MXPA97006801A - Process for the preparation of depolisacarid derivatives substituted by carbamoilo aromat - Google Patents
Process for the preparation of depolisacarid derivatives substituted by carbamoilo aromatInfo
- Publication number
- MXPA97006801A MXPA97006801A MXPA/A/1997/006801A MX9706801A MXPA97006801A MX PA97006801 A MXPA97006801 A MX PA97006801A MX 9706801 A MX9706801 A MX 9706801A MX PA97006801 A MXPA97006801 A MX PA97006801A
- Authority
- MX
- Mexico
- Prior art keywords
- polysaccharide
- organic solvent
- aryl
- carbamates
- process according
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 150000004676 glycans Polymers 0.000 claims abstract description 38
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 38
- 239000005017 polysaccharide Substances 0.000 claims abstract description 38
- 150000004804 polysaccharides Polymers 0.000 claims abstract description 38
- 239000002245 particle Substances 0.000 claims abstract description 26
- 239000000243 solution Substances 0.000 claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 239000000839 emulsion Substances 0.000 claims abstract description 8
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 230000005526 G1 to G0 transition Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 3
- 150000004292 cyclic ethers Chemical class 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 15
- 239000000463 material Substances 0.000 abstract description 14
- -1 alkyl carbamate Chemical compound 0.000 abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 229920002678 cellulose Polymers 0.000 description 13
- 239000001913 cellulose Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229920002284 Cellulose triacetate Polymers 0.000 description 4
- DGTNSSLYPYDJGL-UHFFFAOYSA-N Phenylisocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atoms Chemical group C* 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PWXJULSLLONQHY-UHFFFAOYSA-M N-phenylcarbamate Chemical compound [O-]C(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-M 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical group 0.000 description 3
- 230000001788 irregular Effects 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000010959 steel Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 239000008079 hexane Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 description 1
- NWACCXJCJNDIDK-UHFFFAOYSA-N 1,2,3-tributylbenzene Chemical group CCCCC1=CC=CC(CCCC)=C1CCCC NWACCXJCJNDIDK-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YZNQITSGDRCUKE-UHFFFAOYSA-N 1-chloropropane Chemical group [CH2]CCCl YZNQITSGDRCUKE-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N 3-Pentanone Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N Chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229940087091 Dichlorotetrafluoroethane Drugs 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N Inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 229940029339 Inulin Drugs 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N Trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N [N-]=C=O Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 150000002243 furanoses Chemical group 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N methyl trifluoride Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003214 pyranose derivatives Chemical group 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000000717 retained Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
Abstract
The present invention relates to a process for the preparation of polysaccharide N-aryl carbamates in a suitable form as supports for chromatography, said process comprises adding to the polysaccharide carbamates, which may be substituted in the aryl fraction, a solution which contain N-aryl-1-lower alkyl carbamate of an organic solvent, with vigorous stirring, until the polysaccharide derivative is completely dissolved, and then add thereto an aqueous solution containing a high molecular weight surfactant and with continuous stirring, remove the organic solvent from the as-adsorbed emulsion, and isolate the solid particles and wash and dry them. The as-adsorbed polysaccharide derivatives can be used as support materials for the chromathographic separation of enantiomer
Description
PROCESS FOR THE PREPARATION OF POLYACARID DERIVATIVES SUBSTITUTED BY CARBAMOILO AROMATIC
The invention relates to a process for the preparation of polysaccharide derivatives substituted by aromatic carbamoyl, which find utility as support materials for the chromatographic separation of enantiomers. In Chemistry Letters. pages 739-742 (198). Y. Okamoto et al. Describe a separation material suitable for chromatography, said material consisting of a acroporous silica gel coated with cellulose triacetate and cellulose tribenzoate. This support material is expensive. In addition, only the layer of the cellulose derivative is available for the separation of the enantiomers, so that the separation capacity is not entirely satisfactory. In J. of Cromatography. 351. pages 346-350 C1986), K.-H. Rimbock proposes to use as the stationary phase, powdered microcrystalline tribenzole cellulose obtained by simple precipitation from a solution. The separation capacity of the powder material is insufficient. In addition, the particle size and the external shape of the particles can not be controlled when this process is used. European Patent Number EP-A-0252539 discloses a process for the preparation of porous spherical cellulose particles. In this process, a legal solution is suspended
cellulose triacetate containing a long chain alcohol, with stirring, in an aqueous phase containing a high molecular weight surfactant, usually polyvinyl alcohol or gelatin. After removing the organic solvent, the cellulose triacetate particles thus obtained are isolated and purified, and then saponified. Our own tests showed that the cellulose triacetate particles obtained according to this process, have only a small specific surface area, and only a low separation power for enaptiomers, when they are used as the stationary phase in liquid chromatographic processes. European Patent Number EP-A-0,316,270 discloses cellulose esters in fine particles of aromatic or aromatic-aliphatic carboxylic acids. in the form of essentially round partially crystalline particles, which can actually be used as the stationary phase in chromatographic processes, in particular for the separation of enantiomers, but which are not suitable for all classes of compounds. European Patents Nos. EP-AO.157,364, EP-A-0,147,801, and EP-AO .157,356 disclose polysaccharide carbamates which are suitable for the separation of enantiomers, but in the case of these polymers, it must be taken into consideration that they can be used only after applying to a support. usually with silica.
