Thiazole ring opening

Conclusive evidence for the thiazole ring opening of ( )-2,3,5,6-tetrahydro-6-phenyl-imidazo[2,1 -b]thiazole (78) (tetramisole) by lithium diethylamide was obtained by a single-crystal X-ray diffraction study (78JHC307). 

The aqueous solution is strongly acid (1% w/v pH 3.13). At a pH below 5, solutions can be sterilized at 110° without loss of the vitamin, but it is rapidly destroyed when a solution is heated to this temperature at a pH above 5. Thiamine is very sensitive to alkali in solution at a pH above 7 it is already destroyed at room temperature (thiazole ring opens). The solution exhibits two absorption bands in the ultraviolet, at 233 and 267 mfi. 

Upon addition of 2 moles of alkali to thiamine hydrochloride the quaternary thiazole ring opens to form an acidic sulfhydryl group. This isomeric sulfhydryl form, as well as the disulfide form of both thiamine and TPP, have been prepared. The formula of the sulfhydryl form of TPP is the following ... 

The greater reactivity of the 5-position of selenazoles, compared to thiazoles, toward electrophilic substitution has also been demonstrated (19). Substituents in the 2-position possessing a mesomeric donor effect increase the reactivity, but, as Haginiwa (19) observed, also increase the tendancy to ring Opening,... 

In this chapter we intend to outline the general methods by which the thiazolic ring is synthetized from open-chain compounds. The conversion of one thiazole compound to another is not discussed here, but in appropriate later chapters. Thus the conversion of thiazole carboxylic acids, halogeno-, amino-, hydroxy-, and mercaptothiazoles, to the corresponding unsubstituted thiazoles is treated in Chapters IV through VII, respectively. 

Thus quaternized thiazoles (170) consume two equivalents of OH on titration because the pseudo bases (171) ring open to (172), which form anions (173). Quaternized oxazoles (174) are readily attacked by hydroxide to give open-chain products such as (175) (74AHC(17)99), and quaternized 1,3,4-oxadiazoles behave similarly. Quaternary isothiazoles (e.g. 176) are cleaved by hydroxide (72AHC(l4)l), as are 1,2,4-thiadiazolium salts (177 178). 

Reaction of thiazoles with DMAD illustrates the overall reaction and the rearrangements which may be encountered. Thiazole or 2-methylthiazole (411 R=H and Me, respectively) in DMF reacted with DMAD to give an initial 1,4-dipolar species (412). Reaction with a second DMAD gave the 1 2 molar adduct, presumably (413). Ring opening to (414), followed by cyclization in the alternative mode, resulted in the formation of (415), the structure of which (R = Me) was established by X-ray analysis (78AHC(23)263) (see also Chapter 4.19). 

The Group VI organometallic chemistry is mainly characterized by the occurrence of N- and C-coordination and carbene complex-formation, as well as by some unique cases of Se- (Te-) coordination, ring opening and deselenation. The Group VII organometallic chemistry is known for the carbene and chelate structures of the derivatized thiazoles. 

Treatment of carboxyaldehydes 252 with hydrazine hydrate in ethanolic KOH under refluxing conditions provides an easy entry to the novel imidazo[2,l-4][l,3]thiazole fused diazepinones 253 via lactone ring opening by intramolecular nucleophilic attack of the amino group of the intermediate hydrazone which could not be isolated (Equation 31) <2006TL2811>. 

Novel ring opening reactions of the 1,3-thiazinone moiety of triazolo[5,l- ][l,3]thiazines (13) have been studied Britsun et al. <2005CHE1334>. The experienced transformations are reminiscent of formation of 81 from 79 (Section 11.16.5.1.1). In the frame of this research activity, ring contraction of the thiazine moiety to a thiazole was also observed by the same team <2005CHE782>. 

Sprio et al. reported the preparation of 6-acetylimidazo[2,l-Z)]thiazoles derivatives 57 (74JHC91). TTie synthesis involves substituted 4-(2-thiazo-lyl)aminoisoxazoles 56, which were obtained in good yield by the reaction of N-(3,5-dimethylisoxazol-4-yl) thiourea 55 with a-chloro ketones. Subsequent isoxazole ring opening led to intermediates which readily underwent cyclization by refluxing in acetic acid or ethanol/hydrochloric acid. 

Thermolysis of a solution of epoxide 79 and l,3-thiazole-5(477)-thione derivative 80 in xylene led to the formation of three cycloadducts in 85% overall yield (22). It was expected that the geminal cyano groups of the epoxide would control the regioselectivity of the ring opening such that the anionic terminus of the dipole would be localized on that carbon. Regiochemical control led to a very selective... 

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