Preparation method of glufosinate ammonium salt

Abstract

The invention discloses a glufosinate ammonium salt preparation method, which comprises: adding diethyl malonate and liquid bromine into a first solvent, carrying out a reaction to obtain an intermediate I, adding the intermediate I, potassium phthalimide and a quaternary ammonium salt catalyst into toluene, carrying out a reaction to obtain an intermediate II, and carrying out a reaction on the intermediate II, potassium carbonate and 1, 2, 4-trimethyl-1, 3-pentanediol to obtain the glufosinate ammonium salt. 2, 2-dibromoethane and a phase transfer catalyst are added into a second solvent for a reaction, an intermediate III is obtained, the intermediate III and diethyl methylphosphonite are added into methylbenzene for a reaction under argon, an intermediate IV is obtained, the intermediate IV is added into hydrochloric acid, a reflux reaction, cooling precipitation and drying are performed, an intermediate V is obtained, the intermediate V and water are mixed, ammonia gas is introduced, the pH value is adjusted, and the intermediate III is obtained. And adding methanol, stirring for reaction, cooling, filtering and drying to obtain the glufosinate ammonium salt. According to the method disclosed by the invention, the use of sodium cyanide or hydrocyanic acid can be avoided, a large amount of ammonium chloride which is difficult to separate is avoided, the content of the obtained glufosinate ammonium salt is 90-98%, and the total yield is greater than 68%.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide herbicide synthesis and relates to a method for preparing glufosinate ammonium salt, and specifically relates to a method for preparing glufosinate ammonium salt by taking diethyl malonate as a raw material. Background Art

[0002] Glufosinate ammonium (i.e. glufosinate) is a highly effective, broad-spectrum, contact-type organophosphine herbicide developed by Germany's Hoechst AG (now Bayer). It mainly acts on glutamine synthetase and has the advantages of low toxicity, harmlessness, and easy degradation.

[0003] There are currently three main synthetic methods reported for glufosinate ammonium, namely, the Hyne method, the ketoacid method and the Strecker method.

[0004] Chinese patent document CN102584893A reports the synthesis of glufosinate ammonium salt by the Hein method, which uses diethyl methylphosphite and acrolein as raw materials, obtains the intermediate (3,3-diacetoxy)propylmethylphosphinate isobutyl ester through Michael addition reaction and esterification reaction, and synthesizes the hydantoin intermediate through Bucherer-Bergs reaction with sodium cyanide and ammonium sulfate or ammonium carbonate, and then obtains glufosinate ammonium salt through alkaline hydrolysis with barium hydroxide, and the alkaline hydrolysis can also be carried out under the action of calcium oxide, and finally obtains glufosinate ammonium salt after ammoniation by ammonia gas or ammonia water. Although the salt generated by alkaline hydrolysis of hydantoin is easy to separate, the amount of waste salt generated is large.

[0005]

[0006] Patent documents CN103539815A and US4399287A synthesize glufosinate ammonium salt by the ketoacid method. This method does not produce salts such as ammonium chloride and sodium chloride, and the post-treatment is simple, but the overall yield is low.

[0007]

[0008] The Strecker method is the current domestic industrialization route with low technical barriers and relatively easy operation. The reaction uses diethyl methylphosphite as the raw material and undergoes Michael addition reaction without esterification to obtain the intermediate (3,3-diethoxy)propylmethylphosphinate isobutyl ester, which is then hydrolyzed to obtain 3-ethoxymethylphosphonylpropionaldehyde, which is then reacted with sodium cyanide, ammonium chloride and ammonia water via the Strecker reaction to obtain an aminonitrile intermediate, which is finally hydrolyzed, ammonated and purified to obtain the glufosinate ammonium salt product.

[0009]

[0010] In the above prior art, the preparation methods of glufosinate ammonium salt will produce a large amount of inorganic salts, and highly toxic substances such as NaCN are required, which are difficult to separate and have high costs for treating the three wastes. Summary of the invention

[0011] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a method for preparing glufosinate ammonium salt without introducing sodium cyanide or hydrocyanic acid and without producing a large amount of ammonium chloride as a by-product.

[0012] In order to solve the above technical problems, the present invention adopts the following technical solutions.

