Synthesis of aryl 3‐(2‐imidazolyl)propyl ketones

Abstract

AbstractThe 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 glycol to provide the corresponding iodo ketals. Lithiation of either 1‐methyl‐ or 1‐(triphenylmethyl)imid‐azole 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.