Thiazoles and Benzothiazoles

The H-NMR spectrum of thiazole shown below is simple and first order. It shows the following chemical shifts H-2 8.69 ppm, H-4 7.79 ppm, and H-5 7.22 ppm. It shows down-field values that are distinctive of aromatic hydrogen atoms. Deshielding of C2 is a result of the combined electron-withdrawing effects of the adjoining nitrogen and sulfur. Such a substantial deshielding leads to a further down-field shift for H-2 compared to the other 

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NMR data of unsubstituted benzothiazole show the C3 and C7 peaks being deshielded. The C2 peak appears up-field compared to that in 1,3-thiazole. 

The physical and spectral properties of 1,3-thiazole are similar to those of pyridine in some ways. The electronegative A -atom at the 3-position makes C(2) partially electropositive and consequently susceptible to nucleophilic attack. 

Thiazole is known to occur naturally in various forms. The most widely recognized thiazole lies in the essential vitamin Bi or thiamin in the form of its thiazolium salt. It is a water-soluble vitamin of the B complex. Thiamin pyrophosphate is the essential coenzyme in the enzymatic decarboxylation of pyruvate to aldehyde. 

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A cobalt-catalyzed method for arylation of heteroarenes including thiazole and benzothiazole was reported in 2003 <030L3607>. According to this report, the direct C-5 arylation of thiazole with iodobenzene was carried out in the presence of cobalt catalyst [Co(OAc)2/IMes] and cesium carbonate, and a complete reversal of arylation from C-5 to C-2 was observed with the bimetallic Co/Cu/IMes system. This report has been retracted as the laboratory of the senior author has not been able to reproduce the key results disclosed in the communication <06OL2899>. 

The arylation of heteroaromatic compounds is also achieved by aryl-aryl coupling reaction. The arylation of A-methylimidazole with bromobenzene occurs under palladium catalysis (Equation (62)).72 The arylation of thiazole with aryl iodide occurs at the 2-position under PdCl2(PPh3)2/CuI catalysis.73 In this case, tetrabutylammonium fluoride improves the activity of the catalyst. Alternatively, thiazoles and benzothiazole are efficiently arylated... 

In contrast, thiazoles and benzothiazoles are suitable recipients for the heteroaryl Heck reaction. Treatment of 2-chloro-3,6-diisobutylpyrazine (103) with thiazole led to regioselective addition at C(5), giving rise to adduct 104 [57]. A similar reaction between 2-chloro-3,6-diethylpyrazine (105) and benzo[ >]thiazole took place at C(2) exclusively to afford pyrazinylbenzothiazole 106 [57]. 

By analogy with oxazoles and N-substituted imidazoles, thiazoles and benzothiazoles unsubstituted at C-2 undergo direct metalation at that position, with sodium, lithium, or magnesium reagents (Scheme 91)[79MI1 ... 

Addition reactions of several thiazole and benzothiazole derivatives to DMAD have been reported. Thiazole (383a), for example, gives a 1 2 adduct (384a) on treatment with DMAD, whereas in the reaction of 2-ethylthiazole (383b), a S,6-dihydrothiazolo[3,2-a]azepine (385) is... 

Sections VI,A, B, D, and E give information about indazoles, oxazole, benzoxazole, isoxazole, benzisoxazoles, isothiazole, benziso-thiazoles, and benzothiazole. In addition, Sections II and VI,F,1 refer to quaternization reactions of isoxazole and benzisothiazoles, respectively. 

Dihydro allyl adducts like (254) are obtained by reaction of thiazoles with allyltributyl tin in the presence of alkyl chloroformates acting as activators of the thiazole ring (Scheme 28) (94JOC1319). This reaction most likely takes place via the intermediate azolium salt. Under these conditions even organolithium compounds can add to thiazoles (84TL3633). Similarly, direct ethynylation of thiazole and benzothiazole can be achieved by reaction with bis(tributylstannyl)acetylene (Scheme 29) (94SL557). 

Introduction Pyrroles Indoles Pyridines Thiophenes and Benzo[b]thiophenes Furans and Benzo[b]furans Thiazoles and Benzothiazoles Oxazoles and Benzoxazoles Imidazoles Pyrazines and Quinoxalines Pyrimidines... 

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