KR20230133820A - Method of preparing 3,5-diamino-1,2,4-triazole compound - Google Patents

Abstract

The present application relates to a method of obtaining 3,5-diamino-1,2,4-triazole by reacting solid hydrazine and dicyandiamide under solvent-free conditions.

Description

Method for producing 3,5-diamino-1,2,4-triazole {METHOD OF PREPARING 3,5-DIAMINO-1,2,4-TRIAZOLE COMPOUND}

The present application relates to a method of obtaining 3,5-diamino-1,2,4-triazole by reacting solid hydrazine and dicyandiamide under solvent-free conditions.

3,5-diamino-1,2,4-triazole, C ₂ H ₅ N ₅ ; hereinafter referred to as “3,5-diamino-1,2,4-triazole,” which is rich in nitrogen with a nitrogen content of about 70% DAT") is widely used as a kinase inhibitor, cathode catalyst, and pharmaceutical intermediate. In addition, it is widely used as a precursor for the synthesis of chemical intermediates of many organic materials and high energy density materials.

Conventional DAT synthesis was accomplished through the reaction of dicyandiamide (C ₂ H ₄ N ₄ ) with an aqueous hydrazine solution or hydrazine salt. US registered patent US2648671A discloses a method of producing DAT by using hydrazine salt as a precursor of hydrazine and reacting it with dicyandiamide. Meanwhile, Russian registered patent RU2152389C1 discloses a manufacturing method by setting the molar ratio of hydrazine:nitric acid:dicyandiamide to 1:2:1 and using water as a solvent. The above two manufacturing methods have the disadvantage that the purity of the product DAT is low because DAT salt can be produced as a by-product, and the manufacturing cost is high due to wastewater treatment costs because solvents are used. Additionally, an additional recrystallization process is required to remove the salt from the DAT salt.

Meanwhile, anhydrous hydrazine (H ₂ NNH ₂ ) is so toxic that it cannot be used directly in laboratories or production sites, and an aqueous hydrazine solution diluted in water or hydrazine salt must be used instead. Hydrazine aqueous solution is relatively easy to handle like ammonia aqueous solution, but has the problem of containing a lot of water. As described above, the current DAT manufacturing process has high environmental pollution factors such as waste water generation due to the introduction of acid or base additives in addition to hydrazine and dicyandiamide, and there is a cost burden for separation and recovery due to the use of solvents.

Solid hydrazine is safer and more convenient to use than an aqueous liquid hydrazine solution, and is a solid with completely removed moisture. Although it is a stable solid, solid hydrazine shows high reactivity and selectivity comparable to anhydrous hydrazine, according to the present inventor's patent and paper. It has been reported (Org. Lett., 13, 6386 (2011); Adv. Syn. Catal., 2013, 355, 389.; Republic of Korea registered patent 10-1305053;).

The present application seeks to provide a method of obtaining 3,5-diamino-1,2,4-triazole by reacting solid hydrazine and dicyandiamide under solvent-free conditions.

However, the problem to be solved by the present application is not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

Disclosed herein is 3,5-diamino-1,2,4-triazole, comprising subjecting solid hydrazine and dicyandiamide to a solid reaction to obtain 3,5-diamino-1,2,4-triazole. A method for producing azoles is provided.

The method of obtaining 3,5-diamino-1,2,4-triazole according to embodiments of the present application involves reacting solid hydrazine and dicyandiamide under solvent-free conditions to form 3,5-diamino-1,2,4-triazole. By obtaining 1,2,4-triazole, 1) high yield can be achieved without additional additives, 2) since it is performed under solvent-free conditions, waste water and waste are not generated and the size of the reaction vessel can be reduced. , 3) It saves time and energy because it does not require a separation process, 4) It is easy to store and use and is not dangerous as it uses solid hydrazine that is stable at room temperature, 5) It can be used in an anhydrous environment without water, 6) Since the amount of solid hydrazine used can be accurately controlled, price competitiveness and eco-friendliness can be secured. 7) Since solid hydrazine produced using carbon dioxide is utilized, 3,5-diamino-1, If the production of 2,4-triazole is commercialized, a reduction in carbon dioxide, a greenhouse gas, can be expected.

FIG. 1A is a photograph of DAT synthesized according to Example 1 of the present application, and FIG. 1B is a photograph of DAT synthesized according to Comparative Example 1 of the present application.
Figure 2 is a ¹ H-NMR spectrum of DAT synthesized according to Example 1 herein.
Figure 3 is a ¹³ C-NMR spectrum of DAT synthesized according to Example 1 herein.
Figure 4 is GC-MS data of DAT synthesized according to Example 1 of the present application.
Figure 5 is powder X-ray diffraction (XRD) data of DAT synthesized according to Example 1 of the present application.

