JPH08198836A - Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide - Google Patents
Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimideInfo
- Publication number
- JPH08198836A JPH08198836A JP7031528A JP3152895A JPH08198836A JP H08198836 A JPH08198836 A JP H08198836A JP 7031528 A JP7031528 A JP 7031528A JP 3152895 A JP3152895 A JP 3152895A JP H08198836 A JPH08198836 A JP H08198836A
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- dimethylaminopropyl
- carbodiimide
- reaction
- water
- 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
【０００１】[0001]
【産業上の利用分野】この発明は、医薬、農薬などの合
成、製造時の脱水縮合剤、さらには有機合成用中間体と
して有用な１−エチル−３−（３−ジメチルアミノプロ
ピル）カルボジイミドの効率的な製造方法に関するもの
である。FIELD OF THE INVENTION The present invention relates to a dehydration-condensation agent at the time of synthesizing and manufacturing medicines, agricultural chemicals, etc., and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide useful as an intermediate for organic synthesis. The present invention relates to an efficient manufacturing method.
【０００２】[0002]
【従来の技術】カルボジイミド化合物は、幅広い分野で
利用され、エステル化、アミド化などの脱水縮合反応を
非常に緩和な条件下で反応を進行させることのできる縮
合剤である。特に親水性基を有する１−エチル−３−
（３−ジメチルアミノプロピル）カルボジイミドは、水
溶性カルボジイミドとして知られており、水溶媒中での
反応が可能であることはもとより、有機溶媒中で反応し
た際も生成する尿素体を水洗により除去でき、光学活性
化合物の脱水縮合時にはラセミ化も少ないなど数多くの
利点があり、ジシクロヘキシルカルボジイミドならびに
汎用のカルボジイミドよりも優れている。2. Description of the Related Art Carbodiimide compounds are condensing agents which are used in a wide variety of fields and are capable of advancing dehydration condensation reactions such as esterification and amidation under extremely mild conditions. Especially 1-ethyl-3- having a hydrophilic group
(3-Dimethylaminopropyl) carbodiimide is known as a water-soluble carbodiimide, and not only is it possible to react in an aqueous solvent, but it is also possible to remove the urea body produced during the reaction in an organic solvent by washing with water. However, it has many advantages such as less racemization during dehydration condensation of an optically active compound, and is superior to dicyclohexylcarbodiimide and general-purpose carbodiimide.
【０００３】従来、１−エチル−３−（３−ジメチルア
ミノプロピル）カルボジイミドの合成法としては J.Or
g.Chem.，26 2525（1961）に２種の方法が開示されてい
る。さらに述べるならば、イソシアン酸エチルとＮ，Ｎ
−ジメチル−１，３−プロパンジアミンとを付加反応
し、１−エチル−３−（３−ジメチルアミノプロピル）
尿素を得、これを脱水反応をする方法と、イソチオシア
ン酸エチルとＮ，Ｎ−ジメチル−１，３プロパンジアミ
ンとを付加反応し、１−エチル−３−（３−ジメチルア
ミノプロピル）チオ尿素を脱硫化水素する方法である。Conventionally, J. Or has been used as a synthetic method of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide.
Two methods are disclosed in g. Chem., 26 2525 (1961). More specifically, ethyl isocyanate and N, N
-Addition reaction with dimethyl-1,3-propanediamine, 1-ethyl-3- (3-dimethylaminopropyl)
Urea is obtained, and a method of dehydrating this is used, and ethyl isothiocyanate and N, N-dimethyl-1,3 propanediamine are subjected to an addition reaction to give 1-ethyl-3- (3-dimethylaminopropyl) thiourea. It is a method of desulfurizing hydrogen.
【０００４】うち、後者記載の１−エチル−３−（３−
ジメチルアミノプロピル）チオ尿素を脱硫化水素する方
法としては、酸化水銀、酸化亜鉛さらには、酸化銅など
の脱硫剤によるものが一般的である。またその他の脱硫
化水素の反応としては、ジシクロヘキシルカルボジイミ
ドなどの製造方法で開示されている特開昭５９−７１４
８号においてはＮ置換アミンハライドを利用し、特開平
５−４９５７号ではアルカリ金属塩存在下、次亜塩素酸
塩による方法が開示されている。しかしながら水溶性カ
ルボジイミドである１−エチル−３−（３−ジメチルア
ミノプロピル）カルボジイミドでの脱硫化水素法として
次亜塩素酸塩類の水溶液を適用した例はない。Of these, 1-ethyl-3- (3-
As a method for desulfurizing dimethylaminopropyl) thiourea, a method using a desulfurizing agent such as mercury oxide, zinc oxide and copper oxide is generally used. As another reaction of desulfurized hydrogen, a method for producing dicyclohexylcarbodiimide and the like is disclosed in JP-A-59-714.
