Catalyst and method for preparing 5-methoxy-4, 6-dichloropyrimidine through Kirschner reaction

Abstract

The invention discloses a catalyst and a method for preparing 5-methoxy-4, 6-dichloropyrimidine through Kirschner reaction, and belongs to the technical field of catalysts, the catalyst comprises modified triphenylphosphine, a cocatalyst, a silane coupling agent and a spherical alumina carrier; the cocatalyst is prepared from the following raw materials: lignin, a NaOH solution and a K2S2O8 solution. According to the invention, modified triphenylphosphine is used as a core catalytic active component, and a reaction product of lignin and K2S2O8 in an alkaline environment is ingeniously used as an auxiliary catalyst. Through mediation of a silane coupling agent, the two raw materials are efficiently compounded on a spherical alumina carrier, so that the efficient catalyst special for synthesizing the 5-methoxy-4, 6-dichloropyrimidine through Kirschner reaction is prepared. Compared with the traditional technical means, the method has the advantages that the yield is obviously improved, and the leap in yield is realized. In addition, it is worthy of mentioning that the production process is greatly accelerated, and the overall production efficiency is improved.

Description

Technical Field

[0001] The invention relates to the technical field of catalysts, and in particular to a catalyst and a method for preparing 5-methoxy-4,6-dichloropyrimidine by Krebs reaction. Background Art

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

[0003] In the prior art, silica-alumina catalysts are mostly used, but the specific surface area of ​​silica-alumina catalysts is small, and the chemical properties of silica and alumina are relatively stable, resulting in weak interaction between it and the active components, making it difficult to form effective catalytic synergy, thereby affecting the overall performance of the catalyst.

[0004] Based on this, the present invention designs a catalyst and method for preparing 5-methoxy-4,6-dichloropyrimidine by Krebs 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 a method for preparing 5-methoxy-4,6-dichloropyrimidine by Krebs reaction.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0007] A catalyst for preparing 5-methoxy-4,6-dichloropyrimidine by Krebs reaction;

[0008] It includes modified triphenylphosphine, a co-catalyst, a silane coupling agent, and a spherical alumina carrier;

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

[0010] A method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction comprises the following steps:

[0011] Step 1: preparing a spherical alumina carrier;

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

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

[0014] C. The spherical alumina is subjected to vacuum cooling and pressure reduction in a vacuum precooler, and the cooling temperature is 0-2°C;

[0015] D. washing, drying and calcining the spherical alumina to obtain a spherical alumina carrier;

[0016] Step 2: preparing modified triphenylphosphine;

[0017] A. Dissolve potassium difluorobromoacetate in water to form a potassium difluorobromoacetate solution, heat the solution to 55-68°C, add triphenylphosphine, heat to 80-85°C, and stir for 20-30 minutes while heating;

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

[0019] Step 3: preparing a co-catalyst;

[0020] A. Dissolve lignin in NaOH solution, and introduce nitrogen gas to exhaust air at 70-80°C in a dark environment, then add 7-8 parts of K2S2O8 solution, and stir at 200-300r / min for 40-50min to obtain a mixed solution;

[0021] B. After the pH of the mixed solution is adjusted to acidic, the product is precipitated, and the co-catalyst is obtained after washing and filtering;

[0022] Step 4: preparing a catalyst;

[0023] A. Preheat the silane coupling agent to 55-63° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 200-300 r / min for 25-35 min to obtain a mixture A;

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

[0025] Furthermore, in step one, step A is specifically: 8-12 parts of pseudo-boehmite are mixed with 25-34 parts of nitric acid to form a uniform sol solution.

[0026] Furthermore, in step 2, step A is specifically as follows: dissolving 5-8 parts of potassium difluorobromoacetate in 45-56 parts of water to form a potassium difluorobromoacetate solution, heating the solution to 55-68°C, adding 4-6 parts of triphenylphosphine, heating to 80-85°C, and stirring at a speed of 200-300 r / min for 20-30 min while heating.

