Ferf-butyl carbocation

The essential features of the mechanism for aliphatic nucleophilic substitution at tertiary carbon were established in studies by Hughes and Ingold." ° However, as chemists probed more deeply, the problems associated with the characterization of borderline reaction mechanisms were encountered, and controversy remains to this day about whether these problems have been entirely solved." What is generally accepted is that ferf-butyl derivatives undergo borderline solvolysis reactions through a ferf-butyl carbocation intermediate that is too unstable to diffuse freely through nucleophilic solvents such as methanol and water. The borderline nature of substitution reactions at tertiary carbon is exemplihed by the following observations. 

Begin by performing an AMI geometry optimization on methyl, ethyl, isopropyl, and ferf-butyl carbocations. These carbocations are built as described in Part C of Experiment 20A. Don t forget to specify that each one has a positive charge. Also select a density surface for each one with the electrostatic potential mapped onto the surface. 

When the calculations are completed, display all four density-electrostatic potential maps on the same screen and adjust the color values to the same range as described in Experiment 20C. What do you observe Is the positive charge as localized in the ferf-butyl carbocation as in its methyl counterpart ... 

S]sjl reaction takes place by loss of the leaving group before the nucleophile approaches. 2-Bromo-2-methylpropane spontaneously dissociates to the ferf-butyl carbocation plus Br" in a slow, rate-limiting step, and the intermediate carbocation is then immediately trapped by the nucleophile water in a faster second step. Water is not a reactant in the step whose rate is measured. The energy diagram is shown in Figure 12.10. 

The remarkable thermal stability of the di-ferf-butyl-substituted thiepin 6, due to steric screening, has been demonstrated by its synthesis in an analogous manner to the carbocation rearrangement which provides dibenzothiepins. Under acidic conditions, methanesulfonic acid was eliminated from Ihiopyran 5 to give the thiepin via cationic rearrangement.18... 

FIGURE 3.6 Deprotection of functional groups by acidolysis. Protonation followed by carbocation formation during the removal of ferf-butyl-based protectors by hydrogen chloride.8 One mechanism is involved in generating the ferf-butyl cation, which is the precursor of two other molecules. 

The reactivity of aromatic side chains to undergo dealkylation is in line with the stability of the corresponding carbocations. This indicates the possible involvement of carbocations in dealkylation, which was proved to be the case. The intermediacy of the rm-butyl cation in superacid solution was shown by direct spectroscopic observation.228,229 Additional proof was provided by trapping the ferf-butyl cation with carbon monoxide during dealkylation 230... 

The major difference between the two mechanisms is the second step. The second step in the reaction of ferf-butyl alcohol with hydrogen chloride is the unimolecular dissociation of ferf-butyloxonium ion to tert-butyl cation and water. Heptyloxonium ion, however, instead of dissociating to an unstable primary carbocation, reacts differently. It is attacked by bromide ion, which acts as a nucleophile. We can represent the transition state for this step as ... 

These common features suggest that carbocations are key intermediates in alcohol dehydrations, just as they are in the reaction of alcohols with hydrogen halides. Figure 5.6 portrays a three-step mechanism for the acid-catalyzed dehydration of tert-butyl alcohol. Steps 1 and 2 describe the generation of terf-butyl cation by a process similar to that which led to its formation as an intermediate in the reaction of ferf-butyl alcohol with hydrogen chloride. 

Tertiary alcohols react with sulfuric acid at much lower temperatures than do most primary or secondary alcohols. The reactions typically are SN1 and El by way of a tertiary carbocation, as shown here for ferf-butyl alcohol and sulfuric acid ... 

As is apparent in the last step, isobutane is not alkylated but transfers a hydride to the Cg+ carbocation before being used up in the middle step as the electrophilic reagent (tert-butyl cation 4). The direct alkylation of isobutane by an incipient tert-butyl cation would yield 2,2,3,3-tetramethylbutane,142 which indeed was observed in small amounts in the reaction of ferf-butyl cation with isobutane under stable ion conditions at low temperatures (vide infra). 

