Preparation method of L-refined glufosinate-ammonium

Abstract

The invention relates to the technical field of pesticides and herbicides, in particular to a preparation method of L-refined glufosinate ammonium, which comprises the following steps: firstly, preparing an intermediate from diethylamine, diethyl methylphosphite, a compound # imgabs0 # as shown in a formula III and a second solvent in the presence of an iridium-containing Lewis base catalyst by adopting a one-pot method; and carrying out rearrangement and hydrolysis reaction to obtain the L-refined glufosinate-ammonium. The preparation method of the L-refined glufosinate-ammonium has the advantages of simple process steps, mild reaction conditions, high yield and high ee value.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide herbicides, and in particular to a method for preparing L-glufosinate-ammonium. Background Art

[0002] L-glufosinate, as a broad-spectrum, highly efficient non-selective herbicide, has received extensive attention in the pesticide market in recent years due to its unique herbicidal activity and environmental friendliness. Compared with D-glufosinate, L-glufosinate has significant herbicidal advantages. At the same dose, the herbicidal effect of L-glufosinate is significantly better than that of the D, L-glufosinate mixture. Therefore, the development of an efficient and low-cost method for preparing L-glufosinate is of great significance for reducing the use of pesticides, reducing environmental pollution, and improving agricultural production efficiency.

[0003] At present, the preparation methods of L-glufosinate mainly include asymmetric synthesis, racemic separation and biocatalysis. The asymmetric synthesis method usually starts from chiral raw materials and synthesizes optically pure L-glufosinate through a series of complex chemical reactions; the racemic separation method is to separate the D-type and L-type isomers by chiral separation of racemic DL-glufosinate or its derivatives, thereby obtaining optically pure L-glufosinate; the biocatalysis method mainly includes direct hydrolysis with L-glufosinate derivatives as substrates and selective separation with racemic glufosinate precursors as substrates.

[0004] However, the above methods all have problems such as high cost and low theoretical yield. In order to overcome these shortcomings, researchers began to explore new L-glufosinate-ammonium synthesis processes to improve the preparation efficiency and yield of L-glufosinate-ammonium.

[0005] For example, CN118146258A discloses "a method for preparing refined glufosinate ammonium", which uses an acid solution containing refined glufosinate ammonium hydrochloride to remove acid water, then adds anhydrous ethanol for azeotropic distillation, then adds diethylamine to adjust the pH of the system, and finally crystallizes and separates the solid from the liquid to obtain refined glufosinate ammonium. The refined glufosinate ammonium obtained by this method has a high purity, yield and ee value.

[0006] For example, CN115583967A discloses “a method for preparing refined glufosinate ammonium” which uses L-homoserine as the starting synthetic raw material and is prepared through synthetic steps such as L-2-amino-4-chlorobutyric acid ethyl ester hydrochloride and refined glufosinate ammonium, with high yield and low cost.

[0007] Another example is the preparation method previously disclosed by the applicant in the patent publication number CN117964655A, which uses less organic base, has lower cost, a safe and simple process, and controllable by-products, thereby increasing the yield of L-glufosinate.

[0008] However, as research and development continued, the applicant discovered that the original technology still had many process steps and the temperature of the nucleophilic substitution reaction was relatively high, which had a certain impact on the chiral structure, and there was still room for improvement in yield and ee value.

[0009] Therefore, it is urgent to develop a preparation method for L-fine glufosinate ammonium with simple process steps, mild reaction conditions, high yield and high ee value. Summary of the invention

[0010] The main purpose of the present invention is to provide a method for preparing L-fine glufosinate-ammonium, which has simple process steps, mild reaction conditions, high yield and high ee value.

