Ethyl hydroxyhexanoate

In dicarboxylic acids with one free and one esterified carboxyl group the free carboxyl only may be reduced with hydrides (alanes, boranes). The monoethyl ester or adipic acid was converted by an equimolar amount of borane in tetrahydrofuran at —18° to 25° to ethyl 6-hydroxyhexanoate in 88% yield [971] Procedure 19, p. 209). 

An oven-dried 100 ml flask with a side arm dosed with a septum is fitted with a magnetic stirring bar and a reflux condenser connected to a mercury bubbler. The flask is cooled to room temperature under nitrogen, charged with 4.36 g (0.025 mol) of adipic acid monoethyl ester followed by 12.5 ml of anhydrous tetrahydrofuran, and cooled to —18° by immersion in an ice-salt bath. Then 10.5 ml of 2.39 m (or 25 ml of 1 m) solution of borane in tetrahydrofuran (0.025 mol) is slowly added dropwise over a period of 19 minutes. The resulting clear reaction mixture is stirred well and the ice-salt bath is allowed to warm slowly to room temperature over a 16-hour period. The mixture is hydrolyzed with 15 ml of water at 0°. The aqueous phase is treated with 6 g of potassium carbonate (to decrease the solubility of the alcohol-ester in water), the tetrahydrofuran layer is separated and the aqueous layer is extracted three times with a total of 150 ml of ether. The combined ether extracts are washed with 30 ml of a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give 3.5 g (88%) of a colorless liquid which on distillation yields 2.98 g (75%) of ethyl 6-hydroxyhexanoate, b.p. 79°/0.7 mm. 

In six male volunteers given 46 mg deuterium-labelled di(2-ethylhexyl) adipate [approx. 0.5 mg/kg bw] in com oil, 2-ethylhexanoic acid was the only metabolite that could be determined in the plasma. It had an elimination half-life of 1.65 h. In urine, the following metabolites were identified (percentage fraction of administered deuterium label) 2-ethylhexanoic acid (8.6%), 2-ethyl-5-hydroxyhexanoic acid (2.6%), 2-ethyl-1,6-hexanedioic acid (0.7%), 2-ethyl-5-ketohexanoic acid (0.2%) and 2-ethylhexanol (0.1%). The half-life for elimination of all metabolites excreted in the urine averaged 1.5 h, and none of the metabolites could be detected after 36 h (Loftus et al, 1993). 

Primary hepatocyte cultures may be employed to study species differences in hepatic peroxisome proliferation (lARC, 1995). The effects of di(2-ethylhexyl) adipate and its metabolites in cultured hepatocytes from rats, mice, guinea-pigs and marmosets have been studied (Cornu et al., 1992). In hepatocytes from each species, the parent compound di(2-ethylhexyl) adipate had no effect on peroxisomal cyanide-insensitive palmitoyl-CoA oxidation activity. However, in rat and mouse hepatocytes, the metabolites mono(2-ethylhexyl) adipate, 2-ethylhexanol, 2-ethylhexanoic acid and 2-ethyl-5-hydroxyhexanoic acid at concentrations < 1 mM induced peroxisomal palmitoyl-CoA oxidation. No induction of peroxisomal palmitoyl-CoA oxidation was seen at concentrations < 1 mM for mono(2-ethylhexyl) adipate or < 2 mM for 2-ethylhexanol, 2-ethylhexanoic acid and 2-ethyl-5-hydroxyhexanoic acid in guinea-pig or marmoset hepatocytes (2-ethylhexanol was evaluated only at < 1 mM in marmoset hepatocytes). 

Tertiary alcohols are oxidized in water-dioxane-NaOH to alkoxy radicals, wliich fragmentate to ketone and alkyl radicals R- (Eq. (216) ). The relative rate of cleavage decreases with R in the order sec -butyl > isopropyl > ethyl > propyl > pentyl > isobutyl > methyl 46 8). Likewise, the bisulfite adduct of cyclohexanone is converted in 20% yield to 4-hydroxyhexanoic acid lactone (160) and 3-hydroxycyclohexanoic acid lactone (161) by anodic fragmentation (Eq. (222) ) 469 ... 

