JPS63264536A - Separation agent - Google Patents
Separation agentInfo
- Publication number
- JPS63264536A JPS63264536A JP62094460A JP9446087A JPS63264536A JP S63264536 A JPS63264536 A JP S63264536A JP 62094460 A JP62094460 A JP 62094460A JP 9446087 A JP9446087 A JP 9446087A JP S63264536 A JPS63264536 A JP S63264536A
- Authority
- JP
- Japan
- Prior art keywords
- group
- optically active
- carrier
- separation
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000926 separation method Methods 0.000 title abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 17
- 229910052751 metal Inorganic materials 0.000 claims abstract description 11
- 239000002184 metal Substances 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 abstract description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 21
- 239000000741 silica gel Substances 0.000 abstract description 15
- 229910002027 silica gel Inorganic materials 0.000 abstract description 15
- 238000004587 chromatography analysis Methods 0.000 abstract description 11
- 230000003287 optical effect Effects 0.000 abstract description 11
- 125000006850 spacer group Chemical group 0.000 abstract description 7
- 238000012856 packing Methods 0.000 abstract description 6
- 150000001413 amino acids Chemical class 0.000 abstract description 5
- 239000006087 Silane Coupling Agent Substances 0.000 abstract description 3
- 239000004793 Polystyrene Substances 0.000 abstract description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 abstract description 2
- 229920002223 polystyrene Polymers 0.000 abstract description 2
- 235000002906 tartaric acid Nutrition 0.000 abstract description 2
- 239000011975 tartaric acid Substances 0.000 abstract description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract 1
- LHSHBLXATRZWHU-GWCFXTLKSA-N ethyl 2-[[(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]amino]acetate Chemical compound CCOC(=O)CN[C@@H](C)[C@H](O)C1=CC=CC=C1 LHSHBLXATRZWHU-GWCFXTLKSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000945 filler Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 229960000395 phenylpropanolamine Drugs 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000002148 esters Chemical group 0.000 description 4
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 229920000620 organic polymer Polymers 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical compound OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- -1 aliphatic monocarboxylic acids Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 150000001879 copper Chemical class 0.000 description 3
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229910014033 C-OH Inorganic materials 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910014570 C—OH Inorganic materials 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- JLEJCNOTNLZCHQ-UHFFFAOYSA-N methyl 2-chloropropanoate Chemical compound COC(=O)C(C)Cl JLEJCNOTNLZCHQ-UHFFFAOYSA-N 0.000 description 2
- 239000012022 methylating agents Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZRZHXNCATOYMJH-UHFFFAOYSA-N 1-(chloromethyl)-4-ethenylbenzene Chemical compound ClCC1=CC=C(C=C)C=C1 ZRZHXNCATOYMJH-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000012905 Brassica oleracea var viridis Nutrition 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960003609 cathine Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- BPSIOYPQMFLKFR-UHFFFAOYSA-N trimethoxy-[3-(oxiran-2-ylmethoxy)propyl]silane Chemical compound CO[Si](OC)(OC)CCCOCC1CO1 BPSIOYPQMFLKFR-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Indole Compounds (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
[産業上の利用分野コ
本発明は新規な分離剤に間し1、特にラセミ化合物を光
学分割するためのクロマトクラフィー用充填剤に間する
ものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel separating agent 1, particularly a packing material for chromatography for optically resolving racemic compounds.
[従来の技術]
従来、光学活性基を無機担体或は有機重合物に保持して
なる分離剤とし・では、天然のアミノ酸を原料光学活性
化合物として用いている例があり、たとえは、〜、A、
ダバンコフらによるジャーナル・オブ・クロマトグラフ
ィー82巻359頁(1973) 。[Prior Art] Conventionally, in the case of separation agents in which optically active groups are supported on inorganic carriers or organic polymers, there are examples in which natural amino acids are used as raw material optically active compounds. A,
Davankov et al., Journal of Chromatography, Vol. 82, p. 359 (1973).
C,キュピロンらによるジャーナル・オブ・クロマトグ
ラフィー・204巻185頁(1981) 、ν、A、
ダバンコフらによるクロマトグラフイア 13巻677
頁(1980) 、 G、ギュビッツらによるジャーナ
ル・オブ・ハイ・レゾリューシコン・クロマトグラフィ
ー・アンド・クロマトグラフィー・コミュニケーション
2巻145頁(1979) 、等が知られている。Journal of Chromatography Vol. 204, p. 185 (1981) by C. Cupilon et al., ν, A.
Chromatography by Davankov et al., Volume 13, 677
Page (1980), Journal of High Resolution Chromatography and Chromatography Communication, Vol. 2, p. 145 (1979) by G. Gubitz et al., and others are known.
またフェニルグリシンやターシャリ−ロイシンの如き人
工的に得られるアミノ酸や天然アミノ酸などから誘導さ
れる塩基化合物を用いた例として、W、バークルらのジ
ャーナル・オブ・クロマトグラフィー 192巻143
頁(1980) 、 V、A、ダバンコフらによるクロ
マトグラフイア 13巻339頁(1980)が知られ
ている。Furthermore, as an example of using basic compounds derived from artificially obtained amino acids and natural amino acids such as phenylglycine and tert-leucine, W. Burkle et al., Journal of Chromatography, Vol. 192, 143
Page (1980), Chromatography by V. A. Davankov et al., Vol. 13, p. 339 (1980) are known.
