Thiazole Ring Substitution

With pea-roots, it was found (30) that for a positive effect an-OH group or a group metabolizable to—OH was required. But there was a relatively wide range of positions which this could occupy (see Table VI) and still 

The lowered activity (35%) of compound 10, where a methyl group is substituted for the H at position 2 in the vitamin thiazole, and the complete inactivity of compound 11, where there is —NHa instead of —H at the same position, is very interesting, and indicates that the 2 position can have some effect in determining the metabolic use of the thiazole, since these compounds both contain the 5-CH2-CH2-OH group of the vitamin thia- 

The Activity of Thiaeoles (at 10 M) in the Growth of Isolated Pea-Roots, [ Ae Thiamin 

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An alkyi group occupying the 4-position of the thiazole ring may condense if the 5-position is substituted. 2-Acetamido-4-methy]-5-nitrothiazole (80) and p-cyanobenzaldehyde when refluxed with small amounts of piperidine yield the 4-styryl derivative (81) (Scheme 57) (238, 239). 

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). 

Nucleophilic substitution of the 5-halo substituent on a thiazole ring by a thiocyanato group (348, 362, 370-376) or a thiouronium group (364, 377) affords the thiocyanato and thiouronium precursors."... 

The first mass spectrometric investigation of the thiazole ring was done by Clarke et al. (271). Shortly after, Cooks et al., in a study devoted to bicydic aromatic systems, demonstrated the influence of the benzo ring in benzothiazole (272). Since this time, many studies have been devoted to the influence of various types of substitution upon fragmentation schemes and rearrangements, in the case of alkylthiazoles by Buttery (273) arylthiazoles by Aune et al. (276), Rix et al. (277), Khnulnitskii et al. (278) functional derivatives by Salmona el al. (279) and Entenmann (280) and thiazoles isotopically labeled with deuterium and C by Bojesen et al. (113). More recently, Witzhum et al. have detected the presence of simple derivatives of thiazole in food aromas by mass spectrometry (281). 

The vibrations of the thiazole ring have been assigned in the case of thiazole, using the appellations Wj to Wy for the in-plane vibrations and Fj and Fj for the out-of-plane vibrations (135). For the substituted derivatives, they are classified in series numbered I to X (see Table III-10) (99). 

TABLE III-125. THIAZOLES SUBSTITUTED BY HETEROCYCLIC GROUPS NONADJACENT TO THE THIAZOLE RING... 

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. 

As shown in Eigure 18.17, thiamine is composed of a substituted thiazole ring joined to a substituted pyrimidine by a methylene bridge. It is the precursor of thiamine pyrophosphate (TPP), a coenzyme involved in reactions of carbo-... 

A substituted thiazole ring attached to a reduced imidazole moiety is present in a compound that displays anti hypertensive activity. Reaction of thiourea 61 with methyl iodide to... 

A (3-lactam ring substituted by a thiazole moiety has been reported to be formed simultaneously and under mild condition during the course of a multicomponent reaction [200]. When the 3-dimethylamino-2-isocyanoacrylate was reacted with the aldehyde in the presence of a (3-aminothiocarboxylic acid, substituted l-thiazole-2-yl-methyl-azetidin-2-one was smoothly formed (Scheme 92). Plausible reaction intermediates have been proposed. 

In some cases arylthiazoles undergo preferential substitution in the 5-position of the thiazole ring. In the case of 2-phenyl-2-thiazoline, only the... 

Studies of the nitration of 4-chloromethyl-2-phenylthiazole have shown that the action of nitric acid (d 1.40) in sulfuric acid at 60°C gives the 4-nitrophenyl product and the use of nitric acid in acetic anhydride at 60°C forms the 5-nitrothiazole product. Chlorination and bromination also result in 5-substitution in the thiazole ring and nitration of these products using mixed acid gives the 4-nitrophenyl products. 2-(4-Bromophenyl)-4-chloromethylthiazole also nitrates at the 5-position of the thiazole ring using nitric acid in acetic anhydride below 60°C (65CB3446). 

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