JP2001354662A - Method for producing 2-cyanopiperazine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing the high-quality objective product in good yield in the method for producing 2-cyanopiperazine by reacting a 2-halogenonitrile with ethylenediamine. SOLUTION: The raw material 2-halogenoacrylonitrile is obtained by dehydrohalogenating a dihalogenopropionitrile prepared by halogenating acrylonitrile and the content of the acrylonitrile is <=15 wt.% based on the 2- halogenoacrylonitrile in the method for producing the 2-cyanopiperazine by reacting the 2-halogenoacrylonitrile with the ethylenediamine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing 2-cyanopiperazine. Specifically, it relates to an improvement in a method for producing 2-cyanopiperazine by reacting 2-halogenoacrylonitrile with ethylenediamine. 2-cyanopiperazine is useful as a raw material for synthesis of medicines, agricultural chemicals, etc., for example, Nt-butyl-2-piperazinecarboxamide obtained by reacting 2-cyanopiperazine with t-butanol in the presence of an acid catalyst is It is a raw material for the synthesis of anti-HIV agents (Tetrahedron Letter)
s, 36 , 6419 (1995)).

[0002]

2. Description of the Related Art As a method for producing 2-cyanopiperazine, a method of reacting 2-halogenoacrylonitrile with ethylenediamine (JP-A-9-87254) is effective. In this case, 2-halogenoacrylonitrile as a raw material is produced by halogenating acrylonitrile to dihalogenopropionitrile and then dehydrohalogenating it.

[0003]

In the synthesis of 2-cyanopiperazine by reacting 2-halogenoacrylonitrile with ethylenediamine, the target product is sufficiently purified, but the 2-halogenoacrylonitrile as a raw material is purified. There is a desire to simplify the process by reducing or eliminating the load on the process.

[0004] However, low purity 2-
When chloroacrylonitrile is used, target 2
-There is a problem that the yield of cyanopiperazine decreases. An object of the present invention is to provide a method for producing 2-cyanopiperazine by reacting 2-halogenoacrylonitrile with ethylenediamine to produce a target product with high yield and high quality.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of such circumstances, and as a result, unreacted acrylonitrile contained in crude 2-chloroacrylonitrile as a raw material reacts with ethylenediamine. The effective molar ratio of ethylenediamine / 2-chloroacrylonitrile decreases, and the yield of the desired 2-cyanopiperazine also decreases. Therefore, it is necessary to regulate the amount of unreacted acrylonitrile in the raw material 2-chloroacrylonitrile. Thus, the present invention has been completed.

That is, the gist of the present invention is to provide a method for producing 2-cyanopiperazine by reacting 2-halogenoacrylonitrile with ethylenediamine, wherein dihalogenopropion is obtained by halogenating acrylonitrile from 2-halogenoacrylonitrile as a raw material. A method for producing 2-cyanopiperazine, which is obtained by dehydrohalogenating a nitrile and has an acrylonitrile content of 15% by weight or less based on 2-halogenoacrylonitrile.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, 2-halogenoacrylonitrile as a raw material is obtained by dehydrohalogenating dihalogenopropionitrile obtained by halogenation of acrylonitrile, and contains acrylonitrile. The amount used is 15% by weight or less based on 2-halogenoacrylonitrile.

When the 2-halogenoacrylonitrile is 2-chloroacrylonitrile, the synthesis involves chlorinating acrylonitrile with chlorine in the presence of a catalyst such as dimethylformamide to remove unreacted acrylonitrile and catalyst from the reaction mixture. To obtain dichloropropionitrile, which is then dehydrochlorinated using an aqueous solution of an alkali such as sodium carbonate to obtain the desired 2-chloroacrylonitrile.

[0009] In this case, the method for reducing the content of unreacted acrylonitrile in 2-chloroacrylonitrile is not particularly limited. For example, chlorine is blown into acrylonitrile under bubbling.
When producing dichloropropionitrile, increasing the amount of chlorine introduced to increase the conversion of acrylonitrile, or, after producing dichloropropionitrile, removing unreacted acrylonitrile under reduced pressure, etc. Can be

The reaction between 2-halogenoacrylonitrile and ethylenediamine can be carried out without a solvent, but is preferably carried out in an inert solvent. Examples of the inert solvent include ethers such as tetrahydrofuran, diethyl ether and dibutyl ether; alcohols such as methyl alcohol, ethyl alcohol and butyl alcohol; and (halo) aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene. , Hexane, heptane,
Aliphatic or alicyclic hydrocarbons such as cyclohexane,
Halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, acetonitrile, water and the like are used. Preferably, tetrahydrofuran, toluene, dichloromethane, dichloroethane, chloroform and the like are used. The solvent is usually used in an amount of 1 to 20 times the volume of 2-halogenoacrylonitrile.

When the reaction of the present invention is carried out without a solvent, it is preferable to use ethylenediamine in excess as a solvent. In the reaction of the present invention, as is clear from the reaction formula, hydrohalic acid is generated, and an acid binder is present in the reaction system to trap it. Examples of the acid binder include amines such as triethylamine, pyridine, and dimethylaniline, and sodium hydroxide, potassium hydroxide, and sodium carbonate. The used amount is 1 to 3 equivalents, preferably 1 mol of 2-halogenoacrylonitrile. Is 1-2 equivalents.

In a preferred embodiment of the present invention, ethylenediamine as a reaction raw material is used in excess as an acid binder.
Usually, 1 to 1 mole of 2-halogenoacrylonitrile is used.
In the range of 10 mol, the amount of ethylenediamine used is determined in consideration of the presence or absence of an acid binder and a solvent used together. When a solvent is used in combination but no other acid binder is used, 2
-5 mol or less, preferably 1.5 to 4 mol of ethylenediamine is used per 1 mol of halogenoacrylonitrile.

