A preparation method of trifloxystrobin

Abstract

The present invention provides a method for preparing trifloxystrobin. The method for preparing trifloxystrobin comprises the following steps: using trifloxystrobin characteristic impurities or crude trifloxystrobin containing trifloxystrobin characteristic impurities as raw materials, reacting in the presence of methanol and a base to obtain trifloxystrobin. The preparation method of the present invention uses trifloxystrobin characteristic impurities as starting materials and obtains the target product through a one-step reaction. The conditions of the preparation method are mild and the process is simple. Trifloxystrobin with high yield and high purity can be obtained, which can not only improve the quality of trifloxystrobin but also increase the yield of trifloxystrobin.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of organic compounds, and particularly relates to a preparation method of trifloxystrobin, and more particularly to a method for preparing trifloxystrobin using the characteristic impurities of trifloxystrobin. Background Art

[0002] Trifloxystrobin is a second-generation strobilurin fungicide developed by Syngenta and Bayer. It has the advantages of broad-spectrum, good rainfastness, long residual period and safety to crops. Its structural formula is as follows:

[0003]

[0004] Since trifloxystrobin can be rapidly degraded in soil and water, it has high environmental safety; moreover, trifloxystrobin is a fungicide with chemical kinetic properties, and it can be strongly adsorbed by the plant cuticle, providing excellent protective activity on the plant surface. The suitable crops for trifloxystrobin include wheat, barley, rye, triticale, grapes, apples, peanuts, bananas and vegetables, etc., and it has a wide range of applications. Trifloxystrobin is mainly used for foliar treatment, with strong protective activity and the activity is not affected by the environment. The best application period is the stage of spore germination and the initial stage of disease, but it has activity in all stages of scab.

[0005] Since the advent of trifloxystrobin, it has received extensive attention and applications, and the research and development of its preparation process has also become a research hotspot in the field of pesticide chemistry. The common preparation routes of trifloxystrobin technical are as follows (such as CN111333535A):

[0006]

[0007] In the above process route, trifloxystrobin reacts with (E)-2-(2-bromomethylphenyl)-2-methoxyiminoacetic acid methyl ester (bromooxime ether) to generate the characteristic impurity of trifloxystrobin (E)-2-((E)-2-methoxy-1-(methoxyimino)-2-ethoxy)phenyl-2-(methoxyimino)-2-(2-(((E)-1-(3-(trifluoromethyl)phenyl)ethylideneamino)methoxy)phenyl)acetic acid methyl ester (characteristic impurity), and the reaction formula is as follows:

[0008]

[0009] The characteristic impurities of trifloxystrobin appear as by-products. Since the properties of the characteristic impurities of trifloxystrobin are very similar to those of trifloxystrobin technical drug, it is difficult to remove them during the treatment after the preparation reaction is completed, resulting in the content of this impurity in the trifloxystrobin products prepared by domestic manufacturers generally being as high as 1% or more. At present, the content of this impurity in the products of Bayer, Germany, the first market-oriented supplier of trifloxystrobin, is less than 0.1%. According to the internationally accepted regulations on the registration of equivalent products, if the content of this characteristic impurity is not reduced to below 0.1%, the trifloxystrobin technical drug prepared by other trifloxystrobin technical drug manufacturers other than Bayer will not meet the equivalent requirements, will not be able to achieve equivalent registration, and will not be able to be marketed. Therefore, in order to improve the product quality of trifloxystrobin technical drug, it is very important to develop a new method to reduce the content of this impurity to below 0.1%.

[0010] Therefore, developing a simple, practical, green and environmentally friendly method for removing or reducing the content of the characteristic impurities of trifloxystrobin to below 0.1% is of great significance for improving the product quality of trifloxystrobin, meeting the registration requirements for equivalent products, and realizing market sales. Summary of the invention

[0011] In view of the shortcomings of the prior art, the present invention aims to provide a method for preparing trifloxystrobin. The method uses trifloxystrobin characteristic impurities as starting materials and obtains the target product through a one-step reaction.

