20 18 Preparation of Nitriles Preparation of Nitriles

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20. 18 Preparation of Nitriles

20. 18 Preparation of Nitriles

Preparation of Nitriles are prepared by: nucleophilic substitution by cyanide on alkyl halides (Sections

Preparation of Nitriles are prepared by: nucleophilic substitution by cyanide on alkyl halides (Sections 8. 1 and 8. 13) cyanohydrin formation (Section 17. 7) dehydration of amides

Example CH 3(CH 2)8 CH 2 Cl KCN ethanolwater S N 2 CH 3(CH

Example CH 3(CH 2)8 CH 2 Cl KCN ethanolwater S N 2 CH 3(CH 2)8 CH 2 C (95%) N

Example O CH 3 CH 2 CH 3 KCN H+ OH CH 3 CH

Example O CH 3 CH 2 CH 3 KCN H+ OH CH 3 CH 2 CH 3 C N (75%)

Preparation of Nitriles By dehydration of amides uses the reagent P 4 O 10

Preparation of Nitriles By dehydration of amides uses the reagent P 4 O 10 (often written as P 2 O 5) O (CH 3)2 CHCNH 2 P 4 O 10 200°C (CH 3)2 CHC (69 -86%) N

20. 19 Hydrolysis of Nitriles

20. 19 Hydrolysis of Nitriles

Hydrolysis of Nitriles Hydrolysis of nitriles resembles the hydrolysis of amides. The reaction is

Hydrolysis of Nitriles Hydrolysis of nitriles resembles the hydrolysis of amides. The reaction is irreversible. Ammonia is produced and is protonated to ammonium ion in acid solution. O RCN + 2 H 2 O + H + + RCOH + NH 4

Hydrolysis of Nitriles In basic solution the carboxylic acid product is deprotonated to give

Hydrolysis of Nitriles In basic solution the carboxylic acid product is deprotonated to give a carboxylate ion. O – RCN + H 2 O + HO – RCO + NH 3

Example: Acid Hydrolysis O CH 2 CN CH 2 COH H 2 O NO

Example: Acid Hydrolysis O CH 2 CN CH 2 COH H 2 O NO 2 H 2 SO 4 heat NO 2 (92 -95%)

Example: Basic Hydrolysis O CH 3(CH 2)9 CN 1. KOH, H 2 O, heat

Example: Basic Hydrolysis O CH 3(CH 2)9 CN 1. KOH, H 2 O, heat 2. H+ CH 3(CH 2)9 COH (80%)

Mechanism of Hydrolysis of Nitriles O RC N H 2 O RCNH 2 O

Mechanism of Hydrolysis of Nitriles O RC N H 2 O RCNH 2 O H 2 O RCOH Hydrolysis of nitriles proceeds via the corresponding amide. We already know the mechanism of amide hydrolysis. Therefore, all we need to do is to see how amides are formed from nitriles under the conditions of hydrolysis.

Mechanism of Hydrolysis of Nitriles OH RC N H 2 O RC O NH

Mechanism of Hydrolysis of Nitriles OH RC N H 2 O RC O NH RCNH 2 The mechanism of amide formation is analogous to that of conversion of alkynes to ketones. It begins with the addition of water across the carbon-nitrogen triple bond. The product of this addition is the nitrogen analog of an enol. It is transformed to an amide under the reaction conditions.

20. 20 Addition of Grignard Reagents to Nitriles

20. 20 Addition of Grignard Reagents to Nitriles

Addition of Grignard Reagents to Nitriles NMg. X RC N R'Mg. X diethyl ether

Addition of Grignard Reagents to Nitriles NMg. X RC N R'Mg. X diethyl ether RCR' NH H 2 O RCR' Grignard reagents add to carbon-nitrogen triple bonds in the same way that they add to carbonoxygen double bonds. The product of the reaction is an imine.

Addition of Grignard Reagents to Nitriles NMg. X RC N R'Mg. X diethyl ether

Addition of Grignard Reagents to Nitriles NMg. X RC N R'Mg. X diethyl ether RCR' NH H 2 O RCR' H 3 O + Imines are readily hydrolyzed to ketones. O Therefore, the reaction of Grignard reagents with nitriles can be used as a RCR' synthesis of ketones.

Example C N + CH 3 Mg. I F 3 C 1. diethyl ether

Example C N + CH 3 Mg. I F 3 C 1. diethyl ether 2. H 3 O+, heat O CCH 3 F 3 C (79%)