Preparation process of glufosinate-ammonium intermediate 3-(methyl hydroxyl phosphonyl) propionaldehyde
By employing a novel addition-hydrosilanization-hydrolysis process, using acrylic acid instead of acrolein, and utilizing an arylborane-containing catalyst, the problems of low yield and poor safety in the preparation of glufosinate intermediates have been solved. This process achieves high-yield and environmentally friendly preparation of glufosinate intermediates, making it suitable for industrial production.
Patent Information
- Application Number
- CN202511183596.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-22
- Publication Date
- 2025-12-05
AI Technical Summary
The existing preparation process of glufosinate intermediate 3-(methylhydroxyphosphono)propionaldehyde has problems such as low yield, poor process safety and environmental protection. In particular, the use of highly toxic acrolein as a raw material leads to safety risks and environmental pollution during the production process.
Using diethyl methylphosphonite, acrylic acid, and anhydrous ethanol as raw materials, a three-step reaction route of addition-hydrosilanization-hydrolysis was adopted to replace the traditional acrolein, and an arylborane compound was used as a catalyst to prepare the glufosinate intermediate 3-(methylhydroxyphosphono)propionaldehyde.
It significantly improves the yield of glufosinate intermediates, reduces production costs and safety risks, is suitable for large-scale industrial production, and provides a green and efficient synthesis solution.
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Figure CN121064243A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of pesticide production, and in particular to a preparation process of glufosinate ammonium intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde. BACKGROUND
[0003] The current mature synthesis process of glufosinate ammonium is Strecker process, and 3-(methyl hydroxy phosphinyl) propionaldehyde is an important intermediate in the synthesis process, which is generally synthesized by using diethyl methyl phosphite, propylene aldehyde and ethanol as raw materials, and the process route is as follows. The raw material propylene aldehyde belongs to 3 carcinogens, has a low boiling point, strong volatility, irritation and tear-inducing properties, and has high toxicity. At the same time, the water content of industrial propylene aldehyde is generally about 3%, and diethyl methyl phosphite is easy to hydrolyze in water, so a part of diethyl methyl phosphite will be hydrolyzed in the reaction process, resulting in a decrease in yield.
[0004]
[0005] Therefore, it is urgent to develop a new preparation process of 3-(methyl hydroxy phosphinyl) propionaldehyde to improve the yield, improve the safety and environmental protection of the process, reduce the safety risk and environmental pollution caused by toxic raw materials, and become a key problem to be solved in the field. SUMMARY
[0006] In view of the problems of low yield, poor process safety and environmental protection in the preparation process of glufosinate ammonium intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde in the prior art, the present application provides a preparation process of glufosinate ammonium intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde.
[0007] To solve the above technical problems, the technical scheme provided by the present application is:
[0008] A preparation process of glufosinate ammonium intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde, comprising the following steps:
[0009] S1, diethyl methyl phosphite, acrylic acid and anhydrous ethanol are used as raw materials to perform addition reaction to obtain 3-[ethoxy(methyl) phosphinyl] propionate shown in formula (I);
[0010]
[0011] S2, 3-[ethoxy(methyl) phosphinyl] propionate and triethylsilane are used as raw materials, and an aryl borane compound is used as a catalyst to perform hydrosilylation reaction to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate shown in formula (II);
[0012]
[0013] S3, hydrolyzing 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonate to obtain the oxinactin intermediate 3-(methyl hydroxy phosphinoyl) propionaldehyde.
[0014]
[0015] The traditional process uses acrolein as a key raw material, which has strong volatility, tear-inducing property and definite carcinogenic risk, and the industrial product has a water content of up to 3%, and the presence of water causes uncontrollable hydrolysis of diethyl methyl phosphonate, resulting in a loss of 10% to 15% of the raw material. More seriously, acrolein is extremely easy to polymerize to form tar-like impurities during storage and reaction, which requires additional dehydration and low-temperature protection, greatly increasing the equipment cost (explosion-proof workshop) and operation risk.