European Patent Number EP-A-0,527, 236 discloses aromatic and araliphatic polysaccharide carbamates which are used as the stationary phase for the chromatographic separation of spreads. It is emphasized that the materials thus obtained can be used as such, without being applied to a support. However, extensive experiments on our part showed that the materials thus obtained can not be used according to the conditions indicated for the chromatographic separation of enantiomers. The invention relates to a process for the preparation of polysaccharide N-aryl carbamates in a suitable form as supports for chromatography, said process comprises adding to the polysaccharide carbamates, which may be substituted in the aryl fraction, a solution containing N-aryl-1-lower alkyl carbamate of an organic solvent. with vigorous stirring, until the polysaccharide derivative is completely dissolved, and then add thereto an aqueous solution containing a high molecular weight surfactant, and with continuous stirring, remove the organic solvent from the emulsion thus obtained, and isolate the particles solid and wash and dry them. The polysaccharide particles are obtained in a particle size of 5 to 150 microns, and in particular of 10 to 30 microns, in a rounded form or also in an irregular form. The specific surface area is oreferenoia e 1
to 100 square meters / gram, but in a particularly preferable way from 3 to 35 square meters / gram. The specific surface area can be influenced by the reaction conditions, usually by the choice of solvent, and by the manner in which the reaction is performed, for example, by the rate of addition, agitation, and evaporation, as well as for the proportions of solvent, water, and high molecular weight surfactant. The high molecular weight surfactants are preferably polyvinyl alcohol or carboxymethyl cellulose. It is also possible to use other tepsoactives. such as those described in the National Standard Reference Data System (NSRDS). Nat. Bur. Stand. (E.U.) 36, pages 24-32, United States Government Printing Office (1971), are typically esterified with sulfuric acid of 8 to 16 carbon atoms, for example, lauryl sulfate. Surprisingly, the polysaccharide N-aryl carbamates thus obtained can be used in an excellent manner as supports for the chromatographic separation of spreads without prior application to a support, for example. Silica gel. The invention relates in particular to a process for the preparation of N-phenyl carbamates of polysaccharide in a suitable form as supports for chromatography, said process comprises adding to the polysaccharide carbamates. that can
to be substituted in the phenyl fraction, a solution containing N-phenyl-1-heptyl carbamate from an organic solvent, preferably methylepoyl chloride, with vigorous stirring, until the polysaccharide derivative is completely dissolved, and then added thereto an aqueous solution containing a high molecular weight surfactant, and with continuous agitation, • remove the organic solvent from the emulsion thus obtained, and isolate the solid particles and wash and dry them. The invention relates in particular to the compounds obtained in the Examples. In the foregoing, as well as subsequently herein, radicals and lower compounds will be understood to mean normally those containing up to and including 7 carbon atoms. The polysaccharides are usually cellulose, amylose, chitosan, dextran, xylan, and inulin, which are available as polysaccharides in a high degree of purity. It is preferred to use polysaccharides having a degree of polymerization (number of pyranose and furanose rings) of at least 5. and particularly preferably at least 10, but to ensure a simple handling, it should not exceed 1000. Lower alkyl it is usually alkyl of 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, or butyl, each of which may also be substituted by halogen.