[0012] To achieve this object, the present invention adopts the following technical solutions:

[0013] The invention provides a method for preparing trifloxystrobin, which comprises the following steps: taking trifloxystrobin characteristic impurities or crude trifloxystrobin containing trifloxystrobin characteristic impurities as raw materials, reacting in the presence of methanol and alkali to obtain trifloxystrobin;

[0014] The reaction formula is as follows:

[0015]

[0016] In the present invention, the characteristic impurity of trifloxystrobin or crude trifloxystrobin containing the impurity is used as a starting material, and the target product is obtained through a one-step reaction. The preparation method has mild conditions and a simple process, and can obtain trifloxystrobin with high yield and high purity. The method can remove the impurity in the trifloxystrobin product and improve the quality of trifloxystrobin, and can also convert the impurity into trifloxystrobin, thereby improving the yield of trifloxystrobin.

[0017] Preferably, the mass ratio of the methanol to the raw material is (1-10):1, for example, 1:1, 2:1, 3:1, 4:, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc. (Wherein, the raw material refers to the characteristic impurity of trifloxystrobin or crude trifloxystrobin containing the characteristic impurity of trifloxystrobin.)

[0018] Preferably, the molar ratio of the base to the characteristic impurity of trifloxystrobin is (0.01 - 1):1, and for example, it can be 0.01:1, 0.05:1, 0.1:1, 0.2:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, etc.

[0019] In the present invention, if the crude trifloxystrobin containing the characteristic impurity of trifloxystrobin is used as the raw material, the "molar ratio of the base to the characteristic impurity of trifloxystrobin" refers to the molar ratio of the base to the characteristic impurity of trifloxystrobin contained in the crude trifloxystrobin.

[0020] Preferably, based on the total mass of the crude trifloxystrobin being 100%, the crude trifloxystrobin comprises 95 - 99% of trifloxystrobin and 1 - 5% of the characteristic impurity of trifloxystrobin by mass percentage.

[0021] Based on the total mass of the crude trifloxystrobin being 100%, the mass percentage of trifloxystrobin is 95 - 99%, and for example, it can be 95%, 96%, 97%, 98%, 99%, etc.

[0022] Based on the total mass of the crude trifloxystrobin being 100%, the mass percentage of the characteristic impurity of trifloxystrobin is 1 - 5%, and for example, it can be 1%, 2%, 3%, 4%, 5%, etc.

[0023] Preferably, the base includes an organic base and / or an inorganic base.

[0024] Preferably, the organic base is a methoxide of an alkali metal, preferably sodium methoxide and / or potassium methoxide, and more preferably sodium methoxide.

[0025] Preferably, the inorganic base includes any one or a combination of at least two of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or sodium bicarbonate.

[0026] Preferably, the temperature of the reaction is 20 - 64°C, and for example, it can be 20°C, 30°C, 35°C, 40°C, 42°C, 45°C, 48°C, 50°C, 52°C, 55°C, 58°C, 60°C, 62°C, 64°C, etc.

[0027] Preferably, the time of the reaction is 0.5 - 8 h, and for example, it can be 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 6 h, 7 h, 8 h, etc.

[0028] Preferably, the reaction needs to be post - treated, and the post - treatment includes the following steps: cooling and crystallizing the reaction solution obtained from the reaction, filtering, collecting the solid phase and drying to obtain trifloxystrobin.

[0029] Preferably, the temperature for cooling crystallization is -5 to 5 °C, for example, it can be -5 °C, -4 °C, -3 °C, -2 °C, -1 °C, 0 °C, 1 °C, 2 °C, 3 °C, 4 °C, 5 °C, etc., and preferably 0 °C.

[0030] Preferably, the time for cooling crystallization is 30 to 240 min, for example, it can be 30 min, 50 min, 80 min, 100 min, 120 min, 140 min, 160 min, 180 min, 200 min, 220 min, 240 min, etc.

[0031] Preferably, the method for cooling crystallization includes direct cooling or cooling by adding water.

[0032] Preferably, the drying method used is drying by baking.

[0033] Preferably, the temperature for drying by baking is 20 to 65 °C, for example, it can be 20 °C, 30 °C, 40 °C, 50 °C, 60 °C, 65 °C, etc., and the drying time is 1 to 8 h, for example, it can be 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, etc.

