Post-treatment method of saflufenacil reaction liquid

Abstract

The invention relates to the technical field of pesticide chemical industry, and discloses a post-treatment method of saflufenacil reaction liquid. The post-treatment method comprises the following steps: (1) layering saflufenacil reaction liquid, desolventizing an organic phase, adding a first organic solvent, and stirring; and (2) filtering after stirring, leaching the obtained filter cake with a second organic solvent, and drying to obtain saflufenacil. According to the post-treatment method provided by the invention, the saflufenacil reaction liquid can be simply and efficiently treated, the product yield is up to 90% or above, and the content is about 98%.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide chemical industry, and in particular to a post-treatment method for a saflufenacil reaction solution. Background Art

[0002] Safensulfuron belongs to the pyrimidine class and is a protoporphyrinogen oxidase (PPO) inhibitor. It can be used as a lethal herbicide and can effectively control a variety of broadleaf weeds, including weeds resistant to glyphosate, ALS and triazines. Safensulfuron has a rapid lethal effect and soil residues degrade quickly; it can be mixed with grass weed herbicides (such as glyphosate) and has a good weed control effect. It can be applied to a variety of crop fields and non-arable land, with few restrictions on crop rotation.

[0003] The existing production process of saflufenacil results in a large loss of product, and the yield is only 84% after a series of post-treatments. As the pesticide market continues to decline, the yield requirements for the production of technical drugs are getting higher and higher.

[0004] Chinese patent CN 101821233A discloses a method for synthesizing saflufenacil. The post-processing process disclosed in the patent is: after the reaction is completed, the phases are separated, the organic phase is dried and part of the solvent is removed; during the cooling process, saflufenacil crystallizes, which is filtered, washed with toluene and dried. This method uses a large amount of organic solvent toluene for crystallization and elution, resulting in a large content of the original drug in the mother liquor toluene, and it is difficult to recover, with a yield of only 84%.

[0005] The international journal J Heterocyclic Chem. 2020, 57, 151-156. reported a method for synthesizing saflufenacil. The reported post-treatment method was: let the mixture stand and separate; collect the toluene layer, wash with water (100 mL×2), and dry with anhydrous Na2SO4; remove most of the solvent, add heptane (150 mL), and stir at room temperature for 2 hours, collect the resulting solid by filtration, wash with heptane (100 mL×1), and dry under vacuum at 40°C to obtain saflufenacil with a yield of 86.1%.

[0006] BASF disclosed a method for recovering the original drug from the mother liquor of saflufenacil in the international patent WO 2023 / 232507A1. The patent describes that the proportion of the original drug in the mother liquor is about 10%, and the recovery process is complicated: first, water needs to be added to the mother liquor, and then the pH is adjusted to >8 to extract the target product into the aqueous phase, and then an organic solvent is added to the aqueous phase, and then the pH is adjusted to <2 to back-extract saflufenacil into the organic phase. However, the product obtained in this way contains a large amount of impurities and requires secondary crystallization. In addition, excessive alkalinity during the extraction process can easily lead to the decomposition of saflufenacil, and the decomposition equation is as follows:

[0007]

[0008] Therefore, there is an urgent need to develop a post-treatment method for the saflufenacil reaction solution that is simple to operate and can improve the yield. Summary of the invention

[0009] The purpose of the present invention is to overcome the problems existing in the prior art and to provide a post-treatment method for a saflufenacil reaction solution.

[0010] In order to achieve the above object, the present invention provides a post-treatment method for a saflufenacil reaction solution, wherein the post-treatment method comprises the following steps:

[0011] (1) separating the saflufenacil reaction solution into layers, performing a desolventizing treatment on the organic phase, and then adding a first organic solvent and stirring;

[0012] (2) After the stirring is completed, the mixture is filtered, and the obtained filter cake is rinsed with a second organic solvent, and dried to obtain a pure product of saflufenacil.

[0013] Through the above technical solution, the beneficial technical effects achieved by the present invention are as follows:

[0014] (1) The post-treatment method provided by the present invention can simply and efficiently treat the saflufenacil reaction solution, with a product yield of more than 90% and a content of about 98%;

[0015] (2) After post-treatment by the method of the present invention, the loss of saflufenacil original drug is less than 1%;

[0016] (3) The isooctyl alcohol used in the post-treatment of this method can be recovered by simple distillation, with a recovery rate of more than 98%, and can be reused. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the HPLC liquid phase spectrum of saflufenacil obtained in Example 1 of the present invention;

[0018] Figure 2 It is the HPLC liquid phase spectrum of the isooctyl alcohol mother liquor obtained in Example 1 of the present invention. DETAILED DESCRIPTION

[0019] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0020] The yield described in the present invention is a molar yield.

