Catalysts and methods for the preparation of 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction.

Abstract

This invention discloses a catalyst and method for the preparation of 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, belonging to the field of catalyst technology. The catalyst comprises modified triphenylphosphine, a co-catalyst, a silane coupling agent, and a spherical alumina support. The co-catalyst comprises the following raw materials: lignin, NaOH solution, and K₂S₂O₈ solution. This invention uses modified triphenylphosphine as the core catalytically active component and cleverly utilizes the reaction product of lignin and K₂S₂O₈ under alkaline conditions as an auxiliary catalyst. Through the mediation of the silane coupling agent, these two raw materials are efficiently composited on a spherical alumina support, thereby preparing a highly efficient catalyst specifically for the Krißer reaction synthesis of 5-methoxy-4,6-dichloropyrimidine. Compared with traditional techniques, this invention significantly improves the yield, achieving a leap in production volume. More importantly, this invention greatly accelerates the production process and improves overall production efficiency.

Description

Technical Field

[0001] This invention relates to the field of catalyst technology, specifically to catalysts and methods for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction. Background Technology

[0002] 5-Methoxy-4,6-dichloropyrimidine is an important organic intermediate and a key raw material for the synthesis of the broad-spectrum antibacterial drug sulfadoxine. It has wide applications in the pesticide field and is one of the important intermediates for the synthesis of salicylic acid pyrimidine herbicides. The preparation process of 5-methoxy-4,6-dichloropyrimidine generally includes the Kjeldahl reaction, cyclization reaction, and chlorination reaction.

[0003] In existing technologies, silica-alumina catalysts are often used. However, silica-alumina catalysts have a small specific surface area, and the chemical properties of silica and alumina are relatively stable, resulting in a weak interaction between them and the active components. This makes it difficult to form an effective catalytic synergy, thus affecting the overall performance of the catalyst.

[0004] Based on this, the present invention designs a catalyst and method for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Krißer reaction to solve the above problems. Summary of the Invention

[0005] In view of the above-mentioned shortcomings of the prior art, the present invention provides a catalyst and method for preparing 5-methoxy-4,6-dichloropyrimidine by the Krißer reaction.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] A catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction;

[0008] Including modified triphenylphosphine, co-catalyst, silane coupling agent, and spherical alumina support;

[0009] The co-catalyst comprises the following raw materials: 3-5 parts lignin, 25-36 parts NaOH solution and 7-8 parts K2S2O8 solution.

[0010] A method for preparing a catalyst for the Kjeldahl reaction of 5-methoxy-4,6-dichloropyrimidine includes the following steps:

[0011] Step 1: Preparation of spherical alumina support;

[0012] A. Mix boehmite with nitric acid to form a homogeneous sol solution;

[0013] B. The sol solution is dropped into the oil-salt column to form spherical alumina;

[0014] C. The spherical alumina is cooled by vacuum precooling in a vacuum precooler at a temperature of 0-2℃.

[0015] D. The spherical alumina is washed, dried, and calcined to obtain a spherical alumina carrier;

[0016] Step 2: Preparation of modified triphenylphosphine;

[0017] A. Dissolve potassium difluorobromoacetate in water to form a potassium difluorobromoacetate salt solution. Heat the solution to 55-68℃, add triphenylphosphine, and raise the temperature to 80-85℃ while stirring for 20-30 minutes.

[0018] B. Add benzene, shake thoroughly, and the unreacted triphenylphosphine will dissolve in benzene. Extract the benzene, concentrate the remaining liquid to crystallize out the solid, centrifuge and dry to obtain modified triphenylphosphine.

[0019] Step 3: Preparation of co-catalyst;

[0020] A. Dissolve lignin in NaOH solution, and under light-protected conditions and constant temperature of 70-80℃, purge with nitrogen until all air is expelled. Then add 7-8 parts of K2S2O8 solution and stir the reaction at 200-300r / min for 40-50min to obtain a mixed solution.

