Diesters, half-hydrolysis ester

Sulfur in oxidation state IV can be used to produce a variety of anionic snUbnates, as depicted in Scheme 1.5. Sodium bisulfite can be used to prepare sulfonates of a,b-unsaturated acids and esters, such as those prepared from maleic anhydride. The mechanism involves Michael addition to the activated double bond by the more nucleophilic sulfur atom, and is conducted in an aqueous two-phase system where, for example, a maleate half acid ester or diester is dispersed and heated under narrowly controlled pH conditions to minimize ester hydrolysis and avoid competitive hydroxide addition to the double bond. The resulting classes of surfactants include sulfosuccinates (which are in fact carboxylate sulfonate disalt surfactants) prepared from the maleic half acid esters of fatty alcohols or alcohol ethoxylates. Diesters of maleic are sulfonated by the same type of process to produce surfactants such as the ubiquitous dioctyl sulfosuccinate (DOSS) from the diester of 2-ethylhexyl alcohol and maleic anhydride. 

Use of an intermediate as a starting reactant. Again taking Scheme IX as an example, if intermediate B is stable enough to be isolated or synthesized, its reaction to give C ean be studied independently of its formation from A. (This requires that the A —> B step be irreversible). For example, in the overall hydrolysis of a diester, the intermediate is the half-ester, which usually can be synthesized to serve as a reactant in a separate study,... 

This property of organophosphate esters may be of environmental importance since phosphoric acid diesters are much more soluble and very little is known concerning the environmental toxicity of these compounds. The available data do not provide sufficient descriptions of the experimental methods to determine if the rates are reliable (Barnard et al. 1961 Ciba-Geigy 1984e, 1986 Howard and Deo 1979 Mayer et al. 1981 Wolfe 1980). The majority of reports provide only a minimum of information and exclude important facts such as the duration of the experiments and the concentration of buffers. Despite the lack of experimental detail, published rate constants for base-catalyzed hydrolysis appear to be reasonably consistent and suggest that the hydrolytic half-life of triphenyl phosphate will vary from... 

The isolated dimethyl sebacate can be sold commercially as is or optionally hydrolyzed to sebacic acid. If a higher molecular weight plasticizer diester is required, a transesterification with -ethyl hexanol, for example, gives the desired product plus two equivalents of methanol which is recycled back to the oxycarbonylation reaction. If the free acid is desired, dimethyl sebacate hydrolysis to sebacic acid is carried out using a strong mineral acid such as sulfuric acid. Hydrolysis is nearly quantitative with a selectivity of about 99.5% to diacid and. 5% to the half-ester acid product. Additional recrystallization is used to improve purity if required. 

An approach to the synthesis of a prostaglandin intermediate began with 2-furanacetonitrile (71JOC3191). Friedel-Crafts acylation with pimelic half-ester acid chloride and Wolff-Kishner reduction of the product with concomitant hydrolysis of the nitrile group to acid yielded the diester (78) on diazomethane treatment. Ring opening of the furan by a standard procedure yielded a diketo diester (79) which on refluxing in aqueous methanolic potassium carbonate underwent hydrolysis and cyclization to the diacid (80 Scheme 19). 

The Amano researchers found not just drastically different enantiomeric excesses in the Pseudomonas sp. (Amano AH) lipase-catalyzed hydrolysis of methylene-oxypropionyl or -pivaloyl diesters, but a near-total reversal of specificity. Whereas in cyclohexane the different esters yielded half-esters with 88.8-91.4% e.e. -specificity for a triple mutant ( FVL ) of Amano PS lipase, the same transformation with the same enzyme in diisopropyl ether (DIPE) yielded between 68.1 and > 99% e.e. of the S-product (Figure 12.10) (Hirose, 1992,1995). 

The asymmetric hydrolysis of several cyclic meso-diesters has been accomplished and optically pure monoesters have been obtained. A classical example is the hydrolysis of dimethyl cis-4-cyclohexene-1,2-dicarboxylate, which affords the corresponding nearly optically pure half ester, a versatile synthon for various chiral cyclohexane derivatives (eq 3). ... 

