A method for preparing flumiclorac-pentyl

Abstract

The present application relates to a kind of preparation methods of pethoxamid, comprising the following steps: isobutyryl benzene and 2-ethoxyethylamine are reacted, and intermediate 2 is obtained;Then intermediate 2, chloroacetyl chloride, organic solvent are reacted, after reaction, separation is carried out, and pethoxamid pure product is obtained.Belong to the technical field of pesticide chemical engineering.The present application uses continuous flow tubular reactor in step 1, preferred catalyst, good catalytic effect, short reaction time, high reaction efficiency;In step 2, continuous flow microchannel reactor is used, the yield of product obtained is high and high purity, high safety, high reaction efficiency, with good application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of pethoxamid, and belongs to the technical field of pesticide chemical industry. BACKGROUND

[0002] Pethoxamid, Chinese alias 2-chloro-N-(2-ethoxyethyl)-N-(2-methyl-1-phenyl-1-propenyl)acetamide, is a new acetylchloroaniline herbicide developed by Tokuyama Company of Japan. Pethoxamid shows good herbicidal activity on broadleaf weeds and gramineous weeds, and is mainly used for weed control in corn and soybean fields, and is applied for soil treatment before or at early stage after seedling. It can also be mixed with other herbicides to increase the control effect, especially the control effect on broadleaf weeds. The metabolic pathway of pethoxamid in plants, animals and soil is mainly completed by combining with glutathione. The research on its toxicological evaluation and environmental behavior shows that it is a safe herbicide, and is applied more and more widely.

[0003] There are mainly two methods for preparing pethoxamid reported in the literature: the first method is to react isobutyrylbenzene and 2-ethoxyethylamine under the catalysis of p-toluenesulfonic acid, to obtain a Schiff base, i.e. intermediate 2, by long-time reflux and water separation in a kettle reactor; and then to obtain pethoxamid by reacting intermediate 2 and chloroacetyl chloride under micro-negative pressure in a kettle reactor. Reference documents: Agricultural and Biological Chemistry, 55:11, 2737-2743; patent EP774456 or CN1161326, etc. The synthetic route is as follows:

[0004]

[0005] The first method has the following disadvantages: in step 1-a, it is a kettle reactor, which needs long-time high-temperature reflux until no water is separated, and the catalyst efficiency is not high. In actual production, the reaction time of this step is as long as 36 hours or more, the production capacity and production efficiency are low, the safety is poor, and it is difficult for a small amount of residual raw materials to react completely, resulting in low purity of intermediate 2; in step 1-b, it is a kettle reactor, the reaction time is also long, the temperature is high, the operation is not convenient, and the purity is low in actual production, the product is difficult to separate, the color is deep, and even needs to be purified by column, which causes inconvenience in production, poor economy, large amount of three wastes, etc.

[0006] The second method is that isobutyrylbenzene and 2-ethoxyethylamine are reacted under the catalysis of p-toluenesulfonic acid, sodium hydroxide aqueous solution is used as a base, and a kettle type reaction is used to reflux water for a long time to obtain the Schiff base, i.e., the intermediate 2; then the intermediate 2 and chloroacetyl chloride are reacted in DMF solvent to obtain clomazone. Reference documents are Japanese patent JP2001342167A, patent EP206251 or CN1015364, etc. The synthetic route is as follows:

[0007]

[0008] The second method has the following disadvantages: in step 2-a, a kettle type batch reactor is used, which needs to be refluxed at high temperature for a long time until no water is separated out, and the catalyst efficiency is not high; in actual production, the reaction time of this step is as long as 48 hours or more, the production capacity and production efficiency are low, the safety is poor, and a small amount of residual raw materials are difficult to react completely, resulting in low purity of the intermediate 2; in step 2-b, a kettle type batch reactor is used, the reaction time is also long, the purity is not high, the product yield is as low as 41%, and the separation is difficult, which needs to be purified by column, causing production inconvenience, poor economy, and large amount of three wastes.

[0009] In summary, when clomazone is prepared by using the two methods, especially in industrial production, there are problems such as low efficiency of the kettle type reaction, great safety hazard, low catalyst efficiency, long reaction time, low purity of the intermediate, low product purity and yield, deep color, difficult separation, production inconvenience, poor economy, and large amount of three wastes.