[0034] Preferably, the preparation method of the trifloxystrobin includes the following steps:

[0035] First, methanol and the trifloxystrobin characteristic impurity with a mass ratio of (1 to 10):1 are mixed, and then an alkali is added. The molar ratio of the alkali to the trifloxystrobin characteristic impurity is (0.01 to 1):1. Subsequently, the temperature is raised to 20 to 64 °C and the reaction is carried out for 0.5 to 8 h to obtain a reaction solution; the reaction solution is cooled and crystallized, filtered, and the solid phase is collected and dried to obtain trifloxystrobin.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] (1) In the preparation method of the present invention, the trifloxystrobin characteristic impurity (crude trifloxystrobin containing this impurity) is used as the starting material, and the target product is obtained through a one-step reaction;

[0038] (2) The preparation method of trifloxystrobin provided by the present invention has mild conditions and a simple process, and trifloxystrobin with a high yield and high purity can be obtained;

[0039] (3) The preparation method of trifloxystrobin provided by the present invention can remove this impurity in the trifloxystrobin product, improve the quality of trifloxystrobin, and can also convert this impurity into trifloxystrobin, thereby increasing the yield of trifloxystrobin. Specific Embodiments

[0040] The technical solutions of the present invention will be further described below through specific embodiments. Those skilled in the art should understand that the embodiments are only for helping to understand the present invention and should not be regarded as specific limitations to the present invention.

[0041] The characteristic impurities of the raw materials in the following embodiments of the present invention can be prepared by the prior art (Pasumponkamaraj et al., Letters in Organic Chemistry, 2015, 12, 306 - 310). All other raw materials are conventional products that can be purchased from regular channels.

[0042] Example 1

[0043] Preparing fluxapyroxad from the characteristic impurity of fluxapyroxad

[0044] Add 100 g of methanol and 20 g of the characteristic impurity (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 0.5 g of sodium hydroxide (96%, 0.012 mol), then heat up to 30 °C. After reacting for 4 h and detecting by HPLC that the reaction is complete (normalized raw material <0.1%), obtain reaction solution I; cool reaction solution I to 0 °C, crystallize for 120 min, then filter, collect the solid phase and dry it at 50 °C and -0.085 MPa for 4 h to obtain 10.78 g of fluxapyroxad, with a purity of 96.1% (containing 0.01% characteristic impurity) and a yield of 77.6%.

[0045] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0046] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0047] Example 2

[0048] Preparing fluxapyroxad from the characteristic impurity of fluxapyroxad

[0049] Add 50 g of methanol and 20 g of characteristic impurities (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 0.5 g of sodium methoxide (99%, 0.009 mol), then heat up to 55 °C. After reacting for 2 h and detecting the completion of the reaction by HPLC (normalized raw materials <0.1%), reaction solution I is obtained; after adding 5 g of water, cool reaction solution I to 0 °C and crystallize for 120 min, then filter, collect the solid phase and dry it at 60 °C and -0.08 MPa for 2 h to obtain 12.58 g of trifloxystrobin, with a purity of 99.1% (containing 0.02% characteristic impurities) and a yield of 93.4%.

[0050] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0051] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0052] Example 3

[0053] Preparation of trifloxystrobin using trifloxystrobin characteristic impurities as raw materials

[0054] Add 60 g of methanol and 20 g of characteristic impurities (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 1 g of potassium carbonate (98%, 0.007 mol), then heat up to 64 °C. After reacting for 1 h and detecting the completion of the reaction by HPLC (normalized raw materials <0.1%), reaction solution I is obtained; after adding 2 g of water, cool reaction solution I to 0 °C and crystallize for 240 min, then filter, collect the solid phase and dry it at 20 °C and -0.095 MPa for 8 h to obtain 11.83 g of trifloxystrobin, with a purity of 98.0% (containing 0.05% characteristic impurities) and a yield of 86.8%.

[0055] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0056] 1H-NMR(CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0057] Example 4

[0058] Preparation of trifloxystrobin from crude trifloxystrobin containing trifloxystrobin characteristic impurities

[0059] Add 100 g of methanol and 40 g of crude trifloxystrobin (trifloxystrobin content is 95%, trifloxystrobin characteristic impurity content is 4.6%) to the reaction kettle, start stirring, slowly add 0.2 g of sodium bicarbonate (99%, 0.0023 mol), then heat up to 50 °C. After reacting for 1 h and detecting by HPLC until the reaction is complete (characteristic impurity normalization < 0.1%), obtain reaction solution I; add 11 g of water, then cool reaction solution I to 0 °C and crystallize for 120 min, filter, collect the solid phase and dry it at 65 °C and -0.08 MPa for 1 h to obtain 37.20 g of trifloxystrobin, with a purity of 99.3% (containing 0.03% characteristic impurities) and a yield of 94.1%.

