JPH0723338B2 - Method for producing 2- (6-methoxy-2-naphthyl) propionic acid - Google Patents
Method for producing 2- (6-methoxy-2-naphthyl) propionic acidInfo
- Publication number
- JPH0723338B2 JPH0723338B2 JP62318679A JP31867987A JPH0723338B2 JP H0723338 B2 JPH0723338 B2 JP H0723338B2 JP 62318679 A JP62318679 A JP 62318679A JP 31867987 A JP31867987 A JP 31867987A JP H0723338 B2 JPH0723338 B2 JP H0723338B2
- Authority
- JP
- Japan
- Prior art keywords
- naphthyl
- methoxy
- propionic acid
- acid
- hydroxy
- 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
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
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、消炎、鎮痛、解熱作用を有する有用な医薬品
である２−（６−メトキシ−２−ナフチル）プロピオン
酸の製造法に関する。TECHNICAL FIELD The present invention relates to a method for producing 2- (6-methoxy-2-naphthyl) propionic acid, which is a useful drug having anti-inflammatory, analgesic and antipyretic effects.
２−（６−メトキシ−２−ナフチル）プロピオン酸の製
造法としては、従来、特公昭48−702号公報、特公昭49
−31981号公報などの方法が知られている。As a method for producing 2- (6-methoxy-2-naphthyl) propionic acid, there are conventional methods such as JP-B-48-702 and JP-B-49.
Methods such as -31981 publication are known.
特公昭48−702号公報には、２−メトキシナフタレンよ
り、水素化ナトリウム、ヨウ化メチルを使用し、７段階
を得て２−（６−メトキシ−２−ナフチル）プロピオン
酸を、製造する方法が開示されている。Japanese Patent Publication No. 48-702 discloses a method for producing 2- (6-methoxy-2-naphthyl) propionic acid from 2-methoxynaphthalene using sodium hydride and methyl iodide to obtain 7 steps. Is disclosed.
また、特公昭49−31981号公報には、２−ナフトールよ
り、ジメチルオキソスルホニウムメチライドを、使用
し、７段階を得て２−（６−メトキシ−２−ナフチル）
プロピオン酸を、製造する方法が開示されている。Further, in Japanese Patent Publication No. Sho 49-31981, 2- (6-methoxy-2-naphthyl) is obtained by using dimethyloxosulfonium methylide from 2-naphthol to obtain 7 steps.
A method of making propionic acid is disclosed.
これらの方法は、製造工程が多く、複雑な操作を必要と
し、副原料として危険性の高いものや、高価なものを必
要とするため問題が多い。These methods have many problems because they have many manufacturing steps, require complicated operations, and require highly dangerous auxiliary materials and expensive materials.
また、２−ヒドロキシ−２−（６−メトキシ−２−ナフ
チル）プロピオン酸またはそのエステル誘導体より２−
（６−メトキシ−２−ナフチル）プロピオン酸を製造す
る方法としては、特開昭51−4136号公報、特開昭52−10
5144号公報及び特開昭56−16437号公報がある。これら
公報の方法では、ヨウ化水素酸のような高価なものを必
要とするという問題がある。特開昭51−4136号では、２
−ヒドロキシ−２−（６−メトキシ−２−ナフチル）プ
ロピオン酸より脱水反応により、２−（６−メトキシ−
２−ナフチル）アクリル酸を合成して、これを還元する
方法や、２−ヒドロキシ−２−（６−メトキシ−２−ナ
フチル）プロピオン酸より、２−ハロゲノ−２−（６−
メトキシ−２−ナフチル）プロピオン酸を合成して、こ
れを還元する方法が開示されているが、これらの方法で
は工程が長くなってしまうという問題がある。In addition, 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid or its ester derivative
The method for producing (6-methoxy-2-naphthyl) propionic acid is described in JP-A-51-4136 and JP-A-52-10.
There are JP-A-5144 and JP-A-56-16437. The methods disclosed in these publications have a problem that expensive materials such as hydroiodic acid are required. In JP-A-51-4136, 2
From 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid, 2- (6-methoxy-
A method for synthesizing 2-naphthyl) acrylic acid and reducing it, or 2-halogeno-2- (6--) from 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid.