[0010] Therefore, when clomazone is produced industrially, a preparation method capable of obtaining higher product purity and yield is needed to improve safety, reduce reaction time, improve production capacity, reduce cost, and effectively control the amount of three wastes. SUMMARY

[0011] The problem to be solved by the present application is that the prior art has problems such as low efficiency of the kettle type reaction, great safety hazard, low catalyst efficiency, long reaction time, low purity of the intermediate, low product purity and yield, deep color, difficult separation, production inconvenience, poor economy, and large amount of three wastes when clomazone is prepared, especially in industrial production.

[0012] To solve the above problems, the technical scheme adopted by the present application is to provide a preparation method of clomazone, which comprises the following steps:

[0013]

[0014] Step 1: isobutyrylbenzene and 2-ethoxyethylamine are respectively input into a continuous flow tubular reactor through a laminar flow pump after passing through a high-efficiency mixer to react, after the reaction is completed, cooling, standing and layering, the organic layer is separated to obtain intermediate 2.

[0015] Step 2: intermediate 2, chloroacetyl chloride and an organic solvent are mixed and then input into a reaction module of a continuous flow microchannel reactor through a laminar flow pump to react, after the reaction is completed, separation is performed to obtain pure alachlor.

[0016] Preferably, in step 1, an organic solvent and / or a catalyst can be further added during the reaction, the organic solvent is further preferably toluene and / or chlorobenzene, and the catalyst is selected from at least one of triethylamine, benzyltriethylammonium chloride and benzyltrimethylammonium chloride.

[0017] Further preferably, in step 1, the molar ratio of isobutyrylbenzene to the catalyst is 1:0.0-0.5, and the molar ratio of isobutyrylbenzene to 2-ethoxyethylamine is 1:1.1-3.0.

[0018] Preferably, in step 1, the reaction time is 10-180 minutes, the temperature is 80-135℃, the pressure is 0.1Mpa-3.0Mpa, and the cooling temperature is 15-35℃.

[0019] Preferably, in step 1, the molar ratio of isobutyrylbenzene to 2-ethoxyethylamine is 1:1.1-3.0.

[0020] Preferably, in step 2, the molar ratio of intermediate 2 to chloroacetyl chloride is 1:1.0-1.4, the mass ratio of chloroacetyl chloride to the organic solvent is 1:1.0-4.0, and the organic solvent is selected from toluene and / or chlorobenzene.

[0021] Preferably, in step 2, the reaction time is 1-30 minutes, the temperature is 45-100℃, and the pressure is 0.05Mpa-0.3Mpa.

[0022] Preferably, in step 2, the separation method is as follows: the obtained mixture is washed with alkaline water, water-washed, separated, the organic layer is concentrated under reduced pressure to recover the solvent and separate the front fraction, and then high-vacuum reduced-pressure distillation is performed.

[0023] Further preferably, when the solvent is recovered and the front fraction is separated under reduced pressure, the distillation temperature is 80-140℃, and the vacuum degree is 3.0-25.0 mmHg; when high-vacuum reduced-pressure distillation is performed, the distillation temperature is 160-195℃, and the vacuum degree is 0.5-2.5 mmHg.

[0024] Compared with the prior art, the present application has the following beneficial effects:

[0025] 1.The present application uses isobutyrylbenzene as raw material to prepare Schiff base, i.e.intermediate 2, by using a continuous flow tubular reactor. In step 1, the preferred catalyst has good catalytic effect, short reaction time, and high reaction efficiency. The post-treatment process is simple. By simple liquid separation and distillation, the intermediate 2 can be obtained. Meanwhile, the raw material and solvent are easy to recover, the comprehensive utilization rate of raw material is high, and the industrial production is convenient. The method has high yield, which can be as high as 97.2-98.8%, and high purity of intermediate 2, which can be as high as 97.0-98.1%. The method is safe, economical, and has small amount of waste.