[0027] Furthermore, in step 2, step B is specifically as follows: adding 30-48 parts of benzene, shaking sufficiently, dissolving unreacted triphenylphosphine in benzene, extracting benzene, concentrating the remaining liquid to crystallize solid, centrifuging and drying to obtain modified triphenylphosphine.

[0028] Furthermore, in step three, step A is specifically as follows: 3-5 parts of lignin are dissolved in 25-36 parts of NaOH solution with a pH of 9-10, and nitrogen is introduced into the solution to exhaust the air at a constant temperature of 70-80°C under light-proof conditions, followed by adding 7-8 parts of K2S2O8 solution with a mass fraction of 5-10%, and stirring the reaction at a speed of 200-300 r / min for 40-50 minutes to obtain a mixed solution.

[0029] Furthermore, in step 4, step A is specifically as follows: preheating 32-48 parts of silane coupling agent to 55-63° C. and keeping warm, adding the spherical alumina carrier prepared in step 1, 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 KH-570 or KH-791.

[0031] Compared with the prior art, the present invention has the following beneficial effects: the present invention adopts modified triphenylphosphine as the core catalytic active component, and cleverly utilizes the reaction product of lignin and K2S2O8 in an alkaline environment as an auxiliary catalyst. Through the mediation of a silane coupling agent, these two raw materials are efficiently compounded on a spherical alumina carrier, thereby preparing a highly efficient catalyst specifically for the Krebs reaction to synthesize 5-methoxy-4,6-dichloropyrimidine. Compared with traditional technical means, the present invention significantly improves the yield of 5-methoxy-4,6-dichloropyrimidine and achieves a leap in output. What is more worth mentioning is that the present invention significantly reduces the original three-hour reaction process to only one hour, greatly accelerating the production process and improving overall production efficiency. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Embodiment 1

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

[0035] (1) Preparing a spherical alumina carrier: 12 kg of pseudo-boehmite and 34 kg of nitric acid are mixed to form a uniform sol solution; the sol solution is dripped into an oil-salt column to form spherical alumina; the spherical alumina is subjected to a vacuum precooling machine for a decompression cooling treatment, and the cooling temperature is 2° C.; the spherical alumina is washed, dried, and calcined to obtain a spherical alumina carrier;

[0036] (2) Preparation of modified triphenylphosphine: 8 kg of potassium difluorobromoacetate was dissolved in 56 L of water to form a potassium difluorobromoacetate solution, the solution was heated to 68° C., 6 kg of triphenylphosphine was added, the temperature was raised to 85° C., and the mixture was stirred at a speed of 300 r / min for 30 min while the temperature was raised; 48 kg of benzene was added, the mixture was shaken thoroughly, unreacted triphenylphosphine was dissolved in benzene, benzene was extracted, the remaining liquid was concentrated and crystallized to precipitate solid, and the modified triphenylphosphine was obtained after centrifugal separation and drying;

[0037] (3) preparing a co-catalyst; dissolving 5 kg of lignin in 36 kg of a NaOH solution with a pH of 10, introducing nitrogen gas to exhaust all the air at a constant temperature of 80° C. under light-proof conditions, then adding 8 kg of a 10% K2S2O8 solution, stirring at a speed of 300 r / min for 50 min to obtain a mixed solution; adjusting the pH of the mixed solution to 4, the product precipitated, and the co-catalyst was obtained after washing and filtering;

[0038] (4) Preparation of catalyst: preheat 48 kg of silane coupling agent KH-791 to 63° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at 300 r / min for 35 min to obtain mixture A; add modified triphenylphosphine mixed with a co-catalyst to mixture A in 3 equal portions, stirring at 200-300 r / min while adding, with an interval of 15 min between each addition, to obtain a catalyst.

