JP2937797B2 - Method for producing aminoalkyl sulfonic acids - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel process for producing aminoalkylsulfonic acids. Aminoalkylsulfonic acids are compounds useful as pharmaceuticals, surfactants and the like.

[0002]

2. Description of the Related Art A conventionally known method for producing aminoalkylsulfonic acids using an aziridine compound as a raw material is disclosed in Chemisie Berichte, Vol. 21, pp. 2667-2668 (1).
888), a method of producing aminoethylsulfonic acid by reacting sulfuric acid with an aqueous solution of ethyleneimine, and Japanese Patent Publication No. 40-23007.
A 2 to 8% aqueous solution of ethyleneimine was cooled, and a sulfurous acid gas was rapidly introduced thereto at an upper limit of a liquid temperature of 18 ° C.
After raising the temperature to ６6, the liquid temperature was raised from 35 to 45 ° C., adjusted to pH 6 with sulfurous acid, and then concentrated and purified to produce aminoethylsulfonic acid, and Japanese Patent Publication No. 47-16807. However, by adding ethyleneimine or an ethyleneimine aqueous solution to the sulfite aqueous solution,
A method for producing aminoethylsulfonic acid by adjusting the pH to 4 to 7, and Japanese Patent Application Laid-Open No. 63-243066.
According to the above item, after adding an equimolar amount or less of ethyleneimine to sulfurous acid to a sulfite solution, at least one selected from the group consisting of ammonia, an alkali metal hydroxide, an alkali metal carbonate and an alkali metal sulfite. There is a method for producing aminoethylsulfonic acid by adding various inorganic salts, adjusting the pH of the reaction solution to 4 or more, and causing the reaction to proceed.

[0003]

In any of the above-mentioned methods for producing aminoalkylsulfonic acids using aziridine compounds as raw materials, the pH of the reaction solution is adjusted to 4 or more in order to suppress side reactions. I have. As a method of adjusting the pH, a method of using an excess of ethyleneimine with respect to sulfurous acid or a method of adding a basic compound such as caustic soda or ammonia to the reaction solution has been adopted. However, when the pH of the reaction solution is increased to 4 or more by such an operation, the reaction speed is rapidly increased, and the reaction is exothermic, so that it is extremely difficult to control the temperature in the initial stage of the reaction. However, if the reaction temperature is not controlled while removing a large amount of heat generated by cooling in practice, side reactions occur and the quality of the final product also deteriorates, so this reaction temperature control is indispensable in industry. is there. As a result, excessive equipment is required, resulting in an economic disadvantage.

An object of the present invention is to produce aminoalkylsulfonic acids from an aziridine compound as a raw material.
By using an aqueous bisulfite solution, the pH of the reaction solution
The operation for adjusting the temperature is eliminated, and the reaction temperature can be controlled by adjusting the feed rate to the reactor, so that equipment costs can be significantly reduced and high purity and high yield can be secured. Thus, an industrially advantageous production method can be provided.

[0005]

Means for Solving the Problems As a result of intensive studies, the present inventors have found a novel synthetic method completely different from the conventional method.

That is, the object of the present invention is to provide (A) the general formula (1)

[0007]

[0008]

[0009]

[0010]

[0011]

Embedded image (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
Aziridine compound represented by the following general formula (2):

Embedded image (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
And a reaction product solution containing an aminoalkyl sulfonic acid and a sulfite compound represented by the formula (1) to react with a sulfite gas to convert the sulfite to bisulfite. it <br/> made by the manufacturing method of the luer aminoalkyl sulfonic acids be <br/> and separating the aminoalkyl sulfonic acids and bisulfite aqueous solution by.

[0012] The present invention also, (B) the general formula (1)

Embedded image (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
Aziridine compound represented by the following general formula (2):

Embedded image (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
And a reaction product solution containing an aminoalkyl sulfonic acid and a sulfite compound represented by the formula (1) to react with a sulfite gas to convert the sulfite to bisulfite. by separating the aminoalkyl sulfonic acids and bisulfite solution, the nitrous hydrogen sulfate solution characteristics and to luer aminoalkyl sulphonic acids to be reused in the reaction with the aziridine compound represented by the general formula (1) This is also achieved by a manufacturing method.

[0013]

The aziridine compound represented by the general formula (1) in the present invention includes, for example, ethyleneimine, propyleneimine, N-methylethyleneimine, N-ethylethyleneimine, N-propylethyleneimine, N-methylpropyleneimine. , N-ethylpropyleneimine, N
-Propyl propylene imine and the like.

