Para-hydroxybenzoic acid

TE Haag, DF Loncrini. Esters of para-hydroxybenzoic acid. In JJ Kabara, ed. Cosmetic and Drug Preservation. New York Marcel Dekker, 1984, pp 63-77. 

Phenols are generally named as derivatives of the simplest member of the family, phenol, e.g. < -chlorophenol. Sometimes trivial or special names are also used, e.g. m-cresol. Occasionally, phenols are named as hydroxy-compounds, e.g. para-hydroxybenzoic acid. Numbering is often used to denote the position(s) of the substituent(s) on a phenol skeleton, e.g. 2,4-dinitrophenol. 

Liquid dosage forms which are disperse systems (colloidal, i.e., microspheres, nanoparticles, and micelles suspensions and emulsions) often contain preservatives which are methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid in various combinations. A typical example is the antacid suspensions which have high pH values which make the esters of the preservatives susceptible to hydrolysis. One way to circumvent this problem is to use several preservatives in combination with the hope that some quantities of the preservatives will remain to prevent the suspension from microbial attack. A report showing the assay of the four esters and the parent acid (one of the decomposition products) in drug products in which all the preservatives were used has been given [13]. 

Let s compare the ionization of ortho- and para-hydroxybenzoic acids ... 

These compounds include the methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid. In the United Slates and a number of other countries, the methyl and propyl esters are preferred, while European food processors favor the ethyl and butyl esters. The parabens were first described in 1924 as having antimicrobial activity and initially were used in cosmetic and pharmaceutical products. 

A paired-ion, reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of sweeteners (dulcin, saccharin-Na, and acesulfame-K), preservatives (sodium dehydroacetate, SA, salicyclic acid, BA, succinic acid, methyl-para-hydroxybenzoic acid, ethyl-para-hydroxybenzoic acid, n-propyl-para-hydroxybenzoic acid, n-butyl-para-hydroxybenzoic acid, and isobutyl-para-hydroxybenzoic acid), and antioxidants (3-tertiary-butyl-4-hydroxyanisole and tertiary-butyl-hydroquinone). A mobile phase of acetonitrile-50 ml aqueous tr-hydroxyisobutyric acid solution (pH 4.5) (2.2 3.4 or 2.4 3.6, v/v) containing 2.5 mM hexadecyltrimethylammonium bromide and a Clg column with a flow rate of 1.0 ml/min and detection at 233 nm were used. This method was found to be very reproducible detection limits ranged from 0.15 to 3.00 p,g. The retention factor (k) of each additive could be affected by the concentrations of hexadecyltrimethylammonium bromide and a-hydroxyisobu-tyric acid and the pH and ratio of mobile phase. The presence of additives in dried roast beef and sugared fruit was determined. The method is suitable for routine analysis of additives in food samples (81). 

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... 

The first fibers from a thermotropic liquid crystalline melt whose properties were reported were spun from a copolyester of para-hydroxybenzoic acid (PHB) and PET by workers at Tennessee Eastman Co. The preparation of the copolymer proceeds in two stages. First, / ara-acetoxybenzoic acid is reacted with PET in an acidolysis step to give a copolyester prepolymer, which in the second step is condensed further to a higher degree of polymerization suitable for fiber formation. 

Viscosity. The best summary of the effect of inner H bonds on viscosity is that of Friend and Hargreaves (722). They show in conclusive fashion that the viscosity of orbonded compounds—another reflection of the tendency toward normalcy resulting from internal satisfaction of H bonding capacity. Figure 1-2 shows the structure of ortho- and para-hydroxybenzoic acid. 

Parabens (methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid) are used as preservatives in concentrations of 0.1-0.3% in pharmaceutical formulations and in concentrations of 0.01-0.1% in cosmetics and foods. In such concentrations they are devoid of systemic toxic effects, but allergic reactions have been reported. 

Phenol acids are phenols in which there is also a carboxylic acid group attached to the benzene ring. They include salicylic acid (ortho-hydroxybenzoic acid) and para-hydroxy-benzoic acid (Figure 25.8). Acetylsalicylic acid (aspirin) and sodium salicylate are derivatives of salicylic acid. Like phenol, they have antipyretic and analgesic properties. The methyl, ethyl and propyl esters of para-hydroxybenzoic acid (parabens) are used as preservatives in pharmaceuticals, cosmetics and foodstuffs. 

Chemical structures of salicylic acid (a) and para-hydroxybenzoic acid (b). 

The carboxylation of hydroxyaromatic compounds in the form of alkaline salts (the Kolbe Schmitt reaction) is well known and applied in the synthesis of acids such as salicylic acid, para-hydroxybenzoic acid and orf/to-cresotinic acid. 

This thermodynamic data is taken from the description of a Ueno process (ref. 1) for the preparation of para-hydroxybenzoic acid. 

When carbon tetrachloride is used instead of chloroform a similar condensation takes place the compound formed in this way is a derivative of benzotrichloride and on hydrolysis yields a mixture of ortho- and para-hydroxybenzoic acid. 

Synonyms p-heptylp-hydroxybenzoate heptyl ester of para-hydroxybenzoic acid Heptyl Pelargonate... 

The need for moldable grades of polyester prompted a major research effort in the area of copolymers (the chemistry of the materials described here was developed by Dr. Steve Gottis). To retain the excellent thermal resistance of the p-oxybenzoyl homopolymer (continuous use ten era-ture of 550-600°F, short exposure temperatures of 750-800°F), only completely aromatic systems were investigated. Para- -hydroxybenzoic acid was formulated with several co-monomers. These included the meta and para diaclds (isophthalic and terephthalic acid), and various dlhydroxy aromatic compounds, such as hydroqulnone and resorcinol. 

The aromatic core of the CoQn molecule is derived from the shikimate pathway, which starts with the condensation of erythrose-4-phosphate (E4P) and phosphoe-nolpymvate (PEP). The shikimate pathway leads to the production of the aromatic intermediate chorismate, a precursor for several essential aromatic molecules including aromatic amino acids and folate, which is converted to para-hydroxybenzoic acid (PHB) by the chorismate lyase UbiC. PHB, the first committed intermediate to ubiquinone biosynthesis, is then prenylated with an isoprenoid of varying length, depending on the species (Fig. 15.2). 

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