Process for the production of l-phosphinothricin

Abstract

Compositions and methods for isolating L-glufosinate from a composition comprising L-glufosinate and glutamic acid are provided. The method includes converting the glutamic acid to pyroglutamic acid and then separating the L-glufosinate from the pyroglutamic acid and other components of the composition to yield substantially purified L-glufosinate. The composition comprising L-glufosinate and glutamic acid is subjected to an elevated temperature for a sufficient time to convert the glutamic acid to pyroglutamic acid and then the L-glufosinate is separated from the pyroglutamic acid and other components of the composition to yield substantially purified L-glufosinate. Alternatively, the glutamic acid can be converted to pyroglutamic acid by enzymatic conversion. The purified L-glufosinate is present in the final composition at a concentration of 90% or more of the total of L-glufosinate, glutamic acid, and pyroglutamic acid. In some embodiments, a crystallization step can be used to separate a portion of the glutamic acid from the L-glufosinate in the starting composition. Solid forms of L-glufosinate material, including crystalline L-glufosinate-ammonium, are also described.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 533,944, filed July 18, 2017, and U.S. Provisional Patent Application No. 62 / 653,736, filed April 6, 2018, which are incorporated herein by reference in their entirety.

[0003] field

[0004] This article describes a method for purifying L-glufosinate.

[0005] background

[0006] From a toxicological or environmental perspective, glufosinate is a non-selective foliar herbicide and is considered one of the safest herbicides. Currently, commercially available chemical synthesis methods for glufosinate produce racemic mixtures of L- and D-glufosinate (Duke et al. 2010 Toxins 2:1943-1962). However, L-glufosinate (also known as glufosinate or (S)-2-amino-4-(hydroxy(methyl)phosphono)butyric acid) is far more effective than D-glufosinate (Ruhland et al. (2002) Environ. Biosafety Res. 1:29-37).

[0007] Therefore, there is a need for a method that produces only or primarily the active form of L-glufosinate. Previously, there was no efficient method available for producing pure L-glufosinate or a mixture of D- and L-glufosinate rich in L-glufosinate.

[0008] Overview

[0009] Compositions and methods are provided for separating L-glufosinate from a composition comprising L-glufosinate and glutamate. The method involves converting glutamate to pyroglutamate, and then separating L-glufosinate from the pyroglutamate and other components of the composition to obtain substantially purified L-glufosinate. In one embodiment, the composition comprising L-glufosinate and glutamate is subjected to elevated temperatures for a sufficient time to convert glutamate to pyroglutamate, and then L-glufosinate is separated from the pyroglutamate and other components of the composition to obtain substantially purified L-glufosinate. In another embodiment, glutamate is converted to pyroglutamate by enzymatic conversion, and then pyroglutamate is removed from the composition by ion exchange to obtain a composition comprising substantially purified L-glufosinate. The volume of the composition can be reduced to obtain a concentrated solution of L-glufosinate, or the volume of the composition can be reduced to obtain a solid powder of L-glufosinate. In one embodiment, the purified L-glufosinate is present at a concentration of 70%, 80%, or 90% or higher of the total amount of L-glufosinate, glutamic acid, and pyroglutamic acid in the final composition. In some embodiments, a portion of the glutamic acid in the starting composition is separated from L-glufosinate by a crystallization step prior to the conversion of glutamic acid to pyroglutamic acid. A method for separating 2-oxoglutaric acid (also referred to herein as 2-oxoglutarate) from the composition after the removal of L-glufosinate is also provided herein. For example, 2-oxoglutaric acid can be removed by ion exchange to obtain a composition of substantially purified 2-oxoglutaric acid, which can then be conveniently converted to substantially purified succinic acid.

[0010] The method described herein produces a substantially purified composition of L-glufosinate. In a further embodiment, the method produces a substantially purified 2-oxoglutaric acid composition. Crystalline forms of the L-glufosinate material are also provided. Brief description of the attached diagram

[0012] Figure 1 Showing an XRPD pattern of form A of L-glufosinate ammonium collected using Cu-Kα rays.

[0013] Figure 2 The display shows the thermal data of L-glufosinate form A collected by thermogravimetric analysis (top trace) and differential scanning calorimetry (bottom trace).

[0014] Figure 3 Showing an XRPD pattern of L-gluphosphorus form B collected using Cu-Kα rays.

[0015] Figure 4The display shows the thermal data of L-glufosinate form B collected by thermogravimetric analysis (top trace) and differential scanning calorimetry (bottom trace).

[0016] Figure 5 Showing an XRPD pattern of L-glufosinate form C collected using Cu-Kα rays.

[0017] Figure 6 The display shows the thermal data of L-glufosinate form C collected by thermogravimetric analysis (top trace) and differential scanning calorimetry (bottom trace).

[0018] Figure 7 Showing an XRPD pattern of L-glufosinate form D collected using Cu-Kα rays.

[0019] Figure 8 The display shows the thermal data of L-glufosinate form D collected by thermogravimetric analysis (top trace) and differential scanning calorimetry (bottom trace).

[0020] Figure 9 The XRPD pattern of L-glufosinate hydrochloride form E collected using Cu-Kα rays is shown.

[0021] Detailed description

[0022] Compositions and methods are provided for producing substantially purified L-glufosinate (also known as glufosinate or (S)-2-amino-4-(hydroxy(methyl)phosphono)butyric acid) compositions. U.S. Patent Application No. 15 / 445,254 (“'254 application”), filed February 28, 2017, relates to compositions and methods for producing L-glufosinate, which are incorporated herein by reference. This method involves oxidatively deaminating D-glufosinate to PPO (2-oxo-4-(hydroxy(methyl)phosphono)butyric acid), followed by specific amination of the PPO to L-glufosinate using an amino group from one or more amine donors. By combining these two reactions, the proportion of L-glufosinate in a racemic glufosinate mixture can be significantly increased. Therefore, the method of the '254 application can use a racemic D- / L-glufosinate mixture as a starting mixture and convert the inactive D-form to the active L-form. The method of application '254 produces a composition comprising a mixture of L-glufosinate, PPO, and D-glufosinate, wherein L-glufosinate is the major compound in the mixture of L-glufosinate, PPO, and D-glufosinate. Glutamic acid (referring to L-glutamic acid, D-glutamic acid, or a combination thereof), also referred to as glutamic acid (referring to L-glutamic acid, D-glutamic acid, or a combination thereof), may be present in the composition when glutamic acid or L-glutamic acid is used as an amine donor for the amination of PPO to L-glufosinate.

[0023] The separation of L-glufosinate from 2-oxoglutaric acid, PPO, and glutamic acid in the post-reaction mixture typically requires multiple operations because these components have extremely similar chemical structures and properties. L-Glutamic acid presents the main challenge because it exists in high concentrations relative to L-glufosinate and is structurally similar to it.

[0024] I. Purification Methods

[0025] This document provides a method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamic acid. The method involves converting glutamic acid to pyroglutamic acid to facilitate the separation of L-glufosinate. Glutamic acid can be converted to pyroglutamic acid by subjecting the composition to elevated temperatures for a sufficient period of time to convert most of the glutamic acid to pyroglutamic acid (also referred to herein as pyroglutamic acid). See, for example, PCT 2010 / 013242, US2003 / 0018202, Corma et al. (2007) Chem. Rev. 107:2411-2502, Purwaha et al. (2014) Anal. Chem. 86(12):5633-5637, Dubourg et al. (1956) Bulletin de la Societe Chimique de France 1351-1355, and Helv. Chim. Acta (1958) 181, all of which are incorporated herein by reference. Alternatively, glutamic acid can be converted to pyroglutamic acid via enzymatic conversion. When the resulting mixture is exposed to a cation exchange resin, glufosinate (and glutamic acid, if present) is typically absorbed more strongly than pyroglutamic acid. When the resulting mixture is exposed to an anion exchange resin, pyroglutamic acid is typically absorbed more strongly than glufosinate.

[0026] For the non-enzymatic conversion of glutamate to pyroglutamate, an acidic pH is preferred. If the reaction mixture is not already acidic, an acid may be used to adjust the pH of the reaction mixture. Suitable acids that can be used to adjust the pH include hydrochloric acid, sulfuric acid, trifluoroacetic acid, phosphoric acid, acetic acid, or any other material having a pKa < 5. See, for example, DE3920570C2, which is incorporated herein by reference. The pH can be adjusted to values ​​from about 0.4 to about 7, from about 1.0 to about 6.0, from about 2.0 to about 5.0, or from about 2.5 to about 3.5.

[0027] As noted, the majority of glutamic acid can be converted to pyroglutamic acid by subjecting the composition to an elevated temperature for a sufficient period of time. The elevated temperature can be at least 100°C, at least 110°C, at least 120°C, at least 130°C, at least 140°C, at least 150°C, at least 160°C, at least 170°C, at least 180°C, or at least 190°C. Typically, the elevated temperature can be from about 120°C to about 180°C. Any suitable method for increasing the temperature of the material to the elevated temperature as described above can be used, and these methods are included within the methods described herein. For example, the elevated temperature can be achieved by heating the mixture or composition in an autoclave under moderate pressure; heating pure or high-boiling-point inert solvents using a heating hood, boiling plate, oil, or siloxane bath; recirculating the fluid in a jacketed reactor; or any other method known to those skilled in the art for applying heat. These methods also include the use of hot air guns and open flames.

[0028] As used herein, the term “major” means an amount that constitutes at least 50% of the weight of the component. For example, the term “major” can mean 50 wt.% or more, 55 wt.% or more, 60 wt.% or more, 65 wt.% or more, 70 wt.% or more, 75 wt.% or more, 80 wt.% or more, 85 wt.% or more, 90 wt.% or more, 95 wt.% or more, or 99 wt.% or more.

[0029] As used herein, the terms “substantially pure” or “substantially purified” in relation to a particular component mean that the component is present in the composition in an amount of 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more of the total amount of all components present in the composition.

[0030] The conversion of glutamic acid to pyroglutamic acid allows for a sufficient timeframe to convert most of the glutamic acid into pyroglutamic acid. Typically, most of the glutamic acid is converted in approximately 2 hours to approximately 20 hours (e.g., approximately 2 hours to approximately 15 hours). That is, the conversion time at elevated temperatures can be approximately 2 hours or longer, approximately 3 hours or longer, approximately 4 hours or longer, approximately 5 hours or longer, approximately 6 hours or longer, approximately 7 hours or longer, approximately 8 hours or longer, approximately 9 hours or longer, approximately 10 hours or longer, approximately 11 hours or longer, approximately 12 hours or longer, approximately 13 hours or longer, approximately 14 hours or longer, approximately 15 hours or longer, approximately 16 hours or longer, approximately 17 hours or longer, approximately 18 hours or longer, approximately 19 hours or longer, or approximately 20 hours.

[0031] The reaction mixture can be concentrated before or after the conversion of glutamic acid to pyroglutamic acid. Any concentration method known to those skilled in the art can be used, such as distillation, including vacuum distillation, thin-film evaporation, scraped-film evaporation, total evaporation, reverse osmosis, etc. If desired, the water and other volatile substances removed during concentration can be recycled back into the process. Optionally, the reaction mixture can be concentrated during the conversion of glutamic acid to pyroglutamic acid by removing water vapor and other volatile substances from the reaction mixture, as this method of operation makes the most efficient use of time and energy.

[0032] After glutamic acid is converted to pyroglutamic acid, the reaction mixture can be treated with an adsorbent or other solid material to reduce or remove color without loss of L-glufosinate. Suitable adsorbents include activated carbon (also known as activated char), bone char, etc. Polymer materials, such as those described in U.S. Patent No. 4,950,332 (which is incorporated herein by reference) or other ion exchange resins, are particularly useful for decolorizing the reaction mixture in commercial operations. Other treatment methods known to those skilled in the art can be used to decolorize the reaction mixture.

[0033] In one example, after conversion to pyroglutamic acid, varying amounts of activated charcoal can be added to portions of the same reaction mixture. After mixing for approximately 20 minutes at room temperature, a pre-washing step can be performed. Activated carbon is filtered through the top of the bed. The filter cake is then washed with water, and the filter cake washes are combined with the filtrate. In this example, the recovery and color observations are shown in the table below when pyroglutamic acid is used as an internal standard to check the recovery of L-gluphosphorus from the filtrate relative to the untreated sample.

[0034] Wt% Activated Carbon L-glufosinate recovery Color observation results 0.25 104％ Mild orange 0.5 103％ Mild orange 1.0 98％ Mild orange 3.0 103％ Colorless 5.0 98％ Colorless

[0035] In one embodiment, after converting glutamic acid to pyroglutamic acid, the reaction mixture can be cooled to a temperature below 20°C. In a preferred embodiment, the reaction mixture is adjusted to approximately pH 3 using sulfuric acid prior to the reaction, and then adjusted to approximately pH 6 using sodium hydroxide after the conversion of glutamic acid to pyroglutamic acid, and then cooled to a temperature just above the freezing point of the reaction mixture (e.g., about 5°C or below). Optionally, the reactants are concentrated and / or decolorized as described above prior to cooling. An advantage of this method is that sodium sulfate will precipitate or crystallize from the reaction mixture. The solid sodium sulfate, which can be in anhydrous or hydrated form, is substantially pure and can be removed from the reaction mixture by filtration, centrifugation, or any other suitable method to separate the solid from liquids known to those skilled in the art. Optionally, seeds of anhydrous or hydrated sodium sulfate can be added to the mixture to initiate crystallization.

[0036] Compared to membrane separation processes, the desalination achieved through a combination of evaporation concentration, cooling crystallization, and filtration is not particularly effective. With technological advancements, membrane separators have been used in many industries to achieve various separations. Descriptions of commonly used techniques can be found in "Unit Operations of Chemical Engineering," WLMcCabe, JCSmith and P. Harriott, 6th edition; McGraw-Hill, 2001; ISBN: 0070393664, which provides examples of membrane separation technologies that can be implemented on an industrial scale. The term "nanofiltration" is used to describe separation using membranes with pores larger than those in reverse osmosis membranes but smaller than those in ultrafiltration membranes. Membrane pore size is an important parameter because in many applications, membranes are selected based on differences in membrane size to separate the individual components of a mixture. U.S. Patent No. 5,447,635 (incorporated herein by reference) discloses a membrane separation method in which salts and other low molecular weight solutes are removed from an aqueous solution of the X-ray contrast agent iopamidol. Simultaneously, the iopamidol solution is concentrated. Membrane separation processes can be combined with other unit operations to optimize the purity of the product stream. U.S. Patent No. 5,811,581 (incorporated herein by reference) discloses a method in which an aqueous stream containing iopamidol is purified first by chromatographic separation and then by membrane separation. Examples teach that using combined techniques can yield iopamidol with high purity and high yield.

[0037] Before or after the conversion of glutamic acid to pyroglutamic acid, a membrane can be used to remove inorganic salts and some water from the L-glucopyranoside mixture. The mixture containing L-glucopyranoside can be pumped through a membrane separator, at which point the inorganic salts and some water exit the L-glucopyranoside mixture through the membrane. The salt can include a sodium salt of an acid used to adjust the pH before the glutamic acid conversion, such as sodium sulfate, provided the pH is adjusted using sulfuric acid; or sodium chloride, provided the pH is adjusted using hydrochloric acid. The membrane chosen can allow some glutamic acid and / or pyroglutamic acid to pass through along with the salt and water.

[0038] Suitable membranes can be made from natural or synthetic polymers, including but not limited to cellulose, polycarbonate, polyethylene, polypropylene, polysulfone, polylactic acid, polyacrylamide, polyvinylidine, etc. The polymers can be chemically modified if desired. Alternatively, ceramic membranes can be used. U.S. Patent Nos. 3,556,305; 3,556,992; 3,628,669; 3,950,255 and 3,950,255 disclose methods for preparing membranes and their use in separation methods. Standard equipment for membrane separation can be used for membrane separation. Those skilled in the art will recognize that membranes can be used in a variety of configurations, including but not limited to flat sheets for plate-and-frame configurations or hollow fiber tubes for shell-and-tube configurations. Spiral wound membrane modules can be particularly effective when used for this purpose. U.S. Patent Nos. 3,228,876; 3,401,798; 3,682,317 and 3,682,317 disclose several membrane configurations suitable for commercial operation.

[0039] The L-glufosinate mixture can be pumped through a membrane separator in a single-pass or multi-pass manner to achieve the desired desalination and concentration levels. If necessary, the resulting desalinated and concentrated L-glufosinate mixture can be further purified.

[0040] L-glufosinate can be separated from the pyroglutamic acid and other components of the composition to obtain a substantially purified L-glufosinate composition. The terms "substantially purified L-glufosinate" or "substantially pure L-glufosinate" are used to indicate that the amount of L-glufosinate in the final composition is 70% or higher, 75% or higher, 80% or higher, 85% or higher, 90% or higher, or 95% or higher, of the sum of L-glufosinate, glutamic acid, pyroglutamic acid, and any other components in the final composition.

[0041] In some cases, glutamate can be converted to pyroglutamic acid via enzymatic conversion. See, for example, U.S. Patent No. 3,086,916, which is incorporated herein by reference. In this manner, a glutamine acyl-peptide cyclase (e.g., EC 2.3.2.5) can be added to a composition containing L-glufosinate and glutamate for a sufficient time to convert glutamate to pyroglutamic acid. The duration of sufficient conversion will depend on the activity and concentration of the enzyme used in the reaction. Typically, the time is at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 10 hours, at least 12 hours, or longer.

