KR100967444B1 - Method for preparing of n,n'-subtituted-3,3'-dithiopropioneamide - Google Patents

Abstract

The present invention relates to a process for the preparation of N, N'-disubstituted-3,3'-dithiopropionamide, in particular the reaction of 3-mercaptopropion ester, amine solution, and inorganic salt at a temperature of 5 to 70 ℃ N-substituted-3-mercaptopropionamide prepared by the oxidizing reaction with an oxidizing agent not only can produce a high purity stable N, N'-disubstituted-3,3'-dithiopropionamide in high yield, At the same time, it is easy to control the reaction, and by suppressing the generation of hydrogen sulfide to block the occurrence of chain side reactions by hydrogen sulfide, it is excellent in reaction stability and production of environmentally friendly N, N'-disubstituted-3,3'-dithiopropionamide It is about a method.

N, N'-disubstituted-3,3'-dithiopropionamide, N-substituted-3-mercaptopropionamide, 3-mercaptopropion ester, amine solution, inorganic salt, 3-isothiazolone

Description

Method for preparing N, N'-disubstituted-3,3'-dithiopropionamide {METHOD FOR PREPARING OF N, N'-SUBTITUTED-3,3'-DITHIOPROPIONEAMIDE}

The present invention relates to a method for preparing N, N'-disubstituted-3,3'-dithiopropionamide, and more particularly, to stable N, N'-disubstituted-3,3'-dithiopropion with high purity. Not only can the amide be produced in high yield, but also the reaction can be easily controlled and the generation of hydrogen sulfide is suppressed, thereby preventing the occurrence of chain side reactions by hydrogen sulfide, thereby providing excellent reaction stability and eco-friendly N, N'-disubstitution. A method for producing -3,3'-dithiopropionamide.

Substituted 3-isothiazolones, developed by Crow et al. In 1965, are now used throughout the industry as antimicrobial and antimicrobial agents added to paints, cosmetics, textiles, plastics and the like, including disinfectants.

In a study on the preparation of conventionally substituted 3-isothiazolones, US Pat. No. 3,849,430 discloses N, N'-disubstituted-3,3'-dithiodipropionamide or N-substituted-3-mercaptopropionamide. Disclosed is a method for cyclization by reaction with a halogenating agent.                         

The N, N'-disubstituted-3,3'-dithiodipropionamide may be prepared by thiol acetic acid using 2-mono-substituted acrylate ester, 3-mono-substituted acrylate ester, or di-substituted acrylate ester. And mercury to produce 3-mercaptopropionic acid, the 3-mercaptopropionic acid is oxidized to prepare 3,3'-dithiodipropionic acid, and the 3,3'-dithiodipropionic acid is converted into a gaseous amine. It is prepared by reaction with a compound (formula 1).

[일반식 1]

[Formula 1]

In Formula 1, X and Z are each independently hydrogen or a lower alkyl group, R is each independently hydrogen, an alkyl group, a phenyl group, a cyano group, a sulfone group, or an aminocarbonyl group, and Y is hydrogen, having 1 to 18 carbon atoms. An alkyl group, a cycloalkyl group of up to 10 carbon atoms, an alalkyl group of up to 10 carbon atoms, an aryl group of up to 10 carbon atoms, an aryl group substituted by halogen, an aryl group substituted by lower alkyl, an aryl group substituted by lower alkoxy, cyano alkyl group, Carboalkoxyalkyl group, haloalkyl group, alkoxyalkyl group, aryloxyalkyl group of up to 12 carbon atoms, alkoxyalkyl group of up to 12 carbon atoms, dialkylaminoalkyl group, alkylacyl group of up to 8 carbon atoms, lower alkylsulfone group, aryl of up to 10 carbon atoms Sulfonic group, cyano group, or carbamoyl group.

According to the method of Formula 1, there is an advantage that a stable N, N'-disubstituted-3,3'-dithiodipropionamide can be produced in high yield. However, according to the above method, the purity of N, N'-disubstituted-3,3'-dithiodipropionamide is low, the reaction takes a long time of 48 hours or more, and the use of gaseous amines in terms of safety and environmental aspects There is a problem.

