Organic Chemistry I

Lecturing 9
Alkyl Halides:
Nucleophilic Substitution

Ihsan Ikhtiarudin, M.Si

University of Riau
Pekanbaru
2016

Tugas

Freon

Pesticides

Synthesis of Alkyl Halides

from Alkane

Reaction of Alkyl Halides:

Nucleophilic Substitution

Elimination

Problem 1 :
Substitution or Elimination?

Problem 2

SN2 Reactions

Mechanism:

Key of Mechanism

Examples

Problem 3

Nucleophilicity

Remember it !

NUCLEOPHILICITY

WHAT MAKES A GOOD NUCLEOPHILE?

WHAT IS A
GOOD NUCLEOPHILE ?
SN2 REACTIONS

WHAT IS THE IDEAL NUCLEOPHILE ?

LARGE

..
: ..
Y:

SN2 REACTIONS

STERIC PROBLEMS
no way ! bad

R
SMALL

.. :..
X:

good

: Br

R
Smaller
is better !

R
For an SN2 reaction the nucleophile must find
the back lobe of the sp3 hybrid orbital that the
leaving group is bonded to.

EXPECTED IDEAL NUCLEOPHILES

cyanide

ROD OR SPEAR -:C

N:
SHAPED
+
:N
N
N:
azide

These types
should be
able to find
the target !

SMALL
SPHERES

.. - .. :F:
:Cl:
..
..

Generally this idea is correct.

etc.

OUR NAVE EXPECTATION

We would expect the halides to be good nucleophiles:
ionic radii:
1.36 A
smallest
ion

F-

1.81 A

Cl-

1.95 A

Br -

2.16 A

I-

and we would expect the smallest one (fluoride)

to be the best nucleophile,
.. however, that is not usually the case.

EXPERIMENTAL RESULTS

RELATIVE RATES OF REACTION FOR THE HALIDES

CH3-I + NaX

MeOH

CH3-X + NaI

Rate = k [CH3I] [X-]

k
-

5 x 102

2.3 x 104

6 x 105

Cl

Br
-

2 x 107

slowest

fastest

* MeOH solvates like water but dissolves everything better.

SN2

SOLVATION
Solvation reverses our ideas of size.

HEAT OF SOLVATION
ENERGY IS RELEASED WHEN AN ION IS PLACED IN WATER

F-

gas phase

- 120 Kcal / mole

HEAT OF SOLVATION
F- (g)

F-

H
H
O

O
H
H

SOLVATED
ION

O
water solution

F- (aq)
The interaction between
the ion and the solvent
is a type of weak bond.
Energy is released when
it occurs.
Solvation lowers the
potential energy of the
nucleophile making it
less reactive.

HALIDE IONS
IONIC
RADIUS
1.36 A
smallest
ion

1.81 A

Heats of
solvation
in H2O

- 120

1.95 A

Cl
- 90

Br -

- 75

2.16 A

I-

- 65

Kcal / mole

X(H2O)n
larger n

increasing solvation

smaller n

SMALL IONS SOLVATE MORE THAN LARGE IONS

H O

CH3CH2 O

CH3 O

H
WATERHAS

H
+

H O

H+
polar OH bonds

R N

H
SOLVENT

H
O H

O
+

H O
H

O
H

H O
-

O
H

H
H

H O

Water is a polar molecule.

Negative on the oxygen end, and positive on the hydrogen end.
It can solvate both cations and anions.

SMALL IONS SOLVATE MORE HEAVILY THAN LARGE ONES

strong interaction
with the solvent

O H
H H O
H
H
H O
O
H
H
H H
H O H
O
O
H
H

BETTER
NUCLEOPHILE

H O

H
O
H
solvent
shell

Effective size is larger.

Heavy solvation lowers the
potential energy of the nucleophile.
It is difficult for the solvated nucleophile
to escape the solvent shell.
This ion is less reactive.

