Solvent on Selectivity

At times, selectivity changes drastically with a change in solvent, providing one of the best means available for controlling selectivity. The powerful influence of solvent is insufficiently appreciated and its efficacy often overlooked. There are many examples, so many that it is difficult to make encompassing generalities. 

One very useful, although fallible, generality is that in a series of solvents the extremes of selectivity will be found at the extremes of the dielectric constant with two provisos (a) alcohols sometimes should be considered separately. 

Selected data of Wuesthoff and Richborn 112) on the hydrogenation of the vinylcyclopropane 4 further illustrates the effect of solvent on selectivity as well as the reason for the second proviso. 

The basic solution, which now contains the enolate ion, gives much different results than those obtained in neutral media. More of the hydrogenolysis product (6) is obtained in polar 50% aqueous ethanol than is obtained in the 

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Scheme 2 shows a substitution reaction which is often carried out with solid carbonate in suspension, which is easily removed after reaction by a simple filtration. This reaction was chosen not only to test the handling of suspensions, but also to investigate the influence of different solvents on selectivity and work-up. The results are shown in Table 3. 

A detailed discussion of the influence of pressure, temperature, catalyst variations, and the removal of water from the reaction mixture, as well as the influence of different solvents on selectivity and reaction rates, may be found in [12]. For more details about the reaction mechanism and the chemistry of palladium-alkene-CO complexes cf. [13, 14, 17]. 

Table 4-10. Permeation Rates of Organic Solvents on Selected Plastics ...

In 1961 Berson et al. were the first to study systematically the effect of the solvent on the endo-exo selectivity of the Diels-Alder reaction . They interpreted the solvent dependence of the endo-exo ratio by consideririg the different polarities of the individual activated complexes involved. The endo activated complex is of higher polarity than the exo activated complex, because in the former the dipole moments of diene and dienophile are aligned, whereas in the latter they are pointing in... 

The second important influence of the solvent on Lewis acid - Lewis base equilibria concerns the interactions with the Lewis base. Consequently the Lewis addity and, for hard Lewis bases, especially the hydrogen bond donor capacity of tire solvent are important parameters. The electron pair acceptor capacities, quantified by the acceptor number AN, together with the hydrogen bond donor addities. O, of some selected solvents are listed in Table 1.5. Water is among the solvents with the highest AN and, accordingly, interacts strongly witli Lewis bases. This seriously hampers die efficiency of Lewis-acid catalysis in water. 

First of all, given the well recognised promoting effects of Lewis-acids and of aqueous solvents on Diels-Alder reactions, we wanted to know if these two effects could be combined. If this would be possible, dramatic improvements of rate and endo-exo selectivity were envisaged Studies on the Diels-Alder reaction of a dienophile, specifically designed for this purpose are described in Chapter 2. It is demonstrated that Lewis-acid catalysis in an aqueous medium is indeed feasible and, as anticipated, can result in impressive enhancements of both rate and endo-exo selectivity. However, the influences of the Lewis-acid catalyst and the aqueous medium are not fully additive. It seems as if water diminishes the catalytic potential of Lewis acids just as coordination of a Lewis acid diminishes the beneficial effects of water. Still, overall, the rate of the catalysed reaction... 

Salting-out crystalli tion operates through the addition of a nonsolvent to the magma ia a crystallizer. The selection of the nonsolvent is based on the effect of the solvent on solubiHty, cost, properties that affect handling, iateraction with product requirements, and ease of recovery. The effect of a dding a nonsolvent can be quite complex as it iacreases the volume required for a given residence time and may produce a highly nonideal mixture of solvent, nonsolvent, and solute from which the solvent is difficult to separate. 

The optimum conditions of heavy metals extraction from ordinary chernozem in different solvents are selected both at determination of the mobile forms of elements, and at an estimation of their gross contents. It is established, that the stage of elements extraction in the greater measure depends on time of action and intensity of ultrasonic, nature of selected solvents and determinated elements. It is shown, that for all type of soils the time of low frequency ultrasonic action does not exceed 10 minutes, and the intensity ranges in an interval of 3-4 W/cm. ... 

The effect of temperature, although significant, is not nearly as great as that from the ethanol content and is greatest at low concentrations of the polar solvent. It is clear, that the solute retention is the least at high ethanol concentrations and high temperatures, which would provide shorter analysis times providing the selectivity of the phase system was not impaired. The combined effect of temperature and solvent composition on selectivity, however, is more complicated and to some extent... 

It is seen that the curves in Figure (24) become horizontal between 40°C and 45 °C as predicted by the theory. It is also clear that there is likely source of error when exploring the effect of solvent composition on retention and selectivity. It would be important when evaluating the effect of solvent composition on selectivity to do so over a range of temperatures. This would ensure that the true effect of solvent composition on selectivity was accurately disclosed. If the evaluation were carried out at or close to the temperature where the separation ratio remains constant and independent of solvent composition, the potential advantages that could be gained from an optimized solvent mixture would never be realized. 