Meanwhile, the N-substituted-3-mercaptopropionamide reacts the 3-mercaptopropionic acid prepared as described above with an alcohol to prepare 3-mercaptopropion ester, and the 3-mercaptopropion ester is converted into a gaseous amine. Prepared by reaction with a compound (Formula 2).

[Formula 2]

In Formula 2, X, Y, Z, and R are the same as defined in Formula 1.

According to the method of Formula 2, N-substituted-3-mercaptopropionamide can be prepared in high yield, and the reaction requires a relatively short time of less than 24 hours, but N, N'-disubstituted- The low purity of 3,3'-dithiodipropionamide and the use of gaseous amines still have problems in terms of safety and environment, as well as lowering the yield in subsequent halogenation processes by water produced by oxidation. Therefore, there is a problem that must be removed.

US Pat. No. 4,868,310 discloses a method of preparing N-substituted-3-mercaptopropionamide by simultaneously supplying a mixture of unsaturated nitrile and alcohol and a strong inorganic acid in a suitable organic solvent to form acrylamide and treating it with a thiolating agent. Is disclosed. However, there is still a problem that the method is lowered in purity by side reactions, and a step of removing water generated by oxidation is necessary.

In addition, Korean Patent Application No. 1988-15673 discloses HSCH ₂ CHR ₂ COCl by reacting thionyl halide with HSCH ₂ CH ₂ COOH, treating it with 1 equivalent of chlorine, and then adding an amine (R ₁ −) with an acid trapping agent. A method for preparing N, N'-disubstituted-3,3'-dithiodipropionamide by adding NH ₂ ) 2 equivalents is disclosed. However, the above method has a problem in that purity and yield are lowered by side reactions, water is generated by neutralization of hydrochloric acid generated during the reaction, and a process for removing them is necessary.

Korean Patent Application No. 1997-46173 discloses a reaction of HSCH ₂ CH ₂ COR with a primary amine (R-NH ₂ ) in an aqueous solution and N, N'-disubstituted-3,3'-dithiodipropionamide as an oxidizing agent. It discloses a method for producing. However, the above method can produce high purity N, N'-disubstituted-3,3'-dithiodipropionamide in a high yield when the primary amine is mono methylamine, but the linear alkyl chain of primary amine When the carbon number is 6 or more, the yield decreases due to side reactions such as hydrolysis reaction, oxidation reaction, and removal reaction, and the purity of N, N'-disubstituted-3,3'-dithiodipropionamide is inferior.

Therefore, the side reactions are suppressed irrespective of the carbon number of the linear alkyl chain of the primary amine (R-NH ₂ ), so that the reaction stability is excellent, environmentally friendly, and high-purity N, N'-disubstituted-3,3'-dithiopropion More research is needed on how to produce amides in high yield.

In order to solve the problems of the prior art as described above, the present invention not only can produce a high purity stable N, N'-disubstituted-3,3'-dithiopropionamide in high yield, but also control of the reaction Providing a method for producing N, N'-disubstituted-3,3'-dithiopropionamide which is easy and prevents the generation of hydrogen sulfide, thereby preventing the occurrence of chain side reactions caused by hydrogen sulfide and having excellent reaction stability. The purpose.

Another object of the present invention is to prepare a high-purity substituted 3-isothiazolone in high yield using N, N'-disubstituted-3,3'-dithiopropionamide prepared by the above method It is to provide a method for producing isothiazolone.

In order to achieve the above object, the present invention provides a method for producing N, N'-disubstituted-3,3'-dithiodipropionamide,

a) 3-mercaptopropion ester represented by the following formula (3), for amines

   The liquid and the inorganic salt are reacted at a temperature of 5 to 70 ° C. to formula

   Preparing an N-substituted-3-mercaptopropionamide represented by 2;

   And

b) oxidizing agent N-substituted-3-mercaptopropionamide prepared in step a)

   Oxidation reaction with N, N'-disubstituted-3,3'-di represented by the following Chemical Formula 1

   Preparation of Thiopropionamide                     

It provides a process for the preparation of N, N'-disubstituted-3,3'-dithiopropionamide comprising:

[Formula 1]

