Method for continuously preparing imidacloprid

Abstract

The invention provides a method for continuously preparing imidacloprid, which comprises the following steps: (1) introducing 2-chloro-5-chloromethylpyridine, an imidazolidine solution and an acid-binding agent solution into a microchannel reaction device, and carrying out condensation reaction to obtain a reaction solution; and (2) sequentially carrying out heat preservation treatment and post-treatment on the reaction liquid obtained in the step (1) to obtain the imidacloprid. According to the invention, 2-chloro-5-chloromethylpyridine without solvent dilution, imidazolidine, the acid-binding agent and the organic solvent are taken as raw materials and are directly introduced into the microchannel reaction device for one-step condensation reaction to obtain the imidacloprid reaction liquid crude product, so that the dosage of imidazolidine can be reduced, the reaction time can be shortened, the reaction rate can be improved, continuous production can be realized, and the production cost can be reduced. The method has the advantages of low production cost, high intrinsic safety, high raw material utilization rate, high product selectivity and the like; in addition, a DMF solvent is not needed, the post-treatment process is simplified, and meanwhile, the problem that DMF in the wastewater is difficult to biochemically treat is solved.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for continuously preparing imidacloprid. Background Art

[0002] Imidacloprid (chemical name: 1-(6-chloropyridine-3-pyridylmethyl)-N-nitroimidazolidin-2-ylamine), English name: Imidacloprid) is a nicotine-based super-high efficiency insecticide, colorless crystals with a faint odor. It has the characteristics of broad spectrum, high efficiency, low toxicity, low residue, pests are not easy to develop resistance, and it is safe for humans, livestock, plants and natural enemies. It is mainly used to control piercing-sucking mouthparts pests on crops such as rice, wheat, and cotton, such as aphids, leafhoppers, thrips, whiteflies, potato beetles, and wheat straw flies. After the pests come into contact with the agent, the normal conduction of the central nervous system is blocked, causing them to be paralyzed and die.

[0003] At present, the industrial production of imidacloprid is mainly a traditional batch synthesis method in a kettle, and the main steps are as follows: put caustic soda flakes, an excess of N-nitroimidoimidazolidine (imidazolidine for short) and a solvent (N,N-dimethylformamide, DMF) into the kettle, stir thoroughly, and then slowly drop a mixture of 2-chloro-5-chloromethylpyridine and DMF (dichloroDMF for short) at low temperature, and then heat-insulate to obtain an imidacloprid synthetic solution after the addition is completed. The existing post-processing steps include: firstly subjecting the synthetic solution to vacuum distillation to recover most of the solvent DMF, and then adding an appropriate amount of water and an extractant to the distilled material, heating and washing it with water to separate oil and water, cooling and crystallizing the water layer, centrifuging, and drying to obtain the recovered imidazolidine, and washing the oil layer with water, desolventizing, cooling and crystallizing, centrifuging, and drying to obtain the finished imidacloprid.

[0004] However, in the process of preparing imidacloprid using the traditional batch synthesis method, in order to prevent the reaction system from overheating locally and generating impurities, the reaction rate is controlled by slowly dropping a 2-chloro-5-chloromethylpyridine solution diluted with DMF at low temperature to ensure the reaction yield. In order to ensure that the high-value raw material 2-chloro-5-chloromethylpyridine reacts completely, an excess of imidazolidine is added to the reaction system. The system is a liquid-solid two-phase reaction, with poor heat and mass transfer effects, large raw material consumption, and it is difficult to achieve continuous production; and the post-treatment process is relatively complicated, and it is difficult to completely remove DMF from the system. The solvent dichloroethane is subsequently introduced. The dichloroethane oil layer contains a small amount of DMF. DMF has a high solubility in imidazolidine, so the dichloroethane oil layer contains imidazolidine, which poses a safety risk; in addition, the wastewater generated by the post-treatment contains DMF, which is difficult to treat biochemically.

[0005] In summary, providing a method for producing imidacloprid with high safety, short time consumption, high product yield, simplified process and continuous production is an urgent problem to be solved by those skilled in the art. Summary of the invention

[0006] The purpose of the present invention is to provide a method for continuously preparing imidacloprid, which reduces the dosage of imidazolid, shortens the reaction time, improves the reaction rate, and realizes continuous production. The method has the advantages of low production cost, high intrinsic safety, high raw material utilization rate, high product selectivity, and the like.

