CHEMISTRY- I (FOR ODD
SEMESTER), CY-101
By:
Prof. Vandana Srivastava
Department of Chemistry
Indian Institute of Technology (BHU),
Varanasi
Syllabus
Chemistry- I (For Odd semester), CY-101
Organic Reaction Mechanisms
Nucleophilic Substitution Reactions: Brief review of nucleophilic
substitution reactions at saturated carbon atom, Substitution
reactions at allylic substrates, Mechanism and stereochemistry
of SNi and Neighbouring group participation reactions, Factors
affecting nucleophilic substitution reactions.
Elimination Reactions
Mechanism of E1 and E1cb reactions. Mechanism and
stereochemistry of E2 reactions, anti, syn and pyro Elimination
reactions,
Addition reactions
Mechanism and stereochemistry of electrophilic addition
reactions.
BOOKS
1. R.T. Morrison and R. N. Boyd, Text book
of Organic Chemistry, Prentice Hall, New
Delhi, 6th edition, 1992.
2. P. Sykes, Guide book to Reaction
Mechanism in Organic Chemistry, Longman,
London, 6th edition, 1996.
3. T.W.G. Solomon, C. B. Fryhle Organic
chemistry, John Wiley & Sons, New York. 8th
edition, 2004
SubstitutionReaction
There are three general classes of
substitution reactions, depending on the
following factors.
•Reactant or substituent
•Intermediate – carbocation, carbanion, or
free radical
•Substrate (compound) – aliphatic or
aromatic
ALIPHATIC NUCLEOPHILIC SUBSTITUTION
REACTIONS
Nucleophilic substitution reactions
A reaction in which a nucleophile displaces a leaving group and
takes its position is called a nucleophilic substitution reaction.
In this reaction nucleophile selectively attacks the electrophile
to make a new bond.
R
R
R C LG + Nu R C Nu + LG
R A B R C D
Electrophilic substrate Product
LG= Leaving group
Nu =Nucleophile
Major Factors Involved in the NS Reaction
• Substrate
• Nucleophile
• Leaving group
• Solvent
Substrates for Nucleophilic Substitution
Reactions
In general Alkyl halides are the best substrates for NS reactions
A positively charged (+) species usually attached with a leaving group
Methyl Halides Scondary Halides
Tertiary Halides
H3C
CH3 Cl CH3
CH Cl
CH3 Br H3C C Cl
H3C
CH3 I CH3
H3C
CH3
Primary Halides CH Br
H3C C Br
H3C
CH3CH2 Cl
CH3
CH3CH2 Br H3C CH3
CH I
CH3CH2 I H3C C I
H3C
CH3
Nucleophiles:
A nucleophile is a chemical species that donates an electron pair to
an electrophile. Nucleophiles can be negatively charged molecules or neutral
molecules
Neutral Negatively charged
(Weak nucleophiles) (Strong nucleophiles)
H3C O H H3C O
Methanol Methoxide
H3C S H H3C S
methanthiol thiomethoxide
H
H3C N H H 3C NH
Methylamine Methylamine anion
Leaving groups
A molecular fragment that leaves with a pair of electrons in heterolytic bond cleavage
. Leaving groups are also nucleophiles and consider to be weak Lewis bases
. Leaving groups can be negatively charged molecules or neutral molecules
Halogen leaving groups Sulfonate Leaving groups Neutral leaving groups
O
Br O R N R
R S O >>> HO H H
Cl R
O Water Ammonia
I
Solvents: A medium used for dissolving the reactants
Non-polar solvents are not suitable of NS reaction e.g. Hexane
Types of Nucleophilic substitution reactions
Nucleophilic substitution can occur under different
mechanistic pathways (Majority of them are one of the
following…)
• SN1 (Substitution nucleophilic unimolecular reaction)
• SN2 (Substitution nucleophilic bimolecular reaction)
• SNi (Substitution nucleophilic internal reaction)
Types of nucleophilic substitution
1) SN1 (Substitution nucleophilic unimolecular reaction)
This implies that the rate determining step of the
mechanism depends on the decomposition of a single
molecular species.
Best Example for SN1 reaction: Solvolysis of tert-alkyl halides
CH3 CH3
H2O
H3C C O H + HCl
H3C C Br
CH3 CH3
SN1 Mechanism : Multi-steps reaction (at least two steps)
Step 1 (Dissociation of LG from alkyl carbon)
It is a unimolecular reaction
CH3 CH3
Slow because, Reaction rate only
H3C C Br H3C C + depends on a formation of
Rate Br
CH3 determining CH3 carbocation which is a slow
step
Planar Leaving process.
carbocation group
Step 2 Nucleophilic attack
CH3 CH3 H Rate (R)= k(Substrate)
H2O
C H3C C O
H3C CH3 Fast
CH3 H
For the particular reaction
Step 3 Abstraction of proton by water
Rate (R)= k[(CH3)3CCl]
CH3 H CH3
O
H H
H3C C O H3C C O H + H3O
CH3 H CH3
Energy profile Diagram
Multi-step reactions
have intermediates
and a several
transition states (TS).
