JPH1036358A - Production of 2-thioxo-1, 3-o, n-heterocyclic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject cyclic compound safely in a high yield, capable of being used as a synthetic raw material or an additive for a cosmetic material, etc., by reacting an aminoalcohol compound with carbon disulfide in the presence of a base, and then with hydrogen peroxide in a water soluble organic solvent. SOLUTION: This objective 2-thioxo-1, 3-O, N-heterocyclic compound of formula I (R1 is an alkylene, an aromatic group, etc.; R2 is H, an alkyl, etc.) is obtained by reacting an aminoalcohol compound of the formula: HO-R1 -NHR2 with carbon disulfide in a radio of 1.0-1.5 based on 1 (equivalent) of the amino group in the formula I in the first reaction to form a dithiocarbamic acid salt of formula II (M is an alkali metal), and then reacting the compound of the formula II with hydrogen peroxide in the second reaction by using >=1.0 fold (preferably 1.5-2 fold) thereof based on 1 (equivalent) of the compound of the formula II in an organic solvent. A reaction temperature is at a room temperature or higher, preferably at a refluxing temperature of the solvent or lower, and the reaction proceeds rapidly.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a 2-thioxo-
The present invention relates to a method for producing a 1,3-O, N-heterocyclic compound.

[0002]

2. Description of the Related Art Various processes for producing 2-thioxo-1,3-O, N-heterocyclic compounds are known. For example, (1) a method in which amino alcohol is reacted with carbon disulfide to cause thermal decomposition, (Can. J. Chem., 34 , 815 (1956)),
(2) A method in which amino alcohol is reacted with carbon disulfide in the presence of triethylamine and then with ethyl chlorocarbonate (Synthesis, 12 , 1149 (1985), Acta Chem. S)
cand., 10 , 432 (1956)) (3) A method in which an amino alcohol is reacted with carbon disulfide in the presence of a base and then reacted with lead nitrate (J. Am. Chem. Soc., 72 , 4972 (1950) )), (4)
A method in which amino alcohol, carbon disulfide and iodine are reacted and thermally decomposed (J. Am. Chem. Soc., 74 , 2994 (1952)
), (5) Reaction of amino alcohol with thiophosgene (GB 1,445,324, U.S. Pat. No. 3,821,215)
Is known.

[0003]

However, in the method (1), the yield is extremely low. In the method (2), ethyl chlorocarbonate is relatively expensive, and toxic carbonyl sulfide is formed during the reaction. In (3), a toxic lead compound must be used, and in (4), the yield is low.
(5) has a problem that expensive and toxic thiophosgene is used.

Accordingly, an object of the present invention is to produce a 2-thioxo-1,3-O, N-heterocyclic compound safely and at a high yield.

[0005]

Means for Solving the Problems In order to solve the above-mentioned problems, the chemical formula [3]

[0006]

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(Wherein R ₁ represents an alkylene group, a cycloalkylene group, an aromatic group or a substituent thereof,
₂ represents a hydrogen atom, an alkyl group, or a substituted alkyl group. As an invention for producing the 2-thioxo-1,3-O, N-heterocyclic compound represented by the formula (1), HO-R ₁ -NHR ₂ [1] (where R ₁ and R ₂ are R ₁ and R in the chemical formula [3]
_Same as ₂ . ) Is reacted with carbon disulfide in the presence of a base to give a chemical formula [2]

[0008]

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[0009] (wherein, R _1, R ₂ is the same as R _1, R ₂ in the chemical formula [3], M is an alkali metal atom,. Which an unsubstituted or substituted ammonium) dithiocarbamate represented by It was found that an acid salt was formed and then reacted with hydrogen peroxide in the presence of a water-soluble organic solvent.

In the above reaction, an amino alcohol compound is reacted with carbon disulfide in the presence of a base to form a dithiocarbamate, which is reacted with hydrogen peroxide in a water-soluble organic solvent to form an intermediate. A hydroxy isothiocyanate is formed. This hydroxyisothiocyanate ester undergoes an extremely rapid intramolecular cyclization reaction to give the desired product, 2-thioxo-1,3.
Produces -O, N-heterocyclic compounds. In order to produce this in a shorter time, it may be heated together with a base, if necessary.

Therefore, the above-mentioned cyclic compound can be produced safely and easily without using harmful substances such as thiophosgene and lead nitrate, and without generating toxic gas such as carbonyl sulfide. The rate can also be improved.

