JPH01313445A - Method for catalytic asymmetric and amplifying synthesis of secondary alcohol having high level of optical purity - Google Patents
Method for catalytic asymmetric and amplifying synthesis of secondary alcohol having high level of optical purityInfo
- Publication number
- JPH01313445A JPH01313445A JP63143781A JP14378188A JPH01313445A JP H01313445 A JPH01313445 A JP H01313445A JP 63143781 A JP63143781 A JP 63143781A JP 14378188 A JP14378188 A JP 14378188A JP H01313445 A JPH01313445 A JP H01313445A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- aliphatic
- optical purity
- alicyclic
- catalytic
- 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
- 150000003333 secondary alcohols Chemical class 0.000 title claims abstract description 13
- 230000003197 catalytic effect Effects 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 title claims description 3
- 238000003786 synthesis reaction Methods 0.000 title claims description 3
- 230000003287 optical effect Effects 0.000 title abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- 125000001931 aliphatic group Chemical group 0.000 claims abstract 5
- 125000002723 alicyclic group Chemical group 0.000 claims abstract 4
- 125000003118 aryl group Chemical group 0.000 claims abstract 3
- 125000001424 substituent group Chemical group 0.000 claims abstract 2
- -1 aliphatic aldehyde Chemical class 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 3
- 238000001308 synthesis method Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 150000001414 amino alcohols Chemical class 0.000 claims 1
- 150000003934 aromatic aldehydes Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000470 constituent Substances 0.000 abstract description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 3
- 229940079593 drug Drugs 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 2
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (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〕
本発明は高度の光学純度を有する光学活性第２級アルコ
ールの触媒的不斉増巾合成による製造に関するものであ
る。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to the production of optically active secondary alcohols having a high degree of optical purity by catalytic asymmetric broadening synthesis.
触媒的不斉増巾合成法とは、触媒に用いた光学活性化合
物の光学純度の数倍の光学純度を有する反応生成物を与
える反応を呼び、本発明者により発見されたものである
。The catalytic asymmetric broadening synthesis method refers to a reaction that provides a reaction product having an optical purity several times higher than that of the optically active compound used as a catalyst, and was discovered by the present inventor.
高度の光学純度を有する第２級アルコールは従来は特殊
なケトン化合物の不斉還元反応によって合成出来ること
が数多く報告されている。There have been many reports that secondary alcohols with high optical purity can be synthesized by asymmetric reduction reactions of special ketone compounds.
それらの方法の殆どすべては、光学活性化合物と還元剤
と基質とを化学量論的に用いる方法であり企業的にも採
算のとれる方法ではなく、採用されていない。アルデヒ
ド化合物と光学活性配位子を有する典型有機金属の一７
８℃のような低温での反応によっても光学活性第２級ア
ルコールが合成されることが報告されているが、実用的
ではなかった。Almost all of these methods use an optically active compound, a reducing agent, and a substrate in a stoichiometric manner, and are not commercially profitable and have not been adopted. A typical organic metal containing an aldehyde compound and an optically active ligand (7)
Although it has been reported that an optically active secondary alcohol can be synthesized by a reaction at a low temperature such as 8°C, it has not been practical.
（発明が解決しようとする課題）
少量の光学活性な触媒を用いて大量の光学純度の高い光
学活性化合物を製造する不斉触媒反応は人類の夢であり
、過去有機化学者により精力的に研究が行われてきたが
、成功例は大変少ない。本発明は、アルデヒド化合物の
高度な触媒的不斉増巾アルキル化反応の最初の例である
。(Problem to be solved by the invention) Asymmetric catalytic reactions that produce large amounts of optically active compounds with high optical purity using small amounts of optically active catalysts are a dream of humankind, and organic chemists have actively researched them in the past. have been tried, but there are very few success stories. The present invention is the first example of a highly catalytic asymmetrically enriched alkylation reaction of aldehyde compounds.
多くの典型有機金属化合物が知られているが、殆どの物
はアルデヒド化合物と反応するが、ジアルキル亜鉛は非
極性溶媒の中で反応しないこと、およびアミンなどのル
イス塩基が触媒となり両者の反応が起ることを本発明者
は発見した。Many typical organometallic compounds are known, and most of them react with aldehyde compounds, but dialkylzincs do not react in nonpolar solvents, and Lewis bases such as amines act as catalysts to prevent the reaction between the two. The inventor has discovered that this happens.
