One-step Hydride Transfer Research Articles

Essential Rule Derived from Thermodynamics and Kinetics Studies of Benzopyran Compounds.

Compounds with benzopyran as the core structure play an important role in the total synthesis of antioxidants, drugs, and natural products. Herein, the thermodynamic data of benzopyran compounds and their intermediates were measured and calculated by combining thermodynamics with kinetics. The mechanism of reactions between four benzopyran compounds and organic hydride acceptors was proven to be a one-step hydride transfer. The thermodynamic properties of these compounds and their corresponding intermediates were elucidated. The rationality and accuracy of the electrochemical measurement method were proved. Furthermore, the essential rule of unique structures being present between the C-H bond and para-substituent constants on the benzene ring, as shown in previous studies, was investigated. A simultaneous correlation between thermodynamics and kinetics was found for the hydride transfer reaction, in which the reaction site is connected with the substituent through the benzene ring, a double bond, or a N atom. The likely reason for the correlation between thermodynamic and kinetic is that the benzene ring, double bond, or N atom have the role of transferring the electronic effect. This finding can be applied to the calculation of the activation energy of hydride self-exchange reactions, the prediction of kinetic isotope effects, and explorations of selective reduction processes of hydride transfer in such organic hydride compounds.

A Mechanism Study of Redox Reactions of the Ruthenium-oxo-polypyridyl Complex.

Over the years, RuIV(bpy)2(py)(O)2+([RuIVO]2+) has garnered considerable interest owing to its extensive use as a polypyridine mono-oxygen complex. However, as the active-site Ru=O bond changes during the oxidation process, [RuIVO]2+ can be used to simulate the reactions of various high-priced metallic oxides. In order to elucidate the hydrogen element transfer process between the Ruthenium-oxo-polypyridyl complex and organic hydride donor, the current study reports on the synthesis of [RuIVO]2+, a polypyridine mono-oxygen complex, in addition to 1H and 3H (organic hydride compounds) and 1H derivative: 2. Through 1H-NMR analysis and thermodynamics- and kinetics-based assessments, we collected data on [RuIVO]2+ and two organic hydride donors and their corresponding intermediates and established a thermodynamic platform. It was confirmed that a one-step hydride transfer reaction between [RuIVO]2+ and these organic hydride donors occurs, and here, the advantages and nature of the new mechanism approach are revealed. Accordingly, these findings can considerably contribute to the better application of the compound in theoretical research and organic synthesis.

Reduction of Quinones by NADH Catalyzed by Organoiridium Complexes

Reduction of Quinones by NADH Catalyzed by Organoiridium Complexes

Conversion and Origin of Normal and Abnormal Temperature Dependences of Kinetic Isotope Effect in Hydride Transfer Reactions

The effects of substituents on the temperature dependences of kinetic isotope effect (KIE) for the reactions of the hydride transfer from the substituted 5-methyl-6-phenyl-5,6-dihydrophenanthridine (G-PDH) to thioxanthylium (TX(+)) in acetonitrile were examined, and the results show that the temperature dependences of KIE for the hydride transfer reactions can be converted by adjusting the nature of the substituents in the molecule of the hydride donor. In general, electron-withdrawing groups can make the KIE to have normal temperature dependence, but electron-donating groups can make the KIE to have abnormal temperature dependence. Thermodynamic analysis on the possible pathways of the hydride transfer from G-PDH to TX(+) in acetonitrile suggests that the transfers of the hydride anion in the reactions are all carried out by the concerted one-step mechanism whether the substituent is an electron-withdrawing group or an electron-donating group. But the examination of Hammett-type free energy analysis on the hydride transfer reactions supports that the concerted one-step hydride transfer is not due to an elementary chemical reaction. The experimental values of KIE at different temperatures for the hydride transfer reactions were modeled by using a kinetic equation formed according to a multistage mechanism of the hydride transfer including a returnable charge-transfer complex as the reaction intermediate; the real mechanism of the hydride transfer and the root that why the temperature dependences of KIE can be converted as the nature of the substituents are changed were discovered.

ChemInform Abstract: Energetics of Multistep versus One-Step Hydride Transfer Reactions of Reduced Nicotinamide Adenine Dinucleotide (NADH) Models with Organic Cations and p-Quinones.

