JPS61260073A - Production of 1-amidino-4-formylpiperazine - Google Patents
Production of 1-amidino-4-formylpiperazineInfo
- Publication number
- JPS61260073A JPS61260073A JP60101877A JP10187785A JPS61260073A JP S61260073 A JPS61260073 A JP S61260073A JP 60101877 A JP60101877 A JP 60101877A JP 10187785 A JP10187785 A JP 10187785A JP S61260073 A JPS61260073 A JP S61260073A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- amidino
- amidinopiperazine
- compound
- formic acid
- 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
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明はｌ−７ミジノー４−ホルミルピペラジン類又は
その鉱酸塩の製造法に関する。さらに詳し、くは１−ア
ミジノピペラジン類またはその鉱酸塩を蟻酸と反応させ
てｌ−７ミジノー４−ホルミルピペラジン類を製造する
方法に関する。１−７ミジノー４−ホルミルピペラジン
類又はその鉱酸塩は、医薬品合成用の中間体として極め
て重要な化合物である。・
ｌ−７ミジノー４−ホルミルピペラジン類又はその鉱酸
塩の製造法としては、従来より１−ホルミルピペラジン
とエチル又はメチル−チオメタンイミダミドの鉱酸塩を
反応させて、１−アミジノ−４−ホルミルピペラジンを
得る方法（米国特許４２５８１８８）が知られている。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for producing l-7midino-4-formylpiperazines or mineral acid salts thereof. More specifically, the present invention relates to a method for producing 1-7midino-4-formylpiperazines by reacting 1-amidinopiperazines or mineral acid salts thereof with formic acid. 1-7 midino-4-formylpiperazines or their mineral acid salts are extremely important compounds as intermediates for pharmaceutical synthesis.・ As a method for producing l-7midino-4-formylpiperazines or mineral acid salts thereof, conventionally, 1-formylpiperazine and a mineral acid salt of ethyl or methyl-thiomethanimidamide are reacted to form 1-amidino-4 - A method for obtaining formylpiperazine (US Pat. No. 4,258,188) is known.
しかし、この方法によれば原料の１−ホルミルピペラジ
ンを製造するにあたって、副生成物が多く、分離・精製
が容易でなく、かつ高価となるため、これを用いてのｌ
−アミジノ−４−ホルミルピペラジン類又はその鉱酸塩
の工業的製造法としては満足すべきものではない。However, according to this method, when producing the raw material 1-formylpiperazine, there are many by-products, separation and purification are not easy, and it is expensive.
This method is not satisfactory as an industrial method for producing -amidino-4-formylpiperazines or mineral acid salts thereof.
す ための
本発明は斯かる現状に鑑み、１−１ミジノ−４−ホルミ
ルピペラジン類又はその鉱酸塩の製造法を開発すべく、
鋭意研究を重ねた結果、ついに本発明を完成するに至っ
たものである。In view of the current situation, the present invention aims to develop a method for producing 1-1 midino-4-formylpiperazines or mineral acid salts thereof.
As a result of extensive research, we have finally completed the present invention.
即ち、本発明は一般式（Ｉ）
（式中、Ｒ１、Ｒ２は水素原子又は低級アルキル基を表
わす）
で示される１−アミジノピペラジン類又はその鉱酸塩と
蟻酸を、温度８０〜１３０℃の範囲で反応させることに
よる、一般式（２）（式中、Ｒ１、Ｒ２は前記と同じ）
で示される１−アミジノ−４−ホルミルピペラジン類又
はその鉱酸塩の製造法に係る。That is, the present invention provides 1-amidinopiperazines represented by the general formula (I) (wherein R1 and R2 represent a hydrogen atom or a lower alkyl group) or a mineral acid salt thereof and formic acid at a temperature of 80 to 130°C. The present invention relates to a method for producing 1-amidino-4-formylpiperazines represented by the general formula (2) (wherein R1 and R2 are the same as above) or a mineral acid salt thereof, by reacting at a temperature within a range of 1 to 2.
