Preparation method of 2-chloro-5-methylpyridine

Abstract

The invention provides a preparation method of 2-chloro-5-methylpyridine, in the preparation method, by controlling the reaction pressure when pyridone chloride and phosgene react to generate 2-chloro-5-methylpyridine to be 0.15-1.1 MPa, the solubility of phosgene in a reaction liquid phase can be effectively improved, and the molar ratio of phosgene in a reaction liquid phase system is increased. According to the method, the pyridone chloride and the phosgene can fully react to generate the 2-chloro-5-methylpyridine, so that the utilization rate of the phosgene is increased; and the phenomenon that the pyrolytic intermediate pyridol of pyridone chloride is converted into other impurities due to insufficient phosgene content in a reaction liquid phase and delayed reaction can be effectively avoided. By adopting the continuous preparation operation of the overflow reaction kettle, the yield of the 2-chloro-5-methylpyridine can be further improved, the production cost can be further reduced, and the production efficiency is improved. The method has obvious progressive significance especially for improving the industrial large-scale production efficiency.

Description

Technical Field

[0001] The present invention relates to the field of fine chemicals, and in particular to a method for preparing 2-chloro-5-methylpyridine. Background Art

[0002] In the fine chemical industry, particularly in the preparation of pesticide intermediates, 2-chloro-5-methylpyridine plays a crucial role. As a core raw material, it is directly involved in the synthesis of a series of highly effective, low-toxic pesticides such as imidacloprid, acetamiprid, nitenpyram, and thiacloprid, which play an irreplaceable role in global agricultural pest control. Given its importance, the synthesis of 2-chloro-5-methylpyridine has been a hot topic of industry research. The three main synthetic pathways mentioned in reports include the propionaldehyde-morpholine method, the cyclopentadiene method, and the propionaldehyde-benzylamine method. The first two methods are widely adopted by domestic fine chemical companies due to their ease of operation and readily available raw materials.

[0003] The propionaldehyde-morpholine method, a typical example of the synthesis of 2-chloro-5-methylpyridine, involves multiple chemical reaction steps. First, propionaldehyde and morpholine react to form an intermediate through an addition reaction, followed by a cyclization reaction to form 5-methyl-3,4-dihydropyridin-2(1H)-one (i.e., pyridone), a key step in the synthesis. After obtaining pyridone, it is subsequently reacted with chlorine to form a pyridone chloride adduct, which is then reacted with a chlorinating agent to achieve the synthesis of the target product, 2-chloro-5-methylpyridine. However, this process has significant limitations in actual operation, especially when using phosgene as a chlorinating agent: due to the low solubility of phosgene in the reaction system, a large amount of phosgene must be introduced before it can come into contact with the reactants. Most of the phosgene overflows in gaseous form and is discharged through the exhaust pipe, resulting in a waste of resources.

[0004] Furthermore, the pyridone chloride adduct has poor thermal stability at high temperatures and readily decomposes into the intermediate pyridinol. However, pyridinol cannot continue to participate in the target reaction in an environment with insufficient phosgene concentration, and is converted into other impurities, affecting the purity and yield of the final product. Due to these issues, existing processes for preparing 2-chloro-5-methylpyridine using phosgene as a chlorinating agent generally suffer from low phosgene utilization, long reaction cycles, large amounts of byproducts, and low overall product yields, which have become bottlenecks restricting the efficient and economical production of this intermediate.

[0005] Therefore, improving existing processes, particularly increasing phosgene utilization, shortening reaction time, reducing byproduct formation, and improving product yield, has become a pressing challenge in the field of 2-chloro-5-methylpyridine synthesis. This not only reduces production costs but also directly impacts the quality and competitiveness of downstream pesticide products, playing a significant role in promoting greener and more efficient development in the fine chemical industry. Summary of the Invention

[0006] The main purpose of the present invention is to provide a method for preparing 2-chloro-5-methylpyridine, so as to solve the problems of low phosgene utilization, low reaction conversion rate, long reaction time and low product yield in the prior art when phosgene is used to prepare 2-chloro-5-methylpyridine.

