Many, if not most, redox reactions are coupled to proton transfers. This includes most common sources of chemical potential energy, from the bioenergetic processes that power cells to the fossil fuel combustion that powers cars. These proton-coupled electron transfer or PCET processes may involve multiple electrons and multiple protons, as in the 4 e–, 4 H+ reduction of dioxygen (O2) to water (eq 1), or can involve one electron and one proton such as the formation of tyrosyl radicals from tyrosine residues (TyrOH) in enzymatic catalytic cycles (eq 2). In addition, many multi-electron, multi-proton processes proceed in one-electron and one-proton steps. Organic reactions that proceed in one-electron steps involve radical intermediates, which play critical roles in a wide range of chemical, biological, and industrial processes. This broad and diverse class of PCET reactions are central to a great many chemical and biochemical processes, from biological catalysis and energy transduction, to bulk industrial chemical processes, to new approaches to solar energy conversion. PCET is therefore of broad and increasing interest, as illustrated by this issue and a number of other recent reviews.

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Thermochemistry of Proton-Coupled Electron Transfer Reagents and its Implications

The α-effect and its modulation by solvent

The origin of enhanced reactivity of α-nucleophiles in SN2 reactions was examined on the basis of computational results at the high level G2(+) method for 22 gas-phase reactions:  Nu- + RCl → RNu + Cl- [R = Et and i-Pr; Nu- = HO-, CH3O-, HS-, Cl-, Br-, NH2O-, HOO-, FO-, HSO-, ClO-, and BrO-]. The results clearly indicate the existence of the α-effect, whose size varies depending on the R group and the identity of the α-atom. The α-effect is larger for i-PrCl than EtCl, and for an α-nucleophile with a harder α-atom. Analyses of the present results, together with previously reported ones for MeF and MeCl reactions, reveal that several rationales so far presented to explain the α-effect, such as thermodynamic product stability, transition state (TS) tightness, electrostatic interaction, ET rationale, and polarizability, cannot explain the observed size of the α-effect. The importance of deformation energy on going from the reactant to the TS is presented.

The α-Effect in Gas-Phase SN2 Reactions: Existence and the Origin of the Effect

The relative free radical scavenging activity of β-carotene, lycopene, and torulene toward OOH radicals has been studied using density functional theory. Hydrogen atom transfer (HAT) and radical adduct formation (RAF) mechanisms have been considered. All the possible reaction sites have been included in the modeling, and detailed branching ratios are reported for the first time. The reactions of hydrocarbon carotenoids (Car) with peroxyl radicals, in both polar and nonpolar environments, are predicted to proceed via RAF mechanism, with contributions higher than 98% to the overall OOH + Car reactions. Lycopene and torulene were found to be more reactive than β-carotene. In nonpolar environments the reactivity of the studied carotenoids toward peroxyl radical follows the trend LYC > TOR > BC, whereas in aqueous solutions it is TOR > LYC > BC. OOH adducts are predicted to be formed mainly at the terminal sites of the conjugated polyene chains. The main addition sites were found to be C5 for β-carotene and ly...

Reactions of OOH Radical with β-Carotene, Lycopene, and Torulene: Hydrogen Atom Transfer and Adduct Formation Mechanisms

Second-order rate constants (k(N)) have been measured spectrophotometrically for the reaction of 4-nitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H(2)O containing 20 mol % dimethyl sulfoxide at 25.0 degrees C. The magnitude of the k(N) values increases with increasing the basicity of amines and with increasing the electron-withdrawing ability of the acyl substituent X. The Hammett plots obtained are not linear but show a break or curvature as the acyl substituent X becomes electron withdrawing for all the amines studied, while the Bronsted-type plots are linear with large beta(nuc) values for all the substrates investigated. The nonlinear Hammett plots suggest a change in the rate-determining step upon changing the acyl substituent X, whereas the linear Bronsted-type plots indicate that the rate-determining step does not change upon changing amine basicity. The Yukawa-Tsuno plots obtained are also linear with positive rho(X) and large r values, suggesting that the nonlinear Hammett plots are not due to a change in the rate-determining step upon changing the acyl substituent X, but due to resonance demand of the pi-electron donor substituent on the acyl moiety. The magnitude of the rho(X) and beta(nuc) values increases with increasing the basicity of amines and with increasing the electron-withdrawing ability of the acyl substituent X, respectively, while that of the r values decreases with increasing rho(X) values and amine basicity.

Effect of acyl substituents on the reaction mechanism for aminolyses of 4-nitrophenyl X-substituted benzoates

The second-order rate constants for the reaction between
hydroxide
ion and phenoxide ion with 4-nitrophenyl esters of substituted benzoic
acids in 10% acetonitrile–water (v/v) solution obey Hammett
σ correlations. The values of the Hammett ρ
of 1.67 (kArO) and 2.14 (kOH)
are consistent with a large change in hybridization at the central
carbon by comparison with the ρ value for a standard
reaction where a full sp2 to sp3 change occurs.
The transition state for the concerted reaction thus has a substantially
tetrahedral geometry. The observation of the anti-Hammond
effect whereby the ρ value for the hydroxide ion exceeds
that of the less reactive phenoxide ion is consistent with a concerted,
ANDN, mechanism for these reactions. A stepwise
mechanism, AN + DN, is unlikely to
yield a measurable break in the Hammett correlation for a change in the
benzoyl substituent if the partitioning of the putative tetrahedral
intermediate involves forward and reverse reactions with Hammett
correlations possessing similar ρ values.