[0016] Compared with the prior art, the preparation process of the oxinactin intermediate 3-(methyl hydroxy phosphinoyl) propionaldehyde provided by the present application provides a brand-new synthesis route, which uses acrylic acid instead of the traditional acrolein raw material, completely avoiding the toxicity risk of acrolein, and at the same time, anhydrous ethanol is selected as the raw material, reducing the introduction of water and avoiding the loss of diethyl methyl phosphonate due to hydrolysis, thereby significantly improving the reaction stability and raw material utilization rate; at the same time, the present application innovatively uses an aryl borane compound as a catalyst in the process route, promoting the directional hydrosilylation reaction of 3-[ethoxy(methyl) phosphinoyl] propionate, and high selectivity to generate 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonate, and then through a simple subsequent hydrolysis reaction, a high-yield oxinactin intermediate 3-(methyl hydroxy phosphinoyl) propionaldehyde is prepared.
[0017] The present application significantly improves the yield of the oxinactin intermediate 3-(methyl hydroxy phosphinoyl) propionaldehyde through the addition-hydrosilylation-hydrolysis innovative route, and at the same time, significantly improves the safety and economy of the process, which is more suitable for industrialized large-scale production, and provides a green and efficient new technical scheme for the industrialized production of oxinactin pesticides, which has very important significance for promoting the development of oxinactin pesticides.
[0018] Further, the preparation process of the oxinactin intermediate 3-(methyl hydroxy phosphinoyl) propionaldehyde specifically comprises the following steps:
[0019] S1, adding diethyl methyl phosphonate dropwise into a mixed solution of acrylic acid and anhydrous ethanol, and then warming to 40-50 DEG C to perform addition reaction to obtain 3-[ethoxy(methyl) phosphinoyl] propionate reaction solution;
[0020] S2, adding an aryl borane compound and triethylsilane to the 3-[ethoxy(methyl) phosphinyl] propionate reaction solution, and performing a hydrosilylation reaction at 15℃-30℃, and after the reaction is completed, removing ethanol to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester;
[0021] S3, adding 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester to an acid solution, hydrolyzing, and dehydrating to obtain the oxinamide intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde.
[0022] The first step of the present application efficiently generates 3-[ethoxy(methyl) phosphinyl] propionate through an addition reaction of diethyl methyl phosphonate and acrylic acid in anhydrous ethanol; the second step innovatively generates 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester with high selectivity through a hydrosilylation reaction of 3-[ethoxy(methyl) phosphinyl] propionate; and the third step obtains 3-(methyl hydroxy phosphinyl) propionaldehyde through a simple dilute acid hydrolysis reaction.
[0023] The above three steps are all performed under mild conditions without special equipment, which not only significantly reduces the production energy consumption, but also reduces the dependence on special equipment, thereby reducing the production cost. Meanwhile, the high selectivity of each step effectively reduces the generation of by-products, improves the raw material utilization rate, and significantly improves the yield of the oxinamide intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde. In addition, the process discards the traditional high-toxicity raw material acrolein, and uses low-toxicity and easy-to-handle raw materials and reagents, which greatly reduces the safety risk in the operation process, and the by-products are less and easy to handle, and the environmental performance is significantly improved, thereby providing an efficient, safe, environmentally friendly and economic new technical route for industrial production of oxinamide.
[0024] Further, in S1, the molar ratio of diethyl methyl phosphonate, acrylic acid and anhydrous ethanol is 1:(1.02-1.1):(2-5).
[0025] The preferred raw material ratio is beneficial to improve the conversion rate of diethyl methyl phosphonate.
[0026] Further, in S1, the dropping temperature of diethyl methyl phosphonate is 10℃-30℃.
[0027] The preferred dropping temperature can ensure uniform mixing of materials, and will not prolong the dropping time, and the reaction efficiency and operation safety are considered. In addition, this temperature interval is reasonably connected with the subsequent 40℃-50℃ holding reaction, and after the dropping is completed, it can quickly enter the holding stage without complex temperature rising program, thereby shortening the overall reaction period and further improving the production efficiency, which is more suitable for the rhythm of industrial continuous production.
