Aryl phosphonates and aryl thiophosphonates and methods for their preparation

Abstract

The application discloses aryl phosphonate and aryl thiophosphonate compounds and a preparation method thereof. Under nitrogen protection, aryl hypophosphorous acid, R-XH (X=O, S) reagent is used as a starting material, trifluoromethanesulfonic anhydride, dimethyl sulfoxide and TBAB (tetrabutylammonium bromide) are added in an organic solvent, the aryl hypophosphorous acid, the R-XH (X=O, S) reagent, the trifluoromethanesulfonic anhydride, the dimethyl sulfoxide and the TBAB are reacted at a reaction temperature RT (room temperature)~40 o C for 0.5~3 hours, then the solvent is removed by rotary evaporation, and column chromatography is performed to obtain aryl phosphonate or aryl thiophosphonate compounds. The starting material involved in the preparation method is stable and easy to obtain, the reaction is easy to operate, and the substrate compatibility is good, and a plurality of aryl phosphonate or aryl thiophosphonate compounds can be synthesized by one-pot method in one step.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for preparing arylphosphonates and arylthiophosphonates. Background Technology

[0002] Arylphosphonates and arylthiophosphonates are two important classes of organophosphorus compounds, which are widely used in many areas of human production and life. For example, arylphosphonates can be used as light-converting agents in light-converting films (CN 202111191156), as flame retardants (Liu, Z.; et al. Polymers for Advanced Technologies, 2021, 1–13), and as bioactive molecules (Lassaux, P.; et al. Journal of Medicinal Chemistry, 2010, 53, 4862–4876); arylthiophosphonates can be used as flame retardants (KR101863259B1), as ligands for metal catalysts (Crawford, NRM; et al. Chem. Eur. J. 2008, 14, 319-324), and as synthons for various chemical transformations (Nishiyama, Y.; et al. Org. Lett. 2017, 19, 3899-3902; Sauer, M.; et al. al. Org. Biomol. Chem., 2020, 18, 1567-1571).

[0003] Currently, the industrial synthesis of these two types of compounds is carried out using traditional synthetic methods (Strijtveen, B.; et al. Tetrahedron, 1987, 43, 123-130), namely, the reaction of phenylphosphonic dichloride (PhP(O)Cl2) with R-OH or R-SH reagents under alkaline conditions. However, the phenylphosphonic dichloride (PhP(O)Cl2) phosphorus reagent used in this process is extremely unstable, easily deliquescent and deteriorates, and is highly corrosive, causing strong irritation to the skin and eyes. It is listed as a Class C hazardous chemical in the "List of Hazardous Chemicals (2015 Edition)".

[0004] The methods developed in the field of scientific research for synthesizing these two types of compounds mainly employ the following two strategies: 1. Michaelis-Arbuzov reaction of haloaromatic hydrocarbons with phosphites (P(OR)3) (e.g., Li, C.; et al. Organic metallics, 2020, 39, 3613-3617; Yao, Q.; et al. Tetrahedron Letters, 2006, 47, 277-281); 2. Cross-coupling reaction of haloaromatic hydrocarbons with disubstituted phosphorus oxides (HP(O)R2) (e.g., Zhuang, R.; et al. Organic Letters, 2011, 13, 8, 2110-2113; Kalek, M.; et al. Advanced Synthesis & Catalysis, 2009, 351, 3207-3216). However, the phosphite reagents used in the above strategies are unstable and prone to deliquescence and oxidation by air. Trimethyl phosphite (P(OMe)3), triethyl phosphite (P(OEt)3), and triphenyl phosphite (P(OPh)3) are all listed as hazardous chemicals in the "List of Hazardous Chemicals (2015 Edition)". Moreover, both of these strategies suffer from harsh reaction conditions and low yields. In addition, both of these synthetic strategies require the addition of noble metal catalysts (Ni, Pd, Cu, etc.) to promote the reaction, which leads to low economic efficiency and makes it difficult to replace traditional industrial synthesis methods.

[0005] In summary, current methods for preparing arylphosphonates and arylthiophosphonates, both industrially and in scientific research, have significant limitations and low economic efficiency, making them unsuitable for large-scale industrial production. Therefore, developing synthetic strategies with high reaction efficiency, good substrate compatibility, stable and low-toxicity reagents, and high economic value for the efficient preparation of arylphosphonates and arylthiophosphonates is of significant scientific and practical importance in the phosphorus chemistry industry and basic research on organophosphorus compounds. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide arylphosphonates and arylthiophosphonates and their preparation methods, wherein some products are synthesized for the first time.

