A one-pot method for preparing dialkyl arylphosphonates

Abstract

The invention discloses a method for preparing dialkyl arylphosphonate by a one-pot method, wherein nickel is used to catalyze the reaction of aryl halide, trialkyl phosphite and metal reducing agent, and then an oxidant is added to carry out oxidation reaction, thereby preparing dialkyl arylphosphonate by a one-pot method. The preparation method provided by the invention has the characteristics of mild reaction conditions, no need for anhydrous operation, cheap and easy to obtain raw materials, good substrate universality and easy reaction amplification, etc., commercial and low-cost raw materials are used, and through short and efficient synthesis steps, not only the production cost is reduced, the production efficiency is improved, but also the foundation is laid for the large-scale industrial application of dialkyl arylphosphonate, showing broad industrial application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of aryl phosphonate dialkyl ester, and in particular to a method for preparing aryl phosphonate dialkyl ester by a one-pot process. Background Art

[0002] As a key intermediate with wide applications in organic synthesis, material science, pharmaceutical research and development, nucleic acid chemistry and other fields, aryl dialkyl phosphonates have become one of the hot spots in the field of organic chemistry research. In the field of catalytic chemistry, phosphine ligands play an irreplaceable role, and reactions may produce completely different reaction products due to different ligands. Among the existing phosphine ligands, many contain a structure in which a phosphorus atom is connected to an aromatic group. Aryl dialkyl phosphonates are common intermediates of this structure, such as the biaryl diphosphine ligand BIPEHP, SegPhos ligand and SynPhos ligand.

[0003] In view of the importance of aryl phosphine compounds, the chemical community has been increasingly studying their synthesis methods, and a variety of synthesis strategies have been reported. Among them, the nickel or palladium-catalyzed Arbuzov reaction has attracted widespread attention and has been widely used because of its simple operation, cheap and readily available raw materials, and the product is easy to further modify on the phosphorus atom. For some low-activity halides (such as aryl halides), Hirao et al. disclosed the palladium-catalyzed coupling reaction of aryl halides and phosphite diester compounds. However, the currently known CP bond formation reaction still has many shortcomings, such as harsh reaction conditions, limited substrate universality, expensive catalysts or difficulty in amplification, etc. These problems seriously restrict the industrial production and application of aryl phosphonic acid dialkyl esters. Therefore, it is of great significance to develop a preparation method for aryl phosphonates with mild reaction conditions, no need for anhydrous operation, cheap and readily available raw materials, good substrate universality, and easy reaction amplification to promote the development of this field. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a one-pot method for preparing dialkyl aryl phosphonate, which uses nickel to catalyze the reaction of aryl halide, trialkyl phosphite and metal reducing agent, and then adds an oxidant for oxidation reaction, so as to prepare dialkyl aryl phosphonate in one pot. The preparation method provided by the present invention has the characteristics of mild reaction conditions, no need for anhydrous operation, cheap and easy to obtain raw materials, good substrate universality and easy to scale up the reaction.

[0005] The present invention is achieved through the following technical solutions:

[0006] The present invention provides a one-pot method for preparing dialkyl arylphosphonate, comprising the following steps:

[0007] The aryl halide reacts with a trialkyl phosphite in the presence of a nickel catalyst, a metal reducing agent and an organic solvent, and then an oxidant is added to carry out an oxidation reaction to obtain the aryl dialkyl phosphonate;

[0008] The nickel catalyst is selected from one or more of nickel acetate, nickel chloride, nickel bromide, nickel iodide, nickel trifluoromethanesulfonate, nickel acetylacetonate, nickel (II) chloride ethylene glycol dimethyl ether complex, nickel (II) bromide ethylene glycol dimethyl ether complex, bis (triphenylphosphine) nickel chloride, bis (tricyclohexylphosphine) nickel chloride, 1,2-bis (diphenylphosphine) ethane nickel chloride, 1,3-bis (diphenylphosphine) propane nickel chloride, 1,4-bis (diphenylphosphine) butane nickel chloride and 1,1'-bis (diphenylphosphine) ferrocene nickel chloride.

