Thiazole, 2-bromo

A-4-Thiazoline-2-ones and ring substituted derivatives are usually prepared by the general ring-closure methods described in Chapter II. Some special methods where the thiazole ring is already formed have been used, however. An original synthesis of 4- 2-carboxyphenyl)-A-4-thiazoline-2-one (18) starting from 2-thiocyanato-2-halophenyl-l-3-indandione (19) has been proposed (Scheme 8) (20, 21). Reaction of bicyclic quaternary salts (20) may provide 3-substituted A-4-thiazoline-2-one derivatives (21) (Scheme 9) (22). Sykes et al. (23) report the formation of A-4-thiazoline-2-ones (24) by treatment ef 2-bromo (22) or 2-dimethylaminothiazole (23) quaternary salts with base (Scheme 10). 

In a similar manner, the condensation of diethyl (bromo-oxoalkyl)phosphonates (8) with thioformamide gave the corresponding thiazole (9) (Scheme 5). 

In a similar way, dl-2-(q-hydroxyalkyl)- and 2-(a-alkoxycarbonyl)-4-methyl-5-(/3-hydroxyethyl)thiazoles were synthetized from the corresponding thioamides and 4-hydroxy-3-bromo-2-pentanone (615). 

Pipera2ine-N,AT-dithioacetamide (44) condensed with bromo-acetophenones (482), give the corresponding thiazoles (45) Scheme 22), with R = H, Br, MeO yield is 90 to 95% (482). 

As demonstrated above, nitro derivatives of five-membered heterocycles have found extensive use as antiinfective agents. It is therefore of interest that the nitro derivative of a substituted thiazole was at one time used as an antitrichomonal agent. Bro-mination of 2-aminothiazole (136) (obtained from condensation of thiourea with chloroacetaldehyde) gives the 4-bromo derivative (138) this is then acetylated to 139. Treatment of 139 with nitric acid leads to an interesting displacement of bromine by a nitro group to afford aminitrazole (140)... 

Thiazolo[3,2-/>][l,2,4]triazoles are often sufficiently reactive to be brominated in the thiazole nucleus (see also B,5). Thus, although the unsubstituted substrate and the 2-phenyl and 2-methyl derivatives would not react with NBS in refluxing chloroform, the 5-methyl, 2,5-dimethyl, and 5-methyl-2-phenyl compounds gave 6-bromo products (71JAP71/26498 74JHC459). 

An intermediate a-bromo-a-formylacetate hemiacetal has been prepared by reaction of ethyl (3-ethoxyacrylate with A-bromosuccinimide (NBS). Cyclizat-ion of the in situ formed hemiacetal with thioureas affords 2-amino-1,3-thiazole-5-carboxylates (Scheme 58).141... 

Aminorhodanines 284 reacted with ethyl 2-bromo-3,3-diethoxypropionate to provide 2,3-dihydro-pyrazolo[5,1 -b -thiazoles 285. The mechanism proposed for the cyclization involved via a sequential condensation-sulfur extrusion reaction (Equation 125) <1994JHC1719>. 

With a.-bromo Michael acceptors. Condensation reaction of 2-aminothiazoline with a-bromo-a,/3-unsaturated compounds, commercially available or generated in situ, provided a route to functionalized 2,3,5,6-tetrahydro-imidazo[2,l-3]thiazoles 411 (Equation 187) <1994H(38)2593>. 

Bromo-6-(3-pyridyl)-2,3-dihydro-imidazo[2,l- ]thiazole 481 was reported to be herbicidally active against Setaria, Sinapis, and Stellaria <1996MI247>. 

Bromoacetylthianthrene, which can be produced by direct acylation as well as via bromination of 2-acetylthianthrene (63MI2) (for comparable dibromination of 2,7-diacetylthianthrene, see 64MI1), has been used in its capacity as an a-bromo-ketone to produce thianthren-2-yl-substituted heterocycles such as 55, 56, 57 (63MI2 73BSF1460), and 2-amino-4-(thianthren-2-yl)thiazole (63MI2), by condensation with 2-aminopyridine,... 

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