Thiazolium cations

This bathochromic shift is typical of 77 —> tt transitions. The behavior of the water solution when acidified was attributed by Albert (175) absorption by the thiazolium cation, by analogy with pyridine. However, allowance is made for the very weak basicity of thiazole (pK = 2.52) compared with that of pyridine (pK = 5.2), Ellis and Griffiths (176) consider the differences between the spectrum of thiazole in water and in... 

Salt Formation. As a weaMy basic pyrimidine and a thiazolium cation, thiamine forms both mono- and dipositive salts, eg, the two commercial... 

Anhydro bases can attack the a-position, e.g. of thiazolium cations, with the formation of adducts capable of oxidation to cyanine dyes, e.g. Scheme 18 (see Section 4.02.3.3.4). 

The C-coordinated thiazolium complexes are the result of the proton-induced cyclization reactions (980M513). Thus, complex 1 on protonation with tetrafiuoroboric acid yields the C-coordinated thiazolium structure 2. In turn, the nitrile complex 3 under these conditions is transformed to the thiazolium cationic species 4. Protonation of the amido complex 5 with tetrafiuoroboric acid also results in a cyclization but it proceeds differently. The amino group of the CONH2 moiety is lost and BF3-framework is coordinated via the carbonyl oxygen in an overall neutral complex 6. 

Equilibrium studies. Acidities of thiazolium cations, such as 213, cannot be measured in basic aqueous solution because the hydroxyl adduct ( pseudobase ) 216 of the thiazolium cation is formed rapidly and is subject to base-catalyzed ring opening (Scheme 36).151 In DMSO, formation of the carbene dimer 217 from 213 and 214 is a complicating factor.8 If indicator anion (In") was added to a solution of 213, a very rapid drop in absorbance was followed by a somewhat... 

However, cyanide ion is not suitable for inducing a benzoin-type condensation between two aliphatic aldehydes, since the basic character of this ion induces an aldol condensation between them. In Nature, nevertheless, condensations of this type take place easily. As Breslow proposed in 1958 [8], such condensations are catalysed by thiamine pyrophosphate 6 (or cocarboxylase), the active part of which is the conjugate base of the "thiazolium cation present in it. According to Breslow [8a], the mechanism is, in fact, identical to that described for the cyanide ion (see Scheme 5.7) that is to say, the conjugate base of thiamine (TPP ) reacts with an "aldehyde equivalent -such as an a-ketoacid 2- to generate the corresponding "active aldehyde" 8 with umpoled reactivity, which then reacts with the electrophile to give finally, after elimination of "thiamine anion", a 1,2-D system (9). 

By comparing rates for the thiazolium cation and neutral thiazole it is clear that the positive charge on the a-nitrogen is worth more than a factor of 10 to the exchange rate at the 2-position. Similarly, 2-methyliso-thiazolium iodide (29) exchanges its 5-H approximately 10 times faster than isothiazole itself. Substituent effects for isothiazole are similar to those observed for thiazole and the reaction is catalyzed by OD with... 

In the thiazolium cation the proton in the 2-position is acidic and its removal gives rise to the ylide/carbene 227. This nucleophilic carbene 227 can add, e.g., to an aldehyde to produce the cationic primary addition product 228. The latter, again via C-deprotonation, affords the enamine-like structure 229. Nucleophilic addition of 229 to either an aldehyde or a Michael-acceptor affords compound(s) 230. The catalytic cycle is completed by deprotonation and elimination of the carbene 227. Strictly speaking, the thiazolium salts (and the 1,2,4-triazolium salts discussed below) are thus not the actual catalysts but pre-catalysts that provide the catalytically active nucleophilic carbenes under the reaction conditions used. This mechanism of action of thiamine was first formulated by Breslow [234] and applies to the benzoin and Stetter-reactions catalyzed by thiazolium salts [235-237] and to those... 

There seems to be one example only of a catalytic intermolecular asymmetric Stetter reaction. As shown in Scheme 6.107, Enders reported that the thiazolium cation 243 afforded a moderate enantiomeric excess in the coupling of w-butanal with F-chalcone to give the 1,4-diketone 244 [257]. 

The intramolecular nucleophilic addition of the formyl group to the electron deficient alkene unit in the propenoate (10) affords a benzofuranone when catalysed by a thiazolium salt. However, when NaCN is used as the catalyst, an initial Michael addition to the acrylate function is followed by an intramolecular aldol condensation and the chroman (11) is formed. The corresponding butanoates afford chroman-4-ones under the influence of thiazolium cations, but give benzoxepins in the presence of a basic catalyst (95S1311). 

There has been considerable interest in the reactions of thiazolium cations in aqueous solutions. Most of this interest has been generated by the desire to understand the chemistry of the biologically important thiazolium cation, thiamine (vitamin B,) (70). 

Titration of a neutral aqueous solution of thiamine with standard base produces a one-step titration curve that corresponds to two equivalents of base per mole of thiamine cation.73,156,234-237 The midpoint of this titration curve occurs in the vicinity of pH 9.3 at 25° and is usually designated as pKav. Other thiazolium and benzothiazolium cations show similar two-equivalent titration steps, and values for pKav for a variety of such cations have been measured. Values of pKav in the range 9.3-11.2 have been reported73,74,155,156,234 for various thiazolium cations. 

Basic aqueous solutions of a thiazolium cation contain the ring-opened thiolate anion 74 derived from the pseudobase 72. The observation that the uptake of two equivalents of base for the formation of the thiolate anion... 

In the case of the enaminonitrile XVIIa, coupling through the phenyl ring is observed [127a]. Enamines related to the key intermediate in thiamine diphosphate-dependent enzymatic pathways lead to dimers in a one-electron oxidation via a thiazolium cation radical as intermediate [127b]. Anodic oxidation of enaminones, prepared from / -substituted acetophenones and A,A-dimethylformamide dimethylacetal, afford dimers and substituted furans in fair yield [127c]. 

Thiamine hydrochloride is the usual commercial form of vitamin Bj. The reactive part is the thiazolium cation its reactive center is C2. This carbon atom is extremely electropositive. Its C13 signal appears in the carbonyl region at 179.3 ppm. The double bond is, correspondingly, easy to hydrogenate the methine... 

The mechanism operating in A-heterocyclic carbene-mediated reactions was proposed initially by Breslow in 1958 for the thiazolium salt-catalyzed benzoin condensation (Scheme 6.1). This proposal involves the formation of a carbene as the catalytically active species by deprotonation of the thiazolium cation, which subsequently adds to one molecule of the aldehyde, generating a nucleophilic intermediate known as the Breslow intermediate. Next, this... 

Yu et al. have reported a series of thermoregulated thiazolium based ionic liquids containing polyether moieties attached to thiazolium cation (36, scheme-10). These thermoregulated ionic liquids (36) were used as catalysts in the Stetter reaction (Yu et al. 2010). The ionic liquids were pale yellow, viscous liquids at room temperature. The viscosity was found to increase with the length of the polyether chain. The structures of these ionic liquids were determined by NMR. 

---