Thiamin (1) promotes reactions involving acyl carbanion equivalents derived from benzaldehyde through a covalent intermediate, 2-(1-hydroxybenzyl)thiamin (HBzT, 2). HBzT reverts to benzaldehyde and thiamin in alkaline solution. However, in neutral solution thiamin is not released as HBzT fragments irreversibly into thiazole and pyrimidine derivatives Since thiamin is produced from HBzT only at high pH, protonation of the pyrimidine of HBzT may lead to preference for fragmentation. To test the effect of charge on the reaction pathway, N(1’)-methyl-2-(1-hydroxybenzyl)thiamin (5, MBzT) was prepared. Unlike HEzT, MBzT fragments in acidic, neutral, and alkaline solutions to give ketore 3 and a substituted pyrimidinium ion. Exchange of the C(2 alpha) hydrogen for deuterium is faster than fragmentation with proton removal from C(2 alpha a necessary step preliminary to fragmentation. A mechanism that is consistent with these data converts the C(2 alpha) conjugate base of HBzT to the tautomer in which a proton is removed from the C(2 alpha) and another is added to N(3). This zwitterion apparently fragments by C-N cleavage along with a 1-2 proton shift from nitrogen to carbon. The cleavage step involves an incipient carbanion in the transition state which is stabilized by the positively charged pyrimidine. The path leading to elimination of benzaldehyde is favored only when the neutral pyrimidine is present in much higher concentration than its conjugate acid. The C(2 alpha) conjugate base of 2-(1-hydroxybenzyl)thiamin diphosphate is an intermediate in the reaction catalyzed by benzoylformate decarboxylase where fragmentation of the thiamin derivative would block the normal catalytic process. In that case, forces in the active site of the enzyme must direct reaction away from fragmentation towards release of benzaldehyce.