[0007] In order to solve the above problems, the present invention provides a preparation method of 2-chloro-5-methylpyridine, which comprises the following steps: mixing 5-methyl-3,4-dihydropyridin-2(1H)-one with an organic solvent and heating the mixture to a first reaction temperature; introducing chlorine gas into the mixture to carry out a first reaction to obtain a pyridone chloride reaction solution; continuously introducing the pyridone chloride reaction solution and a catalyst into an overflow reactor from the bottom, and continuously introducing phosgene into the reactor after the material in the overflow reactor submerges the phosgene feed conduit port, and allowing the reactor to cool to 150°C. The materials in the reactor are subjected to a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid; the 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank; wherein the pressure of the second reaction is 0.15 to 1.1 MPa; the tail gas containing phosgene generated in the second reaction is condensed and recovered to continue to participate in the second reaction; the 2-chloro-5-methylpyridine synthetic liquid in the synthetic liquid storage tank is subjected to gas removal, desolventization, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0008] Furthermore, the pressure of the second reaction is 0.5-1.1 MPa.

[0009] Furthermore, the molar ratio of pyridone chloride to phosgene is 1:(1.2-3); preferably, the molar ratio of pyridone chloride to phosgene is 1:(1.2-2).

[0010] Further, when the pressure of the second reaction is below 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:(2-3); or, when the pressure of the second reaction is 0.5-1.1 MPa, the molar ratio of pyridone chloride to phosgene is 1:(1.2-2).

[0011] Furthermore, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine is 1:(1.1-1.5); preferably, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine is 1:(1.2-1.5).

[0012] Furthermore, the second temperature is 90 to 150° C.; preferably, the second temperature is 90 to 130° C.; preferably, the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is 1 to 8 hours; further preferably, the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is 1.5 to 5 hours.

[0013] Furthermore, the catalyst is N,N-dimethylformamide and / or N,N-dimethylacetamide; preferably, the mass ratio of pyridone chloride to the catalyst is 1:(0.01-0.2).

[0014] Furthermore, the organic solvent is one or more of benzene, toluene, dichloroethane and chloroform; preferably, after mixing 5-methyl-3,4-dihydropyridin-2(1H)-one with the organic solvent, the mass concentration of 5-methyl-3,4-dihydropyridin-2(1H)-one in the obtained mixed solution is 30-60%.

[0015] Furthermore, the first reaction temperature is 30-70°C; preferably, the first reaction time is 1.5-3 hours; preferably, the first reaction temperature is 40-60°C.

[0016] Furthermore, the preparation method also includes: controlling the discharge of non-condensable hydrogen chloride and carbon dioxide generated in the second reaction system from the second reaction system to maintain the pressure of the second reaction system; preferably, the condensation temperature is -5 to -20°C; further preferably, the condensation temperature is -10 to -20°C.

[0017] The present invention provides a method for preparing 2-chloro-5-methylpyridine, comprising: first reacting 5-methyl-3,4-dihydropyridin-2(1H)-one with chlorine to produce pyridone chloride; then continuously reacting the produced pyridone chloride with phosgene in an overflow reactor at a pressure of 0.15 to 1.1 MPa; the produced 2-chloro-5-methylpyridine reaction liquid is continuously discharged through an overflow port into a synthesis liquid storage tank; and then subjecting the 2-chloro-5-methylpyridine synthesis liquid in the synthesis liquid storage tank to gas removal, desolventization, decoking, light removal, and rectification to obtain the 2-chloro-5-methylpyridine product. The preparation process also includes condensing and recovering the phosgene-containing tail gas produced in the second reaction for further use in the second reaction. In the preparation method, by controlling the reaction pressure of 2-chloro-5-methylpyridine generated by pyridone chlorine and phosgene reaction at 0.15~1.1MPa, the solubility of phosgene in the reaction liquid phase can be effectively improved to achieve the purpose of increasing the molar ratio of phosgene in the reaction liquid phase system. The above operation, on the one hand, can make pyridone chlorine and phosgene react more fully to generate 2-chloro-5-methylpyridine, thereby improving the utilization rate of phosgene. On the other hand, it is also possible to effectively avoid the conversion of the thermal decomposition intermediate pyridinol of pyridone chlorine due to the deficiency of phosgene content in the reaction liquid phase and the untimely reaction into other impurities, thereby effectively improving the yield of 2-chloro-5-methylpyridine product. The method for preparing 2-chloro-5-methylpyridine provided by the present invention can also further shorten the reaction time and effectively improve production efficiency. In addition, the technical solution provided by the present invention is that in the process in which pyridone chlorine and phosgene are carried out chlorination reaction, an overflow reactor is used to react. During the reaction, the reaction raw materials pyridone chlorine and phosgene can be continuously passed through to react, and the generated product 2-chloro-5-picoline synthetic liquid can be continuously discharged. On the one hand, the operating amount and the manual input cost in the production process can be reduced, and the potential safety hazard in the production process can be reduced; on the other hand, the raw material pyridone chlorine can also be enabled to participate in the reaction in time to generate 2-chloro-5-picoline with a relatively stable structure, and to avoid generating other impurities. This method, especially for the improvement of industrial large-scale production efficiency, has obvious progressive significance.

