JPH0416461B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for producing S-substituted mercaptoamines. S-substituted mercaptoamines are very useful substances as intermediate raw materials for various agricultural chemicals and medicines, as intermediate raw materials for dyes, hair care cosmetics, etc., and as substances that have a radiation damage protection effect. Common methods for producing S-substituted mercaptoamines include () reaction of ethyleneimines and alkyl mercaptans (Chemische Berichte, 85 , 1035-42, 1952);
() Reaction of aminoethyl sulfates and alkyl mercaptans (Fr.1238350); or ()
There are reactions between halogenated alkylamines and alkylmercaptans (Fr.1519829), and ()
Methods using mercaptoamines as raw materials include:
Reaction example with alkyl halides (Chemical Abstracts, Vol.54,
24368i). However, these known methods have the following drawbacks. In other words, (), (), and () have drawbacks such as the need to use carcinogenic ethyleneimine and alkyl mercaptan with a strong odor, and low reaction yields. When starting from amines, they cannot exist stably unless they are in the form of hydrohalides, so there is a problem in that a large amount of alkali is required to proceed with the reaction. In addition, () has the disadvantage that expensive sodium alcoholate must be used in the reaction. Furthermore, since the by-product of salt (), (), and () is unavoidable, if you try to industrially separate them to obtain the desired product, it is inevitable that the equipment and operations will become complicated. There were also some flaws. The present inventors have devoted themselves to a method for producing S-substituted mercaptoamines that does not use harmful substances, is inexpensive, and does not produce salt as a by-product. It was discovered that the dehydration reaction unexpectedly progresses easily when reacting with S-substituted mercaptoamines, and the present invention was completed based on this knowledge. That is, the present invention is based on the general formula () (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) in the presence of an aqueous solution of hydrohalic acid. General formula () characterized by reacting with a monohydric alcohol represented by () ROH () (in the formula, R represents a lower alkyl group) The present invention provides a method for producing S-substituted mercaptoamines represented by the formula (wherein R, ^R1 , ^R2 , ^R3 , ^R4 and X have the same meanings as above). The present invention will be explained in detail below. In the present invention, the mercaptoamines to be reacted with the monohydric alcohol () are compounds represented by the general formula (), such as 2-mercaptoethylamine, 1-methyl-2-mercaptoethylamine, 1,1- Dimethyl-2-mercaptoethylamine, 1-ethyl-2-mercaptoethylamine, 1,1-dimethyl-2-mercaptoethylamine, 2-mercapto-n-propylamine,
2-Methyl-2-mercapto-n-propylamine, 1-methyl-2-mercapto-n-propylamine, 1,2-dimethyl-2-mercapto-n
-propylamine, 2-mercapto-n-butylamine, 1-methyl-2-mercapto-n-butylamine, 1,2-dimethyl-2-mercapto-
Hydrohalides such as chlorine, bromine, iodine or fluorine such as n-butylamine. Furthermore, the monohydric alcohols in the present invention are compounds represented by the general formula (), such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl-1-propanol, 3 -Methyl-1-butanol, 2-butanol, 2-methyl-2-propanol, 3-methyl-1-butanol, 2-methyl-1-pentanol, benzyl alcohol,
These include methylbenzyl alcohol, cyclohexanol, methylamyl alcohol, and octanol. The S-substituted mercaptoamines that are the target substances of the present invention are compounds represented by the general formula () obtained by reacting the above mercaptoamines () and monohydric alcohols (), and are, for example, 2
-Methylthioethylamine, 2-ethylthioethylamine, 2-(n-propylthio)-ethylamine, 2-(isopropylthio)-ethylamine, 2
-(n-butylthio)-ethylamine, 2-(isobutylthio)-ethylamine, 2-(sec-butylthio)-ethylamine, 2-(tert-butylthio)-ethylamine
-ethylamine, 2-(isoamylthio)-ethylamine, 2-(betidylthio)-ethylamine, 2
-(methylbenzylthio)-ethylamine, 2-
(cyclohexylthio)-ethylamine, 2-(2
-methylbutylthio)-ethylamine, 2-(3-
Methyl-1-butylthio)-ethylamine, 2-
(methylamylthio)-ethylamine, 2-(2-
Hydrohalides such as chlorine, bromine, iodine or fluorine such as methylpentylthio)-ethylamine and 2-(octyclthio)-ethylamine. In the present invention, the above-mentioned mercaptoamines () and monohydric alcohols () are reacted in the presence of hydrohalic acid, and as the hydrohalic acid, hydrochloric acid and hydrobromic acid are preferable. Among them, hydrochloric acid is most preferred. Therefore, the halogen atom X in the compound of general formula ()
and the halogen of the hydrohalic acid are preferably the same. If different hydrohalic acids are used, the product S-substituted mercaptoamines will be a mixture of salts of different hydrohalic acids, making separation complicated. The amount of hydrohalic acid used is preferably 1 molar equivalent or more and 10 molar equivalents or less per mole of mercaptoamine. If the amount is less than 1 molar equivalent, the reaction rate will be extremely slow and it is not practical.Also, as the number of moles increases, the reaction time will be shortened, but if it exceeds 10 molar equivalents, the effect will decrease and the reactor will be unnecessarily damaged. This only results in an increase in capacity, which is not economical. For example, when using hydrochloric acid, the concentration of the hydrohalic acid is preferably in the range of 10 to 25% by weight.
