Substituents inductive

The TT-inductive effect describes how an inductive substituent might selectively influence the electron distribution at the o- and -positions of the aromatic nucleus. A familiar example is represented by the... 

Excluding the phenomenon of hyperconjugation, the only other means by which electronic effects can be transmitted within saturated molecules, or exerted by inductive substituents in aromatic molecules, is by direct electrostatic interaction, the direct field effect. In early discussions of substitution this was usually neglected for qualitative purposes since it would operate in the same direction (though it would be expected to diminish in the order ortho > meta > para) as the cr-inductive effect and assessment of the relative importance of each is difficult however, the field effect was recognised as having quantitative significance. ... 

Another approach to evaluating cri was taken by Roberts and Moreland,who defined inductive substituent constants in terms of the acid dissociation constants of 4-substituted bicyclof2.2.2]octane-l-carboxylic acids, 3. 

Finally, in this account of multiparameter extensions of the Hammett equation, we comment briefly on the origins of the a, scale. This had its beginning around 1956 in the a scale of Roberts and Moreland for substituents X in the reactions of 4-X-bicyclo[2.2.2]octane-l derivatives. However, at that time few values of o were available. A more practical basis for a scale of inductive substituent constants lay in the o values for XCHj groups derived from Taft s analysis of the reactivities of aliphatic esters into polar, steric and resonance effects . For the few o values available it was shown that o for X was related to o for XCHj by the equation o = 0.45 <7. Thereafter the factor 0.45 was used to calculate c, values of X from o values of XCH2 . ... 

The rate of acid-catalyzed degradation of the penicillins also depends largely on the nature of their acylamido side chain. Structure-activity-relationship studies undertaken for the rational design of orally active penicillins have shown that the stability in gastric juice increases with the sum of Taft s inductive substituent constants (of values) of the 6-amino side chain [95]. 

A crude justification for such a study can be found in the work of Widing and Levitt [167], who described numerous correlations between adiabatic ionization potentials and Taft s inductive substituent constants (an indirect way of correlating IPs with charges) and in a note by Streitwieser [168], who justified to some extent a dependence of IPs on local charge densities. 

In substituted benzenes, the symmetry is lowered and the transitions into the states that correlate to the B2u and B u states of benzene become allowed by IPA, 2PA, or both. However, when the substituents induce only a weak perturbation on the benzene yr-electron system, the IPA or 2PA spectra of the substituted compounds often closely resemble the spectrum of the unsubstituted parent molecule. Various theoretical models have been developed in an attempt to predict the type of change in the band intensity and characteristics in the 2PA spectra of substituted benzenes and, more generally, of alternant hydrocarbons [34-36]. It was found that the effect of a perturbation is quite different for IP and 2P allowed transitions. In particular, 2P transitions to the state correlated to the benzene B2u state (Lb) are affected more by vibronic coupling than transitions to the state correlated to the benzene Biu state (La, in Platt notation [31,32]). In contrast, inductive perturbations enhance the La band more than the Lb band. The effects of vibronic coupling and inductive substituents are reversed for IP transitions into these states. Experimental... 

Taft separated the resonance from the inductive substituent effects and proposed Equation 2.15. The inductive parameter, ah is based on a obtained from aliphatic systems (see p. 68).14... 

Table 4.5 Examples of the different electronic substitution constants used in QSAR studies. Inductive substituent constants (crO are the contribution the inductive effect makes to Hammett constants and can be used for aliphatic compounds. Taft substitution constants (cr ) refer to aliphatic substituents but use propanoic acid (the 2-methyl derivative of ethanoic acid) as the reference point. The Swain-Lupton constants represent the contributions due to the inductive (.F) and mesomeric or resonance (R) components of Hammett constants. Adapted from An Introduction to the Principles of Drug Design and Action by Smith and Williams 3rd Ed. (1998) Ed. H.J.Smith. Reproduced by permission of Harwood Academic Publishers.

The gas-phase acidity order of haloacetic acids X—CH2—CO2H is H < F < Cl < Br < I, i.e. the order is reversed compared to that in aqueous solution [34a, 122, 132, 239]. Thus, the well-known aqueous acidity order is not caused by the increasing inductive substituent effect (I < Br < Cl < F), as is generally assumed, but rather by solvation effects. 

There is a correlation between Em (Table 45) and three (Taft s, Charton s and Grob s) inductive substituent constants. The best correlation was observed with Grob s parameters for the quinuclidium salts employed as probes in aqueous solutions (Fig. 53). 

The replacement of a C atom in a conjugated system by a heteroatom such as N may be considered the simplest example of a purely inductive substituent effect. The influence on the orbital energies may then be estimated by first-order perturbation theory using the relation... 

Figure 2.26. HOMO and LUMO of naphthalene and azulene together with the orbital energy changes de QMo and 6ci.umo< calculated by first-order perturbation theory for a purely inductive substituent S.

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