Superacid-catalyzed alkylation of adamantane with lower alkenes (ethene, propene, isomeric butenes) has been investigated by Olah et al.151 in triflic acid and triflic acid-B(0S02CF3)3. Only trace amounts of 1 -ferf-butyladamantane (37) were detected in alkylation with 1- and 2-butenes, whereas isobutylene gave consistently relatively good yield of 37. Since isomerization of isomeric 1-butyladamantane under identical conditions did not give even traces of 37, its formation can be accounted for by (r-alkylation, that is, through the insertion of the ferf-butyl cation into the C—H bond (Scheme 5.22). This reaction is similar to that between ferf-butyl cation and isobutane to form 2,2,3,3-tetramethylbutane discussed above (Scheme 5.21). In either case, the pentacoordinate carbocation intermedate, which may also lead to hydride transfer, does not attain a linear geometry, despite the unfavorable steric interactions. 

First, the oxygen is protonated to make it a better leaving group. Then water leaves to produce the ferf-butyl cation. This step is very fast, even at -60°C, so the carbocation is the only product that can be detected as soon as the alcohol is added to the superacid medium. Because there is no nucleophile for the carbocation to react with (the H,0 generated in the reaction is protonated by the strong acid to form HjO+), its lifetime under these conditions is quite long, and it can be studied by a variety of techniques. 

Because a carbocation is sp2 hybridized, with trigonal planar geometry and an empty p orbital, this ion has a cycle of three p orbitals. (Remember that it is not the number of orbitals that determines whether a compound is aromatic or not, but rather the number of electrons in the pi MOs.) The cyclopropenyl carbocation has two electrons in its three pi MOs, so it fits Hiickel s rule and should be aromatic. In fact, cyclopropenyl carbocations are significantly more stable than other carbocations, even though they have considerable angle strain. For example, most carbocations react rapidly with water, a weak nucleophile. In contrast, tri-ferf-butyl-cyclopropenyl perchlorate, a carbocation salt, is stable enough to be recrystallized from water. 

Carbocations are also strong proton acids. The ferf-butyl cation shown above can also lose a proton to a weak base, often the solvent. 

Fig. 6. Plot of proton affinities (PA) of carboxylic acids and esters versus the a value of the substituent R. These values are 1.000 (hydrogen), 0.938 (methyl), 0.915 (ethyl), 0.895 (i-propyl), and 0.883(ferf-butyl), as explained in the chapter on carbocations. Proton affinity data have been taken from Ref. [15]...

In order to enhance the acid lability of ferf-butyl esters, several derivatives have been proposed based on the substitution of one or more methyl groups by residues which increase the stability of the intermediate tertiary carbocation in acidolytic deprotection. Phenyl, cyclopropyl, and adamantyl substituents have been used for such purposes. 

There is direct evidence, from ir and nmr spectra, that the fert-butyl cation is quantitatively formed when ferf-butyl chloride reacts with AICI3 in anhydrous liquid HCl. In the case of alkenes, Markovnikov s rule (p. 1019) is followed. Carbocation formation is particularly easy from some reagents, because of the stability of the cations. Triphenylmethyl chloride and 1-chloroadamantane alkylate activated aromatic rings (e.g., phenols, amines) with no catalyst or solvent. Ions as stable as this are less reactive than other carbocations and often attack only active substrates. The tropylium ion, for example, alkylates anisole, but not benzene. It was noted on p. 476 that relatively stable vinylic cations can be generated from certain vinylic compounds. These have been used to introduce vinylic groups into aryl substrates. Lewis acids, such as BF3 or AIEta, can also be used to alkylation of aromatic rings with alkene units. 

Ethers with a tertiary, benzylic, or allylic group cleave by an S>jl or Ei mechanism because these substrates can produce stable intermediate carbocations. T hese reactions are often fast and take place at moderate temperatures. ferf-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. WeTl see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

The two dimers of (CH3)2C=CH2 are formed by the mechanism shown in Figure 6.16. In step 1 protonation of the double bond generates a small amount of ferf-butyl cation in equilibrium with the alkene. The carbocation is an electrophile and attacks a second molecule of 2-methylpropene in step 2, forming a new carbon-carbon bond and generating a Cg carbocation. This new carbocation loses a proton in step 3 to form a mixture of 2,4,4-trimethyl-l-pentene and 2,4,4-trimethyl-2-pentene. 

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