[発明が解決しようとしている問題点]本発明者らは、
これら公知の分離用充填剤の性能を更に向上せしめるた
め種々研究の結果、本発明に到達したものである。即ち
、光学活性基を保持してなる分離剤は分離、特にラセミ
化合物を光学分割するためのクロマトグラフィー用充填
剤として利用されてきたが、従来原料光学活性(重合物
として使われてきた天然アミノ酸もし・くは人工的に合
成されるアミノ酸もしくはそれらから誘導される塩基も
しくは酸性化合物、酒石酸、或は光学分割されたアリー
ルエチルアミン類については光学分割可能な対象物が限
定されており、これまで分離できなかった化合物へ適用
できる新規な光学活性物質を用いた分離用充填剤が望ま
れていた。[Problem to be solved by the invention] The present inventors
The present invention was achieved as a result of various studies to further improve the performance of these known separation fillers. In other words, separating agents containing optically active groups have been used as chromatographic fillers for separation, especially for optical resolution of racemic compounds, but conventionally, separating agents with optically active groups have been used as fillers for chromatography for optical resolution of racemic compounds. For artificially synthesized amino acids, bases or acidic compounds derived from them, tartaric acid, or optically resolved arylethylamines, the targets that can be optically resolved are limited, and so far, it has not been possible to separate them. There has been a desire for a separating packing material using a new optically active substance that can be applied to compounds for which conventional methods have not been used.
[問題点を解決するための手段]
本発明者らは、従来のかかる問題点について鋭意検討し
た結果、従来の分離用充填剤では分離できなかった化合
物へ適用できる新規な光学活性基を保持し□てなる分離
用充填剤を見い出し、本発明の完成に到ったものである
。即ち、本発明は、下記一般式(1−1)〜(1−4)
で示される光学活性基のいずれか一種が担体に保持され
てなる分離剤に関する。[Means for Solving the Problems] As a result of intensive study on these conventional problems, the present inventors have developed a new optically active group that can be applied to compounds that cannot be separated using conventional separation packing materials. We have discovered a separation filler consisting of □, and have completed the present invention. That is, the present invention provides the following general formulas (1-1) to (1-4)
The present invention relates to a separating agent in which any one of the optically active groups represented by is supported on a carrier.
HH
マ
Ph>(−(IHOPh・・・C−OHOI
II I 11R1)C−N−
Cll−(XZ R1・・・(ニーN−CH−C
XZi II ム IIHR2)
(R2
l H
マ
Ph>(−OHOPh・・・C−0HQI I
I I IIH1・+)−N−
C)l−CXZ R1>C−N−CH−CXZ
i II i II+(R2HR
2
(但し、Phはフェニル基を示し、R1は枝分れを有し
ても良い炭素数1乃至4のアルキル基を示し、R2は水
素原子もしくは炭素数1乃至10のアルキル基、もしく
は炭素数6乃至10のアリール基であることを示す。HH MaPh>(-(IHOPh...C-OHOI
II I 11R1) C-N-
Cll-(XZ R1...(nee N-CH-C
XZi II Mu IIHR2)
(R2 l H MaPh>(-OHOPh...C-0HQI I
I II IIH1・+)-N-
C) l-CXZ R1>C-N-CH-CXZ
i II i II+(R2HR
2 (However, Ph represents a phenyl group, R1 represents an optionally branched alkyl group having 1 to 4 carbon atoms, and R2 represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, or Indicates 6 to 10 aryl groups.
また、Xは一〇−基もしくは−5−基であることを示し
I、Zは水素原子、炭素数1乃至10のアルキル基もし
くは金属であることを示す。)
次に本発明の詳細な説明する。Further, X represents a 10-group or a -5-group, and I and Z represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or a metal. ) Next, the present invention will be explained in detail.
(光学活性基)
本発明において光学活性基とは下記一般式%式%
HH
マ
Ph5−C−OHQ Ph・・・C−01
101,11111
R’>(−N−CH−CXZ R”・・・(’
ニー N−C)!−(’:XZ: 11
ム 11
HR2)I RQ
HH
マ
Ph>(−OHOPh・・・C−OHOI I
I I IIR1・C,−N−
C)l−CXZ R1>c−N−CH−CXZ
:l’l il+
HR2HR2
(但し、phはフェニル基を示し、R1は枝分れを有し
ても良い炭素数1乃至4のアルキル基を示し、R2は水
素原子もしくは炭素数1乃至10のアルキル基、もしく
は炭素数6乃至10のアリール基であることを示す。(Optically active group) In the present invention, the optically active group is the following general formula % HH MaPh5-C-OHQ Ph...C-01
101,11111 R'>(-N-CH-CXZ R"...('
Knee N-C)! -(':XZ: 11
M 11 HR2) I RQ HH MaPh>(-OHOPh...C-OHOI I
I I IIR1・C, -N-
C) l-CXZ R1>c-N-CH-CXZ
: l'l il+ HR2HR2 (However, ph represents a phenyl group, R1 represents an alkyl group having 1 to 4 carbon atoms which may be branched, and R2 represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. group or an aryl group having 6 to 10 carbon atoms.
また、Xは一〇−基もしくは−S−基であることを示し
、Zは水素原子、炭素数1乃至10のアルキル基もしく
は金属であることを示す。)
この光学活性基のより具体的内容は次のようなものであ
る。Further, X represents a 10- group or an -S- group, and Z represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or a metal. ) More specific details of this optically active group are as follows.
