Rearrangements carbocation

Whenever a carbocation is an intermediate in a mechanism, rearrangements are possible. Besides the study of carbocation structures and reactivity in stable ion media, the majority of the information chemists have on carbocation rearrangements comes from SnI solvolysis reactions. A hydrogen, alkyl, or aryl group on a carbon adjacent (p) to the cationic carbon can shift to form a different carbocation. This is called a Wagner-Meerwein shift. Eq. 11.30 shows a thermoneutral example. 

31 shows one example where the only product found in the SnI reaction derives from a carbocation rearrangement. In this example, a primary carbenium ion is formed first, but a methyl migration creates the more stable tertiary carbenium ion. However, the precise timing of such migrations is debated, as we will see below. Since Sn2 reactions are concerted, rearrangements are impossible (Eq. 11.32). 

We have presented carbocation rearrangements in the context of substitution reactions. Yet, rearrangements and issues that are relevant to carbocation structure are applicable to any reaction involving carbocations—namely, additions, eliminations, rearrangements, etc. One example is the acid-catalyzed ring opening of epoxides. 

Roberts, A. A., and Anderson, C. R. Ion Pairs and Hydride Participation in the Acetolysis of Cyclooctyl Tosylate. Tetrahedron Lett., 44,3885 (1%9), and references therein. 

Relative Rate Constants and Activation Parameters for the Acetolysis of 2-Substituted Cyclohexyl Brosylates  

When alcohols are transformed into carbocations, the carbocations themselves are subject to rearrangements. The two rearrangements, known as hydride shifts and alkyl shifts, can occur with most types of carbocations. The rearranged molecules can then undergo further SnI or El reactions. The result is likely to be a complex mixture, unless we can establish a thermodynamic driving force toward one specific product. 

Treatment of 2-propanol with concentrated hydrogen bromide gives 2-bromopropane, as expected. However, exposure of the more highly substituted secondary alcohol 3-methyl-2-butanol to the same reaction conditions produces a surprising result. The expected SnI product, 2-bromo-3-methylbutane, is only a minor component of the reaction mixture the major product is 2-bromo-2-methylbutane. 

Minor product 2-Bromo-3-methylbutane (Normal product) 

Note Color is used to indicate the electrophilic (blue), nucleophilic (red), and leaving-group (green) character of the reacting centers. Therefore, a color may switch from one group or atom to another as the reaction proceeds. 

CHAPTER 9 Further Reactions of Alcohols and the Chemistry of Ethers 

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). 

Rearrangements are an unexpected complication, and it is sometimes difficult to predict when they might occur. We need to look carefully at the structure of any proposed carbocation intermediate and consider whether any such rearrangements are probable. In most cases we shall only need to rationalize such transformations, and will not be trying to predict their possible occurrence. 

Le Chatelier s principle can be used to favor products in dehydration reactions because the alkene product has a lower boiling point than the alcohol reactant. Thus, the alkene can be distilled from the reaction mixture as it is formed, leaving the alcohol and acid to react further, forming more product. 

Sometimes unexpected products are formed in dehydration that is, the carbon skeletons of the starting material and product might be different, or the double bond might be in an unexpected location. For example, the dehydration of 3,3-dimethyl-2-butanol yields two alkenes, whose carbon skeletons do not match the carbon framework of the starting material. 

Because the migrating group in a 1,2-shtft moves with two bonding eiectrons, the carbon it leaves behind now has only three bonds (six eiectrons), giving it a net positive (+) charge. 

The dehydration of 3,3-dimethyl-2-butanol illustrates the rearrangement of a 2° to a 3° carbocation by a 1,2-methyl shift, as shown in Mechanism 9.3. The carbocation rearrangement occurs in Step [3] of the four-step mechanism. 

Step [3] Rearrangement of the carbocation by a 1,2-CH3 shift KEY STEP 3 H 2-shift 

Steps [1], [2], and [4] in the mechanism for the dehydration of 3,3-dimethyl-2-butanol are exactly the same steps previously seen in dehydration protonation, loss of H2O, and loss of a proton. Only Step [3], rearrangement of the less stable 2° carbocation to the more stable 3° carbocation, is new. 

