Solvent Effects on other Equilibria

Not only tautomeric equilibria are subject to considerable solvent effects. Other equilibria, such as rotational and conformational equilibria [81-83], cisitrans (or E/Z) isomerization, valence isomerization [84], ionization, dissociation, and association [85] (some of which are considered in Section 2.6), complex equilibria [86, 163, 262, 263], acid/base equilibria [264, 265] etc., are also strongly affected by the medium. Only a small number of representative examples will be considered in this Section in order to give an idea of how solvents can affect these different kinds of equilibria. 

1 Solvent Effects on Bronsted Acid/Base Equilibria [8-13,104-108, 264, 265] 

Sections 3.3.1 and 4.2.1 dealt with Bronsted acid/base equilibria in which the solvent itself is involved in the chemical reaction as either an acid or a base. This Section describes some examples of solvent effects on proton-transfer (PT) reactions in which the solvent does not intervene directly as a reaction partner. New interest in the investigation of such acid/base equilibria in non-aqueous solvents has been generated by the pioneering work of Barrow et al. [164]. He studied the acid/base reactions between carboxylic acids and amines in tetra- and trichloromethane. A more recent compilation of Bronsted acid/base equilibrium constants, determined in up to twelve dipolar aprotic solvents, demonstrates the appreciable solvent influence on acid ionization constants [264]. For example, the p.Ka value of benzoic acid varies from 4.2 in water, 11.0 in dimethyl sulfoxide, 12.3 in A,A-dimethylformamide, up to 20.7 in acetonitrile, that is by about 16 powers of ten [264]. 

According to Eq. (4-29), protons can be transferred from Bronsted acids A—H to bases B via the hydrogen-bonded covalent and ionic complexes (a) and (b), depending on both the relative acidity and basic strength of A—H and B, respectively, and the solvation capability of the surrounding medium [265, 266]. Eq. (4-29) is simplified because not only 1 1 complexes but 1 2 and higher complexes can be formed in solution. 

Another rather simple example is the acid/base reaction between tropolone and triethylamine, which has been studied using IR and H NMR spectroscopy in various solvents [171], 

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The use of the Gutmann41 donor and acceptor numbers for describing solvent effects on rates, equilibria and other physicochemical properties has met with some success in organic chemistry. 62 63 However, because the donor and acceptor numbers of mixtures of solvents can not be inferred from the values of the pure solvents but must be determined experimentally, and also because the relationships describing the effects of solvent on chemical reactions were found to apply to non-associated solvents of medium to high dielectric constant, there has been very little attempt to introduce this approach into inorganic systems where the commonly used solvents are protic, i.e. associated. However, one such reaction that has been studied was63 equation (34) ... 

The use of the Gutmann" donor and acceptor numbers for describing solvent effects on rates, equilibria and other physicochemical properties has met with some success in organic chemistry. 

At a more detailed level, we note that the solvent effects on the optical rotation have the same origins as solvent effects on the energy itself, as described in detail in other contributions to this book. Most other studies of solvent effects on natural optical activity have focused on the electrostatic contributions. These contributions can be partitioned into direct effects arising from the influence of the dielectric environment on the electronic density of the solute, and into indirect effects arising from the relaxation of the nuclear structure in the solvent. For conformationally flexible molecules, we may also consider a third possible solvent effect due to the changes in the conformational equilibria when going from the gas phase to solution. 

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. ... 

Solvents effect equilibria and rates of reactions, which is not only important in synthesis and catalysis, but in other processes such as the rate of electron transfer. Thus far, the effect of chiral solvents on chiral recognition and enantioselective catalysis has not proven effective, but without further experiments, it is too early to draw any firm conclusions.10 There are many theories and rules relating to solvent effects on reactions, the majority developed with organic processes in mind, and discussions of these are not relevant here. Rather, the importance of solvent selection relevant to coordination chemistry will be illustrated with some key examples. 

It must be stressed that AG° values for 57 and 58 in the same solvent (e.g., MeOH or EtOH 95%) can differ by more than 1.5kJ/moI. Such differences seem to arise from different solvent effects on the two equilibria under scrutiny (despite the very similar structure of 57 and 58). This point of view is strongly supported by the fact that the relevant AH° and AS° values for 57 and 58 are also different. They are 5.19 0.23 kJ/mol and 10.6 + 0.7 J/mol/K for 57 and 5.71 0.12 kJ/mol and 13.8 0.4 J/mol/K for 58, respectively, in 6 4 (v/v) benzene-methanol solution (54). We also observed analogous differences between the equilibria in other derivatives of 1,3-dithianes (54, 98). Support for the hypothesis presented above comes from the work of Tschierske et al. (38), who showed that AG° values for dioxanes 59 and 60 (Scheme 21) differ... 