[0011] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0012] In one aspect, the present invention provides a method for preparing L-glufosinate-ammonium, comprising the following steps:

[0013] (1) Under an inert protective gas atmosphere, the compound represented by formula I

[0014]

[0015] Add to the first solvent, heat and react to obtain the compound shown in formula II

[0016]

[0017] (2) Continue to add hydrochloric acid to the system of step (1), heat and stir, evaporate to dryness after the reaction is completed, then add ethanol and heat to reflux, then cool to 0-10°C and cool to crystallize, filter and dry to obtain L-fine glufosinate hydrochloride, then mix L-fine glufosinate hydrochloride with ammonia water until the pH of the mixed system is 5-6, freeze-dry to obtain L-fine glufosinate crude product, then mix the L-fine glufosinate crude product with 800 mL of methanol and stir for 20-30 minutes, centrifuge and filter, then adjust the pH of the filtrate to 7-8 with ammonia water, and freeze-dry to obtain L-fine glufosinate;

[0018] The compound represented by formula I is composed of diethylamine, diethyl methylphosphite, and a compound represented by formula III

[0019]

[0020] The method is prepared by a one-pot process in the presence of an iridium-containing Lewis base catalyst and a second solvent, wherein X is a halogen, and R1 is any one of a methyl group, an ethyl group, a propyl group and a tert-butyl group.

[0021] Previously, the applicant disclosed a method for preparing L-glufosinate in a patent with publication number CN117964655A, wherein the compound represented by formula III

[0022]

[0023] Reaction with diethyl methylphosphite to produce the compound shown in formula IX

[0024]

[0025] Drawing on the nucleophilic substitution reaction, the reaction conditions require high temperature and negative pressure to occur. The conditions are harsh, and the higher temperature has a certain influence on the chiral structure of the product, affecting the yield and ee value of L-glufosinate ammonium.

[0026] As the company's research and development continues to deepen, the applicant has developed a Lewis base catalyst suitable for nucleophilic substitution reactions, optimized and improved the process steps, and reduced the occurrence of the above-mentioned problems.

[0027] Most of the previous preparation methods use the compound shown in formula I, and then undergo hydrolysis and other reactions to obtain L-glufosinate. The synthesis of the compound shown in formula I is complicated and needs to be carried out in two steps. For example, the preparation method of the compound shown in formula I disclosed in CN116789695A first synthesizes the compounds shown in formulas X-1, X-2 and X-3.

[0028]

[0029] Wherein X and Y are halogen (R2, R3, R4 and R5 correspond to R1, R2, R9 and R10 in the CN116789695A publication, respectively). 10 The application will not repeat its definition), and then any one of the compounds represented by X-1, X-2 and X-3 is reacted with the compound represented by formula III to obtain.

[0030] The present application uses diethylamine, diethyl methylphosphite, and the compound shown in formula III

[0031]

[0032] The compound shown in Formula I can be prepared by a one-pot method in the presence of an iridium-containing Lewis base catalyst with a second solvent. The process is simple and can improve the yield of the compound shown in Formula I without reducing the ee value. The catalyst used is independently developed and prepared, which reduces the purchase cost of the catalyst and can also improve the catalytic efficiency, further improving the yield and ee value of L-fine glufosinate ammonium.

[0033] In some embodiments, the preparation method of the compound shown in formula I specifically comprises the following steps: in an inert protective gas atmosphere, diethylamine and a second solvent are mixed and stirred evenly, and an iridium-containing Lewis base catalyst and diethyl methyl phosphite are added to the system at the same time, and the temperature is raised and stirred for a period of time to obtain a compound shown in formula IV

[0034]

[0035] Then, the compound represented by formula III is added thereto and stirring is continued at a constant temperature. After the reaction is completed, the compound represented by formula I is obtained by distillation under reduced pressure.

[0036] The present application adopts a one-pot method to prepare the compound shown in Formula I, wherein a catalyst prepared by the applicant is used, which not only reduces the temperature and time of the nucleophilic substitution reaction and avoids the reduction of the ee value of the compound shown in Formula I, but also can improve the yield of the compound shown in Formula I. The homemade catalyst has high catalytic efficiency and can also avoid the problem of excessive cost caused by directly purchasing the catalyst.

[0037] In some embodiments, in step (1), the molar ratio of diethylamine, diethyl methylphosphite and the compound represented by formula III is (0.4-0.6):1:(0.5-0.7).