[0018] In summary, the continuous preparation method of 2-chloro-5-methylpyridine provided by the present invention can effectively improve the utilization rate of phosgene, increase the yield of the product in the production process, improve production efficiency, and reduce the production cost of 2-chloro-5-methylpyridine. In particular, since phosgene is a highly toxic and dangerous substance, reducing its usage is of great significance for protecting the environment and improving production safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings, which constitute part of this application, are intended to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are intended to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[0020] Figure 1 The LCMS chart of 2-chloro-5-methylpyridine prepared according to Example 1 of the present invention is shown. DETAILED DESCRIPTION

[0021] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the embodiments.

[0022] As described in the background technology section, the prior art has problems such as low phosgene utilization, low reaction conversion rate, long reaction time and low product yield when using phosgene to prepare 2-chloro-5-methylpyridine.

[0023] In order to solve the above problems, the present invention provides a preparation method of 2-chloro-5-methylpyridine, which comprises: mixing 5-methyl-3,4-dihydropyridin-2(1H)-one with an organic solvent and heating the mixture to a first reaction temperature; introducing chlorine gas into the mixture to carry out a first reaction to obtain a pyridone chloride reaction solution; continuously introducing the pyridone chloride reaction solution and a catalyst into an overflow reactor from the bottom, and continuously introducing phosgene into the reactor after the material in the overflow reactor submerges the phosgene feed conduit port, and allowing the material in the reactor to The material is subjected to a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid; the 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank; wherein the pressure of the second reaction is 0.15 to 1.1 MPa; the tail gas containing phosgene generated in the second reaction is condensed and recovered to continue to participate in the second reaction; the 2-chloro-5-methylpyridine synthetic liquid in the synthetic liquid storage tank is subjected to gas removal, desolventization, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0024] The preparation method first reacts 5-methyl-3,4-dihydropyridin-2(1H)-one with chlorine to produce pyridone chloride. The resulting pyridone chloride and phosgene are then continuously reacted in an overflow reactor at a pressure of 0.15 to 1.1 MPa to produce a 2-chloro-5-methylpyridine reaction solution, which is then continuously discharged through an overflow port into a synthesis liquid storage tank. The 2-chloro-5-methylpyridine synthesis liquid in the synthesis liquid storage tank is then subjected to degassing, desolventization, decoking, light removal, and rectification to obtain the 2-chloro-5-methylpyridine product. The process also includes condensing and recovering the phosgene-containing tail gas produced in the second reaction for further use in the second reaction.

[0025] In the above-mentioned preparation method, by controlling the reaction pressure when pyridone chloride reacts with phosgene to generate 2-chloro-5-methylpyridine at 0.15~1.1MPa, the solubility of phosgene in the reaction liquid phase is increased, and the molar proportion of phosgene in the reaction liquid phase system is increased. On the one hand, the operation of the above-mentioned pressurized reaction can make pyridone chloride and phosgene react more fully to generate 2-chloro-5-methylpyridine, thereby improving the utilization rate of phosgene. In particular, phosgene is a substance with strong toxicity and greater danger, and reducing its usage is of great significance for protecting the environment and improving production safety. On the other hand, it can also effectively avoid the thermal decomposition intermediate pyridinol of pyridone chloride caused by insufficient phosgene content in the reaction liquid phase and untimely reaction, thereby effectively improving the yield of 2-chloro-5-methylpyridine product. In addition, the method for preparing 2-chloro-5-methylpyridine provided by the present invention can further shorten the reaction time and effectively improve the preparation production efficiency. The condensation, recovery and reuse of phosgene in the tail gas not only reduces the consumption of phosgene, but also improves the economy and environmental protection of the reaction.

[0026] Further, the technical solution provided by the present invention is that in the process in which pyridone chlorine and phosgene are subjected to chlorination reaction, an overflow reactor is used to react, and the process reaction raw materials pyridone chlorine and phosgene can be continuously passed into the overflow reactor to carry out chlorination reaction, and the generated product 2-chloro-5-picoline synthetic liquid can be continuously discharged. On the one hand, the operating amount and the labor input cost in the production process can be reduced, and the potential safety hazard in the production process can be reduced; on the other hand, the raw material pyridone chlorine can also be enabled to participate in the reaction to generate 2-chloro-5-picoline with a relatively stable structure in time, thereby avoiding the generation of other impurities and reducing the yield of 2-chloro-5-picoline. This method, especially for the improvement of industrial large-scale production efficiency, has obvious progressive significance.

