Substituent Effects on the Acidity of Phenols

On shaking an ether solution of a phenol and a carboxylic acid with dilute sodium bicarbonate, the carboxylic acid is converted quantitatively to its sodium salt and extracted into the aqueous phase. The phenol remains in the ether phase. 

Phenoxide ion Carbonic acid (stronger base) (stronger acid p = 6.4) 

It is necessary to keep the acidity of phenols in mind when we discuss preparation and reactions. Reactions that produce phenols, when carried out in basic solution, require an acidification step to convert the phenoxide ion to the neutral form of the phenol. 

Many synthetic reactions involving phenols as nucleophiles are carried out in the presence of sodium or potassium hydroxide. Under these conditions the phenol is converted to the corresponding phenoxide ion, which is a far better nucleophile. 

As Table 22.2 shows, most phenols have ionization constants similar to that of phenol itself. Substituent effects, in general, are small. 

Alkyl substitution produces negligible changes in acidities, as do weakly electronegative groups attached to the ring. 

Recall from Section 24.1 that cresols are methyl-substituted derivatives of phenol. 

A meta-nitro group is not directly conjugated to the phenoxide oxygen and thus stabilizes a phenoxide ion to a smaller extent. m-Nitrophenol is more acidic than phenol but less acidic than either o- or p-nitrophenol. 

PROBLEM 24.3 Which is the stronger acid in each of the following pairs Explain 

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Electron releasing substituents attached to the ring have a negligible effect on the acidity of phenols Strongly electron withdrawing groups increase the acidity The compound 4 nitro 3 (tnfluoromethyl)phenol for example is 10 000 times more acidic than phenol... 

This means that substituents that can withdraw electrons conjugatively will have a greater effect on the acidity of phenols (reaction 3.9) than on the acidity of benzoic acids. The difference will only be appreciable at the para position for the meta position, no through resonance is possible. If we make a plot of logATA for the acidities of mcta-substituted phenols against Hammett cr constants, we find that the points lie on a straight line, the slope of which gives the p value for the reaction as +2.23... 

Substituent constants have been widely used in organic chemistry for the interpretation of electronic effects on chemical reactivity [79, 80]. However, it is well known that the character of the electronic effects can differ quite substantially between different chemical systems and that it is not possible to find a universal set of substituent constants. In this section we will demonstrate how the electrostatic potential can be used as an alternative and a complement to the traditional constants in analyses of electronic substituent effects. The main advantage with this approach is that we can study systems whose substituent effects are unknown, or systems for which the substituent effects cannot be described by the traditional constants. An analysis of the electrostatic potential can also provide a direct insight to the effects the substituents have on the electronic structures of the molecules. We will both discuss the classical examples of substituent effects on the acidities of benzoic acid and phenol, and a more novel example, i.e. the substituent effects on the 0-H bond dissociation energy in phenols. 

Substituent effects on the acidities of ortho, meta, and para substituted phenols... 

Take a minute to compare the influence a substituent has on the reactivity of a benzene ring toward electrophilic substitution with its effect on the pK of phenol. Notice that the more strongly deactivating the substituent, the lower the pK of the phenol and the more strongly activating the substituent, the higher the pK of the phenol. In other words, electron withdrawal decreases reactivity toward electrophilic substitution and increases acidity, whereas electron donation increases reactivity toward electrophilic substitution and decreases acidity. 

In principle, the pK of the toluene radical cation can be estimated from the one-electron reduction potential of the radical cation and the C-H bond dissociation enthalpy for toluene (368 kj mor )[62] using equation (5). The resulting pR is ca -10, i.e., considerably more acidic than the phenol radical cation. Nicholas and Arnold have estimated the pfC of the toluene radical cation to between -9 and -13 in acetonitrile which is weU in line with the estimate given here. [32] Since the C-H bond dissociation enthalpies of substituted toluenes seem to be almost invariant with substituent,[63-66] the substituent effect on the pK of... 

The effect of para substituents on the OH torsional barrier in phenols and nitrogen inversion barrier in anilines has been examined by Pople and co-workers (8,9). These topics are discussed in Sections V.A.4 and V.A.5. The results show that in a para-substituted benzene, a w donor and a tt acceptor interact favorably with one another whereas the situation of two tt donors leads to resonance saturation and a destabilizing interaction. Wepster et al. (93,94) have reached similar conclusions on the basis of experimental studies. The relative stabilities of ortho-, meta-, and para-disubstituted benzenes for the substituents CN, OH, and F have been studied by von Niessen (66) using a Gaussian lobe minimal basis set. Radom has calculated the effect of substituents on the acidities of phenols and noted good agreement with available gas-phase data (65). 

The effect of substituents on the acidity and basicity of aniline, and on the acidity of phenol, is given, respectively, by the energy changes in reactions 4-6. 

A study39 of substituent effects on the 15N chemical shift (515N) (Table 10) for 4-substituted anilines in DMSO was interpreted in terms of substituent solvation-assisted resonance (SSAR) effects. Solvation of certain conjugated jr-electron-acceplor (+R) substituents has been found to give significant enhancements in the acidities of anilines, phenols and other acids40,41, and the magnitudes of these enhancements increase with... 

Overall, the acidities of the substituted phenols are largely determined by the stabilization of the corresponding phenolate ions, i.e. the energies of the phenolate HOMOs. There is a similarity between the substituent effect on the latter and the LUMOs of substituted benzenes both can be understood by simple perturbative PMO treatment. ... 

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