[0038] The present application can prevent the problem that the subsequent reaction cannot proceed due to diethylamine replacing two diethyl ester groups in diethyl methyl phosphite by regulating the molar ratio of diethylamine, diethyl methyl phosphite and the compound shown in Formula II.

[0039] In some embodiments, the mass of the iridium-containing Lewis base catalyst is 0.5-0.7% of the total mass of diethylamine, diethyl methylphosphite and the compound represented by formula III.

[0040] The present application can prevent the reaction from proceeding slowly and resulting in a reduced yield by regulating the total mass ratio of the iridium-containing Lewis base catalyst to diethylamine, diethyl methyl phosphite and the compound represented by Formula II. On the other hand, it can prevent an increase in the synthesis cost and the appearance of by-products due to excessively high catalytic activity, thereby reducing the yield of the target product.

[0041] In some embodiments, the heating temperature is 55-65° C., the reaction time of diethylamine and diethyl methylphosphite is 8-10 h, and the reaction time after adding the compound represented by formula II is 10-12 h.

[0042] In some embodiments, the preparation method of the iridium-containing Lewis base catalyst comprises the following steps: dissolving iridium chloride in oxygen-free water, adding a ligand compound to the system, heating to 75-79° C., adding a reducing agent to the system while stirring until no precipitation is generated, filtering, washing with oxygen-free water, and drying to obtain an iridium-containing Lewis base catalyst; the structure of the ligand compound is shown in Formula V:

[0043]

[0044] In some embodiments, the molar ratio of the iridium chloride to the ligand compound is 1:(3-3.2).

[0045] Preferably, the molar ratio of iridium chloride to the ligand compound is 1:3.1.

[0046] The present invention regulates the molar ratio of iridium chloride to the ligand compound to enable iridium to form a stable octahedral coordination structure, thereby further improving the catalytic efficiency.

[0047] In some embodiments, the reducing agent is potassium borohydride and / or sodium borohydride.

[0048] In some embodiments, the method for preparing the ligand compound comprises the following steps:

[0049] S1. Mix 2-naphthocarbonitrile and 4-hydroxyquinoline-8-carbonitrile, add a third solvent, add NaH in batches at -5 to 0°C, then heat to 40 to 50°C and stir at constant temperature for 20 to 22 hours. After the reaction is completed, quench, extract, combine the organic phases, dry and then pass column chromatography to obtain compound A, the structure of which is shown in Formula VI.

[0050]

[0051] S2, compound A in step S1 and the fourth solvent are mixed, hydrogen is introduced, the temperature is raised to 35-45° C. and stirred at a constant temperature for 5-7 hours, and after the reaction is completed, compound B is obtained, the structure of which is shown in formula VII

[0052]

[0053] S3, 4-pyridineacetic acid and thionyl chloride were mixed and stirred at -5 to 0°C for 3 to 5 hours, and after the reaction was completed, the mixture was quenched, extracted, concentrated and dried under reduced pressure to obtain compound C, the structure of which is shown in Formula VIII

[0054]

[0055] S4, mixing the compound C in step S3, the compound B in step S2 and the fifth solvent, adding an acid binding agent, stirring at room temperature for 1 to 2 hours, filtering after the reaction, and performing column chromatography to obtain a ligand compound.

[0056] In some embodiments, the second solvent is any one of methanol, ethanol, N,N-dimethylformamide and tetrahydrofuran.

[0057] In some embodiments, in step (1), the heating temperature is 70-80° C. and the reaction time is 7-9 h.

[0058] In some embodiments, in step (1), the first solvent is any one of toluene, xylene and tetrahydrofuran.

[0059] In some embodiments, in step (2), the heating temperature is 90 to 100° C., and the reaction time is 20 to 24 hours.

