via reactions of cysteine, which provides the N-C-C-S backbone of the ring. Thiamine does not fit this pattern however. Several biosynthesis routes lead to the thiazole ring as required for the formation of thiamine. Sulfur of the thiazole is derived from cysteine. In anaerobic bacteria, the CN group is derived from dehydroglycine. Reactions With a pKa of 2.5 for the conjugate acid, thiazoles are far less basic than imidazole (pKa =7). Deprotonation at C2: the negative charge on this position is stabilized as an ylide; Hauser bases and organolithium compounds react at this site, replacing the proton 2-(trimethylsiliyl)thiazole (with a trimethylsilyl group in the 2-position) is a stable substitute and reacts with a range of electrophiles such as aldehydes, acyl halides, and ketenes Electrophilic aromatic substitution at C5 requires activating groups such as a methyl group in this bromination: Nucleophilic aromatic substitution often requires a leaving group such as chlorine at C2 with Organic oxidation at nitrogen gives the aromatic thiazole N-oxide; many oxidizing agents exist, such as mCPBA; a novel one is hypofluorous acid prepared from fluorine and water in acetonitrile; some of the oxidation takes place at sulfur, leading to non-aromatic sulfoxide/sulfone: Thiazoles are formyl synthons; conversion of R-thia to the R-CHO aldehyde takes place with, respectively, methyl iodide (N-methylation), organic reduction with sodium borohydride, and hydrolysis with Mercury(II) chloride in water. Thiazoles can react in cycloadditions, but in general at high temperatures due to favorable aromatic stabilization of the reactant; Diels-Alder reactions with alkynes are followed by extrusion of sulfur, and the endproduct is a pyridine; in one study, a very mild reaction of a 2-(dimethylamino)thiazole with dimethyl acetylenedicarboxylate (DMAD) to a pyridine was found to proceed through a zwitterionic intermediate in a formal [2+2]cycloaddition to a cyclobutene, then to a 1,3-thiazepine in a 4-electron electrocyclic ring opening and then to a 7-thia-2-azanorcaradiene in a 6-electron electrocyclic ring, closing before extruding the sulfur atom. Thiazolium salts Alkylation of thiazoles at nitrogen forms a thiazolium cation. Thiazolium salts are catalysts in the Stetter reaction and the Benzoin condensation. Deprotonation of N-alkyl thiazolium salts give the free carbenes and transition metal carbene complexes. Alagebrium is a thiazolium-based drug. References Aromatic bases Simple aromatic rings