Bodroux amide synthesis

What is Bodroux amide synthesis?

The Bodroux amide synthesis, first reported by Bodroux in 1904, involves the preparation of substituted amides by reacting a simple aliphatic or aromatic ester with an aminomagnesium halide in a 1:2 ratio at room temperature. However, direct aminolysis of carboxylic esters with primary amines requires high temperatures and the use of an autoclave. In addition to magnesium amides, other metal amides, such as alkali, aluminium, tin, and titanium amides, have been developed.

Bodroux amide synthesis - general reaction scheme
Bodroux amide synthesis

Bodroux amide synthesis has been modified to use lithium aluminum amide, prepared from LiAlH4 and amine in a 1:5 ratio at 25 ºC in Et2O. The formation of a precipitate indicates the completion of the process for preparing lithium aluminum amide, which usually takes 15-30 minutes for unhindered amines, but much longer for hindered amines (e.g., overnight for t-BuNH2). More recent modifications involve the reaction between a carboxylate, amine, and Grignard reagent in a 1:1:1.5 molar ratio for preparing amides.