This cyclic compound can be used as a raw material for synthesizing medical and agricultural chemicals, and can be used as an additive for cosmetics, rubbers, toners for copying, and the like.

[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described in more detail. The amino alcohol compound used as a raw material for the production method of the present invention is generally represented by the chemical formula [1]. HO-R ₁ -NHR ₂ [1] Here, R ₁ represents an alkylene group, a cycloalkylene group, an aromatic group or a substituted product thereof, and R ₂ represents a hydrogen atom, an alkyl group, or a substituted alkyl group. Among these, R
_When an amino alcohol compound having 1 or 2 carbon atoms in the main chain is used, the cyclic compound of the final product becomes a 5- or 6-membered ring, and is more stabilized. Specific examples of such an amino alcohol compound include 2-aminoethanol and 1-aminoethanol.
Amino-2-propanol, 2-amino-1-propanol, 2-amino-2-methyl-1-propanol, 2
-Amino-1-butanol, 2-amino-3-methyl-
1-butanol, 2-amino-3-methyl-1-pentanol, 2-amino-4-methyl-1-pentanol,
2-amino-1-phenylethanol, 2-amino-2
-Phenylethanol, norphenylephrine, noradrenaline, norephedrine, octopamine, 2-amino-1,2-diphenylethanol, 3-amino-1
-Propanol, 3-amino-2,2-dimethyl-1-
And propanol.

The amino alcohol compound may have a condensed ring structure. As such an example, 1-
Examples thereof include amino-1-cyclopentanemethanol, 2-aminocyclohexanol, 2-aminomethylcyclohexanol, 2-aminophenol, and o-aminobenzyl alcohol.

Further, when an alkylene group, a cycloalkylene group, an aromatic group or a substituent thereof is used as R ₁ , the substituted group is not limited to a hydrocarbon group as described above, and may be, for example, a hydroxyl group, a carboxyl group, Halogen group,
It may contain an ether group or the like.

Specific examples of such an amino alcohol compound include 2-amino-1,3-propanediol,
2-amino-2-methyl-1,3-propanediol,
2-amino-2-ethyl-1,3-propanediol,
2-amino-2-hydroxymethyl-1,3-propanediol, 3-amino-1,2-propanediol,
-Amino-3-hydroxy-n-butyric acid, 3-amino-2
-Chloropropanol and the like.

When the amino alcohol compound represented by the chemical formula [1] is reacted with carbon disulfide in the presence of a base, a dithiocarbamate represented by the following chemical formula [2] is produced (hereinafter, this reaction is referred to as "First reaction").

[0018]

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Note that R ₁ and R ₂ in the formula are represented by the chemical formula [1]
Are the same as R ₁ and R ₂ . M is Na,
Represents an alkali metal atom such as K, ammonium or substituted ammonium.

The ratio of the amino alcohol compound and carbon disulfide used in the first reaction is not particularly limited, but preferably, the amount of carbon disulfide used per equivalent of amino group of the amino alcohol compound is 1. 0-1.5
Double equivalent. Since the first reaction proceeds sufficiently when the amount of carbon disulfide used is 1.0 to 1.5 equivalents, it is not preferable in terms of reaction efficiency to add carbon disulfide in an amount exceeding 1.5 equivalents. On the other hand, if the amount of carbon disulfide used is less than 1.0 equivalent, it is not preferable because a thiourea compound is by-produced and the yield is reduced.

Examples of the base used in the first reaction include alkali metal hydroxides, alkali metal alkoxides, ammonia, tertiary amines, and heterocyclic amines. These may be the above base alone or the base dissolved in water. Can be used. Specific examples include an aqueous sodium hydroxide solution,
Potassium hydroxide aqueous solution, aqueous ammonia, and triethylamine are exemplified.

The amount of the base used is preferably one equivalent equivalent to one equivalent of the amino group in the amino compound, since the amino group of the amino alcohol can be easily converted to a dithiocarbamate. If the amount of the base used is too large, the reaction proceeds sufficiently, and there is no effect on the reaction, but it is not preferable in terms of the reaction efficiency. On the other hand, if the amount of the base used is too small, the progress of the reaction becomes slow and by-products are easily formed, which is not preferable.

Further, when the amino alcohol compound has an acidic group such as a carboxyl group, it is necessary to add a base equivalent to the amount of the acidic group and further to add the above amount of the base.

Next, hydrogen peroxide is added to the dithiocarbamate obtained in the first reaction in a water-soluble organic solvent to produce a 2-thioxo-1,3-O, N-heterocyclic compound. (Hereinafter, this reaction is referred to as “second reaction”).

