JP2000212152A - Production of n-substituted glycinonitrile - Google Patents

Abstract

PROBLEM TO BE SOLVED: To suppress the generation of prussic acid and the production of a prussic acid polymer and produce the subject nitrile useful as a synthetic intermediate for insecticides, etc., in high yield by using an aqueous solution of an N-substituted amine or its aqueous solution and an aqueous solution of glycolonitrile as raw materials and limiting the method for feeding the raw material. SOLUTION: (A) An N-substituted amine represented by the formula R1R2NH [R1 and R2 are each H or a (substituted)1-8C alkyl] or its aqueous solution is reacted with (B) an aqueous solution of glycolonitrile while adding the component B thereto to produce the objective nitrile represented by the formula R1R2 NCH2CN. The reactional temperature of the above reaction is preferably kept at the boiling point of the component A or below and the component A is preferably used in an amount equimolar or more with the component B. A substance containing an acidic compound is preferably used as the component B and an organic solvent capable of forming an azeotropic mixture with water, especially toluene or benzene is preferably added to the resultant aqueous solution of the objective nitrile to carry out the azeotropic dehydration at >=80 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel process for producing N-substituted glycinonitriles which can be used as intermediates in the synthesis of insecticides and anti-ulcer drugs.

[0002]

2. Description of the Related Art Conventionally, N-substituted glycinonitriles have been produced by a known Mannich reaction using an N-substituted amine, hydrocyanic acid and formaldehyde, or by another reaction, N-substituted glycinonitrile. A method of synthesizing from a substituted amine and glycolonitrile is known.

In these known methods, for example, starting from dimethylamine, hydrocyanic acid and formaldehyde,
In the process for producing N, N-dimethylaminoacetonitrile, the yield is relatively good when the hydrocyanic acid is used in anhydrous form or as an alkali metal salt with hydrochloric acid;
It is known that N, N-dimethylaminoacetonitrile can be recovered from a water-containing reaction mixture by extraction with chloroform or benzene (J. Amer. Chem. S).
oc., 68, 1607 (1946)).

Further, German Patent No. 2503582 discloses that dimethylamine, hydrocyanic acid, and formaldehyde are used to maintain N, N concentration in a reaction solution at 0.01 to 0.1% by weight.
An example for producing N-dimethylaminoacetonitrile is disclosed.

The drawbacks of these known N-substituted glycinonitriles are, first of all, the use of anhydrous hydrocyanic acid, which requires strict working methods, working environment and production equipment, strict transportation, storage and processing control. The point is that you have to follow the rules. Further, when an alkali metal salt of hydrocyanic acid is used, there is a problem that a salt is formed and a large amount of water containing the salt must be separated by extraction. For these reasons, the known method for producing N-substituted glycinonitrile has a problem that it is particularly difficult to produce it economically.

Further, as a method for producing N, N-dimethylaminoacetonitrile using dimethylamine and glycolonitrile as raw materials, an extraction operation using an organic solvent such as ether is used to produce water in the reaction solution or to obtain N, N-dimethylaminoacetonitrile. To separate a large amount of water contained in water (Justus Liebigs Annalen
der Chemie, 279, 44 (1894)) or gaseous dimethylamine generated by the reaction of an aqueous solution of dimethylamine hydrochloride with NaOH is blown into glycolonitrile to give N, N-
A method of producing dimethylaminoacetonitrile and then purifying it by distillation (J. Org. Chem., 23, 613 (1958)) is known. However, in the former, there is no regulation on the feed order of the raw materials, and the yield of the target product is reduced due to generation of hydrocyanic acid and generation of hydrocyanic acid polymer, and a large amount of water containing hydrocyanic acid is contained in hydrocyanic acid contained therein. This is not an economical method since the wastewater must be decomposed after being decomposed. In the latter distillation purification, N, N-dimethylaminoacetonitrile and water generated by the reaction are azeotropic.
High purity products cannot be obtained in high yield. In addition, when the reaction is carried out in an anhydrous system, since gaseous dimethylamine is used, a pressure-resistant strong and expensive equipment is required, which is not economical.

