Carbanion protonation rates

Statement number 6 has to do with carbon acids and is supported by reference (7). There are, in fact, other references that suggest solvent plays a much more direct role in the kinetics of protonating carbanions than statement number 6 would imply. For example, there is evidence that nuclear reorganization and rehybridization of the carbon atom are too rapid to have much kinetic importance when compared with solvent reorientation. The strong dependence of carbanion protonation rates on the solvent supports this view. These rates are typically much faster in organic solvents, such as DMSO, than in water. A particular reaction that was studied in different solvents (17) is... 

Oxidation of diphenylmethane in basic solutions involves a process where rate is limited by and equal to the rate of ionization of diphenylmethane. The diphenylmethide ion is trapped by oxygen more readily than it is protonated in dimethyl sulfoxide-text-butyl alcohol (4 to 1) solutions. Fluorene oxidizes by a process involving rapid and reversible ionization in text-butyl alcohol solutions. However, in the presence of m-trifluoromethylnitrobenzene, which readily accepts one electron from the carbanion, the rate of oxygen absorption can approach the rate of ionization. 9-Fluorenol oxidizes in basic solution by a process that appears to involve dianion or carbanion formation. Benzhydrol under similar conditions oxidizes to benzophenone by a process not involving carbanion or dianion formation. 

A comparative study of gas-phase and liquid-phase CH acidity of a-substituted cyclopropanes has verified the correctness of an electrostatic model for the effect of solvation on equilibrium acidity 127 among variants of the LCAO MO method, only the semiempirical AMI method accurately predicted the proton affinity of the conjugate carbanions effects of solvation on protonation rates have been desegregated. 

The equilibrium constant for deprotonation of carbon acids is equal to the ratio of the rate constants for formation and reaction of the product carbanion (Scheme I.IA-C). In recent years, kinetic methods have been used to provide solid values of the pKaS for ionization of a wide range of weak carbon acids. These experiments are, in principle, straightforward and require only the determination or estimate of two rate constants - one for the slow and thermodynamically unfavorable generation of the carbanion, and a second for fast downhill carbanion protonation. 

Rate constants for thermodynamically favorable protonation of unstable carbanions are typically very large. These may be determined by direct methods. A description of these direct methods, the most important of which use laser flash photolysis in carbanion generation [29, 30], is outside the scope of this chapter. The indirect methods used to estimate rate constants for carbanion protonation will be described in greater detail, because they provide insight into the nature of the rate determining step for carbanion protonation in water. 

Carbanion protonation in water is a two-step reaction (i) movement of a Bronsted acid into a reactive position, and (ii) proton transfer to carbon. The overall rate constant for carbanion protonation may be limited by either the rate constant for formation of the reactive complex, in which case the overall rate constant for proton transfer can be estimated by using a representative rate constant for the rate-determining transport step, or by the rate constant for proton transfer to carbon. 

Based on the depicted equilibrium and the observed lifetime a rate constant for the forward reaction of 10 NT s" was estimated. The slow protonation rate of the one-electron reduced fullerene n-radical anions can be understood in terms of the charge delocalization and also the hybridization of the generated carbanion. Furthermore, the heterogeneous and hydrophobic environments of the host s interior can be assumed to be beneficial for the slow-down of the protonation dynamics. In homogeneous aqueous solutions the protonation rate should be faster, a hypothesis that was substantiated by recent radiolytic experiments with bisfunctionalized fullerene derivatives. The latter compounds are soluble in aqueous solutions without employing a solubiiizer (host) and give rise to protonation rate constants of 3 x 10 M s" (38). 

In theory two carbanions, (189) and (190), can be formed by deprotonation of 3,5-dimethylisoxazole with a strong base. On the basis of MINDO/2 calculations for these two carbanions, the heat of formation of (189) is calculated to be about 33 kJ moF smaller than that of (190), and the carbanion (189) is thermodynamically more stable than the carbanion (190). The calculation is supported by the deuterium exchange reaction of 3,5-dimethylisoxazole with sodium methoxide in deuterated methanol. The rate of deuterium exchange of the 5-methyl protons is about 280 times faster than that of the 3-methyl protons (AAF = 13.0 kJ moF at room temperature) and its activation energy is about 121 kJ moF These results indicate that the methyl groups of 3,5-dimethylisoxazole are much less reactive than the methyl group of 2-methylpyridine and 2-methylquinoline, whose activation energies under the same reaction conditions were reported to be 105 and 88 kJ moF respectively (79H(12)1343). 

The kinetic method of determining relative acidity suffers from one serious complication, however. This complication has to do with the fate of the ion pair that is formed immediately on removal of the proton. If the ion pair separates and difiuses into the solution rapidly, so that each deprotonation results in exchange, the exchange rate is an accurate measure of the rate of deprotonation. Under many conditions of solvent and base, however, an ion pair may return to reactants at a rate exceeding protonation of the carbanion by the solvent. This phenomenon is called internal return ... 

Obviously the structures and yields of Birch reduction products are determined at the two protonation stages. The ring positions at which both protonations occur are determined kinetically the first protonation or 7t-complex collapse is rate determining and irreversible, and the second protonation normally is irreversible under the reaction conditions. In theory, the radical-anion could protonate at any one of the six carbon atoms of the ring and each of the possible cyclohexadienyl carbanions formed subsequently could protonate at any one of three positions. Undoubtedly the steric and electronic factors discussed above determine the kinetically favored positions of protonation, but at present it is difficult to evaluate the importance of each factor in specific cases. A brief summary of some empirical and theoretical data regarding the favored positions of protonation follows. 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... 

A. Alkaline Hydrolysis. -The low kinetic isotope effect observed in the protonation of carbanions formed in phosphonium salt hydrolysis leads to the idea that there is little breaking of the phosphorus-carbon bond and correspondingly little transfer of a proton to the incipient carbanion in the transition state (87) of the rate-determining step. ... 

H/D exchange of H and Hg protons of sulfone 86 and estimated the difference in the free energies of activation for 79a and 79b to be < 1.2 kcal mol , based on the kjk value of 3 0.5. In the base-catalyzed H/D exchange of 87, kjk = 1.6, where k and k are the rate constants of H/D exchange of H, and H, respectively. Based on the small kjk value. Brown and colleagues suggested that if the carbanion is pyramidal, the steric stabilities of 79a and 79b are almost identical. Meanwhile, based on their C-NMR study Chassaing and Marquet proposed that the hybridization of the carbon atom of the sulfonyl carbanion, PhSOjCHj , would be between sp and sp . 

---