[0042] In some embodiments, a crystallization step may be used to remove a portion of the glutamic acid before converting the remaining glutamic acid to pyroglutamic acid. In this manner, in the first step, a portion of the glutamic acid can be crystallized and removed from the starting composition by filtration, centrifugation, or any other suitable solid-liquid separation method known to those skilled in the art. For example, glutamic acid present in amounts of 0.1 wt.% or higher, 0.5 wt.% or higher, 1 wt.% or higher, 5 wt.% or higher, 10 wt.% or higher, 15 wt.% or higher, or 20 wt.% or higher can be crystallized and removed from the starting composition. The crystallized glutamic acid can be reused, for example, in a subsequent D-gluphosphorus enzymatic conversion process.

[0043] For crystallization, the composition can be adjusted to a pH of about 3 to about 5 (e.g., about 3.5 to about 4.5, about 3.5 to about 3.8, or about 3.7 to about 4.2) by adding an acid. Suitable acids for adjusting the pH include hydrochloric acid, sulfuric acid, trifluoroacetic acid, phosphoric acid, acetic acid, or any other substance having a pKa < 5. See, for example, DE3920570C2, which is incorporated herein by reference.

[0044] In some instances, the temperature of the composition is carefully controlled. In this way, the composition can be heated to temperatures such as approximately 30°C, approximately 35°C, approximately 40°C, etc., before adding the acid. The acid (e.g., concentrated hydrochloric acid or sulfuric acid) is added continuously or in portions at a slow rate to a suitable container containing the reaction mixture. Stirring the mixture during acid addition is preferred and can be done by any suitable method. When well mixed, the addition of acid to the mixture is generally insensitive to the rate of addition when the pH of the mixture is above approximately pH 5, as precipitation or crystallization is generally not observed above pH 5. In the laboratory, using suitable equipment, acid is added at a dropping rate below pH 5, where the dropping rate refers to fractions of less than 0.1 mL, less than 0.2 mL, less than 0.3 mL, less than 0.4 mL per few seconds, so that crystallization of glutamic acid begins before the addition of concentrated hydrochloric acid or sulfuric acid is completed. For example, when operating in the laboratory, approximately 35 mL to 40 mL of 10M sulfuric acid can be added dropwise to a batch of approximately 1 L over a period of time (e.g., 15 to 20 minutes).

[0045] The reaction mixture can then be heated to an elevated temperature of approximately 35°C to approximately 90°C (e.g., approximately 40°C to approximately 80°C, approximately 50°C to approximately 70°C, or approximately 55°C to approximately 65°C) and maintained at the elevated temperature for at least approximately 20 minutes (e.g., at least approximately 25 minutes or at least approximately 30 minutes). In some instances, some of the heat associated with the addition of acid is not immediately dissipated, and the reaction mixture is allowed to slowly self-heat. After maintaining the elevated temperature, the resulting composition is slowly cooled to 0°C over time. Optionally, the composition can be cooled to 0°C over a period of minutes to days and can be maintained for at least approximately 30 minutes, approximately 45 minutes, approximately 50 minutes, or approximately 60 minutes over several hours or days, after which the reactants are filtered.

[0046] One advantage of controlling the temperature as described above is that it produces high-purity glutamic acid crystals that are easy to filter. Optionally, the crystallization method can be carried out in the presence of glutamic acid seed crystals (e.g., glutamic acid crystals added to the mixture during acid addition, glutamic acid crystals left over from a previous batch, or glutamic acid crystals present in a continuous crystallizer) to help the crystals grow to a size that is easy to filter.

[0047] Another advantage of controlling the temperature as described above, and more specifically, lowering the temperature below room temperature, is that more glutamic acid will crystallize, thus reducing the amount of glutamic acid remaining in the filtrate. Optionally, a water-miscible solvent can be added to further reduce the solubility of glutamic acid in the mixture. Adding a water-miscible solvent also allows for achieving a lower temperature without freezing the mixture.

[0048] This method for crystallizing glutamic acid from reactants or starting compositions significantly reduces the amount of glutamic acid in solution. As described above, residual glutamic acid in the reaction mixture or composition can be converted to pyroglutamic acid at elevated temperatures. In the case of a single ion exchange step (i.e., cation or anion exchange, without the need for both cation and anion exchange steps) or other separation methods, the resulting pyroglutamic acid can be easily separated from L-glufosinate, yielding high-purity L-glufosinate and low levels of glutamic acid.

[0049] In one embodiment, an anion exchange resin is used to purify L-glucopyranoside from pyroglutamic acid, 2-oxoglutaric acid, and PPO at ambient temperature or elevated temperatures and at weakly basic, neutral, or acidic pH values. In some instances, the interaction between L-glucopyranoside and the anion exchange resin may not be as strong as the interaction between the anion exchange resin and each of 2-oxoglutaric acid, PPO, and pyroglutamic acid. This difference in interaction behavior can be used to achieve the purification of L-glucopyranoside. In this method, the anion exchange resin can be loaded into a suitable container, such as a tank or column. In some instances, the anion exchange resin is converted to its hydroxyl form using an aqueous solution of a suitable inorganic base (e.g., sodium hydroxide or potassium hydroxide). In some cases, sulfuric acid or an inorganic sulfate or bisulfate is used to convert the anion exchange resin to its sulfuric or bisulfate form. The resin is then equilibrated at a desired temperature by external heating (e.g., by allowing a heat transfer fluid to flow into the jacket of the container) or by pumping fluid through the container at the desired temperature, or both. The resin is equilibrated at the desired pH using dilute acid, dilute base, and / or water. The reaction mixture can be obtained from the glutamate cyclization step, and can optionally be concentrated as described above, and / or optionally decolorized as described above, and adjusted to the same pH as the resin. The reaction mixture can also be adjusted to the same temperature as the resin and typically pumped through the anion exchange resin in a downward flow manner through the container. The effluent from the container can be collected in portions. The portions containing the majority of L-glufosinate can be combined to form a solution of substantially purified L-glufosinate. Without being bound by any particular theory, pyroglutamic acid, 2-oxoglutarate, PPO, and other impurities interact with the anion exchange resin such that the components pass through the column at different rates compared to L-glufosinate, thereby allowing the substantially purified L-glufosinate to be collected in a separate solution.

[0050] As described above, a variety of commercially available anion exchange resins can be used to prepare substantially purified L-glufosinate. Examples of suitable resins include those consisting of a cross-linked copolymer backbone (e.g., made from monovinyl monomers such as styrene, acrylates, etc., and polyvinyl crosslinking agents such as divinylbenzene, etc.). U.S. Patent Nos. 3,458,976 and 6,924,317 (both incorporated herein by reference) disclose other monovinyl monomers and polyvinyl crosslinking agents that can be used to produce suitable copolymer backbone materials. Resins with a wide range of porosities can be used, including microporous and macroporous. The terms “microporous” and “macroporous” refer to the size range of pores in solid particles. Two commonly used methods for determining pore size are nitrogen adsorption-desorption and mercury porosimetry (see WCConnor et al. 1986 Langmuir 2(2):151-154). Those skilled in the art will understand that macroporous materials include both macropores and mesopores; mesopores range in size from about 20 angstroms to about 500 angstroms, and macropores are larger than about 500 angstroms. Microporous materials have micropore sizes of less than 20 angstroms. See PCT / US2016 / 063219, which is incorporated herein by reference. Gel-type resins, such as those described in U.S. Patent Nos. 4,256,840 and 5,244,926, are considered microporous and may also be used, both of which are incorporated herein by reference. Resin particles in the form of beads, i.e., spherical or near-spherical, are particularly useful in the methods of the present invention. The beads may be homogeneous (also referred to as “monodisperse”) or have a Gaussian or polydisperse particle size distribution. “Homogeneous” or “monodisperse” means that at least 90% by volume of the beads have a particle size of about 0.8 to about 1.2, more preferably 0.85 to 1.15 times the volume average particle size. See PCT / US2016 / 063220, which is incorporated herein by reference.

[0051] Resins can be converted into anion exchange resins by functionalization with one or more types of amines. One method of functionalizing the resin involves reacting the copolymer with a chloromethylation reaction followed by reaction with a primary amine, secondary amine, tertiary amine, amino alcohol, polyamine, or ammonia, as described in U.S. Patent No. 6,924,317. Anion exchange resins having an anion capacity of about 0.1 to about 4 mEq / g are suitable for this method, wherein the anion capacity is measured according to ASTM D2187-94 (re-approved in 2004). Resins functionalized with primary and secondary amines are weakly basic anion exchange resins known to those skilled in the art. Resins functionalized with tertiary and tertiary polyamines, known to those skilled in the art as strongly basic anion exchange resins, are particularly suitable for this method. In one embodiment, a mixture of a strongly basic anion exchange resin and a weakly basic anion exchange resin is used to produce substantially purified L-glufosinate.

[0052] The size of the resin particles can be selected to achieve purification at an acceptable pressure drop in an apparatus used for ion exchange methods. The preferred median volume-average diameter of the resin particles used in this method is in the range of about 10 micrometers to about 2000 micrometers. A particularly useful range for the median diameter is about 100 micrometers to about 1000 micrometers. Examples of suitable resins include, but are not limited to, DOWEX. TM MARATHON TM A,DOWEX TM MONOSPHERE TM 550A, DOWEX TM MONOSPHERE TM MSA, DOWEX TM XUR-1525-L09-046, an experimental gel-type, strongly basic anion exchange resin type I (trimethylamine quaternary ammonium salt, chloride form, obtained from Dow Chemical Company) with uniform particle size in the range of 300 micrometers, and other substances known to those skilled in the art.

[0053] In some instances, elevated temperatures are used for separation. The reaction mixture fed into the column, as well as the column itself, can be maintained at temperatures of about 25°C to about 30°C, about 30°C to about 35°C, about 35°C to about 40°C, about 45°C to about 50°C, about 50°C to about 55°C, about 55°C to about 60°C, about 60°C to about 65°C, or about 65°C to about 70°C. The column temperature can be maintained by using a heating jacket fitted over the column wall to allow the heating fluid to flow through the jacketed column, keeping the column within a heated housing, or by any other heating method known to those skilled in the art.

[0054] Separation can be performed within a pH range of approximately 0.4 to 8; specifically, at approximately pH 0.4, 0.6, 1, 2, 3, 4, 5, 6, 7, or 8. Acids that can be used for pH adjustment include hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, acetic acid, and methanesulfonic acid. Bases that can be used for pH adjustment include sodium hydroxide, potassium hydroxide, and ammonium hydroxide.

[0055] As is known in the field of ion exchange separation, resins can be regenerated for reuse. For example, U.S. Patent No. 3,458,439 describes a method for regenerating anion exchange resins. In this regeneration method, the resin is treated with one or more solutions that desorb previously adsorbed components from the resin and return it to a preferred form for separation. Typically, the solution contains an acid or base and optionally an inorganic salt, such as sodium chloride, sodium phosphate, sodium sulfate, ammonium sulfate, etc. In one embodiment, the anion exchange resin can be regenerated with caustic brine (i.e., a mixture of sodium hydroxide and sodium chloride), acidic brine (i.e., a mixture of hydrochloric acid and sodium hydroxide), sulfuric acid (with or without sodium chloride), or sodium chloride alone. Useful caustic brine compositions comprise a sodium hydroxide concentration of about 0.01 M to about 0.5 M and a sodium chloride concentration of about 0.1 M to about 1.5 M. Useful acidic brine compositions comprise a hydrochloric acid concentration of about 0.01 M to about 0.5 M and a sodium chloride concentration of about 0.01 M to about 0.5 M. In some instances, the acidic brine comprises a sulfuric acid concentration of about 0.1 M to about 1.5 M and a sodium chloride concentration of about 0.1 M to about 1.5 M. Optionally, water adjusted to pH 1 with sulfuric acid can be used.

[0056] Certain regeneration methods can be advantageous when used to implement the methods described herein. When used in conjunction with anion exchange resin regeneration methods, methods for producing substantially purified L-glufosinate can also be used to produce substantially purified 2-oxoglutaric acid (also referred to herein as 2-oxoglutaric acid). "Substantially purified 2-oxoglutaric acid" or "substantially pure 2-oxoglutaric acid" means that the amount of 2-oxoglutaric acid in the final composition is 70% or higher, 75% or higher, 80% or higher, 85% or higher, 90% or higher, or 95% or higher compared to the sum of 2-oxoglutaric acid, L-glufosinate, glutamic acid, succinic acid, and pyroglutamic acid in the final composition. After separation using the methods of the present invention, substantially purified 2-oxoglutaric acid can be conveniently and efficiently converted into succinic acid (used as a food additive and dietary supplement).

[0057] In some instances, 2-oxoglutaric acid can be obtained at high concentrations by purifying L-glucopyranoside according to the methods described herein. For example, high concentrations of essentially pure 2-oxaloglutaric acid can be obtained by using aqueous solutions of sodium hydroxide and sodium chloride (e.g., 0.1 M NaOH and 1.5 M NaCl aqueous solution) as eluents in column chromatography (e.g., using anion exchange resin). 2-oxoglutaric acid is a byproduct of PPO amination and cannot be reused in the methods described in '254 application. 2-oxoglutaric acid collected in the fraction leaving the column can be converted to succinic acid by contacting 2-oxoglutaric acid with an excess of dilute hydrogen peroxide at room temperature. See, for example, A. Lopalco and V. JStella (2016) J. Pharm. Sci. 105:2879-2885, which is incorporated herein by reference.

[0058] Succinic acid is widely used as an ingredient or raw material in various commercial products. If desired, the substantially purified succinic acid produced by this method can be further purified, concentrated, and / or separated by means known to those skilled in the art. Substantially purified or substantially pure succinic acid means that the amount of succinic acid in the final composition is 70% or higher, 75% or higher, 80% or higher, 85% or higher, 90% or higher, or 95% or higher compared to the sum of succinic acid, L-glufosinate, glutamic acid, 2-oxoglutarate, and pyroglutamic acid in the final composition.

[0059] In another embodiment, the cation exchange resin can be used to purify L-glufosinate from pyroglutamic acid, 2-oxoglutaric acid, and PPO. In this embodiment, the method can be carried out in two steps. In the first step, the reaction mixture from the glutamic acid cyclization step can be mixed with a cation exchange resin that has been converted to hydrogen form using a suitable acid. Such acids include, but are not limited to, concentrated hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, and methanesulfonic acid. Similarly, the reaction mixture from the glutamic acid cyclization step is adjusted to an acidic pH, i.e., a pH less than about 7.0 (e.g., about 0.5 to about 1.0, about 1.0 to about 2.0, about 2.0 to about 3.0, about 3.0 to about 4.0, about 4.0 to about 5.0, about 5.0 to about 6.0, or about 6.0 to about 6.9). Optionally, the reaction mixture from the glutamic acid cyclization step can be concentrated and / or decolorized as described above before being mixed with the cation exchange resin. When mixed with resin, L-glufosinate and residual glutamic acid are adsorbed onto the resin, while 2-oxoglutarate, PPO, and pyroglutamic acid are not adsorbed. After an appropriate time period, the liquid containing impurities can be separated from the resin containing L-glufosinate. Optionally, after L-glufosinate adsorption is complete, the resin can be washed with a suitable liquid such as water, which displaces the residual solution containing impurities but does not remove L-glufosinate from the resin.

[0060] In the second step, the resin containing L-glufosinate can be mixed with a water-soluble alkali that desorbs L-glufosinate from the resin, forming a substantially purified L-glufosinate solution. Suitable alkalis for removing L-glufosinate from cationic resins include sodium hydroxide, potassium hydroxide, ammonium hydroxide, isopropylamine, ethanolamine, diethanolamine, etc. This method can be carried out by contacting the resin and solution in a batch or flow mode as described above, wherein the resin remains stationary in the container while the solution is passed through. The method can be carried out at suitable temperatures, for example, from about 20°C to about 70°C. That is, temperatures in the range of about 25°C to about 65°C, about 30°C to about 60°C, or about 40°C to about 50°C. The resin can be regenerated by contacting it with a suitable acid, such as hydrochloric acid, sulfuric acid, etc., or a mixture of acid and inorganic salt as described above.

[0061] As mentioned above, many different types of commercially available cation exchange resins can be used for purification. Suitable resins for use as cation exchange resins can consist of copolymer frameworks with varying porosities, i.e., micropores. Gel-type cation exchange resins are also suitable. Suitable resins can have a uniform Gaussian or polydisperse particle size distribution. For this method, those with a bead shape and uniform particle size distribution are likely preferred. The preferred average volume-average diameter of the resin particles used in this method is from about 10 micrometers to about 2000 micrometers, and a particularly useful range for the median diameter is from about 100 micrometers to about 1000 micrometers.

[0062] Resins can be converted into strong acid cation exchange resins by sulfonation. Sulfonation occurs when the resin is contacted with various sulfonating agents such as sulfur trioxide, concentrated sulfuric acid, chlorosulfonic acid, and fuming sulfuric acid (see U.S. Patent Nos. 2,500,149; 2,527,300; and 2,597,439, all of which are incorporated herein by reference). Some resins, such as those comprising carboxylic acid monomers, can act as weak acid cation exchange resins (U.S. Patent Nos. 4,062,817 and 4,614,751, both of which are incorporated herein by reference). Cation exchange resins having a cation capacity of about 0.1 to about 4 milliequivalents per gram, wherein the cation capacity is measured by ASTM D2187-94 (re-approved in 2004), are suitable for this method. Examples of suitable resins include DOWEX. TM 50WX8, DOWEX TM MONOSPHERE TM 99K / 350, DOWEX TM MONOSPHERE TM C,DOWEX TM MARATHON TMMSCs and other substances known to those skilled in the art.

[0063] Those skilled in the art will recognize that multiple resin-containing containers, such as those disclosed in U.S. Patent No. 4,001,113, can be used for efficient operation in flow modes in parallel or tandem operations. Parallel operation allows for the simultaneous purification of the reaction mixture in several similar containers, each containing an ion-exchange resin. In continuous operation, a partially purified L-glufosinate solution of undesirable purity leaving the resin container is fed into a subsequent container containing fresh or regenerated resin to continue the purification process. Immediately after the partially purified L-glufosinate solution is fed into the subsequent container, the reaction mixture not mixed with the resin is fed into the same container. In this way, the position of the reaction mixture shifts to the subsequent containers. This process is repeated for other containers in tandem. In some instances, used resin is regenerated in some containers while the partially purified L-glufosinate solution is fed into fresh or regenerated resin in other containers. This method is particularly suitable for continuous operation.