[0007] The technical solution for implementing the present invention is as follows:

[0008] A method for preparing arylphosphonates and arylthiophosphonates is disclosed. The method uses phenylphosphine and R-XH (X=O,S) reagent as starting materials. Under nitrogen protection, in the presence of trifluoromethanesulfonic anhydride, dimethyl sulfoxide, and TBAB, the molar ratio of arylphosphine, R-XH (X=O,S) reagent, trifluoromethanesulfonic anhydride, dimethyl sulfoxide, and TBAB is 1:2–4:1–4:0.1–1:0–0.3. An organic solvent is added to achieve a solution concentration of 0.067 mol / L. The reaction is carried out at RT–40°C for 0.5–3 hours. The solvent is then removed by rotary evaporation, and the arylphosphonate or arylthiophosphonate compound is obtained by column chromatography.

[0009] Specifically, depending on the R-XH reagent used, the reaction proceeds in the following two types of reactions:

[0010] When the R-XH reagent is R-OH, the reaction pattern is as follows:

[0011] Starting with aryl hypophosphoric acid and R-OH reagent, under nitrogen protection, the reaction was carried out in acetonitrile (an organic solvent) at 40 °C for 1 hour in the presence of trifluoromethanesulfonic anhydride (Tf₂O), dimethyl sulfoxide (DMSO), and TBAB (tetrabutylammonium bromide). After the reaction was completed, the solvent was removed by rotary evaporation, and the aryl phosphonate product was obtained by column chromatography using a mixture of petroleum ether and ethyl acetate (9:1 v / v) as the eluent.

[0012] The aryl hypophosphite is selected from any one of phenyl hypophosphite, (4-methylphenyl) hypophosphite, (4-fluorophenyl) hypophosphite, (4-phenylphenyl) hypophosphite, (4-methoxyphenyl) hypophosphite, and (4-tert-butylphenyl) hypophosphite;

[0013] The R-OH reagent is selected from any one of phenol, 4-fluorophenol, 4-chlorophenol, 4-bromophenol, 4-trifluoromethylphenol, 4-methylphenol, 4-tert-butylphenol, 4-phenylphenol, 2-phenylphenol, 2-methylphenol, 2-bromophenol, 3,4-difluorophenol, 2-bromo-4-methylphenol, 3,4-dimethylphenol, trifluoroethanol, trichloroethanol, and pentafluoropropanol;

[0014] In the aforementioned reaction mode, the molar ratio of aryl hypophosphite, R-OH reagent, trifluoromethanesulfonic anhydride, dimethyl sulfoxide, and TBAB is 1:2~4:1~4:0.1~1:0~0.3.

[0015] When the R-XH reagent is R-SH, the reaction mode is as follows:

[0016] Starting with aryl hypophosphoric acid and R-SH reagent, the reaction was carried out under nitrogen protection in acetonitrile organic solvent at RT (room temperature) for 1 hour in the presence of trifluoromethanesulfonic anhydride (Tf2O) and dimethyl sulfoxide (DMSO). After the reaction was completed, the solvent was removed by rotary evaporation, and the product was obtained by column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 9:1 as the eluent.

[0017] The aryl hypophosphite is selected from either phenyl hypophosphite or (4-methylphenyl) hypophosphite;

[0018] The R-SH reagent is selected from any one of p-methylthiophenol, p-tert-butylthiophenol, p-methoxythiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, 2-methylthiophenol, 3-methylthiophenol, 2,5-dimethylthiophenol, 2-naphthiophenol, and 3-chlorothiophenol.

[0019] In the reaction mode, the molar ratio of aryl hypophosphite, R-SH reagent, trifluoromethanesulfonic anhydride, and dimethyl sulfoxide is 1:2 to 4:1 to 4:0.1 to 2, preferably 1:3:3:0.2.

[0020] The phosphorus reagent, R-XH (X = O, S) reagent, and other reaction reagents involved in the preparation method of this invention are stable, readily available, and have low toxicity. No precious metal catalysts are required. Furthermore, the reaction substrates involved in this invention have good compatibility; in addition to various alcohols and phenols, various thiophenols can also be reacted using this method. This method allows for the one-pot, one-step synthesis of various arylphosphonates and arylthiophosphonates. Among these, the products di(4-tert-butylphenylthio) phenylphosphonate, di(4-methoxyphenylthio) phenylphosphonate, di(4-fluorophenylthio) phenylphosphonate, di(4-chlorophenylthio) phenylphosphonate, di(4-bromophenylthio) phenylphosphonate, di(3-methylphenylthio) phenylphosphonate, di(2,5-dimethylphenylthio) phenylphosphonate, di(2-naphthylthio) phenylphosphonate, di(3-chlorophenylthio) phenylphosphonate, and di(4-methylphenylphosphonate) are synthesized for the first time.