[0026] 2.In step 2, the solution of intermediate 2 is used as raw material to prepare fluazifop-butyl by using a continuous flow microchannel reactor. The amount of chloroacetyl chloride is optimized, and the post-treatment process is optimized. The reaction time is short, the reaction efficiency is high, the solvent toluene or chlorobenzene is easy to recover, the recovery cost is greatly reduced, and the amount of waste is also reduced. The product purification process is simple. By washing and distillation, the product can be obtained. By optimizing the reaction parameters such as feeding ratio, residence time, reaction temperature and pressure, the generation of by-products can be controlled, so the selectivity of the reaction is good. The method is safe, economical, and has small amount of waste. The product yield of the method can be as high as 95.0-99.1%, and the product purity can be as high as 98.5-99.2%. The product content is high, which can be as high as 97.2-98.8%. The product is colorless to white. DETAILED DESCRIPTION

[0027] In order to make the present application more obvious and easy to understand, the preferred embodiments are described in detail as follows:

[0028] In the present application, the percentage not specially mentioned refers to mass concentration or mass percentage.

[0029] Example 1

[0030] A method for preparing fluazifop-butyl, comprising the following steps:

[0031] Step 1: mixed solution preparation: isobutyrylbenzene, toluene, benzyltriethylammonium chloride were prepared into a mixed solution, the mass ratio of isobutyrylbenzene and toluene was 1:6.0, the molar ratio of isobutyrylbenzene and catalyst benzyltriethylammonium chloride was 1:0.01; the prepared mixed solution and 2-ethoxyethylamine were respectively input into the continuous flow tubular reactor through the laminar pump and high-efficiency mixer; the reaction was carried out at the temperature of 125℃ and the reaction pressure of 0.4Mpa, the material flow rate was adjusted, the molar ratio of isobutyrylbenzene and 2-ethoxyethylamine in the reaction material was controlled to be 1:2.5, and the residence time of the material in the continuous flow tubular reactor was controlled to be 60 minutes; after the reaction was completed, the obtained reaction product was cooled to 25℃, and then was allowed to stand to separate into layers, and the organic layer was the toluene solution of the Schiff base, i.e., intermediate 2; after the solvent and 2-ethoxyethylamine were recovered through normal pressure distillation, the intermediate 2 was obtained. When the intermediate 2 was prepared into a toluene solution by adding toluene, the amount of isobutyrylbenzene used in a single batch was calculated, the mass ratio of isobutyrylbenzene and the added toluene was controlled to be 1:2.0, and the toluene solution of the intermediate 2 was obtained for standby use. The result of gas chromatography analysis, excluding the solvent, was that the purity was 98.1%, and the yield of the product in a single batch was calculated to be 98.8% through content determination.

[0032] Step 2: chloroacetyl chloride solution preparation: chloroacetyl chloride and toluene were prepared into a mixed solution, the mass ratio of chloroacetyl chloride and toluene was 1:1.0; the solution of the intermediate 2 obtained in step 1 and the toluene solution of chloroacetyl chloride were respectively input into the reaction module of the continuous flow microchannel reactor through the laminar pump; the reaction was carried out at the temperature of 55℃ and the reaction pressure of 0.2Mpa, the material flow rate was adjusted, the molar ratio of the intermediate 2 and chloroacetyl chloride in the reaction material was controlled to be 1:1.2, and the residence time of the material in the continuous flow microchannel reactor was controlled to be 5 minutes; after the reaction was completed, the obtained mixture was washed with alkaline water, and then was separated into layers; under the conditions that the distillation temperature was 80-130℃ and the vacuum degree was 5.0-7.0mmHg, the organic layer was concentrated under reduced pressure to recover the solvent and separate the front fraction, and then was subjected to high vacuum reduced pressure distillation under the conditions that the distillation temperature was 170-185℃ and the vacuum degree was 1.3-1.7mmHg, to obtain the pure product of clomazone. The purity was 99.2% and the content was 98.8% through gas chromatography analysis, and the yield of the product in a single batch was calculated to be 99.1%. The product was colorless to white.

