2-Bromothiazole, bromination

Acetamido-4-methy)thiazole when enzymatically brominated is converted to a mixture of 2-acetamido-4-methyd 5-bromothiazole (200) and dibromacetamido-4-methyl-5-bro mo thiazole (201) (Scheme 127) (138, 436). 

At elevated temperatures (250-400°C) bromine reacts with thiazole in the vapor phase on pumice to afford 2-bromothiazole when equimolecu-lar quantities of reactants are mixed, and a low yield of a dibromothiazole (the 2,5-isomer) when 2 moles of bromine are used (388-390). This preferential orientation to the 2-position has been interpreted as an indication of the free-radical nature of the reaction (343), a conclusion that is in agreement with the free-valence distribution calculated in the early application of the HMO method to thiazole (Scheme 67) (6,117). 

The bromination with N-bromOsuccinimide in CCU can be accomplished yielding to 2-brOmothiazole (12.5% yield) (27). 

Bromination of 2-brOmothia2ole leads to 2,5-dibromothiazole (5). 2-Bromothiazole can be used as a substrate in a malonic synthesis (72) starting from phenylacetonitrile the a phenyl-(2-thiazoiyl)-acetonitrile is obtained in high yields (84%) (Scheme 11). 

All possible dichloro- or dibromothiazoles are known. The 2.5-dihalogeno derivatives can be prepared from the 5-halogeno-2-aminothiazoles by diazotization/decomposition with CuCl or CuBr (3, 12, 13, 18, 75). The 5-halogeno-2-aminothiazoles can be easily prepared by halogenation of 2-aminothiazole (65, 76-79) 2,5-dibromothiazole can also be prepared by direct bromination of 2-bromothiazole (5). 

Commercially available 2,5-dibromothiazole can be alternatively generated by bromination of thiazole or 2-bromothiazole [5]. 2,4-Dibromothiazole and 2,5-dibromothiazole are among the most useful building blocks in the synthesis of thiazole-containing molecules. Regioselective bromination was achieved at C(4) when 2-amino-6-trifluoromethoxythiazole (4) was treated with bromine in acetic acid to afford 4-bromobenzothiazole 5 [6],... 

Arylthiazole-5-carboxylic acids on treatment with base and bromine yield the corresponding 5-bromothiazole (76AP128). The same behavior is observed for thiazolo[3,2-b][l,2,4]triazoles (91AP49 94MI2). 

Vapor phase bromination of thiazole on pumice at 250-400°C gave 2-bromothiazole (1 1 ratio of bromine to thiazole). With excess bromine,... 

An alternate strategy was utilized in the synthesis of a potential thyroid receptor ligand [30]. Electrophilic bromination was followed by the Miyaura boronic ester synthesis to yield 49 [31]. Suzuki coupling between 49 and 2-bromothiazole was then accomplished to provide 50, a precursor to the derivative 51. Unfortunately, the presence of the thiazole at C(3), in 51 resulted in a decrease in binding affinity and selectivity as compared to the lead compound. 

Proline is a highly effective hgand for the Cul-catalysed displacement of bromine in 3-bromopyridines, 2-bromothiazoles and 5-bromo-l-phenylsulfonylindole by primary amines, morpholine and pyrazole. ... 

In order to test the viability of the halogen-dance reaction on a simple thiazole substrate, we studied the use of 2-bromothiazole in this reaction (60, Scheme 9). This compound was treated with LDA at -78 °C in ethereal solvents, however, under all conditions examined a dark intractable material was produced. We suspect that this is a result of lithiation at the 5-position to provide 61, followed by migration of the bromine to provide 2-lithio-5-bromothiazole (62). This species can then undergo an a-elimination and open to the unstable isocyanide (63), which decomposes to a complex mixture. Although 2-lithiothiazole is known be stable at -78 °C, we postulate that the electron withdrawing nature of the... 

Tervalent phosphorus acid esters, and triphenylphosphine, attack 2-bromothiazole (34) at bromine in alcoholic solvents to give thiazole and the oxidised phosphorus compounds. A similar attack of tris(diethylamino)phosphine on the bromine atom of bromopentafluorobenzene was used to prepare a series of main-group-four pentafluorophenyl derivatives, e.g. (35). A full paper has appeared on the fluoridation of trimethylsilyl phosphites, or phosphoramidites, with sulphury chloride fluoride. The mild conditions allowed the preparation of sensitive nucleoside derivatives, e.g. (36) and (37). 

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