Taft treatment

If the assumptions underlying the Taft treatment of the separation of electronic and steric effects are valid, then the relative rates of acid-catalyzed reactions of esters should be a measure of the steric effect. Taft " accordingly defined a steric constant Es by Eq. (7-52). 

In conclusion, the present treatment offers the opportunity to evaluate the electronic effects played on completely changing one of the ligands present in a certain metal complex (in contrast to the Hammett or Taft treatment, which make reference to the substituents of the same ligand). 

The alternative approach is the attempt to quantify substituent effects, and this has been most successfully done by the Hammett equation and its various extensions (Hammett, 1970). Here one set of free energy data is compared with another set. One set is taken as standard (originally the dissociation constants of benzoic acids) and other rate or equilibrium data are compared (by logarithmic plots). So much has been written about this treatment that discussion here is unnecessary. Absolute values of a (the substituent constant) are not to be expected, in fact one would expect a different a for every reaction (i.e. for every p). In the present context it is important to note that both the Hammett equation and the closely related Taft treatment are based on systems where solvation is known to be important and therefore the application of these treatments using parameters derived from solution phase studies to reactions in the gas phase may be of uncertain value. 

Fig. 10. Taft treatment of the acetolysis of secondary alkyl and l-aryl-2-propyl tosylates. [Lancelot, C. J., Cram, D. Y., Schleyer, P. v. R., in Carbonium ions. Olah,...

Application of the Taft treatment to cyclic and bicyclic systems suffers from the availability of a values only for noncyclic substrates. The Foote-Schleyer correlation238, 239 was proposed as a means for estimating acetolysis rates of cyclic substrates ... 

The solvent may also drastically affect the anchimerically assisted fraction in nucleophilically assisted ionization reactions. As the solvent becomes more nucleophilic, there is greater solvent participation, if possible, at the expense of neighboring group assistance. The data in Table 4 are illustrative of this effect. It is obvious that in both formic acid and acetic acid there is considerable MeO-5 and MeO-6 nucleophilic participation. In ethanol, however, the ratio kjk is diminished as solvent attack (fcj becomes more effective. These effects may be quantitatively assessed. Winstein et alP used a Taft treatment for the system RCH2OBS in estimating the kj portion of the solvolytic rate constant [Eq. (14)]. Values for K/K where /c, is the titrimetrically observed rate constant, were determined. 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Analogous DSP treatments, but with differences with regard to the basis of the calculations, were proposed by Charton (1981) and by Swain s group (Swain and Lupton, 1968 Swain et al., 1983). The potential significance of polarizability effects resulted in a triple substituent parameter treatment (Taft, 1983). A slightly different... 

In the form of treatment developed by Taft and his colleagues since 195660-62, the Hammett constants are analyzed into inductive and resonance parameters, and the sliding scale is then provided by multiple regression on these. Equations 5 and 6 show the basic relationships. 

Recently, Kamlet and Taft introduced new elaborate parameters in order to explain the linear energy relationship for the formation of the hydrogen bond between HBA (hydrogen bond acceptor) and HBD (hydrogen bond donor). They treated several sulphoxides as HBA. The detailed presentations and actual treatments of these parameters have been described in their recent review article72. 

The ionization of benzoic acids in water at 25° was used by Hammett as the standard reaction for the original qp treatment (2a). This reaction and several analogous reactions, e.g., ionization and ester saponification rates of benzoic acids, cinnamic acids, and phenylpropiolic acids, gives ap correlations of relatively high precision. Taft and Lewis classified such reactions in an A category (2f). Reexamination of these A reactions, as well as additional analogous data which have become available subsequently, provided eight reaction series of data of apparently comparable reliability. In the para position, each of these sets of data meets the necessary condition of a minimal basis set... 

I99R. W. Taft and J. S. Murray, in Quantitative Treatments of Solute/Solvent... 

Taft and Topsom151 have fairly recently written an extensive review of the electronic effects of substituents in the gas phase. This article includes a tabulation of substituent inductive and resonance parameters. The inductive parameters (designated Op) are based on measured spectroscopic properties in either the gas phase or in hydrocarbon or similar solvents. The resonance parameters were arrived at through the treatment of 38 gas-phase reactivity series by iterative multiple regression, using the cr values of Bromilow and coworkers155 as the starting point. The of value for NO2 was found to be 0.65 (quoted... 

The new treatment had its origins partly in ab initio molecular orbital calculations of substituent effects and partly in extensive studies of gas-phase proton transfer reactions from about 1980 (Section V.A). Various aspects of this work essentially drew attention to the importance of substituent polarizability. In 1986 Taft, Topsom and their colleagues252 developed a scale of directional substituent polarizability parameters , oa, by ab initio calculations of directional electrostatic polarization potentials at the 3-21G//3-31G level for a large set of CH3X molecules. The oa values were shown to be useful in the correlation analysis of gas-phase acidities of several series of substrates252, and such work has subsequently been extended by Taft and Topsom151. 

Finally, a further refinement of the Lever equation40 allows one, in applying the treatment of ligand electrochemical parameters EL, to account for the presence of eventual aromatic or aliphatic ligands bearing different substituents, i.e. to take into account the Hammett, or Taft, substituent parameters a (above discussed) for a certain ligand. The expression is ... 

Da Silva, V.B., Andrioli, W.J., Carvalho, I., Taft, C.A., Silva, C. Computer-aided molecular design of novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia. J. Theor. Comput. Chem. 2007, 6, 811-21. 

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