[0039] (5) Applying the above catalyst to the Krebs reaction to prepare 5-methoxy-4,6-dichloropyrimidine, comprising the following steps:

[0040] S1: Krebs reaction;

[0041] First, 180 kg of solid sodium ethoxide is put into a reactor, and then 175 kg of methyl methoxyacetate and 260 kg of diethyl oxalate are put into the reactor, and the reaction is carried out for 3 hours, and the temperature is controlled at 60°C. After the reaction is completed, 190 kg of trichloroethylene is added, stirred and diluted, and then 400 kg of water and 200 kg of 30% hydrochloric acid are added to adjust the pH value to 2.0, and trichloroethylene is separated. The water layer is extracted with trichloroethylene for 6 times, and the trichloroethylene solvent is recovered. Finally, the internal temperature is controlled to 100°C, and the decarbonylation is carried out for 5 hours at an internal temperature of 170°C and a vacuum state, and then the vacuum distillation is carried out, and the vacuum degree is ≥-0.095 MPa and the internal temperature is ≤250°C to obtain 200 kg of methyl ethyl methoxymalonate;

[0042] S2: cyclization reaction;

[0043] First, 1000 kg of sodium methoxide is put into a reaction pot, 1.5 kg of the catalyst prepared in step 4 is added, and the mixture is stirred and heated to 50° C., 350 kg of formamide and 200 kg of methyl ethyl methoxymalonate are added, and the mixture is kept warm for 1 hour at a pressure of 2.5 MPa. After the heat preservation is completed, methanol is recovered until no liquid is discharged, and then 600 kg of water is added, and the mixture is cooled to 15° C. and the mixture is discharged. The mixture is centrifuged and dehydrated, and the discharged material is dried; the wet product is dried under reduced pressure at a drying temperature of 100° C. and a vacuum degree of ≥-0.08 MPa for 10 hours, and then dried to obtain 280 kg of 5-methoxy-4,6-dihydroxypyrimidine disodium;

[0044] S3: chlorination reaction;

[0045] First, add 1000 kg of dichloromethane to 280 kg of 5-methoxy-4,6-dihydroxypyrimidine disodium, stir at 20 ° C for 1 hour, cool to 0 ° C, slowly add 800 kg of phosphorus oxychloride and 160 kg of N, N-dimethylaniline, control the temperature below 10 ° C, heat to reflux for 1 hour to evaporate 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 product.

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

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

[0048] Yield = actual target product production / theoretical target product production × 100%;

[0049] The yield was found to be 64%.

[0050] Embodiment 2

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

[0052] (1) Preparing a spherical alumina carrier: 8 kg of pseudo-boehmite is mixed with 25 kg of nitric acid to form a uniform sol solution; the sol solution is dripped into an oil-salt column to form spherical alumina; the spherical alumina is subjected to a vacuum precooling machine for vacuum decompression cooling treatment, and the cooling temperature is 0° C.; the spherical alumina is washed, dried, and calcined to obtain a spherical alumina carrier;

[0053] (2) Preparation of modified triphenylphosphine: 5 kg of potassium difluorobromoacetate was dissolved in 45 L of water to form a potassium difluorobromoacetate solution, the solution was heated to 55° C., 4 kg of triphenylphosphine was added, the temperature was raised to 80° C., and the mixture was stirred at a speed of 200 r / min for 20 min while the temperature was raised; 30 kg of benzene was added, the mixture was shaken thoroughly, unreacted triphenylphosphine was dissolved in the benzene, the benzene was extracted, the remaining liquid was concentrated and crystallized to precipitate a solid, and the modified triphenylphosphine was obtained after centrifugal separation and drying;

[0054] (3) Preparation of a co-catalyst: 3 kg of lignin was dissolved in 25 kg of a NaOH solution with a pH of 9, and nitrogen was introduced into the solution under light-proof conditions and at a constant temperature of 70° C. until all the air was exhausted. Subsequently, 7 kg of a 5% by mass K2S2O8 solution was added, and the mixture was stirred at a speed of 200 r / min for 40 min to obtain a mixed solution. After the pH of the mixed solution was adjusted to 3, the product was precipitated, and the co-catalyst was obtained after washing and filtration.

[0055] (4) Preparation of catalyst: preheat 32 kg of silane coupling agent KH-570 to 55° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 200 r / min for 25 min to obtain mixture A; add modified triphenylphosphine mixed with a co-catalyst to mixture A in two portions, stirring at a speed of 200 r / min, with an interval of 10 min between each addition, to obtain a catalyst.