[0064] Optionally, the volume of solution exiting the ion exchange step containing substantially purified L-glufosinate can be contacted with a water-miscible organic solvent to induce precipitation of the inorganic salt. Solvents suitable for this purpose include acetone, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1-methyl-2-propanol, 1,2-propanediol, and 1,2-ethylenediol. Methanol may be particularly useful in many embodiments. In some embodiments, the volume of solution obtained from the ion exchange step is contacted with one or more volumes (e.g., four volumes) of methanol to form a sodium sulfate precipitate. The precipitate, which contains little or no L-glufosinate, can be readily removed.

[0065] Size-based chromatographic methods (known as size exclusion) or gel filtration chromatography can also be used to purify L-glufosinate from a reaction mixture. In size exclusion chromatography, the solution passes through a container containing a resin with a specific pore size distribution. Without being bound by any particular theory, solutes that are too large to enter the pores of the resin pass through the container relatively quickly. These solutes do not migrate into the resin particles. Solutes that are small enough to enter the pores will migrate into the resin particles and thus remain in the container for a longer period. Other factors besides solute size, such as solute structure, concentration, presence of salts, solution pH, etc., can also affect the resulting separation. Solute separation can occur through various interactions with the resin, namely size exclusion combined with adsorption or ion exchange, or a combination of both. A description of this technique can be found in "ModernSize Exclusion Chromatography: Practice of Gel Permeation and Gel Filtration", 2nd edition, A.M. Striegel, et al., John Wiley and Sons, Inc., 2009; ISBN 9780471201724.

[0066] L-glufosinate mixtures can be purified by passing the mixture through a container of appropriately sized size exclusion resin. Compared to L-glufosinate, smaller, more compact components in the mixture have a longer residence time in the container. All or part of the L-glufosinate in the mixture will be eluted from the column, followed by the elution of other components, including inorganic salts, pyroglutamic acid, and / or glutamic acid.

[0067] Resins for size exclusion chromatography can be prepared using the methods described above for ion exchange resins, with or without functionalization. Other methods for preparing resin beads for size exclusion chromatography are disclosed in U.S. Patents Nos. 3,857,824 and 4,314,032 and British Patent GB 1135302A. Suitable resins are available commercially on a few manufacturers, including but not limited to… HW-40, a product of Tosoh Bioscience; SEPABEADS TM SP825L, DIAION TM HP20SS and DIAION TM HP2MGL, a product of Mitsubishi Chemical Company; and G-10 is a product of GE Life Sciences.

[0068] Simulated moving bed chromatography (“SMB”) can be used in conjunction with ion exchange resins or size exclusion resins to produce substantially purified L-glufosinate. SMB is described in numerous publications, such as “Simulated Moving Bed Technology: Principles, Design and Process Applications”, A. Rodriguez; Butterworth-Heinemann, 2015; ISBN: 978-0128020241 and U.S. Patent Nos. 2,985,589; 4,182,633; 4,319,929; 4,412,866; 5,102,553; 7,229,558; and 7,931,751, all of which are incorporated herein by reference. SMB operation efficiently utilizes both resin and liquid streams, such as a coarse feed stream and an eluent stream. Another advantage of SMB is that the method can be used for the continuous purification of reaction mixtures on a commercial scale. In SMB technology, several containers are connected in series to form a continuous loop. Each container contains resin suitable for separating components. Valves and piping are connected to each container to allow at least four different types of fluids to enter and exit each container; an example of a valve for this purpose is described in U.S. Patent No. 6,431,202. These fluids consist of a mixture to be purified, an eluent, a substantially purified stream of one or more fast-moving components, and a substantially purified stream of one or more slow-moving components. The mixture to be purified and the eluent are fed into the process (meaning fed separately into individual containers), while the fast-moving and slow-moving components are removed from the process. The resin, eluent, temperature, and flow rate used in SMB are selected to obtain a substantially purified product from either the fast-moving or slow-moving component stream. Unbound by any particular theory, this technology utilizes the differential interactions between the components in the mixture and the resin, resulting in different conversion rates of the components through the continuous loop. As a result, the resin can be utilized with greater efficiency and the volume of the eluent can be minimized. In the same manner, the method can be designed such that L-glufosinate can be a fast-moving component or a slow-moving component.

[0069] In one embodiment, SMB separation can be combined with a pretreatment step, wherein one or more components of the mixture are removed prior to SMB operation by contacting the mixture with an adsorbent. Such components removed include PPO, 2-oxoglutaric acid, and colored substances.

[0070] In another embodiment, SMB separation is combined with the membrane separation method as described above. If desired, a membrane separation step can be used to remove inorganic salts and / or water from the solution. The membrane separation operation can be performed before or after SMB separation.

[0071] If passed 1 The method described herein, as determined by H-NMR, can remove approximately 80% or more (e.g., approximately 85% or more, approximately 87% or more, or approximately 90% or more) of unreacted glutamate; however, HPLC and other analytical methods can also be used to determine the percentage.

[0072] This method isolates substantially purified L-glufosinate. Therefore, this method provides compositions of substantially purified L-glufosinate. L-glufosinate can be in the form of crystals, liquids, oils, or amorphous solids. For example, compositions of substantially purified L-glufosinate may contain greater than 70% pure L-glufosinate or material contaminated with less than 30% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid, glutamic acid, or other impurities (said to be present in the raw material and introduced during the reaction, heating, or cooling process of the material, excluding water)); greater than 80% pure L-glufosinate or material contaminated with less than 20% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid, glutamic acid, or other impurities (said to be present in the raw material and introduced during the reaction, heating, or cooling process of the material, excluding water); greater than 85% pure L-glufosinate or material contaminated with less than 15% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid, pyroglutamic acid, pyroglutamic acid, glutamic acid, or other impurities (said to be present in the raw material and introduced during the reaction, heating, or cooling process of the material, excluding water); and more than 85% pure L-glufosinate or material contaminated with less than 15% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid ... Materials contaminated with glutamic acid, glutamic acid, or other impurities (these other impurities are present in the raw materials and are introduced during the reaction, heating, or cooling process of the material (excluding water)); materials containing more than 90% pure L-glufosinate or contaminated with less than 10% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid, glutamic acid, or other impurities (these other impurities are present in the raw materials and are introduced during the reaction, heating, or cooling process of the material (excluding water)); or materials containing more than 95% pure L-glufosinate or contaminated with less than 5% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamic acid, glutamic acid, or other impurities (these other impurities are present in the raw materials and are introduced during the reaction, heating, or cooling process of the material (excluding water)).

[0073] In one embodiment, the volume of the solution containing substantially purified L-glufosinate exiting the ion exchange step can be reduced to a concentrate that can be formulated substantially directly into a herbicide product. Any concentration method known to those skilled in the art can be used, such as distillation (including vacuum distillation), thin-film evaporation, scraped-film evaporation, and membrane-based methods such as total evaporation, reverse osmosis, nanofiltration, ultrafiltration, etc. If desired, the water and solvent removed by concentration can be recycled back into the process.

[0074] In another embodiment, the concentrated L-glufosinate solution can be further concentrated using any of the methods described above until precipitation or crystallization occurs. Optionally, a solvent or solvent mixture can be added at any point in the process to aid water evaporation, thereby increasing the purity of the solid L-glufosinate, thus increasing the yield of substantially purified L-glufosinate, or altering the size and / or shape of the solid particles. Solvents with a solubility in water of at least 10 wt.% are particularly suitable for this purpose. Useful solvents include acetone, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1-methyl-2-propanol, 1,2-propanediol, 1,2-ethylenediol, triethylamine, isopropylamine, and ammonium hydroxide. The solid material produced by precipitation or crystallization can be filtered and dried to obtain a solid containing substantially pure L-glufosinate. If desired, the filtrate can be recycled back into the process. Any suitable filtration and drying equipment can be used for this purpose. If desired, the water and solvent removed by concentration can be recycled back into the process.

[0075] In another embodiment, the volume of the solution containing substantially purified L-glufosinate exiting the ion exchange step can be concentrated until precipitation or crystallization occurs, and then water and other volatile substances present can be evaporated further until a substantially dry solid is obtained. One advantage of using this method is that a filtration step is not required. Optionally, a solvent or solvent mixture can be added at any point to aid water evaporation, such as those solvents that form azeotropes with water, including toluene, 1-butanol, tert-amyl alcohol, etc. Optionally, as described above, components can be added to change the size and / or shape of the solid particles. The solid containing substantially purified L-glufosinate can be obtained as a powder, granules, bulk material, or a mixture thereof. Any suitable equipment for carrying out this method can be used, including rotary evaporators, stirred pan dryers, horizontal shaft stirred dryers, etc. If desired, the dried solid can be homogenized. If desired, the water and solvent removed during the process can be recycled.

[0076] In another embodiment, the volume of the solution containing substantially purified L-glufosinate exiting the ion exchange step can be transferred to a spray dryer. Prior to transfer to the spray dryer, the solution can be partially concentrated, and the partially concentrated mixture can be in solution form, or, if precipitation or crystallization has occurred, in slurry form. The solid obtained after spray drying can be in powder or granule form, containing substantially pure L-glufosinate. In another embodiment, an agent that can improve the flowability of the dried granules or other components can be mixed into the concentrated solution or slurry prior to spray drying. In another embodiment, other materials (such as formulation ingredients) can be mixed into the solution or partially concentrated mixture prior to spray drying.

[0077] II. Solid form

[0078] This article also provides information on various solid forms of L-glufosinate, including crystalline and amorphous forms.

[0079] In some embodiments, L-glufosinate form A is provided. In some embodiments, form A is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 10.1, 10.8, 16.8, 17.2, 18.3, 20.0, 20.2, 21.2, 21.5, 24.1, 24.3, 25.1, 25.6, 26.9, 28.6, 29.0, 29.7, 29.9, 31.9, 33.4, 33.7, 34.5, 34.9, 35.4, 35.7, 36.1, 36.7, 37.1, 37.5, 38.2 and 39.8°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer. For example, an XRPD pattern of form A can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 such peaks.

[0080] In some embodiments, form A is characterized in that the XRPD pattern contains at least six peaks selected from 10.1, 16.8, 18.3, 21.2, 24.1, 24.3, 25.6, 26.9, 28.6, 29.0, and 34.5°2θ, ±0.2°2θ, as determined by a Cu-Kα diffractometer. In some embodiments, form A is characterized in that the XRPD pattern contains at least ten peaks selected from 10.1, 16.8, 18.3, 21.2, 24.1, 24.3, 25.6, 26.9, 28.6, 29.0, and 34.5°2θ, ±0.2°2θ, as determined by a Cu-Kα diffractometer. In some embodiments, form A is characterized in that the XRPD pattern is substantially similar to... Figure 1 Consistent. As described below, form A has been analyzed by ion chromatography, indicating a glufosinate:ammonium ratio of approximately 1.4:1. In some embodiments, form A is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endothermic temperature range from approximately 119 to approximately 123 °C. In some embodiments, the DSC curve is substantially consistent with... Figure 2 The DSC curves shown are consistent.

[0081] L-glufosinate form A can be prepared according to the following method. In some embodiments, the preparation of L-glufosinate form A includes mixing L-glufosinate with a polar solvent (e.g., isopropanol or methanol) or a mixture of a polar solvent and water; maintaining the resulting slurry at a temperature of about 20°C to about 50°C for a period of 1 hour to 14 days; and separating form A from the slurry.

[0082] In some embodiments, L-glufosinate form B is provided. In some embodiments, form B is characterized by an X-ray powder diffraction (XRPD) pattern containing at least three peaks selected from 10.0, 11.4, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.1, 25.5, 26.1, 26.3, and 26.4. ,27.9,28.2,28.4,28.7,29.2,30.2,30.9,31.6,31.7,32.7,33.0,33.3,34.3,35.2,36.7,37.2,37.4,37.8,38.3,38.7 and 39.3°2θ,±0.2°2θ, as determined using a diffractometer with Cu-Kα rays. For example, an XRPD pattern of form B can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, or 38 such peaks.

[0083] In some embodiments, form B is characterized by an XRPD pattern containing at least six peaks selected from 10.0, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.5, 26.3, 26.4, 29.2, 34.3, 35.2 and 37.4°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form B is characterized by an XRPD pattern comprising at least 10 peaks selected from 10.0, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.5, 26.3, 26.4, 29.2, 34.3, 35.2, and 37.4°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form B is characterized by an XRPD pattern that is substantially similar to... Figure 3 Consistent. As described below, form B has been analyzed by ion chromatography, indicating a glufosinate:ammonium ratio of approximately 5.3:1. In some embodiments, form B is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endothermic start at approximately 123°C. In some embodiments, the DSC curve is substantially consistent with... Figure 4 The DSC curves shown are consistent.

[0084] L-glufosinate form B can be prepared according to the following method. In some embodiments, the preparation of L-glufosinate form B includes combining L-glufosinate with a mixture of a polar solvent and water; maintaining the resulting slurry at a temperature of about 20°C to about 50°C for a period of 1 hour to 14 days; and separating form B from the slurry.

[0085] In some embodiments, L-glufosinate form C is provided. In some embodiments, form C is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 9.1, 10.9, 16.1, 16.8, 17.3, 18.3, 20.1, 21.4, 21.8, 22.4, 22.7, 24.1, 24.9, 25.4, 25.6, 26.1, 26.6, 27.7, 28.3, 28.9, 30.8, 31.9, 32.6, 33.6, 33.9, 35.1, 36.6, 37.1, 37.5, 38.3, 38.9 and 39.7°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer. For example, an XRPD pattern of form C can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34 such peaks.

[0086] In some embodiments, form C is characterized in that the XRPD pattern contains at least six peaks selected from 9.1, 16.1, 16.8, 17.3, 21.8, 24.1, 24.9, 25.6, 26.1, 28.3, and 28.9°2θ, ±0.2°2θ, as determined by a Cu-Kα diffractometer. In some embodiments, form C is characterized in that the XRPD pattern contains at least ten peaks selected from 9.1, 16.1, 16.8, 17.3, 21.8, 24.1, 24.9, 25.6, 26.1, 28.3, and 28.9°2θ, ±0.2°2θ, as determined by a Cu-Kα diffractometer. In some embodiments, form C is characterized in that the XRPD pattern is substantially similar to... Figure 5 Consistent. As described below, form C has been analyzed by ion chromatography, indicating a glufosinate:ammonium ratio of approximately 1.4:1. In some embodiments, form C is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endothermic start at approximately 100°C and / or an endothermic start at approximately 131°C. In some embodiments, the DSC curve is substantially consistent with... Figure 6 The DSC curves shown are consistent.

[0087] L-glufosinate form C can be prepared according to the following method. In some embodiments, the preparation of L-glufosinate form C includes contacting L-glufosinate with solvent vapor (e.g., methanol vapor) at a temperature of about 20°C to about 30°C for a period of 1 hour to 14 days; and separating form C.

[0088] In some embodiments, L-glufosinate form D is provided. In some embodiments, form D is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 9.1, 11.6, 13.1, 14.1, 14.4, 16.2, 17.7, 18.2, 18.9, 19.3, 19.7, 21.2, 21.8, 22.4, 23.2, 23.5, 25.3, 25.8, 26.2, 27.2, 28.6, 29.1, 30.0, 30.6, 31.1, 31.6, 32.7, 33.5, 34.4, 34.7, 35.4, 35.9, 36.4, and 37.4°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer. For example, an XRPD pattern of form D can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34 such peaks.

[0089] In some embodiments, form D is characterized in that the XRPD pattern contains at least six peaks selected from 9.1, 17.7, 18.2, 18.9, 22.4, 23.2, 23.5, 26.2, 33.5, and 36.4°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form D is characterized in that the XRPD pattern contains peaks at 9.1, 17.7, 18.2, 18.9, 22.4, 23.2, 23.5, 26.2, 33.5, and 36.4°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form D is characterized in that the XRPD pattern is substantially similar to... Figure 7 Consistent. As described below, form D has been analyzed by ion chromatography, indicating a glufosinate:ammonium ratio of approximately 3.9:1. In some embodiments, form D is characterized by a broad endothermic differential scanning calorimetry (DSC) curve starting at approximately 140°C. In some embodiments, the DSC curve is substantially consistent with... Figure 8 The DSC curves shown are consistent.

[0090] L-glufosinate form D can be prepared according to the following method. In some embodiments, the preparation of L-glufosinate form D includes combining L-glufosinate with a mixture of solvents (e.g., methanol, ethanol, trifluoroethanol, isopropanol, acetone, dimethylacetamide, etc., optionally anhydrous); maintaining the resulting slurry at a temperature of about 50°C to about 60°C for a period of 1 hour to 14 days; and separating form D from the slurry.

[0091] In some embodiments, L-glufosinate hydrochloride form E is provided. In some embodiments, form E is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 13.1, 16.8, 18.2, 19.4, 20.5, 20.9, 21.4, 22.5, 23.4, 25.3, 26.2, 26.5, 26.9, 27.8, 28.1, 30.2, 31.2, 31.5, 32.3, 33.8, 34.4, 35.3, 35.7, 36.3, 36.9, 37.8, 38.2, 38.8 and 39.4°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer. For example, an XRPD pattern of form E can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 such peaks.

