Thiazolium salts acidity

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). 

Although benzoxazolium salts are more acidic than their benzothiazol analogs in position 2, isolation of the corresponding dioxa-diazafulvalenes was unsuccessful (72LA126). Comparable to the 1,3-dithiolium- and 1,3-thiazolium salts, 1,2,4-dithiazolium salts yielded on treatment with triethylamine in acetonitrile at 0°C mixed geometrical isomers of the TTDAF... 

Addition of acyl anions generated from acylsilanes to a,(3-unsaturated ketones using N-heterocyclic carbenes (NHCs) derived from thiazolium salts as catalyst produced 1,4-diketones, which cyclized to form the corresponding furans in good yields under an acidic condition <06JOC5715>. 

Isopropylidene (l,3-thiazol-2-ylidene)malonates (473) were prepared in 52-60% yields in the reactions of (2-methylthio)thiazolium salts (472) and Meldrum s acid (421) at ambient temperature for 5-10 hr (77KGS341). 

Meldrum s acid (421) was reacted with 2-methylthiothiazolo[5,4-thiazolium salt (495) in the presence of triethylamine in ethanol at room temperature for 48 hr to give (thiazolothiazolinylidene)malonate (496) in 55% yield (74UKZ1331). 

It was hoped that ring contraction of the triazinium salt 166 would give imidazo[2,l-6]thiazolium salts (167) on treatment with acid, but instead the free base of 166 was isolated on work-up of the reaction.159 Related pyridotriazine hydrobromides 168 underwent contraction in acid to give imidazopyridinium salts. 

The thiazole-2-thione (51) with an a-halo ketone gives the intermediate (52) which is cyclized by strong acid into the thiazolo[2,3-/ thiazolium salt (53) (77HC(30-i)l). A wide variety of [5,5]-fused systems are prepared in this way. 

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... 

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]. 

Thus, upon CIR of electron-deficient (hetero)aryl halides 11 and phenyl propargyl alcohol 12a, after subsequent Stetter reaction with aldehydes 92 in presence of catalytic amounts of thiazolium salt 93, and after addition of glacial acetic acid and concentrated HCl, the 2,3,5-trisubstituted furans 95 are obtained in moderate to good yields in a one-pot procedure (Scheme 51) [260]. 

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. ... 

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