Proton loss from carbocations

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

The table shows the effect on product ratio of ultrasonic irradiation (Kerry Pulsatron cleaning bath 35 kHz 50 W) during electrolysis. Here there is only 8% of the bicyclohexyl dimeric one-electron product, with approximately 41 % of the two-electron product from nucleophilic capture of the intermediate carbocation. The preponderance of cyclohexene (32 %) over cyclohexane (> 3 %) shows its formation is by proton loss from the carbocation intermediate, since free-radical routes to cyclohexene (i. e. hydrogen atom abstraction) also produce cyclohexane in equal if not greater amounts... 

Methyl migration as in part (a) converts the first-formed secondary carbocation into a more favourable tertiary carbocation, and we see proton loss from this to give the other two products. These are unexceptional there are two possible sites for proton loss. 

Two possible alkenes are produced by proton loss from the carbocation. 

Scheme 7.29. A representation of two potential pathways for proton loss from a carbocation intermediate on the Sn1-E1 reaction surface. Both pathways are followed. It is supposed that proton loss via the pathway labeled (a), which results in the most highly substituted alkene (the Saytzeff product), occurs preferentially because that is the product formed in highest yield. The alkene resulting from pathway (b), the Hofmann product, is also formed. A. W. Hofmann (1818-1895) was a German chemist who was professor of chemistry at the Royal College of Chemistry in London (1845-1864) and then accepted a post as professor at the University of Berlin. Most of Hofmann s work dealt with amines (Chapter 10). Hofmann found, in contrast to Saytzeff, that the least highly substituted alkene is formed when the elimination is carried out on amine quaternary salts (so-called onium salts). This is, in part, presumably due to the close association between the base and the positively charged onium salt as well as to the removal of the proton in the rate-determining step (cf. the E2 reaction). (Note the 82 18 ratio of products shown here should be considered identical, within experimental error, to the 79 21 ratio of Table 7.9.)...

In the example, the conjugate base of the acid is the poor nucleophile HS04, and proton loss from the intermediate carbocation is observed. Dehydration of tertiary alcohols is even easier, often occurring at slightly above room temperature. 

Initially, protonation of the carbonyl oxygen gives a delocalized carbocation (step 1). Now the carbonyl carbon is susceptible to nucleophilic attack by methanol. Proton loss from the initial addnct furnishes the tetrahedral intermediate (step 2). This species is a crucial relay point, because it can react in either of two ways in the presence of the mineral acid catalyst. First, it can lose methanol by the reverse of steps 1 and 2. This process, beginning with protonation of the methoxy oxygen, leads back to the carboxylic acid. The second possibility, however, is protonation at either hydroxy oxygen, leading to elimination of water and to the ester (step 3). All the steps are reversible therefore, either addition of excess alcohol or removal of water favors esterification by shifting the equilibria in steps 2 and 3, respectively. Ester hydrolysis proceeds by the reverse of the sequence and is favored by aqueous conditions. 

The first step is protonation. Because both C3 and C4 need to pick up protons, we protonate on C4. At this point, there s not much we can do except allow H20 to add to the carbocation, even though this is not a bond that is in our list of bonds that need to be made we will need to cleave it later. Addition of 08 to C5, H+ transfer from 08 to 06, and cleavage of the C5-06 bond follow. At this point we still need to make the C1-C5 bond. C5 is clearly electrophilic, so Cl needs to be made nucleophilic. Proton transfer from 08 to C3 and another H+ transfer from Cl to 08 gives the Cl enol, which attacks the C5 carbocation. Another H+ transfer from Cl to 08 is followed by cleavage of the 08-C5 bond, and loss of H+ gives the product. 

We have also investigated the electrooxidation of phenylethanoate, a system where there is no proton-loss pathway from the intermediate carbocation. Tab. 6.14 shows relative product ratios for phenylacetate in similiar conditions to those used for cyclohexane carboxylate, but employing 100 mA cm current density [59,60]. 

If a carbon atom bearing a positive charge is bound with the methyl group, the reaction path consists of a methyl proton loss. This is the intrinsic property of methyl derivatives in the cation-radical state. The deprotonation generates a benzylic-type radical that is rapidly oxidized to a so-called benzylic carbocation, which reacts with a nucleophile as shown in Scheme 3.70. From Scheme 3.70 it is clear that BP-6-methyl can act as an active carcinogen (Cavalieri and Rogan 1995). 

It is thought that the above reactions proceed by abstraction of a benzylic hydride ion by the quinone. Proton loss subsequently occurs from the carbocation (106) leading to the o-quinoneallide which ring-closes to the chromene. 

Overall, ultrasound appears to favor the two-electron mechanism for the reaction, but the greatest effect of sonication upon product distribution was the substantial enhancement of alkene formation. Accordingly it was decided to examine a carboxylate electrooxidation system where there is no proton-loss pathway from the intermediate carbocation, namely using phenylacetate as a substrate. 

The stereochemistry of a solvolysis reaction can be affected if the substrate has a substituent that can donate a pair of electrons to the developing carbocation center. For example, treatment of ( )-t/zreo-3-bromo-2-butanol (19) with HBr gave only the racemic 2,3-dibromobutane (20). There was none of the meso compound that would have been expected if the reaction involved protonation, loss of water, and formation of a free carbocation intermediate. Similarly, reaction of ( )-eri/tizra-3-bromo-2-butanol with HBr gave only meso-2,3-dibromobutane. The reaction of 19 seems best explained by nucleophilic participation of the bromine on the adjacent atom in concert with departure of the water. The result is a bridged intermediate (21) that is the same bromonium ion expected from the electrophilic addition of Br2 to cis-2-butene (Figure 8.13). Back-side attack by bromide ion on either carbon atom involved in the three-membered bromonium ring is equally likely, so a racemic mixture results. 

Both of these observations are considered to arise from the ability of the alkene product(s) to undergo reprotonation and subsequent proton loss under the conditions of the reaction. Thus, since (a) the more highly substituted alkenes are thermodynamically favored and (b) rearrangements arise either for thermodynamic reasons (formation of more stable carbocations) or simple equilibration between ions of identical or near identical energies, both of these processes intrude (Figures 8.17). 

Figure 11.19. Some of the alkenes derived by simple proton loss that are suggested to arise from the common, enzyme-associated a-terpinyl carbocation.

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