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

doi:10.1055/s-2002-20032

PAPER

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;

Abstract

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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

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References

1 Clark JH. Wails D. Bastock TW. In Aromatic Fluorination CRC Press, Int.; Boca Raton: 1996.

2 Filler R. Kobayashi Y. Yagupolskii LM. In Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications Elsevier; Amsterdam: 1993.

3 Resnati G. Soloshnok VA. Fluoroorganic Chemistry: Synthetic Challenges and Biomedical Rewards Tetrahedron Symposia; Tetrahedron 1996, 52: 1

4 McClinton MA. McClinton DA. Tetrahedron 1992, 48: 6555

5 Percy JM. Top. Curr. Chem. 1997, 193: 131

6 Liu X. Wang Q. Liu Y. Fan Y. Ding Z. Synthesis 2000, 435

7 Liu X. Wang Q. Zou J. Synth. Commun. 2000, 30: 119

8 Kroemer RT. Gstach H. Liedl KR. Rode BM. J. Am. Chem. Soc. 1994, 116: 6277

9 Cantacuzene D. Dorme R. Tetrahedron Lett. 1975, 25: 2031

10 Tordeux M. Francese C. Wakselman C. J. Chem. Soc., Perkin Trans. 1 1999, 1951

11 Unemoto T. Ishibara S. J. Am. Chem. Soc. 1993, 115: 2156

12 Rico I. Cantacuzene D. Wakselman C. Tetrahedron Lett. 1981, 22: 3405

13 Manning RE, and Huang HC. inventors; US patent US 5426105. ; Chem. Abstr. 1995, 123, 340134

14 Augusti R. Kascheres C. Tetrahedron 1994, 50: 6723

15 Watanabe Y. Usui H. Kobayashi S. Yoshiwara H. Shibano T. Tanaka T. Morishima Y. Yasuoka M. Kanao M. J. Med. Chem. 1992, 35: 189

16 Liu X. Zou J. Fan Y. Wang Q. Synthesis 1999, 1313

17 Wang Q. Jochims JC. Koehlbrandt S. Dahlenburg L. Al-Talib M. Hamed A. Ismail AE. Synthesis 1992, 710

18 Dewar MJS. Thiel W. J. Am. Chem. Soc. 1977, 99: 4907

19 Mintz MJ. Walling C. Org. Synth. Coll. Vol. V Wiley; New York: 1973. p.184

20 Holland DG. Moore GJ. Tamborski C. J. Org. Chem. 1964, 29: 1562

21 Risaliti A. Tetrahedron 1968, 24: 1889