A Facile Synthesis Of N-Hydroxymethyl Benzamide And Aminal Derivatives

In the first section of this paper, we choose hippuric acid as a model compound to investigate its oxidative decarboxylation induced by S₂O₈^2-/Ag⁺. By using 10 mol% of Ag(I) as catalyst, 1.1 equiv of (NH4)2S₂O₈, 1.0 equiv of zinc(II) sulfate,and CH3CN/water (1/1, v/v) as solvents, oxidative decarboxylation of hippuric acid at 80℃gave N-(hydroxymethyl)benzamide as the major product in the best yield 62%.In the second section, oxidative decarboxylation of N-acyl amino acid induced by S₂O₈^2-/Ag⁺ was carried out in formamide. We found the carboxyl group of N-acyl amino acid can be replaced by a formamido group to give N-acyl-N'-formyl aminal, by using 10 mol% of Ag(I) and 2.0 equiv of (NH4)2S₂O₈ at 50℃. For hippuric acids with 4-Cl or 4-Br, the yield of the corresponding product is 67% or 57%. For hippuric acid with 2-OMe, the highest yield (74%) was obtained.But for hippuric acid with 4-Me, the yield was reduced to 68%.When glycine was replaced by alanine, leucine and valine, the corresponding aminal derivatives were obtained in 71%, 64% and 64% yields, respectively. N- carbobenzoxy glycine gave the corresponding aminal derivative in modest (52%).In contrast to classic methods, our methodology can replace the carboxyl group of N-acyl amino acid with a formamido group in one step. The reagents used is inexpensive and easily available, the reaction condition is mild, and the process is simple, so it provides a facile synthesis of N-acyl-N'-Formyl aminal and could be extended to synthesis of the end-group modified retro-inverso peptide.