[0027] In summary, the method for continuously preparing 2-chloro-5-methylpyridine provided by the present invention can effectively improve the utilization rate of phosgene, reduce the generation of by-products, increase the yield of products in the production process, improve the overall production efficiency, improve the economy and environmental protection of the reaction, and reduce the overall production cost of 2-chloro-5-methylpyridine. In addition, the scheme also has the advantage of being green and environmentally friendly.

[0028] The reaction equation involved in the method for preparing 2-chloro-5-methylpyridine provided by the present invention is:

[0029]

[0030] In a preferred embodiment, the pressure of the second reaction is 0.5 to 1.1 MPa. Controlling the pressure of the second reaction within the above range can more effectively increase the solubility of phosgene, reduce the consumption of phosgene during the preparation process, while maintaining the stability and safety of the reaction system, further improve the reaction efficiency, reduce the formation of by-products during the reaction, and increase the yield of the 2-chloro-5-methylpyridine product.

[0031] In a preferred embodiment, the molar ratio of pyridone chloride to phosgene is 1: (1.2 to 3); by using the method for preparing 2-chloro-5-methylpyridine provided by the present invention, controlling the use ratio of phosgene within the above range can make 2-chloro-5-methylpyridine have a good yield. Compared with the traditional preparation method that needs to control the use ratio of phosgene to 5 to 10 times the molar amount of pyridone chloride to make 2-chloro-5-methylpyridine have a good yield, the technical solution provided by the present invention can achieve the purpose of effectively reducing the consumption of phosgene, and further improve the economy and environmental protection of the reaction. Preferably, the molar ratio of pyridone chloride to phosgene is 1: (1.2 to 2); the above effect is better when the molar ratio of pyridone chloride to phosgene is controlled within the above preferred range.

[0032] In a preferred embodiment, when the pressure of the second reaction is below 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:(2-3); or, when the pressure of the second reaction is 0.5-1.1 MPa, the molar ratio of pyridone chloride to phosgene is 1:(1.2-2); a higher proportion of phosgene is used at a relatively low reaction pressure, and a lower proportion of phosgene is used at a relatively high reaction pressure. This is because increasing the reaction pressure within a certain range can increase the solubility of phosgene in the reaction system, thereby achieving a substantially complete reaction at a lower phosgene molar ratio. This strategy further saves on the amount of phosgene used while ensuring reaction efficiency. The pressure of the second reaction is matched with the molar ratio of pyridone chloride to phosgene in the above manner. A more preferred reaction pressure and reactant ratio can be selected according to the specific conditions of the reaction equipment, both of which can give 2-chloro-5-methylpyridine a better reaction yield and further reduce the amount of phosgene used.

[0033] In a preferred embodiment, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine is 1:(1.1-1.5); 5-methyl-3,4-dihydropyridin-2(1H)-one and chlorine are added in the above ratio during the first reaction to balance the reaction rate and raw material consumption, ensure efficient utilization of chlorine, reduce the formation of by-products, and increase the yield of the target product. Preferably, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine is 1:(1.2-1.5). When the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine during the first reaction is controlled within the above preferred range, the reaction effect is better.

[0034] In a preferred embodiment, the second temperature is 90 to 150 ° C; the chlorination reaction of pyridone chloride and phosgene is carried out at the second temperature, and the temperature of the reaction process is controlled within the above range, so that pyridone chloride and phosgene can fully react to generate 2-chloro-5-methylpyridine; it can also avoid the formation of by-product tar, which is conducive to further improving the yield of 2-chloro-5-methylpyridine products. Preferably, the second temperature is 90 to 130 ° C. Controlling the second temperature within the above preferred range can not only make the reaction effect better, but also further improve the preparation efficiency. Preferably, the retention time of the 2-chloro-5-methylpyridine synthetic solution in the overflow reactor is 1 to 8 hours. The feed flow rate of pyridone chloride can be adjusted according to the capacity of the overflow reactor to achieve the control of the retention time of the second reaction in the overflow reactor, thereby controlling the reaction time of the second reaction. Controlling the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor within the above range can avoid the further conversion of the 2-chloro-5-methylpyridine product into tar impurities due to excessive reaction time, which is conducive to the full reaction of pyridone chloride into the target product 2-chloro-5-methylpyridine. Further preferably, the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is 1.5 to 5 hours. In the second reaction process, controlling the retention reaction time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor within the above preferred range will further improve the yield of the target product 2-chloro-5-methylpyridine.

