JPS6345653B2 - - Google Patents
Info
- Publication number
- JPS6345653B2 JPS6345653B2 JP3124781A JP3124781A JPS6345653B2 JP S6345653 B2 JPS6345653 B2 JP S6345653B2 JP 3124781 A JP3124781 A JP 3124781A JP 3124781 A JP3124781 A JP 3124781A JP S6345653 B2 JPS6345653 B2 JP S6345653B2
- Authority
- JP
- Japan
- Prior art keywords
- ester
- arethrolone
- acid
- trans
- optically
- 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.)
- Expired
Links
- 150000002148 esters Chemical class 0.000 claims description 23
- PUANNVQABXUYKU-VXGBXAGGSA-N (1r,2r)-2-benzamidocyclohexane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCC[C@H]1NC(=O)C1=CC=CC=C1 PUANNVQABXUYKU-VXGBXAGGSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 230000003287 optical effect Effects 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ZCVAOQKBXKSDMS-AQYZNVCMSA-N (+)-trans-allethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OC1C(C)=C(CC=C)C(=O)C1 ZCVAOQKBXKSDMS-AQYZNVCMSA-N 0.000 description 1
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- FMTFEIJHMMQUJI-NJAFHUGGSA-N 102130-98-3 Natural products CC=CCC1=C(C)[C@H](CC1=O)OC(=O)[C@@H]1[C@@H](C=C(C)C)C1(C)C FMTFEIJHMMQUJI-NJAFHUGGSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-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
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- -1 allethrin Chemical compound 0.000 description 1
- 229940024113 allethrin Drugs 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- VEMKTZHHVJILDY-UXHICEINSA-N bioresmethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UXHICEINSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、光学活性なトランス−２−ベンズア
ミドシクロヘキサンカルボン酸を分割剤として使
用する、アレスロロンの光学分割方法に関し、そ
の目的は、光学活性なアレスロロンを、高純度且
つ高収率で得んとするものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for optically resolving allethrone using optically active trans-2-benzamide cyclohexanecarboxylic acid as a resolving agent. This is the desired yield.
アレスロロンは、低毒性殺虫剤として有用なア
レスリンなどのいわゆるピレスロイドと総称され
るエステル類のアルコール成分の１つであり、こ
れには（＋）−体及び（−）−体の２つの光学異性
体が存在する。 Allethrone is one of the alcohol components of esters, collectively called pyrethroids, such as allethrin, which is useful as a low-toxicity insecticide, and it has two optical isomers, the (+)- and (-)- exists.
これら２つの光学異性体のうち、（＋）−体は
（−）−体に比して、そのエステルとしての殺虫効
力がはるかに高いことが知られており、したがつ
て工業的に有利な光学分割方法の開発が望まれて
いる。 Of these two optical isomers, the (+)-isomer is known to have much higher insecticidal efficacy as an ester than the (-)-isomer, and is therefore industrially advantageous. Development of an optical resolution method is desired.
従来公知のアレスロロンの光学分割方法として
は、アレスロロンを、まずアレスロロン・アシツ
ド・サクシネート、アレスロロン・アシツド・フ
タレートなどの半エステルに導いた後、更にこれ
にエフエドリン、１−フエニル−２−（ｐ−トリ
ル）エチルアミン、又は１−フエニルエチルアミ
ンなどの光学活性塩基を作用させて分割する方法
がある〔ベルギー特許第793190号（1971）、特開
昭48−75545号公報、特開昭49−127952号公報、
特開昭49−124046号公報参照〕。 As a conventionally known optical resolution method for allethrone, allethrone is first converted into half esters such as allethrone acid succinate and allethrone acid phthalate, and then ephedrin, 1-phenyl-2-(p-tolyl) ) There is a method of resolution using an optically active base such as ethylamine or 1-phenylethylamine [Belgium Patent No. 793190 (1971), JP-A-48-75545, JP-A-49-127952 ,
See Japanese Patent Application Laid-Open No. 49-124046].
しかしながら、これらの方法は、中間体として
半エステルを経由しなければならないので、多く
の工程数及び複雑な操作が必要となり、また通算
収率も低いことから、工業的実施方法として有利
なものとはいえなかつた。 However, these methods require a large number of steps and complicated operations because they have to pass through a half-ester as an intermediate, and the total yield is low, so they are not advantageous as industrial implementation methods. I couldn't say yes.
本発明者等は、前記の各欠点をもたないアレス
ロロンの光学分割方法について鋭意検討した結
果、分割剤として、光学活性なトランス−２−ベ
ンズアミドシクロヘキサンカルボン酸を用いるこ
とにより、アレスロロンが極めて容易に、しかも
高純度、高収率で光学分割されることを見出し、
更に種々の検討を加え、本発明を完成するに至つ
た。 As a result of intensive study on a method for optically resolving arethrolone that does not have the above-mentioned drawbacks, the present inventors found that by using optically active trans-2-benzamidocyclohexanecarboxylic acid as a resolving agent, arethrolone can be separated extremely easily. , and found that it could be optically resolved with high purity and high yield.