このジアルキル亜鉛特有の反応を利用して広範な研究を
行った結果、光学活性β−アミノアルコールを触媒に用
いた場合に触媒的不斉反応により光学活性第２級アルコ
ールが合成できることを発見し、学術雑誌に発表した（
Ｔｅｔ ｒａｈｅｄ ｒｏｎＬｅｔｔｅｒｓ ２５．２
８２３ （１９８４）） 。しかしこの当時得られる光
学活性アルコールの光学純度はせいぜい４８％であり、
実用的な応用は乏しかった。As a result of extensive research utilizing this reaction unique to dialkylzinc, we discovered that optically active secondary alcohols can be synthesized through catalytic asymmetric reactions when optically active β-amino alcohols are used as catalysts. Published in an academic journal (
Tet rahedron Letters 25.2
823 (1984)). However, the optical purity of the optically active alcohol obtained at that time was at most 48%.
Practical applications were scarce.
本発明者のその後の研究により触媒のβ−アミノアルコ
ールのアミノ基をピペリジル基等の複素環を含むジアル
キル化することにより不斉収率が飛躍的に向上すること
、および炭素についたアルキル基を第３級ブチル基のよ
うにその高さを大きくすることにより、光学純度の高い
光学活性第２級アルコールが合成出来るという発明に導
いた。Subsequent research by the present inventors revealed that the asymmetric yield can be dramatically improved by dialkylating the amino group of the β-amino alcohol catalyst containing a heterocycle such as a piperidyl group, and that the asymmetric yield can be dramatically improved by dialkylating the amino group of the β-amino alcohol catalyst. This led to the invention that an optically active secondary alcohol with high optical purity can be synthesized by increasing the height of the tertiary butyl group.
本発明の特徴は２点ある。第１点は触媒的不斉増巾反応
により光学純度の高い第２級アルコールが高収率で製造
できることであり、第２点は反応はＯ℃〜３０°Ｃの比
較的高い温度でさえも光学純度の高い第２級アルコール
が得られることの２点でおる。The present invention has two features. The first point is that secondary alcohols with high optical purity can be produced in high yields by catalytic asymmetric broadening reactions, and the second point is that the reaction can be carried out even at relatively high temperatures of 0°C to 30°C. The two points are that a secondary alcohol with high optical purity can be obtained.
以下に実施例を示して、更に本発明を説明するが、本発
明はこれによって何等制限を受けるものではない。なお
実施例（２）以下は操作は実施例（１）と同様でおり、
使用する原料および製造物が異なるのみであるので一覧
表で示す。The present invention will be further explained below with reference to Examples, but the present invention is not limited in any way by these examples. Note that in Example (2) and subsequent operations, the operations are the same as in Example (1).
The only difference is the raw materials and products used, so they are shown in a list.
実施例１
窒素気流下、反応容器に光学純度９８％の光学活性（−
）１−ピペリジル−３，３−ジメチルブタノール−２（
１８ｍｍｏｌ ）のヘキサン溶液（１，５１）を入れ、
ジエチル亜鉛（０，９１ｍｏｌ）を加えて３０℃で１時
間反応させた。この溶液を０℃に冷却してベンズアルデ
ヒド（０，９ｍｏｌ ＞をゆっくり加えた。１８時間後
、反応液を希塩酸水溶液（１１）にゆっくり加えて掻き
混ぜた。ヘキサン層を分離して蒸留によってヘキサンを
留去すると光学純度９９％の１−フェニルプロパツール
（［α」２５−３９．９°エタノール中）が収率９５％
で得られた。Example 1 Optical activity (-
) 1-piperidyl-3,3-dimethylbutanol-2(
Add 18 mmol) of hexane solution (1,51),
Diethylzinc (0.91 mol) was added and reacted at 30°C for 1 hour. The solution was cooled to 0°C and benzaldehyde (0.9 mol >) was slowly added. After 18 hours, the reaction solution was slowly added to dilute aqueous hydrochloric acid solution (11) and stirred. The hexane layer was separated and the hexane was removed by distillation. When distilled off, 1-phenylpropanol ([α] 25-39.9° in ethanol) with optical purity of 99% is obtained in 95% yield.
Obtained with.
＊＊この化合物は下記の化学反応式によりラセミ体が合
成され、ジベンゾイル酒石酸（光学活性）との塩の再結
晶により光学分割された。**This compound was synthesized as a racemate according to the chemical reaction formula below, and optically resolved by recrystallization of the salt with dibenzoyltartaric acid (optically active).
［α］２２−７１．５° （エタノール）ｒ２
ｔ−Ｂ ｕ ＣＯＣＨ３＋ ｔ−Ｂ ＬＩ Ｃ０ＣＨ２
Ｂ ｒビナコロン ブロムビナコロン光学
分割
光学活性化合物
全収率は７５％であった。[α]22-71.5° (ethanol) r2 t-B u COCH3+ t-B LI C0CH2
B r Binacolone Brombinacolone optical resolution The total yield of optically active compound was 75%.
実施例２〜５
実施例１と同一の反応条件で不斉増巾反応を行い、その
結果を下記の表１にまとめた。Examples 2 to 5 Asymmetric broadening reactions were carried out under the same reaction conditions as in Example 1, and the results are summarized in Table 1 below.