No. 8 utilizes an N-substituted amine halide, and JP-A-5-4957 discloses a method using hypochlorite in the presence of an alkali metal salt. However, there is no example in which an aqueous solution of hypochlorites is applied as a desulfurization method using 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, which is a water-soluble carbodiimide.
【０００５】[0005]
【発明が解決しようとする課題】１−エチル−３−（３
−ジメチルアミノプロピル）カルボジイミドを効率良
く、工業的に製造する際、従来の技術として開示されて
いる、１−エチル−３−（３−ジメチルアミノプロピ
ル）尿素を脱水反応により得る方法は、反応中間体であ
る尿素体の基本原料であるイソシアン酸エチルの供給の
問題、さらにはその高い毒性と爆発性のために、安全性
の上からも不利である。これに比べ、１−エチル−３−
（３−ジメチルアミノプロピル）チオ尿素からの脱硫化
水素反応による合成法は、原料の入手、取り扱い共に簡
便である。1-Ethyl-3- (3
The method for obtaining 1-ethyl-3- (3-dimethylaminopropyl) urea by a dehydration reaction, which has been disclosed as a conventional technique when efficiently and industrially producing (dimethylaminopropyl) carbodiimide, is a reaction intermediate. It is also disadvantageous in terms of safety due to the problem of supply of ethyl isocyanate, which is the basic raw material for the urea body, and its high toxicity and explosiveness. Compared with this, 1-ethyl-3-
The synthetic method by the dehydrosulfurization reaction from (3-dimethylaminopropyl) thiourea is easy in terms of both acquisition and handling of raw materials.
【０００６】しかし J.Org.Chem.，26 2525（1961）や
特開平４−７７４６４号などに開示されているように、
脱硫剤として酸化水銀、酸化鉛さらには酸化銅などの重
金属が開示されているが、これらの毒性や廃水への微量
混入など、取り扱い上注意しなければならない問題点が
ある。また、その反応収率が必ずしも満足のいくもので
はなく、工業化においても不利な点が多く、より簡便で
工業化可能な合成方法の確立が求められている。However, as disclosed in J. Org. Chem., 26 2525 (1961) and Japanese Patent Laid-Open No. 4-77464,
Although heavy metals such as mercury oxide, lead oxide, and copper oxide are disclosed as desulfurizing agents, there are problems that must be handled with care, such as the toxicity of these and the inclusion of trace amounts in wastewater. Further, the reaction yield is not always satisfactory, and there are many disadvantages in industrialization, and there is a demand for establishment of a simpler and more industrially synthesizable method.
【０００７】[0007]
【課題を解決するための手段】本発明は、水溶性のカル
ボジイミドである１−エチル−３−（３−ジメチルアミ
ノプロピル）カルボジイミドの、簡便で安全性の高い製
造方法を求め鋭意検討を重ねた結果、当該化合物を効率
良くしかも高純度で、工業化においても安全に製造でき
る方法を確立したものである。すなわち本発明は、１−
エチル−３−（３−ジメチルアミノプロピル）チオ尿素
を次亜塩素酸塩で脱硫化水素反応し、１−エチル−３−
（３−ジメチルアミノプロピル）カルボジイミドを製造
する反応において、水と相溶性のない有機溶媒と水との
二相系において、水酸化カリウム存在下に反応させるこ
とを特徴とする１−エチル−３−（３−ジメチルアミノ
プロピル）カルボジイミドの製造方法である。Means for Solving the Problems The present invention has been earnestly studied in search of a simple and highly safe production method of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide which is a water-soluble carbodiimide. As a result, a method for efficiently producing the compound with high purity and safely in industrialization has been established. That is, the present invention is 1-
Ethyl-3- (3-dimethylaminopropyl) thiourea was subjected to a dehydrosulfurization reaction with hypochlorite to give 1-ethyl-3-
In the reaction for producing (3-dimethylaminopropyl) carbodiimide, 1-ethyl-3-, which is characterized by reacting in the presence of potassium hydroxide in a two-phase system of water and an organic solvent incompatible with water. This is a method for producing (3-dimethylaminopropyl) carbodiimide.