[0060] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0061] 1 H-NMR(CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0062] Example 5

[0063] Preparation of trifloxystrobin from crude trifloxystrobin containing trifloxystrobin characteristic impurities

[0064] Add 80 g of methanol and 40 g of crude trifloxystrobin (the content of trifloxystrobin is 95%, and the content of trifloxystrobin characteristic impurities is 4.6%) into the reaction kettle. Start stirring and slowly add 0.05 g of sodium methoxide (99%, 0.0009 mol). Then heat up to 50 °C. After reacting for 40 min, when the reaction is completed as detected by HPLC (the normalization of characteristic impurities < 0.1%), obtain reaction solution I; after adding 8 g of water, cool reaction solution I to 0 °C and crystallize for 120 min, filter, collect the solid phase and dry it at 60 °C and -0.08 MPa for 2 h to obtain 37.52 g of trifloxystrobin with a content of 99.7% (including 0.02% characteristic impurities) and a yield of 95.3%.

[0065] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0066] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0067] Example 6

[0068] Preparation of trifloxystrobin using trifloxystrobin characteristic impurities as raw materials

[0069] Add 100 g of methanol and 20 g of characteristic impurities (content 98%, 0.0327 mol) into the reaction kettle. Start stirring and slowly add 0.375 g of sodium hydroxide (96%, 0.009 mol). Then heat up to 30 °C. After reacting for 4 h, when the reaction is completed as detected by HPLC (the normalization of raw materials < 0.1%), obtain reaction solution I; after cooling reaction solution I to 0 °C and crystallizing for 120 min, filter, collect the solid phase and dry it at 50 °C and -0.085 MPa for 4 h to obtain 11.51 g of trifloxystrobin with a purity of 95.3% (including 0.01% characteristic impurities) and a yield of 82.2%.

[0070] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0071] 11H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0072] Example 7

[0073] Preparation of trifloxystrobin from the characteristic impurity of trifloxystrobin

[0074] Add 100 g of methanol and 20 g of the characteristic impurity (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 0.2 g of sodium methoxide (99%, 0.0037 mol), then heat up to 30 °C. After reacting for 8 h, HPLC detection showed that the reaction was not complete (raw material normalization 2.3%), stop the reaction to obtain reaction solution I; cool reaction solution I to 0 °C and crystallize for 120 min, then filter, collect the solid phase and dry it at 50 °C and -0.085 MPa for 4 h to obtain 12.41 g of trifloxystrobin, with a purity of 98.2% (containing 0.8% of the characteristic impurity) and a yield of 91.3%.

[0075] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0076] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0077] Example 8

[0078] Preparation of trifloxystrobin from the characteristic impurity of trifloxystrobin

[0079] Add 100 g of methanol and 20 g of characteristic impurities (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 2 g of sodium methoxide (99%, 0.037 mol), then heat up to 30 °C. After reacting for 1 h, when HPLC detects that the reaction is complete (normalized raw materials <0.1%), obtain reaction solution I; cool reaction solution I to 0 °C and crystallize for 120 min, then filter, collect the solid phase and dry it at 50 °C and -0.085 MPa for 4 h to obtain 10.50 g of trifloxystrobin, with a purity of 94.4% (containing 0.01% characteristic impurities) and a yield of 74.2%.

[0080] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0081] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0082] Example 9

[0083] Preparation of trifloxystrobin using trifloxystrobin characteristic impurities as raw materials

[0084] Add 50 g of methanol and 20 g of characteristic impurities (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 0.5 g of sodium methoxide (99%, 0.009 mol), then heat up to 15 °C. After reacting for 6 h, when HPLC detects that the reaction is not complete (normalized raw materials 3.5%), obtain reaction solution I; add 5 g of water, then cool reaction solution I to 0 °C and crystallize for 120 min, then filter, collect the solid phase and dry it at 60 °C and -0.08 MPa for 2 h to obtain 12.23 g of trifloxystrobin, with a purity of 97.9% (containing 1.3% characteristic impurities) and a yield of 89.7%.