Hereinafter, with reference to the attached drawings, implementation examples and embodiments of the present invention will be described in detail so that those skilled in the art can easily implement the present invention. However, the present application may be implemented in various different forms and is not limited to the implementation examples and examples described herein. In order to clearly explain the present invention in the drawings, parts that are not related to the description are omitted, and similar parts are given similar reference numerals throughout the specification.

Throughout this specification, when a part is said to be “connected” to another part, this includes not only the case where it is “directly connected,” but also the case where it is “electrically connected” with another element in between. do.

Throughout this specification, when a member is said to be located “on” another member, this includes not only the case where the member is in contact with the other member, but also the case where another member exists between the two members.

Throughout the specification of the present application, when a part “includes” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.

As used herein, the terms “about,” “substantially,” and the like are used to mean at or close to a numerical value when manufacturing and material tolerances inherent in the stated meaning are presented, and to aid understanding of the present application. It is used to prevent unscrupulous infringers from unfairly exploiting disclosures in which precise or absolute figures are mentioned.

The terms “step of” or “step of” as used throughout the specification herein do not mean “step for.”

Throughout this specification, the term "combination(s) thereof" included in the Markushi format expression means a mixture or combination of one or more selected from the group consisting of the components described in the Markushi format expression, It means containing one or more selected from the group consisting of the above components.

Throughout this specification, description of “A and/or B” means “A or B, or A and B.”

Hereinafter, embodiments of the present application have been described in detail, but the present application may not be limited thereto.

The present application is to obtain 3,5-diamino-1,2,4-triazole (3,5-diamino-1,2,4-triazole; DAT) by reacting solid hydrazine and dicyandiamide. It provides a method for producing 3,5-diamino-1,2,4-triazole, including:

In one embodiment of the present application, the solid hydrazine may be represented by the following formula 1:

[Formula 1]

.

In one embodiment of the present application, the 3,5-diamino-1,2,4-triazole may be represented by Formula 2 or Formula 3 below, and possible resonance structures thereof:

[Formula 2]

;

[Formula 3]

.

In one embodiment of the present application, the solid reaction may be performed under solvent-free conditions.

In one embodiment of the present application, the purity of the solid hydrazine and the dicyandiamide may be 99% by mass or more. If the purity is less than 99% by mass, there may be a problem in that the yield of the product is reduced or impurities are generated.

In one embodiment of the present application, the solid reaction may be performed at a temperature ranging from about 80°C to about 120°C, but may not be limited thereto. For example, the solid reaction temperature is about 80°C to about 120°C, about 80°C to about 115°C, about 80°C to about 110°C, about 80°C to about 105°C, about 80°C to about 100°C, about 80°C. ℃ to about 95 ℃, about 80 ℃ to about 90 ℃, about 80 ℃ to about 85 ℃, about 85 ℃ to about 120 ℃, about 85 ℃ to about 115 ℃, about 85 ℃ to about 110 ℃, about 85 ℃ About 105°C, about 85°C to about 100°C, about 85°C to about 95°C, about 85°C to about 90°C, about 90°C to about 120°C, about 90°C to about 115°C, about 90°C to about 110°C. °C, about 90°C to about 105°C, about 90°C to about 100°C, about 90°C to about 95°C, about 95°C to about 120°C, about 95°C to about 115°C, about 95°C to about 110°C, About 95°C to about 105°C, about 95°C to about 100°C, about 100°C to about 120°C, about 100°C to about 115°C, about 100°C to about 110°C, about 100°C to about 105°C, about 105°C In a temperature range of from about 120°C to about 120°C, from about 105°C to about 115°C, from about 105°C to about 110°C, from about 110°C to about 120°C, from about 110°C to about 115°C, or from about 115°C to about 120°C. It may be performed, but may not be limited thereto. If the solid reaction is performed at a temperature range of less than about 80°C, a problem may arise in which the reaction progresses slowly, and if the solid reaction is performed at a temperature range exceeding about 120°C, 3, which is the product of the solid reaction, There may be a problem with the formation of impurities other than 5-diamino-1,2,4-triazole. Additionally, if the solid reaction is not performed in a temperature range of about 80°C to about 120°C, there may be a problem of producing 3,5-diamino-1,2,4-triazole of low purity. The reaction rate may vary depending on the temperature at which the solid reaction is performed, and the reaction can proceed quickly if the mixed powder is placed in a closed container and the temperature is raised.

