Method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether
By optimizing the chlorination, coupling, oxime, and methylation reactions, the problems of high cost and high safety risks in existing methods have been solved, and the preparation of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether with high yield and low energy consumption has been achieved, which is suitable for industrial applications.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- YOUCHUANG CROP PROTECTION CO LTD
- Filing Date
- 2025-11-26
- Publication Date
- 2026-06-25
AI Technical Summary
Existing methods for preparing 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ethers suffer from problems such as high cost, significant safety risks, low yield, and difficulty in industrialization.
1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether was synthesized stepwise using aniline as a starting material through a four-step reaction involving chlorination, coupling, oximeation, and methylation, with optimized conditions for chlorination agent, nitryl ion, base, and solvent.
It simplifies operation, improves conversion and yield at each step, reduces energy consumption and pollution, and is suitable for industrial production.
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Abstract
Description
A method for preparing 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-one-methoxyoxime ether. Background Technology
[0002] 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether is an important intermediate in the synthesis of pesticides and pharmaceuticals. Its reduction by hydrogenation yields hydroxylamine. The chemical formula is as follows:
[0003] The synthesis of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether includes the following methods:
[0004] The method for WO2010063700 is as follows:
[0005] This method requires the reaction of butyllithium, diisopropylamine, and N,N-dimethylformamide at -78°C, which is relatively dangerous, costly, uses iron powder, generates a large amount of solid waste, and is difficult to industrialize.
[0006] The methods for WO2013127764 and WO2013127441 are as follows:
[0007] The raw materials used in this method, ethyl propylene acetate and tert-butyl nitrite, are relatively expensive, and the reaction yields are only 48% and 58%, respectively. The reaction also poses safety risks, has low yields, and generates a lot of waste.
[0008] Patent CN108610290A uses p-chloroaniline as a starting material, and the synthesis method is as follows:
[0009] While this method can reduce costs, the raw materials used, ethyl propylene acetate and tert-butyl nitrite, are relatively expensive, and it also involves diazotization. Both steps involve safety issues, manufacturing processes, and equipment investment.
[0010] Patent CN113004131A uses 2,4,6-trichlorotoluene and a chlorinating agent as raw materials, and the synthesis method is as follows:
[0011] This method is problematic because 2,4,6-trichlorotoluene is expensive and difficult to obtain. The self-synthesis of acetylene-based magnesium halides requires acetylene and n-butylmagnesium chloride. Acetylene is a hazardous chemical with stringent storage and usage conditions, posing a high risk. Furthermore, Grignard reactions place high demands on equipment heat exchange.
[0012] Patent CN117326921A uses trichlorobenzene as a raw material for synthesis, and the synthesis method is as follows:
[0013] The method requires expensive and difficult-to-obtain trichlorobenzene as a raw material, and the catalysts used in each step are also uncommon, resulting in a long reaction time.
[0014] Patent CN115703701A uses microchannels to synthesize 1-(2,4,6-trichlorophenyl)-propyl-2-one from 2,4,6-trichloroaniline, organic nitrites, and isopropyl acetate. However, this method still presents certain technical challenges for production scale-up. Summary of the Invention
[0015] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether.
[0016] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0017] A method for preparing a 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether includes the following steps:
[0018] (1) Chlorination reaction:
[0019] In a solvent, at 0-10℃, aniline (Formula I) was used as a raw material, and a chlorinating agent was added to obtain 2,4,6-trichloroaniline (Formula II) by chlorination reaction.
[0020] (2) Coupling reaction:
[0021] 2,4,6-trichloroaniline (Formula II), isopropyl acetate, and a catalyst are coupled in a solvent under the initiation of nitryl ions to give 1-(2,4,6-trichloro-phenyl)-propyl-2-one (Formula III);
[0022] (3) Oxime reaction:
[0023] In a solvent, under the action of a base, 1-(2,4,6-trichlorophenyl)-propyl-2-one (Formula III) undergoes an oxime reaction with hydroxylamine hydrochloride to give 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime (Formula IV);
[0024] (4) Methylation reaction:
[0025] 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime (Formula IV) is methylated with chloromethane in a solvent under the action of a base to give 1-(2,4,6-trichloro-phenyl)-propyl-2-one-methoxyoxime ether (Formula V).
