A method for preparing 2,3,5,6-pyridinetetramine

Abstract

The application discloses a preparation method of 2,3,5,6-pyridine tetramine, and belongs to the field of high polymer synthesis chemistry. In the application, an amino reagent is used as an amino donor, amino negative ions released by the amino reagent and chlorine atoms in the molecular structure of 2,3,5,6-tetrachloropyridine are subjected to a series of nucleophilic substitution reactions, substitution of chlorine atoms at positions 2, 3, 5 and 6 is realized, and the molecular skeleton of the target product pyridine tetramine is constructed. The reaction process is carried out under the protection of an inert atmosphere such as nitrogen or argon, and an inert solvent such as N, N-dimethylformamide or tetrahydrofuran is used as a reaction medium, so that the occurrence of a side reaction is effectively avoided and the reaction selectivity is improved. In addition, by adding an appropriate amount of a catalyst, for example, an alkali metal halide, the reaction process can be significantly accelerated and the reaction efficiency can be improved, so that the purity of the target product obtained finally can reach more than 90%, and the reaction yield is stable between 83% and 89%, and the application has a good industrial application prospect.

Description

Technical Field

[0001] This invention relates to a method for preparing 2,3,5,6-pyridinetetramine, belonging to the field of polymer synthesis chemistry. Background Technology

[0002] 2,3,5,6-Pyridinetetramine is a nitrogen-containing heterocyclic compound with multiple amino functional groups in its molecular structure, exhibiting good reactivity and diverse application potential. In the field of organic synthesis, this compound is often used as a key intermediate, capable of participating in the construction of various complex organic molecules, and also has wide applications in the preparation of functional materials (such as polymers, optoelectronic materials, and drug molecule design).

[0003] However, current methods for synthesizing 2,3,5,6-pyridinetetramine are relatively limited in existing technologies. Most existing processes have significant shortcomings, such as poor selectivity in the reaction process, resulting in numerous byproducts; the purity of the final product is generally low, making it difficult to meet high-standard application requirements; in addition, many methods involve cumbersome procedures and harsh conditions, requiring high-pressure reactors for catalytic hydrogenation reduction, making existing technologies highly dependent on equipment and the experimental skills of technicians, and posing safety risks, further limiting its large-scale production and practical application. Patent CN109761893A discloses a method that can be used under normal pressure, but after the initial reaction, the subsequent purification steps are complex, requiring catalyst removal, washing with anhydrous alcohol solvent, vacuum distillation of the alcohol solvent, heating of the alcohol solvent, decolorization with activated carbon, and finally pouring into petroleum ether or toluene to obtain the final product.

[0004] Therefore, developing a novel method for the efficient and highly selective preparation of 2,3,5,6-pyridinetetramine, characterized by relatively simple operation, mild reaction conditions, and high efficiency, has become an urgent research need. The realization of such a method would not only help improve the synthetic efficiency and product quality of this compound, but also provide a solid material foundation for the development of high-performance and sustainable polymers, further promoting their widespread use in materials science and industrial applications. This method has significant scientific research value and practical application value. Summary of the Invention

[0005] [Technical Issues] The preparation of 2,3,5,6-pyridinetetramine in the existing technology has the problems of harsh reaction conditions and complex reaction steps.

[0006] [Technical Solution] The technical problem to be solved by this invention is to address the shortcomings of existing technologies by providing a method for preparing 2,3,5,6-pyridinetetramine. This invention utilizes an amino anion provided by an amination reagent to undergo a nucleophilic substitution reaction with the four chlorine atoms on the 2,3,5,6-tetrachloropyridine ring, gradually replacing the chlorine atoms at positions 2, 3, 5, and 6. The entire reaction is carried out under an inert atmosphere and inert solvent protection. Furthermore, the preparation of 2,3,5,6-pyridinetetramine (Formula I) can also be achieved by adding a catalyst.

[0007]

[0008] Formula I The first objective of this invention is to provide a method for preparing 2,3,5,6-pyridinetetramine, the method being as follows: an amination reagent is dispersed in an inert solvent, followed by the slow addition of 2,3,5,6-tetrachloropyridine, and the temperature is gradually increased to 100-250°C, and the reaction is maintained at the temperature for 8-24 h to obtain 2,3,5,6-pyridinetetramine; the reaction process is carried out under an inert atmosphere.

