Acidity substituted benzoic acids

Habid and Malek49 who studied the activity of metal derivatives in the catalyzed esterification of aromatic carboxylic acids with aliphatic glycols found a reaction order of 0.5 relative to the catalyst for Ti(OBu)4, tin(II) oxalate and lead(II) oxide. As we have already mentioned in connection with other examples, it appears that the activation enthalpies of the esterifications carried out in the presence of Ti, Sn and Pb derivatives are very close to those reported by Hartman et al.207,208 for the acid-catalyzed esterification of benzoic and substituted benzoic acids with cyclohexanol. These enthalpies also approach those reported by Matsuzaki and Mitani268 for the esterification of benzoic acids with 1,2-ethanediol in the absence of a catalyst. On the other hand, when activation entropies are considered, a difference exists between the esterification of benzoic acid with 1,2-ethanediol catalyzed by Ti, Sn and Pb derivatives and the non-catalyzed reaction268. Thus, activation enthalpies are nearly the same for metal ion-catalyzed and non-catalyzed reactions whereas the activation entropy of the metal ion-catalyzed reaction is much lower than that of the non-catalyzed reaction. 

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

All equilibrium constants are defined relative to benzoic acid substituted with the simplest R-group, a hydrogen (R = H). Equation 12.9 can be rewritten as a difference in log K values. Substitution of Equation 12.3 shows that crR is a measure of standard free energy change caused by the R-group (Equations 12.10 and 12.11). Because o-R is a logarithm (Equation 12.9), o-R is unitless. 

Carboxyl Benzoic acid Substituted benzoic acids 67... 

Benzoic acids substituted with alkyl, halo, hydroxyl, alkoxyl, cyano, or nitro groups react to give the corresponding substituted anilines in 41-80% yields. The carboxyl group in an a-amino acid does not react with hydrazoic acid the reaction proceeds, however, if the amino group is further removed. This difference in reactivity is shown by the conversion of a-aminoadipic acid to i(-ornithlne (75%). ... 

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 chemical information available through LFER is primarily the reaction constant p, but this value depends upon the substituent constants selected for the construction of the LFER. The u values available are ct, ct", ct" or and Ui, these quantities are listed, for many substituents, in Tables 7-1, 7-3, 7-4, 7-6, and 7-7. A reasonable approach is to plot log k against the substituent constant defined by a standard reaction that is expected to be most like the reaction under study. It is also reasonable to plot log k against several of the ct quantities, seeking the best correlation. [In choosing between two types of substituent constants, it is necessary to make use of substituents for which the two scales (say ct and rr, for example) are not themselves correlated, for otherwise both LFERs will be acceptable. ] The ct or o constants should be applicable to reactions that do not combine reaction sites and para substituents of the + and — type (push-pull systems capable of through resonance) for example, one would not expect ct" or o to provide good correlations for reactions of phenols or anilines substituted with nitro or cyano or for reactions of benzoic acids substituted with amino or methoxy. 

H. A. Pohl, M. E. Hobbs, and P. M. Gross. J. Chem. Phys. 9, 408-14 (1941). Dipole moment C1-C4, benzoic and substituted acetic acids, hydrocarbon solvents. 

Figure 10.13. Adsorption isotherms on Fe(OH)3 of four benzoic acids substituted at the para position with the functional groups shown. (Adapted from K.-H. Kung and M. B. McBride. 1989. Adsorption of para-substituted benzoates on iron oxides. Soil Sci. Soc. Am. I. 53 1673-1678.)...

Figure 2 Schematic representation of acylation of serine proteases by amidinophenyl benzoates deacylation rate (ks) depends on benzoic acid substitution (R).

Fig. 4. Hydrogenation of the ring of acid-substituted aromatic compounds using 5% Rh on AhOa powder as catalyst and 100 ml. solvent. 1) 1 g. catalyst, 0.5 ml. benzene, HOAc 2) 1 g. catalyst, 500 mg. benzoic acid HOAc 3) 1 g. catalyst, 500 mg. phthalic acid, HaO 4) 1 g. catalyst, 500 mg. m-hydroxy-benzoic acid, HOAc 5) 1 g. catalyst, 500 mg. phthalic acid, HOAc 6) 1 g. catalyst, 500 mg. salicylic acid, HOAc 7) 1 g. catalyst, 500 mg. p-hydroxy-benzoic acid, HOAc.

