Rate-determining Proton Transfer Processes

V. Non-Solvolytio Reactions A. Rate-determining Proton Transfer Processes... 

Both kinetic and thermodynamic data on organometallic hydrides should be very useful. The relative rates of proton transfer processes and other reactions determine a good deal of organometallic chemistry. For example, in our synthesis of cis-0s(C0) (CH )H> reactions 2-4, the comparative rates of... 

Kreevoy studied in depth the deoxymercuration of CH3CH(OR)CH2HgI with perchloric and acetic acids in methanol, and found that the process was pseudo-first order in mercurial, with ka. [HA]. Specific hydronium ion catalysis was involved, and solvent HOH/DOD isotope effects were those predicted by the Butler equations for a pre-rate-determining proton transfer. Further studies on what had been termed - and /9-2-methoxy-cyclohexylmercuric iodides under similar conditions, led to similar findings concerning the solvent isotope effects, and correlation of log k with — Hq. This suggested that the transition state differs from substrate only by a proton. 

The latter process is known to involve rate-determining proton transfer to carbon, and since the two reactions are kinetically very similar they probably have similar rate-determining steps. 

Notice that specific acid catalysis describes a situation in which the reactant is in equilibrium with regard to proton transfer, and proton transfer is not rate-determining. On the other hand, each case that leads to general acid catalysis involves proton transfer in the rate-determining step. Because of these differences, the study of rates as a function of pH and buffer concentrations can permit conclusions about the nature of proton-transfer processes and their relationship to the rate-determining step in a reaction. 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

This is the first example of a proton transfer process to a hydride complex with a second-order dependence. Theoretical calculations indicate that the role of the HX molecules is the formation of W-H H-Cl- H-Cl adducts that convert into W-Cl, H2 and HCl2 in the rate-determining state through hydrogen complexes as transition states. 

The proton transfer processes described above induce interesting effects on the geometry of these metal complexes upon protonation (see also Section II). If it is assumed that the equatorial cyano ligands form a reference plane and are stationary for any of these distorted octahedral cyano oxo complexes, the protonation/deprotonation process as illustrated in Scheme 3 is responsible for the oxygen exchange at the oxo sites. This process effectively induces a dynamic oscillation of the metal center along the O-M-O axis at a rate defined by kmv, illustrated in Fig. 15. This rate of inversion is determined by the rate at which the proton is transferred via the bulk water from the one... 

An interesting question then arises as to why the dynamics of proton transfer for the benzophenone-i V, /V-dimethylaniline contact radical IP falls within the nonadiabatic regime while that for the napthol photoacids-carboxylic base pairs in water falls in the adiabatic regime given that both systems are intermolecular. For the benzophenone-A, A-dimethylaniline contact radical IP, the presumed structure of the complex is that of a 7t-stacked system that constrains the distance between the two heavy atoms involved in the proton transfer, C and O, to a distance of 3.3A (Scheme 2.10) [20]. Conversely, for the napthol photoacids-carboxylic base pairs no such constraints are imposed so that there can be close approach of the two heavy atoms. The distance associated with the crossover between nonadiabatic and adiabatic proton transfer has yet to be clearly defined and will be system specific. However, from model calculations, distances in excess of 2.5 A appear to lead to the realm of nonadiabatic proton transfer. Thus, a factor determining whether a bimolecular proton-transfer process falls within the adiabatic or nonadiabatic regimes lies in the rate expression Eq. (6) where 4>(R), the distribution function for molecular species with distance, and k(R), the rate constant as a function of distance, determine the mode of transfer. 

There are two processes that must cooperate for a successful proton transfer, the basis of proton mobility. The first is water reorientation and then the second is proton tunneling. Hence the rate of proton transfer will be limited by whichever of the two processes is slower. One must therefore suspect that the water reorientation is the rate-determining step in the process of proton transfer (because the tunneling through the barrier has dready been shown to be too fast to be consistent with the mobility observed). 

For the second step of the cocaine methyl ester hydrolysis involving the water-assisted proton transfer, the calculated energy barrier, 4.8 kcal/mol, associated with transition state TS2dW-Me, is also lower than the corresponding first step. So, with the direct participation of the solvent water molecule in the proton transfer process, the first step of the hydrolysis in aqueous solution should be rate-determining, whether for the cocaine benzoyl ester hydrolysis or for the cocaine methyl ester hydrolysis. This conclusion provides theoretical support for the design of analogs of the first transition state for the cocaine benzoyl ester hydrolysis to elicit anti-cocaine catalytic antibodies [22,25]. 

Two conditions must be met if the proton transfer step is to be slow and rate-determining (a) k must be smaller than the rate coefficient of a diffusion-controlled reaction, and (b) fe i must be smaller than ku. The first condition is fulfilled in most proton transfer processes to or from carbon. It may be met also in a proton transfer among oxygen, sulfur, or nitrogen atoms if either the acidity of the proton donor or the basicity of the acceptor is extremely low. The second condition, e.g. <1kn, can be fulfilled if the intermediate is sufficiently unstable with respect to decomposition toward the products. In several examples, ku and ft, are of the same order of magnitude, e.g. k [ ku, and the proton transfer step is partially rate-determining. For these cases, the theoretical rate equation must be derived with the aid of the stationary state method Vol. 2, pp. 352-354). 

The anodic behavior of p-aminodiphenylamine (10) in ACN differs considerably from that described above, although the proton-releasing processes play, as before, a decisive role. It was established76 that 10 is first transformed into its radical cation, which rapidly reacts with the parent molecule forming the neutral radical and the protonated form of 10. The neutral radical is oxidized at the same potential (Scheme 6), giving rise to a net two-electron oxidation reaction for two molecules of 10. The experiments performed in the presence of pyridine confirm this mechanism the proton transfer process seems to be the rate-determining step76. 

---