[0009] In one embodiment of the present invention, the molar ratio of the amino group of the amination reagent to 2,3,5,6-tetrachloropyridine is (3~7):1.

[0010] In one embodiment of the present invention, an excess of amination reagent is added to the reaction system, and the molar ratio of the amino group of the amination reagent to 2,3,5,6-tetrachloropyridine in the actual reaction process is (4~6):1.

[0011] In one embodiment of the present invention, the feeding rate of 2,3,5,6-tetrachloropyridine is controlled to be 0.5~1.5 g / min.

[0012] Preferably, the feeding rate of 2,3,5,6-tetrachloropyridine is controlled at 0.6~1.2 g / min.

[0013] In one embodiment of the present invention, the heating rate is controlled to be 1~5 °C / min.

[0014] In one embodiment of the present invention, the rotational speed is controlled at 50~300 rpm throughout the process.

[0015] In one embodiment of the present invention, the concentration of the amination reagent after mixing the inert solvent and the amination reagent is 5% to 30%.

[0016] Preferably, the ratio of the inert solvent to the amination reagent is 20 mL: (1~5) g.

[0017] More preferably, the ratio of the inert solvent to the amination reagent is 20 mL: (2~4) g.

[0018] In one embodiment of the present invention, the inert solvent is selected from aromatic compound solvents or polar aprotic solvents.

[0019] In one embodiment of the present invention, the aromatic compound solvent is selected from one or more of toluene, N,N-xyleneamine, o-xylene, m-xylene, p-xylene, mesitylene, ethylbenzene, n-butadiene, isobutadiene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, 1,2,4-trichlorobenzene, nitrobenzene, and diphenyl ether.

[0020] In one embodiment of the present invention, the polar aprotic solvent is selected from one or more of methyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), hexamethylphosphoric triamine (HMPA), 1,3-dimethyl-2-imidazolinone (DMI), and N-methylpyrrolidone (NMP).

[0021] In one embodiment of the present invention, the amination reagent includes urea, ammonium carbamate, and alkali metal amino compounds.

[0022] Optionally, the alkali metal amino compound is selected from one or more of sodium amino, calcium amino, potassium amino, lithium amino, rubidium amino, cesium amino, and bis(trimethylsilyl)amino reagents.

[0023] Optionally, the bis(trimethylsilyl)amino reagents include one or more of bis(trimethylsilyl)aminolithium, bis(trimethylsilyl)aminosodium, bis(trimethylsilyl)aminopotassium, and bis(trimethylsilyl)aminocalcium.

[0024] In one embodiment of the present invention, a catalyst is also added during the reaction process.

[0025] In one embodiment of the present invention, the molar ratio of the catalyst to 2,3,5,6-tetrachloropyridine is 1:(5~10).

[0026] In one embodiment of the present invention, the catalyst comprises one or more of alkali metal halides, alkaline earth metal halides, quaternary ammonium salts, quaternary phosphine salts, crown ethers, and cryptethers.

[0027] In one embodiment of the present invention, the catalyst alkali metal halide includes one or more of sodium iodide, potassium iodide, sodium bromide, potassium bromide, lithium chloride, and cesium fluoride.

[0028] In one embodiment of the present invention, the alkaline earth metal halide includes one or more of calcium iodide, magnesium bromide, strontium chloride, and barium fluoride.

[0029] In one embodiment of the present invention, the quaternary ammonium salt includes one or more of tetrabutylammonium iodide (TBAI) and tetrabutylammonium bromide (TBAB).

[0030] In one embodiment of the present invention, the quaternary phosphine salt includes one or more of tetraphenylphosphine bromide, tetrabutylphosphine bromide, and triphenylmethylphosphine bromide.

[0031] In one embodiment of the present invention, the crown ether compound includes one or more of 18-crown-6, dibenzo-18-crown-6, 15-crown-5, and dicyclohexano-18-crown-6.

[0032] In one embodiment of the present invention, the cryptether compound includes one or more of 2,2,2-cryptether, cryptether [2.2.1], and cryptether [2.2.2].

