Preparation method of 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether. Comprising the following steps: (1) chlorination reaction: adding a chlorinating agent into aniline serving as a raw material in a solvent at 0-10 DEG C, and carrying out chlorination reaction to obtain 2, 4, 6-trichloroaniline; (2) coupling reaction: carrying out coupling reaction on 2, 4, 6-trichloroaniline, isopropenyl acetate and a catalyst in a solvent under the initiation of nitroxyl ions to obtain 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone; (3) oximation reaction: in a solvent, under the action of alkali, carrying out oximation reaction on the 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone and hydroxylamine hydrochloride, so as to obtain 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone-oxime; and (4) methylation reaction: carrying out methylation reaction on the 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone-oxime and chloromethane in a solvent under the action of alkali to obtain the 1-(2, 4, 6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether. Background Art

[0002] 1-(2,4,6-Trichloro-phenyl)-propyl-2-keto-methoxy oxime ether is an important intermediate for the synthesis of pesticides and medicines. Hydroxylamine can be obtained by hydrogenation reduction. The chemical formula is as follows:

[0003]

[0004] The synthesis of 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether includes the following methods:

[0005] The method of WO2010063700 is as follows:

[0006]

[0007] This method requires the use of butyl lithium, diisopropylamine and N,N-dimethylformamide to react at -78°C, which is relatively dangerous, costly, uses iron powder, produces a large amount of solid waste, and is difficult to industrialize.

[0008] The methods of WO2013127764 and WO2013127441 are as follows:

[0009]

[0010] The raw materials used in this route and method, ethyl propylene acetate and tert-butyl nitrite, are relatively expensive, and the reaction yields are 48% and 58% respectively. The reaction has safety risks, low yields, and a lot of three wastes.

[0011] Patent CN108610290A uses p-chloroaniline as the starting material, and the synthesis method is as follows:

[0012]

[0013] Although this method can reduce costs, the raw materials used, ethyl propylene acetate and tert-butyl nitrite, are relatively expensive and also involve diazotization. Both steps involve safety issues, production and manufacturing, and equipment investment.

[0014] Patent CN113004131A uses 2,4,6-trichlorotoluene and chlorination reagent as raw materials, and the synthesis method is as follows:

[0015]

[0016] The 2,4,6-trichlorotoluene in this method is expensive and difficult to obtain. The self-synthesis of acetylenic magnesium halide requires acetylene and n-butylmagnesium chloride to prepare. Acetylene is a hazardous chemical with harsh storage and use conditions and high risk. At the same time, the Grignard reaction has high requirements for equipment heat exchange.

[0017] Patent CN117326921A uses trichlorobenzene as raw material for synthesis, and the synthesis method is as follows:

[0018]

[0019] The raw material trichlorobenzene of this method is also relatively expensive and difficult to obtain, and the catalysts used in each step are also uncommon, and the reaction time is also relatively long.

[0020] Patent CN115703701A uses a microchannel to synthesize 1-(2,4,6-trichloro-phenyl)-propyl-2-one using 2,4,6-trichloroaniline, organic nitrite, and isopropenyl acetate. This method actually has certain technical challenges for production scale-up. Summary of the invention

[0021] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether.

[0022] In order to achieve the above object, the technical solution adopted by the present invention is:

[0023] A method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether comprises the following steps:

[0024] (1) Chlorination reaction:

[0025] In a solvent, at 0-10°C, aniline (Formula I) is used as a raw material, a chlorinating agent is added, and 2,4,6-trichloroaniline (Formula II) is obtained by chlorination reaction;

[0026] (2) Coupling reaction:

[0027] 2,4,6-trichloroaniline (Formula II), isopropenyl acetate and a catalyst are reacted in a solvent under the initiation of nitroxyl ions to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone (Formula III);

[0028] (3) Oximation reaction:

[0029] In a solvent, under the action of a base, 1-(2,4,6-trichloro-phenyl)-propyl-2-one (Formula III) and hydroxylamine hydrochloride undergo an oximation reaction to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime (Formula IV);

[0030] (4) Methylation reaction:

[0031] 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-oxime (Formula IV) is subjected to a methylation reaction with chloromethane in a solvent under the action of a base to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxyoxime ether (Formula V).

