JPH0550503B2 - - Google Patents

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention is a substance that is blended with methionine, glycogen, vitamins, etc., and has uses such as supplementary use for nutrition, liver protection, detoxification, etc. The present invention relates to a method for producing 2-aminoethanesulfonic acid.

More specifically, N-vinylalkylamide,
For example, using N-vinylacetamide as a starting material,
The present invention relates to a method for producing 2-(alkylamido)ethanesulfonic acid, such as 2-(acetamido)ethanesulfonic acid, by adding a bisulfite salt, and hydrolyzing the same to produce 2-aminoethanesulfonic acid.

(Prior Art and Problems) The following methods are conventionally known as methods for producing 2-aminoethanesulfonic acid.

1) Method of reacting ethyleneimine with sulfur dioxide gas and water (Special Publication No. 1973-23007, Special Publication No. 1973-
16807).

2) Method of reacting 2-aminoethanol acidic sulfate and sodium sulfite (JP-A-Sho
60-8254, Journal of the Chemical Society, 1943, p. 4).

3) A method of reacting a hydrogen halide salt of 2-halogenoethylamine with a sulfite (Unexamined Japanese Patent Publication No. 1989-1999)
23360, Japanese Unexamined Patent Publication No. 60-23361).

4) A method of reacting 2-hydroxyethanesulfonic acid and ammonia under pressure (U.S. patent
1932907).

5) A method of reacting sodium 2-chloroethanesulfonate and ammonia under pressure (Industrial and Engineering Chemistry Vol. 39, p. 906, published in 1947).

6) A method of reacting a 2,2-disubstituted thiazoline with hydrogen peroxide (Japanese Unexamined Patent Publication No. 57-26654), etc.

However, each of these methods has significant drawbacks. That is, in method 1), ethyleneimine, which is extremely toxic and carcinogenic, is used as a raw material. In addition, in the case of method 2), the reaction is very slow, and separation and recovery of by-product monoethanolamine is troublesome. In method 3), a relatively high yield can be obtained only in the case of 2-bromoethylamine, but it requires the use of expensive hydrogen bromide in the synthesis of 2-bromoethylamine, and it is difficult to increase the yield. However, since a large excess of sulfite is used, separation and recovery thereof requires a great deal of cost and labor.

Furthermore, in the case of methods 4) and 5), since the reaction is carried out at high temperature and under pressure, there is a drawback that the equipment becomes expensive. Furthermore, in case 6), there is a disadvantage that hydrogen peroxide is used, which has a high risk of explosion.

As mentioned above, all of the conventionally proposed and practiced methods have major problems as industrial manufacturing methods, and cannot necessarily be said to be satisfactory methods.

(Solution Means According to the Present Invention) As a method for solving the problems of the prior art, the present inventors used N-vinyl alkylamide, which is easily available and easy to handle, as a starting material, such as N-vinylacetamide, and added sulfite to the starting material. It has been discovered that 2-(alkylamido)ethanesulfonic acid can be obtained by regioselective radical addition of a hydrogen salt, and 2-aminoethanesulfonic acid can be obtained in high yield by hydrolyzing this, and the present invention I was able to complete it.

N-vinylalkylamide used as a raw material in the present invention can be produced by thermally decomposing ethylidene bisalkylamide, which is easily obtained from acetaldehyde and an alkylamide.

There are several examples of research on the radical addition reaction of olefin compounds to bisulfite. For example, in US Pat. No. 2,600,287, a radical addition reaction between vinyl chloride and hydrogen sulfite is carried out using oxygen as an initiator, and a radical adduct is obtained with a yield of 90% through a very long reaction time.

In addition, U.S. Patent No. 3,150,169 ^describes a radical addition reaction between an aliphatic olefin having 10 to 20 carbon atoms and hydrogen sulfite using a mixed solvent of water and ethanol.
perbenzoic acid in the presence of ions or Fe ³⁺ ions,
Performed with tert-butyl as initiator, yield
Radical adducts are obtained in 40-80%.

Furthermore, in U.S. Patent No. 2504411, the number of carbon atoms ranges from 2 to 20.
The aliphatic olefin was reacted with ammonium bisulfite to obtain a radical adduct with a yield of 97%.

R.J. Kosyer et al. carried out a radical reaction of perfluoropropene with sodium bisulfite in the presence of an alkaline buffer using benzoyl peroxide as an initiator (Journal of American Chemical Society Vol. 75, p. 4595, published in 1953).

In addition, M.S. Karatsiyu et al. performed a radical reaction between allyl alcohol and sodium bisulfite using oxygen as an initiator, and obtained a radical adduct with a yield of 65% (Journal of Organic Chemistry). Volume 3, page 175, 1938
Published in 2013).

