5- Bromothiazole preparation

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). 

This set of compounds is the most thoroughly studied among derivatives of 2-aminothiazole, thanks to the Beyer group. Heterocychzation methods are most commonly used for their preparation (see Chapter II and Refs. 37, 341, and 513-520). Reaction of 2-diazothiazoles (277) with organometallics provides another synthetic method (Scheme 1711 (521). 2-Hydrazinothiazoles may also be obtained by the action of hydrazine on 2-bromothiazoles (388) or on 2-mercaptothiazoles (522). 

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). 

Amongst the more unusual reactions, 2,3-thiazolo fused pyrido[3,2-d]pyrimidines have been prepared from 3-aminopicolinic acid and 2-bromothiazoles, whilst a similar derivative resulted with allyl isothiocyanate (221 222) <72IJC602). Similar products are also produced in [3 + 3] reactions of 2-aminothiazoles (Section 2.15.5.7.1). 

Ethyl thiazole-4-carboxylate has been prepared by hy-drogenolysis of ethyl 2-bromothiazole-4-carboxylate with Raney nickel in ethanol, by desulfurization of ethyl 2-mercaptothiazole-... 

It has been demonstrated in the literature that the halogen-metal exchange of 2,4-dibromothiazole occurs predominantly at the C(2) position. 2-Stannyl-4-bromothiazole can be prepared using this strategy [32],... 

The preparation of stannylthiazoles via ditin chemistry has not been widely utilized. In one case, the synthesis of 4-tributylstannylthiazole 43 started with selective halogen-metal exchange at C(2) by treating 2,4-dibromothiazole with n-BuLi [33]. Trapping the resulting 2-lithio-4-bromothiazole with propanal and subsequent Jones oxidation secured 4-bromothiazole 42. The Pd-catalyzed reaction of 42 with hexamethyldistannane in the presence of PdCWPhjP provided 4-tributylstannylthiazole 43. 

In addition, Unheim et al. coupled 2-bromothiazole with 2-methylthio-5-stannylpyrimidine (58) to assemble the pyrimidinethiazole 59 [43]. Stannane 58 was prepared by Pd-catalyzed coupling between 2-methylthio-5-bromopyrimidine and hexamethyldistannane in the presence of fluoride ion at ambient temperature. In another case, 2-tributylstannylthiazole was coupled with 2 -deoxyuridine iodide 60 (DMT = dimethoxytrityl) to furnish 5-thiazolyl-2 -deoxyuridine 61 [44]. 

With 2-bromothiazole, however, low yields are obtained and a competitive reaction takes place because the nucleophile PhSH is alkylated by the catalyst TBAB. With 5-nitro-2-chloropyridine (155), bipyridyl sulfide (156) is prepared in high yield by disubstitution with Na2S.219... 

The reagent is prepared by treatment of 2-bromothiazole (Aldrich) with BuLi followed by ClSi(CH3)3 (85% yield). 

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