【０００８】本反応において相間移動触媒は必ずしも添
加の必要はないものの、添加することにより脱硫化水素
反応が温和に進行するため、添加が特に好ましい。本発
明に用いられる１−エチル−３−（３−ジメチルアミノ
プロピル）チオ尿素は有機溶媒中でイソチオシアン酸エ
チルと、Ｎ，Ｎ−ジメチル−１，３−プロパンジアミン
を室温下において付加反応させることにより合成され
る。この合成された１−エチル−３−（３−ジメチルア
ミノプロピル）チオ尿素を精製し、あるいは、精製する
ことなく続けて同一反応容器に水酸化カリウム固体ある
いはその水溶液を添加し、次亜塩素酸塩で脱硫化水素反
応をすることも可能である。In this reaction, it is not always necessary to add the phase transfer catalyst, but the addition thereof is particularly preferable because the dehydrogenation-hydrogenation reaction proceeds gently. The 1-ethyl-3- (3-dimethylaminopropyl) thiourea used in the present invention is obtained by subjecting ethyl isothiocyanate and N, N-dimethyl-1,3-propanediamine to an addition reaction in an organic solvent at room temperature. Is synthesized by. This synthesized 1-ethyl-3- (3-dimethylaminopropyl) thiourea was purified, or solid potassium hydroxide or its aqueous solution was continuously added to the same reaction vessel without purification to obtain hypochlorous acid. It is also possible to carry out a desulfurization hydrogenation reaction with a salt.
【０００９】また、脱硫化水素反応に用いられる有機溶
媒は水と相溶性のない、沸点が１０℃〜１００℃の有機
溶媒、例えばヘキサン、クロロホルム、塩化メチレン、
ジエチルエーテルなどが例示される。この反応は相間移
動触媒の存在下あるいは不存在下、水酸化カリウム水溶
液を添加後、次亜塩素酸塩を加え、さらには水酸化カリ
ウムと次亜塩素酸塩を連続的に加えることにより、脱硫
化水素反応を完全に終了させ、副生物を生成させること
なく高収率で高純度の１−エチル−３−（３−ジメチル
アミノプロピル）カルボジイミドを得られる利点があ
る。The organic solvent used in the dehydrosulfurization reaction is an organic solvent which is incompatible with water and has a boiling point of 10 ° C to 100 ° C, such as hexane, chloroform, methylene chloride,
Examples include diethyl ether and the like. In this reaction, potassium hydroxide aqueous solution is added in the presence or absence of a phase transfer catalyst, then hypochlorite is added, and further potassium hydroxide and hypochlorite are continuously added to desulfurize. There is an advantage that the hydrogen chloride reaction is completely completed, and high-purity 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide can be obtained in high yield without producing by-products.
【００１０】さらに本反応において、アルカリとして水
酸化カリウムの代わりに水酸化ナトリウム、水酸化リチ
ウム等を用いた場合には、反応が完全に終了せずチオ尿
素体が残存し、生成物の純度が低く、不利な点があり、
水酸化カリウムのみ有効であるということは意外ともい
える知見であり、ここに本発明の新規性が存在するもの
である。また、反応のスケールアップにおいてもその容
易性、安全性からも可能であり、大量生産が可能とな
る。なおここで使用される次亜塩素酸塩類は次亜塩素酸
ナトリウム、次亜塩素酸カリウム、次亜塩素酸カルシウ
ムなどが例示され、通常市販されている形態、例えば水
溶液のもので充分使用できる。Furthermore, in the present reaction, when sodium hydroxide, lithium hydroxide or the like is used as the alkali in place of potassium hydroxide, the reaction is not completely completed, the thiourea compound remains, and the purity of the product is Low, there are disadvantages,
It is a surprising finding that only potassium hydroxide is effective, and this is where the novelty of the present invention exists. In addition, scale-up of the reaction is possible because of its easiness and safety, and mass production is possible. Examples of the hypochlorites used here include sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, and the like, which can be sufficiently used in a commercially available form, for example, an aqueous solution.