[0026] The reaction formula is as follows:
[0027] In step (1), the chlorinating agent is one or more of chlorine, sulfonyl chloride, and NCS; chlorine is preferred.
[0028] The molar ratio of chlorinating agent to aniline is 3-3.5:1.
[0029] The solvent in step (1) is one or more of the following: chloroform, dichloroethane, dichloromethane, tetrahydrofuran, methyl-tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, benzene, toluene, and xylene.
[0030] The weight ratio of solvent to aniline is 1 to 10:1.
[0031] The chlorination reaction takes 3-5 hours.
[0032] In step (2), the nitryl ion is the gas generated by passing sulfur dioxide into nitric acid under heating conditions, or the gas generated by heating p-nitrosulfate, with a heating temperature of 30-100℃, preferably 40-60℃.
[0033] In step (2), the molar ratio of isopropyl acetate to 2,4,6-trichloroaniline is 1-8:1; preferably 2-4:1. The molar ratio of catalyst to 2,4,6-trichloroaniline is 0.01-0.2:1.
[0034] The coupling reaction temperature is -10 to 20℃, and the reaction time is 6 to 10 hours.
[0035] In step (2), the catalyst is one or more of the following: alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, copper sulfate, copper acetate, cuprous trifluoromethanesulfonate, or copper chloride.
[0036] In step (2), the solvent is one or more of the following: acetone, acetonitrile, tetrahydrofuran, methyl-tetrahydrofuran, dichloromethane, dichloroethane, chloroform, benzene, toluene, xylene, etc.
[0037] The weight ratio of solvent to 2,4,6-trichloroaniline is 1 to 10:1.
[0038] In step (3), the alkali is one or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, and potassium acetate.
[0039] The molar ratio of the base to 2,4,6-trichloroaniline is 1 to 5:1;
[0040] In step (3), the solvent is one or more of methanol, ethanol, and methyl tert-butyl ether;
[0041] The weight ratio of solvent to 2,4,6-trichloroaniline is 1-5:1;
[0042] The molar ratio of hydroxylamine hydrochloride to 2,4,6-trichloroaniline is 1-2:1.
[0043] The oxime reaction in step (3) is carried out at a temperature of 10–60°C for 1–6 hours.
[0044] In step (4), the alkali is one or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; the molar ratio of the alkali to 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime is 1 to 5:1.
[0045] The solvent in step (4) is acetonitrile, methanol, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, etc.
[0046] The weight ratio of the solvent to 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime is 1-5:1.
[0047] Step (4) Methylation reaction, at a temperature of 10-110℃ for 1-6 hours.
[0048] A method for preparing hydroxylamine, wherein an oxime ether prepared by the method is used as a raw material and hydrogenated to obtain hydroxylamine.
[0049] The advantages of this invention are:
[0050] This invention optimizes the synthesis process of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether and simultaneously optimizes the process of 1-(2,4,6-trichlorophenyl)acetone-2. This allows for one-step purification after oxime synthesis, resulting in high purity and convenience. Furthermore, the oxime methylation synthesis of oxime ethers is very simple, simplifying the entire process. The conversion and yield of each step are relatively good, with good purity, requiring virtually no recrystallization. The overall yield is 67%, and the reaction temperatures of each step are within the easily operable range, resulting in low energy consumption and relatively short reaction times, significantly shortening the overall cycle.
[0051] Compared with other methods, the preparation process of this invention has a wide range of raw material sources, is simple to operate, and requires simple waste treatment. This invention uses aniline as a raw material to prepare 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, simplifying the operation, reducing pollution, and has good industrial application value. At the same time, the conversion rate and yield are also high, showing promising prospects. Detailed Implementation
[0052] The following is a detailed description of specific embodiments of the technical solution of the present invention. It should be understood that the following embodiments are only used to illustrate the present invention, but the present invention is not limited to the scope of the following description:
[0053] The present invention will now be described in conjunction with specific embodiments:
[0054] Example 1
[0055] (1) Chlorination reaction:
[0056] 94 g (1 mol, 99%) of aniline and 200 g (2.1 wt) of dichloroethane were mixed, the temperature was lowered to 5 °C, and 234.3 g (3.3 eq) of chlorine gas was introduced. After the gas was introduced, the mixture was stirred and kept at this temperature for 3 hours. The concentration of aniline was controlled to be <0.5%, and the product concentration was >90%. The solid was collected by direct filtration. 400 g of 10% liquid alkali was added to the solid, and the mixture was filtered again to obtain the product. The product was normalized to 99.2%, with a yield of 84%, and was a pale yellow solid.