Although methods of synthesizing methoxy-2-naphthyl) propionic acid and reducing the same have been disclosed, these methods have a problem that the process becomes long.
また、酸触媒を用いない通常の接触還元は非常に長い反
応時間を必要とし、金属を用いた還元では、多量の金属
を必要とする。その他の方法も工業的には不向きな方法
である。In addition, ordinary catalytic reduction without using an acid catalyst requires a very long reaction time, and reduction with a metal requires a large amount of metal. Other methods are also industrially unsuitable methods.
本発明者らは、このような事情に鑑み、鋭意研究を重ね
た結果、一段階の反応で容易に、２−ヒドロキシ−２−
（６−メトキシ−２−ナフチル）プロピオン酸より、２
−（６−メトキシ−２−ナフチル）プロピオン酸を得る
工業的な方法を見出し本発明を完成させるに到った。In view of such circumstances, the inventors of the present invention have conducted extensive studies, and as a result, 2-hydroxy-2-
From (6-methoxy-2-naphthyl) propionic acid, 2
The present invention has been completed by finding an industrial method for obtaining-(6-methoxy-2-naphthyl) propionic acid.
すなわち、本発明は、２−ヒドロキシ−２−（６−メト
キシ−２−ナフチル）プロピオン酸を低級脂肪酸中で、
無機酸の存在下、水素雰囲気下で金属触媒を用いて還元
することを特徴とする２−（６−メトキシ−２−ナフチ
ル）プロピオン酸の製造法を提供するものである。That is, the present invention provides 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid in a lower fatty acid,
The present invention provides a method for producing 2- (6-methoxy-2-naphthyl) propionic acid, which comprises reducing with a metal catalyst in the presence of an inorganic acid in a hydrogen atmosphere.
本発明における低級脂肪酸は、溶媒として用いられ、そ
れらの具体例としては、ギ酸、酢酸、プロピオン酸、ｎ
−酪酸、iso−酪酸、ｎ−吉草酸、iso−吉草酸,sec−吉
草酸などが挙げられる。これらの中でも、酢酸が好適に
用いられる。低級脂肪酸の使用量は通常、２−ヒドロキ
シ−２−（６−メトキシ−２−ナフチル）プロピオン酸
に対して0.5〜50倍重量、好ましくは２〜20倍重量であ
る。The lower fatty acid in the present invention is used as a solvent, and specific examples thereof include formic acid, acetic acid, propionic acid and n.
-Butyric acid, iso-butyric acid, n-valeric acid, iso-valeric acid, sec-valeric acid and the like. Among these, acetic acid is preferably used. The lower fatty acid is usually used in an amount of 0.5 to 50 times, preferably 2 to 20 times the weight of 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid.
溶液濃度としては、２−ヒドロキシ−２−（６−メトキ
シ−２−ナフチル）プロピオン酸の量が低級脂肪酸の量
に対して２〜65％（重量）、好ましくは10〜35％（重
量）である。As the solution concentration, the amount of 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid is 2 to 65% (weight), preferably 10 to 35% (weight) with respect to the amount of lower fatty acid. is there.
上記の濃度が、あまり低すぎると反応速度が遅くなり、
２−（６−メトキシ−２−ナフチル）プロピオン酸の収
率が低下する。また、あまり濃度が高すぎると均一溶液
にならず、２−（６−メトキシ−２−ナフチル）プロピ
オン酸の収率が低下する。If the above concentration is too low, the reaction speed will slow down,
The yield of 2- (6-methoxy-2-naphthyl) propionic acid decreases. On the other hand, if the concentration is too high, a uniform solution will not be obtained and the yield of 2- (6-methoxy-2-naphthyl) propionic acid will decrease.
本発明における無機酸の具体例としては、硫酸、塩酸、
リン酸、ホウ酸などが挙げられる。これらの中でも、硫
酸が好適に用いられる。Specific examples of the inorganic acid in the present invention include sulfuric acid, hydrochloric acid,
Examples thereof include phosphoric acid and boric acid. Of these, sulfuric acid is preferably used.