Ethyl butanoate, 2-methyl-3-buten-2-ol (111), ethyl acetate, ethyl 3-hydroxyhexanoate (112),... 

As shown in Figure 7 ethyl 3-hydroxyhexanoate, isolated from purple passion fruit possessed the (R)-configuration, comparable to the hydroxyacid ester obtained by the reduction with baker s yeast. In contrary to that methyl 3-hydroxyhexanoate, which was isolated from aroma extracts of pineapple, consisted of the (S)-enantiomer (91 %). ... 

Arising from impaired activity of acetyl CoA carboxylase 2-Ethyl-3-hydroxyhexanoic acid... 

Capillary gas chromatographic investigation of diastereoisomeric derivatives revealed that in analogy to results obtained without precursors the chiral metabolites are present as mixtures of enantiomers. However for only a few of these compounds the ratios of enantiomers are identical with those determined in pineapple without precursors. The enantiomeric compositions of ethyl 3-hydroxyhexanoate and ethyl 3-acetoxyhexanoate are almost opposite to those determined for the naturally occurring methyl esters. 6-Octalactone obtained after addition of 5-oxooctanoic acid to pineapple tissue is almost optically pure (92% S) on the other hand -octalactone is naturally present in pineapple tissue as nearly racemic mixture (Table 1,8). 

Figure 1 shows part of a reconstructed ion chromatogram of a pineapple aroma extract isolated after incubation of pineapple slices with 3-hydroxyhexanoic acid-3-di. GC-MS detection of deuterated compounds showed that the following pathways are active (a) esterification leading to methyl and ethyl esters, (b) dehydration to (E)-2-and (E)-3-hexenoates, and (c) chain elongation to methyl 5-hydroxy octanoate followed by acetylation (methyl 5-acetoxyoctanoate) and cyclization ( 6-octalactone). 

The hypothesis of the existence of the branched-chain parasaccharinic acid now depended solely on the identity of the reduction product, hydroxyhexanoic acid. To support his previous contention that the barium salt of this acid is, indeed, barium 2-ethyl-4-hydroxybutyrate, Kiliani also prepared the calcium salt and found that it, too, closely resembled the corresponding salt of 2-ethyl-4-hydroxybutyric acid. As emphasized by Kiliani, neither the reductions with hydriodic acid and red phosphorus nor the oxidations with nitric acid proceed in good yield to single products. Accordingly, Kihani remained firm in his conviction that his preparation, although it was apparently a mixture, nevertheless contained the branched-... 

PPL catalyzed the polymerization of methyl esters of 5-hydroxypentanoic and 6-hydroxyhexanoic acids.149 In the polymerization of the latter in hexane at 69 °C for more than 50 days, the polymer with DP up to 100 was formed. Relationships between solvent type and polymerization behaviors were systematically investigated hydrophobic solvents such as hydrocarbons and diisopropyl ether were suitable for the enzymatic production of high molecular weight polymer. Pseudomonas sp. lipase catalyzed the polymerization of ethyl esters of 3- and 4-hydroxybu-tyric acids, 5- and 6-hydroxyhexanoic acids, 5-hy-droxydodecanoic acid, and 15-hydroxypentadecanoic acid.157 Oxyacid vinyl esters were demonstrated as new monomers for polyester production under mild reaction conditions, yielding the corresponding polyesters with A/n of several thousands.276... 

Ethyl-(5)-5-hydroxyhexanoate 68 and (5)-5-hydroxyhexanenitrile 69 (Figure 16.18) are key chiral intermediates in the synthesis of anti-Alzheimer s drugs 70 [95]. 

Uses Fragrance in cosmetics Ethyl 3-hydroxyhexanoate CAS 2305-25-1 EINECS/ELINCS 218-973-7 FEMA 3545... 

Synonyms y-Caprolactone Ethyl butyrolactone y-Ethylbutyrolactone 2(3H)-Furanone, 5-ethyldihydro- y-Hexanolactone Hexanolide-1,4 Hexan-4-olide 4-Hydroxyhexanoic acid lactone 4-Hydroxyhexanoic acid y-lactone Tonkalide Classification Nonaromatic lactone Empirical C6H10O2... 

---