[0057] (2) Coupling reaction:
[0058] Add 198.5 g (1 mol) of 2,4,6-trichloroaniline, 800 g (4 wt) of tetrahydrofuran, 8 g (0.05 eq) of ketone sulfate, and 400 g (4 eq) of isopropyl acetate. After addition, cool to 5°C. In another four-necked flask, add concentrated nitric acid and heat to 40-50°C. Slowly pass sulfur dioxide into the nitric acid, and simultaneously pass the generated gas through a condenser to cool it before passing it into the synthesis solution. Stop passing sulfur dioxide when 96 g has been passed. Keep the four-necked flask heated for 1 hour, then stop heating. Meanwhile, keep the synthesis solution at this temperature for 8 hours. Under control, the feedstock 2,4,6-trichloroaniline <1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one >93%. Perform a negative pressure air extraction on the synthesis solution for 0.5 hours to remove nitrate ions. 300g of water was slowly added to the synthesis solution, and the layers separated. The pH of the oil layer was adjusted to about 7-8 with 10% liquid alkali, and then washed once with 200g of water. The solvent tetrahydrofuran and isopropyl acetate were recovered from the oil layer. The remaining crude product was 253g of 1-(2,4,6-trichlorophenyl)-propyl-2-one, with a purity of 94.2%.
[0059] (3) Oxime reaction:
[0060] 253 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 303.6 g of methanol (1.5 wt, based on 2,4,6-trichloroaniline), and 109.2 g of sodium bicarbonate (1.3 eq, based on 2,4,6-trichloroaniline) were added with stirring. 80 g of hydroxylamine hydrochloride (1.15 eq, based on 2,4,6-trichloroaniline) was then added. After the addition was complete, the mixture was kept at 25°C for 3 hours. The feed content was controlled to be <1%, and the mixture was directly filtered. The filter cake was washed twice with 300 g of water. A yellow solid, 220.5 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, was obtained, with a normalization rate of 97.9% and a two-step yield of 85.5%.
[0061] (4) Methylation reaction:
[0062] 25.7 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, 66 g (2.5 wt) of acetonitrile, and 6 g (1.5 eq) of sodium hydroxide were added. The mixture was heated to 60 °C, sealed with a gasket, and 11.2 g (2 eq) of chloromethane was slowly introduced. The mixture was kept at this temperature for 1 hour. The feed content was controlled to <0.5%. Acetonitrile was collected, and 30 g of water and 50 g of toluene were slowly added. The mixture was allowed to separate into layers. The aqueous layer was extracted twice with 10 g of toluene. The combined oil layers were washed once with 10 g of water. The oil layer was heated to recover toluene. The remaining material was subjected to high vacuum (1 kPa) for 0.5 hours. The remaining material was a brown liquid containing 26.9 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, normalized to 94%, with a yield of 95%.
[0063] Example 2
[0064] (1) Chlorination reaction:
[0065] 94 g of aniline (1 mol, 99%) and 200 g of chloroform (2.1 wt) were mixed, the temperature was lowered to 5 °C, and 220.1 g (3.1 eq) of chlorine gas was introduced. After the purging was completed, the mixture was stirred and kept at this temperature for 3 hours. The concentration of aniline was controlled to be <0.5%, and the product concentration was >90%. The solid was collected by direct filtration. 400 g of 10% liquid alkali was added to the solid, and the mixture was filtered again to obtain the product. The product was normalized to 98.1%, with a yield of 79%, and was a yellow solid.