The 2-thioxo-1, produced in the second reaction,
The 3-O, N-heterocyclic compound is represented by the following chemical formula [3].

[0026]

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In the formula, R ₁ and R ₂ represent the chemical formula [1]
Are the same as R ₁ and R ₂ .

The solvent used in the second reaction is a water-soluble organic solvent, for example, alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and dioxane, ketones such as acetone and butanone, acetonitrile, dimethylformamide, and the like. Examples thereof include aprotic polar solvents such as dimethyl sulfoxide and basic solvents such as pyridine. Among them, methanol, ethanol and tetrahydrofuran are preferable. A mixed solvent obtained by adding water to these water-soluble organic solvents can also be provided to the second reaction, but it is preferable that the content of water in the mixed solvent is not high from the viewpoint of the yield of the product.

When a water-soluble organic solvent is used in the first reaction, it is not necessary to isolate and use the obtained dithiocarbamate, and the reaction solution can be directly supplied to the second reaction.

The amount of hydrogen peroxide used in the second reaction is 1.0 equivalent or more, preferably 1.5 to 2 equivalents, per equivalent of dithiocarbamate supplied to the reaction.
Double equivalent. Further addition of hydrogen peroxide does not particularly affect the yield, but is not necessary because the reaction is sufficiently completed with 1.5 to 2 equivalents.

Although the reaction temperature in the second reaction is not particularly limited, this reaction involves a remarkable exotherm, and the reaction heat may be used to cause the reaction in a state in which the water-soluble organic solvent is refluxed. Therefore, the reaction temperature is preferably not lower than room temperature and not higher than the reflux temperature of the water-soluble organic solvent. In particular, when the reaction is performed under reflux of the water-soluble organic solvent, the reaction time can be shortened, and thus the addition of hydrogen peroxide can be completed in a short time, which is more preferable. In addition, the reaction time is sufficient within 1 hour after the addition of hydrogen peroxide since the second reaction itself proceeds very quickly.

In this manner, most heterocyclic compounds can be easily produced. Among the amino alcohol compounds represented by the above chemical formula [1], amino groups having 3 carbon atoms in the main chain of R ₁ are selected. When alcohol is used as a raw material, depending on the compound, a heterocyclic compound may not be formed, and the reaction may be stopped at a preceding intermediate, 3-hydroxyisothiocyanate. In such a case, an intramolecular cyclization reaction can easily be carried out in the presence of a strong base such as sodium hydroxide or potassium hydroxide to obtain a target heterocyclic compound.

The produced heterocyclic compound can be recovered by a general method. For example, the second reaction solution can be filtered to remove sulfur as a by-product, concentrated, extracted with an extraction solvent such as benzene or ethyl acetate, and recovered by distilling off the solvent. Furthermore, when purification is necessary, purification can be performed by recrystallization and column chromatography.

[0034]

【Example】

Example 1 Synthesis of 1,3-oxazolidine-2-thione 0.075 mol of carbon disulfide was placed in 50 ml of an ethanol solution containing 0.05 mol of ethanolamine and ₃ ml of 28% aqueous ammonia (0.05 mol as NH ₃ ). The mixture was stirred at room temperature for 30 minutes. Next, 10 ml of 30% hydrogen peroxide (about 0.09 mol as H ₂ O ₂ ) was added little by little. At this time, the temperature of the reaction solution rose to 70 ° C. or higher. After the completion of the addition of the aqueous hydrogen peroxide, the by-product sulfur was removed by filtration, and the solvent and excess carbon disulfide were distilled off under reduced pressure. H
The conversion was determined to be 96.5% by PLC. The residue was dissolved in hot water, a small amount of solid sodium hydroxide was added thereto, and the released ammonia was removed under reduced pressure. The remaining solid was extracted with a benzene-hexane mixed solution and then recrystallized to obtain 4.68 g of a white crystal of 1,3-oxazolidine-2-thione represented by the formula [4] (yield 90.
7%). The melting point of this compound is 97.1-97.
9 ° C.

[0035]

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Example 2 Using methanol as a solvent and triethylamine as a base The same procedure as in Example 1 was carried out except that the solvent was changed to methanol and the base was changed to triethylamine. At this time, the temperature of the reaction solution rose to 60 ° C. or higher. The conversion was determined by HPLC to be 96.9%. The yield after purification by recrystallization was 90.5%. The melting point of the obtained compound was 97.2 to 97.9 ° C.

