JPS62246530A - Production of optically active 1-butyne-3-ol - Google Patents
Production of optically active 1-butyne-3-olInfo
- Publication number
- JPS62246530A JPS62246530A JP7253486A JP7253486A JPS62246530A JP S62246530 A JPS62246530 A JP S62246530A JP 7253486 A JP7253486 A JP 7253486A JP 7253486 A JP7253486 A JP 7253486A JP S62246530 A JPS62246530 A JP S62246530A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- brucine
- butyn
- solvent
- butyne
- 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
- GKPOMITUDGXOSB-UHFFFAOYSA-N but-3-yn-2-ol Chemical compound CC(O)C#C GKPOMITUDGXOSB-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims abstract description 21
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims abstract description 20
- 230000003287 optical effect Effects 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 abstract description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000004973 liquid crystal related substance Substances 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000796 flavoring agent Substances 0.000 abstract 1
- 235000019634 flavors Nutrition 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、光学活性ｌ−ブチン−３−オールの製法に間
する。光学活性１−ブチン−３−オールは医薬、農薬、
香料、液晶などの原料中間体として重要な化合物である
。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for producing optically active l-butyn-3-ol. Optically active 1-butyn-3-ol is used in pharmaceuticals, agricultural chemicals,
It is an important compound as a raw material intermediate for perfumes, liquid crystals, etc.
（従来技術と問題点）
従来、光学活性体の製造方法としてはラセミ体の光学分
割法或は不斉合成法が知られているが本発明の目的物は
上記のいずれの方法によっても光学活性体の工業的製造
は困難であった。本発明者らは鋭意研究をおこなった結
巣、光学活性なブルシンが本目的物のラセミ体を極めて
効率的に光学分割することを見いだし本発明の完成に至
った。(Prior Art and Problems) Conventionally, racemic optical resolution methods and asymmetric synthesis methods have been known as methods for producing optically active substances. Industrial production of the body was difficult. The present inventors conducted extensive research and found that the optically active brucine can optically resolve the racemic form of the target product extremely efficiently, leading to the completion of the present invention.
（問題点を解決するための手段）
すなわち本発明は、１−ブチン−３−オールのラセミ体
と光学活性なブルシンを有機溶媒中で接触させ、得られ
る１−ブチン−３−オールの一方の対掌体を包接したブ
ルシンの錯体を溶媒から分離した後、その包接錯体を分
解することを特徴とする、光学活性ｌ−ブチン−３−オ
ールの優れた製法を提供するものである。(Means for Solving the Problems) That is, the present invention brings the racemic form of 1-butyn-3-ol and optically active brucine into contact with each other in an organic solvent, and produces one of the resulting 1-butyn-3-ols. The present invention provides an excellent method for producing optically active l-butyn-3-ol, which is characterized in that a complex of brucine containing an enantiomer is separated from a solvent and then the inclusion complex is decomposed.
本発明における原料の１−ブチン−３−オールはラセミ
体でよいが、光学純度の低いものの光学純度を上げる目
的にも利用できる。Although 1-butyn-3-ol, which is a raw material in the present invention, may be a racemate, it can also be used for the purpose of increasing the optical purity of a product with low optical purity.
本発明において、光学分割にもちいる光学活性ブルシン
としてはマチン科の植物の種子中に含まれるなと天然に
存在するｌ−ブルシンを用いれば良い。In the present invention, as the optically active brucine used for optical resolution, l-brucine which is naturally present in the seeds of plants belonging to the Machinaceae family may be used.
使用に供される溶媒としては、１−ブチン−３−オール
の低光学純度物もしくはラセミ体を溶解し、かつ形成し
た包接錯体の溶解度が小さいものがよい。このような溶
媒としては水、アルコール類、ベンゼン、トルエン、ク
ロロホルム、四塩化炭素、塩化メチレン、酢酸メチル、
酢酸エチル、石油エーテル、テトラヒドロフラン、エチ
ルエーテルなどが挙げられる。ま・た、これら溶媒を任
意に混合して用いてもよい。The solvent to be used is preferably one that dissolves the low optical purity or racemic form of 1-butyn-3-ol and has a low solubility for the formed inclusion complex. Such solvents include water, alcohols, benzene, toluene, chloroform, carbon tetrachloride, methylene chloride, methyl acetate,
Examples include ethyl acetate, petroleum ether, tetrahydrofuran, and ethyl ether. Alternatively, any mixture of these solvents may be used.
