Process for the synthesis of phosphazene-based p4-t-bu tetrafluoroborate

Abstract

This invention belongs to the field of phosphazene alkaline catalyst preparation technology, specifically relating to the synthesis process of phosphazene-based P4-t-BU tetrafluoroborate. Using iminotris(dimethylamino)phosphine (compound 1) and N-tert-butyliminophosphine trichloride (compound 2) as raw materials, a condensation reaction is carried out in an anhydrous organic solvent with a sterically hindered tertiary amine as an acid-binding agent and catalyst. After the reaction, the mixture is filtered to remove excess components, and then anion exchange is performed to obtain the target product. This invention, by introducing an inexpensive sterically hindered tertiary amine, significantly reduces the molar ratio of compound 1 to compound 2 from the traditional 7.0:1 to 3.2-3.6:1, the reaction temperature from 110℃ to 60-70℃, and the reaction time to 10-12 hours, while maintaining a total product yield of over 82%. This method significantly reduces production costs, has mild reaction conditions, and simplifies post-processing, making it suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of phosphazene alkaline catalyst preparation technology, specifically relating to the synthesis process of phosphazene-based P4-t-BU tetrafluoroborate. Background Technology

[0002] Phosphazene bases are a class of highly promising phosphorus-containing organic superbases. Based on the number of phosphorus atoms in their molecular structure, they can be classified into different series, such as P1, P2, P3 to P5. Among them, the conjugate acid of P4 phosphazene bases typically has a pKa value of over 40 in acetonitrile. Due to their extremely high basicity, excellent flexible steric hindrance, high thermal stability, and strong solubility in nonpolar aprotic solvents, they have become a focus of attention in polymer chemistry and organic synthesis. In the ring-opening polymerization of epoxides, P4 phosphazene bases and their salts exhibit extremely excellent catalytic activity as highly efficient initiators or catalysts, enabling precise control of the molecular weight and molecular weight distribution of polyether polymers, with zero residual metal ions in the system.

[0003] The tetrafluoroborate of P4-type phosphazene bases is commonly known as phosphazene-based P4-t-BU tetrafluoroborate, with the full name 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphine-2-phosphine]-2λ. 5 ,4λ 5 -Di(phosphazeneonium)tetrafluoroborate, CAS No. 181471-62-5, has the structure shown in Formula I below:

[0004] Formula I.

[0005] Schwesinger R., Schlemper H., Hasenfratz C., et al. Extremely Strong, Uncharged Auxiliary Bases; Monomeric and Polymer-Supported Polyaminophosphazenes (P2-P5)[J]. Liebigs Annalen, 1996, 1996(7): 1055-1081. This paper discloses a multi-step nucleophilic substitution electrophilic condensation reaction of imino-tris(dimethylamino)phosphine (compound 1) and N-tert-butyliminophosphine trichloride (compound 2) in anhydrous tetrahydrofuran. In order to completely replace the three chlorine atoms on the molecule of compound 2, and because the condensation reaction releases a large amount of hydrochloric acid (HCl), the conventional process must rely on an excess of the core raw material compound 1 itself as an acid-binding agent. Therefore, in the conventional synthesis ratio, the molar ratio of compound 1 to compound 2 must reach 7.0:1.0 or higher. The HCl released in the reaction combines with the excess compound 1 to form the hydrochloride precipitate of compound 1. The reaction requires continuous heating at a high temperature of 110°C for up to 24 hours to complete.

[0006] This traditional process has the following significant drawbacks: First, the raw material cost is extremely high. The synthesis of imino-tris(dimethylamino)phosphine (compound 1) is complex and involves many steps, making it an expensive and high-value core raw material. In the traditional process, for every 1 mole of compound 2 consumed, 7 moles of compound 1 are required, with more than 3 moles being wasted as acid-binding agents and converted into byproduct hydrochloride. This results in extremely high overall raw material costs, limiting the large-scale industrial application of this high-value initiator. Second, the reaction conditions are harsh and there are many side reactions. The substitution condensation reaction requires heating at 110°C for 24 hours. This prolonged high-temperature reaction not only places higher demands on industrial equipment but also easily leads to side reactions such as detert-butylation or skeletal rearrangement in heat-sensitive intermediates, negatively impacting the purity of the final product and making crystallization and purification difficult. Furthermore, the post-processing is very cumbersome. The large amount of compound 1 hydrochloride produced requires secondary precipitation and filtration recovery using expensive and irritating 1,1,2-trichloroethane, resulting in lengthy post-processing steps and high industrial elution intensity.