H O

H
H

...smaller
solvent shell
...escapes
easily
more
potential
energy

weak interaction
with the solvent

PROTIC SOLVENTS
H O
H
water

CH3CH2 O

CH3 O

H
methanol

R N

ethanol

H
H

amines

H
H
H O
Water
is
an
example
of
a
protic
solvent.
O
H
O
+ H
H
H
H O
+
X
Mthat have
H O
Protic solvents are those
O
H
H
+
H N-HH or
O S-H bonds.
O-H,
H O
H
H
Protic solvents can form hydrogen bonds and can
solvate both cations and anions.

LARGER IONS ARE BETTER NUCLEOPHILES

IN PROTIC SOLVENTS
THREE FACTORS ARE INVOLVED :

2
3

In protic solvents the larger ions are solvated less

(smaller solvent shell) and they are, therefore,
effectively smaller in size and have more potential
energy.
Since the solvent shell is smaller in a larger ion
it can more easily escape from the surrounding
solvent molecules during reaction. There is more
potential energy.

The larger ions are thought (by some) to be

more polarizable.
see the next slide ..

BASICITY
If everything else is equal, the stronger base is
the better nucleophile.
This principle shows up in a period, where
atoms do not vary appreciably in size, and
solvate to similar extents.

OH- is a better nucleophile than F-

NUCLEOPHILICITY TRENDS
IN PROTIC SOLVENTS

OBSERVED NUCLEOPHILICITY TRENDS

H2O OR OTHER PROTIC SOLVENTS
GROUPIV

VI

VII

increasing nucleophilicity (ROWS)

CH3-

NH2-

OH-

F-

PH2-

SH-

ClBrI-

more solvation,
larger effective size,
lower potential energy

basicity
increasing
nucleophilicity
(COLUMNS)

basicity

APROTIC SOLVENTS

APROTIC SOLVENTS

O
CH3

O
CH3

H C N CH3
CH3

H3C
H3C

O
N

CH3
CH3

dimethylsulfoxide
H3C
CH3
DMSO
dimethylformamide
DMF
hexamethylphosphoramide

O
CH3

C CH3

acetone
if scrupulously
free of water

HMPA

CH3 C N
acetonitrile

APROTIC SOLVENTS
DO NOT HAVE
OH, NH, OR SH BONDS
They do not form
hydrogen bonds.

APROTIC SOLVENTS SOLVATE CATIONS,

BUT NOT ANIONS (NUCLEOPHILES)

H3C

H3C
S
H3C

S + CH3

CH3

CH3

O M+ O
O

crowded

S CH
3

CH3

XThe nucleophile is
free (unsolvated),
and therefore is small
and not hindered by
a solvent shell.

DIMETHYLSUFOXIDE
space-filling

O
S

density - electrostatic potential plot

DIMETHYLFORMAMIDE

CH3
H3C N C H
+

H C N CH3
CH3

nucleophile is free
(unsolvated)

OBSERVED NUCLEOPHILICITY
APROTIC SOLVENTS
GROUPIV

VI

VII

increasing nucleophilicity (ROWS)

CH3-

NH2-

OH-

F-

PH2-

SH-

ClBrI-

increasing
nucleophilicity
(COLUMNS)

decreasing
ionic size
The direction of the red arrow (COLUMNS) represents a
different order than in protic solvents.

basicity

WHY NOT ALWAYS USE

APROTIC SOLVENTS FOR SN2 ?
Mostly, it is a matter of expense.
Water, ethanol, methanol and acetone are much
cheaper, especially water.

Water
free
Methanol $14.70 / L
Ethanol $15.35 / L
Acetone $16.60 / L

DMSO
DMF
HMPA

$47.50 / L
$33.75 / L
$163.40 / L

Cheapest grades available, Aldrich Chemical Co., 2000.

Problem 4

Solvent for SN2 Reaction

Example

Stereochemistry in SN2
Reaction

Problem 5

Examples

Examples

Examples

Problem 6

Problem 7

Problem 8

SN1 Reactions

Mechanism

Key Mechanism

Example

Example

Substitution in C sp

Problem 9

Solvent Effect

Stereochemistry in SN1
Reaction

83

Rearrangements of
Carbocations

Problem 10

Comparison SN2 and SN1

Comparison SN2 and SN1

Problem 11

Thank You