即ち、一般式(1−1)〜(1−4)において、R2は
水素原子もしくは炭素数1乃至10のアルキル基、もし
くは炭素数6乃至10のアリール基である。また、Xは
一〇−基もしくは−5−基であることを示し、Zは水素
原子、炭素数1乃至10のアルキル基、もしくは金属で
あることを示している。より具体的には、R1はメチル
基、エチル基、イソプロピル基、5ec−ブチル基、t
ert−ブチル基が例示されろ。R2は水素原子、メチ
ル基、エチル基、フェニル基、トリル基、ナフチル基な
どが例示される。That is, in the general formulas (1-1) to (1-4), R2 is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 10 carbon atoms. Furthermore, X represents a 10-group or a -5-group, and Z represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or a metal. More specifically, R1 is a methyl group, ethyl group, isopropyl group, 5ec-butyl group, t
An example is the ert-butyl group. Examples of R2 include a hydrogen atom, a methyl group, an ethyl group, a phenyl group, a tolyl group, and a naphthyl group.
Zは、炭素数1乃至lOのアルキル基としてはメチル基
、エチル基などが例示され、金属塩としては銅、亜鉛、
ニッケル、鉄、コバルト、マグネシウム、カルシウム、
ナトリウム、カリウム等が例示される。Examples of the alkyl group having 1 to 10 carbon atoms for Z include methyl group and ethyl group, and examples of metal salts include copper, zinc,
Nickel, iron, cobalt, magnesium, calcium,
Examples include sodium and potassium.
(担体)
本発明に用いられる担体としては、有機物質、又は無機
物質がある。有機物質としては、ポリスチレン、ポリア
ミド、ポリアクリレ−!・などの高分子物質からなる充
填基材があり、無機物質としては、シリカゲル、アルミ
ナ、ガラスピーズなどの無機系充填基材があるがこれら
は混合物或は複合物でもよく、また他の元素化合物との
反応物でもよい。これら担体は粒子状のものが好ましく
、その粒径は0.1μm〜1000μm、好ましくは1
〜100μmである。又、これらの担体は、表面積の大
きい微多孔質のものが好まし・く、その細孔径は10人
〜1oooo入 である。但し、細孔径/粒子径の比は
、1710以下である。(Carrier) The carrier used in the present invention may be an organic substance or an inorganic substance. Organic materials include polystyrene, polyamide, and polyacrylate! There are filling base materials made of polymeric substances such as ・Inorganic materials include inorganic filling base materials such as silica gel, alumina, and glass beads, but these may be mixtures or composites, and other elemental compounds may also be used. It may also be a reaction product with. These carriers are preferably in the form of particles, with a particle size of 0.1 μm to 1000 μm, preferably 1 μm.
~100 μm. Further, these carriers are preferably microporous ones with a large surface area, and the pore diameter is from 10 to 100 mm. However, the ratio of pore size/particle size is 1710 or less.
(合成法)
本発明において、分離剤の合成は、具体的には担体と光
学活性化合物とをスペーサーを介して又は介さずに化学
的に又は物理的に深持してなるものである。その保持量
は、担体に対して0.1〜100重量%、好ましくは1
〜10重量%である。(Synthesis method) In the present invention, the separation agent is specifically synthesized by chemically or physically supporting a carrier and an optically active compound with or without a spacer. The amount retained is 0.1 to 100% by weight, preferably 1% by weight based on the carrier.
~10% by weight.
より具体的な合成法としては次のようである。A more specific synthesis method is as follows.
く光学活性基の合成方法〉
本発明において特徴部分をなす光学活性基は具体的には
、エリトロ−2−アミノ−1−フェニル−1−プロパツ
ール(ノルエフェドリン)の光学活性体、即ち(IS、
2R)体(2)またはく1R12S)体(3)、もしく
はトレオー2−アミノー1−フェニル−1−プロパツー
ル(ノルプソイドエフェドリン)の(IR,2R)体(
4)または(Is、2S)体(5)を出発物質として得
ることができる。Synthesis method of optically active group> Specifically, the optically active group that is a characteristic part of the present invention is an optically active form of erythro-2-amino-1-phenyl-1-propatol (norephedrine), that is, (IS ,
2R) form (2) or 1R12S) form (3), or (IR,2R) form (IR,2R) of threo-2-amino-1-phenyl-1-propatool (norpsoidephedrine).
4) or (Is, 2S) form (5) can be obtained as a starting material.
HH
マ
p h> C−θHPh・・・C−0RC)13酬t″
−、−Nl2 C’H3・・・CN)1
2ム
旧
HHH
マ
Ph)C−CIHPh・・・t” −(l )1(〕H
3・・・CNl2
C)13Thc−Nl2ム
It
H(4) ’
(5)(但し、phはフェニル基を示す。)
即ち、それぞれの光学活性体と例えばブロモ酢酸エチル
のごときカルボメチル化剤、クロロプロピオン酸メチル
などの置換カルボメチル化剤を用いてアルキル化を行っ
た後、エステル部分を水酸化ナトリウムまたは水硫化ナ
トリウム等で金属塩としたのち、酸とするかざらに別の
金属塩に変換することかできる。また、ラセミ体を用い
て反応を行ったのち光学分割してもよい。これら光学活
性体は光学純度の高いものが好ましいが、必ずしも純粋
である必要は無い。HH map h>C-θHPh...C-0RC)13returnt''
-, -Nl2 C'H3...CN)1
2m old
HHH MaPh)C-CIHPh...t”-(l)1(]H
3...CNl2
C) 13Thc-Nl2muIt
H(4)'
(5) (However, ph indicates a phenyl group.) That is, alkylation was performed using each optically active substance and a carbomethylating agent such as ethyl bromoacetate or a substituted carbomethylating agent such as methyl chloropropionate. After that, the ester moiety is converted into a metal salt with sodium hydroxide or sodium hydrosulfide, and then converted into an acid or converted into another metal salt. Alternatively, the racemate may be used for reaction and then optically resolved. These optically active substances preferably have high optical purity, but do not necessarily need to be pure.