[0007] In summary, developing a novel synthesis process for P4-type phosphazene salts that can significantly reduce the addition ratio of the core expensive raw material compound 1, moderate the reaction temperature, simplify the post-processing, and still maintain a high yield is a key technical bottleneck that urgently needs to be addressed to achieve industrial-scale production in this field. Summary of the Invention

[0008] To address the shortcomings of existing technologies, the present invention aims to provide a synthesis process for phosphazene-based P4-t-BU tetrafluoroborate. This process creatively introduces inexpensive and readily available sterically hindered tertiary amines as external acid-binding agents and catalysts, fundamentally changing the traditional reactant ratios and reaction process.

[0009] Another objective of this invention is to reduce the amount of the core expensive raw material compound 1 fed into the reactor, while utilizing the synergistic catalytic effect of the sterically hindered tertiary amine to significantly reduce the temperature required for the reaction, thereby shortening the cycle, reducing energy consumption, lowering costs, and suppressing the occurrence of side reactions.

[0010] The synthesis process of the phosphazene-based P4-t-BU tetrafluoroborate of the present invention comprises the following steps: (1) Substitution condensation reaction: Under the protection of an inert gas, compound 1: imino-tris(dimethylamino)phosphine and sterically hindered tertiary amine acid-binding agent were dissolved in an organic solvent and cooled to -35℃~-25℃; under stirring, an organic solution of compound 2: N-tert-butyliminophosphine trichloride in a cryogenic state of -35℃~-25℃ was slowly added dropwise; after the addition was completed, the cryogenic bath was removed, and the reaction system was slowly heated to room temperature under stirring. Then the system was slowly heated to 60℃~70℃ for reaction, preferably 60℃; after the reaction was completed, the system was cooled, filtered to remove the sterically hindered tertiary amine hydrochloride, and the organic solvent and unreacted sterically hindered tertiary amine were removed from the filtrate under reduced pressure to obtain a viscous crude product; (2) Removal of excess raw materials and purification of intermediates: The crude product is redissolved in a solvent, and 1,1,2-trichloroethane is added dropwise under stirring. The mixture is stirred continuously at room temperature for 0.5 to 1.5 h, preferably 1 h. At this time, the small amount of excess compound 1 remaining in the system will react with the trace acid in the system and be selectively driven by 1,1,2-trichloroethane to completely precipitate out in the form of stable hydrochloride. The mixture is filtered, and the filter cake (mainly the hydrochloride of compound 1) is retained for recovery. The filtrate is collected and the solvent is completely removed under vacuum at 50°C to 60°C to obtain the purified intermediate. (3) Anion exchange: The purified intermediate is dissolved in an aqueous solution. Anion exchange reagent is added at -5℃ to 5℃. After the addition is complete, the anion exchange reaction is carried out by stirring at 0℃ to 5℃. Then, the product is filtered and washed. The product is dried to constant weight under high vacuum at 60℃ to 80℃ to obtain a white solid, which is the target product.

[0011] The molar ratio of compound 1 and compound 2 in step (1) is 3.2:1 to 3.8:1, preferably 3.2:1 to 3.6:1, and more preferably 3.4:1 to 3.6:1. The optimal ratio in the specific embodiment is about 3.5:1.

[0012] The molar ratio of the sterically hindered tertiary amine to compound 2 in step (1) is 3.0:1 to 4.0:1, preferably 3.0:1 to 3.6:1.

[0013] The sterically hindered tertiary amine mentioned in step (1) is one or more of N,N-diisopropylethylamine (DIPEA, Hünig base), tributylamine (TBA), triisobutylamine, tri-n-propylamine and 1,2,2,6,6-pentamethylpiperidine.

