Hydroxybenzoate ester

Scheme 8 Parallel mechanisms for the alkaline hydrolysis of aryl 4-hydroxybenzoate esters...

G. Cevasco et al., A Novel Dissociative Mechanism in Acyl Transfer from Aryl 4-Hydroxybenzoate esters in Aqueous Solution, J. Org. Chem., 1984, 50, 479. 

In the weakly acidic preservatives, activity resides primarily in the unionized molecules and they only have significant efficacy at pHs where ionization is low. Thus, benzoic and sorbic acids (pKa = 4.2 and 4.75, respectively) have limited preservative usefulness above pH 5, while the 4(p)-hydroxybenzoate esters with their non-ionizable ester group and poorly ionizable hydroxyl substituent (pKa ca. 8.5) have moderate protective effect even at neutral pH levels. The activity of quaternary ammonium preservatives and chlorhexidine probably resides with their cations and are effective in products of neutral pH. Formulation pH can also directly influence the sensitivity of microorganisms to preservatives (see Chapter 11). 

Ethanol, benzoic acid, sorbic acid, the hydroxybenzoate esters, phenylethyl alcohol, and glycerin Ascorbic acid, citric acid, sodium metabisulfite, and sodium sulfite... 

A biogenetic flavour is apparent in the formation of dihydroxybenzophenones by the reaction of o-hydroxybenzoate esters with the trianion of heptane-2,4,6-trione (81JOC2260). Acylation of the trianion occurs at 0-25 °C to give a tetraketone which cyclizes under mildly basic conditions to the corresponding benzophenone. A second ring closure takes place when the benzophenone is treated with sodium methoxide, leading to the xanthone (Scheme 188). 

A validated method (No. 63) for the analysis of benzoic acid, sorbic and para-hydroxybenzoic acids in fruit juices has been published in the IFU handbook (Anon, 1995e). In this method the resolution takes place on a C8 reverse-phase column. With this solvent system (methanolic/ammonium acetate, pH 4.55) sorbic and benzoic acids elute quite quickly and the less polar para-hydroxybenzoate esters elute much later. The method does stipulate that caution has to be taken by orange juice due to possible interferences by natural materials in the juice that elute close to benzoic acid. As sorbic and benzoic acids elute quite early in the chromatogram using this method, it would... 

Buffers can also be provided in parenteral formulations to ensure the required pH needed for solubility and/or stability considerations. Other excipients included in parenteral products are preservatives (e.g., benzyl alcohol, p-hydroxybenzoate esters, and phenol), antioxidants (e.g., ascorbic acid, sodium bisulfite, sodium metabisulfite, cysteine, and butyl hydroxy anisole), surfactants (e.g., polyoxyethylene sorbitan monooleate), and emulsifying agents (e.g., polysorbates). An inert gas (such as nitrogen) can also be used to enhance drug stability. Stability and solubility can also be enhanced by the addition of complexation and chelating agents such as the ethylenediaminetetraacetic acid salts. For a more detailed list of approved excipients in parenteral products, the reader should consult the monographs within the USP. 

Although antimicrobial activity is reduced in the presence of nonionic surfactants, such as polysorbate 80, the reduction is less than is the case with hydroxybenzoate esters or quaternary ammonium compounds. 

Antimicrobial activity activity is similar to that of the p-hydroxybenzoate esters (parabens). The greatest activity is against molds and Gram-positive bacteria, with less activity against Gram-negative bacteria. 

In some lignins, 5-10% of the units are esterihed examples includep-hydroxybenzoate esters in lignins from Salix species (56) [69,108] and p-coumarate esters in grass lignins (57) [109-111]. The y-positions in lignin are the ones that primarily are esterified [110]. 

Cure rgtes were roughly comparable (and quite fast) for the control MD D M polymer and its 20% hydroxyester benzoate and acetate derivatives. Some cure loss was observed where of the oxirane groups were replaced with hydroxyacetate, but the tenfold decrease in UV cure rate observed when available oxirane is converted to hydroxybenzoate ester was surprising and unexpected. An explanation becomes obvious, however, on examination of the structure of these polymers ... 

Phenylethanol alone is not routinely used as preservative in eye drops due to too low an antimicrobial activity especially against gram-positive bacteria. Moreover phenylethanol cannot be combined with other preservatives because of its potential to irritate the eye [101]. Hydroxybenzoic esters are also reported to cause a high incidence of eye irritation. Thiomersal is not routinely used due to low antimicrobial activity, allergic reactions and penetration of mercury into the eye. The same is also true but to a much lesser extent for phenylmercuric salts [102-104] (see also Sect. 23.8.4). 