In one embodiment of the present application, the solid reaction may be performed by continuing mixing during the reaction time, but may not be limited thereto.

In one embodiment of the present application, the mixing may be performed by one or more selected from a mortar, a ball mill, a bead mill, and a kneader, but may not be limited thereto. there is. In one embodiment of the present application, the mixing may be performed by mixing the reactants in a mortar and continuously grinding them, or using a dispersion mixer device such as a ball mill, bead mill, and/or kneader, If the temperature is increased in the ball mill and bead mill device, the reaction can proceed very quickly.

In one embodiment of the present application, the sizes of balls and beads used in the ball mill and bead mill may each independently range from about 0.05 mm to about 3 mm, but may not be limited thereto. For example, the sizes of the balls and beads may each independently range from about 0.05 mm to about 3 mm, from about 0.05 mm to about 2.5 mm, from about 0.05 mm to about 2 mm, from about 0.05 mm to about 1.5 mm, and from about 0.05 mm. mm to about 1 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 2.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 1.5 mm, or about 0.1 mm to about 1 mm, It is not limited to this. In one embodiment of the present application, the sizes of the balls and beads may each independently range from about 0.1 mm to about 1 mm. The smaller the size of the balls and beads, the faster the reaction rate can be.

The balls and beads are each independently made of metal such as SUS and carbon steel; and/or metal oxide materials such as alumina, zirconia, and zirconia-yttria; may be used, but may not be limited thereto.

In one embodiment of the present application, the molar ratio of the reactants in the solid reaction may be about 0.5 mol to about 5 mol of the solid hydrazine relative to 1 mol of the dicyandiamide, but may not be limited thereto. If the molar ratio of the reactants in the solid reaction is less than about 0.5 mol of the solid hydrazine to 1 mol of the dicyandiamide, the reaction does not proceed well and unreacted dicyandiamide and the solid hydrazine may remain. , if the solid hydrazine exceeds about 5 mol, unreacted solid hydrazine may remain.

In one embodiment of the present application, the solid reaction may be performed in a pressure range of about 0.1 MPa to about 5 MPa, but may not be limited thereto. For example, the solid reaction is about 0.1 MPa to about 5 MPa, about 0.1 MPa to about 4.5 MPa, about 0.1 MPa to about 4 MPa, about 0.1 MPa to about 3.5 MPa, about 0.1 MPa to about 3 MPa, about 0.1 MPa. It may be performed in a pressure range of from about 2.5 MPa, about 0.1 MPa to about 2 MPa, or about 0.1 MPa to about 1.5 MPa, but may not be limited thereto. In one embodiment of the present application, the solid reaction may be performed in a pressure range of about 0.1 MPa to about 1.5 MPa. Here, if the solid reaction is performed in a pressure range of less than about 0.1 MPa, a problem may occur in which the reaction proceeds slowly, and if the solid reaction is performed in a pressure range exceeding about 5 MPa, a problem in which a hydrazine derivative is produced This can happen.

In one embodiment of the present application, the yield of 3,5-diamino-1,2,4-triazole obtained through the solid reaction is about 80% or more, about 85%, based on the reactant, dicyandiamide. % or more, about 90% or more, or about 95% or more. In one embodiment of the present application, the yield of 3,5-diamino-1,2,4-triazole obtained through the solid reaction is about 95% or more or about 98% based on the reactant, dicyandiamide. It may be more than %.

In one embodiment of the present application, the solid reaction includes: (a) mixing the solid hydrazine and the dicyandiamide in a solid state to obtain a mixed powder; and (b) placing the mixed powder in a reaction vessel and performing a solid reaction to obtain the 3,5-diamino 1,2,4-triazole; but may not be limited thereto.

In one embodiment of the present application, additives may be additionally included during the solid reaction, but may not be limited thereto.

In one embodiment of the present application, the additive may be one or more selected from water, hydrochloric acid, and nitric acid, but may not be limited thereto. Adding additives during the solid reaction promotes the reaction, which may have the advantage of increasing the efficiency of the 3,5-diamino-1,2,4-triazole production process. However, there may be a problem in that DAT salts or other impurities are produced in addition to the product DAT.

In one embodiment of the present application, when the additive is additionally included, the additive may be additionally included in an amount of about 0.1 mol to about 1 mol per 1 mol of the dicyandiamide, but may not be limited thereto. .