[0085] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0086] 11H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0087] Example 10

[0088] Preparation of Trifloxystrobin from Trifloxystrobin Characteristic Impurity as Raw Material

[0089] Add 50 g of methanol and 20 g of characteristic impurity (content 98%, 0.0327 mol) to the reaction kettle, start stirring, slowly add 0.5 g of sodium methoxide (99%, 0.009 mol), then heat up to 65 °C. After reacting for 0.5 h, when HPLC detects that the reaction is complete (normalized raw material < 0.1%), obtain reaction solution I; after adding 5 g of water, cool reaction solution I to 0 °C and crystallize for 120 min, then filter, collect the solid phase and dry it at 60 °C and -0.08 MPa for 2 h to obtain 12.29 g of trifloxystrobin, with a purity of 98.5% (containing 0.03% characteristic impurity) and a yield of 90.7%.

[0090] Detection of the target product: LCMS (EI): m / z = 409 [M + ;

[0091] 1 1H-NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H, CH3), 3.83 (s, 3H, CH3), 4.04 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.22 (m, 1H, ArH), 7.40 (m, 1H, ArH), 7.42 (m, 1H, ArH), 7.44 (m, 1H, ArH), 7.46 (m, 1H, ArH), 7.59 (m, 1H, ArH), 7.81 (m, 1H, ArH), 7.88 (m, 1H, ArH).

[0092] Comparative Example 1

[0093] This comparative example provides a method for preparing trifloxystrobin using 3'-trifluoroacetophenone oxime as the raw material. The method includes the following steps:

[0094]

[0095] Add acetophenone oxime with 3-trifluoromethyl group (12 g, 59.0 mmol), methyl (E)-2-(2'-bromomethylphenyl)-2-oxoacetate O-methyl ketoxime (17.0 g, 59.0 mmol), sodium hydroxide (3.6 g, 88.50 mmol) and 1,2-dichloroethane (24 mL) into the reaction kettle, react at 60 °C for 4 h. After the reaction is completed detected by HPLC, carry out suction filtration, wash with water, concentrate, and recrystallize with petroleum ether to obtain 17.9 g of white solid of trifloxystrobin, with a yield of 71.1% and a purity of 95.4% (containing 4.4% of characteristic impurities).

[0096] Test Example

[0097] Test samples: Trifloxystrobin obtained after drying in Examples 1-10 and trifloxystrobin obtained in Comparative Example 1;

[0098] Test method: Use HPLC to test the purity of trifloxystrobin in the test samples;

[0099] Among them, when using the characteristic impurities of trifloxystrobin as raw materials, the calculation formula for the yield of trifloxystrobin is: Yield of trifloxystrobin (%) = (molar amount of trifloxystrobin after purification / molar amount of characteristic impurities of the raw materials used) × 100%;

[0100] Among them, when using the crude trifloxystrobin containing the characteristic impurities of trifloxystrobin as raw materials, the calculation formula for the yield of trifloxystrobin is: Yield of trifloxystrobin (%) = molar amount of trifloxystrobin after purification in the product / (sum of the molar amounts of characteristic impurities and trifloxystrobin in the raw materials) × 100%;

[0101] Calculate the yield of the reaction, and the test results are shown in Table 1:

[0102] Table 1

[0103] Test sample Trifloxystrobin purity (%) Trifloxystrobin yield (%) Example 1 96.1 77.6 Example 2 99.1 93.4 Example 3 98.0 86.8 Example 4 99.3 94.1 Example 5 99.7 95.3 Example 6 95.3 82.2 Example 7 98.2 91.3 Example 8 94.4 74.2 Example 9 97.9 89.7 Example 10 98.5 90.7 Comparative Example 1 95.4 71.1

[0104] It can be seen from the data in Table 1 that by using the preparation method of trifloxystrobin provided by the present invention (Examples 1-10), the purity of the prepared trifloxystrobin measured by HPLC is between 95.3-99.7%, and the yield is between 74-95.3%.

[0105] By comparing Example 2 and Example 6, it can be seen that the base is preferably the methanol salt of an alkali metal, which can further improve the yield and obtain trifloxystrobin with higher purity.

[0106] By comparing Example 1 with Examples 7 and 8, it can be seen that when the molar ratio of the base to the characteristic impurities is outside the range of (0.01-1):1, it will seriously affect the purity and yield of trifloxystrobin in the obtained product.

