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New synthesis of 2‐nitroimidazoles
Author(s) -
Davis Dwight P.,
Kirk Kenneth L.,
Cohen Louis A.
Publication year - 1982
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570190206
Subject(s) - chemistry , imidazole , nitration , methanol , yield (engineering) , tetrahydrofuran , nitroimidazole , organic chemistry , nitrate , carbanion , medicinal chemistry , materials science , solvent , metallurgy
1‐Triphenylmethylimidazoles are treated with n ‐butyllithium in tetrahydrofuran at 0° to form the 2‐lithio derivatives. The latter species react with n ‐propyl nitrate to give l‐trityl‐2‐nitroimidazoles which, after acid hydrolysis, provide the corresponding 2‐nitroimidazoles. 2‐Nitroimidazole was obtained from imidazole in overall yields of 27–35% 4‐methyl‐2‐nitroimidazole was obtained in 40% overall yield from 4‐methyl‐imidazole. Imidazole‐4,5‐dicarboxylic acid was converted, in several steps, to l‐tritylimidazole‐4‐methanol, and the latter compound was transformed into 2‐nitroimidazole‐4‐methanol in an overall yield of 18%. Protection of the hydroxymethyl function was found to be unnecessary during carbanion formation and nitration. Attempts to nitrate 1‐methylimidazole or 1‐methoxymethylimidazole by the same procedure failed.