REACTIONS OF BENZALDEHYDE WITH THIAZOLIUM SALTS IN ME(2)SO - EVIDENCEFOR INITIAL FORMATION OF 2-(ALPHA-HYDROXYBENZYL)THIAZOLIUM BY NUCLEOPHILIC-ADDITION AND FOR DRAMATIC SOLVENT EFFECTS ON BENZOIN FORMATION

The mechanism of benzoin condensation from benzaldehyde catalyzed by [ 2-C-13]-labeled 3-benzyl- and 3-methylthiazolium salts was examined un der a variety of conditions. At ambient temperatures in dry Me(2)SO, e mploying t-BuOK as the base, several different combinations of these l abeled thiazolium salts and [alpha-C-13]benzaldehyde or [alpha-H-2]ben zaldehyde all pointed to the formation of 2-(alpha-hydroxybenzyl)thiaz olium ion, that under these conditions was Stable for long periods of time, but was converted to benzoin once even a trace of water or metha nol was added to the solution. Analysis of the C-13 NMR spectra of the reaction mixtures indicated that the 2-(alpha-hydroxybenzyl)thiazoliu m ion was produced by nucleophilic addition of the C2 carbanion/ylide to the carbonyl carbon, without rearrangement of the benzaldehyde-C al pha H during the process. H-1 NMR experiments suggested that under the conditions employed, the ylide/carbanion, rather than the dimerized b ithiazolin-2-ylidene is the reactive species that condenses with the a ldehyde. The kinetic isotope effect for a reaction in which the thiazo lium ion was allowed to discriminate between [alpha-H-2]benzaldehyde a nd [alpha-H]benzaldehyde was inverse (k(H)/k(D) = 0.83), also consiste nt with addition at the benzaldehyde a carbon. When there was nearly 1 equiv of t-BuOK added and moisture was not rigorously excluded, 2-(al pha-hydroxybenzyl)thiazolium ion was still very much in evidence as an intermediate and excellent yields of benzoin resulted. In addition, s everal other compounds in much smaller yields, probably including 2-be nzoylthiazoline also appeared to accumulate to NMR-detectable levels. The reaction of thiazolium salts with the aromatic aldehydes, p-anisal dehyde and cinnamaldehyde, in MeOH/MeONa, led to the formation of sign ificant amounts of the corresponding dimethyl acetals, rather than to the benzoin products. Some of the conditions identified in this mechan istic study could be of synthetic utility as well.