JPS6143168A - Production of hydantoin - Google Patents

Production of hydantoin

Info

Publication number
JPS6143168A
JPS6143168A JP16383584A JP16383584A JPS6143168A JP S6143168 A JPS6143168 A JP S6143168A JP 16383584 A JP16383584 A JP 16383584A JP 16383584 A JP16383584 A JP 16383584A JP S6143168 A JPS6143168 A JP S6143168A
Authority
JP
Japan
Prior art keywords
glycinonitrile
alkali metal
aqueous solution
reaction
hydantoin
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
Application number
JP16383584A
Other languages
Japanese (ja)
Other versions
JPH0524898B2 (en
Inventor
Fumihiko Shiyouga
文彦 庄賀
Toshio Morita
利夫 森田
Kazuo Nakayasu
一雄 中安
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Resonac Holdings Corp
Original Assignee
Showa Denko KK
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Showa Denko KK filed Critical Showa Denko KK
Priority to JP16383584A priority Critical patent/JPS6143168A/en
Publication of JPS6143168A publication Critical patent/JPS6143168A/en
Publication of JPH0524898B2 publication Critical patent/JPH0524898B2/ja
Granted legal-status Critical Current

Links

Abstract

PURPOSE:To obtain hydantoin useful as an intermediate for synthesizing drugs and agricultural chemicals, by using glycinonitrile as a starting substance, reacting it with an alkali metal bicarbonate or an alkali metal hydroxide and carbon dioxide, or their mixture in an aqueous solvent. CONSTITUTION:For example, glycolonitrile is reacted with ammonia to give glycinonitrile, which is reacted with an alkali metal bicarbonate in an aqueous solution or an aqueous solution containing a hydrophilic solvent at 60 deg.C or at >=60 deg.C to give hydantion, or, in the reaction, CO2 is added to the aqueous solution or the aqueous solution containing a hydrophilic solvent of glycinonitrile and an alkali metal hydroxide, and reaction is carried out at >=60 deg.C. Introduction of CO2 into the system can prevent decomposition of glycinonitrile, coloring is further reduced, and excess CO2 can be easily recovered and reused by using the alkali metal hydroxide.

Description

【発明の詳細な説明】 本発明は医薬及び農薬合成の中間体とじて有用なヒダン
トインの新規な製造法に関するものである。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing hydantoins useful as intermediates in the synthesis of pharmaceuticals and agricultural chemicals.

従来、ヒダントインの製造はシア、7.、#塩を用いる
方法と、いわゆるBu c b e r e r −B
 e r g s法によっている。しかし、この方法は
一般的に低収率であり、種々の改良法か報告されている
。例えは、グリコロニトリルと重炭酸アンモニウムを密
閉加圧下に反応させた後、酸処理を行なう方法(特公昭
39−24807)や、グリコロニトリルと重炭酸アン
モニウムを常圧上第2級アミン又は第3級アミンの存在
下で反応させる方法(特開昭5O−671)等がある。
Conventionally, hydantoin was produced using shea, 7. , #method using salt and the so-called Bu c b e r e r -B
It is based on the ERGS method. However, this method generally has a low yield, and various improved methods have been reported. For example, there is a method in which glycolonitrile and ammonium bicarbonate are reacted under closed pressure and then treated with an acid (Japanese Patent Publication No. 39-24807), or glycolonitrile and ammonium bicarbonate are reacted under normal pressure with a secondary amine or There is a method of reacting in the presence of a tertiary amine (Japanese Patent Application Laid-Open No. 50-671).

しかし、これらの方法は、グリコロニトリルが特に不安
定であり、この分解が反応生成物の着色の原因になる、
密閉加圧下で反応を行なうためには耐圧設備が必要であ
る、などの操作上及び設備上の問題点があった。
However, these methods require that glycolonitrile is particularly unstable and this decomposition causes coloration of the reaction product.
There were operational and equipment problems, such as the need for pressure-resistant equipment in order to carry out the reaction under closed pressure.

本発明者らは、このような問題点を克服するために鋭意
検討した結果、グリシノニトリルを水性溶液中で、アル
カリ金属の重炭酸塩もしくはアルカリ金属の水酸化物と
2酸化炭素、またはこれらの混合物と反応させることに
よりヒダントインが得られることを見いだし本発明を完
成するに至った。
As a result of intensive studies to overcome these problems, the present inventors have found that glycinonitrile can be mixed with alkali metal bicarbonate or alkali metal hydroxide and carbon dioxide, or with carbon dioxide in an aqueous solution. The present inventors have discovered that hydantoin can be obtained by reacting with a mixture of the following, and have completed the present invention.