Ferro s UV-Chek AM 340 is a hydroxybenzoate ester light stabilizer that is used in conjunction with a HALS. It functions initially as a radical-free... 

The p-hydroxybenzoate esters can be separated with pentane-acetic acid (88 -f 12) on silica gel layers containing a fluorescence indicator [32]. These compounds are then detected in short wave UV radiations as dark spots of fluorescence quenching (Fig. 179). The layers are prepared from silica gel 6 by adding 2 % of the fluorescent material Leuchtstoff ZS-Super (Firm 118) or by using a silica gel, such as silica gel GF254 (Firm 88), which already contains a fluorescent additive. 

As well as the p-hydroxybenzoate esters, sorbic and benzoic acids are also often used in food technology as preservatives. According to Copitjs-Peereboom [20], these preservatives may be satisfactorily separated on cellulose layers (Firm 83) using n-butanol-35% ammonium hydroxide-water (70 + 20 + 10) at chamber saturation. Visualisation is performed with a bromophenol blue-methyl red solution (Rgt. No. 29), followed by spraying with permanganate solution. 

Unusual pyronotropane tropane alkaloids have been fotmd in the family Proteaceae. Tropine and pseudotropine esters of benzoic acid have been isolated from the family Euphorbiaceae. Novel dithiolane esters, along with tropine esters of acetic, propionic, n-butyric, isobutyric, isovaleric, and benzoic acids have been fotmd in the Rhizophoraceae. Calystegines, as well as a 3-hydroxybenzoate ester, have been fotmd in Brassicaceae. The calystegines have been used as chemotaxonomic markers in the Convolvulaceae family [20]. Tropine esters with methoxy-substituted benzoic acids are also characteristic for the later family. 

Cochlearine, C15H19O3N (mp 229°), and a base, C9Hi2( )02N (mp 151°). A total of five alkaloids was shown on a chromatogram (55). Cochlearine was shown to be the m-hydroxybenzoic ester of tropine (56). 

One of the hydroxybenzoic acids is known by the common name salicylic acid Its methyl ester methyl salicylate occurs in oil of wintergreen Methyl salicylate boils over 50°C lower than either of the other two methyl hydroxybenzoates What is the structure of methyl salicylate Why is its boiling point so much lower than that of either of its regioisomers ... 

Methyl salicylate is the methyl ester of o hydroxybenzoic acid Intramolecular (rather than mtermolecular) hydrogen bonding is responsible for its relatively low boiling point... 

First,/)-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) are acetylated to produce the low melting acetate esters which are molten at 200°C. In an inert gas, the two monomers are melted together at 200°C. The temperature is raised to 250—280°C and acetic acid is coUected for 0.5 to 3 h. The temperature is raised to 280—340°C and additional acetic acid is removed in vacuum for a period of 10 to 60 min. The opalescent polymer melt produced is extmded through a spinning jet, foUowed by melt drawdown. The use of the paraUel offset monomer, acetylated HNA, results in the formation of a series of random copolyesters of different compositions, many of which faU within the commercially acceptable melting range of... 

Table 4. Physical and Antimicrobial Properties of />Hydroxybenzoic Acid Esters ...

Perfumes, Flavors, Cosmetics, and Soap. Many naturally occurring esters in essential oils and some synthetic esters are important fragrance and flavor compounds (61,62). They are used in perfumes, flavors, cosmetics, soaps, detergents, and air fresheners. Benzyl, butyl, ethyl, methyl, and phenyl esters of benzoic acid are used as flavors, perfumes, and food preservatives. Glyceryl 4-aminobenzoate [136-44-7] and 2-ethyUiexyl 4-dimethylaminobenzoate [21245-02-3] are used in cosmetic sunscreen preparations. Alkyl esters of 4-hydroxybenzoic acid, called parabens, have been used under various names for fungus infections of the skin, and as preservatives in lotions and creams (101). Soap and cosmetic fragrances use large amounts of amyl and benzyl saHcylate. Benzyl saHcylate [118-58-1] is also used in deodorant sprays. 2-Ethylhexyl saHcylate [118-60-5] and 2-ethylhexyl 4-methoxycinnamate [5466-77-3] are used in sunscreen formulations (102). 

This can be achieved by an indirect method. The lithio derivative is first reacted with a borate ester. Sequential acid hydrolysis and oxidation yields the corresponding hydroxy derivative. This procedure is illustrated by the conversion of 2-lithiobenzo[6]thiophene to 2-hydroxybenzo[6]thiophene, which exists predominantly in the 2(3//)-one tautomeric form (200) <70JCS(C)1926). 

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