normally fluorine or chlorine, for example trifluoromethyl and trichloromethyl. Aryl as such is usually phenyl or naphthyl, for example 1- or 2-naphthyl, or substituted phenyl or naphthyl, usually phenyl or naphthyl which are substituted by lower alkyl, lower haloalkyl. hydroxy, lower alkoxy, lower alkanoyloxy, halogen, cyano, and / or nitro. Aryl is preferably phenyl which is unsubstituted or substituted as indicated above, and more preferably phenyl which is substituted by lower alkyl, usually methyl, and most preferably unsubstituted fepyl. Lower alkoxy is normally normal propoxy, isopropoxy. normal butoxy, or tertiary butoxy, preferably ethoxy and methoxy. Lower alkanoyloxy, usually propionyloxy or pivaloyloxy, and preferably acetyloxy. Halogen is usually chlorine or fluorine, and also bromine and iodine. Lower haloalkyl is typically 2- or 3-lower haloalkyl, such as 2-lower haloalkyl, for example 2-halopropyl, 3-halopropyl, or 3-halo-2-methylpropyl and may be. for example, 2-chloropetroyl, 3-chloropropyl. or 3-clnro-β-methylpropyl. The organic solvent used in the reaction of this Step in useful form has a lower boiling point than
the one with water Suitable solvents are usually aromatic hydrocarbons, halogenated hydrocarbons preferably fluoro- and / or chlorohydrocarbons, cyclic ethers, carboxylic acid esters, and ketones. It is possible to use, for example, benzene, methylene chloride, chloroform, trichlorofluoromethane. chloroethane, trifluorotrichloroethane, dichlorotetrafluoroethane, acetone, methylethyl ketone, diethyl ketone. cyclohexane, tetrahydrofurapo, and dioxane, or mixtures of these solvents. Methylene chloride and tetrahydrofuran are particularly preferred. The process can be carried out by the dropwise addition of the solution of the polysaccharide carbamate, which may be substituted in the aryl fraction. normally 3.5-dimethylphenyl carbamate polysaccharide. or polysaccharide phenyl carbamate, to the aqueous phase, with stirring, and then, with continuous stirring. stirring the organic solvent, conveniently by distillation and with heating to the boiling point of the solvent, and / or under vacuum. The particles are then isolated, usually by filtration or decantation. The particles thus obtained are then purified by washing them normally with a hydrophilic solvent. for example, an alkanol of 1 to 4 carbon atoms, or also with an aqueous solution thereof. The washing is preferably carried out with methanol. The polysaccharide carbamates used in the process
of this invention, which may be substituted in the aryl fraction, are obtained by the reaction of a polysaccharide. normally cellulose or amylose, in a manner known per se, with an unsubstituted or substituted aryl isocyanate. The preferred reaction is carried out with an unsubstituted or substituted phenyl isocyanate. The carbamate is usually prepared by reaction with a suitable isocyanate in the presence of a suitable catalyst. The catalysts used can be Lewis bases, usually tertiary amines, or also Lewis acids. for example a tin compound. The preferred reaction is carried out in the presence of a tertiary base, usually in the presence of pyridine or quinoline which serve at the same time as solvents, but it is also preferred to use a tertiary base of 4- (N, N-dimethylamino) pyridine as a catalyst of the reaction. The conversion of the OH groups to the corresponding carbamates is preferably carried out with unsubstituted or substituted phenyl isocyanates. It is preferred to use phenyl isocyanates substituted by methyl, preferably mono- or di-substituted, or unsubstituted phenyl isocyanates, and the methyl groups may be in the meta or ortho position with respect to each other. With the novel process described at the beginning, polysaccharide N-aryl carbamates in a rounded form or in a
irregular, which have a certain porosity (specific surface area), and a partially crystalline character. This is important with respect to the specific chromatographic separation of enantiomers, since a surprisingly high separation efficiency is achieved in this case. The invention also relates to the use of the polysaccharide derivatives obtained according to the novel process as the stationary phase in the chromatographic processes, in particular to separate enantiomers. The following Examples illustrate the invention in greater detail. The temperatures are given in degrees centigrade, the pressure, where indicated, is given in bar.
