Multi-13C-labeled inhibitors of tubulin assembly: 5-substituted methyl N-(1H-benzimidazol-2-YL)carbamates

Eight methyl N-(1H-benzimidazol-2-yl)carbamates with various 5-substituents were synthesized, each 13C-enriched at carbon 2, and the carbonyl and methoxy carbons. Five were prepared by cyclization involving the appropriate 4-substituted 1,2-diaminobenzene (C6H5CO-, CH3CH2CH2O-, CH3CH2CH2S-, C6H5S- and CH3CH2CH2CH2-), and methyl- 13C N-[imino(methylthio)methyl-13C]carbamate-13C or methyl N,N'-bis(methoxy-13C-carbonyl-13C)carbamimidothionate-13C. The latter were prepared from commercially available 13C-enriched (91-92 atom %) carbon tetrachloride, methanol, and thiourea. The remaining three (5-substituents: C6H5CH(OH)-, C6H5SO- and CH3CH2CH2SO-) were prepared by side-chain reduction or oxidation. The 1H- and 13C-NMR, and the methane CI mass spectral data of the products and intermediates are presented. (author)