[0066] (2) Coupling reaction:
[0067] 198.5 g (1 mol) of 2,4,6-trichloroaniline, 700 g of acetonitrile, 100 g of tetrahydrofuran (total 4 wt), 8 g (0.05 eq) of ketone sulfate, and 400 g (4 eq) of isopropyl acetate were added. After addition, the mixture was cooled to 5°C to obtain the synthesis solution. In another four-necked flask, concentrated nitric acid was added and heated to 40-50°C. Sulfur dioxide was slowly passed into the nitric acid, and the generated gas was cooled through a condenser and then passed into the above synthesis solution. The gas flow was stopped when 96 g of sulfur dioxide had been passed into the solution. The synthesis solution was kept at this temperature for 8 hours under controlled conditions. The feedstock 2,4,6-trichloroaniline was <1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one was >93%. The synthesis solution was then subjected to negative pressure and run at rest for 0.5 hours to remove nitrate ions. 300g of water was slowly added to the synthesis solution, and the layers separated. The pH of the oil layer was adjusted to about 7-8 with 10% liquid alkali, and then washed once with 200g of water. The solvent and isopropyl acetate were recovered from the oil layer. The remaining crude product was 268g of 1-(2,4,6-trichlorophenyl)-propyl-2-one, which was normalized to 94.6%.
[0068] (3) Oxime reaction:
[0069] 268 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 321.6 g of methanol (1.6 wt, based on 2,4,6-trichloroaniline), and 126 g of sodium bicarbonate (1.5 eq, based on 2,4,6-trichloroaniline) were added with stirring. 80 g of hydroxylamine hydrochloride (1.15 eq, based on 2,4,6-trichloroaniline) was then added. After the addition was complete, the mixture was kept at this temperature for 3 hours. The feed content was controlled to be <1%, and the mixture was directly filtered. The filter cake was washed twice with 300 g of water. 224 g of a yellow solid, 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, was obtained, with a normalization rate of 98.1% and a two-step yield of 87%.
[0070] (4) Methylation reaction:
[0071] 25.7 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, 66 g (2.5 wt) of methanol, and 8 g (2 eq) of sodium hydroxide were added to an autoclave. 11.2 g (2 eq) of chloromethane was slowly introduced, and the mixture was heated to 80 °C and maintained at this temperature for 3 hours. The raw material concentration was controlled to <0.5%. Methanol was collected, and 20 g of water and 50 g of toluene were slowly added. The mixture was allowed to separate into layers. The aqueous layer was extracted twice with 10 g of toluene. The combined oil layers were washed once with 10 g of water. The toluene in the oil layer was recovered by heating. The remaining material was subjected to high vacuum (1 kPa) for 0.5 hours. The remaining material was a brown liquid, 27.1 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, normalized to 96%, with a yield of 97.1%.
[0072] Example 3
[0073] (1) Chlorination reaction:
[0074] 94 g (1 mol, 99%) of aniline and 200 g (2.1 wt) of dichloroethane were mixed, the temperature was lowered to 5 °C, and 220.1 g (3.1 eq) of chlorine gas was introduced. After the purging was completed, the mixture was stirred and kept at this temperature for 3 hours. The concentration of aniline was controlled to be <0.5%, and the product concentration was >90%. The solid was collected by direct filtration. 400 g of 10% liquid alkali was added to the solid, and the mixture was filtered again to obtain the product. The product was normalized to 99.1%, with a yield of 85.6%, and was a pale yellow solid.
[0075] (2) Coupling reaction:
[0076] Add 198.5 g (1 mol) of 2,4,6-trichloroaniline, 800 g (4 wt) of toluene, 5.5 g (0.03 eq) of ketone acetate, and 500 g (5 eq) of isopropyl acetate. After addition, cool to 5°C. Add 317.5 g (1 eq) of 40% nitrososulfuric acid dropwise, raise the temperature to 40-50°C, and after addition, keep the synthesis solution at this temperature for 8 hours. Under control, the raw material 2,4,6-trichloroaniline <1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one >90%. Slowly add 300 g of water to the synthesis solution, causing separation. Adjust the pH of the oil layer to about 7-8 with 10% alkali solution, then wash once with 200 g of water. Desolventize the oil layer to recover the solvent and isopropyl acetate. The remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 263 g, normalized to 94.3%.
