Primary Kinetic Hydrogen Isotope Effects Research Articles

Primary kinetic hydrogen isotope effects in deprotonations of a nitroalkane by intramolecular phenolate groups

AbstractRate constants and kinetic isotope effects have been determined for the formation of nitronate anions from the ethers 1‐(2‐methoxyphenyl)‐2‐nitropropane, 7(X = H, L = H and D) and 1‐(2‐methoxy‐5‐nitrophenyl)‐2‐nitropropane, 7(X = NO2, L = H and D), and from the corresponding phenols, 1‐(2‐hydroxyphenyl)‐2‐nitropropane, 3(X = H, L = H and D), and 1‐(2‐hydroxy‐5‐nitrophenyl)‐2‐nitropropane, 3(X = NO2, L = H and D), in aqueous basic medium. For the ethers 7, rates of deprotonation by hydroxide are comparable with those found for deprotonations of 2‐nitropropane, with kH/kD (25 °C) = 7.7 and 7.8, respectively. In both the cases, the isotope effects are conventionally temperature dependent. For the corresponding phenols 3, conditions have been established under which the deprotonations of the nitroalkane are dominated by intramolecular deprotonation by the kinetically first‐formed phenolate anion, with an estimated effective molarity EM ∼ 250. For 3 (X = H, L = H or D), kH/kD (25 °C) = 7.8, with E − E = 6.9 kJ mol−1 and AH/AD = 0.5. For 3(X = NO2, L = H or D), rates of intramolecular deprotonation are reduced 30‐fold, and an elevated kinetic isotope effect is found (kH/kD (25 °C) = 10.7). Activation parameters (E − E = 17.8 kJ mol−1 and AH/AD = 0.008) are compatible with an enhanced tunnelling contribution to reactivity in the H‐isotopomer. Copyright © 2009 John Wiley & Sons, Ltd.

Primary kinetic hydrogen isotope effects in deprotonations of carbon acids

AbstractThe mechanisms of deprotonation of carbon acids are reviewed to emphasise the important kinetic consequences associated with the internal and solvent reorganisation in forming the conjugate base. Some practicalities of measurements of kinetic hydrogen isotope effects are then considered to show how competing reactions, exchange and mechanistic branching might affect these measurements. Finally, isotopic rate ratios (kH/kD) have been collected for non‐enzymic deprotonations of carbon acids for which temperature dependences have also been determined. All examples contain nitro groups. For reactions in hydroxylic solvents, only two examples are found for which kH/kD > 8 at 25 °C (28.8 and 10.7), possibly indicating a tunnelling contribution. In both cases, values of E–E are larger and values of AH/AD smaller than the range expected (E–E = 4.54 kJ mol−1 and 0.7 < AH/AD < 1.4) for effects arising from zero‐point energy differences with no tunnelling contributions. For reactions in aprotic solvents, isotope effects are larger (12.1 < kH/kD < 19.6), but again, the largest of these (19.6 and 15.8) are associated with elevated values of E–E and small values of AH/AD. It is pointed out that behaviour of this type is accommodated by corrections to the semi‐classical model with shallow tunnelling maximised by high symmetrical barriers. No examples have been found in which large effects are associated with large values of AH/AD and small values of E–E.Comparisons are made with two recently reported enzyme‐catalysed reactions involving deprotonation of nitroalkanes. Copyright © 2010 John Wiley & Sons, Ltd.

The primary kinetic hydrogen isotope effect in the deprotonation of a nitroalkane by an intramolecular carboxylate group

