Thermodynamics and Kinetics of the Hydride‐Transfer Cycles for 1‐Aryl‐1,4‐dihydronicotinamide and Its 1,2‐Dihydroisomer

Abstract

Five 1-(p-substituted phenyl)-1,4-dihydronicotinamides (GPNAH-1,4-H(2)) and five 1-(p-substituted phenyl)-1,2-dihydronicotinamides (GPNAH-1,2-H(2)) were synthesized, which were used to mimic NAD(P)H coenzyme and its 1,2-dihydroisomer reductions, respectively. When the 1,4-dihydropyridine (GPNAH-1,4-H(2)) and the 1,2-dihydroisomer (GPNAH-1,2-H(2)) were treated with p-trifluoromethylbenzylidenemalononitrile (S) as a hydride acceptor, both reactions gave the same products: pyridinium derivative (GPNA(+)) and carbanion SH(-) by a hydride one-step transfer. Thermodynamic analysis on the two reactions shows that the hydride transfer from the 1,2-dihydropyridine is much more favorable than the hydride transfer from the corresponding 1,4-dihydroisomer, but the kinetic examination displays that the former reaction is remarkably slower than the latter reaction, which is mainly due to much more negative activation entropy for the former reaction. When the formed pyridinium derivative (GPNA(+)) was treated with SH(-), the major reduced product was the corresponding 1,4-dihydropyridine along with a trace of the 1,2-dihydroisomer. Thermodynamic and kinetic analyses on the hydride transfer from SH(-) to GPNA(+) all suggest that the 4-position on the pyridinium ring in GPNA(+) is much easier to accept the hydride than the 2-position, which indicates that when the 1,4-dihydropyridine is used the hydride donor to react with S, the formed pyridinium derivative GPNA(+) may return to the 1,4-dihydropyridine by a hydride transfer cycle; but when the 1,2-dihydropyridine is used as the hydride donor, the formed pyridinium derivative can not return to the 1,2-dihydropyridine by the hydride reverse transfer from SH(-) to GPNA(+). These results clearly show that the hydride-transfer cycle is favorable for the 1,4-dihydronicotinamides, but unfavorable for the corresponding 1,2-dihydroisomers.

Benzimidazolium Salts as Small, Nonpeptidic and BBB‐Permeable Human Prolyl Oligopeptidase Inhibitors

“…[39] The following N-substituted-1,4-dihydropyridines (N-p-tolyl, N-cHex, and N-a-methylbenzyl) [40] were prepared following a general method. [41] General procedure for the synthesis of benzonaphthyridines 5. ScA C H T U N G T R E N N U N G (OTf) 3 (0.2 mmol) was added to a solution of aldehyde 3 (1 mmol) and aniline 2 (1 mmol) in dry CH 3 CN (4 mL), and the mixture was stirred at room temperature.…”

Photocatalytic CO2 reduction by a mixed metal (Zr/Ti), mixed ligand metal–organic framework under visible light irradiation

“…Both MOFs were tested for photocatalytic CO2 reduction under visible light irradiation. The reaction was conducted in 5 mL of a mixed solution of 4:1 (v/v) acetonitrile (MeCN)-triethanolamine (TEOA, as a sacrificial base), and 0.1 M 1-benzyl-1,4-dihydronicotinamide (BNAH, as a sacrificial reductant) [27][28][29]. The suspension, which contained 5 mg of MOF, was purged with 1 bar of CO2 gas for 30 min followed by light irradiation by a 300 W Xe lamp.…”

Hydride‐Donor Abilities of 1,4‐Dihydropyridines: A Comparison with π Nucleophiles and Borohydride Anions

“…Zhu, Cheng, et al observed the same trend in reactions of 2 h-j with p-trifluoromethylbenzylidenemalononitrile. [12] Solvent effects were studied for the reaction of the dihydropyridine 2 g with 1 f. This reaction was four times faster in acetonitrile (k 2 = 88.8 m À1 s À1 ) than in dichloromethane (Table 3). An increase in the water content of the solution in acetonitrile accelerated the hydride transfer significantly: In 90 % water/10 % acetonitrile the reaction proceeded eight times faster than in 100 % acetonitrile.…”