[0032] The reaction formula is as follows:

[0033]

[0034] In the step (1), the chlorinating agent is one or more of chlorine, sulfuryl chloride, and NCS; preferably chlorine.

[0035] The molar ratio of the chlorinating agent to the aniline is 3-3.5:1.

[0036] 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;

[0037] The weight ratio of the solvent to the aniline is 1 to 10:1.

[0038] The chlorination reaction time is 3-5h.

[0039] In the step (2), the nitroxyl ion is a gas generated by passing sulfur dioxide into nitric acid under heating conditions, or a gas generated by heating p-nitrosulfate, and the heating temperature is 30-100° C., preferably 40-60° C.

[0040] In step (2), the molar ratio of isopropenyl acetate to 2,4,6-trichloroaniline is 1-8:1, preferably 2-4:1. The molar ratio of the catalyst to 2,4,6-trichloroaniline is 0.01-0.2:1.

[0041] The coupling reaction temperature is -10-20°C and the reaction time is 6-10h.

[0042] In step (2), the catalyst is one or more of alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, cupric sulfate, cupric acetate, cuprous trifluoromethanesulfonate or cupric chloride;

[0043] In step (2), the solvent is one or more of acetone, acetonitrile, tetrahydrofuran, methyltetrahydrofuran, dichloromethane, dichloroethane, chloroform, benzene, toluene, xylene, etc.;

[0044] The weight ratio of the solvent to 2,4,6-trichloroaniline is 1 to 10:1.

[0045] 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;

[0046] The molar ratio of the base to 2,4,6-trichloroaniline is 1 to 5:1;

[0047] In step (3), the solvent is one or more of methanol, ethanol, and methyl tert-butyl ether;

[0048] The weight ratio of the solvent to 2,4,6-trichloroaniline is 1-5:1;

[0049] The molar ratio of hydroxylamine hydrochloride to 2,4,6-trichloroaniline is 1-2:1.

[0050] The oximation reaction temperature in step (3) is 10 to 60° C. and the reaction time is 1 to 6 hours.

[0051] In step (4), the base 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 base to 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime is 1 to 5:1;

[0052] The solvent in step (4) is acetonitrile, methanol, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, etc.

[0053] The weight ratio of the solvent to 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime is 1-5:1.

[0054] Step (4) methylation reaction, the temperature is 10 to 110° C., and the time is 1 to 6 hours.

[0055] A method for preparing hydroxylamine, wherein oxime ether prepared by the preparation method is used as a raw material and hydrogenated and reduced to obtain hydroxylamine.

[0056] The advantages of the present invention are:

[0057] The present invention optimizes the synthesis process of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether, and simultaneously optimizes the process of 1-(2,4,6-trichlorophenyl)acetone-2, and can be purified in one step after the synthesis of oxime, with high purity and convenience, and the synthesis of oxime ether by methylation of oxime is also very simple, so that the operation of the whole process is relatively simple. At the same time, the conversion rate and yield of each step are relatively good, the purity is also good, and basically no recrystallization is required, the overall route yield is 67%, and the reaction temperature of each step is in the easy-to-operate region, the energy consumption is also low, and the reaction time of each step is relatively short, and the cycle is greatly shortened.

[0058] Compared with other methods, the preparation process of the method of the present invention has a wide source of raw materials, simple operation, and simple three waste treatment; the present invention uses aniline as a raw material to prepare 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, simplifies the operation, reduces pollution, and has good industrial application value. At the same time, the conversion rate and yield are also high, and it has a good prospect. DETAILED DESCRIPTION

[0059] The specific implementation methods of the technical solution of the present invention are described in detail below. It should be understood that the following examples are only used to illustrate the present invention, but the present invention is not limited to the scope of the following description:

[0060] The present invention will be described below in conjunction with specific embodiments:

[0061] Example 1

[0062] (1) Chlorination reaction:

[0063] 94g (1 mol, 99%) of aniline and 200g (2.1 wt%) of dichloroethane were added, the temperature was lowered to 5°C, 234.3g (3.3eq) of chlorine gas was introduced, and the mixture was stirred and kept warm for 3h. The aniline concentration was controlled to be <0.5%, and the product was >90%. The solid was directly collected by suction filtration, 400g of 10% liquid caustic soda was added to the solid, and the product was obtained by suction filtration, with a normalization of 99.2% and a yield of 84%, as a light yellow solid.

