Method for producing glufosinate-p salt

Abstract

The present disclosure provides a method for producing a glufosinate-P salt. Different from the prior art in which glufosinate is used as raw material, the manufacture method specifically uses crude 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid (containing oxalic acid) as raw material. Based on this raw material, the present disclosure further specifically adds a base for reaction and pre-removes oxalate salts, so that residual oxalic acid after removal is < 0.05%; when the specific base is not ammonia, ammonia in an amount not less than the molar amount of the raw material needs to be supplemented; and then further adds a base to control pH and continuously feeds the material to a one-step enzyme-catalyzed conversion system, thereby obtaining the corresponding glufosinate-P salt. Compared with the conventional process of producing glufosinate-P using racemic glufosinate technical material through two-step enzyme catalysis, the method has characteristics such as a simple process, low production cost, and strong applicability.

Description

METHOD FOR PRODUCING GLUFOSINATE-P SALT CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority of Chinese Patent Application No. 202610500246.8, filed with the China National Intellectual Property Administration on April 15, 2026, and titled with "METHOD FOR PRODUCING GLUFOSINATE-P SALT", which is hereby incorporated by reference in its entirety. FIELD

[0002] The present disclosure relates to the field of chemical engineering, and specifically relates to a method for producing glufosinate-P salt. BACKGROUND

[0003] Glufosinate-P, also known as L-glufosinate, is a broad-spectrum, contact-type, and non- selective herbicide. As an L-amino acid, it can bind to the active site of glutamine synthetase (GS), inhibit glutamine synthesis, cause excessive accumulation of ammonia in plants and disordered nitrogen metabolism, and disintegrate chloroplasts, thereby inhibiting photosynthesis and ultimately causing plant death. Compared with glufosinate, glufosinate-P has advantages such as higher herbicidal activity, a lower use amount, and greater environmental friendliness. At present, the prior art has studied the manufacture of glufosinate-P.

[0004] Patent CN107502647A uses D,L-glufosinate as a raw material, oxidizes D-glufosinate to 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid by D-amino acid oxidase, and then catalytically reduces it to glufosinate-P by amino acid dehydrogenase. However, in the process of oxidizing D- glufosinate to 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid by D-amino acid oxidase, hydrogen peroxide is generated, which easily causes inactivation of the enzyme protein and decomposition of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid; although hydrogen peroxide can be removed by adding additional catalase, in practice the adverse effects of hydrogen peroxide cannot be completely eliminated, and the use of catalase increases additional cost.

[0005] United States patent application US20180030487A1 similarly oxidizes D-glufosinate to 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid by D-amino acid oxidase, and then converts 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid into glufosinate-P by a stereoselective transamination reaction catalyzed by L-amino acid transaminase (L-TA). The transaminase process involved in this patent document has advantages such as high enzyme activity and high stereoselectivity, but also has two major defects: first, the transaminase-catalyzed step is an equilibrium reaction, and transamination requires providing an excess amino donor (an amino acid or organic amine) to ensure a relatively high conversion rate (3 equivalents of amino donor, 90% conversion rate), and the excess amino donor and corresponding by-products will seriously affect the subsequent separation and purification step; second, during synthesis of glufosinate-P, the material decomposition problem will affect smooth progress of the reaction and thereby affect the conversion rate, or if the reaction system contains impurities, such as oxalic acid, that cannot be effectively removed, multiple chain drawbacks may be triggered, such as affecting key indicators including enzyme catalytic activity, product purity, and physicochemical stability. At present, producing different types of glufosinate-P salts also faces certain challenges. SUMMARY

[0006] In view of this, an object of the present disclosure is to provide a method for producing a glufosinate-P salt. The manufacture method can simplify synthesis steps, solve the material decomposition problem, improve the conversion rate, and realize effective manufacture of different glufosinate salts, and has important theoretical and practical application value.

[0007] To achieve this objective, the present disclosure adopts the following technical solutions:

[0008] The present disclosure provides a method for producing a glufosinate-P salt, comprising the following steps:

[0009] S1: adjusting the pH of an aqueous solution of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid containing oxalic acid to 3 to 6 using a desalting base, precipitating a solid, and filtering to obtain an aqueous PPO solution;

[0010] wherein the desalting base comprises ammonia, and in the obtained aqueous PPO solution, the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)- 2-oxobutanoic acid;

[0011] or the desalting base does not comprise ammonia, and after filtration, ammonia is separately added to the aqueous PPO solution to control the molar amount of ammonia in the aqueous PPO solution to be not less than the molar amount of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid;

[0012] S2: adjusting the pH of the aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid to 6 to 9 using a base to obtain a PPO salt solution;

[0013] S3: continuously feeding the PPO salt solution to an enzyme-catalyzed conversion system, performing temperature-maintained reaction and post-treatment to obtain the glufosinate-P salt.

