JPH0210143B2 - - Google Patents
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- Publication number
- JPH0210143B2 JPH0210143B2 JP57048150A JP4815082A JPH0210143B2 JP H0210143 B2 JPH0210143 B2 JP H0210143B2 JP 57048150 A JP57048150 A JP 57048150A JP 4815082 A JP4815082 A JP 4815082A JP H0210143 B2 JPH0210143 B2 JP H0210143B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- dimethylamino
- ethoxy
- carvacrol
- present
- 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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、下記式(2)
で表わされる５―〔２―（ジメチルアミノ）エト
キシ〕カルバクロールアセテート塩酸塩の製法に
関する。[Detailed Description of the Invention] The present invention provides the following formula (2) The present invention relates to a method for producing 5-[2-(dimethylamino)ethoxy]carvacrol acetate hydrochloride represented by:
さらに詳しくは本発明は、下記式(1)
で表わされる５―〔２―（ジメチルアミノ）エト
キシ〕カルバクロールを、クロルベンゼンに溶解
し、この溶液に塩化アセチルを反応させる段階を
含むことを特徴とする５―〔２―ジメチルアミ
ノ）エトキシ〕カルバクロールアセテート塩酸塩
（式２）の製法に関する。 More specifically, the present invention is based on the following formula (1) 5-[2-(dimethylamino)ethoxy] characterized by the step of dissolving 5-[2-(dimethylamino)ethoxy]carvacrol represented by in chlorobenzene and reacting this solution with acetyl chloride. The present invention relates to a method for producing carvacrol acetate hydrochloride (Formula 2).
本発明の方法によれば、アセチル化と塩酸塩の
形成とを一挙に進行せしめ、かつ再結晶工程を加
えることなく、高純度の上記塩酸塩（式２）を高
収率で収得することができる。 According to the method of the present invention, the acetylation and the formation of the hydrochloride can proceed at once, and the highly purified hydrochloride (Formula 2) can be obtained in high yield without adding a recrystallization step. can.
上記５―〔２―（ジメチルアミノ）エトキシ〕
カルバクロールアセテート塩酸塩（式２）は交感
神経を抑制する作用を有し（K.Credner，R.
Graebner；Arzneim.−Forsch.17，305（1967））、
塩酸チモキサミンという名称のもとに、循環器系
用医薬品として医療に供せられ、英国薬局方
（British Pharmacopoeia1980，P455）にも収載
されている有用な化合物である。 The above 5-[2-(dimethylamino)ethoxy]
Carvacrol acetate hydrochloride (formula 2) has the effect of suppressing sympathetic nerves (K. Credner, R.
Graebner; Arzneim.-Forsch. 17 , 305 (1967)),
It is a useful compound that is used medically as a cardiovascular drug under the name thymoxamine hydrochloride, and is also listed in the British Pharmacopoeia (British Pharmacopoeia 1980, P455).
上記５―〔２―（ジメチルアミノ）エトキシ〕
カルバクロールアセテート塩酸塩（式２を製造す
る方法に関しては、ドイツ特許第905738号、英国
特許第745070号、あるいはA.Buzas et al.Bull.
Soc.Chim.France1959，839に開示されている。
これらに記載されている方法の要点は、いずれも
下記に示すものである。 The above 5-[2-(dimethylamino)ethoxy]
For methods of preparing carvacrol acetate hydrochloride (formula 2), see German Patent No. 905,738, British Patent No. 745,070, or A. Buzas et al. Bull.
Soc. Chim. France 1959 , 839.
The main points of the methods described in these documents are all shown below.
