Thermodynamics and kinetics of the hydride-transfer cycles for 1-aryl-1,4-dihydronicotinamide and its 1,2-dihydroisomer.
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.
Zhu
Xiao-Qing
XQ
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry Nankai University, Tianjin 300071 China. xqzhu@nankai.edu.cn
Cao
Lei
L
Liu
Yang
Y
Yang
Yuan
Y
Lu
Jin-Yong
JY
Wang
Jian-Shuang
JS
Cheng
Jin-Pei
JP
D004579:Electron Transport; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011522:Protons; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D011522:Protons; D011725:Pyridines; C015145:dihydronicotinamide; D009243:NAD; D009536:Niacinamide; D009249:NADP; D006859:Hydrogen