Synthesis method of 1-propyl phosphoric anhydride

Abstract

The invention provides a synthesis method of 1-propyl phosphoric anhydride, which comprises the following steps: (a) adding an organic solvent, n-propyl alcohol and triethylamine into a reaction container, cooling to 0 DEG C or less, dropwise adding an organic solvent containing phosphorus trichloride, heating to 20-35 DEG C after dropwise adding, reacting, and filtering, concentrating and distilling to obtain a first intermediate; (b) carrying out reflux reaction on the first intermediate, 1-bromopropane and a catalyst to the end point; recovering unreacted 1-bromopropane under negative pressure, adding water for layering, and discarding a water phase to obtain a second intermediate; (c) co-heating the second intermediate and a hydrochloric acid solution to perform a reflux reaction; after the reaction is finished, carrying out negative pressure distillation, washing to remove residual hydrochloric acid, and concentrating to obtain a third intermediate; and (d) reacting the third intermediate with acetic anhydride in an inert atmosphere, carrying out negative pressure distillation to remove by-product acid, and ending the distillation when no distillate exists. 1-propyl phosphoric anhydride with high yield and high purity is obtained, and the reaction process is economical and environment-friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical products, and particularly relates to a method for synthesizing 1-propyl phosphoric anhydride. Background Art

[0002] 1-Propylphosphonic anhydride, also known as PPACA, propylphosphonic anhydride, propylphosphonic anhydride, and n-propylphosphonic cyclic anhydride, is a colorless to pale yellow transparent liquid primarily used in organic synthesis and lithium batteries. It can be used as a condensing agent and dehydrating agent in the synthesis of certain heterocyclic compounds and pharmaceutical intermediates, and as a novel electrolyte additive for lithium-ion batteries to improve their performance.

[0003] Chinese invention patent application number 202111368250.7 discloses a method for synthesizing 1-propyl phosphoric anhydride, belonging to the field of chemical synthesis technology. The invention uses phosphorus oxychloride and propylmagnesium chloride Grignard reagent as raw materials. In toluene solvent, 1-propyl phosphoric anhydride is obtained through a three-step reaction of substitution, hydrolysis, and dehydration cyclization. This synthesis method requires the use of propylmagnesium chloride Grignard reagent, which is extremely sensitive to water and oxygen.

[0004] Chinese invention patent application number 202410798955.X discloses a method for preparing 1-propyl phosphoric anhydride. The method comprises the following steps: adding diethyl phosphite and an alkaline reagent to an organic solvent, then dropwise adding a halopropane to carry out a substitution reaction. After the reaction is completed, water is added, the mixture is allowed to stand and separate into layers, and the organic layer is concentrated to produce diethyl propyl phosphate. Hydrohalic acid is added to the diethyl propyl phosphate for hydrolysis to produce propyl phosphoric acid. Acetic anhydride and a catalyst are added to the propyl phosphoric acid, the reaction is continued for 8-12 hours, and unreacted acetic anhydride is removed under reduced pressure to produce 1-propyl phosphoric anhydride. This preparation method uses diethyl phosphite as a raw material, which is more expensive than phosphorus trichloride, but there is still room for improvement in cost efficiency. Summary of the Invention

[0005] In order to solve the above technical problems, the object of the present invention is to provide a method for synthesizing 1-propyl phosphoric anhydride.

[0006] In order to solve the above technical problems, the present invention provides a method for synthesizing 1-propyl phosphoric anhydride, comprising the following steps: (a) adding an organic solvent, n-propanol, and triethylamine to a reaction vessel, cooling the temperature to ≤0°C, and dropwise adding an organic solvent containing phosphorus trichloride. After the dropwise addition is complete, heating the reaction to 20-35°C to carry out the reaction, and filtering, concentrating, and distilling to obtain a first intermediate; (b) subjecting the first intermediate, 1-bromopropane, and the catalyst to a reflux reaction to an end point; recovering unreacted 1-bromopropane under negative pressure, then adding water to separate the layers, and discarding the aqueous phase to obtain a second intermediate; (c) heating the second intermediate with a hydrochloric acid solution to perform a reflux reaction; after the reaction is completed, performing vacuum distillation and water washing to remove residual hydrochloric acid, and concentrating to obtain a third intermediate; (d) reacting the third intermediate with acetic anhydride under an inert atmosphere, and performing vacuum distillation to remove the by-product acid. The reaction is terminated when no more distillate is produced, and the product, 1-propylphosphoric anhydride, is collected.

