A method for preparing glufosinate-ammonium

Abstract

The application provides a preparation method of glufosinate-P, comprising the following steps: a) reacting L-homoserine with hydrochloric acid to obtain L-homoserine lactone hydrochloride; b) reacting the L-homoserine lactone hydrochloride with methanol and thionyl chloride to obtain a reaction solution containing a compound shown in formula (II); c) performing a neutralization reaction on the reaction solution containing the compound shown in formula (II) to obtain a reaction solution containing a compound shown in formula (III); d) reacting the reaction solution containing the compound shown in formula (III) with dimethyl methylphosphonate to obtain a glufosinate-P precursor shown in formula (IV); and e) sequentially performing hydrolysis and neutralization on the glufosinate-P precursor to obtain glufosinate-P. The method provided by the application uses L-homoserine as a starting material, does not need an amino protection step, the purity of an intermediate product is greater than or equal to 97%, the total yield of glufosinate-P is greater than or equal to 83%, the process is mild, environmentally friendly and economical, and is suitable for industrial production.

Description

Technical Field

[0001] This application relates to the field of pesticide chemical synthesis technology, and in particular to a method for preparing glufosinate. Background Technology

[0002] L-glufosinate (L-type glufosinate) is a highly effective, low-toxicity, non-selective herbicide with twice the herbicidal activity of racemic DL-type glufosinate. Its chemical name is 4-[hydroxy(methyl)phosphono]-L-homoalanine (CAS No.: 35597-44-5), and its molecular formula is C5H. 12 NO4P is the core variety for controlling glyphosate-resistant weeds.

[0003] The synthetic route using L-homoserine as a starting material has become the most cost-effective approach because the starting material contains a natural chiral center (ee value ≥ 98%) and does not require the construction of an additional chiral structure. For example, Chinese patent application CN119798315A discloses a method for preparing L-glufosinate, which uses an L-homoserine derivative as a starting material and prepares an intermediate in a one-pot process catalyzed by an iridium-containing Lewis base catalyst, followed by rearrangement and hydrolysis to obtain glufosinate. This method has milder reaction conditions than traditional processes and offers improved yield and ee value. However, this method requires the use of an expensive iridium-containing Lewis base catalyst, resulting in higher preparation costs.

[0004] Therefore, it is urgent to develop a low-cost, simplified, chiral, and stable method for preparing L-glufosinate with high yield and high ee value. Summary of the Invention

[0005] In view of this, this application provides a method for preparing glufosinate-ammonium. The method provided by this application is simple, does not require intermediate separation and purification, and can effectively improve the yield and purity.

[0006] This application provides a method for preparing glufosinate-ammonium, comprising the following steps: a) L-homoserine reacts with hydrochloric acid, and the resulting reaction solution is concentrated under reduced pressure and filtered to obtain the first solid and the first filtrate; The first solid is washed with water to obtain a second solid and washing water. The washing water and the first filtrate were combined and concentrated under reduced pressure, and then filtered to obtain the third solid and the second filtrate. The second and third solids were dried to obtain L-homoserine lactone hydrochloride. b) Reaction of L-homoserine lactone hydrochloride with methanol and thionyl chloride yields a reaction solution containing the compound shown in formula (II); c) Neutralize the reaction solution containing the compound shown in formula (II) to obtain the reaction solution containing the compound shown in formula (III); d) The reaction solution containing the compound shown in formula (III) is reacted with dimethyl methylphosphonate to obtain the glufosinate precursor shown in formula (IV); e) The glufosinate precursor is sequentially hydrolyzed and neutralized to obtain glufosinate; (II); (III); (IV).

[0007] In some specific implementations, step a) further includes: The third solid was washed with water to obtain the fourth solid and the second wash water. The second wash water and the second filtrate were combined and concentrated under reduced pressure, and then filtered to obtain the fifth solid and the third filtrate. The second, fourth, and fifth solids were dried to obtain L-homoserine lactone hydrochloride.

[0008] In some specific implementations, step a) further includes: The second filtrate was reacted with L-homoserine and hydrochloric acid.

[0009] In some specific implementations, in step a), the concentration of hydrochloric acid is 18wt%~36wt%; The molar ratio of L-homoserine to hydrochloric acid is 1:1.8~2.3; The reaction temperature is 60℃~100℃, and the time is 6h~12h; The drying time is 6h to 12h.

[0010] In some specific implementations, step b) specifically includes: b1) Mix L-homoserine lactone hydrochloride with methanol to obtain a mixture; b2) The mixture is reacted with thionyl chloride, the resulting reaction solution is concentrated under reduced pressure, and a solvent is added to the resulting solid to obtain a reaction solution containing the compound shown in formula (II).

[0011] In some specific implementations, in step b), the mass concentration of the mixture is 20% to 30%. The temperature at which the mixture is mixed with thionyl chloride is 0°C to 10°C. The molar ratio of L-homoserine lactone hydrochloride to thionyl chloride is 1:2.5~4.0; The reaction temperature is 35℃~45℃, and the time is 7h~12h; The solvent is one or more of chlorobenzene, toluene, or xylene.

[0012] In some specific implementations, step c) specifically includes: Ammonia gas was introduced into the reaction solution containing the compound shown in formula (II), the pH value was adjusted to 7.0~7.5, the reaction was stirred, the reaction solution was filtered and then distilled under reduced pressure to obtain the reaction solution containing the compound shown in formula (III).

