Solvent thiazoles

An intramolecular charge transfer toward C-5 has been proposed (77) to rationalize the ultraviolet spectra observed for 2-amino-5-R-thiazoles where R is a strong electron attractor. Ultraviolet spectra of a series of 2-amino-4-p-R-phenylthiazoles (12) and 2-amino-5-p-R-phenylthiazoles (13) were recorded in alcoholic solution (73), but, reported in an article on pK studies, remained undiscussed. Solvent effects on absorption spectra of 2-acetamido and 2-aminothiazoles have been studied (92). 

They are prepared by the addition of an alcoholic solution of thiazole to the metal salt in the same solvent. 

A 2-methylthio substituent decreases the basicity of thiazole pK = 2.52) by 0.6 pK unit (269). The usual bathochromic shift associated with this substituent in other heterocycles is also found for the thiazole ring (41 nm) (56). The ring protons of thiazole are shielded by this substituent the NMR spectrum of 2-methylthiothiazole is (internal TMS, solvent acetone) 3.32 (S-Me) 7.3 (C -H) 6.95 (Cj-H) (56, 270). Typical NMR spectra of 2-thioalkylthiazoles are given in Ref. 266. 

Tautomerism of the A-2-thiazoline-5-thiones has not been investigated intensively. A recent report shows that 2-phenylthiazo e-5-thiols exist in the thiol form in both polar and nonpolar solvents (563). This behavior is in contrast with that of corresponding thiazolones. Addition reactions involve only the exocyclic sulfur atom, and thiazole-5-thiols behave as typical heteroaromatic thiols towards unsaturated systems, giving sulfides (1533) (Scheme 80) (563),... 

The O-S exchange method in presence of a-halogenated carbonyl compound is a very good one for thiazole compounds. The thioamide is prepared in situ by the action of amide upon phosphorus pentasulphide with solvent. The a-halogenated aldehyde reacts directly. But the O-Se exchange cannot be performed with a-halogenated carbonyl compounds because of the apparition of phosphoric acid. (Scheme 3), The C-Se bond is very sensitive to add pH. 

The ultraviolet absorption spectrum of thiazole was first determined in 1955 in ethanolic solution by Leandri et al. (172), then in 1957 by Sheinker et al. (173), and in 1967 by Coltbourne et al. (174). Albert in 1957 gave the spectrum in aqueous solution at pH 5 and in acidic solution (NHCl) (175). Nonhydroxylic solvents were employed (176, 177), and the vapor-phase spectrum was also determined (123). The results summarized in Table 1-15 are homogeneous except for the first data of Leandri (172). Both bands A and B have a red shift of about 3 nm when thiazole is dissolved in hydrocarbon solvents. This red shift of band A increases when the solvent is hydroxylic and, in the case of water, especially when the solution becomes acidic and the extinction coefficient increases simultaneously. 

TABLE 1-15. ULTRAVIOLET ABSORPTION SPECTRUM OF THIAZOLE IN THE VAPOUR PHASE AND IN DIFFERENT SOLVENTS... 

The thermodynamic study of thiazole and of some of its binary mixtures with various solvents has led to the determination of important practical data, but also to the discovery of association phenomena between thiazole and some solvents and of thiazole self-association. 

Similarly, molar excess functions have been determined for various thiazole-solvent binary mixtures (Table 1-46) (307-310). 

The conclusion of all these thermodynamic studies is the existence of thiazole-solvent and thiazole-thiazole associations. The most probable mode of association is of the n-rr type from the lone pair of the nitrogen of one molecule to the various other atoms of the other. These associations are confirmed by the results of viscosimetnc studies on thiazole and binary mixtures of thiazole and CCU or QHij. In the case of CCU, there is association of two thiazole molecules with one solvent molecule, whereas cyclohexane seems to destroy some thiazole self-associations (aggregates) existing in the pure liquid (312-314). The same conclusions are drawn from the study of the self-diffusion of thiazole (labeled with C) in thiazole-cyclohexane solutions (114). 

PARTIAL MOLAR EXCESS ENTHALPY AT INFINITE DILUTION OF THIAZOLE IN VARIOUS SOLVENTS AT SIS.IS K... 