[0021] Compared with the prior art, the advantages of the present invention are as follows:

[0022] 1. The starting materials and reaction reagents involved in this invention have low toxicity and good stability, avoiding the use of precious metals (Ni, Pd, Cu) and chemicals listed in the "List of Hazardous Chemicals" in traditional synthesis methods. The reagents used in this invention, trifluoromethanesulfonic anhydride (Tf2O) and dimethyl sulfoxide (DMSO), are not only low in toxicity but also inexpensive (Tf2O: 99.5%, 1kg, 850 yuan; DMSO: 99%, 10L, 380 yuan). This makes this invention green and environmentally friendly, with low production costs and high economic efficiency, and it can be used for large-scale industrial production.

[0023] 2. The reaction substrates used in this invention are inexpensive and readily available, with a wide range of choices. For phenolic reagents (R=Ar) in R-OH reactions, phenols containing different functional groups are commercially available and inexpensive. In addition, various R-SH (R=Ar) reagents are also well-suited for this invention; these reagents are also readily available from reagent manufacturers and are inexpensive. Therefore, the wide applicability of the reaction substrates gives this invention good compatibility, enabling the one-pot, one-step reaction to yield arylphosphonates or thioarylphosphonates with diverse structural types.

[0024] 3. Compared with our previous technology (an aryl phosphonate compound and its preparation method, CN202310413990.0), the reaction conditions of this invention are milder and the energy consumption is greatly reduced. The reaction environment is reduced from a high-temperature system (110°C) to 40°C and room temperature (RT). The reaction efficiency is also greatly improved, and the time required to complete the reaction is greatly shortened from 11 hours to 1 hour. Moreover, the reaction yield is significantly improved. Finally, CN 202310413990.0 can only prepare aryl phosphates, while thioaryl phosphonates cannot be prepared well. However, this invention can not only prepare aryl phosphates with higher yields, but also prepare thioaryl phosphonates efficiently. This makes the application scope of this invention wider and the substrate compatibility significantly improved. Detailed Implementation

[0025] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0026] Example 1:

[0027] Using phenylphosphino acid and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0028]

[0029] Phenylacetic acid (28.4 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product, diphenyl phenylphosphonate, was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 95%.

[0030] 1 H NMR (500MHz, CDCl3): δ7.99-7.94(m,2H),7.60-7.57(m,1H),7.51-7.47(m,2H),7.30-7.25(m,4H),7.20-7.17(m,4H),7.15-7.11(m,2H). 31 P NMR (203MHz, CDCl3): δ 11.73. Comparative Example 1:

[0031] [Invention Patent (Application No.: CN202310413990.0)] In our previous technology, using ethyl phenylphosphonate and phenol as raw materials, the reaction formula and experimental steps for preparing the same product are as follows:

[0032]

[0033] Ethyl phenylphosphonate (34.0 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (197.5 mg, 0.7 mmol), DMSO (15.6 mg, 0.2 mmol), and TBAB (9.7 mg, 0.03 mmol) were added sequentially. The reaction was carried out in an oil bath at 90 °C for 11 hours. After the reaction was complete, the reaction solution was concentrated, and the product diphenyl phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 73%.

[0034] The preparation method of the present invention will be discussed using Example 1 and Comparative Example 1 as examples.

[0035] Compared to Comparative Example 1, Example 1 reduced the amount of reaction reagents used. DMSO was reduced from 0.2 mmol (1.0 equivalent) to 0.04 mmol (0.2 equivalent), and Tf₂O was reduced from 0.7 mmol (3.5 equivalent) to 0.6 mmol (3.0 equivalent). This reduction in reagent usage lowered the preparation cost and improved economic efficiency. The reaction temperature was lowered from a high-temperature environment of 90°C to 40°C, reducing energy consumption and increasing operational safety. The reaction time was reduced from 11 hours to 1 hour, and the reaction yield increased from 73% to 95%. The shortened time and increased yield significantly improved the preparation efficiency. Therefore, compared to Comparative Example 1, Example 1 demonstrates a significant improvement in all aspects of the technical solution. This is because the phosphorus reagent (aryl hypophosphite) of this invention represents two completely different reaction approaches compared to the phosphorus reagent (arylphosphonic acid alkyl ester) of the comparative example. In this invention, DMSO acts as a catalyst, stabilizing the phosphorus cation intermediate with ligands and catalyzing the reaction. In the comparative example, dimethyl sulfoxide (DMSO) acts as a cooperating agent for the deprotonation of R-OH and promotes the formation of reaction intermediates. Only when it is present in sufficient quantities as a reactant can it drive the reaction. The two belong to different technical routes.

[0036] The following examples, from two to thirty-four, will demonstrate the universality of the preparation method of the present invention.

