Preparation method of metabolites of triazolopyrimidine sulfonamide herbicides

Abstract

This invention discloses a method for preparing metabolites of triazolopyrimidine sulfonamide herbicides. The method involves reacting the triazolopyrimidine sulfonamide herbicide in an alkaline aqueous solution. After the reaction, the reactants are adjusted to an acidic state, and then stirred, filtered, washed, and dried to obtain the metabolites of the triazolopyrimidine sulfonamide herbicide. This invention provides a method for preparing metabolites of some triazolopyrimidine sulfonamide herbicides. The synthetic route of this invention is simple, and the yield and purity of the products are high, providing material support for environmental and toxicological testing of pesticide metabolites in pesticide registration.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing metabolites of triazolopyrimidine sulfonamide herbicides, and more specifically to a method for preparing 5-hydroxy-N-aryl-1,2,4-triazolopyrimidine-2-sulfonamide. Background Technology

[0002] Triazolopyrimidine sulfonamide herbicides are characterized by low dosage, good weed control effect, and safety for subsequent crops, and have a good market share. Commercially available herbicides in this class include chlorpyrifos, dichlorpyrifos, and diflubenzuron.

[0003] According to the latest domestic pesticide registration policy, pesticide metabolites must be provided for environmental and toxicological testing to assess their risks to the environment, diet, etc. Therefore, the preparation of pesticide metabolites is an important process for completing pesticide registration.

[0004] Formula (1) below represents the metabolites of triazolopyrimidine sulfonamide herbicides in plants and the environment:

[0005] (1);

[0006] In formula (1), R1 represents halogen or COOR, where R represents hydrogen or a lower alkyl group of C1-C4; X and Y represent halogen.

[0007] However, there are currently no reports on the preparation methods of this type of compound. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a simple method for preparing 5-hydroxy-N-aryl-1,2,4-triazolopyrimidine-2-sulfonamide, a metabolite of triazolopyrimidine sulfonamide herbicides, with high yield and purity.

[0009] The technical solution for achieving the objective of this invention is a method for preparing metabolites of triazolidine sulfonamide herbicides, comprising the following steps:

[0010] ① React the triazolopyrimidine sulfonamide herbicide shown in formula (2) in an alkaline aqueous solution;

[0011] (2);

[0012] In formula (2), R1 represents halogen or COOR. In COOR, R represents hydrogen or lower alkyl; X and Y represent halogen; and R2 represents lower alkyl from C1 to C4.

[0013] ②After the reaction in step ① is completed, the reaction material is adjusted to acidity with acid, and then stirred, filtered, washed and dried to obtain the metabolites of the triazolidine sulfonamide herbicide shown in formula (1);

[0014] (1);

[0015] In formula (1), R1 represents halogen or COOR, where R represents hydrogen or a lower alkyl group of C1-C4; X and Y represent halogen.

[0016] In step ① above, the alkali is one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

[0017] In step ① above, the triazolopyrimidine sulfonamide herbicide shown in formula (2) is dispersed in water, and then an alkaline aqueous solution is added dropwise at 0℃~30℃.

[0018] Preferably, in step ①, the triazolopyrimidine sulfonamide herbicide shown in formula (2) is dispersed in water, and then an alkaline aqueous solution is added dropwise at 5℃~10℃.

[0019] In step ① above, the reaction temperature is 0℃~30℃.

[0020] Preferably, in step ① above, the reaction temperature is 5℃~10℃.

[0021] In step ① above, the molar ratio of the triazolopyrimidine sulfonamide herbicide shown in formula (2) to the alkali is 1:1 to 1:5.

[0022] In step ① above, the triazolopyrimidine sulfonamide herbicide shown in formula (2) reacts in an alkaline aqueous solution for 1–3 hours.

[0023] In step ② above, the acid used is one of hydrochloric acid, sulfuric acid, or glacial acetic acid.

[0024] This invention offers several advantages: it provides a method for preparing metabolites of certain triazolopyrimidine sulfonamide herbicides. The method involves reacting the triazolopyrimidine sulfonamide herbicide in an alkaline aqueous solution, followed by acidification with dilute acid to obtain the metabolite, 5-hydroxy-N-aryl-1,2,4-triazolopyrimidine-2-sulfonamide. The synthetic route of this invention is simple, and the product yield and purity are high, providing material support for environmental and toxicological testing of pesticide metabolites in pesticide registration. Attached Figure Description

[0025] Figure 1 This is the mass spectrum of the product from Example 1.

