Caibocation

Concepts such as relative aadity and caibocation stability can be fundamentally related to hardness and electronegativity as defined by DFT. 

TIricooRlinate caibocations are fiequendy called carbonium ions. The terms methyl cation, butyl cation, etc., are used to describe the c >rTesixiiulir.ji tricoordinate cations. Chemical Abstracts uses as specific names methylium, ethyUum, propylium. We will use carbocation as a generic term for trivalent carbon cations. 

Stereochemical analysis can add detail to the mechanistic picture of the Sj l substitution reaction. The ionization mechanism results in foimation of a caibocation intermediate which is planar because of its hybridization. If the caibocation is sufficiently long-lived under the reaction conditions to diffirse away from the leaving group, it becomes symmetrically solvated and gives racemic product. If this condition is not met, the solvation is dissymmetric, and product with net retention or inversion of configuration may be obtained, even though an achiral caibocation is formed. The extent of inversion or retention depends upon the details of the system. Examples of this effect will be discussed in later sections of the chapter. 

A further consequence of the ionization mechanism is that if the same caibocation can be generated firom more than one precursor, its subsequent reactions should be... 

Winstein suggested that two intermediates preceding the dissociated caibocation were required to reconcile data on kinetics, salt effects, and stereochemistry of solvolysis reactions. The process of ionization initially generates a caibocation and counterion in proximity to each other. This species is called an intimate ion pair (or contact ion pair). This species can proceed to a solvent-separated ion pair, in which one or more solvent molecules have inserted between the caibocation and the leaving group but in which the ions have not diffused apart. The free caibocation is formed by diffusion away from the anion, which is called dissociation. 

Attack by a nucleophile or the solvent can occur at either of the ion pairs. Nucleophilic attack on the intimate ion pair would be expected to occur with inversion of configuration, since the leaving group would still shield the fiont side of the caibocation. At the solvent-separated ion pair stage, the nucleophile might approach fiom either fece, particularly in the case where solvent is the nucleophile. Reactions through dissociated carbocations should occur with complete lacemization. According to this interpretation, the identity and stereochemistry of the reaction products will be determined by the extent to which reaction occurs on the un-ionized reactant, the intimate ion pair, the solvent-separated ion pair, or the dissociated caibocation. 

Racemization, however, does not alwiys accompany isotopic scrambling. In the case of 5ec-butyl 4-bromobenzenesulfonate, isotopic scrambling occurs in trifluoroethanol solution witiiout any racemization. Two mechanisms are possible. Scrambling may involve an intimate ion pair in which the sulfonate can rotate with respect to the caibocation without allowing migration to die other face of the caibocation. The alternative is a concerted mechanism, which avoids a caibocation intermediate but violates the prohibition of front-side displacement. ... 

An elaboration of the ion-pair concept includes an ion sandwich in which a preassociation occurs between a potential nucleophile and a reactant. Such an ion sandwich might be a kinetic intermediate which accelerates dissociation. Alternatively, if a caibocation were quite unstable, it might always return to reactant unless a nucleophile was properly positioned to capture the caibocation. 

Jencks has discussed how the gradation from the 8fjl to the 8n2 mechanism is related to the stability and lifetime of the carbocation intermediate, as illustrated in Fig. 5.6. In the 8n 1 mechanism, the carbocation intermediate has a relatively long lifetime and is equilibrated with solvent prior to capture by a nucleophile. The reaction is clearly a stepwise one, and the energy minimxun in which the caibocation mtermediate resides is significant. As the stability of the carbocation decreases, its lifetime becomes shorter. The barrier to capture by a nucleophile becomes less and eventually disappears. This is described as the imcoupled mechanism. Ionization proceeds without nucleophilic... 

A wide range of caibocation stability data has been obtained by measuring the heat of ionization of a series of chlorides and cafbinols in nonnucleophilic solvents in the presence of Lewis acids. Some representative data are given in Table 5.4 These data include the diarylmediyl and triarylmethyl systems for which pX R+ data are available (Table 5.1) and give some basis for comparison of the stabilities of secondary and tertiary alkyl carbocations with those of the more stable aryl-substituted ions. 

Any structural effect which reduces the electron deficiency at the tricoordinate carbon will have flie effect of stabilizing the caibocation. Allyl cations are stabilized by delocalization involving the adjacent double bond. 

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleo diilic substitution reactions. They are primary and do not form caibocation intermediates, but the /-butyl substituent efiTectively hinders back-side attack. The rate of reaction of neopent>i bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, tiie ner rentyl system reacts with rearrangement to the /-pentyl system, aldiough use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary beiuyl system in entry 3 exhibits high, but not complete, inversiotL This is attributed to racemization of the reactant by ionization and internal return. 

In contiaat, die isomer, in which tire double bond is not in a position to participate in die iooizsdon step, reacts 10 times slower than die anti isomer. The reaction product is derived fiom a rearranged caibocation ion that is stabilized by virtue of being allylic. ... 

