Synthesis method of 2, 4-dichlorobutanone

Abstract

The invention belongs to the technical field of pesticide bactericides, and particularly relates to a synthetic method of 2, 4-dichlorobutanone, which comprises the following three steps: S1, preparing an intermediate acetal; s2, preparation of intermediate phospholipid; and S3, preparation of the 2, 4-dichlorobenzene butanone. According to the invention, the use of butyryl chloride is completely abandoned, the generation of high-risk processes and highly toxic byproducts is eliminated from the source, the production safety is remarkably improved, meanwhile, the intermediate separation step is reduced, the equipment investment and energy consumption are reduced, the use of high-risk chemicals such as triphosgene and thionyl chloride is avoided, and the production cost is reduced. The method has the advantages that the safety of the production process is further improved, only by-products (such as ethanol, water and the like) easy to treat are generated in the reaction process, the treatment cost is reduced, no malodorous gas is discharged, the environment of the production field is greatly improved, and the requirements of green chemistry and sustainable development are met.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide fungicides, and particularly relates to a method for synthesizing 2,4-dichlorobutyrophenone. Background Art

[0002] As an important chemical intermediate, 2,4-dichlorobutyrophenone has a wide range of applications in pesticide fungicides, particularly as a key raw material for the synthesis of the triazole fungicide penconazole. With its high efficacy and low toxicity, penconazole is highly effective in controlling pathogens of the Powdery Mildew family, Venturia, and other pathogenic Ascomycetes, Basidiomycetes, and Deuteromycetes on crops such as pumpkins, grapes, pome fruits, and vegetables.

[0003] The synthesis method of penconazole is disclosed in patent CN102584726A - a method for preparing the fungicide penconazole. 2,4-dichlorobutyrophenone is used as a raw material and is synthesized through Darzen condensation, potassium borohydride reduction, esterification, and synthesis. The reaction route is as follows: ; Therefore, the research on the synthesis method of 2,4-dichlorobutyrophenone has always been a hot topic in the chemical industry.

[0004] Currently, the synthesis of 2,4-dichlorobutyrophenone primarily relies on n-butyric acid as a raw material, through chlorination and acylation steps. Specifically, a common method involves chlorinating n-butyric acid with thionyl chloride or solid phosgene to produce butyryl chloride, which is then reacted with m-dichlorobenzene in a Friedel-Crafts acylation reaction to produce 2,4-dichlorobutyrophenone. However, this synthetic route presents significant safety and environmental concerns.

[0005] There are two routes to synthesize butyryl chloride: Route 1: For example, patent CN102199083A - A chemical synthesis method for n-butyryl chloride, wherein n-butyric acid and bis(trichloromethyl) carbonate are phosgenated at 50-100°C in the presence of an organic amine to produce n-butyryl chloride with a yield of 89.2% and a content of 98.7%. The reaction route is as follows: ; This route requires solid phosgene and produces highly toxic phosgene during the reaction, posing a significant occupational health and safety risk. The phosgenation reaction is a high-risk process, and the use of malodorous n-butyric acid creates a poor production environment. Route 2: As described in "Synthesis of Butyryl Chloride" published by Tian Yuan, Li Cunxi, Wang Liye et al., thionyl chloride is slowly added dropwise to butyric acid at 60°C under the catalysis of caprolactam to carry out a chlorination reaction to prepare butyryl chloride with a yield of 75.8%. The reaction route is as follows: ; This route uses thionyl chloride for chlorination, which is a high-risk process. It also uses butyric acid with a foul odor, and the production site environment is poor.

[0006] The synthesis route for 2,4-dichlorobutyrophenone, as described in "Research on the Synthesis of 2,4-Dichlorobutyrophenone" published by Wu Xiang, Ma Yong, Yang Zhenyu, et al., involves a Friedel-Crafts acylation reaction of m-dichlorobenzene with butyryl chloride in the presence of aluminum chloride to produce 2,4-dichlorobutyrophenone in a yield of 94.4%. The reaction route is as follows: ; This route uses butyryl chloride and m-dichlorobenzene to carry out a Friedel-Crafts acylation reaction. The by-product is hydrochloric acid gas, which carries some butyryl chloride. After being absorbed by water, the by-product hydrochloric acid is obtained. The by-product hydrochloric acid contains butyric acid with a foul odor, making the by-product hydrochloric acid extremely difficult to handle and the processing cost is high.

