Influence of the structures of α-halo ketones and thioamides on the Hantzsch synthesis of thiazoles and thiazolo[5,4-b]indoles. A new approach to 4-acetyl-2-methyl-4H-thiazolo[5,4-b]indole
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In reactions with some α-halo ketones (3-bromo-1,1,1-trifluoropropan-2-one, 1-acetyl-2-bromoindolin-3-one, and α-bromoacetophenone), thioacetamide and a series of thioamides of aromatic and heteroaromatic acids are transformed into 4-hydroxy-Δ2-thiazolines rather than into thiazoles (the expected Hantzsch reaction products). To the contrary, thiazoles are produced in the reactions of the same α-halo ketones with thioamides of phenylacetic, diphenylacetic, 3-indolylacetic, or cyanoacetic acids. The abnormal course of the Hantzsch reaction in the former case results from the fact that 4-hydroxy-Δ2-thiazolines, which are intermediates in the thiazole synthesis, undergo virtually no dehydration under the Hantzsch reaction conditions. The ease of dehydration of hydroxythiazolines under the conditions of the thiazole synthesis and the possibility of the spontaneous thiazole synthesis depend on the nature of the substituent at position 2 and, consequently, on the structure of the starting thioamide. The Me, Ar, and Het substituents impede dehydration, whereas substituents containing the α-methylene (methine) unit at the C(2) atom of the thiazoline moiety substantially facilitate this reaction. The conditions for the dehydration of 4-acetyl-2-methyl-8b-hydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indole under basic catalysis were found, and a new procedure was developed for the preparation of thiazoles and 2-R-thiazolo[5,4-b]indoles, whose synthesis presents difficulties or is impossible under standard conditions.
Key wordsthiazoles 2-R-thiazolo[5,4-b]indoles Hantzsch reaction thioamides α-halo ketones structure 4-hydroxy-Δ2-thiazolines 2-R-4-acetyl-8b-hydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indoles dehydration
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- 8.Pat. RF 2024525; Byul. izobret. [Invention Bull.], 1994, 23 (in Russian).Google Scholar
- 9.Pat. RF 2009141; Byul. izobret. [Invention Bull.], 1994, 5 (in Russian).Google Scholar
- 10.J. V. Metzger, in Comprehensive Heterocyclic Chemistry, Eds A. R. Katritzky and C. W. Rees, Pergamon, Oxford, UK, 1984, Vol. 6, p. 236.Google Scholar
- 11.H. Singh, S. Singh, and A. S. Cheema, J. Ind. Chem. Soc., 1975, 53, 682.Google Scholar
- 12.K. Arakawa, T. Miyasaka, and H. Ohtsuka, Chem. Pharm. Bull., 1972, 20, 1041.Google Scholar
- 14.K. M. Murav’eva and M. N. Shchukina, Zh. Obshch. Khim., 1960, 30, 2334 [J. Gen. Chem. USSR, 1960, 30 (Engl. Transl.)].Google Scholar
- 15.V. S. Velezheva, A. Yu. Lepeshkin, O. A. Fedotova, V. I. Shvedov, K. F. Turchin, A. L. Sedov, and O. S. Anisimova, Khim.-farm. Zh., 1996, 30, No. 10, 37 [Pharm. Chem. J., 1996, 30, 643 (Engl. Transl.)].Google Scholar
- 17.V. Velezheva, A. Lepeshkin, and K. Turchin, Programme and Abstrs, 11th Europ. Symp. on Organic Chemistry (Goteborg, July 23–28, 1999), Goteborg, 1999, P181.Google Scholar