Carbocation stabilization

Carbocations stabilized by functional groups can also effect 3-alkylalion of indoles. From a synthetic point of view the most important are jV.jV-dialkyl-methyleneiminium ions which can be generated under Mannich conditions from formaldehyde and secondary amines[13]. The products, 3-(A/,A-dialkyl-aminornethyl)indoles, are useful synthetic intermediates (see Chapter 12). 

FIGURE 4 13 The order of carbocation stability is methyl < primary < second ary < tertiary Alkyl groups that are directly attached to the positively charged car bon stabilize carbocations... 

One important experimental fact is that the rate of reaction of alcohols with hydro gen halides increases m the order methyl < primary < secondary < tertiary This reac tivity order parallels the carbocation stability order and is readily accommodated by the mechanism we have outlined... 

Like carbocations free radicals are stabilized by alkyl substituents The order of free radical stability parallels that of carbocation stability... 

A theory is our best present interpretation of why things happen the way they do The modern ver Sion of Markovnikov s rule which is based on mecha nistic reasoning and carbocation stability recasts the rule in terms of theoretical ideas Mechanisms and explanations grounded in them belong to the theory part of the scientific method... 

Clearly the steric crowding that influences reaction rates in 8 2 processes plays no role in Stvfl reactions The order of alkyl halide reactivity in 8 1 reactions is the same as the order of carbocation stability the more stable the carbocation the more reactive the alkyl halide... 

The major influence of the methyl group is electronic The most important factor IS relative carbocation stability To a small extent the methyl group sterically hinders the ortho positions making attack slightly more likely at the para carbon than at a single ortho carbon However para substitution is at a statistical disadvantage because there are two equivalent ortho positions but only one para position... 

The lone pair on oxygen cannot be directly involved m carbocation stabilization when attack is meta to the substituent... 

Sections How substituents control rate and regioselectivity m electrophilic aro 12 10-12 14 matic substitution results from their effect on carbocation stability An electron releasing substituent stabilizes the cyclohexadienyl cation inter mediates corresponding to ortho and para attack more than meta... 

This IS a frequently used proce dure for the preparation of alkenes The order of alcohol reactivity paral lels the order of carbocation stability R3C > R2CH > RCH2 Benzylic al cohols react readily Rearrangements are sometimes observed... 

The triarylmethyl cations are particularly stable because of the conjugation with the aryl groups, which delocalizes the positive charge. Because of their stability and ease of generation, the triarylmethyl cations have been the subject of studies aimed at determining the effect of substituents on carbocation stability. Many of these studies used the characteristic UV absorption spectra of the cations to determine their concentration. In acidic solution, equilibrium is established between triarylearbinols and the corresponding carbocations. 

One of the most important and general trends in organic chemistry is the increase in carbocation stability with additional alkyl substitution. This stability relationship is fundamental to imderstanding many aspects of reactivity, especially of nucleophilic... 

Very stable carbocation (stabilized by both alkoxy function and aromaticity)... 

Reaction with hydrogen halides (Section 4.7) The order of alcohol reactivity parallels the order of carbocation stability R3C" > RjCH"" > RCHj " > CHb. Benzylic alcohols react readily. 

Electrophilic addition of HX to an alkene involves a two-step mechanism, the overall rate being given by the rate of the initial protonation step. Differences in protonation energies are usually explained by considering differences in carbocation stability, but the relief or buildup of strain can also be a factor. One of the following alkenes protonates much more easily than the other. 

The second point to explore involves carbocation stability. 2-Methyl-propene might react with H+ to form a carbocation having three alkyl substituents (a tertiary ion, 3°), or it might react to form a carbocation having one alkyl substituent (a primary ion, 1°). Since the tertiary alkyl chloride, 2-chloro-2-methylpropane, is the only product observed, formation of the tertiary cation is evidently favored over formation of the primary cation. Thermodynamic measurements show that, indeed, the stability of carbocations increases with increasing substitution so that the stability order is tertiary > secondary > primary > methyl. 

One way of determining carbocation stabilities is to measure the amount of energy required to form the carbocation by dissociation of the corresponding alkyl halide, R-X - R+ + X . As shown in Figure 6.10, tertiary alkyl halides dissociate to give carbocations more easily than secondary or primary ones. As a result, trisubstituted carbocations are more stable than disubstituted ones, which are more stable than monosubstituted ones. The data in Figure 6.10 are taken from measurements made in the gas phase, but a similar stability order is found for carbocations in solution. The dissociation enthalpies are much lower in solution because polar solvents can stabilize the ions, but the order of carbocation stability remains the same. 

What we have not yet seen is how these two points are related. Why does the stability of the carbocation intermediate affect the rate at which it s formed and thereby determine the structure of the final product After all, carbocation stability is determined by the free-energy change AG°, but reaction rate is determined by the activation energy AG. The twro quantities aren t directly related. 

Figure 6.16 The hypothetical structure of a transition state for alkene protonalion. The transition slate is closer in both energy and structure to the carbocation than to the alkene. Thus, an increase in carbocation stability (lower AG°) also causes an increase in transition-state stability (lower AG >, thereby increasing the rate of its formation.

Aikene chemistry is dominated by electrophilic addition reactions. When HX reacts with an unsymmetrically substituted aikene, Markovnikov s rule predicts that the H will add to the carbon having fewer alky) substituents and the X group will add to the carbon having more alkyl substituents. Electrophilic additions to alkenes take place through carbocation intermediates formed by reaction of the nucleophilic aikene tt bond with electrophilic H+. Carbocation stability follows the order... 

Markovnikov s rule. 191-193 alkene additions and, 191-193 alkyne additions and. 263 carbocation stability and. 192-193 Hammond postulate and, 198-199 hydroboration and. 224-225 oxymercu ration and, 222 Mass number (A), 4 Mass spectrometer, double-focusing, 411... 

Another structural feature that increases carbocation stability is the presence, adjacent to the cationic center, of a heteroatom bearing an unshared pair," for example, oxygen," nitrogen," or halogen. Such ions are stabilized by resonance ... 

Additional evidence for the SnI mechanism, in particular, for the intermediacy of carbocations, is that solvolysis rates of alkyl chlorides in ethanol parallel carbocation stabilities as determined by heats of ionization mea.sured in superacid solutions (p. 219). It is important to note that some solvolysis reactions proceed by an Sn2 mechanism." ... 

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