[0007] Optimally, in step (a), the organic solvent is dichloromethane, and when the organic solvent containing phosphorus trichloride is added dropwise, the temperature is controlled to be ≤5°C and the addition time is controlled to be ≤6 hours.

[0008] Furthermore, in step (a), the molar ratio of n-propanol, triethylamine and phosphorus trichloride is 6-11:8-9.5:2, and the molar amount of n-propanol is greater than the molar amount of triethylamine.

[0009] Furthermore, in step (a), when the organic solvent containing phosphorus trichloride is added dropwise, a conduit is used to guide the generated smoke into the absorption liquid containing sodium hydroxide; After the reaction, filter with filter cloth, weigh the mother liquor and then concentrate it under normal pressure; when it is concentrated to 50-65% of the initial concentration, filter it again with filter cloth, and after filtration, concentrate it under negative pressure at a vacuum degree of ≤-0.095Mpa, and filter it to 110℃~120℃ until there is no obvious distillate. The filtrate is filtered again through a microporous membrane and subjected to negative pressure distillation at a vacuum degree of ≤-0.01Mpa; the temperature is raised to 130°C~135°C to distill out the first intermediate, and the first 5% is cut off and used as the fore-distillate.

[0010] Optimally, in step (b), the catalyst is a mixture of potassium iodide and tetrabutylammonium bromide, and the molar ratio of potassium iodide to tetrabutylammonium bromide is 1:1-3.

[0011] Furthermore, in step (b), the temperature at the beginning of the reflux is 90-100° C., and the temperature is continuously increased according to the reaction time so that the temperature at the end of the reaction is 120-125° C.

[0012] Optimally, in step (c), hydrochloric acid solution is added in multiple times to maintain the reaction process.

[0013] Furthermore, in step (c), a reflux reaction is carried out at 85-95°C for 3-4 hours, and a catheter is used to introduce the solution into an absorption liquid containing sodium hydroxide; hydrochloric acid solution is added in multiple times, and the temperature is increased so that the temperature is 95-101°C at the end of the reaction.

[0014] Optimally, in step (d), when the solution is distilled to 115-125°C and becomes a black liquid, the nitrogen is turned off, the negative pressure distillation is started and the temperature is raised to 140°C and the distillation is continued until no more distillates are produced.

[0015] The synthesis method of 1-propyl phosphoric anhydride adopts readily available and inexpensive materials such as n-propanol, triethylamine, and phosphorus trichloride as raw materials, realizes the total synthesis of 1-propyl phosphoric anhydride through multi-step reactions, obtains 1-propyl phosphoric anhydride with high yield and high purity, and the reaction process is economical and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The synthetic route of 1-propyl phosphoric anhydride of the present invention is as follows; Figure 2 is the NMR spectrum of the first intermediate of the present invention; Figure 3 The figure is the nuclear magnetic spectrum of 1-propyl phosphoric anhydride of the present invention. DETAILED DESCRIPTION

[0017] The synthesis method of 1-propyl phosphoric anhydride of the present invention comprises the following steps: (a) adding an organic solvent, n-propanol and triethylamine into a reaction vessel, cooling the reaction vessel to ≤0°C, dropwise adding an organic solvent containing phosphorus trichloride, raising the temperature to 20-35°C after the dropwise addition is complete for reaction, filtering, concentrating and distilling to obtain a first intermediate; (b) subjecting the first intermediate, 1-bromopropane and a catalyst to a reflux reaction to an end point; recovering unreacted 1-bromopropane under negative pressure, subsequently adding water to separate layers, and discarding the aqueous phase to obtain a second intermediate; (c) co-heating the second intermediate with a hydrochloric acid solution for a reflux reaction; after the reaction is completed, subjecting the reaction vessel to negative pressure distillation, washing with water to remove residual hydrochloric acid, and concentrating to obtain a third intermediate; and (d) subjecting the third intermediate to a reaction with acetic anhydride under an inert atmosphere, subjecting the reaction vessel to negative pressure distillation to remove by-product acid, and completing the reaction when no more distillates are produced, and collecting the product 1-propyl phosphoric anhydride.

