Thiazole-2-carboxylic acid ethyl ester

Preparation 2-amino-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester... 

Preparation of 2-(2-morpholin-4-yl-ethyl)-4-trifluoromethyl-thiazole-5 -carboxylic acid ethyl ester (general procedure)... 

Amino-2-(methylthio)thiazole-4-carboxylic acid ethyl ester 195 reacted with benzoyl isothiocyanate (Scheme 86) to furnish thiazolo[5,4-d]pyrimidine-2-one 196 [119],... 

Esters of 2-thiazole carboxylic acids (75) (383) are also prepared from ethyl monothiooxamate (74) (Scheme 34), and several compounds of this type with hydrogen, alkyl, or aryl groups in the 4- or 5-position (201, 209, 210, 242, 294) or a nitro group in the 5-position (674) have been reported. 

The most widely used method for the preparation of carboxylic acids is ester hydrolysis. The esters are generally prepared by heterocyclization (cf. Chapter II), the most useful and versatile of which is the Hantzsch s synthesis, that is the condensation of an halogenated a- or /3 keto ester with a thioamide (1-20). For example ethyl 4-thiazole carboxylate (3) was prepared by Jones et al. from ethyl a-bromoacetoacetate (1) and thioformamide (2) (1). Hydrolysis of the ester with potassium hydroxide gave the corresponding acid (4) after acidification (Scheme 1). 

Ethyl thiazole-4-carboxylate 4-ThiazolecarboxyIic acid, ethyl ester (8,9) (14527-43-6)... 

The acylation of 5-hydroxymethylimidazo[2,l-h]thiazoles 96 (with, e.g., R = H, R = Ph) has been reported (80FES896). In line with expectations, ethyl esters of imidazol[2,l-6]thiazole carboxylic acids on basic hydrolysis... 

Methylimidazo[2,l-h]thiazole-5-carboxylic acid was obtained by alkaline hydrolysis of the corresponding ethyl ester. Subsequent decarboxylation was achieved by heating with hydrochloric acid [92JCS(P1)2029]. 

Azole approach. Sulfomycimine (523 R = H), from acid hydrolysis of the antibiotic sulfomycine, can be synthesized by the condensation of thiazole-4-carboxylic acid with DL-threonine ethyl ester, followed by cyclization and ester hydrolysis (77H(8)46l). 

Finally, some of the methods for carboxylic acid reduction (Section 1.12.2) have also been applied to esters. Thus, the ethyl ester of thiazole-2-caiboxylic acid has been reduced electrochemically to the corresponding aldehyde, and some of the high temperature metal oxide catalyzed hydrogenations have been used on esters. ... 

Thiete structures have been suggested as fragmentation products in the mass spectra of a thietane fused to a 3-lactam, an ortho disulfide of a thiolbenzoate ester, -propanethiol, thiirane carboxylic acid esters, isothiazoles, thiazoles, 1,3-dithiole 2-thiones, 1,3-dithiolene-2-ones, S-ethyl thio-benzoate, and thianaphthene sulfones. Tetramethylthiete may have been formed on thermolysis of the p-toluenesulfonyl-hydrazone of 2,2,4,4-tetramethyl-3-thietanone. " Thiete 2-thione may be an intermediate in the decomposition of 1,2-ditholium salts by the action of bases. " 2,2-Diphenyl-2H-thiete is suggested as an intermediate in the reaction of diphenyldiazomethane with 1,2,3-benzo-thiadiazole which yields 9-phenylthioxanthene and three other products. ... 

Cyclization occurs directly through catalysis by the acid liberated when a pyridine-2(lH)-thione is heated with an a-halo acid ester. The most convenient method for preparing the thiazole, however, seems to be the cyclization of (2-pyridinethio)acetic acids in acetic anhydride in the presence of pyridine. Without base catalysis the reaction is slow, which suggests a mixed anhydride intermediate. Mixed anhydride formation with ethyl chlorofor-mate in pyridine, or carboxyl activation by DCC in pyridine, gives the mesoionic product. The cyclization reaction and the chemical stability of the thiazole are adversely affected by a pyridine 6-substituent. The initially formed acylpyridinium salt (407) undergoes rapid tautomerization to the aromatic thiazole form equilibrium between the forms (407) and (408) is verified by rapid deuteration at C-2 (R1 = H) in AcOH-d (81H(15)1349). 

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