[0037] Example 2:

[0038] Using phenylphosphino acid and 4-fluorophenol as raw materials, the reaction formula and experimental steps are as follows:

[0039]

[0040] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-fluorophenol (89.6 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-fluorophenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 95%.

[0041] 1 H NMR (400MHz, CDCl3): δ7.89-7.83(m,2H),7.57-7.53(m,1H),7.46-7.41(m,2H),7.08-7.04(m,4H),6.91-6.87(m,4H). 31P NMR (162MHz, CDCl3): δ 12.64. 19 F NMR (376MHz, CDCl3): δ-117.5.

[0042] Example 3:

[0043] Using phenylphosphinoic acid and 4-chlorophenol as raw materials, the reaction formula and experimental steps are as follows:

[0044]

[0045] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-chlorophenol (102.4 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-chlorophenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 92%.

[0046] 1 H NMR (400MHz, CDCl3): δ7.88-7.82(m,2H),7.57-7.53(m,1H),7.46-7.41(m,2H),7.19-7.16(m,4H),7.06-7.00(m,4H). 31 PNMR (162MHz, CDCl3): δ 12.45.

[0047] Example 4:

[0048] Using phenylphosphinoic acid and 4-bromophenol as raw materials, the reaction formula and experimental steps are as follows:

[0049]

[0050] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-bromophenol (138.4 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-bromophenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 91%.

[0051] 1 H NMR (500MHz, CDCl3): δ7.95-7.91(m,2H),7.65-7.61(m,1H),7.54-7.49(m,2H),7.42-7.39(m,4H),7.08-7.06(m,4H). 31 PNMR (203MHz, CDCl3): δ 12.29.

[0052] Example 5:

[0053] Using phenylphosphino acid and 4-trifluoromethylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0054]

[0055] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-trifluoromethylphenol (129.6 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-trifluoromethylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 70%.

[0056] 1 H NMR (400MHz, CDCl3): δ8.01-7.95 (m, 2H), 7.68-7.64 (m, 1H), 7.60-7.52 (m, 6H), 7.33 (d, J = 8Hz, 4H). 31 PNMR (162MHz, CDCl3): δ 13.01. 19 F NMR (376MHz, CDCl3): δ-62.2.

[0057] Example 6:

[0058] Using phenylphosphinoic acid and 4-methylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0059]

[0060] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-methylphenol (86.4 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-methylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 93%.

[0061] 1 H NMR (500MHz, CDCl3): δ7.96-7.92(m,2H),7.58-7.55(m,1H),7.49-7.45(m,2H),7.06(s,8H),2.27(s,6H). 31 PNMR (203MHz, CDCl3): δ 11.88.

[0062] Example 7:

[0063] Using phenylphosphino acid and 4-tert-butylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0064]

[0065] Phenylacetic acid (28.4 mg, 0.2 mmol) and 4-tert-butylphenol (120.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-tert-butylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 85%.

[0066] 1 H NMR (500MHz, CDCl3): δ7.81-7.76 (m, 2H), 7.50-7.47 (m, 1H), 7.40-7.35 (m, 6H), 7.27 (d, J = 10.0Hz, 4H), 1.27 (s, 18H). 31 PNMR (203MHz, CDCl3): δ 50.16.

[0067] Example 8:

[0068] Using phenylphosphino acid and 4-phenylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0069]

[0070] Phenylated phosphonic acid (28.4 mg, 0.2 mmol) and 4-phenylphenol (136.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-phenylphenyl) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 86%.

[0071] 1 H NMR (500MHz, CDCl3): δ8.05-8.00(m,2H),7.64-7.60(m,1H),7.54-7.50(m,10H),7.42-7.39(m,4H),7.34-7.27(m,6H). 31 PNMR (203MHz, CDCl3): δ 12.19.

[0072] Example 9:

[0073] Using phenylphosphino acid and 2-phenylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0074]

[0075] Phenylacetic acid (28.4 mg, 0.2 mmol) and 2-phenylphenol (136.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2-phenylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 78%.

[0076] 1 H NMR (500MHz, CDCl3): δ7.37-7.34(m,3H),7.29-7.15(m,18H),7.12-7.08(m,2H).31 P NMR (203MHz, CDCl3): δ 11.58.

[0077] Example 10:

[0078] Using phenylphosphinoic acid and 2-methylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0079]

[0080] Phenylephrine (28.4 mg, 0.2 mmol) and 2-methylphenol (86.4 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2-methylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 79%.

[0081] 1 H NMR (500MHz, CDCl3): δ8.03-7.98(m,2H),7.63-7.60(m,1H),7.53-7.49(m,2H),7.22(d,J= 10.0Hz,2H),7.16(d,J=5.0Hz,2H),7.11-7.07(m,2H),7.04(t,J=5.0Hz,2H),2.20(s,6H). 31 PNMR (203MHz, CDCl3): δ 11.35.

