Synthesis process of chlorbenzuron

Abstract

The invention relates to a synthesis process of chlorbenzuron, which comprises the following steps: 1) reacting o-chlorobenzamide with triphosgene in the presence of an organic solvent and a catalyst to prepare o-chlorobenzoyl isocyanate; and 2) carrying out a reaction on the o-chlorobenzoyl isocyanate and parachloroaniline to prepare the chlorbenzuron as shown in a formula IV. According to the method disclosed by the invention, the catalyst is added, so that the reaction activation energy can be effectively reduced, the reaction can be carried out under relatively mild conditions, meanwhile, the reaction yield and the product purity are improved, and industrial production is facilitated.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a chlorbenzuron synthesis process. BACKGROUND

[0002] Chlorbenzuron is a benzoyl urea insecticide, which has the characteristics of high efficiency, low toxicity, long residual period and no environmental pollution. As a chitin synthesis inhibitor, chlorbenzuron mainly affects the larvae of Lepidoptera and Diptera through stomach toxicity, and shows good insecticidal activity to Lepidoptera larvae, especially to Lepidoptera larvae. Chlorbenzuron is widely used in the prevention and control of peach leaf roller, tea black moth, tea looper, cabbage caterpillar, cabbage looper, wheat armyworm, corn borer and other Lepidoptera pests. In addition, it is also used for preventing and controlling onion and garlic vegetables, and toilet fly larvae and mosquito larvae in dead water.

[0003] CN101293858A discloses a chlorbenzuron synthesis method using phosgene as raw material. Phosgene is introduced into the toluene solution of p-chloroaniline to prepare p-chlorophenyl isocyanate, and then the p-chlorophenyl isocyanate is reacted with substituted formamides to prepare chlorbenzuron. The total yield of the two-step reaction is 82%, and the purity is greater than 95%. The reaction route is relatively cheap in raw materials, high in yield, and suitable for industrialization. The disadvantages are high reaction temperature and high toxicity of phosgene and isocyanate. The reaction formula is as follows:

[0004]

[0005] Hongyu Wang et al. (Chemcal Communications, 2018, 54(78), 10989) reported that chlorbenzuron compounds were prepared by oxidation reaction under the action of photosensitizer and blue light irradiation. The reaction condition is mild, but the cost of photosensitizer is high, the cost is high, and the yield of single-step reaction is only 62%. The reaction formula is as follows:

[0006]

[0007] In addition, benzoyl urea compounds can also be synthesized by reacting benzoyl isocyanate with substituted amine, such as the production route of fluazuron as follows:

[0008]

[0009] This reaction is a nucleophilic addition reaction, which is suitable for laboratory synthesis. Starting from benzamide, benzoyl isocyanate is generated by reacting with oxalyl chloride, and then nucleophilic addition reaction occurs with substituted aniline in an aprotic solvent to obtain the product. The reaction route has mild conditions and high yield, and basically all substituted anilines can react; the disadvantage is that benzoyl isocyanate is too active and can easily polymerize at room temperature and in air, so it should be prepared and used immediately, and it is not suitable for direct industrial production.

[0010] In view of the above-mentioned defects in the prior art, the present inventors provide a synthetic process of chlorbenzuron, which can greatly improve the yield of reaction and the purity of product, and has mild reaction conditions, cheap catalyst, and good industrial application value. SUMMARY

[0011] The present application aims to provide a synthetic process of chlorbenzuron to solve the technical problems of low reaction yield, harsh conditions and non-industrialization in the prior art.

[0012] In a first aspect, the present application provides a synthetic process of chlorbenzuron, which comprises the following steps: 1) reacting o-chlorobenzamide represented by Formula I with solid phosgene (BTC) in the presence of an organic solvent and a catalyst to obtain o-chlorobenzoyl isocyanate represented by Formula II;

[0013] 2) reacting o-chlorobenzoyl isocyanate represented by Formula II with p-chloroaniline represented by Formula III to obtain chlorbenzuron represented by Formula IV, and the reaction route is as follows:

[0014]

[0015] In step 1), the catalyst is selected from one or a combination of cuprous chloride, cuprous bromide and cuprous iodide.

