JPH0521109B2 - - Google Patents
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- Publication number
- JPH0521109B2 JPH0521109B2 JP1645885A JP1645885A JPH0521109B2 JP H0521109 B2 JPH0521109 B2 JP H0521109B2 JP 1645885 A JP1645885 A JP 1645885A JP 1645885 A JP1645885 A JP 1645885A JP H0521109 B2 JPH0521109 B2 JP H0521109B2
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- epoxy
- butanol
- phenylthio
- butanediol
- 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 - Lifetime
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- Epoxy Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、光学活性な天然物や医薬などの合成
において、有用な合成中間体である光学活性３，
４−エポキシ−１−ブタノールの製法に関するも
のである。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to optically active 3, which is a useful synthetic intermediate in the synthesis of optically active natural products and pharmaceuticals.
This invention relates to a method for producing 4-epoxy-1-butanol.
従来の技術
光学活性３，４−エポキシ−１−ブタノールの
公知の製法としては、D.L.Bogerらは、天然のＬ
−リンゴ酸から７段段にも亘る反応により(R)−
（＋）−３，４−エポキシ−１−ブタノール（〔α〕
23 D＋23.42°（C5.00、CH2Cl2）、73％ee）を得てい
る例があり（J.Org.Chem.、1981、46、1208）、
またK.B.Sharplessらはホモアリルアルコールの
不斉エポキシ化より(R)−（＋）−３，４−エポキシ
−１−ブタノール（64％ee）を得ている（Eur.
Pat.Appl.、EP46、033）。しかしこのように光学
純度が極めて低いものでしかない。Prior Art As a known method for producing optically active 3,4-epoxy-1-butanol, DL Boger et al.
-By a 7-step reaction starting from malic acid (R)-
(+)-3,4-epoxy-1-butanol ([α]
There is an example of obtaining 23D +23.42° ( C5.00 , CH 2 Cl 2 ), 73% ee) (J.Org.Chem., 1981 , 46, 1208).
Furthermore, KBSharpless et al. obtained (R)-(+)-3,4-epoxy-1-butanol (64% ee) by asymmetric epoxidation of homoallylic alcohol (Eur.
Pat.Appl., EP46, 033). However, the optical purity is extremely low.
また、反応の前後における光学活性の保存を問
わないラセミ体化合物についてならば一般的なエ
ポキシ化合物の合成法のひとつとして、β−ヒド
ロキシスルフイドをエポキシ化合物に変換する方
法がC.R.Johnsonらにより報告されている（J.
Am.Chem.Soc.、1973、95、3429）。 In addition, CR Johnson et al. reported a method for converting β-hydroxysulfide into an epoxy compound, which is one of the general synthesis methods for epoxy compounds for racemic compounds, regardless of the preservation of optical activity before and after the reaction. (J.
Am.Chem.Soc., 1973 , 95, 3429).
発明が解決しようとする問題点
そこで、光学活性なβ−ヒドロキシスルフイド
構造を持つジオール類に副反応を防止するために
保護基を用いずしかもラセミ化させることなく光
学活性なエポキシ化合物に変換することが可能で
あれば、光学活性３，４−エポキシ−１−ブタノ
ールと新製法として有用である。Problems to be Solved by the Invention Therefore, in order to prevent side reactions, diols having an optically active β-hydroxysulfide structure are converted into optically active epoxy compounds without using a protective group and without racemization. If possible, it would be useful as optically active 3,4-epoxy-1-butanol and a new manufacturing method.
問題点を解決するための手段
我々は、β−ヒドロキシスルフイド構造を持
つ、光学活性２−フエニルチオ−１，４−ブタン
ジオールに対して、特許請求の範囲に記載の方法
を適用したところ、意外にもラセミ化を起すこと
なく、光学活性３，４−エポキシ−１−ブタノー
ルが高い光学純度で得られることを見出した。Means for Solving the Problems We applied the claimed method to optically active 2-phenylthio-1,4-butanediol having a β-hydroxysulfide structure. It has surprisingly been found that optically active 3,4-epoxy-1-butanol can be obtained with high optical purity without causing racemization.
さらに詳しくは、光学活性２−フエニルチオ−
１，４−ブタンジオールを、塩化メチレン、クロ
ロホルム、アセトニトリル、エチルエーテルなど
の不活性溶媒中、−20℃〜＋80℃において、トリ
メチルオキソニウム テトラフルオロボレート、
トリエチルオキソニウム テトラフルオロボレー
ト、銀テトラフルオロボレートとヨウ化メチル、
などのＳ−アルキル化剤を１当量作用させ、対応
するスルホニウム塩とした後、水、エタノール、
塩化メチレン、クロロホルム、アセトニトリル、
エチルエーテルなどの溶媒中−78℃〜＋80℃にお
いて、トリメチルアミン、水酸化トリメチルベン
ジルアンモニウム、炭酸水素ナトリウム、炭酸カ
リウム、水酸化カリウム、tert−ブトキシカリウ
ムなどの塩基１当量で処理することにより、光学
活性３，４−エポキシ−１−ブタノールが得られ
る。 More specifically, optically active 2-phenylthio-
1,4-butanediol was dissolved in trimethyloxonium tetrafluoroborate, trimethyloxonium tetrafluoroborate, in an inert solvent such as methylene chloride, chloroform, acetonitrile, or ethyl ether at -20°C to +80°C.
Triethyloxonium tetrafluoroborate, silver tetrafluoroborate and methyl iodide,
After reacting with 1 equivalent of S-alkylating agent such as to form the corresponding sulfonium salt, water, ethanol,
methylene chloride, chloroform, acetonitrile,
Optical activity can be achieved by treatment with 1 equivalent of a base such as trimethylamine, trimethylbenzylammonium hydroxide, sodium bicarbonate, potassium carbonate, potassium hydroxide, or potassium tert-butoxy in a solvent such as ethyl ether at -78°C to +80°C. 3,4-epoxy-1-butanol is obtained.
