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


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.