Preparation method of 3, 6-dichloropyridazine

Abstract

The invention discloses a preparation method of 3, 6-dichloropyridazine, and belongs to the technical field of chemistry. According to the method, 3, 6-dihydroxypyridazine is used as a raw material, an organic solvent and triphenylphosphine oxide are combined to form a dichlorotriphenylphosphine intermediate state which is used as a chlorinating agent, dihydroxyl is substituted to generate 3, 6-dichloropyridazine, triphenylphosphine oxide and solid light are used as raw materials, heating reaction is performed to prepare 3, 6-dichloropyridazine, meanwhile, a one-pot method can be adopted in the two-step reaction, and operation is easy and convenient. The novel preparation method for synthesizing 3, 6-dichloropyridazine provided by the invention has the advantages of low raw material cost, high yield, high gas phase purity and no pollution, is suitable for industrial production, can meet industrial requirements, provides a new idea for later preparation of 3, 6-dichloropyridazine, has the remarkable advantages of high gas phase purity and high yield, and is suitable for industrial production. Wide application prospects are realized.

Description

Technical Field

[0001] This invention belongs to the field of chemical technology, specifically relating to a method for preparing 3,6-dichloropyridazine. Background Technology

[0002] 3,6-Dichloropyridazine is a nitrogen-containing heterocyclic compound with applications in multiple fields, particularly in pharmaceutical chemistry. It can be used to prepare drug molecules such as sulfachlorpyridazine, which are used as sulfonamide antibiotics in poultry farming.

[0003] The existing technologies disclose three main methods for synthesizing 3,6-dichloropyridazine: (1) Using 3,6-dihydroxypyridazine as raw material, chloroform as solvent, and phosphine oxychloride as chlorinating agent at 65℃ The method involves substituting trichlorfon to produce crude 3,6-dichloropyridazine, which is then purified by column chromatography with a yield of 87%. However, this method results in excessive trichlorfon, a large volume of acidic wastewater during post-treatment, and a high phosphorus content in the wastewater. It does not meet environmental protection requirements; other polymerization reactions can easily occur during the reaction, resulting in low yield and high risk; purification requires column chromatography, which consumes a large amount of silica gel, leading to high costs and a large amount of solid waste, making it unsuitable for industrial scale-up. Similar synthesis methods use phosphine trichloride, phosphine pentachloride, chlorine, thionyl chloride, etc., as chlorinating agents, and suffer from the same problems as above, including significant environmental pollution, high costs, and low yield.

[0004] (2) Using hydrochloric acid as a catalyst and N-chlorosuccinimide (NCS) as a chlorinating agent under relatively mild conditions. The reaction can proceed, but the impurity succinimide mentioned above easily forms salt with hydrochloric acid and precipitates out. As the reaction continues, hydrochloric acid, which acts as a catalyst, needs to be continuously added. The more salt precipitated, the worse the fluidity of the reaction solution becomes, which can easily lead to material encapsulation, incomplete reaction, and other side effects, resulting in a lower yield. At the same time, adding hydrochloric acid can easily lead to other polymerization reactions, further reducing the yield, making it unsuitable for industrial production.

[0005] (3) Using 3,6-dihydroxypyridazine as raw material, thionyl chloride as solvent, and curing agent as chlorinating agent, 4-dihydroxypyridazine... The method of using methylaminopyridine as a catalyst to replace the synthesis of 3,6-dichloropyridazine has a long reaction time, requires a large amount of solidification, and easily generates sulfur-containing wastewater and acid-containing wastewater during quenching, resulting in significant environmental pollution.

[0006] In summary, existing methods for synthesizing 3,6-dichloropyridazine suffer from problems such as high cost, numerous side effects, significant pollution, and low recovery rate. There is an urgent need for a simple, easy-to-implement, low-pollution, low-cost, and high-yield method for synthesizing 3,6-dichloropyridazine. Summary of the Invention

[0007] Based on the above requirements, the purpose of this invention is to provide a method for preparing 3,6-dichloropyridazine. Through single-factor experiments, a simple, safe, pollution-free, gas-phase pure, and high-yield synthesis process for 3,6-dichloropyridazine is obtained, which has important reference value for the industrial and large-scale production of 3,6-dichloropyridazine.