[0028] In addition, although there is a dropwise adding operation in S1, it is completely different from the super slow dropwise adding operation in the traditional process due to the toxicity of the raw material (acrolein) or the violent release of reaction heat: on the one hand, the stability of acrylic acid is better than that of acrolein, no strong volatile toxic substances are released during the dropwise adding process, and the operation safety is significantly improved; on the other hand, the reaction system can stably release the reaction heat during the incubation stage at 40-50°C, and there is no need to control the temperature by prolonging the dropwise adding time, so the dropwise adding operation is only a conventional material mixing method and will not restrict the production efficiency as in the traditional process.
[0029] Further, in S1, the time of the addition reaction is 3-5h.
[0030] Further, in S2, the aryl borane-containing compound is triphenyl borane or tris(pentafluorophenyl) borane.
[0031] The preferred catalyst can direct the promotion of the hydrosilylation reaction of 3-[ethoxy(methyl) phosphinyl] propionic acid ester, strictly control the reaction to stay at the stage of generating 3-triethylsiloxy-3-ethoxy propyl methyl phosphonate, greatly reduce the side reactions such as over-reduction, and ensure the high selectivity of the target intermediate.
[0032] Further, in S2, the molar ratio of the aryl borane-containing compound to 3-[ethoxy(methyl) phosphinyl] propionic acid ester is (0.001-0.01):1.
[0033] The preferred catalyst is added in an amount that can ensure the sufficient progress of the hydrosilylation reaction while effectively reducing the production cost.
[0034] Further, in S2, the molar ratio of triethylsilane to 3-[ethoxy(methyl) phosphinyl] propionic acid ester is (1.05-1.1):1.
[0035] Further, in S2, the time of the hydrosilylation reaction is 10-20h.
[0036] Further, in S3, the acid solution is a hydrochloric acid solution, a methyl sulfonic acid solution or a sulfuric acid solution with a hydrogen ion concentration of 0.05-0.1 mol / L, and the mass ratio of the acid solution to 3-triethylsiloxy-3-ethoxy propyl methyl phosphonate is (1-2):1.
[0037] Further, in S3, the temperature of the hydrolysis is 40-50°C, and the time of the hydrolysis is 2-5h.
[0038] Specifically, in S3, the dehydration is performed by vacuum dehydration, the temperature of the vacuum dehydration is 55-60°C, the pressure is -0.09 to -0.095 MPa, and the time is 30-60 min.
[0039] It should be noted that in S3, the 3-(methylhydroxyphosphinyl)propanal intermediate of glufosinate is obtained in the form of a solution by removing part of the water through pressure reduction dehydration, without removing all the water, which not only avoids the increase of energy consumption and the loss of product concentration caused by excessive dehydration, but also directly meets the material state requirements of the next step reaction, saves additional operations such as solvent re-dissolution, significantly simplifies the process flow, and improves the production continuity and efficiency.
[0040] The preparation process of the glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal provided by the present application innovatively adopts a three-step reaction route of addition-silane hydrogenation-hydrolysis, and replaces the traditional highly toxic raw material propylene aldehyde with acrylic acid, thereby avoiding the risk of toxicity from the source, significantly improving the yield of the glufosinate target intermediate, and the total yield of the three-step reaction can reach more than 95%. The entire process has mild reaction conditions, significantly reduces the equipment cost and process safety risk, is suitable for large-scale industrial production application, provides a new efficient and green technical solution for large-scale production of glufosinate, and has a wide application prospect. BRIEF DESCRIPTION OF DRAWINGS
[0041] Figure 1 Gas chromatogram of 3-[ethoxy(methyl)phosphinyl]propionic acid ethyl ester prepared in step one of Example 1 of the present application;
[0042] Figure 2 Gas chromatogram of 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester prepared in step two of Example 1 of the present application;
[0043] Figure 3 Liquid chromatogram of the glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal prepared in step three of Example 1 of the present application. DETAILED DESCRIPTION
[0044] In order to make the purpose, technical scheme and advantages of the present application clearer and more apparent, the present application will be further described in detail below in combination with examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application.
[0045] The prior art for preparing 3-(methylhydroxyphosphinyl) propionaldehyde generally synthesizes the same from diethyl methylphosphonate, acrolein and ethanol, the reaction yield is low, and the process has high safety risk. In order to effectively improve the production efficiency, improve the product yield and process safety, the present application improves the prior production process of 3-(methylhydroxyphosphinyl) propionaldehyde: diethyl methylphosphonate, acrylic acid and anhydrous ethanol are subjected to an addition reaction to prepare 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester, then the 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester and triethylsilane can be subjected to a hydrosilylation reaction under the catalysis of an aryl borane compound to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester with high yield and purity, and the 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is subjected to hydrolysis to obtain 3-(methylhydroxyphosphinyl) propionaldehyde with high purity and high yield.