[0021] B. After adjusting the pH of the mixed solution to acidic, the product precipitates out. After washing and filtration, the co-catalyst is obtained.

[0022] Step 4: Prepare the catalyst;

[0023] A. Preheat the silane coupling agent to 55-63℃ and keep it at that temperature. Add the spherical alumina carrier prepared in step one and stir at 200-300 r / min for 25-35 min to obtain mixture A.

[0024] B. Add the modified triphenylphosphine, which is a catalyst, to mixture A in 2-3 portions, stirring at a speed of 200-300 r / min while adding, with an interval of 10-15 min between each addition, to obtain the catalyst.

[0025] Furthermore, in step one, step A specifically involves mixing 8-12 parts of boehmite with 25-34 parts of nitric acid to form a homogeneous sol solution.

[0026] Furthermore, in step two, step A specifically involves dissolving 5-8 parts of potassium difluorobromoacetate in 45-56 parts of water to form a potassium difluorobromoacetate salt solution. The solution is then heated to 55-68°C, and 4-6 parts of triphenylphosphine are added. The temperature is then raised to 80-85°C, while stirring at a speed of 200-300 r / min for 20-30 min.

[0027] Furthermore, in step two, step B specifically involves adding 30-48 parts of benzene, shaking thoroughly, dissolving unreacted triphenylphosphine in the benzene, extracting the benzene, concentrating the remaining liquid to crystallize out the solid, centrifuging and drying to obtain modified triphenylphosphine.

[0028] Furthermore, in step three, step A specifically involves dissolving 3-5 parts of lignin in 25-36 parts of NaOH solution with a pH of 9-10. Under light-protected conditions and a constant temperature of 70-80°C, nitrogen gas is introduced until the air is completely expelled. Subsequently, 7-8 parts of K2S2O8 solution with a mass fraction of 5-10% are added, and the mixture is stirred at a speed of 200-300 r / min for 40-50 min to obtain a mixed solution.

[0029] Furthermore, in step four, step A specifically involves: preheating 32-48 parts of silane coupling agent to 55-63℃ and maintaining the temperature, adding the spherical alumina carrier obtained in step one, and stirring at a speed of 200-300 r / min for 25-35 min to obtain mixture A.

[0030] Furthermore, the silane coupling agent is selected from KH-570 or KH-791.

[0031] Compared to existing technologies, this invention offers the following advantages: It utilizes modified triphenylphosphine as the core catalytically active component and cleverly employs the reaction product of lignin and K₂S₂O₈ under alkaline conditions as an auxiliary catalyst. Through the mediation of a silane coupling agent, these two raw materials are efficiently composited onto a spherical alumina support, thereby preparing a highly efficient catalyst specifically for the Krißer reaction to synthesize 5-methoxy-4,6-dichloropyrimidine. Compared to traditional techniques, this invention significantly improves the yield of 5-methoxy-4,6-dichloropyrimidine, achieving a leap in production volume. More importantly, this invention drastically reduces the reaction process from three hours to just one hour, greatly accelerating the production process and improving overall production efficiency. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0033] Example 1

[0034] This embodiment provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0035] (1) Preparation of spherical alumina carrier: 12 kg of boehmite and 34 kg of nitric acid were mixed to form a uniform sol solution; the sol solution was dropped into an oil-salt column to form spherical alumina; the spherical alumina was subjected to vacuum cooling in a vacuum precooler at a temperature of 2 °C; the spherical alumina was washed, dried and calcined to obtain the spherical alumina carrier;

[0036] (2) Preparation of modified triphenylphosphine: Dissolve 8 kg of potassium difluorobromoacetate in 56 L of water to form a potassium difluorobromoacetate salt solution. Heat the solution to 68 °C, add 6 kg of triphenylphosphine, and raise the temperature to 85 °C. Stir at 300 r / min for 30 min while raising the temperature. Add 48 kg of benzene and shake thoroughly. Unreacted triphenylphosphine dissolves in benzene. Extract the benzene. Concentrate the remaining liquid to crystallize the solid. After centrifugation and drying, the modified triphenylphosphine is obtained.