[0035] In a preferred embodiment, the catalyst is N,N-dimethylformamide and / or N,N-dimethylacetamide; preferably, the mass ratio of pyridone chloride to catalyst is 1:(0.01-0.2). Using the above catalyst and controlling the catalyst usage within the above range can effectively promote the reaction of the pyridone chloride adduct and phosgene, improve product selectivity, and make the reaction more economically and environmentally feasible.

[0036] By way of example and not limitation, the organic solvent is one or more of benzene, toluene, dichloroethane, and chloroform, any solvent capable of carrying out the second reaction of the present invention. Preferably, after mixing 5-methyl-3,4-dihydropyridin-2(1H)-one with the organic solvent, the mass concentration of 5-methyl-3,4-dihydropyridin-2(1H)-one in the resulting mixed solution is 30-60%. Controlling the concentration of pyridinone within the above range can further increase the reaction rate, promote the smooth progress of the reaction, reduce raw material waste, and improve the operability of the reaction.

[0037] In a preferred embodiment, the first reaction temperature is 30-70° C.; preferably, the first reaction time is 1.5-3 hours; preferably, the first reaction temperature is 40-60° C. Controlling the first reaction temperature within the above range can further improve the conversion rate and selectivity of the raw material 5-methyl-3,4-dihydropyridin-2(1H)-one, allowing the reaction to proceed smoothly while further preventing premature thermal decomposition of pyridinone chloride to form pyridinol and other impurities.

[0038] In a preferred embodiment, the preparation method provided by the present invention further comprises: controlling the discharge of non-condensable gases such as hydrogen chloride and carbon dioxide produced in the second reaction system from the second reaction system to maintain the pressure of the second reaction system. The pressure of the second reaction system is maintained by timely discharging non-condensable gases such as hydrogen chloride and carbon dioxide in the reaction system from the second reaction system. Preferably, the condensation temperature is -5 to -20°C. By controlling the condensation temperature within the above range, the phosgene that has not reacted in time in the system can be condensed and refluxed into the overflow reactor to continue participating in the reaction. Further preferably, the condensation temperature is -10 to -20°C.

[0039] The present application is further described in detail below with reference to specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in this application.

[0040] Example 1

[0041] 5-methyl-3,4-dihydropyridin-2(1H)-one and dichloromethane were mixed in a reaction kettle to form a mixed solution with a mass concentration of 40%. The mixed solution was heated to 40°C, and chlorine gas was introduced into the solution to carry out a first reaction to obtain a pyridinone chloride reaction solution. During the first reaction, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine gas was 1:1.3, and the first reaction time was 2 hours.

[0042] The pyridone chloride reaction solution obtained above and the catalyst N,N-dimethylformamide are continuously introduced into an overflow reactor from the bottom. After the material in the overflow reactor submerges the phosgene feed conduit, phosgene is continuously introduced into the reactor, and the material in the reactor undergoes a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid. The 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank. During this reaction, the second temperature is 100°C, the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.1, the pressure of the second reaction is 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:1.3, and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to 2 hours. The tail gas containing phosgene produced by the second reaction is condensed and recovered at -15°C and then continued to participate in the second reaction. During the second reaction, the non-condensable gases hydrogen chloride and carbon dioxide produced in the second reaction system must be discharged from the second reaction system in a timely manner to maintain the pressure of the second reaction system at 0.5 MPa.

[0043] The 2-chloro-5-methylpyridine synthetic liquid obtained in the synthetic liquid storage tank is subjected to gas removal, solvent removal, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0044] The 2-chloro-5-methylpyridine prepared above was sampled and subjected to LCMS test. The LCMS graph of the obtained 2-chloro-5-methylpyridine was as follows: Figure 1 As shown in the figure, it can be seen that [M+H] + =129.2, thus it can be seen that the prepared product is 2-chloro-5-methylpyridine.

[0045] Example 2

[0046] 5-methyl-3,4-dihydropyridin-2(1H)-one and toluene are mixed in a reaction kettle to form a mixed solution with a mass concentration of 40%. The mixed solution is heated to 40°C, and chlorine gas is introduced into the solution to carry out a first reaction to obtain a pyridinone chloride reaction solution. During the first reaction, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine gas is 1:1.2, and the first reaction time is 2 hours.