[Formula 2]

(3)

In Formula 1, Formula 2, and Formula 3,

X, and Z are each independently hydrogen or an alkyl group having up to 8 carbon atoms, preferably X and Z are hydrogen,

Y is hydrogen, an alkyl group of 1 to 18 carbon atoms, a cycloalkyl group of up to 10 carbon atoms, an alalkyl group of up to 10 carbon atoms, an aryl group of up to 10 carbon atoms, an aryl group substituted with halogen, an aryl group substituted with alkyl of up to 8 carbon atoms, An aryl group substituted by alkoxy of up to 8 carbon atoms, cyano alkyl group, carboalkoxyalkyl group, haloalkyl group, alkoxyalkyl group, aryloxyalkyl group of up to 12 carbon atoms, alkoxyalkyl group of up to 12 carbon atoms, dialkylaminoalkyl group, up to 8 carbon atoms Is an alkylacyl group, an alkylsulphone group of up to 8 carbon atoms, an arylsulphone group of up to 10 carbon atoms, a cyano group, or a carbamoyl group, preferably a methyl group or an octyl group.

The present invention also provides a substituted 3-isothiazolone represented by the following formula (4) comprising the step of reacting the N, N'-disubstituted-3,3'-dithiopropionamide prepared by the above method with a halogenating agent Provides a method for preparing:

[Formula 4]

In the formula (4),

R ₁ , and R ₂ are each independently hydrogen, halogen, or an alkyl group having up to 8 carbon atoms

Y is hydrogen, an alkyl group of 1 to 18 carbon atoms, a cycloalkyl group of up to 10 carbon atoms, an alalkyl group of up to 10 carbon atoms, an aryl group of up to 10 carbon atoms, an aryl group substituted with halogen, an aryl group substituted with alkyl of up to 8 carbon atoms, An aryl group substituted by alkoxy of up to 8 carbon atoms, cyano alkyl group, carboalkoxyalkyl group, haloalkyl group, alkoxyalkyl group, aryloxyalkyl group of up to 12 carbon atoms, alkoxyalkyl group of up to 12 carbon atoms, dialkylaminoalkyl group, up to 8 carbon atoms An alkylacyl group, an alkyl sulfone group having up to 8 carbon atoms, an aryl sulfone group having up to 10 carbon atoms, a cyano group, or a carbamoyl group.                     

Hereinafter, the present invention will be described in detail.

The inventors of the present invention have been studying a method for producing a high-purity N, N'-disubstituted-3,3'-dithiopropionamide with high yield in a stable and environmentally friendly manner. In the reaction with amines, the main cause of the decrease in yield and purity is hydrogen sulfide (H ₂ S), which is generated primarily during the reaction, and minimizes the generation of hydrogen sulfide when the 3-mercaptopropion ester is reacted with the primary amine. As a result of the application of the reaction conditions and the additives, it is possible to produce high purity stable N, N'-disubstituted-3,3'-dithiopropionamide in high yield by blocking the occurrence of chain side reactions caused by hydrogen sulfide. At the same time, it is easy to control the reaction, and by suppressing the generation of hydrogen sulfide, it prevents the occurrence of chain side reactions by hydrogen sulfide, confirming that the reaction stability is excellent and environmentally friendly. Therefore, the present invention has been completed based on this.

The N, N'-disubstituted-3,3'-dithiopropionamide of the present invention is reacted with a 3-mercaptopropion ester, an amine solution, and an inorganic salt represented by Chemical Formula 3 at a temperature of 5 to 70 ° C. After the N-substituted-3-mercaptopropionamide represented by Formula 2 is prepared, the n-substituted-3-mercaptopropionamide is oxidized with an oxidizing agent.

The present invention is described in detail as follows.

a) Preparation of N-substituted-3-mercaptopropionamide

This step is to prepare N-substituted-3-mercaptopropionamide by reacting the 3-mercaptopropion ester, amine solution, and inorganic salt at a temperature of 5 to 70 ℃ (Scheme 1). At this time, the reaction can be carried out in a solvent or a solvent-free.

