Azoles. Part 5. Metal-halogen exchange reactions of polybromoimidazoles

Abstract

1,2-Dilithiated imidazoles were prepared by treating 2-bromo-4,5-dichloro- and 2,4,5-tribromoimidazole with 2 equivalents of butyl-lithium and trapped with various electrophiles to give moderate yields of the 2-substituted 4,5-dihalogeno compounds (4)–(10). The 4,5-dibromoimidazole (4), prepared in this way, was converted into the 1-protected derivatives (18)–(22)(protecting group = CH2CH2SO2Ph, CH2CO2Et, CPh3, SO2Ph, SO2C6H4Me-4). 4-Bromo-5-chloro-1-tritylimidazole was prepared similarly. Successive treatment of 4,5-dibromoimidazole with 2 equivalents of butyl-lithium, benzophenone, and acid gave a low yield of 4(5)-bromoimidazol-5(4)-yldiphenylmethanol (11). Whereas 1-protected 2,4,5-tribromoimidazoles [P = CH2OMe, CH2OEt, CH2Ph, CH2C6H4OMe-4, CH2C6H3(OMe)2-3,4] reacted at both the 2- and 5-bromine atoms with 1 equivalent of butyl-lithium, they reacted with 1 equivalent of other organometallic reagents (EtMgBr, MeLi, s-BuLi, PhLi) regioselectively at the 2-position and the intermediate organometallic compounds were either hydrolysed or quenched with benzophenone, to give the corresponding 1-protected 4,5-dibromoimidazoles (13)–(17) and compound, (25), respectively, in good yields. Compounds (13)–(17) were treated with a further equivalent of butyl-lithium and the resulting imidazol-5-yl-lithium derivatives were either quenched with an electrophile or hydrolysed with water; e.g. 1-benzyl-4-bromoimidazol-5-yl-lithium was treated with dimethylformamide (DMF), carbon dioxide, methyl chloroformate, and elemental sulphur to give compounds (33)–(36), respectively. Other 1-protected 4-bromoimidazole-5-carbaldehydes, (31), (32), and (37)–(40) were prepared similarly from the corresponding 4,5-dibromoimidazole.