[0092] In some embodiments, form E is characterized in that the XRPD pattern contains at least six peaks selected from 16.8, 18.2, 20.5, 21.4, 22.5, 22.9, 23.4, 25.3, 30.2, and 31.2°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form E is characterized in that the XRPD pattern contains at least ten peaks selected from 16.8, 18.2, 20.5, 21.4, 22.5, 22.9, 23.4, 25.3, 30.2, and 31.2°2θ, ±0.2°2θ, as determined by a diffractometer using Cu-Kα rays. In some embodiments, form E is characterized in that the XRPD pattern is substantially similar to... Figure 9 Consistent. As described below, form E, indicating stoichiometric amounts of L-glufosinate and chloride, has been analyzed by ion chromatography.

[0093] L-glufosinate hydrochloride form E can be prepared according to the following method. In some embodiments, the preparation of L-glufosinate hydrochloride form E includes combining L-glufosinate with water and hydrochloric acid; adding a solvent (e.g., methanol, ethanol, trifluoroethanol, isopropanol, acetone, dimethylacetamide, etc.) to the resulting mixture; maintaining the mixture at a temperature of about 20°C to about 30°C for a period of 1 hour to 14 days; and separating form E from the mixture.

[0094] III. Composition

[0095] This document also describes compositions comprising the above-described L-glufosinate. In some embodiments, the composition substantially comprises L-glufosinate and an acceptable cationic or anionic salt form, such as a sodium salt, potassium salt, hydrochloride salt, sulfate salt, ammonium salt, or isopropylammonium salt. The composition may also comprise a mixture of L-glufosinate, PPO, and D-glufosinate, wherein L-glufosinate is the principal compound. In other words, L-glufosinate is present in the composition in an amount greater than about 50 wt.% (e.g., greater than about 55 wt.%, greater than about 60 wt.%, greater than about 65 wt.%, greater than about 70 wt.%, greater than about 75 wt.%, greater than about 80 wt.%, greater than about 85 wt.%, greater than about 90 wt.%, or greater than about 95 wt.%).

[0096] The purified L-glufosinate described herein is a composition applicable to crop fields for the prevention or control of weeds. The composition can be formulated as a liquid for field spraying. L-glufosinate is present in the composition in an effective amount. As used herein, an effective amount refers to about 10 g of active ingredient per hectare to about 1,500 g of active ingredient per hectare, for example, about 50 g to about 400 g or about 100 g to about 350 g. In some embodiments, the active ingredient is L-glufosinate. For example, the amount of L-glufosinate in the composition may be about 10 g, about 50 g, about 100 g, about 150 g, about 200 g, about 250 g, about 300 g, about 350 g, about 400 g, about 450 g, about 500 g, about 550 g, about 600 g, about 650 g, about 700 g, about 750 g, about 800 g, about 850 g, about 900 g, about 950 g, about 1,000 g, about 1,050 g, about 1,100 g, about 1,150 g, about 1,200 g, about 1,250 g, about 1,300 g, about 1,350 g, about 1,400 g, about 1,450 g, or about 1,500 g L-glufosinate per hectare.

[0097] The herbicide compositions described herein (including concentrates that require dilution before application to plants) comprise L-glufosinate (i.e., the active ingredient), optionally some residual D-glufosinate and / or PPO, and one or more adjuvant components in liquid or solid form.

[0098] Compositions are prepared by mixing the active ingredient with one or more adjuvants (e.g., diluents, enrichments, carriers, surfactants, organic solvents, humectants, or conditioning agents) to obtain compositions in the form of finely granulated solids, pellets, solutions, dispersions, or emulsions. Therefore, the active ingredient can be used with adjuvants such as finely granulated solids, organically derived liquids, water, wetting agents, dispersants, emulsifiers, or any suitable combination of these. From an economic and convenience standpoint, water is the preferred diluent. However, not all compounds are resistant to hydrolysis, and in some cases, it may be necessary to use a non-aqueous solvent medium, as understood by those skilled in the art.

[0099] Optionally, one or more additional components may be added to the composition to produce a formulated herbicide composition. Such formulated compositions may include L-glufosinate, a carrier (e.g., a diluent and / or solvent), and other components. The formulated composition contains an effective amount of L-glufosinate. Optionally, L-glufosinate may be present in the form of L-glufosinate. The amount of L-glufosinate present may be 10% to 30% of the weight of the formulated composition. For example, the amount of L-glufosinate present may be 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, or 30% of the weight of the formulated composition. Optionally, L-glufosinate is present in an amount of 12.25% or 24.5% of the weight of the formulated composition.

[0100] In some instances, the formulated composition may include one or more surfactants. Suitable surfactants for use in the formulated composition include sodium alkyl ether sulfate. The surfactant may be present in an amount of 10% to 40% by weight of the formulated composition. For example, the surfactant may be present in an amount of 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, or 40% by weight of the formulated composition. Optionally, sodium alkyl ether sulfate may be present in an amount of 11.05%, 15.8%, 22.1%, or 31.6% by weight of the formulated composition.

[0101] The formulated composition may optionally include one or more solvents (e.g., organic solvents). Optionally, the solvent may be 1-methoxy-2-propanol, dipropylene glycol, ethylene glycol, and mixtures thereof. The amount of one or more solvents present may be 0.5% to 20% of the weight of the formulated composition. For example, the total amount of solvent in the composition may be 0.5% to 18%, 5% to 15%, or 7.5% to 10% of the weight of the formulated composition.

[0102] Optionally, the solvent comprises a combination of two solvents. For example, the solvent in the formulation may include 1-methoxy-2-propanol and dipropylene glycol. For example, 1-methoxy-2-propanol may be present in an amount of 0.5% to 2% by weight of the formulated composition. For example, 1-methoxy-2-propanol may be present in an amount of 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0% by weight of the formulated composition. Optionally, 1-methoxy-2-propanol may be present in an amount of 0.5% or 1.0% by weight of the formulated composition. The amount of dipropylene glycol present may be 4% to 18% by weight of the formulated composition. For example, the amount of dipropylene glycol present may be 4%, 6%, 8%, 10%, 12%, 14%, 16% or 18% of the weight of the prepared composition. Optionally, the amount of dipropylene glycol present may be 4.3% or 8.6% of the weight of the prepared composition.

[0103] The formulated composition may also include one or more polysaccharide humectants. Examples of suitable polysaccharide humectants include, for example, alkyl polysaccharides, pentoses, high-fructose corn syrup, sorbitol, and molasses. The amount of polysaccharide humectants such as alkyl polysaccharides present in the formulated composition may be 4%-20% by weight of the formulated composition. For example, the total amount of polysaccharide humectants in the composition may be 4%-18%, 4.5%-15%, or 5%-10% by weight of the formulated composition. In some examples, the total amount of polysaccharide humectants such as alkyl polysaccharides present in the formulated composition may be 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, or 18% by weight of the formulated composition. Optionally, alkyl polysaccharides may be present in an amount of 3.2%, 4.9%, 6.2%, or 9.8% by weight of the formulated composition.

[0104] The formulated composition may also include a diluent. Suitable diluents include water and other aqueous components. Optionally, the diluent is present in an amount essential to produce the composition ready for packaging or use.

[0105] In one example, the formulated composition comprises 12.25% L-glufosinate by weight of the formulation; 31.6% sodium alkyl ether sulfate by weight of the formulation; 1% 1-methoxy-2-propanol by weight of the formulation; 8.6% dipropylene glycol by weight of the formulation; 9.8% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 36.75% water by weight of the formulation.

[0106] In another example, the formulated composition comprises 24.5% L-glufosinate by weight of the formulation; 31.6% sodium alkyl ether sulfate by weight of the formulation; 1% 1-methoxy-2-propanol by weight of the formulation; 8.6% dipropylene glycol by weight of the formulation; 9.8% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 36.75% water by weight of the formulation.

[0107] In another example, the formulated composition comprises 12.25% L-glufosinate by weight of the formulation; 15.8% sodium alkyl ether sulfate by weight of the formulation; 0.5% 1-methoxy-2-propanol by weight of the formulation; 4.3% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 62.25% water by weight of the formulation.

[0108] In another example, the formulated composition comprises 24.5% L-glufosinate by weight of the formulation; 22.1% sodium alkyl ether sulfate by weight of the formulation; 1% 1-methoxy-2-propanol by weight of the formulation; 6.2% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 46.2% water by weight of the formulation.

[0109] In another example, the formulated composition comprises 12.25% L-glufosinate by weight of the formulation; 22.1% sodium alkyl ether sulfate by weight of the formulation; 1% 1-methoxy-2-propanol by weight of the formulation; 6.2% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 58.45% water by weight of the formulation.

[0110] In another example, the formulated composition comprises 12.25% L-glufosinate by weight of the formulation; 11.05% sodium alkyl ether sulfate by weight of the formulation; 0.5% 1-methoxy-2-propanol by weight of the formulation; 3.1% alkyl polysaccharide by weight of the formulation; and water. In some embodiments, the formulated composition comprises 73.1% water by weight of the formulation.

[0111] The total amount of water can vary and will depend in part on the quantity and amount of other components in the formulated composition. Other components applicable to the compositions provided herein are described in U.S. Patent Nos. 4,692,181 and 5,258,358, the entire contents of which are incorporated herein by reference.

[0112] The compositions formulated herein, particularly liquids and soluble powders, may contain one or more surfactants as additional adjuvant components, in an amount sufficient to readily disperse the given composition in water or oil. Incorporating surfactants into compositions significantly enhances their effectiveness. Surfactants used herein include wetting agents, dispersants, suspending agents, and emulsifiers. Anionic, cationic, and nonionic agents can be used in the same manner.

[0113] Suitable wetting agents include alkylbenzenes and alkylnaphthalene sulfonates, sulfated fatty alcohols, amines or amides, long-chain esters of sodium isothiosulfate, esters of sodium sulfosuccinate, sulfated or sulfonated fatty acid ester petroleum ether sulfonates, sulfonated vegetable oils, ditert-tert-acetylenic glycols, polyoxyethylene derivatives of alkylphenols (especially isooctylphenol and nonylphenol), and polyoxyethylene derivatives of mono-higher fatty acid esters of hexyl alcohols (e.g., sorbitan). Exemplary dispersants include methylcellulose, polyvinyl alcohol, sodium lignin sulfonate, polymeric alkylnaphthalene sulfonate, sodium naphthalene sulfonate, polymethylene bisnaphthalene sulfonate, and sodium N-methyl-N-(long-chain acid) laurate.

[0114] A water-dispersible powder composition comprising one or more active ingredients, an inert solids filler, and one or more wetting agents and dispersants can be prepared. The inert solids filler is typically mineral-derived, such as natural clay, diatomaceous earth, and synthetic minerals derived from silica. Examples of such fillers include kaolinite, palygorskite clay, and synthetic magnesium silicate. The water-dispersible powder described herein may optionally comprise about 5 to about 95 parts by weight of the active ingredient (e.g., about 15 to 30 parts by weight of the active ingredient), about 0.25 to 25 parts by weight of the wetting agent, about 0.25 to 25 parts by weight of the dispersant, and about 4.5 to about 94.5 parts by weight of the inert solids filler, all parts being based on the weight of the total composition. If necessary, about 0.1 to 2.0 parts by weight of the inert solids filler may be replaced with a corrosion inhibitor or an antifoaming agent, or both.

[0115] Aqueous suspensions can be prepared by dissolving or mixing water-insoluble active ingredients together and grinding them in the presence of a dispersant to obtain a concentrated slurry with extremely fine particles. The resulting concentrated aqueous suspension is characterized by its extremely small particle size, thus providing very uniform coverage when diluted and sprayed.

[0116] Emulsifiable oils are typically solutions of active ingredients in solvents that are immiscible or partially immiscible with water, as well as surfactants. Suitable solvents for the active ingredients described herein include hydrocarbons and water-immiscible ethers, esters, or ketones. Emulsifiable oil compositions typically contain about 5 to 95 parts of the active ingredient, about 1 to 50 parts of the surfactant, and about 4 to 94 parts of the solvent, all based on the total weight of the emulsifiable oil.

[0117] The compositions formulated herein may also contain other additives, such as fertilizers, phytotoxicants and plant growth regulators, pesticides, etc., used as adjuvants or in combination with any of the adjuvants described above. The compositions formulated herein may also be mixed with other materials, such as fertilizers, other phytotoxic agents, etc., and applied in a single application.

[0118] In each of the formulation types described herein, such as liquid and solid formulations, the concentration of the active ingredient may be the same.

[0119] In some embodiments, the composition may comprise 2-oxoglutaric acid as a major component. 2-oxoglutaric acid is an important dicarboxylic acid and a key intermediate in the tricarboxylic acid cycle and amino acid metabolism. 2-oxoglutaric acid can be isolated from the reaction mixture by methods such as those described in French Patent No. 07199, which is incorporated herein by reference. 2-oxoglutaric acid compositions can be formulated with pharmaceutical excipients and carriers, food additives, or components for forming biomaterials. As described in Li et al., Bioprocess Biosyst Eng, 39:967-976 (2016), 2-oxoglutaric acid compositions can be used in a variety of applications, including for the synthesis of pharmaceuticals, food additives, and biomaterials.

