JPS6050187B2 - Method for producing mercaptoamines - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing mercaptoamines.

Mercaptoamines are extremely useful substances as raw materials for various pharmaceuticals, intermediate raw materials for hair care cosmetics, etc., and substances with radiation damage protection.

The following methods are known as methods for producing mercaptoamines. (A) A method in which alkylene imine is applied to a large excess of hydrogen sulfide in an alcoholic solution when cold (A)
nn, 566, 210 (1950); J, Chem, S.
oc, 1944, 5).

(b) A method in which alkylene imine and dialkyl ketone are reacted and then treated with hydrogen sulfide and then with hydrohalic acid (Bul, soc, chim, F, 1964, 2
493; Ann, 566, 210 (1950); Japanese Patent Publication No. 50-29444; Japanese Patent Publication No. 4156-1983).

←→ A method in which oxazoline is treated with hydrogen sulfide and then hydrolyzed in an aqueous solution of hydrochloric acid (Japanese Patent Application Laid-open No. 54-12850 Tan). (--) A method in which an aminoalkyl sulfate is reacted with ammonium hydrosulfide or an alkali hydrosulfide, and then treated with hydrochloric acid (Japanese Patent Publication No. 53-3365). J (ho)
A method of hydrolyzing 2-mercaptothiarizone with hydrochloric acid or hydrobromic acid (J, Org, Chern, 25
869 (1960); Ber, 31, 2832 (18
98) O However, among these methods, methods (a) to ←→ have the disadvantage of using carcinogenic alkylene imine or toxic hydrogen sulfide, and (
Because the reaction conditions are alkaline in the method, in addition to the target substance 2-mercaptoethylamine, the oxidized dimers of bis(2-aminoethyl) sulfides and 2-mercaptoethylamine, which are difficult to separate, are The side effect of bis(2-aminoethyl) disulfides, which is a compound, is unavoidable.

Therefore, there is a problem that the purity of 2-mercaptoethylamines and the yield of 2-mercaptoethylamines are lowered. Furthermore, the method (e) has the disadvantage that toxic hydrogen sulfide is produced as a by-product in an equivalent amount to the product.
As described above, each of the known manufacturing methods has problems from an industrial perspective. The present inventors have completed the present invention as a result of intensive research into a method for producing mercaptoamines that does not use toxic alkylene imines and does not produce hydrogen sulfide as a by-product.

That is, 2-(2''-aminoethylthio)-2 represented by the general formula (1) (wherein Rl, R2, R3 and R4 represent a hydrogen atom or a lower alkyl group, and X represents a halogen atom) - General formula (■) characterized by hydrolyzing a thiazoline dihydrohalide derivative with hydrohalic acid (in the formula,
This is a method for producing mercaptoamines represented by Rl, R2, R3, R4 and x have the same meanings as in general formula (1).

2-(2″-aminoethylthio).-2 used in the present invention
-Thiazoline dihydrohalides have the general formula (■) (wherein, Rl, R2, R3, R
4 represents a hydrogen atom or a lower alkyl group) and a 2-mercaptothiarizone derivative represented by the general formula (■) (wherein Rl, R2, R3 and R4 are the same as in the general formula (■), represents a halogen atom)
It has been found that it can be obtained almost quantitatively by reacting -halogenoethylamine with a hydrogen halide salt derivative in a nonpolar solvent.

Therefore, the compound of general formula (1) can be easily obtained by this method. Examples of the compound of general formula (1) include 2-(2″-aminoethylthio)-2-thiazoline dihydromide, 2-(2″-aminoethylthio)-2-thiazoline dihydrochloride, 2-(
2″-amino-1″-methylethylthio)-5-methyl-2-thiazoline dihydrochloride, 2-(2″-
Amino-J2″-methylethylthio)-4-methyl-2
-Thiazoline dihydrochloride, 2-(2″-amino-1″-dimethyl-2″-dimethylethylthio)-4
-dimethyl-5-dimethyl-2-thiazoline dihydrochloride, 2-(2''-amino-1''-n-butylethylthio)-5-n-butyl-2-thiazoline dihydrochloride, 2-(2''-amino-2'' -n-butylethylthio)-4-n-butyl-2-thiazoline dihydroiodide and the like. Hydrohalic acids used for hydrolysis include hydrochloric acid with a concentration of 15% or more, hydrobromic acid with a concentration of 10% or more, and hydroiodic acid with a concentration of 10% or more, and concentrations below these are impractical due to slow decomposition rates.

The amount of hydrohalic acid used may be such that the amount of hydrogen halide contained ranges from 1 molar equivalent to 20 molar equivalents of the compound of general formula (1) to be hydrolyzed.

If the amount is less than this, the hydrolysis will be extremely slow and it is not practical. On the other hand, if the amount is more than 20 equivalents, the effect of further increasing the decomposition rate will be small. Furthermore, the general formula (1
) It is preferable to use a hydrohalic acid having the same halogen atom as that of the compound.