EXAMPLE 1 4 grams of 3,5-dimethylphenyl carbamate cellulose, are moistened with 15 milliliters of methanol, and then a solution of 12.8 grams of N-phenyl-1-heptyl carbamate in 105 milliliters of methylene chloride is added. Then this solution is stirred until the cellulose derivative is completely dissolved. Then 96 milliliters of a 5 percent aqueous solution of polyvinyl alcohol (Serva, molecular weight of about 90,000) are added dropwise to this solution for 2 1/2 hours at room temperature and with vigorous stirring (500 rpm). Then the emulsion is heated slowly to 42 ° C. and the methylene chloride is distilled (approximately 2 hours).
After cooling, the residue is isolated by filtration, washed in increments with 500 milliliters of water and then with 200 milliliters of methanol. The product thus obtained is suspended twice in succession in 200 milliliters of methanol, stirred, and isolated by filtration. Subsequently, the product is dried at room temperature. Performance: 3.7 grams. The material consists of rounded particles that have a particle size of 20 to 30 microns. Specific surface area according to BET: 3.7 square meters / gram. Column packing: 2.5 grams of the material thus obtained is suspended in 25 milliliters of a mixture of hexane / 2-propanol (85:15, percentage by volume), and packed by the paste method on a steel column (25 centimeters x 0.4 centimeters) at a flow rate of 2 milliliters / minute for 3 hours.
Example 2 5 grams of cellulose phenyl carbamate are moistened with 15 milliliters of methanol, and then a solution of 16 grams of N-phenyl-1-heptylic carbamate in 150 milliliters of methylene chloride is added. This solution is stirred until the cellulose derivative is completely dissolved. To this solution, 20 milliliters of a 5% aqueous solution of polyvinyl alcohol are added dropwise (Serva, weight
molecular weight of approximately 90,000) for 2-1 / 2 hours at room temperature and with vigorous stirring (400 rpm). The emulsion is then heated slowly to 42 ° C, and the methylene chloride is distilled (approximately 2 hours). After cooling, the residue is isolated by filtration, washed in increments with 500 milliliters of water, and upon conclusion is suspended with 200 milliliters of metapol. it is stirred and isolated by filtration. Subsequently, the product is dried at room temperature. Yield: 4.5 grams. The material consists of rounded particles that have a particle size of 10 to 30 microns. Specific surface area according to BET: 31.0 square meters / gram. Column packing: 2.5 grams of the material obtained are suspended in 25 milliliters of ethanol. and stir for 1 hour. Then the suspension is subjected to filtration, and the filter cake is suspended in 25 milliliters of a mixture of hexane / 2-proanol (90:10, percent by volume), and packed by the paste method in a column steel (25 centimeters by 0.4 centimeters), at a flow rate of 2 milliliters / minute for 3 hours. Example 3 5 grams of cellulose phenyl carbamate are moistened with 15 milliliters of methanol, and then a solution of
16 grams of N-phenyl-1-heptyl carbamate in 300 milliliters of methylene chloride. This solution is stirred until the cellulose derivative is completely dissolved. To this solution 240 milliliters of a 1 percent aqueous solution of carboxymethyl cellulose (highly viscous) are added dropwise for 2-1 / 2 hours at room temperature and with vigorous stirring (400 rpm). The emulsion is then slowly heated to 42 ° C, and methylene chloride is distilled (approximately 2 hours). After cooling, the residue is isolated by filtration, washed with 500 milliliters of water and, finally, with 200 milliliters of methanol. The product thus obtained is suspended twice in succession in 200 milliliters of methanol, stirred and isolated by filtration. Subsequently, the product is dried at room temperature. Yield: 4.7 grams. The material consists of irregular particles that have a particle size of about 10 microns. Specific surface area according to BET: 5.1 square meters / gram. Column packing: 2.5 grams of the material thus obtained are suspended in 25 milliliters of ethanol, and stirred for 1 hour. Then the suspension is subjected to filtration, and the filter cake is suspended in 25 milliliters of a mixture of he? Apo / 2-pro-anolol (90:10 percentage by volume), and packed by the method