[0009] Furthermore, the metal reducing agent is selected from one or more of magnesium powder, magnesium chips, zinc powder, aluminum powder, manganese powder and iron powder.

[0010] Furthermore, the solvent is selected from one or more of water, dichloromethane, ethyl acetate, tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, toluene, benzene and chloroform.

[0011] Furthermore, the oxidant is selected from one or more of m-chloroperbenzoic acid, tert-butyl peroxide, di-tert-butyl peroxide, hydrogen peroxide, oxygen, sodium chlorate, sodium hypochlorite, potassium permanganate and iodine.

[0012] Furthermore, the structural formula of the aryl halide is Ar-X, wherein Ar is an aryl group or a heteroaryl group, and the aryl group or the heteroaryl group is optionally substituted by one or more substituents selected from alkyl, alkoxy, alkenyl, nitro, fluorine, trifluoromethyl, ester, cyano or phenyl, and X is a halogen.

[0013] Preferably, Ar is phenyl, 2-methylphenyl, 3-methylbenzene, 4-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl or 3-nitrophenyl.

[0014] Furthermore, the structural formula of the trialkyl phosphite is P(OR) 3 , wherein R is an alkyl group.

[0015] Preferably, R is a C1-C8 alkyl group.

[0016] Furthermore, the structural formula of the dialkyl arylphosphonate is Ar-PO(OR) 2 , wherein Ar is an aryl or heteroaryl group, the aryl or heteroaryl group is optionally substituted by one or more substituents selected from alkyl, alkoxy, alkenyl, nitro, fluorine, trifluoromethyl, ester, cyano or phenyl, and R is an alkyl group.

[0017] Preferably, Ar is phenyl, 2-methylphenyl, 3-methylbenzene, 4-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl or 3-nitrophenyl.

[0018] Preferably, R is a C1-C8 alkyl group.

[0019] Furthermore, the molar ratio of the nickel catalyst, the aryl halide, the trialkyl phosphite, the metal reducing agent and the oxidizing agent is (0.01-1):10:(10-200):(10-100):(10-200), preferably (0.5-1):10:(10-20):(10-15):(10-20).

[0020] Furthermore, the reaction temperature is 0-70°C.

[0021] Furthermore, the temperature of the oxidation reaction is 0-70°C.

[0022] Furthermore, the reaction time is 1-120h.

[0023] Furthermore, the oxidation reaction time is 0.1-5h.

[0024] Furthermore, after the oxidation reaction is completed, a solvent is added for extraction, followed by column chromatography or distillation.

[0025] In a specific embodiment, an aromatic bromide, a trialkyl phosphite, a nickel catalyst, a metal reducing agent and a solvent are added to a reaction bottle, and after stirring the reaction at 0-70° C. for a period of time, an oxidant is added, and after the reaction is completed, a solvent is added for extraction, and then column chromatography or distillation is performed to obtain the aromatic dialkyl phosphonate.

[0026] Beneficial effects of the present invention:

[0027] The present invention utilizes a nickel catalyst and a metal reducing agent to realize the reaction of an aryl halide with a trialkyl phosphite in the same reaction vessel to generate an intermediate aryl dialkyl phosphite, which is then oxidized by an oxidant to obtain the target product aryl dialkyl phosphonate, and the whole reaction temperature is controlled at 0-70°C. This process simplifies the traditional synthesis route, avoids complex operations, significantly improves the yield, and the process is simple and easy. In addition, the method uses commercial and low-cost raw materials, and through short and efficient synthesis steps, it not only reduces production costs and improves production efficiency, but also lays a foundation for the large-scale industrial application of aryl dialkyl phosphonates, showing broad industrial application prospects. DETAILED DESCRIPTION

