Solvent nucleophilicity measurement

Rate increases with increasing po larity of solvent as measured by its dielectric constant e (Section 8 12) Polar aprotic solvents give fastest rates of substitution solvation of Nu IS minimal and nucleophilicity IS greatest (Section 8 12)... 

We consider first the Sn2 type of process. (In some important Sn2 reactions the solvent may function as the nucleophile. We will treat solvent nucleophilicity as a separate topic in Chapter 8.) Basicity toward the proton, that is, the pKa of the conjugate acid of the nucleophile, has been found to be less successful as a model property for reactions at saturated carbon than for nucleophilic acyl transfers, although basicity must have some relationship to nucleophilicity. Bordwell et al. have demonstrated very satisfactory Brjinsted-type plots for nucleophilic displacements at saturated carbon when the basicities and reactivities are measured in polar aprotic solvents like dimethylsulfoxide. The problem of establishing such simple correlations in hydroxylic solvents lies in the varying solvation stabilization within a reaction series in H-bond donor solvents. 

It is claimed that a measures electrophilic assistance by the solvent, b measures nucleophilic assistance, and that at least three, and sometimes four, parameters are required to perform a dissection into these separate effects. These workers also decomposed Y into ir and a contributions, and N into tt and p contributions. Abraham et al. have compared the performance of Eqs. (8-79) and (8-80) and find that they are about equally successful in correlating data. 

For lack of a better system, the ratio of rate in an ethanol-water mixture of the same Y value as acetic acid to rate in the much less nucleophilic acetic acid, ( Etoii/ acoh) yj has served as a measure of sensitivity to solvent nucleophilicity. More recently, the problem has received renewed attention, and two groups have proposed possible approaches.114 Of the two proposals, that of Bentley, Schadt, and Schleyer is easier to apply. Their scheme defines the solvent nucleophilicity, N, by Equation 5.21, where k is the solvolysis rate constant of methyl tosylate in... 

In contrast to typical mono- or acyclic substrates (e. g.,isopropyl), 2-adaman-tyl derivatives are also found to be insensitive to changes in solvent nucleophilicity. A variety of criteria, summarized in Table 13, establish this point. In all cases, the behavior of 2-adamantyl tosylate is comparable to that observed for its tertiary isomer but quite unlike that observed for the isopropyl derivative. Significant nucleophilic solvent participation is indicated in the solvolysis reactions of the isopropyl system. The 2-adamantyl system, on the other hand, appears to be a unique case of limiting solvolysis in a secondary substrate 296). The 2-adamantyl/ isopropyl ratios in various solvents therefore provide a measure of the minimum rate enhancement due to nucleophilic solvent assistance in the isopropyl system 297). 

The value of kd was obtained from the determination of triplet lifetimes by measuring the decay of phosphorescence and found to be insensitive to changes in solvent polarity. The k2 values derived from Eqs. 10 and 11 were correlated with solvent parameters using the linear solvation energy relationship described by Abraham, Kamlet and Taft and co-workers [18] (Eq. 12), which relates rate constants (k) to four different solvation parameters (1) or the square of the Hildebrand solubility parameter (solvent cohesive energy density), (2) n or solvent dipolarity or polarizability, (3) a, or solvent hydrogen bond donor acidity (solvent electrophilic assistance), and (4) or solvent hydrogen bond acceptor basicity (solvent nucleophilic assistance). 

Solvent coordination number, 134, 403 Solvent effects, 385, 418 initial and transition state, 418 kinetic measures of, 427 Solvent ionizing power parameter, 430 Solvent isotope effects, 272, 300 Solvent nucleophilicity, 431 Solvent participation, covalent, 429 Solvent polarity, 399, 425 Solvent polarity parameter, 436 Solvent properties, 389 Solvent-separated complex, 152 Solvent sorting, 404 Solvent structure, 402 Solvophobic interaction, 395 Solvophobicity parameter, 427 Sound absorption chemical, 145 classical, 145... 

