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Synthesis of aryl 3‐(2‐imidazolyl)propyl ketones
Author(s) -
Davis Frank S.,
Huang LiangFu,
Bauer Ludwig
Publication year - 1995
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570320340
Subject(s) - chemistry , imidazole , butyllithium , methyl iodide , medicinal chemistry , aryl , hydrolysis , ketone , sodium hydride , ethylene glycol , iodide , alkylation , aqueous solution , organic chemistry , alkyl , catalysis
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 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.