Nucleophilic displacement at the benzoyl centre: a study of the change in geometry at the carbonyl carbon atom

The principal conclusion of this work is that the identity reaction of 2,4-dinitrophenolate ion with 2,4-dinitrophenyl 4-methoxy-2,6-dimethylbenzoate has an open transition state, namely one with very weak bonds to entering and departing ligands. The transition state possesses a Kreevoy tightness parameter (τ) of 0.18. The open transition state arises from the stabilising effect of the acyl group substituents on the benzoylium ion and their destabilising effect on the putative tetrahedral intermediate as well as the weak basicities of the nucleophile and nucleofuge. This is the first example of an open transition state in an acyl group transfer which does not require the assistance of a negatively charged internal nucleophile.The data for 2,4-dinitrophenyl acetate may be employed to calculate an identity rate constant (Kii) for the reaction of 2,4-dinitrophenolate ion with the ester. This data may be fitted to a theoretical Lewis–Kreevoy plot (log Kii vs. pKi) possessing both positive and negative values of βii(slope of the line). Microscopic medium effects place a limit to the accuracy of predictions of rate constants, including Kii, from linear free energy relationships.

An open transition state in carbonyl acyl group transfer in aqueous solution

Rate constants have been measured for the reaction of substituted phenolate ions with aryl acetate esters and with aryl N-methylisonicotinate esters in aqueous solution. A new method is demonstrated for determining βeq for group transfer from 4-nitrophenyl esters; it employs the rate constant for the reaction of 2,6-difluorophenolate ion with substituted phenyl ester as a surrogate for the reactivity of the 4-nitrophenolate ion and yields βeq= 1.55 for the N-methylisonicotinyl transfer reaction. The Bronsted-type plot of the rate constant for phenolate ion attack on 4-nitrophenyl N-methylisonicotinate is linear over a range of pKa values from 5.5 to 10 and provides good evidence for a concerted displacement mechanism for this reaction. The reactivity of the N-methylisonicotinate esters to phenolate ions is some 300 times larger than that of the corresponding acetate esters but the larger βnuc value (0.90 compared with 0.74) suggests a ‘later’ transition structure. Calibration of the β values with the corresponding βeq gives a Leffler αnuc= 0.58 and 0.42 for N-methylisonicotinate and acetate respectively, which contrasts with the order expected from reactivity–selectivity. The tighter transition structure indicated by comparison of these α values is explained by a less favourable acylium ion in the case of the N-methylisonicotinyl transfer reaction.

Transfer of a positively charged acyl group between substituted phenolate ion nucleophiles: the brønsted β for the calibrating equilibrium for N-methylisonicotinyl (4-carbonyl-N-methylpyridinium) transfer

The bimolecular reactions of azide, 2-iodosobenzoate, and acetohydroxamate ions and methoxyamine nucleophiles with substituted phenyl acetates possess Yukawa-Tsuno type correlations with substantia...

Alpha-effect nucleophiles and azide ion: effective charge studies of displacement reactions at esters

The reaction of imidazole in aqueous solution with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters obeys the rate law: k(obs) - k(background) = k2[Im] + k3[Im]2 where [Im] is the imidazole concentration present as free base. The parameters k2 and k3 fit Bronsted type free energy correlations against the pKa of the leaving phenol with betaLg values of -0.65 and -0.42 respectively. The imidazolysis is insensitive to catalysis by general bases and yet k3 for the 3-cyanophenyl ester possesses a deuterium oxide solvent isotope effect of 4.43 consistent with rate limiting proton transfer. A special catalytic function is proposed for decomposition of the tetrahedral addition intermediate (T+/-) via k3 whereby the catalytic imidazole interacts electrophilically with the leaving phenolate ion and removes a proton from the nitrogen in the rate limiting step with subsequent non-rate limiting ArO-C bond fission. This is consistent with the change in effective charge on the leaving oxygen in the transition structure of k3 which is more positive (-0.42) than that expected (-0.60) for the equilibrium formation of the zwitterion intermediate. The catalytic function at the leaving oxygen is likely to be an electrophilic role of the NH as a hydrogen bond donor. In the k2 step the deuterium oxide solvent isotope effect of 1.51 for the 3-cyanophenyl ester and the betaLg of -0.65 are consistent with rate limiting expulsion of the phenolate ion from the T+/- intermediate. The absence of general base catalysis of imidazolysis rules out the established mechanism for aminolysis of esters where T+/- is stabilised by a standard rate limiting proton transfer. The kinetically equivalent term for k3 where T- reacts with the imidazolium ion as an acid catalyst would require this step to be rate limiting and involve proton transfer not consistent with departure of the good aryl oxide leaving group.

Reaction of imidazole with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters: special base catalysis by imidazole

Matthew J. Colthurst

Papers

Nucleophilic displacement at the benzoyl centre: a study of the change in geometry at the carbonyl carbon atom

An open transition state in carbonyl acyl group transfer in aqueous solution

Transfer of a positively charged acyl group between substituted phenolate ion nucleophiles: the brønsted β for the calibrating equilibrium for N-methylisonicotinyl (4-carbonyl-N-methylpyridinium) transfer

Alpha-effect nucleophiles and azide ion: effective charge studies of displacement reactions at esters

Reaction of imidazole with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters: special base catalysis by imidazole