Method for preparing refined glufosinate-ammonium

Abstract

The invention provides a method for preparing refined glufosinate-ammonium, which comprises the following steps of: a) converting a compound as shown in a formula II and methyl phosphite into a compound as shown in a formula III through an Abrchiff reaction; in the formula (I), R1 is alkyl or aryl with 1 to 12 carbon atoms; and b) hydrolyzing the compound as shown in the formula III, and converting into a compound as shown in a formula I or a salt thereof, so as to obtain refined glufosinate-ammonium. Compared with the prior art, the preparation method provided by the invention has the advantages that specific raw materials are selected to be matched with specific process steps, overall better interaction is realized, glufosinate-ammonium containing enantiomers in all proportions is successfully prepared, sulfur-containing raw materials and reagents are not required to be used, the three wastes are few, the operation is simple, and the potential industrialization value is realized.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemical industry, and more specifically to a method for preparing refined glufosinate ammonium. Background Art

[0002] Glufosinate ammonium, also known as L-type glufosinate ammonium, is a broad-spectrum, contact-type, and lethal herbicide. As an L-type amino acid isolated from the fermentation broth of biological bacteria by Bayer AG of Germany and Meiji Confectionery Co., Ltd. of Japan in the 1970s, it can bind to the active site of glutamine synthetase (GS), inhibit glutamine synthesis, lead to excessive accumulation of ammonia in plants, nitrogen metabolism disorders, disintegration of chloroplasts, thereby inhibiting photosynthesis and ultimately leading to plant death. Compared with glufosinate ammonium, L-glufosinate has the advantages of higher herbicidal activity, less dosage, and more environmental friendliness.

[0003] In 2016, patent CN106083922A disclosed a method of synthesizing L-homoserine lactone hydrogen halide using L-methionine and α-halogenated carboxylic acid as reaction raw materials, promoting the reaction through a quaternary ammonium salt phase transfer catalyst, protecting the amino group, and then using dihalogenated sulfoxides, triphosgene (BTC) and other halogenating agents for ring opening halogenation, and then reacting with methylphosphite diester under the action of a catalyst through an Abuzov reaction, hydrolyzing under acidic conditions to obtain refined glufosinate ammonium, with a total yield of 69.2%. The starting raw material of this method is the sulfur-containing compound L-methionine, and there are many sulfur-containing wastes during the synthesis process, and the amino group needs to be protected, which increases the synthesis cost.

[0004] The synthetic route is as follows:

[0005]

[0006] In 2021, patent WO2021143712 disclosed a method using L-homoserine lactone hydrochloride as the starting material, chlorinating with thionyl chloride, neutralizing with an inorganic base, purifying and separating to obtain chlorohomoserine ethyl ester, and then reacting with diethyl methylphosphonate through the Abzov reaction, and hydrolyzing under acidic conditions to obtain refined glufosinate ammonium, with a total yield of 48.6%. This method theoretically requires 2 equivalents of thionyl chloride, and produces sulfur-containing waste gas, hydrogen chloride and waste salt in the process, which is not friendly to the environment.

[0007] The synthetic route is as follows:

[0008]

[0009] In summary, how to solve the problems of complex operation, three wastes treatment, low yield, etc. in the synthesis process of refined glufosinate ammonium is of great significance for the clean production of refined glufosinate ammonium and the improvement of the process level. Summary of the invention

[0010] In view of this, the object of the present invention is to provide a method for preparing refined glufosinate ammonium, which can solve a series of problems in the prior art such as long reaction steps, low yield, and more three wastes.

[0011] The present invention provides a method for preparing refined glufosinate-ammonium, comprising the following steps:

[0012] a) converting the compound represented by formula II with methylphosphite through the Abuzov reaction to the compound represented by formula III;

[0013]

[0014] Among them, R 1 C1~C 12 Alkyl or aryl;

[0015] b) hydrolyzing the compound represented by formula III to convert it into the compound represented by formula I or its salt to obtain refined glufosinate-ammonium;

[0016]

[0017] Preferably, the R 1 It is methyl, ethyl, propyl, isopropyl, n-butyl, pentyl, heptyl, phenyl or p-tolyl.

[0018] Preferably, the Abuzov reaction in step a) is carried out without solvent or in an organic solvent; the organic solvent is selected from chlorobenzene, mesitylene, xylene, toluene, ethanol or methanol.