If different hydrohalic acids are used, the mercaptoamine produced will be a mixture of salts of different hydrohalic acids, making separation complicated. Although it is sufficient to carry out the hydrolysis at a temperature of 50'C or higher, it is preferable to carry out the hydrolysis under reflux in view of the decomposition rate.

If the reaction temperature is increased by applying pressure, the decomposition can be further accelerated. The decomposition time varies depending on the temperature, acid concentration, and type of acid, but is from 3 hours to 3 hours.

After the reaction is completed, the reaction mixture is concentrated to dryness to obtain the hydrogen halide salt of mercaptoamines of the general formula (■) as crystals of high purity J in a high yield.

As described above, the present invention hydrolyzes the compound of general formula (1) without producing toxic hydrogen sulfide as a by-product, and by producing bis(2-aminoethyl) sulfide, which is difficult to separate from the target substance. A method for easily producing mercaptoamines of general formula (■) in high yield and purity without producing by-products of bis(2-aminoethyl) disulfides, which are oxidized dimers of compounds and target substances. It is.

The present invention will be explained below with reference to Examples.

Example-1 32.4 g (0.1 mol) of 2-(2-aminoethylthio)-2''-thiazoline dihydrobromide was dissolved in 80 ml of 15% hydrobromic acid and heated under reflux for a specific time.

Thereafter, the mixture was concentrated to dryness under reduced pressure to obtain 30.7 g of white crystals of 2-mercaptoamine hydrobromide (melting point: 159-160°C). The yield was 97%, and the purity as determined by the iodine method was 98.5%. Example-2 23.5y (0.1 mol) of 2-(2″-aminoethylthio)-2-thiazoline dihydrochloride was dissolved in 100ml of 36% hydrochloric acid and heated under reflux for (t) hours.

Thereafter, it was concentrated to dryness under reduced pressure to produce white crystals of 2-mercaptoethylamine hydrochloride 22.3y (melting point 71-72°C).
) was obtained. Yield: 98%, purity by iodine method: 99.0
It was %. Example-3 2-(2-amino-2″-methylethylthio)-4-methyl-2-thiazoline dihydrochloride 26.3y(
0.1 mol) in 100 ml of 36% hydrochloric acid,
The mixture was heated under reflux for 8 hours under pressure of K9/C.

Thereafter, it was concentrated to dryness at normal pressure to produce white crystals of 2-amino-1-propathiol hydrogen chloride (24.8y) (melting point 90-91°C).
) was obtained. Yield 97%, purity by iodine method 98.0
It was %. Example-4 2-(2-amino-1″-methylethylthio)-5-methyl-2-thiazoline dihydrochloride (26.3 da(4).1 mol) was dissolved in 100 ml of 20% hydrochloric acid, (
4) The mixture was heated under reflux for an hour.

Thereafter, it was concentrated to dryness under reduced pressure, and 25.0 g of white crystals of 1-amino-2-propanethyl hydrogen chloride (melting point 91-9
7C) was obtained. Yield: 98%, purity by iodine method: 98%
．． It was 3%. Example-52-(2″-amino-1″
-Dimethyl-2''-dimethylethylthio)-4-dimethyl-5-dimethyl-2-thiazoline dihydrochloride (34.7 V(a).1 mole) in 120 ml of 20% hydrochloric acid
and heated under reflux for 4 hours.

Thereafter, it was concentrated to dryness under reduced pressure and 3-amino-3-methyl-2
-White crystals of methyl-2-butanethiol hydrogen chloride 3
2.9f1 (melting point 240°C or higher) was obtained. Yield 97%
The purity as determined by the iodine method was 98.7%. Example-
6 2-(2″-amino-1″-n-butylethylthio)-
34.7 q (0.1 mol) of 5-n-butyl-2-thiazoline dihydrochloride was dissolved in 100 mt of 36% hydrochloric acid and heated under reflux for an hour.

Thereafter, the mixture was concentrated to dryness under reduced pressure to obtain 32.9y of white crystals of 2-mercapto-2-butylethylamine hydrogen chloride (no clear melting point). The yield was 97%, and the purity as determined by the iodine method was 98.4%. Elemental analysis C6Hl6NS
Example-7 as Cl In a reaction flask equipped with a stirrer, a thermometer, and a reflux condenser, 5.96 f of 2-mercaptothiazoline (50 rT1 m
01), 2-bromoethylamine hydrobromide 1
0.25y (50rT1m01), and toluene 10
0TrLL was charged.

Claims (1)

[Claims] 1 General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R
_1, R_2, R_3 and R_4 represent a hydrogen atom or a lower alkyl group, and X represents a halogen atom). General formula (II), which is characterized by being hydrolyzed by
, R_3, R_4 and X have the same meanings as in general formula (I)).