本発明での作用機構については必ずしも明らかではない
が、グリシノニトリルと重炭酸塩よりの重炭酸イオン(
HCO3”’)との反応と思われ、このことは従来知ら
れていなかった。すなわち従来ヒダントインの生成は、
カルバミン酸(Nl2 C00H)によるとされている
。(王化誌旦旦、494 (1964)) 次に、本発明をさらに詳細に説明する。
Although the mechanism of action in the present invention is not necessarily clear, the bicarbonate ion produced by glycinonitrile and bicarbonate (
This is thought to be a reaction with HCO3"'), and this was not previously known. In other words, the production of hydantoin was
It is said to be due to carbamic acid (Nl2C00H). (Wangka Ji Dandan, 494 (1964)) Next, the present invention will be explained in more detail.

本発明を実施するには、まずグリシノニトリルとアルカ
リ金属の重炭酸塩を、水溶液あるいは親水性溶媒を含む
水溶液中にて、60°Cあるいはそれより高い温度下で
反応させる。この際、グリシノニトリルとアルカリ金属
の水酸化物の水溶液あるいは親水性i容媒を含む水溶液
に2酸化炭素を加え60°Cあるいはそれより高い温度
下で反応させてもよい。
To carry out the present invention, glycinonitrile and an alkali metal bicarbonate are first reacted in an aqueous solution or an aqueous solution containing a hydrophilic solvent at a temperature of 60° C. or higher. At this time, carbon dioxide may be added to an aqueous solution of glycinonitrile and an alkali metal hydroxide or an aqueous solution containing a hydrophilic i-vehicle and the reaction may be carried out at a temperature of 60° C. or higher.

前者の方法において、系内に2rti化炭素を吹き込む
ことによりグリシノニトリルの分解が防止され、着色が
一層少ないなと、さらに好ましい結果が得られる。この
場合、余剰の2酸化炭素はアルカリ金属の水酸化物を用
いることにより容易に回収、再使用できる。
In the former method, the decomposition of glycinonitrile is prevented by blowing 2rti carbon into the system, and more favorable results such as less coloring can be obtained. In this case, excess carbon dioxide can be easily recovered and reused by using an alkali metal hydroxide.

反応終了後、反応生成物を冷却し、得られる白色結晶を
ろ別し、水より再結晶してヒダントインを得る。あるい
は、反応生成物に酸を加え加熱した後冷却すれば、副生
ずるヒダントイン酸が環化されてヒダントインになりさ
らに好ましい結果が得られる。
After the reaction is completed, the reaction product is cooled, and the resulting white crystals are filtered off and recrystallized from water to obtain hydantoin. Alternatively, if an acid is added to the reaction product, heated, and then cooled, the by-produced hydantoic acid is cyclized to hydantoin, and a more preferable result can be obtained.

本発明で使用するグリシノニトリルは、例えば、グリコ
ロニトリルとアンモニアと8反応物を直接、あるいはそ
の精製物、また(よその水溶液などを用いることができ
る。
As the glycinonitrile used in the present invention, for example, a reaction product of glycolonitrile, ammonia, and 8 can be used directly, or a purified product thereof, or an aqueous solution of another product can be used.

アルカリ金属の重炭酸塩としては、重炭酸カリウム、重
炭酸ナトリウム、重炭酸リチウム(溶液中でのみ存在)
などを使用することができる。
Alkali metal bicarbonates include potassium bicarbonate, sodium bicarbonate, and lithium bicarbonate (present only in solution)
etc. can be used.

また、水酸化カリウム、水酸化ナトリウム、水酸化リチ
ウムの水溶液あるいは親水性溶媒を含む水溶液に2酸化
炭素を作用させてもよい。
Further, carbon dioxide may be allowed to act on an aqueous solution of potassium hydroxide, sodium hydroxide, lithium hydroxide, or an aqueous solution containing a hydrophilic solvent.

親水性溶媒としては、メタノール、エタノール、エチレ
ングリコール、トリメチレングリコールなとのアルコー
ル水溶液、その他ジオキサンなどが適宜用いられる。
As the hydrophilic solvent, aqueous alcohol solutions such as methanol, ethanol, ethylene glycol, trimethylene glycol, and dioxane are used as appropriate.