Mivacurium chloride is a non-depolarizing muscle relaxant, a benzylisoquinolinium diester compound with a duration of approximately twice that of suxamethonium. In vitro (1), it is metabolized to a significant extent by plasma cholinesterase, and minimally by acetylcholinesterase. The rate of metabolism in vitro is directly related to plasma cholinesterase activity. In pooled human plasma the rate of hydrolysis of mivacurium was 70% that of suxamethonium. Its half-life is 5-10 minutes compared with 2-5 minutes for suxamethonium. The in vitro hydrolysis of mivacurium by purified human plasma cholinesterase occurs at 88% of the rate for suxamethonium (2). There was a poor correlation between the duration of action of bolus doses of mivacurium and the plasma cholinesterase activity in individual patients (2), a finding that has also been reported by others (3). However, the average infusion rate to maintain around 95 % blockade in individual patients correlated significantly with the patients plasma cholinesterase activities (4). While metabolites have been detected in both urine and bile, mivacurium seems to depend principally on ester hydrolysis for its plasma clearance, so that reduced activity of plasma cholinesterase is likely to result in a prolonged duration of action. 

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. 

Hydrolysis of the ester functions of dimethyl 2,2-bis(4-methoxyphenyl)-277-naphtho[l,2-6]pyran-5,6-dicarboxylate and cyclisation of the resulting dicarboxylic acid yields the cyclic anhydride 51. Reduction affords a mixture of two isomeric furano-fused naphthopyrans. Treatment of the anhydride with primary amines provides a route to the corresponding pyrrole derivatives. Both types of hetero-fused naphthopyrans show a red shift relative to the starting naphthopyran diester and reduced half-lives <01 WOP32661>. 

Phosphoric and sulfuric acid derivatives possess crucial properties that allow them to uniquely fill their many roles in biochemistry. Phosphoric acid may be esterified to form a monoester, diester, or triester (Figure 1). Sulfuric acid may be esterified at one or two positions, to form a monoester or a diester. Sulfate diesters are highly reactive, and have not been found in nature nor do phosphate triesters occur naturally. The hydrolysis of both phosphate and sulfate esters are thermodynamically favorable, but nucleophiles are repelled by the negative charge of the ionized forms. The resulting kinetic stability of phosphate monoesters and diesters, and of sulfate monoesters, is a major factor in their suitability for biological roles. For example, the half-life for hydrolysis of alkyl phosphate dianions by water is approximately 1.1 X 10 years k=2 x 10 s ) at 25°C. Such species... 

Another total synthetic plan to obtain showdomycin (4) was that which started from the Diels-Alder adduct 108 and comprised the key step of enzymatic hydrolysis of the diester 109 to the half ester 110 (81JA6739) (Scheme 21). 

In kinetic resolutions (Scheme 3.2-3.5) it is often the case that one of the products is required, while the other is not and must be discarded or recycled (e.g. racemised). Such operations can be wasteful or expensive. On the other hand, the biotransformation of wcso-compounds or prochiral compounds allows for the possibility of preparing an optically pure compound in quantitative yield. In Scheme 3.7, two examples of the use of meso-compounds are described. The diester (11) is made up of a complex dicarboxylic acid unit derivatised as the dimethyl ester. Pig liver esterase catalyses the hydrolysis of one of the ester groups to give the acid (12) (95% e.e.) in 96% yield. This compound is an excellent precursor of the natural product neplanocin. Note that the acid (12) is not a substrate for pie, and thus the reaction stops at the half-way stage. The compound (13), like (11), possesses a plane of symmetry. Hydrolysis catalysed by porcine pancreatic lipase (ppl) affords the alcohol (14) (>98% e.e.) in quantitative yield. The latter compound has been used to make fluorocarbocyclic adenosine (C -adenosine), a stable analogue of the naturally occurring nucleoside adenosine. 

Enzymes which catalyse the hydrolysis of esters and lipids are often capable of high enantioselection. Pig liver esterase (PLE) has been widely used for the enantioselective synthesis of half-esters from diesters.1 1 Methods based on such enzymes have the advantage over oxidases in that no cofactor is necessary. 

This first chemoenzymatic synthesis [48] is not included m Fig. 1 but can be considered as a preparation of A-ring synthons in general in the steroid field, and particularly in area of vitamin D (Scheme 9). The stereo control of the quaternary chiral carbon center is one of the important subjects in asymmetrical synthesis. This issue prompted research on the use of chiral monoester 197, which can be obtained in multihundred gram scale by the pig liver esterase (PLE)-mediated hydrolysis of the corresponding symmetrical diester 196 [49]. Thus, an efficient methodology was developed for the preparation of chiral cyclohexene derivatives from cw-diester 196, using PLE in a biphasic system using phosphate buffer and acetone, to afford the chiral half-ester 197. Scheme 9 shows the efficient... 

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