[0007]

DISCLOSURE OF THE INVENTION The present invention relates to a process for producing N-substituted glycinonitrile, wherein N-substituted glycinonitrile is used as a starting material.
By using a substituted amine or an aqueous solution thereof and an aqueous solution of glycolonitrile, and by limiting the method of feeding the raw materials, generation of hydrocyanic acid and generation of hydrocyanic acid polymer are suppressed, and an N-substituted glycinonitrile aqueous solution is obtained in high yield Further, an object of the present invention is to provide a method for efficiently removing water in a reaction solution by an azeotropic dehydration method, and finally producing a N-substituted glycinonitrile in a high yield and a high purity by distillation purification. I do.

[0008]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for producing N-substituted glycinonitrile in high yield and high purity from N-substituted amine and glycolonitrile. By using an N-substituted amine or an aqueous solution thereof and an aqueous solution of glycolonitrile and performing a reaction by determining a raw material feed method, a reaction temperature, and a molar ratio, the N-substituted glycinonitrile is converted into an aqueous solution. A high yield is obtained by removing the water in the reaction solution efficiently using an azeotropic dehydration solvent, removing the azeotropic dehydration solvent by distillation, and then distilling the N-substituted glycinonitrile. It has been found that N-substituted glycinonitriles can be produced economically with high efficiency and high purity, and the above-mentioned problems can be solved. Thus, the present invention has been completed.

That is, the present invention provides (1) the following formula (1)
[Formula 3]

Embedded image (In the formula, R ¹ and R ² may be the same or different and each represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and the alkyl group is an alkyl group or an alkoxy group having 1 to 4 carbon atoms. Which may be substituted)
-Reacting with a substituted amine or an aqueous solution thereof while adding an aqueous solution of glycolonitrile;

Embedded image (Wherein R ¹ and R ² have the same definition as in the case of formula (1)). (1) wherein the N-substituted amine or the aqueous solution of N-substituted amine is carried out at a boiling point or lower, and (3) the N-substituted amine is at least equimolar to glycolonitrile. The production method according to (1), characterized in that it is used, and (4) the production method according to (1), which is characterized by using an aqueous solution of glycolonitrile containing an acidic compound, (5) N obtained by the method described in (1) above.
-A method for dehydrating an aqueous solution of N-substituted glycinonitrile, comprising adding an organic solvent azeotropic with water to an aqueous solution of substituted glycinonitrile and performing azeotropic dehydration, and (6) an azeotropic dehydration solvent, The dehydration method according to (5), which is toluene or benzene, and (7) the dehydration method according to (5), wherein azeotropic dehydration is performed at 80 ° C. or less. .

[0010]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, the starting material N-
Examples of the substituted amine include ammonia, methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, di (n-propylamine), methylethylamine, methoxyethylamine, di (methoxyethylamine), piperidine, and morpholine. ,
When an N-substituted amine aqueous solution is used, its concentration is not particularly limited, and may be any concentration.

In the present invention, it is essential that the reaction between the N-substituted amine and glycolonitrile is carried out while adding an aqueous solution of glycolonitrile to the N-substituted amine or an aqueous solution thereof. Conversely, when the reaction is carried out while adding the N-substituted amine to the aqueous solution of glycolonitrile, the glycolonitrile is easily decomposed, causing hydrocyanic acid generation and hydrocyanic acid polymer formation. Is not preferred because the yield of N-substituted glycinonitrile is reduced.

When the aqueous solution of glycolonitrile is added to the N-substituted amine or the aqueous solution thereof, the temperature of the reaction solution is usually in the range of -10 to 120 ° C., and particularly when the N-substituted glycinonitrile is obtained with good yield. In the above, it is preferable that the N-substituted amine is hardly vaporized during the reaction. That is, when the reaction is performed while adding the aqueous solution of glycolonitrile, the reaction temperature is preferably adjusted to be equal to or lower than the boiling point of the raw material N-substituted amine or the aqueous solution thereof.