[0013] In some specific implementations, in step c), the molar ratio of ammonia to the compound shown in formula (II) is 1.2 to 1.4:1; The stirring reaction time is 30 min to 60 min; The vacuum distillation temperature is 40℃~50℃, and the vacuum degree is -0.09MPa~-0.095MPa.

[0014] In some specific implementations, in step d), the molar ratio of the compound containing formula (III) to dimethyl methyl phosphate is 1:1.05~1.5; The reaction temperature is 110℃~140℃, and the time is 4h~6h; Step d) further includes: condensing the chloromethane gas produced by the reaction sequentially through a primary condenser at -10℃ to -5℃ and a secondary condenser at -20℃ to -15℃, and then dehydrating it through a 4A molecular sieve drying tower.

[0015] In some specific implementations, step e) specifically includes: The glufosinate precursor was mixed with hydrochloric acid and hydrolyzed. After hydrolysis, the reaction solution was cooled, ammonia gas was introduced for neutralization, crystallized, filtered, and the filter cake was vacuum dried to obtain glufosinate-ammonium. The concentration of the hydrochloric acid is 20wt%~30wt%; The molar ratio of the glufosinate precursor to hydrochloric acid is 1:2.5~3; The hydrolysis temperature is 90℃~100℃, and the time is 6h~8h; The cooling temperature is 25℃~35℃; The neutralization process involves setting the pH value to 5.0-5.5 and taking 1-2 hours. The crystallization temperature is 0℃~5℃, and the time is 10h~14h; The vacuum drying temperature is 60℃~70℃, the vacuum degree is -0.09MPa~-0.095MPa, and the time is 3h~4h.

[0016] This application uses L-homoserine as a starting material to prepare glufosinate via a four-step core process: lactone formation, methyl esterification, Arbuzov reaction, and hydrolysis crystallization. This process eliminates the need for amino protection steps and expensive catalysts. Key steps employ an in-situ reaction linkage design, resulting in intermediate product purity ≥97%. No additional intermediate separation and purification steps are required, simplifying the process by more than 30% compared to existing technologies. Furthermore, the reaction conditions for each step are mild (temperature 35℃~130℃, primarily at atmospheric pressure), making them easy to control and safe. Simultaneously, this application employs multiple vacuum concentrations and water-washed filter cakes to ensure L-homoserine lactone hydrochloride purity ≥98%, laying the foundation for maintaining chirality in subsequent steps. Subsequent hydrolysis and neutralization steps effectively avoid racemization of the chiral center, eliminating the risk of additional purity fluctuations in the finished product. The use of solvents such as chlorobenzene ensures the selectivity of the Arbuzov reaction, resulting in glufosinate precursor purity ≥97%, and product quality stability superior to existing processes. Experimental results show that the final product yield of the preparation method provided in this application is ≥70%, with a purity ≥96%, significantly improving overall production efficiency. Furthermore, this application demonstrates that reusing the mother liquor can further improve the overall product yield and purity, with the overall product yield reaching over 83% and the purity reaching over 97%. Attached Figure Description

[0017] Figure 1 This is a liquid chromatogram of the glufosinate-ammonium product in Example 1 of this application; Figure 2 This is a liquid chromatogram of the glufosinate-ammonium product in Example 2 of this application. Detailed Implementation

[0018] It should be understood that the expression “one or more of…” individually includes each of the objects described after the expression, as well as various different combinations of two or more of the described objects, unless otherwise understood from the context and usage. The expression “and / or” combined with three or more described objects should be understood to have the same meaning, unless otherwise understood from the context.

[0019] The terms “including,” “having,” or “containing,” including the use of their grammatical synonyms, should generally be understood as open-ended and non-restrictive, for example, not excluding other unstated elements or steps, unless otherwise specifically stated or understood from the context.

[0020] It should be understood that the order of steps or the sequence of actions is not important as long as this application remains operational. Furthermore, two or more steps or actions can be performed simultaneously.

[0021] The use of any and all instances or exemplary language such as “e.g.” or “including” herein is merely intended to better illustrate the application and does not constitute a limitation on the scope of the application unless the claims are made. No language in this specification should be construed as indicating that any unclaimed element is essential to the practice of this application.

[0022] Furthermore, the numerical ranges and parameters used to define this application are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible. However, any numerical value inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise explicitly stated, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately." Here, "approximately" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specific value or range.

[0023] This application provides a method for preparing glufosinate-ammonium, comprising the following steps: a) L-homoserine reacts with hydrochloric acid, and the resulting reaction solution is concentrated under reduced pressure and filtered to obtain the first solid and the first filtrate; The first solid is washed with water to obtain a second solid and washing water. The washing water and the first filtrate were combined and concentrated under reduced pressure, and then filtered to obtain the third solid and the second filtrate. The second and third solids were dried to obtain L-homoserine lactone hydrochloride. b) Reaction of L-homoserine lactone hydrochloride with methanol and thionyl chloride yields a reaction solution containing the compound shown in formula (II); c) Neutralize the reaction solution containing the compound shown in formula (II) to obtain the reaction solution containing the compound shown in formula (III); d) The reaction solution containing the compound shown in formula (III) is reacted with dimethyl methylphosphonate to obtain the glufosinate precursor shown in formula (IV); e) The glufosinate precursor is sequentially hydrolyzed and neutralized to obtain glufosinate; (II); (III); (IV).

[0024] This application uses L-homoserine as the starting material to prepare glufosinate via a four-step core process: lactoneation, methylation, Arbuzov reaction, and hydrolysis crystallization. The reaction route is as follows:

[0025] This application uses L-homoserine as a starting material, which is mixed with hydrochloric acid and reacted to obtain L-homoserine lactone hydrochloride as shown in formula (I): (I).

