JPH0730062B2 - Asymmetric hydrogenation method of ketopantolactone - Google Patents
Asymmetric hydrogenation method of ketopantolactoneInfo
- Publication number
- JPH0730062B2 JPH0730062B2 JP61000444A JP44486A JPH0730062B2 JP H0730062 B2 JPH0730062 B2 JP H0730062B2 JP 61000444 A JP61000444 A JP 61000444A JP 44486 A JP44486 A JP 44486A JP H0730062 B2 JPH0730062 B2 JP H0730062B2
- Authority
- JP
- Japan
- Prior art keywords
- platinum
- carbon catalyst
- quina
- ketopantolactone
- alkaloid
- 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
Links
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 title claims description 12
- HRTOQFBQOFIFEE-UHFFFAOYSA-N 2-dehydropantolactone Chemical compound CC1(C)COC(=O)C1=O HRTOQFBQOFIFEE-UHFFFAOYSA-N 0.000 title claims description 9
- 238000000034 method Methods 0.000 title claims description 8
- 239000003054 catalyst Substances 0.000 claims description 23
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 4
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SERHXTVXHNVDKA-BYPYZUCNSA-N (R)-pantolactone Chemical compound CC1(C)COC(=O)[C@@H]1O SERHXTVXHNVDKA-BYPYZUCNSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- SERHXTVXHNVDKA-UHFFFAOYSA-N pantolactone Chemical compound CC1(C)COC(=O)C1O SERHXTVXHNVDKA-UHFFFAOYSA-N 0.000 description 1
- 229940115458 pantolactone Drugs 0.000 description 1
- SIEVQTNTRMBCHO-UHFFFAOYSA-N pantolactone Natural products CC1(C)OC(=O)CC1O SIEVQTNTRMBCHO-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- -1 α-keto acid ester Chemical class 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
- Furan Compounds (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】 （イ）産業上の利用分野 本発明は、キナ−アルカロイドで修飾した白金−炭素触
媒を使用することを特徴とするケトパントラクトンの不
斉水素化法に関するものである。DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application The present invention relates to a method for asymmetric hydrogenation of ketopantolactone, which comprises using a platinum-carbon catalyst modified with a quina-alkaloid. .
（ロ）従来の技 本発明者等は、先に特開昭55−35060号公報においてキ
ナ−アルカロイドで修飾した白金−炭素触媒を使用する
α−ケト酸エステルの不斉水素化法を提案した。(B) Conventional technique The present inventors previously proposed a method for asymmetric hydrogenation of an α-keto acid ester using a platinum-carbon catalyst modified with a quina-alkaloid in JP-A-55-35060. .
（ハ）考案が解決しようとする問題点 これまでにケトパントラクトンを不斉水素化する方法に
ついては、種々の研究が行われている。(C) Problems to be solved by the invention Various studies have been conducted so far on methods for asymmetric hydrogenation of ketopantolactone.
しかし、触媒の調製及び生成物の分離操作が簡単且つ容
易な修飾固体触媒を使用してケトパントラクトンを比較
的高い不斉収率で不斉水素化する方法は知られていな
い。However, there is no known method for asymmetric hydrogenating ketopantolactone with a relatively high asymmetric yield using a modified solid catalyst which is easy and easy to perform catalyst preparation and product separation.
（ニ）問題点を解決するための手段 本発明者らは、ケトパントラクトンを容易に不斉水素化
して医薬品原料、食品添加物及び飼料添加物等として工
業上有用な光学活性を持つＤ−パントラクトンを比較的
高い収率で得る方法について鋭意検討の結果、本発明を
完成するに至った。(D) Means for Solving the Problems The present inventors can easily asymmetric hydrogenate ketopantolactone to industrially useful D- as a pharmaceutical raw material, food additive, feed additive, etc. As a result of extensive studies on a method for obtaining pantolactone in a relatively high yield, the present invention has been completed.
即ち、本発明はキナ−アルカロイドで修飾した白金−炭
素触媒を使用することを特徴とするケトパントラクトン
の不斉水素化法に関するものである。That is, the present invention relates to a method for asymmetric hydrogenation of ketopantolactone characterized by using a platinum-carbon catalyst modified with a quina-alkaloid.
本発明に使用されるキナ−アルカロイドとしては種々の
ものが使用出来るが、入手の容易性等から、キニン
（−）、キニジン（＋）、シンコニン（＋）及びシンコ
ニジン（−）の使用が有利である。Although various kinds of quina-alkaloids can be used in the present invention, quinine (-), quinidine (+), cinchonine (+) and cinchonidine (-) are advantageous because of easy availability. is there.