AbstractThe rates of racemization of optically active nitropentanoic acid, and 4‐deuteronitropentanoic have been compared. The rate ratio (kie) is kH/kD = 5.68(±0.17) at 31°C, in good agreement with that determined by Lewis et al. for base‐catalysed deprotonations using iodine‐trapping methods. In a more detailed study, optically active 4‐nitro‐4‐phenylbutanoic acid (NPBA) has also been prepared and rates of racemization measured in dimethoxyethane:water. With less than a full equivalent of triethylamine, rates are proportional to [Et3N:]/[NPBA]. For 1 < [Et3N:]/[NPBA] < 2, rates are independent of the ratio, consistent with racemization being dominated by deprotonation of the nitroalkane by the intramolecular carboxylate group. The solvent isotope effect is = 0.73(±0.04) and rates of exchange with D2O are equal to rates of racemization. Comparison with rates of racemization by acetate of the methyl ester yielded an effective molarity (EM = 13.7) for the intramolecular carboxylate. The kie for racemizations of NPBA and 4‐deutero‐NPBA is kH/kD = 5.78 at 25°C, and for 20 < T < 50°C, E − E = 5.5(±0.1) and AH/AD = 0.63(±1.03). For the acetate catalysed racemizations of the methyl ester, 25°C, kH/kD = 7.43 with E − E = 5.2 kJ mol−1 and AH/AD = 1.08. In neither case is there any indication of a major tunnelling contribution on the isotopic rate ratio. A hitherto unrecognised mode of decomposition of nitronic acids, involving direct reaction with dissolved oxygen, has been identified. Copyright © 2008 John Wiley & Sons, Ltd.

Kinetics and Mechanism of Oxidation of Some Substituted Benzhydrols by N-Bromosuccinimide

N-bromosuccinimide (NBS) oxidation of some substituted benzhydrols (4-Cl-, 4-Me-, 4-OMe-, 4-NO2−, 4,4′-dimethyl-, 4,4′-dichloro-, 4,4′-dimethoxy-, and 4-methyl-2-nitro-) yields corresponding benzophenones in the presence of Hg(OAc)2. The reaction is first-order in [NBS], [substrate], and [H+]. A study on the primary kinetic hydrogen isotope effect and solvent isotope effect suggest that C-H and O-H stretching frequencies are affected in the transition state. Activation parameters for the rate-determining step have been evaluated. The results are in accord with the linear free energy relationship (LFER). The linear plot of log(k obs/k 0) vs. σ+ (ρ = −0.69)and Bunnett plots support the existence of proton-transfer in the rate-determining step. Rate behavior in different solvent compositions suggests dipolar-dipolar interaction in the absence of acid and ion-dipolar interaction in the presence of acid. Two different mechanisms have been suggested: cyclic transition state with unprotonated N-bromosuccinimide (NBS) in the absence of acid and noncyclic transition state with protonated NBS in the presence of acid.

Spin-forbidden deprotonation of aqueous nitroxyl (HNO).

The first mechanistic study of a spin-forbidden proton-transfer reaction in aqueous solution is reported. Laser flash photolysis of alkaline trioxodinitrate (N(2)O(3)(2)(-), Angeli's anion) is used to generate a nitroxyl anion in its excited singlet state ((1)NO(-)). Through rapid partitioning between protonation by water and electronic relaxation, (1)NO(-) produces (1)HNO (ground state, yield 96%) and (3)NO(-) (ground state, yield 4%), which comprise a unique conjugate acid-base couple with different ground-state multiplicities. Using the large difference between reactivities of (1)HNO and (3)NO(-) in the peroxynitrite-forming reaction with (3)O(2), the kinetics of spin-forbidden deprotonation reaction (1)HNO + OH(-) --> (3)NO(-) + H(2)O is investigated in H(2)O and D(2)O. Consistent with proton transfer, this reaction exhibits primary kinetic hydrogen isotope effect k(H)/k(D) = 3.1 at 298 K, which is found to be temperature-dependent. Arrhenius pre-exponential factors and activation energies of the second-order rate constant are found to be: log(A, M(-)(1) s(-)(1)) = 10.0 +/- 0.2 and E(a) = 30.0 +/- 1.1 kJ/mol for proton transfer and log(A, M(-)(1) s(-)(1)) = 10.4 +/- 0.1 and E(a) = 35.1 +/- 0.7 kJ/mol for deuteron transfer. Collectively, these data are interpreted to show that the nuclear reorganization requirements arising from the spin prohibition necessitate significant activation before spin change can take place, but the spin change itself must occur extremely rapidly. It is concluded that a synergy between the spin prohibition and the reaction energetics creates an intersystem barrier and is responsible for slowness of the spin-forbidden deprotonation of (1)HNO by OH(-); the spin prohibition alone plays a minor role.