[0026] Specifically, this application involves mixing L-homoserine and hydrochloric acid and reacting them under stirring. In some specific implementations, the concentration of the hydrochloric acid is 18wt%~36wt%, preferably 20wt%~36wt%. In some specific implementations, the molar ratio of L-homoserine to hydrochloric acid is 1:1.8~2.3, preferably 1:1.9~2.1. In some specific implementations, the reaction temperature is 60℃~100℃, preferably 70℃~90℃, and the reaction time is 6h~12h, preferably 8h~10h.

[0027] After the reaction is complete, the resulting reaction solution is concentrated under reduced pressure and filtered to obtain a first solid and a first filtrate. The first solid is then washed with water to obtain a second solid and washing water. The washing water and the first filtrate are combined and concentrated under reduced pressure, then filtered to obtain a third solid and a second filtrate. The second and third solids are dried to obtain L-homoserine lactone hydrochloride. This application uses a method of multiple reduced pressure concentrations and water washing of the filter cake for post-processing L-homoserine lactone hydrochloride, which not only ensures the purity of L-homoserine lactone hydrochloride but also its yield. In some specific implementations, the vacuum degree of the reduced pressure concentration is -0.090 MPa to -0.100 MPa, preferably -0.095 MPa. In some specific implementations, when washing the first solid with water, the mass ratio of water to the first solid is 1:2 to 4, preferably 1:3. In some specific implementations, the temperature of the water is 20℃ to 30℃, preferably 25℃.

[0028] This application employs multiple vacuum concentrations to purify and recover L-homoserine lactone hydrochloride. In some specific implementations, this can be done two or three times. When using two vacuum concentrations, the specific steps include: The obtained reaction solution was concentrated under reduced pressure and filtered to obtain a first solid and a first filtrate. The first solid was then washed with water to obtain a second solid and washing water. The washing water and the first filtrate were then combined and concentrated under reduced pressure, filtered to obtain a third solid and a second filtrate. The second solid and the third solid were dried to obtain L-homoserine lactone hydrochloride. When using triple vacuum concentration, the specific steps include: The obtained reaction solution was concentrated under reduced pressure and filtered to obtain a first solid and a first filtrate. The first solid was then washed with water to obtain a second solid and washing water. The washing water and the first filtrate were then combined and concentrated under reduced pressure, and filtered to obtain a third solid and a second filtrate. The third solid was then washed with water to obtain a fourth solid and a second washing water. The second washing water and the second filtrate were then combined and concentrated under reduced pressure, and filtered to obtain a fifth solid and a third filtrate. The second solid, the fourth solid, and the fifth solid were dried to obtain L-homoserine lactone hydrochloride.

[0029] The process parameters for vacuum concentration, filtration, and washing with water in the above steps can be used interchangeably, and this application does not impose any special restrictions on them.

[0030] After obtaining the filter cake or washed filter cake, it is vacuum dried for use in the next reaction step. In some specific implementations, the drying temperature is 60℃~100℃, preferably 70℃~90℃, and the drying time is 6h~12h, preferably 8h~10h. In some specific implementations, after drying, the water content of the L-homoserine lactone hydrochloride is less than 0.5%.

[0031] To further improve the yield of L-homoserine lactone hydrochloride, this application preferably returns the second and / or third filtrate to the reaction of L-homoserine and hydrochloric acid for recycling.

[0032] After obtaining L-homoserine lactone hydrochloride, it is reacted with methanol and thionyl chloride to give a reaction solution containing the compound shown in formula (II). Specifically, it includes the following: b1) Mix L-homoserine lactone hydrochloride with methanol to obtain a mixture; b2) The mixture is reacted with thionyl chloride, the resulting reaction solution is concentrated under reduced pressure, and a solvent is added to the resulting solid to obtain a reaction solution containing the compound shown in formula (II).

[0033] This application first dissolves L-homoserine lactone hydrochloride in methanol to obtain a mixture. In some specific implementations, the mass concentration of the mixture is 20% to 30%, preferably 22% to 28%.

[0034] After obtaining the mixture, it is mixed with thionyl chloride. Specifically, this application first cools the mixture to 0℃~10℃, preferably 2℃~8℃, adds thionyl chloride dropwise, and then heats up to react. In some specific implementations, the molar ratio of L-homoserine lactone hydrochloride to thionyl chloride is 1:2.0~4.0, preferably 2.1~2.5. In some specific implementations, the reaction temperature is 35℃~45℃, preferably 37℃~42℃, and the time is 7h~12h, preferably 8h~10h. After the reaction is complete, the obtained reaction solution is concentrated under reduced pressure, and a solvent is added to the obtained solid to obtain a reaction solution containing the compound shown in formula (II). In some specific implementations, the temperature of the reduced pressure concentration is 25℃~35℃, and the vacuum degree is -0.090MPa~-0.095MPa. In some specific implementations, the solvent includes, but is not limited to, chlorobenzene, toluene, xylene, etc., preferably chlorobenzene. Using chlorobenzene as a solvent ensures the selectivity of the Arbuzov reaction, resulting in a purity of ≥97% for the glufosinate precursor. In some specific implementations, the mass ratio of the solvent to the compound shown in formula (II) is 2~5:1, preferably 2.5~4:1.

[0035] After obtaining the reaction solution containing the compound shown in formula (II), it is subjected to a neutralization reaction, specifically including the following steps:

[0036] Ammonia gas was introduced into the reaction solution containing the compound shown in formula (II), the pH value was adjusted to 7.0~7.5, the reaction was stirred, the reaction solution was filtered and then distilled under reduced pressure to obtain the reaction solution containing the compound shown in formula (III).