Free energy changes of each elementary step involved in the formal hydride transfer (H(-)(T)) reactions (including the so-called H(-)(T) and multistep H(-)(T) mechanisms) of the reduced nicotinamide adenine dinucleotide (NADH) models with various cations and quinones (17) were investigated either by direct thermodynamic measurements or by calculations from thermochemical cycles. Based on the energetic data thus derived, combined with kinetic observations (particularly kinetic isotope effects), the mechanistic characteristics of the NADH-mediated reductions were systematically analyzed. Practical guidelines that resulted from these analyses suggest that a mutistep mechanism (e(-)-H(*) or e(-)-H(+)-e(-)) would be followed if the energy gap of the initial electron transfer [DeltaG(e(-)(T))] between the NADH model compound and the reducing substrate is considerably smaller than the empirical critical limit of 1.0 V for an endothermic e(-)(T). In contrast, if DeltaG(e(-)(T)) is much greater than 1.0 V, a concerted one-step H(-)(T) may take place. The guideline also suggests that a hybrid mechanism is possible if the DeltaG(e(-)(T)) is in an intermdiate situation.

A Mechanistic Dichotomy in Scandium Ion-Promoted Hydride Transfer of an NADH Analogue: Delicate Balance between One-Step Hydride-Transfer and Electron-Transfer Pathways

The rate constant (kH) of hydride transfer from an NADH analogue, 9,10-dihydro-10-methylacridine (AcrH2), to 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) increases with increasing Sc(3+) concentration ([Sc(3+)]) to reach a constant value, when all TolSQ molecules form the TolSQ-Sc(3+) complex. When AcrH2 is replaced by the dideuterated compound (AcrD2), however, the rate constant (kD) increases linearly with an increase in ([Sc(3+)]) without exhibiting a saturation behavior. In such a case, the primary kinetic deuterium isotope effect (kH/kD) decreases with increasing ([Sc(3+)]). On the other hand, the rate constant of Sc(3+)-promoted electron transfer from tris(2-phenylpyridine)iridium [Ir(ppy)3]to TolSQ also increases linearly with increasing ([Sc(3+)]) at high concentrations of Sc(3+) due to formation of a 1:2 complex between TolSQ*- and Sc(3+), [TolSQ*--(Sc(3+)2], which was detected by ESR. The significant difference with regard to dependence of the rate constant of hydride transfer on ([Sc(3+)]) between AcrH2 and AcrD2 in comparison with that of Sc3+-promoted electron transfer indicates that the reaction pathway is changed from one-step hydride transfer from AcrH2 to the TolSQ-Sc3+ complex to Sc3+-promoted electron transfer from AcrD2 to the TolSQ-Sc3+ complex, followed by proton and electron transfer. Such a change between two reaction pathways, which are employed simultaneously, is also observed by simple changes of temperature and concentration of Sc3+.

Transient Species in the Stepwise Interconversion of NADH and NAD+

AbstractFor Abstract see ChemInform Abstract in Full Text.

Transient species in the stepwise interconversion of NADH and NAD+.

Two mechanisms of the interconversion of NADH and NAD+ in the coenzyme itself and in its analogues are discussed: a one-step hydride transfer and a stepwise electron-proton-electron transfer. Direct characterization of the transient species in the stepwise process and inversion of the stability order of the keto and enol tautomers is presented. The nonenzymatic and enzyme-mediated reactions of selected pyridinium salts that affect the NADH <==>NAD+ equilibrium are discussed in terms of their potential cytotoxicity.

Thermal and photoinduced reduction of some benzyl bromides by an NAD(P)H model: the effect of electron withdrawing groups on mechanism and reactivity

A series of compounds o-bromomethylbenzylidene-malononitrile (1), dimethyl o-bromomethyl-benzylidenemalonate (2) and mthyl alpha-cyano-o-bromomethylcinnamate (3) were reduced in the dark and under irradiation by an NAP(P)H model, 1-benzyl-1,4-dihydronicotinamide (BNAH). Two different mechanisms were found, i.e. one-step hydride transfer (polar pathway) and multi-step sequence initiated by single electron transfer (SET pathway). The effect of electron-withdrawing groups on the reactivity of the Substrates were discussed in terms of Hammett substituent constants, C-13 NMR chemical shift values and cyclic voltammetric redox potentials, mid their correlations. (C) 2002 Elsevier Science Ltd. All rights reserved.