[0060] Compared with the prior art, the present invention has the following beneficial effects:

[0061] (1) The preparation method of L-glufosinate-ammonium of the present invention uses diethylamine, diethyl methyl phosphite, the compound shown in formula III and a second solvent as main raw materials. First, the compound shown in formula I is synthesized by a one-pot method by referring to the nucleophilic substitution reaction, and then L-glufosinate-ammonium is obtained through hydrolysis and other steps. The preparation method has simple process steps, mild reaction conditions, high yield and high ee value.

[0062] (2) The present invention uses a homemade Lewis base catalyst to catalyze diethylamine, diethyl methylphosphite and the compound of formula III to synthesize the compound of formula I in a one-pot process, thereby reducing the reaction temperature and time, reducing the process steps, and obtaining a higher product yield and ee value.

[0063] (3) The ligand compound of the present invention contains a large number of ionic bonds, hydrogen bonds and coordination bonds, which can make iridium form a more stable octahedral structure, thereby improving the stability of the catalyst during use. At the same time, the phenyl groups therein can form π-π stacking to further improve the high temperature resistance and structural stability of the catalyst, thereby improving the catalytic efficiency. In addition, the ligand contains a large number of pyridine structures, which can increase the basicity of the catalyst and can cooperate with iridium to catalyze nucleophilic substitution reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0065] Figure 1 is the nuclear magnetic resonance spectrum of compound A in Preparation Example 1;

[0066] Figure 2 is the nuclear magnetic resonance spectrum of compound B in Preparation Example 1;

[0067] Figure 3 is the nuclear magnetic resonance spectrum of compound C in Preparation Example 1;

[0068] Figure 4 is the nuclear magnetic resonance spectrum of the ligand compound in Preparation Example 1;

[0069] Figure 5 is the nuclear magnetic resonance spectrum of the compound represented by formula IV in Example 1;

[0070] Figure 6is the nuclear magnetic resonance spectrum of the compound represented by formula I in Example 1;

[0071] Figure 7 This is the nuclear magnetic resonance spectrum of the compound represented by formula II in Example 1. DETAILED DESCRIPTION

[0072] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. 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.

[0073] Preparation Example 1

[0074] The preparation method of the ligand compound comprises the following steps:

[0075] S1. 14.1 g of 2-naphthocarbonitrile and 15.6 g of 4-hydroxyquinoline-8-carbonitrile were mixed, 210 mL of tetrahydrofuran was added, 0.22 g of NaH was added in batches at -3 °C, and then the temperature was raised to 45 °C and stirred at a constant temperature for 21 h. After the reaction was completed, the mixture was quenched, extracted, and the organic phases were combined, dried, and subjected to column chromatography to obtain compound A, the structure of which is shown in Formula VI.

[0076] The yield is 52.1%;

[0077] according to Figure 1 It can be seen that the NMR data analysis of compound A is as follows: 1 H NMR(500MHz,)δ8.81(d,J=5.0Hz,1H),8.42-8.30(m,2H),8.06-7.93(m,1H),7.92-7.84(m,1H),7. 67(dd,J=5.0,2.3Hz,1H),7.55-7.45(m,2H),7.23(dd,J=10.03,2.5Hz,1H),7.12(d,J=5.0Hz,1H);

[0078] S2, 15.4g of compound A in step S1 and 800mL of ammonia water were mixed, hydrogen was introduced, the temperature was raised to 40°C and stirred at a constant temperature for 6h, and after the reaction was completed, compound B was obtained, the structure of which is shown in Formula VII

[0079] The yield is 89.8%;

[0080] according to Figure 2 It can be seen that the NMR data analysis of compound B is as follows: 1H NMR(500MHz,)δ8.62(d,J=5.0Hz,1H),8.14(dd,J=10.0,1.3Hz,1H),7.86(ddd ,J=10.0,8.1,2.0Hz,2H),7.72-7.68(m,1H),7.47(dd,J=10.0,1.3Hz,1H),7.4 4-7.35(m,3H),7.11(dd,J=10.0,2.4Hz,1H),7.06(d,J=5.0Hz,1H),4.31(q,J= 5.0Hz,1H),4.22-4.12(m,3H),4.03-3.94(m,3H),3.90(td,J=5.0,5.8Hz,1H);