[0033] In one embodiment of the present invention, the inert atmosphere includes at least one of nitrogen (N2) and argon (Ar).

[0034] In one embodiment of the present invention, after the reaction is completed, the mixture is allowed to cool naturally to room temperature, and ice water is slowly added while stirring to quench the reaction.

[0035] In one embodiment of the present invention, the reaction product is purified after the reaction is terminated.

[0036] In one embodiment of the present invention, the purification includes acid adjustment, filtration to remove impurities, and column chromatography purification.

[0037] In one embodiment of the present invention, the acidification is achieved by adjusting the pH to neutral using an acidic solution.

[0038] In one embodiment of the present invention, the eluent used in the column chromatography purification includes a mixed solution of petroleum ether and ethanol.

[0039] In one embodiment of the present invention, the volume ratio of petroleum ether to ethanol is (8~12):1.

[0040] In one embodiment of the present invention, the specific steps of the method are as follows: (1) Reaction preparation: Disperse an appropriate amount of amination reagent in 50-60 mL of inert solvent; introduce inert gas, exhaust the air, and maintain an inert atmosphere throughout the process; (2) Feeding: Under stirring, add 2,3,5,6-tetrachloropyridine to the solvent in step (1) at a feeding rate of 0.5~1.5 g / min; (3) Reaction: After the feeding is completed, the reaction temperature is gradually increased to 100-250℃ at a heating rate of 1-5℃ / min, and the reaction is maintained at this temperature for 8-24 h; (4) Purification: After the reaction is completed, the reaction solution is cooled to room temperature, and 20-40 mL of ice water is slowly added dropwise. The reaction is terminated by stirring for 8-15 min. The pH of the solution is adjusted to neutral with acid, and the solid impurities generated are removed by filtration. The filtrate is passed through a chromatographic column and purified by elution with petroleum ether and ethanol to obtain 2,3,5,6-pyridinetetramine product.

[0041] The present invention also provides the use of the method in the preparation of 2,3,5,6-pyridinetetramine or products containing 2,3,5,6-pyridinetetramine.

[0042] [Beneficial Effects] (1) Flexible selection of raw materials and reagents: Ammoniating reagents have a wide range of choices, covering urea, ammonium carbamate, alkali metal amino compounds (such as sodium amino, calcium amino, potassium amino, lithium amino, rubidium amino, cesium amino), and bis(trimethylsilyl)amino reagents (such as lithium bis(trimethylsilyl)amino, sodium bis(trimethylsilyl)amino, potassium bis(trimethylsilyl)amino, calcium bis(trimethylsilyl)amino, etc.), which can be adapted according to specific reaction requirements. The selection of reaction solvents is also highly flexible. Various inert solvents such as toluene, chlorobenzene, DMF, NMP, and DMI can be selected according to the reaction temperature, raw material solubility, and reaction activity, effectively ensuring the stable progress of the reaction. There are various catalyst matching methods, which do not rely on scarce or high-cost materials. All raw materials are easy to obtain and have a wide range of procurement channels, which significantly reduces the preparation threshold and is conducive to large-scale application.

[0043] (2) Strong reaction controllability and few byproducts: During the reaction, the continuous introduction of inert protective gas (such as nitrogen, argon, etc.) effectively isolates air and moisture, thereby preventing the amination reagent from becoming ineffective due to oxidation or hydrolysis. At the same time, by combining catalysts such as alkali metal halides and crown ethers, the reactivity of amino anions can be significantly improved, and the selective substitution of chlorine atoms on the pyridine ring can be promoted, effectively inhibiting the formation of byproducts such as diamino and triaminopyridines, so that the purity of the target product can be stably maintained at over 90%, thus improving the overall efficiency and economy of the reaction.

[0044] (3) Simple operation and wide adaptability: The reaction process is highly simplified, consisting of only three core steps: "feeding - heating reaction - post-treatment purification", without the need for complex pretreatment processes or special equipment support. The reaction conditions have a wide range of adaptability, the reaction temperature can be flexibly adjusted between 100~250℃, and the reaction time can be controlled between 8~24 h according to actual needs. This system is suitable for small-scale fine preparation at the laboratory level, and can also be well adapted to pilot-scale and even scale-up production. It is easy to implement and has strong process scalability.

