腈加水可以分解為伯酰胺。由于伯酰胺會繼續(xù)水解為羧酸，一般要控制水解的條件。目前有許多方法報(bào)道，有時(shí)需要根據(jù)底物的特性選擇酸性，堿性或中性的水解條件。作為中性的條件，也有文獻(xiàn)報(bào)道使用鎳或鈀催化劑的方法。

在酸性條件下與飽和碳相連的氰基，可以在酸中很方便的水解轉(zhuǎn)化為酰胺，并在條件較為劇烈時(shí)，很容易進(jìn)一步水解成酸。但乙烯基或芳基腈的水解條件則要求劇烈得多，一般需要強(qiáng)酸條件，而且一般不會進(jìn)一步水解。

在堿性條件下，利用過氧化氫氧化的方法可在室溫下短時(shí)間內(nèi)水解腈為伯酰胺，這是一個較為可靠的方法。利用NaOH(aq.)-CH₂Cl₂相轉(zhuǎn)移催化體系，DMSO-K₂CO₃體系^[2]可以用于各種腈水解為伯酰胺。

1.1 鹽酸水解腈為伯酰胺示例^[3]

In a 3-l. three-necked round-bottomed flask equipped withglass joints are placed 200 g. (1.71 moles) of benzyl cyanide and 800 ml. of 35% hydrochloric acid. The flask is fitted with a reflux condenser, a thermometer,and an efficient mechanical stirrer.  At a bath temperature of about 40° themixture is stirred vigorously.  Within aperiod of 20–40 minutes the benzyl cyanide goesinto solution.  During this time, thetemperature of the reaction mixture rises about 10° above that of the bath.  The homogeneous solution is kept in the bathwith, or without, stirring for an additional 20–30 minutes.  The warm water in the bath is replaced by tapwater at about 15–20°, and the thermometer is replaced by a dropping funnel from which 800 ml. of cold distilledwater is added with stirring.  After theaddition of about 100–150 ml., crystals begin to separate.  When the total amount of water has been added,the mixture is cooled externally with ice water for about 30 minutes.  The cooled mixture is filtered by suction.  Crude phenylacetamideremains on the filter and is washed with two 100-ml. portions of water.  The crystals are then dried at 50–80°.  The yield of crude phenylacetamideis 190–200 g. (82–86%).

1.2 濃硫酸水解不飽和腈為伯酰胺示例^[4]

To 106 g of 84 % sulfuric acid, was added 50 g ofacrylonitrile.  After stirring for 30 minat r.t., the resulting mixture was heated to 95 ℃, and stirred for 2 h.  After cooling, the solid was collected bysuction, 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 wasfiltered off, and the filtrate was cooled. The precipitate was collected by filtration, and the filter cake waswashed by water, dried in vacuum to give the desired product.

1.3  H₂O₂-K₂CO₃-DMSO體系水解腈為伯酰胺示例^[1]

To a stirred solution of 4-chlorobenzonitrile (1.37 g,0.01 mol) in DMSO (3 ml), cooled in a ice bath, was added 30% H₂O₂(1.2 ml) and K₂CO₃, the reaction was allowed to warm upto r.t. (strong exothermic effect was observed).  After 5 min., distilled water (50 ml) wasadded, cooling applied, and the product was collected by filtration, yield 85%.

1.4       NaOH(aq.)-CH₂Cl₂相轉(zhuǎn)移催化體系水解腈為伯酰胺^[2]

To a magneticallystirred dichloromethane solution (1.5 ml) of o-tolunitrile (0.5 g, 4.27mmol) cooled in an ice bath, are added 30% hydrogen peroxide (2.0 ml),tetrabutylammonium hydrogen sulfate (0.290 g, 0.85 mmol), and a 20% aqueoussolution of sodium hydroxide (1.6 ml). The reaction mixture is allowed to warm up to r.t. and maintained understirring.  After 1.6 h, dichloromethaneis added, the organic layer is separated, washed with brine, and dried withsodium sulphate.  The solvent is removedunder reduced pressure to leave a white solid from which pure o-toluamide is obtained by chromatography on silicagel.  Yield 0.485 g (97%).

2  Ritter反應(yīng)

碳正離子加成到腈基的氮原子上生成的腈鹽加水分解得到相應(yīng)的酰胺加水可以分解為酰胺。一般能產(chǎn)生碳正離子化合物都可以發(fā)生這類反應(yīng)。由于醇或烯烴在濃硫酸或其他強(qiáng)酸加熱條件下反應(yīng)，一般在次條件下穩(wěn)定的腈都可用于該類反應(yīng)。

這類反應(yīng)通過腈和酸在溶劑中反應(yīng)，但對于乙腈來說，直接用乙腈中反應(yīng)即可，對于其他較為復(fù)雜，沸點(diǎn)較高的底物，一般用冰醋酸稀釋。

一般鹵代物用于這一反應(yīng)比烯烴和醇要差，但用亞硝基四氟硼酸鹽（NOBF₄）和亞硝基六氟磷酸鹽(NOPF₆ )可以室溫以下反應(yīng)^[5]。這兩個試劑也可直接拔除三取代碳上的氫生成碳正離子。

而通過鹵素或有機(jī)硒等對烯烴加成，得到的碳正性的中間體也可用于對乙腈的加成^[7]。如果所用的是環(huán)狀烯烴，則為反式加成。

2.1  Ritter反應(yīng)示例一^[8]  

A solution of 5.3 g (0.1 mol ) of acrylonitrile, 50ml of acetic acid and 7.4 g of ^tbutylalcohol in an ice-bath wastreated with conc. sulfuric acid (10.1 g, 0.1 mol) with stirring so asto keep the temperature below 40 ℃ during the addition and subsequent reaction (an hour), the reactionmixture was poured onto 200 g of ice, the product filtered and air dried, yield10 g (yield 80 %).  The product could berecrystallized from benzene.

2.2  Ritter反應(yīng)示例二^[9]

To a mixture of alcohol (10 mmol) andtrimethylsilyl cyanide (20 mmnol), cooled to - 15°C in an ice-salt bath, undernitrogen, is added concentrated sulfuric acid (30 mmol) dropwise with vigorousstirring (caution: highly exothermic).  Afterthe addition, the cold bath is removed and the mixture is stiffed at ambienttemperature for 18 hrs. Tile mixture is then poured onto ice, and neutralizedwith 50% NaOH solution to pH = 7.  Theaqueous is extracted with t-BuOMe or CHCl ₃, and the combinedorganic extracts are washed with brine, and dried over MgSO₄.  The crude product is purified by recrystallization(solid) or flash chromatography (oil).

相關(guān)反應(yīng)：Ritter反應(yīng)

Reference：

1.      Synthesis 1989, 949

2.      Synthesis 1980, 243

3.      Organic Syntheses, Coll. Vol. 1963,4, 760;

4.      Org. Syn., Coll. Vol. 1973,5,73; 1955,3, 66,88;

5.      J. Org. Chem., 1980,3235

6.      Tetrahedron Lett. 2002,1397

7.      J. Org. Chem. 1981, 4727

8.      J. Am. Chem. Soc. 1951, 4076

9.      Tetrahedron Lett. 1996, 8129

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