The reaction between 2-halogenoacrylonitrile and ethylenediamine is usually carried out at -20 to 100 ° C.
It is preferable to carry out the reaction at 20 to 60 ° C in view of the reaction rate and the yield. The reaction pressure may be a pressure at which the reaction system maintains a liquid phase. Usually, the reaction is carried out at normal pressure, but if desired, the reaction may be carried out under reduced or increased pressure. The reaction can be most simply carried out by charging an inert solvent, ethylenediamine and an acid binder into a reactor, and dropwise adding 2-halogenoacrylonitrile thereto with stirring. Since this reaction is an exothermic reaction, it is appropriately cooled if desired.

The separation and purification of 2-cyanopiperazine from the reaction product can be carried out by any conventional separation and purification method. For example, a salt produced as a by-product from the reaction solution is precipitated and separated by filtration. An acid is added to the filtrate to precipitate 2-cyanopiperazine as its acid addition salt, which is collected by filtration.
The acid to be added is preferably an inorganic acid such as hydrochloric acid, sulfuric acid, or hydrobromic acid, and the amount thereof is 1 to 5 equivalents, preferably 1 to 3 equivalents, per 1 mol of 2-cyanopiperazine.

When an acid addition salt of 2-cyanopiperazine is dissolved in water to form an aqueous solution, and neutralized with sodium hydroxide or the like, 2-cyanopiperazine is released. This is extracted with an organic solvent such as ethyl acetate, and then the organic solvent is removed by evaporation, whereby 2-cyanopiperazine can be isolated.

[0016]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.
It is not limited to the embodiment. Example 1 (Production of 2-chloroacrylonitrile) 48.8 kg of acrylonitrile and 8.1 kg of dimethylformamide were charged into a 100 L supply tube and a reactor equipped with a stirrer.
At 30 ° C., chlorine was introduced into the raw material liquid under stirring through a supply pipe while bubbling, and a chlorination reaction was carried out to obtain a reaction liquid containing dichloropropionitrile.

Unreacted acrylonitrile was distilled off from the reaction solution under reduced pressure at 30 ° C. and 670 Pa. Next, the remaining reaction solution was sufficiently washed with water to remove dimethylformamide, and 71 kg of distilled water was added to the obtained crude dichloropropionitrile. At ３０30 ° C., 198 kg of a 19% aqueous sodium carbonate solution was added dropwise to carry out a dehydrochlorination reaction.

After completion of the reaction, the aqueous layer was removed from the reaction solution by liquid separation to obtain 52 kg of 2-chloroacrylonitrile liquid. It had a purity of 95% and was substantially free of acrylonitrile (the amount of acrylonitrile relative to 2-chloroacrylonitrile was 0% by weight). (Production of 2-cyanopiperazine) Ethylenediamine 51
5.0 g and 750.5 g of toluene were charged into a 3-liter separable flask with a jacket, and 263 g of 2-chloroacrylonitrile obtained above was added to 25 g of the flask.
It dripped under the temperature condition of -30 degreeC. Add distilled water 10
After adding 20 g and stirring, the toluene layer was removed by liquid separation to obtain 1173.1 g of an aqueous solution of 2-cyanopiperazine. This aqueous solution contained 243 g of 2-cyanopiperazine, and the yield based on 2-chloroacrylonitrile was 76.4%.

Comparative Example 1 (Production of 2-chloroacrylonitrile) After producing dichloropropionitrile, the method for producing 2-chloroacrylonitrile of Example 1 was repeated except that unreacted acrylonitrile was not distilled off from the reaction solution under reduced pressure. The reaction was performed in the same manner.
The obtained 2-chloroacrylonitrile has a purity of 75%,
It contained 25% by weight of acrylonitrile (33.3% by weight of acrylonitrile based on 2-chloroacrylonitrile).

(Production of 2-cyanopiperazine) Using the crude 2-chloroacrylonitrile thus obtained, a reaction was carried out in the same manner as in the production method of 2-cyanopiperazine in Example 1, to obtain 198 g of 2-cyanopiperazine. . The yield based on 2-chloroacrylonitrile was 62.5%. Comparative Example 2 (Production of 2-chloroacrylonitrile) A reaction was carried out in the same manner as in the method for producing 2-chloroacrylonitrile of Example 1, except that the supply amount of chlorine was reduced and acrylonitrile was not distilled under reduced pressure. 50% by weight of 2-chloroacrylonitrile and 50% by weight of acrylonitrile (2-
Acrylonitrile amount to chloroacrylonitrile 1
(00% by weight).

(Production of 2-cyanopiperazine) Using the crude 2-chloroacrylonitrile thus obtained, a reaction was carried out in the same manner as in the production method of 2-cyanopiperazine in Example 1, to obtain 158 g of 2-cyanopiperazine. . The yield based on 2-chloroacrylonitrile was as low as 50%.

[0022]

According to the present invention, the amount of ethylenediamine used can be reduced, and high-quality 2-cyanopiperazine can be produced in high yield.

Claims (3)

[Claims] In a method for producing 2-cyanopiperazine by reacting 2-halogenoacrylonitrile with ethylenediamine, 2-halogenoacrylonitrile as a raw material is obtained by dehalogenating dihalogenopropionitrile obtained by halogenating acrylonitrile. And the acrylonitrile content is 2-
A method for producing 2-cyanopiperazine, which is 15% by weight or less based on halogenoacrylonitrile. 2. The method for producing 2-cyanopiperazine according to claim 1, wherein the 2-halogenoacrylonitrile is 2-chloroacrylonitrile. 3. The method for producing 2-cyanopiperazine according to claim 1, wherein the amount of ethylenediamine used is 1 mol or less per 1 mol of 2-halogenoacrylonitrile.