Thiazolium Research Articles

ChemInform Abstract: Benzoin Condensation Reactions of 5‐Membered Heterocyclic Compounds Catalyzed by Thiazolium Salts.

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Three-component cyclocondensations. Two methods for the efficient preparation of 5-aminothiazolium salts via the reaction of isocyanides either with dimethylthioformamide and imino chloro sulfides or benzaldimines and aryl chlorothioformates

Treatment of imino chloro sulfides with dimethylthioformamide and isocyanides at room temperature provides selectively the 5-amino-4-(dimethylamino)-2-(methylthio) (or phenylthio)thiazolium salts. Similarly, the reactions of p-tolyl chlorothionoformate and phenyl chlorodithioformate with a mixture of benzaldimine and isocyanide afford rapidly the 5-amino-4-phenylthiazolium salts. We suggest that these reactions involve the N-(thiocarbonyl)formamidinium and benzylideniminium chlorides as transient intermediates, which are trapped by isocyanides according to a [1+4] cycloaddition process. The structure of the thiazolium salts and some of their reactivities are discussed

The reaction of 3-methylthiazolium derivatives with superoxide

3-Methylbenzothiazolium salts were allowed to react with superoxide to afford dimeric bis[ o-( N-formyl- N-methylamino)phenyl]disulfides and 3-methyl-2-benzothiazolones. The reaction was applied to monocyclic thiazolium salts, and novel ten-membered ring compounds were formed whose structures were elucidated by X-ray crystallographic analysis. These results prompted us to alternative synthesis of the ring compound, and bithiazolium salts were revealed to afford them by the reaction with superoxide.

Carbon-carbon bond formation mediated by papain chemically modified by thiazolium salts

Alkylation of the active site cysteine with 2-bromomethyl- N-methyl- or 2-bromomethyl-N-benzylthiazolium bromide afforded a protein with no detectable protease activity but the ability to mediate carbon-carbon bond formation with or 6-oxoheptanal as substrate.

Approaches to chemically modified enzymes as synthetic catalysts

Attempts to introduce new catalytic activities of potential use in synthetic transformations into enzyme active sites are described. Substitution of the naturally occurring zinc in carboxypeptidase A by several metals known to catalyse hydrogenation was investigated; a new protein characterised as a rhodium carboxypeptidase was isolated but it failed to show activity as a hydrogenation catalyst for the reduction of a series of dehydroamino acid amides. Horse liver alcohol dehydrogenase was investigated for its potential to act as an oxygen transferase via Lewis acid catalysis. A series of cyclohexenyl and phenylribosides together with new alkenyl(arenyl)oxymethylenoxyethanols was prepared for evaluation as substrates; in the course of this study, novel neighbouring group participation by the oxygen atom of a chloromethyl ether was observed. Although the binding of potential oxygen acceptors (alkenes and aromatic compounds) and oxygen donors (hydrogen peroxide and alkyl hydroperoxides) was demonstrated, oxygen transfer did not occur with the combinations investigated. In contrast to the failure of the above metalloenzymes to catalyse new reactions, papain modified at the active site sulfhydryl group by thiazolium salts and pyridinium salts was shown to exhibit reactions characteristic of the covalently attached cofactor. Thus the thiazolopapains acted as decarboxylation catalysts for pyruvate and, the pyridinopapains could be reduced to dihydropyridines which reduced electrophilic carbonyl substrates with small enantiomeric excess.

New evidence supporting bis(thiazolin-2-ylidene)s as the actual catalytic species in the benzoin condensation.

Polymethylene-bridged (n= 2-8) thiazolium and benzothiazolium salts (plus bases) are used as catalysts for the benzoin condensation and it is found that catalytic activity depends strongly on the methylene bridge length. This result supports a previous postulation that bis (thiazolin-2-ylidene)s, and not thiazolin-2-ylidenes, are the catalytic species in the benzoin condensation catalyzed by thiazolium salts plus base.

