Carboxylic acid esters diesters

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

HO A phosphoric acid monoester HO A phosphoric acid diester 0 1 R" A phosphoric acid triester A carboxylic acid ester... 

The chemical diversity of carboxylic acid esters (R-CO-O-R ) originates in both moieties, i.e., the acyl group (R-CO-) and the alkoxy or aryloxy group (-OR7). Thus, the acyl group can be made up of aliphatic or aromatic carboxylic acids, carbamic acids, or carbonic acids, and the -OR7 moiety may be derived from an alcohol, an enol, or a phenol. When a thiol is involved, a thioester R-CO-S-R7 is formed. The model substrates to be discussed in Sect. 7.3 will, thus, be classified according to the chemical nature of the -OR7 (or -SR7) moiety, i.e., the alcohol, phenol, or thiol that is the first product to be released during the hydrolase-catalyzed reaction (see Chapt. 3). Diesters represent substrates of special interest and will be presented separately. 

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

Pig Liver Esterase (PLE). This is the more used car-boxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1, CAS 9016-18-6) which physiologically catalyzes the hydrolysis of carboxylic acid esters to the free acid anion and alcohol. PLE is a serine hydrolase which has been widely used for the preparation of chiral synthons and these applications have been fully reviewed. An active-site model for interpreting and predicting the specificity of the enzyme has been published. In the pioneering studies of the enzyme applications field, PLE was used for the chiral synthesis of mevalonolactone. Prochiral 3-substituted glutaric acid diesters... 

Although prochiral or chiral alcohols and carboxylic acid esters initially served as the primary classes of substrates, compounds susceptible to processing via these two routes now encompass diols, a- and 3-hydroxy acids, cyanohydrins, chlorohydrins, diesters, lactones, amines, diamines, amino alcohols, and a-and 3-amino acid derivatives. Gotor and Arroyo have reviewed the use of biocatalysts for the preparation of pharma-eeutical intermediates and fine ehemieals. Some specific examples are indieated below. 

Substituted 4-chloropyrimidine-5-carboxylic acid esters react with 3-(alkylamino)- or 3-(aryl-amino)propanoic acid esters to give diesters suitable for Dieckmann cyclization. The resulting dihydropyrido[2,3-r/]pyrimidines are then oxidized to the corresponding pyrido[2,3-<7]-pyrimidin-5(8//)-oncs 17. 53-157... 

Nalorphine Dinicotinate. 7,8-Didehydro-4,5-epoxy-t7-(2-propenyl>morphtnan-3,6-diol bis(3-pyridine-corboxylatel (ester) N-allylnormorphine dinicotinate bis-(nicotinic acid) diester of N-allylnormorphine N-ally I normorphine bisfpyridine-3-carboxylic acid) ester nalorphine bis(nlcotlnate) Nimelan. CjjH N.Oj mo] wt 521.55. C 71.39%, H 5.22%, N 8,06%, O 15.34%. Prepn Pongratz, Zirm, Afonatsh. 91, 396 (1960). 

Occurrence I. occurs as the 0-3-, 0-5-, or 0-20-monoesters and as the 3,20-O-diester in many Euphor-biaceae, e. g.. Euphorbia ingens. The acid components are mainly highly unsaturated carboxylic acids. Esters of 5- and 20-deoxyingenol, 13- and 16-hydroxyinge-nol, and of 16-hydroxy-20-deoxyingenol have been isolated. 

A serious limitation of this powerful analytical technique is the inability to detect and quantify Gin and Asn m an amino acid mixture In the acid-catalyzed esterification reaction, the amides (Gin and Asn) are rapidly deaminated and converted to the same derivatives as those formed by Glu and Asp, respectively. Consequently, summations of both Glu and Gin concentrations and Asp and Asn concentrations are determined by this method. It has been shown that when Gin is heated to a temperature of about 100°C in an acidified alcoholic medium, rapid conversion to glutamic acid diester takes place. Pyrrolidone carboxylic acid ester has been shown by mass spectrometry to be a cyclized intermediate (Fig 2). This intermediate reaches its maximum concentrahon after heating at 100°C for 5-10 mm (Collins and Summer, 1978). 