[Example 3] Using sodium hydroxide as a base The same procedure as in Example 1 was carried out except that the solvent was changed to methanol and the base was changed to sodium hydroxide. At this time, the temperature of the reaction solution rose to 60 ° C. or higher. The conversion was determined by HPLC to be 86.0%. The yield after purification by recrystallization was 80.2%. The melting point of the obtained compound was 97.1 to 97.8 ° C.

Example 4 R-(-)-4-ethyl-
Synthesis of 1,3-oxazolidine-2-thione R-(-)-2-amino-1-butanol 0.05mo
l, 0.075 mol of carbon disulfide was added to 50 ml of an ethanol solution containing 0.05 mol of triethylamine, and the mixture was stirred at room temperature for 30 minutes. Next, 8 ml of 30% hydrogen peroxide (about 0.07 mol as H ₂ O ₂ ) was added little by little. At this time, the temperature of the reaction solution rose to 70 ° C. or higher. After the completion of the addition of the aqueous hydrogen peroxide, the by-product sulfur was removed by filtration, and the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue was dissolved in hot water, a small amount of insoluble matter was removed by filtration, and the mixture was extracted with ethyl acetate. After distilling off ethyl acetate, the obtained oil was purified by silica gel chromatography using chloroform-acetone as an eluent to obtain an R-formula represented by the formula [5].
5.88 g (89.6% yield) of (-)-4-ethyl-1,3-oxazolidine-2-thione was obtained.

[0039]

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Example 5 (-)-4-methyl-5-
Synthesis of phenyl-1,3-oxazolidine-2-thione 0.075 mol of carbon disulfide was added to 50 ml of a methanol solution containing 0.05 mol of (-)-norephedrine and 0.05 mol of triethylamine, followed by stirring at room temperature for 30 minutes. . Then, 9 ml of 30% hydrogen peroxide (H ₂ O ₂
About 0.08 mol) was added little by little. On this occasion,
The temperature of the reaction solution rose to 60 ° C. or higher. After the completion of the addition of the aqueous hydrogen peroxide, the by-product sulfur was removed by filtration, and the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue is suspended in cold water,
Extracted with benzene. After washing the benzene layer with 1 M hydrochloric acid, the aqueous layer was washed with distilled water until the pH of the aqueous layer became neutral, and the benzene layer was concentrated to obtain 9.97 g of a pale yellow liquid. Purification by silica gel chromatography using acetone-chloroform (1/9) as an eluent gave a colorless non-colored mixture of (-)-4-methyl-5-phenyl-1,3-oxazolidine-2-thione represented by the formula [6]. 9.63 g (yield 99.7%) of a crystalline solid was obtained.

[0041]

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Example 6 5-Hydroxymethyl-
Synthesis of 1,3-oxazolidine-2-thione 3-amino-1,2-propanediol 0.05mo
1, 3 ml of 28% ammonia water (0.05 as NH ₃₎
mol) was added to 50 ml of a methanol solution containing 0.075 mol of carbon disulfide, and the mixture was stirred at room temperature for 30 minutes. Next, 10 ml of 30% hydrogen peroxide (about 0.09 mol as H ₂ O ₂ ) was added little by little. At this time, the temperature of the reaction solution rose to 60 ° C. or higher. After the completion of the addition of the aqueous hydrogen peroxide, the by-product sulfur was removed by filtration, and the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue was suspended in distilled water, solid ammonia was added in a small amount to remove the liberated ammonia under reduced pressure, and then concentrated. The residue was extracted with acetone to obtain a pale yellow acetone-soluble liquid. Purification was performed by silica gel chromatography using acetone-chloroform (4/6) as an eluent, and 6.69 g of colorless crystals of 5-hydroxymethyl-1,3-oxazolidine-2-thione represented by the formula [7] (yield: 99). 0.6%). The melting point of the obtained compound was 57.6 to 59.6 ° C.