Scheme 1

Hydrogen sulfide generated during the reaction of the 3-mercaptopropion ester, the amine solution, and the inorganic salt becomes a hydrosulfide anion (HS ⁻ ) in the reaction system and is highly reactive as a nucleophile. Reaction with both N-substituted-3-mercaptopropionamide (product) and N, N'-disubstituted-3,3'-dithiodipropionamide (product) lowers the yield and results in the resulting side reaction product. It exists together with and causes purity.

Therefore, the present invention uses an inorganic salt in the production of N-substituted-3-mercaptopropionamide, the inorganic salt is combined with the -SH functional group of the 3-mercaptopropion ester in a dissolved state to suppress the generation of hydrogen sulfide In addition, by increasing the basicity in the reaction system to increase the chemical bonding reaction rate of the amine and the ester.

The amine solution is preferably included in 1 to 2 equivalents relative to the 3-mercaptopropion ester. If the content is less than 1 equivalent, the yield of N-substituted-3-mercaptopropionamide is lowered. If the content is more than 2 equivalents, the amount of unreacted amine after the reaction is increased to increase the manufacturing cost.                     

The inorganic salt may be a conventional inorganic salt, and particularly preferably a compound containing sulfite ions, and examples thereof include Na ₂ SO ₃ , K ₂ SO ₃ , NaHSO _3, and the like.

The inorganic salt is preferably included in an amount of 0.01 to 0.5 equivalents based on 3-mercaptopropion ester. If the content is less than 0.01 equivalent, the effect of suppressing side reactions caused by hydrogen sulfide is insignificant, and if the content exceeds 0.5 equivalent, there is a problem that the solubility is lowered and inefficient.

In the present invention, when using a solvent, water or an organic solvent may be used. In this case, the organic solvent may be methanol, ethanol, chlorobenzene, acetonitrile, dichloromethane, toluene, 1-butanol, methylene chloride, chloroform, hexane, cyclohexane, or benzene.

The reaction is preferably carried out for about 24 hours at a temperature of 5 to 70 ℃. If the temperature is less than 5 ℃ the liquid reactant and product phase change to a solid may proceed very slow reaction, if it exceeds 70 ℃ thermal decomposition of the starting material occurs, the amount of hydrogen sulfide increases 3 The loss of the mercaptopropion ester raw material itself occurs, and there is a problem that the amount of undesirable side reaction substances due to the reactivity of hydrogen sulfide increases.

According to the present invention as described above it can significantly reduce the amount of hydrogen sulfide generation, preferably hydrogen sulfide is generated in a maximum of 0.5 equivalents relative to the 3-mercaptopropion ester.                     

b) N, N'-disubstituted-3,3'-dithiopropionamide

In this step, N-substituted-3-mercaptopropionamide prepared in step a) is oxidized in an aqueous solution or an organic solvent to oxidize N, N'-disubstituted-3,3'-dithiopropionamide. Preparing step (Scheme 2).

Scheme 2

The oxidant may be iodine, air, oxygen, hydrogen peroxide aqueous solution or the like.

When using oxygen or air as gas as the oxidant, the reaction temperature is easily controlled due to the slight exotherm during oxidation, and when iodine is used, side reactions that do not occur peroxide do not occur, and when the aqueous hydrogen peroxide solution is used, the reaction is easily controlled. In terms of safety and environment, it can also have an excellent effect. In particular, the hydrogen peroxide aqueous solution is preferably used at a concentration of at least 10% by weight in order to avoid the problem that the amount of the reactant increases to decrease the reaction efficiency.

The oxidizing agent is preferably included in 0.5 to 5.5 equivalents based on oxygen relative to N-substituted-3-mercaptopropionamide. If the content is less than 0.5 equivalents, there is a problem in that a side reaction occurs by the remaining mercaptan, and if it exceeds 5.5 equivalents, there is a problem in that peroxidized side reactions remain.

If the aqueous solution or the organic solvent is not added during the reaction, it may cause agitation.

The organic solvent may be the same as the organic solvent used in the preparation of N-substituted-3-mercaptopropionamide of step a).

The reaction is preferably carried out for about 0.5 hours.