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0029] The present invention provides a one-pot method for preparing dialkyl arylphosphonate, comprising the following steps: an aryl halide Ar-X and a trialkyl phosphite P(OR) are reacted to form a dialkyl arylphosphonate; 3 The reaction is carried out in the presence of a nickel catalyst, a metal reducing agent and an organic solvent, and then an oxidant is added to carry out an oxidation reaction to obtain the aromatic phosphonic acid dialkyl ester Ar-PO(OR) 2 , the reaction equation is as follows:

[0030]

[0031] The present invention is further described below in conjunction with specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0032] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods, and the materials, reagents, etc. used are all available from commercial sources unless otherwise specified.

[0033] Example 1

[0034] One-pot preparation of diethyl (3-methoxyphenyl)phosphonate (structural formula: ), including the following steps:

[0035] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol m-methoxybromobenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphinoethane)nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 2.06 g of the product (3-methoxyphenyl) diethyl phosphonate was obtained by distillation, with a yield of 84.4%.

[0036] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.42-7.29(m,3H),7.12-7.03(m,1H),4.23-3.97(m,4H),3.84(s,3H),1.34(t,J=7.2Hz,6H).

[0037] Example 2

[0038] One-pot preparation of diethyl (3,5-dimethoxyphenyl)phosphonate (structural formula: ), including the following steps:

[0039] 12mmol manganese powder (0.66g), 10mmol 1-bromo-3,5-dimethoxybenzene, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphine) nickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 50°C for 10 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 2.31g product (3,5-dimethoxyphenyl) diethyl phosphonate with a yield of 84.2%.

[0040] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ6.96 (d, J = 4, 1H), 6.92 (d, J = 4, 1H), 4.17-4.06 (m, 4H), 3.834 (s, 6H), 1.33 (t, J = 8Hz, 6H).

[0041] Example 3

[0042] One-pot preparation of diethyl benzo[d][1,3]dioxolane-5-ylphosphonate (structural formula: ), including the following steps:

[0043] To the reaction flask, 12 mmol magnesium chips (0.29 g), 10 mmol 4-bromo-1,2-methylenedioxybenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphine)ethane nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 30°C for 12 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and the product 2.21 g of diethyl benzo[d][1,3]dioxolane-5-ylphosphonate was obtained by distillation, with a yield of 85.6%.

[0044] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3):7.41-7.35(m,1H),7.21(dd,J=12.8,1.2Hz,1H),6.90(dd,J=7.9,3.6Hz,1H),6.04(s,2H),4.20-3.98(m,4H),1.32(t,J=7.2Hz,6H).

[0045] Example 4

[0046] One-pot preparation of diethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)phosphonate (structural formula: ), including the following steps:

[0047] 12mmol zinc powder (0.78g), 10mmol 6-bromo-1,4-benzoxane, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphinoethane)nickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 60°C for 10 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 2.36g of the product (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)phosphonic acid diethyl ester with a yield of 86.7%.

[0048] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.33-7.24(m,2H),6.99-6.92(m,1H),4.32-4.23(m,4H),1.33(t,J=7.2Hz,6H).

[0049] Example 5

[0050] One-pot preparation of diethyl phenylphosphonate (structural formula: ), including the following steps:

[0051] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol bromobenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphinoethane) nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 1.86 g of the product diethyl phenylphosphonate was obtained by distillation, with a yield of 86.8%.

[0052] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ7.74-7.82(m,2H),7.48-7.55(m,1H),7.39-7.46(m,2H),3.99-4.17(m,4H),1.32(t,J=7.2Hz,6H).

[0053] Example 6

[0054] One-pot preparation of dimethylphenylphosphonate (structural formula: ), including the following steps:

[0055] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol bromobenzene, 15 mmol trimethyl phosphite (1.88 g), 1.0 mmol 1,2-bis(diphenylphosphinoethane) nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and the product 1.55 g dimethylphenylphosphonate was obtained by distillation, with a yield of 83.2%.

