Synthesis 2012; 44(22): 3453-3464
DOI: 10.1055/s-0032-1316800
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Functionalized Fused-Ring Heterocycles from Tautomers of 2-(Thiazole, Oxazole, Benzothiazole, and Benzoxazole)-1-phenylethenols and 1,3-Diacid Chlorides or N-(Chlorocarbonyl) Isocyanate

Hondamuni I. De Silva*
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA   Fax: +1(662)3251618   Email: [email protected]   Email: [email protected]
Sabornie Chatterjee
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA   Fax: +1(662)3251618   Email: [email protected]   Email: [email protected]
William P. Henry
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA   Fax: +1(662)3251618   Email: [email protected]   Email: [email protected]
Charles U. Pittman Jr.*
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA   Fax: +1(662)3251618   Email: [email protected]   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 15 August 2012

Accepted after revision: 18 September 2012

Publication Date:
17 October 2012 (online)


2-Methylthiazole, 2,4,5-trimethylthiazole, 2,4,5-trimethyloxazole, 2-methylbenzothiazole, and 2-methylbenzoxazole were each reacted with benzoyl chloride in acetonitrile–triethylamine to generate (Z)-2-(heterocyclic)-1-phenylvinyl benzoates. Base hydrolysis of these vinyl benzoates formed (Z)-2-(heterocyclic)-1-phenylethenols, which exist in both keto and enol tautomeric forms. These tautomers were used as starting materials for fused-ring heterocycle syntheses. Reactions with 2,2-dialkyl-1,3-diacid chlorides in acetonitrile–triethylamine afforded their corresponding 5,6-ring-fused 8-benzoyl-6,6-dialkyl-6H-thiazolo-, 8-benzoyl-2,3,6,6-tetramethyl-6H-thiazolo-, 8-benzoyl-2,3,6,6-tetramethyl-6H-oxazolo-, 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]thiazolo-, and 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]oxazolo[3,2,-a]pyridinedione derivatives. The 5,6,6-tri-ring fused species, 10-benzoyl-7,8-dihydropyrano[2,3-d]thiazolo[3,2-a]pyridin-5(6H)-one, was formed in the reaction of the tautomers of (Z)-1-phenyl-2-(thiazol-2-yl)ethenol with cyclobutane-1,1-dicarbonyl dichloride via a ring expansion after­ 5,6-ring fusion. Functionalized 5,6-ring-fused 8-benzoyl-6H-thiazolo- and 8-benzoyl-6H-oxazolo[3,2-f]pyrimidine-5,7-diones, and 4-benzoyl-1H-benzo[4,5]thiazolo- and 4-benzoyl-1H-benzo[4,5]oxazolo[3,2-c]pyrimidine-1,3(2H)-diones were also synthesized by reacting the (Z)-2-(heterocyclic)-1-phenylethenol tautomers with N-chlorocarbonyl isocyanate in THF–triethylamine.

Supporting Information

  • References

    • 1a Popsavin M, Spaic S, Svircev A, Kojic V, Bogdanovic G, Popsavin G. Bioorg. Med. Chem. 2006; 16: 5317
    • 1b Zagade AA, Senthilkumar GP. Der Pharma Chemica 2011; 3: 523, and references cited therein
    • 1c Kashyap SJ, Garg VK, Sharma PK, Kumar N, Dudhe R, Gupta JK. Med. Chem. Res. 2012; 21: 2123 ; and references cited therein
    • 1d Davyt D, Serra G. Mar. Drugs 2010; 8: 2755 ; and references cited therein
  • 2 Broom NJ. P, Elder JS, Hannan PC. T, Pons JE, O’Hanlon PJ, Walker G, Wilson J, Woodall P. J. Antibiot. 1995; 48: 1336
    • 3a Kudo Y, Okamura N, Furumoto S, Tashiro M, Furukawa K, Maruyama M, Itoh M, Iwata R, Yanai K, Arai H. J. Nucl. Med. 2007; 48: 553
    • 3b Sato Y, Yamada M, Yoshida S, Soneda T, Ishikawa M, Nizato T, Suzuki K, Konno F. J. Med. Chem. 1998; 41: 3015
    • 3c Shrivastava B, Sharma V, Lokwani P. Pharmacologyonline 2011; 1: 236
    • 4a Chua MS, Shi DF, Wrigley S, Bradshaw TD, Hutchinson I, Shaw PN, Barett DA, Stanley L, Sausville EA, Stevens MF. G. J. Med. Chem. 1999; 42: 381
    • 4b Stevens MF. G, McCall CJ, Lelieveld P, Alexander P, Richter A, Davies DE. J. Med. Chem. 1994; 37: 1689
    • 4c Khokra SL, Arora K, Mehta H, Aggarwal A, Yadav M. Int. J. Pharm. Sci. Res. 2011; 2: 1356
  • 5 De Silva HI, Henry WP, Pittman Jr. CU. Synthesis 2012; in press; DOI: 10.1055/s-0032-1316790. Separate syntheses of 3a,b from 32 and 4a,b from 33 were also performed in our laboratory by S. Chatterjee as part of his PhD dissertation research. This work also employed both KOH in MeOH and n-propylamine in CH2Cl2 for the hydrolysis step
  • 6 Zhou A, Pittman CU. Jr. Tetrahedron Lett. 2005; 46: 2045
  • 7 Zhou A, Pittman CU. Jr. Synthesis 2006; 37
  • 8 Ye G, Zhou A, Henry WP, Song Y, Chatterjee S, Beard DJ, Pittman Jr. CU. J. Org. Chem. 2008; 73: 5170
  • 9 Chatterjee S, Ye G, Pittman CU. Jr. Tetrahedron Lett. 2010; 51: 1139
  • 10 Chatterjee S, Ye G, Song Y, Barker BL, Pittman CU. Jr. Synthesis 2010; 3384
  • 11 CCDC-894286–894288 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336 033; E-mail: [email protected]].
  • 12 Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
  • 13 Spek AL. Acta Crystallogr., Sect. A 1990; 46: 34