[0045] (4) The product has strong practicality and broad application prospects: The prepared 2,3,5,6-pyridinetetramine has high purity and stable chemical structure. As an important nitrogen-containing heterocyclic compound, it can be directly used as an organic synthesis intermediate, functional material monomer and drug molecule precursor, and is widely used in many fields such as medicine, materials, and pesticides. This preparation method effectively solves the bottleneck problems of low product purity and limited application range in traditional processes, showing significant practical value and broad market potential.

[0046] (5) Simple and efficient post-processing: Most of the byproducts generated in the reaction are water-soluble inorganic halides (such as sodium chloride, calcium chloride, etc.), which can be quickly removed by a simple filtration step, making the operation convenient. Product purification only requires conventional column chromatography technology, and commonly used eluents (such as ethyl acetate, petroleum ether, etc.) are easy to recover and reuse. There is no need to rely on complex high-pressure separation equipment or special purification processes, which greatly reduces the cost of subsequent processing and the impact on the environment, meeting the requirements of green chemistry.

[0047] In summary, this invention utilizes 2,3,5,6-tetrachloropyridine as the core reactant, successfully and efficiently achieving the conversion process that completely and efficiently replaces all four chlorine atoms in the 2,3,5,6-tetrachloropyridine molecule with amino groups. The final yield of the product consistently reaches over 80%, while the purity of the product exceeds 90%. Furthermore, this synthetic route generates few byproducts with well-defined properties, which are easily separated and removed using conventional post-processing methods. This makes the entire purification process simple and efficient, significantly reducing the complexity and cost of the purification process, and is beneficial for industrial scale-up and practical applications. Attached Figure Description

[0048] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention in the above and / or other aspects will become clearer.

[0049] Fig. 1 Compound of Example 1 1 H NMR spectrum; Fig. 2 Compound of Example 1 13 C NMR spectrum; Fig. 3 The image shows the infrared spectrum of the compound in Example 1. Detailed Implementation

[0050] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0051] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0052] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0053] In the following examples, the products were measured using a 400 MHz Bruker nuclear magnetic resonance instrument: the deuteration reagent was tetramethylsilane (TMS) as an internal standard, the concentration of the 1H NMR spectrum was about 8 mg / mL, and the concentration of the 1C NMR spectrum was about 20 mg / mL. The deuteration reagent was tetramethylsilane (TMS).

[0054] ATR-FTIR was tested using a Bruker Tensor II infrared spectrometer with 32 scans.

[0055] Product yield = Amount of raw materials used to produce the desired product ÷ Amount of raw materials fed into the plant × 100%.

[0056] Example 1: A method for preparing 2,3,5,6-pyridinetetramine This embodiment provides a method for preparing 2,3,5,6-pyridinetetramine, using 1,3-dimethyl-2-imidazolinone (DMI) solvent and sodium amino and 2,3,5,6-tetrachloropyridine as reactants, as detailed below: (1) Add 50 mL of 1,3-dimethyl-2-imidazolinone solvent, dried over 4 Å molecular sieves for 24 h, to a dry four-necked flask, followed by 10 g of sodium amino powder. Stir (200 rpm) during the addition process to ensure the solid is fully dispersed in the solvent. Then, continuously purge with high-purity nitrogen for 30 min to displace and purge air from the flask. Maintain a stable nitrogen atmosphere throughout the operation to provide sufficient inert protection for subsequent reactions. (2) Under stirring (200 rpm), slowly add 8 g of 2,3,5,6-tetrachloropyridine to the flask at a feeding rate of 0.6 g / min to prevent excessive local reaction and ensure that the reaction system is uniform and stable. (3) After the addition is complete, continue stirring (200 rpm) and gradually heat the reaction system to 180°C at a rate of 1°C / min, and keep it at this temperature for 20 h; wherein, the molar ratio of sodium amino to 2,3,5,6-tetrachloropyridine is controlled to be about 6:1. (4) After the reaction is complete, place the flask in room temperature environment to cool naturally. When the temperature drops to room temperature, stir at 220 rpm and slowly add 20 mL of ice water at a rate of 1 mL / min while stirring at 200 rpm for 10 min. Then, use dilute hydrochloric acid solution to adjust the pH value to 7.0, filter and collect the filtrate. (5) The obtained filtrate was separated and purified by column chromatography using a silica gel column with petroleum ether and anhydrous ethanol (9:1, v:v) as the eluent, and finally 2,3,5,6-pyridinetetramine was obtained.