本発明における出発原料である１−アミジノピペラジン
類とは、一般式（Ｉ）で示される化合物であり、具体的
には１−アミジノピペラジン、１−アミジノ−２−メチ
ルピペラジン、１−アミジノ−３−メチルピペラジン、
１−ア更シノー２．５−ジメチルピペラジン、１−アミ
ジノ−２，６−ジメチルピペラジン、１−アミジノ−２
−エチルピペラジン、１−アミジノ−３−エチルピペラ
ジン等が挙げられる。1-amidinopiperazine, which is a starting material in the present invention, is a compound represented by the general formula (I), and specifically, 1-amidinopiperazine, 1-amidino-2-methylpiperazine, 1-amidino-3 - methylpiperazine,
1-amidino-2,5-dimethylpiperazine, 1-amidino-2,6-dimethylpiperazine, 1-amidino-2
-ethylpiperazine, 1-amidino-3-ethylpiperazine, and the like.
本発明における鉱酸塩としては、塩酸塩・臭化水素酸塩
・硫酸塩・硝酸塩・燐酸塩・炭酸塩等が挙げられる。Examples of mineral acid salts in the present invention include hydrochlorides, hydrobromides, sulfates, nitrates, phosphates, carbonates, and the like.
本発明の方法としては、反応容器に一般式（Ｉ）に示さ
れる１−アミジノピペラジン類又はその鉱酸塩と蟻酸、
不活性溶媒（又は未使用）を仕込み、攪拌下に反応を行
なうことにより、高収率で１−アミジノ−４−ホルミル
ピペラジン類又はその鉱酸塩が生成される。In the method of the present invention, a 1-amidinopiperazine represented by general formula (I) or a mineral acid salt thereof and formic acid are placed in a reaction vessel.
By charging an inert solvent (or unused) and carrying out the reaction with stirring, 1-amidino-4-formylpiperazines or mineral acid salts thereof are produced in high yield.
反応溶媒としては、通常水が用いられるが必要ならばメ
タノール、エタノール、プロパツールの様な低級アルコ
ール類や、ベンゼン、い。As a reaction solvent, water is usually used, but if necessary, lower alcohols such as methanol, ethanol, propatool, or benzene may be used.
反応温度としては、８０℃〜１３０℃の範囲であるが、
好ましくは１００〜１３０℃の範囲である。又、反応時
間は１時間以上であれば特に限定されないが、好ましく
は２〜１０時間の範囲である。The reaction temperature is in the range of 80°C to 130°C,
Preferably it is in the range of 100 to 130°C. Further, the reaction time is not particularly limited as long as it is 1 hour or more, but is preferably in the range of 2 to 10 hours.
本反応に使用される蟻酸の量は、１−アミジノ−ピペラ
ジン類又はその鉱酸塩に対して、当モル以上あれば、特
に限定されないが、好ましくは当モル〜５倍モルの範囲
である。The amount of formic acid used in this reaction is not particularly limited as long as it is equal to or more than 1 mole of 1-amidino-piperazines or mineral acid salts thereof, but is preferably in the range of 1 to 5 moles.
発明の効果
本発明の反応で、生成される１−７ミジノー４−ホルミ
ルピペラジン類又はその鉱酸塩は、例えば反応液を濃縮
すれば、メタノールを加え、ｐ別するだけで反応液から
容易に分離・精製される。Effects of the Invention The 1-7 midino-4-formylpiperazines or mineral acid salts thereof produced in the reaction of the present invention can be easily removed from the reaction solution by simply adding methanol and separating the solution, for example, by concentrating the reaction solution. Separated and purified.
また１−７ミジノピペラジン類又はその鉱酸塩に対して
、高収率で得ることが出き、しかも反応が極めて高選択
的に起こるために、目的物の分離・精製が極めて容易で
あり、高純度の１−７ミジノー４−ホルミルピペラジン
類又はその鉱酸塩が得られるという利点があり、工業的
にも極めて有利で菖る。In addition, 1-7 midinopiperazines or their mineral salts can be obtained in high yields, and the reaction occurs with extremely high selectivity, making separation and purification of the target product extremely easy. This method has the advantage of producing highly pure 1-7 midino-4-formylpiperazines or mineral acid salts thereof, and is extremely advantageous from an industrial perspective.
実施例
以下に実施例を掲げて本発明を具体的に説明するが、本
発明はこれら実施例に限定されるものではない。EXAMPLES The present invention will be specifically explained with reference to Examples below, but the present invention is not limited to these Examples.