[0037] (3) Preparation of co-catalyst: 5 kg of lignin was dissolved in 36 kg of NaOH solution with pH 10. Under light-protected conditions and constant temperature of 80 °C, nitrogen gas was introduced until the air was exhausted. Then, 8 kg of K2S2O8 solution with a mass fraction of 10% was added. The mixture was stirred at 300 r / min for 50 min to obtain a mixed solution. After adjusting the pH of the mixed solution to 4, the product precipitated. After washing and filtration, the co-catalyst was obtained.

[0038] (4) Preparation of catalyst: 48 kg of silane coupling agent KH-791 was preheated to 63°C and kept at that temperature. The spherical alumina support obtained in step one was added and stirred at 300 r / min for 35 min to obtain mixture A. Modified triphenylphosphine mixed with catalyst was added to mixture A in 3 equal parts while stirring at 200-300 r / min, with an interval of 15 min each time, to obtain the catalyst.

[0039] (5) The above catalyst is applied to the Krisselbach reaction to prepare 5-methoxy-4,6-dichloropyrimidine, including the following steps:

[0040] S1: Krohne reaction;

[0041] First, 180 kg of solid sodium ethoxide was added to the reactor, followed by 175 kg of methyl methoxyacetate and 260 kg of diethyl oxalate. The reaction was carried out for 3 hours at a temperature of 60°C. After the reaction was completed, 190 kg of trichloroethylene was added and stirred to dilute the mixture. Then, 400 kg of water and 200 kg of 30% hydrochloric acid were added to adjust the pH to 2.0. The trichloroethylene was separated, and the aqueous layer was extracted with trichloroethylene 6 times to recover the trichloroethylene solvent. Finally, the internal temperature was controlled to 100°C. Under a vacuum condition at an internal temperature of 170°C, decarbonylation was carried out for 5 hours. Then, the mixture was distilled under reduced pressure. The sample was collected at a vacuum of ≥-0.095 MPa and an internal temperature of ≤250°C to obtain 200 kg of methyl ethyl methoxymalonate.

[0042] S2: Cycling reaction;

[0043] First, 1000 kg of sodium methoxide was added to a reaction vessel, along with 1.5 kg of the catalyst prepared in step four. The mixture was stirred and heated to 50°C, then 350 kg of formamide and 200 kg of methyl ethyl methoxymalonate were added. After the addition was complete, the mixture was kept at 2.5 MPa for 1 hour. After the heat treatment was completed, methanol was recovered until no liquid was discharged. Then, 600 kg of water was added, and the mixture was cooled to 15°C. The product was then discharged by centrifugation and dehydration. The wet product was then dried under reduced pressure at 100°C and a vacuum degree ≥ -0.08 MPa for 10 hours. The product was then dried to obtain 280 kg of disodium 5-methoxy-4,6-dihydroxypyrimidine.

[0044] S3: Chlorination reaction;

[0045] First, add 1000 kg of dichloromethane to 280 kg of disodium 5-methoxy-4,6-dihydroxypyrimidine and stir at 20°C for 1 hour. Then, cool the mixture to 0°C and slowly add 800 kg of phosphorus oxychloride and 160 kg of N,N-dimethylaniline dropwise, keeping the temperature below 10°C. After the addition is complete, heat the mixture under reflux for 1 hour to distill off the dichloromethane. Pour the residue into 3000 kg of ice water, stir for 1 hour, filter, and recrystallize with ethanol to obtain 253 kg of the product.

[0046] The product was characterized by infrared and mass spectrometry analysis, which confirmed that the product was 5-methoxy-4,6-dichloropyrimidine.