[0081] S3, 14.0g 4-pyridineacetic acid and 36.4g thionyl chloride were mixed and stirred at -3°C for 4h, quenched after the reaction, extracted, concentrated and dried under reduced pressure to obtain compound C, the structure of which is shown in Formula VIII

[0082] The yield is 98.6%;

[0083] according to Figure 3 It can be seen that the NMR data analysis of compound C is as follows: 1 H NMR(500MHz,)δ8.65-8.45(m,1H),7.33-7.08(m,1H),4.40(d,J=15.0Hz,1H),4.12(d,J=10.0Hz,0H);

[0084] S4, 15.56g of compound C in step S3, 15.8g of compound B in step S2 and 282mL of N,N-dimethylformamide were mixed, 21g of potassium bicarbonate was added, and the mixture was stirred at a constant temperature of 27°C for 1.5h. After the reaction was completed, the mixture was filtered and subjected to column chromatography to obtain a ligand compound with a yield of 95.2%. The total yield of the ligand compound was calculated to be 46.1%.

[0085] according to Figure 4 It can be seen that the NMR data analysis of the ligand compound is as follows: 1H NMR(500MHz,)δ8.62(d,J=5.0Hz,1H),8.59-8.54(m,4H),8.27-8.19(m,2H),8.14(d d,J=10.0,1.3Hz,1H),7.72(dd,J=10.0,1.2Hz,2H),7.69-7.65(m,1H),7.51(dd,J= 10.0,1.3Hz,1H),7.45-7.33(m,3H),7.20(dd,J=10.0,1.9Hz,1H),7.17-7.12(m,3H ), 7.06 (d, J = 5.0Hz, 1H), 4.84 (d, J = 5.0Hz, 2H), 4.36 (d, J = 5.0Hz, 2H), 3.62 (s, 4H).

[0086] Preparation Example 2

[0087] The preparation method of an iridium-containing Lewis base catalyst comprises the following steps: dissolving 15.8 g of iridium chloride in 1 L of oxygen-free water, adding 88 g of a ligand compound into the system, heating the system to 77° C., dripping a 12 wt % sodium borohydride solution into the system while stirring until no precipitation is generated, filtering, washing with oxygen-free water, and drying to obtain the iridium-containing Lewis base catalyst;

[0088] The structure of the ligand compound is shown in Formula V:

[0089]

[0090] Wherein, the ligand compound is prepared by Preparation Example 1.

[0091] Example 1

[0092] The preparation method of L-fine glufosinate-ammonium comprises the following steps:

[0093] (1) Under N2 atmosphere, 36.6 g of diethylamine and 1.5 L of tetrahydrofuran were mixed and stirred evenly. At the same time, 1.6 g of iridium-containing Lewis base catalyst and 136 g of diethyl methyl phosphite were added to the system. The temperature was raised to 60°C and stirred for 9 hours to obtain a compound shown in Formula IV.

[0094]

[0095] Then, 99.4 g (0.6 mol) of the compound represented by formula III was added thereto.

[0096]

[0097] Continue stirring at constant temperature for 11 hours. After the reaction is completed, perform vacuum distillation to obtain the compound shown in Formula I.

[0098]

[0099] The calculated yield of the compound represented by formula I is 97.9%; the ee value is 99.76%;

[0100] according to Figure 5 It can be seen that the NMR analysis of the compound shown in formula IV is as follows: 1 H NMR (500MHz,) δ3.97 (p, J = 5.0Hz, 1H), 2.99 (p, J = 10.0Hz, 2H), 1.47 (d, J = 5.0Hz, 2H), 1.14 (t, J = 5.0Hz, 1H), 0.92 (t, J = 10.0Hz, 3H);

[0101] according to Figure 6 It can be seen that the NMR analysis of the compound shown in Formula I is as follows: 1 H NMR(500MHz,)δ4.14(qd,J=5.0,2.0Hz,1H),3.67-3.52(m,1H),3.13(d,J=10.0Hz,1H),2.93(pd,J=1 0.0,1.4Hz,2H),2.04-1.88(m,0H),1.45(d,J=5.0Hz,2H),1.23(t,J=5.0Hz,2H),0.94-0.84(m,3H);