[0014] Preferably, the sterically hindered tertiary amine in step (1) is N,N-diisopropylethylamine and 1,2,2,6,6-pentamethylpiperidine.

[0015] In traditional processes, since no external alkali is introduced, the core reactant compound 1, which is a strong basic molecule, must act as an acid-binding agent to neutralize the three hydrogen chloride (HCl) molecules removed during the reaction. Therefore, theoretically, the reaction requires at least 6 moles of compound 1, but in practice, up to 7 moles of compound 1 must be added to ensure the reaction is complete.

[0016] For a long time, it has been widely believed in the field that this reaction system is extremely sensitive to alkaline environments. Because compound 2 and its intermediates have high electrophilic activity, the introduction of a highly reactive external base can easily trigger side reactions such as nucleophilic substitution or amine exchange, leading to product complexity. Therefore, conventional processes strictly avoid the use of external bases, relying instead on an excess of the expensive starting material compound 1 itself to capture the HCl generated during the reaction.

[0017] In this study, we unexpectedly discovered that the nucleophilicity of sterically hindered tertiary amines with specific structures is greatly suppressed due to the large steric hindrance on the nitrogen atom, thus preventing the expected side reactions from occurring during the multi-step condensation process of the macromolecule. It is precisely because sterically hindered tertiary amines possess strong electron-withdrawing and basic binding capabilities, and because their large steric hindrance and suppressed nucleophilic substitution ability allow them to preferentially and specifically capture HCl released during condensation, thereby replacing the acid-binding function of compound 1.

[0018] More importantly, during the research and development process, this application also discovered that the sterically hindered tertiary amine forms a transition state complex with higher reactivity with the reaction intermediate, exerting a significant synergistic catalytic effect throughout the multi-step condensation process of the macromolecule. This catalytic effect successfully breaks down the traditional reaction kinetic barrier, allowing the sterically hindered condensation reaction, which originally required a high temperature of 110°C to overcome, to now proceed efficiently and completely under mild conditions of 60-70°C. This significant synergistic catalytic effect is the basis for this unexpected discovery, enabling the realization of this invention.

[0019] In step (1), the reaction temperature is controlled to not exceed -20°C during the process of adding compound 2.

[0020] The organic solvent mentioned in step (1) is tetrahydrofuran (THF), dioxane, or chlorobenzene, and its moisture content is controlled below 50 ppm.

[0021] The molar ratio of the amount of 1,1,2-trichloroethane added in step (2) to the initial feed molar ratio of compound 2 in step (1) is 1.8:1 to 2.2:1.

[0022] The reaction time for heating to 60℃~70℃ in step (1) is 6~12h, preferably 10~12h.

[0023] The anion exchange reagent in step (3) is an aqueous solution of tetrafluoroboric acid or tetrafluoroborate.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: 1) This invention breaks through the technical barrier of not being able to use external alkali, and reduces the molar ratio of the expensive core raw material compound 1 from 7.0 times to 3.4~3.6 times. This means that the consumption of the core raw material is reduced by about 50% to prepare the same mass of target phosphazene-based P4-t-BU tetrafluoroborate, which greatly lowers the economic threshold for industrial-scale production.

[0025] 2) The reaction temperature of this invention is significantly reduced from 110℃ in the original process to 60-70℃. This reduction in temperature avoids potential carbonization, decomposition, or dealkylation side reactions that could occur with materials at prolonged high temperatures of 110℃, resulting in a lighter reaction solution color, significantly improved crude product purity, and a stable overall product yield of over 82%. Without the addition of a sterically hindered tertiary amine, the reaction is practically impossible at 60℃. With the introduction of the sterically hindered tertiary amine, the reaction can be efficiently completed under mild conditions of 60-70℃. This is not a simple equilibrium shift, but rather due to its unexpected "synergistic catalytic effect."

