Method for preparing herbicide compound

Abstract

The present invention belongs to the field of organic chemical synthesis, and specifically relates to a method for preparing a herbicide compound. The method for preparing a compound comprises the following steps: subjecting compound I to a cyclization reaction to prepare compound II and byproduct aa, then adding a metal salt to decompose the byproduct, and conducting separation, so as to obtain target compound II. The preparation method of the present invention has a high yield, a high product purity and a simple process, and is suitable for industrial production.

Description

A method for preparing a herbicide compound Technical Field

[0001] This invention belongs to the field of organic chemical synthesis, and specifically relates to a method for preparing a herbicide compound. Background Technology

[0002] Weed control is a crucial link in achieving efficient agriculture. Therefore, in addition to developing new, efficient, safe, and economical herbicides with different modes of action, exploring a synthesis method for herbicide compounds that is suitable for industrial production, characterized by high yield, low cost, high product purity, and simple post-processing, is also of significant practical value. Summary of the Invention

[0003] To address the aforementioned problems in the prior art, this invention provides a method for preparing herbicide compounds.

[0004] The technical solution adopted in this invention is as follows:

[0005] A method for preparing a herbicide intermediate includes the following steps: Compound I Compound II was prepared by cyclization reaction. and by-products Subsequently, metal salts were added to decompose the byproducts, and the target compound II was obtained by separation.

[0006] This invention also provides a method for preparing a herbicide compound, comprising the following steps:

[0007] (1) Compound I Compound II was prepared by cyclization reaction. and by-products Subsequently, metal salts were added to decompose the byproducts, and the target compound II was obtained by separation.

[0008] (2) Compound II reacts with compound III to give compound IV, as shown in the following reaction formula:

[0009] Where Hal represents halogen, X represents hydrogen or halogen, and Y represents halogen.

[0010] In one specific embodiment, X represents hydrogen and Y represents chlorine, X represents chlorine and Y represents chlorine, or X represents chlorine and Y represents bromine.

[0011] In one specific embodiment, the reaction of compounds II and III is carried out in the presence of an alkaline solution and a catalyst.

[0012] In another specific embodiment, the alkaline solution is an inorganic alkaline aqueous solution, such as NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.

[0013] In another specific embodiment, the catalyst is selected from at least one of TBAB, 18-crown ether-6, tetrabutylammonium chloride, or benzyltriethylammonium chloride.

[0014] In another specific embodiment, the molar ratio of compound II to compound III is 1 to 2:1.

[0015] In one specific embodiment, the reaction of compound II with compound III to obtain compound IV specifically includes the following steps:

[0016] (1) Dissolve compound III in an organic solvent and then react it with an aqueous solution of compound II;

[0017] (2) After the organic phase is dehydrated by azeotropic reaction, HCl gas is introduced to carry out the reaction.

[0018] (3) Mix the aqueous phase from step (1) and the organic phase from step (2), add an alkaline solution and react completely, then obtain compound IV through post-treatment.

[0019] In another specific embodiment, the organic solvent is at least one of toluene, dichloroethane, DMSO, dioxane, dichloromethane (DCM), or ethyl acetate.

[0020] In another specific embodiment, the alkaline solution is an inorganic alkaline aqueous solution, such as NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.

[0021] In one specific embodiment, the cyclization reaction is carried out in the presence of an alkaline solution; preferably, the alkaline solution is an inorganic alkaline aqueous solution, such as NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.

[0022] In one specific embodiment, the metal salt is selected from copper salts, cuprous salts, ferrous salts, ferrous salts, or cobalt salts.

[0023] In one specific embodiment, the decomposition process is carried out under alkaline conditions; preferably, the decomposition process is carried out at 40–80°C.

[0024] In one specific embodiment, the separation process includes the following steps:

[0025] (1) Add an alkaline solution to the reaction system to precipitate copper salt, cuprous salt, ferric salt or ferrous salt into hydroxide, then dehydrate to generate oxide, add activated carbon, stir and filter to obtain compound II solution.

[0026] Alternatively (2) add an alkaline solution to the reaction system to precipitate the cobalt salt as hydroxide, and filter to obtain a solution of compound II.

[0027] In another specific embodiment, the metal salt is a corresponding inorganic acid salt or organic acid salt, such as one or more combinations selected from sulfates, sulfites, bisulfites, nitrates, nitrites, halides (such as chlorides, fluorides, bromides, iodides), formates, acetates, trifluoroacetates, citrates, lactates, malates, trifluoromethanesulfonates, or bis(trifluoromethanesulfonyl)imide salts.

[0028] In one specific embodiment, compound I is obtained by reacting chloropentanoyl chloride with hydroxylamine hydrochloride, as shown in the following reaction formula:

[0029] In another specific embodiment, hydroxylamine hydrochloride is first dissolved in water and then dissociated under alkaline conditions, followed by the addition of chloropentanoyl chloride to allow it to react in the presence of an alkali and a solvent.