[0014] Preferably, in the aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid has a mass content of 5 wt% to 80 wt%.

[0015] Preferably, in the aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the oxalic acid has a mass content of 0.1 wt% to 10 wt%.

[0016] Preferably, the desalting base or base is independently any one or more selected from the group consisting of ammonia gas, aqueous ammonia, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, monomethylamine, dimethylamine, isopropylamine, and monoethanolamine.

[0017] Preferably, the desalting base or the base is independently introduced in the form of a solid or an aqueous base solution, and the aqueous base solution has a mass concentration of 5% to 99.9%.

[0018] Preferably, in step S1, adjusting pH using the desalting base is performed at a temperature of <semantics>0∘<annotation encoding="application / x-tex">0^{\circ}< / annotation>< / semantics>C to <semantics>35∘<annotation encoding="application / x-tex">35^{\circ}< / annotation>< / semantics>C.

[0019] Preferably, step S2 is performed in a continuous reactor.

[0020] Preferably, in the continuous reactor, the aqueous PPO solution and the base are mixed, and the mixing is performed at a temperature of 0°C to 35°C.

[0021] Preferably, the enzyme-catalyzed conversion system is a solution containing amino acid dehydrogenase, isopropanol dehydrogenase, isopropanol, and a coenzyme.

[0022] Preferably, the mass of the amino acid dehydrogenase or the isopropanol dehydrogenase is 1% to 15% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, the mass of the coenzyme is 0.01% to 5% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, and the mass of the isopropanol is 33% to 100% of the mass of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid.

[0023] Preferably, the continuous feeding is performed for a duration of 1 h to 24 h, and the temperature-maintained reaction is performed at a temperature of 35°C to 45°C.

[0024] Preferably, the post-treatment comprises: filtering and concentrating to obtain a glufosinate-P salt technical material, and crystallizing to obtain a glufosinate-P salt.

[0025] Preferably, the crystallizing is performed using a solvent selected from the group consisting of methanol, ethanol, isopropanol, n-butanol, n-hexane, acetonitrile, toluene and mixtures thereof.

[0026] Preferably, the glufosinate-P salt is one or more selected from the group consisting of glufosinate-P ammonium salt, glufosinate-P sodium salt, glufosinate-P potassium salt, glufosinate- P monomethylamine salt, glufosinate-P dimethylamine salt, glufosinate-P isopropylamine salt, and glufosinate-P monoethanolamine salt.

[0027] Preferably, the glufosinate-P salt has a purity of 98.5% or more, an oxalic acid content of less than 0.05%, and a yield of 97% or more.

[0028] Compared with the prior art, the beneficial effects of the present disclosure are as follows:

[0029] In the method for producing a glufosinate-P salt provided by the present disclosure, different from the prior art in which glufosinate is used as a raw material, the present disclosure specifically uses crude 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid (containing oxalic acid) as a raw material, and has advantages of wide raw material sources, low cost, direct connection to an upstream synthesis process, no need to carry out complex purification and refining, and substantially reduced raw material pretreatment cost. Based on this raw material, the present disclosure further specifically adds a desalting base for reaction, and pre-removes oxalate salts, so that residual oxalic acid after removal is <semantics><0.05%<annotation encoding="application / x-tex">< 0.05\%< / annotation>< / semantics>, and then further adds a base to control pH and continuously feeds the material to a one-step enzyme-catalyzed conversion system, thereby obtaining the corresponding glufosinate-P salt. Compared with the conventional process of producing glufosinate-P using racemic glufosinate technical material by two-step enzyme catalysis, the method has characteristics such as a simple process, low production cost, and strong applicability. BRIEF DESCRIPTION OF DRAWINGS

[0030] FIG. 1 is a chromatogram obtained after the glufosinate-P ammonium salt produced in Example 1 was tested using the national standard GB / T 43172-2023 method.

[0031] FIG. 2 is a sample chromatogram obtained from the glufosinate-P ammonium salt produced in Example 1 using the oxalic acid quantitative test method of the present disclosure.

[0032] FIG. 3 is a reference standard chromatogram obtained from an oxalic acid standard sample using the oxalic acid quantitative test method of the present disclosure. DETAILED DESCRIPTION

[0033] The technical solutions of the present disclosure will be clearly and completely described below in conjunction with examples of the present disclosure. Obviously, the described examples are only some, rather than all, examples of the present disclosure. All other examples obtained by a person of ordinary skill in the art based on the examples of the present disclosure without creative effort shall fall within the scope of protection of the present disclosure.

[0034] It should be noted that 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid is abbreviated as PPO.

[0035] In the present disclosure, the "aqueous PPO solution" referred to below means an aqueous solution obtained after oxalate salts are filtered out from an aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid.

