Preparation method of chloropyridine and derivatives thereof

Abstract

The invention belongs to the technical field of organic fine chemical engineering, and particularly relates to a preparation method of chloropyridine and a derivative thereof, which comprises the following preparation steps: putting 2-amino-3-methylpyridine and / or 2-amino-5-methylpyridine into a solvent, adding a catalyst under a stirring condition, heating, introducing chlorine gas, reacting for 5-15 hours, filtering, washing and drying to obtain the chloropyridine and the derivative thereof. And stopping introducing the chlorine gas, carrying out heat preservation reaction for 1-3 hours, cooling, carrying out heat preservation reaction for 1-4 hours, and separating to obtain the chloropyridine and the derivative thereof. The preparation method disclosed by the invention is simple to operate, less waste is generated, the yield of the prepared chloropyridine and the derivative thereof is high, and particularly, the yield of 2-chloro-5-trichloromethylpyridine and 2-chloro-3-trichloromethylpyridine can reach 85% or above.

Description

Technical Field

[0001] The invention belongs to the technical field of organic fine chemicals, and specifically relates to a preparation method of chloropyridine and its derivatives. Background Art

[0002] Chloropyridine and its derivatives are important intermediates in chemical production and are widely used in people's production and life. 3-Methylpyridine pesticides (such as imidacloprid, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, etc.) are widely used in the field of pesticides because of their broad spectrum, high efficiency, and safety. In addition, 3-methylpyridine is also often used in the pharmaceutical industry for the synthesis of nicotinic acid, vitamin B, nicotinamide and other substances. 2-Chloro-5-trichloromethylpyridine and 2-chloro-3-trichloromethylpyridine are two relatively important chloropyridine compounds. In industrial production, 2-chloro-5-methylpyridine is usually used for deep chlorination or 2-chloro-5-chloromethylpyridine is used for deep chlorination to prepare 2-chloro-5-trichloromethylpyridine. In addition, 3-methylpyridine can also be used as a raw material to directly chlorinate and prepare 2-chloro-5-trichloromethylpyridine, but this method has many by-products and is difficult to separate, so its application range is limited.

[0003] Patent CN 105061300 A discloses a method for synthesizing chloropyridine and its derivatives, which uses aminopyridine and its derivatives to react to generate chloropyridine and its derivatives. The method is characterized in that phosphorus trichloride, phosphorus oxychloride or thionyl chloride and nitric acid are added to a solution of aminopyridine and its derivatives, and the chloropyridine and its derivatives are obtained by stirring the reaction. Although the chloropyridine compounds (2-chloro-5-methylpyridine, 2-chloro-3-ethylpyridine, 3-chloro-2-methylpyridine, 2,3-dichloropyridine) in Examples 1-4 of the patent have high yields and purities, the relevant content of the synthesis of 2-chloro-5-trichloromethylpyridine and 2-chloro-3-trichloromethylpyridine is not disclosed. Patent US4241213 introduces a method for preparing 2-chloro-5-trichloromethylpyridine by dissolving 3-methylpyridine in a carbon tetrachloride solution at 300-500°C through gas phase chlorination; Patent application number CN201410069430 introduces a method for preparing N-oxy-3-methylpyridine using 3-methylpyridine as a raw material, and then deeply chlorinating it to prepare 2-chloro-5-trichloromethylpyridine; however, the yield of 2-chloro-5-trichloromethylpyridine in these two patents is low and difficult to separate.

[0004] Based on the problems existing in the prior art, a method for preparing chloropyridine and its derivatives with high yield, easy operation and low cost is developed, which is of great significance for further expanding the application of pyridine and its derivatives in the fields of pesticides and medicines. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention provides a method for preparing chloropyridine and its derivatives. The method is simple to operate, produces less waste, and has a high yield of the prepared chloropyridine and its derivatives, especially 2-chloro-5-trichloromethylpyridine and 2-chloro-3-trichloromethylpyridine, with a yield of more than 85%.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] The present invention provides a method for preparing chloropyridine and its derivatives, comprising the following preparation steps:

[0008] Put 2-amino-3-methylpyridine or 2-amino-5-methylpyridine into a solvent, add a catalyst under stirring, increase the temperature, introduce chlorine gas to react for 5-15 hours, stop introducing chlorine gas and keep the temperature to react for 1-3 hours, reduce the temperature, keep the temperature to react for 1-4 hours, separate, and obtain chloropyridine and its derivatives.

[0009] In some embodiments, the reaction scheme of the chloropyridine and its derivatives is as follows:

[0010]

[0011] Among them, R represents -CH3 and R' represents -CCl3.

