JPS6253938A - Production of p-hydroxyacetophenone - Google Patents
Production of p-hydroxyacetophenoneInfo
- Publication number
- JPS6253938A JPS6253938A JP60193571A JP19357185A JPS6253938A JP S6253938 A JPS6253938 A JP S6253938A JP 60193571 A JP60193571 A JP 60193571A JP 19357185 A JP19357185 A JP 19357185A JP S6253938 A JPS6253938 A JP S6253938A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxyacetophenone
- reaction
- aluminum chloride
- chloride
- acetylating agent
- 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.)
- Pending
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)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は医薬品の原料として有用なＰ−ヒドロキシアセ
トフェノンの選択的な製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for selectively producing P-hydroxyacetophenone, which is useful as a raw material for pharmaceuticals.
〈従来技術〉
Ｐ−ヒドロキシアセトフェノンの製造方法として、フェ
ノールと塩化アセチル混合物又は酢酸フェニルに塩化ア
ルミニウムを作用させ、Ｆｒ１ｅｓ転位を起こさせる方
法が知られている。<Prior Art> As a method for producing P-hydroxyacetophenone, a method is known in which a mixture of phenol and acetyl chloride or phenyl acetate is reacted with aluminum chloride to cause Fr1es rearrangement.
（Ｏｒｇａｎｉｃ ｒｅａｃｔｉｏｎ ｖｏｌ、 １．
３５７頁）その他に、メトキシアセトフェノンＴｈＪＪ
化アルミニウム存在下、ベンゼン中で加熱することたよ
シ９．高収率でＰ−ヒドロキシアセトフェノンを得てい
る例がある。（Ｊ、 Ｐｒａｋｔ、 Ｃｈｅｍ、 ｅ
１４７巻。(Organic reaction vol. 1.
(page 357) In addition, methoxyacetophenone ThJJ
9. Heating in benzene in the presence of aluminum chloride.9. There are examples of obtaining P-hydroxyacetophenone in high yield. (J, Prakt, Chem, e
Volume 147.
２９３頁、 １９３７年）
〈発明が解決しようとする問題点〉
しかしながら、これらの方法には以下に述べるような欠
点がある。即ち、前者のＦｒ１ｅｓ転位反応を利用する
方法においては、炭素数３コ以上のアシル化剤の例、た
とえばＰ−ヒドロキシプロピオフェノンの場合等につい
ては、条件によってＰ位選択性が高く優れた方法と言え
るが（ソ連特許３４５．１２７ ） 、本発明の目的物
であるＰ−ヒドロキシアセトフェノンの場合高々７５％
であり、０〜ヒドロキシアセトフエノンが１０〜２０チ
副生ずる。従って純度の高い？−ヒドロキシアセトフェ
ノンを得るためには、水蒸気蒸留によシ〇一体を除去し
た後、さらに再結晶法で精製しなければならず、効率が
悪い。(Page 293, 1937) <Problems to be Solved by the Invention> However, these methods have the following drawbacks. That is, in the former method that utilizes the Fr1es rearrangement reaction, in the case of an acylating agent having 3 or more carbon atoms, such as P-hydroxypropiophenone, depending on the conditions, it may be an excellent method with high P position selectivity. However, in the case of P-hydroxyacetophenone, which is the object of the present invention, it is at most 75%.
and 10 to 20 hydroxyacetophenones are produced as by-products. Is it therefore highly pure? - In order to obtain hydroxyacetophenone, it is necessary to remove the cylindrical material by steam distillation and then further purify it by recrystallization, which is inefficient.
後者の方法は、高価な臭化アルミニウムを使用している
こと等工業的に有利ではない。The latter method is not industrially advantageous because it uses expensive aluminum bromide.
く問題点を解決するための手段〉
本発明者らは、工業的に不利な上記の製法に替わる、選
択性が良く、しかも効率の良いＰ−ヒドロキシアセトフ
ェノンの製造法を確立すべく、鋭意検討した結果、アル
コキシベンゼンとアセチル化剤及び塩化アルミニウムと
のフリーデル・クラフッ反応によシ生成するＰ−アルコ
キシアセトフェノンを含む溶液にさらに塩化アルミニウ
ムを作用させ、エーテル開裂反応によシＰ−アルコキシ
アセトフェノンを単離することな（、Ｐ−ヒドロキシア
セトフェノンに誘導できることを見出し、本発明に至っ
た。Means for Solving the Problems> The present inventors have conducted extensive studies in order to establish a method for producing P-hydroxyacetophenone that is highly selective and efficient, replacing the industrially disadvantageous production method described above. As a result, aluminum chloride was further applied to a solution containing P-alkoxyacetophenone produced by the Friedel-Crach reaction between alkoxybenzene, an acetylating agent, and aluminum chloride, and P-alkoxyacetophenone was produced by an ether cleavage reaction. It was discovered that P-hydroxyacetophenone can be derived without isolation, leading to the present invention.