An excess of alkali may be added at the start, in which condition potassium permanganate is used for oxidizing ortho-substituted derivatives of toluene. Thus, o-toluic acid yields phthalic acid. Substituted cinnamic acids are oxidized to the corresponding benzoic acids. Triphenylmethane is oxidized to the corresponding alcohol, diphenylmethane4,o the ketone, and oleic acid to dihydroxystearic acid. 

A. Hammett Substitution Constant (o). It is a measure of either the electron-withdrawing or electron-donating capability of a substituent i.e., the functional moiety). Hammet substitution constant may be determined conveniently by actual measurement of the dissociation of a series of benzoic acid substituted derivatives vis-a-vis the dissociation of pure benzoic acid itself. 

By oxidation of the labeled products [28 and 29 or 30ab] to labeled benzoic and substituted benzoic acids followed by assay of these purified acids for carbon-14, the relative migratory abilities of the Ar groups with respect to phenyl were determined. Thus in the dehydration, with phosphorus pentoxide in xylene, of a series of carbinols (27, X = OH), the following migratory aptitudes (Ar Ph) were determined p-xenyl, 1-3 m-tolyl, 1-6 p-i-propylphenyl, l-8 3,4-dimethyl-phenyl, 1-9 p-tolyl, 2-0 p-ethylphenyl, 2-2 p-t-butylphenyl, 3-2 and p-anisyl, 21-2. Burr (1953) demonstrated the p-tolyl phenyl migration ratio to be 2-5 during the solvolysis of 2-phenyl-2- p-tolylethyl-l-i C tosylate (27, Ar = p-tolyl, X = tosyl). In a series of deaminations of the primary amines (27, X = NH ) and 31 (Ar = p-tolyl and o-tolyl) the p-tolyl phenyl (1 2), p-biphenyl phenyl (1 0) p-anisyl phenyl... 

The triketones can be separated into two parts for analysis of the structure-activity relationships, namely the benzoyl and the dione moieties. Each part can be examined independently, as they appear to play distinct and different roles in the overall expression of herbicidal activity [1]. Apart from the necessity of an ortho-substituent on the phenyl ring, it was established that 2,4,- or 2,3,4-benzoic acid substitution patterns were required for optimal activity, with the 2,5-... 

Other novel co-condensation products, given in Scheme 21, are obtained by using different benzoic acids, substituted phenols, and methanal [160]. 

Salih Agirtas, M., MetinQelebi, Sel9ukGumus. (2013). New water soluble phenoxy phenyl diazenyl benzoic acid substituted phthalocyanine derivatives Synthesis, antioxidant activities, atypical aggregation behavior and electronic properties. Dyes and Pigments 99, 423 31. 

The earliest and best known relationship was devised by Hammett [2] and is based on such an equilibrium, namely the dissociation constants of nuclear substituted benzoic acids. Hammett substituent constants a are given by Equation (8), where Kq represents the dissociation constant for benzoic acid and K represents the dissociation constant for a derivative of benzoic acid substituted by the group to which the substituent constant belongs. 

Also in other series of growth substances indications are found that substitutions not compatible with auxin activity may lead to an antiauxin character of the respective compound, as e.g. for benzoic acids and phenoxy-acetic acids substituted in the 4- or 2,6-positions respectively . ... 

Treatment of methyl p-methylbenzoate with 1.2 equiv of trimethylsilyldiethylarnine and 1.3 equiv of methyl iodide in toluene, followed by gradual heating to 90 °C over a period of 4h and additional stirring at 100-110 °C provides the corresponding trimethyl silyl ester. Subsequent hydrolysis affords p-methylbenzoic acid in 85% yield based on 90% conversion (reaction monitored by GC) (eq 8). Benzoic esters substituted with an electron-donating substituent such as methyl or methoxy groups are more readily dealkylated in contrast with electron-deficient esters, such as with chlorine atom substituent, or aliphatic carboxylic acid esters. 

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