Thiazole and Derivatives

Thiazole is only sulfonated under forcing conditions due to the presence of the electron-withdrawing hetero nitrogen atom thus heating the heterocycle with oleum at 250 °C in the presence of mercury(II) sulfate catalyst yields the 5-sulfonic acid (65%).  

2- Aminothiazole 179, with chlorosulfonic acid, gives the sulfamic acid 180 which on heating rearranges to 2-aminothiazole-5-sulfonic acid 181 (Equation 

Isothiazole is also sulfonated by oleum to yield the 4-sulfonic acid derivative in both thiazole and isothiazole the orientation of sulfonation is in agreement with the calculated r-electron density patterns of the parent heterocycles.  

3- Chloroisothiazole 182, by refluxing with excess chlorosulfonic acid (nine equivalents) for 2 days, yields the 4-sulfonyl chloride 183 which, by subsequent 

The sulfonamide 184 is an intermediate in the synthesis of herbicidal N-(pyrimidine aminocarbonyl) thiazolesulfonamides. In addition, several sulfonyl derivatives of isoxazole, pyrazole and thiazole have shown antifungal activity. Benzothiazole 185 is reported to react with chlorosulfonic acid to only give a salt later repetition of the reaetion with chlorosulfonic acid at both RT and 100 °C confirmed this result. On the other hand, when benzothiazole 185 was heated with excess chlorosulfonic acid (six equivalents) at 150 °C (4i hours), followed by boiling with thionyl chloride (2 hours), the reaction gave the sulfonyl chloride as a gum. Subsequent treatment with amines afforded a mixture of the 4-and 7-sulfonamides 186 and 187 respectively (Equation 49).  

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Reaction with salts and esters of thiocarbamic acid 2-hydroxy thiazoles and derivatives... 

With S heterocyclic ligands With thiazole and derivatives With halogeno thiazoles [CuCl2 2-Br-CjH2NS)2] room 1.84 trans square planar coordination suggested 72D13... 

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

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. 

This volume is intended to present a comprehensive description of the chemistry of thiazole and its monocyclic derivatives, based on the chemical literature up to December, 1976. It is not concerned with polycyclic thiazoles, such as benzo- or naphthothiazole, nor with hydrogenated derivatives, such as thiazolines or thiazolidines later volumes in this series are devoted to these derivatives. The chemistry of thiamine has also been excluded from the present volume because of the enormous amount of literature corresponding to the subject and is developed in another volume. On the other hand, a discussion of selenazole and its monocyclic derivatives has been included, and particular emphasis has been given to the cyanine dyes derived from thiazolium salts. 

Chapters III to VII discuss the general properties of thiazoles having hydrocarbon and functional substituents, respectively. A special chapter (Chapter VIII) is devoted to mcso-ionic thiazoles, and Chapter IX describes the thiazolium salts and their numerous cyanine dyes derivatives. The last chapter concerns the monocyclic selenazoles. 

TABLE 1-16 ULTRAVIOLET ABSORPTION SPECTRA OF THIAZOLE AND ITS MONOMETHYL DERIVATIVES... 

Quantum chemistry methods allow the prediction of the ultraviolet transitions in good agreement with the experimental values in the case of thiazole and its three methyl derivatives (Table 1-18). A very weak absorption has been indicated at 269.5 nm that could correspond to an n- TT transition given by calculation at 281.5 nm (133). Ultraviolet absorption spectroscopy has been investigated in connection with steric interactions in the A-4-thiazoline-2-thione (74) series (181). It was earlier demonstrated by NMR technique that 4-alkyl-3 isopropyl-A-4-thiazoline-2-thiones exist in solution as equilibrium mixtures of two conformers (75 and 76), the relative populations of which vary with the size of R4 (182) for R4 = rBu the population of rotamer A is 100%, whereas for R4 = Me it is only 28%. Starting from the observed absorption wavelength for... 

The frequencies of suite III are usually lower for disubstituted (especially 2,4-dihalo and 2,5-disubstituted thiazoles) and those of the corresponding monosubstituted derivatives. 

For 4-monosubstituted derivatives, the frequencies of suite V are near those of the mode of thiazole, and for the 2- and 5-ones the frequencies of suite VI are near those of the mode of thiazole. 

The chemical shifts of in natural abundance have been measured for thiazole and many derivatives (257,258). They are given in Tables 1-37 and T38. These chemical shifts are strongly dependent on the nature of the substituent CNDO/2 calculations have shown (184) that they correlate well with the ((t+tt) net charge of the atom considered. As a consequence, the order of the resonance signals is the same for protons and for carbon atoms. 

The normal boiling point of 2-methylthiazole is 17 0= 128.488 0.005°C. The purity of various thiazoles was determined cryometrically by Handley et al. (292), who measured the precise melting point of thiazole and its monomethyl derivatives. Meyer et al. (293, 294) extended this study and, from the experimental diagrams of crystallization (temperature/degree of crystallization), obtained the true temperatures of crystallization and molar enthalpies of fusion of ideally pure thiazoles (Table 1-43). 

The molar diamagnetic susceptibility of thiazole and some derivatives was initially determined by the classical Curie-Cheneveau method (5,315,316) and later confirmed by a method (317) based on the difference of NMR proton chemical shift of a sample of tetramethylsilane immersed in the liquid to be investigated, according to the shape (cylindrical or spherical) of the sample tube (Table 1-47) (318),... 

Potentiometric determinations of the pK of thiazole and essentially its alkyl derivatives are summarized in Table T50. The most reliable values are given by Phan-Tan-Luu et al. (321), who realized a critical study of the classical Henderson method for the determination of pK. ... 

Rg. 1-15. Correlation between pK and electronic and solvation parameters (in arbitrarv units) for thiazole and its three monomethyJ derivatives (133). 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

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