JPS61140561A - Production of aziridine-2-nitrile or aziridine-2-carboxylic acid amide - Google Patents

Abstract

PURPOSE:To produce the titled compound in high yield, by reacting an inexpensive chlorine compound consisting of 2,3-dichloropropionitrile or 2- chloroacrylonitrile as a raw material with ammonia in a solvent at a specific temperature. CONSTITUTION:2,3-Dichloropropionitrile or 2-chloroacrylonitrile is reacted with ammonia in a solvent at 20-200 deg.C reaction temperature to give aziridine-2-nitrile or aziridine-2-carboxylic acid amide. In the reaction, one of the reaction products is producible selectively by choosing a condition. Namely, aziridine-2-nitrile is obtained when a solvent such as an alcohol, an ether, an aromatic hydrocar bon, an aliphatic hyderocarbon, or its mixed solvent is used as the solvent, and aziridine-2-carboxylic acid amide is obtained with a mixed solvent of the solvent and water, or >=150 equivalents water based on a substrate is used in the reaction system. A mixture of both the compounds is obtained in case of water solvent.

Description

[Detailed Description of the Invention] Good 1f (7 summer old) This invention relates to 2,3-dichloropropionitrile or 2-
The present invention relates to a method for producing aziridine-2-nitrile and/or aziridine-2=carboxylic acid amide from chloroacrylonitrile.

Both aziridine-2-nitrile and aziridine-2-carboxylic acid amide are compounds that themselves and their derivatives have physiological activity such as antitumor activity, and are also used as intermediates for pharmaceuticals, agricultural chemicals, α-amino acids, etc. It is a compound useful as a raw material for synthetic resins, etc.

Problem 1: The following two methods are known for producing aziridine-2-nitrile.

(1) 2.3-SibaO propionitrile or 2
- A method of reacting haloacrylonitrile (chlorine and bromine as halogens) with liquid ammonia (Japanese Patent Publication No. 46-3
1850).

(2) 2,3-dibromopropionitrile or 2
- A process for reacting bromoacrylonitrile with liquid ammonia in the presence of triethylamine (Anoew, C
hea+, Int, Ed, Engl,
, 1 yu.

151 (1972)).

Although these methods are useful to some extent, they each have their own problems. In other words, method (1) is applicable only when bromine is used as the halogen.
There is no description of the isolated yield of nitrile. When the present inventors conducted a follow-up test using chlorine as the halogen under the same conditions as in the method, the yield of aziridine-2-nitrile was extremely lower than in the case of bromine (see Comparative Example 1). Therefore, this method cannot be said to be industrially advantageous in terms of raw material economy. Furthermore, method (2) cannot be said to be industrially advantageous for the same reason as method (1).

On the other hand, the following three methods are known as methods for producing aziridine-2-carboxylic acid amide.

(3) Method by reaction of 2.3-dibromopropionic acid ester or 2-bromoacrylic acid amide with liquid ammonia (Swiss Patent No. 362.078 <19
57), and He+v.

C11m, ACta, raw 9.359 (1966)
).

(4) Method by reaction of aziridine-2-carboxylic acid ester with liquid ammonia or alcoholic ammonia (Chem, 3er, 93°1632
(1960) and West German Patent (Publication) No. 2,748
．． No. 015 (1976)).

(5) Method for partially hydrolyzing aziridine-2-nitrile (East German Patent No. 129.551 (1977) and J. Prakt, CheIIl, 321
.

712 (1979)).

However, these methods may also have problems. In other words, method (3) does not include any description of the yield of aziridine-2-carboxylic acid amide and uses a bromine compound as a raw material, so it cannot be said to be an industrially advantageous method in terms of economic efficiency. In this method, when a chlorine compound is used instead of a bromine compound, almost no aziridine-2-carboxylic acid amide is obtained (see Comparative Example 2). On the other hand, methods (4) and (5) have a yield of about 80% and about 9%, respectively.
Although it is as high as 5%, it is difficult to obtain the aziridine compound as a raw material, and therefore these methods cannot be called industrial methods either.

Summary of the Invention The present inventors have conducted intensive studies on industrial production methods for aziridine-2-nitrile and aziridine-2-carboxylic acid amide using inexpensive chlorine compounds as raw materials, and have found that 2,3-
A method of the present invention using dichloropropionitrile or 2-chloroacrylonitrile as a raw material has been completed.