[0036] The present disclosure provides a method for producing a glufosinate-P salt, comprising the following steps:

[0037] S1: adjusting the pH of an aqueous solution of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid containing oxalic acid to 3 to 6 using a desalting base, precipitating a solid, and filtering to obtain an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid;

[0038] It should be noted that the desalting base is divided into the following two cases:

[0039] when the desalting base comprises ammonia, preferably controlling the molar amount of ammonia in the obtained aqueous PPO solution to be not less than the molar amount of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid;

[0040] or, when the desalting base does not comprise ammonia, after filtration, preferably separately adding ammonia to the aqueous PPO solution to control the molar amount of ammonia in the aqueous PPO solution to be not less than the molar amount of 4-(hydroxymethylphosphinyl)- 2-oxobutanoic acid.

[0041] The purpose of the above operation is to control the molar amount of ammonia in the aqueous PPO solution to be not less than the molar amount of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid, because conversion of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid into glufosinate-P requires at least ammonia in an amount equal to the molar amount of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid.

[0042] S2: adjusting the pH of the aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid to 6 to 9 using a base to obtain a PPO salt solution;

[0043] S3: continuously feeding the PPO salt solution to an enzyme-catalyzed conversion system, performing temperature-maintained reaction and post-treatment to obtain the glufosinate-P salt.

[0044] According to the present disclosure, a raw material is first provided, namely, an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, which may be produced using an oxalate ester as a raw material. Compared with the conventional prior art in which glufosinate is used as a raw material, the present disclosure specifically uses crude 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid (containing oxalic acid) as a raw material, so that feed solution synthesized upstream can be directly used, eliminating the separation, purification, and drying steps for producing solid glufosinate, and significantly reducing raw material cost and complexity of pretreatment processes.

[0045] The present disclosure does not particularly limit the method for producing the aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid using an oxalate ester as a raw material, and manufacture may be carried out according to methods well known to those skilled in the art.

[0046] In some embodiments of the present disclosure, in the aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid has a mass content of 5 wt% to 80 wt%, for example, may be 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, or 80 wt%. In the aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the oxalic acid has a mass content of 0.1 wt% to 10 wt%, for example, may be 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, or 10 wt%.

[0047] According to the present disclosure, the aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid is preferably adjusted to a pH of 3 to 6 using a desalting base, for example, the pH may be 3, 3.5, 4, 4.5, 5, 5.5, or 6, a solid is precipitated, and filtration is performed to obtain a desalted aqueous PPO solution. In the present disclosure, the reason for adjusting the pH to 3 to 6 is that by utilizing the common ion effect and the stronger acidity of oxalic acid relative to other carboxylic acids, as well as the solubility variation of oxalates with pH in the presence of carboxylic compounds, oxalic acid can be precipitated in the form of an oxalate salt by controlling the amount of base, thereby achieving high-efficiency separation of the oxalate salt from 4-(hydroxymethylphosphinyl)-2-oxobutyric acid in the reaction system. After the removal of the oxalate salt, the residual oxalic acid is less than 0.05%.

[0048] In some embodiments of the present disclosure, the pH of the aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid is adjusted using the desalting base preferably at a temperature of 0°C to 35°C, preferably 0°C to 30°C, more preferably 0°C to 20°C, more preferably 0°C to 10°C, and more preferably 2°C to 10°C.

[0049] The present disclosure preferably controls the above temperature to be 0°C to 35°C because the PPO decomposition rate is slow within this temperature range; if the temperature is lower than 0°C, the solution will freeze; conversely, if the temperature is higher than 35°C, the PPO decomposition rate will be accelerated.

[0050] The desalting base may be any one or more selected from the group consisting of ammonia gas, aqueous ammonia, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, monomethylamine, dimethylamine, isopropylamine, and monoethanolamine. The aqueous ammonia has a mass fraction of 5% to 30%, for example, may be 5%, 10%, 15%, 20%, 25%, or 30%.

[0051] Specifically, the desalting base may be introduced in the form of a solid or an aqueous base solution. When introduced in the form of an aqueous base solution, the aqueous base solution preferably has a mass concentration of 5% to 99.9%, more preferably 5 to 80%, and further preferably 5 to 60%.

[0052] During addition of the desalting base, the present disclosure utilizes the common ion effect and the stronger acidity of oxalic acid relative to other carboxylic acids, as well as the solubility variation of oxalates with pH in the presence of carboxylic compounds, to precipitate oxalic acid in the form of solid oxalates by controlling the amount of base, thereby achieving high- efficiency separation from 4-(hydroxymethylphosphinyl)-2-oxobutyric acid in the reaction system. After the removal of the oxalate salt, the residual oxalic acid is less than 0.05%.

[0053] It is further noted that, when ammonia is used as the desalting base for removing oxalate salts and the pH is adjusted to 3 to 6, the ammonia source in the system is already sufficient. After the solid is precipitated and filtered, an aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid can be obtained.

