Preparation method of penconazole active compound

Abstract

The invention belongs to the technical field of pesticide chemistry, and particularly relates to a preparation method of a penconazole active compound, which comprises the following steps: by taking 2-(2, 4-dichlorophenyl) valeraldehyde and 1, 2, 4-triazole as starting raw materials, condensing and reducing under the action of a catalyst to obtain a penconazole crude product, and recrystallizing to obtain the penconazole active compound. Compared with the prior art, the penconazole active compound prepared by the invention has the advantages that the conversion rate of the raw materials is greatly improved, the problem that a derivative is generated by using potassium borohydride as a reducing agent is solved, so that the penconazole has atom economy and environmental protection property, the process flow is simpler, the operation steps of subsequent treatment and the use of a solvent are reduced, and the cost is reduced. The method is simple in operation and low in energy consumption, impurities in the penconazole preparation process are effectively removed, the purification rate and the yield of the penconazole technical are greatly improved, and the strict requirements for high-quality pesticides in agricultural production are met.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide chemistry, and particularly relates to a method for preparing penconazole technical. Background Art

[0002] Penconazole is a systemic triazole fungicide with protective, therapeutic and eradication effects. It is also a sterol demethylation inhibitor. It can be absorbed by crop roots, stems, leaves and other tissues and transmitted upward. The results of indoor activity determination and field efficacy tests show that it has a good control effect on grape white rot. Its chemical name: 1-[2-(2,4-dichlorophenyl)pentyl]-1H-1,2,4-triazole, CAS number: 66246-88-6.

[0003] At present, there are many synthetic processes for penconazole, such as Ge Zhongqun et al. Research on a new synthetic process for the fungicide penconazole. "Fine Chemical Intermediates". 2013, Vol. 43 (No. 3), 18-19, 32. and Wang Jin et al. Research on the synthetic process of penconazole. "Zhejiang Chemical Industry". 2006, Vol. 37 (No. 2), 2, 14. It is recorded that 2-(2,4-dichlorophenyl) valeraldehyde is used as the starting material, and penconazole technical is obtained through reduction, sulfonation and condensation. The sulfonation reaction in this process route requires the use of methylsulfonyl Chlorine is a highly toxic substance and poses a great safety hazard, making it very unsafe. Potassium borohydride is used as a reducing agent in the reduction process, which will produce potassium metaborate, which is not environmentally friendly. In order to avoid the use of the highly toxic substance methylsulfonyl chloride, concentrated sulfuric acid and 2-(2,4-dichlorophenyl)pentanol have been used to participate in the esterification reaction. Although this avoids the environmental problems caused by the use of the highly toxic substance methylsulfonyl chloride, the reaction has poor stability, low yield, low safety of raw and auxiliary materials, and the use of a more dangerous feeding method increases the probability of safety accidents, and the safety factor is low.

[0004] There are studies on a series of problems in the process of synthesizing penconazole in the prior art, such as patent application CN115626899A - a method for producing penconazole, which uses 2-(2,4-dichlorophenyl)pentanol as a raw material to obtain a finished penconazole product through bromination, condensation and purification, solving the problems of poor stability, low yield and low safety factor in the current process of synthesizing penconazole. However, although the existing penconazole production method can ensure the safety of penconazole synthesis, due to the relatively severe bromination reaction conditions, by-products are easily generated, and the conversion rate of the raw materials is difficult to be effectively improved, which seriously affects the subsequent treatment and purification rate of penconazole. Therefore, a new technical solution is needed to solve the above technical problems. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing penconazole technical, so as to solve the problem that the current penconazole production method proposed in the above background technology is difficult to effectively improve the conversion rate of raw materials, thereby seriously affecting the subsequent treatment and purification rate of penconazole.

[0006] To achieve the above object, the present invention provides the following technical scheme: a method for preparing penconazole technical, which uses 2-(2,4-dichlorophenyl)pentanal and 1,2,4-triazole as starting materials, first condenses and reduces under the action of a catalyst to obtain a crude penconazole product, and then recrystallizes to obtain the penconazole technical; The specific preparation steps are as follows: S1. Add 2-(2,4-dichlorophenyl)pentanal and 1,2,4-triazole into toluene, and carry out condensation reaction under the action of a catalyst at 112-114°C for 8-12 hours to obtain (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole. After the condensation reaction, the toluene needs to be removed and recovered at a temperature of ≤120°C / -0.095Mpa. The molar ratio of 1,2,4-triazole to 2-(2,4-dichlorophenyl)pentanal is 1.2-2:1, and the catalyst is p-toluenesulfonic acid and polyethylene glycol 600. The reaction equation is as follows: ; S2. Methanol is added to the (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole obtained in S1, and a reduction reaction is first performed under the action of hydrogen and a catalyst at 10-15°C for 2-6 hours to obtain a crude product of penconazole. After the reduction reaction is completed, the catalyst is removed by suction when the content of (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole is less than 0.5%, and then methanol is removed and recovered at a temperature of ≤80°C / -0.095Mpa, and then the original product of penconazole is obtained by recrystallization from n-hexane, wherein the catalyst is Pt / C, and the reaction equation is as follows: .