また、次に述べる様に担体に化学的に保持する場合には
合成経路を様々にかえることが出来ろことから必ずしも
上記方法による必要はない。Furthermore, as will be described below, in the case of chemically retaining on a carrier, the synthesis route can be changed in various ways, so it is not necessarily necessary to use the above method.
(スペーサー)
本発明においてスペーサーとは、担体と光学活性基とを
結合させろ役目を持つもので、例えば、担体としてシリ
カゲル、アルミナ、カラスビーズなとの無機系充填基材
を用いた時は各種シランカップリング剤が用いられる。(Spacer) In the present invention, a spacer has the role of binding a carrier and an optically active group. For example, when an inorganic filling base material such as silica gel, alumina, or glass beads is used as a carrier, various silica A coupling agent is used.
その他次のようなものが使用できる。即ち、一般式(1
−1)〜(1−4)で示されろ光学活性基の光学活性を
損なうことなく反応しろる基を持つ三官能以上の物質或
は担体と比較的強い相互作用を持ちうる、上記条件を満
たす単官能の物質があげられる。例えば、一般式(1−
1)〜(1−4)の光学活性基が、カルボン酸および酸
無水物、酸ハライド、エステルなどのその誘導体とアミ
ドを形成した残基である場合、ハロゲン化物、エポキシ
ドなどと反応した残基である場合、アル宇ヒト、イミン
と反応し・たのち還元した残基である場合、及び長鎖の
脂肪族モノカルボン酸またはその誘導体、長鎖のモノハ
ロゲン化物、モノエポキシドなどと反応した残基である
場合が例示される。Other items that can be used include: That is, the general formula (1
-1) to (1-4), the above conditions can have a relatively strong interaction with a trifunctional or higher functional substance or carrier having a reactive group without impairing the optical activity of the optically active group. Examples include monofunctional substances that satisfy this requirement. For example, the general formula (1-
When the optically active groups of 1) to (1-4) are residues that have formed amides with carboxylic acids and their derivatives such as acid anhydrides, acid halides, and esters, residues that have reacted with halides, epoxides, etc. , residues reacted with alkyl acids, imines, and then reduced, and residues reacted with long-chain aliphatic monocarboxylic acids or their derivatives, long-chain monohalides, monoepoxides, etc. An example is a group.
く1ヒ学的に保持する方法〉
化学的に一般式(1−1)〜(1−4)の光学活性基を
結合させる方法としては、シランカップリング剤で処理
したシリカゲル、”wしくは官能基を有する有機重合物
と直接反応させる方法、例えば、担体にエポキシ基を有
している場合にはアミノ基による開環付加させることが
出来る。また、アミノ基とカルボン酸またはその誘導体
によるアミド化、アミノ基とハライドや上シル基なとの
置換によるアルキル化、もしくはイソシアン酸との尿素
結合によっても化学結合させることができる。しかし、
一般式(1−1)〜(1−4)の光学活性基を予め結合
させたシランカップリング剤を無機充填基材に反応させ
てもよい。また一般式(1)の光学活性基を予め結合さ
せた重合性化合物を単独重合或は池の重合性化合物と共
重合させて充填剤としてもよく、例えば°、p−クロロ
メチルスチレン、クリシジルメタクリレート、アクリル
酸およびその誘導体、メタアクリル酸およびその誘導体
に一般式(1−1)〜(1−4)の光学活性基を予め結
合させた化合物が例示される。1) Method of chemically retaining> As a method of chemically bonding the optically active groups of general formulas (1-1) to (1-4), silica gel treated with a silane coupling agent, A method of directly reacting with an organic polymer having a functional group, for example, when the carrier has an epoxy group, ring-opening addition with an amino group is possible.Also, an amide reaction with an amino group and a carboxylic acid or its derivative can be performed. Chemical bonding can also be achieved by alkylation by substituting an amino group with a halide or supersyl group, or by urea bonding with isocyanic acid.However,
A silane coupling agent to which optically active groups of general formulas (1-1) to (1-4) have been bonded in advance may be reacted with the inorganic filling base material. In addition, a polymerizable compound to which an optically active group of the general formula (1) has been bonded in advance may be used as a filler by homopolymerization or copolymerization with a polymerizable compound such as °, p-chloromethylstyrene, chrycidyl, etc. Examples include methacrylate, acrylic acid and its derivatives, and compounds in which optically active groups of general formulas (1-1) to (1-4) are bonded in advance to methacrylic acid and its derivatives.