[0046] The preparation process of 3-(methylhydroxyphosphinyl) propionaldehyde provided by the embodiments of the present application specifically comprises the following steps:
[0047] S1, diethyl methylphosphonate is added dropwise into a mixed solution of acrylic acid and anhydrous ethanol, the temperature is raised to 40-50 DEG C after dropping, an addition reaction is carried out, and 3-[ethoxy(methyl) phosphinyl] propionate reaction liquid is obtained;
[0048] S2, aryl borane compound and triethylsilane are added into the 3-[ethoxy(methyl) phosphinyl] propionate reaction liquid, a hydrosilylation reaction is carried out at 15-30 DEG C, ethanol is removed after the reaction is completed, and 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is obtained;
[0049] S3, 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is added into an acid solution, hydrolysis and dehydration are carried out, and the ammonium glufosinate intermediate 3-(methylhydroxyphosphinyl) propionaldehyde is obtained. The specific process route is as follows:
[0050]
[0051] In order to detect the content of the ammonium glufosinate intermediate 3-(methylhydroxyphosphinyl) propionaldehyde prepared, high performance liquid chromatography is used to detect the product, and the specific method is as follows:
[0052] The ammonium glufosinate intermediate 3-(methylhydroxyphosphinyl) propionaldehyde is subjected to a derivatization reaction with 2,4-dinitrophenylhydrazine (DNPH) in an amount of 2-4 times of the molar amount of the 3-(methylhydroxyphosphinyl) propionaldehyde at 60 DEG C for 20 min to obtain 3-(methylhydroxyphosphinyl) propionaldehyde derivative, then liquid chromatography detection is carried out according to the external standard method, and the specific detection conditions are as follows:
[0053] The chromatographic column is CLCODS C18 (6.0mm*150mm*5um).
[0054] Mobile phase: methanol: acetonitrile: water = 27.5: 27.5: 45;
[0055] Flow rate: 1.0 mL / min;
[0056] Column temperature: 25℃;
[0057] Detection wavelength: 360 nm.
[0058] The content of 3-[ethoxy(methyl)phosphono]propionic acid ethyl ester and 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonic acid ethyl ester was determined by gas chromatography, and the gas chromatography conditions were as follows:
[0059] Gas chromatography column: DM-624, 30m*0.53mm*3.0μm;
[0060] Temperature rising program: 70℃ injection, then temperature rising to 230℃ at a rate of 15℃ / min, keeping for 20min. The detector temperature was 250℃ for detection.
[0061] In order to better illustrate the present application, the following examples are further illustrated by examples.
[0062] Example 1
[0063] Preparation process of a glufosinate intermediate 3-(methyl hydroxy phosphono) propionaldehyde:
[0064] Step one, 69.4g (98%, 0.5mol) of diethyl methyl phosphonate was added dropwise to a mixture of 37.5g (98%, 0.5mol) of acrylic acid and 115g (2.5mol) of anhydrous ethanol, the reaction temperature was controlled at 10℃, after the dropwise addition was completed, the temperature was raised to 40℃ and kept for 5h, to obtain an addition product 3-[ethoxy(methyl)phosphono]propionic acid ethyl ester solution 222g, content 46.6%, yield 99.5%;
[0065] Step two, 0.26g (97%) of tris(pentafluorophenyl)borane and 61.8g (98%) of triethylsilane were added to the 3-[ethoxy(methyl)phosphono]propionic acid ethyl ester solution obtained in step one, and stirred at 15℃ for 20h. Ethanol was removed by distillation under reduced pressure to obtain 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonic acid ethyl ester 166.4g, content 95.4%, yield 98.5%;
[0066] Step three, 333 g of 0.1 mol / L dilute hydrochloric acid was added to 165.8 g of 3- triethylsilyloxy-3-ethoxypropyl methyl phosphonate obtained in step two, hydrolyzed at 50 °C for 2 h, then dehydrated at 60 °C under reduced pressure of -0.095 MPa for 30 min to obtain 3- (methylhydroxyphosphinoyl) propanal concentrated solution 142.6 g, content 46.5%, yield 99.6%, total yield of three steps 97.6%.