In Formula 1, Formula 2, and Formula 3, X and Z are hydrogen, and Y is a methyl group and an octyl group. For example, 3-mercaptomethylpropion ester according to the present invention may be a methylamine or octylamine solution, and Inorganic salts were reacted to prepare N-methyl-3-mercaptopropionamide, and the N-methyl-3-mercaptopropionamide was oxidized with an oxidizing agent to form N, N'-dimethyl-3,3'-dithiodi. Propionamide can be prepared.

According to the production method of the present invention as described above, not only in the production of N-substituted-3-mercaptopropionamide, but also hydrogen sulfide acting as a very dangerous substance in the process due to the strong corrosiveness, biotoxicity and irritating odor of hydrogen sulfide gas itself. By suppressing it can have an excellent effect in terms of safety and environment, and it is easy to control the reaction and at the same time high purity N, N'-disubstituted-3,3'-dithiopropionamide and substituted 3-isothiazolone There is an advantage that can be obtained in high yield.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the scope of the present invention is not limited to the following examples.

EXAMPLE

Example 1

60 g of 3-mercaptomethyl propion ester, 129 g of n-octylamine solution, and 1 g of sodium sulfite were added to a glass reactor equipped with a stirrer and a condenser at room temperature. This reaction was carried out in a solvent-free state while maintaining the temperature in the reactor at 5 ° C. to obtain N-octyl-3-mercaptopropionamide. After adding 200 g of methanol as a solvent, 8.5 g of oxygen was added as an oxidizing agent by attaching a gas diffuser, followed by oxidation to obtain solid N, N'-dimethyl-3,3'-dithiodipropionamide.

Example 2

In the same manner as in Example 1, except that the temperature in the reactor was maintained at 25 ℃ when N-octyl-3-mercaptopropionamide was prepared in Example 1, the solid N, N'-dimethyl-3,3 '-Dithiodipropionamide was obtained.

Example 3

In the same manner as in Example 1, except that the temperature in the reactor was maintained at 50 ° C. to prepare N-octyl-3-mercaptopropionamide in Example 1, the solid N, N′-dimethyl-3,3 '-Dithiodipropionamide was obtained.

Comparative Example 1

In Example 1, except that N-octyl-3-mercaptopropionamide was prepared in the same manner as in Example 1 except that the temperature in the reactor was maintained at 80 ° C., the solid N, N′-dimethyl-3,3 '-Dithiodipropionamide was obtained.

Comparative Example 2

In Example 1, N-octyl-3-mercaptopropionamide was prepared in the same manner as in Example 1, except that sodium sulfite, which is an inorganic salt, was not added and the temperature in the reactor was maintained at 50 ° C. N, N'-dimethyl-3,3'-dithiodipropionamide was obtained.

Purity, yield, reaction conversion rate, and hydrogen sulfide production amount were determined using the solid N, N'-dimethyl-3,3'-dithiodipropionamide obtained in Examples 1 to 3 and Comparative Examples 1 or 2 by the following method. It measured and the result is shown in following Table 4.

A) Purity-analyzed by HPLC.

B) Yield-Calculated by quantifying and summing the amount of starting material recovered in the filtrate.

C) Reaction Conversion Rate—The amount of methanol generated during the reaction was quantitatively analyzed by gas chromatography according to the method shown in Table 1 to determine the reaction conversion rate of the amidated reaction.

column STABILWAX-DB, CAM, or equivalent column Column temperature 40 ° C (1 min) → 10 ° C (1 min) → 240 ° C (2 min) Sample introduction temperature 200 ℃ Detector temperature 250 ℃ Create calibration curve Dissolve the methanol standard in distilled water, prepare three or more concentrations at 0.1 ~ 1.0 mg / L, and inject 1 μl into the gas chromatograph to measure the height or area of the peaks.

D) Hydrogen sulfate generation amount-The amount collected through the condenser at the top of the reactor was measured according to the hydrogen sulfide absorbance spectroscopy (Table 2) and Table 3 below.                     