[0030] In another specific embodiment, the solvent is at least one selected from DMF, DMA, acetonitrile, dichloroethane, DMSO, dioxane, dichloromethane, or ethyl acetate.

[0031] In another specific embodiment, the base is selected from at least one of inorganic bases (such as NaOH, KOH, K2CO3, Na2CO3, Cs2CO3, KF, CsF, etc.) or organic bases (such as pyrazole, triethylamine, N,N-diisopropylethylamine, pyridine, DIEA, potassium trimethylsilanol, AcOK, AcONa, MeONa, EtONa, t-BuONa, t-BuOK, etc.).

[0032] In another specific embodiment, the molar ratio of chloropentanoyl chloride to hydroxylamine hydrochloride is 1:1 to 2.

[0033] The metal salts described in this invention refer to compounds composed of metal (such as alkali metals, alkaline earth metals, and transition metals) cations and nonmetal anions.

[0034] The preparation method of this invention has high yield, high product purity, and simple process, making it suitable for industrial production. Detailed Implementation

[0035] The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims.

[0036] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0037] Example 1: Different metal ions decompose four-membered ring isomers Effect comparison

[0038] Add 100g of compound II to each of the 250mL reaction flasks. An aqueous solution of compound II (liquid chromatographic normalized purity 93.5%, and the liquid chromatographic normalized purity of the four-membered ring isomer 6.0%) was prepared. Then, 10% aqueous solutions of different metal salts (0.16 times the equivalent of the four-membered ring isomers) were added to the reaction flask. The temperature was raised to 65℃ and the pH was adjusted to 9.0–9.5. The mixture was stirred for 10 hours, and samples were taken for analysis. For reactions with a liquid chromatographic normalized purity >0.2% for the four-membered ring isomers, the reaction time was extended, and samples were taken again after stirring at this temperature for 20 hours. Representative liquid chromatographic results are shown in the table below. a: Because of its poor solubility, cuprous chloride solid was added.

[0039] The results in the table above show that copper salts and cuprous salts, excluding the four-membered ring isomers, showed the best effect, with the normalized purity of the byproducts decreasing to 0.1-0.2% after 10 hours of heating and stirring. Iron salts, ferrous salts, and cobalt salts showed slightly worse effect, with the normalized purity of the byproducts decreasing from 6.0% to 3.5-4.4% after 10 hours of heating and stirring. Even after 30 hours, the normalized purity of the byproducts still decreased to 0.1-0.2%.

[0040] Example 2 Preparation method

[0041] (1) First, add 480g of deionized water to a 3L four-necked flask and cool it to 15℃. Then, add 120.0g of hydroxylamine hydrochloride and adjust the pH to 8.0-9.0 with 30% alkali solution. After the hydroxylamine hydrochloride has dissociated, add 1200g of dichloromethane. Maintain the temperature at 15℃ and begin adding 241.2g of chloropentanoyl chloride dropwise, while simultaneously adding 30% alkali solution to adjust the pH to 8.0-9.0. After the chloropentanoyl chloride has been added, stop adding the 30% alkali solution. Stir for 30 minutes at 15℃, then filter. Dry the filter cake to obtain 242.4g of compound I with a purity of 95.9% and a reaction yield of 97.3%.

[0042] (2) Add 600g of deionized water to a 3L four-necked flask, cool to 15℃, and then add 253.0g of compound I. The system is a white suspension with pH = 3.5–4.0. Maintain the temperature at 15℃ and add 30% liquid alkali dropwise to adjust the pH to 11.0–12.0. The addition is completed in about 22 hours, consuming a total of 429.1g of liquid alkali. After the reaction is complete, the system becomes a pale yellow clear solution. Add 13.5g of 10% copper chloride solution to decompose the four-membered ring isomer of compound II. The temperature was raised to 65°C and the pH adjusted to 9.0–9.5. The mixture was stirred for 9–10 hours until the four-membered ring completely decomposed. Then, 30% liquid alkali was added to adjust the pH of the reaction solution to 12.0–13.0. The temperature was maintained at 65°C, and stirring continued for 6 hours to convert copper chloride into copper hydroxide precipitate. The copper hydroxide then dehydrated to form copper oxide. Finally, activated carbon was added, and the mixture was stirred at room temperature for 5 hours before filtration. The resulting aqueous solution of compound II could be directly used in the next reaction (purity 98.0%, yield 93%).