実施例６〜１４
他のアルデヒドとジエチル亜鉛との不斉増巾反応の実施
例は下記の表２にまとめた。Examples 6-14 Examples of asymmetric broadening reactions between other aldehydes and diethylzinc are summarized in Table 2 below.
本発明は医薬品、農薬その他のファインケミカルの製造
に大変有効な反応であると同時に、本発明によって製造
される光学活性第２級アルコールは医薬品、農薬などの
重要な構成物質である。The present invention is a very effective reaction for producing pharmaceuticals, agricultural chemicals, and other fine chemicals, and at the same time, the optically active secondary alcohol produced by the present invention is an important constituent of pharmaceuticals, agricultural chemicals, and the like.
Claims (1)
アミノアルコール類の触媒の存在下に反応せしめること
を特徴とする光学活性第２級アルコールの触媒的不斉増
巾合成法。（２）下記一般式（ I ） Ｒ＾１ＣＨＯ（ I ） （但しＲ＾１ＣＨＯは脂肪族アルデヒド、脂環式アルデ
ヒドおよび芳香族アルデヒドを表わす）で示されるアル
デヒド類と下記一般式（II）Ｒ＾２＿２Ｚｎ（II） （但しＲ＾２は脂肪族および脂環式アルキル基を含む） で示されるジアルキル亜鉛とを少量の光学活性β−アミ
ノアルコール類と反応せしめ、加水分解することを特徴
とする下記一般式（III） ▲数式、化学式、表等があります▼（III） （但しＲ＾１、Ｒ＾２は前記に同じ） で示される光学活性第２級アルコールの触媒的不斉増巾
合成法。 （３）触媒として使用される光学活性β−アミノアルコ
ールが下記一般式（IV） ▲数式、化学式、表等があります▼（IV） （但しＲ＾３は嵩さを有する置換基を表わし、Ｒ＾４は
脂肪族、脂環式、芳香族基を含みＮと共に複素環を形成
してもよい） で示されることを特徴とする請求項１又は２記載の光学
活性第２級アルコールの触媒的不斉増巾合成法。[Scope of Claims] (1) Aldehydes and dialkylzinc are optically active β-
A method for catalytic asymmetric broadening synthesis of optically active secondary alcohols, characterized by carrying out the reaction in the presence of an amino alcohol catalyst. (2) Aldehydes represented by the following general formula (I) R^1CHO (I) (where R^1CHO represents an aliphatic aldehyde, an alicyclic aldehyde, and an aromatic aldehyde) and the following general formula (II) R^ 2_2Zn(II) (However, R^2 includes an aliphatic and alicyclic alkyl group) The following method is characterized by reacting dialkyl zinc represented by 2_2Zn(II) with a small amount of optically active β-amino alcohol and hydrolyzing it. General formula (III) ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) (However, R^1 and R^2 are the same as above) Catalytic asymmetric broadening synthesis method for optically active secondary alcohols . (3) The optically active β-amino alcohol used as a catalyst has the following general formula (IV) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) (However, R^3 represents a bulky substituent, and R The catalytic method of optically active secondary alcohol according to claim 1 or 2, wherein ^4 includes an aliphatic, alicyclic, or aromatic group and may form a heterocycle with N. Asymmetric broadening synthesis method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63143781A JPH01313445A (en) | 1988-06-13 | 1988-06-13 | Method for catalytic asymmetric and amplifying synthesis of secondary alcohol having high level of optical purity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63143781A JPH01313445A (en) | 1988-06-13 | 1988-06-13 | Method for catalytic asymmetric and amplifying synthesis of secondary alcohol having high level of optical purity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01313445A true JPH01313445A (en) | 1989-12-18 |
| JPH0525864B2 JPH0525864B2 (en) | 1993-04-14 |
Family
ID=15346859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63143781A Granted JPH01313445A (en) | 1988-06-13 | 1988-06-13 | Method for catalytic asymmetric and amplifying synthesis of secondary alcohol having high level of optical purity |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01313445A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007297285A (en) * | 2006-04-27 | 2007-11-15 | Kobe Univ | Method for preparing optically active hydroxy compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6468A (en) * | 1987-02-27 | 1989-01-05 | Ajinomoto Co Inc | Tertiary amino-alcohol compound and production of optically active secondary alcohol using said compound |
-
1988
- 1988-06-13 JP JP63143781A patent/JPH01313445A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6468A (en) * | 1987-02-27 | 1989-01-05 | Ajinomoto Co Inc | Tertiary amino-alcohol compound and production of optically active secondary alcohol using said compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007297285A (en) * | 2006-04-27 | 2007-11-15 | Kobe Univ | Method for preparing optically active hydroxy compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0525864B2 (en) | 1993-04-14 |
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