【００１１】[0011]
【作用】本発明の１−エチル−３−（３−ジメチルアミ
ノプロピル）カルボジイミドの製造法について用いる水
酸化カリウムと次亜塩素酸塩の添加量は、脱硫化水素さ
れる１−エチル−３−（３−ジメチルアミノプロピル）
チオ尿素１当量に対し、水酸化カリウム１〜３当量、よ
り好ましくは２〜２．５当量であり、次亜塩素酸塩は、
水酸化カリウムの１．５〜２．５倍の当量を必要とす
る。それ以下の添加量では反応が終了せずチオ尿素が残
存してしまう。次亜塩素酸塩を過剰に添加することはカ
ルボジイミドの劣化を起こす要因となる。In the method for producing 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide of the present invention, potassium hydroxide and hypochlorite are added in an amount of 1-ethyl-3-dehydrogenated. (3-dimethylaminopropyl)
With respect to 1 equivalent of thiourea, potassium hydroxide is 1 to 3 equivalents, more preferably 2 to 2.5 equivalents, and hypochlorite is
It requires 1.5 to 2.5 times the equivalent of potassium hydroxide. If the amount added is less than that, the reaction does not end and thiourea remains. Excessive addition of hypochlorite causes deterioration of carbodiimide.
【００１２】反応温度は−２０℃〜５０℃が好ましく、
より好ましくは−１０℃〜２０℃である。−２０℃未満
では生成物の安定性には寄与せず、反応速度が遅くなる
のみであり、工業化においても不利である。他方、５０
℃より高い温度においては脱硫化水素反応により得られ
たカルボジイミドが存在しているアルカリの影響によ
り、カルボジイミド基に水が付加され尿素体に変化して
しまうため、好ましくない。また、同時にカルボジイミ
ドの重合による劣化も見られるなど、品質的に不充分で
ある。The reaction temperature is preferably -20 ° C to 50 ° C,
More preferably, it is -10 ° C to 20 ° C. If it is less than -20 ° C, it does not contribute to the stability of the product and only slows down the reaction rate, which is also disadvantageous in industrialization. On the other hand, 50
At a temperature higher than ° C, water is added to the carbodiimide group to change to a urea body under the influence of the alkali in which the carbodiimide obtained by the desulfurization reaction is present, which is not preferable. Further, at the same time, deterioration due to polymerization of carbodiimide is also observed, and the quality is insufficient.
【００１３】[0013]
実施例 １ 水３０ｍｌ、水酸化カリウム２４．６ｇ、クロロホルム
１５０ｍｌ、１−エチル−３−（３−ジメチルアミノプ
ロピル）チオ尿素３７．９ｇ、相間移動触媒としてＢＴ
ＥＡＣ（ベンジルトリエチルアンモニウムクロライド）
０．１ｇを還流冷却器付の反応容器中で攪拌下冷却しな
がら、１３．５％の次亜塩素酸ナトリウム水溶液４６０
ｇを０〜１０℃で滴下し脱硫化水素反応を行い、同温度
で２時間攪拌した。反応後分液し、クロロホルム層を
得、飽和炭酸カリウム水溶液１００ｍｌで洗浄後脱水
し、クロロホルムを減圧留去し、真空乾燥後１−エチル
−３−（３−ジメチルアミノプロピル）カルボジイミド
２８．２ｇを得た。収率９０．８％、ＨＰＬＣでの純度
分析で９９％、ＦＴ−ＩＲにより２１２７ｃｍ-1のＮ＝
Ｃ＝Ｎ（カルボジイミド）のピークを認め、さらに不純
物のチオ尿素体、尿素体に起因する１５５０ｃｍ-1Ｃ＝
Ｓ、１６３５ｃｍ-1Ｃ＝Ｏのピークを全く認めない事を
確認した。Example 1 30 ml of water, 24.6 g of potassium hydroxide, 150 ml of chloroform, 37.9 g of 1-ethyl-3- (3-dimethylaminopropyl) thiourea, BT as a phase transfer catalyst
EAC (benzyltriethylammonium chloride)
While cooling 0.1 g under stirring in a reaction vessel equipped with a reflux condenser, 13.5% sodium hypochlorite aqueous solution 460
g was added dropwise at 0 to 10 ° C to carry out a desulfurization reaction, and the mixture was stirred at the same temperature for 2 hours. After the reaction, liquid separation was performed to obtain a chloroform layer, which was washed with 100 ml of a saturated aqueous solution of potassium carbonate and then dehydrated, chloroform was distilled off under reduced pressure, and vacuum drying was performed, and 28.2 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide was added. Obtained. Yield 90.8%, purity analysis 99% by HPLC, N = 2127 cm -1 by FT-IR
A peak of C = N (carbodiimide) was observed, and further 1550 cm −1 C = due to the impurity thiourea form and urea form
It was confirmed that the peak of S, 1635 cm -1 C = O was not observed at all.