[0012] In some embodiments, the solvent is one or more of o-dichlorobenzene, dichlorobenzotrifluoride, and trichlorobenzotrifluoride.

[0013] Preferably, the solvent is trichlorotoluene trifluoride.

[0014] In some embodiments, the molar ratio of the solvent to 2-amino-3-methylpyridine or 2-amino-5-methylpyridine is (0-5):1.

[0015] Preferably, the molar ratio of the solvent to 2-amino-3-methylpyridine or 2-amino-5-methylpyridine is 3:1.

[0016] In some embodiments, the temperature is increased to 50°C-180°C.

[0017] Preferably, the temperature is increased to 135°C-155°C.

[0018] In some embodiments, the cooling is to 0°C-50°C.

[0019] Preferably, the temperature is lowered to 10°C-25°C.

[0020] In some embodiments, the catalyst is prepared by:

[0021] (1) putting glucosamine and boric acid into deionized water, adding nano-alumina under stirring conditions, evaporating the water after dispersion, mixing the obtained solid with sodium carbonate and grinding it, calcining it under a nitrogen atmosphere, cooling it to room temperature, washing it to neutrality, and drying it to obtain a nitrogen-boron doped carbon carrier;

[0022] (2) dispersing the nitrogen-boron-doped carbon support obtained in step (1) in an aqueous hydrochloric acid solution under ultrasonic conditions, adding a metal salt thereto, continuing ultrasonication for 10-20 minutes, stirring at 75-100° C. until dry, and cooling to room temperature to obtain a black solid;

[0023] (3) The black solid obtained in step (2) is heated to 300-350° C. in a hydrogen atmosphere, kept warm, and cooled to room temperature in a hydrogen atmosphere to obtain a catalyst.

[0024] In some embodiments, the mass ratio of glucosamine, boric acid and nano-alumina in step (1) is (2-3):(1-2):1.

[0025] Preferably, the nano-alumina is γ-Al2O3, and its average particle size is 10-50nm.

[0026] In some embodiments, the mass ratio of solid to sodium carbonate in step (1) is 1:(1-5).

[0027] Preferably, in step (1), the mass ratio of solid to sodium carbonate is 1:3.5.

[0028] In some embodiments, the heating rate of calcination in step (1) is 5-10°C / min, the calcination temperature is 650-950°C, and the calcination time is 1-3h.

[0029] Preferably, the heating rate of calcination in step (1) is 7.5°C / min, the calcination temperature is 800°C, and the calcination time is 2h.

[0030] In some embodiments, the metal salt in step (2) comprises iron salt, copper salt and palladium salt in a molar ratio of iron, copper and palladium of (5-10):(4-8):1.

[0031] Preferably, the metal salt in step (2) comprises iron salt, copper salt and palladium salt in a molar ratio of 8:6:1 among iron, copper and palladium.

[0032] In some embodiments, the metal salt is used in an amount of 1-5 wt % of the nitrogen-boron doped carbon support.

[0033] Preferably, the amount of the metal salt used is 2.8 wt % of the nitrogen-boron doped carbon support.

[0034] In some embodiments, the heating rate in step (3) is 4-7°C / min, and the heating is maintained for 1-2h.

[0035] Preferably, the heating rate in step (3) is 5°C / min and the temperature is kept for 1.5h.

[0036] In some embodiments, the catalyst is used in an amount of 0.5-5 wt % of 2-amino-3-methylpyridine or 2-amino-5-methylpyridine.

[0037] Preferably, the catalyst is used in an amount of 1-3 wt % of 2-amino-3-methylpyridine or 2-amino-5-methylpyridine.

[0038] More preferably, the catalyst is used in an amount of 1.5 wt % of 2-amino-3-methylpyridine or 2-amino-5-methylpyridine.

[0039] In some embodiments, the yield of the chloropyridine and its derivatives is above 85%.

[0040] In some embodiments, the separation operation is: after removing the solvent by reduced pressure distillation, column chromatography separation is performed using silica gel GF254, and the eluent used is composed of ethyl acetate and petroleum ether in a volume ratio of 1:20, and the crude product obtained by elution is recrystallized with anhydrous ethanol and vacuum dried to obtain chloropyridine and its derivatives.

[0041] The invention uses a pyridine thermal chlorination reaction combined with a Sandmeyer reaction for an amino-substituted methylpyridine one-pot method to prepare 2-chloro-3-trichloromethylpyridine and 2-chloro-5-trichloromethylpyridine, thereby providing a new synthesis idea for the synthesis of chlorine-substituted 3-trichloromethylpyridine.

