Method for purifying l-glufosinate

Abstract

To provide a composition and method for isolating L-glufosinate from a composition comprising L-glufosinate and glutamate.SOLUTION: Provided is a method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamate by converting a significant amount of glutamate to pyroglutamate to facilitate isolation of L-glufosinate, the method including the steps of reacting an L-glufosinate composition comprising L-glufosinate and glutamate at an elevated temperature for a sufficient period of time to convert a majority of the glutamate to pyroglutamate, and isolating L-glufosinate from pyroglutamate and other components of the composition to obtain a composition of substantially purified L-glufosinate (90% or more of the sum of L-glufosinate, glutamate, and pyroglutamate).SELECTED DRAWING: None

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS 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, the entire contents of which are incorporated herein by reference.

[0002] Described herein is a method for purifying L-glufosinate. [Background technology]

[0003] The herbicide glufosinate is a nonselective, foliar-applied herbicide that is considered to be one of the safest herbicides from a toxicological or environmental standpoint. Current commercial chemical synthesis methods for glufosinate produce a racemic mixture of L- and D-glufosinate (Duke et al. 2010 Toxins 2:1943-1962). However, L-glufosinate (also known as phosphinothricin or (S)-2-amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid) is much more potent than D-glufosinate (Ruhland et al. (2002) Environ. Biosafety Res. 1:29-37).

[0004] Thus, there is a need for a method to produce only or primarily the active L-glufosinate form.Heretofore, no effective method has been available to produce pure L-glufosinate or to produce a mixture of D- and L-glufosinate enriched in L-glufosinate. Summary of the Invention

[0005] Compositions and methods for isolating L-glufosinate from a composition comprising L-glufosinate and glutamate are provided. The method includes converting glutamate to pyroglutamate, followed by isolating L-glufosinate from pyroglutamate and other components of the composition to obtain substantially purified L-glufosinate. In one embodiment, a composition comprising L-glufosinate and glutamate is exposed to an elevated temperature for a sufficient time to convert glutamate to pyroglutamate, followed by isolating L-glufosinate from pyroglutamate and other components of the composition to obtain substantially purified L-glufosinate. In another embodiment, after converting glutamate to pyroglutamate by enzymatic conversion, pyroglutamate is removed from the composition by ion exchange to obtain a composition comprising substantially purified L-glufosinate. The volume of the composition may be reduced to obtain a concentrated L-glufosinate solution, or a solid L-glufosinate powder. In one embodiment, the purified L-glufosinate is present in the final composition at a concentration of 70% or more, 80% or more, or 90% or more of the total of L-glufosinate, glutamate, and pyroglutamate. In some embodiments, a portion of the glutamate in the starting composition is separated from L-glufosinate by a crystallization process before converting glutamate to pyroglutamate. Also provided herein is a method for isolating 2-oxoglutaric acid (also referred to herein as 2-oxoglutarate) from the composition after removing L-glufosinate. The 2-oxoglutaric acid can be removed, for example, by ion exchange, to obtain a composition of substantially pure 2-oxoglutaric acid, which can then be readily converted to substantially pure succinic acid.

[0006] The methods described herein produce compositions of substantially pure L-glufosinate. In further embodiments, the methods produce compositions of substantially pure 2-oxoglutaric acid. Crystalline forms of the L-glufosinate material are also provided. [Brief description of the drawings]

[0007] [Figure 1] FIG. 1 shows the XRPD pattern of L-glufosinate ammonium form A collected with Cu-Kα radiation. [Diagram 2] 1 shows temperature data collected by thermogravimetry (top line) and differential scanning calorimetry (bottom line) for L-glufosinate ammonium form A. [Diagram 3] 1 shows the XRPD pattern of L-glufosinate form B collected with Cu-Kα radiation. [Figure 4] 1 shows temperature data collected by thermogravimetry (top line) and differential scanning calorimetry (bottom line) for L-glufosinate form B. [Diagram 5] FIG. 1 shows the XRPD pattern of L-glufosinate ammonium form C collected with Cu-Kα radiation. [Figure 6] 1 shows temperature data collected by thermogravimetry (top line) and differential scanning calorimetry (bottom line) for L-glufosinate ammonium form C. [Figure 7] 1 shows an XRPD pattern of L-glufosinate form D collected with Cu-Kα radiation. [Figure 8] 1 shows temperature data collected by thermogravimetry (top line) and differential scanning calorimetry (bottom line) for L-glufosinate form D. [Figure 9] FIG. 1 shows the XRPD pattern of L-glufosinate hydrochloride form E collected with Cu-Kα radiation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Compositions and methods for producing substantially purified compositions of L-glufosinate (also known as phosphinothricin or (S)-2-amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid) are provided. U.S. Patent Application Serial No. 15 / 445,254, filed February 28, 2017 (the "'254 Application"), which is incorporated herein by reference, relates to compositions and methods for producing L-glufosinate. The method involves the oxidative deamination of D-glufosinate to PPO (2-oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid) followed by specific amination of PPO to L-glufosinate using the amine group of one or more amine donors. By combining these two reactions, the proportion of L-glufosinate in racemic glufosinate mixtures can be substantially increased. Thus, the method of the '254 application can use a racemic D- / L-glufosinate mixture as a starting mixture and can convert the inactive D-form to the active L-form. The method of the '254 method produces a composition that includes a mixture of L-glufosinate, PPO, and D-glufosinate, with L-glufosinate being the predominant compound in the mixture of L-glufosinate, PPO, and D-glufosinate. Glutamate (which refers to L-glutamate, D-glutamate, or a combination of the two), also known as glutamic acid (which refers to L-glutamic acid, D-glutamic acid, or a combination of the two), can be present in the composition when glutamate or L-glutamate is used as the amine donor in the amination of PPO to L-glufosinate.

[0009] Separation of L-glufosinate from 2-oxoglutarate, PPO, and glutamic acid in the post-reaction mixture typically requires multiple steps because the chemical structures and properties of these components are very similar. L-glutamic acid poses a major challenge because it is present in higher concentrations than L-glufosinate and is structurally similar to L-glufosinate.

[0010] I. Purification method Provided herein is a method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamate. The method includes converting glutamate to pyroglutamate to facilitate isolation of L-glufosinate. Glutamate can be converted to pyroglutamate by exposing the composition to an elevated temperature for a sufficient time to convert a majority of the glutamate to pyroglutamate (also referred to herein as pyroglutamic acid). See, for example, PCT 2010 / 013242, US 2003 / 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, glutamate can be converted to pyroglutamate by an enzymatic conversion reaction. When the resulting mixture is exposed to a cation exchange resin, glufosinate (and glutamate, if present) typically adsorbs more strongly than pyroglutamic acid. When the resulting mixture is exposed to an anion exchange resin, pyroglutamic acid typically adsorbs more strongly than glufosinate.

[0011] For the non-enzymatic conversion of glutamic acid to pyroglutamic acid, an acidic pH is preferred. If the reaction mixture is not originally acidic, an acid can 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 substance with a pKa<5. See, for example, DE 3920570 C2, which is incorporated herein by reference. The pH can be adjusted to a value of about 0.4 to about 7, a value of about 1.0 to about 6.0, a value of about 2.0 to about 5.0, or a value of about 2.5 to about 3.5.

[0012] As shown, glutamate can be converted to pyroglutamate by exposing the composition to an elevated temperature for a sufficient time to convert most of the glutamate to pyroglutamate. The elevated temperature may 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 may range from about 120°C to about 180°C. Any method suitable for raising the temperature of a material to an elevated temperature as described above may be used and is encompassed in the methods described herein. For example, elevated temperatures can be achieved by heating the mixture or composition in an autoclave under moderate pressure, heating in a neat or high boiling inert solvent using a heating mantle, boiling plate, oil bath, or silicone bath, recirculating fluids in a jacketed reaction vessel, or any other method used to provide heat known to those skilled in the art. The use of a heat gun and an open flame is also encompassed in these methods.

[0013] As used herein, the term "major portion" of an ingredient refers to an amount of at least 50% by weight of that ingredient. For example, the term "major portion" can refer to 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more by weight of the ingredient.

[0014] As used herein, the terms "substantially pure" or "substantially purified," in reference 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 sum of all components present in the composition.

[0015] The conversion of glutamate to pyroglutamate is allowed to proceed for a sufficient time so that most of the glutamate is converted to pyroglutamate. Generally, most of the glutamate is converted in about 2 hours to about 20 hours (e.g., about 2 hours to about 15 hours). That is, the conversion time at high temperature may be about 2 hours or more, about 3 hours or more, about 4 hours or more, about 5 hours or more, about 6 hours or more, about 7 hours or more, about 8 hours or more, about 9 hours or more, about 10 hours or more, about 11 hours or more, about 12 hours or more, about 13 hours or more, about 14 hours or more, about 15 hours or more, about 16 hours or more, about 17 hours or more, about 18 hours or more, about 19 hours or more, or about 20 hours.

[0016] The reaction mixture can be concentrated before or after the conversion of glutamic acid to pyroglutamic acid. Any concentration means known to those skilled in the art can be used (distillation, including vacuum distillation, thin film evaporation, wiped film evaporation, pervaporation, reverse osmosis, etc.). Water and other volatile materials removed by concentration can be recycled for use in the process, if desired. Optionally, the reaction mixture can be concentrated during the conversion of glutamic acid to pyroglutamic acid by removing water vapor and other volatile materials from the reaction mixture, but this mode of operation makes the most efficient use of time and energy.

[0017] After conversion of glutamic acid 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 charcoal (also known as activated carbon), bone charcoal, and the like. Polymeric materials such as those described in U.S. Pat. No. 4,950,332, incorporated herein by reference, or other ion exchange resins can be particularly useful in commercial operations for decolorizing the reaction mixture. Other treatments known to those skilled in the art can be used to decolorize the reaction mixture.

[0018] In one example, after conversion to pyroglutamic acid, various amounts of activated carbon may be added to some of the same reaction mixture. After mixing for about 20 minutes at room temperature, the activated carbon may be filtered on top of a pre-washed bed of Celite®. The filter cake is then washed with water and cake wash combined with the filtrate. In this example, the filtrate is then checked for L-glufosinate recovery relative to the untreated sample using pyroglutamic acid as an internal standard, and the following table shows the recovery and color observations.

[0019] TIFF2024001023000001.tif70169

[0020] In one embodiment, after conversion of glutamic acid to pyroglutamic acid, the reaction mixture may be cooled to a temperature below 20°C. In a preferred embodiment, the reaction mixture is adjusted to about pH 3 using sulfuric acid prior to the reaction, then adjusted to about pH 6 with sodium hydroxide after 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 less). Optionally, the reaction product is concentrated and / or decolorized as described above before cooling. The advantage of this procedure is that sodium sulfate precipitates or crystallizes from the reaction mixture. Solid sodium sulfate, which may be in anhydrous or hydrated form, is substantially pure and can be removed from the reaction mixture by filtration, centrifugation, or any other suitable means known to those skilled in the art of separating solids from liquids. Optionally, seeds of anhydrous or hydrated sodium sulfate can be added to the mixture to initiate crystallization.

[0021] The removal of salts achieved by a combination of evaporation, cooling crystallization and filtration is not particularly efficient when compared to membrane separation. With the great development of technology, membrane separators are used in many industries to achieve various separations, and a general technical description can be found in "Unit Operations of Chemical Engineering", WL McCabe, JC Smith and P. Harriott, sixth edition; McGraw-Hill, 2001; ISBN: 0070393664. Reverse osmosis and ultrafiltration, described in "Ultrafiltration Handbook", M. Cheryan, Technomic Publishing, 1986; ISBN: 0877624569, are examples of membrane separation practiced on an industrial scale. The term "nanofiltration" is used to describe separations using membranes with pores larger than those of reverse osmosis membranes but smaller than those of ultrafiltration membranes. In many applications, the membrane pore size is an important parameter, since the membrane is selected to separate the components of a mixture according to their size difference. US Patent No. 5,447,635, incorporated herein by reference, discloses a membrane separation method to remove salts and other low molecular weight solutes from an aqueous solution of iopamidol, an X-ray contrast agent, and simultaneously concentrate the iopamidol solution.Membrane separation can be used in combination with other unit operations to optimize the purity of product streams.US Patent No. 5,811,581, incorporated herein by reference, discloses a process in which a water stream containing iopamidol is first purified by chromatographic separation, followed by membrane separation, and examples teach that the combined technology can be used to obtain iopamidol in high purity and high yield.

[0022] Either before or after the conversion of glutamic acid to pyroglutamic acid, inorganic salts and some water may be removed from the L-glufosinate mixture using a membrane. The mixture containing L-glufosinate may be pumped through a membrane separator, where inorganic salts and some water pass through the membrane and away from the L-glufosinate mixture. The salt may include the sodium salt of the acid used to adjust the pH prior to the conversion of glutamic acid, e.g., sodium sulfate if sulfuric acid is used to adjust the pH, or sodium chloride if hydrochloric acid is used to adjust the pH. The membrane selected may allow some glutamic acid and / or pyroglutamic acid to pass through along with the salt and water.

[0023] Suitable membranes may be made of natural or synthetic polymers, including but not limited to cellulose, polycarbonate, polyethylene, polypropylene, polysulfone, polylactic acid, polyacrylamide, polyvinylidine, and the like. The polymers may be chemically modified, if desired. Alternatively, ceramic membranes may be used. U.S. Pat. Nos. 3,556,305, 3,556,992, 3,628,669, and 3,950,255 disclose methods for making membranes and their use in separation processes. Standard equipment for membrane separations may be used for membrane separations. Those skilled in the art will recognize that membranes may be used in a number of configurations, including but not limited to flat sheets in a plate and frame configuration or hollow fiber tubes in a shell and tube configuration. Spiral wound membrane modules may be particularly efficient when used for this purpose. US Pat. Nos. 3,228,876, 3,401,798, and 3,682,317 disclose several membrane configurations suitable for commercial operation.

[0024] The L-glufosinate mixture can be pumped through a membrane separator in a single pass or in multiple passes to reach the desired level of desalting and concentration. The resulting desalted and concentrated L-glufosinate mixture can be further purified, if desired.

[0025] L-glufosinate can be isolated from pyroglutamate and other components of the composition to obtain a substantially purified composition of L-glufosinate. 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 more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more of the sum of L-glufosinate, glutamate, pyroglutamate, and other components in the final composition.

[0026] Optionally, glutamate can be converted to pyroglutamate by an enzymatic conversion reaction. See, for example, U.S. Patent No. 3,086,916, which is incorporated herein by reference. In this manner, glutaminyl-peptide cyclotransferase (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 pyroglutamate. The amount of time sufficient for conversion depends on the activity and concentration of the enzyme used in the reaction. Generally, this time will be 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 more.

[0027] In some embodiments, before converting the remaining glutamate to pyroglutamate, a crystallization step can be used to remove a portion of glutamate.In this manner, in the first step, a portion of glutamate 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, 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 5% by weight or more, 10% by weight or more, 15% by weight or more, or 20% by weight or more of the glutamate present can be crystallized and removed from the starting composition.The crystallized glutamate can be reused, for example, in the subsequent enzymatic conversion reaction of D-glufosinate.