[0057] The specific synthesis route is as follows:

[0058] The product yield was determined using a 400 MHz Bruker nuclear magnetic resonance instrument, and the purity was 99% as determined by high performance liquid chromatography (HPLC). Figs. 1-3 ).

[0059] Table 1: 2,3,5,6-Pyridinium tetramine 1 H NMR and 13 C NMR data

[0060] Example 2: A method for preparing 2,3,5,6-pyridinetetramine This embodiment provides a method for preparing 2,3,5,6-pyridinetetramine, using N,N-dimethylamine (DMA) solvent and calcium amino and 2,3,5,6-tetrachloropyridine as reactants, as detailed below: (1) Add 50 mL of N,N-dimethylamine solvent, dried over 4 Å molecular sieves for 24 h, to a dry four-necked flask, followed by 12.5 g of aminocalcium powder. Stir (250 rpm) during the addition process to ensure the solid is fully dispersed in the solvent. Then, continuously purge with high-purity nitrogen for 30 min to displace and purge air from the flask. Maintain a stable nitrogen atmosphere throughout the operation to provide sufficient inert protection for subsequent reactions. (2) Under stirring (250 rpm), slowly add 8 g of 2,3,5,6-tetrachloropyridine to the flask at a feeding rate of 0.7 g / min; (3) After the addition is complete, continue stirring (250 rpm) and gradually heat the reaction system to 180°C at a rate of 3°C / min, and keep it at this temperature for 12 h; wherein, the molar ratio of aminocalcium to 2,3,5,6-tetrachloropyridine is controlled to be about 3:1; (4) After the reaction is complete, place the flask in a room temperature environment to cool naturally. When the temperature drops to room temperature, stir at 200 rpm and slowly add 20 mL of ice water at a rate of 2 mL / min while stirring for 30 min to ensure thorough mixing. Then, use dilute hydrochloric acid solution to adjust the pH value to 7.0, filter and collect the filtrate. (5) The obtained filtrate was separated and purified by column chromatography using a silica gel column with petroleum ether and ethanol (10:1, v:v) as the eluent, and finally 2,3,5,6-pyridinetetramine was obtained.

[0061] The specific synthesis route is as follows:

[0062] The product yield was approximately 89%, and the purity was 91.3%, as determined by high performance liquid chromatography (HPLC). Measured using a 400 MHz Bruker nuclear magnetic resonance instrument, the product yield was found to be approximately 89%.

[0063] Example 3: A method for preparing 2,3,5,6-pyridinetetramine This embodiment provides a method for preparing 2,3,5,6-pyridinetetramine, using o-dichlorobenzene (ODCB) solvent and potassium amino and 2,3,5,6-tetrachloropyridine as reaction raw materials, as detailed below: (1) Add 60 mL of o-dichlorobenzene solvent, dried for 24 h using 4 Å molecular sieves, to a dry four-necked flask. Then add 14.2 g of potassium amino powder and 0.8 g of sodium iodide as a catalyst. Stir (300 rpm) during the addition process to ensure that the solid is fully dispersed in the solvent. Afterward, continuously purge with high-purity argon gas for 30 min to replace and purge the air in the flask. Maintain a stable argon atmosphere throughout the operation to provide sufficient inert protection for the subsequent reaction. (2) Under stirring (300 rpm), slowly add 8 g of 2,3,5,6-tetrachloropyridine to the flask at a feeding rate of 0.8 g / min; (3) After the addition is complete, continue stirring (300 rpm) and gradually heat the reaction system to 170℃ at a rate of 2℃ / min, and keep it at this temperature for 9 h; wherein, the molar ratio of potassium amino to 2,3,5,6-tetrachloropyridine is controlled to be about 5.5:1; the molar ratio of sodium iodide to 2,3,5,6-tetrachloropyridine is 1:7; (4) After the reaction is complete, place the flask in room temperature environment to cool naturally. When the temperature drops to room temperature, stir at 200 rpm and slowly add 25 mL of ice water at a rate of 1 mL / min while stirring for 15 min to ensure thorough mixing. Then, use dilute hydrochloric acid solution to adjust the pH value to 7.0, filter and collect the filtrate. (5) The obtained filtrate was separated and purified by column chromatography using a silica gel column with petroleum ether and ethanol (12:1, v:v) as the eluent, and finally 2,3,5,6-pyridinetetramine was obtained.