[0082] Example 11:

[0083] Using phenylphosphino acid and 2-bromophenol as raw materials, the reaction formula and experimental steps are as follows:

[0084]

[0085] Phenylacetic acid (28.4 mg, 0.2 mmol) and 2-bromophenol (138.4 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2-bromophenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 82%.

[0086] 1 H NMR (500MHz, CDCl3): δ8.17-8.12(m,2H),7.64-7.60(m,1H),7.55-7.50(m,2H),7.47-7.44(m,2H),7.24-7.20(m,2H),7.02-6.99(m,2H). 31 PNMR (203MHz, CDCl3): δ 12.43.

[0087] Example 12:

[0088] Using phenylphosphinoic acid and 3,4-difluorophenol as raw materials, the reaction formula and experimental steps are as follows:

[0089]

[0090] Phenylacetic acid (28.4 mg, 0.2 mmol) and 3,4-difluorophenol (104.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(3,4-difluorophenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 90%.

[0091] 1 H NMR (400MHz, CDCl3): δ7.88-7.82(m,2H),7.60-7.56(m,1H),7.49-7.44(m,2H),7.05-6.96(m,3H),6.89-6.94(m,2H). 31 P NMR (162MHz, CDCl3): δ 13.03. 19F NMR(376MHz, CDCl3): δ-133.5(d,J F-F =22.6Hz), -141.2(d,J F-F =18.8Hz).

[0092] Example 13:

[0093] Using phenylphosphinoic acid and 2-bromo-4-methylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0094]

[0095] Phenylacetic acid (28.4 mg, 0.2 mmol) and 2-bromo-4-methylphenol (149.6 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2-bromo-4-methylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 82%.

[0096] 1 H NMR (500MHz, CDCl3): δ8.14-8.09(m,2H),7.62-7.59(m,1H),7.52-7.48(m,2H),7.34-7.31(m,4H),7.01-6.99(m,2H),2.26(s,6H). 31 PNMR (203MHz, CDCl3): δ 12.50.

[0097] Example 14:

[0098] Using phenylphosphinoic acid and 3,4-dimethylphenol as raw materials, the reaction formula and experimental steps are as follows:

[0099]

[0100] Phenylacetic acid (28.4 mg, 0.2 mmol) and 3,4-dimethylphenol (97.6 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(3,4-dimethylphenyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 63%.

[0101] 1 H NMR (500MHz, CDCl3): δ7.97-7.93(m,2H),7.59-7.56(m,1H),7.50-7.46(m,2H),7.01-6.97(m,4H),6.90-6.88(m,2H),2.18(s,6H),2.18(s,6H). 31 P NMR (203MHz, CDCl3): δ 11.68.

[0102] Example 15:

[0103] Using phenylphosphinoic acid and 2,2,2-trifluoroethanol as raw materials, the reaction formula and experimental steps are as follows:

[0104]

[0105] Phenylated phosphonic acid (28.4 mg, 0.2 mmol) and 2,2,2-trifluoroethanol (80.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2,2,2-trifluoroethyl) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 77%.

[0106] 1 H NMR (500MHz, CDCl3): δ7.86-7.81(m,2H),7.68-7.64(m,1H),7.56-7.52(m,2H),4.51-4.34(m,4H). 31 PNMR (203MHz, CDCl3): δ 21.40.

[0107] Example 16:

[0108] Using phenylphosphinoic acid and 2,2,2-trichloroethanol as raw materials, the reaction formula and experimental steps are as follows:

[0109]

[0110] Phenylephrine (28.4 mg, 0.2 mmol) and 2,2,2-trichloroethanol (119.2 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2,2,2-trichloroethyl) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 82%.

[0111] 1 H NMR (400MHz, CDCl3): δ7.89-7.83(m,2H),7.60-7.55(m,1H),7.49-7.44(m,2H),4.67-4.62(m,2H),4.60-4.55(m,2H). 31 PNMR (162MHz, CDCl3): δ 19.21.

[0112] Example 17:

[0113] Using phenylphosphinoic acid and 2,2,3,3,3-pentafluoro-1-propanol as raw materials, the reaction formula and experimental steps are as follows:

[0114]

[0115] Phenylacetic acid (28.4 mg, 0.2 mmol) and 2,2,3,3,3-pentafluoro-1-propanol (120.0 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, and this process was repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product, di(2,2,3,3,3-pentafluoro-1-propanol) phenylphosphonate, was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 73%.