[0064] (2) Coupling reaction:

[0065] Add 198.5g (1mol) of 2,4,6-trichloroaniline, 800g (4wt) of tetrahydrofuran, 8g (0.05eq) of sulfate ketone, and 400g (4eq) of isopropenyl acetate. After adding, cool to 5°C. Add concentrated nitric acid to another four-necked bottle, heat to 40-50°C, slowly pass sulfur dioxide into the nitric acid, and cool the generated gas through a condenser and pass it into the synthetic liquid. After monitoring that 96g of sulfur dioxide has been passed, stop passing it, keep the four-necked bottle heated for 1h, and stop heating. At the same time, the synthetic liquid is kept warm for 8h, and the central control shows that the raw material 2,4,6-trichloroaniline is less than 1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one is greater than 93%. The synthetic liquid is pulled under negative pressure for 0.5h to remove nitroxyl ions. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash once with 200g of water. Desolventize the oil layer to recover the solvent tetrahydrofuran and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 253g, normalized to 94.2%;

[0066] (3) Oximation reaction:

[0067] Add 253g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 303.6g of methanol (1.5wt, based on 2,4,6-trichloroaniline), 109.2g of sodium bicarbonate (1.3eq, based on 2,4,6-trichloroaniline), stir and add 80g of hydroxylamine hydrochloride (1.15eq, based on 2,4,6-trichloroaniline), add and keep warm at 25℃ for 3h. The raw material is controlled to be <1%, and the filter cake is directly filtered and rinsed with 300g of water twice. A yellow solid, 220.5g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime, normalized to 97.9%, and a two-step yield of 85.5% is obtained.

[0068] (4) Methylation reaction:

[0069] Add 25.7g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime, 66g (2.5wt) of acetonitrile, and 6g (1.5eq) of sodium hydroxide, heat to 60°C, seal with air bag, slowly introduce 11.2g (2eq) of methyl chloride, and keep warm for 1h. Central control, raw material <0.5%. Take out acetonitrile, slowly add 30g of water and 50g of toluene, separate into layers, extract the water layer twice with 10g of toluene, wash the combined oil layer with 10g of water once, heat the oil layer to recover toluene, and pull the remaining material under high vacuum 1Kpa for 0.5h. The remaining material is 26.9g of brown liquid 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether, normalized to 94%, and the yield is 95%.

[0070] Example 2

[0071] (1) Chlorination reaction:

[0072] 94g (1 mol, 99%) of aniline and 200g (2.1 wt%) of chloroform were added, the temperature was lowered to 5°C, 220.1g (3.1 eq) of chlorine gas was introduced, and the mixture was stirred and kept warm for 3 hours. The aniline concentration was controlled to be <0.5%, and the product was >90%. The solid was directly collected by suction filtration, 400g of 10% liquid caustic soda was added to the solid, and the product was obtained by suction filtration, with a normalization of 98.1% and a yield of 79%, as a yellow solid.

[0073] (2) Coupling reaction:

[0074] Add 198.5g (1mol) of 2,4,6-trichloroaniline, 700g of acetonitrile, 100g of tetrahydrofuran (4wt in total), 8g (0.05eq) of sulfate ketone, and 400g (4eq) of isopropenyl acetate. After adding, cool to 5°C to use as the synthetic liquid. In another four-necked bottle, add concentrated nitric acid, heat to 40-50°C, slowly pass sulfur dioxide into the nitric acid, and at the same time, cool the generated gas through a condenser and pass it into the above synthetic liquid. After monitoring that 96g of sulfur dioxide has been passed, stop passing it. At the same time, the synthetic liquid is kept warm for 8h, and the central control shows that the raw material 2,4,6-trichloroaniline is <1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one is >93%. The synthetic liquid is pulled under negative pressure for 0.5h to remove nitroxyl ions. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash once with 200g of water. Desolventize the oil layer to recover the solvent and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 268g, normalized to 94.6%;

[0075] (3) Oximation reaction:

[0076] Add 268g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 321.6g of methanol (1.6wt, based on 2,4,6-trichloroaniline), 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), add and keep warm for 3h. The raw material is controlled to be <1%, and the filter cake is directly filtered and rinsed with 300g of water twice. A yellow solid, 224g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime, normalized to 98.1%, and a two-step yield of 87%.

