Taft equationPPT Kusum

8/3/2019 Taft equationPPT Kusum

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Dr. Kusum ahlawat


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Taft equation The Taft equation is a linear free energy

relationship (LFER) used in physical organicchemistryin the study ofreaction mechanisms

and in the development ofquantitative structureactivity relationships for organic compounds. Itwas developed byRobert W. Taft in 1952 as amodification to the Hammett equation.While theHammett equation accounts for how field,

inductive, and resonance effects influence reactionrates, the Taft equation also describes the stericeffects of a substituent. The Taft equation iswritten as:
http://en.wikipedia.org/wiki/Free-energy_relationshiphttp://en.wikipedia.org/wiki/Free-energy_relationshiphttp://en.wikipedia.org/wiki/Free-energy_relationshiphttp://en.wikipedia.org/wiki/Physical_organic_chemistryhttp://en.wikipedia.org/wiki/Physical_organic_chemistryhttp://en.wikipedia.org/wiki/Free-energy_relationshiphttp://en.wikipedia.org/wiki/Reaction_mechanismhttp://en.wikipedia.org/wiki/Reaction_mechanismhttp://en.wikipedia.org/wiki/Physical_organic_chemistryhttp://en.wikipedia.org/wiki/Reaction_mechanismhttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/w/index.php?title=Robert_W._Taft&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Robert_W._Taft&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Robert_W._Taft&action=edit&redlink=1http://en.wikipedia.org/wiki/Organic_compoundhttp://en.wikipedia.org/w/index.php?title=Robert_W._Taft&action=edit&redlink=1http://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/w/index.php?title=Substituent_field_effect&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Substituent_field_effect&action=edit&redlink=1http://en.wikipedia.org/wiki/Inductive_effecthttp://en.wikipedia.org/wiki/Mesomeric_effecthttp://en.wikipedia.org/w/index.php?title=Substituent_field_effect&action=edit&redlink=1http://en.wikipedia.org/wiki/Inductive_effecthttp://en.wikipedia.org/wiki/Mesomeric_effecthttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Substituenthttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Substituenthttp://en.wikipedia.org/wiki/Substituenthttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Steric_effectshttp://en.wikipedia.org/wiki/Mesomeric_effecthttp://en.wikipedia.org/wiki/Inductive_effecthttp://en.wikipedia.org/w/index.php?title=Substituent_field_effect&action=edit&redlink=1http://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/w/index.php?title=Robert_W._Taft&action=edit&redlink=1http://en.wikipedia.org/wiki/Organic_compoundhttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/wiki/Reaction_mechanismhttp://en.wikipedia.org/wiki/Physical_organic_chemistryhttp://en.wikipedia.org/wiki/Physical_organic_chemistryhttp://en.wikipedia.org/wiki/Free-energy_relationshiphttp://en.wikipedia.org/wiki/Free-energy_relationship


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where log(ks/kCH3) is the ratio of the rate of thesubstituted reaction compared to the referencereaction, * is the polar substituent constant that

describes the field and inductive effects of thesubstituent, Es is the steric substituent constant, *is the sensitivity factor for the reaction to polareffects, and is the sensitivity factor for the reaction

to steric effects.
http://en.wikipedia.org/wiki/Reaction_ratehttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Reaction_rate


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Polar Substituent Constants, *

Polar substituent constants describe the way a substituentwill influence a reaction through polar (inductive, field,and resonance) effects. To determine * Taft studied thehydrolysis ofmethylesters (RCOOMe). The use of esterhydrolysis rates to study polar effects was first suggested byIngold in 1930.[6] The hydrolysis of esters can occurthrough either acid and base catalyzed mechanisms, bothof which proceed through a tetrahedralintermediate. Inthe base catalyzed mechanism the reactant goes from a

