JPH0417186B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for industrially obtaining mercaptoamine p-toluenesulfonic acid salts with high purity and high yield.

Mercaptoamines are extremely useful substances with a wide range of uses, including pharmaceutical intermediates, agricultural chemicals, rubber drugs, photographic drugs, and photoresists, but they are used in the form of various salts depending on the purpose. Among these, p-toluenesulfonate is a useful salt. Methods for producing p-toluenesulfonate of mercaptoamine include (1) a method in which thiazolidines are hydrolyzed with p-toluenesulfonic acid (monohydrate) in methanol, and (2) a method in which cysteamine hydrochloride and triethylamine are dissolved in benzene. After mixing in a vacuum and diluting in ether to precipitate and remove crystals, the separated liquid is added to p-toluenesulfonate (monohydrate) in methanol benzene and heated to react (J.Org.
Chem. 1965, 30 , p. 1508) is only known.

However, method (1) requires a long time of 10 days for hydrolysis, and method (2) uses a variety of solvents such as benzene, ether, and methanol, which may mix and cause repeated use. However, there are many difficulties in industrial implementation, such as the complicated recovery process and the need to separate triethylamine hydrochloride and recover and recycle it as triethylamine.

On the other hand, a production method using a neutralization reaction of free cysteamine and p-toluenesulfonic acid is also considered.
This free cysteamine is a sublimable and unstable compound, and is difficult to handle as it is, which poses a practical problem.

The present inventors have conducted intensive studies on a method for producing mercaptoamine p-toluenesulfonic acid salt that improves the drawbacks of the conventional method. The present inventors have discovered that white crystals of mercaptoamine p-toluenesulfonate can be easily precipitated by adding mercaptoamine mineral salts or an aqueous solution thereof to an aqueous solution and/or an organic solvent solution and performing salt exchange, and have thus arrived at the present invention. .

That is, the present invention is based on the general formula () ^Mineral acid salts ^of mercaptoamines ^{represented by} The present invention provides a method for producing mercaptoamine p-toluenesulfonic acid salts, which comprises reacting mercaptoamine p-toluenesulfonic acid salts with ammonium salts, alkali metal salts, or alkaline earth metal salts of p-toluenesulfonic acid in an aqueous solution and/or an organic solvent. be.

The mineral acid salts of mercaptoamines used in the method of the present invention are those represented by the general formula (), and examples of the mineral acid salts include hydrochloric acid, hydrobromic acid,
These include hydrohalic acids such as hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, with hydrochloric acid being particularly preferred. Specific compounds include 2-mercaptoethylamine, 2-mercaptopropylamine, 2-mercapto-2-methylpropylamine, 2-mercapto-1-methylethylamine, 2-mercapto-
1-methylpropylamine, 2-mercapto-
1,1-dimethylethylamine, 2-mercapto-1,2-dimethylpropylamine, 2-mercaptobutylamine, 2-mercapto-2-methylbutylamine, 2-mercaptohexylamine,
Examples include the various mineral acid salts mentioned above, such as 2-mercapto-1-hydroxymethylethylamine.

Further, the salt of p-toluenesulfonic acid used in the method of the present invention is an ammonium salt, an alkali metal salt, or an alkaline earth metal salt, and examples of the alkali metal salt include lithium, sodium, potassium, rubidium, and cesium. alkaline earth metal salts include beryllium, magnesium,
There are salts such as strontium and barium.

As the ammonium salt, alkali metal salt or alkaline earth metal of p-toluenesulfonic acid, pre-prepared crystals may be used by dissolving them in water and/or organic solvent solution. It may be prepared by adding a solid or aqueous solution of an alkali metal or alkaline earth metal hydroxide to a water and/or organic solvent solution.

There are no restrictions on the amount of ammonium salt, alkali metal salt, or alkaline earth metal salt of p-toluenesulfonic acid used in terms of reaction, but in order to simplify the purification process, reaction with mineral acid salts of mercaptoamines is recommended. 0.9 to 1.1 times the equivalent amount, preferably 0.99 to 1.1 times the mole amount
It is 1.01 mole times.

The order in which the raw materials are added is usually to crystallize mineral acid salts of mercaptoamines to a water and/or organic solvent solution of an alkali metal salt or alkaline earth metal salt of p-toluenesulfonic acid prepared in advance, or to a solution in water or an organic solvent. It can be added in the reverse order. Alternatively, a predetermined amount of p-toluenesulfonic acid and a mineral acid salt of mercaptoamines may be added to the solvent, and then an aqueous solution of an alkali metal or alkaline earth metal may be added thereto.

The organic solvents used here include aliphatic alcohols such as butanol and ethylene glycol, aliphatic amino alcohols such as 2-aminoethanol, sulfur-containing inert organic solvents such as dimethyl sulfoxide and sulfolane, and nitrogen-containing inert organic solvents such as dimethylformamide. active organic solvents, etc. The amount of these solvents varies depending on the reactants and the type of solvent, but p-toluenesulfonate of mercaptoamines 1
It is 0.5 to 30 times the weight, preferably 2 to 10 times the weight.

There is no particular restriction on the reaction temperature, and the reaction may be carried out at elevated pressure or normal pressure.From the viewpoint of the reaction, there is no particular need for elevated pressure, but the reaction can be carried out under elevated pressure if necessary. Further, from the viewpoint of reaction operation, the temperature can be arbitrarily selected as long as it is below the boiling point. However, in order to precipitate only the target product among the reaction products and not precipitate by-product inorganic salts, the temperature is usually preferably 50° C. or lower, although it varies depending on the type of reactant and solvent used.

