Thiazole derivatives

In the first chapter, devoted to thiazole itself, specific emphasis has been given to the structure and mechanistic aspects of the reactivity of the molecule most of the theoretical methods and physical techniques available to date have been applied in the study of thiazole and its derivatives, and the results are discussed in detail The chapter devoted to methods of synthesis is especially detailed and traces the way for the preparation of any monocyclic thiazole derivative. Three chapters concern the non-tautomeric functional derivatives, and two are devoted to amino-, hydroxy- and mercaptothiazoles these chapters constitute the core of the book. All discussion of chemical properties is complemented by tables in which all the known derivatives are inventoried and characterized by their usual physical properties. This information should be of particular value to organic chemists in identifying natural or Synthetic thiazoles. Two brief chapters concern mesoionic thiazoles and selenazoles. Finally, an important chapter is devoted to cyanine dyes derived from thiazolium salts, completing some classical reviews on the subject and discussing recent developments in the studies of the reaction mechanisms involved in their synthesis. 

III. Alkyl, Aryl, Aralkyl aud Related Thiazole Derivatives... 

Among the thiazole derivatives known for a long time, but whose structure was not at once acknowledged as such, leading to some controversies, are so-called thiocyanoacetic acid, thiohydantoine, rhodanine, mercaptothiazole, and sulfuvinuric acid. 

DIPOLE MOMENTS CALCULATED FOR VARIOUS THIAZOLE DERIVATIVES... 

Thiazole derivatives Calcd (Debye) Ref. Measured (DebyeJ Ref. 

Dipole moments were calculated for a large number of thiazole derivatives the corresponding results are reported in Table 1-8. 

Out-of-Plane Vibrations, yCH and yCD. In accordance with all the proposed assignments (201-203), the bands at 797 and 716 cm correspond to yCH vibrators, which is confirmed by the C-type structure observed for these frequencies in the vapor-phase spectrum of thiazoie (Fig. 1-9). On the contrary, the assignments proposed for the third yCH mode are contradictory. According to Chouteau et al. (201), this vibration is located at 723 cm whereas Sbrana et al. (202) prefer the band at S49cm and Davidovics et al. (203) the peak at 877 cm This last assignment is the most compatible with the whole set of spectra for the thiazole derivatives (203) and is confirmed by the normal vibration mode calculations (205) (Table 1-25). The order of decreasing yCH frequencies, established by the study of isotopic and substituted thiazole derivatives, is (203) yC(4)H > 70(2)13 > yC(5)H. Both the 2- and 4-positions, which seem equivalent for the vCH modes, are quite different for the yCH out-of-plane vibrations, a fact related to the influence observed for the... 

The infrared and Raman studies of thiazole derivatives are numerous (111,173,197-226) though often only fragmentary. The only studies leading to a complete assignment of the observed bands are those of Chouteau and Davidovics et al. (201,203.204,227,228). 

For thiazole derivatives containing polyatomic substituents, such as CH3, C2H5, C,Hg, NH, ND2. and NfCH ), the assumption was made... 

The observed order for the yfCH) bending vibrations in various mono-and disubstituted thiazole derivatives is yC,4,H> yQjjH > Usu-... 

FABLE 1-29. LIMITING FREQUENCIES OF THE VARIOUS RING VIBRATIONS OF THIAZOLE DERIVATIVES... 

Thiazole derivatives Carbon of substituent in a position of the carbon Carbon of substituent in 0 position of the carbon ... 

TABLE 1-41. IONIZATION POTENTIALS AND APPARITION POTENTIALS (eV) MEASURED FOR VARIOUS THIAZOLE DERIVATIVES 091)... 

No nitration of thiazole occurs with the classical nitration reagents, even in forcing conditions (341-343). In a study concerning the correlation between the ability of thiazole derivatives to be nitrated and the HNMR chemical shifts of their hydrogen atoms, Dou (239) suggested that only those thiazoles that present chemical shifts lower than 476 Hz can be nitrated. From the lowest field signal of thiazole appearing at 497 Hz one can infer that its nitration is quite unlikely. Thiazole sulfonation occurs... 

The same situation is observed in the series of alkyl-substituted derivatives. Electron-donating alkyl substituents induce an activating effect on the basicity and the nucleophilicity of the nitrogen lone pair that can be counterbalanced by a deactivating and decelerating effect resulting from the steric interaction of ortho substituents. This aspect of the reactivity of thiazole derivatives has been well investigated (198, 215, 446, 452-456) and is discussed in Chapter HI. 

The only reduction investigated more recently on thiazole derivatives concerns the action of sodium borohydride upon thiazolium salts chosen as model molecules for thiamine (478-480). 

In a study aimed at identifying thiazole derivatives, Travagli (485) obtained the ring cleavage of 2-aminothiazoIes (205) by their phenyl-hydrazinolysis in acetic acid. 

Extension of the Hantzsch s Synthesis to Thiazole Carboxylic and Thiazole Acetic Acids (Table II-IO). Mono-, di-, and tricarboxylic acids are among the most easily prepared thiazole derivatives. 

Treatment of a-thiocyanatoketones at low temperature with dry hydrogen chloride in ether solution gives satisfactory yields of 2-chloro-thiazole derivatives (188). The use of phosphorus pentachloride leads to the same results, but in this case chlorination can also occur at the 5-position (Scheme 97) (18, 68). 

Carbon disulfide readily reacts with a-aminonitriles giving 2-mercapto-5-aminothiazoles (213), (271, 293) which can be converted to 5-aminothiazoles unsubstituted in the 2-position (Scheme 110 and Table II-34a). If this reaction is carried out in the presence of benzyl chloride in phosphorus tribromide, a 2-S-substituted thiazole derivative (214) is obtained in quantitative yield (Scheme 111), with R = hydrogen or phenyl (68, 304). 

The spectra of substituted thiazole derivatives, especially the methyl derivatives, can be used to determine harmonic and combination bands of the T(ch) modes 27(c.,h> T(c.hi + T[Pg.351]

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