Solvent effects examples

Peroxycarbamic acid derivatives are very reactive epoxidizing agents that can be employed under mild conditions and are practically independent of the solvent effect examples are the reagent (probably 40) prepared from carbonylditriazole with H2O2 and A-benzoylperoxycarbamic acid The latter is very useful for... 

PEP theory has also been applied to modelling the free energy profiles of reactions in solution. An important example is the solvent effect on the SN2 reaction... 

Although there are examples of enzymes which maintain their catalytic activity even when ciystallized, they normally work in their natural (i.e., aqueous) environment. This is the reason why the majority of the simulations are carried out applying a technique that accounts for solvent effects. But what is the effect of a solvent ... 

The rate constants for the catalysed Diels-Alder reaction of 2.4g with 2.5 (Table 2.3) demonstrate that the presence of the ionic group in the dienophile does not diminish the accelerating effect of water on the catalysed reaction. Comparison of these rate constants with those for the nonionic dienophiles even seems to indicate a modest extra aqueous rate enhancement of the reaction of 2.4g. It is important to note here that no detailed information has been obtained about the exact structure of the catalytically active species in the oiganic solvents. For example, ion pairing is likely to occur in the organic solvents. 

Another example is the acidities of a series of carboxylic acids. It is known that the substitution effect on these compounds also depends on the environment. The behavior of the halo-substituted acetic acids is one of the prototype problems for the solvent effect on acidity The order in strength of the haloacetic acids in the gas phase is... 

Among many examples of the solvent effects on chemical equilibria and reactions, the solvent effect on tautomerization has been one of the most extensively studied. Experi-... 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

A decisive solvent effect is also observed with other a,/ -epoxy ketones. Specifically, 3jS-hydroxy-16a,17a-epoxypregn-5-en-20-one and its acetate do not react with thiocyanic acid in ether or chloroform. However, the corresponding thiocyanatohydrins are formed by heating an acetic acid solution of the epoxide and potassium thiocyanate. As expected, the ring opening reaction is subject to steric hindrance. For example, 3j6-acetoxy-14f ,15f5-epoxy-5) -card-20(22)-enoIide is inert to thiocyanic acid in chloroform, whereas the 14a,15a-epoxide reacts readily under these conditions.Reactions of 14a,15a-epoxides in the cardenolide series yields isothiocyanatohydrins, e.g., (135), in addition to the normal thiocyanatohydrin, e.g., (134). 

Other measures of nucleophilicity have been proposed. Brauman et al. studied Sn2 reactions in the gas phase and applied Marcus theory to obtain the intrinsic barriers of identity reactions. These quantities were interpreted as intrinsic nucleo-philicities. Streitwieser has shown that the reactivity of anionic nucleophiles toward methyl iodide in dimethylformamide (DMF) is correlated with the overall heat of reaction in the gas phase he concludes that bond strength and electron affinity are the important factors controlling nucleophilicity. The dominant role of the solvent in controlling nucleophilicity was shown by Parker, who found solvent effects on nucleophilic reactivity of many orders of magnitude. For example, most anions are more nucleophilic in DMF than in methanol by factors as large as 10, because they are less effectively shielded by solvation in the aprotic solvent. Liotta et al. have measured rates of substitution by anionic nucleophiles in acetonitrile solution containing a crown ether, which forms an inclusion complex with the cation (K ) of the nucleophile. These rates correlate with gas phase rates of the same nucleophiles, which, in this crown ether-acetonitrile system, are considered to be naked anions. The solvation of anionic nucleophiles is treated in Section 8.3. 

To go from experimental observations of solvent effects to an understanding of them requires a conceptual basis that, in one approach, is provided by physical models such as theories of molecular structure or of the liquid state. As a very simple example consider the electrostatic potential energy of a system consisting of two ions of charges Za and Zb in a medium of dielectric constant e. 

Ultimately physical theories should be expressed in quantitative terms for testing and use, but because of the eomplexity of liquid systems this can only be accomplished by making severe approximations. For example, it is often neeessary to treat the solvent as a continuous homogeneous medium eharaeterized by bulk properties such as dielectric constant and density, whereas we know that the solvent is a molecular assemblage with short-range structure. This is the basis of the current inability of physical theories to account satisfactorily for the full scope of solvent effects on rates, although they certainly can provide valuable insights and they undoubtedly capture some of the essential features and even cause-effect relationships in solution kinetics. Section 8.3 discusses physical theories in more detail. 

