A process for the preparation of a glufosinate ammonium salt

Abstract

The application discloses a preparation method of ammonium glufosinate, which comprises the following steps: adding diethyl malonate and liquid bromine into a first solvent to react to obtain intermediate I; adding the intermediate I, potassium phthalimide and a quaternary ammonium salt catalyst into toluene to react to obtain intermediate II; adding the intermediate II, potassium carbonate, 1,2-dibromoethane and a phase transfer catalyst into a second solvent to react to obtain intermediate III; adding the intermediate III and diethyl methyl phosphonite into toluene to react under argon to obtain intermediate IV; adding the intermediate IV into hydrochloric acid to react under reflux; cooling, precipitation, drying to obtain intermediate V; mixing the intermediate V with water, passing in ammonia and adjusting pH value; adding methanol and stirring to react; cooling, filtering and drying to obtain ammonium glufosinate. The method can avoid using sodium cyanide or hydrocyanic acid, and no large amount of difficult-to-separate ammonium chloride is generated, the content of the obtained ammonium glufosinate is 90% to 98%, and the total yield is greater than 68%.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pesticide herbicide synthesis, and relates to a preparation method of glufosinate ammonium, in particular to a method for preparing glufosinate ammonium from diethyl malonate as raw material. BACKGROUND

[0002] Glufosinate ammonium (glufosinate) is a high-efficiency, broad-spectrum and contact-kill type organic phosphine herbicide developed by German Hoes Company (now Bayer), which mainly acts on glutamine synthetase and has the advantages of low toxicity, harmlessness and easy degradation.

[0003] At present, there are mainly three methods for synthesizing glufosinate ammonium, namely the hydantoin method, the keto acid method and the Strecker method.

[0004] The patent document CN102584893A reports the synthesis of glufosinate ammonium by the hydantoin method. In this method, diethyl methyl phosphite and acrolein are used as raw materials, and an intermediate (3,3-diacetyloxy) propyl methyl phosphinate isobutyl ester is obtained through Michael addition reaction and esterification reaction. The intermediate is reacted with sodium cyanide and ammonium sulfate or ammonium carbonate through Bucherer-Bergs reaction to synthesize hydantoin intermediate, and then the glufosinate ammonium salt is obtained by alkaline hydrolysis of barium hydroxide. The alkaline hydrolysis can also be carried out under the action of calcium oxide, and finally the glufosinate ammonium salt is obtained after ammoniation of ammonia gas or ammonia water. Although the salt generated by the alkaline hydrolysis of hydantoin is easy to separate, the amount of waste salt generated is large.

[0005]

[0006] The patent documents CN103539815A and US4399287A synthesize glufosinate ammonium by the keto acid method. This method does not produce salts such as ammonium chloride and sodium chloride, and the post-treatment is simple, but the total yield is low.

[0007]

[0008] The Strecker method is the current domestic industrialization route, which has low technical barriers and relatively easy operation. The reaction uses diethyl methyl phosphite as raw material, and after Michael addition reaction, esterification is not needed, and the intermediate (3,3-diethoxy) propyl methyl phosphinate isobutyl ester is obtained. Then, 3-ethoxymethyl phosphonyl propyl aldehyde is obtained by hydrolysis, and then the amino cyanide intermediate is obtained by Strecker reaction of sodium cyanide, ammonium chloride and ammonia water. Finally, glufosinate ammonium salt product is obtained by hydrolysis, ammoniation and purification.

[0009]

[0010] In the prior art, the preparation methods of glufosinate ammonium salt all produce a large amount of inorganic salt, and need to use NaCN and other toxic substances, and have the problems of difficult separation, high cost of waste treatment, etc. SUMMARY

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

[0012] To solve the above technical problems, the present application adopts the following technical solutions.

