Nucleophilic substitution solvent/solvation effects

For carbon-carbon bond-formation purposes, S 2 nucleophilic substitutions are frequently used. Simple S 2 nucleophilic substitution reactions are generally slower in aqueous conditions than in aprotic organic solvents. This has been attributed to the solvation of nucleophiles in water. As previously mentioned in Section 5.2, Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions (Scheme 6.1). In alkylations of phenoxide ions by benzylic chlorides, S/y2 substitutions can occur both at the phenoxide oxygen and at the ortho and para positions of the ring. In fact, carbon alkylation occurs in water but not in nonpolar organic solvents and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para). The effects of phenol substituents and of cosolvents on the rates of the competing alkylation processes... 

The enhanced nucleophilicity of weakly solvated fluoride ions, solubilized in non-polar solvents as their alkali metal salts by [18]crown-6, has been studied. The wide range of SN2 reactions possible with this system is illustrated in Table 3. Under equivalent conditions in the absence of crown ether no substitution occurs. Similar effects are seen with many nucleophiles which, even if soluble in the solvent employed, show increased nucleophilic substitution rates in the presence of crown ethers (B-78MI52104). However, the monocyclic crown compound exposes the cation on two sides to approach by the counteranion (see Figures lb, c and d for illustrations of this effect in the crystalline state). The resultant ion pairs that form in non-polar solvents reduce the reactivity of the anion. 

Increasing die effective nucleophilicity of an ion allows S 2 substitution reactions to occur under milder conditions. An anion will become a better nucleophile when it is less effectively solvated and when it is further separated from its counterion. Methods that can achieve these changes include selection of a tetraafldammomum counterion [see Eqs. (6) and (6)], addition of a crown ether or a cryptand [see Eq. (7)], and use of a solvent that effectively solvates cations [see Eqs. (1) and (2)]. 

Short-lived organic radicals, electron spin resonance studies of, 5, 53 Small-ring hydrocarbons, gas-phase pyrolysis of, 4, 147 Solid state, tautomerism in the, 32, 129 Solid-state chemistry, topochemical phenomena in, 15, 63 Solids, organic, electrical conduction in, 16, 159 Solutions, reactions in, entropies of activation and mechanisms, 1, 1 Solvation and protonation in strong aqueous acids, 13, 83 Solvent effects, reaction coordinates, and reorganization energies on nucleophilic substitution reactions in aqueous solution, 38, 161 Solvent, protic and dipolar aprotic, rates of bimolecular substitution-reactions in,... 

The study of reactions of isolated ions and molecules in the gas phase without interference from solvents has led to very surprising results. Gas-phase studies of proton-transfer and nucleophilic substitution reactions permit the measurement of the intrinsic properties of the bare reactants and make it possible to distinguish these genuine properties from effects attributable to solvation. Furthermore, these studies provide a direct comparison of gas-phase and solution reactivities of ionic reactants. It has long been assumed that solvation retards the rates of ion-molecule reactions. Now, using these new techniques, the dramatic results obtained make it possible to show the extent of this retardation. For example, in a typical Sn2 ion-molecule reaction in the gas phase, the substrates react about 10 times faster than when they are dissolved in acetone, and about 10 ( ) times faster than in water cf. Table 5-2 in Section 5.2). 

In solution, all participants in a chemical reaction are solvated the reactants and the products—and the transition state. Our examination of these must include any solvent molecules that help make up the structures and help determine their stabilities. And so, in Chapter 7, using as our examples the nucleophilic substitution reactions the students have just studied, we show how reactivity— and, with it, the course of reaction—is affected by the solvent. We show just how enormous solvent effects can be that the presence of a solvent can speed up—or slow down—a reaction by a factor of l(P that a change from one solvent to another can bring about a miUionfold change in reaction rate. 

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