That is, the method for producing aziridine-2-nitrile and/or aziridine-2-carboxylic acid amide according to the present invention involves heating 2,3-dichloropropionitrile or 2-chloroacrylonitrile at 20°C to 200°C in the presence of a solvent. ℃
It is characterized by reacting with ammonia at a reaction temperature of .

According to the present invention, the problems of the prior art described above are solved.

The method of the present invention uses heating conditions (20°C to 20°C
00°C) using a solvent, it is an industrial method that provides aziridine-2-nitrile and aziridine-2-carboxylic acid amide in high yields previously unobtainable from inexpensive chlorine compound raw materials. This is a valuable method.

Moreover, in the method of the present invention, only aziridine-2-nitrile or only aziridine-2-carboxylic acid amide can be selectively produced by controlling the conditions.

Zunawara, 2,3-dichloropropionitrile or 2
- By reacting chloroacrylonitrile with ammonia at a reaction temperature of 20°C to 200°C in the presence of a solvent such as alcohols, ethers, aromatic hydrocarbons, aliphatic hydrocarbons, or a mixed solvent thereof. , aziridine-2-nitrile is selectively obtained in good yield. On the other hand, a mixture of aziridine-2-nitrile and aziridine-2-carboxylic acid amide can be obtained in good yield by reaction in a mixed solvent of the above-mentioned solvent and water as a reaction solvent or in an aqueous solvent. Furthermore, in this reaction system, for the substrate,
By carrying out the reaction using 150 equivalents or more of water, aziridine-2-carboxylic acid amide can be selectively obtained in good yield.

Examples of the solvent used in this case include alcohols, ethers, aromatic hydrocarbons, aliphatic hydrocarbons, and the like.

Alcohols include methanol, ethanol, n-propertool, 1=propertool, n-butanol, i-
Butanol, 5ec-butanol, ethylene glycol, cellosolve, etc. are ethers, diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, etc. are examples of aromatic hydrocarbons, benzene, toluene, xylene, etc. are examples of aliphatic hydrocarbons. is n-
Examples include hexane, n-hebutane, n-octane, cyclohexane, and the like. Among them, methanol, ethanol, 1-propanol, toluene, etc. are preferable.

Ammonia The preferred amount of ammonia to be used for each raw material is 2.
For 3-dichloropropionitrile, it is 3 to 200 equivalents, and for 2-chloroacrylonitrile, it is 2 to 200 equivalents.
It is 200 equivalents. A more preferable amount for each raw material is 10 to 100, and a further preferable amount is 20 to 100.
60 equivalents.

In addition, the concentration of ammonia in the solvent is 1% by weight to 95% by weight.
% by weight, preferably from 5% to 80% by weight. When the solubility of ammonia in the solvent at normal pressure is lower than the concentration of ammonia in the solvent used, it is preferable to carry out the reaction in a pressurized system.

The reaction temperature and time for the aziridine-2-
It is an important factor for the yield of nitrile. Usually 2
A suitable temperature range is 0°C to 200°C for 0.05 hours to 48 hours.

The combination of reaction temperature and time is important and varies depending on the type and concentration of the substrate, the type of solvent, the concentration of ammonia, etc., but especially the reactivity of the substrate with ammonia and the amount of aziridine-2-nitrile produced. It is necessary to create a combination that takes decomposition or sequential reactions into consideration. That is, at high temperatures, for example 100° C. or higher, a short period of time, for example within 4 hours, is preferred, particularly 0.1 hour to 2 hours. Further, at a relatively low temperature, for example, 50° C. or lower, the heating time is preferably 0.5 hours or more, particularly preferably 1 to 30 hours.

In this case, the reaction may be carried out using a mixed solvent to which water is added or only water as a solvent under the conditions shown in case (1).

In this case, the amount of water relative to the substrate greatly influences the production ratio of aziridine-2-nitrile and aziridine-2-carboxylic acid amide. In other words, if the amount of water is relatively large,
For example, at 80 equivalents or more relative to the substrate, aziridine-2
- When the formation of carboxylic acid amide becomes dominant and the amount of water is relatively small, for example, when the amount of water is less than 70% relative to the substrate,
The formation of aziridine-2-nitrile becomes predominant.

In this case, aziridine-2-2-
Only carboxylic acid amide can be selectively obtained.

Tomo-Nao-1 In the following analysis, raw materials and products were analyzed by high performance liquid chromatography.

10.0 g of 2,3-dichloropropionitrile (80,6+an+ol) and 56 tJ (932 u+of) of 1-propanol were placed in a 300 m reactor and stirred. Here, ammonia 56y (3,29n) was added while cooling.
ol), and then reacted at 60°C for 4 hours.