[0033] Example 2

[0034] A method for preparing clomazone, comprising the following steps:

[0035] Step 1: mixed solution preparation: isobutyrylbenzene, toluene, benzyltrimethylammonium chloride were prepared into a mixed solution, in which the mass ratio of isobutyrylbenzene and toluene was 1:5.0, and the molar ratio of isobutyrylbenzene and catalyst benzyltrimethylammonium chloride was 1:0.01; the prepared mixed solution and 2-ethoxyethylamine were respectively input into the continuous flow tubular reactor through the laminar pump and high-efficiency mixer; the reaction was carried out at a temperature of 120℃ and a reaction pressure of 0.5Mpa, the material flow rate was adjusted, the molar ratio of isobutyrylbenzene and 2-ethoxyethylamine in the reaction material was controlled to be 1:2.5, and the residence time of the material in the continuous flow tubular reactor was controlled to be 50 minutes; after the reaction was completed, the obtained reaction product was cooled to 20℃, and then was allowed to stand to separate into layers, and the organic layer was a toluene solution of the Schiff base, i.e., intermediate 2; after the solvent and 2-ethoxyethylamine were recovered by atmospheric distillation, the obtained intermediate 2 was obtained. When toluene was further added to prepare a toluene solution, the amount of isobutyrylbenzene used in a single batch was calculated, the mass ratio of isobutyrylbenzene and the added toluene was controlled to be 1:2.0, and the obtained toluene solution of intermediate 2 was prepared for standby use. The result of gas chromatography analysis, excluding the solvent, was: purity 97.5%, and the yield of the product in a single batch was calculated to be 97.4% by content determination.

[0036] Step 2: chloroacetyl chloride solution preparation: chloroacetyl chloride and toluene were prepared into a mixed solution, in which the mass ratio of chloroacetyl chloride and toluene was 1:2.0; the solution of intermediate 2 obtained in step 1 and the toluene solution of chloroacetyl chloride were respectively input into the reaction module of the continuous flow microchannel reactor through the laminar pump; the reaction was carried out at a temperature of 65℃ and a reaction pressure of 0.1Mpa, the material flow rate was adjusted, the molar ratio of intermediate 2 and chloroacetyl chloride in the reaction material was controlled to be 1:1.1, and the residence time of the material in the continuous flow microchannel reactor was controlled to be 4 minutes; after the reaction was completed, the obtained mixture was washed with alkaline water, and then was subjected to liquid separation; under the conditions that the distillation temperature was 85-125℃ and the vacuum degree was 5.0-7.0mmHg, the organic layer was subjected to reduced pressure concentration to recover the solvent and separate the front fraction, and then was subjected to high vacuum reduced pressure distillation under the conditions that the distillation temperature was 175-184℃ and the vacuum degree was 1.4-1.6mmHg, to obtain the pure product of clomazone. The pure product of clomazone was obtained. The purity was 98.7% and the content was 97.9% by gas chromatography analysis, and the yield of the product in a single batch was calculated to be 98.1%. The product was colorless to white.

[0037] Example 3

[0038] A method for preparing clomazone, comprising the following steps:

[0039] Step 1: mixed solution preparation: isobutyrylbenzene, chlorobenzene, triethylamine are prepared into a mixed solution, the mass ratio of isobutyrylbenzene and chlorobenzene is 1:4.0, the molar ratio of isobutyrylbenzene and catalyst triethylamine is 1:0.2; the prepared mixed solution and 2-ethoxyethylamine are respectively input into the continuous flow tubular reactor through the laminar pump and the high-efficiency mixer; the reaction is carried out at the temperature of 120℃ and the reaction pressure of 0.4Mpa, the material flow rate is adjusted, the molar ratio of isobutyrylbenzene and 2-ethoxyethylamine in the reaction material is controlled to be 1:2.2, and the residence time of the material in the continuous flow tubular reactor is controlled to be 30 minutes; after the reaction is completed, the obtained reaction product is cooled to 25℃, and is left to separate into layers, and the organic layer is the chlorobenzene solution of the Schiff base, i.e. intermediate 2; after the solvent and 2-ethoxyethylamine are recovered through normal pressure distillation, the intermediate 2 is obtained. When chlorobenzene is added again to prepare a chlorobenzene solution, the amount of isobutyrylbenzene used in a single batch is calculated, the mass ratio of isobutyrylbenzene and the added chlorobenzene is controlled to be 1:2.0, the chlorobenzene solution of the intermediate 2 is obtained, and is ready for use. The result of gas chromatography analysis, excluding the solvent, is: the purity is 97.0%, and the yield of the product in a single batch is calculated to be 97.2% through content determination.