[0037] In some specific implementations, ammonia gas is introduced into the reaction solution at room temperature, and the ammonia introduction is stopped when the pH value reaches 7.0-7.5. In some specific implementations, the molar ratio of ammonia gas to the compound shown in formula (II) is 1.2-1.4:1, preferably 1.25-1.35:1. In some specific implementations, the stirring reaction time is 30-60 min, preferably 35-55 min. After the reaction is complete, the reaction solution is filtered, and the filtrate is subjected to vacuum distillation to remove part of the solvent, obtaining a reaction solution containing the compound shown in formula (III). In some specific implementations, the vacuum distillation temperature is 40℃-50℃, and the vacuum degree is -0.09MPa to -0.095MPa. In some specific implementations, the removal of part of the solvent involves removing approximately one-quarter to one-half of the solvent.

[0038] After obtaining the reaction solution containing the compound shown in formula (III), it is subjected to an Arbuzov reaction with dimethyl methylphosphonate to obtain the glufosinate precursor shown in formula (IV). In some specific implementations, the molar ratio of the compound shown in formula (III) to dimethyl methylphosphonate is 1:1.05 to 1.5, preferably 1:1.05 to 1.1. In some specific implementations, the reaction temperature is 110°C to 140°C, preferably 120°C to 130°C, and the reaction time is 4h to 6h, preferably 4.5h to 5.5h.

[0039] The Arbuzov reaction yields the glufosinate precursor shown in formula (IV) along with chloromethane gas. Preferably, the chloromethane gas is treated as follows: Chloromethane gas is condensed sequentially through a primary condenser at -10℃ to -5℃ and a secondary condenser at -20℃ to -15℃, and then dehydrated through a 4A molecular sieve drying tower.

[0040] This application adopts a combined recovery process of "first-stage condensation (-10℃~-5℃) + second-stage condensation (-20℃~-15℃) + 4A molecular sieve drying", with a chloromethane recovery rate of ≥99%. This process avoids resource waste and reduces raw material loss costs, while also eliminating the need for investment and maintenance of special equipment for the treatment of chlorine-containing waste gas, reducing emissions of waste gas, wastewater, and solid waste, and meeting the requirements of green chemical production.

[0041] After obtaining the glufosinate precursor shown in formula (IV), it is sequentially hydrolyzed and neutralized to obtain glufosinate. Specifically, it includes the following steps: The glufosinate precursor was mixed with hydrochloric acid and hydrolyzed. After hydrolysis, the reaction solution was cooled, neutralized by ammonia gas, crystallized, filtered, and the filter cake was vacuum dried to obtain glufosinate.

[0042] This application involves hydrolyzing the glufosinate precursor with hydrochloric acid. In some specific implementations, the concentration of the hydrochloric acid is 20wt%~30wt%, preferably 22wt%~28wt%. In some specific implementations, the molar ratio of the glufosinate precursor to hydrochloric acid is 1:2.5~3, preferably 1:2.6~2.8. In some specific implementations, the hydrolysis temperature is 90℃~100℃, preferably 92℃~98℃, and the time is 6h~8h, preferably 6.5h~7.5h.

[0043] After hydrolysis, the resulting reaction solution is cooled and then neutralized by introducing ammonia gas. In some specific implementations, the cooling temperature is 25℃~35℃, preferably 27℃~32℃. In some specific implementations, ammonia gas is introduced to adjust the pH value to 5.0~5.5, i.e., the neutralized pH value is 5.0~5.5. The reaction is carried out under stirring for 1h~2h, preferably 1.2h~1.8h.

[0044] After neutralization, the reaction solution is cooled for crystallization. In some specific implementations, the crystallization temperature is 0℃~5℃, and the time is 10h~14h, preferably 11h~13h. After crystallization, the solution is filtered to obtain wet glufosinate-ammonium. The wet product is then vacuum dried to obtain glufosinate-ammonium. In some specific implementations, the vacuum drying temperature is 60℃~70℃, the vacuum degree is -0.09MPa~-0.095MPa, and the time is 3h~4h.

[0045] This application uses L-homoserine as a starting material to prepare glufosinate via a four-step core process: lactone formation, methyl esterification, Arbuzov reaction, and hydrolysis crystallization. This process eliminates the need for amino protection steps and expensive catalysts. Key steps employ an in-situ reaction linkage design, resulting in intermediate product purity ≥97%. No additional intermediate separation and purification steps are required, simplifying the process by more than 30% compared to existing technologies. Furthermore, the reaction conditions in each step are mild (35℃~130℃, primarily at atmospheric pressure), making them easy to control and safe. Multiple vacuum concentrations and water washing of the filter cake ensure L-homoserine lactone hydrochloride purity ≥98%, laying the foundation for maintaining chirality. Subsequent hydrolysis and neutralization steps effectively avoid racemization of the chiral center, eliminating the risk of additional purity fluctuations in the finished product. The use of solvents such as chlorobenzene ensures Arbuzov reaction selectivity, resulting in glufosinate precursor purity ≥97%, and product quality stability superior to existing processes. Experimental results show that the final product yield of the preparation method provided in this application is ≥70%, with a purity ≥96%, significantly improving overall production efficiency. Furthermore, this application demonstrates that reusing the mother liquor can further improve the overall product yield and purity, with the overall product yield reaching over 83% and the purity reaching over 97%.