However, all of these known methods involve radical reactions between chemically very stable unsubstituted olefins, halogen elements, or hydroxyl group-substituted olefins and hydrogen sulfite; - Research on the radical addition reaction between vinylalkylamides and bisulfites has never been attempted.

The present inventors have intensively investigated the previously unknown radical addition reaction of N-vinylalkylamide to bisulfite, and have discovered that 2-
We have discovered a method to obtain (alkylamido)ethanesulfonic acid.

In order to obtain high yields of 2-(alkylamido)ethanesulfonic acid, side reactions such as polymerization and hydrolysis of the raw material N-vinylalkylamide, Markovnikov-type addition of bisulfite, etc. are suppressed, and reaction conditions are controlled. It is important to set it optimally.

The reaction is preferably carried out in the presence of a solvent that can dissolve some or all of the raw materials. Examples include water, alcohols such as methanol, ethanol, isopropanol, acetone, ketones such as methyl ethyl ketone, acetonitrile, N,N-dimethylformamide, formamide, N,N-dimethylacetamide, dimethylsulfoxide, N,N-dimethylformamide, formamide, N,N-dimethylacetamide, dimethylsulfoxide, , N′-trimethylurea,
Examples include polar solvents such as N,N,N',N'-tetramethylurea.

Among these solvents, water is particularly preferred. Further, two or more of these solvents may be used in combination, and a combination of water and an organic solvent is preferably selected, and a combination of water and methanol or ethanol is more preferably selected.

As the hydrogen sulfite, sodium hydrogen sulfite, potassium hydrogen sulfite, ammonium hydrogen sulfite, etc. are used.

These bisulfites may be used alone, but to obtain the desired product in high yield, a basic inorganic salt such as an alkali hydroxide such as sodium hydroxide or a sulfite such as sodium sulfite is usually used in combination. ,
The reaction is preferably carried out by adjusting the pH of the reaction solution to 55-8, preferably 6.5-7.0.

The amount of acidic sulfite may be an equivalent to a slight excess relative to the N-vinylalkylamide, and usually 1 to 2 equivalents are used. Using a large excess is not preferable from the viewpoint of post-processing, cost, etc. In addition, the amount of basic inorganic salt used together with acidic sulfite is
0.2-2.0 equivalents are used. If the amount is less than this, the yield will decrease, and if it is in excess, it is undesirable from the viewpoint of post-processing, economics, etc.

As the radical initiator, commonly used azo compounds, peroxides, etc. can be used. Typical examples thereof include azobisisobutyronitrile, benzoyl peroxide, and the like. Also, in particular, 2,2'-azobis(2-amidinopropane)
Water-soluble azobis compounds such as dihydrochloride and 2,2'-azobis[2-(imidazolinyl)propane] dihydrochloride can also be used.

The reaction temperature depends on the reactivity of the radical initiator used. Generally, the reaction may be carried out at a temperature range of 0 to 150<0>C, more preferably 40 to 120<0>C. In order to avoid side reactions such as hydrolysis of N-vinylalkylamide and Markovnikov addition of bisulfite, it is preferable to carry out the reaction at a high temperature for a relatively short time. The reaction time is usually suitable for 5 minutes to 3 hours.

The order of addition of the reaction components is in principle arbitrary. Care must be taken, however, that the starting N-vinylalkylamide and bisulfite do not come together in the absence of a radical initiator.
This is because in that case undesirable by-products may be produced.

Thus, for example, the bisulfite and the radical initiator can be charged first and the N-vinylalkylamide added, or the bisulfite can be charged first and the radical initiator and the N-vinylalkylamide added in this order. or N-
The vinyl alkylamide can be charged first and the bisulfite and radical initiator added.

Additionally, all reaction components can be added to the reaction vessel simultaneously. Moreover, a method in which the reaction components are dissolved in a solvent and added dropwise is preferably used.

2-(alkylamido)ethanesulfonic acid is
After isolation by a conventional method, it can be converted to 2-aminoethanesulfonic acid by hydrolysis with an alkali or acid, but the intermediate 2-(alkylamido)ethanesulfonic acid does not necessarily need to be isolated. There is no. That is, an alkali or acid is directly added to the reaction mixture of the radical addition reaction between N-vinylalkylamide and hydrogen sulfite to perform hydrolysis, and then 2-aminoethanesulfonic acid is isolated by a conventional post-treatment method. You can.

