Y, solvent parameter

Predicting the solvent or density dependence of rate constants by equation (A3.6.29) or equation (A3.6.31) requires the same ingredients as the calculation of TST rate constants plus an estimate of and a suitable model for the friction coefficient y and its density dependence. While in the framework of molecular dynamics simulations it may be worthwhile to numerically calculate friction coefficients from the average of the relevant time correlation fiinctions, for practical purposes in the analysis of kinetic data it is much more convenient and instructive to use experimentally detemiined macroscopic solvent parameters. 

Langhals has described a remarkable relationship of most of the empirieal solvent parameters [Z. t (30), Y, ete.] to composition in binary solvent mixtures ... 

The Aspen NRTL-SAC solvent database was identified from the list of solvents presented in the pharmaceutical based International Committee on Harmonization s guidelines for residual solvents in API [28], Hexane, Acetonitrile and Water were selected as the basis for the X, Y and Z segments respectively, the binary interaction parameters for the segments together with molecular descriptors in terms of X,Y and Z segments were then regressed from experimental vapour-liquid and liquid-liquid equilibrium data from the Dechema database. The list of solvent parameters that were used in the case study are given in Table 13. 

Three solvent parameters are shown to contribute to these variations the polarity Y, jc, the polarizability P, 8, and the acidity E, a. 

Evaluation of solvent-sensitive properties requires well-defined referena i ran eis. A macroscopic parameter, dielectric constant, does not always give interpretable correlations of data. The first microscopic measure of solvent polarity, the Y-value, based on the solvolysis rate of t-butyl chloride, is particularly valuable for correlating solvolysis rates. Y-values are tedious to measure, somewhat complicated in physical basis, and characterizable for a limited number of solvents. The Z-value, based on the charge-transfer electronic transition of l-ethyl-4-carbomethoxy-pyridinium iodide , is easy to measure and had a readily understandable physical origin. However, non-polar solvent Z-values are difficult to obtain b use of low salt solubility. The Et(30)-value , is based on an intramolecular charge-transfer transition in a pyridinium phenol b ne which dissolves in almost all solvents. We have used the Er(30)-value in the studies of ANS derivatives as the measure of solvent polarity. Solvent polarity is what is measured by a particular technique and may refer to different summations of molecular properties in different cases. For this reason, only simple reference processes should be used to derive solvent parameters. 

Menet et al. [6] have compared performances of CCC and preparative HPLC owing to a separation of two antibiotics X and Y. The CCC apparatus used was a centrifugal partition chromatograph (CPC, Sanki LLN) of 250 mL internal volume. For this purpose, classical parameters of preparative-scale chromatography were calculated experimental duration, including the sample preparation and the separation time, solvent consumption, including the volume of the mobile phase, the stationary phase and the injection solvent, and purity of the purest fraction in Y. The parameter purity in Y was chosen because Y is the solute most difficult to purify because of its physical properties (particularly hydrophobicity) which are close to those of the main impurities. The hourly yield (g/h) is defined as the ratio of the recovered quantity to the experimental duration. The volumic yield (g/L) is defined as the ratio of the recovered quantity to the solvent consumption. Table 1 summarizes the results of... 

The values of Z and 7 values belong to a class of solvent parameters based on various standard physical processes (electromagnetic transition, dielectric constant, NMR chemical shift, etc.. In the context of similarity these parameters are not directly useful for mechanistic studies because the reference process is a physical property rather than a chemical reaction. The parameters Z and are often linearly related to the Grunwald-Winstein Y value (Figure 14) and provide a secondary definition of Y values which are inaccessible via the chemical definition of those parameters. 

In Peterson et al. s 1977 work (32), they showed that the early equation of Swain et al. (31), equation 3, could be recast in terms comparable to those of the N-Y equation, equation 4. In Chapter 21, Peterson applies similar techniques to show that the A and B values of the recent Swain LFER, equation 5, can also be converted to N and Y values. Some interesting conclusions result from this investigation. By use of the Swain data, the advantages of the statistical approach are extended to the more narrowly defined N and Y values. A major criticism of the Swain approach is that most of the A and B parameters appear, from this work, to be artifacts that arise from the extraction of two parameters from data sets that need only one solvent parameter for correlation for most solvents, the A and B values are proportional. Only for hydroxylic and amine solvents are the A and B parameters shown to be meaningful. Peterson concludes that the A-B values represent two independent sets of data, one set that can be converted into N and Y, and another set that appears to be meaningless. For Swain s rebuttal to related arguments, see reference 40a. 

From the deviations, a scale of nucleophilicity was derived. Halogenated acetic acids were included, on the basis of reactivities with halonium ions. Other scales appeared from the Schleyer group (5, 6) at about the same time. The various nucleophilicity scales were used to correlate solvolysis rates by now familiar four-parameter equations AG = N + mY or AG = sN + mY. (G — free energy N = solvent nucleophilicity Y = solvent ionizing power s = sensitivity m = sensitivity.) Previously, parameters for such equations had not been determined. 

If the nonreaction solvents (the majority of the Swain solvents) exhibit linearity between two solvent parameters, the solvent properties can be represented by only one parameter. For the nonreaction solvents, the converted N values are independent of the converted Y values only to the extent that small deviations from linearity exist in the plot of N versus Y. The scaling... 

---