[0007] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention uses inexpensive and easily available 2-(2,4-dichlorophenyl)pentanal and 1,2,4-triazole as starting materials, effectively reducing the preparation cost, and then efficiently generates (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole intermediates through a retraction reaction under the action of a catalyst, greatly improving the conversion rate of the raw materials, and then obtains a crude penconazole product through a reduction reaction under the action of a catalyst and hydrogen, effectively avoiding the use of potassium borohydride as a catalyst. The problem of generating derivatives by reducing agents is solved, making penconazole more atom-economical and environmentally friendly. The relatively mild reaction conditions are used to effectively reduce the generation of by-products, thereby simplifying the process of penconazole, reducing the operation steps and solvent usage of subsequent treatments, and effectively reducing energy loss. The impurities in the preparation process of penconazole are effectively removed through the process of n-hexane recrystallization, which greatly improves the purification rate and yield of penconazole technical, meeting the strict requirements for high-quality pesticides in agricultural production; 2. The present invention uses p-toluenesulfonic acid and polyethylene glycol as catalysts for the condensation reaction, so that the conversion rate of the raw materials is effectively improved, thereby obtaining a high content of (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole intermediate, effectively improving the condensation recovery rate, and also effectively avoiding the safety problems caused by the use of highly toxic substances. Pt / C is used as a catalyst for the reduction reaction in combination with hydrogen as a reducing agent, which not only improves the conversion rate of the (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole intermediate, but also improves the reduction yield. At the same time, the process flow of penconazole is effectively simplified, the operation steps and solvent usage of subsequent treatments are reduced, the production efficiency is improved, the production cost is reduced, and the purification rate of penconazole technical is guaranteed; 3. The present invention adopts common and easily recyclable organic solvents (such as toluene, methanol, and n-hexane) as solvents for condensation, reduction, and recrystallization, so that there is no solvent residue in the obtained penconazole technical, thereby greatly improving the content of penconazole technical, effectively avoiding the generation of three wastes, reducing environmental pollution, conforming to the development trend of green chemistry, and providing a more efficient and environmentally friendly fungicide for agricultural production. DETAILED DESCRIPTION

[0008] The following examples are used to further illustrate the content of the present invention, but do not limit the application of the present invention. Embodiment 1:

[0009] In a 1000 ml four-necked flask, add 118 g of 98% 2-(2,4-dichlorophenyl)valeraldehyde and 42.3 g of 98% 1,2,4-triazole, and then add 1.0 g of p-toluenesulfonic acid and 600 g of polyethylene glycol. 1.0 g and 400 g toluene, then heated to 112-114°C and refluxed for dehydration until no water was removed, the reaction time was 10 hours, after the reaction was completed, the temperature was lowered to below 40°C, 200 g of water was added, stirred for 30 minutes, and allowed to stand for stratification, 200 g of water was added to the organic phase for washing once, the upper organic phase was taken, the temperature was raised and the pressure was reduced to recover toluene, the temperature was controlled to be ≤120°C / -0.095Mpa, and the temperature was lowered to 30°C after all the toluene was removed, to obtain 141.09 g of (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole, the content was 97%, and the condensation reaction yield was 97%; Then, 141.09 g of the above-obtained 97% (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole was added into a 1000 ml four-necked flask, and 400 g of methanol and 1.5 g of Pt / C (platinum carbon) catalyst were added. The temperature was controlled at 10-15°C, hydrogen was introduced, and the reaction was kept warm for 4 hours. Samples were taken for gas chromatography analysis. When the (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole content was <0. .5%, filter out the catalyst Pt / C, then heat and reduce pressure to recover methanol, control the temperature ≤80℃ / -0.095Mpa, after methanol recovery is completed, 141.44g of crude penconazole is obtained, the content is 95.5%, and the reduction reaction yield is 98%. Finally, the crude penconazole is added with 300g of n-hexane, recrystallized, and dried to obtain 137.90g of 98.5% penconazole technical, the recrystallization yield is 96.04%, and the total yield is 91.3% (calculated as 2-(2,4-dichlorophenyl)pentanal). Embodiment 2:

