Deprotonation of carbocations

Fig. 1 A plot of logs of rate constants for deprotonation of carbocations against pKa in aqueous solution at 25°C.

A mechanism for the formation of these three alkenes is shown m Figure 5 9 Dissociation of the primary alkyloxonmm ion is accompanied by a shift of hydride from C 2 to C 1 This avoids the formation of a primary carbocation leading instead to a sec ondary carbocation m which the positive charge is at C 2 Deprotonation of this carbo cation yields the observed products (Some 1 butene may also arise directly from the pri mary alkyloxonium ion)... 

Section 5 17 In the absence of a strong base alkyl halides eliminate by an El mech anism Rate determining ionization of the alkyl halide to a carbocation is followed by deprotonation of the carbocation... 

How Does Structure Determine Organic Reactivity Partitioning of Carbocations between Addition of Nucleophiles and Deprotonation... 

The quantitation of products that form in low yields requires special care with HPLC analyses. In cases where the product yield is <1%, it is generally not feasible to obtain sufficient material for a detailed physical characterization of the product. Therefore, the product identification is restricted to a comparison of the UV-vis spectrum and HPLC retention time with those for an authentic standard. However, if a minor reaction product forms with a UV spectrum and HPLC chromatographic properties similar to those for the putative substitution or elimination reaction, this may lead to errors in structural assignments. Our practice is to treat rate constant ratios determined from very low product yields as limits, until additional evidence can be obtained that our experimental value for this ratio provides a chemically reasonable description of the partitioning of the carbocation intermediate. For example, verification of the structure of an alkene that is proposed to form in low yields by deprotonation of the carbocation by solvent can be obtained from a detailed analysis of the increase in the yield of this product due to general base catalysis of carbocation deprotonation.14,16... 

Fig. 1 Free energy reaction coordinate profiles for hydration and isomerization of the alkene [2] through the simple tertiary carbocation [1+], The rate constants for partitioning of [1 ] to form [l]-OSolv and [3] are limited by solvent reorganization (ks = kteorg) and proton transfer (kp), respectively. For simplicity, the solvent reorganization step is not shown for the conversion of [1+] to [3], but the barrier for this step is smaller than the chemical barrier to deprotonation of [1 ] (kTtOTg > kp).

It is often difficult to understand at an intuitive level the explanation for the effect of changing substituents on the rate constant ratio kjkp for partitioning of carbocations between nucleophilic addition of solvent and deprotonation. In these cases, insight into the origins of the changes in this rate constant ratio requires a systematic evaluation of substituent effects on the following ... 

Fig. 4 Free energy reaction coordinate profiles that illustrate a change in the relative kinetic barriers for partitioning of carbocations between nucleophilic addition of solvent and deprotonation resulting from a change in the curvature of the potential energy surface for the nucleophile addition reaction. This would correspond to an increase in the intrinsic barrier for the thermoneutral carbocation-nucleophile addition reaction.

To what extent are the variations in the rate constant ratio /cs//cpobserved for changing structure of aliphatic and benzylic carbocations the result of changes in the Marcus intrinsic barriers Ap and As for the deprotonation and solvent addition reactions It is not generally known whether there are significant differences in the intrinsic barriers for the nucleophile addition and proton transfer reactions of carbocations. 

Values of Kadd for the addition of water (hydration) of alkenes to give the corresponding alcohols. These equilibrium constants were obtained directly by determining the relative concentrations of the alcohol and alkene at chemical equilibrium. The acidity constants pATaik for deprotonation of the carbocations by solvent are not reported in Table 1. However, these may be calculated from data in Table 1 using the relationship pA ik = pATR + logA dd (Scheme 7). 

The more favorable partitioning of [1+ ] to form [l]-OH than to form [2] must be due, at least in part, to the 4.0 kcal mol-1 larger thermodynamic driving force for the former reaction (Kadd = 900 for conversion of [2] to [l]-OH, Table 1). However, thermodynamics alone cannot account for the relative values of ks and kp for reactions of [1+] that are limited by the rate of chemical bond formation, which may be as large as 600. A ratio of kjkp = 600 would correspond to a 3.8 kcal mol-1 difference in the activation barriers for ks and kp, which is almost as large as the 4.0 kcal mol 1 difference in the stability of [1]-OH and [2]. However, only a small fraction of this difference should be expressed at the relatively early transition states for the reactions of [1+], because these reactions are strongly favored thermodynamically. These results are consistent with the conclusion that nucleophile addition to [1+] is an inherently easier reaction than deprotonation of this carbocation, and therefore that nucleophile addition has a smaller Marcus intrinsic barrier. However, they do not allow for a rigorous estimate of the relative intrinsic barriers As — Ap for these reactions. 

Fig. 5 Logarithmic plots of rate-equilibrium data for the formation and reaction of ring-substituted 1-phenylethyl carbocations X-[6+] in 50/50 (v/v) trifluoroethanol/water at 25°C (data from Table 2). Correlation of first-order rate constants hoh for the addition of water to X-[6+] (Y) and second-order rate constants ( h)so1v for the microscopic reverse specific-acid-catalyzed cleavage of X-[6]-OH to form X-[6+] ( ) with the equilibrium constants KR for nucleophilic addition of water to X-[6+]. Correlation of first-order rate constants kp for deprotonation of X-[6+] ( ) and second-order rate constants ( hW for the microscopic reverse protonation of X-[7] by hydronium ion ( ) with the equilibrium constants Xaik for deprotonation of X-[6+]. The points at which equal rate constants are observed for reaction in the forward and reverse directions (log ATeq = 0) are indicated by arrows.