After further various studies, the present invention was completed.
すなわち、本発明は、光学的に不純なアレスロ
ロンを、光学活性なトランス−２−ベンズアミド
シクロヘキサンカルボン酸又はその反応性誘導体
と反応させて、そのエステルに導き、該ジアステ
レオマーエステルを分別結晶した後、これを加水
分解することにより、光学活性なアレスロロンを
得ることを特徴とする、アレスロロンの光学分割
方法を提供するものである。 That is, the present invention involves reacting optically impure arethrolone with optically active trans-2-benzamidocyclohexanecarboxylic acid or a reactive derivative thereof to form an ester thereof, and fractionally crystallizing the diastereomeric ester. The present invention provides a method for optically resolving allethrone, which is characterized in that optically active allethrone is obtained by hydrolyzing the same.
本発明方法において、原料として用いるアレス
ロロンは、通常ラセミ体であるが、（＋）−体と
（−）−体との比は、特に制限されるものでない。 In the method of the present invention, arethrolone used as a raw material is usually racemic, but the ratio of the (+)- and (-)- isomers is not particularly limited.
また、光学的に不純な上記アレスロロンを、光
学活性なトランス−２−ベンズアミドシクロヘキ
サンカルボン酸とのエステルに導く場合、それ
は、該カルボン酸自体、又はその酸ハライド若し
くは酸無水物等の反応性誘導体と、該アレスロロ
ンとを、通常のエステル化反応条件下で反応させ
ることにより、容易に目的のエステルを得ること
ができる。しかしながら、最も一般的には、（＋）
−又は（−）−トランス−２−ベンズアミドシク
ロヘキサンカルボン酸を、塩化チオニル、五塩化
りん、三塩化りん、ホスゲンなどの酸塩素化剤と
反応させて、該光学活性カルボン酸の酸塩化物と
した後、この酸塩化物とアレスロロン原料とを、
ベンゼン、トルエン、キシレン、クロロホルム、
ヘキサン、エーテル、テトラヒドロフランなどの
不活性有機溶媒中に溶かし、この中にピリジン、
ピコリン、ルチジン、コリジンなどのピリジン系
塩基やトリエチルアミンなどを滴下することによ
り目的の結晶性のエステルが得られる。 Furthermore, when the above-mentioned optically impure arethrolone is converted into an ester with optically active trans-2-benzamidocyclohexanecarboxylic acid, it is possible to form an ester with the optically active trans-2-benzamidocyclohexanecarboxylic acid, or with a reactive derivative thereof such as an acid halide or acid anhydride. , and the arethrolone under normal esterification reaction conditions, the desired ester can be easily obtained. However, most commonly (+)
-or (-)-Trans-2-benzamidocyclohexanecarboxylic acid was reacted with an acid chlorinating agent such as thionyl chloride, phosphorus pentachloride, phosphorus trichloride, or phosgene to form an acid chloride of the optically active carboxylic acid. After that, this acid chloride and arethrolone raw material,
benzene, toluene, xylene, chloroform,
Pyridine, dissolved in an inert organic solvent such as hexane, ether, or tetrahydrofuran,
The desired crystalline ester can be obtained by dropping a pyridine base such as picoline, lutidine, or collidine, or triethylamine.
次に、このエステルを分別結晶法により、（＋）
−アレスロロンのエステルと（−）−アレスロロ
ンのエステルとに分離し、更にこのエステルを水
又は水を含む溶媒中で、塩基の存在下又は不在下
に加水分解を行うことにより、光学活性のアレス
ロロンを得ることができる。 Next, this ester was converted to (+) by a fractional crystallization method.
Optically active arethrolone is produced by separating the ester of -allethrone and the ester of (-)-allethrone, and further hydrolyzing this ester in water or a solvent containing water in the presence or absence of a base. Obtainable.
分別結晶の際の溶媒は、（＋）−アレスロロンの
エステルと（−）−アレスロロンのエステルの溶
解度に適当な差を有するものであれば何ら制限は
なく、例えばベンゼン、トルエンなどの芳香族炭
化水素、ｎ−ペンタン、ｎ−ヘキサンなどの脂肪
族炭化水素、メタノール、エタノール、プロパノ
ールなどの低級アルコール、及びこれらの混合溶
媒、更にこれらと水との混合溶媒を挙げることが
できる。 The solvent for fractional crystallization is not particularly limited as long as it has an appropriate difference in solubility between the (+)-arethrolone ester and the (-)-arethrolone ester, such as aromatic hydrocarbons such as benzene and toluene. , aliphatic hydrocarbons such as n-pentane and n-hexane, lower alcohols such as methanol, ethanol and propanol, mixed solvents thereof, and mixed solvents of these and water.
