Linear free energy relationships substitution

The applicability of the two-parameter equation and the constants devised by Brown to electrophilic aromatic substitutions was tested by plotting values of the partial rate factors for a reaction against the appropriate substituent constants. It was maintained that such comparisons yielded satisfactory linear correlations for the results of many electrophilic substitutions, the slopes of the correlations giving the values of the reaction constants. If the existence of linear free energy relationships in electrophilic aromatic substitutions were not in dispute, the above procedure would suffice, and the precision of the correlation would measure the usefulness of the p+cr+ equation. However, a point at issue was whether the effect of a substituent could be represented by a constant, or whether its nature depended on the specific reaction. To investigate the effect of a particular substituent in different reactions, the values for the various reactions of the logarithms of the partial rate factors for the substituent were plotted against the p+ values of the reactions. This procedure should show more readily whether the effect of a substituent depends on the reaction, in which case deviations from a hnear relationship would occur. It was concluded that any variation in substituent effects was random, and not a function of electron demand by the electrophile. ... 

Linear Free-Energy Relationships for Metal Substitution... 

FIGURE 8.9. Linear free-energy relationship for the effect of metal substitution on e2 and e3 in staphylococcal nuclease (see text for details). 

Ledaal and co-workers (101-105) have proposed a linear free energy relationship for predicting the percent zwitterion formed at the rth carbon atom in substituted quinones, substituted dibenzoylethylenes, and substituted acetylenes. Fliszar and Granger (106) have proposed the equation... 

Taft RW Jr. Linear free-energy relationships from rates of esterification and hydrolysis of aliphatic and ortho-substituted benzoate esters. / Am Chem Soc 1952 74 2729-32. 

In conforming to an expected linear free energy relationship, the Ce(lV) oxidation of various 1,10-phenanthroline and bipyridyl complexes of Ru(II) in 0.5 M sulphuric acid are consistent with the requirements of the Marcus treatment . The results for the oxidation of the 3- and 5-sulphonic-substituted ferroin complexes by Ce(IV) suggest that the ligand does not function as an electron mediator, and that the mechanism is outer-sphere in type. Second-order rate coefficients for the oxidation of Ru(phen)j, Ru(bipy)3, and Ru(terpy)3 are 5.8x10, 8,8 X 10, and 7.0 x 10 l.mole . sec, respectively, in 0.5 M H2SO4 at 25 °C a rapid-mixing device was employed. 

In a broad sense, one may include the Free-Wilson equation within the class of linear free energy relationships (LFER). It is also subjected to the assumption of additivity of the contributions to the biological activity by substituent groups at different substitution sites. The assumption requires, for example, that there is no hydrogen bonding interaction between the various substitution groups. 

Quite early on (p. 361) in this discussion of linear free energy relationships consideration was restricted to the side-chain reactions of m- and p-substituted benzene derivatives. The reactions of o-substituted benzene derivatives, and indeed of aliphatic compounds, were excluded because of the operation of steric and other effects, which led to non-linear, or even to apparently random, plots. 

A comparison of the rate constants for the [Cun(FLA)(IDPA)]+-cata-lyzed autoxidation of 4/-substituted derivatives of flavonol revealed a linear free energy relationship (Hammett) between the rate constants and the electronic effects of the para-substituents of the substrate (128). The logarithm of the rate constants linearly decreased with increasing Hammett o values, i.e. a higher electron density on the copper center yields a faster oxidation rate. 

Non-Marcusian linear free energy relationships (if I may again be permitted that barbarism) provide direct evidence for this type of potential surface in octahedral ligand substitution reactions. Both dissociative (e.g., the chloropentaamine of cobalt(III)) and associative systems (e.g., chloropentaaquo chromium(III)) may have values of slopes for the linear free energy relationships indicating non-Marcusian behavior. 

Linear-free-energy relationships such as the Hammett and Taft equations [Lowry and Richardson, 1987] have been used to correlate copolymerization behavior with structure, but the approach is limited to considering a series of monomers that are similar in structure. Walling [1957] applied the Hammett equation to copolymerization among various meta- and para-substituted styrenes. The Taft equation in the form... 

Modification of Chemical Structure of Drug The use of a Hammett linear free-energy relationship to investigate the effects of substituents on the rates of aromatic side-chain reactions such as hydrolysis of esters has been alluded to earlier vis-a-vis attainment of optimum stability [9,10]. Degradation of erythromycin under acidic pH conditions is inhibited by substituting a methoxy group for the C-6 hydroxyl as found for the acid stability of clathromycin, which is 340 times greater than that of erythromycin [70]. 

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