Synthetic method of alpha, beta-diphosphorus oxide

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an alpha, beta-diphosphorus oxide compound, which comprises the following steps: reacting imine and diphenylphosphine oxide serving as raw materials in tetrahydrofuran by taking aluminum trichloride as a catalyst, and performing post-treatment after the reaction to obtain the alpha, beta-diphosphorus oxide compound. Wherein imine contains a group R, diphenyl phosphine oxide contains a group R1, R is selected from one of aryl, furan and thiophene, and R1 is independently selected from one of hydrogen, alkyl and halogen. The method is simple and safe to operate, the selection of the catalyst and the solvent is green and environment-friendly, the method is an economical, environment-friendly and efficient synthesis method, the diversity of the structure of the alpha, beta-diphosphorus oxide compound can be increased, the method can be applied to practical operations such as synthesis and research and development of the alpha, beta-diphosphorus oxide compound, and the problem that the alpha, beta-diphosphorus oxide compound has high purity is solved. And the preparation process of the beta-diphosphorus oxide compound is relatively complicated and is not environment-friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing an alpha, beta-diphosphine oxide compound. Background Art

[0002] α,β-diphosphine oxides are an important class of organophosphorus compounds. They play an important role in chemical synthesis, materials science, and biomedicine due to their unique structure and diverse reaction characteristics. In the field of chemical synthesis, they can be used as catalysts. In the field of biomedicine, these compounds can be used to synthesize a variety of biologically active molecules, especially in anticancer drugs and antiviral drugs; in the field of materials science, these compounds can be used as modifiers or additives to improve the properties of materials, such as for the manufacture of materials with high fire resistance and high stability.

[0003] This type of compound contains two phosphorus oxygen groups (P=O), located at the α and β positions of the organic molecule, respectively. This structure gives this type of compound special chemical properties and application potential. α, β-diphosphorus oxide compounds have high chemical stability and reactivity, which makes them exhibit unique reactivity in a variety of reactions. For example, the phosphorus oxygen bond in diphosphorus oxide compounds usually has a strong polarity, which enables them to participate in a variety of nucleophilic and electrophilic reactions. Especially in phosphorus-containing organic synthesis, α, β-diphosphorus oxide compounds are often used as key intermediates or functionalization reagents.

[0004] At present, there are many methods for synthesizing α, β-diphosphine oxides, mainly the following common synthetic routes:

[0005] 1) Reaction of phosphites with alkyl halides: Through the reaction of phosphites with alkyl halides, phosphorus oxygen groups can be introduced at different positions of the molecule to obtain the target diphosphine oxygen compound.

[0006] 2) Wittig-Horner reaction: The olefins generated by the Wittig-Horner reaction can be further oxidized to the corresponding diphosphine oxides.

[0007] 3) Oxidation reaction: α, β-diphosphorus oxides can be directly generated by selective oxidation of phosphorus-containing compounds. This method is simple and efficient, so it has a wide range of applications in industrial production.

[0008] Currently, although Wan's team has developed stereoselective phosphonocyanation and diphosphitylation of N, N-dimethylenaminoketone, the process is relatively complicated and potassium tert-butoxide is used in the synthesis process, which is harmful to the environment. Therefore, it is necessary to develop a new and more environmentally friendly method for synthesizing α, β-diphosphooxy compounds. Summary of the invention

[0009] The present invention aims to provide a method for synthesizing an α, β-diphosphorus oxide compound to solve the problem that the preparation process of the α, β-diphosphorus oxide compound is relatively complicated and not environmentally friendly.

[0010] In order to achieve the above-mentioned object, the scheme of the present invention is: a method for synthesizing an α, β-diphosphine oxide compound, comprising a synthesis reaction: the raw materials are an imine as shown in formula (2) and diphenylphosphine oxide as shown in formula (3), the catalyst is aluminum trichloride, and the solvent is tetrahydrofuran; the product is an α, β-diphosphine oxide compound as shown in formula (1);

[0011]

[0012] Wherein, R is selected from one of aromatic groups, furan and thiophene; R1 is independently selected from one of hydrogen groups, alkyl groups and halogen groups. Moreover, the substitution mode of R1 is single substitution or multiple substitution.