【００１４】実施例 ２ 実施例１のクロロホルムの代わりに塩化メチレンを用い
て同方法で反応し、１−エチル−３−（３−ジメチルア
ミノプロピル）カルボジイミド２７．９ｇを得た。収率
８９．９％、ＨＰＬＣでの純度は９８．７％であった。Example 2 Methylene chloride was used instead of chloroform in Example 1 and the reaction was carried out in the same manner to obtain 27.9 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. The yield was 89.9% and the purity by HPLC was 98.7%.
【００１５】実施例 ３ 実施例１のクロロホルムの代わりにベンゼンを用いて同
方法で反応し、１−エチル−３−（３−ジメチルアミノ
プロピル）カルボジイミド２６．８ｇを得た。収率８
６．３％、ＨＰＬＣでの純度は９７．９％であった。Example 3 Using benzene instead of chloroform in Example 1, the reaction was carried out in the same manner to obtain 26.8 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. Yield 8
The purity was 6.3% and the purity by HPLC was 97.9%.
【００１６】実施例 ４ イソチオシアン酸エチル１７．４ｇ、クロロホルム７５
ｍｌを還流冷却器付きの反応容器中で攪拌下、室温で
Ｎ，Ｎ−ジメチル−１，３−プロパンジアミン２０．４
ｇ、クロロホルム７５ｍｌの溶液を滴下し、同温度で一
夜攪拌し、付加反応を行うことにより１−エチル−３−
（３−ジメチルアミノプロピル）チオ尿素を得た。さら
に、同反応液を冷却し、水酸化カリウム２４．６ｇを水
３０ｍｌで溶解したものを加え、引き続いて１３．５％
の次亜塩素酸ナトリウム水溶液４６０ｇを０℃〜１０℃
で滴下し、脱硫化水素反応を行い、実施例１と同様の処
理方法により１−エチル−３−（３−ジメチルアミノプ
ロピル）カルボジイミド２６．７ｇを得た。収率８６．
０％であり、ＨＰＬＣでの分析の結果、純度９８．８％
で、ＦＴ−ＩＲによりチオ尿素体、尿素体のピークを認
めなかった。Example 4 17.4 g of ethyl isothiocyanate and 75 of chloroform
ml at room temperature under stirring in a reaction vessel equipped with a reflux condenser, N, N-dimethyl-1,3-propanediamine 20.4
g, a solution of 75 ml of chloroform was added dropwise, and the mixture was stirred overnight at the same temperature to carry out an addition reaction to give 1-ethyl-3-
(3-Dimethylaminopropyl) thiourea was obtained. Further, the reaction solution was cooled, and 24.6 g of potassium hydroxide dissolved in 30 ml of water was added, followed by 13.5%.
Sodium hypochlorite aqueous solution 460g of 0 ℃ ~ 10 ℃
Was added dropwise to carry out a desulfurization reaction, and 26.7 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide was obtained by the same treatment method as in Example 1. Yield 86.
0%, and as a result of analysis by HPLC, the purity is 98.8%.
Therefore, peaks of thiourea form and urea form were not observed by FT-IR.
【００１７】実施例 ５ 実施例１の反応組成において相間移動触媒であるＢＴＥ
ＡＣ無添加で反応し、１−エチル−３−（３−ジメチル
アミノプロピル）カルボジイミド２６．４ｇを得た。収
率８５．０％、ＨＰＬＣでの純度は９８．４％であっ
た。Example 5 BTE which is a phase transfer catalyst in the reaction composition of Example 1
The reaction was carried out without addition of AC to obtain 26.4 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. The yield was 85.0% and the purity by HPLC was 98.4%.
【００１８】比較例 １ 実施例１のクロロホルムの代わりにトルエンを用い同方
法で反応し、１−エチル−３−（３−ジメチルアミノプ
ロピル）カルボジイミド１６．７ｇを得た。収率５３．
８％であった。Comparative Example 1 Using toluene instead of chloroform in Example 1 and reacting in the same manner, 16.7 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide was obtained. Yield 53.