[0019] Preferably, in step a), the molar ratio of the compound represented by formula II to methylphosphite is 1:(1-2).

[0020] Preferably, the temperature of the Abuzov reaction in step a) is 50° C. to 150° C., and the time is 10 h to 15 h.

[0021] Preferably, the hydrolysis process in step b) is carried out under acidic conditions.

[0022] Preferably, the acidic condition is provided by hydrochloric acid; the concentration of the hydrochloric acid is 5% to 37%.

[0023] Preferably, the hydrolysis temperature in step b) is 25° C. to 110° C., and the time is 6 h to 10 h.

[0024] Preferably, after the hydrolysis in step b), the process further comprises:

[0025] Crystallization separation process.

[0026] Preferably, the crystallization solvent in the crystallization separation process in step b) is methanol, ethanol or acetonitrile.

[0027] The present invention provides a method for preparing refined glufosinate ammonium, comprising the following steps: a) converting a compound represented by formula II and methylphosphinate into a compound represented by formula III through an Abuzov reaction; wherein R 1 C1~C 12 alkyl or aryl; b) hydrolyzing the compound represented by formula III to convert it into the compound represented by formula I or its salt to obtain refined glufosinate-ammonium. Compared with the prior art, the preparation method provided by the present invention selects specific raw materials and specific process steps to achieve overall good interaction, successfully prepares glufosinate-ammonium including all proportions of enantiomers, does not require the use of sulfur-containing raw materials and reagents, has less three wastes, is simple to operate, and has potential industrial value. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The refined glufosinate-ammonium obtained in Example 1 of the present invention 1 HNMR data;

[0029] Figure 2 HPLC data of refined glufosinate-ammonium obtained in Example 4 of the present invention;

[0030] Figure 3 HPLC data of refined glufosinate-ammonium obtained in Example 5 of the present invention;

[0031] Figure 4 HPLC data of refined glufosinate-ammonium obtained in Example 6 of the present invention;

[0032] Figure 5 HPLC data of refined glufosinate-ammonium obtained in Example 11 of the present invention;

[0033] Figure 6 , Figure 7 LC-MS data of raw material II in Example 1 of the present invention. DETAILED DESCRIPTION

[0034] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] The present invention provides a method for preparing refined glufosinate-ammonium, comprising the following steps:

[0036] a) converting the compound represented by formula II with methylphosphite through the Abuzov reaction to the compound represented by formula III;

[0037]

[0038] Among them, R 1 C1~C 12 Alkyl or aryl;

[0039] b) hydrolyzing the compound represented by formula III to convert it into the compound represented by formula I or its salt to obtain refined glufosinate-ammonium;

[0040]

[0041] The present invention provides a method for preparing refined glufosinate ammonium, which uses fermentation or chemical synthesis of o-alkane / aroyl-L-homoserine or its enantiomers or a mixture of all proportions of enantiomers as a starting material, and undergoes simple abzov and hydrolysis reactions to prepare L-glufosinate ammonium acid or D-glufosinate ammonium or a mixture of all proportions of enantiomers thereof. The method is a completely new synthesis route, and the overall technical route is as follows:

[0042]

[0043] The present invention first converts the compound represented by formula II and methylphosphite into the compound represented by formula III through the Abuzov reaction; wherein the alkyl or aryl acid ester is a characteristic byproduct of this type of reaction.

[0044] In the present invention, R 1 C1~C 12 The alkyl or aryl group is preferably methyl, ethyl, propyl, isopropyl, n-butyl, pentyl, heptyl, phenyl or p-tolyl. In a preferred embodiment of the present invention, o-alkane / aroyl-L-homoserine is used as a raw material.

[0045] In the present invention, the Abuzov reaction is preferably carried out without solvent or in an organic solvent, more preferably in an organic solvent; the organic solvent is preferably selected from chlorobenzene, mesitylene, xylene, toluene, ethanol or methanol, more preferably chlorobenzene, mesitylene, xylene or toluene, and even more preferably chlorobenzene or mesitylene. The present invention has no particular limitation on the source of the organic solvent, and commercially available products known to those skilled in the art can be used.

[0046] In the present invention, the molar ratio of the compound represented by formula II to methylphosphite is preferably 1:(1-2).