In an SN1 there is loss
of the leaving group
generates an
intermediate
carbocation which is
then undergoes a
rapid reaction with the
nucleophile..
Energy profile Diagram
Examples for SN1 reaction
H3C H2C Ph Ph
water H2O
H3C
C Br
H3C
C OH2 + Br Ph C Cl Ph C O H
H3C H3C
Ph Ph
H3C H3C
H3C
C Br
MeOH H3C
C OMe + Br CH3 H
H2O
H3C H3C Ph C Br Ph C O H
Ph Ph
CH3 Ph
MeOH
Ph C Cl Ph C O Me
CH3 Ph
Stereochemistry
Ideally SN1 reaction
provides Racemic
Mixture
Types of nucleophilic substitution
2) SN2 (Substitution nucleophilic bimolecular reaction)
Rate of the reaction depends on two substrates.
Example:
H H O H
CH3COONa H
C C + Br-
H Br H3C O H
CH3COOH
Kinetic data show that the rate of reaction depends on the concentration of both
reactants, which suggests a bimolecular reaction with a one-step mechanism. This
is an example of an SN2 (substitution nucleophilic bimolecular) mechanism.
SN2 Mechanism : Single step reaction
One step reaction: nucleophilic attack and dismiss of a leaving group takes
place simultaneously .
H H H H
H CH3COO
C Br CH3COO C Br CH3COO C H + Br
H H H
5-Membered Transition State
CH3COO
Examples of SN2 reactions
Energy profile diagram
Stereochemistry of the SN2 reaction
• All SN2 reactions proceed with backside attack of the
nucleophile, resulting in inversion of configuration at a
stereogenic center.
examples of SN2 inversion of
configuration: The Walden Inversion.
Factors affecting SN1 and SN2
Nucleophilic reactions are mainly defended on the following
factors
• Substrate (Primary Vs Secondary Vs Tertiery carbon )
• Nucleophile ( charged Vs neutral)
• Leaving group
• Solvent (polar protic Vs polar aprotic)
Substrates Play Important Role in Deciding
Mechanism of the NS reaction
More Stable carbocation: More number of hyperconjugation
and Inductive effect
SN1 Reactions
Most preferable Less preferable not preferable
R R H
R
H C LG H C LG
R C LG R C LG
R H H
H
tert- Sec- Pri- Methyl-
not preferable Less preferable Most preferable
SN2 Reactions
Less steric hindrance for the back side attack
SN1 Reaction Rate
SN2 Rate of the reaction
KI
R Br R I
Acetone
Nucleophile
• Negatively charged nucleophiles like HO¯ and HS¯ are used as
salts with Li+, Na+, or K+ counterions to balance the charge.
Since the identity of the counterion is usually inconsequential,
it is often omitted from the chemical equation.
Prefers SN2 Mechanism Prefers SN1 Mechanism
Nucleophile in predicting SN1 vs SN2 mechanisms:
• The strong nucleophile favors an SN2 mechanism.
• The weak nucleophile favors an SN1 mechanism.
H2O
H H H
CH3OH
Ph C Cl Ph C O CH3 + H3C O C Ph
H3C H3C CH3
It will follow SN1 reaction
H H
CH3O-
Ph C Cl H3C O C Ph
H3C CH3
It will follow SN2 reaction
The Nucleophile: Size effect
• Nucleophilicity does not parallel basicity when steric
hindrance becomes important.
• Steric hindrance is a decrease in reactivity resulting from the
presence of bulky groups at the site of a reaction.
• Steric hindrance decreases nucleophilicity but not basicity.
• Sterically hindered bases that are poor nucleophiles are
called nonnucleophilic bases.
Leaving Group in predicting SN1 vs SN2
mechanisms:
• The leaving group is the third factor. A better leaving group
increases the rate of both SN1 and SN2 reactions.
Solvent effect: Polar protic solvent
Polar protic solvent has a hydrogen atom attached to a
strongly electronegative element (e.g. oxygen) that forms
hydrogen bonds.
-Polar protic solvent solvate cations and anions effectively
while aprotic solvents do not solvate anions to any appreciable
extend.
-Polar protic solvents are more suitable for S N1 reactions, while
aprotic solvents are used for SN2 reactions
Example of polar protic solvents
Polar Protic solvent in SN1 reaction
R R
water
R
C Br
R
C OH + Br
R R
Stabilization
Polarization
Polar Protic solvent in SN2 reaction
For SN2 reaction: We need Strong Nucleophile e.g. NaOMe
Nucleophile
H H H
MeONa
C MeO C H + Cl-
H Cl
H
Solvent effect: Polar Aprotic solvents
• Polar aprotic solvents are those solvents whose molecules do
not have a hydrogen atom that's attached to an atom of an
electronegative element.