[0028] For crystallization, an acid can be added to adjust the pH of the composition to 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). Acids suitable for adjusting the pH include hydrochloric acid, sulfuric acid, trifluoroacetic acid, phosphoric acid, acetic acid, or any other substance with a pKa<5. See, for example, DE 3920570 C2, which is incorporated herein by reference.

[0029] In some cases, the temperature of the composition is carefully controlled. In this manner, the composition can be heated to a temperature of about 30°C, about 35°C, about 40°C, etc., followed by the addition of acid. The acid, for example, concentrated hydrochloric acid or sulfuric acid, is added to a suitable container containing the reaction mixture either continuously or in portions at a slow rate. It is preferable to stir the mixture during the addition of the acid, which can be achieved by any suitable means. When the pH of the mixture exceeds about pH 5, the addition of acid to the mixture after thorough mixing is generally not sensitive to the addition rate, since precipitation or crystallization is generally not observed above pH 5. In the laboratory, the addition of acid at a pH below 5 is performed at a dropwise rate using suitable equipment, where dropwise rate means less than 0.1 mL, less than 0.2 mL, less than 0.3 mL, less than 0.4 mL portions every few seconds, so that glutamic acid crystallization begins before the addition of concentrated hydrochloric acid or sulfuric acid is completed. For example, in a laboratory setting, about 35 mL-40 mL of 10 M sulfuric acid can be added dropwise over a period of time (eg, 15-20 minutes) to a batch having a volume of about 1 L.

[0030] The reaction mixture may then be heated to an elevated temperature of about 35°C to about 90°C (e.g., about 40°C to about 80°C, about 50°C to about 70°C, or about 55°C to about 65°C) and held at the elevated temperature for at least about 20 minutes (e.g., at least about 25 minutes or at least about 30 minutes). In some cases, some of the heat associated with the addition of the acid is not immediately removed, causing the reaction mixture to slowly self-heat. After being held at an elevated temperature as described above, the resulting composition is then slowly cooled to 0°C over time. Optionally, the composition may be cooled to 0°C over a duration of several minutes to several days, and may be held for at least about 30 minutes, about 45 minutes, about 50 minutes, about 60 minutes, several hours, or several days before filtering the reaction product.

[0031] One advantage of the above temperature control is that it produces high purity glutamate crystals that are easy to filter. Optionally, the crystallization process 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 remaining from a previous batch, or glutamic acid crystals present in a continuous crystallizer) to help grow the crystals to a size suitable for easy filtering.

[0032] Another advantage of the above temperature control, more specifically lowering to a 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. The addition of a water-miscible solvent also allows a lower temperature to be achieved without freezing the mixture.

[0033] The present method of crystallizing glutamic acid from a reaction product or starting composition significantly reduces the amount of glutamic acid in solution. Residual glutamic acid in the reaction mixture or composition can be converted to pyroglutamic acid at the elevated temperatures described above. The resulting pyroglutamic acid is easily separated from L-glufosinate in a single ion exchange step (i.e., either cation or anion exchange, not requiring both cation and anion exchange steps) or other separation techniques, resulting in high purity L-glufosinate with low glutamic acid levels.

[0034] In one embodiment, an anion exchange resin is used to purify L-glufosinate from pyroglutamic acid, 2-oxoglutarate, and PPO at ambient or elevated temperatures and slightly basic, neutral, or acidic pH. In some cases, the interaction between L-glufosinate and the anion exchange resin may not be as strong as the interaction between the anion exchange resin and 2-oxoglutarate, PPO, and pyroglutamate, respectively. This difference in interaction behavior can be used to achieve purification of L-glufosinate. In this procedure, the anion exchange resin may be packed into a suitable container, such as a tank or column. In some cases, an aqueous solution of a suitable inorganic base, such as sodium hydroxide or potassium hydroxide, is used to convert the anion exchange resin to the hydroxy form. In some cases, sulfuric acid or an inorganic sulfate or bisulfate is used to convert the anion resin to the sulfate or bisulfate form. The resin is then equilibrated at the desired temperature through external heating (e.g., flowing a heat transfer fluid through the jacket of the vessel) or by pumping a fluid through the vessel 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 glutamic acid crystallization process, optionally concentrated as described above and / or optionally decolorized according to the procedure 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 pumped through the anion exchange resin in the vessel (typically in a downward flow). The effluent leaving the vessel can be collected in portions. The effluent portions containing most of the L-glufosinate can be combined to form a solution of substantially purified L-glufosinate. Without being bound to any particular theory, it is believed that pyroglutamic acid, 2-oxoglutaric acid, PPO, and other impurities interact with the anion exchange resin such that these components move through the column at a different rate than L-glufosinate, thereby allowing substantially purified L-glufosinate to be collected in a separate solution.

[0035] A wide variety of commercially available anion exchange resins can be used to prepare substantially purified L-glufosinate as described above. Examples of suitable resins include those composed of crosslinked copolymer backbones (e.g., those made with monovinyl monomers such as styrene, acrylates, and polyvinyl crosslinkers such as divinylbenzene). U.S. Patents 3,458,976 and 6,924,317, both of which are incorporated herein by reference, disclose other monovinyl monomers and polyvinyl crosslinkers that can be used to generate suitable copolymer backbone materials. Resins made with various porosities, such as microporosity and macroporosity, may also be used. The terms "microporosity" and "macroporosity" refer to the pore size range of the pores in the solid particles. Two common methods for determining pore size are nitrogen adsorption-desorption and mercury porosimetry (see WC Connor et al. 1986 Langmuir 2(2):151-154). Those skilled in the art understand that macroporous materials contain both macropores and mesopores, with mesopores ranging in size from about 20 angstroms to about 500 angstroms, and macropores greater than about 500 angstroms. Microporous materials have micropores that are less than 20 angstroms in size. See PCT / US2016 / 063219, which is incorporated herein by reference. Gel-type resins such as those described in U.S. Pat. Nos. 4,256,840 and 5,244,926, both of which are incorporated herein by reference, are considered microporous and can be used as well. Resin particles in the form of beads, meaning spherical or nearly spherical, are particularly useful in the present method. The beads may be uniform (also known as "monodisperse"), Gaussian, or polydisperse in particle size distribution. "Uniform" or "monodisperse" means that at least 90% by volume of the beads have a particle size that is 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.

[0036] The resin can be converted to an anion exchange resin by functionalizing it with one or more types of amines. One way in which the resin can be functionalized is by reacting the copolymer with a primary amine, a secondary amine, a tertiary amine, an amino alcohol, a polyamine, or ammonia after chloromethylation reaction, as described in U.S. Pat. No. 6,924,317. Anion exchange resins having an anion capacity of about 0.1 to about 4 milliequivalents per gram as measured according to ASTM D2187-94 (reapproved in 2004) are suitable for use in the present method. Resins functionalized with primary and secondary amines are known to those skilled in the art as weak base anion resins. Resins functionalized with tertiary amines and quaternary polyamines are known to those skilled in the art as strong base anion exchange resins and are particularly suitable for use in the present method. In one embodiment, a mixture of strong base anion exchange resin and weak base anion exchange resin is used to produce substantially purified L-glufosinate.

[0037] The size of the resin particles can be selected to achieve purification under acceptable pressure drops in the equipment used for the ion exchange process. The preferred median volume average particle size of the resin particles used in the present method ranges from about 10 microns to about 2000 microns, with a particularly useful range of median diameters from about 100 microns to about 1000 microns. Examples of suitable resins include, but are not limited to, DOWEX™ MARATHON™ A, DOWEX™ MONOSPHERE™ 550A, DOWEX™ MONOSPHERE™ MSA, DOWEX™ XUR-1525-L09-046, laboratory gel type strong base anion resin (Type I) (trimethylamine quaternary ammonium chloride form available from the Dow Chemical Company) with a uniform particle size in the 300 micron range, and others known to those skilled in the art.

[0038] In some cases, high temperatures are utilized for the separation. The reaction mixture fed to the column and the column itself can be maintained at a temperature 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 temperature of the column can be maintained by flowing a heated fluid through a jacketed column, by using a heating mantle applied to the column wall, by maintaining the column in a heated enclosure, or by any other heating means known to those of skill in the art.

[0039] The separation can be carried out at a pH in the range of about pH 0.4 to pH 8, i.e., about pH 0.4, about pH 0.6, about pH 1, about pH 2, about pH 3, about pH 4, about pH 5, about pH 6, about pH 7, or about pH 8. Acids that can be used to adjust the pH include hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, acetic acid, methanesulfonic acid, etc. Bases that can be used to adjust the pH include sodium hydroxide, potassium hydroxide, ammonium hydroxide, etc.

[0040] As is known in the art 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 resins. In such a regeneration process, the resin is treated with one or more solutions to desorb previously adsorbed components from the resin and return the resin to a form suitable for separation. Typically, the solutions contain either an acid or a base and optional inorganic salts such as sodium chloride, sodium phosphate, sodium sulfate, ammonium sulfate, etc. In one embodiment, the anion exchange resin can be regenerated using 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 compositions of caustic brine include sodium hydroxide at a concentration of about 0.01M to about 0.5M and sodium chloride at a concentration of about 0.1M to about 1.5M. Useful compositions of acidic brine include hydrochloric acid at a concentration of about 0.01 M to about 0.5 M and sodium chloride at a concentration of about 0.1 M to about 1.5 M. In some examples, the acidic brine includes sulfuric acid at a concentration of about 0.1 M to about 1.5 M and sodium chloride at a concentration of about 0.1 M to about 1.5 M. Optionally, water adjusted to a pH of 1 with sulfuric acid may be used.

[0041] Certain regeneration methods may be advantageously used in the practice of the methods described herein. The methods used to produce substantially purified L-glufosinate, when combined with an anion exchange resin regeneration method, can also be used to produce substantially purified 2-oxoglutaric acid (also referred to herein as 2-oxoglutarate). By substantially purified 2-oxoglutarate or substantially pure 2-oxoglutarate, it is intended that the amount of 2-oxoglutarate in the final composition is 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more of the total of 2-oxoglutaric acid, L-glufosinate, glutamate, succinic acid, and pyroglutamate in the final composition. After being isolated using the present method, substantially purified 2-oxoglutaric acid can be easily and efficiently converted to succinic acid (used as a food additive and dietary supplement).

[0042] In some cases, substantially purified 2-oxoglutarate can be obtained in high concentrations by purifying L-glufosinate according to the methods described herein. For example, using an aqueous solution of sodium hydroxide and sodium chloride (e.g., an aqueous solution of 0.1 M NaOH and 1.5 M NaCl) as an eluent in a column chromatography method (e.g., using an anion exchange resin) allows for obtaining substantially pure 2-oxoglutarate in high concentrations. 2-oxoglutarate is a by-product of the amination of PPO and cannot be reused in the process described in the '254 application. The 2-oxoglutarate collected in the fractions exiting the column can be converted to succinic acid by contacting the 2-oxoglutarate with an excess of dilute hydrogen peroxide at room temperature. See, for example, A. Lopalco and VJ Stella (2016) J. Pharm. Sci. 105:2879-2885, which is incorporated herein by reference.

[0043] Succinic acid is used in large quantities as an ingredient in or starting material for a wide range of commercial products. The substantially purified succinic acid produced by this method can be further purified, concentrated and / or isolated by means known to those skilled in the art, if desired. By substantially purified succinic acid or substantially pure succinic acid, it is intended that the amount of succinic acid in the final composition is 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more of the total of succinic acid, L-glufosinate, glutamate, 2-oxoglutarate, and pyroglutamate in the final composition.

[0044] In another embodiment, a cation exchange resin may be used to purify L-glufosinate from pyroglutamic acid, 2-oxoglutarate, and PPO. In this embodiment, the procedure may be carried out in two steps. In the first step, the reaction mixture from the glutamic acid cyclization step may 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 of less than about 7.0 (e.g., a pH of 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 may be concentrated and / or decolorized as described above before being mixed with the cation resin. Upon mixing with the resin, L-glufosinate and residual glutamic acid adsorb onto the resin, while 2-oxoglutarate, PPO, and pyroglutamate do not. After a suitable period of time, the liquid containing impurities can be separated from the resin containing L-glufosinate. Optionally, after adsorption of L-glufosinate is complete, the resin may be washed with a suitable liquid, such as water, to remove the residual liquid containing impurities without removing L-glufosinate from the resin.

[0045] In a second step, the resin containing L-glufosinate may be mixed with a water-soluble base, thereby desorbing L-glufosinate from the resin to form a solution of substantially purified L-glufosinate. Suitable bases for removing L-glufosinate from the cationic resin include sodium hydroxide, potassium hydroxide, ammonium hydroxide, isopropylamine, ethanolamine, diethanolamine, and the like. This procedure can be operated in a batch mode, as described above, by contacting the resin with the solution, or in a flow mode, in which the resin is held stationary in a vessel and the solution passes through it. This procedure can be carried out at a suitable temperature, for example, from about 20° C. to about 70° C., i.e., a temperature 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 (hydrochloric acid, sulfuric acid, etc.) or a mixture of an acid and an inorganic salt, as described above.

[0046] Many different types of commercially available cation exchange resins can be used for the above purification. Resins suitable for use as cation exchange resins can be composed of copolymer backbones of various porosities, i.e., microporous or microporous. Gel-type cation exchange resins are also suitable. Suitable resins can have uniform, Gaussian, or polydisperse particle size distributions. Those with bead shape and uniform particle size distributions can be suitable for the present process. The preferred volume mean diameter of the resin particles used in the present process ranges from about 10 microns to about 2000 microns, with a particularly useful median diameter range of about 100 microns to about 1000 microns.

[0047] The resin can be converted to a strong acid cation exchange resin by subjecting it to a sulfonation reaction. Sulfonation occurs when the resin is contacted with various sulfonating agents, such as sulfur trioxide, concentrated sulfuric acid, chlorosulfonic acid, oleum, etc. (see U.S. Pat. Nos. 2,500,149, 2,527,300, and 2,597,439, all of which are incorporated herein by reference). Some resins, such as those containing carboxylic acid monomers, can function as weak acid cation resins (see U.S. Pat. Nos. 4,062,817 and 4,614,751, both of which are incorporated herein by reference). Cation exchange resins with a cation capacity of about 0.1 to about 4 milliequivalents per gram as measured by ASTM D2187-94 (reapproved in 2004) are suitable for use in the present method. Examples of suitable resins include DOWEX™ 50WX8, DOWEX™ MONOSPHERE™ 99K / 350, DOWEX™ MONOSPHERE™ C, DOWEX™ MARATHON™ MSC, and others known to those skilled in the art.