[0018] The organic solvent is dichloromethane, and the temperature is controlled to be ≤5°C and the addition time is controlled to be ≤6 hours during the dropwise addition of the organic solvent containing phosphorus trichloride. In step (a), the molar ratio of n-propanol, triethylamine, and phosphorus trichloride is 6-11:8-9.5:2, and the molar amount of n-propanol is greater than the molar amount of triethylamine. In step (a), when an organic solvent containing phosphorus trichloride is added dropwise, smoke generated is introduced into an absorption liquid containing sodium hydroxide using a catheter; after the reaction, the reaction is filtered through a filter cloth, the mother liquor is weighed, and then concentrated under normal pressure; when the reaction is concentrated to 50-65% of the initial reaction volume, the reaction is filtered again through a filter cloth, and after filtration, negative pressure concentration is performed at a vacuum degree of ≤-0.095 MPa. After distillation to 110° C.-120° C., no obvious distillate is produced, and the filtrate is filtered to obtain the filtrate; the filtrate is filtered again through a microporous membrane, and negative pressure distillation is performed at a vacuum degree of ≤-0.01 MPa; the temperature is raised to 130° C.-135° C., and the first intermediate is distilled to obtain the first intermediate, and the first 5% is cut off and used as the fore-distillate.

[0019] In step (b), the catalyst is a mixture of potassium iodide and tetrabutylammonium bromide, and the molar ratio of potassium iodide to tetrabutylammonium bromide is 1:1 to 3. In step (b), the temperature at the beginning of the reflux is 90°C to 100°C, and the temperature is continuously increased according to the reaction time until the temperature reaches 120°C to 125°C at the end of the reaction.

[0020] In step (c), add hydrochloric acid solution several times to maintain the reaction process. In step (c), reflux reaction is carried out at 85-95°C for 3-4 hours, and a catheter is used to introduce the absorption liquid containing sodium hydroxide; add hydrochloric acid solution several times, and increase the temperature so that the temperature is 95-101°C at the end of the reaction. In step (d), when the temperature is evaporated to 115-125°C, the solution becomes a black liquid, turn off the nitrogen, start negative pressure distillation and increase the temperature to 140°C to continue distillation until there is no more distillate. The present invention will be further described below with reference to the embodiments shown in the accompanying drawings. Example 1

[0021] This embodiment provides a method for synthesizing 1-propyl phosphoric anhydride, such as Figure 1 As shown, the following steps are included: (a) 2500 g of dichloromethane (DCM), 601 g of n-propanol (PA), and 909 g of triethylamine (Et3N) were added to a 5000 ml reactor, and the mixture was stirred in an ice-water bath to cool to 0° C.; then, 1500 g of dichloromethane (i.e., a mixed solution of phosphorus trichloride and dichloromethane) containing 343.5 g of TCP was added dropwise, generating a large amount of white smoke (the smoke in the reactor was introduced into an absorption solution containing sodium hydroxide (a 0.1 mol / L sodium hydroxide aqueous solution in this embodiment) using a catheter); the temperature during the addition process was strictly controlled not to exceed 5° C., and the addition time was controlled to be 6 hours. After the addition was completed, the temperature was raised to 30° C., stirred for 1 hour, and then filtered through a filter cloth (to obtain a mother liquor). The mother liquor was weighed and concentrated under normal pressure (the dichloromethane evaporated was recovered and reused). When the concentration reached 60% (60% of the original mass), the mother liquor was filtered through a filter cloth again; After filtration, replace the receiving bottle for the back distillation to start negative pressure concentration of the mother liquor (the vacuum degree needs to reach -0.095Mpa), and keep it for half an hour after evaporating to 110℃~120℃ without obvious distillation (the back distillation product is excess triethylamine and n-propanol, which can be converted to the feed amount after HPLC measurement). After confirming that there is no distillation, filter it, and filter the filtrate again through a microporous membrane (the filtered solids are all co-produced high-purity triethylamine hydrochloride). The filtrate is 473g of the first intermediate crude product. The first intermediate crude product is subjected to high vacuum negative pressure distillation (heating to 130℃~135℃ at -0.01Mpa to evaporate the product), pinch off the first 5% of the distilled product as the front distillation, and 449g of the first intermediate (purity 90%, yield 77.6%) is distilled. Figure 2 shown.

