Thiazole Sandmeyer reaction

Halothiazoles are usually obtained from 2-aminothiazoles through the Sandmeyer reaction. Nevertheless, ammonolysis has sometimes proved useful for the preparation of 2-aminothiazole derivatives. Detweiler et al. (18) obtained 2-(u-pyridinylamino)thiazole (1) from 2-bromothiazole (Scheme 1). The reaction is easier if a nitro group occupies the 5-position of the thiazole ring (19-21). Ethylene diamine derivatives undergo this reaction with 2-haiothiazoles (22-24). 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Two of the most frequently used approaches for halothiazole synthesis are direct halogenation of thiazoles and the Sandmeyer reaction of aminothiazoles. The third method, an exchange between a stannylthiazole and a halogen, is not practical in the context of palladium chemistry simply because the stannylthiazole can be used directly in a Stille coupling. 

Electrophilic substitution reactions of substituted 2,1-benziso-thiazoles have already been discussed. The only other functionally substituted compound so far studied in any detail is the 3-amino derivative (87). This compound is readily diazotized and the dia-zonium salt formed (88) couples with tertiary aromatic amines yielding azo dyes.117,119-121 The salt (88) also undergoes the usual Sandmeyer reactions, and other 3-substituted derivatives, such as the cyano compound (89) may be prepared.111 Acylation of the amine (87) yields diacyl derivatives which appear to possess the 3-acylimino structure (90).111... 

Salicylaldehyde, Schiff base with, 99 Salmonella typhi, 152 Salts, of acetamido thiazoles, 91 Sandmeyer reaction, in halothiazoles synthesis, 12... 

Aminothiazoles are invaluable intermediates for the preparation of 2-unsubstituted-thiazoles by diazotization followed by reduction with hypophosphorous acid. Application of the Sandmeyer reaction leads to 2-halogeno- and 2-cyano-thiazoles. 

Aminothiazole can be diazotized. The diazonium salt is reduced to thiazole by hypophosphorous acid. By means of the Sandmeyer reaction, 2-halothiazoles and 2-cyanothiazole are obtained. 

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