本発明において、１−ブチン−３−オールの低光学純度
物もしくはラセミ体は、光学活性ブルシンに対して、通
常０．１〜１０キル使用される“が包接錯体の晶析率や
分割された目的物の光学純度などを考慮して、その比を
決定できる。In the present invention, the low optical purity or racemic form of 1-butyn-3-ol is usually used in a range of 0.1 to 10 kills for optically active brucine, which is determined by the crystallization rate of the inclusion complex and the resolution. The ratio can be determined by considering the optical purity of the target product.
本発明において、１−ブチン−３−オールの低光学純度
物もしくはラセミ体と光学活性ブルシンの接触は通常−
２０℃〜１００℃の温度で０．５〜１００時間行なうの
がよく、好ましくは一１０℃〜５０℃の温度で０．５〜
５０時間行なうのがよい。この接触によって、１−ブチ
ン−３−オールの低光学純度物もしくはラセミ体のうち
の一方の対掌体が光学活性ブルシンに包接され、その錯
体が晶析する。In the present invention, the contact between the low optical purity product or racemate of 1-butyn-3-ol and the optically active brucine is usually -
It is best to carry out the reaction at a temperature of 20°C to 100°C for 0.5 to 100 hours, preferably at a temperature of -10°C to 50°C for 0.5 to 100 hours.
It is best to do this for 50 hours. Through this contact, one of the enantiomers of the low optical purity product or racemate of 1-butyn-3-ol is included in the optically active brucine, and the complex is crystallized.
晶析した１−ブチン−３−オールの低光学純度物もしく
はラセミ体のうちの一方の対掌体と光学活性ブルシンの
包接錯体は、濾葉した後、カラムクロマトグラフにより
分離したり、また、減圧下もしくは常圧で加温すること
により、目的とする光学活性なｌ−ブチン−３−オール
を光学活性ブルシンから分離することができる。その際
のカラムクロマトグラフの展開溶媒や蒸留による分離の
際の温度や減圧度は、適宜選択することが出来る。The inclusion complex of one of the crystallized enantiomers of the low optical purity or racemic form of 1-butyn-3-ol and optically active brucine is filtered and then separated by column chromatography, or By heating under reduced pressure or normal pressure, the desired optically active l-butyn-3-ol can be separated from optically active brucine. At that time, the developing solvent for column chromatography and the temperature and degree of vacuum during separation by distillation can be selected as appropriate.
回収された光学活性ブルシンは、上記の操作処理を行な
ってもその光学純度を損なうことなく再び分割剤として
使用できる。なお、１−ブチン−３−オールのもう一方
の対掌体は、晶析した１−ブチン−３−オールの一方の
対掌体と光学活性ブルシンの包接錯体をｆ別した後の母
液から得られる。The recovered optically active brucine can be used again as a resolving agent without losing its optical purity even after the above-mentioned operations. The other enantiomer of 1-butyn-3-ol was obtained from the mother liquor after separation of the crystallized one enantiomer of 1-butyn-3-ol and the inclusion complex of optically active brucine. can get.
また、得られた光学活性ｌ−ブチン−３−オールを用い
てブルシンを光学分割することもできる。Moreover, brucine can also be optically resolved using the obtained optically active l-butyn-3-ol.
（作用効果）
従来、光学活性１−ブチン−３−オールを容易に得る方
法はなく、誘導体化によりジアステレオマーとしたもの
を液体クロマトグラフィーにより分離するか、誘導体を
液体クロマトグラフィーもしくは酵素などにより光学分
割する方法が考えられるのみであった。本発明は天然か
ら容易に得られる光学活性ブルシンを用いて光学活性１
−ブチン−３−オールを容易に得る方法を提供するもの
であり、これらの問題点を解決するものである。(Effects) Conventionally, there is no easy way to obtain optically active 1-butyn-3-ol; either diastereomers obtained by derivatization are separated by liquid chromatography, or derivatives are separated by liquid chromatography or enzymes. The only method that could be considered was optical separation. The present invention uses optically active brucine, which is easily obtained from nature, to achieve optical activity 1.
The present invention provides a method for easily obtaining -butyn-3-ol and solves these problems.
さらに光学活性１−ブチン−３−オールは容易にその光
傘純度を保ったまま水素添加反応等により、種々の光学
活性アルコールに変換出来る。Further, optically active 1-butyn-3-ol can be easily converted into various optically active alcohols by hydrogenation reaction or the like while maintaining its halo purity.
