760CHAPTER NINETEENCarboxylic Acids

We already know what happens when simple esters are treated with alkoxide bases— they undergo the Claisen condensation (Section 21.1). Simple esters have acid dissocia- tion constants Kaof approximately 10 2(pKa2) and are incompletely converted to their enolates with alkoxide bases. The small amount of enolate that is formed reacts by nucleophilic addition to the carbonyl group of the ester.

(2-Cyclopentenyl)acetic acid (96–9%)

762CHAPTER NINETEENCarboxylic Acids

764CHAPTER NINETEENCarboxylic Acids

Glycerol esters are hydrolysed to glycerol and the corresponding carboxylic acids (see Figure 1). The hydrolysis is catalysed by intestinal lipase (Tietz, 1986), which attacks the ester bonds at carbons 1 and 3. The ester bond at carbon 2 is more resistant to hydrolysis, possibly because of its stereochemistry and steric hindrance. The -monoglyceride can, however, spontaneously isomerise to the -form (3-acylglycerol), permitting further hydrolysis to yield glycerol.

Cyclopentene-4-carboxylic acid (6%)

In general, aliphatic esters of propylene glycol, lactic acid, and pyruvic acid are expected to be hydrolysed to their component alcohol and carboxylic acids. The hydrolysis is catalysed by classes of enzymes recognized as carboxylesterases or esterases (Heymann, 1980), the most important of which are the B-esterases, which, in mammals, predominate in hepatocytes (Heymann, 1980; Anders, 1989). The rates of hydrolysis follow first-order kinetics, with hydrolysis of the straight-chain esters occurring approximately 100 times more rapidly than that of branched-chain esters (Butterworth et al., 1975; Longland et al., 1977; Grundschober, 1977; Leegwater & van Straten, 1979).

766CHAPTER NINETEENCarboxylic Acids


In resting women who received intravenous injections of [2-14C]pyruvate, analysis of blood glucose 1 h later showed 96% conversion of pyruvic acid to glucose (Hostetler et al., 1969). When [2-14C]pyruvate was incubated with liver slices from fasted normal rats, 86% had been used after 90 min of incubation. Of the radiolabel associated with metabolized pyruvic acid, 23% was associated with glycogen and glucose, 16% with CO2, and 16% with lactic acid. In the presence of glycerol, the use of pyruvic acid was increased to 95%, accompanied by a decrease in conversion to glycogen (16%) and CO2 (8.6%) and an increase in the production of lactic acid (Teng et al., 1953).

Step (c) Synthesis of 5-Methyl-2-oxohexanoic Acid

Section 19.13Among the reactions of carboxylic acids, their conversion to acyl chlorides, primary alcohols, and esters were introduced in earlier chapters and were reviewed in Table 19.5.

2-Oxohexanoic acid | C6H10O3 | CID 159664 ..

(d)10-Undecenoic acid (also called undecylenic acid,it is used, in combination with its zinc salt, to treat fungal infections such as athlete’s foot)

6-Aminohexanoic acid ≥98.5% (NT) | Sigma-Aldrich

Section 19.18Carboxylic acids are readily identified by the presence of strong infrared absorptions at 1700 cm 1(CœO) and between 2500 and 3500 cm 1 (OH), a 1H NMR signal for the hydroxyl proton at 10–12 ppm, and a 13C signal for the carbonyl carbon near 180 ppm.

5,5-Dimethyl-4-oxohexanoic acid | 57965-24-9 | …

Propylene glycol can be oxidized to lactic acid one of two pathways, depending on whether the glycol is phosphorylated (Rudney, 1954; Miller & Bazzano, 1965). Instudies with rat liver, the free glycol was successively oxidized to lactaldehyde, methylglyoxal (pyuvaldehyde), and lactic acid (see pathway 1, Figure 6) (Ting et al., 1964; Miller & Bazzano, 1965), while the phosphorylated glycol followed the pathway of acetyl phosphate, lactaldehyde phosphate, lactyl phosphate, and lactic acid (Ruddick, 1972; see pathway 2, Figure 6). Lactate is subsequently converted to pyruvate, which enters the citric acid cycle and/or the gluconeogenesis pathway (Ruddick, 1972; Wittman & Bawin, 1974).