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Taft equationPPT Kusum

Taft equationPPT Kusum

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Published by: Kusum Ahlawat on Nov 25, 2011
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the Taft equation also describes the steric effects of a substituent. It was developed by Robert W. and resonance effects influence reaction rates.Taft equation  The Taft equation is a linear free energy relationship (LFER) used in physical organic chemistry in the study of reaction mechanisms and in the development of quantitative structure activity relationships for organic compounds. Taft in 1952 as a modification to the Hammett equation.While the Hammett equation accounts for how field. The Taft equation is written as: . inductive.

σ* is the polar substituent constant that describes the field and inductive effects of the substituent. Es is the steric substituent constant. ρ* is the sensitivity factor for the reaction to polar effects. where log(ks/kCH3) is the ratio of the rate of the substituted reaction compared to the reference reaction. . and δ is the sensitivity factor for the reaction to steric effects.

field. . and resonance) effects.Polar Substituent Constants.[6] The hydrolysis of esters can occur through either acid and base catalyzed mechanisms. both of which proceed through a tetrahedral intermediate. To determine σ* Taft studied the hydrolysis of methyl esters (RCOOMe). while in the acid catalyzed mechanism a positively charged reactant goes to a positively charged intermediate. In the base catalyzed mechanism the reactant goes from a neutral species to negatively charged intermediate in the rate determining (slow) step. σ*  Polar substituent constants describe the way a substituent will influence a reaction through polar (inductive. The use of ester hydrolysis rates to study polar effects was first suggested by Ingold in 1930.


 Due to the similar tetrahedral intermediates. Taft proposed that under identical conditions any steric factors should be nearly the same for the two mechanisms and therefore would not influence the ratio of the rates. However. because of the difference in charge buildup in the rate determining steps it was proposed that polar effects would only influence the reaction rate of the base catalyzed reaction since a new charge was formed .

48 is included to make σ* similar in magnitude to the Hammett σ values . The factor of 1/2. log(ks/kCH3)A is ratio of a rate of the acid catalyzed reaction compared to the reference reaction. and ρ* is a reaction constant that describes the sensitivity of the reaction series.He defined the polar substituent constant σ* as: where log(ks/kCH3)B is the ratio of the rate of the base catalyzed reaction compared to the reference reaction. For the definition reaction series. ρ* was set to 1 and R = methyl was defined as the reference reaction (σ* = zero).

Es  Although the acid catalyzed and base catalyzed hydrolysis of esters gives transition states for the rate determining steps that have differing charge densities. Es was defined as: . Due to this. Taft thus assumed that steric effects would influence both reaction mechanisms equally. their structures differ only by two hydrogen atoms. the steric substituent constant Es was determined from solely the acid catalyzed reaction.Steric Substituent Constants. as this would not include polar effects.

 where ks is the rate of the studied reaction and kCH3 is the rate of the reference reaction (R = methyl). ethyl. For the definition reaction series δ was set to 1 and Es for the reference reaction was set to zero. and tert- . the value for phenyl is much larger than that for tert-butyl. This equation is combined with the equation for σ* to give the full Taft equation. because context will have an effect on steric interactions[7] some Es values can be larger or smaller than expected.[8]  From comparing the Es values for methyl. isopropyl. However. For example. butyl. it is seen that the value increases with increasing steric bulk. the tert-butyl group is larger. δ is a reaction constant that describes the susceptibility of a reaction series to steric effects. axial strain values. When comparing these groups using another measure of steric bulk.

Meyers has defined Va values that are derived from the volume of the portion of the substituent that is within 0. other steric parameters that are independent of kinetic data have been defined.Other Steric Parameters for LFERs  In addition to Taft’s steric parameter Es.[10]  Sensitivity Factors  Polar Sensitivity Factor. Charton has defined values v that are derived from van der Waals radii.[9] Using molecular mechanics.3 nm of the reaction center. ρ* .

When the steric effects of substituents do not significantly influence the reaction rate the Taft equation simplifies to a form of the Hammett equation: . the polar sensitivity factor ρ* for Taft plots will describe the susceptibility of a reaction series to polar effects.Polar Sensitivity Factor. ρ*  Similar to ρ values for Hammett plots.

If -1 > ρ*. positive charge is built up and the reaction is mildly sensitive to polar effects. Similar to the Hammett ρ value: If ρ* > 1. The polar sensitivity factor ρ* can be obtained by plotting the ratio of      the measured reaction rates (ks) compared to the reference reaction (kCH3) versus the σ* values for the substituents. the reaction accumulates positive charge and is accelerated by electron donating groups. If 1 > ρ* > 0. . the reaction is not influenced by polar effects. the reaction accumulates negative charge in the transition state and is accelerated by electron withdrawing groups. If 0 > ρ* > -1. If ρ* = 0. This plot will give a straight line with a slope equal to ρ*. negative charge is built up and the reaction is mildly sensitive to polar effects.

Steric Sensitivity Factor. δ Similar to the polar sensitivity factor. increasing steric bulk increases the reaction rate and sterics effects are lessened in the transition state. If δ is positive. increasing steric bulk decreases the reaction rate and steric effects are greater in the transition state. . When a reaction series is not significantly influenced by polar effects. Similarly to the Hammett ρ value. the steric sensitivity factor δ for a new reaction series will describe to what magnitude the reaction rate is influenced by steric effects. while a shallow slope will correspond to little to no sensitivity. the Taft equation reduces to: A plot of the ratio of the rates versus the Es value for the substituent will give a straight line with a slope equal to δ. If δ is negative. the magnitude of δ will reflect to what extent a reaction is influenced by steric effects: A very steep slope will correspond to high steric sensitivity.

Reactions Influenced by Polar and Steric Effects  When both steric and polar effects influence the reaction rate the Taft equation can be solved for both ρ* and δ through the use of standard least squares methods for determining a bivariant regression plane. Taft outlined the application of this method to solving the Taft equation in a 1957 paper .

The formation of a covalent bond between penicillins and HSA as a result of aminolysis with lysine residues is believed to be involved in penicillin allergies. Sandri and co-workers[12] have used Taft plots in studies of polar effects in the aminolysis of βlactams. As a part of their mechanistic studies Sandri and co-workers plotted the rate of aminolysis versus calculated σ* values for 6 penicillins and found no correlation. In a recent example. suggesting that the rate is influenced by other effects in addition to polar and steric effects . They have looked at the binding of β-lactams to a poly(ethyleneimine) polymer.Taft Plots in QSAR  The Taft equation is often employed in biological chemistry and medicinal chemistry for the development of quantitative structure activity relationships (QSAR). which functions as a simple mimic for human serum albumin (HSA).

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