[0013] The working principle and beneficial effects of this scheme are as follows: In this scheme, α, β-diphosphine oxide compounds are synthesized using two compounds, imine and diphenylphosphine oxide, as raw materials, aluminum chloride as a catalyst, and tetrahydrofuran as a solvent. No water is added during the synthesis process, the synthesis process is simple and safe to operate, the selection of catalysts and solvents is green and environmentally friendly, and the cost of raw materials is low. It is an economical, environmentally friendly, and efficient synthesis method, which effectively solves the problem that the preparation process of α, β-diphosphine oxide compounds is relatively complicated and not environmentally friendly. In addition, "the substitution mode of R1 is single substitution or multiple substitution" in this scheme means that the number of substitutions of R1 on the benzene ring is one or more.

[0014] Optionally, the molar ratio of the imine to diphenylphosphine oxide is 1:2.2 to 1:3. The above ratio can ensure sufficient reaction between the substrates and ensure the yield of the product.

[0015] Optionally, the molar ratio of the imine to aluminum chloride is 1:2 to 1:3. Under the above ratio, the amount of catalyst is appropriate.

[0016] Optionally, the synthesis reaction time is 6 to 24 hours. The above reaction time can ensure that the reaction is fully carried out without affecting the quality of the product.

[0017] Optionally, the temperature of the synthesis reaction is 50° C. The above reaction temperature is a suitable temperature, at which a large amount of by-products will not be generated to affect the quality of the product.

[0018] Optionally, the molar ratio of imine to diphenyl is 1:2.2, the molar ratio of imine to aluminum chloride is 1:2, the temperature of the synthesis reaction is 50°C, and the duration of the synthesis reaction is 16 hours. The above reaction conditions are optimized reaction conditions, and the product quality and yield obtained using the above reaction conditions are relatively ideal.

[0019] Optionally, the synthesis reaction further includes a purification step: after the synthesis reaction, a mixed solution containing α, β-diphosphine oxide is obtained, the organic layer is extracted with ethyl acetate, and the solvent is removed to obtain a crude product; the crude product is purified by silica gel column chromatography to obtain a pure product. The pure product of α, β-diphosphine oxide is obtained through the purification step.

[0020] Optionally, the method of purifying the crude product by silica gel column chromatography is as follows: dissolving the crude product with dichloromethane, loading the dichloromethane solution of the crude product into a 30 cm long silica gel column, eluting the silica gel column with an eluent and collecting the eluate, and concentrating the eluate under reduced pressure to obtain a pure product. Silica gel column chromatography is an effective means for separating and purifying α, β-diphosphine oxide from the crude product.

[0021] Optionally, the eluent is a mixed solution of methanol and dichloromethane, and the volume ratio of methanol to dichloromethane is 1: 100. The above eluent has a good elution effect on α, β-diphosphine oxides and can effectively separate α, β-diphosphine oxides from other impurities. DETAILED DESCRIPTION

[0022] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0023] Example 1

[0024] This embodiment provides a method for synthesizing 2,3-bis(diphenylphosphoryl)-1-phenylpropan-1-one (Compound 1), and the reaction equation is shown in Formula (4).

[0025]

[0026] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-phenylprop-2-ene-1-one (0.57 mmol), diphenylphosphine oxide (1.25 mmol), and aluminum trioxide (1.14 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 16 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. After the eluate was concentrated under reduced pressure, pure compound 1 was obtained. In this embodiment, 283 mg of compound 1 was collected, and the yield was 93%.

