JPH08277254A - Purification of 1-ethyl-3-(3dimethylaminopropyl) carbodiimide - Google Patents
Purification of 1-ethyl-3-(3dimethylaminopropyl) carbodiimideInfo
- Publication number
- JPH08277254A JPH08277254A JP10682595A JP10682595A JPH08277254A JP H08277254 A JPH08277254 A JP H08277254A JP 10682595 A JP10682595 A JP 10682595A JP 10682595 A JP10682595 A JP 10682595A JP H08277254 A JPH08277254 A JP H08277254A
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- carbodiimide
- dimethylaminopropyl
- azeotropic distillation
- hydrocarbon solvent
- 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.)
- Ceased
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (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果的な精製方法に関するものであ
る。FIELD OF THE INVENTION The present invention relates to a dehydration condensing agent at the time of synthesis of medicines, agricultural chemicals, etc., and 1-ethyl-3- (3-dimethylaminopropyl) useful as an intermediate for organic synthesis.
The present invention relates to an effective method for purifying carbodiimide.
【０００２】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。[0002] Carbodiimide compounds are condensing agents which are used in a wide variety of fields and which can carry out dehydration condensation reactions such as esterification and amidation under extremely mild conditions. Particularly, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide having a hydrophilic group is known as a water-soluble carbodiimide, and it is possible to react in an aqueous solvent as well as to react in an organic solvent. Also in this case, the produced urea body can be removed by washing with water, and there are many advantages such as less racemization during dehydration condensation of the optically active compound, and it is superior to dicyclohexylcarbodiimide and general-purpose carbodiimide.
【０００３】[0003]
【従来の技術】従来、１−エチル−３−（３−ジメチル
アミノプロピル）カルボジイミドの精製方法としては、
Journal of Organic Chemistry 26，2525 に開示されて
いる分子蒸留法が一般的である。また、特開平４−７７
４６４号は、この化合物を真空蒸留により精製を行って
いる例も開示されている。しかしながら、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
精製方法に共沸蒸留を用いた例はない。2. Description of the Related Art Conventionally, as a method for purifying 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide,
The molecular distillation method disclosed in Journal of Organic Chemistry 26, 2525 is generally used. In addition, JP-A-4-77
No. 464 also discloses an example in which this compound is purified by vacuum distillation. However, 1-ethyl-
There is no example of using azeotropic distillation as a method for purifying 3- (3-dimethylaminopropyl) carbodiimide.
【０００４】[0004]
【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）カルボジイミドを工業的に
精製する際、先に記述の分子蒸留による方法は、その真
空度が０．２〜０．８Ｔｏｒｒと高く、工業化において
は困難な点が多い。さらに、特開平４−７７４６４号に
開示されている真空蒸留法は５Ｔｏｒｒであるので工業
化可能な条件ではあるが、蒸留温度が高く、熱に対し不
安定である１−エチル−３−（３−ジメチルアミノプロ
ピル）カルボジイミドを大量に精製する場合、熱劣化が
見られる。また、その精製収率も、必ずしも満足いくも
のでなく、より簡便で工業化可能な精製方法の確立が求
められている。1-Ethyl-3- (3
When industrially purifying -dimethylaminopropyl) carbodiimide, the method of molecular distillation described above has a high degree of vacuum of 0.2 to 0.8 Torr, and there are many difficulties in industrialization. Further, the vacuum distillation method disclosed in Japanese Patent Laid-Open No. 4-77464 is industrially viable because the vacuum distillation method is 5 Torr, but the distillation temperature is high and 1-ethyl-3- (3- When a large amount of dimethylaminopropyl) carbodiimide is purified, thermal deterioration is observed. Further, the purification yield is not always satisfactory, and there is a demand for establishment of a purification method that is simpler and can be industrialized.
