Carbon 13 nuclear magnetic resonance studies on formaldehyde reactions with polyfunctional amino-acids

Addition and condensation reactions of formaldehyde with polyfunctional amino-acids and their N alpha-acetyl derivatives have been studied in neutral or mildly acid solutions using 13 C n.m.r. The first addition reaction, giving hydroxymethyls, is fast and incomplete with the amine, guanidyl, hydroxyl, indole and imidazole groups of the side chains, fast and complete with the sulfhydryl group, slow and complete with the amide group. For asparagine, threonine, histidine and tryptophan, the N alpha-hydroxymethyl condenses with the basic group of the side chain to give a cyclic compound. In the case of cysteine, it is the S-hydroxymethyl which condenses with the alpha-amino group. The value of the chemical shifts of the hydroxymethyls and of the methylene bondings will be of help in the study of the reactions of formaldehyde with proteins.