Synthesis of [¹³C₆]3,4-Diaminobenzoic Acid As a Precursor for Stable Isotope Labeled Benzimidazoles

Matthew G. Donahue, University of Southern Mississippi
Nicholas G. Jentsch, University of Southern Mississippi
Casey R. Simons, University of Southern Mississippi

Abstract

The synthesis of [¹³C₆]3,4-diaminobenzoic acid from commercially available [¹³C₆]aniline is described in six steps. Salient features of this route include the preparation of a differentially protected 3,4-diaminobenzonitrile, hydrogen gas free aromatic nitro group reduction with ammonium formate and facile benzimidazole ring closure of the ortho-arylenediamine with triethylorthoformate. This stable-labeled 3,4-diaminobenzoic acid is an ideal [M+6]isotopomer to synthesize complex benzimidazole fragments for mass spectrometry internal assays.