JPS5925357A - Preparation of carvacrol derivative - Google Patents
Preparation of carvacrol derivativeInfo
- Publication number
- JPS5925357A JPS5925357A JP4814982A JP4814982A JPS5925357A JP S5925357 A JPS5925357 A JP S5925357A JP 4814982 A JP4814982 A JP 4814982A JP 4814982 A JP4814982 A JP 4814982A JP S5925357 A JPS5925357 A JP S5925357A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- carvacrol
- ethoxy
- chlorobenzene
- hydrochloride
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、下記の式（１）を有する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
の製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 5-(2-(dimethylamino)ethoxy)carvacrol acetate hydrochloride having the following formula (1).
本発明は、式（２）
を有する５−〔２−（ツメチルアミノ〕エトキシ〕カル
パクロールアセテートヲ、クロルベンゼンに溶解し、こ
の溶液に塩化水素ガスを導入して析出した５−（２−（
ツメチルアミノ）エトキシ〕カルバクロールアセテート
塩酸塩（式１）を単離することを特徴とするものであっ
て、本発明の方法によれは、再結晶という手段をさらに
追加することなく、高純度の塩酸塩（式１）を高収率で
取得することができる。The present invention provides 5-(2-(
The method of the present invention is characterized by isolating carvacrol acetate hydrochloride (formula 1), and the method of the present invention enables the isolation of high-purity hydrochloric acid without additional means of recrystallization. The salt (formula 1) can be obtained in high yield.
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１）は、α−遮断作用を有し、
塩酸チモキサミンという名称のもとに、循環器系医薬品
として医療に供せられ、英国薬局方（Ｂｒｉｔｉｓｈ
Ｐｈａｒｍａｃｏｐｏｅｉａ １９・８Ｌ ｐ ４５５
） Ｋも収載されている有用な化合物である（Ｋ、
Ｃｒｅｄｅｒ、 Ｒ，Ｇｒａｅｂｎａｒ ：Ａｒｚｎｅ
ｌｍｌｔｔｅｌ−Ｆｏｒｓｃｈｕｎｇ１７．３０５ （
１９６７））。5-(2-(dimethylamino)ethoxy)carvacrol acetate hydrochloride (Formula 1) has α-blocking action,
It is used medically as a cardiovascular drug under the name thymoxamine hydrochloride, and is listed in the British Pharmacopoeia.
Pharmacopoeia 19・8L p 455
) K is also a useful compound listed (K,
Creder, R. Graebnar: Arzne
lmlttel-Forschung17.305 (
1967)).
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１）を製造する方法とし
て、Ａ、 Ｂｕｚａａ、 Ｊ、Ｔｅａｔｏ、 Ｊ、 Ｆ
ｒｏｓｓａｒｄ；Ｂｕｌｌ、 Ｓｏｃ。As a method for producing the above 5-(2-(dimethylamino,)ethoxy]carvacrol acetate hydrochloride (Formula 1), A, Buzaa, J, Teato, J, F
rossard; Bull, Soc.
Ｃｈｉｍ、 Ｆｒａｎｃｅ、 １９５９．８３９に下記
に示す方法が報告されている。Chim, France, 1959.839 reports the method shown below.
５−（２−（ジメチルアミノ）エトキシ〕カルバクロー
ルアセテートを、エーテルに溶解し、この溶液に、水冷
下で塩化水素ガスを導入し、析出する上記塩酸塩の結晶
を戸別し、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高純度の塩酸塩（式１
）を得る。5-(2-(dimethylamino)ethoxy)carvacrol acetate is dissolved in ether, hydrogen chloride gas is introduced into this solution under water cooling, the precipitated hydrochloride crystals are separated from each other, and the crystals are dissolved in ether. After thoroughly washing with water to remove excess hydrogen chloride and drying, the crystals were dissolved in ethyl acetate.
Recrystallize from a methanol mixture to obtain high-purity hydrochloride (formula 1
).
上記の方法は、高純度の上記塩酸塩（式１）を得る方法
として一般的に用いられているが、工業的な見地からは
有利な方法であるとはいえない。The above method is generally used to obtain the above hydrochloride salt (Formula 1) with high purity, but it cannot be said to be an advantageous method from an industrial standpoint.
すなわち多量のエーテルを用いることは安全面から好ま
しくなく、酢酸エチル−メタノール混合液を用いて再結
晶することは混合溶媒であυ回収ができず、従って工業
的な製造の工程として望ましいものではない。In other words, using a large amount of ether is undesirable from a safety standpoint, and recrystallization using an ethyl acetate-methanol mixture is a mixed solvent and cannot be recovered, so it is not desirable as an industrial manufacturing process. .
本発明者らは、引火の危険の少ないクロルベンゼンが上
記反応の反応溶媒および式１の化合物の再結晶溶媒とし
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 little risk of ignition, is suitable as a reaction solvent for the above reaction and as a recrystallization solvent for the compound of formula 1, 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−（ツメチルアミノ）エトキシ〕カルバクロー
ルアセデート（式２）を、３０〜４０倍容量のクロルベ
ンゼンに溶解し、この溶液Ｖこ、室温で塩化水素ガスを
尋人し、次いで反応液を加熱還流し、一部析出した結晶
を溶解した後、所定の温度まで冷却する。冷却によって
析出した結晶をｐ取することによって高純度の上記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１）を、高収率で取得しうる。この
ようにして得た上記（式１）の塩酸塩は、そのまま医薬
品として使用しうる純度であるが、盛装に応じテ、クロ
ルベンゼンを用いて再結晶する。5-[2-(Tmethylamino)ethoxy]carvacrol acedate (Formula 2) is dissolved in 30 to 40 times the volume of chlorobenzene, hydrogen chloride gas is poured into the solution at room temperature, and then the reaction solution is is heated to reflux to dissolve some of the precipitated crystals, and then cooled to a predetermined temperature. By collecting the crystals precipitated by cooling, the above 5-
(2-(dimethylamino)ethoxy)carvacrol acetate hydrochloride (Formula 1) can be obtained in high yield. The hydrochloride of the above (Formula 1) thus obtained can be used as it is as a pharmaceutical. Depending on the purity, it is recrystallized using chlorobenzene depending on the packaging.