５―〔２―ジメチルアミノ）エトキシ〕カルバ
クロール（式１）に、過剰の無水酢酸を加え、こ
れに中和剤および触媒としてのピリジンを加えて
加熱反応せしめ、次いでこれに水を加えて反応液
を希釈し、アルカリを加えてアルカリ性とした
後、エーテルで抽出し、エーテルを留去すること
によつてアセテートを取得する。次いで、得られ
たアセテートをエーテルに溶解し、この溶液に、
永冷下で塩化水素ガスを導入し、析出する塩酸塩
（式２）の結晶を別し、この結晶をエーテルで
十分に洗浄し、過剰の塩化水素を除き、乾燥した
後、その結晶を酢酸エチル―メタノール混合液よ
り再結晶して目的とする塩酸塩（式２）を得てい
る。この方法は操作が煩雑であり、多量の溶媒や
試薬を用い、特にエーテルを多量に用いることは
安全性の点で好ましくなく、工業的な製造方法と
しては有利なものとは言えない。 Excess acetic anhydride was added to 5-[2-dimethylamino)ethoxy]carvacrol (Formula 1), and pyridine as a neutralizing agent and catalyst was added thereto to cause a heating reaction, and then water was added to react. The solution is diluted and made alkaline by adding an alkali, extracted with ether, and the ether is distilled off to obtain acetate. Then, the obtained acetate was dissolved in ether, and to this solution,
Hydrogen chloride gas is introduced under permanent cooling, the precipitated crystals of hydrochloride (formula 2) are separated, and the crystals are thoroughly washed with ether to remove excess hydrogen chloride. After drying, the crystals are treated with acetic acid. The desired hydrochloride (Formula 2) was obtained by recrystallization from an ethyl-methanol mixture. This method is complicated to operate, uses large amounts of solvents and reagents, and especially uses a large amount of ether, which is unfavorable from the viewpoint of safety, and cannot be said to be advantageous as an industrial production method.
本発明者らは、引火の危険の少ないクロルベン
ゼンが上記アセチル化の反応溶媒として好適であ
ることを見い出し、本発明を完成した。 The present inventors have discovered that chlorobenzene, which has a low risk of ignition, is suitable as a reaction solvent for the acetylation, and has completed the present invention.
本発明の方法を次に示す。 The method of the present invention is shown below.
５―〔２―（ジメチルアミノ）エトキシ〕カル
バクロール（式１）を、30〜40倍量のクロルベン
ゼンに溶解し、これに塩化アセチル１〜1.5倍当
量を加えた後、室温に一夜放置するか、または３
〜４時間加熱還流する。この際、式１の化合物に
対して0.1〜0.2倍モルの無水酢酸を加えると式２
の化合物の収率が向上する。次いで反応液を永水
で冷却し、析出した結晶を取すると、高純度の
５―〔２―（ジメチルアミノ）エトキシ〕カルバ
クロールアセテート塩酸塩（式２）を高収率で取
得することができる。本発明の方法により得た上
記塩酸塩は、そのまま医薬品として使用しうる純
度のものであるが、必要に応じて、クロルベンゼ
ンを用いて再結晶する。 Dissolve 5-[2-(dimethylamino)ethoxy]carvacrol (Formula 1) in 30 to 40 times the amount of chlorobenzene, add 1 to 1.5 times the equivalent of acetyl chloride, and then leave it at room temperature overnight. or 3
Heat to reflux for ~4 hours. At this time, if 0.1 to 0.2 times the mole of acetic anhydride is added to the compound of formula 1, formula 2
The yield of the compound is improved. Next, the reaction solution is cooled with permanent water and the precipitated crystals are collected to obtain highly pure 5-[2-(dimethylamino)ethoxy]carvacrol acetate hydrochloride (Formula 2) in a high yield. . The hydrochloride obtained by the method of the present invention has a purity that can be used as a medicine as it is, but if necessary, it is recrystallized using chlorobenzene.
本発明において、原料として用いる５―〔２―
（ジメチルアミノ）エトキシ〕カルバクロール
（式１）は高純度のものであることが好ましい。 In the present invention, 5-[2-
(Dimethylamino)ethoxy]carvacrol (Formula 1) is preferably of high purity.
本発明者らが先に発明した方法（特願昭56―
145553号、特願昭56―145554号および特願昭57―
7528号）によつて得られるカルバクロール（式
１）は本発明の原料として好適であり、高純度の
アセテート塩酸塩（式２）に高収率で変換され
る。 The method invented by the present inventors (patent application 1983-
No. 145553, Patent Application No. 145554 and Patent Application No. 1982-
Carvacrol (Formula 1) obtained by the method (No. 7528) is suitable as a raw material for the present invention and is converted to highly pure acetate hydrochloride (Formula 2) in high yield.