[0007] Prior art research addresses the problems associated with the synthesis of 2,4-dichlorobutyrophenone, such as patent CN103304394A, a method for synthesizing 2,4-dichlorobutyrophenone. This method uses m-dichlorobenzene as a raw material, catalyzed by a supported acid catalyst, and then reacts with butyryl chloride to produce 2,4-dichlorobutyrophenone. While this method improves catalyst reusability and raw material utilization, reducing environmental pollution, it still relies on butyryl chloride as a key intermediate, failing to completely address raw material toxicity and byproduct disposal issues, nor does it completely eliminate the high-risk process and foul odor. Therefore, a new technical solution is needed to address these technical issues. Summary of the Invention

[0008] The object of the present invention is to provide a method for synthesizing 2,4-dichlorobutyrophenone, so as to solve the problems raised in the above-mentioned background art that the current 2,4-dichlorobutyrophenone synthesis process still relies on butyryl chloride as a key intermediate, fails to completely solve the problems of raw material toxicity and by-product disposal, and also fails to completely get rid of the high-risk process and foul odor.

[0009] To achieve the above object, the present invention provides the following technical solution: a method for synthesizing 2,4-dichlorobutyrophenone, comprising the following specific steps: S1. Using 2,4-dichlorobenzaldehyde as a starting material, dissolving it in anhydrous ethanol and reacting it with triethyl orthoformate at 40-50° C. for 5-7 hours under the action of p-toluenesulfonic acid to generate an intermediate acetal, wherein the molar ratio of 2,4-dichlorobenzaldehyde to triethyl orthoformate is 1:1.02-1.05, and the weight ratio of 2,4-dichlorobenzaldehyde to anhydrous ethanol is 1:3-5; S2. Dissolving the intermediate acetal obtained in S1 in dichloroethane and reacting it with triethyl phosphite in the presence of anhydrous aluminum chloride to produce an intermediate phospholipid, wherein the molar ratio of the intermediate acetal to triethyl phosphite and anhydrous aluminum chloride is 1:1.05-1.08:1.09-1.15, the weight ratio of 2,4-dichlorobenzaldehyde to dichloroethane is 1:4-6, the reaction temperature is 0-10°C, and the reaction time is 4-6 hours; S3. Condensing the intermediate phospholipid obtained in S2 with propionaldehyde under the condition of sodium methoxide and then hydrolyzing with 30% sulfuric acid to obtain 2,4-dichlorobutyrophenone, wherein the molar ratio of the intermediate phospholipid to propionaldehyde, sodium methoxide and 30% sulfuric acid is 1:1.1-1.2:1.25-1.35:1.5-1.8, the condensation reaction temperature is 50-60°C for 7-9 hours, and the hydrolysis temperature is 80°C for 6-8 hours; Its synthetic route is as follows: .

[0010] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention uses 2,4-dichlorobenzaldehyde as a starting material and directly synthesizes the target product through a three-step reaction of acetalization, phospholipidation, and condensation hydrolysis. The use of butyryl chloride is completely abandoned, and the generation of high-risk processes and highly toxic by-products is eliminated at the source, significantly improving production safety. At the same time, the intermediate separation step is also reduced, reducing equipment investment and energy consumption. On this basis, odorless and relatively safe raw materials (such as 2,4-dichlorobenzaldehyde, triethyl orthoformate, triethyl phosphite, etc.) are selected, effectively avoiding the use of high-risk chemicals such as solid phosgene and dichloride, further improving the safety of the production process. In addition, only easily handled by-products (such as ethanol and water) are generated during the reaction, reducing treatment costs. At the same time, no odorous gas is emitted, significantly improving the production site environment, and meeting the requirements of green chemistry and sustainable development. 2. The present invention optimizes the material ratio to ensure sufficient contact and efficient conversion between reactants, effectively improves the selectivity and yield of the reaction, helps reduce the formation of by-products, and thus improves the purity of the target product. On this basis, by specifying the reaction conditions of each step (including temperature, pressure, time, etc.), it helps to reduce errors in the operation process, improve the consistency of product quality, and further improve the yield of the product. At the same time, it also reduces the use of harmful solvents and reduces environmental pollution. As a result, the synthesis method of 2,4-dichlorobutyrophenone has a high degree of controllability and repeatability, which is conducive to the stable implementation of industrial production. 3. The present invention first heats up the atmospheric distillation and then switches to negative pressure distillation, and gradually cools down to a low temperature for insulation, which helps to stably generate the intermediate acetal and efficiently carry out the subsequent reactions. Through specific temperature control, the condensation reaction of the intermediate phospholipid and propionaldehyde and the subsequent hydrolysis reaction are promoted, effectively avoiding the use of high-risk chemicals and highly toxic substances, improving the safety of the production process, and also improving the utilization rate of raw materials and reducing production costs. On this basis, by precisely controlling the material ratio, the yield of 2,4-dichlorobutyrophenone reaches more than 92%, and its content can reach more than 99%. Compared with the existing synthesis process, it has more market value, helps to increase the economic benefits of the enterprise, and meets the synthesis demand of high-quality pesticide fungicide penconazole; 4. The 2,4-dichlorobutyrophenone synthesized by the present invention can be directly used in the preparation process of penconazole. Due to its high purity, it can effectively improve the total yield of penconazole synthesis while reducing the interference of impurities on subsequent reactions, which has significant industrial chain synergistic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 The chromatogram and analysis results table of the intermediate acetal of the present invention; Figure 2 The chromatogram and analysis results table of the intermediate phospholipid of the present invention; Figure 3 The chromatogram and analysis result table of 2,4-dichlorobutyrophenone of the present invention are shown. DETAILED DESCRIPTION