また加水分解は、例えば水酸化ナトリウム、水
酸化カリウムなどの塩基を用い、好ましくは５℃
以下、より好ましくは０℃で行うことにより、容
易に目的を達成することができる。 Hydrolysis is preferably carried out at 5°C using a base such as sodium hydroxide or potassium hydroxide.
Hereinafter, the objective can be easily achieved by carrying out the reaction more preferably at 0°C.
本発明方法において、光学分割剤として（−）
−トランス−２−ベンズアミドシクロヘキサンカ
ルボン酸を用いるときは、目的生成物として
（＋）−アレスロロンが得られ、また（＋）−トラ
ンス−２−ベンズアミドシクロヘキサンカルボン
酸を用いれば、（−）−アレスロロンが目的生成物
として得られる。 In the method of the present invention, as an optical resolving agent (-)
When -trans-2-benzamidocyclohexanecarboxylic acid is used, (+)-allethrone is obtained as the desired product, and when (+)-trans-2-benzamidocyclohexanecarboxylic acid is used, (-)-arethrolone is obtained. Obtained as the desired product.
なお、本発明方法で使用する光学活性なトラン
ス−２−ベンズアミドシクロヘキサンカルボン酸
は、例えば(1)欧文日本化学会誌（Bull.Chem.
Soc.Japan.）43、2230（1970）、(2)有機合成化学協
会誌28、866（1970）、(3)特開昭50−130739号など
に示される方法で得ることができる。 The optically active trans-2-benzamidocyclohexanecarboxylic acid used in the method of the present invention is described, for example, in (1) Bull.Chem.
Soc. Japan.) 43 , 2230 (1970), (2) Journal of the Society of Organic Synthetic Chemistry 28 , 866 (1970), (3) JP-A-50-130739, etc.
次に、実施例により更に詳細に本発明を説明す
るが、本発明はこれによつて限定されるものでは
ない。 Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.
実施例
（−）−トランス−２−ベンズアミドシクロヘ
キサンカルボン酸4.94ｇ（0.02モル）に塩化チオ
ニル８mlを加え、55〜60℃で30分間反応させたの
ち、塩化チオニルを留去する。更に乾燥エーテル
25mlを加え、30分間還流させエーテルを完全に除
くと、（−）−トランス−２−ベンズアミドシクロ
ヘキサンカルボン酸の酸塩化物が得られる。この
酸塩化物に対して等モルの（±）アレスロロン
（3.04ｇ）を加え、更に乾燥ベンゼン25mlを加え
る。そこに、ピリジンの15％乾燥ベンゼン溶液15
mlをかくはんしながらゆつくり滴下する。２時間
かくはんを続けたのち、約250mlの水中に全体を
あけ、よく振りベンゼン層を分け取る。水層はベ
ンゼン50mlで抽出し、先に分取したベンゼン部に
合わせる。このベンゼン溶液を、3N HCl、５％
Na2CO3水溶液、水の順で洗浄し、無水硫酸ナト
リウムを加え、１晩放置乾燥したのち、ベンゼン
を留去すると（−）−トランス−２−ベンズアミ
ドシクロヘキサンカルボン酸（±）アレスロロン
エステルが得られる（収量7.91ｇ）。Example 8 ml of thionyl chloride is added to 4.94 g (0.02 mol) of (-)-trans-2-benzamidocyclohexanecarboxylic acid, and the mixture is reacted at 55 to 60°C for 30 minutes, and then thionyl chloride is distilled off. more dry ether
Add 25 ml and reflux for 30 minutes to completely remove the ether, yielding the acid chloride of (-)-trans-2-benzamidocyclohexanecarboxylic acid. Add equimolar (±) arethrolone (3.04 g) to the acid chloride, and then add 25 ml of dry benzene. There, a 15% dry benzene solution of pyridine 15
Slowly drip ml while stirring. After stirring for 2 hours, pour the whole mixture into about 250ml of water and shake well to separate the benzene layer. Extract the aqueous layer with 50 ml of benzene and combine with the benzene portion collected earlier. This benzene solution was mixed with 3N HCl, 5%
After washing with Na 2 CO 3 aqueous solution and water in that order, adding anhydrous sodium sulfate and drying overnight, benzene was distilled off to produce (-)-trans-2-benzamidocyclohexanecarboxylic acid (±)arethrolone ester. (yield 7.91 g).
