Superacidic reaction conditions, stable

The extent to which rearrangement occurs depends on the structure of the cation and foe nature of the reaction medium. Capture of carbocations by nucleophiles is a process with a very low activation energy, so that only very fast rearrangements can occur in the presence of nucleophiles. Neopentyl systems, for example, often react to give r-pentyl products. This is very likely to occur under solvolytic conditions but can be avoided by adjusting reaction conditions to favor direct substitution, for example, by use of an aptotic dipolar solvent to enhance the reactivity of the nucleophile. In contrast, in nonnucleophilic media, in which fhe carbocations have a longer lifetime, several successive rearrangement steps may occur. This accounts for the fact that the most stable possible ion is usually the one observed in superacid systems. 

Two chapters in this volume describe the generation of carbocations and the characterization of their structure and reactivity in strikingly different milieu. The study of the reactions in water of persistent carbocations generated from aromatic and heteroaromatic compounds has long provided useful models for the reactions of DNA with reactive electrophiles. The chapter by Laali and Borosky on the formation of stable carbocations and onium ions in water describes correlations between structure-reactivity relationships, obtained from wholly chemical studies on these carbocations, and the carcinogenic potency of these carbocations. The landmark studies to characterize reactive carbocations under stable superacidic conditions led to the award of the 1994 Nobel Prize in Chemistry to George Olah. The chapter by Reddy and Prakash describes the creative extension of this earlier work to the study of extremely unstable carbodications under conditions where they show long lifetimes. The chapter provides a lucid description of modern experimental methods to characterize these unusual reactive intermediates and of ab initio calculations to model the results of experimental work. 

As discussed previously, several types of reactive dications and superelectrophiles have been directly observed using NMR spectroscopy. These experiments have all used low temperatures (— 100°C to — 30°C) and superacidic conditions to generate the observable reactive dications and superelectrophiles. Some reactive dications and superelectrophiles are stable at low temperatures and can be directly observed by NMR, but at higher temperatures they readily cleave and decompose. The low temperatures also slow down proton exchange reactions and enable the ions to be observed as static species. 

The dicationic species have also been obtained from /3-ketoacids, fi-ketoesters, and /-i-ketoamides in superacid solutions (Table 1, entries 2-4). Diprotonated acetoacetic acid (75) can be observed by low-temperature NMR under stable ion conditions.34 Likewise, diprotonated methylacetoacetate (77) can be observed by NMR at temperatures lower than — 80°C in FS03H-SbF5-SC>2 solution.35 With ethyl acetoac-etate in HF-SbFs, the equilibrium constant for the dication-monocation equilibrium has been estimated to be at least 107, indicating virtually complete conversion to the superelectrophile.35 The /3-ketoamide (78) is found to give the condensation products 95 in good yield from CF3SO3H and the superelectrophile 79 is proposed as the key intermediate in the condensation reaction (eq 25 ).27... 

The preparation of high polymers under living polymerization conditions requires that the polymerization is carried out in the presence of counterions which do not lead to irreversible termination 27 29). Noncomplex counterions, derivatives of strong protic acids (superacids), e.g. the CF3SOf anion, may react with cationic growing species. This reaction is reversible and affects only the polymerization kinetics but not the molecular weights 30). These counterions are classified as stable. 

Reaction kinetics, theoretical calculations and finaUy the observation of such species by NMR in superacids as stable dications point out the rehabihty of this mechanistical hypothesis under superacidic conditions. 

It is not possible to examine alkyl cations such as er -butyl cation under similar conditions because of the intervention of a myriad of condensation, cyclization, and rearrangement reactions. In 96% sulfuric acid, fer -butanol is converted within minutes to a mixture containing 50% alkanes and 50% cyclopentenyl cations. " One of the major developments in organic chemistry during the decade of the 1960 s was the application of NMR spectroscopy in so-called superacid media to probe the structure of carbonium ions. The most obvious use of this technique is in examining alkyl cations and other less stable ions, the p s of which are not readily measured. In fact, the method is so versatile and the information gained so much more valuable than simple stability measurements that it is now the method of first choice in probing carbonium ion structure. 

C provides direct support for the dictum that tertiary carbonium ions are more stable than secondary, which are more stable than primary. Primary and secondary alcohols are protonated under these conditions, and the protonated alcohols are the species observed (entry 1), while tert-butyl alcohol yields ter/-butyl cation at rates too fast to measure. The rates of cleavage of protonated primary and secondary alcohols depend on their structure. Protonated sec-butanol cleaves with rearrangement to (CH3)3C and water slowly at -60°C, protonated isobutanol cleaves with rearrangement at —30°C, and protonated n-butanol at 0°C. It is typical of reactions in superacid media that the most stable ion of a particular class is observed because, under conditions in which the ions are long-lived, intramolecular hydride shifts and rearrangement processes occur that lead ultimately to the most thermodynamically... 

Chiral bromohydrin derivatives reacted under acidic conditions with very high stereoselectivity (essentially stereospecific). This points to a mechanism involving a chiral bromonium ion as the reactive intermediate. The protonation of chloroethane by the carborane superacid H(CHBuClii) proceeds via a shared-proton intermediate that decays by HCl loss to form the carbocation-like ethyl carborane. This reacts with a second EtCl to form the Et2Cl+ cation. The transannular electrophilic bromination of a polycyclic system with two C=C in close proximity was studied by computational methods. The initial bromonium was found to rearrange into more stable carbocations through reaction with the nearby carbon—carbon double bond. 

It is important to point out that thermodynamic equilibria of hydrocarbons and those of derived carbocations are substantially different. Under appropriate conditions (traditional acid catalysts, longer contact time), the thermodynamic equilibrium mixture of hydrocarbons can be reached. In contrast, when a reaction mixture in contact with excess of strong (super) acid is quenched, a product distribution approaching the thermodynamic equilibrium of the corresponding carbocations may be obtained. The two equilibria can be very different. Since a large energy difference in the stability of primary < secondary < tertiary carbocations exists, in excess of superacid solution, generally the most stable tertiary cations predominate. This allows, for example, isomerization of n-butane to isobutane to proceed past the equilibrium concentrations of the neutral hydrocarbons, as the er -butyl cation is by far the most stable butyl cation. 

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