For example, 2° carbocation A rearranges to the more stable 3° carbocation by a 1,2-hydride shift, whereas carbocation B does not rearrange because it is 3° to begin with. 

We first need to draw the cation that will be produced after protonation by trifluoroacetic acid (a strong acid) and loss of water. 

We can then consider migrating a methyl group from the carbon adjacent to the positive charge, which would give a tertiary carbocation. 

In competition between substitution and elimination, substitution is favored by good nucleophiles and modest steric demands. Elimination is favored by strong, nonnucleo-philic, or bulky bases, low-polarity solvents, and high steric demand. 

Carbocations formed in El reactions may rearrange to give more stable species. 

---

Why do carbocations rearrange The answer is straightforward once we recall that tertiary carbocations are more stable than secondary carbocations (Section 4 10) Thus rearrangement of a secondary to a tertiary carbocation is energetically favorable As... 

Like alcohol dehydrations El reactions of alkyl halides can be accompanied by carbocation rearrangements Eliminations by the E2 mechanism on the other hand nor mally proceed without rearrangement Consequently if one wishes to prepare an alkene from an alkyl halide conditions favorable to E2 elimination should be chosen In prac tice this simply means carrying out the reaction m the presence of a strong base... 

Alkene synthesis via alcohol dehydration is complicated by carbocation rearrangements A less stable carbocation can rearrange to a more sta ble one by an alkyl group migration or by a hydride shift opening the possibility for alkene formation from two different carbocations... 

Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes... 

CARBOCATION REARRANGEMENTS IN HYDROGEN HALIDE ADDITION TO ALKENES... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

Hydride shift (Section 5 13) Migration of a hydrogen with a pair of electrons (H ) from one atom to another Hydnde shifts are most commonly seen in carbocation rearrange ments... 

The alkyl-bridged structures can also be described as comer-protonated cyclopropanes, since if the bridging C—C bonds are considered to be fully formed, there is an extra proton on the bridging carbon. In another possible type of structure, called edge-protonated cyclopropanes, the carbon-carbon bonds are depicted as fully formed, with the extra proton associated with one of the bent bonds. MO calculations, structural studies under stable-ion conditions, and product and mechanistic studies of reactions in solution have all been applied to understanding the nature of the intermediates involved in carbocation rearrangements. 

Carbocation rearrangements occur in the reactions of some secondary alco hols with DAST, thus isobutyl alcohol gives a mixture of isobutyl fluoride and tert-hxAy] fluonde [95] (Table 6), and both bomeol and isoborneol rearrange to the same 3-fluoro-2 2,3-tnraethylbicyclo[2 2 IJheptane (72-74%) accompanied by camphene [95]... 

ThomsonNOW Click Organic Interactive to use a web-based palette to predict products from simple carbocation rearrangements. 

Evidence for the Mechanism of Electrophilic Additions Carbocation Rearrangements... 

Carbocation rearrangements can also occur by the shift of an alkyl group with its ejection pair. For example, reaction of 3,3-dimethyJ-l-butene with HCI Leads to an equal mixture of unrearranged 2-chloro-3,3-dimethyTbutane and rearranged 2-chloro-2,3-dimethyibutane. In this instance, a secondary carbocation rearranges to a more stable tertiary carbocation by the shift of a methyl group. 

The (Ticdcl-Crafts reaction of benzene with 2-chloro-3-methylbutane in the presence of AICI3 occurs with a carbocation rearrangement. What is the structure of the product ... 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

Isoborneol (Problem 27.37) is converted into camphene on treatment with dilute sulfuric acid. Propose a mechanism for the reaction, which involves a carbocation rearrangement. 

Propose a mechanism for the biosynthesis of the sesquiterpene trichodiene from famesyl diphosphate. The process involves cyclization to give an intermediate secondary carbocation, followed by several carbocation rearrangements. 

---