[0047] The yield of 5-methoxy-4,6-dichloropyrimidine prepared in this example was determined.

[0048] Yield = Actual target product yield / Theoretical target product yield × 100%;

[0049] The measured yield was 64%.

[0050] Example 2

[0051] This embodiment provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0052] (1) Preparation of spherical alumina carrier: 8 kg of boehmite and 25 kg of nitric acid were mixed to form a uniform sol solution; the sol solution was dropped into an oil-salt column to form spherical alumina; the spherical alumina was subjected to vacuum cooling in a vacuum precooler at a temperature of 0°C; the spherical alumina was washed, dried and calcined to obtain the spherical alumina carrier.

[0053] (2) Preparation of modified triphenylphosphine: Dissolve 5 kg of potassium difluorobromoacetate in 45 L of water to form a potassium difluorobromoacetate salt solution. Heat the solution to 55 °C, add 4 kg of triphenylphosphine, and heat to 80 °C while stirring at 200 r / min for 20 min. Add 30 kg of benzene and shake thoroughly. Unreacted triphenylphosphine dissolves in benzene. Extract benzene and concentrate the remaining liquid to crystallize out the solid. After centrifugation and drying, the modified triphenylphosphine is obtained.

[0054] (3) Preparation of co-catalyst: Dissolve 3 kg of lignin in 25 kg of NaOH solution with pH 9. Under light-protected conditions and constant temperature of 70 °C, purge with nitrogen until the air is exhausted. Then add 7 kg of K2S2O8 solution with a mass fraction of 5% and stir at 200 r / min for 40 min to obtain a mixed solution. After adjusting the pH of the mixed solution to 3, the product precipitates. After washing and filtration, the co-catalyst is obtained.

[0055] (4) Preparation of catalyst: 32 kg of silane coupling agent KH-570 was preheated to 55°C and kept at that temperature. The spherical alumina support obtained in step one was added and stirred at 200 r / min for 25 min to obtain mixture A. Modified triphenylphosphine mixed with catalyst was added to mixture A in two portions, while stirring at 200 r / min, with an interval of 10 min between each addition, to obtain the catalyst.

[0056] (5) The above catalyst was applied to the Kriß reaction to prepare 5-methoxy-4,6-dichloropyrimidine by the method of Example 1, and the yield was 65%.

[0057] Example 3

[0058] This embodiment provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0059] (1) Preparation of spherical alumina carrier: 11 kg of boehmite and 28 kg of nitric acid were mixed to form a uniform sol solution; the sol solution was dropped into an oil-salt column to form spherical alumina; the spherical alumina was subjected to vacuum cooling in a vacuum precooler at a temperature of 0°C; the spherical alumina was washed, dried and calcined to obtain the spherical alumina carrier;

[0060] (2) Preparation of modified triphenylphosphine: Dissolve 6 kg of potassium difluorobromoacetate in 52 L of water to form a potassium difluorobromoacetate salt solution. Heat the solution to 66 °C, add 5 kg of triphenylphosphine, and raise the temperature to 81 °C. Stir at 220 r / min for 23 min while raising the temperature. Add 38 kg of benzene and shake thoroughly. Unreacted triphenylphosphine dissolves in benzene. Extract the benzene. Concentrate the remaining liquid to crystallize the solid. After centrifugation and drying, the modified triphenylphosphine is obtained.

[0061] (3) Preparation of co-catalyst: Dissolve 3 kg of lignin in 34 kg of NaOH solution with pH 10. Under light-protected conditions and constant temperature of 78 °C, purge with nitrogen until the air is exhausted. Then add 8 kg of K2S2O8 solution with a mass fraction of 8% and stir at 260 r / min for 42 min to obtain a mixed solution. After adjusting the pH of the mixed solution to 3, the product precipitates. After washing and filtration, the co-catalyst is obtained.