The thus obtained crystals of mercaptoamine p-toluenesulfonate salts are separated and simply dried under reduced pressure to obtain a product with a high purity of 97% or more. If the adhering mother liquor is replaced by washing with water or an organic solvent, a product with a higher purity of 99% or more can be obtained.

In addition, in the liquid after separating the mercaptoamine p-toluenesulfonates, some of the by-produced alkali metal or alkaline earth metal mineral acid salts and the mercaptoamine p-toluenesulfonates are dissolved. Therefore, by concentrating this, separating out the precipitated mineral acid salt crystals, and circulating this solution to the initial reaction solution, the active ingredient can be almost quantitatively converted to the target product, mercaptoamine p- Toluenesulfonate salts can be obtained.

Hereinafter, embodiments of the present invention will be specifically described with reference to Examples.

Example 1 Add 100 c.c. of water to a 300 c.c. four-necked flask equipped with a stirrer, thermometer, and cooling tube, and dissolve 38.0 g (0.2 mol) of p-toluenesulfonic acid (monohydrate) therein. death,
While cooling, add 16.7 g (0.2 g) of 48% caustic soda aqueous solution.
mol) to prepare an aqueous solution of sodium p-toluenesulfonate. Next, a 50% aqueous solution of 22.7 g (0.2 mol) of 2-mercaptoethylamine hydrochloride was added.
Drop while keeping the temperature at 30℃. Results of separating the precipitated crystals, drying them under reduced pressure at 60-70℃ for 2 hours, and analyzing their purity.
It was 96.7% (coarse crystal). Furthermore, the purity of the product washed with water during crystal separation and dried in the same manner was 99.2% (fine crystals). Melting point 165−
The temperature was 167°C, and the results of elemental analysis were as follows.

C H N S Analytical value (%) 42.59 6.34 5.64 25.77 Theoretical value (%) 43.37 6.02 5.62 25.70 Further, when checking for contamination by by-product sodium chloride, it was found to be 97 ppm. One pass yield is
It was 53%.

Example 2 100 c.c. of water was added to the same apparatus as in Example 1, and 38.0 g (0.2
24.7 g (0.2 mol) of a 30% aqueous calcium hydroxide solution was added dropwise while cooling to prepare an aqueous solution of calcium p-toluenesulfonate. Next, a 70% aqueous solution of 31.6 g (0.2 mol) of 2-mercaptoethylamine hydrobromide was added dropwise while cooling so that the temperature did not exceed 50°C. The precipitated crystals were separated and dried, and the purity of the crude crystals was 97.1%.
In addition, the purity of the crystals after washing with water is 99.4%, and the yield is
It was 62%.

Example 3 Add 100 c.c. of water to the same apparatus as in Example 1, dilute 16.7 g (0.2 mol) of 48% caustic soda,
p-Toluenesulfonic acid (monohydrate) while cooling.
Add 38.0 g (0.2 mol) dropwise to prepare an aqueous solution of sodium p-toluenesulfonate. Next, 40 g of a 70% aqueous solution of 2-mercaptoethylamine nitrate.
(0.2 mol) is added dropwise under cooling. When the precipitated crystals were separated and dried, the purity of the crude crystals was determined to be 97.5.
It was %. In addition, the purity of the crystals after washing with water is 99.5.
%, the obtained 2-mercaptoethylamine p-
Toluene sulfonate was 68%.

Example 4 A 50% aqueous solution of 25.5 g (0.2 mol) of 3-mercapto-2-aminopropane hydrochloride was added dropwise to an aqueous solution of sodium p-toluenesulfonate prepared in the same manner as in Example 3 under cooling, and the precipitated crystals were precipitated. was separated and subjected to the same post-treatment as in Example 1. Purity of crude crystals
The purity of the fine crystal was 99.0%.

Example 5 100 c.c. of water was added to the same apparatus as in Example 1, and 38.0 g of p-toluenesulfonic acid (monohydrate) was added thereto.
(0.2 mol) and 25% ammonia water in this
13.6 g (0.2 mol) was added dropwise while cooling, and p-
Prepare an aqueous solution of toluenesulfonic acid ammonium salt. Next, 2-mercaptobutylamine hydrochloride
Add 28.5 g (0.2 mol) of a 50% aqueous solution dropwise while maintaining the temperature at 40°C. After aging for 30 minutes, it was cooled to 20°C, the precipitated crystals were separated, dried under reduced pressure at 60 to 70°C for 2 hours, and analyzed for purity, yielding 95.8% crude crystals. Further, this was further repulped with water, and the crystals were separated and re-dried, and the purity of the purified crystals was 98.7%. The ash content of this product was less than 0.01%.

Example 6 Ethylene glycol was added to the same apparatus as in Example 1.
Prepare 100 c.c. and add 38.8 g (0.2 mol) of sodium p-toluenesulfonate. Next, a 30% ethylene glycol solution containing 40.8 g (0.2 mol) of mercaptoethylamine hydroiodide is added dropwise while maintaining the temperature at 30°C. After 30 minutes of aging, the precipitated crystals were separated, dried under reduced pressure at 60-70℃ for 2 hours, and analyzed for purity.
95.6% crude crystals were obtained. The purity of the crystals washed with water and dried in the same way is 98.5%.
It was hot. The ash content of this product was less than 0.1%.

Claims (1)

[Claims] 1 General formula () (In the formula, R ¹ , R ² , R ³ and R ⁴ represent a hydrogen atom, a lower alkyl group, a hydroxy-substituted alkyl group, and may be the same or different) A method for producing mercaptoamine p-toluenesulfonic acid salts, which comprises reacting the salt with an ammonium salt, alkali metal salt or alkaline earth metal salt of p-toluenesulfonic acid.