Type of Reactions

Nucleophilic reactions:
nucleophilic substitution (SN)

leaving
group

+
Nu
Nucleophile
-

C X

nucleophilic
substitution

C Nu +

X-

http://chemistry.boisestate.edu/rbanks/organic/sn2.gif

Mechanism
the two processes take place simultaneously; designated SN2
S = substitution
N = nucleophilic
2 = bimolecular (two species are involved in the ratedetermining step)
bond breaking between carbon and the leaving group is
entirely completed before bond forming with the
nucleophile begins. This mechanism is designated SN1 where
S = substitution
N = nucleophilic
1 = unimolecular (only one species is involved in the ratedetermining step)
4

SN2 reaction: bimolecular nucleophilic substitution

the nucleophile attacks the reactive center from

the side opposite the leaving group

H
HO

C
H

Br

HO

Br

HH

HO C

Br

H
H

Transition state with

simultaneous bond breaking
and bond forming
5

SN1 reaction: unimolecular nucleophilic substitution

SN1 illustration
Step 1: ionization of the C-X bond gives a
carbocation intermediate

H3C
C

Br

slow, rate
determining

CH3
C+

Br

H3 C
H3 C

H3 C CH3

A carbocation intermediate;
carbon is trigonal planar

S N1
Step 2: reaction of the carbocation (an
electrophile) with methanol (a nucleophile) gives an
oxonium ion
CH3
CH3 O
H

C+

H3 C CH3

fast

OCH3

H3 C
O
H

CH3
C

CH3
CH3

H3 C
+

CH3
C O

H3 C
H3 C

Step 3: proton transfer completes the reaction

H3 C
H3C
H3 C

+
O

CH3
H

+ O

H
CH3

fast

H3C
H3 C
H3C

CH3
C O

+
+H O

CH3
7

SN1
For an SN1 reaction at a stereocenter, the product is a
racemic mixture
the nucleophile attacks with equal probability from either
face of the planar carbocation intermediate

C6 H5
C

Cl

Cl
(R)-Enantiomer

-Cl

C6 H5
C+
H

C6H5

CH3 OH
+

-H

Cl
Planar carbocation
(achiral)

C6H5
+

CH3 O C
H

C OCH3
H

Cl
Cl
(S)-Enantiomer

(R)-Enantiomer

A racemic mixture

Effect of variables on SN Reactions

the nature of substituents bonded to the atom attacked

by nucleophile
the nature of the nucleophile
the nature of the leaving group
the solvent effect

Effect of substituents on SN2

10

Effect of substituents on SN1

11

Effect of substituents on SN reactions

SN1 reactions
governed by electronic factors,
factors namely the relative
stabilities of carbocation intermediates
relative rates: 3 > 2 > 1 > methyl
SN2 reactions
governed by steric factors,
factors namely the relative ease of
approach of the nucleophile to the site of reaction
relative rates: methyl > 1 > 2 > 3

12

Nucleophilicity
Two important features:
An anion is a better
nucleophile than a
uncharged conjugated acid
strong bases are good
nucleophiles

Effectiveness Nucleophile
good

moderate

Br-, I CH3 S- , RSHO-, CH3 O-, ROO

O
CH3 CO-, RCOCH3 SH, RSH, R2 S
NH3 , RNH2 , R2 NH, R3 N
H2 O

poor

CH3 OH, ROH

O
O
CH3 COH, RCOH
13

Leaving Group

14

Solvent Effect
Protic solvent:
solvent a solvent that contains an -OH group
these solvents favor SN1 reactions; the greater the
polarity of the solvent, the easier it is to form
carbocations in it
Protic
Solvent
Water
Formic acid
Methanol
Ethanol
Acetic acid

Structure
H2 O

Polarity
of Solvent

HCOOH
CH3OH
CH3CH2OH
CH3COOH
15

Solvent Effect
Aprotic solvent:
solvent does not contain an -OH group
it is more difficult to form carbocations in aprotic
solvents
aprotic solvents favor SN2 reactions
Aprotic
Solvent

Structure

Polarity of
Solvent

O
Dimethyl sulfoxide CH3SCH3
(DMSO)
O
CH3CCH3
Acetone
Dichloromethane
Diethyl ether

CH2Cl2
(CH3CH2)2 O

16

Summary of SN1 and SN2

Type of
Haloalkane

SN 2

SN 1

Methyl
CH3 X

SN 2 is favored.

SN 1 does not occur. The methyl

cation is so unstable that it is
never observed in solution.

Primary
RCH2 X

SN 2 is favored.

SN 1 does not occur. Primary

carbocations are so unstable that
they are never observed in solution.

Secondary
R2 CHX

SN 2 is favored in aprotic
solvents with good
nucleophiles.

SN 1 is favored in protic solvents

with poor nucleophiles.

Tertiary
R3 CX

SN 2 does not occur because

of steric hindrance around
the substitution center.
Substitution Inversion of configuration.
at a
The nucleophile attacks
stereocenter the stereocenter from the
side opposite the leaving
group.