[0054] However, when the desalting base does not comprise ammonia, after the solid is precipitated and filtered, ammonia in an amount not less than the molar amount of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid needs to be supplemented, because conversion of PPO into glufosinate-P requires at least ammonia in an amount equal to the molar amount of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid.

[0055] Then, according to the present disclosure, the aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid is adjusted with a base to a pH of 6 to 9, preferably 7 to 9, further preferably 7 to 8.5, further preferably 7.8 to 8.5, for example, may be 6, 6.5, 7, 7.5, 7.8, 8, 8.5, or 9, thereby obtaining a PPO salt solution. In this step, the added base and the introduction form of the base are the same as the selection ranges of the desalting base in step S1 described above, and are not repeated here. In this step, the pH is controlled to 6 to 9 because the catalytic activity of the enzyme is optimal within this range. The PPO salt may be any one or more of an ammonium salt, a sodium salt, a potassium salt, a monomethylamine salt, a dimethylamine salt, an isopropylamine salt, or a monoethanolamine salt, and the specific type of salt is related to the type of base added.

[0056] It should be noted that the base and the desalting base may be the same or different, and are not particularly limited.

[0057] In some embodiments of the present disclosure, the aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid is preferably mixed with the base in a continuous reactor, and the mixing is performed at a temperature of 0°C to 35°C, preferably 0°C to 30°C, more preferably 0°C to 20°C, more preferably 0°C to 10°C, and more preferably 2°C to 10°C.

[0058] The present disclosure does not particularly limit the type of the continuous reactor, and examples include, but are not limited to, a tubular reactor.

[0059] Then, the obtained PPO salt solution is continuously fed to an enzyme-catalyzed conversion system, and a temperature-maintained reaction is performed, followed by post- treatment, to obtain the glufosinate-P salt.

[0060] In some embodiments of the present disclosure, the PPO salt solution produced by mixing in the continuous reactor is preferably continuously fed to the enzyme-catalyzed conversion system. The continuous feeding time depends on the mixing time of the continuous reactor, and the continuous feeding is performed for a duration of 1 h to 24 h, for example, may be 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, 11 h, 12 h, 15 h, 18 h, 21 h, or 24 h.

[0061] In the present disclosure, the enzyme-catalyzed conversion system is a solution containing amino acid dehydrogenase, isopropanol dehydrogenase, isopropanol, and a coenzyme; the mass of the amino acid dehydrogenase and the isopropanol dehydrogenase is 1% to 15% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, for example, may be 1%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%. The coenzyme may specifically be NADP (nicotinamide adenine dinucleotide phosphate) or NAD (nicotinamide adenine dinucleotide), and its mass is 0.01 to 5% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, for example, may be 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5%; and the mass of the isopropanol is 33% to 100% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, for example, may be 33%, 35%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0062] After the PPO salt solution is continuously fed to the enzyme-catalyzed conversion system, the reaction is preferably carried out at 35°C to 45°C for 1 h to 24 h, more preferably at 35°C to 40°C for 5 h to 12 h, and the complete consumption of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid as detected by LC-MS is regarded as the endpoint of the reaction. During the above reaction, the PPO salt and ammonia form an imine intermediate, which generates glufosinate-P and by-product acetone under catalysis by isopropanol and the coenzyme.

[0063] After completion of the above reaction, post-treatment is preferably performed. The post- treatment means: filtering and concentrating the reaction product to obtain a glufosinate-P salt technical material, and crystallizing to obtain the glufosinate-P salt.

[0064] The glufosinate-P salt technical material has a mass concentration of 5% to 70%, for example, may be 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.

[0065] The solvent used for the above crystallization is any one or more selected from the group consisting of methanol, ethanol, isopropanol, n-butanol, n-hexane, acetonitrile, and toluene.

[0066] In the present disclosure, the finally produced glufosinate-P salt is any one or more selected from the group consisting of glufosinate-P ammonium salt, glufosinate-P sodium salt, glufosinate-P potassium salt, glufosinate-P monomethylamine salt, glufosinate-P dimethylamine salt, glufosinate-P isopropylamine salt, and glufosinate-P monoethanolamine salt.

