Benzoic Acids and Related Compounds

3 Phenolic Acids, Salicins and Other C5-C1 Compounds 7.L3.1 Benzoic Acids and Related Compounds 

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New aspects of the chemistry of 2,4,6-tris(tri-fluoromethyl)benzoic acid and related compounds./. Fluorine Chem. 1991, 52, 99-105. 

Benzoyl peroxide is used mainly in acne treatment and is an irritant. Allergic contact dermatitis to this compound is not infrequent. Eaglstiein (1968) reported two cases. The sensitization rate has been estimated to be 1 %-2.5%. In a human maximization test, 76% became sensitized (Leyden and Kligman 1977). Crossreactions to benzoic acid and related compounds were not found. The drug has been advocated for treatment of chronic leg ulcers. Eight of 16 patients showed positive patch tests to 2% benzoyl peroxide after 6 weeks of leg ulcer treatment with 10% benzoyl peroxide (Jensen et al. 1980). Patients sensitized to benzoyl peroxide may be at risk in certain occupations (e.g., baking and the plastics industry). 

Depends—a palladium-catalyzed iodination of benzoic acid and related compounds generates moderate to excellent yields without protection of the carboxylic add [149]... 

Food preservatives -benzoate salts m [BENZOIC ACID] (Vol 4) -p-hydroxybenzoic acid m [SALICYLIC ACID AND RELATED COMPOUNDS] (Vol 21)... 

SALICYLIC ACID AND RELATED COMPOUNDS. [CAS 69-72-7], Salicylic acid or C H4(OH)(COOH) is a white solid, melting points 159°C, sublimes at 76°C, insoluble in cold water, soluble in hot water, alcohol, or ether. With ferric chloride solution, salicylic acid solutions are colored violet (distinction from benzoic acid). 

Numerous organic acids have been identified in tobacco. These volatile, nonvolatile, and amino acids have been discussed in-depth by Tso [see Chapter 24 in (3973)]. The major nonvolatile acids are 2-hydroxy-l,2,3-propanetricarboxylic (citric), hydroxybutanedioic (malic), and ethanedioic (oxalic). The minor nonvolatile acids are hydroxyacetic (glycolic), butanedioic (succinic), propanedioic acid (malonic), butene-dioic (E) (fumaric acid), and 2-oxopropanoic (pyruvic). The major volatile acids in tobacco are acetic and formic acid minor volatile acids are propanoic, 2-furancarboxylic acid (2-furoic), benzoic, a-methylbutyric, P-methylvaleric, and numerous others. Over forty amino acids and related compounds have been identified in tobacco [Leffingwell (2337)]. 

The AH° variations noted above for acetic acid and benzoic acid are in line with the dome-shaped pK, dependence on temperature first noted by Harned and coworkers for acetic acid and related compounds in the 1930 ... 

Hydroxybenzoic acids may arise by polyketide pathways (primarily in bacteria and fungi), from shikimate and possibly other intermediates of the shikimate pathway, by p-oxi-dation of cinnamic acid and related compounds, and by hy-droxylation of benzoic acid and other Cg-Ci compounds (Leon et al., 1993 Yalpani et al., 1993). 

In contrast to 2,3-dioxygenases, the related ipso/ortho oxygenation of aryl carbox-ylates has received considerable less attention and has hardly been utilized by the synthetic community, so far. Biooxidation of benzoic acid and P-naphthalene carboxylate provide access to corresponding 1,2-dihydroxylated dihydroaryl compounds in excellent stereoselectivity (Scheme 9.35), analogous to TDO- and NDO-mediated ortho/meta oxygenations. Whole-cell-mediated biotransformations were performed with mutant strains of Rahtonia and Pseudomonas and enable access to preparative quantities in >5 gl titers [261,262]. 

Several synthetic routes are available for oxazoles and related compounds. The first one, outlined in Scheme 41, is based on previously discussed syntheses of benzofurans (Scheme 17) and imidazoles (Scheme 40). Thus, a-aroyloxyacetophenones (147), which are obtained by HTIB-induced oxidation of 51 followed by treatment with para-substituted benzoic acids, can be cyclized to oxazoles 148 (95JIC129) (Scheme 41). 