Introduction to a rational design of chiral thiazolium salts

A rational design of chiral thiazolium salts to be used in chiral benzoin condensations is possible from the proposal that bis (thiazolin-2-ylidene)s are the actual catalytic species in the benzoin condensation.

Formose reaction by polymer‐supported thiazolium salts

AbstractThiazolium salt polymers synthesized by quaternization of 4‐(4′‐vinylphenyl)thiazole (VPT) polymers with methyl iodide had a highly catalytic activity for “the formose reaction.” Their catalytic activities were comparable to that of a low molecular weight analog, 3‐methyl‐4‐phenylthiazolium iodide (MPTI). In the reaction catalyzed by the polymer catalyst, a main product, dihydroxyacetone (DHA), was detected by gas‐liquid chromatography. The polymer catalysts were easily recovered from the reaction mixture and reused with a sustained catalytic activity. © 1992 John Wiley & Sons, Inc.

An Efficient and Neutral Catalyst for the Ketalization of Carbonyl Compounds

An efficient ketalization of aldehydes, ketones, and α,β-unsaturated aldehydes using thiazolium salt 1 as a neutral catalyst is described.

Benzoin condensation reactions of 5‐membered heterocyclic compounds

AbstractBenzoin condensation reactions of 2‐thiophenecarboxaldehydes and furfurals have been reexamined with catalysts such as potassium cyanide, cyanide‐resin, and a thiazolium salt. 2‐Thiophenecarboxaldehydes gave both thenoins and thenils while furfurals gave only furoins. Possible routes which might lead to formation of thenils were investigated.

Quinolone antibacterials. 2. 6‐Substituted‐7‐(2‐thiazolyl and thiazolidinyl)quinolones

AbstractA series of 6‐substituted‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐7‐(2‐thiazolyl‐ and thiazolidinyl)quinoline‐3‐carboxylic acids were synthesized. Substitution at the 6‐position was H, F or Cl. The Hantzsch method was used for the preparation of the thiazolylquinolones. The thiazolidinylquinolones were synthesized by quaternization of the corresponding thiazolyl analogues, followed by reduction of the obtained thiazolium salts with sodium borohydride in aqueous solution. Antibacterial activity was tested in vitro. The compounds were inactive against Gram‐negative bacteria but some of them showed good activity against Gram‐positive bacteria and mycobacteria. This activity pattern is rarely found among the quinolone antibacterials.

Quinolone antibacterials. 1. 7‐(2‐substituted‐4‐thiazolyl and thiazolidinyl)quinolones

AbstractA series of 7‐(2‐substituted‐4‐thiazolyl and thiazolidinyl)‐1‐ethyl‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acids and their 6‐fluoro analogues were synthesized. The Hantzsch method was used for the preparation of the thiazolylquinolones. The thiazolidinylquinolones were synthesized by quaternization of the corresponding thiazolyl analogues, followed by reduction of the obtained thiazolium salts with sodium borohydride in aqueous solution. Antibacterial activity was tested in vitro. Most of the compounds were inactive against Gram‐negative bacteria but some of them showed however good activity against Gram‐positive bacteria and mycobacteria. This activity pattern is rarely found among the quinolone antibacterials.

Antibacterial activity of 5-acylaminothiazole derivatives, synthetic drugs related to .BETA.-lactam antibiotics.

Newly synthesized 5-acylaminothiazolium salts and one 5-acylaminothiazolidine, considering their chemical structure and reactivity, have been proposed as potential inhibitors of bacterial serine DD-peptidases. A moderate antibiotic activity with (5-phenylacetylamino-3-thiazolio)acetate and (5-phenylacetylaminothiazolidin-3-yl)acetic acid was observed on Staphylococcus aureus ATCC 25923. The methyl- and tert-butyl esters of the thiazolium salt have shown lower MIC values. Moreover, when introduced into an exponential growth phase culture of S. aureus, the three active thiazolium salts induced a partial lysis indicating an impairing of the bacterial cell wall biosynthesis. The observed time-dependent binding of the best compound to the PBPs of S. aureus was too slow and occurred at too high concentrations to account for its MIC value. Consequently, the antibiotic activity of the thiazolium salts on the S. aureus cells seems not to be satisfactorily explained by a penicillin-like interaction with the PBPs.