[0067] To further refine the present disclosure, in some specific embodiments of the present disclosure, the desalting base added in step S1 is aqueous ammonia, the base added in step S2 is aqueous ammonia, and the glufosinate-P salt finally obtained is glufosinate-P ammonium salt;

[0068] or, the desalting base added in step S1 is sodium hydroxide, the base added in step S2 is sodium hydroxide, and the glufosinate-P salt finally obtained is glufosinate-P sodium salt;

[0069] or, the desalting base added in step S1 is potassium hydroxide, the base added in step S2 is potassium hydroxide, and the glufosinate-P salt finally obtained is glufosinate-P potassium salt;

[0070] or, the desalting base added in step S1 is isopropylamine, the base added in step S2 is isopropylamine, and the glufosinate-P salt finally obtained is glufosinate-P isopropylamine salt;

[0071] or, the desalting base added in step S1 is aqueous ammonia, the base added in step S2 is sodium hydroxide, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P ammonium salt and glufosinate-P sodium salt;

[0072] or, the base added in step S1 is concentrated ammonia water, the base added in step S2 is sodium hydroxide, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P ammonium salt and glufosinate-P sodium salt;

[0073] or, the desalting base added in step S1 is aqueous ammonia, the base added in step S2 is potassium hydroxide, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P ammonium salt and glufosinate-P potassium salt;

[0074] or, the desalting base added in step S1 is aqueous ammonia, the base added in step S2 is isopropylamine, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P ammonium salt and glufosinate-P isopropylamine salt;

[0075] or, the desalting base added in step S1 is sodium hydroxide, the base added in step S2 is aqueous ammonia, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P ammonium salt and glufosinate-P sodium salt;

[0076] or, the desalting base added in step S1 is sodium carbonate, the base added in step S2 is potassium carbonate, and the glufosinate-P salt finally obtained is a mixture of glufosinate-P potassium salt and glufosinate-P sodium salt.

[0077] Tests show that, according to the method provided by the present disclosure, the produced glufosinate-P salt has a purity of 98.5% or more, an oxalic acid content of less than 0.05%, and a yield of 97% or more.

[0078] It can be seen that the manufacture method provided by the present disclosure not only simplifies the synthesis steps, but also avoids the material decomposition problem, can effectively improve the conversion rate and successfully realize effective manufacture of different glufosinate salts, and has important theoretical and practical application value.

[0079] In order to further illustrate the present disclosure, detailed description is provided below through the following examples. The experimental raw materials used in the following examples of the present disclosure are all generally commercially available products. Unless otherwise specified, "%" involved in the following examples and comparative examples are mass percentage.

[0080] Example 1

[0081] 180.1 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, the pH was adjusted to 3.0 with 15% aqueous ammonia (desalting base), the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and 15% aqueous ammonia (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 59.6 g of glufosinate-P ammonium salt, with a purity of 98.8% (oxalic acid content: 0.01%) and a total yield of 99.1%. The chromatogram obtained after testing by the national standard GB / T 43172- 2023 method is shown in FIG. 1. It can be seen that the retention time of the produced glufosinate- P ammonium salt is consistent with that of the glufosinate-P reference standard, and the spectrum is clean without interference from impurity peaks.

[0082] Further, the present disclosure uses an oxalic acid quantitative test method to determine the oxalic acid content in the glufosinate-P ammonium salt produced in Example 1, specifically as follows:

[0083] The glufosinate-P ammonium salt produced in Example 1 was used as a test sample and dissolved in deionized water, and oxalic acid in the test sample was separated and determined using an anion analytical column, with quantification by the external standard method.

[0084] Water: deionized water having conductivity <semantics>≥18.2 MΩ⋅cm<annotation encoding="application / x-tex">\geq 18.2 \text{ M}\Omega \cdot \text{cm}< / annotation>< / semantics>;

[0085] Eluent: potassium hydroxide;

[0086] Anhydrous oxalic acid standard sample: 99.72%;

[0087] Chromatographic conditions of ion chromatograph:

[0088] Chromatographic column: 250 mm×4 mm (i.d.) IonPac AS11-HC anion analytical column;

[0089] Guard column: 50 mm×4 mm (i.d.) IonPac AG11-HC anion guard column;

[0090] Suppressor: ASRS-4mm;

[0091] Flow rate: 1.0 mL / min;

[0092] Injection volume: 25 μL;

[0093] Column temperature: 30°C±2°C;

[0094] Retention time: oxalic acid about 14.6 min;

[0095] Gradient elution conditions are shown in Table 1 below Table 1 [Image disponible dans le document PDF, Image available in the PDF document]

[0096] 1. Manufacture of reference standard: about 0.1 g of anhydrous oxalic acid standard sample was weighed into a 250 mL volumetric flask, diluted to the mark with water and shaken well, and 1 mL was transferred to a 100 mL volumetric flask, diluted to the mark with water and shaken well (about 4 mg / L);

[0097] 2. Manufacture of test sample: about 5.0 g of the test sample was weighed into a 100 mL volumetric flask, diluted to the mark with water and shaken well;

[0098] 3. Calculation method:

[0099] Content of the sample <semantics>%=Peakareaofthesample×WeightofstandardsamplePeakareaofstandardsample×Weightofsample×250<annotation encoding="application / x-tex">\% = \frac{Peak \ area \ of \ the \ sample \times Weight \ of \ standard \ sample}{Peak \ area \ of \ standard \ sample \times Weight \ of \ sample \times 250}< / annotation>< / semantics>.