[0021] A first aspect of the present invention provides a post-treatment method for a saflufenacil reaction solution, wherein the post-treatment method comprises the following steps:

[0022] (1) separating the saflufenacil reaction solution into layers, performing a desolventizing treatment on the organic phase, and then adding a first organic solvent and stirring;

[0023] (2) After the stirring is completed, filtering is performed, and the obtained filter cake is rinsed with a second organic solvent, and dried to obtain saflufenacil.

[0024] For the reaction solution of saflufenacil, the traditional post-processing method uses toluene for stirring, the content of the original drug in the mother liquor is high, the yield of the original drug is low, the operation is complicated, and the loss is large. The present invention solves the problem of large post-processing losses in the original drug synthesis process by mixing the crude saflufenacil after desolventizing with a first organic solvent (such as isooctyl alcohol) and stirring, so that the yield of the product saflufenacil is increased from 86% to more than 90%, the content is about 98%, and the loss of saflufenacil original drug accounts for 0.7-1.0% (relative to the theoretical mass of saflufenacil).

[0025] In some embodiments of the present invention, the saflufenacil reaction solution is prepared by the following method:

[0026] 2-Chloro-5-[3,6-dihydro-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-N-{[methyl-(1-methylethyl)amino]sulfonyl}benzamide, a phase transfer catalyst and a methylating agent are added to a reaction solvent, and the reaction pH is controlled to be 4-6 with liquid alkali to react to obtain a saflufenacil reaction solution.

[0027] In some embodiments of the present invention, the phase transfer catalyst is tetrabutylammonium bromide.

[0028] In some embodiments of the present invention, the methylating agent is dimethyl sulfate.

[0029] The preparation process of the saflufenacil reaction solution can refer to CN 101821233A, for example, the scheme described in Example 2 thereof.

[0030] The reaction route is as follows:

[0031]

[0032] In some embodiments of the present invention, the first organic solvent and the second organic solvent are independently selected from alcohols, esters or ethers with not less than 7 carbon atoms, preferably alcohols, esters or ethers with not less than 8 carbon atoms.

[0033] In some embodiments of the present invention, the first organic solvent and the second organic solvent are independently selected from at least one of 1-heptanol, anisole, n-octanol, isooctyl alcohol, 2-octanol, hexyl acetate and 1-nonanol, preferably isooctyl alcohol and / or hexyl acetate.

[0034] In some embodiments of the present invention, the first organic solvent and the second organic solvent are of the same type.

[0035] In some embodiments of the present invention, hydrochloric acid is used to acidify the reaction solution until the pH of the aqueous layer is 1-2, and the organic phase is subjected to negative pressure desolventizing treatment at 40-45° C. The purpose of adjusting the pH of the aqueous layer is to stabilize saflufenacil.

[0036] In some embodiments of the present invention, the negative pressure condition is -0.1 MPa.

[0037] In some embodiments of the present invention, the ratio of the theoretical mass of saflufenacil to the mass of the first organic solvent is 1:1-10, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, and any value within the range of any two of the above values, preferably 1:1-6, and more preferably 1:2.

[0038] In some embodiments of the present invention, the stirring temperature in step (1) is 0-80°C, preferably 40-45°C.

[0039] In some embodiments of the present invention, the stirring time in step (1) is 20-40 min, preferably 30 min.

[0040] In some embodiments of the present invention, the ratio of the theoretical mass of saflufenacil to the mass of the second organic solvent is 1:0.5-2, preferably 1:1.

[0041] In some embodiments of the present invention, the drying temperature in step (2) is 50-90°C, preferably 75°C.

[0042] In some embodiments of the present invention, the drying time in step (2) is 4-8 hours, preferably 5 hours.

[0043] In some embodiments of the present invention, in step (2), after the stirring is completed, the system temperature is lowered to 15-20° C. and then filtering is performed.

