Preparation of R/S-.gamma.-lipoic acid or R/S-.alpha.-lipoic acid
AssigneeBASF SE
InventorsJoachim Paust, Peter Eckes, Wolfgang Siegel, Friedhelm Balkenhohl, Walter Dobler, Michael Hullmann
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Abstract
A process for preparing R/S-.gamma.-lipoic acid of the formula I or R/S-.alpha.-lipoic acid of the formula II ##STR1## is disclosed.
Claims3
A process for preparing R/S-.gamma.-lipoic acid (6,8-dimercaptooctanoic acid) of the formula I or R/S-.alpha.-lipoic acid of the formula II ##STR19## which comprises A. reacting cyclohexanone in the presence of a suitable free radical initiator with a vinyl alkyl ether of the formula III ##STR20## where R.sup.1 is C.sub.1 -C.sub.3 -alkyl, B. converting the resulting 2-alkoxyethylcyclohexanone of the formula IV ##STR21## by Baeyer-Villiger oxidation with performic acid prepared in situ into a mixture of 8-alkoxy-6-formyloxy-octanoic acid of the formula VII ##STR22## where R.sup.1 is C.sub.1 -C.sub.3 -alkyl, and small amounts of 8-alkoxy-6-hydroxyoctanoic acid of the formula VI and its lactone of the formula V ##STR23## C. reacting the resulting mixture in a conventional manner in the presence of hydrobromic acid or hydriodic acid with thiourea to give R/S-.gamma.-lipoic acid (6,8-dimercaptooctanoic acid) of the formula I, and isolating the latter, or
- D. converting the resulting crude R/S-.gamma.-lipoic acid by aerial oxidation in the presence of catalytic amounts of iron(III) compounds into R/S-.alpha.-lipoic acid of the formula II,
- E. subjecting the resulting crude R/S-.alpha.-lipoic acid to a continuous distillation in a thin film evaporator under 0.02 to 0.2 mbar and at 60.degree.-200.degree. C., and
- F. crystallizing the resulting R/S-.alpha.-lipoic acid distillate.
A process for preparing R/S-.gamma.-lipoic acid (6,8-dimercaptooctanoic acid) of the formula I or R/S-.alpha.-lipoic acid of the formula II ##STR24## which comprises A. reacting cyclohexanone in the presence of ditert-butyl peroxide with a vinyl alkyl ether of the formula III ##STR25## where R.sup.1 is C.sub.1 -C.sub.3 -alkyl, B. converting the resulting 2-alkoxyethylcyclohexanone of the formula IV ##STR26## by Baeyer-Villiger oxidation with performic acid prepared in situ into a mixture of 8-alkoxy-6-formyloxy-octanoic acid of the formula VII ##STR27## where R.sup.1 is C.sub.1 -C.sub.3 -alkyl, and small amounts of 8-alkoxy-6-hydroxyoctanoic acid of the formula VI and its lactone of the formula V ##STR28## C. reacting the resulting mixture in a conventional manner in the presence of concentrated hydrobromic acid with thiourea to give R/S-.gamma.-lipoic acid (6,8-dimercaptooctanoic acid) of the formula I, and isolating the latter, or
- D. converting the resulting crude R/S-.gamma.-lipoic acid by aerial oxidation in the presence of catalytic amounts of iron(III) chloride into R/S-.alpha.-lipoic acid of the formula II,
- E. subjecting the resulting crude R/S-.alpha.-lipoic acid to a continuous distillation in a thin film evaporator under from 0.05 to 0.1 mbar and at a temperature of from 130.degree. to 160.degree. C., and
- F. crystallizing the resulting R/S-.alpha.-lipoic acid distillate from diisopropyl ether or a mixture of hexane and ethyl acetate.
Dependencies are inferred from the claim text.