Diesters, carboxylic acids

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). 

The isolation of saturated and unsaturated acetic acid derivatives in the manganese(m) acetate oxidation of olefins has been reported earlier examples of this oxidation led solely to y-lactones. A one-step synthesis of aeo-di-carboxylic acid diesters has been reported, based on Kolbe electrolysis of oxalic and malonic half-esters in the presence of olefins, and is exemplified in Scheme 2. As part of a study of insect hormone activity, Kolbe electrolysis has been utilized in the preparation of aj9-unsaturated Cj4—Cj7 acid esters with a terminal quaternary alkyl group. The utility of liquid hydrogen fluoride in the Koch carbonylation of olefins has been descried, as has a general study of this reaction. ... 

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). 

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. 

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

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- ... 

Table 3-2. Diesters prepared from carboxylic acids and alcohols using A -carbonyldiimidazole (CDI).

Besides fragmentation or rearrangement, the carboxylic acid anions, formed by an enzymatic hydrolysis, can also act as nucleophiles. Kuhn and Tamm used the asymmetric hydrolysis of meso-epoxy diester 8-28 with PLE to synthesize y-lactone... 

The reaction of cycloheptaamylose with diaryl carbonates and with diaryl methylphosphonates provides a system in which a carboxylic acid derivative can be directly compared with a structurally analogous organo-phosphorus compound (Brass and Bender, 1972). The alkaline hydrolysis of these materials proceeds in twro steps, each of which is associated with the appearance of one mole of phenol (Scheme Y). The relative rates of the two steps, however, are reversed. Whereas the alkaline hydrolysis of carbonate diesters proceeds with the release of two moles of phenol in a first-order process (kh > fca), the hydrolysis of methylphosphonate diesters proceeds with the release of only one mole of phenol to produce a relatively stable aryl methylphosphonate intermediate (fca > kb), In contrast, kinetically identical pathways are observed for the reaction of cycloheptaamylose with these different substrates—in both cases, two moles of phenol are released in a first-order process.3 Maximal catalytic rate constants for the appearance of phenol are presented in Table XI. Unlike the reaction of cycloheptaamylose with m- and with p-nitrophenyl methylphosphonate discussed earlier, the reaction of cycloheptaamylose with diaryl methylphosphonates... 

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 reaction of CO2 with 1,3-butadienes in the presence of Ni catalysts usually gave an isomeric mixture of carboxylic acids 89 and 90 after hydrolysis (Scheme 32).47,48 The oxa-7r-allylnickel complexes 87 and 88 might be the reaction intermediates, which could be formed through oxidative cyclization of Ni(0) with C02 and the dienes. When Me2Zn was used as a transmetallation agent to react with the oxa-7r-allylnickel intermediates under a C02 atmosphere, further carboxylation took place at the 7r-allylnickel unit. Thus, the 1,4-diesters 95 were obtained after acidic hydrolysis and treatment with diazomethane as shown in Scheme 32.47... 

With diiodo compounds, the mono and diesters can be selectively obtained (Eq. 14). These are useful precursors to valuable perfluoro carboxylic acids. 

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. 

A more complex pathway of activation is seen in N-amino acid derivative of phosphoramidic acid diesters of antiviral nucleosides, as exemplified by prodrugs of stavudine (9.79, Fig. 9.14) [153 -155], The activation begins with a carboxylesterase-mediated hydrolysis of the terminal carboxylate. This is followed by a spontaneous nucleophilic cyclization-elimination, which forms a mixed-anhydride pentacycle (9.80, Fig. 9.14). The latter hydrolyzes spontaneously and rapidly to the corresponding phosphoramidic acid monoester (9.81, Fig. 9.14), which can then be processed by phosphodiesterase to the nucleoside 5 -monophosphate, and by possible further hydrolysis to the nucleoside. 

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). 

MeOH (0.122 mL, 3.0 mmol) was added dropwise to a stirred suspension of anhydride 57b (164 mg, 1.0 mmol) and quinidine (0.357 g, 1.1 mmol) in a mixture of toluene and tetra-chloromethane (1/1, 5 mL) at -55 °C under argon. The reaction mixture was stirred at this temperature for 60 h. During this period, the material gradually dissolved. Subsequently, the resulting clear solution was concentrated in vacuo to dryness, and the residue was dissolved in EtOAc. The solution was washed with 2N HCl and, after phase separation, followed by extraction of the aqueous phases with EtOAc the organic layer was dried (MgSO ), filtered and concentrated in vacuo to provide the corresponding hemiester (2//,35)-3-endo-methoxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid as a white solid (192 mg, 98%, 99% ee by chiral-HPLC on the methyl 4-bromophenol diester). 

It may be suspected that the genuinely topotactic (as secured by the molecular precision of the AFM [18]) photodimerization of 2-benzyl-5-benzyli-denecyclopentanone [118] might be a good candidate for a quantitative preparative photo dimerization to give the head-to-tail anti-[2+2] dimer. Early quantitative solid-state [2-1-2] photodimerizations (most of the published mechanistic interpretations of which can no longer be accepted) are listed in [110]. These deal with the anti dimerization of acenaphthylene-1,2-dicarboxylic anhydride, the head-to-head syn dimerization of acenaphthylene-1-carboxylic acid, the syn dimerization of 5,6-dichloroacenaphthylene, and the thermally reversible head-to-tail anti dimerization of seven ( )-2,6-di-f-butyl-4-(2-aryl-ethenyl)pyrylium-trifluoromethanesulfonates. All of these reactions proceed fully specific. On the other hand, quantitative photoconversions of a 1 1 mixed crystal of ethyl and propyl a-cyano-4-[2-(4-pyridyl)ethenyl]cinnamates gives mixtures of diesters with one (A>410 nm) or two cyclobutane rings (no cutoff filter). 

For oxidation of terminal and internal alkynes to carboxylic acids by RuO / Oxone /Na(HC03)/aq. CHjCN-EtOAc (Table 3.4) a mechanism was proposed in which C3H. CCC3H., is oxidised by RuO to the dione via a Ru(Vl) diester (1), with the resulting dione (2) then undergoing Baeyer-Villiger oxidation by HSOj" to give an acid anhydride (3) which was hydrolysed to the acid (Fig. 1.9 R= C3H3) [377]. 

Initially, water can cause the hydrolysis of the anhydride or the isocyanate, Scheme 28 (reaction 1 and 2), although the isocyanate hydrolysis has been reported to occur much more rapidly [99]. The hydrolyzed isocyanate (car-bamic acid) may then react further with another isocyanate to yield a urea derivative, see Scheme 28 (reaction 3). Either hydrolysis product, carbamic acid or diacid, can then react with isocyanate to form a mixed carbamic carboxylic anhydride, see Scheme 28 (reactions 4 and 5, respectively). The mixed anhydride is believed to represent the major reaction intermediate in addition to the seven-mem bered cyclic intermediate, which upon heating lose C02 to form the desired imide. The formation of the urea derivative, Scheme 28 (reaction 3), does not constitute a molecular weight limiting side-reaction, since it too has been reported to react with anhydride to form imide [100], These reactions, as a whole, would explain the reported reactivity of isocyanates with diesters of tetracarboxylic acids and with mixtures of anhydride as well as tetracarboxylic acid and tetracarboxylic acid diesters [101, 102]. In these cases, tertiary amines are also utilized to catalyze the reaction. Based on these reports, the overall reaction schematic of diisocyanates with tetracarboxylic acid derivatives can thus be illustrated in an idealized fashion as shown in Scheme 29. 

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... 

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