[0013] A method for preparing glufosinate ammonium salt comprises the following steps:

[0014] (1) Preparation of intermediate I: diethyl malonate and liquid bromine are added to a first solvent for reaction to obtain intermediate I;

[0015] (2) Preparation of intermediate II: intermediate I, potassium phthalimide and quaternary ammonium salt catalyst are added to toluene, reacted at 110°C to 120°C, filtered after the reaction, and the solvent is evaporated to obtain intermediate II;

[0016] (3) Preparation of intermediate III: adding intermediate II, potassium carbonate, 1,2-dibromoethane and a phase transfer catalyst into a second solvent, reacting at 130°C to 150°C, cooling and filtering after the reaction, and distilling off the solvent to obtain intermediate III;

[0017] (4) Preparation of intermediate IV: intermediate III and diethyl methylphosphite are added to toluene, and reacted at 100°C to 120°C under an argon atmosphere. After the reaction, the solvent is evaporated to obtain intermediate IV;

[0018] (5) Preparation of intermediate V: intermediate IV is added to a hydrochloric acid solution, refluxed for reaction, then cooled to precipitate glufosinate hydrochloride, and dried to obtain intermediate V;

[0019] (6) Preparation of glufosinate ammonium salt: Intermediate V and water are mixed, ammonia gas is introduced, the pH value is adjusted to 8-9, the pH value is stirred and maintained, and then methanol is added, stirred and reacted at 55°C-65°C, cooled, filtered and dried to obtain glufosinate ammonium salt.

[0020] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (1), the molar ratio of diethyl malonate to liquid bromine is 1:1-1.5, and the first solvent includes one or more of dichloromethane, dichloroethane, ethyl acetate and tetrahydrofuran, more preferably dichloromethane.

[0021] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (2), the mass ratio of the toluene to the intermediate I is 2 to 10:1, and the mass ratio of the quaternary ammonium salt catalyst to the intermediate I is 0.01 to 0.1:1.

[0022] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (2), the quaternary ammonium salt catalyst includes one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide.

[0023] The above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (3), the mass ratio of the potassium carbonate to the intermediate II is 0.9-1.2:1, the mass ratio of the 1,2-dibromoethane to the intermediate II is 0.7-0.9:1, the mass ratio of the phase transfer catalyst to the intermediate II is 0.01-0.1:1, and the mass ratio of the second solvent to the intermediate II is 0.5-2:1.

[0024] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (3), the phase transfer catalyst includes one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide, and the second solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

[0025] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (4), the mass ratio of the toluene to the intermediate III is 0.1-1.5:1, and the molar ratio of the intermediate III to the diethyl methylphosphite is 1:1-1.5.

[0026] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (5), the mass fraction of hydrochloric acid in the hydrochloric acid solution is 10% to 30%, and the mass ratio of the hydrochloric acid solution to the intermediate IV is 2 to 10:1.

[0027] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (6), the mass ratio of the intermediate V to water is 1.6-1.8:1, and the mass ratio of the methanol to the water is 10-15:1.

[0028] In the above-mentioned method for preparing glufosinate ammonium salt, preferably, in step (6), the stirring time is 1h to 8h, and the stirring reaction time is 2h to 8h.

[0029] In the present invention, the reaction path for preparing glufosinate ammonium salt using diethyl malonate as a raw material is as follows:

[0030]

[0031] Compared with the prior art, the advantages of the present invention are:

[0032] (1) In the method of the present invention, during the preparation process of the intermediate V, phthalimide is used instead of ammonia water and sodium cyanide (or hydrocyanic acid), and a carboxyl group is introduced from the reaction raw materials, thereby avoiding the use and production of highly toxic substances, and also avoiding the introduction of ammonium salts required in other methods and the large amount of ammonium chloride byproduct that is difficult to separate produced by hydrolysis in the Strecker method. In the present invention, the byproduct is easily separated from the intermediate, and the separation process does not require complicated operations, is simple and efficient, and has good social and economic benefits.

[0033] (2) The content of glufosinate ammonium salt obtained by the method of the present invention is 90% to 98%, and the total yield is greater than 68% based on diethyl malonate. DETAILED DESCRIPTION

[0034] The present invention is further described below in conjunction with specific preferred embodiments, but the protection scope of the present invention is not limited thereby. The materials and instruments used in the following embodiments are commercially available, and the room temperature is usually 20°C to 30°C.