また、該光学活性基を無機担体或は有機重合物に保持す
る場合には、まずエリトロ−2−アミノ−1−フェニル
−1−プロパツール(ノルエフェドリン)の光学活性体
、即ち(Is、2R)体または(IR,2S)体、もし
くはトリオ−2−アミノ−1−フェニル−1−プロパツ
ール(ノルプソイドエフェドリン)の(IR,2R)体
または(IS。In addition, when holding the optically active group on an inorganic carrier or an organic polymer, first the optically active form of erythro-2-amino-1-phenyl-1-propatol (norephedrine), that is, (Is, 2R ) form or (IR,2S) form, or (IR,2R) form or (IS) form of trio-2-amino-1-phenyl-1-propatur (norpseudoephedrine).
2S)体のアミノ基をスペーサーもしくは担体或は重合
性化合物に反応し、そののち例えはフロモ酢酸エチルの
ごときカルホニルメチル化剤、クロロプロピオン酸メチ
ルなどの置換カルボニルメチル化剤を用いてアルキル化
を行ない、以下同様に処理して金属塩としてもよい。The amino group of the 2S) body is reacted with a spacer or carrier or a polymerizable compound, and then alkylated using a carbonyl methylating agent such as ethyl furomoacetate or a substituted carbonyl methylating agent such as methyl chloropropionate. , and thereafter may be treated in the same manner to form a metal salt.
例えば、次式(6)に示すように、(IR,2S)−2
−アミノ−1−フェニル−1−プロパツール((IR,
2S)−ノルエフェドリン)をブロモ酢酸エチルを用い
てアルキル化を行った後、エステル部分を水酸化すトリ
ウムてナトリウム塩としたのち、スペーサーとして、3
−グリシドキシプロピルトリメトキシシランを反応させ
たシリカゲルのグリシジル基に反応させることによって
坦持し、その後銅塩などの金属塩に変換することができ
る。For example, as shown in the following equation (6), (IR,2S)-2
-Amino-1-phenyl-1-propatol ((IR,
After alkylating 2S)-norephedrine) using ethyl bromoacetate, the ester moiety was hydroxylated with thorium to form a sodium salt, and then 3 was added as a spacer.
- It can be supported by reacting glycidyl groups of silica gel with glycidoxypropyltrimethoxysilane, and then converted into metal salts such as copper salts.
phs−−ニーOHNa0H
l + BrCH2CQOC2H5−
−イーj [3−C−N )12
Ph>C−OH
■
CH3b−1: −N)l−CH2−COONaPh)
C−01(/ \
l + Ym(C)130)nSi(C)12
)a−0−CH2Cl(−C)12(H3>C−NH−
CH2COONa
uSO4
QI C)12Cθ2CLJ1/2! I
Ym(CH30)nSi−C)12cH2cH2−0−
CH2()ICH2−N −CH4CH3HO−1’r
4Ph
(但し、Phはフェニル基を示し、Yはシリカゲルを表
す、また、m、および11はその合計が3になる整数で
ある。)
また、次式(7)に示すように、(IR,2S)−2−
アミノ−1−フェニル−1−プロパツール((IR,2
S)−ノルエフェドリン)をスペーサーとして用いる3
−グリシドキシブロビルトリメトキシシランと反応させ
た後、ブロモ酢酸エチルを用いてアルキル化を行い、さ
らにエステル部分を水酸化ナトリウムでナトリウム塩と
しこれをシリカゲルに反応させることによって坦持し、
その後銅塩などの金属塩に変換することもできる。phs--NiOHNa0H l + BrCH2CQOC2H5-
-Ej [3-C-N)12 Ph>C-OH ■ CH3b-1: -N)l-CH2-COONaPh)
C-01(/ \ l + Ym(C)130)nSi(C)12
)a-0-CH2Cl(-C)12(H3>C-NH-
CH2COONa uSO4 QI C)12Cθ2CLJ1/2! I Ym(CH30)nSi-C)12cH2cH2-0-
CH2()ICH2-N -CH4CH3HO-1'r
4Ph (However, Ph represents a phenyl group, Y represents silica gel, and m and 11 are integers whose total sum is 3.) Furthermore, as shown in the following formula (7), (IR, 2S)-2-
Amino-1-phenyl-1-propatol ((IR,2
S)-norephedrine) as a spacer 3
- After reacting with glycidoxybrobyltrimethoxysilane, alkylation is performed using ethyl bromoacetate, and the ester moiety is further converted into a sodium salt with sodium hydroxide and supported by reacting it with silica gel,
It can then be converted into metal salts such as copper salts.