[0008] To achieve the above objectives, the present invention is implemented through the following solution: This invention provides a method for preparing 3,6-dichloropyridazine, the preparation method specifically including the following operations: (1) Dissolve the curing agent in an organic solvent to prepare a curing solution; (2) Mix triphenylphosphine oxide with an organic solvent as a base material, replace with nitrogen and protect with nitrogen, stir and set aside; (3) Add the solidification solution dropwise to the stirred base material. After the dropwise addition is complete, continue to maintain the temperature and stir. After stirring, heat the oil bath and keep it at the temperature to allow the reaction to proceed fully until no triphenylphosphine oxide raw material is detected in the gas chromatography control, and the reaction solution is obtained. (4) Heat the above reaction solution to the theoretical temperature in an oil bath and add 3,6-dihydroxypyridazine in batches; (5) After the material is added, keep it warm and stir to ensure a full reaction; (6) After the reaction is complete, stir and cool down. Filter the obtained reaction solution, recover the solvent from the filtrate, purify the filter cake and dry it to obtain pure 3,6-dichloropyridazine.

[0009] Furthermore, the organic solvent in step (1) or step (2) is at least one of dichloroethane, chloroform, chlorobenzene, and toluene.

[0010] Furthermore, in step (1), the mass ratio of the solidification agent to the organic solvent is 1:2-5.

[0011] Furthermore, in step (2), the mass ratio of triphenylphosphine oxide to organic solvent is 1:3-10.

[0012] Furthermore, the molar ratio of the triphenylphosphine oxide: solid light: 3,6-dihydroxypyridazine is 1-1.1:0.33-0.4:1.

[0013] Furthermore, in step (3), the temperature during the addition of the solidification solution is 15-30℃; the oil bath is heated to 45-55℃; and the reaction time is 2.5-3.5h.

[0014] Furthermore, the stirring time after the solidification solution is added in step (3) is 1-2 hours.

[0015] Furthermore, the batch feeding time in step (4) is 1-2 hours.

[0016] Furthermore, in step (4), the temperature is raised to the theoretical temperature of 60-90℃, and the time for holding and stirring is 2-3 hours.

[0017] Furthermore, in step (5), the temperature for heat preservation is 60-90℃, and the time for heat preservation and stirring is 1-3h.

[0018] Furthermore, in step (6), the temperature is cooled to 10-20°C by stirring.

[0019] Furthermore, in step (6), the filter cake purification solvent is methanol or ethanol, and the purification temperature is 10-40℃.

[0020] Furthermore, the optimized preparation method of 3,6-dichloropyridazine is as follows: the organic solvent is dichloroethane, the mass ratio of the solidification solution to the organic solvent is 1:2.0, the mass ratio of the triphenylphosphine oxide to the organic solvent is 1:5, the temperature at which the solidification solution is added is 15-20℃; the theoretical temperature in step (4) and the heat preservation temperature in step (5) are both 80℃; the purification solvent of the filter cake is methanol.

[0021] Furthermore, an optimized method for preparing 3,6-dichloropyridazine is described below: (1) Dissolve the solidifying agent in dichloroethane at a mass ratio of 1:2.0 to prepare a solidifying agent solution; (2) Triphenylphosphine oxide and dichloroethane are mixed as a base material with a mass ratio of 1:5. Nitrogen is used for purging and protection, and the mixture is stirred before use. (3) Add the curing solution dropwise to the stirred base material. The temperature of the curing solution during dropwise addition is 15-20℃. After the dropwise addition is completed, continue to maintain the temperature and stir for 1 hour. After stirring, heat the oil bath to 50℃ and keep it at the temperature for 3 hours to fully react and obtain the reaction solution. (4) Add 3,6-dihydroxypyridazine to the above reaction solution in batches. The addition time is 1 hour. The molar ratio of triphenylphosphine oxide: solid light: 3,6-dihydroxypyridazine is 1.05:0.37:1. (5) After the material is added, raise the temperature to 80°C and keep it at 80°C for 2 hours with stirring to ensure a full reaction; (6) After the reaction is complete, the mixture is stirred and cooled to 20°C and filtered. The crude filter cake obtained is pulped, filtered and dried in methanol solvent (10-20°C) to obtain pure 3,6-dichloropyridazine.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention does not use excessive amounts of acidic reagents such as phosphine oxychloride and thionyl chloride, and will not produce wastewater containing elements such as P and S, resulting in minimal pollution.