[0016] Preferably, the organic solvent is selected from one or more of aliphatic, alicyclic and aromatic hydrocarbons such as petroleum ether, hexane, heptane, cyclohexane, toluene, xylene; ethers such as diethyl ether, dimethyl ether, tetrahydrofuran, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, alcohols such as methanol, ethanol, esters such as ethyl acetate, tert-butyl acetate. More preferably, the organic solvent is selected from one or more of toluene, xylene, methanol, ethanol, ethyl acetate.

[0017] Preferably, the amount of catalyst is 1-20 mol%, preferably 5-15 mol%, of the compound of Formula I.

[0018] Preferably, the reaction temperature of step 1) is 0-80°C, preferably 10-70°C, more preferably 40-60°C.

[0019] Preferably, the molar ratio of o-chlorobenzamide to solid phosgene in step 1) is 1:(0.2-1), preferably 1:(0.3-0.5), more preferably 1:0.4.

[0020] Preferably, the reaction time of step 1) is 1-12 hours, more preferably 2-8 hours, most preferably 3-4 hours.

[0021] Preferably, after the reaction of step 1) is completed, only the catalyst needs to be removed by filtration, and the solvent is removed under reduced pressure, and the next step reaction can be directly carried out.

[0022] Preferably, the amount of p-chloroaniline in step 2) is 0.8-1.2 times, preferably 0.9-1.1 times, the amount of o-chlorobenzamide in step 1) by molar ratio.

[0023] Preferably, the reaction condition of step 2) is heating reflux reaction.

[0024] Preferably, the reaction time of step 2) is 5-10 hours, preferably 6-8 hours.

[0025] Preferably, after the reaction of step 2) is completed, the following post-treatment steps are further included: cooling the reaction solution to room temperature, filtering, recrystallizing the filter cake, and drying to obtain chlorbenzuron.

[0026] Preferably, the recrystallization solvent is selected from acetone, isobutyl ketone.

[0027] The technical scheme of the present application has the following beneficial effects:

[0028] 1) The catalyst of the present application can effectively reduce the reaction activation energy, so that the reaction can be carried out under relatively mild conditions, saving production costs.

[0029] 2) The method of the present application improves the yield and purity of the product, which is beneficial to industrial production.

[0030] 3) Solid phosgene is safer than gaseous phosgene during storage and transportation due to its solid form, and the reaction operation is simple and convenient. DETAILED DESCRIPTION

[0031] The following detailed description will clearly and completely describe the technical scheme of the present application. Obviously, the described embodiments are part of the embodiments of the present application, but not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0032] Example 1

[0033] 1) In a three-necked flask equipped with a stirrer, a thermometer and a reflux condenser, 11.9 g (0.04 mol) of solid phosgene and 100 mL of dichloroethane were added and stirred to dissolve. Then 0.1 g of cuprous chloride was added, and a solution of 15.6 g (0.1 mol) of o-chlorobenzamide in 100 mL of dichloroethane was added dropwise into the reaction flask within 20 min, and the temperature was raised to 50°C, and the reaction was continued for 4 h. After the reaction was completed by TLC detection, it was cooled to room temperature, filtered, and the filtrate was removed under reduced pressure with an oil pump. The residue was used for the next step reaction.

[0034] 2) The residue of step 1 was dissolved in 100 ml dichloroethane, then added to a three-necked flask with stirring device, 14.0 g (0.1 mol) p-chloroaniline was added, heated to reflux, and kept for 7 hours. The reaction solution was cooled to 0-5 °C, filtered, and the filter cake was recrystallized with acetone to obtain 26.9 g chlorbenzuron crystal, melting point: 198-199 °C.