The c coefficients measure the substrate response to nucleophilicity, dY, and electrophilicity, d2. Again, 80% aqueous ethanol was chosen as the standard solvent, and a set of c values was chosen in accord with supposed mechanistic behavior of model substrates cY = 3c2 for methyl bromide, = c2 for tert-butyl chloride, and 3cx = c2 for (C6H5)3CF. This approach was largely unsuccessful, probably in large part because tert-butyl chloride is assumed to be equally sensitive to nucleophilicity and ionizing power (29). The equation predicts, for example, that tertiary, benzhydryl, and bridgehead substrates are more sensitive to solvent nucleophilicity than typical primary and secondary SN2 substrates (31). 

In Chapter 20, F rca iu derives a novel measure of solvent nu-cleophilicities. First, protonation equilibria of benzene derivatives are used to measure acidity of a set of acids. Then, by measurement of the effect of weakly basic solvents (such as trifluoroacetic acid) on these equilibria, basicities of the solvents are calculated. Interestingly, these solvent basicities compare quite well with the solvent nucleophilicities calculated by Peterson (discussed previously). F rca iu also considers the anion-solvating ability of hydrogen-bonding solvents and concludes, in agreement with Chapter 17 and in disagreement with Chapters 18 and 19, that solvent electrophilicity must be considered as a separate variable. 

Product data cited previously (26, 35-37, 41) support independent evidence from kinetic studies (Table III) that HFIP is even less nucleophilic than TFE. Solubilities of alkali metal salts show the same trend in cation solvating power (18, 19). These diverse results warrant emphasis because Abraham et al. have implied (42) that the solvatochromic parameter P is a measure of solvent nucleophilicity. However, the P values for TFE and HFIP are both zero (43), and the relationship between p and solvent nucleophilicity is therefore questionable. 

Quantitative Scales of Solvent Nucleophilicity. Solvolytic studies in solvents of low nucleophilicity led to renewed interest in quantitative measures of solvent nucleophilicity. Peterson and Waller (44) derived a scale of solvent nucleophilicity (Npw) from the rates of displacement by solvent of tetramethylenehalonium ions (VI) in liquid sulfur dioxide. The reaction is approximately half-order in carboxylic acid, possibly because dimer-monomer preequilibrium occurs (44). More recently, hydrolysis of the iodonium salt (VIII) in competition with anionic or solvent nucleophiles was studied. A scale of nucleophilicity relative to water was obtained by quan-... 

Steric Effects on Solvent Nucleophilicity. The N0Ts values (Table III) show that TFA is, by this measure, less nucleophilic than HFIP. As the rate ratios 2-AdOTs (CH3)2CHOTs in TFA and 97% HFIP were very similar, we initially proposed (17) that solvolyses of (CH3)2CHOTs in these two weakly nucleophilic solvents were kc processes. More detailed studies (4, 50) later showed that solvolyses of secondary tosylates in 100% HFIP were closer to limiting (kc) than those in TFA. This apparent reverse of the order of nucleophilicity could be caused by steric effects (50), which could also contribute to the lower precision of the iN/mY equation (5) in correlations of rate data for secondary substrates for example, for 2-propyl tosylate, solvolyses in TFE and HFIP are predicted to be slower than observed, whereas reaction in CF3C02H is predicted to be faster than observed (3). 

The rates of Via and VIb in different solvents gave somewhat different correlations by the equation log (k/k0) = raY0Ts for aqueous ethanols and for other solvents, with m values of 0.82 and 0.78 for the latter, whereas Vic gave a very scattered correlation by this equation (17). Therefore, the rates were correlated by the equation log (k/k0 = mY0Ts + IN (38), where N is a measure of solvent nucleophilicity and l expresses the dependence on N. For Via, VIb, and Vic, values obtained in this way for m and l were 0.90, 0.91, and 0.93 and 0.26, 0.37, and 0.72, respectively, with correlation coefficients of 0.994, 0.994, and 0.977, repsectively. Whatever the merits of the dual correlation with Y0Ts and N, all three substrates showed enhanced rates in the ethanol solvents compared with the trends for the other solvents this result suggests that nucleophilic interactions are important. 

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