[0047] In the present invention, the temperature of the Abzov reaction is preferably 50°C to 150°C, more preferably 110°C to 140°C, and the time is preferably 10h to 15h, more preferably 11h to 13h.

[0048] In a preferred embodiment of the present invention, the Abuzov reaction is carried out in the absence of a catalyst or in the presence of a catalyst, and the catalyst is preferably selected from Lewis acids such as zinc chloride.

[0049] After obtaining the compound of formula III, the present invention, regardless of whether the intermediate compound of formula III is separated, hydrolyzes the compound of formula III to convert it into the compound of formula I or its salt to obtain refined glufosinate ammonium.

[0050] In the present invention, the hydrolysis process is preferably carried out under acidic conditions; the acidic conditions are preferably provided by hydrochloric acid; the concentration of the hydrochloric acid is preferably 5% to 37%, more preferably 10% to 30%. The present invention has no special restrictions on the source of the hydrochloric acid, and commercially available products known to those skilled in the art can be used.

[0051] In the present invention, the hydrolysis temperature is preferably 25° C. to 110° C., and the hydrolysis time is preferably 6 h to 10 h.

[0052] In the present invention, after the hydrolysis, preferably further comprising:

[0053] Crystallization separation process.

[0054] In the present invention, the crystallization solvent in the crystallization separation process is preferably methanol, ethanol or acetonitrile, more preferably methanol or ethanol. The present invention has no particular limitation on the source of the crystallization solvent, and commercially available products known to those skilled in the art can be used.

[0055] The method for preparing refined glufosinate ammonium provided by the present invention selects specific raw materials to cooperate with specific process step conditions and parameters to achieve overall good interaction: O-alkane / aroyl-L-homoserine or its enantiomers or a mixture of enantiomers in all proportions is used as a starting raw material, and glufosinate ammonium including enantiomers in all proportions is prepared through a two-step reaction, without the need to use sulfur-containing raw materials and reagents, with less three wastes, simple operation, and potential industrial value; the beneficial effects include: (1) the Abzov reaction produces alkyl or aryl acid ester as a by-product, which can significantly reduce the unit consumption of methylphosphite compared with the traditional chloroalkane by-product, and reduce the formation of impurities; (2) the entire process route has a high yield, is simple to operate, has less three wastes, and is green and environmentally friendly.

[0056] The present invention provides a method for preparing refined glufosinate ammonium, comprising the following steps: a) converting a compound represented by formula II and methylphosphinate into a compound represented by formula III through an Abuzov reaction; wherein R 1 C1~C 12 alkyl or aryl; b) hydrolyzing the compound represented by formula III to convert it into the compound represented by formula I or its salt to obtain refined glufosinate-ammonium. Compared with the prior art, the preparation method provided by the present invention selects specific raw materials and specific process steps to achieve overall good interaction, successfully prepares glufosinate-ammonium including all proportions of enantiomers, does not require the use of sulfur-containing raw materials and reagents, has less three wastes, is simple to operate, and has potential industrial value.

[0057] In order to further illustrate the present invention, the following examples are provided for detailed description. The raw materials used in the following examples of the present invention are all commercially available products.

[0058] Example 1

[0059] (1) Synthesis of Compound III:

[0060] Add 50g 98% o-acetyl-L-homoserine (0.30mol) and 136.9g chlorobenzene (1.2mol) to a 500mL four-necked reaction bottle, stir evenly, add 50.7g 98% diethyl methylphosphite (0.36mol), slowly heat to 140°C and react for 12 hours, LC-MS detects the reaction progress until the raw materials are completely consumed. The by-products and the remaining raw materials are distilled off under reduced pressure to obtain the key intermediate III crude product, which is directly used for the next step of hydrolysis without further purification.

[0061] (2) Synthesis of L-phosphinothricin:

[0062] The crude compound III (Compound III is calculated at a yield of 100%) is added to a 1000mL four-necked reaction bottle, 369.5g of a 30% aqueous hydrochloric acid solution is added, the temperature is raised to 100°C and refluxed for hydrolysis for 8 hours, and the reaction is detected by LC-MS. After the reaction is completed, the acid water is removed by rotary evaporation under reduced pressure to obtain a white solid, the pH is adjusted to 3-4, and 48.8g of L-glufosinate ammonium is obtained by recrystallization, with a purity of 96.7%, D:L=2:98, and the total yield of separation is 85.7% calculated based on o-acetyl-L-homoserine. Ammonia is further passed or KOH and NaOH are added to obtain glufosinate ammonium salt and other glufosinate ammonium salts.