[0023] 2. The raw materials of this invention are readily available, there is no loss of triphenylphosphine oxide, and the reaction process only consumes solid light and 3,6-dichloropyridazine, resulting in low cost and suitability for industrial production.

[0024] 3. This invention is simple to operate and easy to implement, with good reaction selectivity and high yield. The 3,6-dichloropyridazine prepared after optimization has a gas phase purity of up to 98.9% and a yield of 94.8%, which has broad application prospects. Detailed Implementation

[0025] The following embodiments are for illustrative purposes only and are not intended to limit the technical solutions described in this invention. Although this specification has described the invention in detail with reference to the above embodiments, those skilled in the art should understand that they can still make modifications or equivalent substitutions to the invention, and all technical solutions and improvements that do not depart from the spirit and scope of the invention should be covered within the scope of the claims of this invention.

[0026] Unless otherwise specified, the experimental methods described in the embodiments are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0027] Example 1: Preparation of 3,6-dichloropyridazine 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and maintain the temperature while adding the solution. Add for 1 hour, then heat the oil bath to 50°C and keep it at that temperature for 3 hours. Gas chromatography detects no triphenylphosphine oxide raw material, and the reaction is complete, obtaining the reaction solution. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (10-20℃), slurried, filtered again to obtain pure product, and dried to obtain pure product A: 14.12g.

[0028] The gas phase purity of the pure product A is 98.9%, and the yield is 94.8%.

[0029] The synthetic route for the 3,6-dichloropyridazine is as follows:

[0030] .

[0031] Examples 2-9 are single-factor experiments conducted based on Example 1 to investigate the effects of the preparation process on the gas phase purity and yield of 3,6-dichloropyridazine. For details, please refer to the examples.

[0032] Example 2: Preparation of 3,6-dichloropyridazine by changing the temperature in step 3). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 45-50℃, add the curing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 2 hours. Gas chromatography showed no triphenylphosphine oxide raw material, indicating the reaction was complete and the reaction solution was obtained. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (10-20℃), slurried, filtered again, and dried to obtain 12.47g of pure product B.

[0033] The gas phase purity of the pure product B is 98.3%, and the yield is 83.7%.

[0034] Example 3: Preparation of 3,6-dichloropyridazine by changing the molar ratio of solidification to light. 1) Preparation of curing solution: Add 21.8g of dichloroethane and 9.79g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 3 hours to complete the reaction. Gas chromatography showed no triphenylphosphine oxide raw material, indicating the end of the reaction and the acquisition of the reaction solution. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (10-20℃), slurried, filtered again to obtain the pure product, and dried to obtain 12.99g of pure product C.

[0035] The gas phase purity of the pure product C is 98.9%, and the yield is 87.2%.

[0036] Example 4: Preparation of 3,6-dichloropyridazine by changing the organic solvent in step 1). 1) Preparation of curing solution: Add 21.8g of chlorobenzene and 10.89g of curing agent to a dry 50mL single-necked flask, stir. Stir to dissolve; 2) Add 124.2g of chlorobenzene and 29.22g of triphenylphosphine oxide to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 3 hours. Gas chromatography showed no triphenylphosphine oxide raw material, indicating the reaction was complete and the reaction solution was obtained. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (10-20℃), slurried, and filtered again to obtain pure product D: 12.71g.

[0037] The gas phase purity of the pure product D is 98.9%, and the yield is 85.3%.