[0026] Figure 2 The image shows the HPLC spectrum of the product from Example 1.

[0027] Figure 3 The image shows the HPLC spectrum of the product from Example 6. Detailed Implementation

[0028] The following describes some of the possible embodiments of the present invention, intended to provide a basic understanding of the invention, and is not intended to identify the key or decisive elements of the invention or limit the scope of protection. It is readily understood that, based on the technical solutions of the present invention, those skilled in the art can propose other interchangeable implementations without altering the essential spirit of the invention. Therefore, the following specific embodiments are merely illustrative examples of the technical solutions of the present invention and should not be considered as the entirety of the invention or as limitations or restrictions on the technical solutions of the present invention.

[0029] This invention provides a method for preparing metabolites of certain triazolopyrimidine sulfonamide herbicides, which have the following general formula:

[0030] (2); In formula (2), R1 represents halogen or COOR, where R represents hydrogen or lower alkyl; X, Y represent halogen; and R2 represents lower alkyl of C1-C4.

[0031] Their metabolites have the following general formula:

[0032] (1); In formula (1), R1 represents halogen or COOR, where R represents hydrogen or a lower alkyl group of C1-C4; X, Y represent halogen.

[0033] The specific implementation method is as follows.

[0034] (Example 1)

[0035] This embodiment prepares the metabolite of chlorpyrifos, and the reaction equation is as follows:

[0036] .

[0037] The preparation method of the metabolites of chlorpyrifos includes the following steps:

[0038] ① Add 21.5g of chlorpyrifos (0.05mol) to 120g of water, stir for 10min, and then add 20% sodium hydroxide aqueous solution dropwise at 5℃~10℃ (total sodium hydroxide added 5g, 0.125mol). After the addition is completed, react at 5℃~10℃ for 1~3h (1.5h in this example).

[0039] Besides sodium hydroxide, other bases can be used, such as lithium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate. The molar ratio of chlorpyrifos to the base is 1:1 to 1:5.

[0040] ② After the reaction was completed, the reaction mixture was adjusted to be acidic with 5%–10% dilute acid. For example, in this embodiment, the pH was adjusted to 1–2. The mixture was stirred for 0.5–1.5 h (1 h in this embodiment), filtered, and the filter cake was washed with water and dried at 60 °C to obtain 19.2 g of methyl 3-chloro-2-[(5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidin-2-yl)sulfonamide]benzoate, with a yield of 87.4% and a purity of 91.23% as determined by HPLC. The mass spectrum of the product is shown in [reference needed]. Figure 1 HPLC chromatograms are shown below. Figure 2 .

[0041] The acid is one of hydrochloric acid, dilute sulfuric acid, and glacial acetic acid; hydrochloric acid is used in this embodiment.

[0042] (Example 2)

[0043] This embodiment prepares a metabolite of chlorpyrifos, and the preparation method includes the following steps:

[0044] ① Add 21.5g of chlorpyrifos (0.05mol) to 120g of water, stir for 10min, and then add 20% sodium hydroxide aqueous solution dropwise at 5℃~10℃ (total sodium hydroxide added 6g, 0.15mol). After the addition is completed, react at 5℃~10℃ for 2 hours.

[0045] ② After the reaction was completed, the pH of the reactants was adjusted to 1-2 with 5%-10% dilute hydrochloric acid, stirred for 1 hour, filtered, the filter cake was washed with water and dried to obtain 19.5 g of methyl 3-chloro-2-[(5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidin-2-yl)sulfonamide]benzoate, with a yield of 88.2% and a purity of 90.7% as determined by HPLC.

[0046] (Example 3)

[0047] This embodiment prepares a metabolite of chlorpyrifos, and the preparation method includes the following steps:

[0048] ① Add 21.5g of chlorpyrifos (0.05mol) to 120g of water, stir for 10min, and then add 20% sodium hydroxide aqueous solution dropwise at 20℃~25℃ (total sodium hydroxide added 5g, 0.125mol). After the addition is completed, react at 20℃~25℃ for 2 hours.

[0049] ② After the reaction was completed, the pH of the reactants was adjusted to 1-2 with 5%-10% dilute sulfuric acid, stirred for 1 hour, filtered, and the filter cake was washed with water and dried to obtain 17.8 g of methyl 3-chloro-2-[(5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidin-2-yl)sulfonamide]benzoate, with a yield of 73.2% and a purity of 82.4% as determined by HPLC.