即ち、本発明は、溶媒中でアルコキシベンゼン。That is, the present invention uses alkoxybenzene in a solvent.
アセチル化剤及び塩化アルミニウムを一５〜１０℃およ
び２０〜５０℃の２段階で反応させることｔ％徴とする
Ｐ−ヒドロキシアセトフェノンの製造法である。This is a method for producing P-hydroxyacetophenone, which involves reacting an acetylating agent and aluminum chloride in two steps at -5 to 10°C and at 20 to 50°C.
本発明の実施に肖っては例えば、）・ロゲン化炭化水素
溶媒中、アセチル化剤及び塩化アルミニウムを加え撹拌
しながら低温でアルコキシベンゼンを滴下し、フリーデ
ルクラフッ反応を行わしめる。In carrying out the present invention, for example, an acetylating agent and aluminum chloride are added in a logenated hydrocarbon solvent, and alkoxybenzene is added dropwise at a low temperature with stirring to carry out a Friedel-Crach reaction.
その反応液にさらに塩化アルミニウムを加え、若干温度
を上げ、エーテル開裂させればよい。反応液は水処理し
、塩化アルミニウムを水層に移行させ、有機層を濃縮す
ることによシＰ−ヒドロキシアセトフェノンを得ること
ができる。Aluminum chloride is further added to the reaction solution, the temperature is slightly raised, and the ether is cleaved. The reaction solution is treated with water, aluminum chloride is transferred to the aqueous layer, and the organic layer is concentrated to obtain P-hydroxyacetophenone.
本発明の反応は、アセチル化剤として塩化アセチルを使
用した場合を例にとると次式で示される。The reaction of the present invention is shown by the following formula, taking as an example the case where acetyl chloride is used as the acetylating agent.
（Ｒはアルキル基）
本反応で使用するアルコキシベンゼンは、特に制限され
ないが安価な点、及びエーテル化の反応の際生成する塩
化アルキルが塩化メチルとなるので、除去しやすいとい
う点でアニソールが良い。(R is an alkyl group) The alkoxybenzene used in this reaction is not particularly limited, but anisole is preferred because it is inexpensive and because the alkyl chloride produced during the etherification reaction becomes methyl chloride, it is easy to remove. .
溶媒としてはハｑゲン化炭化水素系のものが使用でキル
力、アルコキシベンゼンのフリーデルクラフッ反応を行
う場合、生成ケトンと塩化アルミニウムとの錯体の溶解
度が大きい点でエチレンジクロリドが適している。When performing the Friedel-Crach reaction of alkoxybenzene, ethylene dichloride is suitable because it has a high solubility for the complex between the produced ketone and aluminum chloride. .
アセチル化剤としては、塩化アセチル、無水酢酸、酢酸
等が使用されるが、塩化アルミニウムの消費が少ない点
で塩化アセチルが良い。フリーデルクラフッの反応温度
は、〇一体の生成を抑制するため低い方が良いが、適当
な反応速度を得るためには一５〜１０℃の範囲が適して
いる。フリーデルクラフッ反応時に使用する塩化アルミ
ニウム量はアルコキシベンゼンに対し、当モルよシ若干
過剰が収率的に良い。又、フリーデルクラフッ反応液中
のＰ−アルコキシアセトフェノンのエーテル開裂反応時
は１当量をさらに加えるだけで良い。As the acetylating agent, acetyl chloride, acetic anhydride, acetic acid, etc. are used, but acetyl chloride is preferable because it consumes less aluminum chloride. The Friedelkraft reaction temperature should be lower in order to suppress the formation of 〇-1, but in order to obtain a suitable reaction rate, a range of -5 to 10°C is suitable. In terms of yield, the amount of aluminum chloride used in the Friedel-Kraf reaction should be slightly in molar excess relative to the alkoxybenzene. Further, during the ether cleavage reaction of P-alkoxyacetophenone in the Friedel-Kraf reaction solution, it is sufficient to add only 1 equivalent.
反応のさせ方として、フリーデルクラフッ溶液に塩化ア
ルミニウムを加えても、逆に塩化アルミニウムージクロ
ルエタン溶液系にフリーデルクラフッ反応液を加えても
良い。反応温度は２０〜５０℃が良く、それ以下では反
応は遅く、以上ではタール分の副生が多くなる。To carry out the reaction, aluminum chloride may be added to the Friedel-Craft solution, or conversely, the Friedel-Craf reaction solution may be added to the aluminum chloride-dichloroethane solution system. The reaction temperature is preferably 20 to 50°C; below that, the reaction is slow, and above that, a large amount of tar by-product is produced.