[0027] The structure of compound 1 was detected by nuclear magnetic resonance, and the results are as follows:

[0028] 1 H NMR (400MHz, CDCl3) δ7.87–7.76(m,2H),7.70–7.46(m,8H),7.43(d,J=7.3Hz,5H),7.32–7.23(m,4H),7.23–7.13 (m,4H),7.08(t,J=7.7Hz,2H),5.21(dd,J=23.2,11.7Hz,1H),3.58–3.47(m,1H),2.77(dd,J=27.3,13.1Hz,1H). 13C NMR (101MHz, CDCl3) δ195.23 (d, J = 3.1Hz), 137.51, 133.16 (d, J = 6.6Hz), 132.61, 132.45 (d, J = 2.6Hz), 132.14 (d, J =2.7Hz), 132.08 (d, J = 2.5Hz), 131.94 (d, J = 2.6Hz), 131.79, 131.70, 131.65, 131.56, 131.42, 131.33, 130.69, 130. 60,130.47(d,J=2.6Hz),130.41(d,J=1.6Hz),130.35,129.79(d,J=7.4Hz),129.45(d,J=6.8Hz),128.92,128.88, 128.80, 128.77, 128.68 (d, J = 12.0Hz), 128.43, 128.32, 128.20, 127.83, 42.89 (d, J = 50.6Hz), 27.99 (d, J = 64.9Hz). 31 P NMR (162MHz,CDCl3)δ30.62. 31 P NMR (162MHz, CDCl3) δ30.80 (dd, J=97.2, 41.9Hz).HRMS: [M+Na] + m / z calculation for C 33 H 28 O3NaP2:557.1411; found:557.1416.

[0029] The above hydrogen spectrum proves that the compound 1 synthesized in this example is the target product compound 1 in formula (4).

[0030] Example 2

[0031] This embodiment provides a synthesis of 2,3-bis(diphenylphosphoryl)-1-(p-tolyl)propan-1-one (Compound 2), and the reaction equation is shown in Formula (5).

[0032]

[0033] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(p-tolyl)prop-2-en-1-one (0.53 mmol), diphenylphosphine oxide (1.17 mmol), and aluminum trioxide (1.06 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 11 hours. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 2. In this embodiment, 267 mg of compound 2 was collected, and the yield was 92%.

[0034] The structure of compound 2 was detected by nuclear magnetic resonance, and the results are as follows:

[0035] 1 H NMR (400MHz, CDCl3) δ7.84–7.77(m,2H),7.66–7.46(m,8H),7.45–7.38(m,4H),7.37–7.28(m,3H),7.25–7.13(m,5H), 6.88(d,J=8.0Hz,2H),5.18(dd,J=24.0,12.2Hz,1H),3.55–3.46(m,1H),2.76(dd,J=27.9,14.2Hz,1H),2.25(s,3H). 13C NMR(101MHz, CDCl3)δ194.57,143.41,134.99,132.34,132.31,132.25(d,J=3.4Hz),132.00,131 .98,131.85,131.82,131.78,131.69,131.65,131.56,131.37,131.27,130.82(d,J=3.8Hz),130 .64,130.55,130.43,129.85(d,J=3.8Hz),129.47(d,J=3.0Hz),128.81(d,J=0.7Hz),128.69,12 8.56,128.47,128.37,128.25,128.23,128.12,42.67(d,J=52.4Hz),27.94(d,J=65.9Hz),21.54. 31 P NMR (162MHz, CDCl3) δ30.92 (dd, J=138.0, 42.4Hz).HRMS: [M+Na] + m / z calculation for C 34 H 30 O3NaP2:571.1568; found:571.1574.

[0036] The above hydrogen spectrum proves that the compound 2 synthesized in this example is the target product compound 2 in formula (5).

[0037] Example 3

[0038] This embodiment provides a method for synthesizing 2,3-bis(diphenylphosphoryl)-1-(furan-2-yl)propan-1-one (Compound 3), and the reaction equation is shown in Formula (6).

[0039]

[0040] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one (0.61 mmol), diphenylphosphine oxide (1.34 mmol), and aluminum trioxide (1.22 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is placed on a magnetic stirrer for stirring at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 9 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 3. In this embodiment, 291 mg of compound 3 was collected, and the yield was 91%.