[0056] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.78-7.71(m,2H),7.45-7.51(m,1H),7.35-7.42(m,2H),3.67(d,J=11.2Hz,6H).

[0057] Example 7

[0058] One-pot preparation of diisopropyl phenylphosphonate (structural formula: ), including the following steps:

[0059] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol bromobenzene, 15 mmol triisopropyl phosphite (3.12 g), 1.0 mmol 1,2-bis(diphenylphosphinoethane) nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 2.02 g of the product diisopropyl phenylphosphonate was obtained by distillation, with a yield of 83.3%.

[0060] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ7.77-7.84(m,2H),7.49-7.55(m,1H),7.41-7.47(m,2H),4.62-4.74(m,2H),1.37(d,J=6.2Hz,6H),1.22(d,J=6.2Hz,6H).

[0061] Example 8

[0062] One-pot preparation of dibenzyl phenylphosphonate (structural formula: ), including the following steps:

[0063] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol bromobenzene, 15 mmol tribenzyl phosphite (5.28 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 30 mL ethyl acetate was added for extraction. 2.89 g of the product dibenzyl phenylphosphonate was obtained by column chromatography with a yield of 85.4%.

[0064] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.85(m,2H),7.57(m,1H),7.47(m,2H),7.43-7.25(m,10H),5.16-5.07(m,4H).

[0065] Example 9

[0066] One-pot preparation of diethyl (4-methoxyphenyl)phosphonate (structural formula: ), including the following steps:

[0067] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol p-methoxybromobenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 60°C for 12 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 2.16 g of the product (4-methoxyphenyl) diethyl phosphonate was obtained by distillation, with a yield of 88.4%.

[0068] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ7.81-7.66(m,2H),7.02-6.90(m,2H),4.20-3.94(m,4H),3.84(s,3H),1.31(t,J=7.2Hz,6H).

[0069] Example 10

[0070] One-pot preparation of diethyl p-tolylphosphonate (structural formula: ), including the following steps:

[0071] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol p-methylbromobenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 1.88 g of the product diethyl p-tolylphosphonate was obtained by distillation, with a yield of 82.3%.

[0072] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ):7.64(dd,J=12.9,7.8Hz,2H),7.25-7.16(m,2H),4.13-3.93(m,4H),2.34(s,3H),1.25(t,J=6.8Hz,6H).

[0073] Embodiment 11

[0074] One-pot preparation of diethyl o-tolylphosphonate (structural formula: ), including the following steps:

[0075] To the reaction flask, 12 mmol zinc powder (0.78 g), 10 mmol o-methyl bromobenzene, 15 mmol triethyl phosphite (1.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528 mg) and 10 mL tetrahydrofuran were added, and the mixture was stirred at 40°C for 15 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and the mixture was reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction, and 1.62 g of the product o-tolylphosphonic acid diethyl ester was obtained by distillation, with a yield of 71%.

[0076] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ7.89 -7.96(m,1H),7.46-7.40(m,1H),7.30-7.22(m,2H),4.20 -4.02(m,4H),2.59(s,3H),1.34(t,J=7.0Hz,6H).

[0077] Example 12

[0078] One-pot preparation of diethyl (3-nitrophenyl)phosphonate (structural formula: ), including the following steps:

[0079] 12 mmol zinc powder (0.78 g), 10 mmol m-nitrobromobenzene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle and stirred for reaction at 20°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction. 1.49 g product (3-nitrophenyl) diethyl phosphonate was obtained by column chromatography with a yield of 57.5%.

[0080] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ8.68 -8.62(m,1H),8.43-8.38(m,1H),8.19-8.11(m,1H),7.73-7.66(m,1H),4.10-4.27(m,4H),1.37(t,J=7.2Hz,6H).