[0102] (2) Under N2 atmosphere, 141 g (0.5 mol) of the compound represented by formula I in step (1) was added to 1.5 L of toluene, and the temperature was raised to 75°C and the reaction was carried out for 8 hours to obtain the compound represented by formula II

[0103]

[0104] according to Figure 7 It can be seen that the NMR analysis of the compound shown in Formula II is as follows: 1 H NMR(500MHz,)δ5.28(d,J=5.0Hz,1H),4.16(q,J=5.0Hz,2H),3.53-3.30(m,2H), 3.14-3.00(m,3H),2.27(d,J=5.0Hz,3H),2.10-1.93(m,1H),1.34-1.14(m,9H);

[0105] (3) Add 748g of 25wt% hydrochloric acid solution to the system of step (2), heat to 95°C and stir for 22h, evaporate to dryness after the reaction is completed, add 1.36L of ethanol and heat to reflux, cool to 5°C and cool to crystallize, filter and dry to obtain L-fine glufosinate hydrochloride, mix L-fine glufosinate hydrochloride with ammonia water until the pH of the mixed system is 5.5, freeze-dry to obtain L-fine glufosinate crude product, mix L-fine glufosinate crude product with 800mL of methanol and stir for 25min, centrifuge and filter, adjust the pH of the filtrate to 7.5 with ammonia water, and freeze-dry to obtain L-fine glufosinate. The total yield is calculated to be 88.4%, and the ee value is 97.6%.

[0106] Wherein, the iridium-containing Lewis base catalyst is prepared by Preparation Example 2.

[0107] Example 2

[0108] The preparation method of L-fine glufosinate-ammonium comprises the following steps:

[0109] (1) Under N2 atmosphere, 36.6 g (0.5 mol) of diethylamine and 1.5 L of tetrahydrofuran were mixed and stirred evenly. At the same time, 1.55 g of iridium-containing Lewis base catalyst and 170 g (1.25 mol) of diethyl methyl phosphite were added to the system. The temperature was raised to 55°C and stirred for 10 hours to obtain a compound shown in Formula IV.

[0110]

[0111] Then, 103.5 g (0.625 mol) of the compound represented by formula III was added thereto.

[0112]

[0113] Continue stirring at constant temperature for 12 hours. After the reaction is completed, distill under reduced pressure to obtain the compound shown in formula I.

[0114]

[0115] The calculated yield of the compound represented by formula I is 96.9%; the ee value is 99.53%;

[0116] (2) Under N2 atmosphere, 141 g (0.5 mol) of the compound represented by formula I in step (1) was added to 1.5 L of toluene, and the temperature was raised to 80°C and the reaction was carried out for 7 hours to obtain the compound represented by formula II

[0117]

[0118] (3) Add 935g of 28wt% hydrochloric acid solution to the system of step (2), heat to 90°C and stir for 24h, evaporate to dryness after the reaction is completed, add 1.7L of ethanol and heat to reflux, cool to 0°C and cool to crystallize, filter and dry to obtain L-fine glufosinate hydrochloride, mix L-fine glufosinate hydrochloride with ammonia water until the pH of the mixed system is 5, freeze-dry to obtain L-fine glufosinate crude product, mix L-fine glufosinate crude product with 800mL of methanol and stir for 20min, centrifuge and filter, adjust the pH of the filtrate to 7 with ammonia water, and freeze-dry to obtain L-fine glufosinate. The total yield is calculated to be 87.6%, and the ee value is 97.1%.

[0119] Wherein, the iridium-containing Lewis base catalyst is prepared by Preparation Example 2.

