氰转化为酰胺-060123

经典化学合成反应标准操作氰基转化为酯和酰胺

编者：杜晓行

药明康德新药开发有限公司化学合成部

目录

1．前言 (2)

2．氰基转化为酯 (2)

3．氰基转化为酰胺 (2)

3.1丙稀酰胺的合成 (2)

3.2苯乙酰胺的合成 (3)

6.从氰基合成酰胺

6.1氰基水解

腈加水可以分解为伯酰胺。由于伯酰胺会继续水解为羧酸，一般要控制水解的条件。目前有许多方法报道，有时需要根据底物的特性选择酸性，碱性或中性的水解条件。作为中性的条件，也有文献报道使用镍或钯催化剂的方法。

在酸性条件下与饱和碳相连的氰基，可以在酸中很方便的水解转化为酰胺，并在条件较为剧烈时，很容易进一步水解成酸。但乙烯基或芳基腈的水解条件则要求剧烈得多，一般需要强酸条件，而且一般不会进一步水解。

在碱性条件下，利用过氧化氢氧化的方法可在室温下短时间内水解腈为伯酰胺，这是一个较为可靠的方法。利用NaOH(aq.)-CH2Cl2相转移催化体系，DMSO-K2CO3体系[2]可以用于各种腈水解为伯酰胺。

6.1.1盐酸水解腈为伯酰胺示例[3]

HCl, H2O

CN CONH2

In a3-l.three-necked round-bottomed flask equipped with glass joints are placed200g.(1.71 moles)of benzyl cyanide and800ml.of35%hydrochloric acid.The flask is fitted with a reflux condenser,a thermometer,and an efficient mechanical stirrer.At a bath temperature of about40°the mixture is stirred vigorously.Within a period of20–40minutes the benzyl cyanide goes into solution.During this time,the temperature of the reaction mixture rises about10°above that of the bath.The homogeneous solution is kept in the bath with,or without,stirring for an additional20–30minutes.The warm water in the bath is replaced by tap water at about15–20°,and the thermometer is replaced by a dropping funnel from which 800ml.of cold distilled water is added with stirring.After the addition of about100–150 ml.,crystals begin to separate.When the total amount of water has been added,the mixture is cooled externally with ice water for about30minutes.The cooled mixture is filtered by suction.Crude phenylacetamide remains on the filter and is washed with two100-ml. portions of water.The crystals are then dried at50–80°.The yield of crude phenylacetamide is190–200g.(82–86%).

6.1.2浓硫酸水解不饱和腈为伯酰胺示例[4]

CN

CONH 2

1. H 2SO 4

2. NH 3

To 106g of 84%sulfuric acid,was added 50g of acrylonitrile.After stirring for 30min at r.t.,the resulting mixture was heated to 95℃,and stirred for 2h.

After cooling,the solid

was collected by suction,and the filter cake was transferred into a beaker.

To the ice-cooled

solid,was added aq.ammonia with the speed that keep the temperature less than 50℃.The

precipitated ammonium sulphate was filtered off,and the filtrate was cooled.

The precipitate

was collected by filtration,and the filter cake was washed by water,dried in vacuum to give the desired product.

6.1.3H 2O 2-K 2CO 3-DMSO 体系水解腈为伯酰胺示例[1]

Cl

CN

30% H 2O 2, K 2CO 3

DMSO, rt, 5 min

Cl

O

NH 2To a stirred solution of 4-chlorobenzonitrile (1.37g,0.01mol)in DMSO (3ml),cooled in a ice bath,was added 30%H 2O 2(1.2ml)and K 2CO 3,the reaction was allowed to warm up to r.t.(strong exothermic effect was observed).

After 5min.,distilled water (50ml)was added,

cooling applied,and the product was collected by filtration,yield 85%.

6.1.4NaOH(aq.)-CH 2Cl 2相转移催化体系水解腈为伯酰胺[2]

CN

(n -C 4H 9)N +HSO 4-30 % H O , CH Cl NH 2

O To a magnetically stirred dichloromethane solution (1.5ml)of o -tolunitrile (0.5g,4.27mmol)cooled in an ice ba th,are added 30%hydrogen peroxide (2.0ml),tetrabutylammonium hydrogen sulfate

(0.290g,0.85mmol),and a 20%aqueous solution of sodium hydroxide (1.6ml).

The