An old but simple and efficient method to elucidate the oxidation mechanism of NAD(P)H model 1-Aryl-1,4-dihydronicotinamides by cations 2-methyl-5-nitroisoquinolium, tropylium, and xanthylium in aqueous solution.

Cations 2-methyl-5-nitroisoquinolinium (IQ+), tropylium (T+), and xanthylium (Xn+) were treated by an NAD(P)H model 1-(p-substituted phenyl)-1.4-dihydronicotinamide series (1) in buffered aqueous solution to give the corresponding reduced products by accepting hydride. Effects of the 4-substituents of 1 on the reaction rates were investigated. Hammett's linear free energy relationship analysis on the three reactions of 1 provides the reaction constants of -0.48, -2.2, and -1.4 with IQ+, T+, and Xn+ as the hydride acceptors, respectively. Comparison of the present reactions with the reaction examples whose mechanisms are well-known, such as the reaction of 1 with a one-electron oxidant Fe(CN)6(-3), shows that the active site of 1 in the oxidation with IQ+ is at the 4-position on the dihydropyridine ring but that the active site of 1 in the oxidations with T+ and Xn+ is at the 1-position, which is in agreement with the results from the Brønsted-type linear analysis and the relation studies of the logarithm of the second-order rate constants with the oxidation potentials of the hydride donors. According to the dependence of the reaction mechanism on the active site of 1, a conclusion can be made that the reaction of 1 with IQ+ proceeds by direct one-step hydride transfer mechanism, but the reactions of 1 with T+ and Xn+ would take place via multistep hydride transfer mechanism initiated by one-electron transfer.

ChemInform Abstract: A Detailed Investigation into the Oxidation Mechanism of Hantzsch 1,4-Dihydropyridines by Ethyl α-Cyanocinnamates and Benzylidenemalononitriles.

The mechanism for the oxidation of Hantzsch 1,4-dihydropyridine (HEH) by substituted ethyl α-cyanocinnamates (1) and benzylidenemalononitriles (2) has been critically investigated. Replacement of HEH by HEH-4,4-d2 and HEH-N-d gave the observed kinetic isotope effects (KIE) of 5.3–6.0 and 1.2–1.3 for the reactions with 1 and 2, respectively, which suggests C4–H bond dissociation is involved in the rate-limiting step and that the N–H bond dissociation is a non-rate-limiting step. The positive ρ values of 1.78 and 1.67 for the reactions of HEH with 1 and 2, respectively, clearly demonstrate the electrophilic nature of the substrates in the transition state (TS) and so indicate that the hydrogen lost from HEH must be a hydride-like species. Correlation analyses on the kinetics, KIE’s, and activation parameters showed excellent linear dependence on the electronic properties of remote substituents and added further credence to the proposed one-step hydride transfer mechanism. Detailed investigation of the activation parameters not only confirmed the direct H−T mechanism, but also revealed experimentally, for the first time, an entropy-controlled compact TS for the HEH-modeled NAD(P)H oxidations.

A detailed investigation into the oxidation mechanism of Hantzsch 1,4-dihydropyridines by ethyl α-cyanocinnamates and benzylidenemalononitriles

The mechanism for the oxidation of Hantzsch 1,4-dihydropyridine (HEH) by substituted ethyl α-cyanocinnamates (1) and benzylidenemalononitriles (2) has been critically investigated. Replacement of HEH by HEH-4,4-d2 and HEH-N-d gave the observed kinetic isotope effects (KIE) of 5.3–6.0 and 1.2–1.3 for the reactions with 1 and 2, respectively, which suggests C4–H bond dissociation is involved in the rate-limiting step and that the N–H bond dissociation is a non-rate-limiting step. The positive ρ values of 1.78 and 1.67 for the reactions of HEH with 1 and 2, respectively, clearly demonstrate the electrophilic nature of the substrates in the transition state (TS) and so indicate that the hydrogen lost from HEH must be a hydride-like species. Correlation analyses on the kinetics, KIE’s, and activation parameters showed excellent linear dependence on the electronic properties of remote substituents and added further credence to the proposed one-step hydride transfer mechanism. Detailed investigation of the activation parameters not only confirmed the direct H−T mechanism, but also revealed experimentally, for the first time, an entropy-controlled compact TS for the HEH-modeled NAD(P)H oxidations.