[0120] Well-established herbicide compositions can be used in combination with other herbicides. The herbicide compositions described herein are typically applied in combination with one or more other herbicides to control a wider range of undesirable plants. When used in combination with other herbicides, the compounds claimed in this invention can be formulated with, mixed in containers with, or applied sequentially with other herbicides. Some herbicides that can be used in combination with the herbicide compositions described herein include: amide herbicides, such as chlorpyrifos, 6-arylpyridinecarboxylate, flubutyroxypyr, chlorpyrifos, bensulfuron-methyl, brobutyroxypyr, chlorpyrifos, CDEA, sedge, 6-cyclopropylpyridinecarboxylate, tricyclosmetrol, thiamethoxam, thiamethoxam-P, chlorpyrifos, triazolylsulfuron, ethamazolylsulfuron, tetrazolylsulfuron, flumetsulam, flumetsulam, halosafen, butamidazole, isoxaflutole, naphthylchlor, chlorpyrifos, clethodim, chlorpyrifos, chlorpyrifos, chlorpyrifos, and chlorpyrifos; and acetochlor herbicides, such as butyroxypyr, chlorpyrifos, chlorpyrifos, and chlorpyrifos. Acetylmethrin, cyclopropamide, pyrfluthrin, ethoxybenzamide, dioxaflutole, fluthiamethoxam, pyrfluthrin, benzylmethrin, flusulfanilamide, oxazolidinylmethrin, naphthylmethrin, metolachlor, flupyrfluthrin, and propargite; arylalylalanine herbicides, such as acetochlor, isopropoxyl-methyl, and isopropoxyl-M; chlorpyrifos herbicides, such as acetochlor, metolachlor, butachlor, butenazol, isobutachlor, acetochlor, metolachlor, pyrazole, isopropoxyl, S-metolachlor, propachlor, chlorpyrifos, isopropoxyl, propargite, propargite, propargite, terbutaline, metolachlor, and methylbenzylmethrin; sulfonylurea herbicides, for example... Examples of herbicides include: etoxazole, fensulfuron, pyrimisulfan, and fluazinam; sulfonamide herbicides, such as sulfadiazine, fensulfuron, dioxaflutole, and amosulfuron; antibiotic herbicides, such as phosphonopropylamine; benzoic acid herbicides, such as dicamba, dicamba, 2,3,6-TBA, and chlorpyrifos; pyrimidinyloxybenzoic acid herbicides, such as pyrimethanil and pyrimethanil; pyrimidinylthiobenzoic acid herbicides, such as pyrimisulfan; phthalic acid herbicides, such as dimethoate; pyridinecarboxylic acid herbicides, such as chlorpyrifos, pyrimethanil, and chlorpyrifos; quinoline carboxylic acid herbicides, such as dichloroquinoline and quinoxalic acid; and arsenic-containing herbicides, such as dimethylarsine and CM. A. DSMA, hexafluorophosphate, MAA, MAMA, MSMA, potassium arsenite and sodium arsenite; benzoylcyclohexanedione herbicides, such as mesotrione, sulfadiazine, terbufenozide and cyclosulfonone; benzofuranylalkyl sulfonate herbicides, such as furazolidone and ethoxysulfuron; carbamate herbicides, such as sulfadiazine, terbufenozide, chlorpyrifos, benzylamine, dioxin, terbufenozide and terbufenozide; phenylaminocarbamate herbicides, such as abamectin, BCPC, chlorpyrifos, chlorfenapyr, CEPC, chlorpyrifos, chlorfenapyr, CPPC, betaine, betaine, betaine, methyl thiophanate, chlorfenapyr and swep;Cyclohexene oxime herbicides, such as quizalofop-P-ethyl, butyrazosulfuron-methyl, clethodim, cyclobutyrazosulfuron-methyl, thiamethoxam, cyclobutyrazosulfuron-methyl, clethodim, pyrazosulfuron-methyl, and styrazosulfuron-methyl; cyclopropylisoxazole herbicides, such as isoxaflutole and isoxaflutole; dicarboxim herbicides, such as pyrimethanil, indole-methyl, flumethrin, flumiclorac, propyzamide, and flumipropyn; dinitroaniline herbicides, such as diflubenzuron, diflubenzuron, dichlorvos, diflubenzuron, isoxaflutole, methapropalin, sulfadiazine, sulfadiazine, dimethyl propargyl, dimethyl propargyl, cyprofluthrin, and trifluralin; dinitrophenyl Phenolic herbicides, such as dilormetrol, proponitrophenol, pendimethalin, dilormetrol, terlibutrol, DNOC, nitrophenol, and dilormetrol; diphenyl ether herbicides, such as fluroxypyr; nitrophenyl ether herbicides, such as fenvalerate, benzalkonium chloride, methyl methoxypyr, methoxypyr, fenvalerate, acetamiprid, fenvalerate, acetamiprid, fluroxypyr, flufenoxuron, halosafen, quizalofop-p-ethyl, fenvalerate, trifluralin, and ethoxyfluralin; aminodithiocarbamate herbicides, such as dazomet and fenvalerate; halogenated aliphatic herbicides, such as alarac, trichloropropionic acid, cyhalofop-p-ethyl, tetrafluoropropionic acid, hexachloroacetone, iodomethane, and methyl bromide. Alkane, monochloroacetic acid, SMA, and TCA; imidazolinone herbicides, such as imazalil, methoxyfenozide, methyl methazine, metribuzin, quinalazine, and imazalazine ethionate; inorganic herbicides, such as ammonium aminosulfonate, borax, calcium chlorate, copper sulfate, ferrous sulfate, potassium azide, potassium cyanate, sodium azide, sodium chlorate, and sulfuric acid; nitrile herbicides, such as bromofenozide, bromobenzyl, hydroxydimethalin, dimethomorph, carbamate, iodofenozide, and bispyribac-methyl; organophosphorus herbicides, such as acephate, sphagnum molybdate, dimethomorph, phosmet, 2,4-DEP, DMPA, EBEP, phosmet, glyphosate, and piperazine; phenoxy herbicides, such as thiamethoxam. Herbicides such as chlorfenapyr, 2,4-DEB, 2,4-DEP, pendimethalin, disul, sphagnum moss, fenteracol, and trifopsime; phenoxyacetic acid herbicides such as 4-CPA, 2,4-D, 3,4-DA, MCPA, MCPA-thioethyl, and 2,4,5-T; phenoxybutyric acid herbicides such as 4-CPB, 2,4-DB, 3,4-DB, MCPB, and 2,4,5-TB; and phenoxypropionic acid herbicides such as hydroxychloroquine, 4-CPP, D-propionic acid, 3,4-DP, thiamethoxam, chlorophenoxypropionic acid, and methylchloropropionic acid.Aryloxyphenoxypropionic acid herbicides, such as quizalofop-p-ethyl, clofop, cyclofluorophosphate, dichlorophenoxyphenoxypropionic acid, oxadiazon, fenoxaprop-P, thiamethoxam, pyrifluquinazon, quizalofop-p-ethyl, fluazinam, haloxyfop-P-methyl, oxadiazon, oxadiazon, oxadiazon, quizalofop-P-methyl, quizalofop-P-methyl, and trifluorophenoxypropionic acid; phenylenediamine herbicides, such as dichlorophenoxyacetic acid and aminopropoxyacetic acid; pyrazolyl herbicides, such as imidacloprid, pyrazosulfuron, sulfadiazon, benzalkonium chloride, sulfonylpyrazosulfuron, and bensulfuron-methyl; pyrazolylphenyl herbicides, such as isopyrazosulfuron and pyraflufen; pyridazine herbicides, such as pyridafol, pyridafol, and pyridafol; pyridazine ketone herbicides... Herbicides, such as bromoxynil, chlorpyrifos, dimidazon, flupyridaben, dimethoate, chlorpyrifos, and pydanon; pyridine herbicides, such as chlorpyrifos, iodochlor, pyrimethanil, fluthion, fluroxypyr, fluroxypyr, flupyridine, flupyridine, flupyridine, chlorpyrifos, thiamethoxam, and triclopyralid; pyrimidine diamine herbicides, such as isochlor and pyrimethanil; quaternary ammonium herbicides, such as bensulfuron-methyl, diethyl sulfadiazine, fenvalerate, diquat, fenvalerate, and paraquat; thiocyanate-formic acid herbicides, such as butyrate, chlorpyrifos, oat chlorpyrifos, EPTC, quizalofop-p-ethyl, chlorpyrifos, thiamethoxam, quizalofop-p-ethyl, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos Wild valerate and vemothion; thiocarbonate herbicides, such as dimethoate, EXD, and chlorpyrifos; thiourea herbicides, such as metribuzin; triazine herbicides, such as triazine flumethrin, triazine flumethrin, and cyanuric acid; chlorpyrifos herbicides, such as atrazine, clopyralid, cypermethrin, cyclomethanone, glycyrrhizin, cyprofen, cyprofen, cyprofen, cyprofen, cyprofen, cyprofen, terbutaline, and cyprofen; methoxytriazine herbicides, such as atrazine, methamidophos, cypermethrin, cyprofen, cyprofen, cyprofen, cyprofen, cyprofen, and terbutaline; methyl thiotriazine herbicides, such as atrazine, azidophos, cypermethrin, dimethophos, chlorpyrifos, cyprofen, cyprofen, cyprofen, and terbutaline; triazinone herbicides, such as methamidophos, methamidophos, cyprofen, and cyprofen. Benazirone and cyprodinil; triazole herbicides, such as cyprodinil, cyprodinil, triazine, and flumetsulam; triadimefon herbicides, such as azoxystrobin, benzosulfuron, carfentrazone, flumetsulam, propanil, metsulfuron, and thiamethoxam; triazinpyrimidine herbicides, such as chlorpyrifos, dichlorvos, diflusulfuron, pyrimisulfuron, sulfadiazine, penoxsulam, and methoxysulfuron; uracil herbicides, such as flupropamidol, chlorpyrifos, flupropacil, isocillin, cyclopyridoxine, and terbusulfuron; 3-phenyluracil; urea herbicides, such as thiamethoxam, bensulfuron, cyclopyridoxine, chlorpyrifos, flupyrazole, isoxaflurium, isoxaflurium, thiazolyl, terbusulfuron, and terbusulfuron;Phenylacetylurea herbicides, such as anisuron, clodinafop-methyl, chlorobromopropylate, ethoxysulfuron, chlorpyrifos, fenfluroxyfen, oxychlorfenapyr, oxazolidinone, diuron, fenugreek, fenfluroxyfen, flusulfuron, isoproturon, linuron, metribuzin, methyl chlorpyrifos, pyranolol, succinyl sulfadiazine, methoxysulfuron, chlorpyrifos, metribuzin, fenfluroxyfen, para-fenfluroxyfen, succinyl sulfadiazine, cyclohexane, tetraflurium, and thiabendazole; pyrimidinylsulfonylurea herbicides, such as pyrimidinylsulfuron and tetrazolium sulfadiazine. Herbicides such as sulfadiazine, bensulfuron-methyl, chlorpyrifos, cyprosulfuron-methyl, ethoxysulfuron, pyrimisulfuron, flupyrsulfuron, flupyrsulfuron, formamidosulfuron, halosulfuron, essulfuron, mesosulfuron-methyl, nicosulfuron, pyrimethanil, epoxysulfuron, flupyrsulfuron, pyrimisulfuron, sulfadiazine, sulfonylsulfuron, sulfonylsulfuron, and triflupyrsulfuron; triazine sulfonylurea herbicides, such as chlorsulfuron, ethersulfuron, azoxysulfuron, iodosulfuron, mesosulfuron, flusulfuron, and thiophenesulfuron. Herbicides such as sulfadiazine, bensulfuron, flusulfanilamide, and triflusulfuron; thiamethoxam herbicides such as butiamethoxam, sulfadiazine, butiamethoxam, thiamethoxam, and thiamethoxam; and unclassified herbicides such as acrolein, allyl alcohol, chlorpyrifos, pyrazosulfuron, chlorpyrifos, bentazon, cypermethrin, thiamethoxam, calcium cyanamide, chlorpyrifos, chlorfenapyr, fluazinam, cyprodinil, cyprodinil, cyprodinil, cyprodinil, cyprodinil, CPMF The herbicide compositions of the present invention can also be used in combination with glyphosate, dicamba, or 2,4-D on glyphosate-resistant, dicamba-resistant, flupyrfluthrin, fluroxypyr, furazolidone, methyl methacrylate, indomethacin, metribuzin, methyl isothiocyanate, pyrchlorpyrifos, OCH, propyzoxystrobin, oxadiazon, oxadiazon, pentachlorophenol, oxadiazon, phenylmercuric acetate, glyphosate, methyl thiosulfate, pyrimidin, cyclomethonium, cyproconazole, thiocyanate, azoxystrobin, thiamethoxam, thiamethoxam, thiamethoxam, trimethylolpropionate, indomethacin, and glyphosate. The herbicide compositions of the present invention can also be used in combination with glyphosate, dicamba, or 2,4-D on glyphosate-resistant, dicamba-resistant, or 2,4-D-resistant crops. It is generally preferred to use the compositions described herein in combination with herbicides that are selective to the treated crops and supplement the weed spectrum controlled by these compositions at the applied rates. Furthermore, it is generally preferred to apply the compositions described herein and other supplemental herbicides as a combination formulation or as a tank mix.

[0121] IV. Instructions for Use

[0122] The compositions described herein can be used in methods for selectively controlling weeds in fields or any other areas, including, for example, railways, lawns, golf courses, and other areas where weed control is desired. Optionally, the fields or other areas may contain planted seeds or crops resistant to L-gluphosphorus. The method may include applying an effective amount of the composition containing L-gluphosphorus described herein to the field.

[0123] The compositions described herein can be used in crop fields to prevent or control weeds. The compositions can be formulated as liquids for field spraying. L-glufosinate is present in the composition in an effective amount. As used herein, an effective amount refers to about 10 g of active ingredient per hectare to about 1,500 g of active ingredient per hectare, for example, about 50 g to about 400 g or about 100 g to about 350 g. In some embodiments, the active ingredient is L-glufosinate. For example, the amount of L-glufosinate in the composition may be about 10 g, about 50 g, about 100 g, about 150 g, about 200 g, about 250 g, about 300 g, about 350 g, about 400 g, about 500 g, about 550 g, about 600 g, about 650 g, about 700 g, about 750 g, about 800 g, about 850 g, about 900 g, about 950 g, about 1,000 g, about 1,050 g, about 1,100 g, about 1,150 g, about 1,200 g, about 1,250 g, about 1,300 g, about 1,350 g, about 1,400 g, about 1,450 g, or about 1,500 g of L-glufosinate per hectare.

[0124] V. Exemplary Implementation

[0125] Non-restrictive implementation schemes include:

[0126] 1. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamic acid, wherein the separation of L-glufosinate is facilitated by converting glutamic acid to pyroglutamic acid, the method comprising:

[0127] The L-glufosinate composition containing L-glufosinate and glutamic acid is reacted at an elevated temperature for a sufficient time to convert most of the glutamic acid into pyroglutamic acid; and

[0128] The L-glufosinate was separated from the pyroglutamic acid and other components of the composition to obtain a substantially purified composition of L-glufosinate (90% or more of the total of L-glufosinate, glutamic acid and pyroglutamic acid).

[0129] 2. The method of implementation scheme 1, wherein a portion of the initial glutamic acid in the composition is first separated from L-glufosinate by crystallization and filtration, and then the glutamic acid is converted into pyroglutamic acid.

[0130] 3. The method of implementation scheme 2, wherein the isolated glutamate is recycled into an enzymatic reaction combining D-amino acid oxidase and transaminase.

[0131] 4. The method of implementation scheme 1, wherein ion exchange is used to separate L-glufosinate from pyroglutamic acid.

[0132] 5. The method of implementation scheme 4 further includes contacting L-glufosinate separated by ion exchange with methanol to precipitate inorganic salts.

[0133] 6. The method of implementation scheme 1, wherein size exclusion chromatography is used to separate L-glufosinate from pyroglutamic acid.

[0134] 7. The method of embodiment 1, wherein the increased temperature includes a temperature of 120°C to 180°C.

[0135] 8. The method of implementation scheme 1, wherein the sufficient time period includes at least 2 hours.

[0136] 9. The method of implementation scheme 8, wherein the sufficient time period includes 2 hours to 18 hours.

[0137] 10. A method for purifying L-glufosinate, comprising converting excess glutamic acid to pyroglutamic acid to facilitate the separation of L-glufosinate, the method comprising:

[0138] The L-glufosinate composition containing L-glufosinate and glutamate was reacted for a sufficient time in the presence of glutamine acyl-peptide cyclase to convert most of the glutamate to pyroglutamic acid; and

[0139] The L-glufosinate was separated from the pyroglutamic acid and other components of the composition to obtain a substantially purified composition of L-glufosinate (90% or more of the total of L-glufosinate, glutamic acid and pyroglutamic acid).

[0140] 11. The method of implementation scheme 10, wherein the sufficient time period includes at least 2 hours.

[0141] 12. The method of implementation scheme 11, wherein the sufficient time period includes 2 hours to 18 hours.

[0142] 13. The method of implementation scheme 10, wherein ion exchange is used to separate L-glufosinate from pyroglutamic acid.

[0143] 14. The method of implementation scheme 13 further includes contacting L-glufosinate separated by ion exchange with methanol to precipitate inorganic salts.

[0144] 15. The method of implementation scheme 10, wherein size exclusion chromatography is used to separate L-glufosinate from pyroglutamic acid.

[0145] 16. A method for obtaining purified succinic acid as a byproduct from a method for preparing L-glufosinate, the method comprising:

[0146] Using the amino group from glutamic acid present in the composition, PPO is amination to L-glufosinate by transaminase (TA), thereby producing 2-oxoglutaric acid byproduct.

[0147] The L-glufosinate composition containing L-glufosinate, glutamic acid and 2-oxoglutarate is reacted at an elevated temperature for a sufficient period of time to convert most of the glutamic acid into pyroglutamic acid.

[0148] 2-Oxopramic acid was separated from the composition by ion exchange to obtain a composition of substantially purified 2-oxopramic acid; and

[0149] The substantially purified 2-oxoglutaric acid was contacted with hydrogen peroxide to obtain a composition of substantially purified succinic acid.

[0150] 17. The method of embodiment 10 or 16, wherein a portion of the initial glutamic acid in the composition is first separated from L-glufosinate by crystallization and filtration, and then the glutamic acid is converted into pyroglutamic acid.

[0151] 18. The method of implementation scheme 17, wherein an acid is added to crystallize glutamic acid.

[0152] 19. The method of embodiment 18, wherein the acid is selected from sulfuric acid, hydrochloric acid, phosphoric acid, formic acid and acetic acid.

[0153] 20. The method of embodiment 18, wherein the composition is heated to an elevated temperature before, during, or after the addition of the acid.

[0154] 21. The method of embodiment 20, wherein the elevated temperature ranges from about 35°C to about 90°C.

[0155] 22. The method of embodiment 20, wherein the elevated temperature ranges from about 40°C to about 80°C.

[0156] 23. The method of embodiment 20, wherein the elevated temperature ranges from about 50°C to about 70°C.

[0157] 24. The method of embodiment 20, wherein the composition is cooled to a temperature below 25°C after heating.

[0158] 25. The method of embodiment 24, wherein the temperature ranges from about -5°C to about 15°C.

[0159] 26. The method of embodiment 24, wherein the temperature ranges from about 0°C to about 10°C.

[0160] 27. The method of implementation scheme 17, wherein the isolated glutamate is recycled into an enzymatic reaction combining D-amino acid oxidase and transaminase.

[0161] 28. The method of embodiment 1 or 16, wherein the elevated temperature includes a temperature of 120°C to 180°C.

[0162] 29. The method of implementation scheme 10 or 16, wherein the sufficient time period includes at least 2 hours.

[0163] 30. The method of implementation scheme 29, wherein the sufficient time period includes 2 hours to 18 hours.

[0164] 31. The method of embodiment 1 or 16, wherein the pH of the composition is adjusted to <7 by adding an acid before heating to an elevated temperature.

[0165] 32. The method of embodiment 31, wherein the acid is selected from sulfuric acid, hydrochloric acid and phosphoric acid.

[0166] 33. The method of embodiment 31, wherein the pH is adjusted to approximately pH 1 to approximately pH 6.

[0167] 34. The method of embodiment 31, wherein the pH is adjusted to approximately pH 2 to approximately pH 5.

[0168] 35. The method of embodiment 31, wherein the pH is adjusted to approximately pH 3 to approximately pH 4.

[0169] 36. The method of any one of embodiments 1, 10 and 16, wherein the base is added to the composition prior to the ion exchange step.

[0170] 37. A method for obtaining purified succinic acid as a byproduct from a method for preparing L-glufosinate, the method comprising:

[0171] Using the amino group from glutamic acid present in the composition, PPO is amination to L-glufosinate by transaminase (TA), thereby producing 2-oxoglutaric acid byproduct.

[0172] The L-glufosinate composition containing L-glufosinate, glutamic acid and 2-oxoglutarate is reacted at an elevated temperature for a sufficient period of time to convert most of the glutamic acid into pyroglutamic acid.

[0173] 2-Oxopramic acid was separated from the composition by size exclusion chromatography to obtain a composition of substantially purified 2-oxopramic acid; and

[0174] The substantially purified 2-oxoglutaric acid was contacted with hydrogen peroxide to obtain a composition of substantially purified succinic acid.

[0175] 38. The method of embodiment 37, wherein an alkali is added to the composition prior to the size exclusion step.

[0176] 39. The method of embodiment 36 or embodiment 38, wherein the base is selected from sodium hydroxide, potassium hydroxide and ammonium hydroxide.

[0177] 40. The method of embodiment 36 or embodiment 38, wherein the pH of the composition is adjusted to about pH 2 to about pH 8.

[0178] 41. The method of embodiment 36 or embodiment 38, wherein the pH of the composition is adjusted to about pH 3 to about pH 7.

[0179] 42. The method of embodiment 36 or embodiment 38, wherein the pH of the composition is adjusted to about pH 4 to about pH 6.

[0180] 43. The method of embodiment 36 or embodiment 38, wherein the resulting composition is processed by a membrane separator.

[0181] 44. The method of embodiment 36 or embodiment 38, wherein the composition is cooled to a temperature below about 25°C, held for a sufficient period of time, and then filtered.

[0182] 45. The method of implementation scheme 44, wherein the temperature does not exceed about 20°C.

[0183] 46. ​​Method 44 of the implementation scheme, wherein the temperature does not exceed about 10°C.