The palladium(II)-catalyzed olefin carbonylation reaction was first reported more than 30 years ago in studies by Stille and co-workers and James et al. The reaction of carbon monoxide with cis- and tra 5-but-2-ene in methanol in the presence of palladium(II)-chloride and copper(II)-chloride yielded threo- and eryt/zro-3-methoxy-2-methyl-butanoate, respectively. The transformation that was based on the well-known Wacker process for oxidation of ethylene into acetaldehyde in water " is now broadly defined as the Pd(II)-catalyzed oxycarbonylation of the unsaturated carbon-carbon bonds. This domino reaction includes oxypalladation of alkenes, migratory insertion of carbon monoxide, and alkoxylation. Since the development of this process, several transformations mediated by palladium(II) compounds have been described. The direct oxidative bisfunctionalization of alkenes represents a powerful transformation in the field of chemical synthesis. Palladium(II)-promoted carbonylation of alkenes in the presence of water/alcohol may lead to alkyl carboxylic acids (hydrocarboxylation), diesters [bis(aIkoxycarbonyla-tion)], (3-alkoxy carboxylic acids (alkoxy-carboxylation), or (3-alkoxy esters (alkoxy-carbonylation or alkoxy-alkoxy-carbonylation). Particularly attractive features of these multitransformation processes include the following ... 

Treatment of [2- C]malonic acid with acetone in the presence of acetic anhydride and catalytic amounts of concentrated sulfuric acids provides [5- C]Meldrum s acid (419). one of the most versatile low molecular weight building blocks . As summarized in Figure 6.124, its reactivity at C2 is analogous with that of the malonate diesters already discussed. However, the reactivity of the initial adducts differs. For example, hydrolysis or alcoholysis (including tert-BuOH) of the initial adducts with alkyl halides , aldehydes and acyl chlorides gives directly the [2- C]carboxylic acids/esters, a,/3-unsaturated acids/esters and /3-keto acids/esters, respectively, with simultaneous elimination of acetone and In contrast, the 2-(alkoxymethylene)[2- C]malonate... 

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

Just as waxes, fats, and oils are esters of carboxylic acids, phospholipids are diesters of phosphoric acid, H3PO4. 

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

Solutions of Ru3(CO)i2 in carboxylic acids are active catalysts for hydrogenation of carbon monoxide at low pressures (below 340 atm). Methanol is the major product (obtained as its ester), and smaller amounts of ethylene glycol diester are also formed. At 340 atm and 260°C a combined rate to these products of 8.3 x 10 3 turnovers s-1 was observed in acetic acid solvent. Similar rates to methanol are obtainable in other polar solvents, but ethylene glycol is not observed under these conditions except in the presence of carboxylic acids. Studies of this reaction, including infrared measurements under reaction conditions, were carried out to determine the nature of the catalyst and the mechanism of glycol formation. A reaction scheme is proposed in which the function of the carboxylic acid is to assist in converting a coordinated formaldehyde intermediate into a glycol precursor. 

The diester 99 is readily decarboxymethylated, yielding 3,4-diphenyIpyra-zoIe-5-carboxylic acid on heating with aqueous base and the corresponding methyl ester with acetic acid.41... 

Chemical Properties. Trimethylpentanediol, with a primary and a secondary hydroxyl group, enters into reactions characteristic of other glycols. It reacts readily with various carboxylic acids and diacids to form esters, diesters, and polyesters (40). Some organometallic catalysts have proven satisfactory for these reactions, the most versatile being dibutyltin oxide. Several weak bases such as triethanolamine, potassium acetate, lithium acetate, and borax are effective as stabilizers for the glycol during synthesis (41). 

Esters. The monoisobutyrate ester of 2,2,4-trimethyl- 1,3-pentanediol is prepared from isobutyraldehyde in a Tishchenko reaction (58,59). Diesters, such as trimethylpentane dipelargonate (2,2,4-trimethylpentane 1,3-dinonanoate), are prepared by the reaction of 2 mol of the monocarboxylic acid with 1 mol of the glycol at 150—200°C (60,61). The lower aliphatic carboxylic acid diesters of trimethylpentanediol undergo pyrolysis to the corresponding ester of 2,2,4-trimethyl-3-penten- l-ol (62). These unsaturated esters reportedly can be epoxidized by peroxyacetic acid (63). 

Formation of quinuclidine-3-carboxylic acid derivatives (68) from these reactions was conclusive proof of saponification of the ethoxy-carbonyl group at position 2 of the diester (61). A similar reaction takes place with diethyl quinuclidine-2,3-dicarboxylate.100 This is in agreement with the known principle of easier saponification of a- than j8-amino acid esters. Some 3-(j8-acyloxyethyl)-2-diethylaminomethyl-quinuclidines (69, 70)123 on distillation at atmospheric pressure cyclize with loss of ester and formation of a new tricyclic system, quinuclidino[2,3-c]piperidine (72). The same reaction takes place by heating the corresponding amino alcohol (71) with phthalic anhydride in the presence of benzenesulfonic acid.123... 

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