Energetics of Multistep versus One-step Hydride Transfer Reactions of Reduced Nicotinamide Adenine Dinucleotide (NADH) Models with Organic Cations and p-Quinones.

Free energy changes of each elementary step involved in the formal hydride transfer (H(-)(T)) reactions (including the so-called "one-step" H(-)(T) and "multistep" H(-)(T) mechanisms) of the reduced nicotinamide adenine dinucleotide (NADH) models with various cations and quinones (17) were investigated either by direct thermodynamic measurements or by calculations from thermochemical cycles. Based on the energetic data thus derived, combined with kinetic observations (particularly kinetic isotope effects), the mechanistic characteristics of the NADH-mediated reductions were systematically analyzed. Practical guidelines that resulted from these analyses suggest that a mutistep mechanism (e(-)-H(*) or e(-)-H(+)-e(-)) would be followed if the energy gap of the initial electron transfer [DeltaG(e(-)(T))] between the NADH model compound and the reducing substrate is considerably smaller than the empirical critical limit of 1.0 V for an endothermic e(-)(T). In contrast, if DeltaG(e(-)(T)) is much greater than 1.0 V, a concerted one-step H(-)(T) may take place. The guideline also suggests that a "hybrid" mechanism is possible if the DeltaG(e(-)(T)) is in an intermdiate situation.

AlCl3-Promoted Conjugate Reduction of α,β Unsaturated Carbonyl Compounds with 1,3-Dimethyl-2-phenylbenzimidazoline

Abstract The reduction of a variety of α,β-unsaturated carbonyl compounds, except for α,β-unsaturated aldehyde, to the corresponding saturated carbonyl compounds was effectively performed by using 1,3-dimethyl-2-phenylbenzimidazoline (DMBI) as a reducing agent with the aid of AlCl3. The reduction is discussed on the basis of the hydride-donating ability of DMBI, together with the role of AlCl3 as an electrophilic activator for the substrates. The catalytic efficiency of Lewis acids was found to be proportional to the efficiency to form a complex with a carbonyl group. The reduction of 2-cinnamoylpyridine with 2-deuterated DMBI revealed that in the reduction product, a deuterium atom was located at the β-position with respect to the carbonyl group. On the other hand, the reduction of the same substrate with DMBI followed by quenching with D2O gave a reduced product which contained a deuterium label at the α-position. These results were interpreted in terms of a mechanism involving an enolate intermediate produced by either a one-step hydride transfer or a sequential transfer of an electron (e) and a hydrogen atom (H·) from the reducing agent to the substrate.

Hydride transfer reactions. A kinetic study of oxidation of 10-methyl-9-phenylacridan by some π acceptors and a one-electron oxidant

The kinetics of oxidation of 10-methyl-9-phenylacridan (1(H)) and 9-deuterio-10-methyl-9-phenylacridan (1(D)) to 10-methyl-9-phenylacridinium ion (3) by eight oxidants have been investigated. The oxidants included the π-acceptors 1,4-benzoquinone (BQ), 7,7,8,8-tetracyanoquinodimethane (TCNQ), p-bromanil (BA), p-chloranil (CA), tetracyanoethylene (TCNE), 2,3-dicyano-1,4-benzoquinone (DCBQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile (AN), BQ in 50:50 (v/v) AN-water, and the one-electron oxidant tris(2,2′-bipyridyl)cobalt(III), [Formula: see text] in AN. The seven π acceptors cover a 109-fold range of reactivity from BQ to DDQ and the deuterium kinetic isotope effect varies from 11.9 (BQ in AN) to 5.8 (DDQ). For π acceptors (BQ, TCNQ, CA, TCNE, and DCBQ) previously investigated with 10-methylacridan (NMA), 1(H) is less reactive than NMA by factors ranging from 9.1 (BQ) to 1.7 × 102 (TCNE). The isotope effects and relative reactivities for the π acceptor oxidations are most simply explained by a one-step hydride transfer mechanism.

