SYNTHESIS OF ARYL 3-(2-IMIDAZOLYL)PROPYL KETONES

The approach to the title compounds was via lithiation-substitution of N-methyl or N-(triphenylmethyl)imidazole by some iodo ketals. 4-Chloro-4'-halobutyrophenones (halo = F, Cl, Br) were converted by sodium iodide to the corresponding aliphatic iodides which were subsequently ketalized with ethylene glycoI to provide the corresponding iodo ketals. Lithiation of either 1-methyl- or 1-(triphenylmethyl)imidazole with n-butyllithium generated the corresponding 2-lithioimidazoles, in situ, which were then reacted with these iodo ketals to form the corresponding C-2 substituted imidazoles. Dilute aqueous acid hydrolysis released the ketone from the ketal. For N-triphenylmethyl protected imidazoles, the triphenylmethyl group was also hydrolyzed to give triphenylmethanol and 3-(2-imidazolyl)propyl 4-haloaryl ketones. These N-unsubstituted imidazolyl ketones can be alkylated independently with triphenylmethyl chloride to form the corresponding N-triphenylmethyl imidazole derivatives.