また、反応に用いられる金属の重炭酸塩の量は必ずしも
制限はないが、グリシノニトリル1モルに対して一般に
2から1c!モルてあり、好ましくは3から5モルであ
る。反応中CO2ガスを吹き込む場合はグリシノニトリ
ル1モルに対して一般に0.5から5モルであり、好ま
しくは0゜6から2モルである。
Further, the amount of metal bicarbonate used in the reaction is not necessarily limited, but is generally 2 to 1 c! for 1 mole of glycinonitrile. mol, preferably 3 to 5 mol. When blowing CO2 gas during the reaction, it is generally 0.5 to 5 mol, preferably 0.6 to 2 mol, per 1 mol of glycinonitrile.

反応温度についても厳密な制限はないが、通常60から
100″Cであり、さらに好ましくは66から80″C
である二            次に本発明の方法に
ついて代表的な実施例を示しさらに詳細に説明するが、
これらは説明のための単なる例示であり、従って本発明
はこれら  ゛の例によって同等制限されるものではな
い。
There is no strict limit to the reaction temperature, but it is usually 60 to 100"C, more preferably 66 to 80"C.
Next, representative examples of the method of the present invention will be shown and explained in more detail.
These are merely illustrative examples, and the invention is therefore not equally limited by these examples.

グリシノニトリル28.0g (0,5モル)、重炭酸
カリウム150g (1,5モル)を水400rxlに
加える。
28.0 g (0.5 mol) of glycinonitrile and 150 g (1.5 mol) of potassium bicarbonate are added to 400 rxl of water.

70℃まで昇温すると均一になる。そのまま約5時間反
応させる。反応後この水溶液を冷却したところ、沈殿を
生じた。沈殿物をろ過し、水より再結晶し、白色結晶1
4.5gを得た。この結晶は、IR,NMR5元素分析
よりヒダンi・インと固定された。
When the temperature is raised to 70°C, it becomes uniform. Let it react as it is for about 5 hours. When this aqueous solution was cooled after the reaction, precipitation occurred. Filter the precipitate and recrystallize from water to obtain white crystals 1
4.5g was obtained. This crystal was fixed as hydan-i-in by IR and NMR five-element analysis.

実施例2 グリシノニトリル25.5g 、(0,4E1モル)、
水酸化ナトリウム24g (0,60モル)を水300
m1に加える。この水溶液にCO2ガスを0,5モル/
hrで吹き込みながら、75°C!で昇温し、 5時間
反応する。得られた反応液の゛液クロ分析からヒダント
インがグリシノニトリルに対して、45%の収率で生じ
ていることが確かめられた。また、Bucherer 
−Be rgs法でよく見られるヒダントイン酸、ヒダ
ントイン酸アミドは、殆ど生成していないこともゎ明親
書の浄書(内容に変更なし) かった。
Example 2 25.5 g of glycinonitrile (0.4E1 mol),
24 g (0.60 mol) of sodium hydroxide in 300 g of water
Add to m1. Add 0.5 mol/CO2 gas to this aqueous solution.
75°C while blowing with hr! Raise the temperature and react for 5 hours. Liquid chromatography analysis of the resulting reaction solution confirmed that hydantoin was produced at a yield of 45% based on glycinonitrile. Also, Bucherer
It was also found that hydantoic acid and hydantoic acid amide, which are commonly found in the Bergs method, were hardly produced.

実施例3 重炭醜ナトリウム50g (0,80モル)を水300
1に加え、80°Cに昇温する。得られた水溶液に、 
  C02ガスを0.8モル/hrで吹き込みながら、
グリシノニトリルを0.2モル/hrで加えた。 5時
間後グリコロニトリル添加を止めて、さらに5時間加水
より再結晶し、85gのヒダントインを得た。
Example 3 50 g (0.80 mol) of heavy carbon sodium was added to 300 g of water.
Add to step 1 and raise the temperature to 80°C. In the resulting aqueous solution,
While blowing CO2 gas at 0.8 mol/hr,
Glycinonitrile was added at 0.2 mol/hr. After 5 hours, the addition of glycolonitrile was stopped, and the mixture was recrystallized by adding water for another 5 hours to obtain 85 g of hydantoin.

実施例4 グリシノニトリル9.5g (0,17モル)、重炭酸
カリウム50g(0,5モル)を30%メタノール水溶
冶300rnに加え、60’Cで7.5時間反応した。
Example 4 9.5 g (0.17 mol) of glycinonitrile and 50 g (0.5 mol) of potassium bicarbonate were added to a 300 rn 30% methanol water solution and reacted at 60'C for 7.5 hours.

