Synthesis of Highly Substituted Imidazoles from 1,2-Amino Alcohols and Thioamides

Significance

Reported is a synthesis of substituted imidazoles by HgCl₂-assisted cyclocondensation of thioamides with 1,2-aminoalcohols followed by oxidative aromatization of the intermediate dihydroimidazoles. Both steps are performed under mild conditions and provide the target tri- and tetrasubstituted imidazoles in good to excellent preparative yields. Noteworthy, the procedure has been applied to a variety of amino alcohols including ones containing acid-sensitive groups (NBoc) since most of the known protocols for imidazole-ring construction (see: J. R. Davies, P. D. Kane, C. J. Moody Tetrahedron 2004, 60, 3967; M. Gall, B. V. Kamdar J. Org. Chem. 1981, 46, 1575; M. G. Bock et al. J. Med. Chem. 1988, 31, 176) involve catalysis by Lewis acids and do not allow this type of substitution.