[00100] The test results are shown in FIG. 2 and FIG. 3. The peak area of standard sample was 4.314, and the peak area of sample was 5.418. Calculation gave an oxalic acid content of 0.01%.

[00101] Examples 2 to 10

[00102] With reference to Example 1, different desalting bases and bases were investigated, and the resulting products, yields, and other conditions are shown in Table 2.

[00103] Compared with Example 1, the specific steps differed only in the types of desalting base and base used (when the desalting base was not ammonia, ammonia equimolar to 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid was supplemented). The sodium hydroxide and potassium hydroxide used in Examples 2 to 10 were both solids, and the remaining parameters and steps were kept consistent with Example 1. The yield was calculated as glufosinate-P acid in the feed solution after enzymatic conversion, and the oxalic acid content was the content in the final feed solution. Table 2 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[00104] Taking 1Example 3 as an example, the desalting base was sodium hydroxide and was not ammonia. Supplementing ammonia equimolar to 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid means: after sodium hydroxide was used to adjust the pH of the aqueous PPO solution to 3.0, a solid was precipitated, filtration was performed, and 34.1 g of 15% aqueous ammonia (0.3 mol of ammonia) was supplemented into the feed solution to obtain an aqueous PPO solution in which the molar amount of ammonia was not less than the molar amount of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid. The obtained aqueous PPO solution in which the molar amount of ammonia was not less than the molar amount of 4-(hydroxymethylphosphinyl)- 2-oxobutanoic acid and the base, namely sodium hydroxide, were continuously premixed until the pH was 7.5, and continuously added to the enzyme-catalyzed system for reaction. After completion, analysis and quantification were performed.

[00105] For the remaining examples, when the desalting base was not ammonia, ammonia equimolar to 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid was supplemented with reference to the procedure of 1Example 3 above.

[00106] Examples 11 to 17

[00107] With reference to Example 1, desalting by adjusting to different pH values using 15% aqueous ammonia was investigated, and the yields of the resulting products and oxalic acid removal conditions are shown in Table 3.

[00108] The specific steps in Examples 11 to 17 differed from Example 1 only in adjustment to different pH values, and the remaining parameters and steps were kept consistent with Example 1. The yield was calculated as glufosinate-P acid in the feed solution after enzymatic conversion. Table 3 [Image disponible dans le document PDF, Image available in the PDF document]

[00109] As can be seen from Table 2, when the desalting pH is not lower than 3.0, oxalic acid can be efficiently removed and the yield is greater than 99%. However, when the desalting pH is lower than 3.0, for example when the pH is 2.5, a large amount of oxalic acid remains and affects the enzymatic catalysis efficiency, and the yield is only 90.1%, indicating that the oxalic acid removal rate has a significant effect on the yield.

[00110] Examples 18 to 26

[00111] With reference to Example 1, adjustment to different pH values with a base, the yields of the resulting products were investigated, as shown in Table 4.

[00112] The specific steps in Examples 18 to 26 differed from Example 1 in that the base was used to adjust to different pH values, and the remaining parameters and steps were kept consistent with Example 1. The yield was calculated as glufosinate-P acid in the feed solution after enzymatic conversion. Table 4 [Image disponible dans le document PDF, Image available in the PDF document]

[00113] Wherein, 1Example 25 refers that: 15% aqueous ammonia (desalting base) was used to adjust the pH to 3.0, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution, the obtained aqueous PPO solution was adjusted to the corresponding pH in Table 3 using solid sodium hydroxide, and the remaining steps and parameters were kept consistent with Example 1;

[00114] 2Example 26 refers that: sodium hydroxide (desalting base) was used to adjust the pH to 3.0, and after desalting, a solid was precipitated, filtration was performed, and ammonia was supplemented to obtain an aqueous PPO solution in which the molar amount of ammonia was not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid; the obtained aqueous PPO solution was adjusted to the corresponding pH in Table 3 using solid sodium hydroxide, and the remaining steps and parameters were kept consistent with Example 1.

[00115] As can be seen from the data in Table 3, the enzymatic catalysis efficiency differs at different pH values. The results show that good catalytic effects are achieved when the pH is 6 to 9, with a yield greater than 92%; when the pH is 7 to 9, the yield is greater than 96%; when the pH is 7 to 8.5, the yield is greater than 97%; and when the pH is 7.8 to 8.5, the catalytic effect is best, with a yield greater than 99%. Excessively low or excessively high pH values both affect the yield and cause different degrees of decrease.