[0038] Example 5: Preparation of 3,6-dichloropyridazine by changing the solvent ratio in step 2). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 270.4 g of dichloroethane and 29.22 g of triphenylphosphine oxide sequentially to a dry 250 mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 4 hours. Gas chromatography showed no triphenylphosphine oxide raw material, indicating the reaction was complete and the reaction solution was obtained. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 4.0 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (10-20℃), slurried, filtered again to obtain the pure product, and dried to obtain pure product E: 13.57g.

[0039] The gas phase purity of the pure product E is 98.9%, and the yield is 91.1%.

[0040] Example 6: 3,6-Dichloropyridazine was prepared by changing the feeding method of 3,6-dihydroxypyridazine in step 4). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, and add the light-fixing solution from step 1) dropwise over 1 hour. After the dripping is complete, the oil bath temperature is raised to 50°C, and the mixture is stirred while maintaining the temperature. Sampling is carried out under control, and the reaction is maintained at this temperature for 3 hours. Gas chromatography under control detects no triphenylphosphine oxide raw material. The reaction is then complete, and the reaction solution is obtained. 4) Heat the reaction solution to 80℃ in an oil bath and add 11.21g of 3,6-dihydroxypyridazine in one go; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 5 hours, then control the reaction in a central monitoring station until it is complete; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (15-20℃), slurried, filtered again, and dried to obtain 12.59g of pure product F.

[0041] The gas phase purity of the pure product F is 98.6%, and the yield is 84.5%.

[0042] Example 7: Preparation of 3,6-dichloropyridazine by changing the temperature of steps 4) and 5). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, and add the light-fixing solution from step 1) dropwise over 1 hour. After the dripping is complete, the oil bath temperature is raised to 50°C, and the mixture is stirred while maintaining the temperature. Sampling is carried out under control, and the reaction is maintained at this temperature for 3 hours. Gas chromatography under control detects no triphenylphosphine oxide raw material. The reaction is then complete, and the reaction solution is obtained. 4) Heat the reaction solution in an oil bath to 60℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, keep the mixture at 60℃ and stir for 6 hours to complete the reaction; 6) Stir the reaction solution and cool it to 20°C. Filter the solution, recover the solvent from the filtrate, and mix the filter cake with 20g of methanol (10-20°C) to form a slurry. Filter the slurry again to obtain pure product G: 12.50g.

[0043] The gas phase purity of the pure product G is 98.3%, and the yield is 83.9%.

[0044] Example 8: Preparation of 3,6-dichloropyridazine by changing the methanol usage temperature in step 6). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 3 hours. Gas chromatography showed no triphenylphosphine oxide raw material. 4) Heat the reaction solution to 80℃ in an oil bath, and add 11.21g of 3,6-dihydroxypyridazine in batches over a period of 1.0h. 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of methanol (30-40℃), slurried, filtered again to obtain the pure product, and dried to obtain pure product H: 13.15g.

[0045] The gas phase purity of the pure product H is 99.0%, and the yield is 88.3%.

[0046] Example 9: Preparation of 3,6-dichloropyridazine by changing the purification solvent in step 6). 1) Preparation of curing solution: Add 21.8g of dichloroethane and 10.89g of curing agent to a dry 50mL single-necked flask. Stir until dissolved; 2) Add 124.2g of dichloroethane and 29.22g of triphenylphosphine oxide sequentially to a dry 250mL three-necked flask. At room temperature (10-30℃), after nitrogen purging and nitrogen protection, start stirring; 3) Control the temperature inside the three-necked flask to 15-20℃, add the light-fixing solution from step 1), and continue adding for 1 hour. Afterwards, the oil bath temperature was raised to 50°C and kept at that temperature for 3 hours. Gas chromatography showed no triphenylphosphine oxide raw material, indicating the reaction was complete and the reaction solution was obtained. 4) Heat the reaction solution in an oil bath to 80℃, and add 11.21g of 3,6-dihydroxypyridazine in batches. The interval is 1.0h; 5) After feeding is complete, maintain the temperature at 80℃ and stir for 2 hours to complete the reaction; 6) Stir and cool the reaction solution obtained in step 5) to 20°C, filter, and recover the solvent from the filtrate. The filter cake was mixed with 20g of ethanol (10-20℃), slurried, filtered again to obtain pure product, and dried to obtain pure product I: 13.05g.