[0047] The pyridone chloride reaction solution obtained above and the catalyst N,N-dimethylformamide are continuously introduced into an overflow reactor from the bottom. After the materials in the overflow reactor submerge the phosgene feed conduit, phosgene is continuously introduced into the reactor, and the materials in the reactor undergo a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid. The 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank. During this reaction, the second temperature is 130°C, the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.1, the pressure of the second reaction is 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:1.3, and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to 1.5 hours. The tail gas containing phosgene produced by the second reaction is condensed and recovered at -10°C and then continued to participate in the second reaction. During the second reaction, the non-condensable gases hydrogen chloride and carbon dioxide produced in the second reaction system must be discharged from the second reaction system in a timely manner to maintain the pressure of the second reaction system at 0.5 MPa.

[0048] The 2-chloro-5-methylpyridine synthetic liquid obtained in the synthetic liquid storage tank is subjected to gas removal, solvent removal, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0049] Example 3

[0050] 5-Methyl-3,4-dihydropyridin-2(1H)-one and toluene are mixed in a reaction kettle to form a mixed solution with a mass concentration of 40%. The mixed solution is heated to 60°C, and chlorine gas is introduced into the solution to carry out a first reaction to obtain a pyridinone chloride reaction solution. During the first reaction, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine gas is 1:1.5, and the first reaction time is 2 hours.

[0051] The pyridone chloride reaction solution obtained above and the catalyst N,N-dimethylformamide are continuously introduced into an overflow reactor from the bottom. After the materials in the overflow reactor submerge the phosgene feed conduit, phosgene is continuously introduced into the reactor, and the materials in the reactor undergo a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid. The 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank. During this reaction, the second temperature is 90°C, the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.1, the pressure of the second reaction is 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:1.3, and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to 5 hours. The tail gas containing phosgene produced by the second reaction is condensed and recovered at -20°C and then continued to participate in the second reaction. During the second reaction, the non-condensable gases hydrogen chloride and carbon dioxide produced in the second reaction system must be discharged from the second reaction system in a timely manner to maintain the pressure of the second reaction system at 0.5 MPa.

[0052] The 2-chloro-5-methylpyridine synthetic liquid obtained in the synthetic liquid storage tank is subjected to gas removal, solvent removal, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0053] Example 4

[0054] 5-Methyl-3,4-dihydropyridin-2(1H)-one and benzene are mixed in a reaction kettle to form a mixed solution with a mass concentration of 60%. The mixed solution is heated to 30°C, and chlorine gas is introduced into the solution to carry out a first reaction to obtain a pyridinone chloride reaction solution. During the first reaction, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine gas is 1:1.1, and the first reaction time is 3 hours.

[0055] The pyridone chloride reaction solution obtained above and the catalyst N,N-dimethylacetamide are continuously introduced into an overflow reactor from the bottom. After the material in the overflow reactor submerges the phosgene feed conduit, phosgene is continuously introduced into the reactor, and the material in the reactor undergoes a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid. The 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank. During this reaction, the second temperature is 150°C, the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.2, the pressure of the second reaction is 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:1.3, and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to 1 hour. The tail gas containing phosgene produced by the second reaction is condensed and recovered at -5°C and then continued to participate in the second reaction. During the second reaction, the non-condensable gases hydrogen chloride and carbon dioxide produced in the second reaction system must be discharged from the second reaction system in a timely manner to maintain the pressure of the second reaction system at 0.5 MPa.

[0056] The 2-chloro-5-methylpyridine synthetic liquid obtained in the synthetic liquid storage tank is subjected to gas removal, solvent removal, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0057] Example 5

[0058] 5-methyl-3,4-dihydropyridin-2(1H)-one and chloroform are mixed in a reaction kettle to form a mixed solution with a mass concentration of 30%. The mixed solution is heated to 70°C, and chlorine gas is introduced into the mixed solution to carry out a first reaction to obtain a pyridinone chloride reaction solution. During the first reaction, the molar ratio of 5-methyl-3,4-dihydropyridin-2(1H)-one to chlorine gas is 1:1.1, and the first reaction time is 1.5 hours.

[0059] The pyridone chloride reaction solution obtained above and the catalyst N,N-dimethylacetamide are continuously introduced into an overflow reactor from the bottom. After the material in the overflow reactor submerges the phosgene feed conduit, phosgene is continuously introduced into the reactor, and the material in the reactor undergoes a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid. The 2-chloro-5-methylpyridine synthetic liquid is continuously withdrawn from the overflow port of the overflow reactor to a synthetic liquid storage tank. During this reaction, the second temperature is 90°C, the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.01, the pressure of the second reaction is 0.5 MPa, the molar ratio of pyridone chloride to phosgene is 1:1.3, and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to 8 hours. The tail gas containing phosgene produced by the second reaction is condensed and recovered at -8°C and then continued to participate in the second reaction. During the second reaction, the non-condensable gases hydrogen chloride and carbon dioxide produced in the second reaction system must be discharged from the second reaction system in a timely manner to maintain the pressure of the second reaction system at 0.5 MPa.