【０００５】[0005]
【課題を解決するための手段】本発明者は、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）カルボジイミドの簡便かつ高収率の精製方
法を求め鋭意検討を重ねた結果、効率よく高純度で精製
でき、しかも工業化可能な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）カルボジイミドを特定沸点の有機溶媒と
減圧下に共沸蒸留により精製することを特徴とする精製
方法である。共沸蒸留に用いる溶媒としては、常圧下に
おける沸点が１７０℃〜２５０℃の範囲内にある炭化水
素、ハロゲン化炭化水素及びエーテル類、グリコール類
が有効である。Means for Solving the Problems As a result of intensive studies, the present inventors have sought a simple and high-yield purification method for water-soluble carbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. It has established a method that can be efficiently purified with high purity and can be industrialized.
That is, the present invention is a purification method characterized in that 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide is purified by azeotropic distillation under reduced pressure with an organic solvent having a specific boiling point. As the solvent used for the azeotropic distillation, hydrocarbons, halogenated hydrocarbons, ethers and glycols having a boiling point in the range of 170 ° C to 250 ° C under normal pressure are effective.
【０００６】炭化水素としては脂肪族、芳香族、脂環式
炭化水素であり、本発明にいう特定沸点の炭化水素とし
てはデカン、ドデカン、ナフタレン、テトラリン、ｎ−
ブチルベンゼン、シクロヘキシルベンゼン、ジエチルベ
ンゼン、ペンチルベンゼン、ビシクロヘキシル、ジペン
テンデカリンが例示される。さらにこれらを主成分とす
る混合物、例えば灯油などでも良い。The hydrocarbons are aliphatic, aromatic and alicyclic hydrocarbons, and the hydrocarbons having a specific boiling point referred to in the present invention are decane, dodecane, naphthalene, tetralin and n-.
Examples are butylbenzene, cyclohexylbenzene, diethylbenzene, pentylbenzene, bicyclohexyl, and dipentenedecalin. Further, a mixture containing these as main components, such as kerosene, may be used.
【０００７】ハロゲン化炭化水素としては、ジクロロベ
ンゼン、１，２，４−トリクロロベンゼンが例示され
る。さらに、エーテル、グリコール類としては、フェネ
トール、ブチルフェニルエーテル、アシルフェニルエー
テル、メトキシトルエン、ベンジルエチルエーテル、ベ
ラトロール、シネオール、１，２−ジブトキシエタン、
ジエチレングリコールジエチルエーテル、ジプロピレン
グリコール、ジプロピレングリコールモノメチルエーテ
ル、ジプロピレングリコールモノエチルエーテル、トリ
プロピレングリコールモノメチルエーテル、ジエチレン
グリコールモノエチルエーテル、ジエチレングリコール
モノブチルエーテル、ジエチレングリコールモノブチル
エーテルアセタールなどが例示される。さらに本発明の
共沸蒸留は、真空度が５０Ｔｏｒｒ以下、具体的には３
〜５０Ｔｏｒｒ程度の減圧がなされるものであれば充分
であり、薄膜式の蒸留装置や、単蒸留型の装置など任意
の減圧蒸留装置が使用できる。Examples of halogenated hydrocarbons include dichlorobenzene and 1,2,4-trichlorobenzene. Further, as ethers and glycols, phenetol, butyl phenyl ether, acyl phenyl ether, methoxytoluene, benzyl ethyl ether, veratrol, cineol, 1,2-dibutoxyethane,
Examples include diethylene glycol diethyl ether, dipropylene glycol, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, tripropylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, and diethylene glycol monobutyl ether acetal. Furthermore, the azeotropic distillation of the present invention has a vacuum degree of 50 Torr or less, specifically 3
It is sufficient that the pressure is reduced to about 50 Torr, and any vacuum distillation apparatus such as a thin film distillation apparatus or a simple distillation type apparatus can be used.