of pasta on a steel column (25 centimeters by 0.4 centimeters), at a flow rate of 2 milliliters / minute for 3 hours. Test of the chiral stationary phases: The phases of Examples 1 to 3 were tested with different racemates (Table 1). In each case, high pressure liquid chromatography is performed with a Shimadzu LC-6A configuration at a flow rate of 0.7-1 milliliter / minute, and at room temperature. The detection is performed using ultraviolet spectroscopy and polarimetry (Perkin Elmer 241 LC). The separation factor a was determined as the value of the measurement. a = 'z / k'i = (t2-t0) / (tj-to), where k'2 and k'x are the capacity factors of the second and first enantiomers eluted, and tj and tj are the times of retention of the same. t0 is the elution time of tertiary tributyl benzene (non-retained compound). Table 1
Claims (14)
1. A process for the preparation of polysaccharide N-aryl carbamates in a suitable form as supports for chromatography, said process comprises adding to the polysaccharide carbamates, which may be substituted in the aryl fraction, a solution containing N-arylcarbamate. 1-lower alkyl of an organic solvent, with vigorous stirring, until the polysaccharide derivative is completely dissolved, and then add to it an aqueous solution containing a high molecular weight surfactant, and with continuous stirring, remove the organic solvent from the emulsion thus obtained, and isolate the solid particles and wash and dry them.
2. A process for the preparation of polysaccharide N-phenyl carbamates in a suitable form as supports for chromatography, said process comprising adding to the polysaccharide carbamates, which may be substituted in the phenyl fraction, a solution containing carbamate N- phenyl-1-heptyl of an organic solvent, preferably methylene chloride, with vigorous stirring, until the polysaccharide derivative is dissolved, and then adding thereto an aqueous solution containing a high molecular weight surfactant, and with continuous stirring , remove the organic solvent from the emulsion thus obtained, and isolate the solid particles and wash and dry them.
3. A process according to claim 1 or claim 2, wherein the organic solvent has a boiling point lower than that of water.
4. A process according to any of claims 1 to 3, wherein the organic solvent is an aromatic hydrocarbon, a halogenated hydrocarbon, a cyclic ether, or a ketone.
5. A process according to any of claims 1 to 4, wherein the organic solvent is methylene chloride.
6. A process according to claim 1 or claim 2, wherein the high molecular weight surfactant is polyvinyl alcohol.
7. A process according to claim 1 or claim 2, wherein the high molecular weight surfactant is carboxymethyl cellulose. A process according to claim 1 or claim 2, wherein the average diameter of the polysaccharide N-aryl carbamate particles obtained is from 5 to 150 microns. 9. A process according to claim 2, wherein the average diameter of the polysaccharide N-aryl carbamate particles obtained is from 10 to 30 microns. 10. A process according to claim 1 or claim 2, wherein the specific surface area The polysaccharide N-aryl carbamate particles are from 1 to 100 square meters / gram. 11. A process according to claim 1 or claim 2, wherein the specific surface area of the polysaccharide N-aryl carbamate particles obtained is from 3 to 35 square meters / gram. 12. The polysaccharide N-aryl carbamate particles obtainable by the process claimed in claim 1. 13. The use of N-aryl polysaccharide carbamates obtained according to claim 1, as the stationary phase in chromatographic processes. , in particular to separate enantiomers. 14. The use of polysaccharide N-phenyl carbamates obtained according to claim 2, as the stationary phase in chromatographic processes, in particular to separate enantiomers.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH639/95 | 1995-03-07 | ||
CH63995 | 1995-03-07 | ||
PCT/EP1996/000732 WO1996027639A1 (en) | 1995-03-07 | 1996-02-22 | Process for the preparation of aromatic carbamoyl-substituted polysaccharide derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
MX9706801A MX9706801A (en) | 1997-11-29 |
MXPA97006801A true MXPA97006801A (en) | 1998-07-03 |
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