Ph>C−OH/\
1 + Ym(CHaO)nSi(C)1z)3−
0−CI(2cI(CH2Cl13ThC−NH2
OHH
(Ct(30)3S i −C)+2cH2cH2−0
−CH2C)1012−NH−(−g CH3)10−
C−Ph
BrCf12COOC2H5
0)I CH2CO2C2H5
(C)+30)351−C)12c82c)12−0−
CH3COCH3−N −(14CH3穣
HO−C−4Ph
NaO)l
O)I CH2Cf:12Na
(ChO)3Si−CH2CH2CH2−0−CH2C
)IC)Iz−N−Cf14CH3t+o−c4ph
シリカケール (二LISO4
0)I CH2C02Cutz2
I
Ym(CH30)nS i −CH2CH2CH2−0
−CH3COCH3−N −CH4C)+3蓋
HO−C4Ph
(但し、Plqはフェニル基を示し、Yはシリカゲルを
表す、また、m、およびnはその合計が3になる整数で
ある。)
く物理的に保持する方法〉
物理的な方法としてはたとえば、一般式(1−1)〜(
1−4)の光学活性基に長鎖のアルキル基の如き疎水性
の基を導入し、これを疎水性を付与したシリカゲルもし
くは活性炭もしくは疎水性基を有する有機重合物に吸着
せしめて、(呆持することができる。Ph>C-OH/\ 1 + Ym(CHaO)nSi(C)1z)3-
0-CI(2cI(CH2Cl13ThC-NH2OHH(Ct(30)3S i -C)+2cH2cH2-0
-CH2C)1012-NH-(-g CH3)10-
C-Ph BrCf12COOC2H5 0)I CH2CO2C2H5 (C)+30)351-C)12c82c)12-0-
CH3COCH3-N -(14CH3穣HO-C-4Ph NaO)l O)I CH2Cf:12Na (ChO)3Si-CH2CH2CH2-0-CH2C
) IC) Iz-N-Cf14CH3t+o-c4ph Silica kale (2LISO4 0)I CH2C02Cutz2 I Ym(CH30)nS i -CH2CH2CH2-0
-CH3COCH3-N -CH4C)+3LidHO-C4Ph (However, Plq represents a phenyl group, Y represents silica gel, and m and n are integers whose total is 3.) Physically Holding method〉 Examples of physical methods include general formulas (1-1) to (
A hydrophobic group such as a long-chain alkyl group is introduced into the optically active group of 1-4), and this is adsorbed onto silica gel or activated carbon that has been given hydrophobicity, or an organic polymer having a hydrophobic group. can hold.
(光学分割法)
上記分離剤を用いて本発明の光学活性体を得るための手
段としてはガスクロマトグラフィー法、液体クロマトグ
ラフィー法、薄層クロマトグラフィー法などのクロマト
グラフィー法がある。(Optical resolution method) As means for obtaining the optically active substance of the present invention using the above-mentioned separating agent, there are chromatography methods such as gas chromatography, liquid chromatography, and thin layer chromatography.
液体クロマトグラフィーあるいは薄層クロマトグラフィ
ーを行なう場合の展開溶媒としては、該分離剤を溶解ま
たはこれと反応する液体を除いて特に制約はない。該分
離剤を化学的方法て担体に結合したり、架橋により不溶
化した場合には反応性液体を除いては制約はない。いう
までもなく、展開溶媒によって化合物又は光学異性体の
分離特性は変化するので、各種の展開溶媒を検討するこ
とが望ましい。The developing solvent used in liquid chromatography or thin layer chromatography is not particularly limited, except for a liquid that dissolves or reacts with the separating agent. When the separation agent is bonded to a carrier by a chemical method or made insolubilized by crosslinking, there are no restrictions except for the reactive liquid. Needless to say, the separation characteristics of compounds or optical isomers change depending on the developing solvent, so it is desirable to consider various developing solvents.
[実施例コ
以下本発明の分離剤の実施例及び応用例を比較例と共に
示すが、本発明はこれらの実施例に限定されるものでは
ない。[Example 7] Examples and application examples of the separating agent of the present invention will be shown below together with comparative examples, but the present invention is not limited to these examples.
容量比(1(’)、分離係数(α)、分離度(Rs)は
、夫々以下の式により求められる。The capacity ratio (1('), separation coefficient (α), and degree of separation (Rs) are determined by the following formulas, respectively.
[(対掌体の保持時間)−(テーッドタイム)コ、より
強く吸着される対掌
体の容量比
分離係数(α):□
より弱く吸着される対掌
体の容量比
より強く吸着される対掌
体とより弱く吸着される
対掌体の両ピーク間の距
離
分離度(Rs)=2X □
両ピークのバンド幅の合
計
実施例1. (IR,2S)−2−エトキシカルボ
ニルメチルアミノ−1−フェニル−1−プロパツールの
合成。[(retention time of enantiomer) - (taed time), separation coefficient of the volume ratio of the more strongly adsorbed enantiomer (α): □ Distance separation (Rs) between both peaks of the enantiomer and the more weakly adsorbed enantiomer = 2X □ Sum of the bandwidths of both peaks Example 1. Synthesis of (IR,2S)-2-ethoxycarbonylmethylamino-1-phenyl-1-propatol.
(IR,2S)−2−アミノ−1−フェニル−1−プロ
パツール((IR,2S)−ノルエフェドリン) 1.
21gを10m1の塩化メチレンに溶解し、室温で撹拌
する。これにブロム酢酸エチル1.50gを塩化メチレ
ン10m1に溶解して加え3時間攪拌した後、トリエチ
ルアミン1.2mlを加えてさらに攪拌を続ける。(室
温、2時間半) TLCで反応終了を確かめた後、塩化
メチレンを留去し、ベンゼンに置換する。水洗によりト
リエチルアミン・臭化水素塩を除いた後、飽和食塩水で
洗い、有機層を芒硝て乾燥させる。(IR,2S)-2-amino-1-phenyl-1-propatol ((IR,2S)-norephedrine) 1.
21 g are dissolved in 10 ml of methylene chloride and stirred at room temperature. To this was added 1.50 g of ethyl bromoacetate dissolved in 10 ml of methylene chloride and stirred for 3 hours, then 1.2 ml of triethylamine was added and stirring was continued. (Room temperature, 2 and a half hours) After confirming the completion of the reaction by TLC, methylene chloride was distilled off and replaced with benzene. After removing triethylamine/hydrogen bromide by washing with water, wash with saturated saline, and dry the organic layer with sodium sulfate.
