond to the nucleophile

 Nucleophilic substitution at an sp3 hybridised carbon, therefore, involves two

σ bonds: the bond to the leaving group, which is broken, and the bond to the
nucleophile, which is formed.
Two Mechanisms of Nucleophilic Substitution Reactions

1. The SN2 mechanism (substitution nucleophilic bimolecular)

2. The SN1 mechanism (substitution nucleophilic unimolecular)

 The numbers 1 and 2 in the names SN1 and SN2 refer to the kinetic order of the
reactions. It may also indicate the molecularity of the reaction. For example, SN2
means that the kinetics are second order. The number 2 does not refer to the
number of steps in the mechanism. SN2 reaction is a single step process
whereas SN1 reaction is a two-step process.
 SN2 Mechanism
Bond breaking and bond formation occur at the same time.

 Here, the C-X bond is broken as the C-Nu bond is formed, the mechanism has
one-step. The rate of such a bimolecular reaction depends on the concentration
of both the reactants; that is, the rate equation is second order.
 SN2 Mechanism
 Reaction of methyl bromide (CH3Br) with the nucleophile acetate (CH3CO2−)
affords the substitution product methyl acetate (CH3CO2CH3) with loss of Br− as
the leaving group.
 The rate of reaction depends on the concentration of both reactants; that is, the
rate equation is second order. This bimolecular reaction involves a one-step
mechanism in which the C-X bond is broken as the C-Nu bond formed.
 Stereochemistry of the SN2 Reaction
 In backside attack, the nucleophile approaches from the opposite side to the leaving
group of the substrate (A), forming B. In this example, the leaving group was drawn on
the right, so the nucleophile attacks from the left. Because the nucleophile and leaving
group are in the opposite position relative to the other three groups on carbon,
backside attack results in inversion of configuration around the stereogenic centre.

Umbrella Effect!
Inversion of
configuration
 Dependence of Rate of SN2 Reactions
 1) Substrate (methyl > primary > secondary >> tertiary)
-- Because of the steric hinderance due to bulky substituents at the tertiary
carbon, SN2 reactions are nor favoured, these prefer SN1 mechanism.

 2) Nucleophile (negative charge > neutral)

-- stronger is the nucleophile, higher is the reaction rate. For example, CH 3S− is

stronger nucleophile than CH3O−, which is stronger than CH3OH. Similarly, OH− is

stronger than H2O.

 3) leaving group (Y) (Y stabilizes a negative charge)

-- better is the leaving group, higher is the rate. Iodide is the better leaving group
than fluoride. I− > Br− > Cl− > F−

 4) Solvent (needs to be polar and aprotic)

 SN1 Mechanism
Bond breaking occurs before bond formation.

 Here, the C-X bond is broken first and then the C-Nu bond is formed, the
mechanism has two-steps and a carbocation is formed as a reactive intermediate.
The first step is rate-determining, and the rate of such a unimolecular reaction
depends on the concentration of RX only; therefore, the rate equation is first
order.
 SN1 Mechanism
 A nucleophilic substitution reaction with t-butyl bromide [(CH3)3CBr], which also
leads to substitution of Br by I−. Kinetic data show that this reaction rate depends
on the concentration of only one reactant, the alkyl halide; that is, the rate
equation is first order. This suggests a two-step mechanism in which the rate-
determining step involves the alkyl halide only.

Nucleophile Leaving
Product group
Substrate

 Note that the nucleophile is not involved in the slower, rate-limiting step; that means,
the rate of the SN1 reaction does not depend on the concentration of the nucleophile.
SN1 Mechanism
 SN1 Mechanism - Racemization

Nucleophile can approach from

both side of the carbocation.

Racemic
mixture
Elimination Reaction
Carbene
 E1 - The Unimolecular Elimination Reactions
• E1 indicates an elimination, unimolecular reaction.
• The E1 reaction proceeds via a two-step mechanism: the bond to the leaving group
breaks first before the
• The slow step is unimolecular, involving only alkyl halide.
 E1 Elimination vs. SN1 Substitution Reactions

Rate = k[substrate]

 The mechanism of E1 elimination is similar to that of the S N1 reaction: the first step is
the formation of carbocation via heterolytic cleavage.
 E2 Elimination Reactions
Rate = k[substrate][base]

 As in the SN2 reactions, the rate of reaction is dependent on the concentration of both
reaction partners.
 Mechanism of E2 Elimination Reactions

The base (C2H5O−) attacks a neighbouring

C-H bond and begins to remove the H Transition State
atom, at the same time as the alkene (Anti-coplanar)
C=C double bond starts to form and
leaving (Br) group starts to leave.

Neutral alkene is produced when C-H

bond has fully broken, and the X group
(Br) has departed with C-X bond electron
pair (as Br−) and ethanol is formed.
Chloride plays the role of
nucleophile only, not as base.

When Ethoxide plays

the role of base

Ethoxide plays
the role of
nucleophile
B: Nucleophile acts as Base
 Saytzeff's (Zaitsev’s) Rule

Transition states

 According to Zaitsev’s Rule, the most substituted alkene will be formed in an

elimination reaction.
 Zaitsev’s Rule does not apply when the base is very bulky, or the leaving group is
poor, or when a conjugate diene is formed.
Overall Summary
Overall Summary
Overall Summary
Thank You for Your
Attention!