Coenzyme Models. VIII. Reduction of the Schiff Base of Pyridoxal Analogs by 1,4-Dihydronicotinamide

Reduction of Schiff bases by 1-benzyl-1,4-dihydronicotinamide (BzlNH) was performed in refluxing methanol. Protonated imines such as N-(p-nitrobenzylidene)benzylamme hydrochloride (1H+) and N-(4-nitrosalicylidene)benzylamine hydrochloride (1(OH)H+) were reduced to the corresponding aminomethyl derivatives. The NMR product analysis for the reaction of BzlNH and 1H+ in refluxing ethanol-d established that the solvent deuteron was not incorporated into the aminomethylene product. 1(OH), unprotonated species, was partially reducible, whereas 1 was totally unreactive. The facile reduction of 1 occurred in the presence of several amine hydrochlorides (NEt3·HCl, imidazole hydrochloride, N,N,N′,N′-tetramethylethylenediamine dihydrochloride). These results show that the ortho hydroxyl group of 1(OH) facilitates imine reduction not only by polarization of the Schiff base via hydrogen bonding but also by proton transfer. The relative reactivity of the Schiff base to the BzlNH reduction is: 1H+, 1+NEt3·HCl≥1(OH)H+>1(OH)>1(unreactive) This order is similar to that found in “trans-Schiffization” between semicarbazide and the Schiff base of pyridoxal and its analogs, as reported by Gordes and Jencks.