Acylation of nitrogen compounds by carboxylic esters

Acylation of nitrogen compounds by carboxylic esters. The action of carboxylic esters on ammonia or primary or secondary amines generally leads to carboxamides under relatively mild conditions, and the analogous treatment of carboxylic esters with hydrazine and hydroxylamine provides the most important methods of preparing simple carboxhydrazides and carbohydrox-amic acids. 

It often suffices for preparation of unsubstituted amides to stir or shake the ester with concentrated aqueous ammonia, but the conditions required vary widely from case to case. For example, ethyl cyanoacetate754 and concentrated aqueous ammonia afford 88% of the amide in 1 hour without external heating, and methyl fluoroacetate reacts equally rapidly (N.B. a potent poison)  

Fluoroacetamide 765 Methyl fluoroacetate (20 g) is cooled in ice-water and treated with an excess of aqueous ammonia (d 0.88 20 ml). After 1 h the precipitate is filtered off (15 g) and dried this product is almost pure. Evaporation of the mother-liquor makes the yield up to 100%. Recrystallization from chloroform or chloroform-light petroleum gives crystals of m.p. 108°. 

Ethyl fumarate, however, requires 7 hours stirring with concentrated aqueous ammonia at 25-30°,766 and considerably longer time is necessary for aminolysis of methyl methacrylate 767 

Methacrylamide Methyl methacrylate (76 g) is shaken for 7 days with ammonia solution (d 0.885 390 ml). The homogeneous solution is then evaporated in portions in a vacuum (19 mm) on a water-bath (78°), and the crude product is dried over calcium chloride to constant weight (65 g), broken into small pieces, and dissolved in methylene chloride (580 ml) boiling under reflux. The solution is filtered through a filter heated by hot water, and the residue is extracted again with methylene chloride (60 ml). When the filtrates are cooled in an ice-bath, monomeric methacrylamide crystallizes two further fractions can be obtained from the mother liquors, bringing the total yield of material melting at 95-109° up to 48 g (75%). To obtain the pure amide, as thin tablets, m.p. 110-111°, requires repeated recrystallization. 

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