[0026] 3) The technical solution described in this invention reduces the amount of hydrochloride of compound 1 in the waste byproducts, and the amount of 1,1,2-trichloroethane used for precipitation in the post-treatment process is also reduced accordingly, making the filtration operation smoother. This not only reduces the pressure of environmental protection treatment, but also shortens the production cycle of a single batch. Attached Figure Description

[0027] Figure 1 The nuclear magnetic resonance spectrum of Example 1 ( 31 P NMR). Detailed Implementation

[0028] The present invention will be further described below with reference to the embodiments.

[0029] Unless otherwise specified, all raw materials used in the examples were commercially available.

[0030] Compound 1: imino-tris(dimethylamino)phosphine, CAS No.: 49778-01-0, molecular weight 178.2; Compound 2: N-tert-butyliminophosphate trichloride, CAS No.: 18854-80-3, molecular weight 208.5; 1,1,2-Trichloroethane, CAS No.: 79-00-5, Molecular weight 133.404; Phosphazene-based P4-t-BU tetrafluoroborate, full name 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)-n-phosphine-imino]-2λ 5 ,4λ 5 - Di(phosphazene)tetrafluoroborate, CAS No. 181471-62-5, molecular weight 721.5.

[0031] Example 1 The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 50.2 g (280 mmol, 3.5 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 36.1 g (280 mmol, 3.5 molar amounts relative to compound 2) of N,N-diisopropylethylamine (DIPEA) were weighed into a flask and added. Then, 150 mL of tetrahydrofuran (THF, water content ≤20 ppm) treated with anhydrous double aluminum column was added to completely dissolve it. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -25°C. In a separate dry volumetric flask, dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphate trichloride (compound 2) in 20 mL of anhydrous tetrahydrofuran, mix well, and then transfer to a constant pressure dropping funnel. At -25°C, the THF solution of compound 2 was slowly added dropwise into the flask over approximately 45 minutes, controlling the dropping rate. During this period, the thermometer was strictly monitored to ensure the internal temperature of the system did not exceed -20°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 60°C, and maintain the temperature at 60°C with stirring for 12 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was sterically hindered amine hydrochloride. The filtrate was subjected to vacuum distillation to remove THF and unreacted DIPEA, and finally a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0032] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous tetrahydrofuran (THF) is injected into the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold THF and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0033] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0034] Under stirring, 33g of a 40% sodium tetrafluoroborate (NaBF4) aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, then filtered under reduced pressure. The filter cake was washed twice with a small amount of cold water to obtain a white solid, which was then vacuum dried at 70°C to constant weight. Finally, 54.2g of a white, high-purity product was obtained, with a net yield of 93.9% based on compound 2.

[0035] The physical constants and nuclear magnetic resonance spectra of the obtained products were analyzed. 31 Characterization by pNMR, the results are as follows: 31 P NMR (400 MHz, CDCl3): δ = 23.92(q, 2 J pp = 50 Hz, PNHtBu), 12.28 (d, PNMe2). Nuclear magnetic resonance spectrum of Example 1 ( 31 P NMR) such as Figure 1 As shown.

[0036] Melting point (mp): 237℃; completely consistent with the theoretical value in the literature.

[0037] Based on the NMR data and melting point, it can be seen that it belongs to the high-purity target phosphazene-based P4-t-BU tetrafluoroborate.

[0038] Example 2 In this embodiment, tri-n-propylamine (TPA) is used as a sterically hindered tertiary amine acid-binding agent and catalyst.