本発明の方法によれば粗製の５−ＣＺ−（ジメチルアミ
ノ）エトキシ」カルバクロールアセテート（式２）よシ
簡便な方法で、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１）を
高収率で製造することができる。According to the method of the present invention, highly pure 5-[2-(dimethylamino)
Ethoxy]carvacrol acetate hydrochloride (Formula 1) can be produced in high yield.
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
反応溶媒および再結晶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。In the present invention, chlorobenzene, which has little risk of ignition, is used as a reaction solvent and a recrystallization solvent, so it is particularly suitable as an industrial production method.
本発明の実施例を以下に示す。Examples of the present invention are shown below.
実施例
特願昭５６−８８８４９号の方法に準じて合成した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（式２）１４．０ノ（０，０５モル）を、クロ
ルベンゼン５６０ｍ１ｇ溶解し、この溶液に室温で、乾
燥塩化水素ガス約２．５Ｐ（０，０６９モル）を導入し
、白色結晶を析出せしめた後、この反応液を加熱還流し
、上記結晶を溶解せしめて得た、均一な溶液を放冷し、
次いで氷水で冷却した。析出した無色の針状結晶を戸数
し、目的とする５−〔２−（ツメチルアミノ）エトキシ
〕カルノぐクロールアセテート塩酸塩（式１）１５．２
１収率９６．０％）を得た。融点２１１．４〜２１３．
０℃。この結晶の一部をクロルベンゼンより再結晶して
融点２１１．４〜２１３．２℃の５−〔２−（ジメチル
アミン）エトキシ〕カルバクロールアセテート塩酸塩（
式１）を得た。Example 5- Synthesized according to the method of Japanese Patent Application No. 56-88849
(2-(dimethylamino)ethoxy)carvacrol acetate (Formula 2) (14.0 mol) was dissolved in 560 ml of chlorobenzene, and about 2.5 P (0.0 mol) of dry hydrogen chloride gas was dissolved in this solution at room temperature. .
It was then cooled with ice water. The precipitated colorless needle-like crystals were counted and the desired 5-[2-(tumethylamino)ethoxy]carnoguchloracetate hydrochloride (Formula 1) 15.2
1 yield 96.0%) was obtained. Melting point 211.4-213.
0℃. A part of this crystal was recrystallized from chlorobenzene to obtain 5-[2-(dimethylamine)ethoxy]carvacrol acetate hydrochloride (melting point 211.4-213.2°C).
Equation 1) was obtained.
この塩酸塩の元素分析値は次の通９でおった。The elemental analysis values of this hydrochloride were as follows.
Ｃ１６Ｉ（２６ＮＯ３Ｃ）として
Ｃ％ Ｈ係 Ｎ％
創 算（直 ６０．８５ ８．３０
４．４３実測値 ６０．６９ ８．３２
４．４１手隈六ネｉＴｉ正書（方式）
１１石１１５８年９月７日
特許庁長官 若 杉 和 夫殿
１、事１牛の表示
昭和５７６回ケ許願第４８１４９号
２、発明の名称
カルバクロール誘導体の製法
３、補正をする者
４、補正命令の日付
ＩＩ汀トロ５８年８月１０日 （発送日 ■守口５８年
８月３０日）５、ネｄｉ正の対象
明Ｘａｌ＋利の発明の名称の欄
６、補正の内容
（１１明細Ｗの発明の名称を「カルバクロール誘導体の
製法」に訂正する。As C16I (26NO3C), C% H section N% Sokan (Direct 60.85 8.30
4.43 Actual value 60.69 8.32
4.41 Rokune Teguma iTi official text (method) 11 stones 1158 September 7, Director General of the Patent Office Kazuo Wakasugi 1. Cow indication No. 48149 1987 2. Name of the invention Calva Process for producing chloride derivatives 3, Person making the amendment 4, Date of amendment order II, August 10, 1958 (Shipping date ■August 30, 1958) 5, Subject of Nedi Masaaki Name column 6, Contents of amendment (11 The title of the invention in Specification W is corrected to "Process for producing carvacrol derivatives."
Claims (1)
カルパクロールアセテートヲ、クロルベンゼンに溶解し
、この溶液に塩化水素を導入す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の製造方法。[Claims] 5-(2-(dimethylamino)ethoxy represented by the formula)
A method for producing 5-[2-dimethylamino]ethoxy]carvacrol acetate hydrochloride, comprising the steps of dissolving carpacrol acetate in chlorobenzene and introducing hydrogen chloride into this solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4814982A JPS5925357A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4814982A JPS5925357A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5925357A true JPS5925357A (en) | 1984-02-09 |
| JPH029574B2 JPH029574B2 (en) | 1990-03-02 |
Family
ID=12795300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4814982A Granted JPS5925357A (en) | 1982-03-27 | 1982-03-27 | Preparation of carvacrol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5925357A (en) |
-
1982
- 1982-03-27 JP JP4814982A patent/JPS5925357A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH029574B2 (en) | 1990-03-02 |
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