[0007] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0008] The present invention provides a method for continuously preparing imidacloprid, the method comprising the following steps:

[0009] (1) introducing 2-chloro-5-chloromethylpyridine, an imidazolidine solution and an acid binding agent solution into a microchannel reaction device to carry out a condensation reaction to obtain a reaction solution;

[0010] (2) subjecting the reaction solution obtained in step (1) to insulation treatment and post-treatment in sequence to obtain the imidacloprid.

[0011] In the present invention, the raw materials can be mixed before being introduced into the microchannel reaction device, or can be introduced into the microchannel reaction device at the same time; when the acid binding agent in the acid binding agent solution is sodium hydroxide, the reaction equation of the condensation reaction in step (1) is as follows.

[0012]

[0013] The method provided by the present invention uses 2-chloro-5-chloromethylpyridine, imidazolidine, an acid-binding agent and an organic solvent without solvent dilution as raw materials, directly introduces them into a microchannel reaction device for a one-step condensation reaction to obtain a crude imidacloprid reaction solution, can reduce the amount of imidazolidine used, shorten the reaction time, and realize continuous production, and has the advantages of low production cost, high intrinsic safety, high raw material utilization rate, high product selectivity, and the like.

[0014] It is worth noting that the reaction rate is improved by directly feeding 2-chloro-5-chloromethylpyridine at a certain flow rate instead of slowly adding 2-chloro-5-chloromethylpyridine or introducing 2-chloro-5-chloromethylpyridine diluted by a solvent. In addition, the use of a microchannel reaction device as a reaction device effectively solves the problems of poor heat and mass transfer effects and difficulty in continuous production in the prior art. The reaction time is shortened from the traditional several hours to tens of seconds to a few minutes, which significantly improves the reaction rate.

[0015] As a preferred technical solution of the present invention, the purity of the 2-chloro-5-chloromethylpyridine in step (1) is ≥99%, for example, it can be 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7% or 99.8%, etc., but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0016] Preferably, the imidazolidine solution in step (1) comprises N-nitroimidazole and an organic solvent.

[0017] Preferably, the organic solvent includes any one of propyl ether, butyl ether, ethylene dichloride, dichloropropane, carbon tetrachloride, butyl formate, isobutyl formate or ethyl acetate, or a combination of at least two thereof, preferably ethylene dichloride.

[0018] Preferably, the solid content of the imidazolidine solution in step (1) is 1% to 10%, for example, it can be 2%, 3%, 4%, 5%, 6%, 7%, 8% or 9%, etc., but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0019] In the present invention, the solid content refers to the mass content of solids in the solution.

[0020] As a preferred technical solution of the present invention, the acid binding agent solution in step (1) comprises an acid binding agent and an organic solvent.

[0021] It is worth noting that the method adopts a single organic solvent system and does not need to use DMF, which not only simplifies the post-treatment process, but also solves the problem that DMF in wastewater is difficult to biochemically treat.

[0022] Preferably, the preparation method of the acid binding agent solution in step (1) includes the following:

[0023] A solid acid-binding agent and an organic solvent are mixed to obtain an acid-binding agent solution with a solid content of 1% to 10% or a liquid acid-binding agent and an organic solvent are mixed in a volume ratio of 1:(2 to 5) to obtain an acid-binding agent solution.

[0024] In the present invention, the acid binding agent includes a solid acid binding agent or a liquid acid binding agent; if a solid acid binding agent is used for preparation, the solid content of the acid binding agent solution is 1% to 10%, for example, it can be 2%, 3%, 4%, 5%, 6%, 7%, 8% or 9%, etc., but it is not limited to the listed values, and other values ​​within the numerical range are also applicable; if a liquid acid binding agent is used for preparation, the volume ratio of the liquid acid binding agent to the organic solvent is 1:(2 to 5), for example, it can be 1:2.5, 1:3, 1:3.5, 1:4 or 1:4.5, etc., but it is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0025] Preferably, the solid acid binding agent comprises sodium hydroxide and / or potassium hydroxide, preferably sodium hydroxide.

