Phthalate esters, hydrolysis

Structural Requirements for the Inhibition of Phthalate Ester Hydrolysis in Rainbow Trout by Methylenedi-oxyphenyl Compounds. 

Wolfe, N.L., Steen, W.C., and Burns, L.A. Phthalate ester hydrolysis linear free energy relationships, Chemosphere, 9(7/8) 403-408, 1980. 

Wolfe, N. L., W. C. Steen, and L. A. Burns (1980b), Phthalate Ester Hydrolysis Linear Free Energy Relationships, Chemosphere 9, 403-408. 

Other derivatives can be prepared by reaction of the alcohol with an acid anhydride. For example, phthalic or 3-nitrophthalic anhydride (I mol) and the alcohol (Imol) are refluxed for half to one hour in a non-hydroxylic solvent, e.g. toluene or alcohol-free chloroform, and then cooled. The phthalate ester crystallises out, is precipitated by the addition of low boiling petroleum ether or is isolated by ev toration of the solvent. It is recrystallised from water, 50% aqueous ethanol, toluene or low boiling petroleum ether. Such an ester has a characteristic melting point and the alcohol can be recovered by acid or alkaline hydrolysis. 

Phthalate esters are widespread contaminants and the dialkyl phthalates are hydrolyzed before degradation of the resulting phthalate (Eaton and Ribbons 1982), which is discussed in Chapter 8, Part 3. For dimethyl phthalate, dimethyl terephthalate, and dimethyl isophthalate only partial hydrolysis may take place (Li et al. 2005). Cocaine is hydrolyzed to benzoate and ecgonine methyl ester by a strain of Pseudomonas maltophilia (Britt et al. 1992). 

Phthalate esters undergo a step-wise alkaline hydrolysis to monoesters and then to dicarboxylic acids. As a result of the relatively slow rates of this reaction at pH 6-9 and the low water solubility of di-n-octylphthalate, chemical hydrolysis of the compound is not an environmentally important transformation process (EPA 1992a). Hydrolytic half-lives at 25 C and pH 7 and 9 have been estimated to be 107 and 7 years, respectively (Howard et al. 1991). 

Although the metabolism of several phthalate esters has been studied in vitro, essentially all of the in vivo studies have involved DEHP. A summary of these experiments which involved exposure offish to aqueous - C-DEHP is presented in Table IV (11,12). Tissue C was isolated and separated into parent and the various metabolites by preparative thin layer chromatography on silica gel. Metabolites were hydrolyzed where appropriate and identified by gas chromatography-mass spectroscopy. In whole catfish, whole fathead minnow and trout muscle, the major metabolite was the monoester while in trout bile the major metabolite was the monoester glucuronide. The fact that in all cases the major metabolite was monoester or monoester glucuronide despite the differences in species, exposure level and duration, etc. represented by these data, suggests that hydrolysis of DEHP to monoester is important in the biotransformation of DEHP by fish. 

In an homologous series of phthalate diesters (7.24, R = Me, Et, allyl, 2-methoxyethyl, Bu, i-Bu, and PhCH2), hydrolysis by some human and rat liver carboxylesterases was fastest for the diethyl and diallyl esters [50], This suggested a maximal rate of hydrolysis for phthalate esters with a lipophilic-ity (log P in the octanol/water system) of 3 - 4. Interestingly, and compatible with this interpretation, monoesters were not hydrolyzed. However, that re-gioisomeric monoesters are hydrolyzed clearly indicates that factors other than lipophilicity (e.g., steric factors) are also influential. 

R. Mentlein, W. Butte, Hydrolysis of Phthalate Esters by Purified Rat and Human Liver Carboxylesterases , Biochem. Pharmacol. 1989, 38, 3126-3128. 

Optically pure trans-2-phenylcyclohexanol can also be prepared by resolution of the phthalate esters using brucine to obtain the (-t-)-alcohol and strychnine to obtain the (-)-alcohol (after basic hydrolysis of their respective salts).11 Enzyme-catalyzed kinetic resolution of the acetate esters using pig liver esterase4 and pig liver acetone powder12 has been used to prepare both enantiomers of this chiral auxiliary. The hydroboration of 1-phenylcyclohexene with isopinocampheylborane has been reported to give the chiral auxiliary in 97% enantiomeric excess.13... 