[0081] Embodiment 13

[0082] One-pot preparation of diethyl (4-fluorophenyl)phosphonate (structural formula: ), including the following steps:

[0083] 12mmol zinc powder (0.78g), 10mmol bromo-p-fluorobenzene, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 30°C for 14 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 1.89g product (4-fluorophenyl) diethyl phosphonate with a yield of 79%.

[0084] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3):7.84-7.78(m,2H),7.18-7.10(m,2H),4.18-4.01(m,4H),1.32(t,J=7.2Hz,6H).

[0085] Embodiment 14

[0086] One-pot preparation of diethyl (4-cyanophenyl)phosphonate (structural formula: ), including the following steps:

[0087] 12 mmol zinc powder (0.78 g), 10 mmol p-cyanobenzene bromide, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle and stirred at 10°C for 24 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction and distillation to obtain 1.78 g of the product (4-cyanophenyl) diethyl phosphonate with a yield of 74.4%.

[0088] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.99-7.90(m,2H),7.79-7.73(m,2H),4.25-4.05(m,4H),1.36(t,J=7.2Hz,6H).

[0089] Embodiment 15

[0090] One-pot preparation of diethyl (4-acetylphenyl)phosphonate (structural formula: ), including the following steps:

[0091] 12mmol zinc powder (0.78g), 10mmol 4-bromoacetophenone, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 10°C for 20 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 1.90g product (4-acetylphenyl) diethyl phosphonate with a yield of 74.1%.

[0092] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ7.999 -7.91(m,2H),7.89–7.81(m,2H),4.17-3.98(m,1H),2.58(s,3H),1.26(t,J=7.2Hz,6H).

[0093] Example 16

[0094] One-pot preparation of diethyl naphthalene-2-ylphosphonate (structural formula: ), including the following steps:

[0095] 12 mmol zinc powder (0.78 g), 10 mmol 2-bromonaphthalene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle and stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction. 2.16 g of the product diethyl naphthalene-2-ylphosphonate was obtained by column chromatography with a yield of 81.7%.

[0096] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ8.56-8.33(m,1H),7.98-7.83(m,3H),7.81-7.71(m,1H),7.66-7.51(m,2H),4.32-3.97(m,4H), δ1.33(t,J=9.2,6H).

[0097] Embodiment 17

[0098] One-pot preparation of diethyl naphthalene-1-ylphosphonate (structural formula: ), including the following steps:

[0099] 12 mmol zinc powder (0.78 g), 10 mmol 1-bromonaphthalene, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle, stirred and reacted at 55° C. for 10 hours, 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour, and 20 mL ethyl acetate was added after the reaction was completed for extraction, and 2.01 g of the product diethyl naphthalene-1-ylphosphonate was obtained by column chromatography, with a yield of 76.1%.

[0100] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3): δ8.54(d,J=8.4Hz,1H),8.28(dd,J=16.8,7.6Hz,1H),8.06(d,J=8.4Hz,1H),7.90(d,J=8. 2Hz, 1H), 7.63 (t, J = 7.5Hz, 1H), 7.59-7.51 (m, 2H), 4.29-4.03 (m, 4H), 1.34 (t, J = 8.0Hz, 6H).

[0101] Embodiment 18

[0102] One-pot preparation of diethyl (4-(trifluoromethyl)phenyl)phosphonate (structural formula: ), including the following steps:

[0103] 12mmol zinc powder (0.78g), 10mmol p-trifluoromethyl bromobenzene, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 30°C for 15 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 2.08g of the product (4-(trifluoromethyl)phenyl)phosphonic acid diethyl ester with a yield of 73.7%.

[0104] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.99-7.92(m,1H),7.70-7.71(m,1H),4.24-4.04(m,4H),1.33(t,J=9.2Hz,6H).