[0060] The 2-chloro-5-methylpyridine synthetic liquid obtained in the synthetic liquid storage tank is subjected to gas removal, solvent removal, decoking, light removal and rectification to obtain the 2-chloro-5-methylpyridine product.

[0061] Example 6

[0062] The difference between Example 6 and Example 1 is that the pressure of the second reaction is 0.15 MPa, the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 5 hours, and the molar ratio of pyridone chloride to phosgene is 1:3.

[0063] Example 7

[0064] The difference between Example 7 and Example 1 is that the pressure of the second reaction is 0.45 MPa, the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 2 hours, and the molar ratio of pyridone chloride to phosgene is 1:2.

[0065] Example 8

[0066] The difference between Example 8 and Example 1 is that the pressure of the second reaction is 0.5 MPa, the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 1.5 h, and the molar ratio of pyridone chloride to phosgene is 1:1.8.

[0067] Example 9

[0068] The difference between Example 9 and Example 1 is that the pressure of the second reaction is 1.1 MPa, the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 1.5 h, and the molar ratio of pyridone chloride to phosgene is 1:1.2.

[0069] Example 10

[0070] The difference between Example 10 and Example 1 is that the molar ratio of pyridone chloride to phosgene is 1:1.8.

[0071] Example 11

[0072] The difference between Example 11 and Example 1 is that the mass ratio of pyridone chloride to N,N-dimethylformamide is 1:0.05.

[0073] Example 12

[0074] The difference between Example 12 and Example 1 is that the pressure of the second reaction is 0.7 MPa, the temperature of the second reaction is 120° C., and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is controlled to be 1 h.

[0075] Example 13

[0076] The difference between Example 13 and Example 1 is that the temperature of the second reaction is 170° C., and the retention time of the 2-chloro-5-methylpyridine synthetic liquid in the overflow reactor is 2 h.

[0077] Comparative Example 1

[0078] The difference from Example 1 is that the pressure of the second reaction is 0.1 MPa, the mass ratio of pyridone chloride to DMF is 1:0.1, the molar ratio of pyridone chloride to phosgene is 1:2, the second reaction temperature is 90°C, and the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 2 h.

[0079] Comparative Example 2

[0080] The difference between Comparative Example 2 and Example 1 is that the pressure of the second reaction is 0.1 MPa, the molar ratio of pyridone chloride to phosgene is 1:6, and the retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor is 6 h.

[0081] The second reaction temperature, second reaction pressure, retention time of the 2-chloro-5-methylpyridine synthesis solution in the overflow reactor, and molar ratio of pyridone chloride to phosgene during the preparation of 2-chloro-5-methylpyridine in the above-mentioned examples and comparative examples were summarized, and the reaction yield of 2-chloro-5-methylpyridine was calculated. The results are shown in Table 1. The yield of 2-chloro-5-methylpyridine was calculated as follows: moles of 2-chloro-5-methylpyridine product prepared / moles of 5-methyl-3,4-dihydropyridin-2(1H)-one charged × 100%.

[0082] Table 1

[0083]

[0084]

[0085] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0086] Embodiment 1 to embodiment 13 is for utilizing preparation method provided by the present invention to prepare 2-chloro-5-picoline, according to table 1 data, utilize the preparation method of the reaction pressure in the control second reaction process proposed by the present invention in the scope of 0.15~1.1MPa, can make the molar equivalent of phosgene in the reaction process in a relatively small range, the yield of 2-chloro-5-picoline is all more than 90%.And, even if control the retention time of 2-chloro-5-picoline synthetic solution in overflow reactor in a smaller range, also can have good reaction yield.Especially, the preparation parameter control in the second reaction process is within the preferred range, reaction efficiency is better, and the yield of 2-chloro-5-picoline is also higher, can further improve the economy of reaction.

[0087] Preparation method described in comparative example 1 is for carrying out the chlorination of pyridone chlorine and phosgene under normal pressure (0.1MPa), and the mol ratio of pyridone chlorine and phosgene is 1:2 in this process, therefore, the yield of 2-chloro-5-picoline only has 84.1%, and the yield reached with preparation method of the present invention is very different.Be all for carrying out the chlorination of pyridone chlorine and phosgene under normal pressure in comparative example 2, by improving the molar ratio of phosgene in the second reaction process and extending the overall reaction time, although compared with comparative example 1, the yield of 2-chloro-5-picoline increases, but the yield reached with preparation method of the present invention still has larger gap.And, in this comparative example, phosgene consumption is large, and the reaction time is long, and while overall reaction efficiency reduces, also increase preparation cost.