（実施例）
次に、実施例を挙げて本発明を更に具体的に説明するが
、本発明の範囲をこれら実施例に限定するものでないこ
とはいうまでもない。(Examples) Next, the present invention will be described in more detail with reference to Examples, but it goes without saying that the scope of the present invention is not limited to these Examples.
実施例１
１−ブルシン ４．０ｇ （１０，２ｍｍｏ ｌ）をラ
セミ ｌ−ブチン−３−オール ２．５８ｇの５５％水
溶液に加熱溶解し、室温で１２時間放置して析出した結
晶をメタノール５ｍｌから２回再結晶すると１−ブルシ
ンと（＋）−１−ブチン−３−オールの１：１包接化合
物２．４６ｇが無色針状結晶として得られた。この包接
化合物の比旋光度は［α］ｏ−５９，４° （メタノー
ル）であった。この結晶を１５０℃に加熱すると、（＋
）−１−ブチン−３−オール ０．３５ｇが得られた。Example 1 4.0 g (10.2 mmol) of 1-brucine was heated and dissolved in a 55% aqueous solution of 2.58 g of racemic l-butyn-3-ol, and the crystals precipitated after being left at room temperature for 12 hours were dissolved from 5 ml of methanol. After recrystallization twice, 2.46 g of a 1:1 clathrate of 1-brucine and (+)-1-butyn-3-ol was obtained as colorless needle-like crystals. The specific rotation of this clathrate compound was [α]o-59.4° (methanol). When this crystal is heated to 150℃, (+
)-1-butyn-3-ol 0.35 g was obtained.
得られた（＋）−１−ブチン−３−オールの比旋光度は
［α］ｏ＋３１．０” （ｃ＝０．５６゜メタノール
）であった。The specific optical rotation of the obtained (+)-1-butyn-3-ol was [α]o+31.0'' (c=0.56° methanol).
Claims (1)
−３−オールと光学活性なブルシンを溶媒中で接触させ
、得られる前記化合物の一方の対掌体を包接したブルシ
ンの錯体を溶媒から分離した後、その包接錯体を分解す
ることを特徴とする、光学活性１−ブチン−３−オール
の製法。1-Butyn-3-ol, which has low optical purity or is racemic, is brought into contact with optically active brucine in a solvent, and the resulting complex of brucine that includes one enantiomer of the compound is separated from the solvent. A method for producing optically active 1-butyn-3-ol, which comprises decomposing the inclusion complex.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61072534A JPH07571B2 (en) | 1986-04-01 | 1986-04-01 | Process for producing optically active 1-butyne-3-ol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61072534A JPH07571B2 (en) | 1986-04-01 | 1986-04-01 | Process for producing optically active 1-butyne-3-ol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62246530A true JPS62246530A (en) | 1987-10-27 |
| JPH07571B2 JPH07571B2 (en) | 1995-01-11 |
Family
ID=13492108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61072534A Expired - Lifetime JPH07571B2 (en) | 1986-04-01 | 1986-04-01 | Process for producing optically active 1-butyne-3-ol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07571B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0685468A1 (en) | 1994-06-03 | 1995-12-06 | Mochida Pharmaceutical Co., Ltd. | Pyrazine and quinoxaline derivatives and their use as anti-ulcer agents |
| CN102408313A (en) * | 2011-10-20 | 2012-04-11 | 浙江普洛康裕制药有限公司 | Preparation method of R-3-butyne-2-alochol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58150526A (en) * | 1982-03-04 | 1983-09-07 | Ube Ind Ltd | Optically active propargyl alcohol and preparation thereof |
| JPS601145A (en) * | 1983-06-17 | 1985-01-07 | Ube Ind Ltd | Optically active propargyl alcohol derivative and its preparation |
-
1986
- 1986-04-01 JP JP61072534A patent/JPH07571B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58150526A (en) * | 1982-03-04 | 1983-09-07 | Ube Ind Ltd | Optically active propargyl alcohol and preparation thereof |
| JPS601145A (en) * | 1983-06-17 | 1985-01-07 | Ube Ind Ltd | Optically active propargyl alcohol derivative and its preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0685468A1 (en) | 1994-06-03 | 1995-12-06 | Mochida Pharmaceutical Co., Ltd. | Pyrazine and quinoxaline derivatives and their use as anti-ulcer agents |
| CN102408313A (en) * | 2011-10-20 | 2012-04-11 | 浙江普洛康裕制药有限公司 | Preparation method of R-3-butyne-2-alochol |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07571B2 (en) | 1995-01-11 |
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