General medium effects

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

In order to provide a better estimate of the enantioselectivity of the catalyst, we prepared an authentic sample of (+)-chorismate by kinetic resolution of the racemate with 1F7 (37). Circular dichroism spectroscopy confirmed the identity and high optical purity of the recovered, HPLC-purified compound. Initial rate measurements with the individual isomers show that (-)-chorismate is favored over (+)-chorismate by the antibody by a factor of at least 90 to 1 at low substrate concentrations. The slight rate enhancements above background observed for the (+)-isomer may be due to general medium effects rather than interaction with a specific locus on the antibody surface. To test this possibility we are currently examining the ability of the transition state analog 3 to inhibit rearrangement of this optical isomer. 

While Eqs. (11)-(13) are useful in understanding the general medium effects on reaction rates, their ability to quantitatively predict reaction rates will most likely suffer from inaccuracies similar to those experienced with solubility prediction in mixed solvents. Dielectric constant as a single parameter is not capable of quantitating all interactions among solvent and solute molecules. LePree and Connors reported on the use of a phenomenological approach to predict reaction rates in mixed solvents. The approach is similar to the solubility studies reported by Khossravi and Connors and uses complex equilibria to characterize solvent-solute interactions. 

In addition to a generalized medium effect, micelles also have a charge effect that seems to be related to the reaction mechanism. Most of the experiments were made by using CTAX as the cationic and SDS as the anionic surfactant, and the rate constants for reaction of fully micellar bound substrates are designated k+ and k that is, k+ and k are values of k M in cationic and anionic micelles, respectively (54, 55). 

There is no reason why there should be no general medium effect upon the resistivities. The approximate nature of Eqs. (44) and (48a) gives rise to speculations regarding their improvement, which however do not belong to the field of macro-dynamics. The self diffusion of a medium containing solvated macro-molecules was studied by Wang. ... 

The general principle is to treat AG o, as die sum of eontributions from dre three types of pairwise interactions solvent-solvent interactions, which give rise to the general medium effect, solvent-solute interactions, or the solvation effect, and solute-solute interactions (the intersolute effect in the present eontext). Thus we write. 

S.5.2.4 The general medium effect solvent-solvent Interactions... 

The phenomenological theory has been applied by Skwierczynski to the Et values of the Dimroth-Reichardt betaine, a quantity sensitive to the polarity of the medium. The approach is analogous to the earher development. We need only consider the solvation effect. The solute is already in solution at extremely low concentration, so solute-solute interactions need not be accoxmted for. The solvent cavity does not alter its size or shape dining an electronic transition (the Franck-Condon principle), so the general medium effect does not come into play. We write Ej. of the mixed solvent as a weighted average of contributions from the three states ... 

NickeI(II) (rf ).— The mechanism of complex formation for some metal(ii) cations is now so well established, at least for simple ligands, that such reactions, particularly of nickel(n), are used to probe solvent and salt effects on kinetic patterns. Many of these studies are therefore dealt with in the Chapter on medium effects (Part II, Chapter 13). They include the reactions of nickel(n) and of magnes-ium(n) with chloride in aqueous alcohols, of nickel(ii) with imidazole in aqueous ethanol, with malonate in fructose-water solutions, with thiocyanate in methanol-DMSO mixtures, and with murexide or pada in various micellar media, and of several metal(n) cations with fluoride in aqueous salt solutions." In general, medium effects on observed rate constants (lit) for complex formation operate on the pre-association step (/fos) rather than on the interchange process (A i). The Eigen-Wilkins mechanism operates in all these media it has also been shown to operate for the bidentate ligand Etgdtc in DMSO, and even at the surface of a mercury electrode. ... 

A systematic study designed to improve the initially observed enantiomeric enhancement of 18% led to more favorable reaction conditions. Over 50% e.e. could be realized by running the reaction at — 10°C in the absence of solvent. Increasing the proportion of the europium complex to 10mol% dramatically improved the reaction rate but left the e.e. approximately the same. With such a large and complex lanthanide catalyst, the reason for the asymmetric induction is not well understood based upon observation of a variety of shift reagent catalytic processes, it appears that the role of the catalyst is much more important than a general medium effect. 

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