When the amount is less than 10% by weight, the reaction rate is slow and impractical even if the hydrochloric acid is 1 molar equivalent or more.
Moreover, if it exceeds 25% by weight, the vapor pressure of hydrochloric acid becomes high at the maximum temperature of 130 to 140° C. which can be used with industrially inexpensive materials, which is undesirable in terms of equipment maintenance. The amount of monohydric alcohol used in the present invention is
The amount is preferably 1 molar equivalent or more and 8 molar equivalents or less per mole of mercaptoamine. The reaction rate increases as the amount becomes excessive, but if the amount exceeds 8 molar equivalents, the pressure becomes too high when trying to maintain the reaction temperature at a predetermined temperature, and energy consumption during evaporation to dryness increases. For this reason, it is not a good idea in terms of equipment or economy. As described above, the present invention adds 1 mole of mercaptoamine and equivalent mole to 8 moles of monohydric alcohol to 1 mole to 10 moles of hydrohalic acid,
Heating to 100-140℃ under reflux at normal pressure or under pressure,
The reaction is allowed to occur for a predetermined period of time. The reaction time varies depending on the temperature, the concentration of the hydrohalic acid, the type of the hydrohalic acid, the number of equivalents, etc., but is usually 3 to 60 hours. After the reaction is completed, the hydrohalic acid and excess alcohol are distilled off and evaporated to dryness, followed by recrystallization in an organic solvent. This method does not use harmful substances,
Furthermore, the target product of high purity can be easily obtained in high yield without producing salts that are difficult to separate. Hereinafter, embodiments of the present invention will be specifically described with reference to Examples, but the technical scope of the present invention as defined in Article 70 of the Patent Law is not limited thereto. Example 1 22.7 g in 32 g (1 mole) methanol in a 200 4-necked flask equipped with a stirrer, thermometer, and condenser.
(0.2 mol) of 2-mercaptoethylamine hydrochloride and 200 g (1.18 mol) of 21% hydrochloric acid.
was charged and the reaction was carried out at the boiling point (100°C) for 4 hours.
After the reaction was completed, excess methanol and hydrochloric acid were distilled off to obtain a crude product, which was recrystallized from methanol. The melting point of the obtained crystals was 120°C, and as a result of IR and elemental analysis, it was confirmed that the crystals were the desired 2-methylthioethylamine hydrochloride. Yield: 93% based on 2-mercaptoethylamine hydrochloride
It was hot. Elemental analysis C H N S Cl Theoretical value 28.25 7.85 10.98 25.1127.81 Actual value 28.36 7.76 10.89 25.02 27.97 Example 2 2-mercaptoethylamine hydrochloride 2.27 g (0.2 mol) and methanol in a 500 c.c. pressure-resistant glass reaction tube. 25.6 g (0.8 mol) and 50.0 g (0.35 mol) of 25% hydrochloric acid
mol) and immersed in an oil bath at 130°C to carry out a reaction for 24 hours. The maximum pressure during the reaction was 8.7 Kg/cm ² G. After the reaction was completed, the mixture was cooled and the contents were concentrated to dryness using a rotary evaporator, and then recrystallized from methanol. The melting point of the obtained crystals was 120°C, and as a result of IR and elemental analysis, it was confirmed that the crystals were the desired 2-methylthioethylamine hydrochloride. Yield is 95% based on 2-mercaptoethylamine hydrochloride.
It was %. Elemental analysis C H N S Cl Theoretical value 28.25 7.85 10.98 25.11 27.81 Actual value 28.04 7.80 11.02 25.23 27.91 Examples 3 to 5 Synthesis was attempted in the same manner as in Example 1 by varying the amounts of methanol and hydrochloric acid added. The results are summarized in Table 1.

[Table] Examples 6 to 8 Synthesis was attempted in the same manner as in Example 2 while varying the hydrochloric acid concentration. The results are shown in Table-2.

[Table] Examples 9 to 10 Synthesis was attempted in the same manner as in Example 1 using various alcohols instead of methanol, and it was confirmed from IR and elemental analysis that the product was the desired product.

【table】

Claims (1)

[Claims] 1 General formula () (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) in the presence of an aqueous solution of hydrohalic acid. General formula () characterized by reacting with a monohydric alcohol represented by () ROH () (in the formula, R represents a lower alkyl group) A method for producing S-substituted mercaptoamines represented by the formula (wherein R, R ¹ , R ² , R ³ , R ⁴ and X have the same meanings as above).