Indolenines. Reduction by a Dihydropyridine and Addition to Thiols

Indolenines were studied as models for the postulated indolenine intermediate derived from tryptophanyl residues in dehydrogenase enzymes. An indolenine salt (o-chlorophenyl(2-methyl-3H-indolylidene)methane hydrochloride) was rapidly reduced by l-benzyl-l,4-dihydronicotinamide. The products of the reaction were the corresponding indole and pyridinium salt. Similar reduction by 1 -benzyl-1,4-dideuterionicotinamide produced the indole with one deuterium atom in the methylene group, indicating direct transfer of a hydride ion in the reaction. The effect of phenyl substituents on the rate of reduction was examined. Reduction of p-methoxy-, o-chloro-, and p-nitrophenyl(2-methyl-3H-indolylidene)methane hydrochloride by 1 -benzyl-1,4-dihydronicotinamide in ethanol at 25° followed the rate law v = K₂(indolenine)(dihydropyridine), with k₃ = 7,25, and 32 1. mole^-1 sec^-1, respectively. The o-chloroindolenine salt readily added to mercaptobenzene, benzyl mercaptan, and methyl thioglycollate to give the corresponding thioether-indole, o-chlorophenyl(2-methyl-3-indolyl)alkylthio- (or arylthio-) methane. Acidic dithionite reductively cleaved such a thioether-indole adduct to the free indole and mercaptan.