無機酸の使用量は、通常、２−ヒドロキシ−２−（６−
メトキシ−２−ナフチル）プロピオン酸に対して0.01〜
１倍（重量比）、好ましくは0.02〜0.3倍（重量比）で
ある。The amount of the inorganic acid used is usually 2-hydroxy-2- (6-
0.01 to methoxy-2-naphthyl) propionic acid
It is 1 time (weight ratio), preferably 0.02 to 0.3 time (weight ratio).
本発明における金属触媒としては、パラジウム系、ロジ
ウム系、ルテニウム系などの触媒を挙げることができ
る。中でも触媒の取扱の容易さなどの面から、パラジウ
ム金属−炭素（カーボン）水添触媒が好適である。金属
触媒の使用量は、通常、金属重量で２−ヒドロキシ−２
−（６−メトキシ−２−ナフチル）プロピオン酸に対し
て0.00001〜0.1倍（重量比）、好ましくは0.0001〜0.01
倍（重量比）である。Examples of the metal catalyst in the present invention include palladium-based, rhodium-based, and ruthenium-based catalysts. Among them, a palladium metal-carbon (carbon) hydrogenation catalyst is preferable from the viewpoint of easy handling of the catalyst. The amount of the metal catalyst used is usually 2-hydroxy-2 by weight of the metal.
-(6-methoxy-2-naphthyl) propionic acid 0.00001 to 0.1 times (weight ratio), preferably 0.0001 to 0.01
It is twice (weight ratio).
さらに、金属触媒に対する無機酸の使用量は、0.0001〜
1.0倍（重量比）、好ましくは0.0020〜0.2倍（重量比）
である。Further, the amount of the inorganic acid used relative to the metal catalyst is 0.0001-
1.0 times (weight ratio), preferably 0.0020 to 0.2 times (weight ratio)
Is.
反応圧力は、常圧か加圧が好ましい。加圧下では反応時
間が短縮できるし、常圧では、装置の操作が容易であ
る。The reaction pressure is preferably atmospheric pressure or increased pressure. The reaction time can be shortened under pressure, and the device can be easily operated under normal pressure.
反応温度は、通常、常温から150℃、好ましくは、70〜1
30℃である。The reaction temperature is usually from room temperature to 150 ° C, preferably 70 to 1
30 ° C.
あまり温度が高すぎると２−ヒドロキシ−２−（６−メ
トキシ−２−ナフチル）プロピオン酸が脱炭酸してしま
い、収率が低下する。また、あまり温度が低すぎると溶
媒への２−ヒドロキシ−２−（６−メトキシ−２−ナフ
チル）プロピオン酸の溶解度の低下、および反応速度の
低下により収率が低下する。If the temperature is too high, 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid will be decarboxylated and the yield will decrease. On the other hand, if the temperature is too low, the yield decreases due to a decrease in the solubility of 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid in the solvent and a decrease in the reaction rate.
反応時間は、２〜30時間、好ましくは３〜20時間であ
る。The reaction time is 2 to 30 hours, preferably 3 to 20 hours.
反応時間が短すぎると、反応が不十分で収率が低下し、
流すぎると時間当たりの変換の割合が低下して無駄であ
る。If the reaction time is too short, the reaction is insufficient and the yield decreases,
If it flows too much, the rate of conversion per time decreases and it is wasteful.
以下に実施例を示す。 Examples will be shown below.