[00116] Example 27

[00117] 108.1 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 50%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 8.2%) was taken, ammonia gas (desalting base) was introduced to adjust the pH to 6.0, the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and ammonia gas (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 2 hours to a solution consisting of 54.0 g of isopropanol, 0.5 g of isopropanol dehydrogenase, 0.5 g of amino acid dehydrogenase, 0.1 g of NAD, and 100 g of water. The system was maintained at a temperature of 35°C. After completion of addition, the mixture was maintained at the temperature for 24 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from isopropanol to yield 58.9 g of glufosinate-P ammonium salt, with a purity of 98.2% (oxalic acid content: 0.01%) and a total yield of 97.3%.

[00118] Example 28

[00119] 1080.6 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 5%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 0.1%) was taken, monomethylamine (desalting base) was introduced to adjust the pH to 3.0, the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and monomethylamine (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 12 hours to a solution consisting of 21.6 g of isopropanol, 8.1 g of isopropanol dehydrogenase, 8.1 g of amino acid dehydrogenase, 2.7 g of NAD, and 100 g of water. The system was maintained at a temperature of 45°C. After completion of addition, the mixture was maintained at a temperature for 1 hour. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC- MS. The mixture was concentrated, filtered to remove proteins, and crystallized from acetonitrile to yield 63.8 g of glufosinate-P monomethylamine salt, with a purity of 98.3% (oxalic acid content: 0.01%) and a total yield of 98.5%.

[00120] Example 29

[00121] 180.1 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, dimethylamine (desalting base) was introduced to adjust the pH to 3.0, the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and dimethylamine (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 12 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 67.7 g of glufosinate-P dimethylamine salt, with a purity of 98.5% (oxalic acid content: 0.01%) and a total yield of 98.3%.

[00122] Example 30

[00123] 180.1 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, monoethanolamine (desalting base) was introduced to adjust the pH to 3.0, the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and monoethanolamine (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC- MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 72.4 g of glufosinate-P monoethanolamine salt, with a purity of 98.5% (oxalic acid content: 0.01%) and a total yield of 98.1%.

[00124] Example 31

[00125] 180.1 g of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4-(hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, 15% sodium carbonate (desalting base) was added to adjust the pH to 3.0, the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and 50% potassium carbonate (base) were continuously premixed through a tubular reactor at 2°C to 10°C until the pH was 7.5, and was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 62.6 g of a mixture of glufosinate-P sodium salt and glufosinate-P potassium salt, with a glufosinate-P acid content of 85.3% (oxalic acid content: 0.01%) and a total yield of 98.3%.

[00126] Comparative Example 1 - Aqueous PPO solution without oxalic acid removal

[00127] With reference to Example 1, 180.1 g of an aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4- (hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, the pH was adjusted to 7.5 with 15% aqueous ammonia, the temperature was controlled at 2°C to 10°C during the process, filtration for salt removal was not performed, and the mixture was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 50.2 g of glufosinate-P ammonium salt, with a purity of 98.1% (oxalic acid content: 0.50%) and a total yield of 82.8%.

[00128] Comparative Example 2 – Using a batch reaction

[00129] With reference to Example 1, 180.1 g of an aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4- (hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, the pH was adjusted to 3.0 with 15% aqueous ammonia (desalting base), the temperature was controlled at 2°C to 10°C during the process, a solid was precipitated, and filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution and 15% aqueous ammonia (base) were added to a glass flask and mixed at 2°C to 10°C until the pH was 7.5, and then added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC-MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 52.3 g of glufosinate-P ammonium salt, with a purity of 98.7% (oxalic acid content: 0.02%) and a total yield of 86.8%.

[00130] Comparative Example 3 - The temperature uncontrolled during the pH adjustment process

[00131] With reference to Example 1, 180.1 g of an aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid (4- (hydroxymethylphosphinyl)-2-oxobutanoic acid content: 30%, 4-(hydroxymethylphosphinyl)-2- oxobutanoic acid: 0.3 mol, oxalic acid content: 4.9%) was taken, the pH was adjusted to 3.0 with 15% aqueous ammonia (desalting base), the temperature was not controlled during the process, and the highest temperature reached 52°C. After the mixture was cooled to room temperature, filtration was performed to obtain a desalted aqueous PPO solution. The obtained aqueous PPO solution was adjusted to pH 7.5 with 15% aqueous ammonia without temperature control during the process, and was added continuously for 2 hours to a solution consisting of 21.6 g of isopropanol, 5.0 g of isopropanol dehydrogenase, 5.0 g of amino acid dehydrogenase, 0.3 g of NAD, and 100 g of water. The system was maintained at a temperature of 40°C. After completion of addition, the mixture was maintained at the temperature for 6 hours. Reaction was carried out until complete consumption of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid as detected by LC- MS. The mixture was concentrated, filtered to remove proteins, and crystallized from methanol to yield 49.3 g of glufosinate-P ammonium salt, with a purity of 97.5% (oxalic acid content: 0.02%) and a total yield of 80.9%.

