JPS59212465A - Method for purifying aminosulfonic acid compound - Google Patents

Abstract

PURPOSE:To purify and obtain industrially and advantageously the titled compound useful as medicines in high purity, by treating a solution containing a specific aminosulfonic acid compound with both ion exchangers having respectively sulfonic acid groups and quaternary ammonium groups. CONSTITUTION:A solution containing an aminosulfonic acid of the formula (R1 and R2 are H or methyl; X is O or S or C-S bond through no X; n is an integer 1-3) is treated with both of (A) an ion exchanger having sulfonic acid groups and (B) an ion exchanger having quaternary ammonium groups to purify the aminosulfonic acid compound. ''Diaion SK'' series (tradename; manufactured by Mitsubishi Chemical Industries Ltd.), etc. is preferred for the ion exchanger (A), and ''Diaion SA'' series (manufactured by the same company) is preferred for the ion exchanger (B). The use of the above-mentioned method in the final step of the purification process at the removal of impurities to some extent permits the treatment of the compound of the formula in large quantities by using a small amount of the resin.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for purifying aminosulfonic acid compounds, and more specifically, the present invention relates to an aminosulfonic acid compound having both an amine group and a sulfonic acid group and forming an inner salt. This invention relates to a novel method for purifying acid compounds organically and skillfully using ion exchange resins.

Formula [I] 几2 (In the formula, R1 and R1 are the same or different and represent a hydrogen atom or a methyl group; X represents an oxygen or sulfur atom, or represents a carbon-sulfur bond without the intervention of X: n is 1~
Represents an integer of 6. The aminosulfonic acid compounds represented by ) include physiologically important compounds such as taurine, 2-amine ethanol acid sulfate, and 2-aminoethanethiol sulfate (cysteamine-8-sulfate, Bunte salt). There is. For example, taurine has physiological activities such as promoting bile secretion, promoting fat absorption, and antiperspirant properties, and 2-amine ethanol acid sulfate is useful as a raw material or synthetic intermediate for taurine and thiazolidine, and the latter is a compound that is also useful as a raw material for cysteamines, which are substances that play a role in preventing radiation damage.

Aminosulfonic acid compounds that have zwitterions and form inner salts are generally difficult to purify, and therefore a great deal of effort is required to purify them, especially when they are used as medicines. In order to purify compound [I], the fourth
Compound [
Even if 1) was treated, a purification method using such an ion exchanger was impossible because the compound [■] was exchanged and adsorbed by the resin and became 1-mer.

Despite this state of the art, we dared to try a purification method using ion exchange and conducted further research to establish it. In a system where ionic substances such as The present invention was completed based on this completely new technical discovery of separation and elution.

That is, the present invention provides a formula [■] characterized in that a liquid containing the compound CD is treated using both an ion exchanger having a sulfonic acid group and an ion exchanger having a quaternary ammonium group. >W production method of the aminosulfonic acid compound shown. As the ion exchanger having a sulfonic acid group, commercially available strong acidic cation exchange resins having a sulfonic acid group as an exchange group are widely used, such as Diaion 8. series, Diaion PK series (product name of Mitsubishi Chemical Industries, Ltd.) and Amberlite 1R10
0,200 series (trade name, Rohm and Haas Company, USA) is suitable. As the ion exchanger having a quaternary ammonium group, commercially available strong basic anion exchange resins having a quaternary ammonium group as an exchange group are widely used. For example, the Diaion SA series, the Diaion FA series (Mitsubishi Suitable examples include Amberlite IRA-400,900 series (trade name of Rohm and Haas Co., Ltd., USA). However, in any case, the intended purpose cannot be achieved unless treated with both of these ion exchangers.

The oil production method according to the present invention can be carried out advantageously even when inorganic salts and the like that are difficult to separate coexist with compound [I]. For example, since taurine is produced by the reaction of 2-amine ethanol acid sulfate and sodium sulfite, or the reaction of ethyleneimine and sulfuric acid, the presence of inorganic salts such as sodium sulfite or polyethyleneimine sulfite cannot be avoided. Since 2-aminoethanethiol sulfuric acid is produced by the reaction of ethylamine bromide, hydric acid bromide, and sodium thiosulfate, an inorganic salt (sodium bromide) is mixed therein. Therefore, purification in such cases is very advantageous, but in the case of other aminosulfonic acid compounds as well, when inorganic salts etc. are mixed to some extent, the method according to the present invention can separate amino groups and sulfonic acid groups. It can be applied to all compounds represented by the formula CD.

The purification method according to the present invention will be described below with reference to Test Examples and Examples.

Test Example 1 ■ Taurine sample 8.59 (67 meq) ■ 2-aminoethanethiol sulfate i bottle 10.5 r (67 meq) ■ 2-amine ethanol acid sulfate ester sample 9.5 f
(67 milliequivalents) was weighed and dissolved in 150 grams of water each. In this solution, 3.552 (50 meq.) of sodium bicarbonate (Na2SO+) was dissolved, and this solution was mixed with sulfonic acid group type cation exchange resin (product name: Diaion SKI BCH).
)) 60ml (114 meq.) and quaternary ammonium-based anion exchange resin (product name: Amberlite IR)
A-410 (OH)) 74 m (1 [10 meq.)] was passed through a mixed bed column at a Shibama velocity 5 (SV5).