なお、上記のエーテル開裂反応に必要な触媒の塩化アル
ミニウムの添加は、本発明の反応の最初に行ってもよい
。即ち、フリーデルクラフッ反応時にアルコキシベンゼ
ンに対し、およそ２当量添加しておき、フリーデルクラ
フッ反応後温度を上げるだけでエーテル開裂反応を進行
させることもできる。Note that the addition of aluminum chloride as a catalyst necessary for the above-mentioned ether cleavage reaction may be carried out at the beginning of the reaction of the present invention. That is, it is also possible to advance the ether cleavage reaction by adding approximately 2 equivalents to the alkoxybenzene during the Friedel-Craf reaction and simply increasing the temperature after the Friedel-Craf reaction.
〈発明の効果〉
本発明の方法によシ
１）安価な原料を用い
２）簡単な工程で
３）０−ヒドロキシアセトフェノンの副生ヲ押え、高収
率で、高純度（９５％以上）のＰ−ヒドロキシアセトフ
ェノンを得ることができる。<Effects of the Invention> The method of the present invention 1) uses inexpensive raw materials, 2) uses simple steps, 3) suppresses the by-product of 0-hydroxyacetophenone, and produces high yield and high purity (95% or more). P-hydroxyacetophenone can be obtained.
〈実施例〉
実施例−１
撹拌器、コンデンサー、温度計を備えた七パラプルフラ
スコにエチレンジクロリド２．０００ｍ／。<Example> Example-1 Ethylene dichloride 2.000 m/ml was placed in a seven-paraple flask equipped with a stirrer, a condenser, and a thermometer.
Ａｔｃｔ、 ２８０ ｆ （２，１０モル） 、塩化ア
セチル１７２Ｆ（２，１９モル）を仕込み、この混合物
を撹拌しながら水浴で冷却し、０〜２℃を保ちながらメ
トキシベンゼン２１６ｆ（２，Ｑモル）を２時間で滴下
反応した。引続き０〜２℃で１時間熟成を取シ、Ｐ−メ
トキシアセトフェノンの反応を終了した。Atct, 280 f (2.10 mol) and acetyl chloride 172F (2.19 mol) were charged, and the mixture was cooled in a water bath while stirring, and methoxybenzene 216f (2.Q mol) was added while maintaining the temperature at 0 to 2°C. was added dropwise for 2 hours. Subsequently, the mixture was aged at 0 to 2°C for 1 hour to complete the reaction of P-methoxyacetophenone.
その反応液にＡ４９ｇ２６７Ｆ（２，０モル）を加え、
３５〜４０℃で８時間撹拌し、エーテル開裂反応を終了
した。Add A49g267F (2.0 mol) to the reaction solution,
The mixture was stirred at 35-40°C for 8 hours to complete the ether cleavage reaction.
この反応液を水２，０００ｄ中へ徐々に添加し、３０〜
４０℃で錯体分解し、分液後エチレンジクロリド層１，
３７１ｆｉ得た。ガスクロ分析の結果エチレンジクロリ
ド層にはＰ−ヒドロキシアセトフェノン１７，１％、Ｏ
−ヒドロキシアセトフェノン０．１６％が含まれておシ
、メトキシベンゼン基準の収率はＰ−ヒドロキシアセト
フェノン８６．１俤、０−ヒドロキシアセトフェノン０
．８１％であった。Gradually add this reaction solution to 2,000 d of water,
After decomposing the complex at 40°C and separating the layers, an ethylene dichloride layer 1,
I got 371fi. As a result of gas chromatography analysis, the ethylene dichloride layer contained 17.1% P-hydroxyacetophenone and O
-Contains 0.16% of hydroxyacetophenone.The yield based on methoxybenzene is 86.1 units of P-hydroxyacetophenone and 0 units of 0-hydroxyacetophenone.
．． It was 81%.
実施例−２
実施例−１と同一の装置にエチレンジクロリド２．００
０ｄ 、 ＡｔＣ／、３２８０ ｆ （２，１０モル）
、塩化アセチル１７２ ｆ （２，１９モル）を仕込
み、この混合物を撹拌しながら水浴で冷却し、０〜２℃
を保ちなからエトキシベンゼン２４４９（２，０モル）
を２時間で滴下反応した。引続き０〜２℃で１時間熟成
を取り、Ｐ−エトキシアセトフェノンの反応を終了した
。Example-2 2.00 ethylene dichloride was added to the same equipment as Example-1.
0d, AtC/, 3280f (2,10 mol)
, acetyl chloride 172 f (2,19 mol) was charged, and the mixture was cooled with stirring in a water bath and heated to 0-2°C.
Ethoxybenzene 2449 (2,0 mol)
was added dropwise for 2 hours. Subsequently, the mixture was aged at 0 to 2°C for 1 hour to complete the reaction of P-ethoxyacetophenone.
