Thiazoles, arylation

In this chapter we examine in turn the properties of alkyl and aryl-thiazoles that do not possess functional groups bonded directly to the thiazole ring. The general trends are underlined, and the applications of certains thiazole compounds in such areas as polymers, flavorings, and pharmacological and agricultural chemicals are discussed. 

Thin layer chromatography and gas-liquid chromatography have been widely applied for the separation and for the identification of thiazoles in reaction mixtures. From systematic studies it appears that thiazole, alkyl- and aryl-thiazoles and benzothiazoles are best separated on stationary phase of low polarity in GLC and with eluents of low polarity in TLC. It has been possible to correlate, for these series of compounds, the RF of TLC or the specific volume of retention in GLC with the number of carbon atoms in the aliphatic side chain, and also with the rate constants of quaternization of the cyclic nitrogen atom. This last observation indicates a significant participation of the nitrogen atom in the chromatographic processes (67BSF846). 

Nitrothiazole, 576 preparation of, 577 reduction of, 577 ring opening reaction, 577 Nitrothiazoles, chemical shift, proton, 68 coupling constants in EPR, 84 ionization potential, 5 2 reduction of, 381 ultraviolet absorption, 48 Nuclear magnetic resonance, 66 of alkyl thiazoles, 342 of aryl thiazoles, 342 correlation with theoretical calculations, 70... 

PytidylUiiaZOles, table of products, 478 Pyrolysis, of aryl thiazole, 399 Pyrrolothiazine, from thiazole ylide, 95 Pyrrolyl thiazoles, table of products, 471... 

Thienylthiazoles, table of products, 470 Thin-layer chromatography, of alkyl thiazoles, 362 of aryl thiazoles, 362 Thioacetamide, condensation, with bis (o-chloroketone), 194... 

Clifford, A.M. Mercapto aryl thiazoles, (Wingfoot Corp.). U.S. Patent 2,070,522. Chem. Abstracts 31, 2231 (1937). 

Imidazol-2-ylidines and imidazolin-2-ylidenes are the most commonly employed phosphine surrogates in Ru-based metathesis catalysts but a variety of other related carbenes have also been explored. Catalysts 25-29 containing A -aryl-thiazol-2-ylidenes with varying steric bulk of the aryl substituent have been prepared (Figure 9) [29]. 

This reaction has also been used in the syntheses toward diamidino 2,5-bis(aryl)thiazoles exhibiting antiprotozoal activity against Trypanosoma brucei rhodensiense (T. b. r.) and Plasmodium falciparum (P. f), shown below. Here, the synthesis involved conversion of derivatized thiazoles to bromothiazoles as substrates for Suzuki cross-couplings. ... 

Febuxostat 88 is an inhibitor of xanthine oxidase that has been developed by Teijin Pharma as a new drug for the treatment of gout and hyperuricemia [62]. The 2-aryl-thiazole structure is prepared by Teijin via a condensation between 2-chloroacetate 83 and arylthioamide 82 (Scheme 20a) [63]. However, Cipla, a... 

Veenin and Metzgee [47] have separated 4-aryl-thiazoles through adsorption TLC, using solvents of the same type on silica gel G or alumina 6 layers. They used also partiticm chromatography on silica gel G layers which had been impregnated with dimethylformamide cyclohexane saturated with this impregnation agent served as solvent. 

The above-mentioned conditions were recently employed to perform a C5 arylation between 4-methyl-2-(Al-acetyl)aminothiazole and a 4-bromopyridine derivative (eq 28). The arylated thiazole thus obtained was used in the preparation of a selective phosphatidylinositol-3 kinase alpha-inhibitor. 

Aromatic thioamides react with MeC(0)CHClC(0)C02Et to give a 3 1 ratio of ethyl 5-acetyl-2-aryl-thiazole-4-carboxylates and the isomeric products (2). Modifications of the Hantzsch synthesis continue to appear. Thus, 2-aryl-5-aroyl-thiazoles may be prepared from the JV -thioaroyl-iViV-dimethyl-formamidines ArC(S)N=CHNMea and a-bromo-ketones [strictly speaking, this is a Type F (C—N—C—S + C) synthesis], whilst 5-amino-2-phenyl-l,2,3-thiadiazolium salts [e.g. (3)] and compounds with the general structure RCHgCN (e.g. R = CN or COaEt) yield 4-amino-thiazoles. ... 

Amino-4-aryl-thiazoles give Meisenheimer complexes with 2,4,6-trinitro-chlorobenzene. The tautomeric properties of thiazoles continue to attract attention. Unlike most 4-hydroxy-thiazoles, which prefer to exist in their keto-forms, 4-hydroxy-2-methyl-5-phenylthiazole exists as a stable enol. The spectroscopic properties of the meso-ionic thiazole (12 = Me, R = Ph, R = / -ClC H4),... 

Electrophilic Substitution.— 2-Amino-thiazoles and their or 4-substituted derivatives and 2-aryl-thiazoles and their 4-substituted derivatives undergo electrophilic substitution predominantly or exclusively in the 5-position. 2-Aryl-thiazoles may undergo substitution in the non-heteroaromatic ring, particularly (as in the case of 5-ethyl-2-phenylthiazole if the 5-position is blocked or if the non-heteroaromatic ring is activated. Mononitration of 2-(2-thienyl)thiazole occurs exclusively in the vacant a-position of the thiophen ring, and 2-(3-thienyl)-thiazole similarly gives the mononitro-compound (19). The situation is not... 

Miscellaneous Reactions.—2-Aryl-thiazoles, obtained by the reaction of thiazoles with dibenzoyl peroxide in the presence of copper, undergo photolysis in the... 

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