【０００８】[0008]
【作用】本発明で使用される１−エチル−３−（３−ジ
メチルアミノプロピル）カルボジイミドとの共沸蒸留に
用いる有機溶媒は、精製する１−エチル−３−（３−ジ
メチルアミノプロピル）カルボジイミドに対し重量比で
０．２５〜１０倍であればよく、さらに好ましくは１〜
３倍である。これ以下の添加量は１−エチル−３−（３
−ジメチルアミノプロピル）カルボジイミドの安定性に
寄与せず、共沸のための必要量に達しない。当然、１０
倍量を越える添加は不経済である。The organic solvent used for azeotropic distillation with 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide used in the present invention is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide to be purified. The weight ratio may be 0.25 to 10 times, more preferably 1 to
It is three times. The addition amount below this is 1-ethyl-3- (3
-Does not contribute to the stability of dimethylaminopropyl) carbodiimide and does not reach the required amount for azeotropic. Naturally, 10
Adding more than double amount is uneconomical.
【０００９】本発明においてはさらに、常圧下における
沸点が１７０〜２５０℃のものが必須である。１７０℃
以下の溶媒では当該カルボジイミドと共沸し難く、カル
ボジイミドの安定性に寄与しない。沸点が２５０℃以上
の溶媒では、減圧下においても当該カルボジイミドのみ
が単独で分離蒸留されるため、高温下にさらされ、粗１
−エチル−３−（３−ジメチルアミノプロピル）カルボ
ジイミドの熱劣化が見られるなど能率的ではない。Further, in the present invention, a substance having a boiling point of 170 to 250 ° C. under normal pressure is essential. 170 ° C
The following solvents are difficult to azeotrope with the carbodiimide and do not contribute to the stability of the carbodiimide. In a solvent having a boiling point of 250 ° C. or higher, only the carbodiimide concerned is separately distilled even under reduced pressure, so that it is exposed to a high temperature and the crude 1
-Ethyl-3- (3-dimethylaminopropyl) carbodiimide is not efficient such as thermal deterioration.
【００１０】[0010]
【実施例】以下に本発明の実施例を示すが、本発明の範
囲はこれに限定されるものではない。 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
冷却器付き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４６０ｇ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
を減圧留去した。これにジエチルベンゼン３０ｇを加
え、６Ｔｏｒｒで共沸蒸留し、６１〜８３℃の留分をと
ることにより、１−エチル−３−（３−ジメチルアミノ
プロピル）カルボジイミドとジエチルベンゼンの混合物
５４．９ｇを得た。この時の１−エチル−３−（３−ジ
メチルアミノプロピル）カルボジイミドの得量は２４．
９ｇで８０．２％であった。ＨＰＬＣ分析の結果、蒸留
溶媒以外の不純物は認められず、溶媒を除く純度は９
９．７％であった。EXAMPLES Examples of the present invention will be shown below, but the scope of the present invention is not limited thereto. 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, and 0.1 g of benzyltriethylammonium chloride as a phase transfer catalyst were reflux condensers. 13. While cooling under stirring in a reaction vessel equipped with 13.
460 g of 5% sodium hypochlorite aqueous solution was added to 0-10
The mixture was added dropwise at ° 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 carried out to obtain a chloroform layer, which was washed with 100 ml of a saturated aqueous solution of potassium carbonate and then dehydrated, and chloroform was distilled off under reduced pressure. To this, 30 g of diethylbenzene was added, and the mixture was azeotropically distilled at 6 Torr to obtain a fraction at 61 to 83 ° C. to obtain 54.9 g of a mixture of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and diethylbenzene. . At this time, the amount of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide obtained was 24.
It was 80.2% at 9 g. As a result of HPLC analysis, impurities other than the distillation solvent were not found, and the purity excluding the solvent was 9
It was 9.7%.