neutral species to negativelycharged intermediate in therate determining (slow) step, while in the acid catalyzedmechanism a positively charged reactant goes to apositively charged intermediate.
http://en.wikipedia.org/wiki/Hydrolysishttp://en.wikipedia.org/wiki/Methylhttp://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/wiki/Hydrolysishttp://en.wikipedia.org/wiki/Methylhttp://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Acid_catalysishttp://en.wikipedia.org/wiki/Acid_catalysishttp://en.wikipedia.org/wiki/Acid_catalysishttp://en.wikipedia.org/wiki/Tetrahedral_molecular_geometryhttp://en.wikipedia.org/wiki/Reactive_intermediatehttp://en.wikipedia.org/wiki/Reactive_intermediatehttp://en.wikipedia.org/wiki/Tetrahedral_molecular_geometryhttp://en.wikipedia.org/wiki/Reactive_intermediatehttp://en.wikipedia.org/wiki/Rate-determining_stephttp://en.wikipedia.org/wiki/Rate-determining_stephttp://en.wikipedia.org/wiki/Rate-determining_stephttp://en.wikipedia.org/wiki/Reactive_intermediatehttp://en.wikipedia.org/wiki/Tetrahedral_molecular_geometryhttp://en.wikipedia.org/wiki/Acid_catalysishttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/wiki/Methylhttp://en.wikipedia.org/wiki/Hydrolysis


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http://en.wikipedia.org/wiki/File:Wikipedia_ester_hydrolysis.png


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Due to the similar tetrahedral intermediates, Taftproposed that under identical conditions any stericfactors should be nearly the same for the two

mechanisms and therefore would not influence theratio of the rates. However, because of the difference incharge buildup in the rate determining steps it wasproposed that polar effects would only influence the

reaction rate of the base catalyzed reaction since a newcharge was formed


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He defined the polar substituent constant

* as:

where log(ks/kCH3)B is the ratio of the rate of the base catalyzed reactioncompared to the reference reaction, log(ks/kCH3)A is ratio of a rate of theacid catalyzed reaction compared to the reference reaction, and * is a

reaction constant that describes the sensitivity of the reaction series. For thedefinition reaction series, * was set to 1 and R = methyl was defined as the

reference reaction (* = zero). The factor of 1/2.48 is included to make *

similar in magnitude to the Hammett values
http://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/wiki/Hammett_equation


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Steric Substituent Constants, Es

Although the acid catalyzed and base catalyzedhydrolysis of esters gives transition states for the

rate determining steps that have differing chargedensities, their structures differ only by twohydrogen atoms. Taft thus assumed that stericeffects would influence both reaction mechanisms

equally. Due to this, the steric substituent constantEs was determined from solely the acid catalyzedreaction, as this would not include polar effects. Eswas defined as:
http://en.wikipedia.org/wiki/Transition_statehttp://en.wikipedia.org/wiki/Charge_densityhttp://en.wikipedia.org/wiki/Charge_densityhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Charge_densityhttp://en.wikipedia.org/wiki/Charge_densityhttp://en.wikipedia.org/wiki/Transition_state


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where ks is the rate of the studied reaction and kCH3 is the rate of thereference reaction (R = methyl). is a reaction constant that describesthe susceptibility of a reaction series to steric effects. For the definitionreaction series was set to 1 and Es for the reference reaction was set tozero. This equation is combined with the equation for * to give the fullTaft equation.

From comparing the Es values for methyl, ethyl, isopropyl, and tert-butyl, it is seen that the value increases with increasing steric bulk.However, because context will have an effect on steric interactions[7]some Esvalues can be larger or smaller than expected. For example, the

value for phenyl is much larger than that for tert-butyl. Whencomparing these groups using another measure of steric bulk, axialstrain values, the tert-butyl group is larger.[8]
http://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Ethyl_grouphttp://en.wikipedia.org/wiki/Isopropylhttp://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Phenyl_grouphttp://en.wikipedia.org/wiki/Phenyl_grouphttp://en.wikipedia.org/wiki/A_valuehttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/A_valuehttp://en.wikipedia.org/wiki/A_valuehttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/A_valuehttp://en.wikipedia.org/wiki/A_valuehttp://en.wikipedia.org/wiki/Phenyl_grouphttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Tert-butylhttp://en.wikipedia.org/wiki/Isopropylhttp://en.wikipedia.org/wiki/Ethyl_group


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Other Steric Parameters for LFERs

In addition to Tafts steric parameter Es, othersteric parameters that are independent of kineticdata have been defined. Charton has defined

values v that are derived fromvan der Waalsradii.[9] Using molecular mechanics, Meyers hasdefined Va values that are derived from the volumeof the portion of the substituent that is within

0.3 nm of the reaction center.[10] Sensitivity Factors

Polar Sensitivity Factor, *
http://en.wikipedia.org/wiki/Van_der_Waals_radiushttp://en.wikipedia.org/wiki/Van_der_Waals_radiushttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Molecular_mechanicshttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Molecular_mechanicshttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Van_der_Waals_radiushttp://en.wikipedia.org/wiki/Van_der_Waals_radius


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Polar Sensitivity Factor, *

Similar to values for Hammett plots, the polarsensitivity factor * for Taft plots will describe thesusceptibility of a reaction series to polar effects.

