Substituent effects carbocations

Fig. 6.5. Representation of changes in transition-state character in the variable transition state E2 elimination reaetion, showing displacement of transition-state location as a result of substituent effects (a) substituent Z stabilizes catfaanion character of Elcb-like transition state (b) substituent R stabilizes carbocation character of El-like transitions state.

The existence of open carbocation intermediates is supported by the contrast in the pattern of alkyl substituent effects with that found in brominations, where cyclic intermediates are involved. In the latter case substitution of alkyl groups on H2C=CH2 causes a cumulative rate acceleration until all four... 

Scheme 12 Experimental evidence of the relation between the energy gap (As) and the interaction the substituent effects on the stabdities of the carbocations...

Carbocation-carbanion zwitterionic intermediates were proposed for the thermal cleavage of several cyclic compounds. In most of these reactions the ionically dissociating bond belongs to one of four strained ring systems, i.e. cyclopropane (13), cyclobutane (14), cyclobutene (15) or norbornadiene (16). The mechanism is distinguished from the formation of a diradical intermediate through homolysis in terms of solvent and substituent effects... 

These substituent effects are due to the stabilization of the carbocations that result from protonation at the center carbon. Even if allylic conjugation is not important, the aryl and alkyl substituents make the terminal carbocation more stable than the alternative, a secondary vinyl cation. 

Carbocations, as we learned in Chapter 4 of Part A, can readily rearrange to more stable isomers. To be useful in synthesis, such reactions must be controlled and predictable. This goal can be achieved on the basis of substituent effects and stereoelectronic factors. Among the most important rearrangements in synthesis are those directed by oxygen substituents, which can provide predictable outcomes on the basis of electronic and stereoelectronic factors. 

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 ... 

Substituent effect on the stability of the transition state for solvent addition (C, Figure 6). The difference in the values of ks = 1.4 x 107s 1 for the addition of a solvent of 50/50 (v/v) trifluoroethanol/water to Me-[10+] and ks = 1.0 x 109 s-1 for addition of the same solvent to Me-[8+] (Table 1) reflects the balance between (1) the destabilization of X-[10+] resulting from rotation about the —Ca bond, which results in a less stable carbocation and hence an... 

Substituent effects on ks. The replacement of an a-methyl group at the 4-methoxycumyl carbocation CH3-[14+] by an a-ester or a-amide group destabilizes the parent carbocation by 7 kcalmol-1 relative to the neutral azide ion adduct (Scheme 11 and Table 3) and results in 5-fold and 80-fold decreases, respectively, in ks for nucleophilic addition of a solvent 50/50 (v/v) methanol/water.33 These results follow the trend that strongly electron-withdrawing substituents, which destabilize a-substituted 4-methoxybenzyl carbocations relative to neutral adducts to nucleophiles, do not lead to the expected large increases in the rate constants for addition of solvent.28,33,92-95... 

The substitution of an a-oxygen by an a-sulfur or an a-selenium results in a decrease in ks/kp for partitioning of oxocarbenium ions between addition of solvent and deprotonation. The largest effect is observed for the a-selenium substitution. These changes are probably the result of several different effects on carbocation reactivity, each of which contributes to the observed substituent effect on kjkp. 

The relative magnitude of the kinetic effects of two substituents, Rt and R2, on the C0 and carbon atoms of the double bond (Scheme 7) is taken as a measure of the symmetry of the charge development and therefore of bromine bridging in the bromocations. It is assumed that in a bromonium ion the effects of Rx and R2 must be similar, whereas for a /J-bromocarbocation, C+, the effect of Rj must be significantly greater than that of R2. Consequently, the substituent effects are analysed in terms of a multipathway scheme (Scheme 7) where open carbocations and the bridged ion are formed via discrete pathways with rate constants kx, kf and kBr respectively (Ruasse and Dubois, 1974). The rate constant k in (4) is therefore the sum of these three... 

The question of bridged and/or open intermediates has been considered in Section 4, where the data on kinetic substituent effects were discussed with the help of the multipathway scheme (Scheme 7) to determine the relative importance of bromonium and carbocation paths. It is not straightforward to obtain significant p-values for each of them from the complex pa relationship (34) and (35) corresponding to this scheme for an a,/f-Ri,R2... 

Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

The familiarity with qualitative valence bond descriptions of substituent effects in combination with the known substituent effects in carbocations and carbanions led Viehe and his group to the postulate of a captodative effect for free radicals (Stella et ai, 1978 Viehe et al., 1979). They did not seem to be aware of the earlier work which was of a more physical organic character. The fact that carbocations [8] are stabilized by + M substituents, and carbanions [9] by - M substituents, raised the idea that free radicals, as... 

The acid-catalysed hydrolysis of the acylal, 1-phenoxyethyl propionate (13), has been studied using the PM3 method in the gas phase. The kinetics and mechanism of the hydrolysis of tetrahydro-2-furyl and tetrahydropyran-2-yl alkanoates (14) in water and water-20% ethanol have been reported. In acidic and neutral media, kinetics, activation parameters, isotope-exchange studies, substituent effects, solvent effects and the lack of buffer catalysis pointed clearly to an Aai-1 mechanism with formation of the tetrahydro-2-furyl or tetrahydropyran-2-yl carbocation as the rate-limiting step (Scheme 1). There is no evidence of a base-promoted Bac2 mechanism up to pH 12. ... 

A detailed comparison of the rearrangement of 1,3-radicai cations and carbocations derived from tricyclo [3.3.0.0 " ] octanes has shown (by eiectron-transfer oxidation and protonation, respectiveiy) that electronic substituent effects on the diyi sites profoundly influence the regioseiectivities of the Wagner-Meerwein 1,2-shifts. The... 

The most significant conclusion that can be drawn from the data summarized in Table III is that substituent effects do not exert the same overwhelming importance for the thermodynamic stability of the higher homologues of carbenium ions, thus they do not play the dominant role as in carbocation chemistry. This can be traced back on (i) the inherent higher stability of the trivalent cations of the elements Si Pb and (ii) the weakness of the stabilizing interaction (in many cases of ii-type) of the most common substituents with the central element atom. 

Generation and NMR studies of the carbocations from various classes of PAHs under stable ion conditions, in combination with computational studies, provide a powerful means to model their biological electrophiles. These approaches allow the determination of their structures, relative stabilities, charge delocalization modes, and substituent effects, as a way to understand structure/reactivity relationships. 

Computational data enabled charge delocalization modes, substituent effects, and in relevant cases conformational aspects to be addressed, and comparison with experiments were found to be fairly good. Moreover, the calculated relative stabilities of the carbocations correlated reasonably well with the available biological activities. 

Substituent effects Carbocations are formed in the S l reactions. The more stable the carbocation, the faster it is formed. Thus, the rate depends on carbocation stability, since alkyl groups are known to stabilize carbocations through inductive effects and hyperconjugation (see Section 5.2.1). The reactivities of SnI reachons decrease in the order of 3° carbocation > 2° carbocation > 1° carbocation > methyl cation. Primary carbocation and methyl cation are so unstable that primary alkyl halide and methyl halide do not undergo SnI reachons. This is the opposite of Sn2 reactivity. 

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