[0048] Those skilled in the art will recognize that multiple vessels containing resin, such as those disclosed in U.S. Pat. No. 4,001,113, can be used for efficient operation of either flow mode in parallel or serial operation. Parallel operation allows for simultaneous purification of the reaction mixture in several similar vessels, each containing an ion exchange resin. In serial operation, the partially purified L-glufosinate solution of undesired purity leaving the vessel of resin is fed to a subsequent vessel containing fresh or regenerated resin to continue the purification process. Immediately after feeding the partially purified L-glufosinate solution to the subsequent vessel, the reaction mixture that was not mixed with the resin is fed to the same vessel. In this way, the position of the reaction mixture is moved to the subsequent vessel. This process is repeated in other vessels in series. In some cases, the used resin is regenerated in some vessels, while the partially purified L-glufosinate solution is fed to fresh or regenerated resin in other vessels. This method is particularly suitable for continuous operation.

[0049] Optionally, a volume of the solution from the ion exchange process containing substantially pure L-glufosinate can be contacted with a water-miscible organic solvent to cause precipitation of inorganic salts. Solvents that may be useful for this purpose include acetone, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1-methyl-2-propanol, 1,2-propanediol, and 1,2-ethanediol. Methanol may be particularly useful in many embodiments. In some embodiments, a volume of the solution obtained from the ion exchange process is contacted with one or more volumes (e.g., four volumes) of methanol, thus forming a sodium sulfate precipitate. The precipitate containing little or no L-glufosinate can be easily removed.

[0050] Chromatographic methods based on molecular size, known as size exclusion or gel filtration chromatography, can also be used to purify L-glufosinate from the reaction mixture. In size exclusion chromatography, a solution is passed through a vessel containing a resin with a particular pore size distribution. Without being bound to any particular theory, solutes that are too large to enter the pores of the resin pass through the vessel relatively quickly, and these solutes are excluded from entering the resin particles. Solutes that are small enough to enter the pores enter the resin particles and therefore remain in the vessel for a long time. In addition to the size of the solutes, other factors, such as solute structure, concentration, the presence of salts, solution pH, etc., can also affect the degree of separation obtained. It is possible that separation of solutes can occur by multimodal interactions with the resin, i.e., a combination of size exclusion and either adsorption or ion exchange or both. A description of this technique can be found in "Modern Size Exclusion Chromatography: Practice of Gel Permeation and Gel Filtration", second edition, A. M. Striegel, et al., John Wiley and Sons, Inc., 2009; ISBN 9780471201724.

[0051] The L-glufosinate mixture can be purified by passing it through a vessel of a suitable size exclusion resin. Components of the mixture that are smaller in size and more compact in shape will have a longer residence time in the vessel compared to L-glufosinate. All of the L-glufosinate or a portion of the L-glufosinate in the mixture will elute from the column before other components, including inorganic salts, pyroglutamic acid, and / or glutamic acid.

[0052] Resins useful for size exclusion chromatography can be prepared as described above for ion exchange resins, with or without functionalization. U.S. Pat. Nos. 3,857,824 and 4,314,032 and British Patent No. GB1135302A disclose additional methods for preparing resin beads for size exclusion chromatography. Suitable resins are available on an industrial scale from several manufacturers, including, but not limited to, Toyopearl® HW-40 (product of Tosoh Bioscience); SEPABEADS® SP825L, DIAION® HP20SS and DIAION® HP2MGL (products of Mitsubishi Chemical Company); and Sephadex® G-10 (product of GE Life Sciences).

[0053] Simulated moving bed chromatography ("SMB") technology can be used in combination with ion exchange or size exclusion resins to produce substantially purified L-glufosinate. SMB has been 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 operations efficiently utilize resins and liquid streams, such as unpurified feed and eluent streams. Another advantage of SMB is that the method can be used for continuous purification of reaction mixtures on an industrial scale. In the SMB technique, several vessels are connected in series to form a continuous loop. Each vessel contains a resin suitable for the separation of the components. Valves and pipes are connected to each vessel for the passage of at least four different types of fluids into or out of each vessel, examples of valves used for this purpose are described in US Pat. No. 6,431,202. These fluids consist of the mixture to be purified, the eluent, the substantially purified fast moving component(s) stream and the substantially purified slow moving component(s) stream. The mixture to be purified and the eluent are inputs to the process (meaning that they are fed separately into separate vessels), while the fast moving and slow moving components are withdrawn from the process. The resins, eluents, temperatures and flow rates used in the SMB are selected so as to obtain a substantially purified product in either the fast moving component stream or the slow moving component stream. Without being bound to any particular theory, this technique utilizes specific interactions between components in a mixture and the resin, resulting in different rates of translation of the components through successive loops, resulting in more efficient utilization of the resin and reduced eluent volumes.In the same manner, methods can be designed such that L-glufosinate can be the fast moving or slow moving component.

[0054] In one embodiment, the SMB separation may be combined with a pretreatment step in which one or more components of the mixture are removed by contacting the mixture with an adsorbent prior to the SMB operation, such removed components include PPO, 2-oxoglutarate, and color bodies.

[0055] In another embodiment, the SMB separation is combined with the membrane separation procedure described above. The membrane separation step can be used to remove inorganic salts and / or water from the solution, if desired. The membrane separation procedure can be carried out before or after the SMB separation.

[0056] The method described herein comprises: 1 About 80% or more (e.g., about 85% or more, about 87% or more, or about 90% or more) of the unreacted glutamic acid is removed as determined by H-NMR, although HPLC and other analytical methods can also be used to determine the percentage.

[0057] The method isolates substantially pure L-glufosinate. Thus, the method produces a substantially pure L-glufosinate composition. The form of L-glufosinate may be crystalline, liquid, oil, or amorphous solid. For example, a substantially pure L-glufosinate composition can be any of the following: a material that is greater than 70% pure L-glufosinate, or that is contaminated with less than 30% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamate, glutamate, or other impurities, other than water, that are present in the starting materials and that are introduced during reaction, heating, or cooling of the material; a material that is greater than 80% pure L-glufosinate, or that is contaminated with less than 20% D-glufosinate, PPO, 2-oxoglutarate, pyroglutamate, glutamate, or other impurities, other than water, that are present in the starting materials and that are introduced during reaction, heating, or cooling of the material; a material that is greater than 85% pure L-glufosinate, or that is contaminated with less than 15% D-glufosinate, PPO, 2-oxoglutarate, Includes materials that are contaminated with pyroglutamate, glutamate, or other impurities, other than water, that are present in the starting materials and that are introduced during the reaction, heating, or cooling of the materials; materials that are greater than 90% pure L-glufosinate or are contaminated with less than 10% pure D-glufosinate, PPO, 2-oxoglutarate, pyroglutamate, glutamate, or other impurities, other than water, that are present in the starting materials and that are introduced during the reaction, heating, or cooling of the materials; or materials that are greater than 95% pure L-glufosinate or are contaminated with less than 5% pure D-glufosinate, PPO, 2-oxoglutarate, pyroglutamate, glutamate, or other impurities, other than water, that are present in the starting materials and that are introduced during the reaction, heating, or cooling of the materials.

[0058] In one embodiment, a volume of the solution from the ion exchange process containing substantially pure L-glufosinate can be reduced to a concentrate that can be directly incorporated into herbicidal products. Any concentration means known to those skilled in the art can be used, such as distillation (including vacuum distillation), thin film evaporation, wiped film evaporation, and membrane-based methods (pervaporation, reverse osmosis, nanofiltration, ultrafiltration, etc.). Water and solvents removed by concentration can be recycled to the process, if desired.

[0059] 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 during the process to aid in evaporation of water, increase the purity of the solid L-glufosinate, increase the yield of substantially purified L-glufosinate, or modify the size and / or shape of the solid particles. Solvents with a solubility in water of at least 10% by weight 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-ethanediol, 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 filtering and drying equipment may be used for this purpose. The water and solvent removed by concentration can be recycled into the process, if desired.

[0060] In another embodiment, a volume of the solution leaving the ion exchange step containing substantially purified L-glufosinate may be concentrated until precipitation or crystallization occurs, and then evaporation of water and other volatiles present may be continued until a substantially dry solid is obtained. One advantage of using this process is that a filtration step is not required. Optionally, a solvent or solvent mixture, such as one that forms an azeotrope with water (including toluene, 1-butanol, t-amyl alcohol, etc.), may be added at any point to aid in the evaporation of water. Optionally, ingredients may be added to modify the size and / or shape of the solid particles, as described above. The solid containing substantially purified L-glufosinate may be obtained as a powder, granular particles, large chunks, or mixtures thereof. Any equipment suitable for carrying out this procedure may be used, including a rotary evaporator (rotovap), a pan-type agitator dryer, a horizontal shaft agitator dryer, etc. Homogenization of the dried solid may be performed as desired. Water and solvent removed during the process may be recycled as desired.

[0061] In another embodiment, a volume of the solution from the ion exchange step containing substantially purified L-glufosinate can be transferred to a spray dryer. The solution can be partially concentrated before being transferred to the spray dryer, and the partially concentrated mixture can be in the form of a solution or, if precipitation or crystallization occurs, in the form of a slurry. The solid obtained after spray drying can be in the form of a powder or granules and contains substantially pure L-glufosinate. In another embodiment, an agent capable of improving the flowability of the dried particles 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.

[0062] II. Solid form A number of solid forms of L-glufosinate, including crystalline and amorphous forms, are also provided herein.

[0063] In some embodiments, there is provided L-glufosinate ammonium Form A. In some embodiments, Form A is characterized by an X-ray powder diffraction (XRPD) pattern including 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 by a diffractometer using Cu-Kα radiation. For example, the XRPD pattern of Form A can include 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.

[0064] In some embodiments, Form A is characterized by an XRPD pattern comprising 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 with a diffractometer using Cu-Kα radiation. In some embodiments, Form A is characterized by an XRPD pattern comprising 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 with a diffractometer using Cu-Kα radiation. In some embodiments, Form A is characterized by an XRPD pattern substantially according to FIG. 1. Form A was analyzed by ion chromatography, as described below, and exhibited a glufosinate:ammonium ratio of about 1.4:1. In some embodiments, Form A is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endotherm with an onset in the range of about 119 to about 123° C. In some embodiments, the DSC curve is substantially according to the DSC curve shown in FIG.

[0065] L-glufosinate ammonium Form A can be prepared according to the following method: In some embodiments, preparing L-glufosinate ammonium Form A includes combining L-glufosinate ammonium 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 ranging from about 20° C. to about 50° C. for a period ranging from 1 hour to 14 days, and isolating Form A from the slurry.

[0066] In some embodiments, L-glufosinate Form B is provided. In some embodiments, Form B is 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, 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 with a diffractometer using Cu-Kα radiation. For example, the XRPD pattern of form B can include 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 of such peaks.

[0067] In some embodiments, Form B is characterized by an XRPD pattern comprising 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 with a diffractometer using Cu-Kα radiation. 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 radiation. In some embodiments, form B is characterized by an XRPD pattern substantially according to Figure 3. Form B was analyzed by ion chromatography as described below, exhibiting a glufosinate:ammonium ratio of about 5.3:1. In some embodiments, form B is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endotherm with an onset at approximately 123° C. In some embodiments, the DSC curve is substantially according to the DSC curve shown in Figure 4.

[0068] L-glufosinate form B can be prepared according to the following method: In some embodiments, preparing L-glufosinate form B includes combining L-glufosinate ammonium with a mixture of a polar solvent and water, maintaining the resulting slurry at a temperature ranging from about 20° C. to about 50° C. for a period ranging from 1 hour to 14 days, and isolating form B from the slurry.

[0069] In some embodiments, there is provided L-glufosinate ammonium Form C. 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 with a diffractometer using Cu-Kα radiation. For example, the XRPD pattern of Form C can include 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 of such peaks.

[0070] In some embodiments, Form C is characterized by an XRPD pattern comprising 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 diffractometer using Cu-Kα radiation. In some embodiments, Form C is characterized by an XRPD pattern comprising 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 diffractometer using Cu-Kα radiation. In some embodiments, Form C is characterized by an XRPD pattern substantially according to FIG. 5. Form C was analyzed by ion chromatography, as described below, and exhibited a glufosinate:ammonium ratio of about 1.4:1. In some embodiments, Form C is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endotherm with an onset at approximately 100° C. and / or an endotherm with an onset at approximately 131° C. In some embodiments, the DSC curve is substantially according to the DSC curve shown in FIG.

[0071] L-glufosinate ammonium form C can be prepared according to the following method: In some embodiments, preparing L-glufosinate ammonium form C includes contacting L-glufosinate ammonium with solvent vapor (e.g., methanol vapor) at a temperature ranging from about 20° C. to about 30° C. for a period ranging from 1 hour to 14 days, and isolating form C.

[0072] In some embodiments, there is provided L-glufosinate form D. 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 with a diffractometer using Cu-Kα radiation. For example, the XRPD pattern of form D can include 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 of such peaks.

[0073] In some embodiments, form D is characterized by an XRPD pattern comprising 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 radiation. In some embodiments, form D is characterized by an XRPD pattern comprising 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 radiation. In some embodiments, form D is characterized by an XRPD pattern substantially according to Figure 7. Form D was analyzed by ion chromatography as described below, and showed a glufosinate:ammonium ratio of about 3.9:1. In some embodiments, Form D is characterized by a differential scanning calorimetry (DSC) curve exhibiting a broad endotherm with an onset at approximately 140° C. In some embodiments, the DSC curve is substantially according to the DSC curve shown in FIG.

[0074] L-glufosinate form D can be prepared according to the following method: In some embodiments, preparing L-glufosinate form D includes combining L-glufosinate ammonium with a mixture of solvents (e.g., methanol, ethanol, trifluoroethanol, isopropanol, acetone, dimethylacetamide, and the like, which are optionally anhydrous), maintaining the resulting slurry at a temperature ranging from about 50° C. to about 60° C. for a period ranging from 1 hour to 14 days, and isolating form D from the slurry.

[0075] In some embodiments, there is provided L-glufosinate hydrochloride form E. 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 with a diffractometer using Cu-Kα radiation. For example, the XRPD pattern of Form E can include 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.

[0076] In some embodiments, Form E is characterized by an XRPD pattern comprising 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 radiation. In some embodiments, Form E is characterized by an XRPD pattern comprising 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 radiation. In some embodiments, Form E is characterized by an XRPD pattern substantially according to Figure 9. Form E was analyzed by ion chromatography to show the stoichiometry of L-glufosinate and chloride, as described below.

[0077] 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 ammonium 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 ranging from about 20° C. to about 30° C. for a period ranging from 1 hour to 14 days, and isolating form E from the mixture.

[0078] III. Composition Also described herein are compositions comprising the above L-glufosinate. In some embodiments, the composition substantially comprises L-glufosinate and an acceptable cationic or anionic salt form, such as sodium salt, potassium salt, hydrochloride salt, sulfate salt, ammonium salt, or isopropylammonium salt. The composition may additionally comprise a mixture of L-glufosinate, PPO, and D-glufosinate, with L-glufosinate being the predominant compound. In other words, L-glufosinate is present in the composition in an amount of more than about 50% by weight (e.g., more than about 55% by weight, more than about 60% by weight, more than about 65% by weight, more than about 70% by weight, more than about 75% by weight, more than about 80% by weight, more than about 85% by weight, more than about 90% by weight, or more than about 95% by weight).