2-Acyl thiazolium salts as selective agents for the O-acylation of aromatic hydroxylamines

2-Acyl-3,4-dimethylthiazolium triflates, modelled upon the biologically important 2-acyl thiamine derivatives, react in neutral media specifically with the oxygen atom of N-aryl hydroxylami'nes to give rise to tetrahedral intermediates, which collapse to the O-acyl derivatives under mildly basic conditions.

Pressure dependence of the reversible hydrolysis of thiazolium salts

Abstract The hydrolysis of thiazolium salts is studied under varying pressures between 0.1 and 85 MPa. Activation and reaction volumes are obtained for different reaction steps. The results confirm the reaction scheme, where the thiazolium cation forms a pseudobase by addition of an hydroxide ion. The pseudobase can be protonated or can form a ring-opened species, which can further be deprotonated.

ChemInform Abstract: ESR Observation of Enamine Radical Cations from Thiamine (Vitamin B1) and Related Compounds.

AbstractThe reduction of thiamine and thiazolium salts by photochemically generated radicals such as ·CMe2‐OH and ·CH2OH leads to radical cations such as (I) and (II); (IIb) is accompanied by (III).

The effect of strain on the catalytic reactions of bridged thiazolium salts as models of thiamin

The reactivity of bridged thiazolium salts (9) and (10) has been studied; the model (9) with the shorter bridge is unable to catalyse the benzoin condensation reaction and it was shown that this is due to failure of the condensation step (5)→(6), probably owing to the effects of strain.

Regio- and stereoselective conjugate addition of nitrogen nucleophiles to 2-alkenyl n-methylthiazolium iodides. synthesis of d-3-epi-daunosamine and some lincosamine analogues

A two-carbon homologation-amination technology of aldehydes is described. Key steps involve the Michael-type addition of a nitrogen nucleophile (benzylamine, trimethylsilylazide, potassium phtalimide) to a 2-alkenyl N-methylthiazolium salt obtained by olefination of the aldehyde with the phosphorane (1), and the thiazole-to-formyl deblocking. The addition of benzylaminine to the thiazolium salt derived from the acetonide of D- glyceraldehyde occurs with a good level of syn-diastereoselectivity (ds, 85-90 %) in agreement with a modified Felkin-Anh model. This technology is employed in short synthetic routes to D-3- epi-daunosamine from 4-deoxy D-threose and some lincosamine analogues from α-D-dialdogalactopyranose.

Acyloin condensation by polymer supported thiazolium salt: Relation between the catalytic activity and the degree of quarternization

AbstractThiazolium salt polymers were synthesized by the quarternization of thiazole polymers by alkyl halides. It was found that these polymers had high catalytic activities for the acyloin condensation of furfural. The catalytic activities of thiazolium salt polymers increased as the degree of quarternization decreased. This tendency was observed both in the polar solvents such as MeOH and in the nonpolar solvents such as dioxane. From the results of the acyloin condensation catalyzed by more hydrophobic polymer catalyst PTS+–St (which had styrene unit instead of free thiazole unit) and CnPTS+ (which had a long alkyl chain around the active site), it became clear that the hydrophobicity and the steric hindrance around the active site greatly affected the catalytic activity.

A holoenzyme model of thiamin dependent enzymes: polymer catalyst supported thiazolium salt

Comparaison de l'activite catalytique en fonction du pH dans la condensation du furfural en acyloine d'un iodure de thiazolium, du poly([vinyl-4] phenyl-4 thiazole) quaternarise et du meme polymere reticule par le DVB