Preparation method of saflufenacil

Abstract

The invention provides a preparation method of saflufenacil, and belongs to the technical field of herbicide preparation, and the preparation method comprises the following steps: S1, adding flumezopyrim-N-demethylation, a catalyst and sodium acetate into a solvent system while stirring, heating to a specified temperature, preserving heat, then adjusting pH, stirring, sampling and detecting the content of dimethyl impurities, and when the content of the dimethyl impurities is less than or equal to X, stopping stirring; the reaction is finished; s2, after the reaction is finished, the reaction system is subjected to standing, the reaction system is divided into an upper layer and a lower layer, the upper layer is an organic phase, the lower layer is a water phase, the lower-layer water phase is abandoned, the upper-layer organic phase is taken for washing and standing again, the upper-layer organic phase is taken after standing, desolventizing is conducted under reduced pressure till the material is dried, an organic solvent is added, stirring is conducted, and cooling and suction filtration are conducted to obtain saflufenacil. The invention provides a preparation method of saflufenacil. The purposes of reducing the cost of raw materials and improving the yield of saflufenacil are achieved.

Description

Technical Field

[0001] The invention relates to the technical field of herbicide preparation, and in particular to a method for preparing saflufenacil. Background Art

[0002] The chemical name of saflufenacil is 2-chloro-4-fluoro-N-[isopropyl(methyl)aminosulfonyl]-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzamide. It is a uracil herbicide developed and manufactured by BASF. Saflufenacil is mainly absorbed by roots and seedlings, has foliar contact and soil residual activity, and can be bidirectionally conducted in the plant body. It can be conducted upward from the xylem and downward from the phloem, thus being distributed throughout the plant. It is also safe for crops and has a wide range of crop rotation options. Saflufenacil has a variety of characteristics, including fast action, long residual effect, low volatility, and safety for crops, and is suitable for a variety of production systems and non-arable land. It is very active and can achieve excellent weed control effects with very small doses.

[0003] There are two main synthetic routes for saflufenacil: Synthesis route 1: 2-chloro-4-fluorobenzoic acid is used as the starting material, and 5-amino-2-chloro-4-fluorobenzoic acid ethyl ester is obtained through esterification, nitration, and nitro reduction; then acylation with methyl chloroformate, followed by cyclization with 3-amino-4,4,4-trifluorobutenoic acid ethyl ester, and methylation with dimethyl sulfate to obtain compound (A) 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4(trifluoromethyl)-1(2H)pyrimidine]-4-fluorobenzoic acid ethyl ester, and compound (A) is hydrolyzed, chlorinated, and then reacted with N-methyl-N-isopropylsulfonamide to obtain the target compound benzylsulfuronamide. However, this synthesis route has a total of 9 steps, many synthesis steps, and a low overall yield. It needs to be esterified first and then hydrolyzed. In addition, the yield of the last step, that is, the reaction of the chlorinated compound with N-methyl-N-isopropylsulfonamide, is reported to be only 47%.

[0004] Synthesis route 2: 2-chloro-4-fluorobenzoic acid is used as the starting material, and after nitration and acylation, it reacts with N-methyl-N-isopropylsulfonamide to obtain compound (2-chloro-4-fluoro-5-nitrobenzoyl)-N'-isopropyl-N'-methylsulfonamide (B); compound (B) is reduced by nitro group and then reacted with ethyl chloroformate to obtain compound N-[2-chloro-4-fluoro-5-{(ethoxycarbonyl)amino}benzoyl]-N'-isopropyl-N'-methylsulfonamide (C); compound (C) reacts with ethyl 3-amino-4,4,4-trifluorobutenoate for cyclization, and then methylates to obtain the target product benzsulfamide. This synthesis route is short, the yield of each step is high, and it is suitable for industrial production, but this route also has shortcomings. In the last step of methylation, the hydrogen on the sulfonylamino group is also easily methylated, which easily produces by-products.

[0005] With the deepening of the study on benzsulfamide, more and more benzsulfamide intermediates appear, and benzsulfamide is synthesized from the intermediate, which reduces the synthesis steps and improves the synthesis yield. As disclosed in the patent document of publication number CN119613347A, the name is a synthesis method of benzsulfamide, which uses N-(2-chloro-4-fluoro-5-aminobenzoyl)-N'-isopropyl-N'methylsulfonamide as a raw material to react with chloroformate in a strong polar solvent, and then directly adds alkali and 3-amino-4,4,4-trifluoro-2-butenoic acid ethyl ester to the reaction material for cyclization reaction, and the cyclization reaction material is methylated with a methylating agent to obtain benzsulfamide. Although the above technical scheme improves the product yield, the methylating agent used is dimethyl sulfate, etc., and the cost is relatively high. Summary of the invention

[0006] In view of this, the present invention provides a method for preparing saflufenacil, which achieves the purpose of reducing raw material costs and improving the yield of saflufenacil.

