Intrinsic barrier acids

Rates of addition to carbonyls (or expulsion to regenerate a carbonyl) can be estimated by appropriate forms of Marcus Theory. " These reactions are often subject to general acid/base catalysis, so that it is commonly necessary to use Multidimensional Marcus Theory (MMT) - to allow for the variable importance of different proton transfer modes. This approach treats a concerted reaction as the result of several orthogonal processes, each of which has its own reaction coordinate and its own intrinsic barrier independent of the other coordinates. If an intrinsic barrier for the simple addition process is available then this is a satisfactory procedure. Intrinsic barriers are generally insensitive to the reactivity of the species, although for very reactive carbonyl compounds one finds that the intrinsic barrier becomes variable. ... 

Both these methods require equilibrium constants for the microscopic rate determining step, and a detailed mechanism for the reaction. The approaches can be illustrated by base and acid-catalyzed carbonyl hydration. For the base-catalyzed process, the most general mechanism is written as general base catalysis by hydroxide in the case of a relatively unreactive carbonyl compound, the proton transfer is probably complete at the transition state so that the reaction is in effect a simple addition of hydroxide. By MMT this is treated as a two-dimensional reaction proton transfer and C-0 bond formation, and requires two intrinsic barriers, for proton transfer and for C-0 bond formation. By NBT this is a three-dimensional reaction proton transfer, C-0 bond formation, and geometry change at carbon, and all three are taken as having no barrier. 

In the present case the intrinsic barrier ( /4) is small and, therefore, the reactions have a strong dependence on the pK value of the reacting acids, which accounts for the abrupt... 

The numbers in brackets for propylene, isobutylene, iJ-2-butene and 1,3-butadiene entries are at the QCISD(T)//QCISD/6-31G(d) level of theory QCISD(T)/6-31G(d)//B3LYP/6-311- -G(3df,2p) gas-phase intrinsic barriers (AE ) for the epoxidation of -2-butene with dimethyldioxirane (DMDO) and peroxyformic acid are 14.3 and 13.2 kcalmol respectively. 

It has been reported that rates of proton transfer from carbon acids to water or hydroxide ion can be predicted by application of multi-dimensional Marcus theory to a model whereby diffusion of the base to the carbon acid is followed by simple proton transfer to give a pyramidal anion, planarization of the carbon, and adjustment of the bond lengths to those found in the final anion.124 The intrinsic barriers can be estimated without input of kinetic information. The method has been illustrated by application to a range of carbon acids having considerable variation in apparent intrinsic barrier. 

Marcus5 8 taught us that the most appropriate and useful kinetic measure of chemical reactivity is the intrinsic barrier (AG ) rather than the actual barrier (AG ), or the intrinsic rate constant (kQ) rather than the actual rate constant (k) of a reaction. These terms refer to the barrier (rate constant) in the absence of a thermodynamic driving force (AG° = 0) and can either be determined by interpolation or extrapolation of kinetic data or by applying the Marcus equation.5 8 For example, for solution phase proton transfers from a carbon acid activated by a ji-acceptor (Y) to a buffer base, Equation (1), k0 may be determined from Br A ns ted-type plots of logki or... 

Table 1 alicyclic Representative intrinsic rate constants (kQ) and intrinsic barriers ( AGj) for the deprotonation of carbon acids by secondary amines ... 

One of the consequences of the imbalanced nature of the transition state is that the polar effect of a remote substituent may either increase or decrease the intrinsic barrier whether there is an increase or decrease depends on the location of the substituent with respect to the site of charge development. Let us consider a reaction of the type shown in Equation (4). In this situation an electron-withdrawing substituent Z will decrease AG or increase ka. This is because there is a disproportionately strong stabilization of the transition state compared to that of the product anion due to the closer proximity of Z to the charge at the transition state than in the anion. As discussed earlier, this also leads to an exalted BrlAnsted aCH value and is the reason why aCH > Pb for the deprotonation of carbon acids such as 11-13 and others (Table 2). 

The rate of deprotonation of an acid by a base depends on their structures [41], on the solvent and temperature, and on the difference (ApKa) between the pKa of the acid and that of the base. When acid and base have the same pfCa (ApKa=0) the change of free energy for proton transfer becomes zero and the reaction becomes thermoneutral. Under these conditions the rate of proton transfer is limited only by the so-called intrinsic barrier [34], which is particularly sensitive to structural changes in the reaction partners [39]. When ApKa increases, the rate of proton transfer also increases and approaches a limiting value, which depends on the structures of the acid and base and on the experimental conditions. For normal acids (O-H, N-H) in water the rate of proton transfer becomes diffusion-controlled (ka=10loL mol-1 s"1) when ApKa>2, but in aprotic solvents the limiting proton transfer rate can be substantially lower [42]. 

Similar results have been obtained by Baciocchi for the deprotonation of a-substituted 4-methoxytoluenes by 2,6-lutidine and NOs in acetonitrile [145]. In this study, the same values of the Bronsted coefficient (a = 0.24), and of the deuterium kinetic isotope effect (kn/kD = 2.0 for 4-methoxytoluene radical cation) have been obtained with the two bases these results point again towards a highly asymmetric transition state with a very small amount of C-H bond cleavage. Moreover, values of 0.53 and 0.66 eV have been calculated for the intrinsic barrier of the reactions of the radical cations with NO3" and 2,6-lutidine, respectively, again comparable with those observed for acid-base reactions involving carbon acids [140, 141]. 

The barrier to thermodynamically unfavorable deprotonation of carbon acids (AGfl, Fig. 1.1) in water is equal to the sum of the thermodynamic barrier to proton transfer (AG°) and the barrier to downhill protonation of the carbanion in the reverse direction (AGr Eq. (1.2)). The observation of significant activation barriers AGr for strongly thermodynamically favorable protonation or resonance stabilized carbanions shows that there is some intrinsic difficulty to proton transfer. The Marcus equation defines this difficulty with greater rigor as the intrinsic barrier A, which is the activation barrier for a related but often hypothetical thermoneutral proton transfer reaction (Fig. 1.2B) [46]. 

There is only a small barrier for thermoneutral proton transfer between electronegative oxygen or nitrogen acids and bases [31]. These reactions proceed by encounter-controlled formation of a hydrogen-bonded complex between the acid and base (ka, Scheme 1.6), proton transfer across this complex (kp, Scheme 1.6), followed by diffusional separation to products (k a, Scheme 1.6) [31]. Much larger Marcus intrinsic barriers are observed for proton transfer to and from carbon [67]. There are at least two causes for this difference in intrinsic barriers for proton transfer between electronegative atoms and proton transfer at carbon. 

The Marcus intrinsic barriers for deprotonation of carbon acids to form enolates that are stabilized by resonance delocalization of negative charge from carbon to oxygen are larger than for deprotonation of carbon acids to form carbanions where the charge is localized mainly at carbon. 

---