[0022] (b) In a 2000 ml reactor, the first intermediate (208.2 g, 1 mol), 1-bromopropane (123 g, 1 mol), potassium iodide (8.5 g, 0.05 mol, KI) and tetrabutylammonium bromide (0.1 mol, TBAB) were added, stirred, and heated to reflux for 4 hours (the reflux temperature was 95°C at the beginning, and the temperature was uniformly and continuously increased to 120°C~125°C according to the reaction time). After the reaction, vacuum distillation (-0.09 MPa) was performed until no more distillation could be carried out (stop at 140°C). The distillate was 1-bromopropane (recycled). 500 ml of deionized water was added, stirred for 10 minutes, allowed to stand and separate, and the aqueous phase (containing KI and part of TBAB) was discarded to obtain 186.8 g of the second intermediate (yield 89%, purity 98%).

[0023] (c) 150 g of the second intermediate and 600 g of commercially available concentrated hydrochloric acid were added to a 2000 ml reactor, and the temperature was raised to 90° C. for reflux reaction (a tube was connected to the reflux outlet to direct the effluent gas into an absorption solution containing sodium hydroxide, which in this embodiment was a 0.1 mol / L aqueous sodium hydroxide solution). The reaction was refluxed for 3.5 hours. An additional 75 g of concentrated hydrochloric acid was added, and the temperature was continuously raised, with additional concentrated hydrochloric acid (75 g) added every 3 hours for a total of 15.5 hours. The reaction temperature was between 95° C. and 101° C. at the end of the reaction. The temperature was lowered to 80°C and vacuum concentration was started (-0.095 MPa distillation stopped at about 160°C), the temperature was lowered to 100°C, 80 g of water was added, and vacuum concentration was continued until no distillate was produced (about 140°C); after the concentration was completed, the temperature was slowly lowered to 40°C, and a large amount of white solid (the third intermediate) was precipitated, which was sampled for HPLC detection (purity 94%).

[0024] (d) One-pot method: 1100 g of acetic anhydride was added to the white solid, and nitrogen was continuously introduced. The temperature was raised while the reaction was carried out while the acetic anhydride was recovered. When the solution was evaporated to 120°C, a black liquid was formed. The nitrogen was turned off. Vacuum distillation was started (-0.1 MPa) and continued until almost no distillate was produced at 140°C. 210 g of the product, 1-propylphosphoric acid cyclic anhydride (purity 99.6, yield 92%), was collected. Figure 3 shown. Example 2

[0025] This example provides a method for synthesizing 1-propylphosphoric anhydride, which is basically the same as that in Example 1, except that: in step (a), 2500 g of dichloromethane (DCM), 360.6 g of n-propanol (PA), and 909 g of triethylamine (Et3N) are added to a 5000 ml reactor, and the mixture is stirred in an ice-water bath for cooling (0°C); then, 1500 g of dichloromethane (i.e., a mixed solution of phosphorus trichloride (TCP, 343.5 g)) is added dropwise; and 437 g of the first intermediate (purity 84.1%, yield 70.5%) is obtained by distillation. Example 3

[0026] This example provides a method for synthesizing 1-propylphosphoric anhydride, which is basically the same as that in Example 1, except that: in step (a), 2500 g of dichloromethane (DCM), 661.1 g of n-propanol (PA), and 909 g of triethylamine (Et3N) are added to a 5000 ml reactor, and the mixture is stirred in an ice-water bath for cooling (0°C); then, 1500 g of dichloromethane (i.e., a mixed solution of phosphorus trichloride (TCP, 343.5 g)) is added dropwise; and 463.14 g of the first intermediate (purity 90.9%, yield 80.8%) is obtained by distillation.

[0027] Comparative Example 1 This example provides a method for synthesizing 1-propylphosphoric anhydride, which is basically the same as that in Example 1, except that triethylamine is not added, resulting in the inability to effectively neutralize the generated hydrogen chloride in the reaction system, hindering the reaction process and increasing side reactions; 510.14 g of the first intermediate (purity 60.9%, yield 58.7%) is obtained by distillation.

[0028] Comparative Example 2 This example provides a method for synthesizing 1-propylphosphoric anhydride, which is basically the same as that in Example 1, except that potassium iodide is not added, resulting in a significant decrease in the rate of the nucleophilic substitution reaction, incomplete conversion of 1-bromopropane, and reduced yield and purity of the second intermediate. Ultimately, 170.1 g of the second intermediate product (purity 92.8%, yield 76%) was obtained.

