The synthesis of 2-carboxy-6-nitrobenzimidazole 1-oxides by intramolecular oxidation of α-(2,4-dinitrophenylamino)-αβ-unsaturated acyl derivatives

Abstract

In basic solutions of α-(2,4-dinitrophenylamino)αβ-unsaturated acyl derivatives, a 2-nitro-group intramolecularly oxidizes the β-position of the unsaturated acyl chain. Retroaldol cleavage of the oxygenated β-carbon occurs with ring closure of the scission product yielding an aldehyde and a 2-carboxy-6-nitrobenzimidazole 1-oxide (65–75%). This reaction occurs for the methyl ester of α-(2,4-dinitrophenylamino)acrylic acid and its β-substituted anologues, α-(2,4-dinitrophenylamino)crotonate and α-(2,4-dinitrophenylamino)cinnamate, in that respective order of reactivity, as well as the propyl amide of α-(2,4-dinitrophenylamino)acrylic acid. These reactions occur in protic and aprotic solvents with a large number of bases, and a tentative concerted mechanism is proposed. Reaction of N-2,4-dinitrophenylglycine methyl ester with base gives a moderate yield (50–60%) of 2-carboxy-6-nitrobenzimidazole 1-oxide as above. The N-2,4-dinitrophenyl methyl esters of serine, threonine, and β-phenylserine undergo retroaldol scission in base to the corresponding aldehyde and N-2,4-dinitrophenylglycine methyl ester, which quickly undergoes this same ring closure. This reaction occurs with sodium carbonate in methanol but not in dimethylformamide, and in contrast to the intramolecular oxidation is analogous to known base-catalyzed heterocyclic ring closure condensations of active methylene compounds with aromatic nitro-groups. The ring closures of N2,4-dinitrophenylamino-acid derivatives are suggested as reactions possibly useful in N-terminal amino-acid determination of peptides or glycoproteins.