Substituent effects acidities

The effect of structure on acidity was introduced m Section 1 15 where we developed the generalization that electronegative substituents near an lomzable hydrogen increase Its acidity Substituent effects on the acidity of carboxylic acids have been extensively studied... 

Several theories have been proposed to account for substituent-induced changes in the acidities of organic acids. Substituent effects are most clearly illustrated in a symmetrical proton tr sfer reaction such as... 

So far the four metal ions have been compared with respect to their effect on (1) the equilibrium constant for complexation to 2.4c, (2) the rate constant of the Diels-Alder reaction of the complexes with 2.5 and (3) the substituent effect on processes (1) and (2). We have tried to correlate these data with some physical parameters of the respective metal-ions. The second ionisation potential of the metal should, in principle, reflect its Lewis acidity. Furthermore the values for Iq i might be strongly influenced by the Lewis-acidity of the metal. A quantitative correlation between these two parameters... 

The heats of formation of Tt-complexes are small thus, — A//2soc for complexes of benzene and mesitylene with iodine in carbon tetrachloride are 5-5 and i2-o kj mol , respectively. Although substituent effects which increase the rates of electrophilic substitutions also increase the stabilities of the 7r-complexes, these effects are very much weaker in the latter circumstances than in the former the heats of formation just quoted should be compared with the relative rates of chlorination and bromination of benzene and mesitylene (i 3 o6 x 10 and i a-Sq x 10 , respectively, in acetic acid at 25 °C). 

If this electrostatic treatment of the substituent effect of poles is sound, the effect of a pole upon the Gibbs function of activation at a particular position should be inversely proportional to the effective dielectric constant, and the longer the methylene chain the more closely should the effective dielectric constant approach the dielectric constant of the medium. Surprisingly, competitive nitrations of phenpropyl trimethyl ammonium perchlorate and benzene in acetic anhydride and tri-fluoroacetic acid showed the relative rate not to decrease markedly with the dielectric constant of the solvent. It was suggested that the expected decrease in reactivity of the cation was obscured by the faster nitration of ion pairs. 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

Table 19 3 lists the ionization constants of some substituted benzoic acids The largest effects are observed when strongly electron withdrawing substituents are ortho to the carboxyl group An o nitro substituent for example increases the acidity of benzoic acid 100 fold Substituent effects are small at positions meta and para to the carboxyl group In those cases the values are clustered m the range 3 5-4 5... 

Table 36 summarizes the known annular tautomerism data for azoles. The tautomeric preferences of substituted pyrazoles and imidazoles can be rationalized in terms of the differential substituent effect on the acidity of the two NFI groups in the conjugate acid, e.g. in (138 EWS = electron-withdrawing substituent) the 2-NFI is more acidic than 1-NFI and hence for the neutral form the 3-substituted pyrazole is the more stable. 

It is always important to keep in mind the relative nature of substituent effects. Thus, the effect of the chlorine atoms in the case of trichloroacetic acid is primarily to stabilize the dissociated anion. The acid is more highly dissociated than in the unsubstituted case because there is a more favorable energy difference between the parent acid and the anion. It is the energy differences, not the absolute energies, that determine the equilibrium constant for ionization. As we will discuss more fully in Chapter 4, there are other mechanisms by which substituents affect the energy of reactants and products. The detailed understanding of substituent effects will require that we separate polar effects fiom these other factors. 

A comparison of phenol acidity in DMSO versus the gas phase also shows an attenuation of substituent effects, but not nearly as much as in water. Whereas the effect of ubstituents on AG for deprotonation in aqueous solution is about one-sixth that in the gas phase, the ratio for DMSO is about one-third. This result points to hydrogen bonding of the phenolate anion by water as the major difference in the solvating properties of water and DMSO. ... 

Another area of gas-phase substituent effects that has attracted interest is the acidity of simple alcohols. In the gas phase, the order is r-BuOH > EtOH > MeOH 3>... 

This is opposite from the order in solution as revealed by the pK data in water and DMSO shown in Table 4.14. These changes in relative acidity can again be traced to solvation effects. In the gas phase, any substituent effect can be analyzed directly in terms of its stabilizing or destabilizing effect on the anion. Replacement of hydrogen by alkyl substituents normally increases electron density at the site of substitution, but this effect cannot be the dominant one, because it would lead to an ordering of gas-phase acidity opposite to that observed. The dominant effect is believed to be polarizability. The methyl... 

The trend in acidity as a function of substituent is the same but the magnitude of the substituent effects is much larger in the gas phase. (The AAG° for any given substituent is about 10 times larger in the gas phase.)... 

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