[0079] The purified L-glufosinate described herein can be used in compositions useful for application to crop fields for the prevention or suppression of weeds. The compositions may be formulated as liquids for spraying on fields. The L-glufosinate is included in the composition in an effective amount. As used herein, an effective amount means about 10 grams of active ingredient per hectare to about 1500 grams of active ingredient per hectare, for example, about 50 grams to about 400 grams or about 100 grams to about 350 grams. In some embodiments, the active ingredient is L-glufosinate. For example, the amount of L-glufosinate in the composition can be about 10 grams, about 50 grams, about 100 grams, about 150 grams, about 200 grams, about 250 grams, about 300 grams, about 350 grams, about 400 grams, about 450 grams, about 500 grams, about 550 grams, about 600 grams, about 650 grams, about 700 grams, about 750 grams, about 800 grams, about 850 grams, about 900 grams, about 950 grams, about 1000 grams, about 1050 grams, about 1100 grams, about 1150 grams, about 1200 grams, about 1250 grams, about 1300 grams, about 1350 grams, about 1400 grams, about 1450 grams, or about 1500 grams of L-glufosinate per hectare.

[0080] The herbicidal compositions described herein (including concentrates that require dilution before application to plants) contain L-glufosinate (i.e., the active ingredient), optionally a portion of residual D-glufosinate and / or PPO, and one or more adjuvant ingredients in liquid or solid form.

[0081] The composition is prepared by mixing the active ingredient with one or more auxiliary agents (such as diluents, extenders, carriers, surfactants, organic solvents, moisturizers, or conditioning agents) to produce a composition in the form of finely divided particulate solids, pellets, solutions, dispersions, or emulsions.Accordingly, the active ingredient can be combined with auxiliary agents such as finely divided solids, organic liquids, water, wetting agents, dispersants, emulsifiers, or any suitable combinations thereof.From the viewpoint of economy and convenience, water is the preferred diluent.However, not all compounds are resistant to hydrolysis, and those skilled in the art understand that in some cases, this may dictate the use of non-aqueous solvent media.

[0082] Optionally, one or more additional ingredients can be added to the composition to produce a formulated herbicidal composition. Such a formulated composition may include L-glufosinate, a carrier (e.g., a diluent and / or solvent), and other ingredients. The formulated composition includes an effective amount of L-glufosinate. Optionally, L-glufosinate can be present in the form of L-glufosinate ammonium. L-glufosinate ammonium can be present in an amount ranging from 10% to 30% by weight of the formulated composition. For example, L-glufosinate ammonium can be present in an amount of 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, or 30% by weight of the formulated composition. Optionally, L-glufosinate ammonium is present in an amount of 12.25% or 24.5% by weight of the formulated composition.

[0083] In some examples, the formulated composition may include one or more surfactants. Surfactants suitable 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, the sodium alkyl ether sulfate is present in an amount of 11.05%, 15.8%, 22.1%, or 31.6% by weight of the formulated composition.

[0084] 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 one or more solvents may be present in an amount ranging from 0.5% to 20% by weight of the formulated composition. For example, the total amount of solvents in the composition may be present in an amount ranging from 0.5% to 18%, 5% to 15%, or 7.5% to 10% by weight of the formulated composition.

[0085] Optionally, the solvent comprises a combination of two solvents. For example, the solvent in the formulation can comprise 1-methoxy-2-propanol and dipropylene glycol. The 1-methoxy-2-propanol can be present, for example, in an amount of 0.5% to 2% by weight of the formulated composition. For example, the 1-methoxy-2-propanol can 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, the 1-methoxy-2-propanol is present in an amount of 0.5% or 1.0% by weight of the formulated composition. The dipropylene glycol can be present in an amount of 4% to 18% by weight of the formulated composition. For example, dipropylene glycol can be present in an amount of 4%, 6%, 8%, 10%, 12%, 14%, 16%, or 18% by weight of the formulated composition. Optionally, dipropylene glycol is present in an amount of 4.3% or 8.6% by weight of the formulated composition.

[0086] The formulated composition may also include one or more polysaccharide-based moisturizers. Examples of suitable polysaccharide-based moisturizers include, for example, alkyl polysaccharides, pentoses, high fructose corn syrup, sorbitol, and molasses. The polysaccharide-based moisturizers, such as alkyl polysaccharides, may be present in the formulated composition in an amount ranging from 4% to 20% by weight of the formulated composition. For example, the total amount of polysaccharide-based moisturizers in the composition may be 4% to 18%, 4.5% to 15%, or 5% to 10% by weight of the formulated composition. In some examples, the total amount of polysaccharide-based moisturizers, 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%. Optionally, the alkyl polysaccharide can be present in an amount of 3.2%, 4.9%, 6.2%, or 9.8% by weight of the formulated composition.

[0087] Diluents may also be included in the formulated composition. Suitable diluents include water and other aqueous components. Optionally, the diluent is present in an amount necessary to produce a composition ready for packaging or use.

[0088] In one example, the formulated composition includes L-glufosinate ammonium in an amount of 12.25% by weight of the formulation, sodium alkyl ether sulfate in an amount of 31.6% by weight of the formulation, 1-methoxy-2-propanol in an amount of 1% by weight of the formulation, dipropylene glycol in an amount of 8.6% by weight of the formulation, alkyl polysaccharide in an amount of 9.8% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 36.75% by weight of the formulation.

[0089] In another example, the formulated composition includes L-glufosinate ammonium in an amount of 24.5% by weight of the formulation, sodium alkyl ether sulfate in an amount of 31.6% by weight of the formulation, 1-methoxy-2-propanol in an amount of 1% by weight of the formulation, dipropylene glycol in an amount of 8.6% by weight of the formulation, alkyl polysaccharide in an amount of 9.8% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 36.75% by weight of the formulation.

[0090] In another example, the formulated composition includes L-glufosinate ammonium in an amount of 12.25% by weight of the formulation, sodium alkyl ether sulfate in an amount of 15.8% by weight of the formulation, 1-methoxy-2-propanol in an amount of 0.5% by weight of the formulation, dipropylene glycol in an amount of 4.3% by weight of the formulation, alkyl polysaccharide in an amount of 4.9% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 62.25% by weight of the formulation.

[0091] In another example, the formulated composition includes L-glufosinate ammonium in an amount of 24.5% by weight of the formulation, sodium alkyl ether sulfate in an amount of 22.1% by weight of the formulation, 1-methoxy-2-propanol in an amount of 1% by weight of the formulation, alkyl polysaccharide in an amount of 6.2% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 46.2% by weight of the formulation.

[0092] In another example, the formulated composition includes L-glufosinate ammonium in an amount of 12.25% by weight of the formulation, sodium alkyl ether sulfate in an amount of 22.1% by weight of the formulation, 1-methoxy-2-propanol in an amount of 1% by weight of the formulation, alkyl polysaccharide in an amount of 6.2% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 58.45% by weight of the formulation.

[0093] In another example, the formulated composition includes L-glufosinate ammonium in an amount of 12.25% by weight of the formulation, sodium alkyl ether sulfate in an amount of 11.05% by weight of the formulation, 1-methoxy-2-propanol in an amount of 0.5% by weight of the formulation, alkyl polysaccharide in an amount of 3.1% by weight of the formulation, and water. In some embodiments, the formulated composition includes water in an amount of 73.1% by weight of the formulation.

[0094] The total amount of water may vary and will depend in part on the number and amount of other ingredients in the formulated composition. Additional ingredients suitable for use in the formulated compositions listed herein are described in U.S. Patent Nos. 4,692,181 and 5,258,358, both of which are incorporated herein by reference in their entirety.

[0095] The formulation compositions described herein, particularly liquids and soluble powders, can contain one or more surfactants as additional auxiliary components, in sufficient amounts to make a given composition easily dispersible in water or oil.The incorporation of surfactants into a composition significantly enhances its effectiveness.As used herein, surfactants include wetting agents, dispersing agents, suspending agents, and emulsifying agents.Anionic, cationic, and nonionic agents can be used equally well.

[0096] Suitable wetting agents include alkylbenzene and alkylnaphthalene sulfonates, sulfated fatty alcohols, amines or acid amides, long chain acid esters of sodium isothionate, sodium sulfosuccinate esters, sulfated or sulfonated fatty acid esters of petroleum sulfonates, sulfonated vegetable oils, di-tert-acetylene glycol, polyoxyethylene derivatives of alkylphenols (especially isooctylphenol and nonylphenol), and polyoxyethylene derivatives of mono-higher fatty acid esters of hexitol anhydrides (e.g., sorbitan). Exemplary dispersants include methylcellulose, polyvinyl alcohol, sodium lignin sulfonate, polymeric alkylnaphthalene sulfonates, sodium naphthalene sulfonate, polymethylene bisnaphthalene sulfonates, and sodium N-methyl-N-(long chain acid) laurate.

[0097] Water-dispersible powder compositions can be made containing one or more active ingredients, an inert solid extender, and one or more wetting and dispersing agents. The inert solid extender is usually of mineral origin, such as natural clays, diatomaceous earth, and synthetic minerals derived from silica, etc. Examples of such extenders include kaolinite, attapulgite clay, and synthetic magnesium silicate. The water-dispersible powders described herein can optionally contain 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 a wetting agent, about 0.25 to 25 parts by weight of a dispersing agent, and 4.5 to about 94.5 parts by weight of an inert solid extender, where all parts are by weight of the total composition. Optionally, about 0.1 to 2.0 parts by weight of the solid inert extender can be replaced with a corrosion inhibitor or an antifoaming agent, or both.

[0098] Aqueous suspensions can be prepared by dissolving or mixing together and milling an aqueous slurry of water-insoluble active ingredients in the presence of a dispersing agent to obtain a concentrated slurry of finely divided particles. The resulting concentrated aqueous suspension is characterized by its extremely small particle size and therefore provides very uniform coverage when diluted and sprayed.

[0099] Emulsified oils are typically solutions of active ingredients and surfactants together in a water-immiscible or partially water-immiscible solvent. Suitable solvents for the active ingredients described herein include hydrocarbons and water-immiscible ethers, esters, or ketones. Emulsified oil compositions generally contain about 5-95 parts active ingredient, about 1-50 parts surfactant, and about 4-94 parts solvent, where all parts are by weight based on the total weight of the emulsified oil.

[0100] The formulated compositions described herein may also contain other additives, such as fertilizers, plant harmful substances and plant growth regulators, pesticides, etc., used as adjuvants or in combination with any of the above adjuvants. The formulated compositions described herein may also be mixed with other substances, such as fertilizers, other plant harmful substances, etc., or may be applied as a stand-alone application.

[0101] In each formulation type described herein, e.g., liquid and solid formulations, the concentration of the active ingredient may be the same.

[0102] In some embodiments, the composition can include 2-oxoglutarate as a major component. 2-oxoglutarate is an important dicarboxylic acid and one of the key intermediates in the tricarboxylic acid cycle and amino acid metabolism. 2-oxoglutarate can be isolated from the reaction mixture by methods such as those described in French Patent No. 07199, which is incorporated herein by reference. The 2-oxoglutarate composition can be formulated with pharmaceutical excipients and carriers, food additives, or ingredients used to form biomaterials. The 2-oxoglutarate composition can be used in a wide variety of applications, such as the synthesis of drugs, food additives, and biomaterials, as described in Li et al., Bioprocess Biosyst Eng, 39:967-976 (2016).