[0046] The technical solution of the present invention will be clearly and completely described below with reference to embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. The scope of protection of the present invention is not limited by the following embodiments.

[0047] In the following examples, unless otherwise specified, "%" refers to mass fraction.

[0048] The product chromatograms of this embodiment of the invention were obtained under the following conditions:

[0049] Detector: DAD ultraviolet detector; Wavelength: 254nm; Mobile phase: anhydrous copper sulfate aqueous solution (0.002 mol / L): acetonitrile = 95:5; Flow rate: 1.0 mL / min; Chromatographic column: SUMICHIRAL OA-5000L chiral column (5μm, 250 mm × 4.6 mm).

[0050] Example 1

[0051] Step 1: Add 85.1g of L-homoserine (0.7mol, purity 98%) and 112.5ml of 36% concentrated hydrochloric acid (1.47mol, 2.1eq) to a 1000ml four-necked flask. Stir at room temperature for 30min, then heat in an oil bath to 60℃ and stir for 6h. Stop the reaction. After the reaction is complete, concentrate under reduced pressure at -0.095MPa until a large amount of solid precipitates. Stop the concentration, filter, and wash the filter cake once with 40g of deionized water to obtain the primary crystallization product. Collect the filtrate and continue to concentrate under reduced pressure at -0.095MPa until a large amount of solid precipitates. Stop the concentration, filter, and wash the filter cake once with 10g of deionized water to obtain the secondary crystallization product. Place the primary and secondary crystallization products in an 80℃ forced-air drying oven for 6h to obtain 86.5g of L-homoserine lactone hydrochloride with a purity of 98% and a yield of 88%.

[0052] Step 2: Dissolve 86.5g of L-homoserine lactone hydrochloride obtained in Step 1 in 259.5g of methanol to prepare a 25% (w / w) solution. Cool the solution to 10℃ and slowly add 187g of thionyl chloride (dropping rate 1.2mL / min), controlling the system temperature to not exceed 10℃ during the addition. After the addition is complete, raise the temperature to 35℃ and stir for 10h. Take a sample and control the conversion rate of L-homoserine lactone hydrochloride to ≥99%, indicating that the reaction is complete. Concentrate under reduced pressure at -0.095MPa to remove methanol, add 259.5g of chlorobenzene (3 times the mass of L-homoserine lactone hydrochloride), and stir for 30min to obtain 372g of a solution containing the intermediate compound of formula (II).

[0053] Equation (II).

[0054] Step 3: At room temperature, slowly introduce ammonia gas into the solution of 372g of intermediate compound containing formula (II) obtained in step 2, monitor the pH of the system in real time, stop the ammonia introduction when the pH rises to 7.0, continue stirring for 30 min, filter to remove ammonium chloride precipitate; transfer the filtrate to a distillation flask, and distill under reduced pressure at 40℃ and vacuum degree -0.095MPa to remove about 82g of chlorobenzene, and obtain 221g of solution containing intermediate compound containing formula (III).

[0055] Formula (III).

[0056] Step 4: 221g of the solution containing the intermediate compound of formula (III) obtained in Step 3 and 79.67g of dimethyl methylphosphonate (0.642mol) were added to a 500ml four-necked flask. The mixture was heated to 110℃ in an oil bath and stirred for Arbuzov reaction for 5h. A sample was taken, and the conversion rate of the intermediate compound of formula (III) was ≥99%, indicating complete reaction. The chloromethane gas produced in the reaction was sequentially passed through a -10℃ primary condenser and a -20℃ secondary condenser. The condensate was dehydrated by a 4A molecular sieve drying tower to obtain 23g of recovered chloromethane with a purity of 99.2%. After the reaction, 119.4g of glufosinate precursor with a purity of 97.4% was obtained.

[0057] Step 5: Add 278 ml of 18% hydrochloric acid (1.668 mol) to the 119.4 g glufosinate precursor obtained in Step 4. Heat the mixture in an oil bath to 100 °C under normal pressure to remove the byproduct methanol. Hydrolyze and maintain the temperature for 6 h. Take a sample to control the conversion rate of glufosinate precursor to ≥99%, indicating that the reaction is complete. Cool the hydrolysate to 35 °C, slowly introduce ammonia to adjust the pH to 5.0, stir for 2 h, then cool to 0 °C and allow to stand for crystallization for 14 h. Filter to obtain wet glufosinate. Place the wet product under vacuum drying at 60 °C and a vacuum degree of -0.095 MPa for 4 h to obtain 109.3 g glufosinate product with a chemical content of 97.8% and an overall yield of 77.1% for the five-step reaction.

[0058] The reaction process is as follows:

[0059] The finished glufosinate product described in this embodiment was analyzed by liquid chromatography, and the results are shown in [reference needed]. Figure 1 , Figure 1 This is a liquid chromatogram of the glufosinate-ammonium product from Example 1 of this application. Figure 1 As can be seen, the finished product of glufosinate-ammonium prepared in this embodiment has a chemical content of 97.8%.

[0060] Example 2

[0061] Step 1: Add 85.1g L-homoserine (0.7mol, 98% purity), 112.5ml 36% concentrated hydrochloric acid (1.47mol, 2.1eq), and the secondary crystallization mother liquor from Step 1 in Example 1 to a 1000ml four-necked flask. Stir at room temperature for 30min, heat to 60℃ in an oil bath and stir for 6h, then stop the reaction. After the reaction was complete, the solution was concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, and the solution was filtered. The filter cake was washed once with 40 g of deionized water to obtain the primary crystallization product. The filtrate was collected and concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, and the solution was filtered. The filter cake was washed once with 10 g of deionized water to obtain the secondary crystallization product. The wet products of the primary and secondary crystallization products were placed in an 80℃ forced-air drying oven and dried for 6 h to obtain 93.2 g of L-homoserine lactone hydrochloride with a purity of 98.1% and a yield of 95%.