When the steric effects of substituents do notsignificantly influence the reaction rate the Taftequation simplifies to a form of the Hammettequation:
http://en.wikipedia.org/wiki/Hammett_equationhttp://en.wikipedia.org/wiki/Hammett_equation


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The polar sensitivity factor * can be obtained by plotting the ratio ofthe measured reaction rates (ks) compared to the reference reaction(kCH3) versus the * values for the substituents. This plot will give astraight line with a slopeequal to *. Similar to the Hammett value:

If * > 1, the reaction accumulates negative charge in the transitionstate and is accelerated byelectron withdrawing groups. If 1 > * > 0, negative charge is built up and the reaction is mildly

sensitive to polar effects. If * = 0, the reaction is not influenced by polar effects. If 0 > * > -1, positive charge is built up and the reaction is mildly

sensitive to polar effects. If -1 > *, the reaction accumulates positive charge and is accelerated by

electron donating groups.
http://en.wikipedia.org/wiki/Slopehttp://en.wikipedia.org/wiki/Slopehttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Polar_effecthttp://en.wikipedia.org/wiki/Slope


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Steric Sensitivity Factor,

Similar to the polar sensitivity factor, the steric sensitivity factor for a new

reaction series will describe to what magnitude the reaction rate is influencedby steric effects. When a reaction series is not significantly influenced by polareffects, the Taft equation reduces to:

A plot of the ratio of the rates versus the Es value for the substituent will give astraight line with a slope equal to . Similarly to the Hammett value, the

magnitude of will reflect to what extent a reaction is influenced by steric

effects:A very steep slope will correspond to high steric sensitivity, while a shallow

slope will correspond to little to no sensitivity.If is negative, increasing steric bulk decreases the reaction rate and steric

effects are greater in the transition state.If is positive, increasing steric bulk increases the reaction rate and sterics

effects are lessened in the transition state.


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Reactions Influenced by Polar and Steric

Effects

When both steric and polar effects influence thereaction rate the Taft equation can be solved for both* and through the use of standard least squaresmethods for determining a bivariant regression plane.Taft outlined the application of this method to solvingthe Taft equation in a 1957 paper
http://en.wikipedia.org/wiki/Least_squareshttp://en.wikipedia.org/w/index.php?title=Bivariant_regression_plane&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Bivariant_regression_plane&action=edit&redlink=1http://en.wikipedia.org/wiki/Least_squares


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Taft Plots in QSAR

The Taft equation is often employed in biologicalchemistryand medicinal chemistryfor the development ofquantitative structure activity relationships (QSAR). In arecent example, Sandri and co-workers[12] have used Taftplots in studies of polar effects in the aminolysis of-lactams. They have looked at the binding of -lactams to a

poly(ethyleneimine) polymer, which functions as a simplemimic for human serum albumin (HSA). The formation ofa covalent bondbetween penicillins and HSA as a result ofaminolysis with lysine residues is believed to be involvedin penicillin allergies. As a part of their mechanistic

studies Sandri and co-workers plotted the rate ofaminolysis versus calculated * values for 6 penicillins andfound no correlation, suggesting that the rate isinfluenced by other effects in addition to polar and stericeffects
http://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Medicinal_chemistryhttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/wiki/Aminolysishttp://en.wikipedia.org/wiki/Aminolysishttp://en.wikipedia.org/wiki/Aminolysishttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Aminolysishttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Human_serum_albuminhttp://en.wikipedia.org/wiki/Human_serum_albuminhttp://en.wikipedia.org/wiki/Human_serum_albuminhttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Human_serum_albuminhttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Lysinehttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Lysinehttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Penicillinhttp://en.wikipedia.org/wiki/Lysinehttp://en.wikipedia.org/wiki/Covalent_bondhttp://en.wikipedia.org/wiki/Human_serum_albuminhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Beta-lactamhttp://en.wikipedia.org/wiki/Aminolysishttp://en.wikipedia.org/wiki/Taft_equationhttp://en.wikipedia.org/wiki/Quantitative_structure-activity_relationshiphttp://en.wikipedia.org/wiki/Medicinal_chemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Biochemistry


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http://en.wikipedia.org/wiki/File:Taft_plot_example.PNG

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Taft equationPPT Kusum