[0043]

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Example 7 4,4-dimethyl-1,3
Synthesis of -oxazolidine-2-thione 2-amino-2-methyl-1-propanol 0.05m
ol, 0.15 mol of carbon disulfide in 50 ml of a tetrahydrofuran solution containing 0.05 mol of triethylamine.
was added and stirred at room temperature for 30 minutes. Next, 9 ml of 30% hydrogen peroxide (about 0.08 mol as H ₂ O ₂ ) was added little by little. At this time, the temperature of the reaction solution rose to 60 ° C. or higher. After completion of the addition of the aqueous hydrogen peroxide, the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue was suspended in hot water, and by-product sulfur was removed by filtration. After allowing to cool to room temperature, the mixture was extracted with ethyl acetate, and the obtained pale yellow solid was recrystallized from an ethyl acetate-hexane mixture to give 4,4 represented by the formula [8].
5.37 g (yield: 81.9%) of white crystals of -dimethyl-1,3-oxazolidine-2-thione were obtained. The melting point of the obtained compound was 121.5 to 122.6 ° C.

[0045]

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Example 8 Synthesis of tetrahydro-1,3-oxazine-2-thione 0.075 mol of carbon disulfide was placed in 50 ml of a tetrahydrofuran solution containing 0.05 mol of 3-amino-1-propanol and 0.05 mol of triethylamine. And add
Stirred at room temperature for 30 minutes. Then, 30% hydrogen peroxide 8m
1 (about 0.07 mol as H ₂ O ₂ ) was added in small portions. At this time, the temperature of the reaction solution rose to 40 to 50 ° C.
After completion of the addition of the aqueous hydrogen peroxide, the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue was suspended in about 100 ml of ethanol, and by-product sulfur was removed as ethanol insolubles.
4 g of solid sodium hydroxide was added to the ethanol solution, and the mixture was stirred at room temperature for 2 hours. The solution is concentrated and the residue is recrystallized to give the formula

Tetrahydro-1,3 represented by [9]
4.93 g (yield 84.1%) of white crystals of -oxazine-2-thione were obtained. The melting point of the obtained compound is 12
6.5-127.3 ° C.

[0047]

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Example 9 5,5-dimethyl-1,3
Synthesis of -oxazine-2-thione 3-amino-2,2-dimethyl-1-propanol
0.1 mol of carbon disulfide in 50 ml of a tetrahydrofuran solution containing 0.05 mol and 0.05 mol of triethylamine.
5 mol was added, and the mixture was stirred at room temperature for 30 minutes. Then 30
8 ml of hydrogen peroxide (about 0.07 mol as H ₂ O ₂ )
l) was added in small portions. At this time, the temperature of the reaction solution is 30 to
The temperature rose to 40 ° C. After completion of the addition of the aqueous hydrogen peroxide, the solvent and excess carbon disulfide were distilled off under reduced pressure. The residue was suspended in hot water, and the by-product sulfur was removed by filtration. The solution was concentrated and the residue was recrystallized to give 6.83 g (yield 90.9%) of white crystals of 5,5-dimethyl-1,3-oxazine-2-thione represented by the formula [10]. Obtained. The melting point of the obtained compound was 180.2 to 181.1 ° C.

[0049]

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Example 10 Synthesis of hexahydro-2-benzoxazolidinethione 2-aminocyclohexanol 0.05 mol, 28%
In 50 ml of a methanol solution containing ₃ ml of ammonia water (0.05 mol as NH ₃ ), 0.07 carbon disulfide was added.
5 mol was added, and the mixture was stirred at room temperature for 30 minutes. Then 30
% Hydrogen peroxide 6 ml (about 0.05 mol as H ₂ O ₂ )
l) was added in small portions. At this time, the temperature of the reaction solution was 60 ° C.
It rose above. After completion of the addition of the aqueous hydrogen peroxide, the solvent and excess carbon disulfide were distilled off under reduced pressure. The residual yellow solid was suspended in an aqueous sodium hydroxide solution, and by-product sulfur was removed by filtration. When this solution was acidified, 6.56 g (yield 83.5%) of hexahydro-2-benzoxazolidinethione white crystals represented by the formula [11] were obtained. The melting point of the obtained compound was 132.3 to 133.3 ° C.

[0051]

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Example 11 Synthesis of 2-benzoxazolidinethione A 50-m solution of tetrahydrofuran containing 0.05 mol of 2-aminophenol and 0.05 mol of triethylamine
l, add 0.05 mol of carbon disulfide, and add
Minutes. Then, 6 ml of 30% hydrogen peroxide (H ₂ O
₍ About 0.05 mol as ₂ ) was added little by little. At this time, the temperature of the reaction solution was kept at 10 ° C. or lower. After completion of the addition of the hydrogen peroxide solution, the mixture was stirred at room temperature for 1 hour, and concentrated hydrochloric acid was added to make the liquid acidic. The upper layer was taken out of the reaction solution separated into two layers, the concentrated residue was suspended in methanol, and by-product sulfur was removed by filtration. The solution was concentrated to obtain 6.91 g (yield: 91.5%) of a light brown solid of 2-benzoxazolidinethione represented by the formula [12]. The melting point of the obtained compound was 193.0 to 194.6 ° C.

