A method for preparing pretilachlor

Abstract

The application discloses a preparation method of propachlor. By adding a proper amount of a disubstituted amine ether byproduct in the reaction of 2,6-diethyl aniline and chloroethyl propyl ether, the generation of the disubstituted amine ether byproduct in an amine ether synthesis process is inhibited, the selectivity and yield of the amine ether intermediate are significantly improved, and the yield of propachlor is improved. In addition, the disubstituted amine ether byproduct is added as an additive in the amine ether synthesis process, and the disubstituted amine ether byproduct is an inherent impurity in the amine ether synthesis process, so that the disubstituted amine ether byproduct as the additive does not introduce new impurities into the reaction system, and can be separated through a conventional rectification method.

Description

A method for preparing pretilachlor Technical Field

[0001] This application belongs to the field of herbicide technology, specifically relating to a method for preparing pretilachlor. Background Technology

[0002] Pretilachlor is a chloroacetamide herbicide developed by Syngenta. It is a herbicide specifically for rice fields. Its chemical name is 2-chloro-2',6'-diethyl-N-(2-propoxyethyl)-N-acetanilide, and its CAS number is 51218-49-6.

[0003] Currently, the main existing technology for preparing propachlor is the amine ether method, which uses 2,6-diethylaniline as raw material and reacts it with ethylene glycol mono-n-propyl ether (CN102408352A; CN102219654A; Liaoning Chemical Industry, 2000, 29(2):112-113), ethylene glycol mono-n-propyl ether sulfonate (CN102229545A; Liaoning Chemical Industry, 45(6):690-692), chloroethyl propyl ether (US4324580; Zhejiang Chemical Industry, 39(7); 17-18; Chemical Reagents, 33(3):283-285; CN102173998A; CN105272869A; CN104478741A; CN108658791A) or 2-propoxyacetaldehyde (CN105601529A; Journal) (of Chemical & Pharmaceutical Research, 2013, 5(12): 1320-1324) etc. to prepare the key intermediate 2,6-diethyl-N-(2-propoxyethyl)aniline (commonly known as amine ether), and then react with chloroacetyl chloride under alkaline conditions to synthesize propachlor:

[0004] Among the above synthetic routes, the chloroethyl propyl ether route has the advantages of inexpensive raw materials, simple equipment, low cost, and minimal waste. However, its disadvantage is that it easily produces disubstituted amine ether byproducts during the reaction. The yield of monosubstituted amine ether intermediates has always been difficult to improve (Zhejiang Chemical Industry, 39(7); 17-18).

[0005] To improve the selectivity of amine ether intermediates and reduce the formation of disubstituted amine ether byproducts, Wu Jinming et al. from Nantong University reported that amine ether intermediates could be obtained in 90% yield by first reacting 2,6-diethylaniline with sodium hydride in an aprotic solvent to form sodium amine salt, and then reacting it with chloroethylpropyl ether (Chemical Reagents, 33(3):283-285; CN102173998A). However, due to the instability of sodium hydride, this process is not suitable for industrial production. Furthermore, Du Xiaohua et al. from Zhejiang University of Technology reported that adding a novel adjuvant (N,N-di-n-propyl-2-propoxyethylamine) to the reaction of 2,6-diethylaniline with chloroethylpropyl ether improved the fluidity of the reaction system and increased the selectivity and yield of the target product to 96.0% and 89.2%, respectively (CN111100019A; Clean Production Research of Prochloraz, Master's Thesis, Zhejiang University of Technology, Du Jiawei). However, this method requires the use of a specific novel adjuvant, increasing the difficulty of product separation, and the improvement in selectivity for amine ether intermediates is not significant. This invention, through in-depth research, discovered that adding an appropriate amount of disubstituted amine ether byproduct to the reaction of 2,6-diethylaniline with chloroethylpropyl ether can significantly improve the selectivity and yield of amine ether intermediates, thus completing this invention. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for preparing propachlor. This method, by adding an appropriate amount of disubstituted amine ether byproduct to the reaction of 2,6-diethylaniline with chloroethylpropyl ether, can significantly improve the selectivity and yield of the amine ether intermediate, and because no other reagents are introduced, it does not lead to an increase in the difficulty of product separation.