Typical normal-phase operations involved combinations of alcohols and hexane or heptane. In many cases, the addition of small amounts (< 0.1 %) of acid and/or base is necessary to improve peak efficiency and selectivity. Usually, the concentration of polar solvents such as alcohol determines the retention and selectivity (Fig. 2-18). Since flow rate has no impact on selectivity (see Fig. 2-11), the most productive flow rate was determined to be 2 mL miiT. Ethanol normally gives the best efficiency and resolution with reasonable back-pressures. It has been reported that halogenated solvents have also been used successfully on these stationary phases as well as acetonitrile, dioxane and methyl tert-butyl ether, or combinations of the these. The optimization parameters under three different mobile phase modes on glycopeptide CSPs are summarized in Table 2-7. 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

To simplify our discussion, we will consider two specific cases spherical micelles in a selective solvent and selective adsorption on to a solid surface from a selective solvent. 

This subject has been associated with the development of the or and type scales almost from the start74 (see Section II.B), but the first paper in which sulfinyl and sulfonyl groups played a part appears to have been one by Taft and coworkers in 196367. The main object of this paper was to study the effect of solvent on the inductive order by 19F NMR measurements on a large number of mcta-substituted fluorobenzenes in a great variety of solvents. The relationship between the NMR shielding parameter and selected systems as equation 10 ... 

Of course, the influence of organic solvents on enzyme enantioselectivity is not limited to proteases but it is a general phenomenon. Quite soon, different research groups described the results obtained with lipases [28]. For instance, the resolution of the mucolytic drug ( )-trans-sobrerol (11) was achieved by transesteriflcation with vinyl acetate catalyzed by the lipase from Pseudomonas cepacia adsorbed on celite in various solvents. As depicted in Scheme 1.3 and Table 1.5, it was found that t-amyl alcohol was the solvent of choice in this medium, the selectivity was so high ( >500) that the reaction stopped spontaneously at 50% conversion giving both +)4rans-sobrerol and (—)-trans-sobrerol monoacetate in 100% optical purity [29]. 

The experimental evidences that medium engineering might represent an efficient method to modify or improve enzyme selectivity (alternative to protein engineering and to the time-consuming search for new catalysts) were immediately matched by the search for a sound rationale of this phenomenon. The different hypotheses formulated to try to rationalize the effects of the solvent on enzymatic enantioselectivity can be grouped into three different classes. The first hypothesis suggests that... 

However, whatever the mechanism of action is, the effect of solvents on enzyme selectivity is sometimes really dramatic. For example, Hrrose et al. [42] reported that in the Pseudomonas species lipase-catalyzed desymmetrization of prochiral... 

Calo et al. (ref. 5) studied solvent effects on selective bromination of phenol with NBS and found the selectivity of bromination depended on the polarity of the solvents. But thereafter no investigation concerning the solvent effects was reported. We report the effects systematically. 

Solid-surface room-temperature phosphorescence (RTF) is a relatively new technique which has been used for organic trace analysis in several fields. However, the fundamental interactions needed for RTF are only partly understood. To clarify some of the interactions required for strong RTF, organic compounds adsorbed on several surfaces are being studied. Fluorescence quantum yield values, phosphorescence quantum yield values, and phosphorescence lifetime values were obtained for model compounds adsorbed on sodiiun acetate-sodium chloride mixtures and on a-cyclodextrin-sodium chloride mixtures. With the data obtained, the triplet formation efficiency and some of the rate constants related to the luminescence processes were calculated. This information clarified several of the interactions responsible for RTF from organic compounds adsorbed on sodium acetate-sodium chloride and a-cyclodextrin-sodium chloride mixtures. Work with silica gel chromatoplates has involved studying the effects of moisture, gases, and various solvents on the fluorescence and phosphorescence intensities. The net result of the study has been to improve the experimental conditions for enhanced sensitivity and selectivity in solid-surface luminescence analysis. 

Ab initio methods allow the nature of active sites to be elucidated and the influence of supports or solvents on the catalytic kinetics to be predicted. Neurock and coworkers have successfully coupled theory with atomic-scale simulations and have tracked the molecular transformations that occur over different surfaces to assess their catalytic activity and selectivity [95-98]. Relevant examples are the Pt-catalyzed NO decomposition and methanol oxidation. In case of NO decomposition, density functional theory calculations and kinetic Monte Carlo simulations substantially helped to optimize the composition of the nanocatalyst by alloying Pt with Au and creating a specific structure of the PtgAu7 particles. In catalytic methanol decomposition the elementary pathways were identified... 

Note Solvent classification into groups based on solvent polarity selectivity parameters proton acceptor, proton donor, x dipole interactors) and solvent strength on alumina nd on silica gel 0. Physical constants viscosity (t)), surface tension (y), dielectric constant (8). Solvatochromic polarity parameters 7, j.(30) and Ej. ... 

Solvent selectivity is seen as the factor that distinguishes individual solvents that have solvent strengths suitable for separation. In reality, separations result from the competition between the mobile and stationary phases for solutes based on the differences of all intermolecular interactions with the solute in both phases. Solvents can be organized on selectivity scales that are useful for initial solvent selection, but in a chromatographic separation the properties of the stationary phase must be taken into consideration. Methods that attempt to model chromatographic separation need to consider simultaneously mobile and stationary phase properties [38]. 

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