The (thermal) decomposition of thiazol-2-yldiazonium salts in a variety of solvents at 0 C in presence of alkali generates thiazol-2-yl radicals (413). The same radicals result from the photolysis in the same solvents of 2-iodothiazole (414). Their electrophilic character is shown by their ability to attack preferentially positions of high rr-electron density of aromatic substrates in which they are generated (Fig. 1-21). The major... 

Thiazol-2-yl radicals have also been generated by silver oxide oxidation of thiazol-2-ylhydrazine in various aromatic solvents (Scheme 69). The... 

In agreement with the theory of polarized radicals, the presence of substituents on heteroaromatic free radicals can slightly affect their polarity. Both 4- and 5-substituted thiazol-2-yl radicals have been generated in aromatic solvents by thermal decomposition of the diazoamino derivative resulting from the reaction of isoamyl nitrite on the corresponding 2-aminothiazole (250,416-418). Introduction in 5-position of electron-withdrawing substituents slightly enhances the electrophilic character of thiazol-2-yl radicals (Table 1-57). 

Isothiazole itself (283), Rx = Rj = Rj - H, is converted to thiazole in 7% yield, in propylamine as solvent using a low-pressure mercury lamp (642). 

The object of these studies has been the determination of the degree of association in thiazole and its alkyl derivatives. Various solvents have been used cyclohexane (154), carbon tetrachloride (155, 156), benzene and nitrobenzene (157). 

The free-radical reactivity of thiazoles has been well studied with various radicals such as methyl, phenyl, substituted phenyl, cyclohexyl, and aromatic-heterocyclic, in nonpolar solvent or strong acids (180-182). 

Alkyl- and arylthiazoles rearrange undernltraviolel irradiation in different solvents to yield the corresponding isothiazoles or isomeric thiazoles. With alkylthiazoles the overall yields are very low, and it is not possible to use this method preparatively. For arylthiazoles it is possible 2-arylthiazoles. for instance, can be used to prepare 3-arylisothiazoles that are otherwise very difficult to obtain. 

Some studies on the quatemization of arylthiazoles have been published, among them the quatemization of 2-methyI-4-phenyl thiazole in various solvents (263). The order of reactivity is the following 2-methyl-4-phenyl > 2-methyI-4-(3-nitrophenyl) > 2-methyl-4-(2-chlorophenyl) > 2-methyl-4-(4-nitrophenyl). Introduction of a phenyl group in the... 

These a-acylaminoketones also provided a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriel s method). Although yields range from 45 to 80%, substituents are usually restricted to alkyl, aryl and alkoxy derivatives. Thus, reaction of the a-acylaminoketone (4) with P4S1Q gave the thiazole (5), and thiazole (7) itself was prepared in this manner in 62% yield from formylaminoacetal (6) (14CB3163). The corresponding 5-ethoxy compound was obtained from the a-formamidoester and phosphorus pentasulfide in an inert solvent. 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

A solution of 150 g (0J44 mol) of d(+)6-phenyl-2,3,5,6-tetrahydroimida2o[2,1-b] thiazole, d-10-camphorsulfonate in water is treated with 15.5 g (0.378 mol) of 98% sodium hydroxide and the liberated base extracted with chloroform. The chloroform solution Is washed with water followed by sodium chloride solution and dried over magnesium sulfate. Evaporation of the solvent left 72.1 g of residue which crystallized shortly. The free base hereby obtained has a melting point of 60°C to 61.5°C and an opticai rotation + 85.1 (C = 10, CHCI3). 

Method A (in CH,C1,) To a stirred solution of 1 mmol of the aldehyde 1 in 3 mL oT CH2C.l2 is added dropwise a solution ori.5 mmol of 2-(trimethylsilyl)thiazole (3) in 3 mL ofCH2Cl2 at —30 °C. After stirring for 20 h, the solvent is evaporated in vacuo, and the residue is treated with 1 M TBAF (1.5 mmol) in 10 mL of l HK After stirring for 1 h. the solvent is removed under vacuum, and sat. aq NaHC03 is added. The solution is extracted with EtOAc, and the extract is dried over anhyd Na2S04 then the solvent removed under reduced pressure. The residue is chromatographed on a short silica gel column (petrolcum/cthcr/EtOAc, 7 3). 

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