[0103] It is recognized that the formulated herbicidal compositions can be used in conjunction with other herbicides. The herbicidal compositions described herein are often applied in conjunction with one or more other herbicides to control a greater variety of unwanted plants. When used in conjunction with other herbicides, the claimed compounds can be formulated with, tank mixed with, or applied sequentially with one or more other herbicides. Herbicides that can be used in conjunction with the formulated herbicidal compositions described herein include amide herbicides (alidochlor, 6-arylpicolinate, beflubutamid, benzadox, benzipram, bromobutide, cafenstrole, CDEA, chlorthiamid, 6-cyclopropylpicolinate, ciprazole, dimethenamid, dimethenamid-P, diphenamid, epronaz, etonipromide, fentrazamide, flupoxam, fomesafen, halosafen, isobutanol, tetrakisamide ... Carbamide, isoxaben, naproxamide, naptalam, petoxamide, propyzamide, quinonamide, and tebutam, etc.), anilide herbicides (chloranocryl, cisanilide, clomeprop, cypromide, diflufenican, etobenzanide, fenashulam, flufenacet, flufenican, mefenacet, mefluidide, metamifop, monalide, naproanilide, pentanochlor, picolinafen, and propanil, etc.), arylalanine herbicides (Benzoylprop, Flamprop and Flamprop-M, etc.), Chloracetanilide Herbicides (Acetochlor, Alachlor, Butachlor, Butenachlor, Delachlor, Diethathyl, Dimethachlor, Metazachlor, Metolachlor, S-Metolachlor, Pretilachlor, Propacchlor, Propisochlor, Prinachlor, Terbuchlor, Thenylchlor and Xylaclor, etc.), Sulfonanilide Herbicides (Benzofluor , perfluidon, pyrimisulfan and profluazole, etc.), sulfonamide herbicides (asulam, carbasulam, phenashulam and oryzalin, etc.), antibiotic herbicides (bialaphos, etc.), benzoic acid herbicides (chloramben, dicamba, 2,3,6-TBA and tricamba, etc.), pyrimidinyloxybenzoic acid herbicides (bispyribac and pyriminobac, etc.), pyrimidinylthiobenzoic acid herbicides (pyrithiobac, etc.), phthalic acid herbicides (chlorthal, etc.),Picolinic acid herbicides (aminopyralid, clopyralid, picloram, etc.), quinoline carboxylic acid herbicides (quinclorac, quinmerac, etc.), arsenical herbicides (cacodylic acid, CMA, DSMA, hexaflurate, MAA, MAMA, MSMA, potassium arsenite, sodium arsenite, etc.), benzoylcyclohexanedione herbicides (mesotrione, sulcotrione, tefuryltrione, tembotrione, etc.), benzofuranyl alkylsulfonate herbicides (benfuresate, ethofumesate, etc.), carbamate herbicides (asulam, carboxazole cloprid, etc.), luprocarb, dichlormate, phenashulam, carbutilate and terbucarb, etc.), carbanilate herbicides (barban, BCPC, carbaslam, carbetamide, CEPC, chlorbufam, chlorpropham, CPPC, desmedipham, phenisofam, phenmedipham, phenmedipham-ethyl, propham and swep, etc.), cyclohexene oxime herbicides (aloxydim, butroxydim, clethodim, cloproxydim, cycloxydim, profoxydim, sethoxydim, tepraloxydim and tralkoxydim, etc.), cyclopro Pyrisoxazole herbicides (isoxachlorthor and isoxaflutole, etc.), dicarboximide herbicides (benzphendizone, cinidon ethyl, flumezin, flumiclorac, flumioxazin and flumipropine, etc.), dinitroaniline herbicides (benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin, isoproparin, methalproparin, nitralin, oryzalin, pendimethalin, prodiamine, profluralin and trifluralin, etc.), dinitrophenol herbicides (dinophenate, dinoprop, di nosamu, dinoseb, dinoterb, DNOC, ethinofen and medinoterb, etc.), diphenyl ether herbicides (ethoxyfen, etc.), nitrophenyl ether herbicides (acifen, aclonifen, bifenox, clomethoxyfen, clomitrofen, etonipromide, fluorodifen, fluoroglycofen, fluoronitrofen, fomesafen, fuliloxifene, halosafen, lactofen, nitrofen, nitrofluorfen and oxyfluorfen, etc.), dithiocarbamate herbicides (dazomet and metam, etc.),Halogenated aliphatic herbicides (arorac, chloropon, dalapon, flupropanate, hexachloroacetone, iodomethane, methyl bromide, monochloroacetic acid, SMA, TCA, etc.), imidazolinone herbicides (imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, etc.), inorganic herbicides (ammonium sulfamate, borax, calcium chlorate, copper sulfate, ferrous sulfate, potassium azide, potassium cyanate, sodium azide, etc.), , sodium chlorate and sulfuric acid, etc.), nitrile herbicides (bromobornyl, bromoxynil, chloroxynil, dichlobenil, iodobornyl, ioxynil and pyraclonil, etc.), organophosphate herbicides (amiprophos-methyl, anilophos, bensulide, bialaphos, butamiphos, 2,4-DEP, DMPA, EBEP, fosamine, glyphosate and piperophos, etc.), phenoxy herbicides (bromofenoxime, clomeprop, 2,4-DEB, 2,4-DEP, di Fenopentene, Disul, Ervon, Ethonipromide, Fenteracol, Trifopsim, etc.), Phenoxyacetic acid herbicides (4-CPA, 2,4-D, 3,4-DA, MCPA, MCPA-thioethyl, 2,4,5-T, etc.), Phenoxybutyric acid herbicides (4-CPB, 2,4-DB, 3,4-DB, MCPB, 2,4,5-TB, etc.), Phenoxypropionic acid herbicides (Cloprop, 4-CPP, Dichlorprop, Dichlorprop-P, 3,4-DP , fenoprop, mecoprop and mecoprop-P, etc.), aryloxyphenoxypropionic acid herbicides (chloradifop, clodinafop, clofop, cyhalofop, diclofop, fenoxaprop, fenoxaprop-P, fentiaprop, fluazifop, fluazifop-P, haloxyfop, haloxyfop-P, isoxapyrifop, metamifop, propaquizafop, quizalofop, quizalofop-P and trifop, etc.), Phenylenediamine herbicides (dinitramine and prodiamine, etc.), pyrazolyl herbicides (benzofenap, pyrazolate, pyrasulfotole, pyrazoxyfen, pyroxasulfone and topramezone, etc.), pyrazolylphenyl herbicides (fluazolate and pyraflufen, etc.), pyridazine herbicides (credazine, pyridafol and pyridate, etc.), pyridazinone herbicides (bromopyrazone, chloridazon, dimidazon, flufenpyr, metoflurazone, norflurazone, oxapyrazone and picanone, etc.), pyridine herbicides (aminopyralid, Cryodinate, clopyralid, dithiopyr, fluroxypyr, haloxyzin, picloram, picolinafen, pyriclor, thiazopyr, and triclopyr, etc.), pyrimidinediamine herbicides (iprimidam and thioclorim, etc.), quaternary ammonium herbicides (cyperquat, diethamquat, difenzoquat, diquat, morphamquat, and paraquat, etc.), thiocarbamate herbicides (butyrate, cycloate, diallate, EPTC, esprocarb, ethiolate, isopolinate, methiobencarb, molinate, orbencal, etc.), Herbicides (e.g., butyl, pebulate, prosulfocarb, pyributicarb, sulfarate, thiobencarb, thiocarbazil, triallate, and vernalate), thiocarbonate herbicides (e.g., dimexano, EXD, and proxan), thiourea herbicides (e.g., methiuron), triazine herbicides (dipropetrine, triaziflam, and trihydroxytriazine), chlorotriazine herbicides (atrazine, chlorazine, cyanazine, cyprazine, eglinazine, ipazine, mesoprazine, procyazine, proglinazin, propazine, sebutylazine, simazine, terbuthylazine, etc.) methionine and triethazine, etc.), methoxytriazine herbicides (atraton, methometon, prometon, secbumeton, simeton and terbumeton, etc.), methylthiotriazine herbicides (ametryn, aziprothrin, cyanatrin, desmetrin, dimethametryn, metoprothrin, prometryn, simetryn and terbutryn, etc.), triazinone herbicides (ametridione, amivudine, hexazinone, isomethiozine, metamitron and metribuzin, etc.), triazole herbicides (amitrole, cafenstrole, epronaz and flupoxam, etc.),Triazolone herbicides (amicarbazone, bencarbazone, carfentrazone, flucarbazone, propoxycarbazone, sulfentrazone, thiencarbazone methyl, etc.), triazolopyrimidine herbicides (cloransulam, diclosulam, florasulam, flumetsulam, metosulam, penoxsulam, piroxsulam, etc.), uracil herbicides (butafenacil, bromacil, flupropacil, isocyl, lenacil, terbacil, etc.), 3-phenyluracil, urea herbicides (benzthiazuron, cumyluron, cicururon, dichloral urea, diflufenzopyr, isonoruron, isouron, methabenzthiazuron, monisouron, and noruron, etc.), phenylurea herbicides (anithuron, buturon, chlorbromuron, chloreturon, chlorotoluron, chloroxuron, dymron, difenoxuron, dimefuron, diuron, fenuron, fluometuron, fluothiuron, isoproturon, linuron, methiuron, methyldymron, metobenzuron, metobromuron, metoxuron, monolinuron, monuron, nebulon, parafluron, fenobenzuron, siduron, tetrafluron, pyrimidinylsulfuron herbicides (amidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron, ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron, foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron, rimsulfuron, sulfometuron, sulfosulfuron, trifloxysulfuron, etc.), triazinylsulfonylurea herbicides (amidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron, ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron, foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron, rimsulfuron, sulfometuron, sulfosulfuron, trifloxysulfuron, etc.), Herbicides (chlorsulfuron, cinosulfuron, ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron, triasulfuron, tribenuron, triflusulfuron, tritosulfuron, etc.), thiadiazolyl urea herbicides (buthiuron, etidimuron, tebuthiuron, thiazafluron, thidiazuron, etc.), and unclassified herbicides (acrolein, allyl alcohol, aminocyclopyrachlor, azaphenidin, benazolin, bentazon, benzobicyclon, butidazole, calcium cyanamide, cambendichlor,Examples of herbicidal agents include chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin, clomazone, CPMF, cresol, orthodichlorobenzene, dimepiperate, endothal, fluoromidine, fluridone, flurochloridone, flurtamone, fluthiacet, indanofan, methazole, methyl isothiocyanate, nipiraclofen, OCH, oxadiargyl, oxadiazon, oxaziclomefone, pentachlorophenol, pentoxazone, phenylmercuric acetate, pinoxaden, prosulfarin, pyribenzoxim, pyriftalid, quinoclamine, rodetanil, sulglicapin, thidiadiamine, tridiphane, trimeturon, tripropindan and tritac. The herbicidal composition of the present invention can also be used in combination with glyphosate, dicamba or 2,4-D on crops that are tolerant to glyphosate, dicamba or 2,4-D. In general, it is preferred to use the compositions described herein in combination with herbicides that are selective to the crop being treated and that complement the spectrum of weeds controlled by these compositions at the application rates used. More generally, it is preferred to apply the compositions described herein and other complementary herbicides simultaneously, either as a combination formulation or as a tank mix.

[0104] IV. How to use The compositions described herein can be used in a method for selectively controlling weeds in agricultural fields or other locations, including, for example, railroad tracks, lawns, golf courses, and other locations where weed control is desired. Optionally, the agricultural field or other location can include a planted species of crop, or a crop that is tolerant to glufosinate. The method can include applying to the agricultural field a composition comprising an effective amount of L-glufosinate as described herein.

[0105] The compositions described herein are useful for application to crop fields to prevent or suppress weeds. The compositions may be formulated as liquids for spraying on fields. L-glufosinate is included in the composition in an effective amount. As used herein, an effective amount means from about 10 grams of active ingredient per hectare to about 1500 grams of active ingredient per hectare, for example, from about 50 grams to about 400 grams or from about 100 grams to about 350 grams. In some embodiments, the active ingredient is L-glufosinate. For example, the amount of L-glufosinate in the composition can be about 10 grams, about 50 grams, about 100 grams, about 150 grams, about 200 grams, about 250 grams, about 300 grams, about 350 grams, about 400 grams, about 500 grams, about 550 grams, about 600 grams, about 650 grams, about 700 grams, about 750 grams, about 800 grams, about 850 grams, about 900 grams, about 950 grams, about 1000 grams, about 1050 grams, about 1100 grams, about 1150 grams, about 1200 grams, about 1250 grams, about 1300 grams, about 1350 grams, about 1400 grams, about 1450 grams, or about 1500 grams of L-glufosinate per hectare.

[0106] V. Illustrative Embodiments Non-limiting embodiments include: 1. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamate by converting glutamate to pyroglutamate to facilitate isolation of L-glufosinate, comprising: reacting an L-glufosinate composition comprising L-glufosinate and glutamate at an elevated temperature for a sufficient period of time to convert a majority of the glutamate to pyroglutamate; isolating L-glufosinate from pyroglutamate and other components of the composition to obtain a substantially purified (i.e., 90% or more of the sum of L-glufosinate, glutamate, and pyroglutamate) composition of L-glufosinate; A method comprising: 2. The method of embodiment 1, wherein a portion of the initial glutamate in the composition is first separated from the L-glufosinate by crystallization and filtration, and then the glutamate is converted to pyroglutamate. 3. The method of embodiment 2, wherein the separated glutamate is recycled to the enzymatic reaction combining D-amino acid oxidase and a transaminase. 4. The method of embodiment 1, wherein isolation of L-glufosinate from pyroglutamate is carried out using ion exchange. 5. The method of embodiment 4, further comprising contacting the L-glufosinate isolated using ion exchange with methanol to precipitate inorganic salts. 6. The method of embodiment 1, wherein isolation of L-glufosinate from pyroglutamate is carried out using size exclusion chromatography. 7. The method of embodiment 1, wherein the elevated temperature is a temperature of from 120°C to 180°C. 8. The method of embodiment 1, wherein the sufficient time is at least 2 hours. 9. The method of embodiment 8, wherein the sufficient time is from 2 hours to 18 hours. 10. A method for purifying L-glufosinate, comprising converting excess glutamate to pyroglutamate to facilitate isolation of L-glufosinate, comprising: reacting an L-glufosinate composition comprising L-glufosinate and glutamate in the presence of glutaminyl-peptide cyclotransferase for a sufficient period of time to convert a majority of the glutamate to pyroglutamate; isolating L-glufosinate from pyroglutamate and other components of the composition to obtain a substantially purified (i.e., 90% or more of the sum of L-glufosinate, glutamate, and pyroglutamate) composition of L-glufosinate; A method comprising:

[0107] 11. The method of embodiment 10, wherein the sufficient time is at least 2 hours. 12. The method of embodiment 11, wherein the sufficient time is from 2 hours to 18 hours. 13. The method of embodiment 10, wherein isolation of L-glufosinate from pyroglutamate is carried out using ion exchange. 14. The method of embodiment 13, further comprising contacting the L-glufosinate isolated using ion exchange with methanol to precipitate inorganic salts. 15. The method of embodiment 10, wherein isolation of L-glufosinate from pyroglutamate is carried out using size exclusion chromatography. 16. A method for obtaining purified succinic acid as a by-product from a process for making L-glufosinate, comprising: aminating PPO to L-glufosinate by a transaminase (TA) enzyme using an amine group of glutamic acid present in the composition to produce a 2-oxoglutaric acid by-product; reacting an L-glufosinate composition comprising L-glufosinate, glutamate, and 2-oxoglutaric acid at an elevated temperature for a sufficient period of time to convert a majority of the glutamate to pyroglutamate; isolating 2-oxoglutaric acid from the composition by ion exchange to obtain a substantially purified composition of 2-oxoglutaric acid; contacting the substantially purified 2-oxoglutaric acid with hydrogen peroxide to obtain a composition of substantially purified succinic acid; A method comprising: 17. The method of embodiment 10 or 16, wherein a portion of the initial glutamate in the composition is first separated from the L-glufosinate by crystallization and filtration, and then the glutamate is converted to pyroglutamate. 18. The method of embodiment 17, wherein an acid is added to crystallize glutamate. 19. The method of embodiment 18, wherein the acid is selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, formic acid, and acetic acid. 20. The method of embodiment 18, wherein the composition is heated to an elevated temperature before, during, or after the addition of the acid.

[0108] 21. The method of embodiment 20, wherein the elevated temperature is in the range of about 35°C to about 90°C. 22. The method of embodiment 20, wherein the elevated temperature is in the range of about 40°C to about 80°C. 23. The method of embodiment 20, wherein the elevated temperature is in the range of about 50°C to about 70°C. 24. The method of embodiment 20, wherein after heating, the composition is cooled to a temperature below 25°C. 25. The method of embodiment 24, wherein the temperature is in the range of about -5°C to about 15°C. 26. The method of embodiment 24, wherein the temperature is in the range of about 0°C to about 10°C. 27. The method of embodiment 17, wherein the separated glutamate is recycled to the enzymatic reaction combining D-amino acid oxidase and a transaminase. 28. The method of embodiment 1 or 16, wherein the elevated temperature is a temperature of 120°C to 180°C. 29. The method of embodiment 10 or 16, wherein the sufficient time is at least 2 hours. 30. The method of embodiment 29, wherein the sufficient time is from 2 hours to 18 hours.