[0063]

[0064] Embodiments 2 to 7

[0065] The following table refers to Example 1, and lists the yield, purity, and D:L ratio of the Abuzov reaction at different reaction temperatures in different embodiments. The results are shown in Table 1. The compound II feed is 50 g with a purity of 98%, and the molar ratio between related materials remains unchanged. LC-MS is used for central control.

[0066] Table 1

[0067]

[0068]

[0069] It can be seen from Table 1 that high temperature is conducive to the Abuzov reaction, while no reaction occurs at room temperature.

[0070] Embodiments 8 to 12

[0071] The following table refers to Example 1, and lists the yield, purity, and D:L ratio of the Abuzov reaction in different examples under different solvents. The results are shown in Table 2. The compound II feed is 50 g with a purity of 98%, and the molar ratio between related materials remains unchanged. LC-MS is used for central control.

[0072] Table 2

[0073] Example No. Solvent temperature Yield purity D:L 8 Mesitylene 140℃ 83.2％ 97.1％ 2：98 9 Xylene 140℃ 81.8％ 96.7％ 2：98 10 Toluene 110℃ 78.9％ 95.1％ 2：98 11 Ethanol 80℃ 55.1％ 93.9％ 5：95 12 none 140℃ 86.1％ 96.5％ 1：99

[0074] Example 13

[0075] Referring to Example 1, the amount of compound II, the molar ratio of related materials and the reaction temperature remained unchanged, and 0.1 equivalent of zinc chloride was added to catalyze the reaction, and LC-MS was used for central control. After the reaction was completed, L-glufosinate was synthesized with a yield of 86.9%, a purity of 95.7%, and D:L=1:99 through hydrolysis and crystallization.

[0076] Embodiments 14 to 16

[0077] The following table refers to Example 1, and lists the yield, purity, and D:L ratio of the Abuzov reaction under different o-alkane / aroyl-L-homoserine. The results are shown in Table 3. The compound II was fed with 0.3 mol, the molar ratio between related materials and the reaction temperature remained unchanged, and LC-MS was used for in-process control.

[0078] Table 3

[0079] Example No. o-Alkanoyl-L-homoserine Yield purity D:L 14 o-Propionyl-L-homoserine 84.2％ 95.6％ 2：98 15 o-Octanoyl-L-homoserine 78.8％ 96.0％ 3：97 16 o-Benzoyl-L-homoserine 88.1％ 97.2％ 1：99

[0080] Characterization spectrum see Figures 1 to 7 .

[0081] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing refined glufosinate-ammonium, comprising the following steps: a) converting the compound represented by formula II with methylphosphite through the Abuzov reaction to the compound represented by formula III; Among them, R 1 C1~C 12 Alkyl or aryl; b) hydrolyzing the compound represented by formula III to convert it into the compound represented by formula I or its salt to obtain refined glufosinate-ammonium; 2. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: The R 1 It is methyl, ethyl, propyl, isopropyl, n-butyl, pentyl, heptyl, phenyl or p-tolyl.

3. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: The Abuzov reaction in step a) is carried out without solvent or in an organic solvent; the organic solvent is selected from chlorobenzene, mesitylene, xylene, toluene, ethanol or methanol.

4. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: In step a), the molar ratio of the compound represented by formula II to methylphosphonite is 1:(1-2).

5. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: The temperature of the Abuzov reaction in step a) is 50° C. to 150° C., and the time is 10 h to 15 h.

6. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: The hydrolysis process in step b) is carried out under acidic conditions.

7. The method for preparing refined glufosinate-ammonium according to claim 6, characterized in that: The acidic condition is provided by hydrochloric acid; the concentration of the hydrochloric acid is 5% to 37%.

8. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: The hydrolysis temperature in step b) is 25° C. to 110° C., and the time is 6 h to 10 h.

9. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: After the hydrolysis in step b), the method further comprises: Crystallization separation process.

10. The method for preparing refined glufosinate-ammonium according to claim 9, characterized in that: The crystallization solvent in the crystallization separation process in step b) is methanol, ethanol or acetonitrile.

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