Metal–halogen exchange reactions of mono- and poly-halogenoimidazoles

Abstract

4(5)-Bromoimidazole gave a mixture of 4- and 5-bromo-1-methylimidazole on treatment with 1 or 2 mol equiv. of n-butyl-lithium in ether or THF under various reaction conditions followed by addition of dimethyl sulphate. 5-lodo- and 2,4,5-tribromo-1-methylimidazole were prepared similarly. Attempts to exchange the bromine atoms for lithium in 5-bromo- or 2,4,5-tribromo-1-methylimidazole with n-butyllithium failed. 2,4,5-Tribromo-1-ethoxymethylimidazole was prepared by N-1-alkylation of tribromoimidazole with chloromethyl ethyl ether in benzene in the presence of triethylamine. Corresponding alkylation of 2,4,5-tri-iodoimidazole required the use of sodium methoxide in dioxan and gave mainly 1-ethoxymethyl-4,5-di-iodoimidazole. Successive treatment of 2,4,5-tribromo-1-ethoxymethylimidazole with n-butyl-lithium and diphenyl disulphide gave 4,5-dibromo-1-ethoxymethyl-2-phenylthioimidazole which, on further reaction with n-butyl-lithium followed by addition of dimethyl disulphide, gave 4-bromo-1-ethoxymethyl-5-methylthio-2-phenylthioimidazole. 1-Ethoxymethyl-4,5-di-iodoimidazole reacted successively with n-butyl-lithium and diphenyl disulphide to give a mixture of 1-ethoxymethyl-4-iodo-2-phenylthioimidazole (major product) and 1-ethoxymethyl-4-iodo-2,5-bisphenylthioimidazole.