[0026] Preferably, the liquid acid binding agent comprises any one of pyridine, triethylamine, tripropylamine, tributylamine, N,N-dimethylbenzylamine or diisopropylamine, or a combination of at least two thereof.

[0027] As a preferred technical solution of the present invention, the molar ratio of the 2-chloro-5-chloromethylpyridine and the imidazolidine in the imidazolidine solution to the acid binding agent in the acid binding agent solution in step (1) is 1:(1.1-1.8):(1.0-1.1), for example, it can be 1:1.1:1.0, 1:1.2:1.02, 1:1.3:1.04, 1:1.4:1.05, 1:1.5:1.06, 1:1.6:1.07 or, 1:1.7:1.08, 1:1.4:1.05, etc., but is not limited to the listed values, and other values ​​within the numerical range are also applicable, preferably 1:1.2:1.02.

[0028] As a preferred technical solution of the present invention, the temperature of the condensation reaction in step (1) is 20 to 100°C, for example, it can be 30°C, 40°C, 50°C, 60°C, 70°C, 80°C or 90°C, but is not limited to the listed values. Other values ​​within the numerical range are also applicable, preferably 40 to 100°C.

[0029] In the present invention, the initial pressure of the microchannel reaction device in the condensation reaction is normal pressure, and there is no need to control the pressure of the microchannel reaction device subsequently; by controlling the temperature range of the condensation reaction, the reaction rate is improved.

[0030] Preferably, the condensation reaction time in step (1) is 15 to 300 s, for example, it can be 20 s, 40 s, 60 s, 80 s, 90 s, 100 s, 110 s, 120 s, 150 s, 180 s, 200 s, 220 s, 250 s, 280 s or 290 s, but is not limited to the listed values. Other values ​​within the numerical range are also applicable, preferably 60 to 120 s.

[0031] In the present invention, the feed flow rate of the raw material liquid is determined according to the volume of the microchannel reaction device and the residence time of the raw material liquid.

[0032] As a preferred technical solution of the present invention, the heat preservation treatment in step (2) is carried out under stirring.

[0033] Preferably, the temperature of the insulation treatment in step (2) is 20-30°C, for example, it can be 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C or 29°C, but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0034] Preferably, the insulation treatment time in step (2) is 0.5 to 3 h, for example, 1 h, 1.5 h, 2 h or 2.5 h, etc., but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0035] As a preferred technical solution of the present invention, the post-treatment method in step (2) specifically includes:

[0036] (a) washing the reaction solution after the insulation treatment with water for the first time, adjusting the pH, and obtaining an imidazolidine-containing aqueous phase and an imidacloprid-containing crude oil phase after separation;

[0037] (b) washing the oil phase containing the crude imidacloprid obtained in step (a) with water for the second time, and obtaining a second water phase and a second oil phase after separation, and then sequentially performing desolventizing, cooling crystallization, solid-liquid separation and drying on the second oil phase to obtain the imidacloprid finished product.

[0038] In the present invention, the imidazolidine-containing aqueous phase in step (a) is subjected to sequential cooling crystallization, solid-liquid separation and drying to recover the imidazolidine; the second water washing is performed with fresh deionized water.

[0039] As a preferred technical solution of the present invention, the pH value of the solution is adjusted in step (a) to 7-8, for example, it can be 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8 or 7.9, but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0040] In the present invention, the adjusting agent used to adjust the pH includes a dilute acid solution.

[0041] Preferably, the first water washing in step (a) is carried out under stirring.

[0042] Preferably, the temperature of the first water washing in step (a) is 60-75°C, for example, it can be 62°C, 65°C, 66°C, 68°C, 70°C, 72°C, 73°C or 74°C, but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0043] Preferably, the first water washing time in step (a) is 15 to 60 min, for example, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min or 50 min, etc., but is not limited to the listed values, and other values ​​within the numerical range are also applicable.

[0044] As a preferred technical solution of the present invention, the second aqueous phase in step (b) is recycled in the first water washing.

[0045] Preferably, the desolventized fraction in step (b) is reused in step (1) after removing water.