[0040] Step 2: chloroacetyl chloride solution preparation: chloroacetyl chloride, chlorobenzene are prepared into a mixed solution, the mass ratio of chloroacetyl chloride and chlorobenzene is 1:2.0; the solution of the intermediate 2 obtained in step 1 and the chloroacetyl chloride chlorobenzene solution are respectively input into the reaction module of the continuous flow microchannel reactor through the laminar pump; the reaction is carried out at the temperature of 50℃ and the reaction pressure of 0.2Mpa, the material flow rate is adjusted, the molar ratio of the intermediate 2 and chloroacetyl chloride in the reaction material is controlled to be 1:1.2, and the residence time of the material in the continuous flow microchannel reactor is controlled to be 6 minutes; after the reaction is completed, the obtained mixture is washed with alkaline water, washed with water, separated into layers, and then, under the conditions that the distillation temperature is 85-130℃ and the vacuum degree is 4.0-8.0mmHg, the organic layer is concentrated under reduced pressure to recover the solvent and separate the front fraction, and then, under the conditions that the distillation temperature is 170-185℃ and the vacuum degree is 1.3-1.7mmHg, the organic layer is distilled under high vacuum and reduced pressure to obtain the pure product of fluazifop-butyl. The pure product of fluazifop-butyl is obtained. The purity is 98.5% and the content is 97.2% through gas chromatography analysis, and the yield of the product in a single batch is calculated to be 95.0%. The product is colorless to white.

[0041] The above examples are only preferred embodiments of the present application, and are not any form and substantial limitation of the present application. It should be noted that, for ordinary skilled persons in the art, without departing from the present application, a number of improvements and supplements can also be made, which should be regarded as the protection scope of the present application.

Claims

1. A process for the preparation of pendimethalin characterized in that, It comprises the following steps: Step 1: isobutyrylbenzene and 2-ethoxyethylamine are respectively input into a continuous flow tubular reactor through a laminar flow pump after passing through a high-efficiency mixer to react, after the reaction is completed, cooling, standing and separating layers, the organic layer is separated to obtain intermediate 2; Step 2: intermediate 2, chloroacetyl chloride and an organic solvent are mixed and then input into the reaction module of a continuous flow microchannel reactor through a laminar flow pump to react, after the reaction is completed, separation is performed to obtain an enoxacin pure product; In step 1, an organic solvent and a catalyst are further added during the reaction; the catalyst is at least one of triethylamine, benzyltriethylammonium chloride and benzyltrimethylammonium chloride.

2. The production method according to claim 1, wherein The organic solvent is toluene and / or chlorobenzene.

3. The production method according to claim 2, wherein The molar ratio of isobutyrylbenzene to the catalyst is 1:0.0-0.5, and the molar ratio of isobutyrylbenzene to 2-ethoxyethylamine is 1:1.1-3.

0.

4. The production method according to claim 1, wherein In step 1, the reaction time is 10-180 minutes, the temperature is 80-135℃, the pressure is 0.1Mpa-3.0Mpa, and the cooling temperature is 15-35℃.

5. The production method according to claim 1, wherein In step 1, the molar ratio of isobutyrylbenzene to 2-ethoxyethylamine is 1:1.1-3.

0.

6. The production method according to claim 1, wherein In step 2, the molar ratio of intermediate 2 to chloroacetyl chloride is 1:1.0-1.4, and the mass ratio of chloroacetyl chloride to the organic solvent is 1:1.0-4.0; the organic solvent is selected from toluene and / or chlorobenzene.

7. The production method according to claim 1, wherein In step 2, the reaction time is 1-30 minutes, the temperature is 45-100℃, and the pressure is 0.05Mpa-0.3Mpa.

8. The production method according to claim 1, wherein In step 2, the separation method is as follows: the obtained mixture is washed with alkaline water, washed with water, separated, and then the organic layer is concentrated under reduced pressure to recover the solvent and separate the front fraction, and then subjected to high-vacuum reduced-pressure distillation.

9. The production method according to claim 8, wherein When the solvent is recovered and the front fraction is separated by reduced-pressure concentration, the distillation temperature is 80-140℃, and the vacuum degree is 3.0-25.0 mmHg; when high-vacuum reduced-pressure distillation is performed, the distillation temperature is 160-195℃, and the vacuum degree is 0.5-2.5 mmHg.

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