Solvent effects, and rate of nucleophilic

Discussion Catalyst 62 was synthesized in five steps in 86% overall yield from commercially available starting materials, with a single chromatographic purification [68]. The reaction as described by Jacobsen appears to be relatively insensitive to dilution, reagent stoichiometry, and rate of nucleophile addition. Different low-polarity solvents can be used with little effect on product ee-value. In highly polar aprotic solvents, however, the -values were significantly lower, whereas in protic solvents the imine rapidly decomposed. Aliphatic N-Boc imines were not examined due to a lack of useful methods for their synthesis. The inherent elec-trophilicity of the imine was shown to be important, with less-electrophilic N-allyl... 

The protic-dipolar aprotic solvent effect on rates of 8 2 reactions of different charge type is summarized in Table 15. Polar substrates and nucleophiles, which are not H-bohd donors, and anions, which are strong H-bond acceptors, have been deliberately chosen to illustrate the solvent effect. 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

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],... 

A principle applied in physical organic chemistry to account for the effect of solvation on the rates of nucleophilic reactions. This theory states that an increase in the ion-solvating power of the medium will tend to speed up the formation and concentration of charges, thereby inhibiting their breakdown or diffusion. This approach is predicated on the idea that a more polar solvent can potentially stabilize ionic intermediates and alter chemical reactivity. 

Studies of relative rates, activation parameters, kinetic isotope, and solvent isotope effects, and correlation of rates with an acidity function, have elucidated the mechanisms of cyclization of diacetyl aromatics (23-26) promoted by tetramethyl-ammonium hydroxide in DMSO.32 Rate-determining base-catalysed enolate anion formation from (24-26) is followed by relatively rigid intramolecular nucleophilic attack and dehydration whereas the cyclization step is rate determining for (23). 

Steric effects provide examples of hard cases with respect to predicting reactivities. The same might be said to be true of solvent effects for reactions of n-nucleophiles or carbanions. However, while values of N may vary with solvent the differences can be exploited, for example, in promoting a desired reaction in synthesis. Moreover, in attempting to interpret solvent effects, it is possible that comparing measurements of reaction rates and (preferably)... 

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. ... 

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