Polar aprotic solvents also exhibit dipole—dipole interactions,
but they have no O—H or N—H bonds. Thus, they are incapable
of hydrogen bonding.
Examples of polar aprotic solvents
Polar aprotic solvent in SN2 reaction
Polar aprotic solvent increases the reactivity of SN2 reaction
Nucleophile
H H H
MeONa
C MeO C H + Cl-
H Cl
H
Strong “free” Nu
If we consider NaBr as nucleophile in SN2 Rxn NaBr
R Cl R Br
Acetone
• In polar aprotic solvents, nucleophilicity parallels basicity, and the
stronger base is the stronger nucleophile.
• Because basicity decreases as size increases down a column,
nucleophilicity decreases as well. F highest nucleophilicity and I
lowest
Rearrangements in SN1 reactions
examples
H vs alkyl Shift
SNi
( Substitution Nucleophilic Internal)
SNi reaction is a reaction in which substitution of a nucleophile takes place internally
Example
SOCl2
H3C OH H3C Cl + SO2 + HCl
Mechanism O
1) H3C
SOCl2 + HCl
OH H3C O S Cl
fast
O
H3C O
2) Slow
H3C O S Cl H3C Cl
S - SO2
Cl O
Intimate ion pair
Internal Transfer of nucleophile
SNi: stereochemistry Step 1
CH3 CH3 O
SOCl2
Ph C OH Ph C O S Cl + HCl
H H
chiral carbon
(R) -configuration
We get Retention of (R) -configuration
configuration Setp 2
CH3 O CH3 O
Ph C O S Cl Ph C O S
H H Cl
(R) -configuration
Intimate Ion Pair
Setp 3 (stereochemistry
not disturbed)
CH3 O
CH3
Ph C O S
+ SO2
Ph C Cl
H Cl
H Retention of
(R) -configuration configuration
Ion Pair Internal delivery
(stereochemistry (stereochemistry
not disturbed) not disturbed)
SNi reaction
Sni with pridine
Nucleophilic substitution at allylic Carbon
CH2=CH-CH2-X
X
X
What is allylic Carbon? X
An allylic carbon is a Allylic alcohol Allylic Bromide
carbon that attached OH Br
immediate next to the
Br
double bond OH
OH Br
•Allyl halides such as chlorides, bromides
and iodides are good substrates for
substitution reactions.
•A variety of nucleophiles can be used to
generate a range of new functional groups.
Reactivity of Allylic carbon in NS rxn
H2O
OH Less Reactive
Cl
H2O
OH More Reactive
Cl
Solvolysis of allyl halides are >100 Times Faster than
simple alkyl halides
Allyl carbocations are stabilized by resonance
SN1 or SN2 reactions in Allyl substrate
Allylic Substrates can undergo either
SN1 or SN2 depends on substrate,
nucleophile
Simple example
Via SN2 reaction Via SN1 reaction
NaOH H2O
OH Cl OH
More Reactive
Products cannot be distinguished
NaOH H2O
OH Cl OH + HO
H2O H2O
H
HO Cl
H
via SN2 reaction via SN1 reaction
SN1 vs SN1 Prime (SN'1) Reactions
CH3
H3C CH3 H2O H3C CH3
+ HO CH3
Cl OH
80% 20%
Mechanism
tertiary carbocation
H2O CH3
H3C CH3 Dissociation CH3 --------SN1
CH3
Cl CH3 OH
Step-1
Major product due to tertiary carbocation
Allylic rearrangement
H2O CH3
CH3
------- SN'1
HO CH3
CH3
Primary carbocation Prime Reaction
SN1 vs SN1 Prime (SN'1) Reactions
CH3
CH3 H2O H3C CH3
+ HO CH3
Cl CH3 OH
80% 20%
Mechanism
Primary carbocation
H2O CH3
CH3 Dissociation CH3
HO CH3 --------SN1
Cl CH3 CH3
Step-1
CH3
Allylic rearrangement H2O
CH3
OH
CH3 ------- SN'1
CH3
tertiary carbocation Major product due to tertiary carbocation
Prime Reaction
SN2 Vs SN2 prime (SN'2) Reactions
Strong Nucleophile and Prefers SN2 Reaction Path
CH3
H3C CH3 PhSNa H3C CH3
+ PhS CH3
Cl SPh
0% 100%
via SN2 via SN2'
Reaction Pathways
SPh
H3C CH3
CH3
H3C CH3 Cl
PhS CH3
Cl
PhS 100%
Path 1 Path 2
via SN2'
Only Possible path
Not Possible due to steric hindrance
SN2 Vs SN2 prime (SN'2) Reactions
Strong Nucleophile and Prefers SN2 Reaction Path
CH3 CH3
PhSNa
+ PhS CH3
Cl SHPh
0% 100%
SN2 SN2'
Simple SN2
Nu prefers
CH3
CH3 PhSNa H3C CH3
+ PhS CH3
Cl CH3 SPh
0% 100%
Steric Hindrance
• Thank you
