The synthesis of imidazole‐2‐thione nucleosides

Ribosylation of the trimethylsilyl derivative (1b) of imidazole-2-thione (1a) using either stannic chloride or silver perchlorate as catalyst resulted in the formation of the acylated derivatives of 1-(β-D-ribofuranosyl)imidazole-2-thione (3c) and 1,3-di-(β-D-ribofuranosyl)imidazole-2-thione (4c) with the latter predominating (4c:3c, ca. 2:1). The diribosylated nucleoside 4c was shown to be the N,N-disubstituted product rather than the N,S-disubstituted product by 1H nmr and 13C nmr spectroscopy. Employment of the iodine-catalyzed fusion procedure reversed the aforementioned product ratios and provided the monoriboside 3c in excellent yield. When the trimethylsilyl derivative (5b) of 2-methylthioimidazole (5a) was reacted with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (2d) in acetonitrile, the major product was 1,3-di-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-imidazole-2-thione (4b). The formation of 4b in this reaction is thought to arise via the Hilbert-Johnson mechanism.