As a result of the analysis, the conversion rate of 2,3-dichloropropionitrile was 100%, the yield of aziridine-2-nitrile was 77.9%,
The acid amide yield of aziridine-2-carbon was 0%.

11 1 2-chloroacrylonitrile 6 in a 300 II reactor
, 09 (68,6+u+ol) and methanol 46
g (1,44a+ol) was added thereto and stirred. Here,
°Ammonia 46g (2,711 ot) while cooling
After filling the container, the reaction mixture was allowed to react at 80° C. for 2 hours. As a result of analysis, 2-chloroacrylonitrile conversion rate was 100%, aziridine-2-nitrile yield was 81.4%, and aziridine-2-nitrile yield was 81.4%.
The yield of carboxylic acid amide was 0%.

Add 165 g of 10% ammonia water (16.59 (968 mm+ol) as ammonia) to a 300 mg reactor.
Add 148.5g (8.25ml) of water,
It was heated to 50°C. 3.0 g (24.2 mmol) of 2,3-dichloropropionitrile was added thereto, followed by reaction at 50°C for 4 hours.

As a result of the analysis, the conversion rate of 2,3-dichloropropionitrile was 100%, and the yield of aziridine-2-carboxylic acid amide was 89%.
．． The yield of aziridine-2-nitrile was 0%.

78g of 10% ammonia water (7.8g (459mmol) as ammonia, 7.8g (459mmol) as water) was placed in a 1U 200d reactor.
0.2g (3.90nol)) and heated to 50°C. Here, 2.0 g of 2-chloroacrylonitrile
(22.9 mmol) and then heated to 50℃ for 8 hours.
Time reacted. As a result of analysis, the conversion rate of 2-chloroacrylonitrile was 100%, the yield of aziridine-2-carboxylic acid amide was 74.5%, and the yield of aziridine-2-nitrile was 0%.

Example 5 In a 300IIt reactor, 5.0g (40.3ml 1lol) of 2,3-dichloropropionitrile, 15g (469moof) methanol, and 75g (4,17ml) water were added.
moljl) and stirred. This was filled with 14 g (824 nn+ol) of ammonia while cooling, and then reacted at 80° C. for 6 hours. Analysis results 2,3
-Dichloropropionitrile conversion rate was 100%, aziridine-2-nitrile yield was 40.0%, and aziridine-2-carboxylic acid amide yield was 46.3%.

Tomotane 6.0 2-chloroacrylonitrile in a 300m reactor
g (68,6mn+ol), i-Proper Tools 45
g (749 mn+ol), water 45 g (2,50 no.
1) and stirred. After filling 45 g (2,65 ioj!) of ammonia while cooling, 8
The reaction was carried out at 0°C for 2 hours. As a result of analysis, the conversion rate of 2-chloroacrylonitrile was 100%, the yield of aziridine-2-nitrile was 52.5%, and the yield of aziridine-2-carboxylic acid amide was 33.2%.

Comparative Example 1 In a 300 d reactor, 50 g (403 + uoJ) of 2,3-dichloropropionitrile was put, and while cooling, 150 m (91 g, 53.51 Oj) of ammonia was added and reacted at 20°C for 10 hours. Ta.

After distilling off ammonia, the residue was extracted with ether and analyzed, and the yield of aziridine-2-nitrile was 27.3.
%Met. After concentration, distillation under reduced pressure is performed to obtain aziridine-2-
6.4 g (94,01101) of nitrile were obtained. (
Isolated yield: 23.3%) Comparative Example 2 120 m (82 g, 4.82 nol) of ammonia was charged into a 200 Id glass reactor equipped with a cooling tube for dry ice while cooling it in a dry ice-acetone bath. Here, 250q of N-phenyl-2-naphthylamine
After adding 2,3-dichloropropionic acid methyl ester, 4.7 g (29,9n++aol) was added dropwise over 30 minutes. Next, remove the dry ice-acetone bath,
The reaction was carried out under liquid ammonia reflux conditions (-26°C) for 3 hours. After the reaction, the cooling tube was removed and ammonia was distilled off. As a result of extracting and analyzing the residue with isopropanol, the yield of aziridine-2-carboxylic acid amide was only 1.
．． It was 7%.

Claims (1)

[Claims] 2,3-dichloropropionitrile or 2-chloroacrylonitrile is reacted with ammonia in the presence of a solvent at a reaction temperature of 20°C to 200°C,
aziridine-2-nitrile and/or aziridine-
Method for producing 2-carboxylic acid amide.