[0010] In a 1000 ml four-necked flask, add 118 g of 98% 2-(2,4-dichlorophenyl)valeraldehyde and 70.5 g of 98% 1,2,4-triazole, and then add 1.0 g of p-toluenesulfonic acid and 600 g of polyethylene glycol. 1.0 g and 400 g toluene, then heated to 112-114°C for reflux dehydration until no water is removed, the reaction time is 6 hours, after the reaction is completed, the temperature is lowered to below 40°C, 200 g of water is added, stirred for 30 minutes, allowed to stand for stratification, the organic phase is washed once with 200 g of water, the upper organic phase is taken, the temperature is raised and the pressure is reduced to recover toluene, the temperature is controlled to be ≤120°C / -0.095Mpa, after the toluene is completely removed, the temperature is lowered to 30°C to obtain 141.23 g of (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole, the content is 98.1%, and the condensation reaction yield is 98.2%; Then, 141.23 g of the above-obtained 98.1% (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole was added into a 1000 ml four-necked flask, and then 400 g of methanol and a catalyst Pt / C were added. 1.5 grams, control the temperature at 10-15 ° C, introduce hydrogen, keep the temperature for 4 hours, take samples for gas chromatography analysis, and when the content of (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole is less than 0.5%, filter out the catalyst Pt / C, and then increase the temperature and reduce the pressure to recover methanol, control the temperature to ≤80 ° C / -0.095Mpa, and when the methanol is recovered, 142.44 grams of crude penconazole are obtained, with a content of 96.1% and a reduction reaction yield of 98.1%. Finally, 300 grams of n-hexane are added to the crude penconazole, recrystallized, and dried to obtain 138.92 grams of 98.5% penconazole original medicine, with a recrystallization yield of 96.07% and a total yield of 92.5% (calculated as 2-(2,4-dichlorophenyl) valeraldehyde). Embodiment 3:

[0011] In a 1000 ml four-necked flask, add 118 g of 98% 2-(2,4-dichlorophenyl)valeraldehyde and 52.8 g of 98% 1,2,4-triazole, and then add 1.2 g of p-toluenesulfonic acid and 600 g of polyethylene glycol. 1.0 g and 400 g toluene, then heated to 112-114°C for reflux dehydration until no water is removed, the reaction time is 10 hours, after the reaction is completed, the temperature is lowered to below 40°C, 200 g of water is added, stirred for 30 minutes, allowed to stand for stratification, the organic phase is washed once with 200 g of water, the upper organic phase is taken, the temperature is raised and the pressure is reduced to recover toluene, the temperature is controlled to be ≤120°C / -0.095Mpa, after the toluene is completely removed, the temperature is lowered to 30°C, and 141.52 g of (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole is obtained, the content is 98%, and the condensation reaction yield is 98.3%; Then, 141.52 g of the above-obtained 98% (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole was added into a 1000 ml four-necked flask, and 400 g of methanol and 1.5 g of catalyst Pt / C were added. The temperature was controlled at 10-15° C., hydrogen was introduced, and the reaction was kept warm for 4 hours. Samples were taken for gas chromatography analysis. When the (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole content was less than 0.5%, the reaction mixture was stirred for 2 hours. , remove the catalyst Pt / C by suction filtration, then heat and reduce pressure to recover methanol, control the temperature ≤80℃ / -0.095Mpa, and after the methanol is recovered, 143.03 grams of crude penconazole are obtained, with a content of 95.8% and a reduction reaction yield of 98.1%. Finally, the crude penconazole is added with 300 grams of n-hexane, recrystallized, and dried to obtain 139.71 grams of 98.4% penconazole technical, with a recrystallization yield of 96.12% and a total yield of 92.7% (calculated as 2-(2,4-dichlorophenyl)pentanal). Embodiment 4:

[0012] In a 1000 ml four-necked flask, add 118 g of 98% 2-(2,4-dichlorophenyl)valeraldehyde and 63.37 g of 98% 1,2,4-triazole, and then add 1.5 g of p-toluenesulfonic acid and 600 g of polyethylene glycol. 1.0 g and 400 g toluene, then heated to 112-114°C for reflux dehydration until no water is removed, the reaction time is 8 hours, after the reaction is completed, the temperature is lowered to below 40°C, 200 g of water is added, stirred for 30 minutes, and allowed to stand for stratification, 200 g of water is added to the organic phase for washing once, the upper organic phase is taken, the temperature is raised and the pressure is reduced to recover toluene, the temperature is controlled to be ≤120°C / -0.095Mpa, and the temperature is lowered to 30°C after all the toluene is removed, to obtain 141.09 g of (E)-3-(2-(2,4-dichlorophenyl)pent-1-ene-1-yl)-3H-1,2,4-triazole, the content is 98.1%, and the condensation reaction yield is 98.2%; Then, 141.09 g of the above-obtained 98.1% (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole was added into a 1000 ml four-necked flask, and then 400 g of methanol and a catalyst Pt / C were added. 1.5 grams, control the temperature at 10-15 ° C, pass hydrogen, keep the temperature for 4 hours, take samples for gas chromatography analysis, and when the content of (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole is less than 0.5%, filter out the catalyst Pt / C, and then increase the temperature and reduce the pressure to recover methanol, control the temperature to ≤80 ° C / -0.095Mpa, and when the methanol is recovered, 142.14 grams of crude penconazole are obtained, with a content of 96.3% and a reduction reaction yield of 98.2%. Finally, 300 grams of n-hexane are added to the crude penconazole, recrystallized, and dried to obtain 138.7 grams of 98.6% penconazole original medicine, with a yield of 96.21% and a total yield of 92.7% (calculated as 2-(2,4-dichlorophenyl) valeraldehyde).

[0013] The following is a statistical table of relevant data of Examples 1 to 4: ; As can be seen from the above table, the penconazole technical prepared by the present invention greatly improves the conversion rate of raw materials compared with the prior art, solves the problem of generating derivatives due to the use of potassium borohydride as a reducing agent, makes penconazole more atom-economical and environmentally friendly, has a simpler process flow, reduces the operation steps of subsequent treatment and the use of solvents, has low energy loss, effectively removes impurities in the preparation process of penconazole, greatly improves the purification rate and yield of penconazole technical, and meets the strict requirements for high-quality pesticides in agricultural production.

Claims

1. A method for preparing penconazole technical, characterized in that: Using 2-(2,4-dichlorophenyl)pentanal and 1,2,4-triazole as starting materials, condensation and reduction are first performed under the action of a catalyst to obtain a crude product of penconazole, and then recrystallization is performed to obtain the original product of penconazole. The specific preparation steps are as follows: S1. 2-(2,4-dichlorophenyl)pentanal and 1,2,4-triazole are added to toluene, and a condensation reaction is performed under the action of a catalyst to obtain (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole. The reaction equation is as follows: ； S2. Methanol is added to the (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole obtained in S1, and a reduction reaction is first performed under the action of hydrogen and a catalyst to obtain a crude product of penconazole, and then recrystallized from n-hexane to obtain the original drug of penconazole. The reaction equation is as follows: 。 2. The method for preparing a penconazole technical according to claim 1, characterized in that: In S1, the molar ratio of 1,2,4-triazole to 2-(2,4-dichlorophenyl)pentanal is 1.2 to 2:

1.

3. The method for preparing a penconazole technical according to claim 1, characterized in that: In S1, the catalyst is p-toluenesulfonic acid and polyethylene glycol 600.

4. The method for preparing a penconazole technical according to claim 1, characterized in that: In S1, the temperature of the condensation reaction is 112 to 114°C.

5. The method for preparing a penconazole technical according to claim 1, characterized in that: In S1, the condensation reaction time is 8 to 12 hours.

6. The method for preparing penconazole technical according to claim 1, characterized in that: In S1, after the condensation reaction is completed, toluene needs to be removed and recovered at a temperature of ≤120°C / -0.095Mpa.

7. The method for preparing a penconazole technical according to claim 1, characterized in that: In S2, after the reduction reaction is completed, the catalyst is removed by filtration when the content of (E)-3-(2-(2,4-dichlorophenyl)pent-1-en-1-yl)-3H-1,2,4-triazole is less than 0.5%, and then the methanol is removed and recovered at a temperature of ≤80°C / -0.095Mpa.

8. The method for preparing a penconazole technical according to claim 1 or 7, characterized in that: In S2, the catalyst is Pt / C.

9. The method for preparing a penconazole technical according to claim 1 or 7, characterized in that: In S2, the temperature of the reduction reaction is 10 to 15°C.

10. The method for preparing a penconazole technical according to claim 1 or 7, characterized in that: In S2, the reduction reaction time is 2 to 6 hours.

Images