[0035] Example 1

[0036] A method for preparing glufosinate ammonium salt of the present invention comprises the following steps:

[0037] (1) Preparation of Intermediate I: 48 g (0.3 mol) of diethyl malonate and 300 mL of dichloromethane were added to a 500 mL three-necked flask and stirred. At the same time, 48 g (0.3 mol) of liquid bromine was dissolved in 100 mL of dichloromethane and then added dropwise to the three-necked flask. The reaction was allowed to react at room temperature for 18 h. The resulting reaction solution was treated with saturated Na 2 CO 3 The solution was washed 3 times, water was washed 3 times, and the organic phase was washed with anhydrous Na 2 SO 4 After drying, filtering and rotary evaporation, 69.4 g of light yellow oily 2-bromo-1,3-malonic acid diethyl ester, namely intermediate I, was obtained with a yield of 96%.

[0038] (2) Preparation of Intermediate II: 22.2 g (0.12 mol) of potassium phthalimide, 24 g (0.1 mol) of diethyl 2-bromo-1,3-malonate (Intermediate I), 1.2 g (3.7 mmol) of tetrabutylammonium bromide and 240 mL of toluene were added to a four-necked flask and reacted at 120° C. for 10 hours. After the reaction was completed, the potassium bromide byproduct was removed by filtration. 120 mL of water was added to the filtrate, and the phase transfer catalyst was removed by separation. The organic phase was treated with anhydrous Na 2 SO 4After drying, filtering and distilling off the solvent, 29.9 g of diethyl phthalimidomalonate, namely intermediate II, was obtained with a yield of 98%.

[0039] (3) Preparation of Intermediate III: 29.9 g (0.098 mol) of diethyl phthalimidomalonate (Intermediate II) was dissolved in 30 mL of N,N-dimethylformamide, and 27 g (0.196 mol) of potassium carbonate, 21 g (0.112 mol) of 1,2-dibromoethane and 1.5 g (4.6 mmol) of tetrabutylammonium bromide were added. The mixture was reacted at 130° C. for 8 hours, cooled to room temperature, and the potassium carbonate and by-product potassium bromide were filtered out. The solvent was evaporated and the residue was recrystallized from ethanol to obtain 36.3 g of diethyl phthalimido-2-bromoethylmalonate, i.e., Intermediate III, with a yield of 90%.

[0040] (4) Preparation of Intermediate IV: In a 250 mL three-necked flask, 16.3 g (0.12 mol) of diethyl methylphosphite, 36.3 g (0.088 mol) of diethyl phthalimido-2-bromoethylmalonate (Intermediate III) and 20 mL of toluene were added, and the gas was replaced with argon three times. The mixture was stirred and heated to 100° C. under an argon atmosphere for 5 h. After the reaction, the solvent and unreacted raw materials were removed by distillation under reduced pressure to obtain 33.8 g of a phosphine ester intermediate, namely, Intermediate IV, as a light yellow viscous oil. The viscous oil was used directly in the next step without purification.

[0041] (5) Preparation of intermediate V: 300 mL of 30% hydrochloric acid solution and 33.8 g of phosphine ester intermediate (intermediate IV) were added to a 500 mL three-necked flask, and the mixture was refluxed for 5 h. The mixture was cooled to room temperature to precipitate by-product phthalic acid, and the mixture was filtered. The filtrate was further cooled to -5°C to precipitate solid glufosinate hydrochloride. After drying, 17.2 g of white solid was obtained, namely intermediate V, with a yield of 90% (based on intermediate III).

[0042] (6) Preparation of glufosinate ammonium salt: 17.2 g of glufosinate hydrochloride (intermediate V) and 10 g of water were added to a 250 mL three-necked flask and stirred evenly. Ammonia gas was slowly introduced into the reaction solution at room temperature, and the pH was adjusted to 8. The mixture was stirred for 2 h, and the pH was maintained at 8 throughout the process. Subsequently, 100 g of methanol was added and stirred at 60 ° C for 3 h. A white solid precipitated. The mixture was cooled to room temperature, filtered and dried to obtain 14.6 g of glufosinate ammonium salt with a content of 97% and a yield of 90%.