Examples of the bisulfite used in the present invention include alkali metal bisulfites such as sodium bisulfite and potassium bisulfite or ammonium bisulfite, and these can be used as an aqueous solution.

In the reaction of the present invention, an aziridine compound represented by the general formula (1) or an aqueous solution thereof is added to a bisulfite aqueous solution and reacted, or an aziridine compound represented by the general formula (1) or an aqueous solution thereof is added. And an aqueous solution of bisulfite are preferably supplied and mixed simultaneously or intermittently to cause a reaction, and any of a batch system, a continuous system, and a combination of these systems is possible. In any of the reaction modes, the reaction temperature is in the range of 0 to 100 ° C, preferably 30 to 60 ° C. The bisulfite is used in an amount of at least 2 equivalents, preferably 2 to 10 equivalents, to the aziridine compound. This is because in the reaction of an aziridine compound with a bisulfite, the following typical examples (reaction formula (A), ie, an example of an aziridine compound represented by the general formula (1) = ethyleneimine, bisulfite = sodium bisulfite)
This occurs because, in theory, bisulfite is required to be at least twice equivalent to the aziridine compound.

[0016]

Embedded image

Further, in order to control the reaction temperature within the above-mentioned reaction temperature range by adjusting the raw material supply rate to the reactor,
For example, when an aziridine compound represented by the general formula (1) or an aqueous solution thereof is added to an aqueous bisulfite solution to cause a reaction, the supply rate of the aziridine compound or the aqueous solution thereof is adjusted. When the indicated aziridine compound or its aqueous solution and the bisulfite aqueous solution are simultaneously supplied, the supply rates of both are adjusted.

In the present invention, an aminoalkylsulfonic acid and a sulfite-containing reaction represented by the general formula (2) obtained by reacting an aziridine compound represented by the general formula (1) with an aqueous bisulfite solution are provided. While maintaining the liquid temperature at 0 to 60 ° C., preferably 30 to 50 ° C. while stirring the resulting liquid, a sulfurous acid gas is blown therein, and then the liquid temperature is 0 to 60 ° C.
Preferably, crystals precipitated while keeping the temperature at 30 to 50 ° C. are separated by filtration with a centrifugal separator or the like to obtain aminoalkylsulfonic acid crystals, and at the same time, a bisulfite aqueous solution can be obtained as a filtrate. In a reaction when a sulfurous acid gas is blown into a reaction product liquid containing an aminoalkylsulfonic acid and a sulfite, the following typical example (reaction formula (B), that is, an example of aminoalkylsulfonic acid = aminoethylsulfonic acid and sulfite = sodium sulfite) is used. The reaction as shown occurs, converting the sulfite to bisulfite.

[0019]

Embedded image

At this time, the amount of the sulfurous acid gas to be blown is preferably the minimum amount necessary for converting the sulfite in the reaction product liquid before the blowing into hydrogensulfite. That is, with respect to the aziridine compound used as the raw material, 0.9 to
It is preferable to blow 1.2 times equivalent of sulfurous acid gas.
Also in this case, it is desirable to control the supply temperature of the sulfurous acid gas so as to be in the above-mentioned liquid temperature range from the viewpoint of greatly reducing equipment costs. In addition, bisulfite generated by the reaction of blowing sulfur dioxide gas has a higher solubility in water than the sulfite before the reaction, and the difference in solubility with aminoalkylsulfonic acids increases. When the sulfonic acids are crystallized and filtered, the separation from the aminoalkylsulfonic acids is facilitated, and the purity of the aminoalkylsulfonic acids obtained by separation is increased.

Further, in the present invention, a reaction product solution containing an aminoalkylsulfonic acid and a sulfite represented by the general formula (2) obtained by reacting an aziridine compound represented by the general formula (1) with an aqueous bisulfite solution is obtained. While stirring, the sulfuric acid gas is blown in while keeping the liquid temperature at 0 to 60 ° C, preferably 30 to 50 ° C, and then the precipitated crystals are centrifuged while keeping the liquid temperature at 0 to 60 ° C, preferably 30 to 50 ° C. The aminoalkylsulfonic acid crystals and bisulfite are separated by a separator or the like, and the aminoalkylsulfonic acid crystals obtained by separation are dried at 60 to 130 ° C, preferably 80 to 120 ° C, or Alternatively, if necessary, it can be purified by dissolving in water, recrystallizing, separating by the same method as described above, and drying. On the other hand, the aqueous bisulfite solution obtained by separation can be reused for the reaction with the aziridine compound represented by the general formula (1).