Hydrogen sulfide quantitative absorbance method (methylene blue method) sample Absorbent 5 g of zinc sulfide (ZnSO ₄ · 7H ₂ O) was dissolved in about 500 mL of water, and a solution of 6 g of sodium hydroxide in about 300 mL of water was added thereto. Then, 70 g of ammonium sulfate was added with stirring. When the precipitate of zinc hydroxide was dissolved, water was added to make the total amount to 1 L. p-aminodimethylaniline solution 0.1 g of p-aminodimethylaniline-2-hydrochloride was prepared by dissolving in 100 mL of concentrated sulfuric acid (1% sulfuric acid + 3% water). Ferric Chloride Solution 1 g of ferric chloride (FeCl ₃ .6H ₂ O) was prepared by dissolving in 100 mL of dilute sulfuric acid (1% sulfuric acid + 99% water). Hydrogen sulfide standard solution Dissolve about 1 g of sodium sulfide in water to make 100 mL. Take 10 mL of this solution, add 25 mL of iodine solution (N / 10) and 1 mL of hydrochloric acid, close the lid, and leave for 10 minutes. Add starch reagent and add N / 10 Thio Titrated with sodium sulfate solution. The titration value at this time was made into a mL, and the background test was carried out separately, and the titration value was made into b mL.
Take sodium sulfate solution {89.3 / (ba) f} mL (where f is the titer of N / 10 sodium thiosulfate solution), add water to make 100 mL, add 5 mL of this solution, and add absorbent solution to make 1 mL. It was made.
At this time, 1 mL of hydrogen sulfide standard solution corresponds to 0.5 μl of H ₂ S (0 ° C., 760 mmHg). Iodine solution (N / 10) After dissolving by adding about 25 mL of water to 40 g of potassium iodide, about 13 g of iodine was added, and about 1 L of water and 3 drops of hydrochloric acid were added thereto. N / 10 sodium thiorate solution Prepared according to 4.2.1 (3).

Hydrogen sulfide quantitative absorbance method (methylene blue method) Preparation of Sample Solution for Analysis After the aspiration of the sample was completed, the contents solution was transferred to a 250 mL flask, the absorbent bottle was washed with the absorbent solution, combined, and then the absorbent solution was added to make 250 mL to prepare a sample solution for analysis. At this time, the above operation was all performed to avoid direct sunlight. However, in the case where the concentration of the hydrogen sulfide thus prepared was 0.5 µl / mL or more, a part of the solution was taken and diluted with an absorbent solution to prepare a sample solution for analysis. Test Methods Take analytical sample solution and hydrogen sulfide standard solution into a 25 mL volumetric flask of 20 mL each, add 2 mL of p-aminodimethylaniline solution, close the lid and mix gently (but not shake), and immediately add 1 mL of ferric chloride solution. Was added, the lid was closed again, the mixture was gently turned over and mixed, and water was added to make 25 mL. This was preserved for 30 minutes at a constant temperature near room temperature, and then transferred to a 10 mm cell, and the absorbance at wavelength 670 nm was measured with a photophotometer or a photospectrometer. At this time, the control solution was used in the same manner as for the absorbing solution. Calculation C (concentration of hydrogen sulfate in the sample, ppm) = [0.5 × (A / As) × 250 × n] / Vs
C '(concentration of hydrogen sulfate in the sample,%) = C / 10000
Vs: dry sample gas volume
n: Dilution factor when 250 mL of analytical sample solution was prepared and diluted again
A: Absorbance of Sample Solution for Analysis
As: absorbance of hydrogen sulfide standard solution

division Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 water 98 95 92 65 85 Final yield (%) 98 94 91 56 87 Reaction Conversion Rate (%) 87 90 93 85 90 Hydrogen Sulfide Production (g) 0.17 0.78 1.5 5.2 2.1

As shown in Table 4, Examples 1 to 3 prepared according to the present invention had a smaller amount of hydrogen sulfide than Comparative Examples 1 or 2, and thus the reaction product N, N'-disubstituted-3,3 It was confirmed that the purity and yield of the '-dithiodipropionamide was increased. In addition, when the reaction temperature is increased to 70 ° C. or more as in Comparative Example 1, a chain side reaction caused by hydrogen sulfide increases due to an increase in reaction rate, thereby producing solid impurities, and thus N, N′-disubstituted-3, It was confirmed that the purity and yield of 3'-dithiodipropionamide were lowered. In addition, even when the inorganic salt was not used even at the same temperature conditions as in Comparative Example 2, it was confirmed that the purity and yield of N, N'-disubstituted-3,3'-dithiodipropionamide were lowered.

