Crystal structures and properties of mutagenic N-acyloxy-N-alkoxyamides — “most pyramidal” acyclic amides

Abstract

X-Ray data for two N-acyloxy-N-alkoxyamides, a class of direct-acting mutagens, indicate extreme pyramidalisation at the amide nitrogen in keeping with spectroscopic and theoretically determined properties of amides with bisoxo-substitution at nitrogen. The combined electronegativity of two oxygens leads to average angles at nitrogen of 107.8 and 108.1° and |χ_N| of 66° and 65°. The sp³ nature of nitrogen results in negligible amide resonance as evidenced by long N–C(O) bonds, high IR carbonyl stretch frequencies, carbonyl ¹³C NMR data and very low amide isomerisation barriers. In addition, conformations in the solid state support a strong n_O–σ*_NOAc anomeric interaction as predicted by molecular orbital theory. HF/6-31G* calculations on formamide, N-methoxyformamide and N-formyloxy-N-methoxyformamide support these findings.