[0013] A preparation method of glufosinate ammonium salt, comprising the following steps:

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

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

[0016] (3) Preparation of intermediate III: intermediate II, potassium carbonate, 1,2-dibromoethane and phase transfer catalyst are added to a second solvent, and reacted at 130-150℃, then cooled, filtered, and the solvent is evaporated to obtain intermediate III;

[0017] (4) Preparation of intermediate IV: intermediate III and diethyl methyl phosphonite are added to toluene, and reacted at 100-120℃ under argon atmosphere, then the solvent is evaporated to obtain intermediate IV;

[0018] (5) Preparation of intermediate V: intermediate IV is added to hydrochloric acid solution, and refluxed, then cooled, and glufosinate hydrochloride is precipitated, which is 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, stirred and maintained, then methanol is added, and stirred at 55-65℃, then cooled, filtered and dried to obtain glufosinate ammonium salt.

[0020] In the above preparation method of 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] The preparation method of the above glufosinate ammonium, preferably, 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.

[0022] The preparation method of the above glufosinate ammonium, preferably, in step (2), the quaternary ammonium salt catalyst comprises 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 preparation method of the above glufosinate ammonium, 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] The preparation method of the above glufosinate ammonium, preferably, in step (3), the phase transfer catalyst comprises 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 comprises one or more of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

[0025] The preparation method of the above glufosinate ammonium, 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 methyl phosphonite is 1:1-1.5.

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

[0027] The preparation method of the above glufosinate ammonium, 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] The preparation method of the above glufosinate ammonium, preferably, in step (6), the stirring time is 1h-8h, and the stirring reaction time is 2h-8h.

[0029] In the present application, the reaction path for preparing glufosinate ammonium from diethyl malonate is as follows:

[0030]

[0031] Compared with the prior art, the present application has the advantages of:

[0032] (1) In the preparation of intermediate V, the present application uses phthalimide instead of ammonia and sodium cyanide (or hydrocyanic acid) to introduce carboxyl from the reaction raw material, thereby avoiding the use of toxic substances and the generation of by-products, and also avoiding the introduction of ammonium salt required in other methods and the generation of large amounts of by-products of ammonium chloride which are difficult to separate in the hydrolysis of Strecker method. In the present application, the by-products are easily separated from the intermediates, and the separation process is simple, efficient, and has good social and economic benefits.

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

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

[0035] Example 1

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

[0037] (1) Preparation of intermediate I: 48 g (0.3 mol) of diethyl malonate, 300 mL of dichloromethane were added to a 500 mL three-necked flask, and stirred, and 48 g (0.3 mol) of liquid bromine was dissolved in 100 mL of dichloromethane and added dropwise into the three-necked flask, and reacted at room temperature for 18 h. The obtained reaction solution was washed with saturated Na2CO3 solution for 3 times, washed with water for 3 times, and the organic phase was dried with anhydrous Na2SO4. After filtration and rotary evaporation, 69.4 g of 2-bromo-1,3-diacetic acid diethyl ester in the form of light yellow oil was obtained, which was intermediate I, and the yield was 96%.

[0038] (2) Preparation of intermediate II: 22.2 g (0.12 mol) of potassium phthalimide, 24 g (0.1 mol) of 2-bromo-1,3-diacetic acid diethyl ester (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 h. After the reaction was completed, the potassium bromide by-product was removed by filtration, 120 mL of water was added to the filtrate, the phase transfer catalyst was removed by liquid separation, the organic phase was dried with anhydrous Na2SO4, and the solvent was evaporated after filtration to obtain 29.9 g of phthalimido malonic acid diethyl ester, which was intermediate II, and the yield was 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, 27 g (0.196 mol) of potassium carbonate was added, 21 g (0.112 mol) of 1,2-dibromoethane and 1.5 g (4.6 mmol) of tetrabutylammonium bromide were added, and the mixture was reacted at 130°C for 8 hours. After cooling to room temperature, the potassium carbonate and by-product potassium bromide were removed by filtration, the solvent was distilled off, and the residue was recrystallized from ethanol to obtain 36.3 g of diethyl phthalimidomalonate-2-bromoethyl ester, which is intermediate III, at a yield of 90%.

