Alkyl parabens

The use of alkyl parabens as biocides in food, drug, and cosmetics manufacture is widespread, despite controversial claims of links to certain cancers. Industrial syntheses of paraben esters use the Kolbe-Schmitt reaction, principally via the corresponding potassium phenoxide, which favors /jcira-carboxylation. A modification that strongly favors para-subtitution involves potassium ethylcarbonate as a base, which gives a 93% yield of 4-hydroxybenzoic acid (33) from phenol at 225 °C under an atmosphere of 25 atm C02. Additional protocols using carboxylase enzymes under an atmosphere of 02 and with supercritical C02 have been reported to furnish para-carboxylation exclusively and in high yields. 

Figure 6.4 The CMCs of sodium lauryl sulphate solutions in the presence of alkyl parabens., methylparaben O, ethylparaben x, butylparaben. From Goto and Endo [37] with permission.

Table 11. Physical Properties of Alkyl />Hydroxybenzoates (Parabens)...

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). 

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. 

Parabens have some antimicrobial activity but are most effective against yeasts and molds. Although methyl paraben has the least antimicrobial activity, different combinations of methyl paraben with other long-chain parabens can lead to synergy. As the chain length of the paraben s alkyl moiety is increased, their antimicrobial activity increases. 

Aqua, glycerin, cyclomethicone, dicaprylyl carbonate, ascorbic acid, butyrospermum parkii, alcohol cetearyl, octocrylene, glyceryl stearate, C12-15 alkyl-benzoate, cera microcristallina, tocopheryl acetate, vitis vinifera, PEG-40 stearate, sodium carbomer, paraffinum liquid-urn, tetrasodium iminodisucciunate, BHT, phenoxyethanol, methyl paraben, propyl paraben, diazolidinyl urea and parfum. 

Commonly used preservative agents include organic acids such as benzoic acid and salts, the parabens, (alkyl esters ofp-hydroxybenzoic acid), sorbic acid and salts, phenolic compounds, quaternary ammonium compounds, alcohols, and mercurials such as thimerosal in 0.001-0.004% concentration. 

Routledge, E.J., Parker, J., Odum, J., Ashby, J., and Sumpter, J.P., Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic, Toxicol. Appl. Pharmacol., 153, 12-19, 1998. 

Parabens are alkyl esters of p-hydroxyben-zoic acid. The alkyl groups may be one of the following methyl, ethyl, propyl, butyl, or heptyl. Parabens are colorless, tasteless, and odorless (except the methyl paraben). They are nonvolatile and nonhygroscopic. Their solubility in water depends on the nature of the alkyl group the longer the alkyl chain length, the lower the solubility. They differ from benzoic acid in that they have antimicrobial activity in both acid and alkaline pH regions. 

The antimicrobial activity of parabens is proportional to the chain length of the alkyl group. Parabens are more active against molds and yeasts than against bacteria, and... 

The activity of the parabens increases with increasing chain length of the alkyl moiety, but solubility decreases. 

The activity of the parabens increases with increasing chain length of the alkyl moiety, but solubility decreases. Activity may be improved by using combinations of parabens since synergistic effects occur. Ethylparaben is commonly used with methylparaben and propylparaben in oral and topical formulations (such mixtures are commercially available for example, Nipasept (Nipa Laboratories Inc.). Activity has also been reported to be improved by the addition of other excipients see Methylparaben for further information. 

The parabens are effective over a wide pH range and have a broad spectrum of antimicrobial activity, although they are most effective against yeasts and molds. Antimicrobial activity increases as the chain length of the alkyl moiety is increased, but aqueous solubility decreases therefore a mixture of parabens is frequently used to provide effective preservation. Preservative efficacy is also improved by the addition of propylene glycol (2-5%), or by using parabens in combination with other antimicrobial agents such as imidurea see Section 10. 

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). 

If we look at the solvents in the table, we know that water is more polar than ethanol, which in turn is much more polar that chloroform (see Table 6.4). We have already established that our parabens become more nonpolar with increasing alkyl chain length. From this we would expect to see that propyl paraben would be more soluble in chloroform than methyl paraben and that methyl paraben would be more soluble in water than propyl paraben. This can be verified from the data in Table 6.5. From our solubility data, we can see that all of the parabens have a greater level of solubility in relatively more nonpolar solvents (relative to water). We can deduce from this that our analytes are less polar than water but not as nonpolar as chloroform. 

HBA is representative of a class of regio-specifically oxidized aromatic molecules that possess a 1-4 symmetry of carboxyl to hydroxyl groups. It is the chief monomer used in LCP s due to its structural symmetry, availability, and favorable pricing relative to the more expensive multiple ring monomers derived from naphthalene. HBA also finds extensive use as an intermediate in the manufacturing of dyes, pesticides, and pharmaceuticals (/). In addition, the n-alkyl esters of HBA (parabens) are widely used as preservatives in food (e.g. in fruit juices), cosmetics, pharmaceuticals, and technical products (e.g. antifreeze agents) due to their effective bacteriostatic and fungiastatic properties (2). 

In a recent study [51] the incorporation of alky1parabens into sodium lauryl sulfate (NaDDS) micelle and a change of the micellar structure was studied by various methods, among others by the elution volume of the micellar systems from the gel exclusion chromatography. Lauryl-paraben was used with methyl-, ethyl-, and butyl-parabens with a view to studying the effect of alkyl chain length on the solubilization. 

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. 

---