Interpretation of tiie ratio of capture of competing nucleophiles has led to the estimate that bromonium ions have lifetimes on the order of 10 s in methanol. This lifetime is about 100 times longer than fliat for secondary caibocations. There is also direct evidence for the existence of bromonium ions. The bromonium ion related to propene can be observed by NMR spectroscopy when l-bromo-2-fluoropropane is subjected to superacid conditions. The terminal bromine adopts a bridging position in the resulting cation. 

The generation of caibocations from these sources is well documented (see Section 5.4). The reaction of aromatics with alkenes in the presence of Lewis acid catalysts is the basis for the industrial production of many alkylated aromatic compounds. Styrene, for example, is prepared by dehydrogenation of ethylbenzene made from benzene and ethylene. 

Benzyl and allyl alcohols which can generate stabilized caibocations give Friedel-Crafts alkylation products with mild Lewis acid catalysts such as scandium triflate. ... 

To summarize, the most important factor to consider in assessing caibocation stability is the degree of substitution at the positively charged carbon. 

We will see numerous reactions that involve caibocation intermediates as we proceed through the text, so it is important to understand how theii structure determines their- stability. 

One important experimental fact is that the rate of reaction of alcohols with hydrogen halides increases in the order methyl < primary < secondary < tertiary. This reactivity order parallels the caibocation stability order and is readily accommodated by the mechanism we have outlined. 

The rate-determining step in the SnI mechanism is dissociation of the alkyloxo-nium ion to the caibocation. 

As noted eaiTier (Section 4.10) primary caibocations aie too high in energy to be intennediates in most chemical reactions. If primaiy alcohols don t fonn primary caibocations, then how do they undergo elimination A modification of our general mechanism for alcohol dehydration offers a reasonable explanation. For primary alcohols it is... 

Step (2) Ethanol acts as a base to remove a proton from the caibocation to give the alkene products. (Deprotonation step)... 

One possibility is the two-step mechanism of Figure 5.12, in which the carbon-halogen bond breaks first to give a caibocation intennediate, followed by deprotonation of the caibocation in a second step. 

The alkyl halide, in this case 2-bromo-2-methylbutane, ionizes to a caibocation and a halide anion by a heterolytic cleavage of the carbon-halogen bond. Like the dissociation of an alkyloxonium ion to a caibocation, this step is rate-detennining. Because the rate-detennining step is ununolecular—it involves only the alkyl halide and not the base—it is a type of El mechanism. 

The reactivity order parallels the ease of caibocation fonnation Increasing rate of elimination by the El mechanism... 

Piimaiy alcohols do not dehydrate as readily as secondaiy or tertiaiy alcohols, and their dehydration does not involve a primaiy caibocation. A proton is lost from the (3 caibon in the same step in which caibon-oxygen bond cleavage occurs. The mechanism is E2. 

Alkene synthesis via alcohol dehydration is complicated by carbocation rearrangements. A less stable caibocation can reaiiange to a more stable one by an alkyl group migration or by a hydride shift, opening the possibility for alkene foimation from two different caibocations. 

Let s compaie the caibocation intennediates for addition of a hydrogen halide (HX) to an unsymmetrical alkene of the type RCH=CH2 (a) according to Maikovnikov s rule and (b) opposite to Maikovnikov s rule. 

Figure 6.6 focuses on the orbitals involved and shows how the tt electrons of the double bond flow in the direction that generates the more stable of the two possible caibocations. 

The similar yields of the two alkyl chloride products indicate that the rate of attack by chloride on the secondaiy caibocation and the rate of reanangement must be very similai. ... 

The second mechanism is the one followed when addition occurs opposite to Maikovnikov s rule. Unlike electrophilic addition via a caibocation intennediate, this alternative mechanism is a chain reaction involving free-radical intennediates. It is presented in Figure 6.7. 

Reanangements do not nonnally occur, which can mean either of two things. Either caibocations are not intennediates, or if they are, they are captured by a nucleophile faster than they reanange. We shall see in Section 6.16 that the first of these is believed to be the case. 

CleaiTy, the steric crowding that influences reaction rates in Sn2 processes plays no role in SnI reactions. The order of alkyl halide reactivity in SnI reactions is the same as the order of caibocation stability the more stable the caibocation, the more reactive the alkyl halide. 

We have seen this situation before in the reaction of alcohols with hydrogen halides (Section 4.11), in the acid-catalyzed dehydration of alcohols (Section 5.12), and in the conversion of alkyl halides to alkenes by the El mechanism (Section 5.17). As in these other reactions, an electronic effect, specifically, the stabilization of the carbocation intennediate by alkyl substituents, is the decisive factor. The more stable the caibocation, the faster it is fonned. 

Piimaiy caibocations aie so high in energy that then intennediacy in nucleophilic substitution reactions is unlikely. When ethyl bromide undergoes hydrolysis in aqueous fonnic acid, substitution probably takes place by an SN2-like process, in which water is the nucleophile. 

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