Reactions of halonitroimidazoles with nucleophiles (review)

Abstract

On account of their chemical stability, high reactivity, and availability 4(5)-halo-5(4)-nitro-and 2-halo-4(5)-nitroimidazoles have proved useful substrates for the study of reactions with O-, S-, N-, C-, and N,O-nucleophiles. The high reactivity of the halogen atom in the series of 4(5)-halo-5(4)-nitroimidazoles is brought about by the presence of the strong electron-accepting NO 2 group at the "ortho" position. The activating effect of the NO 2 group also extends to the halogen atom at position 2 of the imidazole ring.The products from the reactions of halonitroimidazoles with various nucleophiles have found use in fine organic synthesis, especially in the synthesis of heterocycles with a bridging nitrogen atom, biologically active compounds, and medicinal preparation. Thus, 1-methyl-4-nitro-5-(6-purinyl)mercaptoimidazole has found use under the name azathioprine as a medical preparations in the transplantation of vital organs and the treatment of a series of autoimmune diseases [1][2][3][4].

Properties of haloimidazoles (review)

“…Electron-withdrawing groups (NO 2 , CHO, CF 3 , etc.) at position 5(4) greatly increase the reactivity of the neighboring halogen atom, as demonstrated by the reaction of 4(5)-halo-5(4)-nitroimidazoles with nucleophiles [74] and by the nucleophilic substitution reactions for trifluoromethyl-and formylhaloimidazoles 130 and 131 respectively presented below.…”

“…Thus, the reaction of 4-halo-1-trimethylsilylimidazoles 49a-c with the O-protected ribofuranose 73 and 2-fluoro-1-methylpyridinium tosylate (74) in dichloromethane in the presence of diisopropylethylamine at -30-0°C leads to a mixture of the glycosides 72a-c with the α-configuration (yields 65-75%) and the β-configuration (yields 15-20%). The isomeric 4-haloglycosides are not formed under these conditions.…”