その反応液にＡｔＣ１８２６７ｆ （２，００モル）を
加え、３５〜４０℃で７時間撹拌し、エーテル開裂反応
を終了した。AtC18267f (2,00 mol) was added to the reaction solution and stirred at 35-40°C for 7 hours to complete the ether cleavage reaction.
この反応液を水２，０００ｄ中へ徐々に添加し、３０〜
４０℃で錯体分解し、分液後エチレンジクロリド層１３
６３ｆ’ｉ得た。ガスクロ分析の結果、エチレンジクロ
リド層にはＰ−ヒドロキシアセトフェノン１６．５％、
０−ヒドロキシアセトフェノン０，１５％が含まれてお
シ、エトキシベンゼン基準の収率はＰ−ヒドロキシアセ
トフェノン８２．６俤、０−ヒドロキシアセトフェノン
０．７６％であった。Gradually add this reaction solution to 2,000 d of water,
After decomposing the complex at 40°C and separating the layers, an ethylene dichloride layer 13 is formed.
I got 63f'i. As a result of gas chromatography analysis, the ethylene dichloride layer contained 16.5% of P-hydroxyacetophenone.
It contained 0.15% of 0-hydroxyacetophenone, and the yield based on ethoxybenzene was 82.6% of P-hydroxyacetophenone and 0.76% of 0-hydroxyacetophenone.
実施例−３
実施例−１と同一の装置にエチレンジクロリド２．００
０ ｄ 、 ＡｔＣｌ３５３４ ｆ （４，００モル）
、塩化アセチル１７２ ｆ （２，１９モル）を仕込み
、この混合物を撹拌しながら水浴で冷却し、０〜２℃を
保ちなからメトキシベンゼン２１６ ？ （２モル）’
に２時間で滴下反応した。０〜２℃で１時間熟成？取ム
Ｐ−メトキシアセトフェノンの反応を終了した。Example-3 2.00 ethylene dichloride was added to the same equipment as Example-1.
0 d, AtCl3534 f (4,00 mol)
, acetyl chloride 172 f (2.19 mol) was charged, and the mixture was cooled in a water bath with stirring, maintaining the temperature at 0 to 2°C, and methoxybenzene 216 ? (2 moles)'
The dropwise reaction was carried out in 2 hours. Aged for 1 hour at 0-2℃? The reaction of P-methoxyacetophenone was completed.
引続き３５〜４０℃で１０時間反応し、エーテル開裂反
応を終了した。Subsequently, the reaction was carried out at 35 to 40°C for 10 hours to complete the ether cleavage reaction.
この反応液を水２，０００ｄ中へ徐々に添加し、３０〜
４０℃で錯体分解し、分液後エチレンジクロリド層２，
６８２ｆを得た。Gradually add this reaction solution to 2,000 d of water,
After decomposing the complex at 40°C and separating the layers, an ethylene dichloride layer 2,
I got 682f.
ガスクロ分析の結果、エチレンジクロリド層にＵＰ−ヒ
ドロキシアセトフェノン８．６’Ｏｆ６．０−ヒドロキ
シアセトフェノン０．１６％が含まれておシ、メトキシ
ベンゼン基準の収率はＰ−ヒドロキシアセトフェノン８
４．７％、Ｏ−ヒドロキシアセトフェノン１．６チであ
った。As a result of gas chromatography analysis, the ethylene dichloride layer contained UP-hydroxyacetophenone 8.6'Of6.0-hydroxyacetophenone 0.16%, and the yield based on methoxybenzene was P-hydroxyacetophenone 8.
4.7%, O-hydroxyacetophenone 1.6%.
Claims (1)
アルミニウムを−５〜１０℃および２０〜５０℃の２段
階で反応させることを特徴とするＰ−ヒドロキシアセト
フェノンの製造法。A method for producing P-hydroxyacetophenone, which comprises reacting alkoxybenzene, an acetylating agent, and aluminum chloride in two steps at -5 to 10°C and 20 to 50°C in a solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60193571A JPS6253938A (en) | 1985-09-02 | 1985-09-02 | Production of p-hydroxyacetophenone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60193571A JPS6253938A (en) | 1985-09-02 | 1985-09-02 | Production of p-hydroxyacetophenone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6253938A true JPS6253938A (en) | 1987-03-09 |
Family
ID=16310221
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60193571A Pending JPS6253938A (en) | 1985-09-02 | 1985-09-02 | Production of p-hydroxyacetophenone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6253938A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004506034A (en) * | 2000-08-14 | 2004-02-26 | クエスト・インターナショナル・ビー・ブイ | Production of 3-alkylcycloalkanol |
-
1985
- 1985-09-02 JP JP60193571A patent/JPS6253938A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004506034A (en) * | 2000-08-14 | 2004-02-26 | クエスト・インターナショナル・ビー・ブイ | Production of 3-alkylcycloalkanol |
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