[0109] 31. The method of embodiment 1 or 16, wherein the composition is adjusted to a pH < 7 by adding an acid prior to heating to the elevated temperature. 32. The method of embodiment 31, wherein the acid is selected from the group consisting of sulfuric acid, hydrochloric acid, and phosphoric acid. 33. The method of embodiment 31, wherein the pH is adjusted to about pH 1 to about pH 6. 34. The method of embodiment 31, wherein the pH is adjusted to about pH 2 to about pH 5. 35. The method of embodiment 31, wherein the pH is adjusted to about pH 3 to about pH 4. 36. The method of any one of embodiments 1, 10, and 16, wherein a base is added to the composition prior to the ion exchange step. 37. A method for obtaining purified succinic acid as a by-product from a process for making L-glufosinate, comprising: aminating PPO to L-glufosinate by a transaminase (TA) enzyme using an amine group of glutamic acid present in the composition to produce a 2-oxoglutaric acid by-product; reacting an L-glufosinate composition comprising L-glufosinate, glutamate, and 2-oxoglutaric acid at an elevated temperature for a sufficient period of time to convert a majority of the glutamate to pyroglutamate; isolating 2-oxoglutaric acid from the composition by size exclusion chromatography to obtain a substantially purified composition of 2-oxoglutaric acid; contacting the substantially purified 2-oxoglutaric acid with hydrogen peroxide to obtain a composition of substantially purified succinic acid; A method comprising: 38. The method of embodiment 37, wherein a base is added to the composition prior to the size exclusion step. 39. The method of embodiment 36 or embodiment 38, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, and ammonium hydroxide. 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.

[0110] 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. 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. 43. The method of embodiment 36 or embodiment 38, wherein the resulting composition is processed through a membrane separator. 44. The method of embodiment 36 or embodiment 38, wherein the composition is cooled to a temperature of less than about 25° C., held for a sufficient period of time, and then filtered. 45. The method of embodiment 44, wherein the temperature is about 20° C. or less. 46. ​​The method of embodiment 44, wherein the temperature is about 10° C. or less. 47. The method of embodiment 44, wherein the temperature is about 5° C. or less. 48. The method of embodiment 44, wherein the temperature is about 0° C. or less. 49. The method of embodiment 44, wherein the sufficient time is at least 1 hour. 50. The method of embodiment 49, wherein the sufficient time is from 1 hour to 24 hours.

[0111] 51. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange is performed by contacting the composition with either an anion exchange resin or a cation exchange resin. 52. The method of embodiment 51, wherein the ion exchange resin is composed of a polymeric cross-linked matrix made from a monovinyl monomer and a polyvinyl cross-linker. 53. The method of embodiment 52, wherein the monovinyl monomer is styrene and the polyvinyl crosslinker is divinylbenzene. 54. The method of embodiment 52, wherein the porosity of the ion exchange resin is microporous, mesoporous, or macroporous. 55. The method of embodiment 52, wherein the ion exchange resin is a gel-type resin. 56. The method of embodiment 52, wherein the ion exchange resin has a median particle size of from 10 microns to 2000 microns. 57. The method of embodiment 52, wherein the ion exchange resin has a median particle size of from 100 microns to 1000 microns. 58. The method of embodiment 52, wherein the ion exchange resin is in the form of beads having a uniform particle size distribution. 59. The method of any one or more of embodiments 51 to 58, wherein the ion exchange resin is a strong anion exchange resin. 60. The method of embodiment 59, wherein the anion exchange resin is selected from the group consisting of DOWEX™ MARATHON™ A, DOWEX™ MONOSPHERE™ 550A, DOWEX® MONOSPHERE™ MSA, and DOWEX™ XUR-1525-L09-046, experimental gel type strong base anion exchange resins of uniform particle size in the 300 micron range, and Type I (trimethylamine quaternary ammonium chloride form).

[0112] 61. The method of embodiment 59, wherein the anion exchange resin is used in hydroxy form. 62. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out in the pH range of 3 to 8. 63. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out in the pH range of 4 to 8. 64. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out in the pH range of 5 to 8. 65. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out in the pH range of 6 to 7. 66. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out at a temperature in the range of 20°C to 70°C. 67. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out at a temperature in the range of 30°C to 60°C. 68. The method of any one of embodiments 1, 10, and 16, wherein the ion exchange process is carried out at a temperature in the range of 40°C to 50°C. 69. The method of any one or more of embodiments 51 to 58, wherein the ion exchange resin is a strong cation exchange resin. 70. The method of embodiment 69, wherein the cation exchange resin is used in hydrogen form.

[0113] 71. The method of embodiment 69, wherein the cation exchange resin is selected from the group consisting of DOWEX™ 50WX8, DOWEX™ MONOSPHERE™ 99 K / 350, DOWEX™ MONOSPHERE™ C, and DOWEX™ MARATHON™ MSC. 72. The method of embodiment 69, wherein the ion exchange process is carried out in a pH range of 0.4 to 7. 73. The method of embodiment 69, wherein the exchange process is carried out in a pH range of 0.6 to 7. 74. The method of embodiment 69, wherein the ion exchange process is carried out in the pH range of 1 to 6. 75. The method of embodiment 69, wherein the ion exchange process is carried out in the pH range of 1 to 4.5. 76. The method of embodiment 69, wherein the ion exchange process is carried out at a temperature in the range of 20°C to 70°C. 77. The method of embodiment 69, wherein the ion exchange process is carried out at a temperature in the range of 30°C to 60°C. 78. The method of embodiment 69, wherein the ion exchange process is carried out at a temperature in the range of 40°C to 50°C. 79. The method of any one of embodiments 1, 10, and 16, wherein the composition is concentrated or decolorized, or both, prior to the ion exchange. 80. The method of embodiment 79, wherein the composition is decolorized with activated charcoal or activated carbon.

[0114] 81. The method of embodiment 79, wherein the composition is decolorized with a polymeric material. 82. The method of any one of embodiments 1, 10, and 16, wherein the composition and the ion exchange resin are contacted in batch mode. 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. 84. The method of embodiment 83, wherein the flow mode uses the technique of simulated moving bed chromatography. 85. The method of embodiment 84, wherein the composition is subjected to a pretreatment adsorption step to remove one or more components of the composition prior to simulated moving bed chromatography. 86. A method for regenerating a resin used in any one of the methods of embodiments 1, 10, and 16, comprising contacting the resin with a composition comprising one or more of an acid, a base, water, and an inorganic salt. 87. The method of embodiment 86, wherein the base is sodium hydroxide. 88. The method of embodiment 86, wherein the inorganic salt is selected from the group consisting of sodium chloride, sodium sulfate, ammonium chloride, and ammonium sulfate. 89. The method of embodiment 86, wherein the acid is sulfuric acid. 90. The method of embodiment 86, wherein the composition comprises no more than 0.5 M sodium hydroxide and no more than 1.5 M sodium chloride.

[0115] 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. 92. The method of embodiment 86, wherein the composition comprises no more than 0.5 M sodium chloride. 93. The method of embodiment 86, wherein the composition comprises no more than 0.5 M sodium sulfate. 94. The method of embodiment 86, wherein said regeneration produces a solution of substantially purified 2-oxoglutaric acid. 95. The method of embodiment 94, wherein the solution of substantially purified 2-oxoglutaric acid is contacted with hydrogen peroxide to produce substantially purified succinic acid. 96. The method of any one of embodiments 1, 10, and 16, wherein the substantially purified L-glufosinate is reduced to a concentrate that can be directly formulated into a herbicidal product. 97. The method of any one of embodiments 1, 10, and 16, wherein the substantially purified L-glufosinate is concentrated past the point where crystallization or precipitation occurs, and the resulting solid is filtered and dried. 98. The method of embodiment 97, wherein a solvent is added before, during, or after said concentration. 99. The method of embodiment 98, wherein the solvent is selected from the group consisting of acetone, methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1-methyl-2-propanol, 1,2-propanediol, 1,2-ethanediol, triethylamine, isopropylamine, and ammonium hydroxide. 100. The method of any one of embodiments 1, 10, and 16, wherein the substantially purified L-glufosinate is concentrated to produce a dry solid.

[0116] 101. The method of any one of embodiments 1, 10, and 16, wherein the substantially purified L-glufosinate is spray-dried. 102. The method of any one of embodiments 1, 10, and 16, wherein the substantially purified L-glufosinate is partially concentrated before being spray-dried. 103. The method of any one of embodiments 1, 10, and 16, wherein the formulation ingredients are mixed with the substantially purified L-glufosinate and then spray dried. 104. A method for purifying L-glufosinate from a composition comprising L-glufosinate and glutamate by converting glutamate to pyroglutamate to facilitate isolation of L-glufosinate, comprising: adding sulfuric acid to bring the composition to a pH of 3.7 to crystallize glutamate and remove solid glutamate from the composition; reacting the composition at an elevated temperature for a sufficient period of time to convert a majority of the residual glutamate to pyroglutamate; Reducing the volume of the composition; adding sodium hydroxide until the pH of the composition is between pH 6 and pH 7; cooling the composition to a temperature between 5°C and the freezing point of the mixture (about -10 to -20°C), thereby precipitating sodium sulfate; filtering the sodium sulfate crystals from the composition; contacting the composition with an ion exchange resin to remove pyroglutamic acid to obtain a substantially purified L-glufosinate composition; Reducing the volume of a substantially purified L-glufosinate composition; A method comprising: 105. The method of embodiment 104, wherein the volume of the substantially purified L-glufosinate composition is reduced to a solid. 106. The method of embodiment 104, wherein the volume of the substantially purified L-glufosinate composition is concentrated to a quantity suitable for use in a herbicidal formulation. 107. The method of embodiment 104, wherein the solid glutamate is removed from the composition by filtration or centrifugation. 108. The method of embodiment 104, wherein the volume of the composition is reduced by vacuum distillation, membrane separation, evaporation, thin film evaporation, or wiped film evaporation. 109. The method of embodiment 104, wherein the sodium sulfate crystals are filtered from the composition by filtration or centrifugation. 110. L-glufosinate ammonium form A, characterized by an X-ray powder diffraction (XRPD) pattern including 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 by a diffractometer using Cu-Kα radiation.

[0117] 111. L-Glufosinate ammonium form A according to embodiment 110, wherein the XRPD pattern comprises 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. 112. L-Glufosinate ammonium form A according to 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. 113. L-glufosinate ammonium form A according to embodiment 110, having an XRPD pattern substantially according to FIG. 1. 114. L-glufosinate form B, characterized by an X-ray powder diffraction (XRPD) pattern including 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, 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 by a diffractometer using Cu-Kα radiation. 115. L-Glufosinate form B according to 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. 116. L-glufosinate form B according to 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. 117. L-Glufosinate form B according to embodiment 114, having an XRPD pattern substantially according to FIG. 3. 118. L-glufosinate ammonium form C, characterized by an X-ray powder diffraction (XRPD) pattern including 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 by a diffractometer using Cu-Kα radiation. 119. L-Glufosinate ammonium form C according to embodiment 118, wherein the XRPD pattern comprises 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. 120. L-Glufosinate ammonium form C according to 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.

[0118] 121. L-glufosinate ammonium form C according to embodiment 118, having an XRPD pattern substantially according to FIG. 5. 122. L-glufosinate form D, characterized by an X-ray powder diffraction (XRPD) pattern including 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 by a diffractometer using Cu-Kα radiation. 123. L-Glufosinate form D according to embodiment 122, wherein the XRPD pattern comprises 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. 124. L-Glufosinate form D according to 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. 125. L-Glufosinate form D according to embodiment 122, having an XRPD pattern substantially according to FIG. 7. 126. L-Glufosinate hydrochloride form E, characterized by an X-ray powder diffraction (XRPD) pattern including 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 by a diffractometer using Cu-Kα radiation. 127. L-Glufosinate hydrochloride form E according to embodiment 126, wherein the XRPD pattern comprises 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. 128. L-Glufosinate hydrochloride form E according to 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. 129. L-Glufosinate hydrochloride form E according to embodiment 126, having an XRPD pattern substantially according to FIG. 9. 130. Solid L-glufosinate ammonium, which is X-ray amorphous.

[0119] The following examples are offered by way of illustration and not by way of limitation. EXAMPLES

[0120] Example 1: Deracemization of racemic D / L-glufosinate in a 3 L reaction scale In this example, the reaction was carried out in a 3 L jacketed stirred reaction vessel. The following reagents were added at the beginning of the reaction: 900 mM D,L-glufosinate, 2700 mM glutamate, and 2535 grams of water. After heating to 30° C., the pH was adjusted to 7.8 using approximately 45 grams of 3N NaOH. To the reaction vessel, 0.30 grams of antifoam AF204 (Sigma-Aldrich) and 0.60 grams of catalase dissolved in 10 mL of water were added. The reaction vessel was filled with 188 grams of plastic beads with 6 g of AC302 DAAO and 0.9 g of E. coli gab T transaminase immobilized thereon, followed by 400 grams of water. Oxygen-enriched air (35% O 2 ) was added during the stirred reaction process. 2 , 65% N 2) was introduced at 1.7 VVM (volume of gas per volume of reaction mixture per minute) through two stainless steel sparging stones. HPLC analysis of the reaction demonstrated that equilibrium was reached within 10 h, with an enantiomeric excess of L-glufosinate over D-glufosinate of >99% and a ratio of L-glufosinate to PPO of 90% to 10%. This result demonstrates efficient deracemization of D / L-glufosinate to L-glufosinate by the RgDAAO / EcgabT enzyme couple on a larger scale.

[0121] Example 2: Crystallization of glutamic acid using concentrated hydrochloric acid Following the same procedure as in 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 a pH of 3.7 was reached. The batch was heated to 60° C. in a heating bath and held for 60 minutes. The heating bath was turned off and the batch was allowed to cool to ambient temperature overnight. The batch was cooled to 0° C. and held for 1 hour. The white precipitate was removed by filtration. The molar ratio of L-glufosinate to glutamic acid in the filtrate was determined to be 88:12 by NMR analysis.

[0122] Example 3: Crystallization of glutamic acid using concentrated sulfuric acid Following the same procedure as in 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 a pH of 3.7 was reached. The batch was heated to 60° C. in a heating bath and held for 60 minutes. The heating bath was turned off and the batch was allowed to cool to ambient temperature overnight. The batch was cooled to 0° C. and held for 1 hour. The white precipitate was removed by filtration. The molar ratio of L-glufosinate to glutamic acid in the filtrate was determined to be 85:15 by NMR analysis.

[0123] Example 4: Formation of Pyroglutamic Acid Following the same procedure as in Example 2, a portion of the filtrate was heated in an autoclave at 140° C. for 3.5 hours. NMR analysis of a sample of the reaction product 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 decomposition of L-glufosinate was observed in the NMR results.

[0124] Example 5: Formation of Pyroglutamic Acid Following the same procedure as in Example 3, a portion of the filtrate was further adjusted to pH 3.0 using sulfuric acid. The concentration of L-glufosinate before pH adjustment was about 310 mM. The liquid was then heated to 125° C. in an autoclave for 18 hours. NMR analysis of a sample of the reaction product showed that the molar ratio of L-glufosinate to glutamic acid was 98:2. NMR analysis also confirmed the presence of pyroglutamic acid. No evidence of decomposition of L-glufosinate was observed in the NMR results.

[0125] Example 6: Formation of pyroglutamic acid following concentration of reaction products Following the same procedure as in Example 3, the filtrate was concentrated by vacuum distillation until the concentration of L-glufosinate was about 412 mM. A portion of the concentrate was further adjusted to pH 3.0 using sulfuric acid. The liquid was then heated to 125° C. in an autoclave for 18 hours. NMR analysis of a sample of the reaction product showed that the molar ratio of L-glufosinate to glutamic acid was 98:2. NMR analysis also confirmed the presence of pyroglutamic acid. No evidence of decomposition of L-glufosinate was observed in the NMR results.