[0077] (3) Oxime reaction:
[0078] 263 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 303.6 g of methanol (1.5 wt, based on 2,4,6-trichloroaniline), and 109.2 g of sodium bicarbonate (1.3 eq, based on 2,4,6-trichloroaniline) were added with stirring. 80 g of hydroxylamine hydrochloride (1.15 eq, based on 2,4,6-trichloroaniline) was then added. After the addition was complete, the mixture was kept at this temperature for 3 hours. The feed content was controlled to be <1%, and the mixture was directly filtered. The filter cake was washed twice with 300 g of water. A yellow solid, 216.5 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, was obtained, with a normalization rate of 96.1% and a two-step yield of 82.4%.
[0079] (4) Methylation reaction:
[0080] 26.2 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, 66 g (2.5 wt) of N,N-dimethylformamide, and 6 g (1.5 eq) of sodium hydroxide were added, followed by slow introduction of 11 g (2 eq) of chloromethane. The reaction was carried out at room temperature for 1 hour after the catalytic reaction was completed. The feed content was controlled at <0.5%. 20 g of water and 50 g of toluene were slowly added, and the mixture was allowed to separate into layers. The aqueous layer was washed once with 10 g of water, and the oil layer was heated to recover toluene. The remaining material was subjected to high vacuum (1 kPa) for 0.5 hours. The remaining material was a brown liquid containing 26.4 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, with a normalization rate of 92.1% and a yield of 90.9%.
[0081] Example 4
[0082] (1) Chlorination reaction:
[0083] 94 g (1 mol, 99%) of aniline and 200 g (2.1 wt) of dichloroethane were mixed, the temperature was lowered to 5 °C, and 220.1 g (3.1 eq) of chlorine gas was introduced. After the purging was completed, the mixture was stirred and kept at this temperature for 3 hours. The concentration of aniline was controlled to be <0.5%, and the product concentration was >90%. The solid was collected by direct filtration. 400 g of 10% liquid alkali was added to the solid, and the mixture was filtered again to obtain the product. The product was normalized to 98.9%, with a yield of 82.7%, and was a pale yellow solid.
[0084] (2) Coupling reaction:
[0085] Add 198.5 g (1 mol) of 2,4,6-trichloroaniline, 800 g (4 wt) of dichloroethane, 5 g (0.05 eq) of chloroacetone, and 400 g (4 eq) of isopropyl acetate. After addition, cool to 0-10℃. In another four-necked flask, add 103.5 g (1.5 eq) of sodium nitrite, and slowly add 50% sulfuric acid, controlling the temperature at 10℃. Simultaneously, cool the generated gas through a condenser and then pass it into the synthesis solution. Stop adding 50% sulfuric acid when no gas is released from the sodium nitrite flask. Keep the synthesis solution at this temperature for 8 hours, maintaining the initial concentration. The feedstock 2,4,6-trichloroaniline <1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one >93%. Perform a negative pressure air extraction on the synthesis solution for 0.5 hours to remove nitrate ions. 300g of water was slowly added to the synthesis solution, and the layers separated. The pH of the oil layer was adjusted to about 7-8 with 10% liquid alkali, and then washed once with 200g of water. The solvent and isopropyl acetate were recovered from the oil layer. The remaining crude product was 258g of 1-(2,4,6-trichlorophenyl)-propyl-2-one, with a purity of 94.7%.
[0086] (3) Oxime reaction:
[0087] 258 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 303.6 g of methanol (1.5 wt, based on 2,4,6-trichloroaniline), and 109.2 g of sodium bicarbonate (1.3 eq, based on 2,4,6-trichloroaniline) were added, followed by stirring and the addition of 80 g of hydroxylamine hydrochloride (1.15 eq, based on 2,4,6-trichloroaniline). After the addition was complete, the mixture was kept at this temperature for 3 hours. The feed content was controlled to be <1%, and the mixture was directly filtered. The filter cake was washed twice with 300 g of water. A yellow solid of 218.5 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime was obtained, with a normalization rate of 97.4% and a two-step yield of 84.3%.
[0088] (4) Methylation reaction:
[0089] 25.9 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, 66 g (2.5 wt) of methanol, and 17.9 g (1.3 eq) of potassium carbonate were added to an autoclave. 11 g (2 eq) of chloromethane was slowly introduced, and the mixture was heated to 40 °C and maintained at this temperature for 3 h. The reactant concentration was controlled at <0.5%. Methanol was collected, and 20 g of water and 50 g of toluene were slowly added. The mixture was allowed to separate into layers. The aqueous layer was extracted twice with 10 g of toluene. The combined oil layers were washed once with 10 g of water. The toluene in the oil layer was recovered by heating. The remaining material was subjected to high vacuum (1 kPa) for 0.5 h. The remaining material was a brown liquid: 30 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, normalized to 93.2%, yield 95.1%.