That is, as an example, 50% by weight of N,
If an N-dimethylamine aqueous solution is used, the boiling point of this 50% by weight aqueous solution at normal pressure is 43%.
° C), and by adding glycolonitrile so that the temperature of the reaction solution is maintained at 43 ° C or less, N, N-dimethylamine is not vaporized and the reaction is efficiently performed without being removed outside the system. N, N in high yield
-It is possible to obtain dimethylacetonitrile.

The amounts of the N-substituted amine and glycolonitrile, which are the starting materials, are as follows per mole of glycolonitrile.
Usually, the reaction can be carried out by setting the N-substituted amine in the range of 0.1 to 5 mol. However, in order to suppress the generation of hydrocyanic acid, the N-substituted amine is used per mol of glycolonitrile. It is preferable to use 1 mol or more, and it is more preferable to use 1.0 to 1.1 times mol.
It is more preferable from the viewpoint of economy and the like.

In the present invention, the concentration of the aqueous solution of glycolonitrile as a raw material is not particularly limited, and any concentration can be used. In this case, as the aqueous solution of glycolonitrile, an acidic compound is further added to a solution obtained by reacting an aqueous solution of formalin and a cyanuric acid (eg, 98% by weight hydrocyanic acid) in an equimolar amount in the presence of a trace amount of a metal hydroxide. It is preferable to use a solution which is added and has a pH of about 2 to improve stability. Examples of the acidic compound added at this time include hydrochloric acid and sulfuric acid.

In the present invention, the rate of addition of the N-substituted amine or the aqueous solution of glycolonitrile to be added to the aqueous solution may be such that the above-mentioned reaction temperature is maintained, or the reaction provided with a cooler. The above-mentioned reaction temperature may be maintained while removing heat using a vessel, and an aqueous solution of glycolonitrile may be added.

Next, an organic solvent is used to azeotropically dehydrate the N-substituted glycinonitrile product obtained in the above reaction. The organic solvent used at this time is a compound which azeotropes with water and has a boiling point lower than the boiling point of the azeotropic mixture of water and the azeotropic mixture of water and the N-substituted glycinonitrile and the organic solvent used. For example, toluene, benzene, isopropyl acetate, ethyl acetate, methyl acetate, isopropyl ether, cyclohexane, 4-methyl-2-pentanone and the like can be mentioned. Of these, toluene or benzene is particularly preferred. Although the amount of the organic solvent used is arbitrary, it is preferable to use an amount of 0.1 to 5 times by weight of the N-substituted glycinonitrile.

The temperature inside the reaction vessel when performing the azeotropic dehydration operation can be arbitrarily set, but it is preferable to perform the azeotropic dehydration at 80 ° C. or lower at which the stability of the N-substituted glycinonitrile can be obtained. Further, it is more preferable to carry out azeotropic dehydration by setting the temperature in the kettle to 80 ° C. or lower under reduced pressure. In this case, hydrocyanic acid is hardly detected in the azeotropic dehydration solution.

In the present invention, in the azeotropic dehydration, it is necessary to selectively remove water in order to obtain N-substituted glycinonitrile in high yield, and it is preferable to use a distillation column.
In addition, the organic solvent distilled out of the system together with water may be returned to the kettle again after separation from water.

When removing the organic solvent from the inside of the kettle after dehydration by distillation, a normal pressure system or a reduced pressure system may be used, and the temperature in the kettle is arbitrary, but it is preferably 100 ° C. or less in consideration of stability. preferable. Further, it is preferable to use a distillation column.

In the present invention, when the N-substituted glycinonitrile is distilled, the distillation may be carried out under normal pressure or under reduced pressure.

[0022]

The following examples and comparative examples illustrate the method for producing N-substituted glycinonitriles according to the present invention. In the following, percentages are by weight unless otherwise specified.

