JPS607627B2 - Method for producing piperidine derivatives - Google Patents
Method for producing piperidine derivativesInfo
- Publication number
- JPS607627B2 JPS607627B2 JP52092177A JP9217777A JPS607627B2 JP S607627 B2 JPS607627 B2 JP S607627B2 JP 52092177 A JP52092177 A JP 52092177A JP 9217777 A JP9217777 A JP 9217777A JP S607627 B2 JPS607627 B2 JP S607627B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- propiophenone
- formula
- producing
- piveridino
- 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
Links
Description
【発明の詳細な説明】
本発明は、ピベリジン誘導体の製造方法に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a piverizine derivative.
さらに詳しくは、医薬品または製造中間体として有用な
一般式（式中Ｒはハロゲン原子または低級アルキル基を
表わす。More specifically, the general formula (wherein R represents a halogen atom or a lower alkyl group) is useful as a pharmaceutical product or a manufacturing intermediate.
）で示されるイー置換−３−ピベリジノ−２−メチルー
プロピオフェノンおよびその塩の新規な製造方法に関す
るものである。) The present invention relates to a novel method for producing e-substituted-3-piveridino-2-methyl-propiophenone and its salts.
４−置換−３ーピベリジノ−２−メチループロピオフエ
ノン、たとえば、４′ーメチル−３−ピベリジノー２−
メチループロピオフェノンは、優れた鎮蓮剤として既に
市販されているもので、その副作用は極めて少ないもの
として注目を集めている薬剤である。4-Substituted-3-piveridino-2-methyl-propiophenones, e.g. 4'-methyl-3-piveridino-2-
Methyl-propiophenone is already on the market as an excellent sedative and is attracting attention as it has extremely few side effects.
従来、４′−置換−３ーピベリジノ−２−メチループロ
ピオフェノンの製造方法として、４−置換プロピオフェ
ノンにピベリジンまたはその無機塩とホルムアルデヒド
とを、ニトロアルカンの存在下で反応させる方法（特公
昭４０一２０３９０）が知られている。Conventionally, as a method for producing 4'-substituted-3-piveridino-2-methyl-propiophenone, a method in which 4-substituted propiophenone is reacted with piveridine or an inorganic salt thereof and formaldehyde in the presence of a nitroalkane (in particular, Kosho 40-20390) is known.
しかしながら、この公知方法で使用されるホルムアルデ
ヒドは、その蒸気が粘膜を刺激し、鼻カタル、結膜炎を
惹起し、労働者の安全衛生の観点から望ましいものとは
言い難い。本発明者らは、これら従来法のもつ欠点を除
き、簡単な手段で、収率良く４′一層襖一３−ピベリジ
ノー２ーメチループロピオフエノンおよびその塩を製造
する方法について研究を重ねた結果、一般式（式中Ｒは
ハロゲン原子または低級アルキル基を表わす。However, the vapor of formaldehyde used in this known method irritates mucous membranes and causes nasal catarrh and conjunctivitis, and is therefore not desirable from the standpoint of safety and health for workers. The present inventors have conducted extensive research on a method for producing 4' single-layer fusuma-13-piberidino-2-methyl-propiophenone and its salts in a high yield by a simple means, while eliminating the drawbacks of these conventional methods. As a result, the general formula (wherein R represents a halogen atom or a lower alkyl group) is obtained.
）で示されるメタアクリル酸誘導体と、ピベリジンまた
はこの無機酸塩を反応させることにより、一般式（式中
Ｒは前記と同じ。) by reacting the methacrylic acid derivative represented by the general formula (wherein R is the same as above) with piveridine or its inorganic acid salt.
）で示される４′一置換−３ーピベリジノ−２−メチル
ープロピオフェノンおよびその塩を、簡単にしかも収率
良く製造する方法を見出すに到った。) We have now discovered a method for producing 4'-monosubstituted-3-piveridino-2-methyl-propiophenone and its salts easily and with good yield.
