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Synthesis 2002(3): 0349-0354
DOI: 10.1055/s-2002-20032
PAPER
© Georg Thieme Verlag Stuttgart · New York

A General and Efficient Method for the Synthesis of 9-Trifluoromethylated [1,2,4]Triazolo[1,5-a]azepine Derivatives

Zongbiao Ding, Shijing Xia, Xiaojun Ji, Haiyan Yang, Fenggang Tao, Quanrui Wang*
Department of Chemistry, Fudan University, 200433 Shanghai, P. R. China
Fax: +86(21)65641740; e-Mail: qrwangb@online.sh.cn;
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Publication History

Received 5 September 2001
Publication Date:
28 July 2004 (online)

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Abstract

(1-Chloro-2-trifluoromethylcyclohexyl)azo compounds 3a-d, prepared by oxidation of the hydrazones 2a-d of 2-trifluoromethylcyclohexanone (1) with a slightly excess amount of tert-butyl hypochlorite, react with antimony pentachloride and a nitrile to afford the respective 2,3-disubstituted-9-trifluoromethyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepinium hexachloroantimo­nates 6a-j. The reaction mechanism comprises of the initial cycloaddition of the in situ generated 1-aza-2-azoniaallene salts 4 to the triple bond of nitrile, giving the spiro-substituted 5a-j, followed by rearrangement and concomitant ring enlargement. From 3a-c where R1 = aryl, the salts 6a-h are isolated in high yields. However, if ethyl (1-chloro-2-trifluoromethyl)azocarboxylate (3d) is employed, the neutral N(3)-unsubstituted analogues 7a and 7b are obtained and after usual basic work-up, are converted to picrates 8a and 8b respectively. For one compound 6f, the X-ray diffraction analysis has been carried out in order to confirm the structural assignment. A practical modified procedure for preparation of the crucial starting ketone 1 is also described.

Key words

1-aza-2-azoniaallene cations - cycloaddition - nitriles - ring enlargement - 9-trifluoromethyl-6,7,8,9-tetrahydro-5H-[1,2,4]-triazolo[1,5-a]azepines