[0022]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1 892.0 g of a 35% by weight aqueous sodium bisulfite solution (3.0 mol, based on ethyleneimine) was placed in a 1000 ml four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. After adding 2 equivalents), while stirring, adjust the ethylene imine feed rate to the reactor to control the reaction temperature at 50 ° C. 64.6 g of imine
(1.5 mol) was added dropwise over about 2 hours. After completion of the dropwise addition, stirring was continued at 50 ° C. for 30 minutes. As a result of analyzing the aminoethanesulfonic acid in the obtained reaction solution by liquid chromatography, it was 19.2% by weight, and the reaction yield was 98 mol% with respect to ethyleneimine.

The resulting reaction solution was stirred with stirring (in order to control the reaction temperature at 40 ° C. by adjusting the rate of supply of sulfur dioxide to the reactor) while maintaining the solution temperature at 40 ° C.
5.1 g (1.0 equivalent equivalent to ethyleneimine) was blown in over about 1 hour. Thereafter, the liquid temperature is set to 40
The precipitated crystals were filtered off with a centrifugal separator while keeping the temperature at ° C. After 67.9 g of the separated crystals were dried at 105 ° C. for 2 hours, the purity of aminoethanesulfonic acid in 64.6 g of the obtained crystals was analyzed by liquid chromatography, and as a result, it was 98.7% by weight. The rate of recovery of aminoethanesulfonic acid from the reaction solution was 34.5%. Further, the loss amount of sodium bisulfite to the separated crystals was 1.2 g, which was 0.4% with respect to the charged amount.

984.9 g of the filtrate separated (containing about 3.0 mol of sodium bisulfite and 1.0 mol of aminoethanesulfonic acid) was filtered using the same stirrer, thermometer, dropping funnel and reflux condenser as described above. Into a 1000 ml four-necked flask equipped with an ethyleneimine solution while maintaining the liquid temperature at 50 ° C under stirring (to control the reaction temperature at 50 ° C by adjusting the feed rate of ethyleneimine to the reactor).
3 g (0.52 mol) was added dropwise over about 40 minutes. After completion of the dropwise addition, stirring was continued at 50 ° C. for 30 minutes. As a result of analyzing the aminoethanesulfonic acid in the obtained reaction solution by liquid chromatography, it was 18.3% by weight, and the reaction yield was 98 mol% based on the added ethyleneimine.

[0026]

According to the method of the present invention, when an aminoalkylsulfonic acid useful as a drug or a surfactant is produced from an aziridine compound as a raw material, there is no operation for adjusting the reaction pH, and the reaction temperature control is not performed. Since it becomes easy, equipment costs can be reduced, and high purity and high yield can be secured, which is industrially very advantageous.

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Masao Kitano 14-1, Chidori-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa Prefecture Nippon Shokubai Kawasaki Works (56) References JP-A-63-243066 (JP, A) ( 58) Field surveyed (Int. Cl. ⁶ , DB name) C07C 303/02 C07C 309/14

Claims (2)

(57) [Claims] 1. A compound of the general formula (1) (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
Aziridine compound represented by the following formula (2): (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
To a reaction product solution containing an aminoalkylsulfonic acid and a sulfite compound represented by the formula ( 3) , and further reacted with a sulfite gas to convert the sulfite to a bisulfite, followed by crystallization and filtration from the reaction solution. features and to luer Mino manufacturing method of alkylsulfonic acids that excessive separation of the aminoalkyl sulfonic acids and bisulfite aqueous solution by. 2. A compound of the general formula (1) (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
The aziridine compound represented the ~ 3 alkyl group Table Wa to), resulting formula is reacted with a bisulfite solution (2) ## STR4 ## (Wherein R ¹ and R ² represent a hydrogen atom or a carbon atom 1
To a reaction product solution containing an aminoalkylsulfonic acid and a sulfite compound represented by the formula ( 3) , and further reacted with a sulfite gas to convert the sulfite to a bisulfite, followed by crystallization and filtration from the reaction solution. over the separating aminoalkyl sulphonic acids and bisulfite solution, features and to luer aminoalkyl sulphonic acids to be reused in the reaction with the aziridine compound represented the nitrous hydrogen sulfate aqueous solution in the general formula (1) Manufacturing method.