20.18 Preparation of Nitriles

1
20.18Preparation of Nitriles
2
Preparation of Nitriles
Nitriles are prepared by

• nucleophilic substitution by cyanide onalkyl
  halides (Sections 8.1 and 8.13)
• cyanohydrin formation (Section 17.7)
• dehydration of amides

3
Example
KCN
CH3(CH2)8CH2Cl
ethanol-water
(95)

• SN2

4
Example
KCN
H
(75)
5
Preparation of Nitriles
By dehydration of amides

• uses the reagent P4O10 (often written as P2O5)

(69-86)
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20.19Hydrolysis of Nitriles
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Hydrolysis of Nitriles
Hydrolysis of nitriles resembles the
hydrolysisof amides. The reaction is
irreversible. Ammonia is produced and is
protonated to ammonium ion in acid solution.




2H2O
H
RCN
8
Hydrolysis of Nitriles
In basic solution the carboxylic acid product is
deprotonated to give a carboxylate ion.





HO
H2O
NH3
RCN
9
Example Acid Hydrolysis
(92-95)
10
Example Basic Hydrolysis
CH3(CH2)9CN
(80)
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Mechanism of Hydrolysis of Nitriles
H2O
H2O

• Hydrolysis of nitriles proceeds via
  thecorresponding amide.
• We already know the mechanism of
  amidehydrolysis.
• Therefore, all we need to do is to see how
  amides are formed from nitriles under the
  conditions of hydrolysis.

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Mechanism of Hydrolysis of Nitriles
OH
H2O
RC
NH

• The mechanism of amide formation is analogousto
  that of conversion of alkynes to ketones.
• It begins with the addition of water across
  thecarbon-nitrogen triple bond.
• The product of this addition is the nitrogen
  analog of an enol. It is transformed to an
  amideunder the reaction conditions.

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Step 1
14
Step 1
15
Step 2
16
Step 2
17
Step 3
18
Step 3
19
Step 4

O
H

H
20
Step 4

O

RC
N
H


O
H
H

H
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20.20Addition of Grignard Reagentsto Nitriles
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Addition of Grignard Reagents to Nitriles
R'MgX
H2O
diethylether

• Grignard reagents add to carbon-nitrogen
  triplebonds in the same way that they add to
  carbon-oxygen double bonds.
• The product of the reaction is an imine.

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Addition of Grignard Reagents to Nitriles
R'MgX
H2O
diethylether
H3O
Imines are readily hydrolyzed to
ketones.Therefore, the reaction of Grignard
reagents with nitriles can be used as a synthesis
of ketones.
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Example
CH3MgI
1. diethyl ether
2. H3O, heat
(79)