Cook–Heilbron thiazole synthesis
The Cook–Heilbron thiazole synthesis highlights the formation of 5-aminothiazoles through the chemical reaction of α-aminonitriles or aminocyanoacetates with dithioacids, carbon disulphide, carbon oxysulfide, or isothiocyanates at room temperature and under mild or aqueous conditions.[1][2] Variation of substituents at the 2nd and 4th position of the thiazole is introduced by selecting different combinations of starting reagents.[2]
This reaction was first discovered in 1947 by Alan H. Cook, Sir Ian Heilbron, and A.L Levy, and marks one of the first examples of 5-aminothiazole synthesis with significant yield and diversity in scope.
| Cook-Heilbron thiazole synthesis | |
|---|---|
| Named after | Alan H. Cook Ian Heilbron |
| Reaction type | Ring forming reaction |
Mechanism
In the first step of the
Applications
Few instances of applications of the Cook–Heilbron thiazole synthesis are found in literature.[2] In recent years, modifications of the Hantzsch thiazole synthesis are the most common, partly because of its ease in introducing R- group diversity.[8]
However, in 2008 Scott et al. employed a Cook-Heilbron synthesis in their approach to synthesize novel of pyridyl and thiazolyl bisamide CSF-1R inhibitors for use in novel cancer therapeutics. Thiazoles are essential components of many biologically active compounds making them important features in drug design.[10] Thiazoles are found in a number of pharmacological compounds such as tiazofurin and dasatinib (antineoplastic agents), ritonavir (an anti-HIV drug), ravuconazole (antifungal agent), meloxicam and fentiazac (anti-inflammatory agents) and nizatidine (anti-ulcer agent).[10]
Consequently, understanding and applying a range of approaches to synthesize thiazoles facilitates greater flexibility in both designing drugs as well as optimizing synthetic routes.
Relevance
References