[0184] 47. The method of implementation scheme 44, wherein the temperature does not exceed about 5°C.

[0185] 48. The method of implementation scheme 44, wherein the temperature does not exceed about 0°C.

[0186] 49. The method of implementation scheme 44, wherein the sufficient time period includes at least 1 hour.

[0187] 50. The method of implementation scheme 49, wherein the sufficient time period includes 1 hour to 24 hours.

[0188] 51. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange is carried out by contacting the composition with an anion exchange resin or a cation exchange resin.

[0189] 52. The method of embodiment 51, wherein the ion exchange resin comprises a polymer-based crosslinking matrix, the polymer-based crosslinking matrix being made of a monovinyl monomer and a polyethylene crosslinking agent.

[0190] 53. The method of embodiment 52, wherein the monovinyl monomer is styrene and the polyvinyl crosslinking agent is divinylbenzene.

[0191] 54. The method of embodiment 52, wherein the porosity of the ion exchange resin is microporous, mesoporous or macroporous.

[0192] 55. The method of embodiment 52, wherein the ion exchange resin is a gel-type resin.

[0193] 56. The method of embodiment 52, wherein the ion exchange resin has a median particle size of 10 micrometers to 2000 micrometers.

[0194] 57. The method of embodiment 52, wherein the ion exchange resin has a median particle size of 100 micrometers to 1000 micrometers.

[0195] 58. The method of embodiment 52, wherein the ion exchange resin is in the form of beads having a uniform particle size distribution.

[0196] 59. The method of any one or more of embodiments 51-58, wherein the ion exchange resin is a strong anion exchange resin.

[0197] 60. The method of embodiment 59, wherein the anion exchange resin is selected from DOWEX. TM MARATHON TM A,DOWEX TM MONOSPHERE TM 550A, MONOSPHERE TM MSA and DOWEX TM XUR-1525-L09-046, an experimental gel-type, strongly basic anion exchange resin (trimethylamine quaternary ammonium, chloride form) with uniform particle size in the range of 300 micrometers.

[0198] 61. The method of embodiment 59, wherein the anion exchange resin is used in the form of hydroxyl groups.

[0199] 62. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a pH range of 3-8.

[0200] 63. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a pH range of 4-8.

[0201] 64. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a pH range of 5-8.

[0202] 65. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a pH range of 6-7.

[0203] 66. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a temperature range of 20°C to 70°C.

[0204] 67. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a temperature range of 30°C to 60°C.

[0205] 68. The method of any one of embodiments 1, 10 and 16, wherein the ion exchange method is carried out in a temperature range of 40°C to 50°C.

[0206] 69. The method of any one or more of embodiments 51-58, wherein the ion exchange resin is a strong cation exchange resin.

[0207] 70. The method of embodiment 69, wherein the cation exchange resin is used in the form of hydrogen.

[0208] 71. The method of embodiment 69, wherein the cation exchange resin is selected from DOWEX. TM 50WX8, DOWEX TM MONOSPHERE TM 99K / 350, DOWEX TM MONOSPHERE TM C and DOWEX TM MARATHON TM MSC.

[0209] 72. The method of embodiment 69, wherein the ion exchange method is carried out in a pH range of 0.4-7.

[0210] 73. The method of embodiment 69, wherein the exchange method is carried out in a pH range of 0.6-7.

[0211] 74. The method of embodiment 69, wherein the ion exchange method is carried out in a pH range of 1-6.

[0212] 75. The method of embodiment 69, wherein the ion exchange method is carried out in a pH range of 1-4.5.

[0213] 76. The method of embodiment 69, wherein the ion exchange method is carried out in a temperature range of 20°C to 70°C.

[0214] 77. The method of embodiment 69, wherein the ion exchange method is carried out in a temperature range of 30°C to 60°C.

[0215] 78. The method of embodiment 69, wherein the ion exchange method is carried out in a temperature range of 40°C to 50°C.

[0216] 79. The method of any one of embodiments 1, 10 and 16, wherein the composition is concentrated or decolorized or both are performed prior to the ion exchange.

[0217] 80. The method of embodiment 79, wherein the composition is decolorized with activated carbon or activated carbon.

[0218] 81. The method of embodiment 79, wherein the composition is decolorized with a polymer material.

[0219] 82. The method of any one of embodiments 1, 10 and 16, wherein the composition and the ion exchange resin are contacted in a batch mode.

[0220] 83. The method of any one of embodiments 1, 10 and 16, wherein the composition and the ion exchange resin are contacted in a flow mode.

[0221] 84. The method of embodiment 83, wherein the flow mode uses simulated moving bed chromatography.

[0222] 85. The method of embodiment 84, wherein the composition is subjected to a pretreatment adsorption step to remove one or more components from the composition prior to simulated moving bed chromatography.

[0223] 86. A method for regenerating a resin used in any one of embodiments 1, 10, and 16, wherein the resin is contacted with one or more compositions comprising an acid, a base, water, and an inorganic salt.

[0224] 87. The method of embodiment 86, wherein the base is sodium hydroxide.

[0225] 88. The method of embodiment 86, wherein the inorganic salt is selected from sodium chloride, sodium sulfate, ammonium chloride and ammonium sulfate.

[0226] 89. The method of implementation scheme 86, wherein the acid is sulfuric acid.

[0227] 90. The method of embodiment 86, wherein the composition comprises no more than 0.5M sodium hydroxide and no more than 1.5M sodium chloride.

[0228] 91. The method of embodiment 86, wherein the composition comprises no more than 0.1 M sodium hydroxide and no more than 1.5 M sodium chloride.

[0229] 92. Method 86 of the embodiment, wherein the composition comprises no more than 0.5M sodium chloride.

[0230] 93. The method of embodiment 86, wherein the composition comprises no more than 0.5 M sodium sulfate.

[0231] 94. The method of embodiment 86, wherein the regeneration produces a substantially purified solution of 2-oxoglutaric acid.

[0232] 95. The method of embodiment 94, wherein a solution of substantially purified 2-oxoglutaric acid is contacted with hydrogen peroxide to produce substantially purified succinic acid.

[0233] 96. The method of any one of embodiments 1, 10 and 16, wherein the substantially purified L-glufosinate is reduced to obtain a concentrate which can be directly formulated into a herbicide product.

[0234] 97. The method of any one of embodiments 1, 10 and 16, wherein the substantially purified L-glufosinate is concentrated through a point where crystallization or precipitation occurs, and the resulting solid is filtered and dried.

[0235] 98. The method of embodiment 97, wherein a solvent is added before, during, or after the concentration.

[0236] 99. The method of embodiment 98, wherein the solvent is selected from acetone, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1-methyl-2-propanol, 1,2-propanediol, 1,2-ethylenediol, triethylamine, isopropylamine, and ammonium hydroxide.

[0237] 100. The method of any one of embodiments 1, 10 and 16, wherein substantially purified L-glufosinate is concentrated to produce a dry solid.

[0238] 1011. The method of any one of embodiments 1, 10 and 16, wherein substantially purified L-glufosinate is spray-dried.

[0239] 102. The method of any one of embodiments 1, 10 and 16, wherein the substantially purified L-glufosinate fraction is concentrated prior to spray drying.

[0240] 103. The method of any one of embodiments 1, 10 and 16, wherein the formulation component is mixed with substantially purified L-glufosinate prior to spray drying.

[0241] 104. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamic acid, wherein the separation of L-glufosinate is facilitated by converting glutamic acid to pyroglutamic acid, the method comprising:

[0242] Sulfuric acid is added to bring the composition to pH 3.7, thereby crystallizing glutamic acid and removing solid glutamic acid from the composition;

[0243] The composition is reacted at an elevated temperature for a sufficient period of time to convert most of the remaining glutamic acid into pyroglutamic acid.

[0244] Reduce the volume of the composition;

[0245] Add sodium hydroxide until the pH of the composition is between pH 6 and pH 7;

[0246] Cool the composition to 5°C to the freezing point of the mixture (approximately -10 to -20°C), during which time sodium sulfate precipitates;

[0247] Sodium sulfate crystals are filtered from the composition;

[0248] The composition was contacted with an ion exchange resin to remove pyroglutamic acid, yielding a substantially purified L-glufosinate composition; and

[0249] Reduce the volume of the substantially purified L-glufosinate composition.

[0250] 105. The method of embodiment 104, wherein the volume of the substantially purified L-glufosinate composition is reduced to obtain a solid.

[0251] 106. The method of embodiment 104, wherein the volume of the substantially purified L-glufosinate composition is concentrated to an amount suitable for a herbicide formulation.

[0252] 107. The method of embodiment 104, wherein the solid glutamic acid is removed from the composition by filtration or centrifugation.

[0253] 108. The method of embodiment 104, wherein the volume of the composition is reduced by vacuum distillation, membrane separation, evaporation, thin-film evaporation or scraped-film evaporation.

[0254] 109. The method of embodiment 104, wherein the sodium sulfate crystals are filtered from the composition by filtration or centrifugation.

[0255] 110. L-glufosinate form A, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 10.1, 10.8, 16.8, 17.2, 18.3, 20.0, 20.2, 21.2, 21.5, 24.1, 24.3, 25.1, 25.6, 26.9, 28.6, 29.0, 29.7, 29.9, 31.9, 33.4, 33.7, 34.5, 34.9, 35.4, 35.7, 36.1, 36.7, 37.1, 37.5, 38.2 and 39.8°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer.

[0256] 111. The L-glufosinate form A of embodiment 110, wherein the XRPD pattern comprises at least 6 peaks selected from 10.1, 16.8, 18.3, 21.2, 24.1, 24.3, 25.6, 26.9, 28.6, 29.0 and 34.5°2θ, ±0.2°2θ.

[0257] 112. The L-glufosinate form A of embodiment 110, wherein the XRPD pattern comprises at least 10 peaks selected from 10.1, 16.8, 18.3, 21.2, 24.1, 24.3, 25.6, 26.9, 28.6, 29.0 and 34.5°2θ, ±0.2°2θ.

[0258] 113. L-glufosinate form A of embodiment 110, wherein the XRPD pattern is substantially the same as... Figure 1 Consistent.

[0259] 114. L-glufosinate form B, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 10.0, 11.4, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.1, 25.5, 26.1, 26.3, and 26.4. ,27.9,28.2,28.4,28.7,29.2,30.2,30.9,31.6,31.7,32.7,33.0,33.3,34.3,35.2,36.7,37.2,37.4,37.8,38.3,38.7 and 39.3°2θ,±0.2°2θ, as determined using a diffractometer with Cu-Kα rays.

[0260] 115. The L-glufosinate form B of embodiment 114, wherein the XRPD pattern comprises at least six peaks selected from 10.0, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.5, 26.3, 26.4, 29.2, 34.3, 35.2 and 37.4°2θ, ±0.2°2θ.

[0261] 116. The L-glufosinate form B of embodiment 114, wherein the XRPD pattern comprises at least 10 peaks selected from 10.0, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.5, 26.3, 26.4, 29.2, 34.3, 35.2 and 37.4°2θ, ±0.2°2θ.

[0262] 117. L-glufosinate form B of embodiment 114, wherein the XRPD pattern is substantially the same as... Figure 3 Consistent.

[0263] 118. L-glufosinate form C, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 9.1, 10.9, 16.1, 16.8, 17.3, 18.3, 20.1, 21.4, 21.8, 22.4, 22.7, 24.1, 24.9, 25.4, 25.6, 26.1, 26.6, 27.7, 28.3, 28.9, 30.8, 31.9, 32.6, 33.6, 33.9, 35.1, 36.6, 37.1, 37.5, 38.3, 38.9 and 39.7°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer.

[0264] 119. The L-glufosinate form C of embodiment 118, wherein the XRPD pattern comprises at least 6 peaks selected from 9.1, 16.1, 16.8, 17.3, 21.8, 24.1, 24.9, 25.6, 26.1, 28.3 and 28.9°2θ, ±0.2°2θ.

[0265] 120. The L-glufosinate form C of embodiment 118, wherein the XRPD pattern comprises at least 10 peaks selected from 9.1, 16.1, 16.8, 17.3, 21.8, 24.1, 24.9, 25.6, 26.1, 28.3 and 28.9°2θ, ±0.2°2θ.

[0266] 121. The L-glufosinate form C of embodiment 118, wherein the XRPD pattern is substantially the same as... Figure 5 Consistent.

[0267] 122. L-glufosinate form D, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 9.1, 11.6, 13.1, 14.1, 14.4, 16.2, 17.7, 18.2, 18.9, 19.3, 19.7, 21.2, 21.8, 22.4, 23.2, 23.5, 25.3, 25.8, 26.2, 27.2, 28.6, 29.1, 30.0, 30.6, 31.1, 31.6, 32.7, 33.5, 34.4, 34.7, 35.4, 35.9, 36.4 and 37.4°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer.

[0268] 123. The L-glufosinate form D of embodiment 122, wherein the XRPD pattern comprises at least 6 peaks selected from 9.1, 17.7, 18.2, 18.9, 22.4, 23.2, 23.5, 26.2, 33.5 and 36.4°2θ, ±0.2°2θ.

[0269] 124. The L-glufosinate form D of embodiment 122, wherein the XRPD pattern comprises peaks at 9.1, 17.7, 18.2, 18.9, 22.4, 23.2, 23.5, 26.2, 33.5 and 36.4°2θ, ±0.2°2θ.

[0270] 125. The L-glufosinate form D of embodiment 122, wherein the XRPD pattern is substantially the same as... Figure 7 Consistent.

[0271] 126. L-glufosinate hydrochloride form E, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three peaks selected from 13.1, 16.8, 18.2, 19.4, 20.5, 20.9, 21.4, 22.5, 23.4, 25.3, 26.2, 26.5, 26.9, 27.8, 28.1, 30.2, 31.2, 31.5, 32.3, 33.8, 34.4, 35.3, 35.7, 36.3, 36.9, 37.8, 38.2, 38.8 and 39.4°2θ, ±0.2°2θ, as determined using a Cu-Kα diffractometer.

[0272] 127. The L-glufosinate hydrochloride form E of embodiment 126, wherein the XRPD pattern comprises at least 6 peaks selected from 16.8, 18.2, 20.5, 21.4, 22.5, 22.9, 23.4, 25.3, 30.2 and 31.2°2θ, ±0.2°2θ.

[0273] 128. The L-glufosinate hydrochloride form E of embodiment 126, wherein the XRPD pattern comprises at least 10 peaks selected from 16.8, 18.2, 20.5, 21.4, 22.5, 22.9, 23.4, 25.3, 30.2 and 31.2°2θ, ±0.2°2θ.

[0274] 129. The L-glufosinate hydrochloride form E of embodiment 126, wherein the XRPD pattern is substantially the same as... Figure 9 Consistent.

[0275] 130. Solid L-glufosinate, which is amorphous to X-rays.

[0276] The following examples are provided by way of example and are in no way intended to limit the scope of the invention. Example

[0277] Example 1: Deracemate of racemic D / L-glufosinate at a 3L reaction scale

[0278] In this embodiment, the reaction was carried out in a 3L stirred jacketed reactor. The following reagents were added at the start of the reaction: 900 mM D,L-glufosinate, 2700 mM glutamic acid, and 2,535 g of water. After heating to 30°C, the pH was adjusted to 7.8 using approximately 45 g of 3N NaOH. 0.30 g of defoamer AF204 (Sigma-Aldrich) and 0.60 g of catalase dissolved in 10 mL of water were added to the reactor. 188 g of plastic beads were loaded into the reactor, on which 6 g of AC302 DAAO and 0.9 g of E. coli gab T transaminase were fixed, followed by the addition of 400 g of water. During the stirring of the reaction system, oxygen-rich air (35% O2, 65% N2) was introduced at 1.7 VVM (gas volume / reaction mixture volume / min) through two stainless steel jet stones. HPLC analysis of the reaction showed that equilibrium was reached within 10 hours, with an enantiomeric excess of L-glufosinate relative to D-glufosinate greater than 99%, and an L-glufosinate to PPO ratio of 90%:10%. These results indicate that, on a large scale, D / L-glufosinate can be effectively deracetaminated to L-glufosinate using the RgDAAO / EcgabT enzyme pair.

[0279] Example 2: Crystallization of glutamic acid using concentrated hydrochloric acid

[0280] Following a method similar to Example 1, the beads were removed by filtration, and the filtrate was heated to 35°C. Concentrated hydrochloric acid was slowly added to the batch until the pH reached 3.7. The batch was heated to 60°C in a heating bath and maintained for 60 minutes. The heating bath was turned off, and the batch was allowed to cool to ambient temperature overnight. The batch was then cooled to 0°C and maintained for 1 hour. The white precipitate was removed by filtration. NMR analysis determined that the molar ratio of L-gluphosphorus to glutamic acid in the filtrate was 88:12.

[0281] Example 3: Crystallization of glutamic acid using concentrated sulfuric acid

[0282] Following a method similar to Example 1, the beads were removed by filtration, and the filtrate was heated to 35°C. Concentrated sulfuric acid was slowly added to the batch until the pH reached 3.7. The batch was heated to 60°C in a heating bath and maintained for 60 minutes. The heating bath was turned off, and the batch was allowed to cool to ambient temperature overnight. The batch was then cooled to 0°C and maintained for 1 hour. The white precipitate was removed by filtration. NMR analysis determined that the molar ratio of L-gluphosphorus to glutamic acid in the filtrate was 85:15.

[0283] Example 4: Formation of pyroglutamic acid

[0284] Following a method similar to that in Example 2, a portion of the filtrate was heated to 140°C in an autoclave for 3.5 hours. NMR analysis of the reaction sample showed that the molar ratio of L-glufosinate to glutamic acid was 95:5. NMR analysis also confirmed the presence of pyroglutamic acid. No evidence of L-glufosinate decomposition was observed in the NMR results.