[0077] (4) Methylation reaction:

[0078] 25.7g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime, 66g (2.5wt) of methanol, and 8g (2eq) of sodium hydroxide were added into the autoclave, and 11.2g (2eq) of methyl chloride was slowly introduced, and the temperature was raised to 80°C, and the reaction was kept warm for 3h. In the middle control, the raw material was <0.5%. Methanol was extracted, and 20g of water and 50g of toluene were slowly added. The layers were separated, and the water layer was extracted twice with 10g of toluene, and the combined oil layers were washed once with 10g of water. The oil layer was heated to recover toluene, and the remaining material was pulled under high vacuum at 1Kpa for 0.5h. The remaining material was 27.1g of brown liquid 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether, normalized to 96%, and the yield was 97.1%.

[0079] Example 3

[0080] (1) Chlorination reaction:

[0081] 94g (1 mol, 99%) of aniline and 200g (2.1 wt%) of dichloroethane were added, the temperature was lowered to 5°C, 220.1g (3.1 eq) of chlorine gas was introduced, and the mixture was stirred and kept warm for 3 hours. The aniline concentration was controlled to be <0.5%, and the product was >90%. The solid was directly collected by suction filtration, 400g of 10% liquid caustic soda was added to the solid, and the product was obtained by suction filtration, with a normalization of 99.1% and a yield of 85.6%, as a light yellow solid.

[0082] (2) Coupling reaction:

[0083] Add 198.5g (1mol) of 2,4,6-trichloroaniline, 800g of toluene (4wt), 5.5g (0.03eq) of acetic acid ketone, and 500g (5eq) of isopropenyl acetate. After adding, cool to 5°C. Add 317.5g (1eq) of 40% nitrosylsulfuric acid dropwise, raise the temperature to 40-50°C, and keep the synthetic liquid warm for 8h. In the middle control, the raw material 2,4,6-trichloroaniline is less than 1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one is more than 90%. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash it once with 200g of water. Desolventize the oil layer to recover the solvent and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one is 263g, normalized to 94.3%;

[0084] (3) Oximation reaction:

[0085] Add 263g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 303.6g of methanol (1.5wt, based on 2,4,6-trichloroaniline), 109.2g of sodium bicarbonate (1.3eq, based on 2,4,6-trichloroaniline), stir and add 80g of hydroxylamine hydrochloride (1.15eq, based on 2,4,6-trichloroaniline), add and heat for 3h. The raw material is controlled to be <1%, and the filter cake is directly filtered and rinsed with 300g of water twice. A yellow solid, 216.5g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime, normalized to 96.1%, and the two-step yield is 82.4%.

[0086] (4) Methylation reaction:

[0087] Add 26.2g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime, 66g (2.5wt) of N,N-dimethylformamide, and 6g (1.5eq) of sodium hydroxide, slowly pass 11g (2eq) of methyl chloride, react at room temperature, and react for 1h. In the middle control, the raw material is <0.5%. Slowly add 20g of water and 50g of toluene, separate the layers, wash the water layer with 10g of water once, heat the oil layer to recover toluene, and pull the remaining material under high vacuum 1Kpa for 0.5h. The remaining material is 26.4g of brown liquid 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether, normalized to 92.1%, and the yield is 90.9%.

[0088] Example 4

[0089] (1) Chlorination reaction:

[0090] 94g (1 mol, 99%) of aniline and 200g (2.1 wt%) of dichloroethane were added, the temperature was lowered to 5°C, 220.1g (3.1 eq) of chlorine gas was introduced, and the mixture was stirred and kept warm for 3 hours. The aniline concentration was controlled to be <0.5%, and the product was >90%. The solid was directly collected by suction filtration, 400g of 10% liquid caustic soda was added to the solid, and the product was obtained by suction filtration, with a normalization of 98.9% and a yield of 82.7%, as a light yellow solid.