[0067] The gas chromatogram of 3-[ethoxy(methyl)phosphinoyl]propionic acid ethyl ester prepared in step one is shown in Figure 1. Figure 1 The gas chromatogram of 3- triethylsilyloxy-3-ethoxypropyl methyl phosphonate prepared in step two is shown in Figure 2. Figure 2 The liquid chromatogram of glufosinate intermediate 3-(methylhydroxyphosphinoyl) propanal prepared in step three is shown in Figure 3. Figure 3
[0068] Example 2
[0069] A preparation process of a glufosinate intermediate 3-(methylhydroxyphosphinoyl) propanal:
[0070] Step one, 69.4 g (98%, 0.5 mol) of diethyl methyl phosphonite was added dropwise to a mixture of 40.4 g (98%, 0.55 mol) of acrylic acid and 46 g of anhydrous ethanol (1.0 mol), the reaction temperature was controlled at 20 °C, after the dropwise addition was completed, the temperature was increased to 45 °C and kept for 4 h to obtain an addition product 3-[ethoxy(methyl)phosphinoyl]propionic acid ethyl ester solution 155.5 g, content 66.0%, yield 98.7%;
[0071] Step two, 2.61 g (97%) of tris(pentafluorophenyl)borane and 64.3 g (98%) of triethylsilane were added to the 3-[ethoxy(methyl)phosphinoyl]propionic acid ethyl ester solution obtained in step one, stirred at 30 °C for 10 h, and then ethanol was distilled off under reduced pressure to obtain 3- triethylsilyloxy-3-ethoxypropyl methyl phosphonate 168.4 g, content 94.3%, yield 99.3%;
[0072] Step three, 169 g of 0.1 mol / L dilute hydrochloric acid was added to 3- triethylsilyloxy-3-ethoxypropyl methyl phosphonate obtained in step two, hydrolyzed at 40 °C for 3 h, then dehydrated at 55 °C under reduced pressure of -0.090 MPa for 60 min to obtain 3-(methylhydroxyphosphinoyl) propanal 119.8 g, content 55.3%, yield 99.5%, total yield of three steps 97.5%.
[0073] Example 3
[0074] A preparation process of a glufosinate intermediate 3-(methylhydroxyphosphinoyl) propanal:
[0075] Step one, drop methyl phosphonate diethyl ester 69.4g (98%, 0.5mol) into the mixture of 38.6g acrylic acid (98%, 0.52mol) and 92g (2mol) anhydrous ethanol, control the reaction temperature at 30℃, after drop completion, increase the temperature to 50℃ and keep for 3h, get the addition product 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester solution 200g, content 51.5%, yield 99.0%;
[0076] Step two, add tri (pentafluorophenyl) borane 1.31g (97%) and triethylsilane 64.5g (98%) into the 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester solution obtained in step one, stir at 30℃ for 20h, distill off ethanol under reduced pressure, get 3-triethylsiloxy-3-ethoxylpropyl methyl phosphonate 166.9g, content 94.7%, yield 98.5%;
[0077] Step three, add 0.05mol / L dilute hydrochloric acid 161g into the 3-triethylsiloxy-3-ethoxylpropyl methyl phosphonate obtained in step two, hydrolyze at 50℃ for 3h, then dehydrate at 60℃ under -0.091MPa reduced pressure for 50min, get 3-(methyl hydroxy phosphinyl) propionaldehyde 115.1g, content 57.2%, yield 99.3%, total yield of three steps 96.8%.