Carboxylic Ester Hydrolysis Butyl Benzyl Phthalate... 

Butyl benzyl phthalate is a mixed carboxylic acid ester formed by the condensation of phthalic acid with two different alcohols. No literature values could be found nor any directly applicable QSARs. Based on known reactivity of carboxylic acid esters, any acid hydrolysis should be very slow. Neutral hydrolysis, while reported in the literature for certain reactive esters, is not likely for the phthalate esters. The carboxylic acid esters are most labile to alkaline hydrolysis (Mabey and Mill, 1978). 

The alkaline hydrolysis of phthalate diesters has been fit to the Taft-Pavelich equation (Eq. 9). Dimethyl phthalate (DMP) hydrolyzes to phthalic acid (PA) in two steps DMP + H20->MMP + CH30H and MMP + H20- PA + CH30H. The first step is about 12 times faster than the second, and nearly all the diester is converted to the monoester before product PA is formed. Other diesters are assumed to behave similarly. An LFER was obtained from rate measurements on five phthalate esters (Wolfe et al., 1980b). The reaction constants, p and S, were determined by multiple regression analysis of the measured rate constants and reported values of cr and Es for the alkyl substituents. The fitted intercept compares favorably with the measured rate constant (log kOH = — 1.16 0.02) for the dimethyl ester (for which a and s = 0 by definition). Calculated half-lives under pseudo-first-order conditions (pH 8.0, 30°C) range from about 4 months for DMP to over 100 years for di-2-ethylhexyl phthalate. 

DEHP previously converted in its ferf.-bytyldimethylsilyl derivatives. For the analysis of the intact conjugates of DEHP metabolites by GC, Egestad et al. " prepared the methyl ester trimethylsylil ether derivatives of the major glucuronides. On the other hand, Pietrogrande et al. performed direct GC analysis of the enzymatic hydrolysis products of phthalate esters conjugates without any derivatization step. 

Luminiscence is other technique that has been proposed for the determination of total phthalate esters in water. After hydrolysis of the ester function, a chelate with terbium (111) was formed, and... 

Recently, Blount et al. (2000) summarized a methodology to detect di- -butyl phthalate metabolites in urine. In humans or animals, di- -butyl phthalate is metabolized to mono- -butyl phthalate and oxidative products, which are excreted through the urine and feces. Human urine samples are processed by P-glucuronidase hydrolysis (to release the mono phthalate ester) followed by solid-phase extraction. The eluate is concentrated mono- -butyl phthalate is chromatographically resolved by reverse-phase HPLC, detected by negative ion atmospheric pressure chemical ionization (APCI) tandem mass spectrometry, and quantified by isotope dilution. 

Rowland IR, Cottrell RC, Phillips JC. 1977. Hydrolysis of phthalate esters by the gastro-intestinal contents of the rat. Food Cosmet Toxicol 15 17-21. 

This LEER has been useful for the environmental assessment of phthalate esters for which hydrolysis rate constants have not been measured (Wolfe et al., 1980a). 

The disappearance of a plasticizer from water can be the result of a number of abiotic and biotic processes that can transform or degrade the compound into daughter compounds that have different physicochemical properties from the parent compound. Hydrolysis is a family of chemical reactions where a plasticizer reacts with water. Phthalate esters may hydrolyze to form monoesters and then dicarboxylic acid. It has been predicted that di-(2-ethylhexyl) sebacate will form 2-ethylhexanol and decanedioic acid. Wolfe et al experimentally measured second-order alkaline hydrolysis rate constants for dimethyl, diethyl, di-n-butyl, and di-(2-ethylhexyl) phthalates, and it appears that hydrolysis may be too slow to have a major impact on the fate of most dissolved plasticizers. The estimated hydrolysis half-lives at pH 7 for 20 plasticizers were longer than 100 days. No information was located for diallyl, ditridecyl and diundecyl phthalates. Under alkaline conditions, hydrolysis may be important for tricresyl phosphate and tri-(2-ethylhexyl) trimellitate at pH 8 their predicted half-lives are 3.2 and 12 days respectively. 

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