[0091] (2) Coupling reaction:

[0092] Add 198.5g (1mol) of 2,4,6-trichloroaniline, 800g (4wt) of dichloroethane, 5g (0.05eq) of chlorinated ketone, and 400g (4eq) of isopropenyl acetate. After adding, cool to 0-10°C. In another four-necked bottle, add 103.5g (1.5eq) of sodium nitrite, slowly drip 50% sulfuric acid, control the temperature at 10°C, and at the same time, cool the generated gas through a condenser and pass it into the synthetic liquid. When no gas is released from the sodium nitrite bottle, stop dripping 50% sulfuric acid. At the same time, the synthetic liquid is kept warm for 8h, and the central control shows that the raw material 2,4,6-trichloroaniline is less than 1%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one is more than 93%. The synthetic liquid is pulled under negative pressure for 0.5h to remove nitroxyl ions. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash once with 200g of water. Desolventize the oil layer to recover the solvent and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 258g, normalized to 94.7%;

[0093] (3) Oximation reaction:

[0094] Add 258g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 303.6g of methanol (1.5wt, based on 2,4,6-trichloroaniline), 109.2g of sodium bicarbonate (1.3eq, based on 2,4,6-trichloroaniline), stir and add 80g of hydroxylamine hydrochloride (1.15eq, based on 2,4,6-trichloroaniline), add and heat for 3h. The raw material is controlled to be <1%, and the filter cake is directly filtered and rinsed with 300g of water twice. A yellow solid, 218.5g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime, is obtained, normalized to 97.4%, and the two-step yield is 84.3%.

[0095] (4) Methylation reaction:

[0096] 25.9g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime, 66g (2.5wt) of methanol, and 17.9g (1.3eq) of potassium carbonate were added into the autoclave, 11g (2eq) of methyl chloride was slowly introduced, the temperature was raised to 40°C, and the reaction was kept warm for 3h. In the middle control, the raw material was <0.5%. Methanol was extracted, 20g of water and 50g of toluene were slowly added, the layers were separated, the water layer was extracted twice with 10g of toluene, the combined oil layers were washed once with 10g of water, the oil layer was heated to recover toluene, and the remaining material was pulled under high vacuum at 1Kpa for 0.5h. The remaining material was 30g of brown liquid 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether, normalized to 93.2%, and the yield was 95.1%.

[0097] Example 5

[0098] Take the 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether prepared in Example 2 as the raw material, and hydrogenate to obtain hydroxylamine: 13.8g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-methoxy oxime ether obtained in Example 2, 69g (5wt) of acetic acid, 10g (1eq) of 98% sulfuric acid, and 2.17g of 2% Pt / C containing 55% moisture are put into the autoclave, replaced with hydrogen 3 times, pressurized to 6MPa, stirred, controlled at 20°C, and kept warm for 7h. Pressure relief, middle control, raw material less than 0.5%. Pt / C is recovered by suction filtration and applied. The mother liquor is under a negative pressure of 350KPa, desolventized to 80°C, and acetic acid is recovered. 25g of water and 50g of toluene are added to the remaining material, and the layers are separated. The water layer is extracted twice with 10g of toluene, and the oil layer is combined. The oil layer was washed twice with 10g water, toluene was removed under negative pressure, and the remaining material was pulled under high vacuum at 1Kpa for 0.5h. The remaining material was 14.5g of brown liquid hydroxylamine, normalized to 96.1%, with a yield of 96.3%.

[0099] Comparative Example 1

[0100] (1) Chlorination reaction:

[0101] Same as Example 2.

[0102] (2) Coupling reaction:

[0103] Add 198.5g (1mol) of 2,4,6-trichloroaniline, 700g of acetonitrile, 100g of tetrahydrofuran (4wt in total), 8g (0.05eq) of sulfate ketone, and 400g (4eq) of isopropenyl acetate. After adding, cool to 5°C to use as the synthetic liquid. In another four-necked bottle, add concentrated nitric acid and heat to 100°C. At the same time, cool the generated gas through a condenser and pass it into the above synthetic liquid. When no gas is generated, stop passing it. At the same time, keep the synthetic liquid warm for 8h, and control the raw material 2,4,6-trichloroaniline = 19.2%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one>39%. Negative pressure air pull the synthetic liquid for 0.5h to remove nitroxyl ions. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash once with 200g of water. Desolventize the oil layer to recover the solvent and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 234g, normalized to 43.2%;