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

[0057] Embodiment 3

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

[0059] (1) preparing a spherical alumina carrier; mixing 11 kg of pseudo-boehmite with 28 kg of nitric acid to form a uniform sol solution; dripping the sol solution into an oil-salt column to form spherical alumina; subjecting the spherical alumina to a vacuum precooling machine for vacuum decompression cooling treatment at a cooling temperature of 0° C.; washing, drying, and calcining the spherical alumina to obtain a spherical alumina carrier;

[0060] (2) Preparation of modified triphenylphosphine: 6 kg of potassium difluorobromoacetate was dissolved in 52 L of water to form a potassium difluorobromoacetate solution, the solution was heated to 66° C., 5 kg of triphenylphosphine was added, the temperature was raised to 81° C., and the mixture was stirred at a speed of 220 r / min for 23 min while the temperature was raised; 38 kg of benzene was added, the mixture was shaken thoroughly, unreacted triphenylphosphine was dissolved in the benzene, the benzene was extracted, the remaining liquid was concentrated and crystallized to precipitate a solid, and the modified triphenylphosphine was obtained after centrifugal separation and drying;

[0061] (3) Preparation of a co-catalyst: 3 kg of lignin was dissolved in 34 kg of a NaOH solution with a pH of 10, and nitrogen was introduced into the solution under light-proof conditions and at a constant temperature of 78° C. until all the air was exhausted. Then, 8 kg of a K2S2O8 solution with a mass fraction of 8% was added, and the solution was stirred at a speed of 260 r / min for 42 min to obtain a mixed solution. After the pH of the mixed solution was adjusted to 3, the product precipitated, and the co-catalyst was obtained after washing and filtration.

[0062] (4) Preparation of catalyst: 39 kg of silane coupling agent KH-791 was preheated to 59° C. and kept warm, and the spherical alumina carrier prepared in step 1 was added, and stirred at a speed of 280 r / min for 31 min to obtain a mixture A;

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

[0064] (5) The above catalyst was applied to the Krebs 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 promoter is added;

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

[0068] (1) Preparing a spherical alumina carrier: 11 kg of pseudo-boehmite and 28 kg of nitric acid are mixed to form a uniform sol solution; the sol solution is dripped into an oil-salt column to form spherical alumina; the spherical alumina is subjected to a vacuum precooling machine for vacuum decompression cooling treatment, and the cooling temperature is 0° C.; the spherical alumina is washed, dried, and calcined to obtain a spherical alumina carrier;

[0069] (2) Preparation of modified triphenylphosphine: 6 kg of potassium difluorobromoacetate was dissolved in 52 L of water to form a potassium difluorobromoacetate solution, the solution was heated to 66° C., 5 kg of triphenylphosphine was added, the temperature was raised to 81° C., and the mixture was stirred at a speed of 220 r / min for 23 min while the temperature was raised; 38 kg of benzene was added, the mixture was shaken thoroughly, unreacted triphenylphosphine was dissolved in the benzene, the benzene was extracted, the remaining liquid was concentrated and crystallized to precipitate a solid, and the modified triphenylphosphine was obtained after centrifugal separation and drying;

[0070] (3) Preparation of catalyst: preheat 39 kg of silane coupling agent KH-791 to 59° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 280 r / min for 31 min to obtain mixture A; add modified triphenylphosphine to mixture A in three portions, stirring at a speed of 280 r / min, with an interval of 12 min between each addition, to obtain a catalyst.

[0071] (4) The above catalyst was applied to the Krebs 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 the triphenylphosphine is not modified;

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

[0075] (1) Preparing a spherical alumina carrier: 11 kg of pseudo-boehmite and 28 kg of nitric acid are mixed to form a uniform sol solution; the sol solution is dripped into an oil-salt column to form spherical alumina; the spherical alumina is subjected to a vacuum precooling machine for vacuum decompression cooling treatment, and the cooling temperature is 0° C.; the spherical alumina is washed, dried, and calcined to obtain a spherical alumina carrier;