[0053]

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Table 1 summarizes the reaction solvents, bases and yields used in Examples 1 to 11.

[0055]

[Table 1]

[Comparative Example 1] When water was used as the reaction solvent The reaction was carried out in the same manner as in Example 1 except that the reaction solvent was water. The yield of 1,3-oxazolidine-2-thione is 1
3.7%.

Comparative Example 2 When the reaction solvent was a water-insoluble organic solvent The reaction was carried out in the same manner as in Example 1 except that the reaction solvent was benzene and the base was triethylamine. The yield of 1,3-oxazolidine-2-thione was 29.7%.

Comparative Example 3 Another Production Method (Thermal Decomposition Method) A chloroform solution containing 0.05 mol of ethanolamine (15 ml) was kept at 0 ° C., and carbon disulfide was 0.055 mol.
15 ml of a chloroform solution containing 1 were added over 15 minutes. After stirring at room temperature for 30 minutes, the solvent was distilled off under reduced pressure to obtain a yellow reaction intermediate. This intermediate was heated at 120 ° C. for 2 hours using an oil bath. After cooling, the mixture was extracted with a benzene-hexane mixed solution, and the yield of 1,3-oxazolidine-2-thione was less than 1%.

Comparative Example 4 Other Production Method (Method Using Iodine) 10 ml of a methanol solution containing 0.05 mol of ethanolamine was kept at 0 ° C., and 0.05 mol of carbon disulfide was added over 30 minutes. Next, an iodine-methanol solution having a concentration of 0.15 g / ml was added dropwise until the color of the solution became pale yellow. The solvent was distilled off under reduced pressure at room temperature to obtain a yellow solid as a reaction intermediate. This yellow solid was suspended in 100 ml of water and boiled for 1 hour. The generated sulfur was removed by filtration, concentrated, and then extracted with a benzene-hexane mixed solution. This was recrystallized to give 1,3-oxazolidine-2-thione 0.1.
95 g (18.4% yield) was obtained.

Comparative Example 5 Another Production Method (Method Using Ethyl Chlorocarbonate) A dioxane solution (7.5 ml) containing ethanolamine (0.05 mol) was mixed with triethylamine (0.055 mol), and the mixture was kept at -10 ° C. with disulfide. 0.05mol carbon
Was added dropwise little by little. During that time, the temperature of the reaction solution rose to around room temperature.

After cooling again, 0.0% ethyl chlorocarbonate was added.
55 mol was added slowly. Thereafter, a chloroform solution containing 0.055 mol of triethylamine (15 m) was prepared.
and heated at 50 ° C. for 1 hour. After the precipitate was removed by filtration, the solvent was distilled off under reduced pressure. The residue was converted to benzene
After extraction with a hexane mixture, the mixture was recrystallized to obtain 3.96 g (yield: 76.7%) of 1,3-oxazolidine-2-thione.

The reaction solvents of Comparative Examples 1 to 5
The base used and the yield are summarized in Table 2.

[0063]

[Table 2]

[0064]

According to the present invention, amino alcohol and carbon disulfide are reacted in the presence of a base to form a dithiocarbamate, which is then reacted with hydrogen peroxide in a water-soluble organic solvent. Without using toxic substances such as lead, nitrate and the like, and without generating toxic gases such as carbonyl sulfide.
O, N-heterocyclic compounds can be produced in high yield.

Claims (1)

[Claims] A chemical formula [1] HO-R ₁ -NHR ₂ [1] (wherein R ₁ is an alkylene group, a cycloalkylene group,
R ₂ represents a hydrogen atom,
Represents an alkyl group or a substituted alkyl group. ) Is reacted with carbon disulfide in the presence of a base to give a compound of the formula [2] (Wherein, R _1, R ₂ is, R _1, R in the chemical formula [1]
_{As in 2} , M represents an alkali metal atom, unsubstituted or substituted ammonium. ), And then reacting with hydrogen peroxide in a water-soluble organic solvent to obtain a chemical formula [3] (Wherein, R _1, R ₂ is, R _1, R in the chemical formula [1]
_Same as ₂ . 2-thioxo-1,3-represented by
A method for producing an O, N-heterocyclic compound.