Esters of p-hydroxy-benzoic acid

Finally it has to be pointed out that the antimicrobial esters of p-hydroxy-benzoic acid (/ -hydroxy-benzoates) are not described in this section because of their high acidity they are listed under Acids in Section 6. 

The coefficient of variation for the methyl and propyl esters of p-hydroxy benzoic acid were 3.2% (13 determinations) and 4.8% (14 determinations). 

In a variation of the scheme above, alkylation of p-hydroxy-benzoic acid with cyclohexyl iodide affords the cyclohexyl ether, 55. (Under alkaline reaction conditions, the ester formed concurrently does not survive the reaction.) Acylation of the acid chloride obtained from 55 with the preformed side chain (56) gives cyclomethycaine (57). ... 

The aliphatic-aromatic diacid monomers were prepared from the reaction of bromoalkanoic acid methyl ester and p-hydroxy benzoic acid methyl ester. The polymers of carboxyphenoxy alkanoic add of n = 3, 5, and 7 methylenes were soluble in chlorinated hydrocarbons and melted at temperatures below 100 °C. Copolymers of these monomers melted at lower temperatures than the respective homopolymers. These polymers displayed zero-order hydrolytic degradation profile ranging from 2 to 10 weeks. Increasing the length of the alkanoic chain, decreased the degradation rate of the polymer (Fig. 3). 

In comparison with the lower p-hydroxybenzoic acid alkyl esters the butyl ester is far and away the most effective one and presents an equalized spectrum of effectiveness (see Table 81). However, the application of the butyl ester as a preservative in cosmetics, toiletries and pharmaceuticals is, in spite of its high activity, limited because of its low water solubility and high log POW. But combinations of p-hydroxy-benzoic acid butyl ester with the lower alkyl esters perform excellently. 

The opposite can be observed with acidic analytes as shown in Figure 2.18. Here, with classical RP and methanol at pH 3 the best selectivity and peak shapes were observed. On the other hand, with the shielded phases, acetonitrile gives the best separation. As already discussed, with shield phases the retention of nonpolar components (here peak 6 dimethyl phthalate) is reduced, whereas that of phenolic components (e.g., peak 5 p-hydroxy benzoic acid methyl ester) is increased. 

Acetic anhydride is often used to prepare acetate esters from alcohols and AT-substituted acetamides from amines. For example, aspirin (acetyl-salicylic acid) is prepared commercially by the acetylation of o-hydroxy-benzoic acid (salicylic acid) with acetic anhydride. Acetaminophen, a drug used in over-the-counter analgesics such as Tylenol, is prepared by reaction of p-hydroxyaniline with acetic anhydride. Note that the more nucleophilic -NH2 group reacts, rather than the less nucleophilic -OH group. 

As the effectiveness against bacteria is weak, weaker than the activity against moulds, 2-phenyl ethanol is in general applied in combination with other microbicides, e.g. with p-hydroxy-benzoic acid esters (Section 6.1.10), quaternary ammonium compounds (Section 16-1), p-chloro-m-cresol (Section 5.3.1) for the preservation of cosmetic and pharmaceutical products. It is especially effective in acidic media. 

Antimicrobial action. All p-hydroxybenzoic acid esters have principally a fungistatic action. The p-hydroxy-benzoic acid esters destroy the cell membrane and lead to a protein denaturation in the interior of the cell besides competitive reactions occur with coenzymes (Tatsuguchi, et ah 1991). Under aerobic conditions Paraben is hydrolysed to p-hydroxybenzoic acid. The following decarboxylation of which leads to phenol, [II, 7.1.] (Valkova, et ah, 2001). 

Esters.— The simplest class of compounds present in essential oils are the esters or ethereal salts (p. 140). In our early discussion of these compounds in the aliphatic series it was stated that the odor and flavor of common fruits is probably due to ester compounds and that certain empirical mixtures of esters are used as artificial fruit essences. Artificial apple essence, for example, may be prepared by mixing certain proportions of ethyl nitrite, ethyl acetate and amyl valerate with chloroform, aldehyde and alcohol. An example of an essential oil which consists of a single ester is oil of wintergreen. vAdxh is the methyl ester of salicylic acid, ortho-hydroxy benzoic acid (p. 714). 

Hexachlorocyclotriphosphatriazeneb (also known as phosphonitrilic chloride trimer, PNC) has also been found to promote the polycondensation of carboxylic acids and phenols to yield carboxylic esters in high yields. This process has been successfully applied to the preparation of polyesters directly from p- and m-hydroxy-benzoic acids and also from a combination of dicarboxylic acids and bisphenols (Table 18)13, especially from 4-hydroxy 3,5-dimethoxy benzoic acid (syringic acid) in high yield. 

The migration of methyl to sulphur observed in reactions of o-mercapto-benzoic acid methyl ester with primary aliphatic amines, possibly via an S i mechanism, contributes another example to an extensive list of interactions of aromatic or/Ao-substituents. More conventional nucleophilic substitution processes include syntheses of L-selenomethionine, MeSeCH2 -CHa CH(NH2) C02H, and its c-ethyl and S e-benzyl analogues by treatment of O-toIuene-p-sulphonyl-L-homoserine with appropriate organo-selenium nucleophiles also, analogous reactions of hydroxy-acid... 

Phenolic compounds are widely distributed in plant parts from the roots to the seeds and include phenolic acids, flavo-noids and tannins. The tannins may reduce protein digestibility (Ford and Hewitt, 1979) and perhaps the bioavailability of other nutrients. The flavonoids have been reported to have a number of nutritional and pharmacological activities (Kuhnau, 1976). Phenolic acids include benzoic and cinnamic acid derivatives. The benzoic acid derivatives include p-hydroxy-benzoic, protochate-chuic, vanillic, gallic and syringic acids. The cinnamic acids, p-coumaric, caffeic, ferulic and sinapic are found in most oilseeds used to prepare protein concentrates and frequently occur in the form of esters with quinic acid or sugars. Chlorogenic acid for example is an ester of caffeic acid and quinic acid and is found in several isomeric and derivatized forms. 

The effect of the degree d xrlarization of the ester linkages in low-motecular-weight esters on their reactivity has been examined by studying the reaction of alcoholysis, with ceUulose, of methyl esters of benzoic, p-chloro-, p-hydroxy, p-hydroxy-, p- and o-nitrobenzoic acids, and those of phenyl-, phenoxy-, 2,4-dichlorophenoxy- and monodiloro-acetic adds. The trans-esterification reaction was carried out in non-aqueous dinrethylformamide in the presence of catalysts (sodium methylate, cadmium acetate, p-toluenesulphonic add) at 110-140° C. 

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