Russian Chemical Bulletin

, Volume 56, Issue 7, pp 1441–1446 | Cite as

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

  • A. Yu. Lepeshkin
  • K. F. Turchin
  • A. L. Sedov
  • V. S. Velezheva


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 words

thiazoles 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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Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • A. Yu. Lepeshkin
    • 1
  • K. F. Turchin
    • 1
  • A. L. Sedov
    • 2
  • V. S. Velezheva
    • 2
  1. 1.Center for Drug ChemistryAll-Russian Chemical and Pharmaceutical Research InstituteMoscowRussian Federation
  2. 2.A. N. Nesmeyanov Institute of Organoelement CompoundsRussian Academy of SciencesMoscowRussian Federation

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