実施例1. ２−ヒドロキシ−２−（６−メトキシ−２−ナフチル）
プロピオン酸2.00gと２％（重量）パラジウム−炭素0.0
7gを氷酢酸10ml中に入れておき、10％硫酸水溶液0.5ml
を加え、減圧後に窒素ガスで２回置換し、更に純水素ガ
スで２回置換して、常圧下に、水素雰囲気で反応させ
た。100℃で15.5時間反応させて、放冷後、減圧して窒
素ガスで２回置換して窒素雰囲気にした。減圧下で酢酸
を留去して塩化メチレンを加えて，触媒を濾別した。濾
液は２回水洗して、無水硫酸マグネシウムで乾燥した。Example 1. 2-Hydroxy-2- (6-methoxy-2-naphthyl)
Propionic acid 2.00g and 2% (weight) palladium-carbon 0.0
Put 7g in 10ml glacial acetic acid, 0.5ml 10% sulfuric acid aqueous solution
Was added, and after the pressure was reduced, the atmosphere was replaced with nitrogen gas twice, and further replaced with pure hydrogen gas twice, and the reaction was carried out in a hydrogen atmosphere under normal pressure. After reacting at 100 ° C. for 15.5 hours, the mixture was allowed to cool, depressurized and replaced with nitrogen gas twice to create a nitrogen atmosphere. Acetic acid was distilled off under reduced pressure, methylene chloride was added, and the catalyst was filtered off. The filtrate was washed twice with water and dried over anhydrous magnesium sulfate.
塩化メチレンを留去して得られた固体はトルエンで再結
晶させて1.80gの２−（６−メトキシ−２−ナフチル）
プロピオン酸を得た。２−ヒドロキシ−２−（６−メト
キシ−２−ナフチル）プロピオン酸に対する収率は96％
である。m.p.149.5〜151.5℃ NMRスペクトル、IRスペクトルにより構造を確認した。The solid obtained by distilling off methylene chloride was recrystallized from toluene to give 1.80 g of 2- (6-methoxy-2-naphthyl).
Propionic acid was obtained. The yield based on 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid is 96%.
Is. The structure was confirmed by NMR spectrum and IR spectrum.
NMR（CDCl3）1.57（3H,3.90（3H）,7.10（1H）,7.12（1
H）,7.40（1H）,7.6−7.7（3H） IR（cm-1）3500〜2500,1700 〔発明の効果〕 本発明によれば、一段階の反応で容易、且つ安価に、２
−ヒドロキシ−２−（６−メトキシ−２−ナフチル）プ
ロピオン酸より、２−（６−メトキシ−２−ナフチル）
プロピオン酸を製造することができる。NMR (CDCl 3 ) 1.57 (3H, 3.90 (3H), 7.10 (1H), 7.12 (1
H), 7.40 (1H), 7.6-7.7 (3H) IR (cm -1 ) 3500 to 2500, 1700 [Effect of the invention] According to the present invention, it is possible to easily and inexpensively by a one-step reaction.
From 2-hydroxy-2- (6-methoxy-2-naphthyl) propionic acid, 2- (6-methoxy-2-naphthyl)
Propionic acid can be produced.
Claims (1)
−ナフチル）プロピオン酸を低級脂肪酸中で、無機酸の
存在下、水素雰囲気中でパラジウム系触媒を用いて還元
することを特徴とする２−（６−メトキシ−２−ナフチ
ル）プロピオン酸の製造法。1. 2-Hydroxy-2- (6-methoxy-2)
-Naphthyl) propionic acid is reduced in a lower fatty acid in the presence of an inorganic acid in a hydrogen atmosphere using a palladium-based catalyst to produce 2- (6-methoxy-2-naphthyl) propionic acid. .
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62318679A JPH0723338B2 (en) | 1987-12-18 | 1987-12-18 | Method for producing 2- (6-methoxy-2-naphthyl) propionic acid |
| US07/282,024 US4922010A (en) | 1987-12-18 | 1988-12-07 | Processes for preparing 2-substituted propionic acid and derivatives thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62318679A JPH0723338B2 (en) | 1987-12-18 | 1987-12-18 | Method for producing 2- (6-methoxy-2-naphthyl) propionic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01160941A JPH01160941A (en) | 1989-06-23 |
| JPH0723338B2 true JPH0723338B2 (en) | 1995-03-15 |
Family
ID=18101815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62318679A Expired - Lifetime JPH0723338B2 (en) | 1987-12-18 | 1987-12-18 | Method for producing 2- (6-methoxy-2-naphthyl) propionic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0723338B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5750764A (en) * | 1995-11-17 | 1998-05-12 | Aeci Limited | Synthesis and resolution of propionic acid derivatives |
-
1987
- 1987-12-18 JP JP62318679A patent/JPH0723338B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01160941A (en) | 1989-06-23 |
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