【００１１】実施例２〜７ 実施例１のジエチルベンゼンの代わりに同方法で精製し
た場合の実施例を示す。 使用した溶媒 収率（％） 純度（％） ２ 灯油 ７８．１ ９８．４ ３ ２−オクタノール ７９．４ ９９．５ ４ １−ノナノール ７７．９ ９９．７ ５ ベンジルアルコール ７６．３ ９９．３ ６ シ゛エチレンク゛リコ-ルシ゛エチルエ-テル ８１．１ ９９．５ ７ シ゛エチレンク゛リコ-ルモノフ゛チルエ-テルアセタ-ル ７８．１ ９９．２ Examples 2 to 7 Examples in which purification was carried out by the same method as in Example 1 instead of diethylbenzene will be described. Solvents used Yield (%) Purity (%) 2 Kerosene 78.1 98.4 3 2-Octanol 79.4 99.5 4 1-Nonanol 77.9 99.7 5 Benzyl alcohol 76.3 99.3 6 Ethylene Glycol Diethyl Ether 81.1 99.5 7 Diethylene Glycol Monobutyl Ether Acetate 78.1 99.2
【００１２】比較例 １ 実施例１においてジエチルベンゼンを添加せず無溶媒下
に蒸留した。蒸留中に重合したもようであり、蒸留残が
見られた。１−エチル−３−（３−ジメチルアミノプロ
ピル）カルボジイミド１６．９ｇを得た。収率５４．４
％Comparative Example 1 Distillation was carried out in the same manner as in Example 1 except that diethylbenzene was not added. It seemed to have polymerized during the distillation and a distillation residue was visible. 16.9 g of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide was obtained. Yield 54.4
%
【００１３】比較例 ２ 実施例１においてジエチルベンゼンの代わりにベンゼン
を用い同方法にて蒸留した。共沸留分中の１−エチル−
３−（３−ジメチルアミノプロピル）カルボジイミドは
１５．８ｇであった。収率５０．９％Comparative Example 2 Distillation was carried out in the same manner as in Example 1 except that benzene was used instead of diethylbenzene. 1-Ethyl-in the azeotropic fraction
The amount of 3- (3-dimethylaminopropyl) carbodiimide was 15.8 g. Yield 50.9%
【００１４】比較例 ３ 実施例１においてジエチルベンゼンの代わりにキシレン
を用い同方法にて蒸留した。共沸留分中の１−エチル−
３−（３−ジメチルアミノプロピル）カルボジイミドは
１６．３ｇであった。収率５２．５％Comparative Example 3 Distillation was carried out in the same manner as in Example 1 except that xylene was used instead of diethylbenzene. 1-Ethyl-in the azeotropic fraction
The amount of 3- (3-dimethylaminopropyl) carbodiimide was 16.3 g. Yield 52.5%
【００１５】[0015]
【発明の効果】粗１−エチル−３−（３−ジメチルアミ
ノプロピル）カルボジイミドを精製する際、常圧下にお
いて沸点が１７０℃〜２５０℃の炭化水素溶媒、ハロゲ
ン化炭化水素溶媒、エーテル類、グリコール類の溶媒の
うち１種または２種以上を用い、減圧下に共沸蒸留する
ことにより、従来法では見られない高収率で高純度品が
得られることが判明した。さらにこの方法は１−エチル
−３−（３−ジメチルアミノプロピル）カルボジイミド
の熱劣化も防止するのでスケールアップが可能となり、
真空蒸留を行う真空度、温度とも緩和な条件であるため
工業化も容易でありその効果は大きい。EFFECTS OF THE INVENTION When purifying crude 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, a hydrocarbon solvent having a boiling point of 170 ° C. to 250 ° C. under normal pressure, a halogenated hydrocarbon solvent, ethers, glycol It was found that a highly pure product can be obtained in a high yield, which cannot be obtained by the conventional method, by azeotropically distilling under reduced pressure using one or more of the above-mentioned solvents. Further, this method also prevents thermal deterioration of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, which enables scale-up.
Since the degree of vacuum and the temperature at which the vacuum distillation is performed are mild, industrialization is easy and the effect is great.
Claims (4)
プロピル）カルボジイミドを共沸蒸留で精製する際、常
圧下において沸点が１７０℃〜２５０℃の炭化水素溶
媒、ハロゲン化炭化水素溶媒、エーテル類、グリコール
類の溶媒のうち１種または２種以上の溶媒とともに減圧
下に共沸蒸留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）カルボジイミドの精製
方法。1. When purifying crude 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide by azeotropic distillation, a hydrocarbon solvent having a boiling point of 170 ° C. to 250 ° C. under normal pressure, a halogenated hydrocarbon solvent, 1-Ethyl-3-, which is characterized by performing azeotropic distillation under reduced pressure with one or more solvents of ethers and glycols.