[0062] (4) Preparation of catalyst: 39 kg of silane coupling agent KH-791 was preheated to 59°C and kept at that temperature. The spherical alumina support obtained in step one was added and stirred at 280 r / min for 31 min to obtain mixture A.

[0063] B. Add the modified triphenylphosphine mixed with catalyst to mixture A in three portions, stirring at a speed of 280 r / min while adding, with a 12 min interval between each addition, to obtain the catalyst.

[0064] (5) The above catalyst was applied to the Kriß reaction to prepare 5-methoxy-4,6-dichloropyrimidine by the method of Example 1, and the yield was 62%.

[0065] Comparative Example 1

[0066] The difference from Example 3 is that no co-catalyst was added;

[0067] This comparative example provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0068] (1) Preparation of spherical alumina carrier: 11 kg of boehmite and 28 kg of nitric acid were mixed to form a uniform sol solution; the sol solution was dropped into an oil-salt column to form spherical alumina; the spherical alumina was subjected to vacuum cooling in a vacuum precooler at a temperature of 0°C; the spherical alumina was washed, dried and calcined to obtain the spherical alumina carrier;

[0069] (2) Preparation of modified triphenylphosphine: Dissolve 6 kg of potassium difluorobromoacetate in 52 L of water to form a potassium difluorobromoacetate salt solution. Heat the solution to 66 °C, add 5 kg of triphenylphosphine, and raise the temperature to 81 °C. Stir at 220 r / min for 23 min while raising the temperature. Add 38 kg of benzene and shake thoroughly. Unreacted triphenylphosphine dissolves in benzene. Extract the benzene. Concentrate the remaining liquid to crystallize the solid. After centrifugation and drying, the modified triphenylphosphine is obtained.

[0070] (3) Preparation of catalyst: 39 kg of silane coupling agent KH-791 was preheated to 59 °C and kept at that temperature. The spherical alumina support prepared in step one was added and stirred at 280 r / min for 31 min to obtain mixture A. Modified triphenylphosphine was added to mixture A in three portions, while stirring at 280 r / min, with a 12 min interval between each addition, to obtain the catalyst.

[0071] (4) The above catalyst was applied to the Kriß reaction to prepare 5-methoxy-4,6-dichloropyrimidine by the method of Example 1, and the yield was 52%.

[0072] Comparative Example 2

[0073] The difference from Example 3 is that triphenylphosphine was not modified;

[0074] This comparative example provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0075] (1) Preparation of spherical alumina carrier: 11 kg of boehmite and 28 kg of nitric acid were mixed to form a uniform sol solution; the sol solution was dropped into an oil-salt column to form spherical alumina; the spherical alumina was subjected to vacuum cooling in a vacuum precooler at a temperature of 0°C; the spherical alumina was washed, dried and calcined to obtain the spherical alumina carrier;

[0076] (2) Preparation of co-catalyst: 3 kg of lignin was dissolved in 34 kg of NaOH solution with pH 10. Under light-protected conditions and constant temperature of 78°C, nitrogen gas was introduced until the air was completely removed. Then, 8 kg of K2S2O8 solution with a mass fraction of 8% was added, and the mixture was stirred at 260 r / min for 42 min to obtain a mixed solution. After adjusting the pH of the mixed solution to 3, the product precipitated. After washing and filtration, the co-catalyst was obtained.

[0077] (3) Preparation of catalyst: 39 kg of silane coupling agent KH-791 was preheated to 59 °C and kept at that temperature. The spherical alumina support prepared in step one was added and stirred at 280 r / min for 31 min to obtain mixture A. 5 kg of triphenylphosphine mixed with catalyst was added to mixture A in three portions, and stirred at 280 r / min while adding, with an interval of 12 min between each addition, to obtain the catalyst.

[0078] (4) The above catalyst was applied to the Krijl reaction to prepare 5-methoxy-4,6-dichloropyrimidine by the method of Example 1, and the yield was 58%.