本発明に用いられる出発原料は、市販されている臭化ベ
ンゼン、塩化ベンゼン、沃化ベンゼン、ベンゼン、トル
ェン、エチルベンゼン等とメタアクリル酸の酸塩化物を
、ルイス酸触媒の存在下で反応させる公知の方法により
容易に得ることができる。このようにして得られたメタ
アクリル酸誘導体（１）は、無溶媒あるいは溶媒の存在
下、ピベリジンまたはその無機酸塩と無溶媒あるいは溶
媒中で反応させ、容易に４′一置換−３ーピベリジノー
２−メチループロピオフェノンを得ることができる。使
用するピベリジンまたはその無機酸塩の量は、メタアク
リル酸誘導体に対して同モル以上であれば特に限定され
るものではないが、経済性を考慮し、１．１〜１．３モ
ルが好ましい。The starting material used in the present invention is a known method in which commercially available benzene bromide, benzene chloride, benzene iodide, benzene, toluene, ethylbenzene, etc. are reacted with acid chloride of methacrylic acid in the presence of a Lewis acid catalyst. It can be easily obtained by the following method. The methacrylic acid derivative (1) thus obtained is easily reacted with piverizine or its inorganic acid salt in the absence or presence of a solvent to easily form a 4'-monosubstituted-3-piveridino 2 -Methyl-propiophenone can be obtained. The amount of piveridine or its inorganic acid salt to be used is not particularly limited as long as it is the same mole or more relative to the methacrylic acid derivative, but in consideration of economic efficiency, it is preferably 1.1 to 1.3 moles. .
使用する溶媒はメタノール、エタノール等のアルカノー
ル類、ベンゼン、トルェン等の芳香族炭化水素、ジクロ
ロメタン、クロロホルム等のハロゲン化炭化水素、アセ
トニトリル、ジメチルホルムアミド、ジメチルスルホキ
シド、ニトロメタン、二硫化炭素等の中から選ばれる。The solvent used is selected from alkanols such as methanol and ethanol, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane and chloroform, acetonitrile, dimethylformamide, dimethyl sulfoxide, nitromethane, carbon disulfide, etc. It will be done.
使用する温度は氷袷下から１５び○で可能であるが、室
温で充分に反応するため、外部からの冷劫、加熱は特に
必要がない。反応終了後、減圧下で過剰のピベリジンお
よび溶媒を除去した後、たとえば「エーテルを加え、乾
燥塩化水素ガスを通じることにより容易に４−置換−３
−ピベリジノー２−メチループロピオフェノンの塩酸塩
を得ることができる。The temperature used can be 15 to 15 degrees below freezing, but since the reaction is sufficient at room temperature, there is no particular need for external cooling or heating. After the reaction is completed, excess piverizine and solvent are removed under reduced pressure, and 4-substituted-3 is easily converted by adding ether and passing dry hydrogen chloride gas.
-Piveridino 2-methyl-propiophenone hydrochloride can be obtained.
以下実施例を挙げて説明するが、本発明はこれに限定さ
れるものではない。The present invention will be described below with reference to Examples, but the present invention is not limited thereto.
実施例 １
４′ーブロモ−２ーメチルーアクリロフエノン３．９夕
を１０の‘のエタノールに溶解する。Example 1 3.9 g of 4'-bromo-2-methyl-acrylophenone are dissolved in 10 g of ethanol.
この液にピベリジン２．６の‘を縄拝しながら室温下に
滴下し、さらに６０分間蝿拝して反応させた。反応液を
ＴＬＣ、ガスクロで分析すると原料は完全に消失した。
この反応液を減圧下、エタノールと残存ピベリジンを留
去し、４′ーブロモ−３ーピベリジノー２ーメチループ
ｏピオフェノンを淡黄色オイルとして５．３夕を得た。
反応収率９８％。実施例 ２２・４′ージメチルアクリ
ロフエノン１・４夕を５の‘のエタノールに溶解する。Piveridine 2.6' was added dropwise to this solution at room temperature, and allowed to react for an additional 60 minutes. When the reaction solution was analyzed by TLC and gas chromatography, the raw materials had completely disappeared.
Ethanol and residual piberidine were distilled off from the reaction solution under reduced pressure to obtain 4'-bromo-3-piberidino-2-methylpiophenone as a pale yellow oil.
Reaction yield 98%. Example 2 2.4'-dimethylacrylophenone 1.4 ml is dissolved in 5' of ethanol.