A method for purifying (3-dimethylaminopropyl) carbodiimide.
プロピル）カルボジイミドを共沸蒸留で精製する際、灯
油とともに減圧下に蒸留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
ドの精製方法。2. When purifying crude 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide by azeotropic distillation, it is distilled under reduced pressure together with kerosene, and 1-ethyl-3- (3-). Method for purifying dimethylaminopropyl) carbodiimide.
ロピル）チオ尿素を脱硫化水素反応後、得られた生成物
を共沸蒸留で精製する際に、請求項１記載の有機溶媒あ
るいは灯油から選ばれた一種または二種以上の溶媒とと
もに減圧下に蒸留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）カルボジイミドの精
製方法。3. The organic solvent according to claim 1, or 1-ethyl-3- (3-dimethylaminopropyl) thiourea after the desulfurization reaction, when the product obtained is purified by azeotropic distillation. 1-Ethyl-3, characterized in that it is distilled under reduced pressure together with one or more solvents selected from kerosene.
-(3-Dimethylaminopropyl) carbodiimide purification method.
ロピル）チオ尿素を水酸化カリウム存在下、次亜塩素酸
塩で脱硫化水素反応し、得られた生成物を共沸蒸留で精
製する際、常圧下において沸点が１７０℃〜２５０℃の
炭化水素溶媒、ハロゲン化炭化水素溶媒、エーテル類、
グリコール類の溶媒 あるいは灯油のうちの一種または
二種以上の溶媒とともに減圧下に蒸留することを特徴と
する１−エチル−３−（３−ジメチルアミノプロピル）
カルボジイミドの精製方法。4. 1-Ethyl-3- (3-dimethylaminopropyl) thiourea is subjected to a desulfurization hydrogenation reaction with hypochlorite in the presence of potassium hydroxide, and the obtained product is purified by azeotropic distillation. At that time, a hydrocarbon solvent having a boiling point of 170 ° C. to 250 ° C. under normal pressure, a halogenated hydrocarbon solvent, ethers,
1-Ethyl-3- (3-dimethylaminopropyl), which is distilled under reduced pressure with a solvent of glycols or one or more solvents of kerosene
Purification method of carbodiimide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10682595A JPH08277254A (en) | 1995-04-05 | 1995-04-05 | Purification of 1-ethyl-3-(3dimethylaminopropyl) carbodiimide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10682595A JPH08277254A (en) | 1995-04-05 | 1995-04-05 | Purification of 1-ethyl-3-(3dimethylaminopropyl) carbodiimide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH08277254A true JPH08277254A (en) | 1996-10-22 |
Family
ID=14443557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10682595A Ceased JPH08277254A (en) | 1995-04-05 | 1995-04-05 | Purification of 1-ethyl-3-(3dimethylaminopropyl) carbodiimide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH08277254A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003038193A (en) * | 2001-07-30 | 2003-02-12 | Sumitomo Chem Co Ltd | Method of producing (r)-4-cyano-3-hydroxy-butanoic ester |
| WO2008026680A1 (en) | 2006-08-31 | 2008-03-06 | Kaneka Corporation | Method for stabilizing carbodiimide derivative and stabilized composition thereof |
| JP4610111B2 (en) * | 2001-03-19 | 2011-01-12 | 明治乳業株式会社 | Method for measuring L-carnitine in food |
| 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 |
-
1995
- 1995-04-05 JP JP10682595A patent/JPH08277254A/en not_active Ceased
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4610111B2 (en) * | 2001-03-19 | 2011-01-12 | 明治乳業株式会社 | Method for measuring L-carnitine in food |
| JP2003038193A (en) * | 2001-07-30 | 2003-02-12 | Sumitomo Chem Co Ltd | Method of producing (r)-4-cyano-3-hydroxy-butanoic ester |
| WO2008026680A1 (en) | 2006-08-31 | 2008-03-06 | Kaneka Corporation | Method for stabilizing carbodiimide derivative and stabilized composition thereof |
| 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 |
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