Carbocations, benzylic rearrangements

Rearrangement is especially prevalent with primary alkyl halides of the type RCH2CH2X and R2CHCH2X Aluminum chloride induces ionization with rearrangement to give a more stable carbocation Benzylic halides and acyl halides do not rearrange... 

Because of the high stability of the tertiary ions, these are preferentially formed in the superacid systems from both tertiary and secondary, and even primary, precursors.353 If, however, the tertiary carbocation is not benzylic, rearrangement to a... 

If, however, the tertiary carbocation is not benzylic, rearrangement to a secondary, benzylic ion can be observed ... 

As shown in the following mechanism, reaction is initiated by heterolytic cleavage of the carbon-chlorine bond to form a 2° carbocation, which rearranges to a considerably more stable 3° carbocation by shift of a hydrogen with its pair of electrons (a hydride ion) from the adjacent benzylic carbon. Note that the rearranged carbocation is not only tertiary (hyperconjugation stabilization) but also benzylic (stabilization by resonance delocalization). 

A benzyl carbocation can rearrange to the ion shown below right (called a tropylium ion). 

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

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... 

Benzylic acid rearrangement, 836 Benzylic carbocation, electrostatic potential map of, 377 resonance in, 377 SN1 reaction and, 376-377... 

Unsaturation at the p Carbon. The SnI rates are increased when there is a double bond in the P position, so that allylic and benzylic substrates react rapidly (Table 10.5). The reason is that allylic (p. 221) and benzylic (p. 222) cations are stabilized by resonance. As shown in Table 10.5, a second and a third phenyl group increase the rate still more, because these carbocations are more stable yet. It should be remembered that allylic rearrangements are possible with allylic systems. 

Normally, only a small stoichiometric excess (2-30 mol%) of silane is necessary to obtain good preparative yields of hydrocarbon products. However, because the capture of carbocation intermediates by silanes is a bimolecular occurrence, in cases where the intermediate may rearrange or undergo other unwanted side reactions such as cationic polymerization, it is sometimes necessary to use a large excess of silane in order to force the reduction to be competitive with alternative reaction pathways. An extreme case that illustrates this is the need for eight equivalents of triethylsilane in the reduction of benzyl alcohol to produce only a 40% yield of toluene the mass of the remainder of the starting alcohol is found to be consumed in the formation of oligomers by bimolecular Friedel-Crafts-type side reactions that compete with the capture of the carbocations by the silane.129... 

Estimating stability it is possible to apply criteria commonly used in organic chemistry. Tertiary alkyl carbocation is more stable than the secondary one which is in its turn more stable than the primary one. For the carbon ions of this type the row of the stability is reversed. Allyl and benzyl cations are stable due to the resonance stabilization. The latter having four resonance structures may rearrange to be energetically favorable in the gas phase tropilium cation possessing seven resonance forms (Scheme 5.3). 

Quenching with the bromide nucleophile gives the tertiary bromide. On the other hand, 3-phenylprop-l-ene is protonated to a secondary carbocation. In this case, rearrangement by hydride migration leads to a more favourable benzylic carbocation, and a benzylic bromide is the observed product. 

As a simple example, note that the major products obtained as a result of addition of HBr to the alkenes shown below are not always those initially expected. For the first alkene, protonation produces a particularly favourable carbocation that is both tertiary and benzylic (see Section 6.2.1) this then accepts the bromide nucleophile. In the second alkene, protonation produces a secondary alkene, but hydride migration then leads to a more favourable benzylic carbocation. As a result, the nucleophile becomes attached to a carbon that was not part of the original double bond. Further examples of carbocation rearrangements will be met under electrophilic aromatic substitution (see Section 8.4.1). 

These are all examples of carbocation rearrangements. The approach here is to spot the potential for carbocation formation, then see if an alternative carbocation might be formed by migration of an alkyl gronp, or perhaps hydride, to produce a more favourable carbocation. Favonrable carbocations are typically tertiary, allylic, or benzylic. 

With tamoxifen, loss of the sulfate group cleaves the bond and yields a benzylic carbocation. In the case of diclofenac, the carbonyl carbon is reactive and can react with nucleophiles (Fig. 4.54), but the conjugate can also rearrange and yield a reactive, electrophilic aldehyde. 

You will not be surprised, then, to learn that the tropylium ion is the major peak found in the MS of 7-substituted cyclohepta-l,3,5-trienes, but you may be surprised to find that the benzyl carbocation rearranges to the tropylium ion under MS conditions (Scheme 5.7). 

These experimental observations were explained by invoking the formation of the most stable benzylic carbocation that then undergoes rearrangement via an intermediate phenonium ion72 (Scheme 4.5). This mechanism accounts for cc-p isotope scrambling, and the low amount of isopropylbenzene is in harmony with the involvement of the primary cation. Other observations, in turn, suggest the involvement of the n complex of the arene and the side-chain carbocation.73-75... 

Detailed wide-ranging studies are available on the addition of HC1 and HBr to alkenes. The most useful procedure is to react dry HC1 gas and the alkene neat or in an inert organic solvent. Water or acetic acid may also be used. Alkenes yielding tertiary or benzylic alkyl chlorides react most readily. Styrene, however, adds HC1 only at — 80°C to give a-chloroethylbenzene without polymerization.101 At more elevated (room) temperature polymerization prevails. HBr adds to alkenes in an exothermic process more rapidly than does HC1. Rearrangements may occur during addition indicating the involvement of a carbocation intermediate 102... 

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