[0046] As a preferred technical solution of the present invention, the method comprises the following steps:

[0047] (1) introducing 2-chloro-5-chloromethylpyridine with a purity of ≥99%, an imidazole solution with a solid content of 1% to 10%, and an acid binding agent solution into a microchannel reaction device, and performing a condensation reaction at a temperature of 20 to 100° C. for 15 to 300 seconds to obtain a reaction solution;

[0048] The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:(1.1-1.8):(1.0-1.1);

[0049] The imidazolidine solution comprises N-nitroiminoimidazolidine and an organic solvent;

[0050] The acid binding agent solution comprises an acid binding agent and an organic solvent;

[0051] The preparation method of the acid binding agent solution includes the following situations:

[0052] Mixing a solid acid-binding agent and an organic solvent to obtain an acid-binding agent solution having a solid content of 1% to 10% or mixing a liquid acid-binding agent and an organic solvent in a volume ratio of 1:(2 to 5) to obtain an acid-binding agent solution;

[0053] The solid acid-binding agent includes sodium hydroxide and / or potassium hydroxide; the liquid acid-binding agent includes any one of pyridine, triethylamine, tripropylamine, tributylamine, N,N-dimethylbenzylamine or diisopropylamine, or a combination of at least two of them; the organic solvent includes any one of propyl ether, butyl ether, dichloroethane, dichloropropane, carbon tetrachloride, butyl formate, isobutyl formate or ethyl acetate, or a combination of at least two of them;

[0054] (2) The reaction solution obtained in step (1) is subjected to a heat preservation treatment at a temperature of 20 to 30° C. for 0.5 to 3 h while stirring, and then the reaction solution after the heat preservation treatment is subjected to a first water washing at a temperature of 60 to 75° C. for 15 to 60 min while stirring, and the pH value of the solution is adjusted to 7 to 8, and after separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to desolventizing, cooling crystallization, solid-liquid separation and drying in sequence to obtain the imidacloprid.

[0055] Compared with the prior art, the present invention has the following beneficial effects:

[0056] (1) The method provided by the present invention uses 2-chloro-5-chloromethylpyridine, imidazolidine, an acid-binding agent and an organic solvent without solvent dilution as raw materials, and directly introduces them into a microchannel reaction device for a one-step condensation reaction to obtain a crude imidacloprid reaction solution. The method can reduce the amount of imidazolidine used, shorten the reaction time, increase the reaction rate, and realize continuous production. It has the advantages of low production cost, high intrinsic safety, high raw material utilization rate and high product selectivity. Among them, the purity of the imidacloprid product is more than 98.5%, the content of a single impurity is less than 0.05%, and the product yield is more than 96%;

[0057] (2) The method provided by the present invention adopts a single organic solvent system and does not require the use of DMF, thereby simplifying the post-treatment process and solving the problem that DMF in wastewater is difficult to biochemically treat. DETAILED DESCRIPTION

[0058] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0059] In the following embodiments and comparative examples, the initial pressure of the microchannel reaction device is normal pressure, and there is no need to adjust the pressure in the microchannel reaction device subsequently.

[0060] Example 1

[0061] The present embodiment provides a method for continuously preparing imidacloprid, the method comprising the following steps:

[0062] (1) introducing 2-chloro-5-chloromethylpyridine with a purity of 99.1%, an imidazole solution with a solid content of 5%, and an acid binding agent solution with a solid content of 5% into a microchannel reaction device at the same time, and performing a condensation reaction at a temperature of 90° C. for 20 seconds to obtain a reaction solution;

[0063] The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:1.2:1.02;

[0064] The imidazolidine solution comprises N-nitroimidazole and ethylene dichloride; the acid binding agent solution comprises sodium hydroxide and ethylene dichloride;

[0065] (2) The reaction solution extracted from step (1) is subjected to a heat preservation treatment in a stirred and insulated kettle at a temperature of 22° C. for 2 h, and then continuously extracted to a dissolution kettle, and a water layer is continuously introduced into the water layer for washing, and a first water washing is performed for 20 min under stirring at a temperature of 65° C., and the pH value of the solution is adjusted to 7.5 with dilute hydrochloric acid, and after oil-water separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid product are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after oil-water separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to sequential desolventizing, cooling crystallization, solid-liquid separation and drying to obtain an imidacloprid finished product;

[0066] The imidazolidine-containing aqueous phase is subjected to cooling crystallization, solid-liquid separation and drying in sequence, and then the imidazolidine is recovered;

[0067] The second aqueous phase is reused in the first water washing; the desolventized fraction is reused in step (1) after removing water.