[0042] The present invention significantly improves the yield of 2-chloro-3-trichloromethyl pyridine and 2-chloro-5-trichloromethyl pyridine by strictly controlling the production process parameters. First, 2-amino-3-methyl pyridine and / or 2-amino-5-methyl pyridine are put into a specific chlorinated solvent as reaction raw materials, under the conditions of heating and chlorine, and under the action of a catalyst, chlorine replaces the hydrogen on the methyl in the raw material, and the insulation reaction is carried out for a period of time, so that the reaction is fully carried out, and then the temperature is lowered and the insulation reaction is carried out again. During the insulation process, due to the effect of the catalyst, chlorine in the hydrogen chloride dissolved in the hot chlorination reaction system replaces the amino in the raw material, and finally generates 2-chloro-3-trichloromethyl pyridine and 2-chloro-5-trichloromethyl pyridine. The synthesis process of the present invention uses a non-aqueous solvent, avoids the generation of a large amount of process wastewater, and also prevents the local tarring reaction that may be caused by the introduction of moisture. In addition, the present invention also makes full use of the hydrogen chloride dissolved in the hot chlorination reaction system, avoids the use of hydrochloric acid, and reduces production costs.

[0043] The present invention uses a special catalyst in the synthesis process of 2-chloro-3-trichloromethylpyridine and 2-chloro-5-trichloromethylpyridine. The catalyst uses aminoglucose as a carbon source and a nitrogen source, boric acid as a boron source, and nano-alumina as a hard template. The catalyst is fully mixed with sodium carbonate and then calcined at a high temperature to obtain a nitrogen-boron doped carbon carrier with a certain nitrogen content and high porosity, and active metal iron, copper and palladium are loaded on the carrier to obtain a catalyst with high stability and catalytic performance, which can efficiently activate chlorine and promote the transfer of chlorine atoms, thereby realizing the chlorination reaction on the pyridine molecule. The present invention introduces nitrogen atoms and boron atoms into the catalyst carrier, forms BC bonds, CN bonds and BN bonds under the condition of high-temperature calcination, and they can regulate the electronic structure of the carbon carrier itself, enhance the role of active metal iron, copper and palladium interacting with it, and greatly improve the activation and catalytic effect of the catalyst in actual use. And because of the electronegativity of nitrogen and boron atoms themselves, the N and B atoms in the nitrogen- and boron-doped carbon carriers can produce a unique coupling to establish a new electronic structure, which can enhance the carrier electron cloud density, reduce the adsorption energy of the substrate at the catalytic site, and improve the reaction selectivity. In addition, the coordination ability of nitrogen atoms with iron, copper and palladium can better disperse metal ions, reduce the loss of metal ions, and improve the activity and stability of the catalyst. And the catalyst is easy to separate and will not affect the subsequent purification of the product.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] 1. The present invention provides a method for preparing chloropyridine and its derivatives. The method is simple to operate, produces less waste, makes full use of the hydrogen chloride dissolved in the thermal chlorination reaction system, avoids the use of hydrochloric acid, reduces the production cost, and has a high yield of the prepared chloropyridine and its derivatives, especially 2-chloro-5-trichloromethylpyridine and 2-chloro-3-trichloromethylpyridine, with a yield of more than 85%.

[0046] 2. The present invention uses a special catalyst in the synthesis process of chloropyridine and its derivatives. The catalyst uses biomass derivative amino glucose as a carbon source and a nitrogen source, boric acid as a boron source, and nano-alumina as a hard template. After being fully mixed with sodium carbonate, it is calcined at a high temperature to obtain a nitrogen-boron-doped carbon carrier with high porosity. Then, an active metal salt is loaded on the carrier. The obtained catalyst has the advantages of high catalytic performance and stability, and can significantly improve the yield of chloropyridine and its derivatives. DETAILED DESCRIPTION

[0047] Now describe in detail various exemplary embodiments of the present invention, this detailed description should not be considered as limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing a particular embodiment, and are not used to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the range.

[0048] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. Various modifications and variations may be made to the specific embodiments of the present invention specification without departing from the scope or spirit of the present invention, which will be apparent to those skilled in the art. Other embodiments obtained from the present invention specification will be apparent to the technician. The present application specification and examples are exemplary only.

[0049] The words “include,” “including,” “have,” or “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0050] The nano-alumina used in the present invention is γ-Al2O3 with an average particle size of 20 nm.