[0090] Example 5
[0091] Using 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether prepared in Example 2 as a raw material, hydroxylamine was obtained by hydrogenation: 13.8 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether obtained in Example 2, 69 g (5 wt) of acetic acid, 10 g (1 eq) of 98% sulfuric acid, and 2.17 g of 2% Pt / C (55% moisture content) were added to a high-pressure reactor. The reactor was pressurized to 6 MPa by purging with hydrogen three times, and the stirring was started. The temperature was controlled at 20°C and the reaction was maintained for 7 hours. The pressure was released, and the raw material content was kept below 0.5%. Pt / C was recovered by filtration and reused. The mother liquor was subjected to a negative pressure of 350 kPa and desolventized to 80°C to recover acetic acid. The remaining material was added to 25 g of water and 50 g of toluene, and the layers were separated. The aqueous layer was extracted twice with 10 g of toluene, and the oil layers were combined. The oil layer was washed twice with 10g of water, toluene was removed under negative pressure, and the remaining material was subjected to high vacuum (1 kPa) for 0.5 h. The remaining material was 14.5g of brown liquid hydroxylamine, normalized to 96.1%, with a yield of 96.3%.
[0092] Comparative Example 1
[0093] (1) Chlorination reaction:
[0094] Same as Example 2.
[0095] (2) Coupling reaction:
[0096] 198.5 g (1 mol) of 2,4,6-trichloroaniline, 700 g of acetonitrile, 100 g of tetrahydrofuran (total 4 wt), 8 g (0.05 eq) of ketone sulfate, and 400 g (4 eq) of isopropyl acetate were added. After addition, the mixture was cooled to 5°C to obtain the synthesis solution. In another four-necked flask, concentrated nitric acid was added and heated to 100°C. Simultaneously, the generated gas was cooled through a condenser and then passed into the above synthesis solution. The gas flow was stopped when no more gas was generated. The synthesis solution was kept at this temperature for 8 hours under controlled conditions. The feedstock 2,4,6-trichloroaniline content was 19.2%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one content was >39%. The synthesis solution was then subjected to negative pressure for 0.5 hours to remove nitrate ions. 300g of water was slowly added to the synthesis solution, and the layers separated. The pH of the oil layer was adjusted to about 7-8 with 10% liquid alkali, and then washed once with 200g of water. The solvent and isopropyl acetate were recovered from the oil layer. The remaining crude product was 234g of 1-(2,4,6-trichlorophenyl)-propyl-2-one, with a normalization rate of 43.2%.
[0097] (3) Oxime reaction:
[0098] Add 234g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 321.6g of methanol (1.6wt, based on 2,4,6-trichloroaniline), and 126g of sodium bicarbonate (1.5eq, based on 2,4,6-trichloroaniline). Stir and add 80g of hydroxylamine hydrochloride (1.15eq, based on 2,4,6-trichloroaniline). After the addition is complete, keep warm for 3 hours. The raw material yield is controlled to be <1%, and the product yield is 40.8%. Filter directly, and wash the filter cake twice with 300g of water. Obtain a yellow solid, 85.8g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, normalization 79.4%, two-step yield 27%.
[0099] (4) Methylation reaction:
[0100] Same as in Example 2, 30.1 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether, normalized to 77.1%, yield 87.3%.
[0101] Comparative Example 2
[0102] (1) Chlorination reaction:
[0103] Same as Example 2.