なお、本発明に使用される、光学活性２−フエ
ニルチオ−１，４−ブタンジオールは、マレイン
酸エステルに、シンコニンなどの光学活性アミン
存在下、フエニルチオールを付加させ、光学活性
フエニルチオコハク酸エステルとし、これを水素
化リチウムアルミニウムのような適当な試薬で還
元することで容易に得られる。 The optically active 2-phenylthio-1,4-butanediol used in the present invention is produced by adding phenylthiol to a maleic acid ester in the presence of an optically active amine such as cinchonine. It is easily obtained by reducing the acid ester with a suitable reagent such as lithium aluminum hydride.
作 用
本発明によつて、(S)−（−）−２−フエニルチオ
−１，４−ブタンジオールからは、ラセミ化する
ことなく、立体配置が反転した(R)−（＋）−３，４
−エポキシ−１−ブタノールが得られる。逆に、
(R)−（＋）−２−フエニルチオ−１，４−ブタンジ
オールからは(S)−（−）−３，４−エポキシ−１−
ブタノールが得られる。Effect According to the present invention, from (S)-(-)-2-phenylthio-1,4-butanediol, (R)-(+)-3, whose configuration has been inverted without racemization, can be obtained from (R)-(+)-3, 4
-Epoxy-1-butanol is obtained. vice versa,
From (R)-(+)-2-phenylthio-1,4-butanediol, (S)-(-)-3,4-epoxy-1-
Butanol is obtained.
実施例
(S)−（−）−２−フエニルチオ１，４−ブタンジ
オール（〔α〕23 D−33.7°（C3.50、メタノール）、84
％ee）４ｇを含む塩化メチレン20mlに、トリメチ
ルオキソニウム テトラフルオロボレート３ｇを
加え、窒素化に室温で１時間撹拌してスルホニウ
ム塩とした。Example (S)-(-)-2-phenylthio 1,4-butanediol ([α]) 23 D -33.7° (C3.50, methanol), 84
To 20 ml of methylene chloride containing 4 g of %ee), 3 g of trimethyloxonium tetrafluoroborate was added and stirred at room temperature for 1 hour to obtain a sulfonium salt.
メタノール10mlを加えた後、塩化メチレンを減
圧留去し、残査に２規定のメタノール性水酸化カ
リウム10mlを加え室温で0.5時間撹拌した。40℃
以下でメタノールを減圧留去し、残査をシリカゲ
ルカラムクロマトグラフイー（エーテル）で精製
した後、減圧蒸留（バス温120℃／10mmHg）して
(R)−（＋）−３，４−エポキシ−１−ブタノール
（〔α〕23 D＋26.8°（C5.00、CH2Cl2）、84％ee）を1.
06
ｇを得た。 After adding 10 ml of methanol, methylene chloride was distilled off under reduced pressure, and 10 ml of 2N methanolic potassium hydroxide was added to the residue, followed by stirring at room temperature for 0.5 hour. 40℃
Below, methanol was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (ether), and then distilled under reduced pressure (bath temperature 120℃/10mmHg).
(R)-(+)-3,4-epoxy-1-butanol ([α] 23 D +26.8° (C5.00, CH 2 Cl 2 ), 84% ee) 1.
06
I got g.
発明の効果
本発明により、光学活性２−フエニルチオ−
１，４−ブタンジオールから容易にしかもラセミ
化することなく立体配置が反転した光学活性３，
４−エポキシ−１−ブタノールが得られ、実施例
で示したように84％eeの光学純度と言う従来の方
法では達成されていない優れた効果を示してい
る。Effects of the Invention According to the present invention, optically active 2-phenylthio-
Optically active 3, whose configuration is easily reversed from 1,4-butanediol without racemization.
4-Epoxy-1-butanol was obtained, and as shown in the examples, it shows an excellent effect of optical purity of 84% ee, which has not been achieved by conventional methods.
Claims (1)
ジオールに、Ｓ−アルキル化剤を作用させた後、
塩基で処理することにより、不斉炭素の立体配置
が反転した光学活性３，４−エポキシ−１−ブタ
ノールを製造する方法。1 After allowing an S-alkylating agent to act on optically active 2-phenylthio-1,4-butanediol,
A method for producing optically active 3,4-epoxy-1-butanol in which the configuration of an asymmetric carbon is inverted by treatment with a base.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1645885A JPS61176580A (en) | 1985-02-01 | 1985-02-01 | Production of optically active 3,4-epoxy-1-butanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1645885A JPS61176580A (en) | 1985-02-01 | 1985-02-01 | Production of optically active 3,4-epoxy-1-butanol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61176580A JPS61176580A (en) | 1986-08-08 |
| JPH0521109B2 true JPH0521109B2 (en) | 1993-03-23 |
Family
ID=11916802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1645885A Granted JPS61176580A (en) | 1985-02-01 | 1985-02-01 | Production of optically active 3,4-epoxy-1-butanol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61176580A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101650497B1 (en) * | 2015-03-16 | 2016-08-23 | 전북대학교산학협력단 | Aligned nanofiber manufacturing apparatus |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030089948A (en) * | 2002-05-20 | 2003-11-28 | 삼성정밀화학 주식회사 | Process for preparation of (R)-3,4-epoxy-1-butanol |
-
1985
- 1985-02-01 JP JP1645885A patent/JPS61176580A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101650497B1 (en) * | 2015-03-16 | 2016-08-23 | 전북대학교산학협력단 | Aligned nanofiber manufacturing apparatus |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61176580A (en) | 1986-08-08 |
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