Amide and Acid hydrazides from Esters

Amides cannot be easily prepared by the direct reaction of ammonia or amines withcarboxylic acids because amines function as bases to convert carboxylic acids into their unreactive ammonium carboxylate salts. Although these salts may beconverted into amides by heating to high temperatures (200 C), the forcing natureof these conditions severely limits the applicability of this method.

Amore general method for preparing amides involves a two-step procedure in which the carboxylic acid is first converted to an acid chloride that is then treated with an amine to give the desired amide according to following equation. Acid chlorides are among the most reactive derivatives of carboxylic acids and thus are often used to prepare other organic compounds having an acyl group, including esters and aryl alkyl ketones.

Methyl and ethyl esters react with hydrazine to giveacid hydrazides: RCO2Me + H2NNH2 RCONHNH2 + MeOH The hydrazides are often crystalline and then serve as useful derivatives. Estersof higher alcohols should be converted first to the methyl esters by boiling withsodium methoxide in methanol or ethanol.

Procedure for the preparation of 3-nitrobenzoic acid hydrazide

Methyl 3-nitrobenzoate ester (7 g, 0.041 mol) was dissolved in absolute ethanol (40 mL) and takenin a flask fitted with a reflux condenser. Hydrazine hydrate (80%,13 mL) was added, and then, the reaction mixture was refluxed for 4 hours. The reflux time could be monitored by TLC. After the completion of the reaction, the excess hydrazine and ethanol solvent were distilled off by simple distillation. The crude solid of acid hydrazide was collected, washed with water and recrystallized from 50% aqueous ethanol.Yield 90%, m.p. 152155C.