Unit-5 Types of Organic Reactions Part-I

Nucleophilic Substitution Reaction
& Elimination Reaction :
MBA-Tech Chemical
Dr. Usha Ghosh 1

Classification of Reagents
Nucleophilic Reagents (Nucleophiles)
• Attacks the positive end of a polar

bond or nucleus-loving is known as
nucleophile.
• Generally, negatively charged or
electron rich species are nucleophilic.


e.g. OH , OCH3 ,  
CN , I , CH3 COO , NH2 , CH3 

H2 O, NH3 , NH3 — NH2
.. .. .. ..
H2O, CH3 — O
.. — CH3, C2H5 — OH,
.. NH3,
N
..
All nucleophiles are in general Lewis bases.
Dr. Usha Ghosh 2
Electrophilic Reagents (Electrophiles)
• Attacks a region of high electron

density or electron-loving is known as
electrophile.
• All positively charged or electron
deficient species are electrophilic.
H , CH3 , NO , Cl , Br  , Ag

2
Dr. Usha Ghosh 3

• Neutral reagents which contain an
electron-deficient atom are also
electrophiles.
AlCl3, SO3, BF3, SOCl2, POCl3, FeCl3, ZnCl2
All electrophiles are in general Lewis acids.
Dr. Usha Ghosh 4

Reactions of Alkyl Halides
Dr. Usha Ghosh 5

The SN2 Reaction
• The halogen atom on the alkyl halide is replaced with the

nucleophile (HO-).
• Since the halogen is more electronegative than carbon,
the C—I bond breaks heterolytically and the iodide ion
leaves.
Dr. Usha Ghosh 6

SN2 Mechanism
• Bimolecular nucleophilic substitution (SN2).

• Concerted reaction: New bond forming and old bond
breaking at same time.
• Reaction is second order overall.
• Rate = kr[alkyl halide][nucleophile].
Dr. Usha Ghosh 7

SN2 Energy Diagram
• The SN2 reaction is a one-step reaction.

• Transition state is highest in energy.
Dr. Usha Ghosh 8
© 2013 Pearson Education Inc.
Uses for SN2 Reactions
Dr. Usha Ghosh 9

SN2: Nucleophilic Strength
• Stronger nucleophiles react faster.

• Strong bases are strong nucleophiles, but not all
strong nucleophiles are basic.
Dr. Usha Ghosh 10

Basicity Versus Nucleophilicity
• Basicity is defined by the equilibrium constant for

abstracting a proton.
• Nucleophilicity is defined by the rate of attack on
the electrophilic carbon atom
Dr. Usha Ghosh 11
Steric hindrance (bulkiness)
hinders nucleophilicity
more than it hinders basicity.
Dr. Usha Ghosh 12

Trends in Nucleophilicity
• A negatively charged nucleophile is stronger than its

neutral counterpart:
• Nucleophilicity decreases from left to right:
• Increases down periodic table, as size and

polarizability increase:
Dr. Usha Ghosh 13

Polarizability Effect
Bigger atoms have a soft shell that can start to overlap the carbon
atom from a farther distance.
Dr. Usha Ghosh 14
Solvent Effects: Protic Solvents
• Polar protic solvents have acidic hydrogens (O—H or N—

H) that can solvate the nucleophile, reducing their
nucleophilicity.
• Nucleophilicity in protic solvents increases as the size of
the atom increases.
Dr. Usha Ghosh 15

Solvent Effects: Aprotic Solvents
• Polar aprotic solvents do not have acidic protons and

therefore cannot hydrogen bond.
• Some aprotic solvents are acetonitrile, DMF, acetone, and
DMSO.
• SN2 reactions proceed faster in aprotic solvents.
Dr. Usha Ghosh 16

Crown Ethers
• Crown ethers solvate

the cation, so the
nucleophilic strength
of the anion increases.
• Fluoride becomes a
good nucleophile.
Dr. Usha Ghosh 17

Leaving Group Ability
The best leaving groups are:

• Electron-withdrawing, to polarize the carbon atom.
• Stable (not a strong base) once they have left.
• Polarizable, to stabilize the transition state.
Dr. Usha Ghosh 18

Structure of Substrate on SN2 Reactions
• Relative rates for SN2:
CH3X > 1° > 2° >> 3°
• Tertiary halides do not react via the SN2

mechanism, due to steric hindrance.
Dr. Usha Ghosh 19

Effect of Substituents on the Rates of SN2 Reactions
Dr. Usha Ghosh 20

Steric Effects of the Substrate on SN2 Reactions
• Nucleophile approaches from the back side.

