Taft substituent parameters

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 ... 

Sevilla MD, Becker D, Mengyayo Y (1990b) Structure and reactivity of peroxyl and sulphoxyl radicals from measurement of oxygen-17 hyperfine couplings relationship with Taft substituent parameters. J Chem Soc Faraday Trans 86 3279-3286 Shen X, Lind J, Eriksen TE, Merenyi G (1989) The reaction of the CCI3O2 radical with indoles. J Chem Soc Perkin Trans 2 555-562... 

The philicity of singlet carbenes is an important concept to classify carbenes that was systematically studied by Moss. [9-11] The relative reactivity (selectivity) of a series of singlet carbenes in cyclopropanation reactions with electron rich and electron poor carbenes was used to quantify the carbene philicity. An empirical carbene philicity scale with a parameter niQ- (where X and Y are the substituents at the carbene center) was defined (Figure 1). Electrophilic carbenes show Wqxy values below 1, nucleophilic carbenes above 2, and ambiphiles are between. [10] Ambiphilic carbenes act as an electrophile towards electron-rich alkenes and as a nucleophile towards electron-poor alkenes. The niQ- Y values obey an empirical linear free energy relationship with the Taft substituent parameters and Oj. This allows to estimate the niQ- Y values of unknown carbenes. 

In addition to providing relative reactivity information about aryl fluorides, NMR can be used to calculate the Taft substituent parameters Oj and Or (27-29) (see Table 3). 

The Hammett substituent parameter was used by Hansch as a concise measure of th electronic characteristics of the molecules. Hammett and others (such as Taft) showed the... 

Here again it is possible to find a linear relationship between the log (k/feo) (ko = methyl) values of 2-alkyl- and 2,4-dialkylthiazoles and between the latter value and Tafts Eg parameter (256). The value of 5 for 2,4-dialkylthiazoles is 1.472 with a correlation coefficient of 0.9994. Thus the sensitivity to substituent effects is more marked than in the case of a single substituent in the 2-position. Furthermore, the 4-position is again more sensitive than the 2-position. 

The log(k/ko) value for 4-isopropyl-2,5-dimethylthiazole is twice that expected if the curve were linear, which implies a rate constant 6.5 times smaller than expected. This result can be explained by the existence of a privileged conformation, induced by the presence of the methyl group in the 5-position and that has a lower reactivity (258). This result also leads to a limitation in the use of Tafts Eg parameter to cases where the environment of a substituent does not induce particular conformation for this latter (258). 

Before we close this section we make reference to an extended form of the Hammett equation in which the substituent constant and the reaction constant are separated into contributions from the field effect (F) and the mesomeric effect (R). This procedure was suggested by Taft in 1957 for 4-substituted benzene derivatives. It is called a dual substituent parameter (DSP) equation (Scheme 7-2). 

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... 

Diparametric equation A relationship in which the effect of structure on a property is represented by two parameters, one of which is generally composite. Examples discussed in this work include the LD, CR and MYT equations. Other examples are the Taft, Ehrenson and Brownlee DSP (dual substituent parameter), Yukawa-Tsuno YT and the Swain, Unger, Rosenquist and Swain SURS equations. The DSP equation is a special case of the LDR equation with the intercept set equal to zero. It is inconvenient to use and has no advantages. The SURS equation uses composite parameters which are of poorer quality than... 

Taft steric parameter for para substituent on benzamide side chains. fTaft steric parameter for para substituent on benzyloxy side chains. gTaft steric parameter for para substituent on benzoyloxy side chains. hIndicator variable for polycyclic aromatics I = 1 if present, I = 0 if absent. 

Realistic prediction of the mutagenic activities of this class of mutagens requires a physicochemical evaluation of steric effects of substituents and the most widely utilised measures of such are Taft steric parameters, Es (Table 17).204,210... 

Electron affinities for 35 substituted nitrobenzenes have been reported and provided a comprehensive data set for the examination of substituent effects38. The data were used to derive Taft gas-phase substituent parameters and discussed qualitatively based on frontier orbital molecular theory38. The rate constants for the exo-energetic electron-transfer reactions were found to be close to those predicted by the ADO (average dipole orientation) theory38. 

A plot of the pKa values of anilines in DMSO versus the pKa values of anilinium ions in water is linear with a slope of 1.8. This allows the extrapolation of 41 1 for the pKa of ammonia in DMSO from that of NH4+ in water (9.27)127. Alternatively, the pKa of ammonia in DMSO has been extrapolated105 from the intersystem correlation between the DMSO acidities of NH2X and PhNHX as a value of 35.8. Extrapolation of the pKa value of ammonia from the Taft-like dual substituent parameter (DSP) of NH2X DMSO acidities gave a similar value of 36.6. 

This equation is an elaboration of the dual substituent-parameter (DSP) equation. Its development has been relatively recent, but Taft and Topsom, who have been closely associated with it, have already written a long review article151 involving the equation, and this article will probably acquire the status in respect of the PSP equation that the article of Ehrenson, Brownlee and Taft92 has in connection with the DSP equation. The name Poly Substituent-Parameter Equation was devised by the present author in a short... 

Taft and Topsom s article151 and also Topsom s171 should be consulted for details of the setting up of the scales of substituent parameters. The equation has been applied to a wide range of gas-phase reactivities. (In the multiple regressions an intercept term is often permitted, but usually this turns out to be indistinguishable from zero, as it should be if equation 20 is valid.) For aliphatic and alicyclic saturated systems the resonance term is duly negligible. The roles of field, resonance and polarizability effects are discussed and the interpretat of the various p values is attempted. 

Among Type A relationships, the Hammett and Taft equations are most frequently employed for noncatalytic reactions. When utilizing them for catalytic reactions we must consider the reliability of the substituent parameters and their suitability for the given structural type of reactants. The Hammett equation... 

Analysis of the Hansch descriptors illustrates that increasing the lipophilicity property for this series of compounds will increase the bioactivity in a more dramatic fashion than increasing the Tafts steric parameter. Increasing the water accessible surface area (MOE descriptor) will increase the bioactivity of the compounds. But there is more than just adding lipophilicity and water accessible surface area to the molecules to increase binding affinity. A comparison of the substituents to the bioactivities illustrates that the bulkier X and Y groups increase bioactivity in conjunction with atomic partial charge distribution of the substituents. 

Taft also defined the Es parameter for aromatic ortho substituents in a fashion similar to Eq. 3 4). Charton advanced evidence that the original value is linked rather with the polar substituent effect despite the original definition51. We have shown that the set of Es parameters defined by Eq. 3 and 4 can also be used to rationalize the steric effect of aromatic ortho substituents 7). In general, the ortho substituent effect in biological activity is analyzable as linear combination of substituent parameters 8) (Eq. 5),... 

---