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 -Pr2 NEt, 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
References <A NAME="RM02201SS-1">1 </A>
Tebufenozide (1a ) is commercially available.
<A NAME="RM02201SS-2A">2a </A>
Lidert Z,
Le DP,
Hormann RE, and
Opie TR. inventors; US Patent 5530028.
<A NAME="RM02201SS-3A">3a </A>
James WNJr, and
Aller HE. inventors; US Patent 5358966.
<A NAME="RM02201SS-4">4 </A>
Thomson WT.
Agricultural Chemicals, Book 1, Insecticides
Thomson Publications;
Fresno, CA:
1998.
14th ed..
p.142-144
<A NAME="RM02201SS-5A">5a </A>
Huang LJ.
Kuo SC.
Wang JP.
Ishii K.
Nakamura H.
Chem. Pharm. Bull.
1994,
41:
2036
<A NAME="RM02201SS-5B">5b </A>
Hazarika J.
Kataky JCS.
Ind. J. Heterocycl. Chem.
1997,
7:
47
<A NAME="RM02201SS-5C">5c </A>
Musser JH.
Brown RE.
Loev B.
Bailey K.
Jones H.
Kahen R.
Huang F.
Khandwala A.
Leibowitz M.
J. Med. Chem.
1984,
27:
121
<A NAME="RM02201SS-5D">5d </A>
Khandwala A.
Coutts S.
Dally-Meade V.
Jariwala N.
Musser J.
Brown R.
Jones H.
Loev B.
Weinryb I.
Biochem. Pharmacol.
1983,
32:
3325
<A NAME="RM02201SS-5E">5e </A>
Singh H.
Yadav LDS.
Bhattacharya BK.
J. Ind. Chem. Soc.
1980,
57:
1006
<A NAME="RM02201SS-5F">5f </A>
Meyer RF.
Cummings BL.
J. Heterocycl. Chem.
1964,
1:
186
<A NAME="RM02201SS-6A">6a </A>
Squillacote M.
Felippis JD.
J. Org. Chem.
1994,
59:
3564
<A NAME="RM02201SS-6B">6b </A>
Saegusa Y.
Nakamura S.
Chau N.
Iwakura Y.
J. Polym. Sci.
1983,
21:
637
<A NAME="RM02201SS-7">7 </A>
Gogoi PC.
Kataky JCS.
Heterocycles
1991,
32:
237
<A NAME="RM02201SS-8">8 </A>
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
CH2 Cl2 solution of ethyl carbazate with 3,5-dimethylbenzoyl chloride in the presence of
i -Pr2 NEt. 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.
<A NAME="RM02201SS-9A">9a </A>
Kelley MJ, and
Budenz AM. inventors; US Patent 5675037.