It was 8%.
【００１９】比較例２ 実施例１の水酸化カリウムの代わりに水酸化ナトリウム
を用い、同方法で反応し、１−エチル−３−（３−ジメ
チルアミノプロピル）カルボジイミド２１．４ｇを得
た。収率６８．９％であった。また、ＨＰＬＣの分析の
結果生成物の純度は９２．１％で、４％の未反応チオ尿
素体が存在し、さらにＦＴ−ＩＲによりＣ＝Ｏの１６３
５ｃｍ-1の吸収を認め、尿素体が確認された。Comparative Example 2 Sodium hydroxide was used in place of the potassium hydroxide of Example 1 and the reaction was carried out in the same manner to obtain 21.4 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. The yield was 68.9%. As a result of HPLC analysis, the purity of the product was 92.1%, 4% of unreacted thiourea compound was present, and FT-IR showed 163 of C = O.
Absorption at 5 cm -1 was observed and a urea form was confirmed.
【００２０】[0020]
【発明の効果】１−エチル−３−（３−ジメチルアミノ
プロピル）チオ尿素と次亜塩素酸塩の脱硫反応による１
−エチル−３−（３−ジメチルアミノプロピル）カルボ
ジイミドの製造方法において、水と相溶性のない有機溶
媒との２相系下、水酸化カリウム存在下に脱硫反応する
ことにより、従来法では見られない高純度品が高収率で
得られることが判明した。さらにこの製造方法は、反応
装置ならびに反応の容易性、安全性からも見ても工業化
において経済的であり、重金属を使用しない事により、
公害問題についての大きな改善も見られ、その効果は大
きい。The effect of the desulfurization reaction of 1-ethyl-3- (3-dimethylaminopropyl) thiourea and hypochlorite is 1
In the method for producing -ethyl-3- (3-dimethylaminopropyl) carbodiimide, the desulfurization reaction is carried out in the presence of potassium hydroxide in the presence of potassium hydroxide in a two-phase system with an organic solvent incompatible with water. It was found that a high-purity product having no high purity was obtained. Furthermore, this production method is economical in industrialization from the standpoint of easiness of reaction, reaction, and safety, and by not using heavy metals,
Significant improvements in pollution problems have been seen and their effects are significant.
Claims (6)
プロピル）チオ尿素を次亜塩素酸塩で脱硫化水素反応
し、１−エチル−３−（３−ジメチルアミノプロピル）
カルボジイミドを製造する反応において、水と相溶性の
ない有機溶媒と水との二相系において、水酸化カリウム
の存在下に反応させることを特徴とする１−エチル−３
−（３−ジメチルアミノプロピル）カルボジイミドの製
造方法。1. 1-Ethyl-3- (3-dimethylaminopropyl) thiourea is subjected to a desulfurization reaction with hypochlorite to give 1-ethyl-3- (3-dimethylaminopropyl).
In the reaction for producing carbodiimide, 1-ethyl-3, which is characterized by reacting in the presence of potassium hydroxide in a two-phase system of water and an organic solvent incompatible with water.
A method for producing-(3-dimethylaminopropyl) carbodiimide.
ることを特徴とする請求項１記載の１−エチル−３−
（３−ジメチルアミノプロピル）カルボジイミドの製造
方法。2. The 1-ethyl-3-type according to claim 1, wherein the boiling point of the organic solvent is 10 ° C. to 100 ° C.
A method for producing (3-dimethylaminopropyl) carbodiimide.
５０℃であることを特徴とする請求項１記載の１−エチ
ル−３−（３−ジメチルアミノプロピル）カルボジイミ
ドの製造方法。3. The reaction temperature of the desulfurization hydrogenation reaction is -20 ° C.
The method for producing 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide according to claim 1, wherein the temperature is 50 ° C.
が１−エチル−３−（３−ジメチルアミノプロピル）チ
オ尿素１当量に対し、水酸化カリウムが１〜３当量であ
り次亜塩素酸塩が水酸化カリウムの１．５〜２．５倍の
当量を添加することを特徴とする請求項１記載の１−エ
チル−３−（３−ジメチルアミノプロピル）カルボジイ
ミドの製造方法。4. The amount of potassium hydroxide and hypochlorite added is 1 to 1 equivalent of 1-ethyl-3- (3-dimethylaminopropyl) thiourea, and potassium hydroxide is 1 to 3 equivalents. The method for producing 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide according to claim 1, wherein the chlorate is added in an amount equivalent to 1.5 to 2.5 times that of potassium hydroxide.