上述したように、本発明の方法によれば、従来
の方法に比して、簡単な操作によつて高純度の５
―〔２―ジメチルアミノ）エトキシ〕カルバクロ
ールアセテート塩酸塩（式２）を高収率で取得す
ることができる。本発明においては引火の危険の
少ないクロルベンゼンを溶媒として用いるので、
工業的製法として特に好適である。 As mentioned above, according to the method of the present invention, highly purified
-[2-dimethylamino)ethoxy]carvacrol acetate hydrochloride (Formula 2) can be obtained in high yield. In the present invention, since chlorobenzene, which has a low risk of flammability, is used as a solvent,
It is particularly suitable as an industrial manufacturing method.
以下に本発明の方法の実施例を示す。 Examples of the method of the present invention are shown below.
実施例
特願昭57―7528号の方法によつて得た５―〔２
―（ジメチルアミノ）エトキシ〕カルバクロール
（式１）2.37ｇ（0.01モル）をクロルベンゼン126
mlに溶かしこの溶液に塩化アセチル0.86ｇ
（0.011モル）および無水酢酸0.102ｇ（0.001モル）
を添加し、30分間かきまぜた後、３時間加熱還流
し、均一な反応液を永水にて冷却し、析出した結
晶を取し、５―〔２―ジメチルアミノ）エトキ
シ〕カルバクロールアセテート塩酸塩（式２）
3.03ｇ（収率96％）を融点211.4〜213.0℃を示す
無色針状結晶として得た。Example 5-[2 obtained by the method of Japanese Patent Application No. 57-7528
-(dimethylamino)ethoxy]carvacrol (Formula 1) 2.37g (0.01mol) to chlorobenzene 126
0.86 g of acetyl chloride in this solution dissolved in ml
(0.011 mol) and acetic anhydride 0.102 g (0.001 mol)
was added, stirred for 30 minutes, heated under reflux for 3 hours, cooled the homogeneous reaction solution with permanent water, collected the precipitated crystals, and prepared 5-[2-dimethylamino)ethoxy]carvacrol acetate hydrochloride. (Formula 2)
3.03 g (yield 96%) was obtained as colorless needle crystals with a melting point of 211.4-213.0°C.
元素分析値C16H26NO3Clとして Ｃ％ Ｈ％ Ｎ％ 計算値 60.67 8.33 4.40 実測値 60.68 8.30 4.37 Elemental analysis value C 16 H 26 NO 3 As Cl C% H% N% Calculated value 60.67 8.33 4.40 Actual value 60.68 8.30 4.37
Claims (1)
シ〕カルバクロールを、クロルベンゼンに溶解
し、この溶液に塩化アセチルを加えて反応させる
段階を含むことを特徴とする下記式(2) で表わされる５―〔２―（ジメチルアミノ）エト
キシ〕カルバクロールアセテート塩酸塩の製法。[Claims] 1. The following formula (1) The following formula (2) is characterized by including the step of dissolving 5-[2-(dimethylamino)ethoxy]carvacrol having the formula in chlorobenzene, and adding acetyl chloride to this solution for reaction. A method for producing 5-[2-(dimethylamino)ethoxy]carvacrol acetate hydrochloride represented by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4815082A JPS58167551A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4815082A JPS58167551A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58167551A JPS58167551A (en) | 1983-10-03 |
| JPH0210143B2 true JPH0210143B2 (en) | 1990-03-06 |
Family
ID=12795327
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4815082A Granted JPS58167551A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58167551A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0469241U (en) * | 1990-10-25 | 1992-06-18 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4918057A (en) * | 1972-06-09 | 1974-02-18 |
-
1982
- 1982-03-27 JP JP4815082A patent/JPS58167551A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0469241U (en) * | 1990-10-25 | 1992-06-18 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58167551A (en) | 1983-10-03 |
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