Nucleophilic substitution in quaternary salts of NN′-linked biazoles and related systems.

Abstract

Some reactions of dicationic and monocationic N,N′-linked biazoles and of quaternized 1-(N-azolyl) pyridinium ions with nucleophiles have been studied. Although the pyrrolyl nucleus has been found to be a poor leaving group in these reactions, in other cases nucleophilic attack readily takes place at an azolyl carbon atom, with subsequent elimination of the N-substituent. The 1-methyl-3-(1-methyl-1,2,4-triazol-4-ylio) benzimidazolium dication (1) reacted at room temperature with ammonium, diethylamine, methoxide, hydroxide, and cyanide ions, and with sodium borohydride, giving in all cases the corresponding 2-substituted benzimidazoles in good yield. In the case of the 2,4,6-trimethyl-1-(2-methylpyrazol-1-io)pyridinium dication (6), the reaction with cyanide ion afforded, regioselectively, 5-cyano-1-methylpyrazole, with no trace of the isomeric 3-cyano-1-methylpyrazole.

The synthesis of the cations and dications from N-aminoazoles was easily performed. The reaction of 1-aminobenzimidazole with dehydroacetic acid in aqueous hydrochloric acid gave not only the expected 1-benzimidazol-1-yl-2,6-dimethylpyridin-4(1H)-one (9), but also 3-acetyl-1-benzimidazol-1-yl-4-hydroxy-6-methylpyridin-2(1H)-one (11). In pyridine, a pyran-2,4-dione intermediate (10), isomeric to (11), was also isolated. The quaternization reactions were easily performed, but high temperatures caused cleavage of the N–N bond.