Origin of the Primary Kinetic Hydrogen Isotope Effects on N-dealkylation from N-alkylamine by Hemoproteins

Abstract The atomic level reaction mechanism for N-dealkylation of N,N-dimethylaniline (PhNMe2) by hemoproteins, in which a kinetic hydrogen isotope effect (KHIE) was observed, was investigated by quantum mechanical theoretical calculations. Using quantum mechanical theory, one can determine the primary KHIE by the difference in zero-point vibrational energies on normal vibrational modes which are related to the reaction coordinate of H (D or T) atom abstraction from a C–H (C–D or C–T) bond. On the basis of this idea, we theoretically determined the intramolecular primary KHIE for two cases of hydrogen atom abstraction in N-dealkylation of PhNMe2; i.e., hydrogen atom abstraction from a neutral state and proton abstraction from a cation radical state. When the intramolecular primary KHIE obtained by theoretical calculation was compared with experimental results of the intramolecular KHIE on N-dealkylation of PhNMe2, which was catalyzed by some hemoproteins, it was found that four experimental values can be interpreted only from the primary KHIE. However, many other experimental values can not be interpreted only from the primary KHIE.

Primary kinetic isotope effects in hydride transfer: experimental studies of intramolecular hydride migration and ab initio molecular orbital calculations of model systems

Measurements of the primary kinetic hydrogen isotope effects for the intramolecular migration of hydride accompanying the rearrangements of (i) hydroxy-ketones involving 1,4-migration of hydride between ketonic carbonyl groups and (ii) phenylglyoxal hydrates to their corresponding mandelic acids are described. The results are discussed using ab initio MO calculations of model systems, with a variety of basis sets. The value of such model calculations is demonstrated.

Primary kinetic hydrogen isotope effects in hydride transfer: ab initio MO and experimental studies

Measurement of the primary kinetic hydrogen isotope effects for the intramolecular migration of hydride from alcohol methine to ketonic carbonyl in hydroxy-ketones and their interpretation using ab initio MO calculations show good agreement between theory and experiment.

Isotope effects on hydride transfer between NAD+ analogs

Primary kinetic hydrogen isotope effects (KIE's) for hydride transfer between NAD/sup +/ analogues have been measured for reactions with equilibrium constants ranging from 0.7 to 10/sup 16/. There is no sign of the sharp change in KIE which would signal the change of a rate limiting step in a multistep mechanism, and other evidence also indicates a one-step mechanism. The secondary KIE produced by changing the hydrogen already attached at the acceptor site from H to D is about 10% smaller when the transferred atom is D than when it is H. These results, combined with the values of the primary KIE's, strongly suggest some nuclear tunneling in the reaction coordinate.

Temperature dependence of the primary kinetic hydrogen isotope effect as a mechanistic criterion

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTemperature dependence of the primary kinetic hydrogen isotope effect as a mechanistic criterionHarold KwartCite this: Acc. Chem. Res. 1982, 15, 12, 401–408Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://doi.org/10.1021/ar00084a004RIGHTS & PERMISSIONSArticle Views1242Altmetric-Citations205LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1002 KB) Get e-Alerts Get e-Alerts

The chemistry of nitroso-compounds. Part X. Acid catalysed nitrosation of azulene and 1-nitroazulene

Rates of nitrosation in dilute aqueous HCIO4 and HCI under various conditions are reported for azulene (to form the 1-nitroso-derivative) and 1-nitroazulene. Both reactions show a first-order dependence on substrate, nitrous acid, and solvent acid concentrations, and for azulene the reaction is further catalysed by chloride ion. A primary kinetic hydrogen isotope effect is observed for 1-nitroazulene (KH/KD 2.8) but not for azulene. These results are consistent with the expected A–SE2 pathway characteristic of aromatic electrophilic substitution, where encounter of the reactants is rate limiting for azulene, and proton loss from the Wheland intermediate is rate limiting for 1-nitroazulene. Activation parameters for azulene (ΔH 33 ± 5 kJ mol–1; ΔS 45 ± 7 J K–1 mol–1) are consistent with an encounter-controlled rate. These findings confirm recent deductions from the nitrosation of indoles that highly reactive substrates (pKa–3.5) react on encounter with NOCI and H2ONO+, and suggest that the high reactivity of indoles is not a consequence of reaction at the heterocyclic nitrogen atom.

Rates and kinetic hydrogen isotope effects for the ionization of phenylnitromethane

The general-base catalyzed ionization of phenyl-nitromethane is subject to large primary kinetic hydrogen isotope effects; these effects, their activation parameters, and the Bronsted catalysis coefficient for the reaction are used to discuss possible transition-state structures.