[0007] To achieve the above object, the present invention provides a method for preparing saflufenacil, comprising the following steps: S1, adding fluorophenylpyrimidine-N-demethyl, a catalyst and sodium acetate to a solvent system while stirring, heating to a specified temperature and keeping the temperature, then adjusting the pH, stirring, sampling and detecting the dimethyl impurity content, when the dimethyl impurity content is ≤X, the reaction is completed; S2. After the reaction is completed, the reaction system is allowed to stand. The reaction system is separated into two layers, the upper layer is an organic phase, and the lower layer is an aqueous phase. The lower aqueous phase is discarded, and the upper organic phase is washed with water and allowed to stand again. After standing, the upper organic phase is taken and decompressed to desolventize until the material becomes dry, an organic solvent is added and stirred, and the temperature is reduced and filtered to obtain benzylpyrasulfuron.

[0008] Optionally, the solvent system is a mixture of toluene and tetrahydrofuran; the mass ratio of toluene to tetrahydrofuran is 4-5:1; and toluene is used for stirring the organic solvent.

[0009] Optionally, the mass ratio of the fluorophenylpyrimidine-N-demethyl to sodium acetate is 2:0.9-1.1.

[0010] Optionally, the catalyst is tetrabutylammonium bromide.

[0011] Optionally, the X is 3.5%.

[0012] Optionally, the designated temperature for heating to a designated temperature and keeping warm is 38-42°C.

[0013] Optionally, the pH is adjusted to 3.5-4.

[0014] Optionally, the pH is adjusted using a 15% sodium carbonate solution.

[0015] Optionally, the pH is adjusted and the stirring time is 0.5 to 1 hour; the standing time is 0.5 to 1 hour.

[0016] In order to achieve the above object, the present invention also provides saflufenacil prepared by a method for preparing saflufenacil.

[0017] The above technical solution of the present invention includes at least the following beneficial effects: The technical solution provided by the present invention uses sodium acetate for methylation, and in combination with the use of a catalyst, the product yield is improved, the impurity content is low, and the price of sodium acetate is much lower than that of existing methylation reagents such as dimethyl sulfate, thereby reducing the cost of raw materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is the reaction formula in Example 1 of the present invention. DETAILED DESCRIPTION

[0019] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the following will be combined with the appended drawings of the embodiments of the present invention. Figure 1 , the technical scheme of the embodiment of the present invention is clearly and completely described. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0020] Example 1 A method for preparing saflufenacil comprises the following steps: Step 1: Take a 1000mL four-necked bottle, add 450g toluene and 100g tetrahydrofuran, add 50g fluorophenylpyrimidine-N-demethyl, 3g tetrabutylammonium bromide and 25g sodium acetate to the system under stirring, heat to 40°C, and then quickly drop 55g of 15% sodium carbonate solution prepared in advance into the system, adjust the pH value of the system to 3.8, stop dropping sodium carbonate solution when there is no obvious change in pH, keep warm and stir at 40°C for 30 minutes after the addition is completed, take samples for central control, and the dimethyl impurity is ≤3.5%.

[0021] Step 2: After the reaction is completed, turn off the stirring and transfer the system to a separatory funnel, let it stand for 30 minutes, with the organic phase on top and the aqueous phase on the bottom, and discard the aqueous phase. The organic phase is washed with 100g of water and allowed to stand for 30 minutes, with the organic phase on top and the aqueous phase on the bottom, and the aqueous phase is discarded. Take another 1000mL four-necked bottle, pour the above organic phase into it, and desolventize under reduced pressure until the material becomes dry. After evaporation, add 200g of toluene to the four-necked bottle and stir, cool to 0°C and filter, which is the product of benzylsulfuron, and obtain 47.84g of white solid, with a content of 96.27% and a yield of 93%.

[0022] Example 2 A method for preparing saflufenacil comprises the following steps: Step 1: Take a 1000mL four-necked bottle, add 400g toluene and 100g tetrahydrofuran, add 50g fluorophenylpyrimidine-N-demethyl, 3g tetrabutylammonium bromide and 27.5g sodium acetate to the system under stirring, heat to 42°C, then quickly drop 55g of 15% sodium carbonate solution prepared in advance into the system, adjust the pH value of the system to 4, stop dropping sodium carbonate solution when there is no obvious change in pH, keep warm and stir at 42°C for 60 minutes after the addition is completed, take samples for central control, and the dimethyl impurity is ≤3.5%.

[0023] Step 2: After the reaction is completed, turn off the stirring and transfer the system to a separatory funnel, let it stand for 60 minutes, with the organic phase on top and the aqueous phase on the bottom, and discard the aqueous phase. The organic phase is washed with 100g of water and allowed to stand for 60 minutes, with the organic phase on top and the aqueous phase on the bottom, and the aqueous phase is discarded. Take another 1000mL four-necked bottle, pour the above organic phase into it, and desolventize under reduced pressure until the material becomes dry. After evaporation, add 200g of toluene to the four-necked bottle and stir, cool to 0°C and filter with suction to obtain the benzylsulfuronamide product, and obtain 48.36g of white solid with a content of 97.21% and a yield of 95%.