[0285] Example 5: Formation of pyroglutamic acid

[0286] Following a method similar to that in Example 3, a portion of the filtrate was further adjusted to pH 3.0 with sulfuric acid. Prior to pH adjustment, the concentration of L-glufosinate was approximately 310 mM. The liquid was then heated to 125°C in an autoclave and maintained at that temperature for 18 hours. NMR analysis of the reaction sample showed a molar ratio of L-glufosinate to glutamic acid of 98:2. NMR analysis also confirmed the presence of pyroglutamic acid. No evidence of L-glufosinate decomposition was observed in the NMR results.

[0287] Example 6: Concentrating the reactants and then forming pyroglutamic acid

[0288] Following a method similar to that in Example 3, the filtrate was concentrated to an L-glucopyranoside concentration of approximately 412 mM by vacuum distillation. The pH of a portion of the concentrated solution was further adjusted to 3.0 using sulfuric acid. The liquid was then heated to 125°C in an autoclave and maintained at that temperature for 18 hours. NMR analysis of the reaction sample showed a molar ratio of L-glucopyranoside to glutamic acid of 98:2. NMR analysis also confirmed the presence of pyroglutamic acid. No evidence of L-glucopyranoside decomposition was observed in the NMR results.

[0289] Example 7: Concentrate the reactants, then cool and precipitate sodium sulfate.

[0290] Following a method similar to that in Example 5, the cyclized reaction mixture was concentrated to an L-glufosinate concentration of approximately 404 mM by vacuum distillation and then cooled to room temperature. A 300 mL fraction of the concentrated solution was transferred to a beaker, and the pH was adjusted to 6.2 by adding 11.7 g of solid sodium hydroxide (97%, Sigma-Aldrich). The beaker was placed in a freezer at -20°C for approximately 4 hours, during which time the entire mixture froze. The beaker was then removed from the freezer and placed in an ice bath at approximately 0°C for approximately 4 hours. During this time, the contents were periodically and gently mixed by hand. The contents of the beaker were filtered through a Buchner funnel pre-cooled to approximately 4°C onto filter paper. The filtrate weighed 247 g and had a volume of 215 mL. The L-glufosinate concentration was approximately 550 mM. After draining all liquid, the total weight of the crystals was 115 g; HPLC analysis of the crystals indicated only trace amounts of L-glufosinate and other organic impurities. A 10-gram sample of the dried crystals was transferred to a beaker and placed in an incubator heated to 45°C. Shortly thereafter, almost all of the crystals were observed to melt. (According to Handbook of Chemistry and Physics (63)...) rd Ed. (1982), RCWeast, Ed.; CRC Press, Inc., Boca Raton, FL; B-150), the melting point of sodium sulfate decahydrate is 32.38℃. Remove the beaker from the incubator and place it in a water bath. Bring the water bath to a boil. Eventually, the liquid in the beaker disappears, leaving a solid. After removing all the liquid from the beaker by evaporation, cool the beaker and weigh the remaining solid. Approximately 4.2 grams of solid remain in the beaker.

[0291] Example 8: Formation and purification of pyroglutamic acid using cation exchange resin (batch mode)

[0292] Following a method similar to Example 1, the beads were removed by filtration, and concentrated HCl was slowly added to the batch until the pH reached 4.0. The white precipitate was removed by filtration. A portion of the filtrate was then heated to 140°C for 4 hours in an autoclave. NMR analysis of the reactant sample showed a conversion rate of >94% for glutamic acid to pyroglutamic acid.

[0293] After cooling to room temperature, add 37% HCl to adjust the pH of the solution to 1. The solution is then rinsed with pre-washed DOWEX solution. TM Treatment with 50WX8 cation exchange resin. During treatment, the solution was mixed with the resin for 30 minutes, after which the resin was separated using a filter. The resin was then washed with water and eluted with 4M NH4OH. The eluent was concentrated under vacuum to a solid containing 90-98% pure L-gluphosphorus and 2-10% glutamic acid, both as their monoammonium salts, as determined by NMR.

[0294] Example 9: Purification using anion exchange resin in a column (flow mode)

[0295] A jacketed glass column with a diameter of 1” and a length of 24” is filled with a strong base anion exchange resin (DOWEX). TM XUR-1525-L09-046, an experimental gel-type, uniformly sized, strongly basic anion exchange resin (trimethylamine quaternary ammonium salt, chloride form, from Dow Chemical Company) converted to the hydroxyl form, with a particle size in the 300 μm range. The resin column was heated to approximately 60°C and washed with water until the pH of the effluent was approximately pH 6. 270 mL of a solution prepared in a manner similar to Example 5 was pumped into the column. Before pumping, the solution was adjusted to pH 6 with NaOH and heated to approximately 60°C. The flow rate was approximately 10.5 mL / min. When the reaction mixture had finished feeding into the column, approximately 900 mL of water was adjusted to pH 6 and fed into the column. Approximately 100 mL of column effluent was collected and discarded as an empty volume, and then 65 fractions of approximately 12 mL each were collected using a fraction collector. The fractions were analyzed by HPLC / UV, and Table 1 below shows the concentrations of L-glufosinate and other components.

[0296] Table 1

[0297]

[0298] The last row in Table 1 shows the HPLC results after fractions 7 to 22 were combined into a single solution of essentially purified L-glufosinate.

[0299] Example 10: Purification of concentrated reactants using anion exchange resin in a column (flow mode)

[0300] The solution was prepared in a manner similar to that of Example 5, except that it was concentrated by vacuum distillation. The volume of the solution was reduced by approximately 2.3 times. The pH of the solution was adjusted to 6.7 using NaOH and heated to approximately 60°C. 270 mL of the solution was fed into a strongly basic anion exchange resin (DOWEX) in a manner similar to that of Example 8. TMXUR-1525-L09-046 is an experimental gel-type, strongly basic anion exchange resin (trimethylamine quaternary ammonium salt, chloride form, from Dow Chemical Company) with a uniform particle size in the 300 μm range, converted to the hydroxyl form. Before feeding this solution, the resin column was heated to approximately 60°C and washed with water until the pH of the effluent was approximately pH 6. The flow rate was approximately 10.5 mL / min. When the reaction mixture was fully fed into the column, approximately 900 mL of water was added to adjust the pH to 6 and fed into the column. Approximately 100 mL of column effluent was collected and discarded as a blank volume, and then 66 fractions of approximately 15 mL each were collected using a fraction collector. The fractions were analyzed by HPLC / UV, and Table 2 below shows the concentrations of L-glufosinate and other components.

[0301] Table 2

[0302]

[0303] The last row in Table 2 shows the HPLC results after fractions 6 to 19 were combined into a single solution of essentially purified L-glufosinate.

[0304] Example 11: Purification of concentrated reactants in a column at 35°C using anion exchange resin (flow mode)

[0305] The solution was prepared using a method similar to that in Example 5. The pH of the solution was adjusted to 6.2 using NaOH, and the solution was heated to approximately 35°C. 270 mL of the solution was fed into a strong base anion exchange resin (DOWEX) using a method similar to that in Example 8. TM MONOSPHERE TM 550A (in hydroxide form, a product of Dow Chemical Company). Before feeding this solution, the resin column was heated to approximately 35°C and flushed with water until the pH of the effluent was approximately pH 7. The flow rate was approximately 5.5 mL / min. When the reaction mixture was fully fed into the column, approximately 1000 mL of water was added to adjust the pH to 7 and fed into the column. Approximately 100 mL of column effluent was collected and discarded as a blank volume. Forty-four fractions of approximately 15 mL each were then collected using a fraction collector. The fractions were analyzed by HPLC / UV, and the concentrations of L-glufosinate and other components are shown in Table 3 below.

[0306] Table 3

[0307]

[0308] The last row in Table 3 shows the HPLC results after fractions 5-15 were combined into a single solution of essentially purified L-glufosinate.

[0309] Example 12: Purification of reactants using anion exchange resin in two columns operating in series at 25°C (flow mode)

[0310] Two 24” columns were filled with a strongly basic anion exchange resin (DOWEX). TM XUR-1525-L09-046, an experimental gel-type, uniformly sized, strongly basic anion exchange resin (trimethylamine quaternary ammonium salt, chloride form, from Dow Chemical Company) converted to the hydroxyl form. The column was maintained at approximately 25°C. Piping and multi-port valves were connected to the inlet of each column to allow the addition of the reaction mixture, pH 6 water, or resin regeneration solution, respectively. Piping and multi-port valves were connected to the outlet of the first column so that fluid exiting the first column could be collected via a fractionation collector or transferred to the inlet of the second column. Both columns were flushed with water at approximately pH 6 until the effluent pH was approximately pH 6. The reaction mixture was prepared and adjusted to approximately pH 6.4 in a manner similar to that of Example 5. Approximately 270 mL of the reaction mixture was pumped into the first column at a flow rate of approximately 10.5 mL / min. After feeding the reaction mixture, approximately 210 mL of pH 6 water was fed into the column; therefore, the total volume fed into the first column was 480 mL. Collect a total of 330 mL of fluid effluent from the first column, approximately 15 mL in each fraction. After collecting the last fraction, set the valve to pump the next 150 mL from the first column to the inlet of the second column. After feeding from the first column to the second column, feed approximately 270 mL of the reaction mixture into the inlet of the second column. After feeding from the first column to the second column, feed approximately 270 mL of the reaction mixture into the inlet of the second column, followed by 600 mL of water at pH 6. Thus, a total volume of 1020 mL of material is fed into the second column. All fluid exiting the second column is collected as fractions of approximately 15 mL each. The fractions collected from both columns are analyzed by HPLC. Table 4 below shows the fractions collected from the first column.

[0311] Table 4

[0312]

[0313] The last row in Table 4 shows the HPLC results after fractions 7 to 15 were combined into a single solution of essentially purified L-glufosinate.

[0314] Table 5 below shows the scores collected from the second column.

[0315] Table 5

[0316]

[0317] The last row in Table 5 shows the HPLC results after fractions 12 to 22 were combined into a single solution of essentially purified L-glufosinate.

[0318] Example 13: Production of purified 2-oxoglutaric acid obtained after anion exchange purification and resin regeneration

[0319] Following a method similar to that in Example 8, after feeding water to the column at pH 6, a solution of 0.1 M sodium hydroxide and 1.5 M sodium chloride was fed into the column at approximately 60 °C and approximately 10.5 mL / min; 88 fractions of 15 mL each were collected. HPLC analysis of the fractions showed that 2-oxoglutaric acid eluted in a very narrow range of fractions, as shown in Table 6 below.

[0320] Table 6

[0321]

[0322] 2-Oxopramic acid was not detected in fraction 44 or any other fraction collected after fraction 44, and was selected for analysis. The amount of 2-oxopramic acid in this experiment exceeded the amount expected in a single ion exchange experiment. Unbound from theoretical constraints, it is possible that the resin was not adequately regenerated prior to this experiment.

[0323] Example 14: Production of succinic acid from 2-oxoglutaric acid obtained by anion exchange purification and resin regeneration.

[0324] A fraction containing 180 mM 2-oxoglutarate was produced following a method similar to that of Example 12. 0.266 mL of this fraction was combined with 1.5 molar equivalents of hydrogen peroxide (0.128 M) and diluted to a total volume of 0.5 mL in a container. The container was shaken at 30°C, and samples were taken approximately every 5 minutes for HPLC analysis. After 10 minutes, approximately 70% of the 2-oxoglutamate had been converted to succinic acid.

[0325] Example 15: Decolorization of the reaction mixture obtained after glutamic acid is converted to pyroglutamic acid

[0326] As described above, different amounts of activated carbon (0.25 wt.%, 0.5 wt.%, 1.0 wt.%, 3.0 wt.%, and 5.0 wt.%) were added to a portion of the reaction mixture obtained by converting glutamic acid to pyroglutamic acid. After mixing for approximately 20 minutes at room temperature, the mixture was pre-washed... The top of the filter was filtered with activated carbon. The resulting filter cake was then washed with water, and the cake and filtrate were combined. Pyroglutamic acid was then used as an internal standard to check the recovery of L-gluphosphorus from the filtrate relative to the untreated sample. Table 7 below shows the recovery and color observation results.

[0327] Table 7

[0328] Activated carbon (wt.%) L-glufosinate recovery (%) Color observation results 0.25 104 Mild orange 0.5 103 Mild orange 1.0 98 Mild orange 3.0 103 Colorless 5.0 98 Colorless

[0329] Example 16: Preparation and characterization of L-glufosinate polymorphs

[0330] Two batches of L-glufosinate were received and used in the studies described below. XRPD analysis of one batch confirmed that the sample was X-ray amorphous. IC analysis of the other batch indicated that the ammonium content in the sample was below stoichiometry.

[0331] The solubility of L-glufosinate was determined, indicating that the material is highly soluble in water and poorly soluble in most organic solvents. Organic / aqueous mixtures readily form oils. Organic solubility in solvents such as dimethyl sulfoxide, dimethylacetamide, and N-methyl-2-pyrrolidone generally remains poor. Trifluoroethanol (TFE) was the only organic solvent showing a solubility >2 mg / mL.

[0332] Different crystallization techniques were used to screen polymorphs of L-glufosinate to modify nucleation and growth conditions, thereby investigating thermodynamic and kinetic conditions. Crystallization techniques included pulping at room temperature and elevated temperatures, evaporation, antisolvent addition / precipitation, and cooling. Kinetic factors such as cooling rate, evaporation rate, or antisolvent addition rate were variable in these experiments. Solvent-based techniques, such as vapor stress and heating the L-glufosinate amorphous material above its glass transition temperature, were also used.

[0333] Attempts were made to modify the solvent systems used during polymorph screening; however, due to limited solubility in most organic solvent systems, water or TFE was often added to improve solubility. Experiments in pure solvents typically consisted of long-term slurries at room temperature or elevated temperatures. Hydrate formation was also investigated through crystallization experiments in water and water-organic systems with different water activities; however, gels and oils were observed in many of these solvent systems. Anhydrous conditions were also investigated to determine whether new forms could be generated under these conditions. In these experiments, the L-glufosinate feedstock was pre-dried with a desiccant to remove any potential residual moisture from the feedstock.

[0334] Because substoichiometric amounts of ammonium were observed in some raw materials, selected crystallization experiments were conducted using an excess of ammonium hydroxide. Similarly, several experiments were performed under acidic conditions using HCl.

[0335] Five unique crystalline L-glufosinate materials were observed during the screening process and named Form A, Form B, Form C, Form D, and Form E, respectively. Forms A and C are clearly metastable forms of L-glufosinate, which tend to transform into Form B. Forms B and D are clearly anhydrous crystalline forms of free L-glufosinate. Form E is clearly an HCl salt of L-glufosinate.

[0336] Rapid cooling (CC): An L-glufosinate solution is prepared at elevated temperatures in a selected solvent or solvent mixture. Once a clear solution is obtained after visual inspection, it is filtered through a 0.2 μm or 0.45 μm syringe filter into a preheated vial. The vial is then capped and immediately placed in a pre-cooled reactor below ambient temperature. Solids are collected by centrifugation or vacuum filtration and analyzed.

[0337] Conversion slurry: Form B, with additional peaks, was pulped in ethanol / water (95 / 5 v / v) for one day at ambient temperature. BIPXAZ (Cambridge Structure Database, version 5.38, November 2016) seed crystals with additional peaks and form D were added, and the mixture was pulped at ambient temperature for an extended period. Solids were collected by centrifugation and filtration, and then analyzed.

[0338] Rapid cooling (FC): An L-glufosinate solution is prepared at an elevated temperature in a selected solvent or solvent mixture. Once a clear solution is obtained after visual inspection, it is filtered through a 0.2 μm or 0.45 μm syringe filter into a preheated vial. The vial is then capped and immediately placed at ambient temperature. The solids are collected by centrifugation or vacuum filtration and analyzed.

[0339] Rapid evaporation (FE): Prepare an L-glufosinate solution at ambient temperature in a selected solvent or solvent mixture. Once a clear solution is visually identifiable, filter it through a 0.2 μm or 0.45 μm syringe filter into a clean vial. Then evaporate the solution at ambient temperature. Collect the solids in a sealed vial for analysis.

[0340] Rotary evaporation: L-glufosinate solutions were prepared in various solvents at ambient temperature. The solutions were filtered into clean vials, and the solvent was removed using a rotary evaporator. The solids were collected in sealed vials and then analyzed.

[0341] Slow cooling: L-glufosinate solutions are prepared in a metal block at elevated temperatures in different solvents or solvent mixtures. Once a clear solution is obtained after visual inspection, it is filtered through a 0.2 μm or 0.45 μm syringe filter into preheated vials. The solution is then allowed to cool slowly to ambient temperature. Solids are collected by centrifugation or vacuum filtration and then analyzed.

[0342] Slurry: L-glufosinate slurry is prepared by adding sufficient solids to a given solvent or solvent mixture at ambient temperature or elevated temperature to produce insoluble solids. The mixture is then stirred in sealed vials at ambient temperature, below ambient temperature, or elevated temperature for an extended period. The solids are collected by centrifugation or vacuum filtration and then analyzed.

[0343] Vapor pressure (VS): The L-glufosinate solid was transferred to a 1-dram vial, which was then placed in a 20 mL vial containing solvent. The 1-dram vial was left uncapped, and the 20 mL vial was capped to induce vapor stress. The vapor pressure experiment was conducted at ambient temperature. The solid was separated by decantation and analyzed.

[0344] Vapor diffusion (VD): A concentrated solution of L-glufosinate is prepared in a metal block at ambient temperature using different solvents or solvent mixtures. Once a clear solution is obtained after visual inspection, it is filtered through a 0.2 μm or 0.45 μm nylon syringe filter and placed into a clean vial. The vial is placed uncapped in a larger vial containing the anti-solvent. The larger vial is capped to allow vapor diffusion to occur. The solid is separated by decantation, collected in a sealed vial, and then analyzed.