[0076] (2) Preparation of a co-catalyst: 3 kg of lignin was dissolved in 34 kg of a NaOH solution with a pH of 10, and nitrogen was introduced into the solution until all air was exhausted at a constant temperature of 78° C. in a dark environment, and then 8 kg of a K2S2O8 solution with a mass fraction of 8% was added, and the solution was stirred at a speed of 260 r / min for 42 min to obtain a mixed solution; after the pH of the mixed solution was adjusted to 3, the product was precipitated, and the co-catalyst was obtained after washing and filtering;

[0077] (3) Preparation of catalyst: preheat 39 kg of silane coupling agent KH-791 to 59° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 280 r / min for 31 min to obtain mixture A; add 5 kg of triphenylphosphine mixed with a promoter to mixture A in three portions, stirring at a speed of 280 r / min, with an interval of 12 min between each addition, to obtain a catalyst.

[0078] (4) The above catalyst was applied to the Krebs 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 by Krebs reaction, comprising the following steps:

[0082] Step S1: Krebs reaction;

[0083] First, 180 kg of solid sodium ethoxide is put into a reactor, and then 175 kg of methyl methoxyacetate and 260 kg of diethyl oxalate are put into the reactor, and the reaction is carried out for 3 hours, and the temperature is controlled at 60°C. After the reaction is completed, 190 kg of trichloroethylene is added, stirred and diluted, and then 400 kg of water and 200 kg of 30% hydrochloric acid are added to adjust the pH value to 2.0, and trichloroethylene is separated. The water layer is extracted with trichloroethylene for 6 times, and the trichloroethylene solvent is recovered. Finally, the internal temperature is controlled to 100°C, and the decarbonylation is carried out for 5 hours at an internal temperature of 170°C and a vacuum state, and then the vacuum distillation is carried out, and the vacuum degree is ≥-0.095 MPa and the internal temperature is ≤250°C to obtain 200 kg of methyl ethyl methoxymalonate;

[0084] Step S2: cyclization reaction;

[0085] First, 1000 kg of sodium methoxide is put into a reaction pot, 1.5 kg of silica-alumina catalyst is added, and the mixture is heated to 50°C with stirring, and 350 kg of formamide and 200 kg of methyl ethyl methoxymalonate are added. After the addition is completed, the mixture is kept warm for 3 hours at a pressure of 2.5 MPa. After the heat preservation is completed, methanol is recovered until no liquid is discharged, and then 600 kg of water is added. The mixture is cooled to 15°C, and the mixture begins to be discharged. The mixture is centrifugally dehydrated and dried. The wet product is dried under reduced pressure by rotary drying at a drying temperature of 100°C and a vacuum degree of ≥-0.08 MPa. The mixture is dried for 10 hours and dried to obtain 280 kg of 5-methoxy-4,6-dihydroxypyrimidine disodium.

[0086] Step S3: chlorination reaction;

[0087] First, add 1000 kg of dichloromethane to 280 kg of 5-methoxy-4,6-dihydroxypyrimidine disodium, stir at 20 ° C for 1 hour, cool to 0 ° C, slowly add 800 kg of phosphorus oxychloride and 160 kg of N, N-dimethylaniline, control the temperature below 10 ° C, heat to reflux for 1 hour to evaporate the dichloromethane, pour the residue into 3000 kg of ice water, stir for 1 hour, filter and recrystallize with ethanol to obtain 182 kg of product.

[0088] The obtained 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 measured, and the yield was 46%.

[0090] Comparative Example 4

[0091] The difference from Example 3 is that in step 1, the spherical alumina is not subjected to vacuum precooling and pressure reduction cooling treatment in a vacuum precooler; the measured yield is 59%.

[0092] In summary, the present invention uses modified triphenylphosphine as the main catalytic active ingredient, obtains a co-catalyst by reacting lignin and K2S2O8 in an alkaline solution, and composites the above two raw materials on a spherical alumina carrier under the action of a silane coupling agent, thereby obtaining a catalyst for preparing 5-methoxy-4,6-dichloropyrimidine by Krzalkin reaction. Compared with the prior art, the yield of 5-methoxy-4,6-dichloropyrimidine is effectively improved; and the reaction time of three hours in the original step is shortened to one hour, thereby greatly improving the production efficiency.