[0079] Comparative Example 3

[0080] The difference from Example 3 is that the catalyst used is a silica-alumina catalyst commonly used in the prior art;

[0081] This comparative example provides a method for preparing 5-methoxy-4,6-dichloropyrimidine via the Krißer reaction, comprising the following steps:

[0082] Step S1: Krüger reaction;

[0083] First, 180 kg of solid sodium ethoxide was added to the reactor, followed by 175 kg of methyl methoxyacetate and 260 kg of diethyl oxalate. The reaction was carried out for 3 hours at a temperature of 60°C. After the reaction was completed, 190 kg of trichloroethylene was added and stirred to dilute the mixture. Then, 400 kg of water and 200 kg of 30% hydrochloric acid were added to adjust the pH to 2.0. The trichloroethylene was separated, and the aqueous layer was extracted with trichloroethylene 6 times to recover the trichloroethylene solvent. Finally, the internal temperature was controlled to 100°C. Under a vacuum condition at an internal temperature of 170°C, decarbonylation was carried out for 5 hours. Then, the mixture was distilled under reduced pressure. The sample was collected at a vacuum of ≥-0.095 MPa and an internal temperature of ≤250°C to obtain 200 kg of methyl ethyl methoxymalonate.

[0084] Step S2: Cyclization reaction;

[0085] First, 1000 kg of sodium methoxide was added to a reaction vessel, along with 1.5 kg of silica-alumina catalyst. The mixture was stirred and heated to 50°C. Then, 350 kg of formamide and 200 kg of methyl ethyl methoxymalonate were added. After the addition was complete, the mixture was kept at 2.5 MPa for 3 hours. After the reaction was completed, methanol was recovered until no liquid was discharged. Then, 600 kg of water was added, and the mixture was cooled to 15°C. The product was then discharged by centrifugation and dehydration. The wet product was then dried under reduced pressure at 100°C and a vacuum degree ≥ -0.08 MPa for 10 hours. The product was then dried to obtain 280 kg of disodium 5-methoxy-4,6-dihydroxypyrimidine.

[0086] Step S3: Chlorination reaction;

[0087] First, add 1000 kg of dichloromethane to 280 kg of disodium 5-methoxy-4,6-dihydroxypyrimidine and stir at 20 °C for 1 h. Then, cool the mixture to 0 °C and slowly add 800 kg of phosphorus oxychloride and 160 kg of N,N-dimethylaniline dropwise, keeping the temperature below 10 °C. After the addition is complete, heat the mixture under reflux for 1 h to distill off the dichloromethane. Pour the remaining mixture into 3000 kg of ice water, stir for 1 h, filter, and recrystallize with ethanol to obtain 182 kg of the product.

[0088] The product was characterized and verified to be 5-methoxy-4,6-dichloropyrimidine.

[0089] The yield of 5-methoxy-4,6-dichloropyrimidine prepared in this example was determined to be 46%.

[0090] Comparative Example 4

[0091] The difference from Example 3 is that the spherical alumina was not subjected to vacuum precooling in a vacuum precooler in step one; the yield was measured to be 59%.

[0092] In summary, this invention uses modified triphenylphosphine as the main catalytically active component, and a co-catalyst obtained by reacting lignin and K2S2O8 in an alkaline solution. These two raw materials are then combined onto a spherical alumina support under the action of a silane coupling agent to prepare a catalyst for the Kröller reaction to prepare 5-methoxy-4,6-dichloropyrimidine. Compared with existing technologies, the yield of 5-methoxy-4,6-dichloropyrimidine is effectively improved; and the reaction time of the original three hours is shortened to one hour, significantly improving production efficiency.