[0012] The following examples are used to further illustrate the present invention but are not intended to limit its application. Example 1:

[0013] This embodiment provides a method for synthesizing 2,4-dichlorobutyrophenone, and the specific steps are as follows: In a dry and clean synthesis reactor, add 175kg of 2,4-dichlorobenzaldehyde, 1.75kg of p-toluenesulfonic acid, and 525kg of anhydrous ethanol. Heat to 40-50°C, add 151kg of triethyl orthoformate dropwise, and keep at 40-50°C for 5 hours. Take a sample and test if 2,4-dichlorobenzaldehyde is ≤0.5%. Heat and distill at normal pressure to 100°C, then switch to negative pressure -0.098MPa and distill to 100°C. Cool to 30-40°C and add 700kg of dichloroethane. , 174.3kg of triethyl phosphite, cooled to 0-10℃, added 145.5kg of anhydrous aluminum chloride, kept at 0-10℃ for 4 hours, sampled and tested the intermediate ketal content ≤0.5%, qualified, the materials in the synthesis kettle were added dropwise to the hydrolysis kettle, 534kg of 0-5℃ water was prepared in advance in the hydrolysis kettle, after the addition was completed, the lower organic layer was separated and added to the condensation kettle, first distilled to 100℃ at normal pressure, then distilled to 100℃ at negative pressure of -0.098MPa, cooled to 60℃, added DMF875kg, propionaldehyde 63.8kg, cool to 5-10℃, add 67.5kg sodium methoxide, slowly heat to 50-60℃ and keep warm for 7 hours, take samples to test the intermediate phospholipid content ≤0.5% qualified, vacuum evaporate DMF-0.098MPa to 120℃, cool to 80℃, add 700kg toluene, 350kg water, heat to 50-60℃, stir and wash for 2 hours, let stand and separate, the upper organic layer remains in the condensation kettle, add 490% 30% sulfuric acid kg, heated to 80 ° C for 6 hours, allowed to stand and separate, the toluene layer was then washed with 350 kg of water at 50-60 ° C with stirring, allowed to stand and separate, the toluene layer was heated and distilled to 120 ° C at normal pressure, and then distilled to 120 ° C at a negative pressure of -0.098 MPa, switched to high vacuum (100 Pa) distillation, the bottom temperature of the kettle reached 140 ° C, the gas phase temperature reached 108 ° C, stopped distillation, cooled, and received 201.66 kg of 2,4-dichlorobutyrophenone with a content of 99.1% and a yield of 92.09%. Example 2:

[0014] This embodiment provides a method for synthesizing 2,4-dichlorobutyrophenone, and the specific steps are as follows: In a dry and clean synthesis reactor, add 175kg of 2,4-dichlorobenzaldehyde, 3.5kg of p-toluenesulfonic acid, and 875kg of anhydrous ethanol. Heat to 40-50°C, add 155.4kg of triethyl orthoformate dropwise, and keep at 40-50°C for 7 hours. Take samples for testing and find that 2,4-dichlorobenzaldehyde is ≤0.5%. Heat and distill at normal pressure to 100°C, then switch to negative pressure -0.098MPa and distill to 100°C. Cool to 30-40°C and add 1050kg of dichloroethane. , 179.3kg of triethyl phosphite, cooled to 0-10℃, added 153.5kg of anhydrous aluminum chloride, kept at 0-10℃ for 6 hours, sampled and tested the intermediate ketal content ≤0.5%, qualified, the materials in the synthesis kettle were added dropwise to the hydrolysis kettle, and 667.5kg of 0-5℃ water was prepared in advance in the hydrolysis kettle. After the addition was completed, the lower organic layer was separated and added to the condensation kettle, first distilled to 100℃ at normal pressure, then distilled to 100℃ at negative pressure of -0.098MPa, cooled to 60℃, and added DMF1225kg, propionaldehyde 69.6kg, cool to 5-10℃, add 72.9kg sodium methoxide, slowly heat to 50-60℃ and keep warm for 9 hours, take samples to test the intermediate phospholipid content ≤0.5% qualified, vacuum evaporate DMF-0.098MPa to 120℃, cool to 80℃, add 1050kg toluene, 525kg water, heat to 50-60℃, stir and wash for 2 hours, let stand and separate, the upper organic layer is left in the condensation kettle, add 30% sulfuric acid 588 kg, heated to 80 ° C for 8 hours, allowed to stand and separate, the toluene layer was then washed with 525 kg of water at 50-60 ° C with stirring, allowed to stand and separate, the toluene layer was heated and distilled to 120 ° C at normal pressure, and then distilled to 120 ° C at a negative pressure of -0.098 MPa, switched to high vacuum (100 Pa) distillation, the bottom temperature of the kettle reached 140 ° C, the gas phase temperature reached 108 ° C, stopped distillation, cooled, and received 201.22 kg of 2,4-dichlorobutyrophenyl ketone with a content of 99.05% and a yield of 91.85%. Example 3:

[0015] This embodiment provides a method for synthesizing 2,4-dichlorobutyrophenone, and the specific steps are as follows: In a dry and clean synthesis reactor, 175 kg of 2,4-dichlorobenzaldehyde, 2.1 kg of p-toluenesulfonic acid, and 550 kg of anhydrous ethanol were added, and the temperature was raised to 40-50 ° C. 152 kg of triethyl orthoformate was added dropwise, and the temperature was kept at 40-50 ° C for 6 hours. Samples were taken for testing, and the 2,4-dichlorobenzaldehyde content was ≤0.5%. The temperature was raised and distilled to 100 ° C at normal pressure, and then the pressure was changed to -0.098 MPa and distilled to 100 ° C. The temperature was lowered to 30-40 ° C, and 850 kg of dichloroethane was added. g, 175kg of triethyl phosphite, cooled to 0-10℃, added 149.2kg of anhydrous aluminum chloride, kept at 0-10℃ for 5 hours, sampled and tested the intermediate ketal content ≤0.5%, qualified, the materials in the synthesis kettle were added dropwise to the hydrolysis kettle, 599kg of 0-5℃ water was prepared in advance in the hydrolysis kettle, after the addition was completed, the lower organic layer was separated and added to the condensation kettle, first distilled to 100℃ at normal pressure, then distilled to 100℃ at -0.098MPa under negative pressure, cooled to 60℃, added DMF900kg, propionaldehyde 65kg, cool to 5-10℃, add 69kg sodium methoxide, slowly heat to 50-60℃ and keep warm for 8 hours, take samples to test the intermediate phospholipid content ≤0.5% qualified, vacuum evaporate DMF-0.098MPa to 120℃, cool to 80℃, add 800kg toluene and 400kg water, heat to 50-60℃, stir and wash for 2 hours, let stand and separate, the upper organic layer remains in the condensation kettle, add 30% sulfuric acid 520kg, The temperature was raised to 80°C for reaction for 7 hours, and the mixture was allowed to stand for stratification. The toluene layer was then washed with 400 kg of water at 50-60°C with stirring, and the mixture was allowed to stand for stratification. The toluene layer was heated and distilled to 120°C at normal pressure, and then distilled to 120°C at a negative pressure of -0.098 MPa. High vacuum (100 Pa) distillation was switched. The bottom temperature of the kettle reached 140°C, and the gas phase temperature reached 108°C, and the distillation was stopped. The temperature was lowered to receive 202.05 kg of 2,4-dichlorobutyrophenone with a content of 99.15% and a yield of 92.32%. Example 4:

[0016] This embodiment provides a method for synthesizing 2,4-dichlorobutyrophenone, and the specific steps are as follows: In a dry and clean synthesis reactor, 175 kg of 2,4-dichlorobenzaldehyde, 3 kg of p-toluenesulfonic acid, and 800 kg of anhydrous ethanol were added, the temperature was raised to 40-50 ° C, 154 kg of triethyl orthoformate was added dropwise, and the temperature was kept at 40-50 ° C for 6 hours. The sample was tested for 2,4-dichlorobenzaldehyde ≤ 0.5% and qualified (the chromatogram and analysis results of the intermediate acetal generated in this example are shown in the table below). Figure 1As shown), heat and distill at normal pressure to 100℃, then switch to negative pressure -0.098MPa and distill to 100℃, cool to 30-40℃, add 1000kg of dichloroethane and 178kg of triethyl phosphite, cool to 0-10℃, add 152kg of anhydrous aluminum chloride, keep at 0-10℃ for 5 hours, take samples to detect the content of intermediate ketal ≤0.5%, if qualified, add the materials in the synthesis kettle dropwise to the hydrolysis kettle, which is prepared in advance with 660kg0- 5 ℃ water, after the addition is complete, the lower organic layer is separated and put into the condensation kettle, first distilled to 100 ℃ at atmospheric pressure, then distilled to 100 ℃ under negative pressure of -0.098MPa, cooled to 60 ℃, added DMF1150kg, propionaldehyde 69kg, cooled to 5-10 ℃, added sodium methoxide 71.5kg, slowly heated to 50-60 ℃ and kept warm for 8 hours, and the intermediate phospholipid content is sampled and tested to be ≤0.5% qualified (the intermediate phospholipid chromatogram and analysis results generated in this embodiment are shown in the table below). Figure 2 As shown), DMF was evaporated at a pressure of -0.098 MPa to 120°C, cooled to 80°C, 1000 kg of toluene and 500 kg of water were added, the temperature was raised to 50-60°C, stirred and washed for 2 hours, allowed to stand and delaminate, the upper organic layer was left in the condensation kettle, 580 kg of 30% sulfuric acid was added, the temperature was raised to 80°C and the reaction was carried out for 7 hours, allowed to stand and delaminate, the toluene layer was then washed with 500 kg of water at 50-60°C and stirred, allowed to stand and delaminate, the toluene layer was heated and distilled at atmospheric pressure to 120°C, then distilled to 120°C at a pressure of -0.098 MPa, switched to high vacuum (100 Pa) distillation, the bottom temperature of the kettle reached 140°C, the gas phase temperature reached 108°C, the distillation was stopped, the temperature was lowered, and 200.93 kg of 2,4-dichlorophenyl ketone was received, the content was 99.23%, and the yield was 91.88% (the chromatogram and analysis results of 2,4-dichlorophenyl ketone synthesized in this embodiment are shown in the table below). Figure 3 shown).

Claims

1. A method for synthesizing 2,4-dichlorobutyrophenone, characterized in that: The specific steps are as follows: S1. 2,4-dichlorobenzaldehyde is used as the starting material, dissolved in anhydrous ethanol and reacted with triethyl orthoformate under the action of p-toluenesulfonic acid to form an intermediate acetal; S2, dissolving the intermediate acetal obtained in S1 in dichloroethane and reacting it with triethyl phosphite in the presence of anhydrous aluminum chloride to produce an intermediate phospholipid; S3, condensing the intermediate phospholipid obtained in S2 with propionaldehyde under the condition of sodium methoxide and then hydrolyzing with 30% sulfuric acid to obtain 2,4-dichlorobutyrophenone; Its synthetic route is as follows: 。 2. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S1, the molar ratio of 2,4-dichlorobenzaldehyde to triethyl orthoformate is 1:1.02-1.

05.

3. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that, In S1, the weight ratio of 2,4-dichlorobenzaldehyde to anhydrous ethanol is 1:3-5.

4. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S1, the reaction temperature is 40 to 50°C, and the reaction time is 5 to 7 hours.

5. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that, In S2, the molar ratio of the intermediate acetal to triethyl phosphite and anhydrous aluminum chloride is 1:1.05-1.08:1.09-1.

15.

6. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that, In S2, the weight ratio of 2,4-dichlorobenzaldehyde to dichloroethane is 1:4-6.

7. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S2, the reaction temperature is 0 to 10°C, and the reaction time is 4 to 6 hours.

8. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S3, the molar ratio of the intermediate phospholipid to propionaldehyde, sodium methoxide and 30% sulfuric acid is 1:1.1-1.2:1.25-1.35:1.5-1.

8.

9. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S3, the condensation reaction temperature is 50 to 60° C., and the condensation reaction time is 7 to 9 hours.

10. A method for synthesizing 2,4-dichlorobutyrophenone according to claim 1, characterized in that: In S3, the hydrolysis reaction temperature is 80° C., and the hydrolysis reaction time is 6 to 8 hours.

Images