Thiazolium salts synthesis

Cookson R, Lane RM (1976) Conversion of dialdehydes into cyclic a-ketols by thiazolium salts synthesis of cyclic 2-hydroxy-2-enones. J Chem Soc Chem Commun 1976 804... 

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. 

Examples of different kinds of dyes obtained by usual synthesis starting from bis-thiazolium salts are listed in Tables 41A,BtC, 42, 43A.B-C, 44. 

Thiazolium salts can be obtained successfully by a modification of the Hantzsch s thiazole synthesis. This method is particularly valuable for those thiazolium compounds in which the substituent on the ring nitrogen cannot be introduced by direct alkylation, for example, aryl or heteroaryl thiazolium salts (Scheme 42). 

Thiazolium salts with alkyl (103, 722), arylalkyl (116), aryl (305), or heteroaryl (96) substituents on the nitrogen have been also prepared by this procedure. As in the thiazole series, N-substituted thioamides can be formed directly in the reaction mixture from phosphorus pentasulfide and N-substituted amides (127). These methods are important in the synthesis of thiamine 102 (vitamin Bj) (Scheme 45). 

H-Imidazo[2,l-6]thiazolium chloride, 6,7-dihydro-3-(5-nitro-2-furanyl)-biological activity, 6, 1024 5H-Imidazo[2,l-6]thiazolium salts, 6,7-dihydro-synthesis, 6, 992... 

Enzymatic action, of thiazolocyanines, 80 Ethanol, action on thiazolium salts, 32 Ethoxymethylene diethylmalonate, in synthesis of trimethine thiazolocyanines, 55... 

Ethyl-2-methyi-4-phenylthiazolium salts, on hydrobase of, 39 3-Ethyi-5-methyl-2-(p-dimethylamino-styiyl) thiazolium iodide, 29 Ethyl orthoformate, condensation with, thiazolium salts, 49 in synthesis of. chain-bridged thiazolocyanines, 58 thiazolocyanines. 58... 

Regulating growth factors, of plants, thiazolium salts as, 80 Resonance theory, 68 Rhodacyanines, see Neutrorhodacyanines cationic, tables of, 180 nomenclature of. 27 nonionic dyes, tables of. 184 synthesis of, 64... 

Thiazolium salts, acetanilido derivatives, in synthesis of unsymmetrical tri-methine thiazolocyanines, 55 acetanilido-l,3,5-hexatrienyl. in synthesis of heptamethine thiazolocyanines, 57... 

Pariser-Parr-Pople calculations, 72 calculations of thiazolocyanines, 73 of thiazolium salts, 31 Pentamethine thiazolocyanines, chain-bridged, synthesis of. 58 cleavage of, 63 nomenclature of. 26 synthesis of, 56... 

An orthometallation procedure for the preparation of condensed iso-thiazolium salts from appropriately substituted arenes has been described earlier in this Section (Scheme 117)180 an example illustrating the way in which this approach can be elaborated to the synthesis of condensed 1,2-dithiolylium perchlorates is given in Scheme 123. 

A different approach toward highly substituted pyrroles involving a one-pot sila-Stetter/Paal-Knorr strategy was realized by Bharadwaj and Scheidt (Scheme 6.182) [343]. In this multicomponent synthesis, catalyzed by a thiazolium salt, an acyl anion conjugate addition reaction of an acylsilane (sila-Stetter) was coupled in situ with the conventional Paal-Knorr approach. Employing microwave conditions at 160 °C for 15 min, the acylsilane was combined with the cx/l-unsaturated ketone in... 

The most important and common method for the synthesis of imidazo[2,l-f)]thiazoles [86HC(46)77] is the cyclocondensation of 2-aminothiazoles with a-halo ketones (37YZ308 55CB1109 71JPR977 72YZ51) thiazolium salts of type 47 (Scheme 2) are intermediates. For many years it remained unclear... 

J B azyl-5-(2-hydroxyethyl)-4-mcthyl-l,3-thiazoliiMn chloride, 6, 38 39, 289 7, 16 17. Detailed directions are available Tor preparation of this thiazolium salt, which ll alto commercially available (Fluka). Examples of use of this catalyst in Combination with triethylamine for acyloin condensation are cited. The heterocyclic fbroin can also he prepared with this catalyst. Synthesis of benzoins, however, requires use of a related catalyst, one substituted with an N-melhyl or N-ethyl group ill place of N-benzyl. 

The synthesis of the Stetter thiazolium salt 25 uses a different strategy. The first disconnection is obviously of the benzyl group and then we need the a-chloro-ketone 41 for reaction with thio-formamide. 

As an obvious extension of the benzoin reaction, the cross-coupling of aldehydes or of aldehydes and ketones was first achieved with the thiamine-dependent enzyme benzoylformate decarboxylase. This linked a variety of mostly aromatic aldehydes to acetaldehyde to form the corresponding a-hydroxy ketones, both chemo- and stereoselectively [31]. Synthetic thiazolium salts, developed by Stetter and co-workers and similar to thiamine itself [32], have been successfully used by Suzuki et al. for a diastereoselective intramolecular crossed aldehyde-ketone benzoin reaction during the course of an elegant natural product synthesis [33], Stereocontrol was exerted by pre-existing stereocenters in the specific substrates, the catalysts being achiral. 

The broad scope of the catalytic generation of activated carboxylates was demonstrated by Bode et al. in the diastereoselective synthesis of / -hydroxy esters 79 from a,/ -epoxy aldehydes 80 employing achiral thiazolium salts 81 as precatalysts (Scheme 9.24) [67]. The incorporation of a reducible functionality into the aldehyde substrate is the premise for a catalyst-induced intramolecular redox reaction generating the activated carboxylate 82. 

The most common way to prepare N-heterocyclic carbenes is the deprotonation of the corresponding azolium salts, like imidazolium, triazolium, tetrazolium, pyrazolium, benzimidazolium, oxazolium or thiazolium salts or their partly saturated pendants, with the help of suitable bases. The pJCa value of imidazolium and benzimidazolium salts was determined to be between 21 and 24, which puts them right in between the neutral carbonyl carbon acids acetone and ethyl acetate [41,42], Arguably, imidazolium-based carbenes have proven to be especially versatile and useful and their synthesis should be discussed in more detail. The synthesis of imidazolium salts has been developed over many decades and numerous powerful methods exist [43]. 

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