[0078] Example 4
[0079] A preparation process of a glufosinate intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde:
[0080] Step one, drop methyl phosphonate diethyl ester 69.4g (98%, 0.5mol) into the mixture of 38.6g acrylic acid (98%, 0.52mol) and 92g (2mol) anhydrous ethanol, control the reaction temperature at 30℃, after drop completion, increase the temperature to 50℃ and keep for 3h, get the addition product 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester solution 200g, content 51.5%, yield 99.0%;
[0081] Step two, add triphenylborane 0.13g (95%) and triethylsilane 61.3g (98%) into the 3-[ethoxy(methyl) phosphinyl] propionic acid ethyl ester solution obtained in step one, stir at 15℃ for 20h. Distill off ethanol under reduced pressure, get 3-triethylsiloxy-3-ethoxylpropyl methyl phosphonate 163.4g, content 96.2%, yield 98.3%;
[0082] Step three, 3-[ethyl(methyl)phosphono]propionic acid ethyl ester solution obtained in step two was added with 0.05 mol / L sulfuric acid 327 g, hydrolyzed at 50℃ for 2 h, then dehydrated at 60℃ under -0.094 MPa reduced pressure for 45 min to obtain 3-(methylhydroxyphosphoryl)propanal 137.5 g, content 47.5%, yield 99.1%, total yield of three steps 96.1%.
[0083] Example 5
[0084] A preparation process of a glufosinate intermediate 3-(methylhydroxyphosphoryl)propanal:
[0085] Step one, methylphosphinic acid diethyl ester 69.4 g (98%, 0.5 mol) was added dropwise into a mixture of 37.5 g acrylic acid (98%, 0.5 mol) and 115 g (2.5 mol) anhydrous ethanol, the reaction temperature was controlled at 30℃, after the dropwise addition was completed, the temperature was increased to 50℃ and maintained for 3 h to obtain an addition product 3-[ethyl(methyl)phosphono]propionic acid ethyl ester solution 221.8 g, content 46.5%, yield 99.2%;
[0086] Step two, 3-[ethyl(methyl)phosphono]propionic acid ethyl ester solution obtained in step one was added with triphenylborane 0.63 g (95%) and triethylsilane 64.6 g (98%), stirred at 30℃ for 10 h. Ethanol was distilled off under reduced pressure to obtain 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonate 164.6 g, content 95.8%, yield 98.1%;
[0087] Step three, 3-triethylsilyloxy-3-ethoxypropyl methyl phosphonate obtained in step two was added with 0.1 mol / L methyl sulfonic acid 247 g, hydrolyzed at 50℃ for 2 h, then dehydrated at 55℃ under -0.093 MPa reduced pressure for 45 min to obtain 3-(methylhydroxyphosphoryl)propanal 135.1 g, content 48.6%, yield 99.3%, total yield of three steps 96.6%.
[0088] Example 6
[0089] A preparation process of a glufosinate intermediate 3-(methylhydroxyphosphoryl)propanal:
[0090] Step one, methylphosphinic acid diethyl ester 69.4 g (98%, 0.5 mol) was added dropwise into a mixture of 37.5 g acrylic acid (98%, 0.5 mol) and 115 g (2.5 mol) anhydrous ethanol, the reaction temperature was controlled at 30℃, after the dropwise addition was completed, the temperature was increased to 50℃ and maintained for 3 h to obtain an addition product 3-[ethyl(methyl)phosphono]propionic acid ethyl ester solution 221.8 g, content 46.5%, yield 99.2%;
[0091] Step two, 3-[ethoxy(methyl)phosphinyl]propionic acid ethyl ester obtained in step one was added with triphenylborane 0.63g (95%), triethylsilane 61.3g (98%), and stirred at 20°C for 15h. Ethanol was distilled off under reduced pressure to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester 164.4g, content 95.6%, yield 98.4%;
[0092] Step three, 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester obtained in step two was added with 0.1mol / L sulfuric acid 165g, and hydrolyzed at 40°C for 2h, then dehydrated at 60°C under reduced pressure of -0.09MPa for 30min to obtain 3-(methyl hydroxyphosphinyl)propanal concentrated solution 115.3g, content 56.8%, yield 99.4%, total yield of three steps 96.4%.