[0093] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements 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 catalyst for preparing 5-methoxy-4,6-dichloropyrimidine by Krebs reaction, characterized in that: It includes modified triphenylphosphine, a co-catalyst, a silane coupling agent, and a spherical alumina carrier; The co-catalyst comprises the following raw materials: 3-5 parts of lignin, 25-36 parts of NaOH solution and 7-8 parts of K2S2O8 solution.

2. A method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction as claimed in claim 1, characterized in that: The following steps are involved: Step 1: preparing a spherical alumina carrier; A. Mixing pseudo-boehmite with nitric acid to form a uniform sol solution; B. Dropping the sol solution into the oil-salt column to form spherical alumina; C. The spherical alumina is subjected to vacuum cooling and pressure reduction in a vacuum precooler, and the cooling temperature is 0-2°C; D. washing, drying and calcining the spherical alumina to obtain a spherical alumina carrier; Step 2: preparing modified triphenylphosphine; A. Dissolve potassium difluorobromoacetate in water to form a potassium difluorobromoacetate solution, heat the solution to 55-68°C, add triphenylphosphine, heat to 80-85°C, and stir for 20-30 minutes while heating; B. Add benzene, shake thoroughly, dissolve unreacted triphenylphosphine in benzene, extract benzene, concentrate the remaining liquid to crystallize solid, centrifuge and dry to obtain modified triphenylphosphine; Step 3: preparing a co-catalyst; A. Dissolve lignin in NaOH solution, and introduce nitrogen gas to exhaust air at 70-80°C in a dark environment, then add 7-8 parts of K2S2O8 solution, and stir at 200-300r / min for 40-50min to obtain a mixed solution; B. After the pH of the mixed solution is adjusted to acidic, the product is precipitated, and the co-catalyst is obtained after washing and filtering; Step 4: preparing a catalyst; A. Preheat the silane coupling agent to 55-63° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 200-300 r / min for 25-35 min to obtain a mixture A; B. Add modified triphenylphosphine mixed with a promoter to mixture A in 2-3 portions, stirring at a speed of 200-300 r / min, with an interval of 10-15 minutes between each addition, to obtain a catalyst.

3. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 2, characterized in that: In step one, step A specifically comprises: mixing 8-12 parts of pseudo-boehmite with 25-34 parts of nitric acid to form a uniform sol solution.

4. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 3, characterized in that: In step 2, step A is specifically as follows: 5-8 parts of potassium difluorobromoacetate are dissolved in 45-56 parts of water to form a potassium difluorobromoacetate salt solution, the solution is heated to 55-68° C., 4-6 parts of triphenylphosphine are added, the temperature is raised to 80-85° C., and the temperature is raised while stirring at a speed of 200-300 r / min for 20-30 min.

5. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 4, characterized in that: In step 2, step B is specifically as follows: adding 30-48 parts of benzene, shaking sufficiently, dissolving unreacted triphenylphosphine in benzene, extracting benzene, concentrating the remaining liquid to crystallize solid, centrifuging and drying to obtain modified triphenylphosphine.

6. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 5, characterized in that: In step three, step A is specifically as follows: dissolve 3-5 parts of lignin in 25-36 parts of NaOH solution with a pH of 9-10, introduce nitrogen until the air is exhausted under light-proof conditions and a constant temperature of 70-80°C, then add 7-8 parts of K2S2O8 solution with a mass fraction of 5-10%, stir and react at a speed of 200-300r / min for 40-50min to obtain a mixed solution.

7. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 6, characterized in that: In step 4, step A is specifically as follows: preheat 32-48 parts of silane coupling agent to 55-63° C. and keep warm, add the spherical alumina carrier prepared in step 1, and stir at a speed of 200-300 r / min for 25-35 min to obtain mixture A.

8. The method for preparing a catalyst for 5-methoxy-4,6-dichloropyrimidine by Krebs reaction according to claim 7, characterized in that: The silane coupling agent is KH-570 or KH-791.