[0062] Step 2: Dissolve 93.2g of L-homoserine lactone hydrochloride obtained in Step 1 in 279.7g of methanol to prepare a 25% (w / w) solution. Cool the solution to 10℃ and slowly add 201.8g of thionyl chloride (dropping rate 1.2mL / min), controlling the system temperature to not exceed 10℃ during the addition. After the addition is complete, raise the temperature to 35℃ and stir for 10h. Take a sample and control the conversion rate of L-homoserine lactone hydrochloride to ≥99%, indicating that the reaction is complete. Concentrate under reduced pressure at -0.095MPa to remove methanol, add 279.7g of chlorobenzene (3 times the mass of L-homoserine lactone hydrochloride), and stir for 30min to obtain 401.4g of a solution containing the intermediate compound of formula (II).

[0063] Equation (II).

[0064] Step 3: At room temperature, slowly introduce ammonia gas into the solution of 401.4g of the intermediate compound containing the formula (II) structure obtained in Step 2, monitor the pH of the system in real time, stop the ammonia introduction when the pH rises to 7.0, continue stirring for 30 min, filter to remove ammonium chloride precipitate; transfer the filtrate to a distillation flask, and distill under reduced pressure at 40℃ and a vacuum degree of -0.095MPa to remove about 82g of chlorobenzene, and obtain 238.7g of the solution containing the intermediate compound containing the formula (III) structure.

[0065] Formula (III).

[0066] Step 4: The solution of 238.7g of the intermediate compound containing the formula (III) structure obtained in Step 3 and 85.91g of dimethyl methylphosphonate (0.692mol) were added to a 500ml four-necked flask. The mixture was heated to 110℃ in an oil bath and stirred for Arbuzov reaction for 5h. The conversion rate of the intermediate compound containing the formula (III) structure was ≥99% during the sampling, indicating that the reaction was complete. The chloromethane gas produced by the reaction was sequentially passed through a -10℃ primary condenser and a -20℃ secondary condenser. The condensate was dehydrated by a 4A molecular sieve drying tower to obtain 27.9g of recovered chloromethane with a purity of 99.3%. After the reaction, 128.3g of glufosinate precursor with a purity of 97.8% was obtained.

[0067] Step 5: Add 300 ml of 18% hydrochloric acid (1.8 mol) to 128.3 g of glufosinate precursor obtained in Step 4. Heat the mixture in an oil bath to 100 °C under normal pressure to remove the byproduct methanol. Hydrolyze and maintain the temperature for 6 h. Take a sample to control the conversion rate of glufosinate precursor to ≥99%, indicating that the reaction is complete. Cool the hydrolysate to 35 °C, slowly introduce ammonia to adjust the pH to 5.0, stir for 2 h, then cool to 0 °C and allow to stand for crystallization for 14 h. Filter to obtain wet glufosinate. Place the wet product under vacuum drying at 60 °C and a vacuum degree of -0.095 MPa for 4 h to obtain 118.1 g of finished glufosinate product with a chemical content of 97.6% and an overall yield of 83.2% for the five-step reaction.

[0068] The finished glufosinate product described in this embodiment was analyzed by liquid chromatography, and the results are shown in [reference needed]. Figure 2 , Figure 2 This is a liquid chromatogram of the glufosinate-ammonium product from Example 2 of this application. Figure 2 As can be seen, the finished product of glufosinate-ammonium prepared in this embodiment has a chemical content of 97.6%.

[0069] Example 3

[0070] Step 1: Add 85.1g L-homoserine (0.7mol, 98% purity), 112.5ml 36% concentrated hydrochloric acid (1.47mol, 2.1eq), and the secondary crystallization mother liquor from Step 1 in Example 2 to a 1000ml four-necked flask. Stir at room temperature for 30min, heat to 60℃ in an oil bath and stir for 6h, then stop the reaction. After the reaction was complete, the solution was concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, the solution was filtered, and the filter cake was washed once with 40 g of deionized water to obtain the primary crystallization product. The filtrate was collected and concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, the solution was filtered, and the filter cake was washed once with 10 g of deionized water to obtain the secondary crystallization product. The wet products of the primary and secondary crystallization products were placed in an 80℃ forced-air drying oven and dried for 6 h to obtain 95.7 g of L-homoserine lactone hydrochloride with a purity of 98.9% and a yield of 98.3%.

[0071] Step 2: Dissolve 95.7g of L-homoserine lactone hydrochloride obtained in Step 1 in 287.2g of methanol to prepare a 25% (w / w) solution. Cool the solution to 10℃ and slowly add 206.7g of thionyl chloride (dropping rate 1.2mL / min), controlling the system temperature to not exceed 10℃ during the addition. After the addition is complete, raise the temperature to 35℃ and stir for 10h. Take a sample and control the conversion rate of L-homoserine lactone hydrochloride to ≥99%, indicating that the reaction is complete. Concentrate under reduced pressure at -0.095MPa to remove methanol, add 287.1g of chlorobenzene (3 times the mass of L-homoserine lactone hydrochloride), and stir for 30min to obtain 415.3g of a solution containing the intermediate compound of formula (II).

[0072] Equation (II).

