Substituent effects upon the equilibration of 4-cyano-1,4-dihydro-1-(substituted-benzyl)nicotinamides with 1-(substituted benzyl)nicotinamide cations

Bunting, John W.; Sindhuatmadja, Shinta

doi:10.1021/jo01314a053

Cited by 10 publications

(3 citation statements)

References 4 publications

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“…Parameters derived for these reactions are also included in Table I. -80% H20 (v/v) and at 25 0 C and an ionic strength of 1.0. b Reaction too slow for The kinetics of reduction of 3, 4 (X = CONH2), and 4 (X = CN) by 7 (W = CN, CONHCH3 and CON(CH3)2) were also investigated. For 7 (W = CN), these reactions were quite slow, and rate constants could only be confidently evaluated for 4 (X = CN) which is by far the most reactive of the above isoquinolinium cations.…”

Section: Resultsmentioning

confidence: 99%

“…log (1/slope) = -0.50 pKR+ + 4.9 (6) log k2 = -0.50 pKR+ + 4.9 (7) In terms of Scheme II, eq 6 becomes eq 7, and making use of the relationship in eq 8 previously established3 for isoquinolinium cations, eq 7 may be expressed in the form of eq 9. log fe0H = -0.36pKR+ + 8.84 (8) log k2 = 1.4 log k0H -7.4 (9) Equation 9 shows that assumption of nonproductive complex formation as in Scheme II leads to a linear freeenergy relationship between rates of hydrogen transfer from 4 to isoquinolinium cations and rates of hydroxide ion attack on these same cations. We therefore have (i) evidence for the importance of nonproductive complexes in the kinetic analysis of these systems and (ii) further support for the hydridic nature of the hydrogen atom in the transition state for these reductions.…”

Section: Discussionmentioning

confidence: 99%

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Kinetics of the reduction of isoquinolinium cations by 1,4-dihydronicotinamides

Bunting¹,

Chew²,

Chu³

1982

J. Org. Chem.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kinetics of the reduction of isoquinolinium cations by 1,4-dihydronicotinamides

Bunting¹,

Chew²,

Chu³

1982

J. Org. Chem.

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“…Given the reactivity of pyridinium salts with nucleophiles, which usually leads to dihydropyridines, often with good regioselectivity, we tested the interaction of isocyanides with N -alkylpyridinium salts. Although similar addition processes with cyanide yielded the corresponding 1,4-adducts, all attempts to perform the transformation upon reactive β-substituted pyridinium salts (CN, COCH 3, CO 2 CH 3 ) under a range of reaction conditions (protic or aprotic solvents, different quenching protocols, and a range of temperatures) resulted only in the detection (HPLC-MS) of traces of the expected adducts. It has to be remarked that pyridines are reluctant to undergo Reissert reactions, requiring special conditions, and do not suffer the analogous isocyanide process. 2a, An important difference with the cyanide addition arises here: the initial adduct is now a nitrilium ion, presumably in equilibrium with the starting materials, which may require further stabilization to proceed to the carbamoylated final compounds (Scheme ).…”

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confidence: 99%

Isocyanide Addition to Pyridinium Salts. Efficient Entry into Substituted Nicotinonitrile Derivatives

et al. 2006

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The addition of isocyanides to pyridinium salts is studied. The process takes place efficiently when a carboxamido group is present in the 3 position of the pyridine ring. The outcome of the reaction involves the stabilization of the nitrilium intermediate by the amide, which suffers a mild dehydration, leading regioselectively to beta-cyano-gamma-carbamoyl-1,4-dihydropyridines. In this way, a variety of nicotinamide derivatives were carbamoylated. Extension to quinolinium, isoquinolinium, and N-acylpyridinium salts is also reported. [reaction: see text]

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

Zhu

Cao

Liu

et al. 2003

Chemistry A European J

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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.

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Substituent effects upon the equilibration of 4-cyano-1,4-dihydro-1-(substituted-benzyl)nicotinamides with 1-(substituted benzyl)nicotinamide cations

Cited by 10 publications

References 4 publications

Kinetics of the reduction of isoquinolinium cations by 1,4-dihydronicotinamides

Kinetics of the reduction of isoquinolinium cations by 1,4-dihydronicotinamides

Isocyanide Addition to Pyridinium Salts. Efficient Entry into Substituted Nicotinonitrile Derivatives

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

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