[0116] 1H NMR (500MHz, CDCl3): δ7.85-7.80(m,2H),7.68-7.65(m,1H),7.56-7.52(m,2H),4.60-4.40(m,4H). 31 PNMR (203MHz, CDCl3): δ 21.47. 19 F NMR (470MHz, CDCl3): δ-83.49,-124.42.

[0117] Example 18:

[0118] Using phenylphosphinoic acid and 4-methylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0119]

[0120] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 4-methylbenzylthiophenol (74.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-methylbenzylthio) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 76%.

[0121] 1 H NMR (500MHz, CDCl3): δ7.79-7.74(m,2H),7.51-7.47(m,1H),7.42-7.39(m,2H),7.35-7.33(m,4H),6.78(d,J=10.0Hz,4H),3.76(s,6H). 31 PNMR (203MHz, CDCl3): δ 50.25.

[0122] Example 19:

[0123] Using phenylphosphinoic acid and 4-tert-butylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0124]

[0125] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 4-tert-butylthiophenol (99.6 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-tert-butylphenylthio) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 68%.

[0126] 1 H NMR (500MHz, CDCl3): δ7.81-7.76(m,2H),7.50-7.46(m,1H),7.40-7.35(m,6H),7.29-7.26(m,4H),1.27(s,18H). 31 PNMR (203MHz, CDCl3): δ 50.20.

[0127] Example 20:

[0128] Using phenylphosphinoic acid and 4-methoxythiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0129]

[0130] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 4-methoxybenzylthiophenol (84.0 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-methoxybenzylthio) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 50%.

[0131] 1 H NMR (500MHz, CDCl3): δ7.79-7.74(m,2H),7.51-7.47(m,1H),7.42-7.39(m,2H),7.35-7.33(m,4H),7.28(d,J=10.0Hz,4H),3.76(s,6H). 31 PNMR (203MHz, CDCl3): δ 50.25.

[0132] Example 21:

[0133] Using phenylphosphinoic acid and 4-fluorothiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0134]

[0135] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 4-fluorophenylthiophenol (76.8 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-fluorophenylthio) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 68%.

[0136] 1 H NMR (500MHz, CDCl3): δ7.80-7.75(m,2H),7.54-7.51(m,1H),7.45-7.40(m,6H),6.97(t,J=10.0Hz,4H). 31 P NMR (203MHz, CDCl3): δ49.58 (d, J=4.9Hz). 19 F NMR (470MHz, CDCl3): δ-110.73 (d, J=4.7Hz).

[0137] Example 22:

[0138] Using phenylphosphinoic acid and 4-chlorothiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0139]

[0140] Phenylephrine (28.4 mg, 0.2 mmol) and 4-chlorobenzylthiophenol (86.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-chlorobenzylthio) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 64%.

[0141] 1 H NMR (500MHz, CDCl3): δ7.82-7.77(m,2H),7.56-7.52(m,1H),7.46-7.43(m,2H),7.38-7.36(m,4H),7.26-7.24(m,4H). 31 PNMR (203MHz, CDCl3): δ49.06.

[0142] Example 23:

[0143] Using phenylphosphinoic acid and 4-bromothiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0144]

[0145] Phenylephrine (28.4 mg, 0.2 mmol) and 4-bromophenylthiophenol (113.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(4-bromophenylthio) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 65%.

[0146] 1 H NMR (500MHz, CDCl3): δ7.82-7.77(m,2H),7.56-7.53(m,1H),7.47-7.43(m,2H),7.41-7.39(m,4H),7.32-7.29(m,4H),1.27(s,18H). 31 PNMR (203MHz, CDCl3): δ48.68.

[0147] Example 24:

[0148] Using phenylphosphinoic acid and 2-methylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0149]

[0150] Phenylephrine (28.4 mg, 0.2 mmol) and 2-methylbenzylthiophenol (74.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2-methylbenzylthio) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 70%.

[0151] 1 H NMR (500MHz, CDCl3): δ7.83-7.78(m,2H),7.51-7.46(m,3H),7.42-7.38(m,2H),7.23-7.16(m,4H),7.09-7.05(m,2H),2.33(s,6H). 31 PNMR (203MHz, CDCl3): δ49.14.

[0152] Example 25:

[0153] Using phenylphosphinoic acid and 3-methylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0154]

[0155] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 3-methylbenzylthiophenol (74.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(3-methylbenzylthio) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 66%.

[0156] 1 H NMR (500MHz, CDCl3): δ7.81-7.76(m,2H),7.51-7.47(m,1H),7.41-7.37(m,2H),7.26-7.24(m,4H),7.15-7.10(m,4H),2.26(s,6H). 31 PNMR (203MHz, CDCl3): δ49.78.

