cyclobutyrol

Originator

Hebucol,Logeais,France,1957

Definition

ChEBI: A hydroxy monocarboxylic acid in which the hydroxy group is geminal to a 1-carboxypropyl group on a cyclohexane ring.

Manufacturing Process

Into a balloon flask with two lateral necks furnished with an efficient mechanical agitator and protected from moisture by a calcium chloride guard, there are introduced 12 g (0.185 mol) of pure powdered zinc and 20 ml of a solution of 16.6 g (0.17 mol) of anhydrous cyclohexanone and 31.5 g (0.16 mol) of ethyl α-bromobutyrate in 25 ml of anhydrous benzene. With vigorous stirring in a manner to put the zinc into suspension, the balloon flask is gradually heated in an oil bath to 100°C to 105°C. After a few minutes, a reaction starts, causing violent boiling which is maintained while adding the balance of the reactants. Boiling is then continued for one hour. After cooling, the reaction mixture is turned into a beaker containing 30 ml of sulfuric acid to half (by volume) with ice. After agitation, the mixture is decanted into a container for separation. The aqueous phase is reextracted with benzene. The pooled benzene solutions are washed with dilute (10%) cold sulfuric acid, then with cold sodium carbonate (5%) and then with ice water, and dried over anhydrous sodium sulfate. The benzene is evaporated and the ester, which is ethyl α(hydroxy-1-cyclohexyl) butyrate, is distilled off under reduced pressure. The yield obtained was 17 to 19 g or 49% to 55%.
The ester was saponified with baryta in aqueous methanol as follows:
21.5 g (0.1 mol) of the above ethyl ester is saponified by boiling under reflux for 4 hours, while agitating, with 30 g (0.095 mol) of barium oxide hydrated to 8H2O in 250 ml of a mixture of equal volumes of methanol and water. After concentration to one-half its volume under reduced pressure and filtration, the aqueous solution is washed with ether and then acidified at 0°C with 10% hydrochloric acid. The acid liberated in oily form is extracted with ether. The ether is washed with water, dried and evaporated. The yield is 75-80% (14-15 g of crude acid) which crystallizes spontaneously little by little. It can be crystallized in a mixture of ether and petroleum ether (1:10) or, with better yield, in light gasoline or oil (solubility of the pure acid ranges from 0.3% at 0°C to 100% at the boiling point). The yield of crystals is 75-80%. The α(hydroxy-1-cyclohexyl) butyric acid thus obtained is a colorless crystalline product with a melting point of 81°C to 82°C.

Therapeutic Function

Choleretic