[0050] (Example 4)

[0051] This embodiment prepares a metabolite of chlorpyrifos, and the preparation method includes the following steps:

[0052] ① Add 21.5g of chlorpyrifos (0.05mol) to 120g of water, stir for 10min, and then add 20% potassium hydroxide aqueous solution dropwise at 5℃~10℃ (total potassium hydroxide 7g, 0.125mol). After the addition is completed, react at 5℃~10℃ for 3 hours.

[0053] ② After the reaction was completed, the pH of the reactants was adjusted to 5-6 with 5%-10% dilute glacial acetic acid. The mixture was stirred for 1 hour, filtered, and the filter cake was washed with water and dried to obtain 18.6 g of methyl 3-chloro-2-[(5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidin-2-yl)sulfonamide]benzoate, with a yield of 85.4% and a purity of 92.1% as determined by HPLC.

[0054] (Example 5)

[0055] This embodiment prepares a metabolite of chlorpyrifos, and the preparation method includes the following steps:

[0056] ① Add 21.5g of chlorpyrifos (0.05mol) to 120g of water, stir for 10min, then add 17.2g of potassium carbonate (0.125mol) at 5℃~10℃, and react at 5℃~10℃ for 2 hours.

[0057] ② After the reaction was completed, the pH of the reactants was adjusted to 1-2 with 5%-10% dilute hydrochloric acid, stirred for 1 hour, filtered, and the filter cake was washed with water and dried to obtain 18.1 g of methyl 3-chloro-2-[(5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidin-2-yl)sulfonamide]benzoate, with a yield of 82.7% and a purity of 91.6% as determined by HPLC.

[0058] (Example 6)

[0059] This example prepares a metabolite of dichlorvos, and the reaction formula is as follows:

[0060] .

[0061] The preparation method includes the following steps:

[0062] ① Add 20.3g of dichlorvos (0.05mol) to 120g of water, stir for 10min, and then add 20% sodium hydroxide aqueous solution dropwise at 5℃~10℃ (total sodium hydroxide added: 5g, 0.125mol). After the addition is complete, react at 5℃~10℃ for 1~3h (1.5h in this example). Besides sodium hydroxide, other bases can be used, such as lithium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate. The molar ratio of dichlorvos to the base is 1:1 to 1:5.

[0063] ② After the reaction was completed, the pH of the reactants was adjusted to 1-2 with 5%-10% dilute hydrochloric acid. The mixture was stirred for 1 hour, filtered, and the filter cake was washed with water and dried to obtain 17.6 g of N-(2,6-dichlorophenyl)-5-hydroxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidine-2-sulfonamide, with a yield of 90.4% and a purity of 97.05% as determined by HPLC (HPLC chromatogram shown in [reference needed]). Figure 3 ).

[0064] In addition to hydrochloric acid, either dilute sulfuric acid or glacial acetic acid can be used to adjust the pH value.

[0065] The synthetic route of this invention is simple, and the product yield and purity are high, providing material support for environmental and toxicological tests of pesticide metabolites in pesticide registration.

Claims

1. A method for preparing a metabolite of a triazolopyrimidine sulfonamide herbicide, characterized in that... Includes the following steps: ① The triazolidine sulfonamide herbicide shown in formula (2) is reacted in an alkaline aqueous solution; the triazolidine sulfonamide herbicide shown in formula (2) is dispersed in water, and then an alkaline aqueous solution is added dropwise at 5℃~10℃, the reaction temperature is 5℃~10℃, and the reaction is carried out in an alkaline aqueous solution for 1~3h; the alkali in the alkaline aqueous solution is one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; the molar ratio of the triazolidine sulfonamide herbicide shown in formula (2) to the alkali is 1∶1~1∶5; （2）； ②After the reaction in step ① is completed, the reaction material is adjusted to acidity with acid, and then stirred, filtered, washed and dried to obtain the metabolites of the triazolidine sulfonamide herbicide shown in formula (1); （1）。 2. The method for preparing the metabolite of the triazolopyrimidine sulfonamide herbicide according to claim 1, characterized in that: In step ②, the acid used is one of hydrochloric acid, sulfuric acid, or glacial acetic acid.

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