[0088] In summary, the preparation method of 2-chloro-5-methylpyridine provided by the present invention can effectively improve the utilization rate of phosgene, increase the yield of the product in the production process, improve production efficiency, and reduce the overall production cost of 2-chloro-5-methylpyridine. At the same time, the preparation method also has the advantages of being environmentally friendly and economically feasible.

[0089] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A method for preparing 2-chloro-5-methylpyridine, characterized in that: The preparation method comprises the following steps: Mixing 5-methyl-3,4-dihydropyridin-2(1H)-one with an organic solvent and heating the mixture to a first reaction temperature; introducing chlorine gas therein to carry out a first reaction to obtain a pyridinone chloride reaction solution; The pyridone chloride reaction solution and the catalyst are continuously introduced into the overflow reactor from the bottom, and after the material in the overflow reactor submerges the phosgene feed conduit port, phosgene is continuously introduced into the reactor, and the material in the reactor is subjected to a second reaction at a second temperature to obtain a 2-chloro-5-methylpyridine synthetic liquid; the 2-chloro-5-methylpyridine synthetic liquid is continuously extracted from the overflow port of the overflow reactor to a synthetic liquid storage tank; wherein the pressure of the second reaction is 0.15-1.1 MPa; the tail gas containing the phosgene generated by the second reaction is condensed and recovered to continue to participate in the second reaction; The 2-chloro-5-methylpyridine synthetic liquid in the synthetic liquid storage tank is subjected to degassing, desolventizing, decoking, light removal and distillation to obtain the 2-chloro-5-methylpyridine product.

2. The method for preparing 2-chloro-5-methylpyridine according to claim 1, characterized in that: The pressure of the second reaction is 0.5-1.1 MPa.

3. The method for preparing 2-chloro-5-methylpyridine according to claim 1, characterized in that: The molar ratio of the pyridone chloride to the phosgene is 1:(1.2-3); Preferably, the molar ratio of the pyridone chloride to the phosgene is 1:(1.2-2).

4. The method for preparing 2-chloro-5-methylpyridine according to claim 3, characterized in that: When the pressure of the second reaction is below 0.5 MPa, the molar ratio of the pyridone chloride to the phosgene is 1: (2-3); or, When the pressure of the second reaction is 0.5-1.1 MPa, the molar ratio of the pyridone chloride to the phosgene is 1: (1.2～2)。 5. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 4, characterized in that: The molar ratio of the 5-methyl-3,4-dihydropyridin-2(1H)-one to the chlorine gas is 1:(1.1-1.5); Preferably, the molar ratio of the 5-methyl-3,4-dihydropyridin-2(1H)-one to the chlorine gas is 1:(1.2-1.5).

6. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 4, characterized in that: The second temperature is 90-150° C.; Preferably, the second temperature is 90-130°C; Preferably, the retention time of the 2-chloro-5-methylpyridine synthetic solution in the overflow reactor is 1 to 8 hours; Further preferably, the retention time of the 2-chloro-5-methylpyridine synthetic solution in the overflow reactor is 1.5 to 5 hours.

7. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 4, characterized in that: The catalyst is N,N-dimethylformamide and / or N,N-dimethylacetamide; Preferably, the mass ratio of the pyridone chloride to the catalyst is 1:(0.01-0.2).

8. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 7, characterized in that: The organic solvent is one or more of benzene, toluene, ethylene dichloride and chloroform; Preferably, after the 5-methyl-3,4-dihydropyridin-2(1H)-one is mixed with the organic solvent, the mass concentration of the 5-methyl-3,4-dihydropyridin-2(1H)-one in the obtained mixed solution is 30 to 60%.

9. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 7, characterized in that: The first reaction temperature is 30-70°C; Preferably, the first reaction time is 1.5 to 3 hours; Preferably, the first reaction temperature is 40-60°C.

10. The method for preparing 2-chloro-5-methylpyridine according to any one of claims 1 to 7, characterized in that: The preparation method further comprises: controlling the discharge of non-condensable gas hydrogen chloride and carbon dioxide generated in the second reaction system out of the second reaction system to maintain the pressure of the second reaction system; Preferably, the condensation temperature is -5 to -20°C; More preferably, the condensation temperature is -10 to -20°C.

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