Kinetics of the reduction of 1-methylquinolinium cations by 1-benzyl-1,4-dihydronicotinamide

The reduction of a series of 3-W-1-methylquinolinium cations (1: W = H, Br, CONH2, CO2CH3, CN, NO2) by 1-benzyl-1,4-dihydronicotinamide has been investigated. In all cases the kinetically controlled product from these reactions is the appropriate 3-W-1,4-dihydro-1-methylquinoline. Only for W = Br is any significant amount of the 1,2-dihydro isomer obtained (15% in this case). This kinetic preference for C-4 attack over C-2 attack in dihydronicotinamide reductions contrasts with the kinetically preferred attack at C-2 by hydroxide ion and in borohydride reductions. Rates of reduction were measured for each 1 and also 1,2-dimethyl- and 1,4-dimethylquinolinium cations in 20% CH3CN – 80% H2O, ionic strength 1.0 at 25 °C, under pseudo-first-order conditions. Kinetic saturation due to nonproductive 1:1 complex formation was observed for several cations at high concentrations (&gt; 0.1 M). Second-order rate constants [Formula: see text] were evaluated for each W, and also kinetic isotope effects from second-order rate constants [Formula: see text] for reduction by 1-benzyl-4,4-dideuterio-1,4-dihydronicotinamide. Second-order rate constants are correlated with σp− for W with ρ = 4.5, and are also closely correlated with [Formula: see text] for pseudobase formation at C-4 of these quinolinium cations by: [Formula: see text]. Values of [Formula: see text] vs. [Formula: see text] describe a Westheimer curve reaching a maximum of 5.8 for W = Br and falling to 1.5 for W = NO2 and 4.2 for W = H. These data are consistent with an intrinsic barrier of 2.9 ± 0.5 kcal/mol for hydride transfer between this 1,4-dihydronicotinamide and quinolinium cations. However, quinolinium cations display a dramatically enhanced rate of dihydronicotinamide reduction relative to hydroxide ion attack when compared with isoquinolinium cations. This observation, and the predominance of C-4 rather than C-2 reduction, suggests that these reactions may not be simple one-step hydride transfer processes.

Kinetics of the reduction of C-9 substituted acridinium cations by 1,4-dihydronicotinamides

Second-order rate constants ( k 2) are reported for the reduction of 9-R-10-methylacridinium cations ( 5:R = H, CH 3, CH 3CH 2, C 6H 5CH 2, (CH 3) 2CH, C 6H 5, 4-(CH 3) 2NC 6H 4) by 1-benzyl-1,4-dihydronicotinamide ( 2:R = C 6H 5CH 2) in 20% CH 3CN-80% H 2O at 25°C. All 5:R ≠ H are reduced in the range 20- to 140-fold more slowly than 5:R = H. However, there is no simple relationship between k 2 and the nature of R, nor between k 2 and the second-order rate constant for hydroxide ion attack at C-9 of these cations in pseudobase formation. Rates of reduction of 5 by 1-benzyl-4,4-dideuterio-1,4-dihydronicotinamide allow the calculation of the following kinetic isotope effects in this solvent medium: 5:R, k H k D : H , 1.56; C 6H 5CH 2, 2.7; C 6H 5, 5.4. Substituent effects upon k 2 were evaluated for the reduction of 5 by 1-(X-benzyl)-1,4-dihydronicotinamides, and lead to the following Hammett ϱ parameters: 5:R, ϱ: H, −0.68; C 6H 5CH 2, −0.92; C 6H 5, −0.96. The latter two values require essentially complete unit positive charge generation on the nicotinamide moiety in the rate-determining transition state. It is shown that these Hammett ϱ values and the above isotope effects can only be rationalized by a two-step e − + H • mechanism for hydride transfer from 2 to 5 in this solvent system. This result contrasts with our earlier conclusion of direct, one-step hydride transfer in the reduction of isoquinolinium cations by 2, but is consistent with our observation that acridinium cations are reduced 37500-fold faster by 2 than predicted on the basis of the relative rates of nucleophilic attack (hydroxide ion) on acridinium and isoquinolinium cations. It is suggested that the availability of both Hammett ϱ values and primary kinetic isotope effects will generally allow the establishment of the mechanism of hydride transfer in these systems. Application of these ideas to literature data suggests that 5:R = H is reduced by direct hydride transfer in acetonitrile solution, in contrast to the above result in predominantly aqueous solution. The ready formation of acridanyl radicals by electron transfer to acridinium cations is demonstrated by the formation of Wurster's Blue radical cation upon mixing solutions of acridinium cations with N,N,N′,N′-tetramethyl- p-phenylenediamine.