• It must overlap the back lobe of the C—X sp3 orbital.
Dr. Usha Ghosh 21

Stereochemistry of SN2
SN2 reactions will result in an inversion of

configuration also called a Walden inversion.
Dr. Usha Ghosh 22

Back-Side Attack in the SN2 Reaction
Dr. Usha Ghosh 23

The SN1 Reaction
• The SN1 reaction is a unimolecular

nucleophilic substitution.
• It has a carbocation intermediate.
• Rate = kr[alkyl halide].
• Racemization occurs.
Dr. Usha Ghosh 24

SN1 Mechanism
Step 1: Formation of the carbocation.
Step 2: Attack of the nucleophile.
• If the nucleophile is an uncharged molecule like water or an alcohol, the positively

charged product must lose a proton to give the final uncharged product.
Dr. Usha Ghosh 25

SN1 Mechanism: Step 1
Formation of carbocation (rate-determining step)
Dr. Usha Ghosh 26

• The nucleophile attacks the carbocation,

forming the product.
Dr. Usha Ghosh 27

• If the nucleophile was neutral, a third step

(deprotonation) will be needed.
Dr. Usha Ghosh 28

SN1 Energy Diagram
• Forming the
carbocation is an
endothermic step.
• Step 2 is fast with a
low activation energy.
Dr. Usha Ghosh 29

Rates of SN1 Reactions
• Order of reactivity follows stability of

carbocations (opposite to SN2).
– 3° > 2° > 1° >> CH3X
– More stable carbocation requires less energy
to form.
• A better leaving group will increase the rate
of the reaction.
Dr. Usha Ghosh

30
Solvation Effect
• Polar protic solvent is best because it can solvate

both ions strongly through hydrogen bonding.
Dr. Usha Ghosh 31

Structure of the Carbocation
• Carbocations are sp2 hybridized and trigonal planar. The

lobes of the empty p orbital are on both sides of the
trigonal plane.
• Nucleophilic attack can occur from either side, producing
mixtures of retention and inversion of configuration if the
carbon is chiral.
Dr. Usha Ghosh 32

Carbocation Stability
Carbocations are stabilized by inductive effect and by

hyperconjugation.
Dr. Usha Ghosh 33

Stereochemistry of SN1
The SN1 reaction produces mixtures of enantiomers. There

is usually more inversion than retention of configuration.
Dr. Usha Ghosh 34
Rearrangements
• Carbocations can rearrange to form a more stable

carbocation.
• Move the smallest group on the adjacent carbon:
– Hydride shift: H- on adjacent carbon moves.
– Methyl shift: CH3- on adjacent carbon moves.
Dr. Usha Ghosh 35
Elimination Reactions
• Elimination reactions produce double bonds.

• Also called dehydrohalogenation (-HX).
Dr. Usha Ghosh 36
The E1 Reaction
• Unimolecular elimination.
• Two groups lost: a hydrogen and the halide.
• Nucleophile acts as base.
• The E1 and SN1 reactions have the same
conditions so a mixture of products will be
obtained.
Dr. Usha Ghosh 37

E1 Mechanism
Step 1: Ionization to form a carbocation.
Step 2: Solvent abstracts a proton to form an alkene.
Dr. Usha Ghosh 38

A Closer Look
Dr. Usha Ghosh 39

E1 Energy Diagram
The E1 and the SN1 reactions have the same first step:
Carbocation formation is the rate-determining step for both
mechanisms.
Dr. Usha Ghosh 40

Double Bond Substitution Patterns
tetrasubstituted trisubstituted disubstituted monosubstituted
• The more substituted double bond is more stable.

• In elimination reactions, the major product of the reaction
is the more substituted double bond: Zaitsev’s rule.
Dr. Usha Ghosh 41

Zaitsev’s Rule
• If more than one elimination product is possible,

the most-substituted alkene is the major product
(most stable).
major product
(trisubstituted)
Dr. Usha Ghosh 42
E1 Competes with the SN1
• Substitution results from nucleophilic attack on the

carbocation.
• Ethanol serves as a base in the elimination and as a
nucleophile in the substitution.
Dr. Usha Ghosh 43

A Carbocation Can…
• React with its own leaving group to return

to the reactant.
• React with a nucleophile to form a
substitution product (SN1).
• Lose a proton to form an elimination
product (E1).
• Rearrange to give a more stable
carbocation, then react further.
Dr. Usha Ghosh 44

The E2 Reaction
• Elimination, bimolecular.
• Requires a strong base.
• This is a concerted reaction: The proton is
abstracted, the double bond forms, and the
leaving group leaves, all in one step.
Dr. Usha Ghosh 45

The E2 Mechanism
• Order of reactivity for alkyl halides:

3° > 2 ° > 1°
• Mixture may form, but Zaitsev product
predominates.
Dr. Usha Ghosh 46
E2 Stereochemistry
• The halide and the proton to be abstracted must

be anti-coplanar ( = 180º) to each other for the
elimination to occur.
• The orbitals of the hydrogen atom and the halide
must be aligned so they can begin to form a pi
bond in the transition state.
• The anti-coplanar arrangement minimizes any
steric hindrance between the base and the
leaving group.
Dr. Usha Ghosh 47