[0039] The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 51.6 g (288 mmol, 3.6 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 41.3 g (288 mmol, 3.6 molar amounts relative to compound 2) of anhydrous tri-n-propylamine (TPA) were weighed into a flask and added. Then, 150 mL of chlorobenzene (water content ≤20 ppm) treated with anhydrous double aluminum column was added to completely dissolve the chlorobenzene. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -30°C. Take another dry volumetric flask and dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphoric acid trichloride (compound 2) in 20 mL of anhydrous chlorobenzene. After mixing well, transfer the solution to a constant pressure dropping funnel. At -30°C, the chlorobenzene solution of compound 2 was slowly added dropwise to the flask over approximately 45 minutes, controlling the dropping rate. During this period, the thermometer was strictly monitored to ensure the internal temperature of the system did not exceed -25°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 70°C, and maintain the temperature at 70°C with stirring for 10 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was a hindered amine hydrochloride. The filtrate was then subjected to vacuum distillation to remove chlorobenzene and unreacted tri-n-propylamine. Finally, a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0040] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous chlorobenzene is added to the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold chlorobenzene and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0041] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0042] Under stirring, 33g of a 40% sodium tetrafluoroborate (NaBF4) aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, then filtered under reduced pressure. The filter cake was washed twice with a small amount of cold water to obtain a white solid, which was then vacuum dried at 70°C to constant weight. Finally, 47.5g of a white, high-purity product was obtained, with a net yield of 82.3% based on compound 2.

[0043] 31 The 2NMR spectrum showed characteristic peaks consistent with those of Example 1, and a melting point (mp): 237℃; completely consistent with literature values. This demonstrates that using tri-n-propylamine as an acid-binding catalyst can halve the amount of compound 1 and lower the reaction temperature to 70℃, while achieving a yield of 82.3%.

[0044] Example 3 In this embodiment, tributylamine (TBA) is used as a sterically hindered tertiary amine acid binding agent and catalyst.

[0045] The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 45.9 g (256 mmol, 3.2 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 59.3 g (319.9 mmol, 4.0 molar amounts relative to compound 2) of anhydrous tributylamine (TBA) were weighed into a flask and added. Then, 150 mL of dioxane (water content ≤20 ppm) treated with anhydrous double aluminum column was added to completely dissolve it. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -35°C. Take another dry volumetric flask, dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphate trichloride (compound 2) in 20 mL of anhydrous dioxane, mix well and transfer to a constant pressure dropping funnel; At -35°C, the dioxane solution of compound 2 was slowly added dropwise into the flask over approximately 45 minutes, controlling the dropping rate. During this period, the thermometer was strictly monitored to ensure the internal temperature of the system did not exceed -30°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 65°C, and maintain the temperature at 65°C with stirring for 12 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was a hindered amine hydrochloride. The filtrate was then subjected to vacuum distillation to remove dioxane and unreacted tributylamine. Finally, a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0046] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous dioxane is injected into the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold dioxane and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0047] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0048] Under stirring, 33g of a 40% sodium tetrafluoroborate (NaBF4) aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, then filtered under reduced pressure. The filter cake was washed twice with a small amount of cold water to obtain a white solid, which was then vacuum dried at 75°C to constant weight. A total of 49.3g of a white, high-purity product was finally obtained, with a net yield of 85.5% based on compound 2.

[0049] 31 The 2P NMR spectrum showed characteristic peaks consistent with those of Example 1, and a melting point (mp): 237℃; completely consistent with literature values. This demonstrates that using tributylamine as a binding acid catalyst can halve the amount of compound 1 and lower the reaction temperature to 65℃, while achieving a yield of 85.5%.

[0050] Example 4 In this embodiment, triisobutylamine (TIBA) is used as a sterically hindered tertiary amine binding acid agent and catalyst.

[0051] The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 50.2 g (280 mmol, 3.5 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 45.3 g (244.4 mmol, 3 molar amounts relative to compound 2) of anhydrous triisobutylamine (TIBA) were weighed into a flask and then added to a flask. 150 mL of tetrahydrofuran (THF, water content ≤20 ppm) treated with anhydrous double aluminum column was then added to dissolve it completely. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -35°C. In a separate dry volumetric flask, dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphate trichloride (compound 2) in 20 mL of anhydrous tetrahydrofuran, mix well, and then transfer to a constant pressure dropping funnel. At -35°C, the THF solution of compound 2 was slowly added to the flask over approximately 45 minutes, controlling the dropping rate. During this period, the thermometer was closely monitored to ensure the internal temperature of the system did not exceed -25°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 65°C, and maintain the temperature at 65°C with stirring for 12 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was sterically hindered amine hydrochloride. The filtrate was then subjected to vacuum distillation to remove THF and unreacted triisobutylamine. Finally, a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0052] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous tetrahydrofuran (THF) is injected into the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold THF and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0053] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0054] A 40% (w / w) aqueous solution of tetrafluoroboric acid (HBF4) was slowly added dropwise under stirring until the pH of the system reached 7.0. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, filtered under reduced pressure, and the filter cake was washed twice with a small amount of cold water to obtain a white solid. This solid was then vacuum dried at 70°C to constant weight. A final yield of 50.5 g of a white, high-purity product was obtained, representing a net yield of 87.6% based on compound 2.