ベンゼンを留去した粗生成物は、1.55g(82″0
)であり、シリカゲルのTLC(塩化メチレン:メタノ
−11=9:1)て:江ぼ1スポツトを与えた。これを
ヘキサン−酢酸エチル1:1の溶媒を用いてシリカゲル
カラムにより精製すると(IR,2S) −2−エトキ
シカルボニルメチルアミノ−1−フェニル−1−プロパ
ツール1.48g(78$)が得られた。この化合物の
物性値は次の通りである。The crude product from which benzene was distilled off was 1.55 g (82″0
), and TLC on silica gel (methylene chloride:methanol-11=9:1) gave one spot. When this was purified by a silica gel column using a solvent of hexane-ethyl acetate 1:1, 1.48 g (78 $) of (IR, 2S) -2-ethoxycarbonylmethylamino-1-phenyl-1-propatol was obtained. Ta. The physical properties of this compound are as follows.
比旋光度;[αコ22−40 +2.4’ (C0,
414,EtOH)赤外吸収スペクトル(IR)値(K
Br):3470、1?47.1455.1241 、
1148.703cm−1プロトン核磁気共鳴スペクト
ル(II(−NMR)値(CDC13):δ0.78
(d、 3H,jニアH2)。Specific optical rotation; [αko22-40 +2.4' (C0,
414, EtOH) infrared absorption spectrum (IR) value (K
Br): 3470, 1?47.1455.1241,
1148.703 cm-1 Proton nuclear magnetic resonance spectrum (II (-NMR) value (CDC13): δ0.78
(d, 3H, j near H2).
1.22 (t、、 3)t、jニア)12)、 2.
74 (m、 3H)3.30 (S、 2H)、 4
.08 ((1,2H,j=71(z)。1.22 (t,, 3) t, j near) 12), 2.
74 (m, 3H) 3.30 (S, 2H), 4
.. 08 ((1, 2H, j=71(z).
4.57 (d、 IH,J=4)1z)、 7.23
(s、 5t()ppm実施例2. (IR,2S
)−2−カルボキシメチルアミノニーフェニル−I−プ
ロパツール・モノナトリウム塩の合成。4.57 (d, IH, J=4)1z), 7.23
(s, 5t()ppm Example 2. (IR, 2S
)-2-Carboxymethylaminonyphenyl-I-propatur monosodium salt synthesis.
実施例1て得られたエチルエステル1.45gをエタノ
ール15m;に溶解し、1規定の水酸化ナトリウム水溶
液3.2m!を加え、室温で加水分解した。1.45 g of the ethyl ester obtained in Example 1 was dissolved in 15 m of ethanol, and 3.2 m of a 1N aqueous sodium hydroxide solution was added. was added and hydrolyzed at room temperature.
溶媒を留去した後真空乾燥して固形物(1,17g)を
得た。この化合物の物性値は次の通りである。After the solvent was distilled off, the residue was dried under vacuum to obtain a solid (1.17 g). The physical properties of this compound are as follows.
赤外吸収スペクトル(IR)値(KBr):3400、
1600.1415.1000.760.700cm1
実施例3. 実施例2で得られた(lR,2s) −2
−力ルボキシメチルアミノーl−フェニル−1−プロパ
ツール・モノナトリウム塩とグリシドキシプロビルシラ
ン処理したシリカゲルとの反応。Infrared absorption spectrum (IR) value (KBr): 3400,
1600.1415.1000.760.700cm1
Example 3. (lR,2s) −2 obtained in Example 2
- Reaction of carboxymethylamino l-phenyl-1-propanol monosodium salt with glycidoxypropylsilaned silica gel.
モノナトリウム塩1.17gをメタノール(99,5’
E)20m1に溶解し、グリシドキシプロビルシラン処
理を行なったシリカゲル[Develosil 100
−5.5μm(野村化学)] 7.Ogを加えて、6日
間室温で放置する。シリカゲルを)濾過し、メタノール
で洗った後、′ftL酸銅水溶銅水溶液中銅塩とする。1.17 g of monosodium salt was dissolved in methanol (99,5'
E) Silica gel [Developosil 100] dissolved in 20ml and treated with glycidoxyprobylsilane
-5.5 μm (Nomura Chemical)] 7. Add Og and leave at room temperature for 6 days. After filtering the silica gel and washing with methanol, it is prepared as a copper salt in an aqueous copper solution.
得られた物質の構造式はぎのようなものと推定される。It is presumed that the structural formula of the obtained substance is something similar.
OR’ OHC)12cO2cut/2
シリカケ−110−5i−C)12c82c)12−0
−C)12C)I(H2−N CH4CH31,1
R’ No−C4Ph(但し、式中R
’ 、R”はその両方−または、阿れか一方がメチル基
であるか、もしくはその両方よたはいずれか一方が同一
のシリカゲルであること示す。また、P bはフェニル
基を示す。)応用例1
実施例3で得られた充填剤を用い、種々のラセミ1ヒ合
物の光学分割を行った。即ち、上記充填剤を高速液体ク
ロマトグラフィー用ステンレスカラム(25cm x
0.46cmφ)に充填し、0.25mMのERiM鋼
水溶)夜を溶媒として流速毎分0.5m1(35°C〉
で種々のラセミ化合物の光学分割を行い、表−1の如ぎ
良好な結果を得た。OR' OHC) 12cO2cut/2
Silica case-110-5i-C) 12c82c) 12-0
-C)12C)I(H2-N CH4CH31,1
R' No-C4Ph (however, in the formula R
', R'' indicates that either one or both of them is a methyl group, or that both or one of them are the same silica gel. Also, Pb indicates a phenyl group.) Application Example 1 Optical resolution of various racemic compounds was carried out using the packing material obtained in Example 3. That is, the above packing material was used in a stainless steel column for high performance liquid chromatography (25 cm x
0.46 cmφ) and 0.25 mM ERiM steel water solution) at a flow rate of 0.5 ml/min (35°C)
Optical resolution of various racemic compounds was carried out, and good results were obtained as shown in Table 1.
