Carboxylic acid substituted benzoic acids

A considerable body of data is available on the acidity of substituted benzoic acids Ben zoic acid Itself is a somewhat stronger acid than acetic acid Its carboxyl group is attached to an sp hybridized carbon and ionizes to a greater extent than one that is attached to an sp hybridized carbon Remember carbon becomes more electron withdrawing as its s character increases... 

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 ionisation of m- and p-substituted benzoic acids (44), the hydroxylic solvent is capable of solvating both the undissociated acid (44) and the carboxylate anion (45) obtained from its ionisation. 

In Section IV.B we will discuss the ortho-effect of NO2 as manifested in the ionization of carboxylic and other acids and (in Section IV.C) in the reactions of substituted benzoic acids with diazodiphenylmethane (DDM). Only in the case of the latter system can really satisfactory correlation analysis be taken as the basis for discussion. For most of the other systems discussion will have to be qualitative or, at best, semi-quantitative. 

This group of pesticides comprises different families of chemicals with her-bicidal action including substituted phenols, chlorinated aliphatic acids, chloro-phenoxy alkanoic acids, and substituted benzoic acids, which possess carboxyl or phenolic functional groups capable of ionization in aqueous media to yield anionic species [47,151,168-170]. 

Long ago, Hammett (1940) recognized that for substituted benzoic acids (see Fig. 8.6) the effect of substituents in either the meta or para position on the standard free energy change of dissociation of the carboxyl group could be expressed as the sum of the free energy change of the dissociation of the unsubstituted compound, ArG, and the contributions of the various substituents ArG ... 

Substituent effects on the A,u I reaction have been studied by Bender and Chen55. These authors measured the rates of hydrolysis of a series of 4-substituted 2,6-dimethylbenzoates in 9.70 M sulphuric acid at 25°C, and found that the values for the first-order coefficients with 4-methoxy, 4-methyl, 4-unsubstituted and 4-bromo-compounds (5.0, 0.37, 0.033 and 0.01 x I0 4 sec-1, respectively) are satisfactorily correlated by the Hammett equation, following cr+ with a slope p = —3.22. Since the esters are not fully protonated in 9.70 M H2SOj, part of this factor is due to the effects of the 4-substituent on the protonation equilibrium, p for the protonation of substituted benzoic acids is about — l35, but is likely to be considerably smaller for di-ortho-substituted compounds, since the conjugative interaction of the p-substituents with the protonated carboxyl group requires coplanarity with the ring. 

Hydrogen bonded dimers of 4-RF-substituted benzoic acids [119, 120, 122, 126], /rcyclohexane carboxylic acids [120], and hydrogen bonded complexes of benzoic acids with 4,4 -bipyridine and stilbazole [166, 243-246] can be regarded as supramolecular rod-like mesogens with two fluorinated chains. Figures 33 and 34 show comparisons of selected benzoic acid dimers and their bipyridine and stilbazole complexes. Comparison of the benzoic acid dimers 122 and 123 with -alkyl chains and F-terminated -alkyl chains, respectively, indicates that a single F-atom at the end of the alkyl chain reduces the mesophase stability... 

Another more arbitrary but equally reasonable technique is to choose a single reaction as a model typical of the processes under consideration. The results from study of this reference reaction then could be employed to define the parameters for the substituent groups in other similar reactions. Thus, Hammett (1940) selected the ionization equilibria for substituted benzoic acids in water as a reference reaction and Taft (1956) employed the ionization equilibria of 4-substituted bicyclo[2.2.2]octane-l-carboxylic acids (Roberts and Moreland, 1953) for evaluating the inductive e-constants. The constants so defined are invariant. The validity of this scheme is measured by the agreement between the predictions of the reference reaction and the actual systems under study. 

An electron-donor group destabilizes a conjugate base by donating electron density onto a negatively charged carboxylate anion. A benzoic acid substituted by an electron-donor group has a higher pATa than benzoic acid (pATa = 4.2). 

The ionization of hydroxy-substituted benzoic acids is also affected by chelation. If mtramoleculeir H bonding is possible, the carboxylic acid ionization constant is raised due to the stabilization of the anion (265, 114, 273). This is Ulustrated in Table 5-VII. 

The alkaline hydrolysis of methyl esters of substituted benzoic acids has a Hammett p of 2.23. What would be the Bronsted 3 for the reaction when measured against the of the corresponding benzoic acid Comment on the magnitude of the effective charge at the reaction centre in the transition structure compared with that of the carboxylate anion product in the reference dissociation reaction ... 

Rather interesting conclusions can be drawn from an examination of the serine protease-catalyzed hydrolysis of a series of esters or anilides of basic substituted benzoic acids and amidinophenyl esters of aromatic carboxylic acids [1-10]. They react with the serine proteases like a substrate by acylation of the serine residue of the active center and by simultaneous release of the alcoholic... 

A very strange phenomenon was observed in the acidity of o-trifluoromethyl-substituted benzoic acid whose pKa is equal to that of the parent benzoic acid (Table 1.8) [3, 4]. The 2-fluorobenzoic acid is the strongest among monofluorobenzoic acids, and the same trends of acidity were observed in orthofluoro [5] and trifluoromethylphenols [6] (Table 1.9). The unusual low acidity of o-CF3-benzoic acid may arise from the suppression of the acid dissociation due to the Coulombic repulsion between carboxylate anion and... 

Protection of —COOH (3, 14-15). Full experimental details have been published for the protection of carboxyl groups as the 4,4-dimethyl-A -oxazoline derivatives. The derivatives are stable to Grignard and hydride reagents. This mode of protection was used in the synthesis of various substituted benzoic acids from the corresponding bromo acids. ... 

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