EXAMPLE 1 515.2% aqueous dimethylamine solution (265.2 g, 3.00 mol) was added to 51% dimethylamine aqueous solution.
335.6 g (3.00 mol) of a 30% aqueous solution of glycolonitrile was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 35 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. As a result, an N, N-dimethylaminoacetonitrile aqueous solution was obtained in a yield of 99.8 mol% based on glycolonitrile. Next, 120 g of toluene was added to the reaction solution, and azeotropic dehydration was performed for 4 hours using a distillation column having eight theoretical plates to remove water from the system. At this time, the pressure was reduced to 400 to 100 mmHg so that the temperature in the kettle could be maintained at 80 ° C or lower. The toluene distilled out together with the water was separated from the water and returned to the inside of the kettle. Thereafter, toluene was distilled out of the system at a temperature in the kettle of 80 ° C. or lower / 100 mmHg. The detoluene solution contains 25.2 g of N, N-dimeraminoacetonitrile. The crude N, N-dimethylaminoacetonitrile remaining in the kettle
Distillation under reduced pressure was performed at a temperature of not more than ℃ to obtain 196.1 g of N, N-dimethylaminoacetonitrile (yield: 77.3 mol% / glyconitrile, purity: 99.5%). 26.5 g of N, N-dimethylaminoacetonitrile adhere to the distillation column.

Example 2 Using the distillation column to which N, N-dimethylaminoacetonitrile used in Example 1 was attached, 270.5 g (3.06 mol) of a 51% aqueous dimethylamine solution was added to 335.6 g (3.00 mol) of a 51% aqueous solution of glycolonitrile. Mol) was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 35 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. As a result, an aqueous N, N-dimethylaminoacetonitrile solution based on glycolonitrile
Obtained in a yield of 99.8 mol%. Next, 120 g of the toluene-free solution (containing 25.2 g of N, N-dimethylaminoacetonitrile) obtained in Example 1 was added to the reaction solution, and azeotropic dehydration was performed for 4 hours using a distillation column having eight theoretical plates. Then, water was removed from the system. At this time, the pressure was reduced to 400 to 100 mmHg so that the temperature in the kettle could be maintained at 80 ° C or lower. The toluene distilled out together with the water was separated from the water and returned to the inside of the kettle. After that, the temperature in the kettle is 80 ° C or less / 100mmH.
It was distilled out of the system with g. This detoluene solution contains 25.2 g of N, N-dimethylaminoacetonitrile. Crude N, N-dimethylaminoacetonitrile remaining in the kettle
Distillation under reduced pressure at 100 ° C. or lower gave 248.1 g of N, N-dimethylaminoacetonitrile (yield 97.8 mol% / glyconitrile, purity 99.5%). 26.5 g of N, N-dimethylaminoacetonitrile adhere to the distillation column. Through a series of steps from the reaction to the distillation, the amount of hydrocyanic acid generated was as small as 0.05 mol% / glycoronitrile or less.

Example 3 To 223.9 g (3.00 mol) of 98% diethylamine, 335.6 g (3.00 mol) of a 51% aqueous solution of glycolonitrile was added dropwise over 4 hours while maintaining the temperature of the reaction solution at 45 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. As a result, an N, N-diethylaminoacetonitrile aqueous solution was obtained in a yield of 99.8 mol% based on glycolonitrile. Next, 120 g of toluene was added to the reaction solution, and azeotropic dehydration was performed for 5 hours using a distillation column having eight theoretical plates to remove water from the system. At this time, the degree of pressure reduction was set so that the temperature in the kettle could be maintained at 80 ° C or less.
The test was performed while adjusting the pressure to 400 to 100 mmHg. The toluene distilled out together with the water was returned to the kettle after separation from the water. Thereafter, toluene was distilled out of the system at a temperature in the kettle of 80 ° C. or lower / 100 mmHg.
This detoluene solution contains 33.7 g of N, N-dieluaminoacetonitrile. The crude N, N-diethylaminoacetonitrile remaining in the kettle was distilled under reduced pressure at a temperature of 100 ° C or less in the kettle to obtain 260.4 g of N, N-diethylaminoacetonitrile.
(Yield: 77.0 mol% / glyconitrile, purity: 99.5%). 35.3 g of N, N-diethylaminoacetonitrile adhere to the distillation column.