本発明のキナ−アルカロイドで修飾した白金−炭素触媒
の調製法は、例えば白金−炭素触媒をキナ−アルカロイ
ドのアルコール溶液及びテトラヒドロフラン溶液等に浸
漬して、キナ−アルカロイドを白金−炭素触媒に十分吸
着させ、キナ−アルカロイド溶液を除くことによりキナ
−アルカロイドで修飾された白金−炭素触媒を得ること
が出来る。The quina-alkaloid-modified platinum-carbon catalyst of the present invention can be prepared by, for example, immersing the platinum-carbon catalyst in an alcohol solution of a quina-alkaloid, a tetrahydrofuran solution or the like to sufficiently adsorb the quina-alkaloid to the platinum-carbon catalyst. Then, a platinum-carbon catalyst modified with a quina-alkaloid can be obtained by removing the quina-alkaloid solution.
又、この白金−炭素触媒の修飾は、白金−炭素触媒をキ
ナ−アルカロイド溶液中に数時間、室温で浸漬すること
によって達せられるが、湯浴上で加熱還流すると更に良
い結果が得られることもある。Further, this modification of the platinum-carbon catalyst can be achieved by immersing the platinum-carbon catalyst in the quina-alkaloid solution for several hours at room temperature, but even better results can be obtained by heating under reflux in a hot water bath. is there.
白金−炭素触媒に吸着させるキナ−アルカロイドの量
は、通常飽和吸着量よりも過剰に使用される。この場
合、使用されるキナ−アルカロイド溶液の濃度は0.5〜
３重量％が好ましく、キナ−アルカロイド溶液の使用液
量は５％白金−炭素触媒0.5gに対して30〜100mlが好ま
しい。The amount of the quina-alkaloid to be adsorbed on the platinum-carbon catalyst is usually used in excess of the saturated adsorption amount. In this case, the concentration of the quina-alkaloid solution used is 0.5-
The amount of the quina-alkaloid solution used is preferably 30 to 100 ml per 0.5 g of the 5% platinum-carbon catalyst.
本発明の白金−炭素触媒は、市販品を良く乾燥後キナ−
アルカロイドを十分吸着させて使用することにより容易
に不斉水素化を行うことが出来るが、白金−炭素触媒を
水素又は窒素気流中で予備加熱後キナ−アルカロイドを
吸着させると、更に良い結果が得られる。The platinum-carbon catalyst of the present invention is a commercially available product which is well-dried.
Asymmetric hydrogenation can be easily carried out by sufficiently adsorbing and using alkaloids, but if the platinum-carbon catalyst is preheated in a hydrogen or nitrogen stream and then the quina-alkaloids are adsorbed, even better results are obtained. To be
白金−炭素触媒の予備加熱温度は、250〜400℃が好まし
い。The preheating temperature of the platinum-carbon catalyst is preferably 250 to 400 ° C.
白金−炭素触媒を修飾するキナ−アルカロイドの溶媒と
しては、アルコール及びテトラヒドロフラン等がキナ−
アルカロイドの溶解性が比較的良好で好ましい。Solvents for quina-alkaloids that modify the platinum-carbon catalyst include alcohols and tetrahydrofuran.
Alkaloids are preferred because of their relatively good solubility.
不斉水素化反応は、上述の溶媒を除去したキナ−アルカ
ロイドで修飾された白金−炭素触媒を基質及び反応溶媒
と共にオートクレーブに仕込み、水素加圧下で行われ
る。The asymmetric hydrogenation reaction is carried out under hydrogen pressure by charging the quina-alkaloid-modified platinum-carbon catalyst from which the above solvent has been removed into an autoclave together with the substrate and the reaction solvent.
反応終了後、キナ−アルカロイドで修飾された白金−炭
素触媒を濾別し溶媒を蒸溜によって除き、次に減圧蒸溜
又は晶析等によって目的生成物であるＤ−パントラクト
ンを得ることが出来る。After completion of the reaction, the platinum-carbon catalyst modified with quina-alkaloid is filtered off, the solvent is removed by distillation, and then the desired product D-pantolactone can be obtained by distillation under reduced pressure or crystallization.
反応温度は、特に制限はないが10〜100℃の範囲が好ま
しく、室温でも容易に進行する。The reaction temperature is not particularly limited, but is preferably in the range of 10 to 100 ° C, and the reaction proceeds easily even at room temperature.
又、水素圧力は、常圧〜100kg/cm2の範囲が好ましい。Further, the hydrogen pressure is preferably in the range of normal pressure to 100 kg / cm 2 .
反応溶媒としては、ジエチルエーテル、テトラヒドロフ
ラン、ベンゼン、酢酸エチル及びアルコール等が使用さ
れる。As the reaction solvent, diethyl ether, tetrahydrofuran, benzene, ethyl acetate, alcohol and the like are used.