[0024] Example 3 A method for preparing saflufenacil comprises the following steps: Step 1: Take a 1000mL four-necked bottle, add 500g toluene and 100g tetrahydrofuran, add 50g fluorophenylpyrimidine-N-demethyl, 3g tetrabutylammonium bromide and 22.5g sodium acetate to the system under stirring, heat to 38°C, and then quickly drop 55g of 15% sodium carbonate solution prepared in advance into the system, adjust the pH value of the system to 3.5, stop dropping sodium carbonate solution when there is no obvious change in pH, keep warm and stir at 42°C for 40 minutes after the addition is completed, take samples for central control, and the dimethyl impurity is ≤3.5%.

[0025] Step 2: After the reaction is completed, turn off the stirring and transfer the system to a separatory funnel, let it stand for 40 minutes, with the organic phase on top and the aqueous phase on the bottom, and discard the aqueous phase. The organic phase is washed with 100g of water and allowed to stand for 40 minutes, with the organic phase on top and the aqueous phase on the bottom, and the aqueous phase is discarded. Take another 1000mL four-necked bottle, pour the above organic phase into it, and desolventize under reduced pressure until the material becomes dry. After evaporation, add 200g of toluene to the four-necked bottle and stir, cool to 0°C and filter with suction to obtain the benzylsulfuronamide product, and obtain 47.66g of white solid with a content of 96.18% and a yield of 93%.

[0026] Comparative Example 1 Compared with Example 1, the only difference is that benzyltriethylammonium bromide is used instead of tetrabutylammonium bromide as the catalyst, and the other raw materials and operations are the same as those in Example 1.

[0027] Comparative Example 2 Compared with Example 1, the only difference is that sodium dodecyl sulfate trimethylammonium chloride is used instead of tetrabutylammonium bromide as the catalyst, and the other raw materials and operations are the same as those in Example 1.

[0028] Comparative Example 3 Compared with Example 1, the only difference is that polyethylene glycol 400 is used instead of tetrabutylammonium bromide as the catalyst, and the other raw materials and operations are the same as those in Example 1.

[0029] The product quality and content of Example 1 and Comparative Examples 1 to 3 are statistically shown in Table 1.

[0030] Table 1 Product quality and content of Example 1 and Comparative Examples 1 to 3

[0031] As can be seen from Table 1, the present invention uses tetrabutylammonium bromide as a catalyst to work together with sodium acetate to improve the yield of saflufenacil, and uses sodium acetate to reduce the cost of raw materials.

[0032] The above are preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing saflufenacil, characterized in that: The following steps are involved: S1, adding fluorophenylpyrimidine-N-demethyl, a catalyst and sodium acetate to a solvent system while stirring, heating to a specified temperature and keeping the temperature, then adjusting the pH, stirring, sampling and detecting the dimethyl impurity content, when the dimethyl impurity content is ≤X, the reaction is completed; S2. After the reaction is completed, the reaction system is allowed to stand. The reaction system is separated into two layers, the upper layer is an organic phase, and the lower layer is an aqueous phase. The lower aqueous phase is discarded, and the upper organic phase is washed with water and allowed to stand again. After standing, the upper organic phase is taken and decompressed to desolventize until the material becomes dry, an organic solvent is added and stirred, and the temperature is reduced and filtered to obtain benzylpyrasulfuron.

2. The method for preparing saflufenacil according to claim 1, characterized in that: The solvent system is a mixture of toluene and tetrahydrofuran; the mass ratio of toluene to tetrahydrofuran is 4-5:1; and toluene is used for stirring the organic solvent.

3. The method for preparing saflufenacil according to claim 1, characterized in that: The mass ratio of the fluorophenylpyrimidine-N-demethyl to sodium acetate is 2:0.9-1.

1.

4. The method for preparing saflufenacil according to claim 1, characterized in that: The catalyst is tetrabutylammonium bromide.

5. The method for preparing saflufenacil according to claim 1, characterized in that: The X is 3.5%.

6. The method for preparing saflufenacil according to claim 1, characterized in that: The designated temperature for heating to the designated temperature and keeping warm is 38-42°C.

7. The method for preparing saflufenacil according to claim 1, characterized in that: The pH is adjusted to 3.5-4.

8. The method for preparing saflufenacil according to claim 1, characterized in that: The pH was adjusted using 15% sodium carbonate solution.

9. The method for preparing saflufenacil according to claim 1, characterized in that: The pH value is adjusted and the stirring time is 0.5 to 1 hour; the standing time is 0.5 to 1 hour.

10. Saflufenacil prepared by the method for preparing saflufenacil according to any one of claims 1 to 9.

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