JPH023676A - Production of aminoalkylthiol sulfate - Google Patents

Abstract

PURPOSE:To obtain the subject compound by reacting halogenoamine hydrohalides or aminoalkyl sulfates with thiosulfates in the presence of an alkaline catalyst, electrodialyzing the resultant reaction solution and removing inorganic salts. CONSTITUTION:Halogenoalkylamine hydrohalides (e.g., 2-aminoethyl chloride) expressed by formula I (R1 and R2 are H or alkyl; n is 2-4; X is halogen) or aminoalkyl sulfates (e.g., 2-aminoethyl chloride sulfate) expressed by formula II are reacted with thiosulfates in the presence of an alkaline catalyst to provide a reaction solution containing aminoalkylthiol sulfates expressed by formula III. The resultant reaction solution is then electrodialyzed to remove inorganic salts and afford aminoalkylthiol sulfates. Separation can be extremely readily carried out in high purity by the above-mentioned method. The afore-mentioned compound is useful as an intermediate for medicines, intermediate raw material for cosmetics and also as a substance having radiation protecting action.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention is a novel method for producing aminoalkylthiol sulfates! +!
! The aminoalkylthiol sulfates obtained by the present invention are extremely useful substances as pharmaceutical intermediates, cosmetic intermediate raw materials, and substances with radiation prevention effects.

(Prior art) Conventionally, known production methods for obtaining aminoalkylthiol sulfates include: (1) Reacting halogenoalkylamines with sodium thiosulfate, removing inorganic salts from the reaction solution, and concentrating the P solution to dryness. After that, the remaining inorganic salts are removed by mixing a lower alcohol such as methanol or ethanol with water, and then recrystallization is performed.

■ Aminoalkyl sulfates and ammonium thiosulfate or metal thiosulfates are reacted in the presence of an alkaline catalyst, the inorganic salts are separated from the reaction solution, the filtrate is concentrated to dryness, and then mixed with lower alcohols such as methanol or ethanol and water. The remaining inorganic salts are further removed by mixing and combing.
A method of concentrating to dryness (Japanese Unexamined Patent Publication No. 57-67555) is known.

(Problems to be Solved by the Invention) Conventionally, in the above method, a complicated separation and purification method is performed in order to isolate the target product, aminoalkylthiol sulfuric acid, from the reaction solution, so it is not economical as an industrial production method. I cannot say that it is.

The present inventors conducted intensive research to improve the problems of the above-mentioned conventional methods, and found that hydrogen halides of halogenoalkylamines or aminoalkyl sulfates were reacted with thiosulfates in the presence of alkaline wax. The inventors have discovered that the product aminoalkylthiol sulfates can be separated very easily and with high purity by electrodialyzing the resulting reaction solution and removing the :Qlfi salt, leading to the present invention. .

(Means for Solving the Problems) The present invention has the general formula <I) Nl+21c). −X −+1X ・(I
>(In the formula, R and R2 are hydrogen or lower alkyl groups, and may be the same or different, and n is an integer of 2 to 6.

X represents a halogen atom, or a hydrogen halide salt of a halogenoalkylamine represented by the formula (II) N)+2-(C). -05031+...(
ff> (in the formula, R and R2 are hydrogen or lower alkyl groups, which may be the same or different, and n is an integer of 2 to 6) to thiosulfate in the presence of an alkaline catalyst. General formula (II) obtained by reacting with salts
I) Nll□−(C), −55031+ −(vl
) (wherein R1° and n match those of general formula (I) or (II).) A reaction solution containing aminoalkylthiols represented by formula (I) or (II) is electrodialyzed to remove inorganic salts. This invention relates to a method for producing aminoalkylthiol sulfates.

The present invention enables the separation and purification of aminoalkylthiol sulfates obtained by reacting hydrogen halide salts of halogenoalkyl amines or aminoalkyl sulfate esters with thiosulfates under an alkaline catalyst without performing complicated operations. This method provides an easy method and is industrially advantageous.

Examples of general formula (I) used in the present invention include 2-aminoethyl chloride, 2-aminopropyl chloride, 1-methyl-2-aminoethyl chloride,
1-Methyl-2-amino 10-pyl chloride, 2-methyl-2-aminoethyl chloride, 2-methyl-2-aminopropyl chloride, l-ethyl-2-aminoethyl chloride, 1-ethyl-2-aminopropyl chloride , 1,1-dimethyl-2-aminoethyl chloride, 1,1-dimethyl-2-aminopropyl chloride and the like, and the corresponding bromide hydrobromide.