[0126] Example 7: Concentration of reaction products followed by cooling and precipitation of sodium sulfate Following a procedure similar to that of Example 5, the reaction product after the cyclization reaction was concentrated by vacuum distillation to a concentration of about 404 mM L-glufosinate and then cooled to room temperature. A 300 mL portion of the concentrate was transferred to a beaker and the pH was adjusted to 6.2 by adding 11.7 grams of solid sodium hydroxide (97%, Sigma-Aldrich). The beaker was placed in a freezer at -20°C for about 4 hours, during which time the entire mixture was frozen. The beaker was removed from the freezer and placed in an ice bath at about 0°C for about 4 hours. Periodically during this time, the contents were mixed gently by hand. The contents of the beaker were filtered onto filter paper using a Büchner funnel that had been pre-cooled to about 4°C. The weight of the filtrate was 247 grams and the volume of the filtrate was 215 mL. The concentration of L-glufosinate was about 550 mM. The total weight of the crystals after all the liquid was drained off was 115 grams, and HPLC analysis of the crystals showed only trace amounts of L-glufosinate and other organic impurities. A 10 gram portion of the dried crystals was transferred to a beaker, and the beaker was placed in an incubator heated to 45°C. Shortly thereafter, nearly all of the crystals were observed to melt. The melting point of sodium sulfate decahydrate is calculated according to the Handbook of Chemistry and Physics (63 rd Ed. (1982), RC Weast, Ed.; CRC Press, Inc., Boca Raton, FL; page B-150) was 32.38°C. The beaker was removed from the incubator and placed in a water bath. The water bath was brought to a boil. Eventually, the liquid in the beaker disappeared, leaving behind solids. After all the liquid had been removed from the beaker by evaporation, the beaker was cooled and the remaining solids were weighed. Approximately 4.2 grams of solids remained in the beaker.

[0127] Example 8: Formation of pyroglutamic acid and purification by cation exchange resin (batch mode) Following a procedure similar to that of 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. in an autoclave for 4 hours. NMR analysis of a sample of the reaction product showed that over 94% of the glutamic acid was converted to pyroglutamic acid.

[0128] After cooling to room temperature, the solution was adjusted to pH 1 by adding 37% HCl. The solution was treated with pre-washed DOWEX™ 50WX8 cation exchange resin. In this treatment, the solution was mixed with the resin for 30 minutes, after which the resin was isolated on a filter. The resin was then washed with water and then washed with 4M NH 4 The eluent was concentrated under vacuum to give a solid containing 90-98% pure L-glufosinate and 2-10% glutamic acid, both of which were determined by NMR to be their monoammonium salts.

[0129] Example 9: Purification using an anion exchange resin in a column (flow mode) A jacketed glass column (1 inch diameter and 24 inches long) was packed with strong base anion exchange resin (DOWEX™ XUR-1525-L09-046, laboratory gel type strong base anion resin (Type I) with uniform particle size in the range of 300 microns (trimethylamine quaternary ammonium chloride form available from the Dow Chemical Company)) that had been converted to the hydroxy form. The resin column was heated to about 60° C. and flushed with water until the pH of the effluent was about pH 6. The column was pumped with 270 mL of a solution prepared according to a procedure similar to that of Example 5, and the solution was adjusted to pH 6 with NaOH and heated to about 60° C. The flow rate was about 10.5 mL / min. When the reaction mixture was completely fed to the column, about 900 mL of water adjusted to pH 6 was fed to the column. After collecting approximately 100 mL of column effluent and discarding it as void volume, 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.

[0130] [Table 1]

[0131] The last row of Table 1 shows the HPLC results after fractions 7-22 were combined into a single solution of substantially purified L-glufosinate.

[0132] Example 10: Purification of concentrated reaction product using anion exchange resin in a column (flow mode) A solution was prepared following the same procedure as in Example 5, except that the solution was concentrated by vacuum distillation. The volume of the solution was reduced by about 2.3 times. The solution was adjusted to pH 6.7 using NaOH and heated to about 60° C. Following the same procedure as in Example 8, 270 mL of the solution was fed to a strong base anion resin (DOWEX® XUR-1525-L09-046, experimental gel type strong base anion resin (Type I) with uniform particle size in the range of 300 microns (trimethylamine quaternary ammonium chloride form available from the Dow Chemical Company)) that had been converted to hydroxy form. Before feeding the solution, the resin column was heated to about 60° C. and flushed with water until the pH of the effluent was about pH 6. The flow rate was about 10.5 mL / min. When the reaction mixture was completely fed to the column, about 900 mL of water adjusted to pH 6 was fed to the column. After collecting approximately 100 mL of column effluent and discarding it as void volume, 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.

[0133] [Table 2]

[0134] The last row of Table 2 shows the HPLC results after fractions 6-19 were combined into a single solution of substantially purified L-glufosinate.

[0135] Example 11: Purification of concentrated reaction products using anion exchange resin in a column at 35°C (flow mode) A solution was prepared according to the same procedure as in Example 5. The solution was adjusted to pH 6.2 using NaOH and heated to about 35° C. Following the same procedure as in Example 8, 270 mL of the solution was loaded onto a strong base anion resin (DOWEX® MONOSPHERE® 550A in hydroxy form, a product of the Dow Chemical Company). Before loading the solution, the resin column was heated to about 35° C. and flushed with water until the pH of the effluent was about pH 7. The flow rate was about 5.5 mL / min. When loading of the reaction mixture onto the column was completed, about 1000 mL of water adjusted to pH 7 was loaded onto the column. After collecting about 100 mL of the column effluent and discarding it as void volume, 44 fractions of about 15 mL each were collected using a fraction collection device. The fractions were analyzed by HPLC / UV, and Table 3 below shows the concentrations of L-glufosinate and other components.

[0136] [Table 3]

[0137] The last row of Table 3 shows the HPLC results after fractions 5-15 were combined into a single solution of substantially purified L-glufosinate.

[0138] Example 12: Purification of reaction products using anion exchange resin in two columns operated in series at 25°C (flow mode) Two 24-inch columns were packed with strong base anion resin (DOWEX™ XUR-1525-L09-046, experimental gel-type strong base anion resin (Type I) with uniform particle size in the range of 300 microns (trimethylamine quaternary ammonium chloride form available from the Dow Chemical Company)) that had been converted to the hydroxy form. The columns were maintained at a temperature of about 25° C. Tubing and a multiport valve were connected to the inlet of each column to allow for the separate addition of reaction mixture, pH 6 water, or resin regenerant. Tubing and a multiport valve were connected to the outlet of the first column to allow the fluid exiting the first column to be either collected by a fractionator or transferred to the inlet of the second column. Both columns were flushed with water at about pH 6 until the pH of the effluent was about pH 6. The reaction mixture was prepared according to a procedure similar to that of Example 5 and adjusted to about pH 6.4. About 270 mL of the reaction mixture was pumped into the first column at a flow rate of about 10.5 mL / min. After the reaction mixture was fed, about 210 mL of pH 6 water was fed into the column, so the total volume fed into the first column was 480 mL. A total of 330 mL of fluid exiting the first column was collected in fractions of about 15 mL each. After the last fraction was collected, the valve was set to pump the next 150 mL exiting the first column into the inlet of the second column. After feeding the second column from the first column, about 270 mL of the reaction mixture was fed into the inlet of the second column, followed by 600 mL of pH 6 water. Thus, a total volume of 1020 mL was fed into the second column. All fluid exiting the second column was collected in fractions of about 15 mL. The fractions collected from both columns were analyzed by HPLC. Table 4 below shows the fractions collected from the first column.

[0139] [Table 4]

[0140] The last row of Table 4 shows the HPLC results after fractions 7-15 were combined into a single solution of substantially purified L-glufosinate.

[0141] Table 5 below shows the fractions collected from the second column.

[0142] [Table 5]

[0143] The last row of Table 5 shows the HPLC results after fractions 12-22 were combined into a single solution of substantially purified L-glufosinate.

[0144] Example 13: Formation of purified 2-oxoglutaric acid obtained after anion exchange purification and resin regeneration Following a similar procedure as in Example 8, after the column had been loaded with water adjusted to pH 6, a solution of 0.1 M sodium hydroxide and 1.5 M sodium chloride was loaded onto the column at about 10.5 mL / min at about 60° C. and 88 fractions of 15 mL each were collected. HPLC analysis of the fractions showed that 2-oxoglutaric acid eluted over a very narrow range of fractions as shown in Table 6 below.

[0145] [Table 6]

[0146] 2-oxoglutarate was not detected in fraction 44 or in any other fractions collected after fraction 44 and selected for analysis. The amount of 2-oxoglutarate in this experiment exceeds that predicted in a single ion exchange experiment. Without wishing to be bound by theory, it is possible that the resin was not fully regenerated prior to this experiment.

[0147] Example 14: Production of succinic acid from 2-oxoglutaric acid obtained after anion exchange purification and resin regeneration Following a procedure similar to that of Example 12, a fraction containing 180 mM 2-oxoglutarate was produced. A 0.266 mL sample 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 the vessel. The vessel was shaken at 30° C. and sampled for HPLC analysis approximately every 5 minutes. After 10 minutes, approximately 70% of the 2-oxoglutamic acid had been converted to succinic acid.

[0148] Example 15: Decolorization of the reaction mixture obtained after conversion of glutamic acid to pyroglutamic acid Various amounts (0.25%, 0.5%, 1.0%, 3.0%, and 5.0% by weight) of activated carbon were added to a portion of the reaction mixture resulting from the conversion of glutamic acid to pyroglutamic acid described above. After mixing for about 20 minutes at room temperature, the activated carbon was filtered on top of a pre-washed bed of Celite®. The resulting filter cake was then washed with water, and the cake was combined with the filtrate. The filtrate was then tested for L-glufosinate recovery relative to the untreated sample using pyroglutamic acid as an internal standard. Table 7 below shows the recovery and color observations.

[0149] [Table 7]

[0150] Example 16: Preparation and characterization of L-glufosinate polymorphs Two lots of L-glufosinate ammonium were received and used in the study described below. XRPD analysis of one of the two lots confirmed that the sample was X-ray amorphous. IC analysis of the other lot indicated that the ammonium content of the sample was substoichiometric.

[0151] The solubility level of L-glufosinate ammonium was determined, showing that the material was very soluble in water and poorly soluble in most organic solvents. Organic / aqueous mixtures tended to cause oil formation. Organic solubility remained generally low in solvents such as dimethylsulfoxide, dimethylacetamide, and N-methyl-2-pyrrolidone. Trifluoroethanol (TFE) was the only organic solvent that showed a solubility above 2 mg / mL.

[0152] A polymorph screening of L-glufosinate ammonium was performed using various crystallization techniques, varying the conditions for nucleation and growth to explore both thermodynamic and kinetic conditions. Crystallization techniques included slurrying at room and elevated temperatures, evaporation, anti-solvent addition / precipitation, and cooling. Kinetic factors such as cooling rate, evaporation rate, or anti-solvent addition rate were varied during these experiments. Non-solvent based techniques such as vapor stress and heating above the glass transition temperature of L-glufosinate ammonium amorphous material were also utilized.

[0153] Attempts were made to vary the solvent system utilized during the polymorph screen, but solubility was limited in most organic solvent systems, and in many cases water or TFE was added to improve solubility. Neat solvent experiments generally consisted of extended slurries at room or elevated temperatures. Hydrate formation was also examined through crystallization experiments performed in water and aqueous-organic systems with variable water activity, but gels and oils were observed in many of these solvent systems. Anhydrous conditions were also examined to determine whether new forms could be generated under anhydrous conditions. In these experiments, the L-glufosinate ammonium starting material was pre-dried over a desiccant to remove any possible residual moisture from the starting material.

[0154] Selected crystallization experiments were performed utilizing excess ammonium hydroxide since substoichiometric amounts of ammonium were observed in some of the starting materials, as well as a few experiments performed under acidic conditions using HCl.

[0155] Five unique crystalline L-glufosinate materials were observed during screening and designated Form A, Form B, Form C, Form D, and Form E. Forms A and C are believed to be metastable forms of L-glufosinate ammonium that tend to convert to Form B. Forms B and D are believed to be anhydrous crystalline forms of the L-glufosinate free form. Form E is believed to be the L-glufosinate HCl salt.

[0156] Crash Cooling (CC): A solution of L-glufosinate ammonium was prepared in the selected solvent or solvent mixture at elevated temperature. Once a clear solution was obtained after visual observation, the solution was filtered through a 0.2 μm or 0.45 μm syringe filter into a pre-heated vial. The vial was then capped and immediately placed in a pre-cooled reaction vessel at below ambient temperature. Solids were collected by centrifugation or vacuum filtration and analyzed.

[0157] Conversion Slurry: Form B with additional peaks was slurried in ethanol / water (95 / 5 v / v) at ambient temperature for 1 day. BIPXAZ seeds with additional peaks (Cambridge Structural Database, Version 5.38, November 2016) and Form D were added and the mixture was slurried for an extended period at ambient temperature. The solids were collected by centrifugal filtration and then analyzed.

[0158] Fast Cooling (FC): A solution of L-glufosinate ammonium was prepared in the selected solvent or solvent mixture at elevated temperature. Once a clear solution was obtained after visual observation, the solution was filtered through a 0.2 μm or 0.45 μm syringe filter into a pre-warmed vial. The vial was then capped and immediately placed at ambient temperature. The solids were collected by centrifugation or vacuum filtration and analyzed.

[0159] Fast Evaporation (FE): A solution of L-glufosinate ammonium was prepared in the selected solvent or solvent mixture at ambient temperature. Once a clear solution was obtained after visual observation, the solution was filtered through a 0.2 μm or 0.45 μm syringe filter into a clean vial. The solution was then allowed to evaporate at ambient temperature. The solids were collected in a closed vial and then analyzed.

[0160] Rotary Evaporation: Solutions of L-glufosinate ammonium 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 closed vials and then analyzed.

[0161] Slow Cooling: Solutions of L-glufosinate ammonium were prepared in various solvents or solvent mixtures at elevated temperatures in metal blocks. Once a clear solution was obtained after visual observation, the solution was filtered through a 0.2 μm or 0.45 μm syringe filter into a pre-warmed vial. The solution was then allowed to cool slowly to ambient temperature. Solids were collected by centrifugation or vacuum filtration and then analyzed.

[0162] Slurry: A slurry of L-glufosinate ammonium was prepared by adding enough solids to a given solvent or solvent mixture at ambient or elevated temperature such that undissolved solids were present. The mixture was then stirred in a sealed vial at ambient, sub-ambient or elevated temperatures for an extended period of time. The solids were collected by centrifugation or vacuum filtration and then analyzed.