[0051] Preparation Example 1

[0052] The steps for preparing the catalyst used in Examples 1-7 and Comparative Examples 1-2 are:

[0053] (1) 2.5 g of glucosamine and 1.5 g of boric acid were placed in 30 mL of deionized water, and 1 g of nano-alumina was added under stirring at 150 r / min. After being fully dispersed, the water was evaporated to dryness at 120° C., and then 2 g of the obtained solid was mixed with 7 g of sodium carbonate and ground to pass through an 80-mesh sieve. The mixture was heated to 800° C. in a nitrogen atmosphere at a heating rate of 7.5° C. / min, calcined for 2 h, cooled to room temperature, washed with deionized water until neutral, and dried at 100° C. to constant weight to obtain a nitrogen-boron-doped carbon carrier;

[0054] (2) dispersing 1 g of the nitrogen-boron-doped carbon support obtained in step (1) in 20 mL of 1.5 wt% hydrochloric acid aqueous solution under 30 KHz ultrasonic conditions, adding 0.028 g of metal salt thereto, continuing ultrasonication for 15 min, stirring at 90° C. until dry, and cooling to room temperature to obtain a black solid;

[0055] (3) The black solid obtained in step (2) was heated to 325° C. at 5° C. / min in a hydrogen atmosphere, kept at this temperature for 1.5 h, and cooled to room temperature in a hydrogen atmosphere to obtain a catalyst.

[0056] The metal salts used include ferric chloride, cuprous chloride and palladium chloride in a molar ratio of 8:6:1 among iron, copper and palladium.

[0057] Example 1

[0058] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0059] Under stirring condition of 150r / min, 1.08g catalyst was added to 1mol 2-amino-3-methylpyridine, the temperature was raised to 50°C, chlorine was introduced to react for 15h, the introduction of chlorine was stopped and the reaction was kept warm for 3h, the temperature was lowered to 0°C, and the reaction was kept warm for 4h. After the solvent was removed by vacuum distillation, silica gel GF254 was used for column chromatography separation. The eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and dried in vacuo to obtain 2-chloro-3-trichloromethylpyridine.

[0060] Example 2

[0061] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0062] 1 mol of 2-amino-3-methylpyridine was placed in 5 mol of 2,4,6-trichlorotrifluorotoluene, 3.24 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 180°C, chlorine was introduced to react for 5 h, the introduction of chlorine was stopped and the reaction was kept warm for 1 h, the temperature was lowered to 50°C, the reaction was kept warm for 1 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation. The eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0063] Example 3

[0064] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0065] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 10°C, the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and column chromatography was performed on silica gel GF254. The eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0066] Example 4

[0067] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0068] 1 mol of 2-amino-3-methylpyridine was placed in 6 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 20°C, the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation, the eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20, the crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0069] Example 5

[0070] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0071] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 6.5 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 20°C and the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation, the eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20, and the crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0072] Example 6

[0073] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0074] 1 mol of 2-amino-5-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 135°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 25°C, the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation. The eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-5-trichloromethylpyridine.

[0075] Example 7

[0076] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0077] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 200°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 20°C, the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation, the eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20, and the crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0078] Comparative Example 1

[0079] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0080] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of dichloroethane, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 20°C, the reaction was kept warm for 3 h, the solvent was removed by vacuum distillation, and silica gel GF254 was used for column chromatography separation. The eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0081] Comparative Example 2

[0082] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0083] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of catalyst was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine was introduced to react for 10 h, the introduction of chlorine was stopped, the temperature was immediately lowered to 20°C, and the reaction was kept warm for 3 h. After the solvent was removed by vacuum distillation, silica gel GF254 was used for column chromatography separation, and the eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0084] Comparative Example 3

[0085] A method for preparing chloropyridine and its derivatives comprises the following preparation steps:

[0086] 1 mol of 2-amino-3-methylpyridine was placed in 3 mol of 2,4,6-trichlorotrifluorotoluene, 1.62 g of ferric chloride was added under stirring at 150 r / min, the temperature was raised to 145°C, chlorine gas was introduced to react for 10 h, the introduction of chlorine gas was stopped and the reaction was kept warm for 2 h, the temperature was lowered to 20°C, and the reaction was kept warm for 3 h. After the solvent was removed by vacuum distillation, silica gel GF254 was used for column chromatography separation, and the eluent used was composed of ethyl acetate and petroleum ether in a volume ratio of 1:20. The crude product obtained by elution was recrystallized with anhydrous ethanol and vacuum dried to obtain 2-chloro-3-trichloromethylpyridine.

[0087] Yield of chloropyridine and its derivatives

[0088] The purity of the chloropyridine and its derivatives obtained in each embodiment and comparative example was analyzed by HPLC, and the yield of chloropyridine and its derivatives in each embodiment and comparative example was calculated. Specific data are shown in Table 1.

