Carbocation mechanisms

How do we know that the carbocation mechanism for electrophilic addition reactions of alkenes is correct The answer is that we don t know it s correct at least we don t know with complete certainty. Although an incorrect reaction mechanism can be disproved by demonstrating that it doesn t account for observed data, a correct reaction mechanism can never be entirely proved. The best we can do is to show that a proposed mechanism is consistent with all known facts. If enough facts are accounted for, the mechanism is probably correct. 

What evidence is there to support the carbocation mechanism proposed for the electrophilic addition reaction of alkenes One of the best pieces of evidence was discovered during the 1930s by F. C. Whitmore of the Pennsylvania State University, who found that structural rearrangements often occur during the reaction of HX with an alkene. For example, reaction of HC1 with 3-methyl-1-butene yields a substantial amount of 2-chloro-2-methylbutane in addition to the "expected" product, 2-chloro-3-methylbutane. 

Evidence in support of a carbocation mechanism for electrophilic additions comes from the observation that structural rearrangements often take place during reaction. Rearrangements occur by shift of either a hydride ion, H (a hydride shift), or an alkyl anion, R-, from a carbon atom to the adjacent positively charged carbon. The result is isomerization of a less stable carbocation to a more stable one. 

Rearrangement is possible even with a non-carbocation mechanism. The rearrangement could occur before the attack on the ring takes place. It has been shown that treatment of CH3 CH2Br with AlBt3 in the absence of any aromatic compound... 

In the acid-catalysis method, a proton or Lewis acid is used as the catalyst and the reaction is carried out at temperatures between -30 and 100°C. This is a Friedel-Crafts process with a carbocation mechanism" (illustrated for a proton acid... 

This kind of reaction can proceed in solution by a carbocation mechanism, but in the radiation-induced case, it proceeds almost exclusively by a radical mechanism. In most cases, the radiation initiates reactions that are of chain character. 

Geranyl diphosphate and farnesyl diphosphate are analogues of dimethylallyl diphosphate that contain two and three C5 subunits respectively they can undergo exactly the same SnI reactions as does dimethylallyl diphosphate. In all cases, a carbocation mechanism is favoured by the resonance stabilization of the allylic carbocation. Dimethylallyl diphosphate, geranyl diphosphate, and farnesyl diphosphate are precursors for natural terpenoids and steroids. 

Accordingly, the E2 mechanism becomes relatively favourable, even with tertiary substrates, when we use a strong base or more concentrated base. We are thus more likely to get an El mechanism when we have a tertiary centre, and weak bases or bases in low concentration. Obviously, polar solvents are also going to be conducive to carbocation mechanisms (see Section 6.2.3). Just as acidic conditions help to favour SnI reactions, they also going to favour El reactions. 

Further, it is noted that most of them involve inversion of stereochemistry at the particular centre, a feature of the concerted nature of these rearrangements, so that as one group leaves another approaches from the rear. Thus, we have the features of Sn2 reactions in a carbocation mechanism. 

Further evidence against the ECbECN carbocation mechanism is claimed by Sartori and co-workers [186] from their work on the fluorination of N,N-dime-thyltrifluoromethanesulphonamides at different temperatures (-15°C and + 5°C). According to the carbocation mechanism, it is stated, introduction of fluorine atoms into the sulphonamide should take place stepwise, first in one methyl group and then into the other however, detailed examination of the reaction mixture by 19F NMR spectroscopy showed no trace of compounds containing the moieties... 

Thus, an assessment of the present situation would suggest, on balance, that experimental evidence appears to support the Radical Mechanism over the Carbocation Mechanism, although a number of important questions remain far from being resolved. 

In the argument against the ECbECN concept, much, perhaps too much, store has been placed by critics on observations which seem to undermine the zipper mechanism in the apparent belief that this mechanism is axiomatic with the ECbECN as a whole. However, as has been shown, changing physico-chemical properties of progressively fluorinated products inevitably result in different adsorptive forces for these compounds, with possible desorption from the electrode as a consequence this situation could apply equally well with products formed via a carbocation mechanism as with radically generated compounds, even though, as originally stated, the implication is otherwise. 

The reaction also takes place with other bases (e.g., LiH,213 Na in ethylene glycol, NaH, NaNH2) or with smaller amounts of RLi, but in these cases side reactions are common and the orientation of the double bond is in the other direction (to give the more highly substituted olefin). The reaction with Na in ethylene glycol is called the Bamford-Stevens reaction,214 For these reactions two mechanisms are possible—a carbenoid and a carbocation mechanism.215 The side reactions found are those expected of carbenes and carbocations. In general, the carbocation mechanism is chiefly found in protic solvents and the carbenoid mechanism in aprotic solvents. Both routes involve formation of a diazo compound (34) which in some cases can be isolated. 