この液にピベリジン１・３の【を鷹拝しながら室温下に
滴下し、さらに２０分間蝿拝して反応させた。反応液を
ＴＬＣ、ガスクロで分析すると原料は完全に消失し、生
成物は標品と完全に一致した。この反応液を減圧下、エ
タノールと残存するピベリジンを留去し、４′ーメチル
ー３ーピベリジノー２−メチループロピオフェノンをオ
イルとして２．１夕を得た。反応収率９８％。このオイ
ルを２５の上のエーテルに溶解し、損拝しながら乾燥塩
化水素ガスを吹込むと、白色結晶が沈澱する。Piveridine 1.3 was added dropwise to this solution at room temperature while stirring, and allowed to react for an additional 20 minutes. When the reaction solution was analyzed by TLC and gas chromatography, the raw materials completely disappeared, and the product was found to be completely identical to the standard product. Ethanol and remaining piberidine were distilled off from the reaction solution under reduced pressure to obtain 4'-methyl-3-piberidino-2-methyl-propiophenone as an oil. Reaction yield 98%. When this oil is dissolved in ether above 25 and dry hydrogen chloride gas is blown into the solution, white crystals are precipitated.
炉別し乾燥すると、４′ーメチルー３ーピベリジノー２
−メチループロピオフェノンの塩酸塩として２．４夕を
得た。取得率９９％。実施例 ３４′−エチル−２ーメ
チルーアクリロフエノン１．５夕を６の‘のクロロフオ
ルムに溶解する。After oven-drying, 4'-methyl-3-piberidino2
-2.4 hours were obtained as the hydrochloride of methyl-propiophenone. Acquisition rate 99%. Example 3 1.5 hours of 4'-ethyl-2-methyl-acrylophenone are dissolved in 6 hours of chloroform.
この液にピベリジン１．３夕を燭拝しながら室温下に滴
下し、さらに２０分間燈拝して反応させた。反応液をＴ
ＬＣ、ガスクロで分析すると原料は完全に消失した。ク
ロロフオルムと残存するピベリジンを蟹去し、４′ーェ
チルー３ーピベリジノ−２ーメチルーブロピオフェノン
をオイルとして２．２タ得た。実施例 ４
エタノールの替わりにトルェン６の‘を使う以外は、実
施例２の方法と全く同様にして４′−メチル一３ーピベ
リジノー２ーメチルーブ。To this solution, 1.3 liters of Piverizine was added dropwise at room temperature while stirring, and the mixture was allowed to react for an additional 20 minutes. The reaction solution is
Analysis by LC and gas chromatography revealed that the raw materials had completely disappeared. The chloroform and remaining piveridine were removed by distillation to obtain 2.2 t of 4'-ethyl-3-piveridino-2-methyl-propiophenone as an oil. Example 4 4'-Methyl-13-piberidino-2-methylbenzene was prepared in exactly the same manner as in Example 2, except that toluene 6' was used instead of ethanol.
Claims (1)
。 ）で示されるメタアクリル酸誘導体と、ピペリジンまた
はその無機酸塩を反応させることを特徴とする一般式▲
数式、化学式、表等があります▼ （式中Ｒは前記と同じ。 ）で示される４′−置換−３−ピペリジノ−２−メチル
−プロピオフエノンおよびその塩の製造方法。[Claims] 1. A methacrylic acid derivative represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (in the formula, R represents a halogen atom or a lower alkyl group) and piperidine or its inorganic acid salt. General formula characterized by reaction ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R is the same as above.) A method for producing 4'-substituted-3-piperidino-2-methyl-propiophenone and its salts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52092177A JPS607627B2 (en) | 1977-08-02 | 1977-08-02 | Method for producing piperidine derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52092177A JPS607627B2 (en) | 1977-08-02 | 1977-08-02 | Method for producing piperidine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5427571A JPS5427571A (en) | 1979-03-01 |
| JPS607627B2 true JPS607627B2 (en) | 1985-02-26 |
Family
ID=14047140
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52092177A Expired JPS607627B2 (en) | 1977-08-02 | 1977-08-02 | Method for producing piperidine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS607627B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT505225A1 (en) * | 2007-04-26 | 2008-11-15 | Sanochemia Pharmazeutika Ag | Tolperisone and their pharmaceutical acceptable salts and hydrates production for use as active substance in pharmaceutical formulation for drugs, for treatment and therapy of Alzheimer's disease, involves converting methylpropiophenone |
-
1977
- 1977-08-02 JP JP52092177A patent/JPS607627B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5427571A (en) | 1979-03-01 |
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