実施例１
温度計、攪拌器、滴下ロート、還流冷却器の備わった１
００−の四ツロフラスコに、１−アミジノピペラジンの
−Ｌ Ｈ２ＳＯ４塩２（Ｉ（０，１１３％Ｊｌ／） ト
８Ｑ９７；蟻酸１３ Ｆ（０，２２６モル）を仕込み、
内温１１５℃で２時間攪拌した。次いで、減圧下に水と
過剰量の蟻酸を留去し、内温５０℃でメタノール５０−
を仕込んで、３０分間の攪拌を行なった。内温を室温ま
で冷却し、反応物を濾過し、結晶をメタノール５０−で
洗浄して、乾燥したｌ−アニジノー４−ホル電ルビペラ
ジンの−ｙ ＨｓＳＯ４塩２ Ｇ、 ４ ｆを得た。、
１−アミジノピペラジンのΣＨ２ＳＯ４塩に対する１−
アミジノ−４−ホルミルピペラジンの４Ｈ２ＳＯａ塩の
収率は、８８．１％であった。Example 1 1 equipped with a thermometer, stirrer, dropping funnel, and reflux condenser
00- was charged with 1-amidinopiperazine -L H2SO4 salt 2(I (0,113% Jl/) 8Q97; formic acid 13F (0,226 mol),
The mixture was stirred for 2 hours at an internal temperature of 115°C. Next, water and excess formic acid were distilled off under reduced pressure, and methanol was added at an internal temperature of 50°C.
was charged and stirred for 30 minutes. The internal temperature was cooled to room temperature, the reaction product was filtered, and the crystals were washed with 50-methanol to obtain the dried -y HsSO4 salt of l-anidino-4-phorubiperazine 2G, 4f. ,
1- for ΣH2SO4 salt of 1-amidinopiperazine
The yield of the 4H2SOa salt of amidino-4-formylpiperazine was 88.1%.
実施例２
反応后、水と蟻酸の留去を行わなかった他は、実施例１
と同操作を行なった所、１−アミジノ−４−ホルミルピ
ペラジンのＬ Ｈ！ｌ！ＳＯ４塩ｘｓｙを得たつ（収率
６４．８％）
実施例３
１−アミジノピペラジンの”−Ｈ１ｔ！ＳＯａ塩の代り
に、１−アミ１シノー２．５−ジメチルピペー１０、
ｌ
フンノのｉ門２．５Ｏ４２３ｆ （，０，、＄ １３モ
ル）を使用した他゛は、実施例１と同様に操９作した所
、１−ホルミル−２，５−ジメチル−４・−ホル。Example 2 Example 1 except that water and formic acid were not distilled off after the reaction.
When the same operation was performed, LH! of 1-amidino-4-formylpiperazine was obtained. l! SO4 salt xsy was obtained (yield 64.8%) Example 3 Instead of "-H1t!SOa salt of 1-amidinopiperazine, 1-amidinopiperazine 2.5-dimethyl pipet 10,
1-Formyl-2,5-dimethyl-4-formyl-2-formyl-2,5-dimethyl-4-formyl .
ミルピペラジンの４Ｈ２ＳＯａ ２２．４１を得た。4H2SOa of milpiperazine 22.41 was obtained.
（収率８５％）(yield 85%)
Claims (1)
を表わす） で示される１−アミジノピペラジン類又はその鉱酸塩と
蟻酸を温度８０〜１３０℃の範 囲で反応させることを特徴とする一般式（２）▲数式、
化学式、表等があります▼（２） （式中、Ｒ＾１、Ｒ＾２は前記と同じ） で示される１−アミジノ−４−ホルミル ピペラジン類を製造する方法。[Claims] General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1 and R^2 represent a hydrogen atom or a lower alkyl group) 1- General formula (2) ▲ mathematical formula, characterized by reacting amidinopiperazines or their mineral acid salts with formic acid at a temperature in the range of 80 to 130°C,
There are chemical formulas, tables, etc. ▼(2) (In the formula, R^1 and R^2 are the same as above) Method for producing 1-amidino-4-formylpiperazines.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60101877A JPS61260073A (en) | 1985-05-13 | 1985-05-13 | Production of 1-amidino-4-formylpiperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60101877A JPS61260073A (en) | 1985-05-13 | 1985-05-13 | Production of 1-amidino-4-formylpiperazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61260073A true JPS61260073A (en) | 1986-11-18 |
| JPH0578549B2 JPH0578549B2 (en) | 1993-10-29 |
Family
ID=14312187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60101877A Granted JPS61260073A (en) | 1985-05-13 | 1985-05-13 | Production of 1-amidino-4-formylpiperazine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61260073A (en) |
-
1985
- 1985-05-13 JP JP60101877A patent/JPS61260073A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0578549B2 (en) | 1993-10-29 |
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