E2 Stereochemistry
Dr. Usha Ghosh 48

E1 or E2 Mechanism?
• Tertiary > secondary • Tertiary > secondary

• Base strength unimportant • Strong base required
(usually weak)
• Good ionizing solvent • Solvent polarity not
important.
• Rate = k[alkyl halide] • Rate = k[alkylhalide][base]
• Zaitsev product • Zaitsev product
• No required geometry • Coplanar leaving groups
(usually anti)
• Rearranged products • No rearrangements
Dr. Usha Ghosh 49

Substitution or Elimination?
• Strength of the nucleophile determines order:

Strong nucleophiles or bases promote
bimolecular reactions.
• Primary halides usually undergo SN2.
• Tertiary halides are a mixture of SN1, E1, or E2.
They cannot undergo SN2.
• High temperature favors elimination.
• Bulky bases favor elimination.
Dr. Usha Ghosh 50

Secondary Alkyl Halides
• Secondary alkyl halides are more challenging:

– Strong nucleophiles will promote SN2/E2.
– Weak nucleophiles promote SN1/E1.
• Strong nucleophiles with limited basicity favor SN2.
Bromide and iodide are good examples of these.
Dr. Usha Ghosh 51

Solved Problem 1
Predict the mechanisms and products of the following reaction.
Solution
Dr. Usha Ghosh 52

Solved Problem 2
Predict the mechanisms and products of the following reaction.
Solution
Dr. Usha Ghosh 53

Electrophilic Substitution Reaction
Dr. Usha Ghosh 54

Electrophilic Aromatic Substitution
Background
• The characteristic reaction of benzene is electrophilic aromatic
substitution—a hydrogen atom is replaced by an electrophile.
Dr. Usha Ghosh 55

• Benzene does not undergo addition reactions like other
unsaturated hydrocarbons, because addition would yield a
product that is not aromatic.
• Substitution of a hydrogen keeps the aromatic ring intact.
• There are five main examples of electrophilic aromatic
substitution.
Dr. Usha Ghosh 56

• Regardless of the electrophile used, all electrophilic aromatic
substitution reactions occur by the same two-step mechanism—
addition of the electrophile E+ to form a resonance-stabilized
carbocation, followed by deprotonation with base, as shown below:
Dr. Usha Ghosh 57

• The first step in electrophilic aromatic substitution forms a
carbocation, for which three resonance structures can be drawn.
To help keep track of the location of the positive charge:
Dr. Usha Ghosh 58

• The energy changes in electrophilic aromatic substitution are
shown below:
Dr. Usha Ghosh 59

Electrophilic Aromatic Substitution
Dr. Usha Ghosh 60

Electrophilic Aromatic Substitution: General
Mechanism
Dr. Usha Ghosh 61

Friedel Crafts Alkylation
Charles Friedel James Crafts

Dr. Usha Ghosh 62
Friedel-Crafts Alkylation
Dr. Usha Ghosh 63

Dr. Usha Ghosh 64
Friedel Crafts Alkylation
Dr. Usha Ghosh 65

Friedel-Crafts Alkylation
Dr. Usha Ghosh 66

Friedel-Crafts Acylation
• In Friedel-Crafts acylation, a benzene ring is treated with an

acid chloride (RCOCl) and AlCl3 to form a ketone.
• Because the new group bonded to the benzene ring is called
an acyl group, the transfer of an acyl group from one atom to
another is an acylation.
Dr. Usha Ghosh 67

• In Friedel-Crafts acylation, the Lewis acid AlCl3 ionizes the carbon-
halogen bond of the acid chloride, thus forming a positively charged
carbon electrophile called an acylium ion, which is resonance
stabilized.
• The positively charged carbon atom of the acylium ion then goes on to
react with benzene in the two step mechanism of electrophilic
aromatic substitution.
Dr. Usha Ghosh 68

Three additional facts about Friedel-Crafts alkylation should be
kept in mind.
[1] Vinyl halides and aryl halides do not react in Friedel- Crafts
alkylation.
Dr. Usha Ghosh 69

Friedel-Crafts Acylation
Dr. Usha Ghosh 70

Friedel-Crafts Acylation: Mechanism
Dr. Usha Ghosh 71

Limitation of Friedel-Crafts Reaction
Dr. Usha Ghosh 72

Limitation of Friedel-Crafts Reaction
Dr. Usha Ghosh 73

Synthetic Application of Friedel-Crafts Reaction
Dr. Usha Ghosh 74

[2] Rearrangements can occur.
These results can be explained by carbocation

rearrangements.
Dr. Usha Ghosh 75

Dr. Usha Ghosh 76
Rearrangements can occur even when no free carbocation is
formed initially.
Dr. Usha Ghosh 77

