Soluble methyl hydroxybenzoate

Synonyms E219 methyl 4-hydroxybenzoate sodium salt sodium methyl hydroxybenzoate soluble methyl hydroxybenzoate. 

Synonyms. Sodium Methylparaben Soluble Methyl Hydroxybenzoate. Proprietary Name. Nipagin M Sodium C8H7Na03 = 174.1 CAS—5026-62-0... 

The use of preservative eombinations may be used to extend the range and speetrum of preservation. Thus, in the series of alkyl esters of 4-hydroxybenzoic (/ -hydroxybenzoic) acid (parabens), water solubility deereases in the order methyl, ethyl, propyl and butyl ester. By eombining these produets it is possible to aehieve a situation where both the aqueous and oil phase of an emulsion are proteeted. 

These esters of p-hydroxybenzoic acid have been used primarily to prevent growth of molds but in higher concentrations possess some weak antibacterial activity. Their effective use is limited by low aqueous solubility and by reports of stinging and burning sensations related to their use in the eye. They bind to a number of nonionic surfactants and polymers, thereby reducing their bioactivity. They are used in combination, with the methyl ester at 0.03-0.1% and the propyl ester at 0.01-0.02%. Parabens have also been shown to promote corneal absorption [140]. 

Protection of carboxylic acids. The 2-(2-pyridyl)ethyl group is useful for protection of amino acids. The esters are obtained by reaction with 1 and DCC/1-hydroxybenzo-triazole. The group provides higher solubility in protic solvents, and is stable to both acids and bases. It is removed by treatment with methyl iodide and a weak base. 

Acidic preservatives are the most widely used for oral preparations, such as the p-Hydroxybenzoic acid esters and salts of benzoic acid. These are adequately soluble in aqueous systems and possess both antifungal and antibacterial properties. Methyl and propyl p-hydroxybenzoic acid are often used together in a 10 1 ratio. Concomitant use of multiple esters makes possible a higher total preservative concentration owing to the independent solubilities of each and, according to some researchers, maximizes the antimicrobial effect. 

McDonald C, Lindstrom RE. The effect of urea on the solubility of methyl p-hydroxybenzoate in aqueous sodium chloride solution. / Pharm Pharmacol 1974 26 39 5. 

Methylparaben, NF. Methyl p-hydroxybenzoate. or mcthylparaben. is a white crystalline powder. It is soluble in water and alcohol but only slightly soluble in nonpolei... 

The alkyl esters (methyl, ethyl, and propyl) of p-hydroxybenzoic acid (the parabens) are widely used for their antifungal properties. The preservative effect of parabens tends to increase with increasing molecular mass. The methyl ester appears to be more effective against molds, whereas the propyl ester is more effective against yeasts (favored for oils and fats, for solubility reasons) (Gonzalez, Gallego, and Valcarcel, 1998). 

It should be mentioned that several more drastic simplifications of cocaine appeared on the scene even earlier. The only survivor is ethyl p-aminobenzoate (benzocaine, Table 13-6, No. 5). The others of interest were methyl p-amino-m-hydroxybenzoate (ortho-form), which, like benzocaine, was nontoxic, highly insoluble, and therefore not suitable for parenteral administration. Orthoform has no activity on intact skin, but it was useful as a powder on painful wounds. It was superseded commercially by the position isomer p-hydroxy-m-aminobenzoate methyl ester for reasons of cost since large-scale production of orthoform (as the pure, correct isomer) presented difficulties at the time. It should be pointed out that water-soluble hydrochlorides of the aminobenzoates can be prepared however, their solutions are much too acidic to inject. 

Beilstein Handbook Reference) AI3-24370 Benzoic acid, 2-hydroxy-, 2-methylpropyl ester BRN 2615955 EINECS 201-729-9 FEMA Mo, 2213 2-lsobutoxycarbonyiphenol Isobutyl o-hydroxybenzoate Isobutyl salicylate 2-Methyl-1-propyl salicylate 2-Methylpropyl o-hydroxybenzoate NSC 62140 Salicylic acid, isobutyl ester. Used in perfumery. Liquid mp n 6.9 bp = 261 d = 1.0639 7.m = 238 rtm (cyclohexane) insoluble in HzO, soluble in EtOH, EtzO, CCl4. 

As p-hydroxybenzoic acid esters present a relatively high pKa value (approx. 8.5), their antimicrobial action is less dependent on the pH value of the type of food to be preserved. In this respect they are superior to the organic preservative acids. Unfavourably, as in the case of phenol, p-hydroxybenzoic acid esters may be linked to some extent to proteins, emulsifiers or other food components on account of their phenolic hydroxylic-group and thus be inactivated. The antimicrobial action of the p-hydroxybenzoic acid esters is proportional to the alkyl chain length. Thus the antimicrobial action of the methyl ester is some 3 to 4 times, that of the ethyl ester some 5 to 8 times, that of the propyl ester about 25 times as powerful as phenol (Thompson, 1994). However, superimposed on this effect may be the water solubility of the esters, which is inversely proportional to the alkyl chain length. Since the activity spectra of the individual p-hydroxybenzoic acid esters are different, the application of mixtures can be profitable. 

The alkyl esters of p-hydroxybenzoic acid (PHB parabens) are quite stable. Their solubility in water decreases with increasing alkyl chain length (methyl butyl). The esters are mostly soluble in 5% NaOH. 

In addition, 4-hydroxybenzoic add is widely used together with its alkyl esters (generally known as parabens) and salts. The most common are methyl-, ethyl-, propyl- and butyl- esters and are generally known as methylparaben, ethylparaben, etc. The antimicrobial activity of these chanicals increases as the carbon number of the alkyl chain increases, while, by contrast, their water solubility decreases in parallel. The antimicrobial activity of the individual esters is generally selective, so their mixtures offer powerful antimicrobial activity against an extremely broad spectrum of microorganisms This is the reason why a lot of cosmetics and skin care products are preserved with parabens both in Europe and the United States. 

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