SN 1 is favored because of the ease of

formation of tertiary carbocations.
Racemization. The carbocation
intermediate is planar, and attack by
the nucleophile occurs with equal
probability from either side.
17

 Competing

Reaction: Elimination

-Elimination:
Elimination removal of atoms or groups of atoms from
adjacent carbons to form a carbon-carbon double bond
we study a type of -elimination called
dehydrohalogenation (the elimination of HX)

C C
H X
An alkyl
halide

CH3 CH2 O-Na+

CH3 CH2 OH

Base
C

An alkene

CH3 CH2 OH

Na+X 18

-Elimination
There are two limiting mechanisms for -elimination
reactions
E1 mechanism: at one extreme, breaking of the C-X
bond is complete before reaction with base breaks
the C-H bond
E2 mechanism: at the other extreme, breaking of the
C-X and C-H bonds is concerted

19

E2 Mechanism
A one-step mechanism; all bond-breaking and
bond-forming steps are concerted

20

E1 Mechanism
Step 1: ionization of C-X gives a carbocation intermediate
CH3
CH2 -C-CH3

slow, rate
determining

Br

CH3
CH3 -C-CH3 +
+
(A carbocation
intermediate)

Br

Step 2: proton transfer from the carbocation intermediate to a

base (in this case, the solvent) gives the alkene
H

O
H3 C

CH3
+ H-CH2 -C-CH3
+

fast

CH3
H +
O H + CH2 =C-CH3
H3 C

Nucleophile
-> acting as a
strong base
21

Elimination
Saytzeff rule: the major product of a elimination is the more
stable (the more highly substituted) alkene
Br

CH3 CH2 O Na

2-Bromo-2methylbutane

CH3 CH2 OH

Br

+
2-Methyl-2-butene
(major product)

CH3 O-Na+

CH3 OH
1-Bromo-1-methylcyclopentane

2-Methyl-1butene

1-Methylcyclopentene
(major product)

Methylenecyclopentane

22

Elimination Reactions
Summary of E1 versus E2 Reactions for Haloalkanes
Haloalkane
Primary
RCH2 X

E1
E1 does not occur.
Primary carbocations are
so unstable that they are
never observed in solution.

E2
E2 is favored.

Secondary Main reaction with weak

Main reaction with strong
R2 CHX bases such as H2 O and ROH. bases such as OH- and OR-.
Tertiary
R3 CX

Main reaction with weak

Main reaction with strong
bases such as H2 O and ROH. bases such as OH- and OR-.
23

SN1 versus E1
Reactions of 2 and 3 haloalkanes in polar protic solvents give
mixtures of substitution and elimination products
E1
CH3
CH3 C I
CH3
CH3
CH3 C Cl
CH3

-I-Cl-

CH3
CH3 C +
CH3

SN1
H2O

CH3
CH2 C
+ H+
CH3
CH3
CH3 C OH + H+
CH3

CH3
SN1
CH3 C OCH3 + H+
CH3 OH
CH3
24

SN2 versus E2
It is considerably easier to predict the ratio of SN2 to E2
products

Attack of base on a -hydrogen by

E2 is only slightly affected by
branching at the -carbon; alkene
formation is accelerated

R R
H C
C leaving group

SN2 attack of a nucleophile is R

R
impeded by branching at the
- and -carbons

25

Summary of S vs E for Haloalkanes

for methyl and 1haloalkanes
Methyl
CH3X

SN2

Primary
RCH2 X

SN2

The main reaction with strong bases such as OH- and

EtO-. Also, the main reaction with good
nucleophiles/weak bases, such as I- and CH3 COO-.

E2

The main reaction with strong, bulky bases, such as

potassium tert-butoxide.

SN1

SN1/ E1

The only substitution reactions observed

SN1 reactions of methyl halides are never observed.
The methyl cation is so unstable that it is never
formed in solution.

Primary cations are never formed in solution; therefore,

S N1 and E1 reactions of primary halides are never observed.
26

Summary of S vs E for Haloalkanes

for 2 and 3 haloalkanes
Secondary SN2
R2CHX
E2
SN1/ E1
Tertiary
R3CX

SN2
E2
SN1/ E1

The main reaction with weak bases/good nucleophiles,

such as I- and CH3COO-.
The main reaction with strong bases/good nucleophiles
such as OH- and CH3CH2O-.
Common in reactions with weak nucleophiles in polar
protic solvents, such as water, methanol, and ethanol.
SN 2 reactions of tertiary halides are never observed
because of the extreme crowding around the 3 carbon.
Main reaction with strong bases, such as HO- and RO-.
Main reactions with poor nucleophiles/weak bases.

27

Summary of S vs E for Haloalkanes

Examples: predict the major product and the mechanism for
each reaction
1.

Cl

2.

3.

4.

80C
H2O

+ NaOH

Br
Br

+ (C2 H5) 3N
-

+ -

+ Na I

30C
CH2 Cl2

SN2, weak base, good nucleophil

+ CH3O Na
Cl

Elimination, strong base, high temp.

methanol

acetone

SN1 (+Elimination), strong base, good

nucleophil, protic solvent

No reaction,
I is a weak base (SN2)
I better leaving group than Cl
28