このエステルをトルエンを用い80％程度の再結
晶収率で３回再結晶すると、（−）−トランス−２
−ベンズアミドシクロヘキサンカルボン酸（＋）
−アレスロロンエステルが、エステルの理論収量
に対し52％の収率で得られる〔収量1.98ｇ、融点
158〜161℃、〔α〕25 D−41.6゜（Ｃ＝1.0メタノー
ル）〕。 When this ester is recrystallized three times using toluene with a recrystallization yield of about 80%, (-)-trans-2
-Benzamidocyclohexanecarboxylic acid (+)
- Arethrolone ester is obtained in a yield of 52% of the theoretical yield of ester [yield 1.98 g, melting point
158-161°C, [α] 25 D -41.6° (C = 1.0 methanol)].
こうして得た（−）−トランス−２−ベンズア
ミドシクロヘキサンカルボン酸（＋）−アレスロ
ロンエステル1.83ｇを、メタノール50mlに溶か
し、水酸化ナトリウム4.00ｇを水10mlとメタノー
ル15mlの混合溶媒に溶かしたものを加え、反応液
を０〜５℃に保ちながら約40時間反応させる。反
応終了後、反応液を室温に戻し、減圧下に大部分
のメタノールを留去した後、エーテル抽出を行
う。無水硫酸マグネシウムで乾燥後、エーテルを
減圧留去し、淡黄色の油状物を得る。この油状物
を減圧蒸留で精製して（＋）−アレスロロンを得
る。沸点90〜113℃／0.15mmHg、収量0.40ｇ、
〔α〕20 D＋6.39゜（Ｃ＝14.1、95％エタノール）、光
学
純度87.5％。 1.83 g of (-)-trans-2-benzamidocyclohexanecarboxylic acid (+)-arethrolone ester thus obtained was dissolved in 50 ml of methanol, and 4.00 g of sodium hydroxide was dissolved in a mixed solvent of 10 ml of water and 15 ml of methanol. Then, the reaction solution is kept at 0 to 5°C and reacted for about 40 hours. After the reaction is completed, the reaction solution is returned to room temperature, most of the methanol is distilled off under reduced pressure, and then extracted with ether. After drying over anhydrous magnesium sulfate, the ether was distilled off under reduced pressure to obtain a pale yellow oil. This oil is purified by vacuum distillation to obtain (+)-arethrolone. Boiling point 90-113℃/0.15mmHg, yield 0.40g,
[α] 20 D +6.39° (C = 14.1, 95% ethanol), optical purity 87.5%.
また、抽出残液はコンゴーレツド酸性にするこ
とにより、1.16ｇの（−）−トランス−２−ベン
ズアミドシクロヘキサンカルボン酸が回収され
た。回収率98％。 Furthermore, by making the extraction residue acidic, 1.16 g of (-)-trans-2-benzamidocyclohexanecarboxylic acid was recovered. Recovery rate 98%.
更に分別結晶の際の液から回収されたエステ
ルを集め、加水分解すると、（−）−アレスロロン
に富むアレスロロンが得られた。収量0.35ｇ、
〔α〕20 D−1.96゜（Ｃ＝9.2、95％エタノール）、光学
純度26.8％。 Further, the esters recovered from the liquid during fractional crystallization were collected and hydrolyzed to obtain allethrone rich in (-)-arethrolone. Yield 0.35g,
[α] 20 D −1.96° (C = 9.2, 95% ethanol), optical purity 26.8%.
Claims (1)
光学的に不純なアレスロロンを、光学活性なトラ
ンス−２−ベンズアミドシクロヘキサンカルボン
酸又はその反応性誘導体と反応させて、そのエス
テルに導き、該ジアステレオマーエステルを分別
結晶した後、これを加水分解することにより、光
学活性なアレスロロンを得ることを特徴とする、
アレスロロンの光学分割方法。1 In a method for optically resolving arethrolon,
Optically impure arethrolone is reacted with optically active trans-2-benzamidocyclohexanecarboxylic acid or a reactive derivative thereof to form an ester thereof, and the diastereomeric ester is fractionally crystallized and then hydrolyzed. By obtaining optically active arethrolone,
Optical splitting method for Arethroron.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3124781A JPS57145827A (en) | 1981-03-06 | 1981-03-06 | Optical resolution of allethrolone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3124781A JPS57145827A (en) | 1981-03-06 | 1981-03-06 | Optical resolution of allethrolone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57145827A JPS57145827A (en) | 1982-09-09 |
| JPS6345653B2 true JPS6345653B2 (en) | 1988-09-12 |
Family
ID=12326037
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3124781A Granted JPS57145827A (en) | 1981-03-06 | 1981-03-06 | Optical resolution of allethrolone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57145827A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0289965U (en) * | 1988-12-28 | 1990-07-17 |
-
1981
- 1981-03-06 JP JP3124781A patent/JPS57145827A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0289965U (en) * | 1988-12-28 | 1990-07-17 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57145827A (en) | 1982-09-09 |
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