Date of Award
1982
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Abstract
The carbene chemistry of thiazolium salts was demonstrated. First, 5-carbethoxy-3,4-dimethylthiazolium iodide 7 yielded 5,5'-bicarbethoxy-3,3';4,4'-bi-dimethyl-(DELTA)('2,2')-bi-thiazoline 8. Thiazolium salts 3-benzyl-5-carbethoxy-4-methylthiazolium bromide and 3-benzylbenzothiazolium bromide yielded the rearranged dimers 2-(5-carbethoxy-4-methylthiazol-2-yl)-5-carbethoxy-2,3-dibenzyl-4-methylthiazolidine and 2-(benzothiazol-2-yl)-2,3-dibenzylbenzothiazoline, respectively. The O-trityl ether, N-benzyl salt of the thiamine thiazole yielded the corresponding rearranged dimer. Importantly, thiamine yielded the rearranged dimer (cis,trans)-2-{5-(2-hydroxyethyl)-4-methyl-thiazol-2-yl}-2,3-di-{(4-amino-2-methylpyrimidin-5-yl) methyl}-3a-methylperhydrofuro-(2,3-d)thiazole. The mechanism of rearranged dimer formation is through carbene dimerization followed by a 1,3-sigmatropic rearrangement of a benzyl (or a pyrimidinyl-methyl) group. Salt 7 reacted with benzaldehyde in NEt(,3) to yield 2-benzoyl-5-carbethoxy-3,4-dimethyl-(2-H)-thiazoline. Ketone 2-benzoyl-3-methylbenzothiazoline 23 rearranged in acid to 2-(1-hydroxybenzyl)-3-methylbenzothiazolium chloride 24. Salt 24 released benzaldehyde in pyridine, but rearranged to ketone 23 in NEt(,3) demonstrating that ketones 22 and 23 are stable carbene addition products. Addition of the thiamine carbene to aldehydes yields the "active aldehyde" and its ketone isomer as the kinetic products. The intermediacy of these products is demonstrated by the isolation of acyloin products and the cis and trans isomers of HET ketone 4 and HBT ketone 3. HET and HBT are obtained only after acidification of the reaction mixture; the instability of HET under the condition of the Mizuhara acyloin test and the Risinger preparation was demonstrated. The C-2 H-D exchange of thiazolium salts suggests that the function of sulfur is to stabilize the carbene and the function of the pyrimidinyl group is as an intramolecular nucleophilic catalyst.
Recommended Citation
Doughty, Michael Bernard, "The Catalytic Mechanism of Thiamine in Enzymatic and Non-Enzymatic Systems: Carbene Chemistry of the Thiazolium Ring and Novel Intramolecular Nucleophilic Catalysis by the Aminopyrimidinyl Group." (1982). LSU Historical Dissertations and Theses. 3800.
https://repository.lsu.edu/gradschool_disstheses/3800
Pages
240
DOI
10.31390/gradschool_disstheses.3800