Example 4 Using the distillation column to which N, N-diethylaminoacetonitrile used in Example 3 was attached, 335.6 g (3.00 mol) of a 51% aqueous solution of glycolonitrile was added to 270.5 g (3.06 mol) of a 51% aqueous solution of diethylamine. Was added dropwise over 4 hours while maintaining the temperature of the reaction solution at 45 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. As a result, an N, N-diethylaminoacetonitrile aqueous solution was obtained at a yield of 99.8 mol% based on glycolonitrile. Next, 120 g of the toluene-free solution (containing 33.7 g of N, N-diethylaminoacetonitrile) obtained in Example 3 was added to this reaction solution, and the number of theoretical plates was 8
Azeotropic dehydration was carried out for 5 hours using a distillation column of the stage, and water was removed from the system. At this time, the pressure was adjusted to 400 to 100 mmHg so that the temperature in the kettle could be maintained at 80 ° C. or lower. The toluene distilled out together with the water was returned to the kettle after separation from the water. Thereafter, toluene was distilled out of the system at a temperature in the kettle of 80 ° C. or lower / 100 mmHg. This detoluene solution contains 33.7 g of N, N-diethylaminoacetonitrile. Crude N, N remaining in the kettle
-Diethylaminoacetonitrile was distilled under reduced pressure at a temperature of 100 ° C. or less in a kettle, and 328.1 g of N, N-diethylaminoacetonitrile (yield 97.0 mol% / glyconitrile, purity
99.5%). 35.3 g of N, N-diethylaminoacetonitrile adhere to the distillation column. Through a series of steps from the reaction to the distillation, the amount of hydrocyanic acid generated was as small as 0.05 mol% / glycoronitrile or less.

Example 5 To 265.2 g (3.00 mol) of a 51% aqueous dimethylamine solution was added 51%
335.6 g (3.00 mol) of a 30% aqueous glycolonitrile solution was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 35 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. As a result, an N, N-dimethylaminoacetonitrile aqueous solution was obtained in a yield of 99.8 mol% based on glycolonitrile.
Next, 120 g of toluene was added to the reaction solution, and the number of theoretical plates was 8;
Using a stage distillation column, azeotropic dehydration was performed for 11 hours under normal pressure, and water was removed from the system. The temperature in the kettle at this time was 90 to 112 ° C. The toluene distilled out together with the water was returned to the kettle after separation from the water. Thereafter, toluene was distilled out of the system at a temperature of 80 ° C / 100 mmHg in the kettle. The detoluene solution contains 25.2 g of N, N-dimeraminoacetonitrile. Crude N remaining in the kettle
N-Dimethylaminoacetonitrile was distilled under reduced pressure at a temperature of 100 ° C. or less in a kettle to obtain 178.6 g of N, N-dimethylaminoacetonitrile (yield: 70.4 mol% / glyconitrile, purity: 99.5%). 26.5 g of N, N-dimethylaminoacetonitrile adhere to the distillation column.

Comparative Example 1 A 51% aqueous solution of glycolonitrile (335.6 g, 3.00 mol) was added to
265.2 g (3.00 mol) of a 51% aqueous dimethylamine solution was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 35 ° C. (that is, the addition of the reactants in Example 1 was reversed). . After the addition, the mixture was further stirred at the same temperature for 1 hour. The yield of the aqueous solution of N, N-dimethylaminoacetonitrile was 79.8 mol% based on glycolonitrile.

Comparative Example 2 515.2% aqueous dimethylamine solution (265.2 g, 3.00 mol) was added to 51% dimethylamine aqueous solution.
335.6 g (3.00 mol) of a 30% aqueous solution of glycolonitrile was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 60 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. The yield of the aqueous solution of N, N-dimethylaminoacetonitrile was 61.8 mol% based on glycolonitrile, and the amount of hydrocyanic acid was 0.6 mol% based on glycolonitrile.