[0007] A method for preparing propachlor according to the present invention includes the following steps:

[0008] (1) Amine ether synthesis process

[0009] 2,6-Diethylaniline (DEA), chloroethylpropyl ether (chloro ether), sodium hydroxide solution, and a certain amount of disubstituted amine ether byproduct were added as additives to an amine ether synthesis reactor for reaction. After the reaction was complete, the mixture was washed with alkali and distilled to obtain excess 2,6-diethylaniline, amine ether intermediate, and disubstituted amine ether byproduct sequentially. The reaction formula is as follows:

[0010]

[0011] The disubstituted amino ether byproduct has the following structural formula:

[0012] (2) Acylation process

[0013] The amine ether intermediate prepared in step (1), toluene, and sodium carbonate were added to an acylation reactor. The temperature was controlled at ≤50℃, and chloroacetyl chloride was added dropwise. After the reaction was completed, propachlor was obtained. The reaction formula is as follows:

[0014]

[0015] According to the aforementioned method of the present invention, the molar ratio of 2,6-diethylaniline (DEA) and chloroethylpropyl ether (chloro ether) is 1:1 to 4:1, preferably 2-3:1.

[0016] In step (1), the concentration of sodium hydroxide solution is 10wt% to 50wt%, preferably 40wt% to 50wt%, and the molar ratio of sodium hydroxide to chloroethyl propyl ether (chloro ether) is 0.5 to 2:1, preferably 1:1.

[0017] In step (1), the molar ratio of the disubstituted byproduct to chloroethylpropyl ether (chloroether) is 0.05-0.2:1, preferably 0.1:1.

[0018] In step (1), the reaction temperature is 120-200℃, preferably 160-180℃, more preferably 170℃; the reaction time is 4-24h, preferably 8-12h, and even more preferably 8-10h.

[0019] In step (1), the alkaline washing uses sodium carbonate solution, sodium hydroxide solution and / or sodium bicarbonate solution; preferably sodium hydroxide solution.

[0020] According to the aforementioned preparation method of the present invention, in step (2), the temperature is controlled to be ≤20℃, preferably ≤10℃, and the molar ratio of the amine ether intermediate to chloroacetyl chloride is 1:1-2, preferably 1:1.1-1.5; the molar ratio of the amine ether intermediate to sodium carbonate is 1:1-2, preferably 1:1.1-1.5. The reaction temperature of the heat preservation reaction is 30-50℃, preferably 40-50℃, and the reaction time of the heat preservation reaction is 0.5-2h, preferably 1h.

[0021] In step (2), after the reaction is complete, the mixture is washed with water and separated. The fraction at 100-105℃ / -0.0099MPa is collected by vacuum distillation to obtain propachlor.

[0022] Compared with the prior art, the preparation method of the present invention has the following advantages:

[0023] This invention, by adding an appropriate amount of disubstituted amino ether byproducts to the reaction of 2,6-diethylaniline with chloroethylpropyl ether, suppresses the formation of disubstituted amino ether byproducts in the amino ether synthesis process, significantly improving the selectivity and yield of amino ether intermediates, and thus increasing the yield of propachlor. Furthermore, since the disubstituted amino ether byproducts are inherent byproducts in the amino ether synthesis process, they do not introduce new impurities into the reaction system and can be separated using conventional distillation methods. Detailed Implementation

[0024] The present invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, the methods used herein are conventional methods in the art, and the reagents and / or raw materials used are obtained through conventional commercial channels.

[0025] Example 1: Synthesis of amine ether intermediates

[0026]

[0027] 2,6-Diethylaniline (149 g, 1 mol), chloroethylpropyl ether (40.67 g, 0.33 mol), 40 wt% sodium hydroxide solution (0.33 mol), and disubstituted amine ether byproduct (10.7 g, 0.033 mol) were added as additives to an amine ether synthesis reactor and reacted at 170 °C for 10 h with stirring. After the reaction was complete, the mixture was washed with 32% NaOH solution, separated, and the organic phase was distilled to obtain excess 2,6-diethylaniline (-0.099 MPa, 170 °C), an amine ether intermediate (-0.099 MPa, 200 °C), and a disubstituted amine ether byproduct. The amine ether intermediate contained 75.8 g, with a purity of 96.5% and a yield (based on chloroethylpropyl ether) of 93.3%.

[0028] Example 2 Synthesis of amine ether intermediates

[0029] 2,6-Diethylaniline (149 g, 1 mol), chloroethylpropyl ether (61 g, 0.5 mol), 40 wt% sodium hydroxide solution (0.5 mol), and disubstituted amine ether byproduct (16 g, 0.05 mol) were added as additives to an amine ether synthesis reactor and reacted at 180 °C for 8 h with stirring. After the reaction was complete, the mixture was washed with 32% NaOH solution, separated, and the organic phase was distilled to obtain excess 2,6-diethylaniline (-0.099 MPa, 170 °C), an amine ether intermediate (-0.099 MPa, 200 °C), and a disubstituted amine ether byproduct. The amine ether intermediate weighed 111.4 g, with a purity of 97.1% and a yield (based on chloroethylpropyl ether) of 92.0%.