[0043] The above is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as above in the preferred embodiment, it is not used to limit the present invention. Any technician familiar with the art can make many possible changes and modifications to the technical solution of the present invention by using the methods and technical contents disclosed above without departing from the spirit and technical solution of the present invention, or modify it into an equivalent embodiment of equivalent changes. Therefore, any simple modification, equivalent replacement, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention, still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for preparing glufosinate ammonium salt, characterized in that: The following steps are involved: (1) Preparation of intermediate I: diethyl malonate and liquid bromine are added to a first solvent for reaction to obtain intermediate I; (2) Preparation of intermediate II: intermediate I, potassium phthalimide and quaternary ammonium salt catalyst are added to toluene, reacted at 110°C to 120°C, filtered after the reaction, and the solvent is evaporated to obtain intermediate II; (3) Preparation of intermediate III: adding intermediate II, potassium carbonate, 1,2-dibromoethane and a phase transfer catalyst into a second solvent, reacting at 130°C to 150°C, cooling and filtering after the reaction, and distilling off the solvent to obtain intermediate III; (4) Preparation of intermediate IV: intermediate III and diethyl methylphosphite are added to toluene, and reacted at 100°C to 120°C under an argon atmosphere. After the reaction, the solvent is evaporated to obtain intermediate IV; (5) Preparation of intermediate V: intermediate IV is added to a hydrochloric acid solution, refluxed for reaction, then cooled to precipitate glufosinate hydrochloride, and dried to obtain intermediate V; (6) Preparation of glufosinate ammonium salt: Intermediate V and water are mixed, ammonia gas is introduced, the pH value is adjusted to 8-9, the pH value is stirred and maintained, and then methanol is added, stirred and reacted at 55°C-65°C, cooled, filtered and dried to obtain glufosinate ammonium salt.

2. The method for preparing glufosinate ammonium according to claim 1, characterized in that: In step (1), the molar ratio of the diethyl malonate to the liquid bromine is 1:1-1.5, and the first solvent includes one or more of dichloromethane, dichloroethane, ethyl acetate and tetrahydrofuran.

3. The method for preparing glufosinate ammonium according to claim 1, characterized in that: In step (2), the mass ratio of the toluene to the intermediate I is 2-10:1, and the mass ratio of the quaternary ammonium salt catalyst to the intermediate I is 0.01-0.1:

1.

4. The method for preparing glufosinate ammonium according to claim 1, characterized in that: In step (2), the quaternary ammonium salt catalyst includes one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide.

5. The method for preparing glufosinate ammonium according to claim 1, characterized in that: In step (3), the mass ratio of the potassium carbonate to the intermediate II is 0.9-1.2:1, the mass ratio of the 1,2-dibromoethane to the intermediate II is 0.7-0.9:1, the mass ratio of the phase transfer catalyst to the intermediate II is 0.01-0.1:1, and the mass ratio of the second solvent to the intermediate II is 0.5-2:

1.

6. The method for preparing glufosinate ammonium according to claim 1, characterized in that: In step (3), the phase transfer catalyst includes one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide and tetramethylammonium iodide, and the second solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

7. The method for preparing glufosinate ammonium according to any one of claims 1 to 6, characterized in that: In step (4), the mass ratio of the toluene to the intermediate III is 0.1-1.5:1, and the molar ratio of the intermediate III to diethyl methylphosphite is 1:1-1.

5.

8. The method for preparing glufosinate ammonium according to any one of claims 1 to 6, characterized in that: In step (5), the mass fraction of hydrochloric acid in the hydrochloric acid solution is 10% to 30%, and the mass ratio of the hydrochloric acid solution to the intermediate IV is 2 to 10:

1.

9. The method for preparing glufosinate ammonium according to any one of claims 1 to 6, characterized in that: In step (6), the mass ratio of the intermediate V to water is 1.6-1.8:1, and the mass ratio of the methanol to water is 10-15:

1.

10. The method for preparing glufosinate ammonium according to any one of claims 1 to 6, characterized in that: In step (6), the stirring time is 1 h to 8 h, and the stirring reaction time is 2 h to 8 h.

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