[0105] Embodiment 19

[0106] One-pot preparation of methyl 4-(diethoxyphosphoryl)benzoate (structural formula: ), including the following steps:

[0107] 12mmol zinc powder (0.78g), 10mmol methyl p-bromobenzoate, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 10°C for 20 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction. 2.15g of the product 4-(diethoxyphosphoryl)benzoic acid methyl ester was obtained by column chromatography with a yield of 78.9%.

[0108] The H NMR spectrum of the product is as follows:1 H NMR (400 MHz, CDCl 3 ): δ8.17-8.06(m,2H),7.93-7.84(m,2H),4.17-4.11(m,4H),3.95(s,3H),1.35(t,J=7.2Hz,6H).

[0109] Embodiment 20

[0110] One-pot preparation of diethyl (5,6,7,8-tetrahydronaphthalene-2-yl)phosphonate (structural formula: ), including the following steps:

[0111] 12mmol zinc powder (0.78g), 10mmol 6-bromo-1,2,3,4-tetrahydronaphthalene, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 40°C for 10 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 2.34g product (5,6,7,8-tetrahydronaphthalene-2-yl) diethyl phosphonate with a yield of 87.2%.

[0112] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.53(d,J=13.2Hz,1H),7.46(m,1H),7.14(m,1H),4.08(m,4H),2.78(m,4H),1.79(m,4H)1.33(t,J=7.2Hz,6H).

[0113] Embodiment 21

[0114] One-pot preparation of diethyl (3,4-dimethoxyphenyl)phosphonate (structural formula: ), including the following steps:

[0115] 12mmol zinc powder (0.78g), 10mmol 3,4-dimethoxybromobenzene, 15mmol triethyl phosphite (2.49g), 1.0mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528mg) and 10mL tetrahydrofuran were added to the reaction bottle and stirred at 60°C for 10 hours. 16mmol hydrogen peroxide (1.7mL) was added and reacted for 1 hour. After the reaction, 20mL ethyl acetate was added for extraction and distillation to obtain 2.35g product (3,4-dimethoxyphenyl) diethyl phosphonate with a yield of 85.7%.

[0116] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.43-7.38(m,1H),7.30-7.28(d,1H),6.96-6.92(m,1H),4.15-4.08(m,4H),3.92(s,3H),3.90(s,3H),1.32(t,J=7.2Hz,6H,).

[0117] Embodiment 22

[0118] One-pot preparation of diethyl pyridin-3-ylphosphonate (structural formula: ), including the following steps:

[0119] 12 mmol zinc powder (0.78 g), 10 mmol 3-bromopyridine, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethanenickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle and stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction and distillation to obtain 1.52 g of the product diethyl pyridin-3-ylphosphonate with a yield of 70.6%.

[0120] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ8.97(d,J=6.4Hz,1H),8.80-8.75(m,1H),8.17-8.08(m,1H),7.46-7.39(m,1H),4.25-4.07(m,4H),1.34(t,J=7.2Hz,6H).

[0121] Embodiment 23

[0122] One-pot preparation of diethyl [1,1'-biphenyl]-4-ylphosphonate (structural formula: ), including the following steps:

[0123] 12 mmol zinc powder (0.78 g), 10 mmol 4-bromobiphenyl, 15 mmol triethyl phosphite (2.49 g), 1.0 mmol 1,2-bis(diphenylphosphino)ethane nickel chloride (528 mg) and 10 mL tetrahydrofuran were added to the reaction bottle and stirred at 40°C for 10 hours. 16 mmol hydrogen peroxide (1.7 mL) was added and reacted for 1 hour. After the reaction, 20 mL ethyl acetate was added for extraction. 2.62 g of the product [1,1'-biphenyl]-4-ylphosphonic acid diethyl ester was obtained by column chromatography with a yield of 90.3%.

[0124] The H NMR spectrum of the product is as follows: 1 H NMR (400 MHz, CDCl 3 ): δ7.89(dd,J=13.2,8.4Hz,2H),7.68(dd,J=8.4,4.0Hz,2H),7.64-7.37(m,5H),4.24-4.05(m,4H),1.36(t,J=7.2Hz,6H).