Comparative Example 3 51% dimethylamine aqueous solution (252.0 g, 2.85 mol) was added to 51% dimethylamine aqueous solution.
335.6 g (3.00 mol) of a 30% aqueous glycolonitrile solution was added dropwise over 3 hours while maintaining the temperature of the reaction solution at 35 ° C. After the addition, the mixture was further stirred at the same temperature for 1 hour. The yield of the aqueous solution of N, N-dimethylaminoacetonitrile was 94.6 mol% based on glycolonitrile, and the amount of hydrocyanic acid was 0.4 mol% based on glycolonitrile.

COMPARATIVE EXAMPLE 4 To 1320 g (7.34 mol) of a 25% aqueous dimethylamine solution was added 37%
660 g (8.14 mol) of formalin are added dropwise at 25 ° C or lower. After the completion of the dropwise addition, 396 g (7.75 mol) of 96% NaCN was added thereto while maintaining the temperature of the reaction solution at 25 ° C. or lower, and after the completion of the addition, the mixture was stirred at 25 ° C. for 1 hour. Then, after adding 610 cc (7.10 mol) of concentrated hydrochloric acid, the mixture is stirred for 15 hours. Extract with chloroform or benzene, and dry the organic layer with magnesium sulfate or the like. After filtration, the organic layer is concentrated to remove the organic solvent. The crude N, N-dimethylaminoacetonitrile remaining in the kettle was distilled to obtain 450 g of N, N-dimethylaminoacetonitrile. The yield of N, N-dimethylaminoacetonitrile by this operation is based on dimethylamine.
73 mol%.

[0032]

According to the present invention, an aqueous solution of glycolonitrile is added to an N-substituted amine or an aqueous solution thereof to form N-substituted glycinonitrile, an organic solvent azeotropic with water is added, and water is removed by azeotropic dehydration. Thereafter, the organic solvent is removed, and N-
The method of the present invention for obtaining a substituted glycinonitrile is a more economical and safer method than before, and has made it possible to produce an N-substituted glycinonitrile in a higher yield and a higher purity. .

Continued on front page (72) Inventor Hideo Ogata 1900 Togo, Mobara-shi, Chiba Mitsui Chemicals Co., Ltd. (72) Inventor Atsushi Atsushi 1900 Togo, Mobara-shi, Chiba Pref. 1900 Togo, Mobara-shi, Chiba F-term (reference) 4H006 AA02 AC54 BA66 BB11 BB15 BB16 BB17 BC10 BC31 BC35 BD20 BU32 NB16 QN30

Claims (7)

[Claims] 1. A compound represented by the following formula (1): (In the formula, R ¹ and R ² may be the same or different and each represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and the alkyl group is an alkyl group or an alkoxy group having 1 to 4 carbon atoms. Which may be substituted)
Wherein the reaction is carried out while adding an aqueous solution of glycolonitrile to the substituted amine or an aqueous solution thereof, characterized by the following formula (2): (Wherein R ¹ and R ² have the same definition as in formula (1)). 2. The method according to claim 1, wherein the reaction is carried out at a reaction temperature equal to or lower than the boiling point of the raw material N-substituted amine or the aqueous solution of N-substituted amine. 3. The method according to claim 1, wherein the N-substituted amine is used in an amount equal to or more than the mole of glycolonitrile. 4. The method according to claim 1, wherein an aqueous solution of glycolonitrile containing an acidic compound is used. 5. N-type obtained by the method according to claim 1.
A method for dehydrating an aqueous solution of N-substituted glycinonitrile, comprising adding an organic solvent azeotropic with water to an aqueous solution of substituted glycinonitrile and performing azeotropic dehydration. 6. The method according to claim 5, wherein the azeotropic dehydration solvent is toluene or benzene. 7. The dehydration method according to claim 5, wherein the azeotropic dehydration is performed at 80 ° C. or lower.