[3] Other functional groups that form carbocations can also
be used as starting materials.
Dr. Usha Ghosh 78

Each carbocation can then go on to react with benzene to form
a product of electrophilic aromatic substitution. For example:
Dr. Usha Ghosh 79

Starting materials that contain both a benzene ring and an
electrophile are capable of intramolecular Friedel-Crafts
reactions.
Dr. Usha Ghosh 80

1) Why is benzene less reactive than an alkene?
The pi electrons of benzene are delocalized over 6 atoms,

thus making benzene more stable and less available for
electron donation.
While an alkene’s electrons are localized between two
atoms, thus making it more nucleophillc and more reactive
toward electrophiles.
Dr. Usha Ghosh 81

2) Show how the other two resonance structures can be
deprotonated in step two of electrophillic aromatic
substitution.
H E
B
E
H E
B
E
Dr. Usha Ghosh 82

H E
B
E
Dr. Usha Ghosh 83

3) What product is formed when benzene is reacted with each
of the following alkyl halides?
a)
CH(CH3)2
+ (CH3)2CHCl
AlCl3
b)
Cl
+
AlCl3
Dr. Usha Ghosh 84

c) O
+ H CH C CH2CH3
3 2 AlCl3
Cl
Dr. Usha Ghosh 85

4) What acid chloride is necessary to produce each product
from benzene using a Friedal-Crafts acylation?
a)
O
O
CH2CH2CH(CH3)2
Cl CH2CH2CH(CH3)2
b)
O
O
Cl
Dr. Usha Ghosh 86

c)
O O
Cl
Dr. Usha Ghosh 87

5) Draw a stepwise mechanism for the following
friedal-Crafts alkylation?
CH2CH3
+ CH3CH2Cl
AlCl3
Formation of Electrophile
CH3CH2Cl AlCl3 H3CH2C Cl AlCl3
Dr. Usha Ghosh 88

• end
Dr. Usha Ghosh 89

Unit-5 Types of Organic Reactions Part-I

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Unit-5 Types of Organic Reactions Part-I

Uploaded by

Copyright:

Available Formats

Nucleophilic Substitution Reaction

& Elimination Reaction :

Dr. Usha Ghosh 1

• Attacks the positive end of a polar

• Attacks a region of high electron

H , CH3 , NO , Cl , Br  , Ag

Dr. Usha Ghosh 3

AlCl3, SO3, BF3, SOCl2, POCl3, FeCl3, ZnCl2

All electrophiles are in general Lewis acids.

Dr. Usha Ghosh 4

Dr. Usha Ghosh 5

• The halogen atom on the alkyl halide is replaced with the

Dr. Usha Ghosh 6

• Bimolecular nucleophilic substitution (SN2).

Dr. Usha Ghosh 7

• The SN2 reaction is a one-step reaction.

Dr. Usha Ghosh 9

• Stronger nucleophiles react faster.

Dr. Usha Ghosh 10

• Basicity is defined by the equilibrium constant for

Dr. Usha Ghosh 12

• A negatively charged nucleophile is stronger than its

• Nucleophilicity decreases from left to right:

• Increases down periodic table, as size and

Dr. Usha Ghosh 13

• Polar protic solvents have acidic hydrogens (O—H or N—

Dr. Usha Ghosh 15

• Polar aprotic solvents do not have acidic protons and

Dr. Usha Ghosh 16

• Crown ethers solvate

Dr. Usha Ghosh 17

The best leaving groups are:

Dr. Usha Ghosh 18

• Relative rates for SN2:

CH3X > 1° > 2° >> 3°

• Tertiary halides do not react via the SN2

Dr. Usha Ghosh 19

Dr. Usha Ghosh 20

• Nucleophile approaches from the back side.

Dr. Usha Ghosh 21

SN2 reactions will result in an inversion of

Dr. Usha Ghosh 22

Dr. Usha Ghosh 23

• The SN1 reaction is a unimolecular

Dr. Usha Ghosh 24

Step 1: Formation of the carbocation.

Step 2: Attack of the nucleophile.

• If the nucleophile is an uncharged molecule like water or an alcohol, the positively

Dr. Usha Ghosh 25

Formation of carbocation (rate-determining step)

Dr. Usha Ghosh 26

• The nucleophile attacks the carbocation,

Dr. Usha Ghosh 27

• If the nucleophile was neutral, a third step

Dr. Usha Ghosh 28

Dr. Usha Ghosh 29

• Order of reactivity follows stability of

Dr. Usha Ghosh

• Polar protic solvent is best because it can solvate

Dr. Usha Ghosh 31

• Carbocations are sp2 hybridized and trigonal planar. The

Dr. Usha Ghosh 32

Carbocations are stabilized by inductive effect and by