Solvent effects, and rate of nucleophilic substitution

The direction and extent of the effect of solvent polarity on reaction rates of nucleophilic substitution reactions are summarized by the Hughes-Ingold rules, shown in Table 1.9 [26], These rules do not account for the entropic effects or any specific solvent-solute interactions such as H-bonding, which may lead to extra stabilization of reactants or transition states [27],... 

Salt Effects. Dissolved salts may also affect the rates of nucleophilic substitution and elimination in aqueous solution through their influence on the relative stabilities of the reactants, transition states, and other reactive intermediates. The nonspecific effects of increasing ionic strength are therefore analogous to those arising from increasing solvent polarity (281. and are sometimes referred to as "salt effects."... 

Neglecting solvent effects is extremely hazardous. Equilibria and kinetics can be dramatically altered by the nature of the solvent For example, the rate of nucleophilic substitution reactions spans 20 orders of magnitude in going from the gas phase to polar and nonpolar solvents. A classical example of a dramatic solvent effect on equilibrium is the tautomerism between 1 and 2. In the gas phase, the equilibrium lies far to the left, while in the solution phase, 2 dominates because of its much larger dipole moment." Another classical example is that the trend in gas-phase acidity of aliphatic alcohols is reverse of the well-known trend in the solution phase in other words, in the solution phase, the relative acidity trend is R3COH < R2CHOH < RCH2OH, but the opposite is true in the gas phase. ... 

Secondary haloalkanes may react by either an Sfjl or an 8 2 mechanism, depending on the nucleophile and solvent. The competition between electronic and steric factors and their effects on relative rates of nucleophilic substitution reactions of haloalkanes are summarized in Figure 7.3. 

Tertiary haloalkanes react by an S l mechanism because 3° carbocation intermediates are relatively stable and tertiary haloalkanes are protected against backside attack. In fact, 3° haloalkanes are never observed to react by an mechanism. In contrast, halomethanes and primary haloalkanes are never observed to react by an mechanism. They have little crowding around the reaction site and react ty an Sj 2 mechanism because methyl and primary carbocations are unstable. Secondary haloalkanes may react by either 8, 1 or 8, 2 mechanisms, depending on the nucleophile and solvent. The competition between electronic and steric factors and their effects on relative rates of nucleophilic substitution reactions of haloalkanes are summarized in Figure 9.3. 

The solubility of ionic substances in relatively nonpolar aprotic solvents can be greatly enhanced by using catalytic quantities of macrocyclic polyethers, such as 18-crown-6, the structure of which is shown in Fig. 5.5. These macrocyclic ethers selectively solvate the cation, both enhancing solubility and also leaving the anion in a very weakly solvated state. The anions behave under these conditions as highly reactive species, sometimes termed naked anions. A study of the relative rates of nucleophilic substitution on benzyl tosylate by potassium salts in acetonitrile in the presence of 18-crown-6 revealed a pronounced leveling effect. " All the potassium halides (fluoride, chloride, bromide, and iodide) were approximately equal in their reactivity. Potassium acetate was observed to be almost ten times more reactive than potassium iodide under these conditions—a reversal of the normal reactivity of acetate ion versus iodide ion in nucleophilic substitution reactions. As measured by cHji values in Table 5.5, iodide is 3 log units, i.e., 10 times, more reactive than acetate ion in the protic solvent methanol. 

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,... 

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, 5,173 Solvent-induced changes in the selectivity of solvolyses in aqueous alcohols and related mixtures, 27, 239... 

The rate of nucleophilic addition to cyclopropyl-substituted cations is little affected by the cyclopropyP Thus there was little difference in the rate of reaction of Ph l HR and PhCR2 (R = Ph or c-Pr) with NH3, w-Pr3N, and n-Bu N in methylene chloride solvent except for Ph3C which was less reactive by factors of 10-20. Steric factors were evidently responsible for the latter effect ... 

The effect of a solvent on the rate of the two-step aromatic nucleophilic substitution reactions of primary or secondary amines are sometimes complicated by the acid-base equilibrium (30) and by the fact that the transition state,... 

Apart from these inherent properties, which affect the rate of SN1 substitution, there are several external factors that may have an effect. First, it is preferable to have a weak incoming nucleophile. This is because, if it were strong, then it might attack the carbon centre that is to form the carbonium ion, and so change the mechanistic pathway from unimolecular to bimolecular. Hence, a weak nucleophile favours an SN1 substitution route, because it does not promote an SN2 route. There are, however, other important factors concerning the solvent. Suggest whether a solvent of high or low polarity would favour the SN1 reaction. 

Effect of solvent on rate Rate increases with increasing polarity of solvent as measured by its dielectric constant e. (Section 8.12) Polar aprotic solvents give fastest rates of substitution solvation of Nu is minimal and nucleophilicity is greatest. (Section 8.12)... 

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