[0035] The total yield of two steps was 87.3%, and the content was 98.8% by HPLC internal standard method.

[0036] Example 2

[0037] 1) A three-necked flask was charged with 11.9 g (0.04 mol) of solid phosgene and 100 mL of toluene with stirring, temperature control and reflux condenser. Then 0.14 g of cuprous bromide was added, and 100 mL of dichloroethane solution of 15.6 g (0.1 mol) of o-chlorobenzamide was added dropwise into the reaction bottle within 20 min, and the temperature was raised to 60 °C, and the reaction was continued for 4 h. After cooling to room temperature, filtration was carried out, and the filtrate was desolventized under oil pump reduced pressure, and the residue was used for the next step reaction.

[0038] 2) The residue of step 1 was dissolved in 100 ml dichloroethane, then added to a three-necked flask with stirring device, 14.0 g (0.1 mol) p-chloroaniline was added, heated to reflux, and kept for 7 hours. The reaction solution was cooled to 0-5 °C, filtered, and the filter cake was recrystallized with acetone to obtain 26.9 g chlorbenzuron crystal, melting point: 198-199 °C.

[0039] The total yield of two steps was 87.3%, and the content was 98.8% by HPLC internal standard method.

[0040] Example 3

[0041] The difference from Example 1 is that the amount of solid phosgene in step 1) is 14.8 g (0.05 mol), and other conditions are the same as Example 1. The total yield of two steps is 88.2%, and the content is 97.3% by HPLC internal standard method.

[0042] Example 4

[0043] The difference from Example 1 is that the reaction temperature of step 1) is 40 °C, and other conditions are the same as Example 1. The total yield of two steps is 82.1%, and the content is 99.3% by HPLC internal standard method.

[0044] Comparative Example 1

[0045] The difference from Example 1 is that cuprous chloride catalyst was not added in step 1), while other conditions were the same as in Example 1. The results showed that the reaction in step 1) was difficult to proceed.

Claims

1. A process for synthesizing diflubenzuron, comprising the following steps: 1) reacting o-chlorobenzoamide of Formula I with solid phosgene (BTC) in the presence of an organic solvent and a catalyst to obtain o-chlorobenzoyl isocyanate of Formula II; 2) The o-chlorobenzoyl isocyanate shown in Formula II is reacted with p-chloroaniline shown in Formula III to prepare diflubenzuron shown in Formula IV. The reaction route is as follows: in: Step 1) The catalyst is selected from one or a combination of cuprous chloride, cuprous bromide, and cuprous iodide.

2. The method according to claim 1, characterized in that, Step 1) The organic solvent is selected from one or more aliphatic, alicyclic, and aromatic hydrocarbons.

3. The method according to claim 1 or 2, characterized in that, The amount of catalyst used is 1 mol% to 20 mol% of the compound of formula I.

4. The method according to claim 1 or 2, characterized in that, Preferably, the reaction temperature in step 1) is 40–60°C.

5. The method according to claim 1 or 2, characterized in that, In step 1), the molar ratio of o-chlorobenzamide to solid phosgene is 1:(0.2-1).

6. The method according to claim 1 or 2, characterized in that, The reaction time for step 1) is 2 to 8 hours.

7. The method according to claim 1 or 2, characterized in that, In step 2), the amount of p-chloroaniline fed is 0.8-1.2 times that of o-chlorobenzamide in step 1), expressed as a molar ratio.

8. The method according to claim 1 or 2, characterized in that, The reaction conditions for step 2) are heating and reflux reaction.

9. The method according to claim 1 or 2, characterized in that, The reaction time for step 2) is 5 to 10 hours.

10. The method according to claim 1 or 2, characterized in that, Step 2) After the reaction is complete, the following post-processing steps are also included: cool the reaction solution to room temperature, filter, recrystallize the filter cake, and dry to obtain diflubenzuron; The solvent for recrystallization is selected from acetone and isobutyl ketone.

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