[0163] Vapor Stress (VS): L-glufosinate ammonium solids were transferred to a 1-dram vial, which was then placed into a 20 mL vial containing solvent. The 1-dram vial was left open and the 20 mL vial was capped to allow vapor pressurization to occur. Vapor pressurization experiments were performed at ambient temperature. Solids were isolated by decantation and analyzed.

[0164] Vapor Diffusion (VD): Concentrated solutions of L-glufosinate ammonium were prepared in various solvents or solvent mixtures at ambient temperature in a metal block. When a clear solution was obtained after visual observation, the solution was filtered through a 0.2 μm or 0.45 μm nylon syringe filter into a clean vial. This vial, with the lid open, was placed into a larger vial containing antisolvent. The lid of the larger vial was closed and vapor diffusion was allowed to occur. Solids were isolated by decantation, collected in a closed vial, and then analyzed.

[0165] Differential Scanning Calorimetry (DSC): DSC was performed using a Mettler Toledo TGA / DSC 3+. Temperature calibration was performed using NIST traceable indium metal. Temperature calibration was performed using adamantane, phenyl salicylate, indium, tin, and zinc. Samples were placed in aluminum DSC pans, covered with lids, and weights were accurately recorded. An aluminum pan configured as the sample pan and weighed was placed on the control side of the cell. A hole was drilled in the pan lid prior to sample analysis. Data was acquired using a heating rate of 10°C / min over the range of ambient to 350°C, or cycled from ambient to -30°C to 250°C.

[0166] 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 tracked indium metal. Samples were placed in aluminum DSC pans and the weights were accurately recorded. The pans were covered with laser pinhole pierced lids and the lids were crimped. The weighed crimped aluminum pans were placed on the control side of the cell. Data were obtained with a base heating rate of 2°C / min from ambient to 300°C using amplitude modulation of ±0.08°C and time of 60 seconds. The glass transition temperatures recorded are taken from the inflection point of the step change in the reverse heat flow vs. temperature curve.

[0167] Thermogravimetric (TG) Analysis: TG analysis was performed using a Mettler Toledo TGA / DSC3+ analyzer or a TA Instruments Q5000 IR thermogravimetric analyzer. Q5000 IR. Temperature calibration was performed using phenyl salicylate, indium, tin, and zinc. Samples were placed in aluminum pans. Samples were sealed, the lid was pierced, and then placed in a TG furnace. The furnace was heated under nitrogen. Data was acquired using a heating rate of 10°C / min over the range of ambient to 350°C.

[0168] Nuclear Magnetic Resonance (NMR) Spectroscopy: Solution NMR spectra were acquired at SSCI using an Agilent DD2-400 spectrometer. 2 Samples were prepared by dissolving in 0.3% TSP-d2. Additional data are available in 2 O / TSP-d2 or CF 3 CD 2 OD at Spectral Data Services, Inc. (Champaign, Illinois). Data acquisition parameters are given for each plot of the first spectrum in the data section of this report.

[0169] Polarized Light Microscopy (PLM): Polarized light microscopy was performed using an optical microscope with crossed polarizers or a stereo microscope with a first order red compensator.

[0170] X-ray Powder Diffraction (XRPD) Reflection Mode: XRPD patterns were collected on a PANalytical X'Pert PRO MPD diffractometer using an incident beam of Cu Kα radiation generated using a long fine focus source and a nickel filter. The diffractometer was configured using a symmetric Bragg-Brentano geometry. Prior to analysis, a silicon specimen (NIST SRM 640e) was analyzed to verify that the observed position of the Si 111 peak matched the NIST certified position. Sample preparations were prepared as annular thin layers in the center of a silicon zero-background substrate. Anti-scatter slits (SS) were used to minimize background caused by air. Soller slits for the incident diffracted beam were used to minimize spread from axial divergence. Diffraction patterns were collected using a scanning position sensitive detector (X'Celerator) positioned 240 mm from the sample and data collector software v. 2.2b.

[0171] XRPD transmission mode: XRPD patterns were collected on a PANalytical X'Pert PRO MPD diffractometer using an incident beam of Cu radiation generated using an Optix long, finely focused source. An elliptically graded multilayer mirror was used to focus the Cu Kα X-rays through the specimen and onto the detector. Prior to analysis, a silicon specimen (NIST SRM 640e) was analyzed to verify that the Si 111 peak observation position matched the NIST certified position. Sample specimens were sandwiched between 3 μm thick membranes and analyzed in transmission geometry. A beam stop, short anti-scatter extensions, and an anti-scatter knife edge were used to minimize background caused by air. A Soller slit for the incident diffracted beam was used to minimize spread from axial divergence. Diffraction patterns were collected using a scanning position sensitive detector (X'Celerator) positioned 240 mm from the specimen and data collector software v. 2.2b.

[0172] 1. Form A L-glufosinate ammonium Form A was first prepared from an IPA slurry of material withdrawn from the aqueous solution. Form A was the most frequently observed material prepared during testing, but was often observed as a mixture with Form D, Form C, or X-ray amorphous material. Form A was produced from several long-term slurries at elevated temperatures or room temperature.

[0173] In one example, Form A was isolated from a 7-day slurry in 93 / 7 v / v methanol / water. The XRPD pattern of the sample showed that it was composed primarily of a single crystalline phase (Figure 1). An additional minor peak was observed at a diffraction angle of about 19.0°. 1 The H NMR spectrum was consistent with L-glufosinate and contained chemical shifts consistent with methanol. Ion chromatography analysis indicated an ammonium content of 6.4 wt%, less than would be expected for the theoretical monoammonium salt (9.1 wt%) and slightly less than the as-received material (7.0 wt%). Thermal analysis of the material was consistent with the anhydrous / unsolvated form. No significant DSC events were observed prior to a large endotherm at approximately 123°C (onset). A significant change in the TGA slope was observed around this temperature, suggesting a potential dissolution / decomposition event. It was noted that the thermal behavior of this sample was very similar to L-glufosinate form B. The sample was again analyzed by XRPD and found to have converted to form B upon storage over desiccant with additional minor peaks. This result suggests that form A is metastable and prone to conversion.

[0174] A new sample of Form A was prepared by slurrying as-received L-glufosinate ammonium in methanol with approximately a molar excess of ammonium hydroxide. However, the thermal analysis of this sample (Figure 2) was consistent with the previous analysis and showed minimal weight loss before the onset of significant weight loss at approximately 116°C, likely due to the onset of decomposition of the material. A single endotherm was observed with an onset at approximately 119°C. The data suggests a dissolution / decomposition event.

[0175] 2. Form B Form B of L-glufosinate was first observed in a multi-step crystallization involving slurrying L-glufosinate ammonium in IPA / water to form a gel and reslurrying the gel in acetone at room temperature. Form B was recovered from several slurries, including organic-water mixtures that typically have higher water activity. The XRPD pattern of Form B was successfully determined (FIG. 3), although several additional minor peaks were observed in the pattern. Indeed, Form B was typically observed along with additional minor peaks.

[0176] Form B is 1 It was characterized by 1 H NMR, IC, DSC, and TGA. 1 The H NMR spectrum was consistent with L-glufosinate and did not indicate any residual organic solvent. Ion chromatography analysis of the different Form B samples showed only a small amount of ammonium content (0.17 wt%), suggesting that Form B is a crystalline form of the L-glufosinate zwitterion, rather than an ammonium salt. Thermal analysis of the samples (Figure 4) was consistent with a nonsolvated / anhydrous crystalline form. No significant thermal events were observed prior to the large endotherm (onset) at 123 °C. A significant change in the slope of the TGA was also observed near this temperature, suggesting that this is likely a dissolution / decomposition event. No significant changes were observed in the XRPD patterns of the samples upon storage for 47 days on desiccant.

[0177] 3. Form C Form C, along with a small amount of Form A, was prepared via the stress of L-glufosinate ammonium and MeOH vapor. The XRPD pattern of Form C was determined and several peaks consistent with Form A were observed (FIG. 5). 1 The H NMR spectrum was consistent with L-glufosinate, but ion chromatography indicated that the ammonium content was less than stoichiometric (6.3 wt.%, compared to 9.1 wt.% for the theoretical monosalt and 7.0 wt.% for the as-received material).

[0178] A sample of Form C with a small amount of Form A was stored under desiccant for 36 days and XRPD analysis of the sample showed conversion to Form B with a small amount of Form A and some additional minor peaks. IC analysis also showed a significant loss of ammonium content over time (3.2 wt% compared to initial 6.3 wt%). The results suggest that Form C is metastable and prone to forming ammonium salts conversion / dissociation upon prolonged storage under desiccant.

[0179] Form C, along with a small amount of Form A, was successfully reconstituted via steam stress with MeOH. 1 H NMR analysis was consistent with the chemical structure of L-glufosinate. Thermal analysis showed two overlapping broad endotherms at 100° C. and 131° C. (FIG. 6). Approximately 10% weight loss was observed in the endotherm, followed by gradual weight loss on continued heating.

[0180] 4. Form D Form D was typically prepared as a mixture with Form A from several room temperature or high temperature slurries during polymorph screening. Mixtures of Form A and Form D were 1 H NMR analysis was found to be consistent with the chemical structure of L-glufosinate. No significant changes were observed in the XRPD patterns of the Form D samples plus a small amount of Form A upon storage over desiccant.

[0181] Form D was isolated from a 3-day slurry at 60° C. in 50 / 50 v / v TFE / acetone. The XRPD pattern of Form D (FIG. 7) showed that it is composed primarily or exclusively of a single crystalline phase. Ion chromatography analysis showed an ammonium content of 2.3 wt.%, significantly less than would be expected for the theoretical monoammonium salt (9.1 wt.%). Based on the substoichiometric amount of ammonium present, Form D is believed to be a crystalline form of the L-glufosinate zwitterion. Thermal analysis of the sample (FIG. 8) showed a consistent gradual weight loss and a change in slope at approximately 151° C., suggesting the onset of decomposition. A very broad endotherm was observed with an onset of about 140° C., suggesting a dissolution / decomposition event.

[0182] 5. Form E Form E was observed during initial screening in the as-received samples and in samples crystallized from aqueous acetone and HCl. 1 The H NMR spectrum is consistent with L-glufosinate, with peak shifts suggesting potential ionization differences. IC analysis showed only traces of ammonium along with less than stoichiometric amounts of chloride. The results suggest that Form E is a form of L-glufosinate HCl rather than a form of L-glufosinate ammonium.

[0183] 6. Amorphous Materials X-ray amorphous material was recovered from slurries in solvents such as N-methyl-2-pyrrolidone (NMP), tetrahydrofuran (THF), and 2,2,2-trifluoroethanol (TFE) that were maintained at temperatures ranging from 50°C to 60°C for extended periods of time (e.g., 12 days). 1 H NMR analysis was consistent with the structure and showed the presence of minor unknown peaks. Thermal analysis of the material revealed an apparent glass transition Tg at about 55 °C.

[0184] It is to be understood that the terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting. The scope of the present invention is limited only by the appended claims. Unless otherwise specified, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. When a range of values ​​is recited, it is to be understood that each intervening value between the upper and lower limits of the range, to one-tenth of the unit of the lower limit, and any other stated or intervening value within this stated range, is encompassed within the scope of the present invention, unless expressly indicated otherwise. The upper and lower limits of these subranges may be independently included within these subranges and are also encompassed within the scope of the present invention, subject to any specifically excluded limit in the stated range. Where a stated range includes one or both of the limits, ranges excluding either or both of the included limits are also included in the present invention. Certain ranges are presented herein with the term "about" or "around" preceding the numerical values. The terms "about" and "approximately" are used herein to provide literal support for the exact numerical value that precedes the term, as well as a numerical value near the numerical value that the term precedes, or an approximation of the numerical value that the term precedes. In determining whether a numerical value is near or near a specifically recited numerical value, the near or near unrecited numerical value may be a numerical value that is substantially equivalent to the specifically recited numerical value within the meaning presented. When "X" is a value modified by "about" or "approximately", "about X" or "approximately X" generally refers to a value of 0.95X to 1.05X (e.g., including 0.98X to 1.02X or 0.99X to 1.01X). Any reference to "about X" or "approximately X" specifically refers to a value of at least X, 0.95X, 0.96X, 0.97X, 0.98X, 0.99X, 1.01X, 1.02X, 1.03X, 1.04X, and 1.05X. Thus, "about X" and "approximately X" are intended to teach and provide descriptive support for a claim limitation, such as "0.98X."

[0185] All publications, patents, and patent applications cited herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Furthermore, each cited publication, patent, or patent application is incorporated by reference herein to disclose and describe the subject matter in connection with the publication citation. The citation of any publication is for its disclosure prior to the filing date of the present application and should not be construed as an admission that the invention described herein is not entitled to antedate the publication by reason of prior invention. Further, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed.

[0186] It should be noted that the claims may be drafted to exclude any optional element. Thus, this statement is intended to serve as a literal justification for the use of exclusive terms such as "solely," "only" and the like in conjunction with the recitation of claim elements, or the use of "negative" limitations. As will be apparent to one of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has separate components and features that may be readily separated from or combined with the features of any of the other embodiments without departing from the scope or spirit of the invention. Any recited method may be performed in the order of events recited, or in any other order that is logically possible. Although any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention, representative exemplary methods and materials are described herein.

Claims

1. L-glufosinate crystals characterized by an X-ray powder diffraction (XRPD) pattern comprising at least 3 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, 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 when determined with a diffractometer using Cu-Kα radiation.

2. The L-glufosinate crystals according to claim 1, wherein the XRPD pattern comprises at least 6 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.

3. The L-glufosinate crystals according to claim 1, 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.

4. The L-glufosinate crystals according to claim 1, wherein the XRPD pattern is as shown in Figure 3.

5. L-glufosinate ammonium crystals characterized by an X-ray powder diffraction (XRPD) pattern comprising at least 3 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 when determined with a diffractometer using Cu-Kα radiation. **Claim 6**: The L-glufosinate ammonium crystal according to claim 5, 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. **Claim 7**: The L-glufosinate ammonium crystal according to claim 5, 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. **Claim 8**: The L-glufosinate ammonium crystal according to claim 5, wherein the XRPD pattern is as shown in Figure 1. **Claim 9**: L-glufosinate ammonium crystals characterized by an X-ray powder diffraction (XRPD) pattern comprising at least 3 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 when determined with a diffractometer using Cu-Kα radiation. **Claim 10**: The L-glufosinate ammonium crystal according to claim 9, 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. **Claim 11**: The L-glufosinate ammonium crystal according to claim 9, 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. **Claim 12**: The L-glufosinate ammonium crystal according to claim 9, wherein the XRPD pattern is as shown in Figure 5.

13. L-glufosinate crystals 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 when determined with a diffractometer using Cu-Kα radiation.

14. The L-glufosinate crystals according to claim 13, wherein the XRPD pattern comprises 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.

15. The L-glufosinate crystals according to claim 13, 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.

16. The L-glufosinate crystals according to claim 13, wherein the XRPD pattern is as shown in Figure 7.

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