However, a careful study of the experimental data has led to some general trends. For instance, the nature of the final products depends heavily on the alkali cations used in the starting compounds sodium and lithium phenoxides reacting under similar experimental conditions yield the related salicylates as major products [18] (Scheme 5.1), whereas potassium, rubidium, and cesium phenoxides yield mixtures of 2-hydroxy-benzoic acid and 4-hydroxy-benzoic acid [1] (Scheme 5.2). As a rule of thumb, the yield of p-hydroxybenzoic acid generally increases with the increasing ionic radius of the alkali metal. Both, temperature and C02-pressure were also reported to be paramount in the selectivity of the carboxylation ... 

If we take a series of compounds which are related by structural substitutions, such as benzene derivatives, then we can assign the effects of the structural changes to the ratio KBJKB. if we select this property as a standard. Such a system of correlation was first proposed by Hammett and revised and extended by Jaff " to account for the effects of meta and para substituents on the reactivity of benzene derivatives. For convenience, the ionization constant of benzoic acia queous solution at 25°C was chosen as standard and for each meta or para substituent a, a value of ionization constant for benzoic acid and Ka the ionization constant of the corresponding, substituted benzoic acid. 

Hammett LFER. An LFER with broad implications was developed in the 1930s by Hammett (1937) to explain substituent effects on reactions of meta- or para-substituted benzene compounds. Hammett found that hydrolysis of substituted ethyl benzoates, ionization of substituted benzoic acids, and many related reactions are affected by nature and position of aromatic substituents, and that the effect could be predicted quantitatively. Using rate and equilibrium constants for ionization of benzoic acid as references, Hammett defined the LFER ... 

The carboxypeptidase family of enz5Tnes also includes carboxypeptidase G2 (CPG2) which catalyses the cleavage of C-terminal glutamate from folate (28.24) and related compounds such as methotrexate (in which NH2 replaces the OH group in the pterin group, and NMe replaces NH in the 4-amino benzoic acid unit). 

Other compounds such as benzoic acid and pyrazole, which can effect similar concerted proton transfer and avoid charged species, also catalyze this and related reactions Another type of bifunctional catalysis has been noted with a, co-diamines in which one of the amino groups is primary and the other tertiary. These substituted diamines are from several times to as much as 1000 times more reactive toward imine formation than monofunctional amines. This is attributed to a catalytic intramolecular proton transfer. 

Competitive adsorption of micro-organics is illustrated in Fig. 6 for (a) two compounds with different solubilities, phenol being 30 times less soluble than benzoic acid, and (b) two compounds of similar solubility, benzoic acid and p-chlorophenol [40]. Inhibition of the adsorptive capacity is apparent in both cases but the extent of the interference is different. The high discrepancy observed for the couple phenol - benzoic acid may be related to a favored adsorption of the compound of low solubility (benzoic acid), this parameter being no longer a decisive factor as initial concentration decreases. For the second binary system, similar solubilities for both organics lead to closer adsorption capacities. 

C9H9NO3, Mr 179.17, mp. 187-188 °C. H. occurs in the urine of most mammals, especially herbivorous animals. It was first isolated by J. v. Liebig from horse urine (= Greek hippou ouron). The biosynthesis proceeds from benzoic acid or related aromatic compounds and glycine under the action of hippuricase (EC 3.5.1.14). 

Dumas, working with the French apothecary Pierre Francois Guillaume Boullay, first proposed that the ethylene group (a two-carbon chain) could serve as the radical base for alcohol and related compounds. The concept of radicals received further support when Liebig and Wohler published their work on oil of bitter almonds. They found a family of compounds— benzoic acid, benzoin, benzaldehyde, benzoyl chloride, benzoyl bromide, benzoyl iodide, benzoyl cyanide, benzoyl... 

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