[0043] (3) The reaction to prepare the target compound from compound II and compound III-1 is divided into the following three stages:

[0044] First stage reaction: Add 400g of an aqueous solution of compound II (11.54% purity) (compound II exists in two isomers in aqueous solution) and 3.56g of TBAB to a 1000mL four-necked flask, and adjust the pH to 7.5-8.0 with 30% concentrated hydrochloric acid. Raise the temperature to 85℃, and begin adding 211.5g of a 50% toluene solution of compound III-1 dropwise, simultaneously adding 30% liquid alkali, maintaining the pH at 7.5-8.0. The addition is completed after 1 hour, and stirring continues for 7 hours at 85℃. Take a sample, allow it to stand, separate the layers, temporarily store the aqueous phase, and use the organic phase (a mixture of the target compound and a) for the next stage reaction.

[0045] Second stage reaction: The organic phase was refluxed with toluene to remove water until the water content in the organic phase was ≤450ppm. Then the temperature was lowered to 30-40℃, HCl gas was introduced, and the mixture was stirred for 9 hours. A sample was taken for control to confirm that the normalized purity of a in liquid chromatography was less than 0.05%.

[0046] NMR of compound a: 1 HNMR (300MHz, CDCl3) δ7.59 (d, J = 3Hz, 1H), 7.38 (d, J = 6Hz, 1H), 7.31 (dd, J1 = 6Hz, J2 = 3Hz, 1H), 5.15 (s, 2H), 4.14 (s, 2H), 1.27 (s, 6H).

[0047] The third stage of the reaction: The aqueous phase separated in the first stage was added to the organic phase generated in the second stage, and the pH was adjusted to 7.5-8.0 with 30% liquid alkali. The temperature was raised to 85℃, and the mixture was stirred for 6 hours. Samples were taken for monitoring to confirm that b was completely converted to the target compound. At 85℃, the pH was adjusted to 8.0-9.0 with 30% NaOH solution, and the aqueous phase was separated by standing. The organic phase was washed with 103g of process water, and then toluene was removed by vacuum distillation to obtain 115.1g of the target compound (purity 94.3%, yield 94.2%).

[0048] Example 3 Preparation method

[0049] The reaction to prepare the target compound from compound II and compound III-2 can be divided into the following three stages:

[0050] First stage reaction: 6349.3g of an aqueous solution of compound II (10.0% purity) and 49.5g of TBAB were added to a 10L reactor. The pH was adjusted to 7.5–8.0 with 30% concentrated hydrochloric acid. The temperature was raised to 85℃, and 1960g of a toluene solution (50% purity) of compound III-2 was added dropwise simultaneously with 30% liquid alkali, maintaining the pH at 7.5–8.0. The addition was completed after 2 hours, and the mixture was stirred for another 15 hours at 85℃. Samples were taken for central control, allowed to stand, and separated. The aqueous phase was temporarily stored, while the organic phase (a mixture of the target compound and C) was used for the next stage reaction.

[0051] Second stage reaction: The organic phase was refluxed with toluene to remove water until the water content in the organic phase was ≤450ppm. Then, the temperature was lowered to 30-40℃, HCl gas was introduced, and the mixture was stirred for 2 hours. A sample was taken for control to confirm that the normalized purity of c was less than 0.05%. The second stage reaction was then completed.

[0052] The third stage of the reaction: The aqueous phase separated in the first stage was added to the organic phase generated in the second stage, and the pH was adjusted to 7.5–8.0 with 30% liquid alkali. The temperature was raised to 85°C, and the mixture was stirred for 20 hours. Samples were taken for monitoring to confirm that III-2 was completely converted to the target compound. At 85°C, the pH was adjusted to 8.0–9.0 with 30% NaOH solution, and the aqueous phase was separated by standing. The organic phase was washed with 1000g of process water, and then toluene was removed by vacuum distillation to obtain 1378g of the target compound (purity 95.2%, yield 95.4%).

[0053] Example 4 Preparation method

[0054] The reaction to prepare the target compound from compounds II and III-3 can be divided into the following three stages:

[0055] First stage reaction: 7852.8g of an aqueous solution of compound II (10.0% purity) and 61.2g of TBAB were added to a 10L reactor. The pH was adjusted to 7.5–8.0 with 30% concentrated hydrochloric acid. The temperature was raised to 85℃, and 2000g of a toluene solution (50% purity) of compound III-3 was added dropwise simultaneously with 30% liquid alkali, maintaining the pH at 7.5–8.0. The addition was completed after 1 hour, and the mixture was stirred for another 16 hours at 85℃. Samples were taken for central control, allowed to stand, and separated. The aqueous phase was temporarily stored, while the organic phase (a mixture of the target compound and d) was used for the next stage reaction.

[0056] Second stage reaction: The organic phase was refluxed with toluene to remove water until the water content in the organic phase was ≤450ppm. Then, the temperature was lowered to 30-40℃, HCl gas was introduced, and the mixture was stirred for 2 hours. A sample was taken for control to confirm that the normalized purity of d was less than 0.05%. The second stage reaction was then completed.

