Thermodynamics and kinetics of the hydride-transfer cycles for 1-aryl-1,4-dihydronicotinamide and its 1,2-dihydroisomer

Xiao Qing Zhu, Lei Cao, Yang Liu, Yuan Yang, Jin Yong Lu, Jian Shuang Wang, Jin Pei Cheng

Research output: Contribution to journalArticlepeer-review


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-H2) 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-H2) and the 1,2-dihydroisomer (GPNAH-1,2-H2) 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.

Original languageEnglish (US)
Pages (from-to)3937-3945
Number of pages9
JournalChemistry - A European Journal
Issue number16
StatePublished - Aug 18 2003
Externally publishedYes


  • Hydride transfer
  • Kinetics
  • Nicotinamide
  • Thermodynamics

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


Dive into the research topics of 'Thermodynamics and kinetics of the hydride-transfer cycles for 1-aryl-1,4-dihydronicotinamide and its 1,2-dihydroisomer'. Together they form a unique fingerprint.

Cite this