[0068] Example 2

[0069] The present embodiment provides a method for continuously preparing imidacloprid, the method comprising the following steps:

[0070] (1) introducing 2-chloro-5-chloromethylpyridine with a purity of 99.5%, an imidazolidine solution with a solid content of 8%, and an acid binding agent solution with a solid content of 8% into a microchannel reaction device at the same time, and performing a condensation reaction at a temperature of 60° C. for 100 seconds to obtain a reaction solution;

[0071] The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:1.2:1.02;

[0072] The imidazolidine solution comprises N-nitroimidoimidazolidine and dichloropropane; the acid binding agent solution comprises potassium hydroxide and dichloropropane;

[0073] (2) The reaction solution extracted from step (1) is subjected to a heat preservation treatment in a stirred and insulated kettle at a temperature of 30° C. for 1 hour, and then continuously extracted to a dissolution kettle, and the water layer is continuously introduced into the water washing kettle, and the first water washing is carried out for 15 minutes under stirring at a temperature of 70° C., and the pH value of the solution is adjusted to 7.5 with dilute hydrochloric acid, and after oil-water separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after oil-water separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to sequential desolventizing, cooling crystallization, solid-liquid separation and drying to obtain an imidacloprid finished product;

[0074] The imidazolidine-containing aqueous phase is subjected to cooling crystallization, solid-liquid separation and drying in sequence, and then the imidazolidine is recovered;

[0075] The second aqueous phase is reused in the first water washing; the desolventized fraction is reused in step (1) after removing water.

[0076] Example 3

[0077] The present embodiment provides a method for continuously preparing imidacloprid, the method comprising the following steps:

[0078] (1) introducing 2-chloro-5-chloromethylpyridine with a purity of 99.3%, an imidazole solution with a solid content of 1%, and an acid binding agent solution into a microchannel reaction device at the same time, and performing a condensation reaction at a temperature of 40° C. for 200 seconds to obtain a reaction solution;

[0079] The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:1.2:1.02;

[0080] The imidazolidine solution comprises N-nitroimidazole and carbon tetrachloride; the acid binding agent solution comprises triethylamine and carbon tetrachloride in a volume ratio of 1:2;

[0081] (2) The reaction solution extracted from step (1) is subjected to a heat preservation treatment in a stirred and insulated kettle at a temperature of 20° C. for 2.5 hours, and then continuously extracted to a dissolution kettle, and a water layer is continuously introduced into the water layer for washing, and a first water washing is performed for 25 minutes at a temperature of 60° C. under stirring, and the pH value of the solution is adjusted to 7.5 with dilute hydrochloric acid, and after oil-water separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after oil-water separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to sequential desolventizing, cooling crystallization, solid-liquid separation and drying to obtain an imidacloprid finished product;

[0082] The imidazolidine-containing aqueous phase is subjected to cooling crystallization, solid-liquid separation and drying in sequence, and then the imidazolidine is recovered;

[0083] The second aqueous phase is reused in the first water washing; the desolventized fraction is reused in step (1) after removing water.

[0084] Example 4

[0085] The present embodiment provides a method for continuously preparing imidacloprid, the method comprising the following steps:

[0086] (1) introducing 2-chloro-5-chloromethylpyridine with a purity of 99.6%, an imidazole solution with a solid content of 6%, and an acid binding agent solution into a microchannel reaction device at the same time, and performing a condensation reaction at a temperature of 80° C. for 70 seconds to obtain a reaction solution;

[0087] The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:1.2:1.02;

[0088] The imidazolidine solution comprises N-nitroimidazole and ethyl acetate; the acid binding agent solution comprises pyridine and ethyl acetate in a volume ratio of 1:2;

[0089] (2) The reaction solution extracted from step (1) is subjected to a heat preservation treatment in a stirred and insulated kettle at a temperature of 22° C. for 2 h, and then continuously extracted to a dissolution kettle, and a water layer is continuously introduced into the water washing kettle, and a first water washing is performed for 20 min under stirring at a temperature of 60° C., and the pH value of the solution is adjusted to 7.5 with dilute hydrochloric acid, and after oil-water separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid product are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after oil-water separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to sequential desolventizing, cooling crystallization, solid-liquid separation and drying to obtain an imidacloprid finished product;

[0090] The imidazolidine-containing aqueous phase is subjected to cooling crystallization, solid-liquid separation and drying in sequence, and then the imidazolidine is recovered;

[0091] The second aqueous phase is reused in the first water washing; the desolventized fraction is reused in step (1) after removing water.