In one embodiment of the present application, a lubricating solvent may be additionally included during the solid reaction, but may not be limited thereto. When a lubricating solvent is additionally included during the solid reaction, an additional process of separating the product and the lubricating solvent may be required.

In one embodiment of the present application, the lubricating solvent may include an alcohol having 1 to 15 carbon atoms, but may not be limited thereto. Specifically, the alcohol may include one or more selected from methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, and possible isomers thereof. It may not be limited.

In one embodiment of the present application, the lubricating solvent may include an ether having 2 to 16 carbon atoms, but may not be limited thereto. Specifically, the ether may include one or more selected from dimethyl ether, diethyl ether, THF, and dioxin, but may not be limited thereto.

In one embodiment of the present application, the lubricating solvent may include an aliphatic hydrocarbon having 5 to 15 carbon atoms, but may not be limited thereto. Specifically, the aliphatic hydrocarbon may include one or more selected from pentane, hexane, heptane, and possible isomers thereof, but may not be limited thereto.

In one embodiment of the present application, the lubricating solvent may include an aromatic hydrocarbon having 6 to 15 carbon atoms, but may not be limited thereto. Specifically, the aromatic hydrocarbon is benzene; toluene; xylene; and aromatic carbon compounds substituted with heteroatoms such as oxygen and nitrogen, but may not be limited thereto.

In one embodiment of the present application, the lubricating solvent may include polyol, but may not be limited thereto. Specifically, the polyol may include one or more selected from ethylene glycol, glycerol, erythritol, xylitol, and mannitol, but may not be limited thereto.

Hereinafter, the present application will be described in more detail using examples. However, the following examples are merely illustrative to aid understanding of the present application, and the content of the present application is not limited to the following examples.

[Example]

<Example 1: Preparation of 3,5-diamino-1,2,4-triazole (3,5-diamino-1,2,4-triazole, DAT) through solid reaction>

0.076 g of solid hydrazine and 0.042 g of dicyandiamide were placed in a mortar and mixed evenly, then placed in a reaction vessel and reacted at 100°C for 10 to 20 hours to obtain 0.048 g of DAT. The yield of DAT was 98% based on the reactant, dicyandiamide. The results of elemental quantitative analysis for the DAT (measuring equipment: Thermo Flash 2000, Flash EA1112; unit %) are shown in the table below.

C H N Calculated value (%) 24.24 5.09 70.67 Experimental value (%) 23.98 4.90 71.05

Figure 1 is a photograph of DAT synthesized according to Example 1 of the present application, showing that it is a white powder.

Figure 2 is a ¹ H-NMR spectrum of DAT synthesized according to Example 1 herein. D6-DMSO solvent was used, and the measured values are as follows. δ(ppm) = 10.23(s, 1H, NH), 5.08(s, 2H, NH ₂ ), 4.49(s, 2H, NH ₂ )

Figure 3 is a ¹³ C-NMR spectrum of DAT synthesized according to Example 1 herein. D6-DMSO solvent was used, and only one peak at 159.3 ppm was observed.

Figure 4 is GC-MS data of DAT synthesized according to Example 1 of the present application. The observed m/z peaks are 43, 57, and 99.

Figure 5 is powder X-ray diffraction (XRD) data of DAT synthesized according to Example 1 of the present application. The X-ray diffraction peak of the synthesized DAT coincides with the peak of the JCPDS data of DAT, and the peaks correspond to the solid hydrazine and dicyandiamide used as reactants; and peaks of substances other than DAT as products were not observed.

Through the above analysis results, it was confirmed that the DAT powder synthesized according to Example 1 of the present application had high purity.

<Example 2: Preparation of DAT through reaction temperature control>

In Example 1, the reaction temperature was adjusted to less than 80°C and greater than 120°C, and the reaction was performed under other conditions the same. When the reaction temperature was less than 80°C, reactants remained and the yield of DAT product was less than 20%. On the other hand, when the reaction temperature was above 120°C, the mass and yield of the obtained DAT product were almost the same as Example 1, but trace impurities were observed.

<Example 3: Preparation of DAT through reaction time control>

In Example 1, the reaction time was adjusted to 5 hours and 40 hours, and the reaction was performed with other conditions remaining the same. When the reaction time was 5 hours, reactants remained and the yield of DAT product was less than 50%. On the other hand, when the reaction time was 40 hours, the mass and yield of the obtained DAT product were almost the same as in Example 1.