[0093] Comparative example 1
[0094] A preparation process of glufosinate ammonium intermediate 3-(methyl hydroxyphosphinyl)propanal:
[0095] Step one, methyl phosphite 69.4g (98%, 0.5mol) was added dropwise into a mixture of 37.5g acrylic acid (98%, 1mol) and 115g (2.5mol) anhydrous ethanol, the reaction temperature was controlled at 30°C, after the dropwise addition was completed, the temperature was increased to 50°C and kept for 3h to obtain 3-[ethoxy(methyl)phosphinyl]propionic acid ethyl ester solution 221.7g, content 46.5%, yield 99.1%;
[0096] Step two, 3-[ethoxy(methyl)phosphinyl]propionic acid ethyl ester solution obtained in step one was added with triphenylphosphine 0.68g (95%), triethylsilane 64.5g (98%), and stirred at 15°C for 20h, ethanol was distilled off under reduced pressure to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester 161.1g, content 83.2%, yield 83.1%;
[0097] Step three, 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester obtained in step two was added with 0.05mol / L sulfuric acid 242g, and hydrolyzed at 50°C for 2h, then dehydrated at 60°C under reduced pressure of -0.095MPa for 30min to obtain 3-(methyl hydroxyphosphinyl)propanal concentrated solution 114.9g, content 48.6%, yield 99.4%, total yield of three steps 81.9%.
[0098] The above only describes the preferred embodiments of the present application and is not used to limit the present application, any modification, equivalent replacement or improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims
1. A process for the preparation of glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal, characterized in that, The method comprises the following steps: S1, addition reaction is carried out by using diethyl methyl phosphonate, acrylic acid and anhydrous ethanol as raw materials, to obtain 3-[ethoxy(methyl) phosphinyl] propionate shown in formula (I); S2, hydrosilylation reaction is carried out by using 3-[ethoxy(methyl) phosphinyl] propionate and triethylsilane as raw materials, and using an aryl borane compound as a catalyst, to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester shown in formula (II); S3, 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is hydrolyzed to obtain the oxinactin intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde.
2. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 1, characterized in that, Specifically, the method comprises the following steps: S1, diethyl methyl phosphonate is added dropwise into a mixed solution of acrylic acid and anhydrous ethanol, and then the temperature is raised to 40-50 DEG C, to carry out addition reaction, to obtain 3-[ethoxy(methyl) phosphinyl] propionate reaction liquid; S2, an aryl borane compound and triethylsilane are added into the 3-[ethoxy(methyl) phosphinyl] propionate reaction liquid, and hydrosilylation reaction is carried out at 15-30 DEG C, and then ethanol is removed after the reaction is completed, to obtain 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester; S3, 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is added into an acid solution, and then hydrolysis and dehydration are carried out, to obtain the oxinactin intermediate 3-(methyl hydroxy phosphinyl) propionaldehyde.
3. Process for the preparation of glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 1 or 2, characterized in that, In S1, the molar ratio of diethyl methyl phosphonate, acrylic acid and anhydrous ethanol is 1:(1.02-1.1):(2-5).
4. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 2, characterized in that, In S1, the dropping temperature of diethyl methyl phosphonate is 10-30 DEG C.
5. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal as claimed in claim 2, wherein, In S1, the time of the addition reaction is 3-5 h.
6. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 1 or 2, characterized in that, In S2, the aryl borane compound is triphenylborane or tris(pentafluorophenyl) borane.
7. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 6, characterized in that, In S2, the molar ratio of the aryl borane compound to 3-[ethoxy(methyl) phosphinyl] propionate is (0.001-0.01):
1.
8. The process of claim 2 for the preparation of glufosinate intermediate 3- (methylhydroxyphosphinyl)propanal, characterized in that, In S2, the molar ratio of triethylsilane to 3-[ethoxy(methyl) phosphinyl] propionate is (1.05-1.1):
1.
9. The process of preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal according to claim 2, characterized in that, In S2, the time of the hydrosilylation reaction is 10-20 h.
10. The process for preparing glufosinate intermediate 3-(methylhydroxyphosphinyl)propanal as claimed in claim 2, wherein, In S3, the acid solution is a hydrochloric acid solution, a methyl sulfonic acid solution or a sulfuric acid solution with a hydrogen ion concentration of 0.05-0.1 mol / L, and the mass ratio of the acid solution to 3-triethylsiloxy-3-ethoxypropyl methyl phosphonate ethyl ester is (1-2):1; and / or In S3, the hydrolysis temperature is 40-50 DEG C, and the hydrolysis time is 2-5 h.