[0057] The third stage of the reaction: The aqueous phase separated in the first stage was added to the organic phase generated in the second stage, and the pH was adjusted to 7.5–8.0 with 30% liquid alkali. The temperature was raised to 85°C, and the mixture was stirred for 20 hours. Samples were taken for monitoring to confirm that III-3 was completely converted to the target compound. At 85°C, the pH was adjusted to 8.0–9.0 with 30% NaOH solution, and the aqueous phase was separated by standing. The organic phase was washed with 1000g of process water, and then toluene was removed by vacuum distillation to obtain 1492.5g of the target compound (purity 96.3%, yield 96.7%).

[0058] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A method for preparing a herbicide intermediate, characterized in that, Includes the following steps: Compound I Compound II was prepared by cyclization reaction. and by-products Subsequently, metal salts were added to decompose the byproducts, and the target compound II was obtained by separation.

2. A method for preparing a herbicide compound, characterized in that, Includes the following steps: (1) Compound I Compound II was prepared by cyclization reaction. and by-products Subsequently, metal salts were added to decompose the byproducts, and the target compound II was obtained by separation. (2) Compound II reacts with compound III to give compound IV, as shown in the following reaction formula: Where Hal represents halogen, X represents hydrogen or halogen, and Y represents halogen.

3. The preparation method according to claim 2, characterized in that, X represents hydrogen and Y represents chlorine, X represents chlorine and Y represents chlorine, or X represents chlorine and Y represents bromine.

4. The preparation method according to claim 2 or 3, characterized in that, The reaction of compounds II and III is carried out in the presence of an alkaline solution and a catalyst; preferably, the alkaline solution is an inorganic alkaline aqueous solution; the catalyst is selected from at least one of TBAB, 18-crown ether-6, tetrabutylammonium chloride or benzyltriethylammonium chloride; more preferably, the molar ratio of compound II to compound III is 1 to 2:

1.

5. The preparation method according to claim 4, characterized in that, The reaction of compound II with compound III to yield compound IV specifically includes the following steps: (1) Dissolve compound III in an organic solvent and then react it with an aqueous solution of compound II; (2) After the organic phase is dehydrated by azeotropic reaction, HCl gas is introduced to carry out the reaction. (3) Mix the aqueous phase in step (1) and the organic phase in step (2), add an alkaline solution and react completely, then obtain compound IV after post-treatment; Preferably, the organic solvent is at least one of toluene, dichloroethane, DMSO, dioxane, dichloromethane (DCM), or ethyl acetate; or the alkaline solution is an inorganic alkaline aqueous solution.

6. The preparation method according to any one of claims 1-5, characterized in that, The cyclization reaction is carried out in the presence of an alkaline solution; preferably, the alkaline solution is an inorganic alkaline aqueous solution.

7. The preparation method according to any one of claims 1-6, characterized in that, The metal salt is selected from copper salts, cuprous salts, ferrous salts, ferrous salts, or cobalt salts; preferably, the decomposition process is carried out under alkaline conditions; more preferably, the decomposition process is carried out at 40–80°C.

8. The preparation method according to any one of claims 1-7, characterized in that, The separation process includes the following steps: (1) Add an alkaline solution to the reaction system to precipitate copper salt, cuprous salt, ferric salt or ferrous salt into hydroxide, then dehydrate to generate oxide, add activated carbon, stir and filter to obtain compound II solution. Alternatively (2) add an alkaline solution to the reaction system to precipitate the cobalt salt as hydroxide, and filter to obtain a solution of compound II.

9. The preparation method according to any one of claims 1-8, characterized in that, The metal salt is a corresponding inorganic acid salt or organic acid salt, such as one or more combinations selected from sulfates, sulfites, bisulfites, nitrates, nitrites, halides, formates, acetates, trifluoroacetates, citrates, lactates, malates, trifluoromethanesulfonates, or bis(trifluoromethanesulfonyl)imide salts.

10. The preparation method according to any one of claims 1-9, characterized in that, Compound I is obtained by reacting chloropentanoyl chloride with hydroxylamine hydrochloride, as shown in the following reaction formula: Preferably, hydroxylamine hydrochloride is first dissolved in water and then dissociated under alkaline conditions, followed by the addition of chloropentanoyl chloride to allow the reaction to proceed in the presence of a base and a solvent; more preferably, the solvent is at least one of DMF, DMA, acetonitrile, dichloroethane, DMSO, dioxane, dichloromethane, or ethyl acetate; and the base is selected from at least one of organic or inorganic bases. Preferably, the molar ratio of chloropentanoyl chloride to hydroxylamine hydrochloride is 1:1 to 2.

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