表−1
ラセミ化合物 容量比 分離係数 分離度に’Lk
’o α Rs
Oし一バリン 7.50 8,28 1.10
1.10DL−イソロイシン8,94 9.90
1.11 1.15OL−tert−ロイシン6.
58 7.65 1.16 1.OQ[比−プロリ
ン 9,73 8.74 1.11 0.87
[)L−7/l、ギニン9.05 9.75 1.0
8 0.55HCI塩
DL−アスパラギン4.39 3.75 1.17
1.380し−アスパラギン5.22 6.05
1.16 1.06酸
りし−フェニル 10.2 11.6 1.14
1.15アラニン
OL−チロシン 8.28 10.1 1.22
1.51Dし一すジンHCI塩 ?、43 7.1
5 1.04 −−−−Dし−セリン 4.4
0 4.72 1.0? 0.56DL−スレオ
ニン 4,61 5.04 1.09 0.83表
−1つづき
ラセミ化合物 容量比 分離係数 分離度に’L
k’o α Rs
DL−トリプト 16.2 18.7 1,15
0.83フアン
0L−N−を二BZ−フ エ 9,92 9
,10 1.09 −−ニルアラニン
0L−N−CBZ−3,563,341,07−−アラ
ニン
0L−N−CBZ−4,744,361,09−−バリ
ン
DL−N−C8Z−3,503,1? 1.10
0.95アスパラキンTable-1 Racemic compound Volume ratio Separation factor 'Lk for resolution
'o α Rs O Shiichivaline 7.50 8,28 1.10
1.10DL-isoleucine 8,94 9.90
1.11 1.15OL-tert-leucine6.
58 7.65 1.16 1. OQ [ratio - Proline 9,73 8.74 1.11 0.87
[) L-7/l, Guinin 9.05 9.75 1.0
8 0.55HCI salt DL-asparagine 4.39 3.75 1.17
1.380 - Asparagine 5.22 6.05
1.16 1.06 Acid Phenyl 10.2 11.6 1.14
1.15 Alanine OL-Tyrosine 8.28 10.1 1.22
1.51D Shiichisujin HCI salt? , 43 7.1
5 1.04 ----D Serine 4.4
0 4.72 1.0? 0.56DL-Threonine 4,61 5.04 1.09 0.83Table-1Continued Racemic compound Volume ratio Separation factor Separation degree 'L
k'o α Rs DL-trypto 16.2 18.7 1,15
0.83 Fan 0L-N- to 2 BZ-F 9,92 9
,10 1.09--Nylalanine 0L-N-CBZ-3,563,341,07--Alanine 0L-N-CBZ-4,744,361,09--Valine DL-N-C8Z-3,503, 1? 1.10
0.95 Asparaquine
Claims (1)
基のいずれか一種が担体に保持されてなる分離剤。 ▲数式、化学式、表等があります▼(1−1)▲数式、
化学式、表等があります▼(1−2) ▲数式、化学式、表等があります▼(1−3)▲数式、
化学式、表等があります▼(1−4) (但し、Phはフェニル基を示し、R^1は枝分れを有
しても良い炭素数1乃至4のアルキル基を示し、R^2
は水素原子もしくは炭素数1乃至10のアルキル基、も
しくは炭素数6乃至10のアリール基であることを示す
。 また、Xは−O−基もしくは−S−基であることを示し
、Zは水素原子、炭素数1乃至10のアルキル基もしく
は金属であることを示す。)[Scope of Claims] A separating agent comprising any one of optically active groups represented by the following general formulas (1-1) to (1-4) supported on a carrier. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1-1)▲Mathematical formulas,
There are chemical formulas, tables, etc. ▼ (1-2) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1-3) ▲ Mathematical formulas,
There are chemical formulas, tables, etc.▼(1-4) (However, Ph represents a phenyl group, R^1 represents an alkyl group having 1 to 4 carbon atoms which may have branching, and R^2
represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 10 carbon atoms. Further, X represents an -O- group or a -S- group, and Z represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or a metal. )
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62094460A JPH0796504B2 (en) | 1987-04-17 | 1987-04-17 | Separation agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62094460A JPH0796504B2 (en) | 1987-04-17 | 1987-04-17 | Separation agent |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS63264536A true JPS63264536A (en) | 1988-11-01 |
JPH0796504B2 JPH0796504B2 (en) | 1995-10-18 |
Family
ID=14110883
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP62094460A Expired - Lifetime JPH0796504B2 (en) | 1987-04-17 | 1987-04-17 | Separation agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH0796504B2 (en) |
-
1987
- 1987-04-17 JP JP62094460A patent/JPH0796504B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JPH0796504B2 (en) | 1995-10-18 |
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