[0092] Example 5

[0093] This embodiment provides a method for continuously preparing imidacloprid, except that the molar ratio of 2-chloro-5-chloromethylpyridine, imidazolidine in the imidazolidine solution and the acid binding agent in the acid binding agent solution in step (1) is 1:0.8:1.02; other conditions are the same as those in Example 2.

[0094] Example 6

[0095] This embodiment provides a method for continuously preparing imidacloprid, except that the molar ratio of 2-chloro-5-chloromethylpyridine, imidazolidine in the imidazolidine solution and the acid binding agent in the acid binding agent solution in step (1) is 1:1.2:0.8; other conditions are the same as those in Example 2.

[0096] Example 7

[0097] This embodiment provides a method for continuously preparing imidacloprid, except that the temperature of the condensation reaction in step (1) is 20° C.; other conditions are the same as those in Example 2.

[0098] Example 8

[0099] This embodiment provides a method for continuously preparing imidacloprid, except that the temperature of the condensation reaction in step (1) is 120° C.; other conditions are the same as those in Example 2.

[0100] Example 9

[0101] This embodiment provides a method for continuously preparing imidacloprid, except that the condensation reaction time in step (1) is 10 s; other conditions are the same as those in Example 2.

[0102] Example 10

[0103] This embodiment provides a method for continuously preparing imidacloprid, except that the time of the condensation reaction in step (1) is 350 s; other conditions are the same as those in Example 2.

[0104] Embodiment 11

[0105] This embodiment provides a method for continuously preparing imidacloprid, except that the insulation treatment time in step (2) is 20 minutes; other conditions are the same as those in Example 2.

[0106] Comparative Example 1

[0107] This comparative example provides a method for preparing imidacloprid in a conventional kettle batch manner, the method comprising the following steps:

[0108] (1) adding an excess of caustic soda flakes, an excess of N-nitroimidazole and DMF solvent into a reaction kettle, stirring thoroughly, and then gradually dropping a mixture of 2-chloro-5-chloromethylpyridine and DMF therein, wherein the molar ratio of 2-chloro-5-chloromethylpyridine, N-nitroimidazole and caustic soda flakes is 1:2.8:1.1, dropping for 6 hours, and keeping warm for 4 hours to obtain an imidacloprid synthetic solution;

[0109] (2) The imidacloprid synthetic liquid obtained in step (1) is subjected to reduced pressure distillation, and most of the DMF solvent is recovered and reused in the reactor. Then, dichloroethane and the water layer are added to the distilled material, and the temperature is raised to dissolve, and then the water layer is stirred and washed. After oil and water separation, the obtained water layer is cooled and crystallized, solid-liquid separated and dried to obtain recovered imidazolid. The obtained oil layer enters a water washing tower and is washed with fresh deionized water. The materials in the water washing tower are then continuously layered, and the water layer is reused to the dissolving kettle for washing. The washed oil layer is subjected to desolventizing, cooling and crystallizing, solid-liquid separation, and drying to obtain the imidacloprid finished product, wherein the dichloroethane recovered by desolventizing is reused in the dissolving step.

[0110] The purity and impurity content of the imidacloprid products obtained in the above examples and comparative examples were detected by HPLC instrument, and the corresponding product yields were calculated. The results are shown in Table 1.

