cis-4-Hydroxycyclohexanecarboxylic acid

Solid

White to Almost white powder to crystal. Melting point: 148.0 to 152.0 °C.

ChEBI: 4-Hydroxycyclohexylcarboxylic acid is a hydroxy monocarboxylic acid.

20 g of methyl 4-hydroxycyclohexanecarboxylate was dissolved in 80 mL of methanol, L ice water bath add 5mol / L sodium hydroxide 40mL, After completion of the dropwise addition, the mixture was stirred at room temperature overnight, 150 mL of water was added thereto, and the mixture was extracted twice with ethyl acetate, The ethyl acetate layer was discarded, The aqueous phase was adjusted to pH 3 with 1 mol / L HCl, Ethyl acetate 50mL extraction twice, The ethyl acetate layers were combined, washed twice with saturated brine, Dried and decolorized. After filtration, ethyl acetate was recovered to obtain 16 g of a white solid. Yield: 90percent.Step a: To a stirred solution of 4-oxocyclohexane-1-carboxylic acid (1.0 g, 7.03 mmol) in MeOH (65 mL), at RT, sodium borohydride (0.53 g, 14.07 mmol) was added portion-wise and the resulting reaction mixture was stirred at RT for lh. The mixture was then concentrated under vacuum and the residue was taken up with DCM and aqueous iN HC1. The organic phase was washed with water, dried and concentrated under reduced pressure to give 4-hydroxycyclohexane-1-carboxylic acid (0.62 g) that was used as such in the next step.a cis-trans-4-hydroxycyclohexanecarboxylic acid 184 g (1.07 mol) cis-trans-4-hydroxycyclohexanecarboxylic acid ether ester (lit.: JACS 70, (1948) 1898) are heated to reflux in 1.81 of water with 119.8 g (2.14 mol) potassium hydroxide for 3 h. After acidification with conc. hydrochloric acid and extraction with methylene chloride, there are obtained 146 g of acid of the m.p. 111-115 C., i.e. 94% of theory.Part C Six parts of the product obtained in Part B, 50 parts of 20% aqueous potassium hydroxide and 50 parts by volume of methanol were refluxed for 1 hour, the mixture acidified with hydrochloric acid and saturated with sodium chloride. The mixture was extracted several times with methylene chloride and the extracts combined, dried over sodium sulfate and the solvent evaporated. The resultant solid was recrystallized from ethyl acetate. A yield of 4.2 parts of trans-4-hydroxycyclohexane carboxylic acid was obtained having a melting point of 149-151 C.a cis-trans-4-hydroxycyclohexanecarboxylic acid 184 g (1.07 mol) cis-trans-4-hydroxycyclohexanecarboxylic acid ether ester (lit.: JACS 70, (1948) 1898) are heated to reflux in 1.81 of water with 119.8 g (2.14 mol) potassium hydroxide for 3 h. After acidification with conc. hydrochloric acid and extraction with methylene chloride, there are obtained 146 g of acid of the m.p. 111°-115° C., i.e. 94percent of theory.Part C Six parts of the product obtained in Part B, 50 parts of 20percent aqueous potassium hydroxide and 50 parts by volume of methanol were refluxed for 1 hour, the mixture acidified with hydrochloric acid and saturated with sodium chloride. The mixture was extracted several times with methylene chloride and the extracts combined, dried over sodium sulfate and the solvent evaporated. The resultant solid was recrystallized from ethyl acetate. A yield of 4.2 parts of trans-4-hydroxycyclohexane carboxylic acid was obtained having a melting point of 149°-151° C.

Cis-4-Hydroxycyclohexanecarboxylic acid is a metabolite of p-hydroxybenzoic acid. It is the major metabolite in the urine of rats treated with exogenous p-hydroxybenzoic acid. It has been found to have immunosuppressive activities in rat hepatocytes, as well as metabolic disorders that are related to hyperglycemia or diabetes mellitus.