[0104] (3) Oximation reaction:

[0105] Add (2) crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one 234g, methanol 321.6g (1.6wt, based on 2,4,6-trichloroaniline), sodium bicarbonate 126g (1.5eq, based on 2,4,6-trichloroaniline), stir and add hydroxylamine hydrochloride 80g (1.15eq, based on 2,4,6-trichloroaniline), after adding, keep warm for 3h. The raw material is controlled at <1%, the product is 40.8%, directly filtered, and the filter cake is rinsed twice with 300g of water. A yellow solid, 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime 85.8g, normalized to 79.4%, two-step yield 27%.

[0106] (4) Methylation reaction:

[0107] Same as Example 2, 30.1 g of 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, normalized to 77.1%, yield 87.3%.

[0108] Comparative Example 2

[0109] (1) Chlorination reaction:

[0110] Same as Example 2.

[0111] (2) Coupling reaction:

[0112] Add 198.5g (1 mol) of 2,4,6-trichloroaniline, 700g of acetonitrile, 100g of tetrahydrofuran (4wt in total), 0.8g (0.005eq) of sulfate ketone, and 400g (4eq) of isopropenyl acetate. After adding, cool to 5°C to use as the synthetic liquid. In another four-necked bottle, add concentrated nitric acid, heat to 40-50°C, slowly pass sulfur dioxide into the nitric acid, and at the same time, cool the generated gas through a condenser and pass it into the above synthetic liquid. After monitoring the sulfur dioxide to be passed in 96g, stop passing it in. At the same time, the synthetic liquid is kept warm for 8h, and the central control is that the raw material 2,4,6-trichloroaniline = 5%, and the product 1-(2,4,6-trichloro-phenyl)-propyl-2-one = 24%. The synthetic liquid is pulled under negative pressure for 0.5h to remove nitroxyl ions. Slowly add 300g of water to the synthetic liquid, separate the layers, adjust the pH of the oil layer to about 7-8 with 10% liquid alkali, and then wash once with 200g of water. Desolventize the oil layer to recover the solvent and isopropenyl acetate, and the remaining crude product 1-(2,4,6-trichloro-phenyl)-propyl-2-one 213g, normalized to 29.3%;

[0113] (3) Oximation reaction:

[0114] Add 213g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 238.2g of methanol (1.2wt, based on 2,4,6-trichloroaniline), 92.4g of sodium bicarbonate (1.1eq, based on 2,4,6-trichloroaniline), stir and add 69.5g of hydroxylamine hydrochloride (1.0eq, based on 2,4,6-trichloroaniline), add and heat for 3h. Filter directly, rinse the filter cake with 300g of water twice. Obtain yellow solid, 77.2g of 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime, normalized to 64.1%, two-step yield 19.6%.

[0115] (4) Methylation reaction:

[0116] Same as Example 2, 37.3 g of 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, normalized to 61.7%, yield 86.4%.

[0117] Comparative Example 3

[0118] (1) Chlorination reaction:

[0119] Same as Example 2.

[0120] (2) Coupling reaction:

[0121] Same as Example 2.

[0122] (3) Oximation reaction:

[0123] Add 268g of crude 1-(2,4,6-trichloro-phenyl)-propyl-2-one, 321.6g of methanol (1.6wt, based on 2,4,6-trichloroaniline), 64.8g of sodium methoxide (1.2eq, based on 2,4,6-trichloroaniline), stir and add 80g of hydroxylamine hydrochloride (1.15eq, based on 2,4,6-trichloroaniline), add and keep warm for 3h. Central control, raw material 61.9%, product 35.3%. Filter directly, and rinse the filter cake with 300g of water twice. Obtain yellow solid, 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime 54g, normalized to 83%, two-step yield 17.7%.

[0124] (4) Methylation reaction:

[0125] Same as Example 2, 28.4 g of 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, normalized to 80.2%, yield 85.9%.

[0126] Comparative Example 4

[0127] (1) Chlorination reaction:

[0128] Same as Example 2.

[0129] (2) Coupling reaction:

[0130] Same as Example 2.

[0131] (3) Oximation reaction:

[0132] Same as Example 2.