[0111] Table 1

[0112] Imidacloprid purity The content of single impurity Imidacloprid yield Example 1 98.9％ All <0.02% 97.0％ Example 2 98.6％ All <0.04% 96.1％ Example 3 98.7％ All <0.03% 96.5％ Example 4 98.6％ All <0.03% 96.4％ Example 5 97.6％ Some impurity content>0.10% 91.0％ Example 6 97.9％ Some impurity content>0.10% 95.2％ Example 7 98.5％ All <0.04% 96.5％ Example 8 98.0％ All <0.06% 95.8％ Example 9 95.0％ Some impurity content>0.15% 90.0％ Example 10 98.1％ All <0.06% 96.0％ Embodiment 11 97.9％ All <0.06% 95.7％ Comparative Example 1 98.1％ All <0.10% 90.5％

[0113] From Table 1, we can see that:

[0114] (1) The method provided in Examples 1-4 of the present invention has the advantages of high safety, short time consumption, high product yield, and continuous production, wherein the purity of the imidacloprid product is above 98.5%, the content of a single impurity is less than 0.05%, and the product yield is above 96%;

[0115] (2) It can be seen from the comparison between Example 2 and Examples 5-6 that when the amount of imidazolidine is too small, the raw material 2-chloro-5-chloromethylpyridine and the acid binding agent are not completely reacted, resulting in an increase in side reactions, an increase in impurity content, a decrease in product quality, and a low product yield; when the amount of the acid binding agent is too small, the reaction system cannot reach the required alkaline environment, so that part of the raw materials cannot fully participate in the reaction, resulting in a waste of raw materials and a decrease in product yield, while promoting the progress of side reactions, resulting in an increase in impurities and a decrease in product quality;

[0116] (3) By comparing Example 2 with Examples 7-8, it can be seen that when the condensation reaction is carried out at 20°C, although the continuous production of imidacloprid can be achieved, the reaction rate decreases; when the temperature of the condensation reaction is too high, the reaction speed is too fast and the side reactions increase, resulting in a decrease in product quality and a decrease in yield;

[0117] (4) Comprehensive Example 2 and Example 9-10 comparison shows that when the condensation reaction time is too short, it is not conducive to the reaction to proceed fully, resulting in increased impurity content, decreased product quality, and low product yield; when the condensation reaction time is too long, the side reactions increase slightly, resulting in increased impurity content and decreased product quality;

[0118] (5) By comparing Example 2 with Example 11, it can be seen that when the insulation treatment time is too short, the impurity content increases due to incomplete reaction, the product quality decreases, and the product yield is low;

[0119] (6) As can be seen from Comparative Example 1, in order to ensure that the high-value raw material 2-chloro-5-chloromethylpyridine is completely reacted, the single impurity content in the product is less than 0.1%, and an excess of imidazolidine needs to be added to the reaction system, which increases the production cost. In addition, the heat and mass transfer effect of the reactor is poor, the raw material consumption is large, the product yield is low, and it is difficult to achieve continuous production. In addition, it is difficult to completely remove DMF from the reaction system, the subsequent treatment is difficult, and there are certain safety risks.

[0120] The applicant declares that the present invention illustrates the detailed structural features of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed structural features, that is, it does not mean that the present invention must rely on the above-mentioned detailed structural features to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the components selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for continuously preparing imidacloprid, characterized in that: The method comprises the following steps: (1) introducing 2-chloro-5-chloromethylpyridine, an imidazolidine solution and an acid binding agent solution into a microchannel reaction device to carry out a condensation reaction to obtain a reaction solution; (2) subjecting the reaction solution obtained in step (1) to insulation treatment and post-treatment in sequence to obtain the imidacloprid.

2. The method according to claim 1, characterized in that The purity of the 2-chloro-5-chloromethylpyridine in step (1) is ≥99%; Preferably, the imidazolidine solution in step (1) comprises N-nitroimidazole and an organic solvent; Preferably, the organic solvent comprises any one or a combination of at least two of propyl ether, butyl ether, ethylene dichloride, dichloropropane, carbon tetrachloride, butyl formate, isobutyl formate or ethyl acetate, preferably ethylene dichloride; Preferably, the solid content of the imidazolidine solution in step (1) is 1% to 10%.

3. The method according to claim 1 or 2, characterized in that: The acid binding agent solution in step (1) comprises an acid binding agent and an organic solvent; Preferably, the preparation method of the acid binding agent solution in step (1) includes the following: Mixing a solid acid-binding agent and an organic solvent to obtain an acid-binding agent solution having a solid content of 1% to 10% or mixing a liquid acid-binding agent and an organic solvent in a volume ratio of 1:(2 to 5) to obtain an acid-binding agent solution; Preferably, the solid acid binding agent comprises sodium hydroxide and / or potassium hydroxide, preferably sodium hydroxide; Preferably, the liquid acid binding agent comprises any one of pyridine, triethylamine, tripropylamine, tributylamine, N,N-dimethylbenzylamine or diisopropylamine, or a combination of at least two thereof.