[0073] Step 3: At room temperature, slowly introduce ammonia gas into the solution of 415.3g of the intermediate compound containing the formula (II) structure obtained in Step 2, monitor the pH of the system in real time, stop the ammonia introduction when the pH rises to 7.0, continue stirring for 30 min, filter to remove ammonium chloride precipitate; transfer the filtrate to a distillation flask, and distill under reduced pressure at 40℃ and a vacuum degree of -0.095MPa to remove about 84.8g of chlorobenzene, and obtain 244.7g of the solution containing the intermediate compound containing the formula (III) structure.

[0074] Formula (III).

[0075] Step 4: The solution of 244.7g of the intermediate compound containing the formula (III) structure obtained in Step 3 and 88.9g of dimethyl methylphosphonate (0.716mol) were added to a 500ml four-necked flask. The mixture was heated to 110℃ in an oil bath and stirred for Arbuzov reaction for 5h. The conversion rate of the intermediate compound containing the formula (III) structure was ≥99% during the sampling, indicating that the reaction was complete. The chloromethane gas produced by the reaction was sequentially passed through a -10℃ primary condenser and a -20℃ secondary condenser. The condensate was dehydrated by a 4A molecular sieve drying tower to obtain 28.9g of recovered chloromethane with a purity of 99.2%. After the reaction, 132.8g of glufosinate precursor with a purity of 98.1% was obtained.

[0076] Step 5: Add 313 ml of 18% hydrochloric acid (1.88 mol) to 132.8 g of glufosinate precursor obtained in Step 4. Heat the mixture in an oil bath to 100 °C under normal pressure to remove the byproduct methanol. Hydrolyze and maintain the temperature for 6 h. Take a sample to control the conversion rate of glufosinate precursor to ≥99%, indicating that the reaction is complete. Cool the hydrolysate to 35 °C, slowly introduce ammonia to adjust the pH to 5.0, stir for 2 h, then cool to 0 °C and allow to stand for crystallization for 14 h. Filter to obtain wet glufosinate. Place the wet product under vacuum at 60 °C and a vacuum degree of -0.095 MPa for 4 h to obtain 122.98 g of finished glufosinate product with a chemical content of 97.7% and an overall yield of 86.4% for the five-step reaction.

[0077] Example 4

[0078] Step 1: Add 85.1g L-homoserine (0.7mol, 98% purity), 112.5ml 36% concentrated hydrochloric acid (1.47mol, 2.1eq), and the secondary crystallization mother liquor from Step 1 in Example 3 to a 1000ml four-necked flask. Stir at room temperature for 30min, heat to 60℃ in an oil bath and stir for 6h, then stop the reaction. After the reaction was complete, the solution was concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, the solution was filtered, and the filter cake was washed once with 40 g of deionized water to obtain the primary crystallization product. The filtrate was collected and concentrated under reduced pressure at -0.095 MPa until a large amount of solid precipitated. Concentration was stopped, the solution was filtered, and the filter cake was washed once with 10 g of deionized water to obtain the secondary crystallization product. The wet products of the primary and secondary crystallization products were placed in an 80℃ forced-air drying oven and dried for 6 h to obtain 96.57 g of L-homoserine lactone hydrochloride with a purity of 98.2% and a yield of 99.8%.

[0079] Step 2: Dissolve 96.57g of L-homoserine lactone hydrochloride obtained in Step 1 in 289.71g of methanol to prepare a 25% (w / w) solution. Cool the solution to 10℃ and slowly add 209.88g of thionyl chloride (dropping rate 1.2mL / min), controlling the system temperature to not exceed 10℃ during the addition. After the addition is complete, raise the temperature to 35℃ and stir for 10h. Take a sample and control the conversion rate of L-homoserine lactone hydrochloride to ≥99%, indicating that the reaction is complete. Concentrate under reduced pressure at -0.095MPa to remove methanol, add 289.71g of chlorobenzene (3 times the mass of L-homoserine lactone hydrochloride), and stir for 30min to obtain 421.64g of a solution containing the intermediate compound of formula (II).

[0080] Equation (II).

[0081] Step 3: At room temperature, slowly introduce ammonia gas into the solution of 421.64g of the intermediate compound containing the formula (II) structure obtained in Step 2, monitor the pH of the system in real time, stop the ammonia introduction when the pH rises to 7.0, continue stirring for 30 min, filter to remove ammonium chloride precipitate; transfer the filtrate to a distillation flask, and distill under reduced pressure at 40℃ and a vacuum degree of -0.095MPa to remove about 86.1g of chlorobenzene, and obtain 248.43g of the solution containing the intermediate compound containing the formula (III) structure.

[0082] Formula (III).

[0083] Step 4: The solution containing 248.43 g of the intermediate compound with structure (III) obtained in Step 3 and 90.2 g of dimethyl methylphosphonate (0.727 mol) were added to a 500 ml four-necked flask. The mixture was heated to 110 °C in an oil bath and stirred for an Arbuzov reaction for 5 h. A sample was taken, and the conversion rate of the intermediate compound containing structure (III) was ≥99%, indicating complete reaction. The chloromethane gas produced in the reaction was sequentially passed through a -10 °C primary condenser and a -20 °C secondary condenser. The condensate was dehydrated by a 4A molecular sieve drying tower to obtain 29.4 g of recovered chloromethane with a purity of 99.1%. After the reaction, 134.7 g of glufosinate precursor with a purity of 98% was obtained.