When the effluent was concentrated to dryness, ■ Taurine 4.4f (recovery rate 53%)
) 2-aminoethanethiol sulfate 4.59 (recovery rate 40%) (3) 2-aminoethanol acidic sulfate ester 5.4r
(Recovery rate 57) (Na2SO4/Amberlite I RA-41oc
oi) equivalence ratio=0.5) is recovered.

(The resin groups used in 1 to 1 are trade names of Mitsubishi Chemical Industries, Ltd. and the Rohm and Haas Company of the United States.) Test Example 2 Weighed 8.34 (67 meq.) of taurine sample and poured it into 150 m/! of water. dissolve in In this solution, each of Na2SO4 ■ay, ■2.37t (33 meq.
6t (60 milliequivalents), ■4.73f (67 milliequivalents).

■5.689 (80mm twill), (6) 6.39
Dissolve 7.1F (100 meq.) of P (90 meq.) - This solution was passed through the same volume of mixed bed column as in Test Example 1 at Sv5, and the recovery rate of taurine was measured by the formol method. The results shown in Table 1 below were obtained.

Table 1 (A) Nat 804/Amberlite IRA-4
10 [oxr) equivalent ratio, where ■, ■, and ■ are acidic liquid outflow, so this acid portion is subtracted to convert the recovery rate) Test Example 6 Taurine sample 8.6 t (67 milliequivalents) and Na 2S
O44,26f (60 meq.) in water 15otnlVC
Dissolve and pass through the same amount of mixed bed column as in Test Example 1 at sv5. After passing through the solution, a solution of Na1SO42,84f (40 mm) dissolved in 140 mm of water was passed in the same manner.
The taurine content of the effluent at the once-through roll call where the acidic solution flows out and the effluent after the through-flow point were each measured by the formol method.

Taurine recovery rate flow-through point m [66% Torsion recovery rate 98% As is clear from the above test example, compound [I] was applied to both an ion exchange resin having a sulfonic acid group and an ion exchange resin having a quaternary ammonium group. When purification is carried out using an anion exchange resin, the recovery rate of compound CI) increases as the amount of coexisting inorganic salt increases. Almost the entire amount is absorbed, and t4 comes out at 7. However, no altitude + 3 Ai
An increase in m causes its leakage and a decrease in purity, but
In the presence of inorganic salts up to about 60% of the exchange capacity, the effluent is only the highly purified compound [l'), and the adsorption loss at that time is also suppressed to within about 40% of the exchange capacity.

Here, leakage of inorganic salts appears in the form of outflow of acidic liquid by increasing the exchange capacity of the cation exchange resin used than the exchange capacity of the anion exchange resin, so it is easy to monitor.

In other words, purification methods using both strongly acidic ion exchange resins and weakly basic ion exchange resins do not have the ability to decompose neutral salts, and because the weakly basic ion exchange resins have little ion-trapping ability, some ions leakage cannot be avoided. On the other hand, this purification method, which uses a strongly basic ion exchange resin with a quaternary ammonium group that has the ability to decompose neutral salts and has a strong ion-trapping ability, can also be used to treat reaction solutions. However, especially when carried out at the end of the purification process after some impurities have been removed, it is possible to process a large amount of compound [I) using a small amount of resin, and it is a useful method for obtaining highly pure compound CI). It is particularly excellent as an industrial purification method.

Next, examples of the present invention will be described.

Example 1 Ethyleneimine 71 [1r (16,5 mol) and 5O21
107f (17,5-El) A taurine aqueous solution synthesized using 1 ton of Yoshi water as a solvent is converted into a sulfonic acid group-type cationic anti-fat agent (Product name: Diaion SK1.8 (H”))
The solution was passed through a hot bed type column of 1.2 t and 1 t of primary, secondary amine type anion/exchange resin (trade name: Diaion WA 21 [OH)). Half of the effluent was further mixed with 50 mg of sulfonic acid type cation exchange resin (product name: Diaion 5KIB (+)) and quaternary ammonium type anion exchange resin (product name: Amberlite In, A-410[
:OH]) 37raI! The liquid is passed through a mixed bed column with If the effluent that did not pass through the column and the effluent treated with the 2-Shika column were concentrated under reduced pressure and then dried separately, purified taurine 932y (yield 90.4) was obtained.
%) and 9291 (yield: 90.1). Of these two types of crystals, the one that did not pass through the quaternary ammonium type anion father conversion resin showed leakage to the compound and sulfate, but no leakage was observed in the one that did.

Example 2 A 2-aminoethanethiol sulfuric acid aqueous solution synthesized from ethylamine bromide, hydrobromide and sodium thiosulfate was treated in the same manner as in Example 1, resulting in purified 2-amino with excellent purity. Ethanethiol sulfuric acid was obtained.

Agent Patent Attorney 1) Parent Male

Claims (1)

[Scope of Claims] The following formula (1) represents a carbon-sulfur bond without the intervention of X; n represents an integer from 1 to 6). 1. A method for purifying an aminosulfonic acid compound, the method comprising treating an aminosulfonic acid compound with both an ion exchanger and an ion exchanger.