Substituted thiazole-5-carboxylates

Fong, M., Janowski, W.K., Prager, R.H. and Taylor, M.R. (2004) A convenient synthesis of 2-substituted thiazole-5-carboxylates. Australian Journal of Chemistry, 57 (6), 599-604. 

Similarly, ethyl (or methyl) a-formyl chloroacetate (69), Rj = H, and its substituted derivatives, condensed with thioformamide or higher thioamides give 5-ethyl- or 5-rnethyl-thiazole carboxylates (70) in good... 

Abbott (Brooks et al. (Abbott), 1998a Woods et al. (Abbott), 1998) published two patent applications in which the carboxyl moiety of indomethacin was substituted with an iminooxy or substituted thiazole. On the other hand, Kotobuki Seiyaku (Tomiyama et al. (Kotobuki Seiaku Co. LTD), 1998) used a novel approach, exchanging the indole nucleus for an azulene (Jimenez et al., 2000). 

Dimethylthiazole has been prepared from chloroacetone and thioacetamide,1 but forming the required thioacetamide in the reaction mixture is to be preferred since no additional manipulation is involved. The method here described is substantially that of E. Merck.2 Other substituted thiazoles can be prepared by practically the same method.2 2,4-Dimethylthiazole has been obtained by dry distillation of 2-methylthiazyl-4-acetic acid,3 and also by heating 2,4-dimethylthiazole-5-carboxylic acid with calcium oxide.4... 

Also, a novel synthesis of methyl 5-substituted thiazole-4-carboxylates (43) was reported. The reaction of methyl ( )- and/or (Z)-3-substituted 3-bromo-2-isocyanoacrylates (40) with hydrogen sulfide (1.2eq) and triethylamine at room temperature afforded the desired thiazoles (43) in good yield. The substitution reaction of the first sulfide with 40 may proceed with... 

On account of the high degree of stability of the thiazole ring a large variety of substituted derivatives yield thiazolecarboxylic acids upon oxidation. The oxidation of a methyl group or a substituted methyl group to a carboxyl group has been accomplished in a few instances. 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

Acidic and basic hydrolysis of ethyl 4-oxo-4//-pyrido[l, 2-u]pyrimidin-3-carboxylates gave 3-carboxylic acid derivatives (OlMIPl). Stirring rerr-butyl ( )-3-(2-hydroxy-8-[2-(4-isopropyl-l, 3-thiazol-2-yl)-l-ethenyl]-4-oxo-4//-pyrido[l,2-u]pyrimidin-3-yl)-2-propenoate in CF3CO2H at room temperature yielded ( )-3-substituted 2-propenoic acid. 

The cyclizations of conjugated nitrile ylides forming substituted oxazoles and thiazoles were computed up to the MP4/6-31H-G level [OOJOC47]. Relative to 23, oxazole-4-carboxylic acid24 is stabilized by about -38.1 kcal/mol (Scheme 18). 

The present procedure is illustrative of a mild and general method for preparing thiazoles substituted in the 4-position with electron-withdrawing substitutents such as carbethoxy, cyano, and p-toluenesulfonyl. Thus condensation of ethyl isocyanoacetate with various thiono esters affords the parent ethyl thiazole-4-carboxylate as well as a series of analogs bearing substituents in the... 

An access to iV-substituted 4,6-dioxo-imidazo[3,4-c]thiazoles 185 was developed considering first the reaction of 2-chloroethylisocyanate with methyl thiazolidine 4-carboxylate 183 that generated the ureide 184. Cyclization of the imidazole ring occurred in acidic medium via an addition-elimination mechanism and delivered the imidazothiazole 185 (Equation 81) <2001MI1117>. 

Gyorgydeak et al. (69) converted a series of 2-substituted 3-acyl-l,3-thiazoli-dine-4-carboxylic acids (113) into the corresponding pyrrolo[l,2-c]thiazoles (115)... 

Furans, thiophenes, thiazoles and pyrroles all reacted smoothly with alkylydenecyclopropanes in the presence of a palladium catalyst and added tributylphosphone, to give the allylated heterocycles as product. Thus furane-2-carboxylic ester on treatment with the butyl substituted alkylydenecyclopropane gave the 5-allyl-2-furanecarboxylate in good yield (6.96.).128... 

The cyclodehydration of 2-substituted-A/-acylthiazolidine-4-carboxylic acids yields bicyclic munchnones. This mesoionic ring system acts as a cyclic azomethine ylid and can undergo 1,3-dipolar cycloaddition reactions with dipolarophiles. A range of chiral pyrrolo[l,2-c]thiazoles have been prepared by this method both intermolecularly and intramolecularly. 

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