[0044] According to a particularly preferred embodiment of the present invention, a post-treatment method of a saflufenacil reaction solution comprises the following steps:

[0045] The reaction liquid of saflufenacil is acidified with hydrochloric acid until the pH value of the aqueous layer of the reaction liquid reaches 1-2, and the organic phase is subjected to negative pressure (P=-0.1MPa) desolventizing treatment at 40-45°C; after the organic solvent in the reaction liquid is completely removed, 2 times the mass (based on the theoretical mass of saflufenacil) of isooctyl alcohol is added; after the isooctyl alcohol is added, stirring treatment is carried out at 40-45°C for 30 minutes; the system temperature is reduced to 15-20°C and then filtered, and the filter cake is rinsed with isooctyl alcohol (0.5 times the mass*2, based on the theoretical mass of saflufenacil); the wet product of saflufenacil is dried at 75°C for 5h to obtain saflufenacil; the isooctyl alcohol mother liquor (filtrate+rinsing liquid) is directly distilled and recovered, and the recovered isooctyl alcohol can be directly used for stirring.

[0046] The present invention will be described in detail below through examples.

[0047] In the following examples and comparative examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, if no manufacturer is specified, are all conventional products that can be obtained through commercial channels.

[0048] Example 1

[0049] First, 40.0 g (0.0785 mol, content 95.5%) of 2-chloro-5-[3,6-dihydro-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-N-{[methyl-(1-methylethyl)amino]sulfonyl}benzamide, 2.5 g (0.0078 mol) of tetrabutylammonium bromide (=TBAB) and 13.4 g (0.106 mol) of dimethyl sulfate were added to a mixture of toluene, water and THF (tetrahydrofuran) at 25° C. and the mixture was heated to 40° C. A pH of 5.3-5.5 was then established in the reaction mixture by addition of 10% aqueous NaOH solution. The mixture was stirred at 40° C. for 1 hour, during which time 10% aqueous NaOH solution was continuously added so that the pH was kept constant at 5.3-5.5. After 1 hour, the addition of 10% aqueous NaOH solution was stopped, at which point the pH dropped back to 4.4-4.5. The mixture was stirred at a pH of 4.4-4.5 and 40° C. for further 5.5 hours to obtain a saflufenacil reaction solution.

[0050] The reaction solution of saflufenacil was acidified with hydrochloric acid until the pH of the aqueous layer of the reaction solution reached 1, the aqueous layer was washed with toluene, the organic phases were combined, and the organic phases were subjected to negative pressure (P=-0.1MPa) desolventizing treatment at 45°C; after the organic solvent in the reaction solution was completely removed, 78.6g of isooctyl alcohol was added, and after the isooctyl alcohol was added, the reaction solution was stirred at 45°C for 30min; the system temperature was lowered to 20°C and then filtered, and the filter cake was rinsed with isooctyl alcohol (19.6g*2); the obtained saflufenacil wet product was dried at 75°C for 5h to obtain 38.1g of saflufenacil, with a content of 98.2% and a yield of 95.1%. The filtrate obtained by suction filtration and the rinse liquid after rinsing were combined into isooctyl alcohol mother liquor, in which the saflufenacil technical accounted for 0.7% (relative to the theoretical mass of saflufenacil).

[0051] Example 2

[0052] First, 60 g (0.1177 mol, content 95.5%) of 2-chloro-5-[3,6-dihydro-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-N-{[methyl-(1-methylethyl)amino]sulfonyl}benzamide, 3.9 g (0.0118 mol) of tetrabutylammonium bromide (=TBAB) and 20.2 g (0.159 mol) of dimethyl sulfate were added to a mixture of toluene, water and THF (tetrahydrofuran) at 25° C. and the mixture was heated to 40° C. A pH of 5.3-5.5 was then established in the reaction mixture by addition of 10% aqueous NaOH solution. The mixture was stirred at 40° C. for 1 hour, during which time 10% aqueous NaOH solution was continuously added so that the pH was kept constant at 5.3-5.5. After 1 hour, the addition of 10% aqueous NaOH solution was stopped, at which point the pH dropped back to 4.4-4.5. The mixture was stirred at a pH of 4.4-4.5 and 40° C. for further 5.5 hours to obtain a saflufenacil reaction solution.