[0064] The specific synthesis route is as follows:

[0065] The product yield was approximately 87%, and the purity was 94.5%, as determined by high performance liquid chromatography (HPLC). Measured using a 400 MHz Bruker nuclear magnetic resonance instrument, the product yield was found to be approximately 87%.

[0066] Example 4: A method for preparing 2,3,5,6-pyridinetetramine This embodiment provides a method for preparing 2,3,5,6-pyridinetetramine, using N-methylpyrrolidone (NMP) solvent and sodium bis(trimethylsilyl)amino and 2,3,5,6-tetrachloropyridine as reactants, as detailed below: (1) Add 55 mL of N-methylpyrrolidone (NMP) solvent (water content ≤0.05%) that has been dried for 24 h using 4Å molecular sieves to a dry four-necked flask, followed by 32.6 g of sodium bis(trimethylsilyl)aminocyanide powder, and then 1.47 g of 18-crown-6 as a catalyst. Stirring (220 rpm) is maintained during the addition process to ensure the solid is fully dispersed in the solvent. Afterwards, high-purity nitrogen is continuously purged for 30 min to replace and remove air from the flask. A stable nitrogen atmosphere is maintained throughout the operation to provide sufficient inert protection for subsequent reactions and prevent the hydrolysis and oxidation of sodium bis(trimethylsilyl)aminocyanide. (2) Under stirring (220 rpm), slowly add 8 g of 2,3,5,6-tetrachloropyridine to the flask at a feeding rate of 1.2 g / min. (3) After the addition is complete, continue stirring (220 rpm) and gradually heat the reaction system to 190℃ at a rate of 5℃ / min, and keep the reaction at this temperature for 19 h; wherein, the molar ratio of bis(trimethylsilyl)aminosodium to 2,3,5,6-tetrachloropyridine is controlled to be about 4.8:1; the molar ratio of 18-crown-6 to 2,3,5,6-tetrachloropyridine is 3:20; (4) After the reaction is complete, place the flask at room temperature and allow it to cool naturally to below 25°C. While stirring at 220 rpm, add 35 mL of ice water dropwise at a rate of 2 mL / min. After the addition is complete, continue stirring at 220 rpm for 12 min to ensure complete quenching. Then, use 1 mol / L dilute sodium hydroxide solution to adjust the pH to 10.5. After stirring for 10 min, filter and collect the filtrate. Slowly add 37% concentrated hydrochloric acid to the filtrate to adjust the pH to 1.0~1.5. Heat to 80°C and reflux for 6 h to complete the hydrolysis and desilication. After the hydrolysis is complete, cool to room temperature and use 1 mol / L dilute sodium hydroxide solution to adjust the pH to 8.0-8.5. (5) The obtained solution was separated and purified by column chromatography. Column chromatography was performed using a silica gel column with methanol and ammonia as eluent (10:1, v:v). The target fraction was collected, and the 2,3,5,6-pyridinetetramine product was finally obtained.

[0067] The specific synthesis route is as follows:

[0068] The product yield was approximately 83% and the purity was 92.8% as determined by high performance liquid chromatography (HPLC) using a 400 MHz Bruker nuclear magnetic resonance instrument.