[0157] Example 26:

[0158] Using phenylphosphinoic acid and 2,5-dimethylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0159]

[0160] Phenylephrine (28.4 mg, 0.2 mmol) and 2,5-dimethylbenzylthiophenol (82.8 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(2,5-dimethylbenzylthio) phenylphosphonate was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 67%.

[0161] 1 H NMR (500MHz, CDCl3): δ7.82-7.77(m,2H),7.50-7.46(m,1H),7.41-7.37(m,2H),7.27(s,2H),7.06-7.00(m,4H),2.28(s,6H),2.20(s,6H). 31 PNMR (203MHz, CDCl3): δ49.28.

[0162] Example 27:

[0163] Using phenylphosphinoic acid and 2-naphthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0164]

[0165] Phenylephrine (28.4 mg, 0.2 mmol) and 2-naphthiophenol (96 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product, di(2-naphthio) phenylphosphonate, was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 71%.

[0166] 1H NMR (500MHz, CDCl3): δ7.96(s,2H),7.86-7.81(m,2H),7.75-7.73(m,2H),7 .68(d,J=10.0Hz,4H),7.49-7.41(m,7H),7.37-7.33(m,2H),1.27(s,18H). 31 PNMR (203MHz, CDCl3): δ49.70.

[0167] Example 28:

[0168]

[0169] Phenylenephosphonic acid (28.4 mg, 0.2 mmol) and 3-chlorobenzylthiophenol (85.8 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, repeated three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated, and the product di(3-chlorobenzylthio) phenylphosphonic acid was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 57%.

[0170] 1 H NMR (500MHz, CDCl3): δ7.83-7.78(m,2H),7.57-7.54(m,1H),7.75-7.73(m,2H), 7.48-7.42(m,4H),7.39-7.36(m,2H),7.33-7.26(m,2H),7.21(t,J=10.0Hz,2H). 31 P NMR (203MHz, CDCl3): δ49.07.

[0171] Example 29:

[0172] Using [1,1'-biphenyl]-4-ylphosphonic acid and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0173]

[0174] [1,1'-biphenyl]-4-ylphosphonic acid (43.6 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, and this process was repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product [1,1'-biphenyl]-4-ylphosphonic acid diphenyl ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent, with a yield of 87%.

[0175] 1 H NMR (500MHz, CDCl3): δ8.05-8.01(m,2H),7.73-7.71(m,2H),7.62-7.61(m,2H),7.49-7. 45(m,2H),7.42-7.39(m,1H),7.32-7.29(m,4H),7.23-7.21(m,4H),7.17-7.14(m,2H),. 31 P NMR (203MHz, CDCl3): δ 11.92.

[0176] Example 30:

[0177] Using 4-methylphenylphosphine and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0178]

[0179] 4-Methylphenylphosphonic acid (31.2 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product 4-methylphenylphosphonic acid diphenyl ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 85%.

[0180] 1 H NMR (400MHz, CDCl3): δ7.87-7.81(m,2H),7.30-7.25(m,6H),7.20-7.17(m,4H),7.15-7.10(m,2H),2.40(s,3H),. 31PNMR (162MHz, CDCl3): δ 12.54.

[0181] Example 31:

[0182] Using 4-fluorophenylphosphinoic acid and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0183]

[0184] 4-Fluorophenylphosphonic acid (32 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product 4-fluorophenylphosphonic acid diphenyl ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 83%.

[0185] 1 H NMR (400MHz, CDCl3): δ8.01-7.94(m,2H),7.32-7.26(m,4H),7.21-7.13(m,8H). 31 PNMR (162MHz, CDCl3): δ 10.66. 19 F NMR (376MHz, CDCl3): δ-104.1.

[0186] Example 32:

[0187] Using 4-methoxyphenylphosphinoic acid and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0188]

[0189] 4-Methoxyphenylphosphonic acid (34.4 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube, and this process was repeated three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product 4-methoxyphenylphosphonic acid diphenyl ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent, with a yield of 81%.

[0190] 1H NMR (400MHz, CDCl3): δ7.91-7.86(m,2H),7.30-7.25(m,4H),7.20-7.11(m,6H),6.99-6.96(m,2H),3.84(s,3H). 31 PNMR (162MHz, CDCl3): δ 12.72.

[0191] Example 33:

[0192] Using 4-tert-butylphenylphosphinoic acid and phenol as raw materials, the reaction formula and experimental steps are as follows:

[0193]

[0194] 4-tert-butylphenylphosphonic acid (39.6 mg, 0.2 mmol) and phenol (75.3 mg, 0.8 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube three times. Then, 3 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in an oil bath at 40 °C for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product 4-tert-butylphenylphosphonic acid diphenyl ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 82%.