There is a 4kcalmol 1 smaller intrinsic barrier As for nucleophilic addition of water to the benzylic carbocations X-[6+] than for deprotonation of X-[6+] by solvent. This difference reflects the greater ease of direct addition of solvent to the charged benzylic carbon of X-[6+] than of proton transfer at the adjacent a-methyl carbon. This may result in some way from the greater number of bonds formed and cleaved in the proton transfer than in the nucleophile addition reaction. However, it is our impression that there is little or no theoretical justification for generalizations of this type. 

Fig. 6 Hypothetical free energy reaction coordinate profiles for the interconversion of X-[8]-OH and X-[9] (R = H) and X-[10]-OH and X-[ll] (R = CH3) through the corresponding carbocations. The arrows indicate the proposed eifects of the addition of a pair of ortAo-methyl groups to X-[8]-OH, X-[8+] and X-[9] to give X-[10]-OH, X-[10+] and X-[ll]. A Effect of a pair of or/Ao-methyl groups on the stability of cumyl alcohols. B Effect of a pair of or/Ao-methyl groups on the stability of cumyl carbocations. C Effect of a pair of ortho-methyl groups on the stability of the transition state for nucleophilic addition of water to cumyl carbocations. D Effect of a pair of orf/io-methyl groups on the stability of the transition state for deprotonation of cumyl carbocations.

The partitioning of ferrocenyl-stabilized carbocations [30] between nucleophile addition and deprotonation (Scheme 18) has been studied by Bunton and coworkers. In some cases the rate constants for deprotonation and nucleophile addition are comparable, but in others they favor formation of the nucleophile adduct. However, the alkene product of deprotonation of [30] is always the thermodynamically favored product.120. In other words, the addition of water to [30] gives an alcohol that is thermodynamically less stable than the alkene that forms by deprotonation of [30], but the reaction passes over an activation barrier whose height is equal to, or smaller than, the barrier for deprotonation of [30], These data require that the intrinsic barrier for thermoneutral addition of water to [30] (As) be smaller than the intrinsic barrier for deprotonation of [30] (Ap). It is not known whether the magnitude of (Ap — As) for the reactions of [30] is similar to the values of (Ap - As) = 4-6 kcal mol 1 reported here for the partitioning of a-methyl benzyl carbocations. 

The addition of two orf/io-methyl groups to ring-substituted cumyl carbocations results in greater steric crowding at the tetrahedral nucleophile adducts than at the corresponding a-methyl styrenes. This results in a decrease in ks for reaction of the carbocation with a nucleophilic solvent relative to kp for deprotonation of the carbocation. 

The incorporation of the alkene product of carbocation deprotonation into an aromatic system results in the expected changes in the absolute rate constant kp and the product rate constant ratio kjkp for reaction of the carbocation. 

Different rate-determining steps are observed for the acid-catalyzed hydration of vinyl ethers (alkene protonation, ks kp) and hydration of enamines (addition of solvent to an iminium ion intermediate, ks increasing stabilization of a-CH substituted carbocations by 71-electron donation from an adjacent electronegative atom results in a larger decrease in ks for nucleophile addition of solvent than in kp for deprotonation of the carbocation by solvent. 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67 Perchloro-organic chemistry structure, spectroscopy and reaction pathways, 25, 267 Permutational isomerization of pentavalent phosphorus compounds, 9, 25 Phase-transfer catalysis by quaternary ammonium salts, 15, 267 Phosphate esters, mechanism and catalysis of nucleophilic substitution in, 25, 99 Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in permutational isomerization, 9, 25... 

The protonation of carbenes by acids has been studied by PAC. Using sterically hindered acids to prevent collapse of the ion pair, the heat of reaction can be obtained and used to determine the p as of the resultant carbocations (Fig. 4).56 The results indicate that deprotonation of the carbocations to generate carbenes should be possible with strong hindered bases. This method has only rarely been used in the literature.1-57... 

In the first step, 01 attacks P9 and displaces Cl 10. After deprotonation of N3, a carbocation at C2 (stabilized by resonance with N4) is formed. Addition-elimination then gives the product. An alternative and reasonable mechanism would have C7 attack C2 before the C2-01 bond cleaves (addition-elimination type mechanism), but the conventional wisdom is that the reaction proceeds through the nitrlium ion intermediate. 

The broken C13-C3 and new C13-C4 bonds suggest a 1,2-alkyl shift of C13 from C3 to a C4 carbo-cation, leaving a carbocation at C3. The broken C9-C11 and new C3-C11 bonds suggest a 1,2-shift of Cl 1 from C9 to a C3 carbocation, leaving a carbocation at C9. Since a shift of Cl 1 from C9 to C3 could only occur after C3 and C9 were connected, this suggests that the C3-C9 bond is formed first. Such a bond would be formed from a C9 carbocation with a C3=C4 n bond. The C9 carbocation could be formed from 6 or 9. Attack of the C3=C4 K bond on C9 puts a carbocation at C4. Then C13 shifts from C3 to C4. That puts a carbocation at C3. Then Cl 1 shifts from C9 to C3. Finally, deprotonation of C8 gives the product. 

In a deep-seated rearrangement like this, it s sometimes easier to work backwards from the product. The n bond at C8=C9 in 12 suggests that the last step is deprotonation of C8 of a carbocation at C9, C. Carbocation C might have been formed from carbocation D by a 1,2-alkyl shift of Cl 1 from C9 to C3. Carbocation D might have been formed from carbocation E by a 1,2-alkyl shift of C13 from C3 to C4. Carbocation E might have been formed from carbocation F by attack of a C3=C4 n bond on a C9... 

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