チル−１，３−プロパンジアミンとを有機溶媒中で付加
反応せしめ、生成した１−エチル−３−（３−ジメチル
アミノプロピル）チオ尿素を単離することなく、水と相
溶性のない有機溶媒と水との二相系において水酸化カリ
ウムと次亜塩素塩で脱硫化水素反応を行うことを特徴と
する１−エチル−３−（３−ジメチルアミノプロピル）
カルボジイミドの製造方法。5. Ethyl isothiocyanate and N, N-dimethyl-1,3-propanediamine are subjected to an addition reaction in an organic solvent to produce 1-ethyl-3- (3-dimethylaminopropyl) thiourea as a simple substance. 1-ethyl-3- (3-, characterized in that a desulfurization hydrogenation reaction is carried out with potassium hydroxide and hypochlorite in a two-phase system of water and an organic solvent incompatible with water without separation. Dimethylaminopropyl)
Method for producing carbodiimide.
の存在下あるいは、不存在下に反応することを特徴とす
る１−エチル−３−（３−ジメチルアミノプロピル）カ
ルボジイミドの製造方法。6. A method for producing 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, which comprises reacting the reaction according to any one of claims 1 to 5 in the presence or absence of a phase transfer catalyst. .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7031528A JPH08198836A (en) | 1995-01-26 | 1995-01-26 | Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7031528A JPH08198836A (en) | 1995-01-26 | 1995-01-26 | Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH08198836A true JPH08198836A (en) | 1996-08-06 |
Family
ID=12333702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7031528A Pending JPH08198836A (en) | 1995-01-26 | 1995-01-26 | Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH08198836A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008026680A1 (en) | 2006-08-31 | 2008-03-06 | Kaneka Corporation | Method for stabilizing carbodiimide derivative and stabilized composition thereof |
| JP2012001476A (en) * | 2010-06-16 | 2012-01-05 | Kawaguchi Kagaku Kogyo Kk | Method for producing carbodiimide compound |
| JP2014047208A (en) * | 2012-09-04 | 2014-03-17 | Osaka City Univ | Method of producing carbodiimide compound |
| CN104193654A (en) * | 2014-09-03 | 2014-12-10 | 山东金城医药化工股份有限公司 | Preparation method of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride |
| CN109053494A (en) * | 2018-08-29 | 2018-12-21 | 山东金城柯瑞化学有限公司 | The method of purification of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride |
| CN109369458A (en) * | 2018-09-14 | 2019-02-22 | 山东金城柯瑞化学有限公司 | The preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride |
| CN109369459A (en) * | 2018-10-09 | 2019-02-22 | 淄博天堂山化工有限公司 | Thiourea-uv Method produces N, the method for N '-di-t-butyl carbodiimide |
| CN109400503A (en) * | 2018-11-01 | 2019-03-01 | 山东汇海医药化工有限公司 | A method of improving 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCI m. p |
-
1995
- 1995-01-26 JP JP7031528A patent/JPH08198836A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008026680A1 (en) | 2006-08-31 | 2008-03-06 | Kaneka Corporation | Method for stabilizing carbodiimide derivative and stabilized composition thereof |
| JP2012001476A (en) * | 2010-06-16 | 2012-01-05 | Kawaguchi Kagaku Kogyo Kk | Method for producing carbodiimide compound |
| JP2014047208A (en) * | 2012-09-04 | 2014-03-17 | Osaka City Univ | Method of producing carbodiimide compound |
| CN104193654A (en) * | 2014-09-03 | 2014-12-10 | 山东金城医药化工股份有限公司 | Preparation method of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride |
| CN109053494A (en) * | 2018-08-29 | 2018-12-21 | 山东金城柯瑞化学有限公司 | The method of purification of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride |
| CN109369458A (en) * | 2018-09-14 | 2019-02-22 | 山东金城柯瑞化学有限公司 | The preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride |
| CN109369459A (en) * | 2018-10-09 | 2019-02-22 | 淄博天堂山化工有限公司 | Thiourea-uv Method produces N, the method for N '-di-t-butyl carbodiimide |
| CN109400503A (en) * | 2018-11-01 | 2019-03-01 | 山东汇海医药化工有限公司 | A method of improving 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCI m. p |
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