As the alkali used for hydrolysis, alkali hydroxides such as sodium hydroxide and potassium hydroxide are preferably used, and as the acid, mineral acids such as hydrochloric acid and sulfuric acid are preferably used. These usage amounts are 1.1 of the theoretical amount.
~20 times is appropriate. If the amount is below this range, the reaction will be very slow, and if the amount is above this range, it is unfavorable in terms of post-treatment and economic efficiency.

Next, the present invention will be explained in more detail based on examples.

Example 1 A 100 ml three-necked flask equipped with a Dimroth condenser and nitrogen gas blowing tube is charged with 620 mg of sodium bisulfite, 760 mg of sodium sulfite, and 250 mg of 2,2'-azobis(2-amidinopropane) dihydrochloride. Add 40ml of water to this and stir with a magnetic stirrer to dissolve it evenly.

After heating this solution to 100°C while passing nitrogen gas, 510 mg of N-vinylacetamide was added to 100 mg of water.
ml solution is added dropwise over 10 minutes. After further heating at the same temperature for 50 minutes, sodium hydroxide
Add 1.0 g and perform hydrolysis at the same temperature for 1 hour.

After the reaction mixture was cooled, it was determined to contain 793 mg of sodium 2-aminoethanesulfonate by high performance liquid chromatography (internal standard method). This corresponds to 89% of the theoretical value based on the charged N-vinylacetamide.

Example 2 A 50 ml two-necked flask equipped with a Dimroth condenser and nitrogen gas blowing tube is charged with 500 mg of N-vinylacetamide, 650 mg of sodium bisulfite, 780 mg of sodium subrite, and 250 mg of azobisisobutyronitrile. Add 20 ml of water and 10 ml of ethanol to this, stir well with a magnetic stirrer, and pass through nitrogen gas thoroughly.
Immerse in an oil bath at 100℃. After heating at the same temperature for 1 hour, 1.0 g of sodium hydroxide was added and hydrolysis was carried out at 80°C for 2 hours.

Analysis in the same manner as in Example 1 confirmed the production of 646 mg of sodium 2-aminoethanesulfonate. This corresponds to 75% of the theoretical value based on the charged N-vinylacetamide.

Example 3 Sodium bisulfite 800mg, sodium sulfite 600mg and azobisisobutyronitrile 200mg
After carrying out the reaction operation in exactly the same manner as in Example 1 except for using Amberlite IR-120B (H type), the reaction mixture was passed through a column packed with 30 ml of a strongly acidic cation exchange resin Amberlite IR-120B (H type). 40 more in resin
After washing with 1 ml of pure water, this washing solution was combined with the previously treated solution and passed through a column packed with 30 ml of weakly basic anion exchange resin Amberlite IR-45 (OH type). After washing the resin with another 40 ml of pure water, it was combined with the treatment solution and evaporated to dryness using a rotary evaporator. The residue was recrystallized from water to obtain 474 mg of 2-aminoethanesulfonic acid. This corresponds to 63% of the theoretical value based on the charged N-vinylacetamide.

Example 4 A radical addition reaction was carried out in the same manner as in Example 1, except that 1.25 g of sodium bisulfite, 1.51 g of sodium sulfite, and 250 mg of 2,2'-azobis[2-(imidazolinyl)propane] dihydrochloride were used. . After the reaction, transfer the reaction mixture to 50 ml of strongly acidic cation exchange resin Amberlite IR-120B (H type).
was processed through a column packed with After washing the resin with 70 ml of pure water, this washing solution was combined with the previous treatment solution, concentrated using a rotary evaporator, and evaporated to dryness. The residue was recrystallized from ethanol to give pure N-acetyl taurine 811.
mg (81% yield).

^1H -NMR spectrum: (ppm, measured in _D2O ) 2.10 (3H, s), 3.13 (2H, q) 3.51 (2H, q) Then 670 mg (4 mmol) of N-acetyl taurine
into a 25 ml eggplant flask and add 10 ml of H ₂ O and
240 mg of NaOH was added, and the mixture was heated and stirred at a bath temperature of 110°C for 1 hour. After cooling the reaction mixture, adjust the pH to 4~ with 5N hydrochloric acid.
5, the solvent was evaporated to dryness using a rotary evaporator. Methanol-water was added to the obtained residue to dissolve it, and the mixture was allowed to cool for a while to precipitate crystals. This was taken and dried to obtain 451 mg of taurine (yield 90%).

Claims (1)

[Claims] 1 Adding a bisulfite to N-vinylalkylamide to obtain 2-(alkylamido)ethanesulfonic acid, which is then hydrolyzed 2
- A method for producing aminoethanesulfonic acid.