Convenient Preparation of Halo-1,3-thiazoles: Important Building Blocks for Materials and Pharmaceutical Synthesis

Abstract

Convenient, scalable and high-yielding approaches to 2,5- and 2,4-dibromo-1,3-thiazole are reported that offer significant improvements over previously reported approaches. 2,5-Dibromo-1,3-thiazole was generated in two steps from commercially inexpensive 2-amino-1,3-thiazole, whereas 2,4-dibromo-1,3-thiazole was generated in a single step from commercially inexpensive 1,3-thiazolidine-2,4-dione. As part of this study, convenient approaches to 2-bromo- and 2-iodo-1,3-thiazole were also developed.

Key words

halogenation - bromine - iodine - 1,3-thiazole - heterocycles

References

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  2-Bromo-1,3-thiazole is an article of commerce (e.g., $118/mol from Oakwood Products, Inc. as of the submission date of this paper).

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  The most attractive literature approach to 2-bromo-1,3-thiazole proceeds from commercially inexpensive 2-amino-1,3-thiazole ($17/mol from Alfa Aesar) in 75% yield.^6a Use of 2-amino-1,3-thiazole purchased from Acros Organics resulted in an isolated yield of only 40%, whereas 2-amino-1,3-thiazole purchased from Alfa Aesar gave 86% yield. Removal of the copper salts by filtration through Celite, followed by extraction of the filtrate, resulted in a 7% decrease in isolated yield of 2-bromo-1,3-thiazole compared to steam distillation of the crude material. Alternate approaches to 2-bromo-1,3-thiazole have also been reported. See, for example:

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16

2-Amino-5-bromo-1,3-thiazole is commercially available ($3509/mol from Accela ChemBio, Inc.)

26

POBr₃ is commercially available ($766/mol from Alfa Aesar).