These same equations formally bring the quantitative study of solvent effects on equilibria and rates of elementary processes to that of solvent effects on the chemical potentials of the dissolved species or, in other words, to that of the energetics of solvent-solute interactions. In the forthcoming section, we restrict ourselves to the study of polar species (excluding free ions ) in polar... 

On the other hand, the effects on dissociation equilibria of the presence of small quantities of water in common solvents used in the ordinary analytical laboratory have to be considered. The presence of water decreases the pH scale of the solvent according to the water concentration and should be controlled. 

Solvent effects on acid-base equilibria are naturally most marked when the solvent itself enters into the equilibrium, as is the case for the conventional definition of acid strength by means of the equilibrium A-fSH B4-SH2 (where SH is the solvent). The existence of such an equilibrium implies that the solvent has some basic properties. Similarly, the occurrence of the reaction B + SH A-f S (where S is the anion derived by abstracting a proton from the solvent) implies that the solvent is acidic. The most important factor determining qualitative behaviour in a wide range of solvents is the acidic or basic nature of the solvent, as determined by its chemical nature. In a preliminary classification we can neglect other factors, notably the effect of dielectric constant on the association of ions or the forces between them. 

More recently it has become apparent that proton equilibria and hence pH can be equally important in aprotic and other non-aqueous solvents. For example, the addition of a proton donor, such as phenol or water, to dimethylformamide has a marked effect on the i-E curve for the reduction of a polynuclear aromatic hydrocarbon (Peover, 1967). In the absence of a proton donor the curve shows two one-electron reduction waves. The first electron addition is reversible and leads to the formation of the anion radical while the second wave is irreversible owing to rapid abstraction of protons from the solvent by the dicarbanion. 

In conjugated molecules one or other of the possible protonation sites may be more or less favoured by solvation effects and for this reason sites of protonation are often solvent dependent. In some instances, similar stability of two possible cations results in tautomeric equilibria and these too may be solvent dependent. Just as solute-solvent interactions have an effect on the relative stability of two possible cations formed from a conjugated molecule, so in solid salts stability relationships depend on the mode of packing of ions, which determines interactions with the nearest neighbours. Therefore the types of cation observed in solid salts are not necessarily the most stable ones in solution. 

Another important type of observation from conductance experiments involves the effect of small quantities (1-2% W/W) of additives on dissociative equilibria. Obviously in any study where the equilibrium between two reactive species is relevant the possible disturbance of that equilibrium by traces of other components in the system is very important In kinetic studies of polymerisations it is usual to carry out experiments in which the concentrations of both initiator and monomer are varied systematically. While it is anticipated that the former will effect the position of equilibrium between free ions and ion pair species, it is easily overlooked that the latter may also have a significant influence, particularly if the polarity of the monomer differs substantially from that of the solvent... 

The SM2/AM1 model was used to examine anomeric and reverse anomeric effects and allowed to state that aqueous solvation tends to reduce anomeric stabilization [58]. Moreover, SM2/AM1 and SM3/PM3 models were accounted for in calculations of the aqueous solvation effects on the anomeric and conformational equilibria of D-glucopy-ranose. The solvation models put the relative ordering of the hydroxymethyl conformers in line with the experimentally determined ordering of populations. The calculations indicated that the anomeric equilibrium is controlled primarily by effects that the gauche/trans 0-C6-C5-0 hydroxymethyl conformational equilibrium is dominated by favorable solute-solvent hydrogen bonding interactions, and that the rotameric equilibria were controlled mainly by dielectric polarization of the solvent [59]. On the other hand, Monte Carlo results for the effects of solvation on the anomeric equilibrium for 2-methoxy-tetrahydropyran indicated that the AM1/SM2 method tends to underestimate the hydration effects for this compound [60]. 

If the purpose of a calculation is to probe the inherent properties of a molecule as a thing in itself, or of a phenomenon centered on isolated molecules, then we do not want the complication of solvent. For example, a theoretically oriented study of the geometry and electronic structure of a novel hydrocarbon, e.g. pyramidane [6], or of the relative importance of diatropic and paratropic ring currents [7], properly examines unencumbered molecules. On the other hand, if we wish, say, to calculate from first principles the pZa of acids in water, we must calculate the relevant free energies in water [8]. Noteworthy too is the fact that solvation, in contrast to gas phase treatments, is somewhat akin to molecules in bulk, in crystals [9]. Here a molecule is solvated by its neighbors in a lattice, although the participants have a much more limited range of motion than in solution. Rates, equilibria, and molecular conformations are all affected by solvation. Bachrach has written a concise review of the computation of solvent effects with numerous apposite references [10]. 

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