Substituent Effects in Substituted Benzoic Acids

TABLE 20.6 Substituent Effects on Acidity of p-Substitutcd Benzoic Aci h 

Since it s much easier to measure the acidity of a substituted bem acid than to determine the relative reactivity of an aromatic ring tow electrophilic substitution, the correlation between the two effects is u for predicting reactivity. If we want to know the effect of a certain s stituent on electrophilic reactivity, we can simply find the acidity of the a responding benzoic acid. Practice Problem 20.1 gives an example. 

Because inductive effects operate through r bonds and are dependent on distance, the effect of halogen substitution decreases as the substituent moves farther from the carboxyl. For instance, 2-chlorobutanoic acid has pK = 2.86,3-chlorobutanoic acid has pi a = 4.05, and 4-chlorobutanoic acid has pKa = 4.52, similar to that of butanoic acid itself (Table 20.5). 

Problem 20.5 Without looking at a table of pi., values, rank the substances in each of the following groups in order of increasing acidity  

Problem 20.6 Dicarboxylic acids have two dissociation constants, one for the initial dissociation into a monoanion and one for the second dis.sodation into a dianion. For oxalic acid, HOOC-COOH, the first ionization constant has pKi = 1.2 and the second ionization constant has pK 2 = 4.2. Why is the second carboxyl group so much less acidic than the first  

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Reynolds and co-workers (61,62,95-100) have used ab initio and other theoretical and nmr chemical shift data to examine substituent effects in substituted benzenes. Systems studied in this way include substituted benzoic acids (61), styrenes (62,98), phenylacetylenes (99), and phenylalkanes (96). Particular emphasis has been placed on the separation of field, inductive, and resonance effects. 

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... 

For sets nos. 1, 2, and 3 of Table XXVII, eq. (1) appears to hold for ionization of ortho substituted benzoic acids (f =. 048 —. 058), with Kj = Pi I= 1.6 . 1. This result is reasonable for field effects transmitted only throu the molecular cavity i.e., the lines of force do not pass through appreciable solvent of high dielectric constant (the solvent is presumably excluded by the close proximity of the CO2H center and the substituent) (36). It is further of interest that eq. (1) fails for the ionization of ortho substituted benzoic acids in solvents of high OH content (sets nos. 4, 5, and 6 of Table XXVII). 

The extra base-weakening effect, when the substituent is in the o-position, is due in part to the short distance over which its inductive effect is operating, and also to direct interaction, both steric and by hydrogen bonding, with the NH2 group (cf. the case of o-substituted benzoic acids, p. 63). o-Nitroaniline is such a weak base that its salts... 

The earliest successful parameterization of electrical effects is that of Hammett6-8. Burkhardt reported the existence of QSRR two years before Hammett but did not develop a general relationship9. Hammett defined the am and ap constants using the ionization constants (Kx) of 3- and 4-substituted benzoic acids in water at 25 °C as the reference set and hydrogen as the reference substituent (i.e. K ) to which all others are compared. For hydrogen the values of the am and ap constants were defined as zero. 

In the second edition of his book33 Stewart proposed a parallel between the rate of esterification of 2-substituted benzoic acids and the molecular weights of the substituents, the nitro group strongly deviating from this relationship. The first actual attempt to define a set of steric parameters is due to Kindler39. It was unsuccessful these parameters were later shown to be a function of electrical effects. The first successful parametrization of the steric effect is due to Taft40, who defined the steric parameter Es for aliphatic systems by the expression ... 

Other papers in the series Chemometrical Analysis of Substituent Effects are on additivity of substituent effects in dissociation of 3,4-178 or 3,5-179disubstituted benzoic acids in organic solvents and on the ort/zo-effect180. In the last-mentioned, data for the dissociation of ortto-substituted benzoic acids in 23 solvents are combined with data on the reactions with DDM (Section IV.C) and with other rate and equilibrium data bearing on the behaviour of o/t/ o-substituents to form a matrix involving data for 69 processes and 29 substituents. 

A related comparison of remote substituent effects on acidities is provided by the data in Table 6-20. Here, the acidities of/ -substituted benzoic acids complexed to chromium tricarbonyl are related to the acidity of the parent compound. 

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