[0084] Step 5: Add 317 ml of 18% hydrochloric acid (1.907 mol) to 134.7 g of glufosinate precursor obtained in Step 4. Heat the mixture in an oil bath to 100 °C under normal pressure to remove the byproduct methanol. Hydrolyze and maintain the temperature for 6 h. Take a sample to control the conversion rate of glufosinate precursor to ≥99%, indicating that the reaction is complete. Cool the hydrolysate to 35 °C, slowly introduce ammonia to adjust the pH to 5.0, stir for 2 h, then cool to 0 °C and allow to stand for crystallization for 14 h. Filter to obtain wet glufosinate. Place the wet product under vacuum drying at 60 °C and a vacuum degree of -0.095 MPa for 4 h to obtain 125.78 g of finished glufosinate product with a chemical content of 97.3% and an overall yield of 88.3% for the five-step reaction.

[0085] The above description is merely a preferred embodiment of this application, but the scope of protection of this application is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in this application, based on the technical solution and inventive concept of this application, should be included within the scope of protection of this application.

Claims

1. A method for preparing glufosinate-ammonium, characterized in that, Includes the following steps: a) L-homoserine reacts with hydrochloric acid, and the resulting reaction solution is concentrated under reduced pressure and filtered to obtain the first solid and the first filtrate; The first solid is washed with water to obtain a second solid and washing water. The washing water and the first filtrate were combined and concentrated under reduced pressure, and then filtered to obtain the third solid and the second filtrate. The second and third solids were dried to obtain L-homoserine lactone hydrochloride. b) Reaction of L-homoserine lactone hydrochloride with methanol and thionyl chloride yields a reaction solution containing the compound shown in formula (II); c) Neutralize the reaction solution containing the compound shown in formula (II) to obtain the reaction solution containing the compound shown in formula (III); d) The reaction solution containing the compound shown in formula (III) is reacted with dimethyl methylphosphonate to obtain the glufosinate precursor shown in formula (IV); e) The glufosinate precursor is sequentially hydrolyzed and neutralized to obtain glufosinate; （Ⅱ）； （Ⅲ）； （Ⅳ）。 2. The preparation method according to claim 1, characterized in that, Step a) further includes: The third solid was washed with water to obtain the fourth solid and the second wash water. The second wash water and the second filtrate were combined and concentrated under reduced pressure, and then filtered to obtain the fifth solid and the third filtrate. The second, fourth, and fifth solids were dried to obtain L-homoserine lactone hydrochloride.

3. The preparation method according to claim 1, characterized in that, Step a) further includes: The second filtrate was reacted with L-homoserine and hydrochloric acid.

4. The preparation method according to any one of claims 1 to 3, characterized in that, In step a), the concentration of hydrochloric acid is 18wt%~36wt%; The molar ratio of L-homoserine to hydrochloric acid is 1:1.8~2.3; The reaction temperature is 60℃~100℃, and the time is 6h~12h; The drying time is 6h to 12h.

5. The preparation method according to claim 4, characterized in that, Step b) specifically includes: b1) Mix L-homoserine lactone hydrochloride with methanol to obtain a mixture; b2) The mixture is reacted with thionyl chloride, the resulting reaction solution is concentrated under reduced pressure, and a solvent is added to the resulting solid to obtain a reaction solution containing the compound shown in formula (II).

6. The preparation method according to claim 5, characterized in that, In step b), the mass concentration of the mixture is 20%~30%; The temperature at which the mixture is mixed with thionyl chloride is 0°C to 10°C. The molar ratio of L-homoserine lactone hydrochloride to thionyl chloride is 1:2.0~4.0; The reaction temperature is 35℃~45℃, and the time is 7h~12h; The solvent is one or more of chlorobenzene, toluene, or xylene.

7. The preparation method according to claim 4, characterized in that, Step c) specifically includes: Ammonia gas was introduced into the reaction solution containing the compound shown in formula (II), the pH value was adjusted to 7.0~7.5, the reaction was stirred, the reaction solution was filtered and then distilled under reduced pressure to obtain the reaction solution containing the compound shown in formula (III).

8. The preparation method according to claim 7, characterized in that, In step c), the molar ratio of ammonia to the compound shown in formula (II) is 1.2 to 1.4:1; The stirring reaction time is 30 min to 60 min; The vacuum distillation temperature is 40℃~50℃, and the vacuum degree is -0.09MPa~-0.095MPa.

9. The preparation method according to claim 4, characterized in that, In step d), the molar ratio of the compound containing formula (III) to dimethyl methyl phosphate is 1:1.05~1.5; The reaction temperature is 110℃~140℃, and the time is 4h~6h; Step d) further includes: condensing the chloromethane gas produced by the reaction sequentially through a primary condenser at -10℃ to -5℃ and a secondary condenser at -20℃ to -15℃, and then dehydrating it through a 4A molecular sieve drying tower.

10. The preparation method according to claim 4, characterized in that, Step e) specifically includes: The glufosinate precursor was mixed with hydrochloric acid and hydrolyzed. After hydrolysis, the reaction solution was cooled, ammonia gas was introduced for neutralization, crystallized, filtered, and the filter cake was vacuum dried to obtain glufosinate-ammonium. The concentration of the hydrochloric acid is 20wt%~30wt%; The molar ratio of the glufosinate precursor to hydrochloric acid is 1:2.5~3; The hydrolysis temperature is 90℃~100℃, and the time is 6h~8h; The cooling temperature is 25℃~35℃; The neutralization process involves setting the pH value to 5.0-5.5 and taking 1-2 hours. The crystallization temperature is 0℃~5℃, and the time is 10h~14h; The vacuum drying temperature is 60℃~70℃, the vacuum degree is -0.09MPa~-0.095MPa, and the time is 3h~4h.

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