Methyl phthalate, 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). 

Chemical/Physical. Under alkaline conditions, dimethyl phthalate will initially hydrolyze to methyl hydrogen phthalate and methanol. The monoester will undergo hydrolysis forming o-phthalic acid and methanol (Wolfe et al., 1980 Kollig, 1993). A second-order rate constant of 6.9 X 10 /M-sec was reported for the hydrolysis of dimethyl phthalate at 30 °C and pH 8. At 18 °C, the second-order rate constant was 3.1 x lO /M-sec in 1 mM NaOH (Wolfe et al., 1980). Also, hydrolysis half-lives of 3.2 yr was reported at pH 7 and at pH 9 11.6 and 25 d at 30 and 18 °C, respectively (Wolfe et al., 1980). 

While a carboxylate anion is a potent nucleophile in an intramolecular reaction it is not powerful enough to displace methoxide or an unprotonated amine, unless the nucleophile and the carbonyl group are held even more rigidly than in the phthalate system. Kirby and Lancaster (referred to by Kirby and Fersht, 1971) have found that such displacement can occur in disubstituted maleate monoesters and amides. The estimated rate constant for cyclization of N-methyl dime thy Imaleamic acid [equation (41)] is 16,000 times greater than that for the unsubstituted compound. Below pH 5-6 hydrolysis of the cyclic anhydride becomes rate-determining. 

It is not possible to prepare biaryls containing a free carboxyl group directly by the diazo reaction. No biaryl is formed when (a) diazotized aniline and sodium benzoate, (b) diazotized anthranilic acid and aqueous sodium benzoate, or (c) diazotized anthranilic acid and benzene are used as components in the reaction.13 On the other hand, the reaction proceeds normally if methyl benzoate is used in reaction (a) or when methyl anthranilate replaces the anthranilic acid in (b) and in (c). The success of the diazohydroxide reaction appears to lie in the ability of the non-aqueous liquid to extract the reactive diazo compound from the aqueous layer.4 However, esters and nitriles can be prepared from esters of aromatic amino acids and cyanoanilines and also by coupling with esters of aromatic acids, and from the products the acids can be obtained by hydrolysis. By coupling N-nitrosoacetanilide with ethyl phthalate, ethyl 4-phenylphthalate (VIII) is formed in 37% yield. 

It is interesting to note that there are certain esters for which none of these mechanisms of hydrolysis is completely satisfactory. It has been found, for example, that the hydrolysis of optically active rc-methyl cin-namyl or a,7-dimethylallyl hydrogen phthalate gave a racemized product in weakly alkaline solution but an optically active product in the presence of more concentrated alkali 19... 

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. 

Process and reaction monitoring. We have used TLC to monitor the time required for completion of the methylation reaction (Shantha, Decker and Hennig, 1993) and to study the formation of artifacts due to methylation of phthalates present in lipid samples (Shantha and Ackman, 1991b). TLC has been used to study the extent of hydrolysis of lipase-catalysed hydrolysis of triglycerides, phospholipase-catalysed hydrolysis of phospholipids and to study the activity of the enzymes. We have used TLC to study the extent of synthesis of acylated amino acids, and TLC has also been used to study the success of radiosynthesis. 

Some polymerizable esters can be used as a copolymerizable internal plasticizer in technical applications. The best known of the group is diallyl phthalate (DAP), which is used to replace styrene, divinyl benzene, or methyl methacrylate in unsaturated polyester resins. It has a very low vapour pressure (300°C boiling point), leading to significant reduction in loss through evaporation. It considerably improves properties such as hardness, chemical resistance, hydrolysis resistance, electrical properties, and product life. It is particularly used in electrical applications, can be employed (after suitable preparation) in cold-cure systems, and shows high affinity to glass fibre. DAP can also be used as a reactive plasticizer with PVC resins. 

Although commercially available, 1-trimethylsilyloxy-1,3-butadiene (1) can be easily prepared by silylation of crotonaldehyde. It has often been used as a reactive diene in Diels-Alder reactions. For example, reaction with dimethyl acetylenedicarboxylate (2) affords the cyclohexadiene diester (3) in 68% yield. This initial Diels-Alder adduct can be converted into two different aromatic products by the proper choice of conditions namely, thermal elimination affords the phthalate (4), while oxidation produces the phenol (5), hoth in good yield (eq 1). Reaction with methyl 3-nitroacrylate (6) followed hy hydrolysis of the initial adduct (7) and elimination of the -nitro group leads to the cyclohexadienol (8) (eq 2). Many other Diels-Alder reactions of this type have been carried out using (1), as shown in Table 1. In general, the endo adduct is favored, especially at lower temperatures. 

Danishefsky s diene with methyl acetylenedicarboxylate gives the phenol, dimethyl 4-hydroxy-<9-phthalate on hydrolysis. 

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