[0125] Embodiment 24

[0126] One-pot preparation of diethyl (3-methoxyphenyl)phosphonate (structural formula: ), including the following steps:

[0127] To the reaction flask, 11 mol zinc powder (719.3 g), 10 mol m-methoxybromobenzene, 12 mol triethyl phosphite (1.99 kg), 1.0 mol 1,2-bis(diphenylphosphino)ethane nickel chloride (264 g) and 10 L tetrahydrofuran were added, stirred and reacted at 60 ° C for 15 hours, 12.2 mol hydrogen peroxide (1.3 L) was added and reacted for 5 hours. After the reaction, ethyl acetate was added for extraction, and 2.13 kg of the product (3-methoxyphenyl) diethyl phosphonate was obtained by distillation, with a yield of 87.2%.

[0128] Obviously, the above embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art should understand that other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A one-pot method for preparing dialkyl arylphosphonates, characterized in that: The following steps are involved: The aryl halide reacts with a trialkyl phosphite in the presence of a nickel catalyst, a metal reducing agent and a solvent, and then an oxidant is added to carry out an oxidation reaction to obtain the aryl dialkyl phosphonate; The nickel catalyst is selected from one or more of nickel acetate, nickel chloride, nickel bromide, nickel iodide, nickel trifluoromethanesulfonate, nickel acetylacetonate, nickel (II) chloride ethylene glycol dimethyl ether complex, nickel (II) bromide ethylene glycol dimethyl ether complex, bis (triphenylphosphine) nickel chloride, bis (tricyclohexylphosphine) nickel chloride, 1,2-bis (diphenylphosphine) ethane nickel chloride, 1,3-bis (diphenylphosphine) propane nickel chloride, 1,4-bis (diphenylphosphine) butane nickel chloride and 1,1'-bis (diphenylphosphine) ferrocene nickel chloride.

2. The method according to claim 1, characterized in that The metal reducing agent is selected from one or more of magnesium powder, magnesium chips, zinc powder, aluminum powder, manganese powder and iron powder.

3. The method according to claim 1, characterized in that The oxidant is selected from one or more of m-chloroperbenzoic acid, tert-butyl peroxide, di-tert-butyl peroxide, hydrogen peroxide, oxygen, sodium chlorate, sodium hypochlorite, potassium permanganate and iodine.

4. The method according to claim 1, characterized in that The structural formula of the trialkyl phosphite is P(OR)3, wherein R is an alkyl group.

5. The method according to claim 1, characterized in that: The structural formula of the aryl halide is Ar-X, wherein Ar is an aryl group or a heteroaryl group, and the aryl group or the heteroaryl group is optionally substituted by one or more substituents selected from alkyl, alkoxy, alkenyl, nitro, fluorine, trifluoromethyl, ester, cyano or phenyl, and X is a halogen.

6. The method according to claim 1, characterized in that The structural formula of the dialkyl arylphosphonate is Ar-PO(OR)2, wherein Ar is an aryl group or a heteroaryl group, and the aryl group or the heteroaryl group is optionally substituted by one or more substituents selected from alkyl, alkoxy, alkenyl, nitro, fluorine, trifluoromethyl, ester, cyano or phenyl, and R is an alkyl group.

7. The method according to claim 5 or 6, characterized in that: Ar is phenyl, 2-methylphenyl, 3-methylbenzene, 4-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl or 3-nitrophenyl.

8. The method according to claim 1, characterized in that: The molar ratio of the nickel catalyst, the aryl halide, the trialkyl phosphite, the metal reducing agent and the oxidizing agent is (0.01-1):10:(10-200):(10-100):(10-200).

9. The method according to claim 1, characterized in that: The reaction temperature is 0-70°C.

10. The method according to claim 1, characterized in that The reaction time is 1-120h.

Images