<Example 4: Preparation of DAT by adjusting the molar ratio of reactants>

In Example 1, the molar ratio of the dicyandiamide and the solid hydrazine reactant was adjusted differently, and the reaction was performed under the same conditions. When the molar ratio of dicyandiamide and solid hydrazine was about 1:0.5 or less, the DAT yield was less than 10% and the reaction did not proceed well, and unreacted dicyandiamide and solid hydrazine remained. When the molar ratio of dicyandiamide and solid hydrazine was about 1:5 or more, a lot of unreacted hydrazine remained and other hydrazine derivatives were produced.

<Example 5: Preparation of DAT through reaction pressure control>

In Example 1, the pressure of the solid reaction was adjusted differently, and the reaction was performed with other conditions remaining the same. When the reaction pressure was less than about 0.1 MPa, the production rate of DAT was slow and the yield was less than 10%, and when the reaction pressure was 1 MPa, the obtained products and yield were almost the same as Example 1.

<Example 6: Preparation of DAT containing water as an additive>

Under the same conditions as in Example 1, water was added at a ratio of 1 mole to 1 mole of dicyandiamide. The obtained product and yield were almost the same as Example 1, but an additional process of drying the water in the product was required.

<Example 7: Preparation of DAT containing hydrochloric acid as an additive>

Under the same conditions as in Example 1, the reaction was performed by adding hydrochloric acid. When hydrochloric acid was added at a ratio of 0.2 mole to 1 mole of dicyandiamide, the yield of the DAT product was about 95%. When hydrochloric acid was added in a ratio of more than 1 mole to 1 mole of dicyandiamide, the yield of DAT product was less than about 10%, and the content of chlorine compounds, including hydrazine chloride, was more than 90%.

<Comparative Example 1: Preparation of DAT using liquid hydrazine aqueous solution>

In Example 1, 50 μL of the same molar amount of hydrazine monohydrate (64-65%) was added instead of solid hydrazine, and the reaction was performed under the same other conditions. After the reaction, the solid compound was separated and dried, and the yield of the obtained product was about 30%. The produced DAT was colored yellow or pink, and the color varied depending on the reaction conditions (Figure 1b).

<Comparative Example 2: Hydrazine hydrochloride (NH ₂ NH ₂ ·Manufacture of DAT using HCl)>

In Example 1, 0.07 g of the same molar amount of hydrazine hydrochloride was added instead of solid hydrazine, and the reaction was performed under the same other conditions. After the reaction, the solid compound was separated and dried, the yield of the obtained product was about 30%, and the produced solid contained impurities such as ammonium chloride (NH ₄ Cl).

The description of the present application described above is for illustrative purposes, and those skilled in the art will understand that the present application can be easily modified into other specific forms without changing its technical idea or essential features. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. For example, each component described as single may be implemented in a distributed manner, and similarly, components described as distributed may also be implemented in a combined form.

The scope of the present application is indicated by the claims described below rather than the detailed description above, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present application. .

Claims (11)

Obtaining 3,5-diamino-1,2,4-triazole by solid reaction of solid hydrazine and dicyandiamide
Method for producing 3,5-diamino-1,2,4-triazole, including.
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the solid reaction is carried out under solvent-free conditions.
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the solid reaction is carried out in a temperature range of 80°C to 120°C.
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the solid reaction is carried out with continuous mixing during the reaction time.
According to claim 4,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the mixing is performed by one or more selected from a mortar, a ball mill, a bead mill, and a kneader.
According to claim 1,
The molar ratio of the reactants in the solid reaction is 0.5 mol to 5 mol of the solid hydrazine relative to 1 mol of the dicyandiamide.
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the solid reaction is carried out in a pressure range of 0.1 MPa to 5 MPa.
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the yield of 3,5-diamino-1,2,4-triazole is 80% or more based on the dicyandiamide.
According to claim 1,
The method for producing 3,5-diamino-1,2,4-triazole is carried out without an acid additive such as hydrochloric acid or nitric acid. .
According to claim 1,
A method for producing 3,5-diamino-1,2,4-triazole, wherein the 3,5-diamino-1,2,4-triazole is a white solid.
According to claim 1,
The solid reaction is,
(a) mixing the solid hydrazine and the dicyandiamide in a solid state to obtain a mixed powder; and
(b) placing the mixed powder in a reaction vessel and performing a solid reaction to obtain the 3,5-diamino-1,2,4-triazole;
A method for producing 3,5-diamino-1,2,4-triazole, comprising: