Generation of Hydrogen Cyanide from the Reaction of Oxyma (Ethyl Cyano(hydroxyimino)acetate) and DIC (Diisopropylcarbodiimide)

Evolution of hydrogen cyanide (HCN) during amino acid activation using the reagent combination ethyl cyano­(hydroxyimino)­acetate (Oxyma)/diisopropylcarbodiimide (DIC) is observed under ambient conditions (20 °C) in N,N-dimethylformamide (DMF). Concentration versus time profiles obtained by 1H NMR spectroscopy in the presence and absence of amino acids indicate that HCN is formed upon addition of DIC to the reaction mixture and that HCN evolution continues to occur even after amino acid activation is complete when Oxyma and DIC are used in excess amounts relative to the amino acid. A mechanism for the reaction between Oxyma and DIC is proposed, and evidence for its validity was gathered by NMR spectroscopy.