[0053] The reaction solution of saflufenacil was acidified with hydrochloric acid until the pH of the aqueous layer of the reaction solution reached 1.5, the aqueous layer was washed with toluene, the organic phases were combined, and the organic phases were subjected to negative pressure (P=-0.1MPa) desolventizing treatment at 40°C; after the organic solvent in the reaction solution was completely removed, 117.9g of isooctyl alcohol was added; after the isooctyl alcohol was added, the reaction solution was stirred for 30min at 40°C; the system temperature was lowered to 20°C and then filtered, and the filter cake was rinsed with isooctyl alcohol (29.5g*2); the obtained saflufenacil wet product was dried at 75°C for 5h to obtain 56.8g of saflufenacil, with a content of 98.5% and a yield of 95.0%. The filtrate obtained by suction filtration and the rinse liquid after rinsing were combined into isooctyl alcohol mother liquor, in which the saflufenacil technical drug accounted for 0.9% (relative to the theoretical mass of saflufenacil).

[0054] Example 3

[0055] Safensulfuron was obtained according to the method of Example 1, except that isooctyl alcohol was replaced by hexyl acetate.

[0056] 38.0 g of saflufenacil was obtained, with a content of 98.2% and a yield of 95.0%. The saflufenacil technical drug accounted for 1.0% (relative to the theoretical mass of saflufenacil) in the obtained hexyl acetate mother liquor.

[0057] Embodiment 4-9

[0058] Safensulfuron was obtained according to the method of Example 1, except that isooctyl alcohol was replaced by other organic solvents. The yields are shown in Table 1.

[0059] Table 1

[0060]

[0061] Examples 10-13

[0062] The method of Example 1 was used to obtain saflufenacil, except that the mass of isooctyl alcohol used in stirring was replaced by other masses. The yield and content of saflufenacil are shown in Table 2.

[0063] Table 2

[0064]

[0065] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A post-treatment method for a saflufenacil reaction solution, characterized in that: The post-processing method comprises the following steps: (1) separating the saflufenacil reaction solution into layers, performing a desolventizing treatment on the organic phase, and then adding a first organic solvent and stirring; (2) After the stirring is completed, filtering is performed, and the obtained filter cake is rinsed with a second organic solvent, and dried to obtain saflufenacil.

2. The post-processing method according to claim 1, wherein: The saflufenacil reaction solution is prepared by the following method: 2-Chloro-5-[3,6-dihydro-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-N-{[methyl-(1-methylethyl)amino]sulfonyl}benzamide, a phase transfer catalyst and a methylating agent are added to a reaction solvent, and the reaction pH is controlled to be 4-6 with liquid alkali to react to obtain a saflufenacil reaction solution.

3. The post-processing method according to claim 2, wherein: The phase transfer catalyst is tetrabutylammonium bromide; Preferably, the methylating agent is dimethyl sulfate.

4. The post-processing method according to any one of claims 1 to 3, wherein: The first organic solvent and the second organic solvent are independently selected from alcohols, esters or ethers having not less than 7 carbon atoms, preferably alcohols, esters or ethers having not less than 8 carbon atoms; Preferably, the first organic solvent and the second organic solvent are independently selected from at least one of 1-heptanol, anisole, n-octanol, isooctyl alcohol, 2-octanol, hexyl acetate and 1-nonanol, preferably isooctyl alcohol and / or hexyl acetate; Preferably, the first organic solvent and the second organic solvent are of the same type.

5. The post-processing method according to any one of claims 1 to 4, wherein: Acidify the reaction solution with hydrochloric acid until the pH of the aqueous layer is 1-2, and perform negative pressure desolventizing treatment on the organic phase at 40-45°C; Preferably, the negative pressure condition is -0.1 MPa.

6. The post-processing method according to any one of claims 1 to 5, wherein: The ratio of the theoretical mass of saflufenacil to the mass of the first organic solvent is 1:1-10, preferably 1:1-6, and more preferably 1:

2.

7. The post-processing method according to any one of claims 1 to 6, wherein: The stirring temperature in step (1) is 0-80°C, preferably 40-45°C; Preferably, the stirring time in step (1) is 20-40 min, preferably 30 min.

8. The post-processing method according to any one of claims 1 to 7, wherein: The ratio of the theoretical mass of saflufenacil to the mass of the second organic solvent is 1:0.5-2, preferably 1:

1.

9. The post-processing method according to any one of claims 1 to 8, wherein: The drying temperature in step (2) is 50-90°C, preferably 75°C; Preferably, the drying time in step (2) is 4-8 hours, preferably 5 hours.

10. The post-processing method according to any one of claims 1 to 9, wherein: In step (2), after the stirring is completed, the system temperature is lowered to 15-20° C. and then filtered.

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