[0107] By comparing Example 1 with Examples 9 and 10, it can be seen that the reaction temperature will affect the purity and yield of trifloxystrobin in the obtained product.

[0108] From the comparison between Example 1 and Comparative Example 1, it can be seen that for the method of preparing trifloxystrobin using 3'-trifluoroacetophenone oxime as the raw material, the reaction yield is relatively low. Trifloxystrobin reacts with methyl (E)-2-(2-bromomethylphenyl)-2-methoxyiminoacetate (bromooxime ether) to form the characteristic impurity of trifloxystrobin, methyl (E)-2-((E)-2-methoxy-1-(methoxyimino)-2-ethoxy)phenyl-2-(methoxyimino)-2-(2-(((E)-1-(3-(trifluoromethyl)phenyl)ethylideneamino)methoxy)phenyl)acetate (characteristic impurity).

[0109] The applicant declares that the present invention uses the above-mentioned examples to illustrate the preparation method of trifloxystrobin described in the present invention. However, the present invention is not limited to the above-mentioned examples, that is, it does not mean that the present invention must rely on the above-mentioned examples to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent substitution of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc. all fall within the protection scope and the disclosure scope of the present invention.

Claims

1. A preparation method of trifloxystrobin, characterized in that, The preparation method of the trifloxystrobin includes the following steps: Using the trifloxystrobin characteristic impurity or the crude trifloxystrobin containing the trifloxystrobin characteristic impurity as the raw material, reacting in the presence of methanol and a base to obtain trifloxystrobin; The base includes an organic base and / or an inorganic base; the organic base is the methanol salt of an alkali metal; the inorganic base includes any one or a combination of at least two of sodium carbonate, potassium carbonate or sodium bicarbonate; the molar ratio of the base to the trifloxystrobin characteristic impurity is (0.01 - 1):1; The reaction formula is as follows:

2. The preparation method of trifloxystrobin according to claim 1, characterized in that, The mass ratio of the methanol to the raw material is (1 - 10):

1.

3. The preparation method of trifloxystrobin according to claim 1, characterized in that, The crude trifloxystrobin includes 95 - 99% of trifloxystrobin and 1 - 5% of trifloxystrobin characteristic impurity by mass percentage.

4. The preparation method of trifloxystrobin according to claim 1, characterized in that, The organic base is sodium methoxide and / or potassium methoxide.

5. The preparation method of trifloxystrobin according to claim 4, characterized in that, The organic base is sodium methoxide.

6. The preparation method of trifloxystrobin according to claim 1, characterized in that, The temperature of the reaction is 20 - 64 °C.

7. The preparation method of trifloxystrobin according to claim 1, characterized in that, The time of the reaction is 0.5 - 8 h.

8. The preparation method of trifloxystrobin according to claim 1, characterized in that, The reaction needs to be post-treated, and the post-treatment includes the following steps: Cooling and crystallizing the reaction solution obtained from the reaction, filtering, collecting the solid phase and drying to obtain trifloxystrobin.

9. The preparation method of trifloxystrobin according to claim 8, characterized in that, The temperature of the cooling and crystallization is -5 - 5 °C.

10. The preparation method of trifloxystrobin according to claim 9, characterized in that, The temperature of the cooling and crystallization is 0 °C.

11. The preparation method of trifloxystrobin according to claim 8, characterized in that, The time of the cooling and crystallization is 30 - 240 min.

12. The preparation method of trifloxystrobin according to claim 8, characterized in that, The mode of the cooling and crystallization includes direct cooling or cooling by adding water.

13. The preparation method of trifloxystrobin according to claim 8, characterized in that, The drying method used is drying by baking.

14. The preparation method of trifloxystrobin according to claim 13, characterized in that, The temperature of the drying by baking is 20 - 65 °C, and the time of the drying by baking is 1 - 8 h.

15. The preparation method of trifloxystrobin according to claim 1, characterized in that, The preparation method of the trifloxystrobin includes the following steps: First, mix methanol and trifloxystrobin characteristic impurity with a mass ratio of (1 - 10):1, then add a base, the molar ratio of the base to the trifloxystrobin characteristic impurity is (0.01 - 1):1, and then heat up to 20 - 64 °C and react for 0.5 - 8 h to obtain a reaction solution; cool and crystallize the reaction solution, filter, collect the solid phase and dry to obtain trifloxystrobin.

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