[0055] 31 The ¹H NMR spectrum showed characteristic peaks consistent with those of Example 1, and a melting point (mp): 237 °C; completely consistent with literature values. This demonstrates that using triisobutylamine as an acid-binding catalyst can halve the amount of compound 1 and lower the reaction temperature to 65 °C, while achieving a yield of 87.6%.

[0056] Example 5 In this embodiment, 1,2,2,6,6-pentamethylpiperidine is used as a sterically hindered tertiary amine binding acid agent and catalyst.

[0057] The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 50.2 g (280 mmol, 3.5 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 47.2 g (303.7 mmol, 3.8 molar amounts relative to compound 2) of 1,2,2,6,6-pentamethylpiperidine were weighed into a flask and added. Then, 150 mL of tetrahydrofuran (THF, water content ≤20 ppm) treated with anhydrous double aluminum column was added to completely dissolve it. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -33°C. In a separate dry volumetric flask, dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphate trichloride (compound 2) in 20 mL of anhydrous tetrahydrofuran, mix well, and then transfer to a constant pressure dropping funnel. At -33°C, the THF solution of compound 2 was slowly added to the flask over approximately 45 minutes, controlling the dropping rate. During this period, the thermometer was closely monitored to ensure the internal temperature of the system did not exceed -28°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 60°C, and maintain the temperature at 60°C with stirring for 12 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was a hindered amine hydrochloride. The filtrate was subjected to vacuum distillation to remove THF and unreacted 1,2,2,6,6-pentamethylpiperidine. Finally, a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0058] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous tetrahydrofuran (THF) is injected into the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold THF and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0059] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0060] Under stirring, 33g of a 40% (w / w) aqueous solution of tetrafluoroboric acid (HBF4) was slowly added dropwise. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, then filtered under reduced pressure. The filter cake was washed twice with a small amount of cold water to obtain a white solid, which was then dried under vacuum at 70°C to constant weight. A final yield of 53.2g of a white, high-purity product was obtained, representing a net yield of 92.2% based on compound 2.

[0061] 31 The 1,2,2,6,6-pentamethylpiperidine NMR spectrum showed characteristic peaks consistent with those of Example 1, and a melting point (mp): 237 °C; completely consistent with literature values. This demonstrates that using 1,2,2,6,6-pentamethylpiperidine as a binding acid catalyst can halve the amount of compound 1 and lower the reaction temperature to 60 °C, achieving a yield of 92.2%, making it one of the best sterically hindered tertiary amines besides DIPEA in this invention.

[0062] Comparative Example 1 The existing synthesis process of phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: Following the preparation method of Example 1, 99.8 g (560 mmol, 7.0 molar amounts relative to Compound 2) of Compound 1 was dissolved in 100 mL of anhydrous tetrahydrofuran (THF) in a 500 mL three-necked flask. The solution was cryogenically cooled to -30 °C under full nitrogen protection. Under conditions where the internal temperature does not exceed -30°C, 13.7 mL (16.7 g, 80.0 mmol) of 20 mL THF solution of compound 2 was added dropwise over a period of 50 minutes. After the addition is complete, allow the system to slowly return to room temperature. Then, the THF solvent must be removed under reduced pressure. Place the remaining mixture in an oil bath and heat it to a high temperature of 110°C for 24 hours (the literature cited in the background does not react at 60°C due to the lack of external alkali catalysis, so 110°C is required) to obtain a viscous liquid crude product.