[0120] Example 3

[0121] The preparation method of L-fine glufosinate-ammonium comprises the following steps:

[0122] (1) Under N2 atmosphere, 36.6 g (0.5 mol) of diethylamine and 1.5 L of tetrahydrofuran were mixed and stirred evenly. At the same time, 1.72 g of iridium-containing Lewis base catalyst and 113 g (0.83 mol) of diethyl methyl phosphite were added to the system. The temperature was raised to 65°C and stirred for 8 hours to obtain a compound shown in Formula IV.

[0123]

[0124] Then, 96.2 g (0.58 mol) of the compound represented by formula III was added thereto.

[0125]

[0126] Continue stirring at constant temperature for 10 hours. After the reaction is completed, perform vacuum distillation to obtain the compound shown in formula I.

[0127]

[0128] The calculated yield of the compound represented by formula I is 97.2%; the ee value is 99.86%;

[0129] (2) Under N2 atmosphere, 141 g (0.5 mol) of the compound represented by formula I in step (1) was added to 1.5 L of toluene, and the temperature was raised to 70°C and the reaction was carried out for 9 hours to obtain the compound represented by formula II

[0130]

[0131] (3) Add 621g of 30wt% hydrochloric acid solution to the system of step (2), heat to 100°C and stir for 22h, evaporate to dryness after the reaction is completed, add 1.1L ethanol and heat to reflux, cool to 10°C and cool to crystallize, filter and dry to obtain L-fine glufosinate hydrochloride, mix L-fine glufosinate hydrochloride with ammonia water until the pH of the mixed system is 6, freeze-dry to obtain L-fine glufosinate crude product, mix L-fine glufosinate crude product with 800mL methanol and stir for 30min, centrifuge and filter, adjust the pH of the filtrate to 8 with ammonia water, and freeze-dry to obtain L-fine glufosinate. The total yield is calculated to be 87.9%, and the ee value is 97.3%.

[0132] Wherein, the iridium-containing Lewis base catalyst is prepared by Preparation Example 2.

[0133] Example 4

[0134] The preparation method of L-fine glufosinate-ammonium is the same as that of Example 1, except that 92 g of diethyl methyl phosphite is used.

[0135] The calculated yield of the compound represented by formula I was 50.6%.

[0136] Example 5

[0137] The preparation method of L-glufosinate-ammonium is the same as that of Example 1, except that the iridium-containing Lewis base catalyst is 2.5 g.

[0138] The calculated yield of the compound represented by formula I is 93.8%.

[0139] Example 6

[0140] The preparation method of L-glufosinate-ammonium is the same as that of Example 1, except that in step (1), diethyl methyl phosphite and the compound represented by formula III are added to the system simultaneously for reaction.

[0141] The calculated yield of the compound represented by formula I was 92.3%.

[0142] Example 7

[0143] The preparation method of L-glufosinate-ammonium is the same as that of Example 1, except that the reaction temperature in step (1) is 90°C.

[0144] The calculated ee value of the compound represented by formula I is 97.6%.

[0145] Comparative Example 1

[0146] The preparation method of L-fine glufosinate-ammonium is the same as that of Example 1, except that an equal mass of 2,4,6-trimethylpyridine is used instead of the iridium-containing Lewis base catalyst.

[0147] The calculated yield of the compound represented by formula I was 94.3%.

[0148] Result analysis: The preparation methods of L-fine glufosinate in Examples 1 to 3 have higher yields and ee values, and the conditions in the preparation process are relatively mild; in Example 4, the yield of the compound shown in Formula I is reduced due to the change in the molar ratio of diethylamine, diethyl methylphosphite and the compound shown in Formula III, and L-fine glufosinate cannot be effectively synthesized; in Example 5, the reaction activity is high, the by-products increase, and the yield of the compound shown in Formula I is reduced due to the change in the ratio of the total mass of the iridium-containing Lewis base catalyst to diethylamine, diethyl methylphosphite and the compound shown in Formula III; in Example 6, diethyl methylphosphite and the compound shown in Formula III are added to the system at the same time for reaction, resulting in a reduction in the yield of the compound shown in Formula I; in Example 7, the ee value of the compound shown in Formula I is reduced due to the increase in the reaction temperature; in Comparative Example 1, the yield of the compound shown in Formula I is reduced under the same temperature conditions due to the use of an equal mass of 2,4,6-trimethylpyridine instead of the iridium-containing Lewis base catalyst.