A new mechanism, called the methane-formaldehyde mechanism, has been put forward for the transformation of the equilibrium mixture of methanol and dimethyl ether, that is, for the formation of the first C-C bond.643 This, actually, is a modification of the carbocation mechanism that suggested the formation of ethanol by methanol attaching to the incipient carbocation CH3+ from surface methoxy.460,462 This mechanism (Scheme 3.3) is consistent with experimental observations and indicates that methane is not a byproduct and ethanol is the initial product in the first C-C bond formation. Trimethyloxonium ion, proposed to be an intermediate in the formation of ethyl methyl ether,447 was proposed to be excluded as an intermediate for the C-C bond formation.641 The suggested role of impurities in methanol as the reason for ethylene formation is highly speculative and unsubstantiated. 

The pH dependence of the action of fumarate hydratase indicates participation of both an acidic and a basic group with pfCa values of 5.8 and 7.1.56 See Chapter 9 for additional information. However, either anion or carbocation mechanisms might be possible. That the cleavage of the C-H bond is not rate limiting is suggested by the observation that malate containing 2H in the pro-R position is dehydrated at the same rate as ordinary malate. If the anion mechanism (Eq. 13-13) is correct, the 2H from the pro-R position of specifically labeled malate might be removed rapidly, while the loss of OH could be slower. If so, the 2H would be "washed out" of L-malate faster than could happen by conversion to fumarate followed by rehydration to malate. In fact, the opposite was observed. 

Reaction type 6B of Table 10-1 is allylic rearrangement with simultaneous condensation with another molecule. The reaction, which is catalyzed by prenyl-transferases,3073 occurs during the polymerization of polyprenyl compounds (Fig. 22-1,Eqs. 22-2,22-3). Experimental evidence favors a carbocation mechanism for all of these reactions.308 309 See Chapter 22. 

Both famesyltransferases70 761 and geranylgeranyl-transferases72/77 78b have been characterized, and the three- dimensional structure of the former has been established.73 75-76 The two-domain protein contains a seven-helix crescent-shaped hairpin domain and an a,a-barrel similar to that in Fig. 2-29. A bound zinc ion in the active site may bind the -S group of the substrate protein after the famesyl diphosphate has been bound into the active site.76 79 These enzymes are thought to function by a carbocation mechanism as shown in Eq. 22-3 and with the indicated inversion of configuration.71... 

Ring closure at the ends of the lycopene molecule to form the carotenes can be formulated most readily through an acid-catalyzed carbocation mechanism (Eq. 22-11). Loss of one or the other of two protons adjacent to the positive charge leads to the (3 ring of (3-carotene or to the a ring of a-carotene.110/123a Compounds with c only one ring may also be... 

The formation of sesquiterpenes by a carbocation mechanism means that there is considerable scope for rearrangements of the Wagner-Meerwein type. So far, only occasional hydride migrations have been invoked in rationalizing the examples considered. Obviously, fundamental skeletal rearrangements will broaden the range of natural sesquiterpenes even further. That such processes do occur has been proven beyond doubt by appropriate labelling experiments, and... 

Cumene hydroperoxide degradation. The degradation of the cumene hydroperoxide proceeds via a carbocation mechanism. In the first step, a pair of electrons on the oxygen of the hydroperoxide s hydroxyl group is attracted to a proton of the H30+ molecule, forming an oxonium ion. 

The Fischer esterification proceeds via a carbocation mechanism. In this mechanism, an alcohol is added to a carboxylic acid by the following steps ... 

Table 11.2 Addition Reactions Following a Carbocation Mechanism...

Fig. 13. Model of propylene molecule adsorption on clusters containing a bridged hydroxyl group. The arrows indicate the atom motions corresponding to different mechanisms of the double-bond migration (black arrows, carbocation mechanism white arrows, carbanion mechanism in the case of the synchronous mechanism these motions are simultaneous).

The dehydration of alcohols under mild conditions is affected by copper(II) Lewis acids. Copper sulfate has long been utilized as a dehydrating agent. An example of its effectiveness for alcohol dehydration is demonstrated in the conversion of the sensitive propargylic alcohol 1 to enyne 2 (Sch. 1) [4]. A carbocation mechanism is suggested by the formation of bis ethers in these reactions [5]. The addition of pyridine... 

Thioacetals readily eliminate to vinylsnlfides at room temperature in the presence copper(I) triflate [46]. Acyclic (75) and cyclic (77) substrates react equally well (Sch. 20). The a-ketothioacetal 79 furnished furan 80, presumably via a carbocation mechanism, and the diene 82 resulted from sequential elimination of two sulfides from 81. 

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