[0063] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous tetrahydrofuran (THF) is injected into the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour to allow excess compound 1, which acted as an acid-binding agent, to precipitate as a hydrochloride salt. The precipitate was filtered off, and the solvent was removed from the filtrate under vacuum to obtain a purified phosphazene chloride intermediate. (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0064] A 40% (w / w) aqueous solution of tetrafluoroboric acid (HBF4) was slowly added dropwise under stirring until the pH of the system reached 7.0. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, filtered under reduced pressure, and the filter cake was washed twice with a small amount of cold water to obtain a white solid. This solid was then vacuum dried at 60°C to constant weight. Finally, 52.1 g of a white, high-purity phosphazene-based P4-t-BU tetrafluoroborate product was obtained, with a net yield of 90.4% based on compound 2.

[0065] Comparative Example 2 The synthesis process of the aforementioned phosphazene-based P4-t-BU tetrafluoroborate involves the following steps: (1) Substitution condensation reaction: In a standard three-necked flask equipped with a mechanical stirrer and a gas inlet and outlet of 500 mL, the system was first completely purged three times with a stream of high-purity nitrogen (purity ≥99.99%). Under continuous nitrogen protection, 45.9 g (256 mmol, 3.2 molar amounts relative to compound 2) of imino-tris(dimethylamino)phosphine (compound 1) and 26.0 g (256 mmol, 3.2 molar amounts relative to compound 2) of anhydrous triethylamine (TEA) were weighed into a flask and added. Then, 150 mL of tetrahydrofuran (water content ≤20 ppm) treated with anhydrous double aluminum column was added to completely dissolve it. Turn on the mechanical stirrer and place the three-necked flask in a low-temperature ethanol thermostat bath to allow the solution to cool slowly until the internal temperature of the system stabilizes at -30°C. In a separate dry volumetric flask, dissolve 13.7 mL (16.7 g, 80.0 mmol) of N-tert-butyliminophosphoric acid trichloride (compound 2) in 20 mL of anhydrous tetrahydrofuran. After mixing thoroughly, transfer the solution to a constant-pressure dropping funnel. At -25°C, control the dropping rate and slowly add the tetrahydrofuran solution of compound 2 to the flask over approximately 45 minutes. During this period, strictly monitor the thermometer to ensure the internal temperature of the system does not exceed -20°C. After the addition is complete, remove the low-temperature ethanol cooling bath and allow the reaction system to slowly heat up under stirring. When the internal temperature of the system naturally rises to room temperature (about 20°C), turn on the external constant temperature water bath heating device to slowly heat the reaction system to 65°C, and maintain the temperature at 65°C with stirring for 10 hours. After the reaction was completed, heating was stopped, and the reaction solution was cooled to room temperature. The reaction solution was then filtered, and the residue was a hindered amine hydrochloride. The filtrate was then subjected to vacuum distillation to remove tetrahydrofuran and unreacted triethylamine. Finally, a highly viscous, light yellow, transparent crude product was obtained at the bottom of the flask.

[0066] (2) Removal of excess raw materials and refining of intermediates: After the above viscous crude product has cooled to room temperature (20°C), 100 mL of anhydrous tetrahydrofuran is added to the flask, and stirring is started to completely redissolve the crude product. Subsequently, 15 mL (21.3 g, 160 mmol) of 1,1,2-trichloroethane was added with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 1 hour. At this point, it could be observed that a large amount of fine white crystalline precipitate rapidly formed in the originally slightly turbid solution. This precipitate was identified as the hydrochloride salt formed by excess compound 1 and residual acid. The mixture was filtered under reduced pressure using a sintered glass funnel. The filter cake was washed twice with a small amount of cold tetrahydrofuran and collected for the resource recovery of compound 1. The combined filtrate was collected in a clean flask and evaporated to dryness again at 50°C. All low-boiling-point solvents were removed under vacuum to obtain a purified phosphazene chloride intermediate.

[0067] (3) Anion exchange: The refined phosphazene chloride intermediate was completely dissolved in 150 mL of water, and the solution was cooled to 2.5 ± 2.5 °C in an ice-water bath.

