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Synthesis of 4,4‐dimethyl‐3,4‐dihydro‐3,3,5‐trisubstituted‐2 H ‐pyrazoles and N ‐benzoyl derivatives: Method for “Hydrolysis” of unreactive amides and carbamates
Author(s) -
Baumstark Alfons L.,
Choudhary Anil,
Vasquez Pedro C.,
Dotrong My
Publication year - 1990
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.5570270233
Subject(s) - chemistry , yield (engineering) , dimethyl sulfate , reagent , hydrolysis , dimethyl sulfoxide , benzoyl chloride , toluene , medicinal chemistry , aryl , organic chemistry , catalysis , alkyl , carbamate , materials science , metallurgy
Addition of organolithium reagents to 4,4‐dimethyl‐3,5‐disubstituted‐4 H ‐pyrazoles produced a series of 4,4‐dimethyl‐3,4‐dihydro‐3,3,5‐trisubstituted‐2 H ‐pyrazoles, 2–6 , in good yield. The reaction was stereoselective: addition of organolithium compounds occurred only to carbon‐3 of 4,4‐dimethyl‐3‐alkyl‐5‐aryl‐4 H ‐pyrazoles. The 3,4‐dihydro‐2 H ‐pyrazoles were found to be of high sensitivity to oxygen. For long term storage and ease of handling, N‐benzoyl derivatives were synthesized. Removal of the protecting group could not be accomplished by use of many standard sets of conditions. Deprotection was accomplished in high yield by reaction of the N‐benzoyl‐4,4‐dimethyl‐3,4‐dihydro‐3,3,5‐trisubstituted‐2 H ‐pyrazoles with anhydrous potassium t ‐butoxide in toluene [heated under reflux (ultra‐pure argon)] in the presence of a phase transfer catalyst (18‐Crown‐6). Cleavage of a N‐carbamate derivative was also achieved by this phase transfer approach. This methodology should be applicable to the hydrolysis of unreactive amides and carbamates in general.