According to the present invention, not only in the production of N-substituted-3-mercaptopropionamide, but also by inhibiting hydrogen sulfide, which acts as a very dangerous substance in the process due to the strong corrosiveness, biotoxicity and irritating odor of the hydrogen sulfide gas itself. In terms of excellent effects, it is easy to control the reaction and at the same time obtain high purity N, N'-disubstituted-3,3'-dithiopropionamide and substituted 3-isothiazolone in high yield. It can be effective.

Claims (8)

In the method for producing N, N'-disubstituted-3,3'-dithiodipropionamide, a) N-substituted-3-mercaptopropionamide represented by the following formula (2) by reacting the 3-mercaptopropion ester represented by the following formula (3), a liquid amine, and an inorganic salt at a temperature of 5 to 70 ℃ Manufacturing step; And b) N-substituted-3-mercaptopropionamide prepared in step a) is oxidized with an oxidizing agent to prepare N, N'-disubstituted-3,3'-dithiopropionamide represented by the following Chemical Formula 1 Steps to Method for producing N, N'-disubstituted-3,3'-dithiopropionamide comprising: [Formula 1]

[Formula 2]

(3)

In Formula 1, Formula 2, and Formula 3, X, and Z are each independently hydrogen or an alkyl group having up to 8 carbon atoms, Y is hydrogen, an alkyl group of 1 to 18 carbon atoms, a cycloalkyl group of up to 10 carbon atoms, an alalkyl group of up to 10 carbon atoms, an aryl group of up to 10 carbon atoms, an aryl group substituted with halogen, an aryl group substituted with alkyl of up to 8 carbon atoms, An aryl group substituted by alkoxy of up to 8 carbon atoms, cyano alkyl group, carboalkoxyalkyl group, haloalkyl group, alkoxyalkyl group, aryloxyalkyl group of up to 12 carbon atoms, alkoxyalkyl group of up to 12 carbon atoms, dialkylaminoalkyl group, up to 8 carbon atoms An alkylacyl group, an alkyl sulfone group having up to 8 carbon atoms, an aryl sulfone group having up to 10 carbon atoms, a cyano group, or a carbamoyl group. The method of claim 1, A method for producing N, N'-disubstituted-3,3'-dithiopropionamide, wherein the liquid amine of step a) is included in 1 to 2 equivalents relative to 3-mercaptopropion ester. The method of claim 1, N, N'-disubstituted-3,3'-dithio, wherein the inorganic salt of step a) is at least one selected from the group consisting of Na ₂ SO ₃ , K ₂ SO ₃ , and NaHSO ₃ containing sulfite ions Method for preparing propionamide. The method of claim 1, Method for preparing N, N'-disubstituted-3,3'-dithiopropionamide wherein the inorganic salt of step a) is contained in an amount of 0.01 to 0.5 equivalents based on 3-mercaptopropion ester. The method of claim 1, The organic solvent selected from the group consisting of methanol, ethanol, chlorobenzene, acetonitrile, dichloromethane, toluene, 1-butanol, methylene chloride, chloroform, hexane, cyclohexane, and benzene; A method for producing N, N'-disubstituted-3,3'-dithiopropionamide carried out under water or solvent-free. The method of claim 1, N, N'-disubstituted-3,3 in which hydrogen sulfide is produced at a maximum of 0.5 equivalents to 3-mercaptopropion ester when the 3-mercaptopropion ester, the liquid amine, and the inorganic salt of step a) are reacted Method for preparing '-dithiopropionamide. The method of claim 1, The method of producing N, N'-disubstituted-3,3'-dithiopropionamide selected from the group consisting of iodine, air, oxygen, and hydrogen peroxide aqueous solution. The method of claim 1, Method for producing N, N'-disubstituted-3,3'-dithiopropionamide that the oxidizing agent of step b) is contained in 0.5 to 5.5 equivalents based on oxygen relative to N-substituted-3-mercaptopropionamide.