[0068] Under stirring, 33g of a 40% sodium tetrafluoroborate (NaBF4) aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred in an ice-water bath for 2 hours, then filtered under reduced pressure. The filter cake was washed twice with a small amount of cold water to obtain a white solid, which was then vacuum dried at 70°C to constant weight. A total of 40.7g of a white, high-purity product was finally obtained, with a net yield of 70.5% based on compound 2.

[0069] 31 The 1NMR spectrum showed characteristic peaks consistent with those of Example 1, and a melting point (mp): 237℃; completely consistent with literature values. This demonstrates that using triethylamine as an acid-binding catalyst can halve the amount of Compound 1 and lower the reaction temperature to 65℃, while achieving a yield of 70.5%.

[0070] In Examples 1-5 of this invention, the introduction of low-cost sterically hindered tertiary amines reduced the amount of high-value core raw material compound 1 from 99.8g to about 50g, directly saving nearly half of the core raw material cost for production.

[0071] In Comparative Example 1, without the addition of a sterically hindered tertiary amine, a high-temperature heating of 110°C was required to drive the condensation. However, due to the synergistic catalytic effect of the sterically hindered tertiary amine, the reaction temperature of this invention was lowered to 60-70°C. This not only greatly saves industrial energy consumption but also reduces the heat resistance rating of the equipment.

[0072] Despite the significant reduction in reaction temperature and the amount of expensive raw materials used, the yield of this invention remains firmly maintained at a high level of 82.3% to 93.9%, fully demonstrating the enormous driving effect of the new process of this invention on industrial production.

Claims

1. A synthesis process for phosphazene-based P4-t-BU tetrafluoroborate, characterized in that, It is prepared by the following steps: (1) Substitution condensation reaction: Compound 1: imino-tris(dimethylamino)phosphine and sterically hindered tertiary amine acid-binding agent were dissolved in an organic solvent and cooled to -35℃~-25℃; under stirring, an organic solution of compound 2: N-tert-butyliminophosphine trichloride was added dropwise; after the addition was complete, the temperature was raised to 60℃~70℃ for reaction; after the reaction was completed, the mixture was cooled, the sterically hindered tertiary amine hydrochloride was removed by filtration, and the organic solvent was removed from the filtrate under reduced pressure to obtain the crude product; (2) Removal of excess raw materials and purification of intermediates: The crude product is redissolved in a solvent, 1,1,2-trichloroethane is added, and the mixture is stirred to convert the excess compound 1 in the system into hydrochloride precipitate. The mixture is filtered, and the solvent is removed from the filtrate under vacuum to obtain the purified intermediate. (3) Anion exchange: The purified intermediate is dissolved in an aqueous solution, anion exchange reagent is added to carry out anion exchange reaction, and the target product is obtained after crystallization, washing and drying.

2. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The molar ratio of compound 1 and compound 2 in step (1) is 3.2:1 to 3.6:

1.

3. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The molar ratio of the sterically hindered tertiary amine to compound 2 in step (1) is 3.0:1 to 4.0:

1.

4. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The sterically hindered tertiary amine mentioned in step (1) is one or more of N,N-diisopropylethylamine, tributylamine, triisobutylamine, tri-n-propylamine and 1,2,2,6,6-pentamethylpiperidine.

5. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 4, characterized in that, The sterically hindered tertiary amine mentioned in step (1) is N,N-diisopropylethylamine and 1,2,2,6,6-pentamethylpiperidine.

6. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, In step (1), the reaction temperature is controlled to not exceed -20°C during the process of adding compound 2.

7. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The organic solvent mentioned in step (1) is tetrahydrofuran, dioxane, or chlorobenzene.

8. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The reaction time for raising the temperature to 60℃~70℃ in step (1) is 10~12h.

9. The synthesis process of phosphazene-based P4-t-BU tetrafluoroborate according to claim 1, characterized in that, The anion exchange reagent in step (3) is an aqueous solution of tetrafluoroboric acid or tetrafluoroborate.

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