DIAMINOMETHANE DIHYDROCHLORIDE, A NOVEL REAGENT FOR THE SYNTHESIS OF PRIMARY AMIDES OF AMINO-ACIDS AND PEPTIDES FROM ACTIVE ESTERS

Amide formation from acids, N-protected amino acids and peptides was a chieved in an easy and convenient way by treating ''active esters'' su ch as succinimidyl or 4-nitrophenyl esters or acyl chlorides with diam inomethane dihydrochloride in dioxane in the presence of Et3N. Diamino methane dihydrochloride behaves as a slow ammonia-releasing agent. The method is a good alternative to the use of concentrated aqueous ammon ia; it avoids solubility problems and allows better control of the sto ichiometry of the reaction and of the pH. It gives good yields and doe s not induce racemization. The mechanism of the reaction is discussed. (C) Munksgaard 1993.