[0133] (4) Methylation reaction:

[0134] 25.9g (0.1mol) of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime, 66g (2.5wt) of toluene, and 6g (1.5eq) of sodium hydroxide were added into the autoclave, and 11g (2eq) of methyl chloride was slowly introduced, and the temperature was raised to 80°C, and the temperature was kept for 3h. During the control, the raw material was >97%. No reaction occurred.

[0135] As can be seen from the above embodiments and comparative examples, in comparative example 1, due to the high heating temperature of the nitroxyl ion in the coupling reaction of step (2), the nitroxyl ion decomposition cannot be stably present, so the yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime is significantly reduced. In comparative example 2, due to the small amount of copper sulfate catalyst used in the coupling reaction of step (2), the coupling reaction cannot compete with the deamination reaction, so the yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime is significantly reduced. In comparative example 3, due to the use of sodium methoxide as the base in the oximation reaction of step (3), the hydroxylamine hydrochloride decomposes too quickly and cannot react in time, so the yield of 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-oxime is significantly reduced. In comparative example 4, due to the use of toluene instead of methanol in the methylation reaction of step (4), the solubility of methyl chloride is small and the concentration is too dilute to induce the reaction, so the methylation reaction cannot occur. Therefore, the specific reaction conditions of the present invention can ensure that the reaction yield is above 90%. After the conditions of the comparative example are changed, the reaction yield is significantly affected. The present invention uses aniline as a raw material to prepare 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, simplifies the operation, reduces pollution, and has good industrial application value. At the same time, the conversion rate and yield are also high, and it has a good prospect.

[0136] The above examples are only for illustrating the technical concept and technical features of the present invention, and cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the essence of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether, characterized in that: The steps include: (1) Chlorination reaction: In a solvent, at 0-10°C, aniline is used as a raw material, a chlorinating agent is added, and 2,4,6-trichloroaniline is obtained through a chlorination reaction; (2) Coupling reaction: 2,4,6-trichloroaniline, isopropenyl acetate and a catalyst are reacted in a solvent under the initiation of nitroxyl ions to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-one; (3) Oximation reaction: In a solvent, under the action of a base, 1-(2,4,6-trichloro-phenyl)-propyl-2-one and hydroxylamine hydrochloride undergo an oximation reaction to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-one-oxime; (4) Methylation reaction: 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-oxime, in a solvent, under the action of a base, undergoes a methylation reaction with methyl chloride to obtain 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether.

2. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (1), the chlorinating agent is one or more of chlorine, sulfuryl chloride, and NCS; the molar ratio of the chlorinating agent to aniline is 3-3.5:1; The solvent in step (1) is one or more of chloroform, dichloroethane, dichloromethane, tetrahydrofuran, methyl-tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, benzene, toluene and xylene; and the weight ratio of the solvent to aniline is 1 to 10:

1.

3. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: The chlorination reaction time is 3-5h.

4. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (2), the nitroxyl ion is a gas generated by passing sulfur dioxide into nitric acid under heating conditions, or a gas generated by heating nitrosylsulfuric acid, or a gas generated by sodium nitrite in the presence of an acid, etc., and the heating temperature is 30-100°C.

5. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (2), the molar ratio of isopropenyl acetate to 2,4,6-trichloroaniline is 1-8:1; The coupling reaction temperature is -10-20°C and the reaction time is 6-10h.

6. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (2), the catalyst is one or more of alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, cupric sulfate, cupric acetate, cuprous trifluoromethanesulfonate or cupric chloride; and the molar ratio of the catalyst to 2,4,6-trichloroaniline is 0.01-0.2:

1. The solvent in step (2) 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. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (3), the base 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 base 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. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: The oximation reaction temperature in step (3) is 10 to 60° C. and the reaction time is 1 to 6 hours.

9. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: In step (4), the base 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 base to 1-(2,4,6-trichloro-phenyl)-propyl-2-ketone-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-trichloro-phenyl)-propyl-2-ketone-oxime is 1-5:

1.

10. The method for preparing 1-(2,4,6-trichloro-phenyl)-propyl-2-keto-methoxy oxime ether according to claim 1, characterized in that: Step (4) methylation reaction, the temperature is 10 to 110° C., and the time is 1 to 6 hours.

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