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Synthesis 2001(13): 1965-1970
DOI: 10.1055/s-2001-17703
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Novel Convenient Synthesis of 1,3,4-Oxadiazol-2-ones and -thiones from N-tert-Butyldiacylhydrazines

Mark J. Mulvihill*, Duyan V. Nguyen, Brian S. MacDougall, Damian G. Weaver, William D. Mathis
Rohm and Haas Company, 727 Norristown Road, Spring House, Pennsylvania, 19477, USA
Fax: +1(914)3453565; e-Mail: mark.mulvihill@osip.com;
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Publication History

Received 4 May 2001
Publication Date:
10 August 2004 (online)

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Abstract

An attractive, novel, convenient process for the preparation of 3,5-disubstituted-3H-[1,3,4]-oxadiazol-2-ones and -thiones from the reaction of various equivalent and non-equivalent N-tert-butyldiacylhydrazines with potassium tert-butoxide followed by treatment with phosgene or thiophosgene, respectively, has been discovered. The 3,5-disubstituted-3H-[1,3,4]-oxadiazol-2-ones and -thiones are confirmed both analytically and chemically. Various equivalent and non-equivalent N-tert-butyldiacylhydrazines are conveniently synthesized from the reaction of tert-butylhydrazine hydrochloride in the presence of i-Pr2NEt, with acid chloride #1 followed by subsequent treatment with acid chloride #2. Both the syntheses of 3,5-disubstituted-3H-[1,3,4]-oxadiazol-2-ones and -thiones, as well as N-tert-butyldiacylhydrazines, are easily performed on multigram scales.

Key words

cyclization - heterocycles - regioselectivity - hydrazine - phosgene

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1

Tebufenozide (1a) is commercially available.

8

We decided to further chemically validate the structure of 4a utilizing Gogoi’s method [7] for the synthesis of 3,5-disubsti-tuted-3H-[1,3,4]-oxadiazol-2-ones. We synthesized N’-(3,5-dimethylbenzoyl)hydrazinecarboxylic acid ethyl ester from the reaction of a CH2Cl2 solution of ethyl carbazate with 3,5-dimethylbenzoyl chloride in the presence of i-Pr2NEt. Reaction of N’-(3,5-dimethylbenzoyl)hydrazinecarboxylic acid ethyl ester with POCl3 afforded 5-(3,5-dimethylphenyl)-3H-[1,3,4]-oxadiazol-2-one (7), which was analytically identical to compound 7 synthesized via Scheme [2] (Table [2] ). Benzoylation of 7 with 4-ethylbenzoyl chloride afforded 5-(3,5-dimethylphenyl)-3-(4-ethylbenozyl)-3H-[1,3,4]-oxadiazol-2-one (4a), which was identical in all respects to 4a synthesized via our phosgene/N-tert-butyldiacylhydrazine route.