[0104] (2) Coupling reaction:
[0105] 198.5 g (1 mol) of 2,4,6-trichloroaniline, 700 g of acetonitrile, 100 g of tetrahydrofuran (total 4 wt), 0.8 g (0.005 eq) of ketone sulfate, and 400 g (4 eq) of isopropyl acetate were added. After addition, the mixture was cooled to 5°C to obtain the synthesis solution. In another four-necked flask, concentrated nitric acid was added and heated to 40-50°C. Sulfur dioxide was slowly passed into the nitric acid, and the generated gas was cooled through a condenser and then passed into the above synthesis solution. The gas was stopped after 96 g of sulfur dioxide had been passed into the solution. The synthesis solution was kept at this temperature for 8 hours under central control. The feedstock 2,4,6-trichloroaniline was 5%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one was 24%. The synthesis solution was then subjected to negative pressure and run at rest for 0.5 hours to remove nitrate ions. 300g of water was slowly added to the synthesis solution, and the layers separated. The pH of the oil layer was adjusted to about 7-8 with 10% liquid alkali, and then washed once with 200g of water. The solvent and isopropyl acetate were recovered from the oil layer. The remaining crude product was 213g of 1-(2,4,6-trichlorophenyl)-propyl-2-one, with a purity of 29.3%.
[0106] (3) Oxime reaction:
[0107] 213 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 238.2 g of methanol (1.2 wt, based on 2,4,6-trichloroaniline), and 92.4 g of sodium bicarbonate (1.1 eq, based on 2,4,6-trichloroaniline) were added with stirring, followed by the addition of 69.5 g of hydroxylamine hydrochloride (1.0 eq, based on 2,4,6-trichloroaniline). After the addition was complete, the mixture was kept at this temperature for 3 hours. The mixture was then directly filtered, and the filter cake was washed twice with 300 g of water. A yellow solid of 77.2 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime was obtained, with a normalization rate of 64.1% and a two-step yield of 19.6%.
[0108] (4) Methylation reaction:
[0109] Same as Example 2, 37.3 g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-methoxyoxime ether, normalization 61.7%, yield 86.4%.
[0110] Comparative Example 3
[0111] (1) Chlorination reaction:
[0112] Same as Example 2.
[0113] (2) Coupling reaction:
[0114] Same as Example 2.
[0115] (3) Oxime reaction:
[0116] 268 g of crude 1-(2,4,6-trichlorophenyl)-propyl-2-one, 321.6 g of methanol (1.6 wt, based on 2,4,6-trichloroaniline), and 64.8 g of sodium methoxide (1.2 eq, based on 2,4,6-trichloroaniline) were added with stirring, followed by the addition of 80 g of hydroxylamine hydrochloride (1.15 eq, based on 2,4,6-trichloroaniline). After the addition was complete, the mixture was kept at this temperature for 3 hours. Under control, the feed yield was 61.9% and the product yield was 35.3%. The mixture was directly filtered, and the filter cake was washed twice with 300 g of water. A yellow solid, 54 g of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, was obtained, with a normalization rate of 83% and a two-step yield of 17.7%.
[0117] (4) Methylation reaction:
[0118] Same as Example 2, 28.4 g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-methoxyoxime ether, normalized to 80.2%, yield 85.9%.
[0119] Comparative Example 4
[0120] (1) Chlorination reaction:
[0121] Same as Example 2.
[0122] (2) Coupling reaction:
[0123] Same as Example 2.
[0124] (3) Oxime reaction:
[0125] Same as Example 2.
[0126] (4) Methylation reaction:
[0127] 25.9 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, 66 g (2.5 wt) of toluene, and 6 g (1.5 eq) of sodium hydroxide were added to an autoclave. 11 g (2 eq) of chloromethane was slowly introduced, and the mixture was heated to 80 °C and maintained at this temperature for 3 hours. Under control, the reactant content was >97%. No reaction occurred.
[0128] As can be seen from the above examples and comparative examples, in Comparative Example 1, the heating temperature of the nitryl ions in the coupling reaction of step (2) was too high, resulting in the instability of the nitryl ions and thus a significantly reduced yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime. In Comparative Example 2, the amount of copper sulfate catalyst used in the coupling reaction of step (2) was too small, causing the coupling reaction to fail to compete with the deamination reaction, thus a significantly reduced yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime. In Comparative Example 3, the use of sodium methoxide as the base in the oximation reaction of step (3) resulted in the rapid decomposition of hydroxylamine hydrochloride, preventing timely reaction, thus a significantly reduced yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime. In Comparative Example 4, the use of toluene instead of methanol in the methylation reaction of step (4) resulted in the low solubility and dilute concentration of chloromethane, preventing the reaction from occurring, thus the methylation reaction could not occur. Therefore, the specific reaction conditions of this invention can guarantee a reaction yield of over 90%, while changes in the conditions of the comparative experiment significantly affect the reaction yield. This invention prepares 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether from aniline, simplifying the operation, reducing pollution, and possessing good industrial application value. Simultaneously, it also exhibits high conversion and yield, showing promising prospects.
