Substituted cyclodextrins and process for chromatographic separation of chiral organic compounds

Abstract

Substituted cyclodextrins of the general formula ##STR1## in which R 2 and R 6 mean straight-chain or branched alkyl or alkenyl groups with 1 to 8 carbon atoms or cycloalkyl groups with 5 to 8 carbon atoms which can be the same or different, and R 3 represents a straight-chain or branched alkyl or alkenyl group, which can be the same or different to the residues R 2 and R 6 , with 1 to 8 carbon atoms or a cycloalkyl group with 5 to 8 carbon atoms, or an acyl group with an optionally substituted, saturated or olefinically unsaturated aliphatic or cycloaliphatic or with an aromatic hydrocarbon residue with 1 to 8 carbon atoms, and n=6 or 7, a process for their production, and a process for the separation of chiral organic compounds by chromatographic separation processes in which the substituted cyclodextri are used as stationary phase.

We claim: 
     
       1. A substituted cyclodextrin of the formula ##STR3## in which R 2 , R 3  and R 6  each independently is an alkyl or alkenyl group having 1 to 8 carbon atoms, or a cycloalkyl group having 5 to 8 carbon atoms, or R 3  may be an acyl group having 1 to 8 carbon atoms or an acyl group substituted with an aromatic hydrocarbon radical or a saturated or olefinically unsaturated aliphatic or cycloaliphatic radical having 1 to 8 carbon atoms, and n is 6 or 7,   with the exclusion of those compounds wherein R 2  =R 3  =R 6  =methyl, n=6 or 7, R 2  =R 3  =R 6  =ethyl, n=7, R 2  =R 6  =allyl, R 3  =methyl, n=7, R 2  =R 6  =prop-1-enyl, R 3  =methyl, n=7, R 2  =R 6  =methyl, R 3  =n-butyl, n=7, R 2  =R 6  =methyl, R 3  =benzoyl, n=7 and R 2  =R 3  =alkyl or acyl, R 6  . .=C>4.!..Iadd.>C 4  .Iaddend.-alkyl.   
     
     
       2. A substituted cyclodextrin according to claim 1, wherein the alkyl and/or acyl groups have 3 to 6 carbon atoms. 
     
     
       3. A subsututed cyclodextrin according to claim 1, wherein R 2 , R 3  and R 6  are alkyl or alkenyl groups with 3 to 6 carbon atoms or R 3  may be an acetyl group. 
     
     
       4. A substituted cyclodextrin according to claim 1, wherein R 2  and R 6  each is e n-pcntyl-group and R 3  is an acetyl group. 
     
     
       5. A process for the production of a substituted cyclodextrin according to claim 1, which comprises dissolving an α- or β-cyclodextrin in an anhydrous solvent, adding a pulverted alkali hydroxide, and reacting the cyclodextrin with an alkyl halide. 
     
     
       6. A process according to claim 5, including the further step of reacting the product with an acylating agent in an anhydrous solvent containing an amine. 
     
     
       7. A process according to claim 5 wherein the anhydrous solvent is aprotic. 
     
     
       8. A process according to claim 6 wherein the anhydrous solvent is aprotic. . .9. A process according to claim 6, 7 or 8 wherein the reactions are carried out under inert gas..!.. .10. In the chrormatographic separation of individual chiral organic organic compounds from a mixture by contacting the mixture with a stationary phase, the improvement which comprises employing as the stationary phase a substituted cyclodextrin 
     
     
        according to claim 1..!.11. A separation process according to claim 10, wherein the contact is made with the chiral organic compounds in gas 
     
     
        phase. 12. A separation process according to claim 10, wherein the chiral 
     
     
        organic compounds are enantiomers. 13. A separation process according to claim 12, wherein the enantiomers are selected from the group consisting of alcohols, polyols, 1,5-anhydro-alditols; hydroxy esters, aldols, lactones, spiro-acetals, amines, amino-alcohols, amino-acid esters and a 
     
     
        trifluoroacetylation product of any of the foregoing. 14. A separation process according to claim 13, wherein the enantiomers are polyols selected from the group consisting of diols, polyols containing more than 
     
     
        two hydroxy groups and monosaccharides. 15. A separation process according 
     
     
        to claim 14, wherein the enantionmers are methylglycosides. .Iadd.16.  A process according to claims 5, 6, 7 or 8 wherein the reactions are carried out under inert gas. .Iaddend..Iadd.17. In the chromatographic separation of individual chiral organic compounds from a mixture by contacting the mixture with a stationary phase, the improvement which comprises employing as the stationary phase a substituted cyclodextrin of the formula ##STR4## in which R 2 , R 3  and R 6  each independently is an alkyl or alkenyl group having 1 to 8 carbon atoms, or a cycloalkyl group having 5 to 8 carbon atoms, or R 3  may be an acyl group having 1 to 8 carbon atoms or an acyl group substituted with an aromatic hydrocarbon radical or a saturated or olefinically unsaturated aliphatic or cycloaliphatic radical having 1 to 8 carbon atoms, and n is 6 or 7,   with the exclusion of those compounds wherein   R 2  =R 3  =R 6  =methyl, n=6 or 7, and   R 2  =R 6  =allyl, R 3  =methyl, n=7, and   R 2  =R 6  =prop-1-enyl, R 3  =methyl, n=7, and   R 2  =R 6  =methyl, R 3  =n-butyl, n=7. .Iaddend.