[00132] As can be seen from the comparison among Comparative Example 1, Comparative Example 2, and Comparative Example 3, the content of oxalic acid impurities in the aqueous PPO solution affects the enzymatic catalysis effect of the reaction, which in turn leads to a decrease in yield. In addition, when a batch reaction is used, because the concentration of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid is relatively high during the early stage of the catalysis process and it cannot be converted into glufosinate-P in time, selectivity is reduced and the yield decreases. Meanwhile, during the pH adjustment process of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid, if the temperature is not controlled, temperature rise due to neutralization heat release causes partial decomposition of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid, thereby leading to a decrease in yield.

[00133] Therefore, by designing the process of temperature-controlled pH adjustment and desalting-coupled continuous reaction described above, the present disclosure effectively eliminates the enzymatic catalysis inhibition effect of oxalic acid impurities, and avoids selectivity and yield losses caused by local high concentration and thermal decomposition of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid. At the same time, based on a differentiated base neutralization strategy, different salt forms of glufosinate-P are directionally synthesized, thereby greatly increasing product yield while enriching the system of methods for producing glufosinate- P salt-form products.

[00134] The above description of the disclosed examples enables those skilled in the art to implement or use the present disclosure. Various modifications to these examples will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other examples without departing from the spirit or scope of the present disclosure. Therefore, the present disclosure is not to be limited to the examples shown herein, but is to be accorded the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for producing a glufosinate-P salt, comprising the following steps: S1: adjusting the pH of an aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid to 3 to 6 using a desalting base, precipitating a solid, and filtering to obtain an aqueous PPO solution; wherein the desalting base comprises ammonia, and in the obtained aqueous PPO solution, the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)- 2-oxobutanoic acid; or the desalting base does not comprise ammonia, and after filtration, ammonia is separately added to the aqueous PPO solution to control the molar amount of ammonia in the aqueous PPO solution to be not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid; S2: adjusting the pH of the aqueous PPO solution in which the molar amount of ammonia is not less than the molar amount of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid to 6 to 9 using a base to obtain a PPO salt solution; S3: continuously feeding the PPO salt solution to an enzyme-catalyzed conversion system, performing temperature-maintained reaction and post-treatment to obtain the glufosinate-P salt.

2. The method according to claim 1, wherein in the aqueous solution of 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the 4- (hydroxymethylphosphinyl)-2-oxobutanoic acid has a mass content of 5 wt% to 80 wt%; in the aqueous solution of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid containing oxalic acid, the oxalic acid has a mass content of 0.1 wt% to 10 wt%.

3. The method according to claim 1 or 2, wherein the desalting base or the base is independently any one or more selected from the group consisting of ammonia gas, aqueous ammonia, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, monomethylamine, dimethylamine, isopropylamine, and monoethanolamine; the desalting base or the base is independently introduced in the form of a solid or an aqueous base solution, and the aqueous base solution has a mass concentration of 5% to 99.9%.

4. The method according to any one of claims 1 to 3, wherein in step S1, adjusting pH using the desalting base is performed at a temperature of 0°C to 35°C.

5. The method according to any one of claims 1 to 3, wherein step S2 is performed in a continuous reactor; in the continuous reactor, the aqueous PPO solution and the base are mixed, and the mixing is performed at a temperature of 0°C to 35°C.

6. The method according to any one of claims 1 to 5, wherein the enzyme-catalyzed conversion system is a solution containing amino acid dehydrogenase, isopropanol dehydrogenase, isopropanol, and a coenzyme; the mass of the amino acid dehydrogenase or the isopropanol dehydrogenase is 1% to 15% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, the mass of the coenzyme is 0.01% to 5% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid, and the mass of the isopropanol is 33% to 100% of the mass of 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid.

7. The method according to any one of claims 1 to 6, wherein the continuous feeding is performed for a duration of 1 h to 24 h, and the temperature-maintained reaction is performed at a temperature of 35°C to 45°C.

8. The method according to any one of claims 1 to 7, wherein the post-treatment comprises: filtering and concentrating to obtain a glufosinate-P salt technical material, and crystallizing to obtain a glufosinate-P salt.

9. The method according to claim 8, wherein the crystallizing is performed using a solvent selected from the group consisting of methanol, ethanol, isopropanol, n-butanol, n-hexane, acetonitrile, toluene and mixtures thereof; the glufosinate-P salt is one or more selected from the group consisting of glufosinate-P ammonium salt, glufosinate-P sodium salt, glufosinate-P potassium salt, glufosinate-P monomethylamine salt, glufosinate-P dimethylamine salt, glufosinate-P isopropylamine salt, and glufosinate-P monoethanolamine salt.

10. The method according to any one of claims 1 to 9, wherein the glufosinate-P salt has a purity of 98.5% or more, an oxalic acid content of less than 0.05%, and a yield of 97% or more.