反応液の液クロ分析からヒダントインが50%の収率て
生成していた。
Liquid chromatography analysis of the reaction solution revealed that hydantoin was produced at a yield of 50%.

特 許 出 願 人   昭和電工株式会社手 続 補
 正 書(方式) 昭和53年12月夕日
Patent applicant Showa Denko Co., Ltd. Procedure amendment (method) Sunset in December 1978

Claims (1)

【特許請求の範囲】[Claims] グリシノニトリルを水性溶液中で、アルカリ金属の重炭
酸塩もしくはアルカリ金属の水酸化物と2酸化炭素また
はこれらの混合物と反応させることを特徴とするヒダン
トインの製造方法。
A method for producing hydantoins, which comprises reacting glycinonitrile with an alkali metal bicarbonate or an alkali metal hydroxide and carbon dioxide or a mixture thereof in an aqueous solution.
JP16383584A 1984-08-06 1984-08-06 Production of hydantoin Granted JPS6143168A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP16383584A JPS6143168A (en) 1984-08-06 1984-08-06 Production of hydantoin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP16383584A JPS6143168A (en) 1984-08-06 1984-08-06 Production of hydantoin

Publications (2)

Publication Number Publication Date
JPS6143168A true JPS6143168A (en) 1986-03-01
JPH0524898B2 JPH0524898B2 (en) 1993-04-09

Family

ID=15781646

Family Applications (1)

Application Number Title Priority Date Filing Date
JP16383584A Granted JPS6143168A (en) 1984-08-06 1984-08-06 Production of hydantoin

Country Status (1)

Country Link
JP (1) JPS6143168A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7569701B2 (en) 2002-04-10 2009-08-04 Nippon Zoki Pharmaceutical Co., Ltd. Crystal form of 5-hydroxy-1-methylimidazolidin-2,4-dione

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7569701B2 (en) 2002-04-10 2009-08-04 Nippon Zoki Pharmaceutical Co., Ltd. Crystal form of 5-hydroxy-1-methylimidazolidin-2,4-dione
US7858806B2 (en) 2002-04-10 2010-12-28 Nippon Zoki Pharmaceutical Co., Ltd. Crystal form of 5-hydroxy-1-methylhydantoin

Also Published As

Publication number Publication date
JPH0524898B2 (en) 1993-04-09

Similar Documents

Publication Publication Date Title
JPS6351358A (en) Production of ditertiary butyl dicarbonate
US4230869A (en) Process for preparing 5-(4-hydroxyphenyl)hydantoin
JPS6143168A (en) Production of hydantoin
Aresta et al. Reaction of alkali-metal tetraphenylborates with amines in the presence of CO2: a new easy way to aliphatic and aromatic alkali-metal carbamates
JPS62286964A (en) Production of oxiracetam
AU723133B2 (en) Process for producing 1-chlorocarbonyl-4-piperidinopiperidine or hydrochloride thereof
JP3061315B2 (en) Method for producing dialkyl dicarbonate
JPS61212567A (en) Method for preventing discoloration in production of hydantoin
JPS6178769A (en) Production of hydantoin
US4082752A (en) Process for fluorination of uracil
US4084056A (en) Method of producing substituted phenyl carbamates
JPH07252205A (en) Method for producing oxyamine compounds
JP3040265B2 (en) Method for producing dialkyl dicarbonate
JPH04295456A (en) Method of manufacturing n-monosubstituted or n,n- disubstituted urea
JPH03181458A (en) Production of oxiracetam
JPH09202751A (en) Production of di-tertiary-butyl dicarbonate
JPH08157444A (en) Production of aminoethanesulfonic acid
JPH09176101A (en) Production of p-nitrophenylhydrazine
JPH0489466A (en) Production of 0-methylisourea sulfate
JPH09255644A (en) Production of adipic acid dihydrazide
JPH0859594A (en) Production of n-mono-t-butyloxycarbonyl alkylenediamine
JP2003321458A (en) Method for producing hydantoin
JPH0665168A (en) Method for purifying glycine
EP0078853A1 (en) Process for preparing beta-chloroalanine
JPS6183164A (en) Preparation of hydrantoin

Legal Events

Date Code Title Description
EXPY Cancellation because of completion of term