Unexpected Heteroannulation and Chlorination of Benzothiadiazine Derivatives Mediated by DDQ

Abstract

In the course of studies directed toward the synthesis of new tubulin polymerization inhibitors, several benzothiadiazine derivatives were prepared. The oxidative dehydrogenation reaction with DDQ unexpectedly led to heteroannulation and chlorination of the benzothiadiazine tricycles. A rationale for their formation is proposed.

Key words

benzothiadiazine - oxidative dehydrogenation - heteroannulation - radical reaction - diastereoselectivity

• References

• 1a Gallet S, Lebegue N, Flouquet N, Berthelot P, Pierre A, Renard P, Pfeiffer B. International Patent PCT FR 04/00234, 2004
• 1b Gallet S, Lebegue N, Flouquet N, Berthelot P, Pierre A, Renard P, Pfeiffer B. International Patent PCT FR 04/00235, 2004
• 1c Lebegue N, Gallet S, Flouquet N, Carato P, Pfeiffer B, Renard P, Leonce S, Pierre A, Chavatte P, Berthelot P. J. Med. Chem. 2005; 48: 7363
• 2 Gallet S, Flouquet N, Carato P, Pfeiffer B, Renard P, Leonce S, Pierre A, Berthelot P, Lebegue N. Bioorg. Med. Chem. 2009; 17: 1132
• 3 Lecoeur M, Verones V, Vaccher C, Bonte JP, Lebegue N, Goossens JF. Eur. J. Pharm. Sci. 2012; 45: 559
• 4 Bourdon F, Lecoeur M, Verones V, Vaccher C, Lebegue N, Dine T, Kambia N, Goossens JF. J. Pharm. Biomed. Anal. 2013; 80: 69
• 5a Chern JW, Tao PL, Wang KC, Gutcait A, Liu SW, Yen MH, Chien SL, Rong JK. J. Med. Chem. 1998; 41: 3128
• 5b Boverie S, Antoine MH, de Tullio P, Somers F, Becker B, Sebille S, Lebrun P, Pirotte B. J. Pharm. Pharmacol. 2001; 53: 973
• 6a Fu PP, Harvey RG. Chem. Rev. 1978; 78: 317
• 6b Comprehensive Organic Synthesis . Trost BM, Fleming I. Pergamon; Oxford: 1992
• 7a Jackman LM. Adv. Org. Chem. 1960; 2: 329
• 7b Ahluwalia VK, Ghazanfari FA, Arora KK. Synthesis 1981; 526
• 7c Ahluwalia VK, Jolly RS. Synthesis 1982; 74
• 7d Fu PP, Harvey RG. Tetrahedron Lett. 1977; 2059
• 7e Abad A, Agulló C, Arnó M, Domingo LR, Zaragozá RJ. J. Org. Chem. 1988; 53: 3761
• 8a Chern JW, Rong JG. Tetrahedron Lett. 1991; 32: 2935
• 8b Chern JW, Liaw YC, Chen CS, Rong JG, Huang CL, Chan CH, Wang AH. J. Heterocycles 1993; 36: 1091
• 9 See experimental for details.
• 10 Clark M, Cramer RD. III, van Opdenbosch N. J. Comput. Chem. 1989; 10: 982
• 11 SYBYL 6.9.1, Tripos Inc., 1699 South Hanley Road, St. Louis, MO 63144-2913, USA.
• 12 Respectively, 13.47 and 13.75 kcal/mol for the trans-conformers and 14.62 and 14.91 kcal/mol for the cis-conformers. See Supporting Information for details.
• 13a Oikawa Y, Yoshioka T, Yonemitsu O. Tetrahedron Lett. 1982; 23: 885
• 13b Chandrasekhar S, Sumithra G, Yadav JS. Tetrahedron Lett. 1996; 37: 1645
• 13c Weissman SA, Zewge D. Tetrahedron 2005; 61: 7833
• 14 Jung HH, Floreancig PE. Tetrahedron 2009; 65: 10830
• 15 Navale TS, Thakur K, Rathore R. Org. Lett. 2011; 13: 1634
• 16 Pragnacharyulu PV. P, Abushanab E. Tetrahedron Lett. 1997; 38: 3683
• 17 Ito S, Phong LT, Komatsu T, Igarashi N, Otsubo S, Sakai Y, Ohno A, Aramaki S, Tanaka Y, Uno H, Oba T, Hiratani K. Eur. J. Org. Chem. 2009; 5373