44- Thiazolines thiazolium salts

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. 

Certain bifunctional nucleophiles allow cyclization after ring opening. The formation of 2-thiazolium salts (71JHC40S) and the analogous production of 2-amino-2-thiazolines (191) from aziridines and thiocyanic acid fall into this category (72JOC4401). 

In order to vary the electronic situation at the carbene carbon atom a number of carbo- and heterocycle-annulated imidazolin-2-ylidenes like the benzobis(imida-zolin-2-ylidenes) [58-60] and the singly or doubly pyrido-annulated A -heterocyclic carbenes [61-63] have been prepared and studied. Additional carbenes derived from a five-membered heterocycle like triazolin-5-ylidenes 10 [36], which reveals properties similar to the imidazolin-2-ylidenes 5 and thiazolin-2-ylidene 11 [37] exhibiting characteristic properties comparable to the saturated imidazolidin-2ylidenes 7 have also been prepared. Bertrand reported the 1,2,4-triazolium dication 12 [64]. Although all attempts to isolate the free dicarbene species from this dication have failed so far, silver complexes [65] as well as homo- and heterobimetallic iridium and rhodium complexes of the triazolin-3,5-diylidene have been prepared [66]. The 1,2,4-triazolium salts and the thiazolium salts have been used successfully as precatalysts for inter- [67] and intramolecular benzoin condensations [68]. 

Thiazoles are deactivated towards electrophilic substitution, and thus direct reaction with hydride re-ductants to give thiazolines should be facilitated. There are indeed some examples of this type of reaction, but it is more common to reduce N-alkylated thiazolium salts (209). These compounds are converted first by reaction with sodium borohydride into 4-thiazolines (210), which in protic solvents become protonated and undergo further reduction to yield thiazolidines (211). Similarly the isoquinoli-nium salt (213), formed by the acid-promoted cyclization of the isoquinoline (212), is converted into the tetrahydroisoquinoline (214) (presumably via an intermediate 1,2-dihydroisoquinoline) by reaction with sodium borohydride. ... 

The reaction of thiazolium salt 229 with DBU in ethanol or tetrahydrofuran involved a competition yielding thiazoline 230, ylide 231, and acetaldehyde (79JA2752). Ylide 231 was also generated from the 3-benzyl-4-methyl-thiazolium salt 232 and DBU. Ylide 231 was trapped with different electrophiles. The reactions of 230 with sources of electrophilic sulfur mimic the pyruvate dehydrogenese-mediated production of enzyme-bound acetyl-dihydrolipoic acid. 

The use of thiazolium salts enables the benzoin condensation to proceed at room temperature. It can also be performed in dipolar aptotic solvents or under phase transfer conditions. Thiazolium salts such as vitamin Bi, thiazolium salts attached to y-cyclodextrin, macrobicyclic thiazolium salts, thiazolium carboxylate, ° naphtho[2,l-d]thiazolium and benzothiazolium salts catalyze the benzoin condensation and quaternary salts of 1-methylbenzimidazole and 4-(4-chlorophenyl)-4//-1,2,4-triazole are reported to have similar catalytic activity. Alkylation of 2-hydroxyethyl-4-methyl-l,3-thiazole with benzyl chloride, methyl iodide, ethyl bromide and 2-ethoxyethyl bromide yields useful salts for catalyzing 1,4-addition of aldehydes to activated double bonds. Insoluble polymer-supported thiazolium salts are catalysts for the benzoin condensation and for Michael addition of aldehydes. Electron rich al-kenes such as bis(l,3-dialkylimidazolidin-2-ylidenes) bearing primary alkyl substituents at the nitrogen atoms or bis(thiazolin-2-ylidene) bearing benzyl groups at the nitrogen atoms are examples of a new class of catalyst for the conversion of ArCHO into ArCHOHCOAr. 

Castells, J., Lopez-Calahorra, F., Domingo, L. Postulation of bis(thiazolin-2-ylidene)s as the catalytic species in the benzoin condensation catalyzed by a thiazolium salt plus base. J. Org. Chem. 1988, 53,4433-4436. 

The hydrogen atoms at position 2 of dihydrothiazines of types 51 and 80 are expected to display acidic properties this behavior has been reported only in the case of the thiazolium salt 54, which afforded the arylidene derivative 134 with an aromatic aldehyde. When treated with hydrogen peroxide in acetic acid, the dihydrothiazinone 135a was converted into the 2-hydroxy derivative 135b by contrast, compound 97 afforded the thiazoline 136 (Section V,C,2,b). Clearly the position of the equilibrium between the two possible products is dramatically influenced by the nature of the Af-substituent. 

Reactions of Thiazolium Salts. - Base-induced attack of thiazolium salts and rearrangement of subsequent 2-hydroxy-A -thiazoline was studied by u.v. kinetic spectroscopy (two consecutive irreversible steps).The first step was the nucleophilic attack of OH on C-2 of (103 R = H or Me), affording the thiazoline (104), with measured third-order rate constants. The second step was the nucleophilic cyclization of the thiolate (105) to form the thietans (106) (Scheme 9). 

Meso-ionic Thiazoles.—Successive treatment of 5-acylamino-AMhiazoline-2-thiones (73) with methyl iodide and alkali yields products that have been recognized as meso-ionic 5-acylimino-2-methylthio-thiazoles (75) (see also these Reports, Vol. 2, p. 614). This formulation supersedes the thiazolium salt structure by which certain members of this series have previously been represented. The methylthio-group of (75) is readily replaced on treatment with nucleophilic reagents such as potassium hydrosulphide, di-cyanomethide ion, amines, etc., with formation of 2-substituted 5-acyl-amino-A -thiazolines [e.g. (76)]. ... 

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