[0345] Differential Scanning Calorimetry (DSC): DSC was performed using a Mettler Toledo TGA / DSC 3+. Temperature calibration was performed using NIST-traceable indium. Temperature calibration was also performed using adamantane, phenyl salicylate, indium, tin, and zinc. The sample was placed in a covered aluminum DSC pan, and the weight was accurately recorded. A weighing pan configured as the sample pan was placed on the reference side of the sample cell. The pan cover was punctured before sample analysis. Data were obtained using a heating rate of 10 °C / min over the range of ambient temperature to 350 °C, or by cycling from ambient temperature to -30 °C to 250 °C.

[0346] Modulated DSC data were obtained on a TA Instruments Q2000 differential scanning calorimeter equipped with a refrigerated cooling system (RCS). Temperature calibration was performed using NIST-traceable indium. The sample was placed in an aluminum DSC pan, and its weight was precisely recorded. The pan was covered with a lid perforated with a laser needle, and the lid was rolled up. Data were obtained by placing the weighed, rolled-up aluminum pan on the reference side of the cell, using a modulation amplitude of ±0.08 °C and a period of 60 seconds, with a basic heating rate of 2 °C / min from ambient temperature to 300 °C. The reported glass transition temperature was obtained from the inflection point of the step change in the reversible heat flow versus temperature profile.

[0347] Thermogravimetric (TG) Analysis: TG analysis was performed using a Mettler Toledo TGA / DSC3+ analyzer or a TA Instruments Q5000IR thermogravimetric analyzer. Temperature calibration was performed using phenyl salicylate, indium, tin, and zinc. The sample was placed in an aluminum pan. The sample was sealed, the cap punctured, and then inserted into the TG furnace. The furnace was heated in a nitrogen atmosphere. Data were obtained at a heating rate of 10 °C / min over a range from ambient temperature to 350 °C.

[0348] Nuclear Magnetic Resonance (NMR) Spectroscopy: NMR spectra of the solution were acquired in SSCI using an Agilent DD2-400 spectrometer. Samples were prepared by dissolving a small amount of sample in D2O / TSP-d2. Additional data were acquired in D2O / TSP-d2 or CF3CD2OD by Spectral Data Services, Inc., Champaign, Illinois. Data collection parameters are shown in the first respective figure of the spectra in the Data section of this report.

[0349] Polarized light microscopy (PLM): Polarized light microscopy is performed using an optical microscope with a cross polarizer or a stereo microscope with a first-order red compensator.

[0350] X-ray powder diffraction (XRPD), reflection mode: XRPD patterns were collected using a PANalytical X'Pert PRO MPD diffractometer with a Cu Kα incident beam generated by a long fine-focusing source and a nickel filter. The diffractometer used a symmetrical Bragg-Brentano geometry configuration. Prior to analysis, a silicon sample (NIST SRM 640e) was analyzed to verify that the observed Si 111 peak position was consistent with the NIST-certified position. The sample was prepared as a circular thin layer centered on a silicon zero-background substrate. An anti-scattering slit (SS) was used to minimize background generated by air. Soler slits for the incident and diffracted beams were used to minimize broadening from axial divergence. Diffraction patterns were collected using a scanning position-sensitive detector (X'Celerator) at a distance of 240 mm from the sample and data collection software v.2.2b.

[0351] XRPD, transmission method: XRPD patterns were collected using a PANalytical X'Pert PRO MPD diffractometer, with an incident beam of Cu rays generated by an Optix long fine focusing source. Cu Kα X-rays were focused through the sample and onto the detector using an elliptical graded multilayer mirror. Prior to analysis, a silicon sample (NIST SRM 640e) was analyzed to verify that the observed Si 111 peak position was consistent with the NIST-certified position. The sample was sandwiched between 3 μm thick films for transmission geometry analysis. Beam stop, short antiscattering extension, and antiscattering blades were used to minimize background from air. Soler slits for the incident and diffracted beams were used to minimize broadening from axial divergence. Diffraction patterns were collected using a scan position-sensitive detector (X'Celerator) at a distance of 240 mm from the sample and data collection software v.2.2b.

[0352] 1. Form A

[0353] L-Glufosinate form A is first prepared from an IPA slurry that has been stripped from an aqueous solution. Form A is the most frequently observed material during the study, although it is often observed as a mixture with forms D, C, or X-ray amorphous materials. Form A is generated from several long-term slurries at elevated temperatures or room temperature.

[0354] In one case, form A was isolated from a 7-day slurry in 93 / 7v / v methanol / water. The XRPD pattern of the sample indicated that it was mainly composed of a single-crystal phase. Figure 1 Small additional peaks were observed at a diffraction angle of ~19.0°. This material... 11H NMR spectra were consistent with L-glufosinate and contained chemical shifts consistent with methanol. Ion chromatography analysis indicated an ammonium content of 6.4 wt%, which was less than theoretically expected for a monoammonium salt (9.1 wt%) and slightly less than the received material (7.0 wt%). Thermal analysis of the material was consistent with the anhydrous / unsolvated form. No significant events were observed in DSC prior to a large endothermic reaction at ~123 °C (initial). A significant change in the TGA slope was observed near this temperature, suggesting a potential melting / decomposition event. The thermal behavior of this sample was noted to be remarkably similar to that of L-glufosinate form B. Reanalysis of the sample by XRPD revealed that form A had converted to form B with smaller additional peaks after storage on a desiccant. The results suggest that form A is metastable and prone to conversion.

[0355] A novel form, sample A, was prepared by reacting the received L-glufosinate with a ~1 mole excess of ammonium hydroxide in methanol to form a slurry. However, thermal analysis of this sample ( Figure 2 Consistent with previous analyses, minimal weight loss was observed, followed by a significant weight reduction likely due to material decomposition initiating at ~116°C. A single endothermic reaction was observed, starting at ~119°C. This data suggests a melting / decomposition event.

[0356] 2. Form B

[0357] Form B of L-glufosinate was initially observed from a multi-step crystallization process involving the slurrying of L-glufosinate in IPA / water to form a gel, followed by re-slurrying the gel in acetone at room temperature. Form B was recovered from several slurries, which typically involved organic-water mixtures with high water activity. XRPD patterns of form B were successfully indexed. Figure 3 However, several smaller additional peaks were observed in this pattern. In fact, form B, with smaller additional peaks, is typically observed.

[0358] The characteristic of form B is that 1 H NMR, IC, DSC and TGA. 1 ¹H NMR spectra were consistent with L-glufosinate and no residual organic solvents were observed. Ion chromatography analysis of different forms of sample B showed only trace amounts of ammonium (0.17 wt%), suggesting that form B is not an ammonium salt but a crystalline form of the L-glufosinate zwitterion. Thermal analysis of the samples ( Figure 4 Consistent with the unsolvated / anhydrous crystal form. No significant thermal events were observed prior to the large endothermic event at 123 °C (initial). A significant change in the TGA slope was also observed near this temperature, suggesting a possible melting / decomposition event. No significant changes in the XRPD pattern of the sample were observed after 47 days of storage on a desiccant.

[0359] 3. Form C

[0360] Form C, having a minor form A, was prepared by pressing L-glufosinate with MeOH vapor. The XRPD pattern of form C was indexed; however, several peaks consistent with form A were observed. Figure 5 ). 1 1H NMR spectra were consistent with L-glufosinate; however, ion chromatography showed that the ammonium content was below stoichiometry (6.3 wt%, compared to the theoretical single salt of 9.1 wt% and the received material of 7.0 wt%).

[0361] Samples of form C, containing a minor A form, were stored in a desiccant for 36 days. XRPD analysis of the samples showed a conversion to form B, which contains a minor A form and some minor additional peaks. IC analysis also showed a significant decrease in ammonium content during this period (3.2 wt% compared to the initial 6.3 wt%). These results suggest that form C is metastable and tends to undergo ammonium salt conversion / dissociation during prolonged storage in a desiccant.

[0362] Form C, with minor form A, was successfully re-prepared using vapor stress of MeOH. The new sample... 1 ¹H NMR analysis confirmed the chemical structure of L-glufosinate. Thermal analysis revealed two overlapping broad endothermic peaks at 100 °C and 131 °C. Figure 6 A weight loss of ~10 wt% was observed under endothermic conditions, followed by a gradual weight loss upon continued heating.

[0363] 4. Form D

[0364] Form D is prepared from several slurries obtained from polymorph screening at room temperature or elevated temperatures, typically a mixture with Form A. (By...) 1 1H NMR analysis revealed that the mixture of forms A and D was chemically consistent with L-glufosinate. No significant changes were observed in the XRPD pattern of the sample containing form D plus minor form A after storage on a desiccant.

[0365] Form D was separated from the slurry over three days at 60°C in 50 / 50 v / v TFE / acetone. XRPD pattern of Form D ( Figure 7 The sample was found to be primarily or solely composed of a single crystalline phase. Ion chromatography analysis indicated an ammonium content of 2.3 wt%, significantly lower than the expected content of the theoretical monoammonium salt (9.1 wt%). Based on the present subchemically calculated amount of ammonium, form D is likely the crystalline form of the L-glufosinate zwitterion. Thermal analysis of the sample ( Figure 8 The study showed a consistent gradual weight loss and a slope change around 151 °C, suggesting the initiation of decomposition. A very wide endothermic period was observed, with an initiation at ~140 °C, suggesting a melting / decomposition event occurred.

[0366] 5. Form E

[0367] During the initial screening, form E was observed; this was a sample received as is, and it was a sample crystallized from an aqueous solution of acetone containing HCl. Form E... 1 The 1H NMR spectrum is consistent with L-glufosinate, but a peak shift suggests a potential difference in ionization. IC analysis showed only trace amounts of ammonium and stoichiometric amounts of chloride. The results suggest that form E is not L-glufosinate but rather L-glufosinate HCl.

[0368] 6. Amorphous materials

[0369] X-ray amorphous materials were collected from slurries in solvents such as N-methyl-2-pyrrolidone (NMP), tetrahydrofuran (THF), and 2,2,2-trifluoroethanol (TFE) and maintained at 50-60°C for extended periods (e.g., 12 days). Amorphous L-glufosinate... 1 ¹H NMR analysis was consistent with the structure and showed the presence of a small, unknown peak. Thermal analysis of the material revealed a distinct glass transition temperature (Tg) at ~55 °C.

[0370] It should be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. The scope of the invention will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Where numerical ranges are provided, it should be understood that, unless the context clearly specifies otherwise, each interim value being one-tenth of the lower limit unit, between the upper and lower limits of the range, and any other embodiment or interim value of the range is included within the scope of the invention. The upper and lower limits of these smaller ranges may be independently included within the smaller range and also within the scope of the invention, subject to any expressly excluded limitations within the range. When the range includes one or both limits, the invention also includes ranges excluding any or both of those. Certain ranges are given herein, wherein numerical values ​​are preceded by the terms “about” or “approximately”. The terms “about” and “approximately” are used herein to provide textual support for precise figures preceding them and figures close to or approximating those preceding the term. In determining whether a number is close to or approximates a numerical value of a specific statement, the close to or approximate numerical value can be a number that, in the context in which the number is presented, provides a substantial equivalence to the numerical value of that particular statement. If “X” is a value modified by “about” or “approximately”, then “about X” or “approximately X” generally refers to a value from 0.95X to 1.05X, including, for example, from 0.98X to 1.02X or from 0.99X to 1.01X. Any reference to “about X” or “approximately X” specifically refers to at least the values ​​X, 0.95X, 0.96X, 0.97X, 0.98X, 0.99X, 1.01X, 1.02X, 1.03X, 1.04X, and 1.05X. Therefore, “about X” and “approximately X” are intended to teach and provide written support for a requested limitation, such as “0.98X”.

[0371] All publications, patents, and patent applications cited in this specification are incorporated herein by reference as if each individual publication, patent, or patent application were expressly and individually indicated to be incorporated by reference. Furthermore, each cited publication, patent, or patent application is incorporated herein by reference to disclose and describe the subject matter relating to the cited publication. References to any publication represent its publication prior to the filing date, but should not be construed as an admission that the invention described herein is not entitled to precede that publication by virtue of a prior invention. Additionally, the publication date provided may differ from the actual publication date, which may require independent verification.

[0372] It should be noted that the claims may be drafted to exclude any optional elements. Accordingly, this statement is intended as a preliminary basis for the use of exclusive terms such as "solely" or "only" in conjunction with the recitation or "negative" limitation of the claim elements. It will be apparent to those skilled in the art, upon reading this disclosure, that each individual embodiment described and exemplified herein has discrete elements and features that are readily separable from or combined with features of any of the other several embodiments without departing from the scope or spirit of the invention. Any recounted method may be performed in the order of the recounted events or in any other logically possible order. Although any methods and materials similar to or equivalent to those described herein may also be used in the implementation or testing of the invention, representative exemplary methods and materials are described here.

Claims

1. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamic acid by converting an excess amount of glutamic acid to pyroglutamic acid to facilitate isolation of L-glufosinate, the method comprising: reacting an L-glufosinate composition comprising L-glufosinate and glutamic acid at an elevated temperature for a sufficient time period to convert a substantial amount of the glutamic acid to pyroglutamic acid; and separating L-glufosinate from the pyroglutamic acid and other components of the composition to obtain a substantially purified L-glufosinate composition comprising 90% or more L-glufosinate based on the sum of L-glufosinate, glutamic acid and pyroglutamic acid, wherein ion exchange is used to separate L-glufosinate from pyroglutamic acid.

2. The method of claim 1, wherein a portion of the initial glutamic acid is first separated from L-glufosinate in the composition by crystallization and filtration, and then the glutamic acid in the composition is converted to pyroglutamic acid.

3. The method of claim 2, wherein the separated glutamic acid is recycled to an enzymatic reaction for converting D-glufosinate to L-glufosinate using D-amino acid oxidase and transaminase and glutamic acid.

4. The method of claim 1, wherein the elevated temperature comprises a temperature of 120°C to 180°C.

5. The method of claim 1, wherein the sufficient time period comprises at least 2 hours.

6. The method of claim 5, wherein the sufficient time period comprises 2 hours to 18 hours.

7. A method for purifying L-glufosinate from a composition comprising glutamic acid by converting an excess amount of glutamic acid to pyroglutamic acid to facilitate isolation of L-glufosinate, the method comprising: reacting an L-glufosinate composition comprising L-glufosinate and glutamic acid in the presence of glutaminyl-peptide cyclotransferase for a sufficient time period to convert a substantial amount of the glutamic acid to pyroglutamic acid; and separating L-glufosinate from the pyroglutamic acid and other components of the composition to obtain a substantially purified L-glufosinate composition comprising 90% or more L-glufosinate based on the sum of L-glufosinate, glutamic acid and pyroglutamic acid, wherein ion exchange is used to separate L-glufosinate from pyroglutamic acid.

8. The method of claim 7, wherein the sufficient time period comprises at least 2 hours.

9. The method of claim 8, wherein the sufficient time period comprises 2 hours to 18 hours.

10. The method of claim 1 or 7, further comprising a method for purifying 2-oxoglutaric acid as a byproduct from a method of making L-glufosinate, comprising: aminating PPO to L-glufosinate by transaminase (TA) using an amine group from glutamic acid; separating 2-oxoglutaric acid from the composition by ion exchange to obtain a substantially purified 2-oxoglutaric acid composition; and contacting the substantially purified 2-oxoglutaric acid with hydrogen peroxide to obtain a substantially purified succinic acid composition.

11. The method of claim 1 or 7, wherein a portion of the initial glutamic acid in the composition is first separated from L-glufosinate by crystallization and filtration, and then the glutamic acid is converted into pyroglutamic acid.

12. The method of claim 1 or 7, wherein an acid is added to cause glutamic acid crystallization.

13. The method of claim 12, wherein the acid is selected from sulfuric acid, hydrochloric acid, phosphoric acid, formic acid, and acetic acid.

14. The method of claim 12, wherein the composition is heated to an elevated temperature before, during, or after the addition of the acid.

15. The method of claim 14, wherein the acid is selected from sulfuric acid, hydrochloric acid, and phosphoric acid.

16. The method of claim 14, wherein the pH is adjusted to pH 3 to pH 4.

17. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamic acid, wherein the separation of L-glufosinate is facilitated by converting glutamic acid to pyroglutamic acid, the method comprising: Sulfuric acid is added to bring the composition to pH 3.7, thereby crystallizing glutamic acid and removing solid glutamic acid from the composition; The composition is reacted at an elevated temperature for a sufficient period of time to convert most of the remaining glutamic acid into pyroglutamic acid. Reduce the volume of the composition; Add sodium hydroxide until the pH of the composition is between pH 6 and pH 7; The composition is cooled to 5°C to the freezing point of the mixture, which is -10 to -20°C, during which time sodium sulfate precipitates. Sodium sulfate crystals are filtered from the composition; The composition was contacted with an ion exchange resin to remove pyroglutamic acid and to obtain a composition of substantially purified L-glufosinate. and Reduce the volume of the substantially purified L-glufosinate composition.

18. The method of claim 17, wherein the volume of the substantially purified L-glufosinate composition is reduced to obtain a solid.

19. The method of claim 17, wherein the volume of the substantially purified L-glufosinate composition is concentrated to an amount suitable for a herbicide formulation.

20. The method of claim 17, wherein the solid glutamic acid is removed from the composition by filtration or centrifugation.

21. The method of claim 17, wherein the volume of the composition is reduced by vacuum distillation, membrane separation, evaporation, thin-film evaporation, or scraped-film evaporation.

22. The method of claim 17, wherein the sodium sulfate crystals are filtered from the composition by filtration or centrifugation.

23. The method of claim 1, claim 7 or claim 17, further comprising contacting the L-glufosinate separated by ion exchange with methanol to precipitate the inorganic salt.

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