[0129] The above examples are merely illustrative of the technical concept and features of the present invention and should not be construed as limiting the scope of protection of the present invention. All equivalent transformations or modifications made in accordance with the essence of the present invention should be included within the scope of protection of the present invention.
Claims
1. A process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methoxyoxime ether, characterized in that: Includes the following steps: (1) Chlorination reaction: In a solvent, at 0-10℃, aniline was used as a raw material, and a chlorinating agent was added to obtain 2,4,6-trichloroaniline through a chlorination reaction. (2) Coupling reaction: 2,4,6-trichloroaniline, isopropyl acetate, and a catalyst were coupled in a solvent under the initiation of nitryl ions to give 1-(2,4,6-trichloro-phenyl)-propyl-2-one; (3) Oxime reaction: In a solvent, under the action of a base, 1-(2,4,6-trichlorophenyl)-propyl-2-one undergoes an oxime reaction with hydroxylamine hydrochloride to give 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime; (4) Methylation reaction: 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime, in a solvent and under the action of a base, undergoes a methylation reaction with chloromethane to give 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether.
2. Process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, In step (1), the chlorinating agent is one or more of chlorine, sulfonyl chloride, and NCS; the molar ratio of the chlorinating agent to aniline is 3-3.5:
1. In step (1), the solvent is one or more of chloroform, dichloroethane, dichloromethane, tetrahydrofuran, methyl-tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, benzene, toluene, and xylene; the weight ratio of the solvent to aniline is 1 to 10:
1.
3. Process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, The chlorination reaction takes 3-5 hours.
4. The process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, In step (2), the nitrate ions are gases produced by passing sulfur dioxide into nitric acid under heating conditions, or gases produced by heating nitrososulfuric acid, or gases produced by sodium nitrite in the presence of acid, etc., with a heating temperature of 30-100℃.
5. The process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, In step (2), the molar ratio of isopropyl acetate to 2,4,6-trichloroaniline is 1-8:1; The coupling reaction temperature is -10 to 20℃, and the reaction time is 6 to 10 hours.
6. The process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, In step (2), the catalyst is one or more of the following: alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, copper sulfate, copper acetate, cuprous trifluoromethanesulfonate, or copper chloride; the molar ratio of the catalyst to 2,4,6-trichloroaniline is 0.01 to 0.2:
1. In step (2), the solvent is one or more of acetone, acetonitrile, tetrahydrofuran, methyl-tetrahydrofuran, dichloromethane, dichloroethane, chloroform, benzene, toluene, xylene, etc.; the weight ratio of the solvent to 2,4,6-trichloroaniline is 1 to 10:
1.
7. A process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, In step (3), the alkali is one or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, and potassium acetate; the molar ratio of the alkali to 2,4,6-trichloroaniline is 1 to 5:
1. In step (3), the solvent is one or more of methanol, ethanol, and methyl tert-butyl ether; the weight ratio of the solvent to 2,4,6-trichloroaniline is 1-5:
1. The molar ratio of hydroxylamine hydrochloride to 2,4,6-trichloroaniline is 1-2:
1.
8. A process for the preparation of l-(2,4,6-trichloro-phenyl)-propyl-2-ketone- methyloxyoxime ether according to claim 1, characterized in that, The oxime reaction in step (3) is carried out at a temperature of 10–60°C for 1–6 hours.
9. The method for preparing 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether according to claim 1, characterized in that, In step (4), the alkali is one or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide; the molar ratio of the alkali to 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime is 1 to 5:
1. The solvent in step (4) is acetonitrile, methanol, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, etc. The weight ratio of the solvent to 1-(2,4,6-trichlorophenyl)-propyl-2-one-oxime is 1-5:
1.
10. The method for preparing 1-(2,4,6-trichlorophenyl)-propyl-2-one-methoxyoxime ether according to claim 1, characterized in that, Step (4) Methylation reaction, at a temperature of 10-110℃ for 1-6 hours.