[0030] Example 3 Synthesis of amine ether intermediates

[0031] 2,6-Diethylaniline (149 g, 1 mol), chloroethylpropyl ether (61 g, 0.5 mol), 40 wt% sodium hydroxide solution (0.5 mol), and disubstituted amine ether byproduct (12.85 g, 0.04 mol) were added as additives to an amine ether synthesis reactor and reacted at 170 °C for 10 h with stirring. After the reaction was complete, the mixture was washed with 32% NaOH solution, separated, and the organic phase was distilled to obtain excess 2,6-diethylaniline (-0.099 MPa, 170 °C), an amine ether intermediate (-0.099 MPa, 200 °C), and a disubstituted amine ether byproduct. The amine ether intermediate weighed 113.1 g, with a purity of 96.8% and a yield (based on chloroethylpropyl ether) of 93.1%.

[0032] Comparative Example 1

[0033] No disubstituted amino ether byproducts were added; otherwise, the process was the same as in Example 1.

[0034] The conversion rate of chloroethylpropyl ether (chloro ether) (to generate amine ether) was 88.2%, the conversion rate of the side reaction (to generate disubstituted byproducts) was 9.0%, and the molar yield of amine ether was 78.5%.

[0035] Example 4 Acylation Process

[0036]

[0037] An amine ether intermediate (121.8 g, 0.5 mol), toluene (200 mL), and sodium carbonate (79.5 g, 0.75 mol) were added to an acylation reactor. The temperature was controlled at ≤10℃. Chloroacetyl chloride (70 g, 0.625 mol) was added dropwise over 30 minutes. After the addition was complete, the temperature was slowly raised to 40℃ and the reaction was maintained at this temperature for 1 hour. The mixture was washed three times with 200 mL of water. The liquid was separated, and the organic phase was collected by vacuum distillation (-0.0099 MPa, 100-105℃) to obtain 153.3 g of the product pretilachlor, with a purity of 96.3% and a yield of 94.9%.

Claims

1. A method for preparing pretilachlor, characterized in that, The process includes the following steps: (1) Amine ether synthesis: 2,6-diethylaniline, chloroethylpropyl ether, sodium hydroxide solution, and a certain amount of disubstituted amine ether byproducts are added as additives to the amine ether synthesis reactor for reaction. After the reaction is complete, excess 2,6-diethylaniline, amine ether intermediates, and disubstituted amine ether byproducts are obtained successively by alkaline washing and distillation. The reaction formula is as follows: The disubstituted amino ether byproduct has the following structural formula: The molar ratio of 2,6-diethylaniline to chloroethylpropyl ether is 2-3:1; the molar ratio of sodium hydroxide to chloroethylpropyl ether is 1:1; the molar ratio of the disubstituted byproduct to chloroethylpropyl ether is 0.1:1; (2) Acylation process: The amine ether intermediate prepared in step (1), toluene and sodium carbonate are added to the acylation kettle, the temperature is controlled to ≤50℃, chloroacetyl chloride is added dropwise, and after the reaction is completed, propachlor is obtained; the reaction formula is as follows:

2. The method for preparing pretilachlor according to claim 1, characterized in that, In step (1), the reaction temperature is 120-200℃; the reaction time is 4-24h.

3. The method for preparing pretilachlor according to claim 2, characterized in that, In step (1), the reaction temperature is 160-180℃ and the reaction time is 8-12h.

4. The method for preparing pretilachlor according to claim 1, characterized in that, In step (2), the temperature is controlled to be ≤20℃, the molar ratio of the amine ether intermediate to chloroacetyl chloride is 1:1-2, and the molar ratio of the amine ether intermediate to sodium carbonate is 1:1-2.

5. The method for preparing pretilachlor according to claim 4, characterized in that, In step (2), the temperature is controlled to be ≤10℃, the molar ratio of the amine ether intermediate to chloroacetyl chloride is 1:1.1-1.5, and the molar ratio of the amine ether intermediate to sodium carbonate is 1:1.1-1.

5.

6. The method for preparing pretilachlor according to claim 1, characterized in that, In step (2), the reaction temperature of the heat preservation reaction is 30-50℃, and the reaction time of the heat preservation reaction is 0.5-2h.

7. The method for preparing pretilachlor according to claim 6, characterized in that, In step (2), the reaction temperature of the heat preservation reaction is 40-50℃, and the reaction time of the heat preservation reaction is 1h.

8. The method for preparing pretilachlor according to claim 1, characterized in that, In step (2), after the reaction is complete, the mixture is washed with water and separated. The fraction at 100-105℃ / -0.0099MPa is collected by vacuum distillation to obtain propachlor.

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