Dehydration of an amide

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

The mechanism for the dehydration of an amide with thionyl chloride is shown below ... 

The dehydration of an amide containing an acid-sensitive acetal group to a cyano acetal like /3,/3-diethoxypropionitrile has been carried out with phosphorus pentoxide in the presence of triethylamine. ... 

Dehydration of an amide. DCC in pyridine dehydrales curbobenzoxy-i -asparagine (1) to the corresponding nitrile (2)." ... 

A procedure for the preparation of 2-ethylhexanonitrile shows that the conditions required for the dehydration of an amide are much the same as for the preparation of an acid chloride. 

RCONHi — RC=N. In theory the dehydration of an amide should require only 0.33 mole of phosphorus pentoxide, but procedures for the dehydration of isobutyr-amide, nicotinamide, and fumaramide all call for use of a large excess of reagent. 

Dehydration of an amide [1, 234, after citation of ref. 25]. Liberek et al,25a used this method but instead of the carbobcnzoxy group they used the trityl group, which can be removed with 50% acetic acid. 

Amides undergo dehydration. Useful dehydrating agents include SOCl2, P4O10 (P20 ), (AcO)20, and POCl3/A. The product is a nitrile, and in fact, dehydration of an amide is one method to produce aryl nitriles. Figure 12-38 shows the synthesis of 2-ethylhexanenitrile from 2-ethylhexanamide with a 94-percent yield. 

Nitriles can also be prepared via the dehydration of an amide. Many reagents can be used to accomplish the transformation. One such reagent is thionyl chloride (SOCI2). 

Reactions.—It has been known for many years that nitriles can be converted into amides by heating them in a weakly basic medium in the presence of hydrogen peroxide. This conversion may be carried out just as easily using potassium hydroxide-t-butyl alcohol in the absence of hydrogen peroxide. The reverse reaction, dehydration of an amide, can be carried out by using a new reagent (13), which is the adduct of a nitrile and sulphuric anhydride. ... 

Nitrile Process. Fatty nitriles are readily prepared via batch, Hquid-phase, or continuous gas-phase processes from fatty acids and ammonia. Nitrile formation is carried out at an elevated temperature (usually >250° C) with catalyst. An ammonia soap which initially forms, readily dehydrates at temperatures above 150°C to form an amide. In the presence of catalyst, zinc (ZnO) for batch and bauxite for continuous processes, and temperatures >250° C, dehydration of the amide occurs to produce nitrile. Removal of water drives the reaction to completion. 

DV Kashelikar, C Ressler. An oxygen-18 study of the dehydration of asparagine amide by N,N -dicyclohexylcarbodiimide and p-toluenesulfonyl chloride. J Am Chem Soc 86, 2467, 1964. 

Many methods for the dehydration of primary amides to nitriles involve the use of strong acids and/or other reagents which are incompatible with sensitive functionality. French workers have recently described an unusual, mild, efficient (64-92%) and fairly general procedure for the RCONH2 —> RCN transformation which simply involves heating a mixture of the amide, an aldehyde and formic acid under reflux in acetonitrile for 12 hours. The following observations were made ... 

Dehydration of amides to aitriles. When a mixture of an amide and (I) in the ratio of 3 1 is heated at temperatures above 100°, nitrile.s are formed rapidly and in high yield (usually in the range 75-100%). The dehydration can also be carried out by refluxing the reactants in a solvent (usually chlorobenzene). In many cases, a ratio of amide to (1) of 6 1 is effective. 

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