4. The method according to any one of claims 1 to 3, characterized in that: The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution in step (1) is 1:(1.1-1.8):(1.0-1.1).

5. The method according to any one of claims 1 to 4, characterized in that: The temperature of the condensation reaction in step (1) is 20 to 100° C., preferably 40 to 100° C.; Preferably, the condensation reaction time in step (1) is 15 to 300 s, preferably 60 to 120 s.

6. The method according to any one of claims 1 to 5, characterized in that: The heat preservation treatment in step (2) is carried out under stirring; Preferably, the temperature of the heat preservation treatment in step (2) is 20 to 30° C. Preferably, the heat preservation treatment time in step (2) is 0.5 to 3 hours.

7. The method according to any one of claims 1 to 6, characterized in that: The post-processing method in step (2) specifically includes: (a) washing the reaction solution after the insulation treatment with water for the first time, adjusting the pH, and obtaining an imidazolidine-containing aqueous phase and an imidacloprid-containing crude oil phase after separation; (b) washing the oil phase containing the crude imidacloprid obtained in step (a) with water for the second time, and obtaining a second water phase and a second oil phase after separation, and then sequentially performing desolventizing, cooling crystallization, solid-liquid separation and drying on the second oil phase to obtain the imidacloprid finished product.

8. The method according to claim 7, characterized in that In step (a), the pH value of the solution is adjusted to 7 to 8; Preferably, the first water washing in step (a) is carried out under stirring; Preferably, the temperature of the first water washing in step (a) is 60-75°C; Preferably, the first water washing time in step (a) is 15 to 60 minutes.

9. The method according to claim 7 or 8, characterized in that: Step (b) the second aqueous phase is reused in the first water washing; Preferably, the desolventized fraction in step (b) is reused in step (1) after removing water.

10. The method according to any one of claims 1 to 9, characterized in that: The method comprises the following steps: (1) introducing 2-chloro-5-chloromethylpyridine with a purity of ≥99%, an imidazole solution with a solid content of 1% to 10%, and an acid binding agent solution into a microchannel reaction device, and performing a condensation reaction at a temperature of 20 to 100° C. for 15 to 300 seconds to obtain a reaction solution; The molar ratio of the imidazolidine in the 2-chloro-5-chloromethylpyridine and imidazolidine solution to the acid binding agent in the acid binding agent solution is 1:(1.1-1.8):(1.0-1.1); The imidazolidine solution comprises N-nitroiminoimidazolidine and an organic solvent; The acid binding agent solution comprises an acid binding agent and an organic solvent; The preparation method of the acid binding agent solution includes the following situations: Mixing a solid acid-binding agent and an organic solvent to obtain an acid-binding agent solution having a solid content of 1% to 10% or mixing a liquid acid-binding agent and an organic solvent in a volume ratio of 1:(2 to 5) to obtain an acid-binding agent solution; The solid acid-binding agent includes sodium hydroxide and / or potassium hydroxide; the liquid acid-binding agent includes any one of pyridine, triethylamine, tripropylamine, tributylamine, N,N-dimethylbenzylamine or diisopropylamine, or a combination of at least two of them; the organic solvent includes any one of propyl ether, butyl ether, dichloroethane, dichloropropane, carbon tetrachloride, butyl formate, isobutyl formate or ethyl acetate, or a combination of at least two of them; (2) The reaction solution obtained in step (1) is subjected to a heat preservation treatment at a temperature of 20 to 30° C. for 0.5 to 3 h while stirring, and then the reaction solution after the heat preservation treatment is subjected to a first water washing at a temperature of 60 to 75° C. for 15 to 60 min while stirring, and the pH value of the solution is adjusted to 7 to 8, and after separation, an aqueous phase containing imidazolid and an oil phase containing a crude imidacloprid are obtained, and then the obtained oil phase containing the crude imidacloprid is subjected to a second water washing, and after separation, a second aqueous phase and a second oil phase are obtained, and then the second oil phase is subjected to desolventizing, cooling crystallization, solid-liquid separation and drying in sequence to obtain the imidacloprid.

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