[0195] 1 H NMR (400MHz, CDCl3): δ7.93-7.87(m,2H),7.53-7.50(m,2H),7.31-7.27(m,4H),7.22-7.18(m,4H),7.16-7.11(m,2H),1.34(s,9H). 31 PNMR (162MHz, CDCl3): δ 12.34.

[0196] Example 34:

[0197] Using 4-methylphenylphosphinoic acid and 4-methylthiophenol as raw materials, the reaction formula and experimental steps are as follows:

[0198]

[0199] 4-Methylphenylphosphonic acid (31.2 mg, 0.2 mmol) and 4-methylbenzylthiophenol (74.4 mg, 0.6 mmol) were added to a 10 mL reaction tube. The air in the reaction tube was replaced with nitrogen using a double-row tube three times. Then, 0.5 mL of acetonitrile, trifluoromethanesulfonic anhydride (169.3 mg, 0.6 mmol), and DMSO (3.1 mg, 0.04 mmol) were added sequentially. The reaction was carried out in a reactor at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated, and the product 4-methylphenylphosphonic acid di(4-methylphenylthio) ester was obtained by column chromatography using a 9:1 (v / v) mixture of petroleum ether and ethyl acetate as eluent, with a yield of 56%.

[0200] 1 H NMR (500MHz, CDCl3): δ7.69-7.65(m,2H),7.33-7.30(m,4H),7.22-7.20(m,2H),7.07(d,J=10.0Hz,4H),2.39(s,3H),2.30(s,6H). 31 PNMR (203MHz, CDCl3): δ 50.25.

[0201] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details of the above embodiments. Within the scope of the technical concept of the present invention, various equivalent transformations can be made to the technical solutions of the present invention, and all such equivalent transformations fall within the protection scope of the present invention. It should also be noted that this patent was supported by the National Natural Science Foundation of China (22001225) and the Natural Science Foundation of Shandong Province (ZR2020MB021), and this patent is one of the research results of the aforementioned funded projects.

Claims

1. A method for preparing arylphosphonates and arylthiophosphonates, characterized in that, When the product is an arylphosphonate Starting with aryl hypophosphoric acid and R-OH reagent, under nitrogen protection, and in the presence of trifluoromethanesulfonic anhydride (Tf₂O) and dimethyl sulfoxide (DMSO) in an organic solvent, at RT (room temperature) ~ 40°C o The reaction was carried out at C for 0.5 to 3 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation. The aryl phosphonate was obtained by column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent. The aryl hypophosphite is selected from any one of phenyl hypophosphite, (4-methylphenyl) hypophosphite, (4-fluorophenyl) hypophosphite, (4-phenylphenyl) hypophosphite, (4-methoxyphenyl) hypophosphite, and (4-tert-butylphenyl) hypophosphite; The R-OH reagent is selected from any one of phenol, 4-fluorophenol, 4-chlorophenol, 4-bromophenol, 4-trifluoromethylphenol, 4-methylphenol, 4-tert-butylphenol, 4-phenylphenol, 2-phenylphenol, 2-methylphenol, 2-bromophenol, 3,4-difluorophenol, 2-bromo-4-methylphenol, 3,4-dimethylphenol, trifluoroethanol, trichloroethanol, and pentafluoropropanol; The molar ratio of the arylphosphite, R-OH reagent, trifluoromethanesulfonic anhydride, and dimethyl sulfoxide is 1: 2-4: 1-4: 0.1-1; When the product is a thioarylphosphonate Starting with aryl hypophosphoric acid and R-SH reagent, under nitrogen protection, and in the presence of trifluoromethanesulfonic anhydride (Tf₂O) and dimethyl sulfoxide (DMSO), in an organic solvent, at RT (room temperature) ~ 40 °C. o The reaction was carried out at C for 0.5 to 3 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation. The product was obtained by column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent. The aryl hypophosphite is selected from either phenyl hypophosphite or (4-methylphenyl) hypophosphite; The R-SH reagent is selected from any one of p-methylthiophenol, p-tert-butylthiophenol, p-methoxythiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, 2-methylthiophenol, 3-methylthiophenol, 2,5-dimethylthiophenol, 2-naphthiophenol, and 3-chlorothiophenol. The molar ratio of the aryl hypophosphoric acid, R-SH reagent, trifluoromethanesulfonic anhydride, and dimethyl sulfoxide is 1:2-4:1-4:0.1-1.

2. The preparation method according to claim 1, characterized in that... The organic solvent is selected from acetonitrile.

3. The preparation method according to claim 1, characterized in that... When the product is a thioarylphosphonate, the molar ratio of the aryl hypophosphite, R-SH reagent, trifluoromethanesulfonic anhydride, and dimethyl sulfoxide is 1:3:3:0.2.

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