[0089] Table 1

[0090]

[0091]

[0092] As shown in Table 1, the yields of 2-chloro-3-trichloromethylpyridine in Examples 2 and 3 and 2-chloro-5-trichloromethylpyridine in Example 6 are both relatively high, reaching more than 85%. In Example 1, no solvent was used during the reaction, which affected the reaction process of the substance, resulting in a decrease in the yield of 2-chloro-3-trichloromethylpyridine.

[0093] Compared with Example 3, the amount of solvent used in the preparation process of Example 4 is changed, and the solvent used in Comparative Example 1 is dichloroethane. The change of the solvent has a greater impact on the solute, and the energy of the transition state and the activation energy of the reaction cannot be reduced, and the reaction rate and the product yield are significantly reduced; the amount of catalyst used in the preparation process of Example 5 is changed, resulting in agglomeration of the catalyst, a decrease in the surface area of ​​the catalyst, a decrease in the catalytic efficiency, and a decrease in the product yield; the temperature of the heating process in Example 7 becomes larger, which may cause the occurrence of side reactions in the reaction, resulting in a decrease in the product yield.

[0094] Compared with Example 3, in the preparation process of Comparative Example 2, no insulation was performed after the temperature reaction, and the reaction was not fully carried out, resulting in a reduced product yield; the catalyst used in the preparation process of Comparative Example 3 was ferric chloride. When the same amount was used, the catalytic effect of ferric chloride was not as good as that of the catalyst prepared in the present invention, resulting in reduced reaction speed and product yield.

[0095] The above is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present application. Although the present application is disclosed as above in the preferred embodiment, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution.

Claims

1. A method for preparing chloropyridine and its derivatives, characterized in that: The method comprises the following preparation steps: Put 2-amino-3-methylpyridine or 2-amino-5-methylpyridine into a solvent, add a catalyst under stirring, increase the temperature, introduce chlorine gas to react for 5-15 hours, stop introducing chlorine gas and keep the temperature to react for 1-3 hours, reduce the temperature, keep the temperature to react for 1-4 hours, separate, and obtain chloropyridine and its derivatives.

2. The method for preparing chloropyridine and its derivatives according to claim 1, characterized in that: The solvent is one or more of o-dichlorobenzene, dichlorobenzotrifluoride, and trichlorobenzotrifluoride.

3. The method for preparing chloropyridine and its derivatives according to claim 2, characterized in that: The molar ratio of the solvent to 2-amino-3-methylpyridine or 2-amino-5-methylpyridine is (0-5):

1.

4. The method for preparing chloropyridine and its derivatives according to claim 1, characterized in that: The temperature is raised to 50°C-180°C.

5. The method for preparing chloropyridine and its derivatives according to claim 1, characterized in that: The cooling is to cool to 0°C-50°C.

6. The method for preparing chloropyridine and its derivatives according to claim 1, characterized in that: The preparation steps of the catalyst are: (1) dissolving glucosamine and boric acid in deionized water, adding nano-alumina under stirring conditions, evaporating the water after dispersion, mixing the obtained solid with sodium carbonate and grinding it, calcining it under a nitrogen atmosphere, cooling it to room temperature after calcination, washing it to neutrality, and drying it to obtain a nitrogen-boron doped carbon carrier; (2) dispersing the nitrogen-boron-doped carbon support obtained in step (1) in an aqueous hydrochloric acid solution under ultrasonic conditions, adding a metal salt thereto, continuing ultrasonication for 10-20 minutes, stirring at 75-100° C. until dry, and cooling to room temperature to obtain a black solid; (3) The black solid obtained in step (2) is heated to 300-350° C. in a hydrogen atmosphere, and then kept warm. After the heat preservation is completed, the black solid is cooled to room temperature in a hydrogen atmosphere to obtain a catalyst.

7. The method for preparing chloropyridine and its derivatives according to claim 6, characterized in that: In the step (1), the mass ratio of glucosamine, boric acid and nano-alumina is (2-3):(1-2):

1.

8. The method for preparing chloropyridine and its derivatives according to claim 6, characterized in that: The metal salt in step (2) comprises iron salt, copper salt and palladium salt in a molar ratio of iron, copper and palladium of (5-10):(4-8):

1.

9. The method for preparing chloropyridine and its derivatives according to claim 6, characterized in that: The catalyst is used in an amount of 0.5-5 wt % of 2-amino-3-methylpyridine or 2-amino-5-methylpyridine.

10. The method for preparing chloropyridine and its derivatives according to any one of claims 1 to 9, characterized in that: The yield of the chloropyridine and its derivatives reaches more than 85%.

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