[0029] Comparative Example 3 This example provides a method for synthesizing 1-propylphosphoric anhydride, which is essentially the same as that in Example 1, except that tetrabutylammonium bromide is not added in step (b), resulting in a lower reaction rate. The reaction requires heating to reflux for 16 hours to achieve a yield close to that in Example 1.

[0030] The above embodiments are intended only to illustrate the technical concepts and features of the present invention. Their purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made in accordance with the spirit of the present invention are intended to be covered by the scope of protection of the present invention.

Claims

1. A method for synthesizing 1-propyl phosphoric anhydride, characterized in that: The following steps are involved: (a) adding an organic solvent, n-propanol, and triethylamine to a reaction vessel, cooling the temperature to ≤0°C, and dropwise adding an organic solvent containing phosphorus trichloride. After the dropwise addition is complete, heating the reaction to 20-35°C to carry out the reaction, and filtering, concentrating, and distilling to obtain a first intermediate; (b) subjecting the first intermediate, 1-bromopropane and the catalyst to a reflux reaction to an end point; Unreacted 1-bromopropane is recovered under negative pressure, and then water is added to separate the layers, and the water phase is discarded to obtain the second intermediate; (c) heating the second intermediate with a hydrochloric acid solution to perform a reflux reaction; after the reaction is completed, performing vacuum distillation and water washing to remove residual hydrochloric acid, and concentrating to obtain a third intermediate; (d) reacting the third intermediate with acetic anhydride under an inert atmosphere, and performing vacuum distillation to remove the by-product acid. The reaction is terminated when no more distillate is produced, and the product, 1-propylphosphoric anhydride, is collected.

2. The method for synthesizing 1-propyl phosphoric anhydride according to claim 1, wherein: In step (a), the organic solvent is dichloromethane, and when the organic solvent containing phosphorus trichloride is added dropwise, the temperature is controlled to be ≤5°C and the addition time is controlled to be ≤6 hours.

3. The method for synthesizing 1-propyl phosphoric anhydride according to claim 2, wherein: In step (a), the molar ratio of n-propanol, triethylamine and phosphorus trichloride is 6-11:8-9.5:2, and the molar amount of n-propanol is greater than the molar amount of triethylamine.

4. The method for synthesizing 1-propyl phosphoric anhydride according to claim 3, wherein: In step (a), when the organic solvent containing phosphorus trichloride is added dropwise, the generated smoke is introduced into the absorption liquid containing sodium hydroxide through a conduit; After the reaction, filter with filter cloth, weigh the mother liquor and then concentrate it under normal pressure; when it is concentrated to 50-65% of the initial concentration, filter it again with filter cloth, and after filtration, concentrate it under negative pressure at a vacuum degree of ≤-0.095Mpa, and filter it to 110℃~120℃ until there is no obvious distillate. The filtrate is filtered again through a microporous membrane and subjected to negative pressure distillation at a vacuum degree of ≤-0.01Mpa; the temperature is raised to 130°C~135°C to distill out the first intermediate, and the first 5% is cut off and used as the fore-distillate.

5. The method for synthesizing 1-propyl phosphoric anhydride according to claim 1, wherein: In step (b), the catalyst is a mixture of potassium iodide and tetrabutylammonium bromide, and the molar ratio of potassium iodide to tetrabutylammonium bromide is 1:1-3.

6. The method for synthesizing 1-propyl phosphoric anhydride according to claim 5, wherein: In step (b), the temperature at the beginning of the reflux is 90-100° C., and the temperature is continuously increased according to the reaction time so that the temperature is 120-125° C. at the end of the reaction.

7. The method for synthesizing 1-propyl phosphoric anhydride according to claim 1, wherein: In step (c), hydrochloric acid solution is added in multiple times to maintain the reaction process.

8. The method for synthesizing 1-propyl phosphoric anhydride according to claim 7, wherein: In step (c), the reaction is refluxed at 85-95° C. for 3-4 hours and introduced into an absorption solution containing sodium hydroxide using a catheter; hydrochloric acid solution is added in multiple portions and the temperature is raised so that the temperature is 95-101° C. at the end of the reaction.

9. The method for synthesizing 1-propyl phosphoric anhydride according to claim 1, wherein: In step (d), when the temperature reaches 115-125° C., the solution becomes a black liquid. The nitrogen is turned off, and the vacuum distillation is started and the temperature is raised to 140° C. The distillation is continued until no more distillates are produced.

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