Examples of formula (II) include 2-aminoethyl sulfate, 2-aminopropyl sulfate, 1-methyl-2-aminoethyl sulfate, -
Methyl-2-aminopropyl sulfate, 2-methyl-2-aminoethyl sulfate, 2-methyl-2-aminopropyl sulfate, 1-ethyl-2-aminoethyl sulfate, 1-ethyl-2-aminopropyl sulfate Examples include ester, 1,1-dimethyl-2-aminoethyl sulfate, 1,1-dimethyl-2-aminopropyl [acid ester, etc.].

In the present invention, water is normally used as a solvent, but principle 1
It can also be used as a mixed solvent of alcohol-based solvent and water to dissolve. Examples of such alcoholic solvents include methanol, ethanol, inglobinol, and the like.

The present invention is carried out at temperatures ranging from 50° C. to the boiling point of the solvent used after dissolving the reactants in the solvent. A higher reaction temperature is preferable in terms of reaction rate, and if necessary, the reaction may be carried out under pressure. Does the reaction time depend on the reaction temperature and reaction? & It usually takes 2 to 20 hours depending on the degree of iFA.

The electrodialysis device used in the present invention is a commonly used one in which cation exchange membranes and anion exchange membranes are arranged alternately,
A pair of ti are arranged at both ends. In a chamber with an anion exchange membrane on the anode side and a cation exchange membrane on the cathode side, ionized cations move toward the cathode, pass through the cation exchange membrane, and then move to the next room where they pass through the anion exchange membrane. thwarted.

In addition, anions move toward the anode, pass through the anion exchange membrane, and move to the next chamber, where cations and anions accumulate due to the principle of 0 or more, where their permeation is blocked by the cation exchange membrane. Every other room has a chamber where ions are removed.

As a result, a chamber for concentration and a chamber for desalination are created. The desalting solution flows out from the chamber where desalination is performed, and the solution flowing out from the chamber where condensation is performed is a concentrated solution. For example, AC-110 (Asahi Kasei ■
(manufactured by).

The aminoalkylthiol sulfuric acid obtained by the present invention can be obtained as an aqueous solution, but if necessary, it can be concentrated to dryness to obtain a powder.

(Examples) Next, the present invention will be specifically explained with reference to Examples, but these are merely illustrative and the present invention is not limited to these Examples.

Example 1 16°3g of sodium thiosulfate in 100.0+r pure water
After dissolving 2-chloroethylamine hydrochloride 50% aqueous solution 23, keep the temperature below 30℃.
．． 2g (0.1lol) was added dropwise. Sodium hydroxide was added to this mixture to adjust the pH to 9.0. Thereafter, the temperature was slowly increased and the mixture was stirred and heated at reflux temperature for 15 hours. The obtained reaction solution was passed through an ion exchange membrane [A
It was applied to an electrodialysis device using C-110 (manufactured by Asahi Kasei ■).The electrode solution was a 5% aqueous sodium sulfate solution, and the concentrated solution was a 5% aqueous sodium chloride solution.The desalted solution obtained by electrodialysis By concentrating and crystallizing 2-aminoethylthiol sulfuric acid, 14.2 g of white crystals (yield: 90
%)Obtained. The r liquid was circulated to the reaction system or to the desalting step from the reaction solution.

Example-2 Potassium thiosulfate 19°0g in 100.0g pure water (
After dissolving 2-aminoethyl sulfate (14°1tt), maintain the temperature below 30°C.
(0,111 ol) was added and dissolved. Potassium hydroxide was added to this mixture to adjust the pl to 18.0.

Thereafter, the temperature was slowly increased and the mixture was stirred and heated at reflux temperature for 20 hours. The obtained reaction solution was passed through an ion exchange membrane [
It was applied to an electrodialysis device using AC-110 <manufactured by Asahi Kasei@>. A 5% aqueous sodium sulfate solution was used as the electrode solution, and 5% potassium sulfate was used as the concentrated a solution.

The desalted solution obtained by electrodialysis was concentrated and then crystallized to obtain 14° white crystals of 2-aminoethanethiol sulfuric acid (yield 93%).

Furnace liquid is reaction system or The reaction solution was recycled to the desalting step.

Claims (1)

[Claims] (1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼... (I) (In the formula, R_1 and R_2 are hydrogen or lower alkyl groups, which may be the same or different. n is 2 to is an integer of 6. X represents a halogen atom. R_1 and R_2 are hydrogen or lower alkyl groups, which may be the same or different. n is an integer of 2 to 6. The general formula (III
) ▲There are mathematical formulas, chemical formulas, tables, etc.▼... (III) (In the formula, R_1, R_2 and n match those of the general formula (I) or (II).) 1. A method for producing aminoalkylthiol sulfates, which comprises electrodialyzing a reaction solution containing them to remove inorganic salts.