Another method for studying solvent effects is the extrathermodynamic approach that we described in Chapter 7 for the study of structure-reactivity relationships. For example, we might seek a correlation between og(,kA/l ) for a reaction A carried out in a series of solvents and log(/ R/A R) for a reference or model reaction carried out in the same series of solvents. A linear plot of og(k/iJk ) against log(/ R/ linear free energy relationship (LFER). Such plots have in fact been made. As with structure-reactivity relationships, these solvent-reactivity relationships can be useful to us, but they have limitations. 

Numerous authors have devised multiple linear regression approaches to the eorrelation of solvent effects, the intent being to widen the applieability of the eorrelation and to develop insight into the moleeular factors controlling the eorrelated proeess. For example, Zilian treated polarity as a eombination of effeets measured by molar refraction, AN, and DN. Koppel and Palm write... 

We now consider a type of analysis in which the data (which may consist of solvent properties or of solvent effects on rates, equilibria, and spectra) again are expressed as a linear combination of products as in Eq. (8-81), but now the statistical treatment yields estimates of both a, and jc,. This method is called principal component analysis or factor analysis. A key difference between multiple linear regression analysis and principal component analysis (in the chemical setting) is that regression analysis adopts chemical models a priori, whereas in factor analysis the chemical significance of the factors emerges (if desired) as a result of the analysis. We will not explore the statistical procedure, but will cite some results. We have already encountered examples in Section 8.2 on the classification of solvents and in the present section in the form of the Swain et al. treatment leading to Eq. (8-74). 

The reactions of enamines as 1,3-dipolarophiles provide the most extensive examples of applications to heterocyclic syntheses. Thus the addition of aryl azides to a large number of cyclic (596-598) and acyclic (599-602) enamines has led to aminotriazolines which could be converted to triazoles with acid. Particular attention has been given to the direction of azide addition (601,603). While the observed products suggest a transition state in which the development of charges gives greater directional control than steric factors, kinetic data and solvent effects (604-606) speak against zwitterionic intermediates and support the usual 1,3-dipolar addition mechanism. 

In connection with electronic strucmre metlrods (i.e. a quantal description of M), the term SCRF is quite generic, and it does not by itself indicate a specific model. Typically, however, the term is used for models where the cavity is either spherical or ellipsoidal, the charge distribution is represented as a multipole expansion, often terminated at quite low orders (for example only including the charge and dipole terms), and the cavity/ dispersion contributions are neglected. Such a treatment can only be used for a qualitative estimate of the solvent effect, although relative values may be reasonably accurate if the molecules are fairly polar (dominance of the dipole electrostatic term) and sufficiently similar in size and shape (cancellation of the cavity/dispersion terms). 

Illuminati and Marino reported an interesting example of the dependence of solvent effects on the position of the reacting center relative to the aza group. The rate constants for the reaction of 2- and 4-chloroquinoline with piperidine were compared in three different solvents, methanol, piperidine, and toluene. These data are reported in Table III. Three main points are apparent from these data (a) the different response of the two substrates to the action of the solvent, (b) the rates for 2-chloroquinoline in the three solvents tend to cluster around the highest reactivity level shown by 4-chloroquinoline in... 

A careful use of solvent effects should be of great assistance in synthetic chemistry. For example, it may be predicted from the solvent effects described above that in the reaction of 2,4-dichloroquinohne with piperidine the a y ratio should increase in the less polar solvents, although the result might be obscured by the mutual influence of the two chlorine substituents. Nitro-activated benzenes support this prediction since ortho para ratios of 4.2 in methanol and 69 in benzene were observed in the reaction of 2,4-dichloronitrobenzene with piperidine. ... 

The effect of solvent on the rate, E, and dS can be derived from the data on haloquinolines and their A-oxides (Tables X and XI), on halonitronaphthalenes (Tables XII and XIII), and on halodinitro-naphthalenes (Table XVI). Depending on the nature of the reaction, the relative reactivity of two compounds can be substantially different in different solvents. For example, piperidination of 2-chloroquinoline (Table X, lines 3 and 4) compared to 2-chloroquinoxaline (Table XV,... 

Figure 2.7 Gas clnomatogram obtained for 500 jl1 of diluted gasoline in -pentane inti O-duced by concunent eluent evaporation, using w-heptane as the co-solvent. Reprinted from Journal of High Resolution Chromatography, 11, K. Grob and E. Muller, Co-solvent effects for preventing broadening or loss of early eluted peaks when using concunent eluent evaporation in capillary GC. Part 2 w-heptane in w-pentane as an example , pp. 560-565, 1988, with permission from Wiley-VCH.

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