[0047] The gas phase purity of the pure product I is 98.9%, and the yield is 87.6%.

[0048] By combining the same preparation method with different factors in Examples 1-9, and observing the gas phase purity and yield of the prepared 3,6-dichloropyridazine, it can be seen that the 3,6-dichloropyridazine prepared by the method described in Example 1 has the best performance. This invention provides a method for preparing 3,6-dichloropyridazine with high gas phase purity and yield. The preparation process is simple, pollution-free, and low-cost, making it suitable for industrial production. The optimization of the synthesis method of 3,6-dichloropyridazine has reference value for energy saving, environmental protection, cost reduction and efficiency improvement in subsequent large-scale production.

[0049] The above embodiments are merely illustrative of the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions claimed by the present invention.

Claims

1. A method for preparing 3,6-dichloropyridazine, characterized in that, The preparation method specifically includes the following operations: (1) Dissolve the curing agent in an organic solvent to prepare a curing solution; (2) Mix triphenylphosphine oxide with an organic solvent as a base material, replace with nitrogen and protect with nitrogen, stir and set aside; (3) Add the solidification solution dropwise to the stirred base material. After the dropwise addition is complete, continue to maintain the temperature and stir. After stirring, heat the oil bath and keep it at the temperature to allow the reaction to proceed fully until no triphenylphosphine oxide raw material is detected in the gas chromatography control, and the reaction solution is obtained. (4) Heat the above reaction solution to the theoretical temperature in an oil bath and add 3,6-dihydroxypyridazine in batches; (5) After feeding is complete, keep the mixture warm and stir to ensure a full reaction; (6) After the reaction is complete, stir and cool down. Filter the obtained reaction solution, recover the solvent from the filtrate, purify the filter cake and dry it to obtain pure 3,6-dichloropyridazine.

2. The preparation method according to claim 1, characterized in that, The organic solvent in step (1) or step (2) is at least one of dichloroethane, chloroform, chlorobenzene and toluene.

3. The preparation method according to claim 1, characterized in that, In step (1), the mass ratio of solidification to organic solvent is 1:2-5.

4. The preparation method according to claim 1, characterized in that, In step (2), the mass ratio of triphenylphosphine oxide to organic solvent is 1:3-10.

5. The preparation method according to claim 1, characterized in that, The molar ratio of the triphenylphosphine oxide: solid light: 3,6-dihydroxypyridazine is 1-1.1:0.33-0.4:

1.

6. The preparation method according to claim 1, characterized in that, In step (3), the temperature during the addition of the solid solution is 15-30℃; the oil bath is heated to 45-55℃; and the reaction time is 2.5-3.5h.

7. The preparation method according to claim 1, characterized in that, In step (4), the oil bath is heated to the theoretical temperature of 60-90℃, and the time for batch feeding is 1-2 hours.

8. The preparation method according to claim 1, characterized in that, The temperature for heat preservation in step (5) is 60-90℃, and the time for heat preservation and stirring is 1-3h.

9. The preparation method according to claim 1, characterized in that, In step (6), the filter cake is purified by methanol or ethanol, and the purification temperature is 10-40℃.

10. The preparation method according to any one of claims 1-9, characterized in that, The optimized preparation method of 3,6-dichloropyridazine is as follows: the organic solvent is dichloroethane, the mass ratio of the solidification solution to the organic solvent is 1:2.5, the mass ratio of the triphenylphosphine oxide to the organic solvent is 1:5, the temperature of the solidification solution during dropwise addition is 15-20℃; the theoretical temperature in step (4) and the heat preservation temperature in step (5) are both 80℃; the purification solvent of the filter cake is methanol.

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