Thiazoliums

The amino group is expected to have decreased reactivity in thiazolium salts. 2-Amino-4,5-trimethylene thiazole (224) heated in diluted HQ at 80°C, however, gives the product 227a (463). The probable mechanism is shown in Scheme 139. This mechanism suggests a retro-Hantzsch ... 

Thiazolium derivatives unsubstituted at the 2-position (35) are potentially interesting precursors of A-4-thiazoline-2-thiones and A-4-thiazoline-2-ones. Compound 35 in basic medium undergoes proton abstraction leading to the very active nucleophilic species 36a and 36b (Scheme 16) (43-46). Special interest has been focused upon the reactivity of 36a and 36b because they are considered as the reactive species of the thiamine action in some biochemical reaction, and as catalysts for several condensation reactions (47-50). 

It is noteworthy that some catalysts convert thioethers to quaternary salts where the reactive electrophilic center is no longer one of the two C centers but the C sp center of the thiazolium salt (284. 285). Thus... 

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. 

II. General Synthetic Methods for Thiazole and Thiazolium Salts... 

Cyanine Dyes Derived from Thiazolium Salts "N... 

Rhodacyanines possess two chromophoric systems. They are at the same time neutrocyanine derivatives, which involves position 5 of the ketomethylene, and methine cyanine, which involves position 2. Following lUPAC s standard nomenclature rules, structure 7 is named 3-ethyl-4-phenyl-2- 4-oxo-3-ethyl-5-[2-(3-ethy]-2,3-dihydro-benzo-l,3-thiazo-lylidene)ethylidene]-tetrahydro-l,3-thiazolylidene-methyl -1.3-thiazolium iodide (Scheme 5). It implies that the 4-phenyl thiazole ring having the... 

Cvanine Dves Derived from Thiazolium Saits... 

In styryl compounds, a part of the methine chain is replaced by a phenyl group. Their name is based on the nuclei from which they are issued 3-ethyl-5-methyl-2-(p-dimethylaminostyryl)thiazolium iodide (Scheme 7). 

One may find many publications in the literature on the theoretical aspects of thiazolium quaternary salts, because of the biological importance of thiamine and their use as catalysts for benzoin condensation. 

Thiazolium salts can be obtained either directly by slight modifications of ring-closure methods, already described for the parent bases, or by classical quaternization of the bases, the detailed mechanism of which have been reported in Chapter III the quaternization is best represented by a classical SNj mechanism, the solvent playing an important part (14) unless the reaction is run without any solvent. 

The thiazolium ring, as most heterocycloammoniums, is a Lewis acid conferring to the carbon atom in the 2-position the carbocationic property of adding the free pair of a base either organic or mineral that may be the molecule of solvent as ROH (Scheme 11). For many nuclei of suitable acidity, these equilibria can be observed in dilute solution by means of absorption spectra when species A and C possess different characteristics (24). For example, benzothiazolium and benzoxazolium in methanol and ethanol give at 10 mole liter 8 and 54% of the alkoxy derivatives for the former and 29 and 90% for the latter respectively. 

Besides the well-known lower basicity of ethanol, these data illustrate the greater acidity of benzoxazolium compared with benzothiazolium. The relative pK. values of the quaternary salts obtained in acetonitrile when treated with tetrabutylammonium hydroxide are 18.3 and 17.6, respectively (25). Those of 2-methyl 4-phenyl thiazolium and 2.4-dimethyl thiazolium are 20.5 and 21.8 under the same conditions (25). 

The thiazolium is not acidic enough for observing directly solvation of the molecule (or an hydrolysis and subsequent cleavage of the ring) (24) without adding a base, as it is the case for benzoxazolium or benzothiazolium. With the same dilution (10 mole liter ), it is necessary to add sodium ethylate to the solution of 2-methyl-4.5-diphenylthiazolium to observe the equilibrium described above. A new band appears in the UV spectrum at 320 nm that is attributed to the ethoxy derivative by analogy to what has been observed with other benzothiazoliums (26),... 

Chiefly in an hydrophobic medium, a base can extract the proton on position 2 leading to a reactive intermediate (able to give subsequent condensation) that could be an ylid (35, 36) or a carbene (37), though no dimer has ever been isolated as is the case with benzothiazolium (32, 38). Two mechanisms have been proposed for explaining the particular reactivity of thiazolium ... 

At first, the dimeric nature of the base isolated from 3-ethyl-2-methyl-4-phenylthiazolium was postulated via a chemical route. Indeed the adduct of ICH, on a similar 2-ethylidene base is a 2-isopropylthiazolium salt in the case of methylene base it is an anilinovinyl compound identified by its absorption spectrum and chemical reactivity (45-47). This dimeric structure of the molecule has been definitively established by its NMR spectrum. It is very similar to the base issued from 2.3-dimethyl-benzo thiazolium (48). It corresponds to 2-(3 -ethyl-4 -phenyl-2 -methylenethiazolinilydene)2-methyl-3-ethyl-4-phenylthiazoline (13). There is only one methyl signal (62 = 2.59), and two series of signals (63= 1.36-3.90, 63= 1.12-3.78) correspond to ethyl groups. Three protons attributed to positions T,5,5 are shifted to a lower field 5.93, 6.58, and 8.36 ppm. The bulk of the ten phenyl protons is at 7.3 ppm (Scheme 22). 

As a whole, 2 moles of quinolinium react with one of thiazolium together with 2 moles of base. This explains the traditional interest of making the condensation with an excess of quinolinium salt in order to get the maximum yield (50. 51). 

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