[0069] Example 5: A method for preparing 2,3,5,6-pyridinetetramine This embodiment provides a method for preparing 2,3,5,6-pyridinetetramine, using N,N-dimethylamine (DMA) solvent and ammonium carbamate and 2,3,5,6-tetrachloropyridine as reaction raw materials, as detailed below: (1) Add 50 mL of N,N-dimethylamine solvent, dried over 4 Å molecular sieves for 24 h, to a dry four-necked flask, followed by 12.5 g of ammonium carbamate powder. Stir (250 rpm) during the addition process to ensure the solid is fully dispersed in the solvent. Then, continuously purge with high-purity nitrogen for 30 min to displace and purge air from the flask. Maintain a stable nitrogen atmosphere throughout the operation to provide sufficient inert protection for subsequent reactions. (2) Under stirring (250 rpm), slowly add 8 g of 2,3,5,6-tetrachloropyridine to the flask at a feeding rate of 0.7 g / min; (3) After the addition is complete, continue stirring (250 rpm) and gradually raise the temperature of the reaction system to 250℃ at a rate of 2℃ / min, and keep the reaction at this temperature for 8 h; wherein, the molar ratio of ammonium carbamate to 2,3,5,6-tetrachloropyridine is controlled to be about 4.3:1; (4) After the reaction is complete, place the flask in a room temperature environment to cool naturally. When the temperature drops to room temperature, stir at 200 rpm and slowly add 20 mL of ice water at a rate of 2 mL / min while stirring for 30 min to ensure thorough mixing. Then, use dilute hydrochloric acid solution to adjust the pH value to 7.0, filter and collect the filtrate. (5) The obtained filtrate was separated and purified by column chromatography using a silica gel column with petroleum ether and ethanol (10:1, v:v) as the eluent, and finally 2,3,5,6-pyridinetetramine was obtained.

[0070] The specific synthesis route is as follows:

[0071] The product yield was approximately 84%, and the purity was 94.6%, as determined by high performance liquid chromatography (HPLC). The analysis was performed using a 400 MHz Bruker nuclear magnetic resonance instrument.

[0072] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing 2,3,5,6-pyridinetetramine, characterized in that, The method is as follows: the amination reagent is uniformly dispersed in an inert solvent, and then 2,3,5,6-tetrachloropyridine is added in batches. The temperature is gradually increased to 100~250℃ at a certain heating rate, and the reaction temperature is maintained to obtain 2,3,5,6-pyridinetetraamine. An inert atmosphere is maintained during the reaction process.

2. The method according to claim 1, characterized in that, The molar ratio of the amino group of the amination reagent to 2,3,5,6-tetrachloropyridine is (3~7):1; Preferably, the amination reagent includes urea, ammonium carbamate, and alkali metal amino compounds.

3. The method according to claim 2, characterized in that, The alkali metal amino compound is selected from one or more of the amination reagents, including sodium amino, calcium amino, potassium amino, lithium amino, rubidium amino, cesium amino, and bis(trimethylsilyl)amino reagents.

4. The method according to claim 1, characterized in that, The concentration of the amination reagent after mixing the inert solvent and the amination reagent is 5% to 30%.

5. The method according to claim 1 or 3, characterized in that, The inert solvent is selected from aromatic compound solvents or polar aprotic solvents; Preferably, the aromatic compound solvent is selected from one or more of toluene, N,N-xyleneamine, o-xylene, m-xylene, p-xylene, mesitylene, ethylbenzene, n-butadiene, isobutadiene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, 1,2,4-trichlorobenzene, nitrobenzene, and diphenyl ether. Preferably, the polar aprotic solvent is selected from one or more of methyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamine, 1,3-dimethyl-2-imidazolinone, and N-methylpyrrolidone.

6. The method according to claim 1, characterized in that, A catalyst is added during the reaction; Preferably, the molar ratio of the catalyst to 2,3,5,6-tetrachloropyridine is 1:(5~10). Preferably, the catalyst comprises one or more of alkali metal halides, alkaline earth metal halides, quaternary ammonium salts, quaternary phosphine salts, crown ethers, and cryptanes.

7. The method according to claim 1, characterized in that, 2,3,5,6-Tetrachloropyridine was slowly added in batches to the pre-stirred amination reagent solution, with inert gas protection throughout the process.

8. The method according to claim 1, characterized in that, The inert atmosphere includes one or more inert gases such as nitrogen and argon; Preferably, the inert atmosphere is selected from nitrogen or argon.

9. The method according to claim 1, characterized in that, After the reaction is complete, allow it to cool naturally to room temperature, then slowly add ice water while stirring to quench the reaction. Optionally, the reaction product can be purified after the reaction is terminated.

10. Use of the method according to any one of claims 1 to 9 in the preparation of 2,3,5,6-pyridinetetramine or products containing 2,3,5,6-pyridinetetramine.

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