[0040] (4) Preparation of intermediate IV: 16.3 g (0.12 mol) of diethyl methylphosphonite, 36.3 g (0.088 mol) of diethyl phthalimidomalonate-2-bromoethyl ester (intermediate III), and 20 mL of toluene were added to a 250 mL three-necked flask, and the mixture was stirred under argon atmosphere, and then the temperature was raised to 100°C for 5 hours. After the reaction, the solvent and unreacted raw material were removed by distillation under reduced pressure to obtain 33.8 g of phosphonate intermediate, which is intermediate IV, as a yellowish viscous oil. The viscous oil was used in the next reaction without purification.

[0041] (5) Preparation of intermediate V: 300 mL of 30% hydrochloric acid solution and 33.8 g of the phosphonate intermediate (intermediate IV) were added to a 500 mL three-necked flask, and the mixture was refluxed for 5 hours. After cooling to room temperature, the by-product phthalic acid was precipitated and filtered. The filtrate was further cooled to -5°C, and the solid thus precipitated was dried to obtain 17.2 g of amifostine hydrochloride, which is intermediate V, as a white solid at a yield of 90% (based on intermediate III).

[0042] (6) Preparation of amifostine ammonium salt: 17.2 g of amifostine hydrochloride (intermediate V) and 10 g of water were added to a 250 mL three-necked flask, and the mixture was stirred. 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 hours while maintaining the pH at 8. Then, 100 g of methanol was added, and the mixture was stirred at 60°C for 3 hours. A white solid was precipitated, and the mixture was cooled to room temperature. The solid was filtered and dried to obtain 14.6 g of amifostine ammonium salt at a content of 97% and a yield of 90%.

[0043] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application in any form. Although the present application has been disclosed with the preferred embodiments as above, it is not intended to limit the present application. Any person skilled in the art, without departing from the spirit and technical solutions of the present application, can make many possible changes and modifications to the technical solutions of the present application, or modify equivalent embodiments with 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 application, without departing from the technical solutions of the present application, still belongs to the protection scope of the technical solutions of the present application.

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: Add Intermediate I, potassium phthalimide and quaternary ammonium salt catalyst to toluene and react at 110°C to 120°C. After the reaction is complete, filter and evaporate the solvent to obtain Intermediate II. (3) Preparation of Intermediate III: Add Intermediate II, potassium carbonate, 1,2-dibromoethane and a phase transfer catalyst to a second solvent and react at 130°C to 150°C. After the reaction is complete, cool, filter and evaporate the solvent to obtain Intermediate III. (4) Preparation of Intermediate IV: Intermediate III and diethyl methylphosphinate were added to toluene and reacted at 100°C to 120°C under an argon atmosphere. After the reaction, the solvent was evaporated to obtain Intermediate IV; (5) Preparation of intermediate V: intermediate IV is added to a hydrochloric acid solution, refluxed, and then cooled to precipitate glufosinate hydrochloride, which is then dried to obtain intermediate V; (6) Preparation of glufosinate ammonium salt: Mix the intermediate V with water, introduce ammonia gas, adjust the pH value to 8-9, stir and maintain the pH value, then add methanol, stir and react at 55°C-65°C, cool, filter and dry to obtain glufosinate ammonium salt; The reaction path is as follows: 。 2. The method for preparing glufosinate ammonium according to claim 1, wherein In step (1), the molar ratio of the diethyl malonate to the liquid bromine is 1:1 to 1.5, and the first solvent is one or more of dichloromethane, dichloroethane, ethyl acetate and tetrahydrofuran.

3. The method for preparing glufosinate ammonium according to claim 1, wherein 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.

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

1.

6. The method for preparing glufosinate ammonium according to claim 1, wherein In step (3), the phase transfer catalyst is 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 is N , N -dimethylformamide, N , N - one or more of 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 to 1.5:1, and the molar ratio of the intermediate III to the diethyl methylphosphite is 1:1 to 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 the 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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