又、反応溶媒中に、白金−炭素触媒の修飾に使用したも
のと同一のキナ−アルカロイドを少量添加して不斉水素
化反応を行うと、不斉収率が向上する場合もある。In addition, if a small amount of the same quina-alkaloid used for modifying the platinum-carbon catalyst is added to the reaction solvent to carry out the asymmetric hydrogenation reaction, the asymmetric yield may be improved.
以下に実施例を挙げ本発明を詳細に説明するが、本発明
はこれらに限定されるものではない。Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.
実施例1. 乾燥した５％白金−炭素触媒0.5％を１％シンコニジン
エタノール溶液40ml中に加え、湯浴上で３時間加熱還流
させる。次に、遠心分離器を使用してシンコニジンエタ
ノール溶液を除去後、シンコニジン修飾５％白金−炭素
触媒とケトパントラクトン8g及びベンゼン50mlを内容積
100mlのオートクレーブに仕込み、水素初圧60kg/cm2、
室温で不斉水素化を行った。Example 1. Dried 5% platinum-carbon catalyst 0.5% is added to 40 ml of 1% cinchonidine ethanol solution, and heated under reflux for 3 hours on a water bath. Next, after removing the cinchonidine ethanol solution using a centrifuge, cinchonidine-modified 5% platinum-carbon catalyst, 8 g of ketopantolactone and 50 ml of benzene were added to the internal volume.
Charged in a 100 ml autoclave, hydrogen initial pressure 60 kg / cm 2 ,
Asymmetric hydrogenation was performed at room temperature.
反応は、１時間以内にほぼ理論量の水素を吸収して終了
した。The reaction was completed within an hour by absorbing a theoretical amount of hydrogen.
反応液からシンコニジン修飾５％白金−炭素触媒を濾別
し、蒸溜によって溶媒を留去した後、ゆっくりと３℃ま
で冷却し晶析した。手早く濾過し6.2gの結晶を得た。こ
の結晶の旋光度を測定すると▲〔α〕20 D▼−0.45（C2.
5水）であった。従って、下式で表されるＤ−パントラ
クトンの不斉収率は36％であった。The cinchonidine-modified 5% platinum-carbon catalyst was filtered off from the reaction solution, the solvent was distilled off, and the mixture was slowly cooled to 3 ° C for crystallization. Quick filtration gave 6.2 g of crystals. The optical rotation of this crystal was measured as ▲ [α] 20 D ▼ −0.45 (C2.
It was 5 water). Therefore, the asymmetric yield of D-pantolactone represented by the following formula was 36%.
実施例２〜８ ケトパントラクトンの量、水素化温度、キナアルカロイ
ドの種類及び反応溶媒を変化させた他は、実施例１と同
様にして不斉水素化を行った。不斉水素化条件及びその
結果を表１に示す。 Examples 2 to 8 Asymmetric hydrogenation was carried out in the same manner as in Example 1 except that the amount of ketopantolactone, the hydrogenation temperature, the type of quinalkaloid and the reaction solvent were changed. The asymmetric hydrogenation conditions and the results are shown in Table 1.
───────────────────────────────────────────────────── フロントページの続き 審査官 星野 紹英 ─────────────────────────────────────────────────── --Continued front page Examiner Shoei Hoshino
Claims (1)
触媒を使用することを特徴とするケトパントラクトンの
不斉水素化法。1. A method for asymmetric hydrogenation of ketopantolactone, which comprises using a platinum-carbon catalyst modified with a quina-alkaloid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61000444A JPH0730062B2 (en) | 1986-01-06 | 1986-01-06 | Asymmetric hydrogenation method of ketopantolactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61000444A JPH0730062B2 (en) | 1986-01-06 | 1986-01-06 | Asymmetric hydrogenation method of ketopantolactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62158268A JPS62158268A (en) | 1987-07-14 |
| JPH0730062B2 true JPH0730062B2 (en) | 1995-04-05 |
Family
ID=11473966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61000444A Expired - Lifetime JPH0730062B2 (en) | 1986-01-06 | 1986-01-06 | Asymmetric hydrogenation method of ketopantolactone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0730062B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6646135B1 (en) | 1999-06-23 | 2003-11-11 | Roche Vitamins Inc. | Continuous process for the enantioselective hydrogenation of alpha ketocarbonyl compounds |
| EP1291336A3 (en) * | 2001-09-05 | 2003-10-08 | Solvias AG | Preparation of optically active alpha-hydroxyethers |
| CN109705065B (en) * | 2018-12-29 | 2022-10-14 | 上海应用技术大学 | A kind of method for asymmetric catalytic synthesis of D-(-)-pantolactone |
-
1986
- 1986-01-06 JP JP61000444A patent/JPH0730062B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62158268A (en) | 1987-07-14 |
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