[0093] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, The catalyst for preparing 5-methoxy-4,6-dichloropyrimidine by the Kresch reaction comprises modified triphenylphosphine, a cocatalyst, a silane coupling agent and a spherical alumina carrier; the cocatalyst comprises the following raw materials: 3-5 parts of lignin, 25-36 parts of a NaOH solution and 7-8 parts of a K2S2O8 solution; and the method for preparing the catalyst for preparing 5-methoxy-4,6-dichloropyrimidine by the Kresch reaction comprises the following steps: Step one: preparing a spherical alumina carrier; A. mixing pseudo-boehmite and nitric acid to form a uniform sol solution; B. dropping the sol solution into an oil-salt column to form spherical alumina; C. vacuumizing and depressurizing the spherical alumina in a vacuum pre-cooling machine and cooling the spherical alumina to a temperature of 0-2 ℃; D. washing, drying and calcining the spherical alumina to obtain the spherical alumina carrier; Step two: preparing modified triphenylphosphine; A. dissolving potassium difluorobromacetate in water to form a potassium difluorobromacetate salt solution, heating the solution to 55-68 ℃, adding triphenylphosphine, increasing the temperature to 80-85 ℃, and stirring at a speed of 200-300 r / min for 20-30 min while increasing the temperature; B. adding benzene, fully shaking, extracting benzene, concentrating the remaining liquid to crystallize solid, and drying the solid by centrifugation to obtain modified triphenylphosphine; Step three: preparing a cocatalyst; A. dissolving lignin in a NaOH solution, under light-proof conditions and at a constant temperature of 70-80 ℃, purging nitrogen until the air is exhausted, then adding 7-8 parts of a K2S2O8 solution, and stirring at a speed of 200-300 r / min for 40-50 min to obtain a mixed solution; B. adjusting the pH of the mixed solution to be acidic, and then precipitating the product, which is washed and filtered to obtain the cocatalyst; Step four: preparing the catalyst; A. preheating the silane coupling agent to 55-63 ℃ and keeping the temperature, adding the spherical alumina carrier prepared in step one, and stirring at a speed of 200-300 r / min for 25-35 min to obtain a mixture A; B. adding the modified triphenylphosphine mixed with the cocatalyst to the mixture A in 2-3 portions, stirring at a speed of 200-300 r / min while adding, and intervaling 10-15 min each time to obtain the catalyst.

2. The process according to claim 1 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, In step one, step A specifically comprises: mixing 8-12 parts of pseudo-boehmite and 25-34 parts of nitric acid to form a uniform sol solution.

3. The process according to claim 2 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, In step two, step A specifically comprises: dissolving 5-8 parts of potassium difluorobromacetate in 45-56 parts of water to form a potassium difluorobromacetate salt solution, heating the solution to 55-68 ℃, adding 4-6 parts of triphenylphosphine, increasing the temperature to 80-85 ℃, and stirring at a speed of 200-300 r / min for 20-30 min while increasing the temperature.

4. The process according to claim 3 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, In step two, step B specifically comprises: adding 30-48 parts of benzene, fully shaking, extracting benzene, concentrating the remaining liquid to crystallize solid, and drying the solid by centrifugation to obtain modified triphenylphosphine.

5. The process according to claim 4 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, In step three, step A is specifically as follows: 3-5 parts of lignin are dissolved in 25-36 parts of NaOH solution with pH of 9-10, under light-proof condition, constant temperature of 70-80 DEG C, nitrogen is introduced until air is exhausted, then 7-8 parts of K2S2O8 solution with mass fraction of 5-10% is added, stirring is carried out at a speed of 200-300 r / min for 40-50 min, and a mixed solution is obtained.

6. The process according to claim 5 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, In step four, step A is specifically as follows: 32-48 parts of silane coupling agent are preheated to 55-63 DEG C and kept, and the spherical alumina carrier prepared in step one is added, stirring is carried out at a speed of 200-300 r / min for 25-35 min, and a mixture A is obtained.

7. The process according to claim 6 for the preparation of a catalyst for the preparation of 5-methoxy-4,6-dichloropyrimidine by the Knoevenagel reaction, characterized in that, The silane coupling agent is selected from KH-570 or KH-791.