[0149] Finally, it should be noted that the above specific implementation methods are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to examples, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for preparing L-fine glufosinate-ammonium, characterized in that: The steps include: (1) Under an inert protective gas atmosphere, the compound represented by formula I Add to the first solvent, heat and react to obtain the compound shown in formula II (2) Continue to add hydrochloric acid to the system of step (1), heat and stir, evaporate to dryness after the reaction is completed, then add ethanol and heat to reflux, then cool to 0-10°C and cool to crystallize, filter and dry to obtain L-fine glufosinate hydrochloride, then mix L-fine glufosinate hydrochloride with ammonia water until the pH of the mixed system is 5-6, freeze-dry to obtain L-fine glufosinate crude product, then mix the L-fine glufosinate crude product with 800 mL of methanol and stir for 20-30 minutes, centrifuge and filter, then adjust the pH of the filtrate to 7-8 with ammonia water, and freeze-dry to obtain L-fine glufosinate; The compound represented by formula I is composed of diethylamine, diethyl methylphosphite, and a compound represented by formula III The method is prepared by a one-pot process in the presence of an iridium-containing Lewis base catalyst and a second solvent, wherein X is a halogen, and R1 is any one of a methyl group, an ethyl group, a propyl group and a tert-butyl group.

2. The method for preparing L-fine glufosinate-ammonium according to claim 1, characterized in that: The preparation method of the compound shown in formula I specifically comprises the following steps: in an inert protective gas atmosphere, diethylamine and a second solvent are mixed and stirred evenly, and an iridium-containing Lewis base catalyst and diethyl methyl phosphite are added to the system at the same time, and the mixture is heated and stirred for a period of time to obtain a compound shown in formula IV Then, the compound represented by formula III is added thereto and stirring is continued at a constant temperature. After the reaction is completed, the compound represented by formula I is obtained by distillation under reduced pressure.

3. The method for preparing L-fine glufosinate-ammonium according to claim 2, characterized in that: In step (1), the molar ratio of diethylamine, diethyl methylphosphite and the compound represented by formula III is (0.4-0.6):1:(0.5-0.7).

4. The method for preparing L-fine glufosinate-ammonium according to claim 2, characterized in that: The mass of the iridium-containing Lewis base catalyst is 0.5-0.7% of the total mass of diethylamine, diethyl methylphosphite and the compound represented by formula III.

5. The method for preparing L-fine glufosinate-ammonium according to claim 2, characterized in that: The heating temperature is 55-65° C., the reaction time of diethylamine and diethyl methylphosphite is 8-10 hours, and the reaction time after adding the compound represented by formula II is 10-12 hours.

6. The method for preparing L-fine glufosinate-ammonium according to claim 1, characterized in that: The preparation method of the iridium-containing Lewis base catalyst comprises the following steps: dissolving iridium chloride in oxygen-free water, adding a ligand compound into the system, heating to 75-79° C., adding a reducing agent dropwise into the system while stirring until no precipitation is generated, filtering, washing with oxygen-free water, and drying to obtain the iridium-containing Lewis base catalyst; the structure of the ligand compound is shown in Formula V:

7. The method for preparing L-fine glufosinate-ammonium according to claim 2, characterized in that: The second solvent is any one of methanol, ethanol, N,N-dimethylformamide and tetrahydrofuran.

8. The method for preparing refined glufosinate-ammonium according to claim 1, characterized in that: In step (1), the heating temperature is 70-80° C. and the reaction time is 7-9 hours.

9. The method for preparing L-fine glufosinate-ammonium according to claim 1, characterized in that: In step (1), the first solvent is any one of toluene, xylene and tetrahydrofuran.

10. The method for preparing L-fine glufosinate-ammonium according to claim 1, characterized in that: In step (2), the heating temperature is 90-100° C. and the reaction time is 20-24 h.

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