Patent GB-805298-A (GB)
Title: Derivatives of octanoic acid
Filed: 1955-07-14
Abstract: The invention comprises compounds of the formula R0OOC(CH2)4CH(SR*)CH2CH2OH (wherein R0 is hydrogen, a hydrocarbon group, an alkali metal or one equivalent of an alkaline earth metal and R* is hydrogen, an acyl group, an alkali metal or one equivalent of an alkaline earth metal, except that when R0 is hydrogen R* is not acyl) including their (+)- and (-)-enantiomorphs; and their preparation by treating a 7-monoester of a 3-acylthio-7-carboxyheptanoyl halide with an alkali-metal borohydride and treating the reaction mixture with acid until it is no longer alkaline to produce the corresponding ester of a 6-acylthio-8-hydroxyoctanoic acid which by treatment with about one equivalent of an inorganic base may be converted to the corresponding 6-thiol-8-hydroxyoctanoic acid ester.  This with a further equivalent of an alkali or alkaline earth metal base gives a metal salt or with 2 equivalents of base gives the dimetal salt of the free acid (also obtainable by treatment of the 6-acylthio-8-hydroxyoctanoic acid ester with about 3 equivalents of base or by treatment of the corresponding thiol with 2 equivalents of base) which on acidification gives 6-thiol-8-hydroxyoctanoic acid.  In examples: (1) 3-acetylthio-7-carboethoxy-heptanoyl chloride is reduced with sodium borohydride in dioxan at 20 DEG  to 25 DEG  C. and the reaction mixture is treated with water at less than 10 DEG  C. to give, on acidification and working up, ethyl 6 - acetylthio - 8 - hydroxyoctanoate with, as a by-product, some ethyl 6-thio-8-hydroxyoctanoate; (2) and (3) the (+)-and (-)-enantiomorphs of ethyl 6-acetylthio-8-hydroxyoctanoate are similarly prepared from, respectively, the (-)- and (+)-enantiomorphs of 3-acetylthio-7-carboethoxyheptanoyl chloride; (4) ethyl 6 - butyrylthio - 8 - hydroxyoctanoate is prepared from 3-butyrylthio-7-carboethoxyheptanoyl chloride as in (1), and it is stated that methyl 6 - propionylthio - 8 - hydroxyoctanoate, phenyl 6 - benzoylthio - 8 - hydroxyoctanoate and ethyl 6 - phenylacetylthio - 8 - hydroxyoctanoate may be similarly prepared; (5) ethyl 6 - acetylthio - 8 - hydroxyoctanoate in ethanol is treated with sodium hydroxide, with warming, until the sodium hydroxide is no longer consumed rapidly and the mixture is cooled and acidified to pH 3 to give, on working up, ethyl 6-thiol-8-hydroxyoctanoate which on further treatment with a base and then acid gives 6-thiol-8-hydroxyoctanoic acid, the (+)-and (-)-enantiomorphs of which are prepared similarly; (6) ethyl 6-butyrylthio-8-hydroxyoctanoate yields, on controlled hydrolysis as in (5), ethyl 6-thiol-8-hydroxyoctanoate and it is stated that the methyl, propyl, benzyl and phenyl ester may be similarly prepared and may all be hydrolysed to 6-thiol-8-hydroxyoctanoic acid; (7) ethyl 6-acetylthio-8-hydroxyoctanoate is refluxed with sodium hydroxide in methanol containing a trace of zinc dust to give, on working up, 6-thiol-8-hydroxyoctanoic acid; (8) and (9) the (+)- and (-)-enantiomorphs of ethyl 6-acetylthio-8-hydroxyoctanoate are similarly converted to optical isomers of 6-thiol-8-hydroxyoctanoic acid.  Specifications 805,297, 805,299 and 805,300 also are referred to.