[0041] The structure of compound 3 was detected by nuclear magnetic resonance, and the results are as follows:

[0042] 1 H NMR(400MHz, CDCl3)δ7.84(dd,J=10.4,7.9Hz,2H),7.71–7.60(m,4H),7.59–7.40(m,8H),7.30(dt,J=11.4,5.3Hz,3H),7.25–7.17(m,4 H),6.70(d,J=3.5Hz,1H),6.17(dd,J=3.6,1.6Hz,1H),5.00(dd,J=23.4,11.5Hz,1H),3.52–3.40(m,1H),2.74(dd,J=27.5,13.6Hz,1H). 13 C NMR (101MHz, CDCl3) δ182.47 (d, J = 3.1Hz), 152.29, 146.03, 132.38 (d, J = 2. 8Hz),132.04(d,J=2.6Hz),131.83(d,J=2.7Hz),131.68,131.59,131.49,1 31.40,131.31,131.22,130.81,130.72,128.89,128.78,128.67,128.29,1 28.17,128.05,117.55,112.48,42.97(d,J=51.3Hz),27.11(d,J=64.9Hz).31 P NMR (162MHz, CDCl3) δ30.84 (dd, J=103.6, 41.7Hz).HRMS: [M+Na] + m / z calculation for C 31 H 26 O4NaP2:547.1204; found:547.1210.

[0043] The above hydrogen spectrum proves that the compound 3 synthesized in this example is the target product compound 3 in formula (6).

[0044] Example 4

[0045] This embodiment provides a method for synthesizing 2,3-bis(di-p-tolylphosphoryl)-1-phenylpropan-1-one (Compound 4), and the reaction equation is shown in Formula (7).

[0046]

[0047] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-phenylprop-2-ene-1-one (0.57 mmol), bis(4-methylphenyl)phosphine oxide (1.25 mmol), and aluminum trioxide (1.14 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 14 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, separated, the organic layers are combined, and washed twice with saturated brine, the organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 4. In this embodiment, 292 mg of compound 4 was collected, and the yield was 87%.

[0048] The structure of compound 4 was detected by NMR, and the results are as follows:

[0049] 1H NMR (400MHz, CDCl3) δ7.66 (dd, J=11.0, 8.1Hz, 2H), 7.56–7.45 (m, 4H), 7.44–7.35 (m ,4H),7.29(t,J=7.4Hz,1H),7.20(d,J=7.5Hz,4H),7.08(t,J=7.8Hz,2H),7.00(dd, J=7.9,2.2Hz,2H),6.95–6.88(m,2H),5.14(dd,J=24.1,12.5Hz,1H),3.49–3.36(m, 1H), 2.72 (dd, J=28.6, 14.3Hz, 1H), 2.35 (d, J=3.1Hz, 6H), 2.22 (s, 3H), 2.14 (s, 3H). 13 CNMR (101MHz, CDCl3) δ195.47 (d, J = 3.8Hz), 142.82 (d, J = 2.8Hz), 142.55 (d, J = 2.9Hz), 142.39 (d, J = 2.8Hz), 142.20 (d, J =2.8Hz),137.49,132.24,131.81,131.72,131.64,131.55,131.45,131.35,130.68,130.58,129.48(d,J=2.7Hz),129.3 6(d,J=2.4Hz),129.11,128.97(d,J=3.7Hz),128.83,128.47,127.92(d,J=43.6Hz),127.51,127.13(d,J=2.2Hz),126.4 0(d,J=53.0Hz), 43.07(d,J=52.5Hz), 28.31(d,J=66.5Hz), 21.60(d,J=3.0Hz), 21.45(d,J=0.9Hz), 21.37(d,J=1.0Hz). 31 P NMR (162MHz, CDCl3) δ31.42 (dd, J=155.2, 41.8Hz).HRMS: [M+Na] + m / z calculation for C 37 H 36 O3NaP2:613.2037; found:613.2039.

[0050] The above hydrogen spectrum proves that the compound 4 synthesized in this example is the target product compound 4 in formula (7).

[0051] Example 5

[0052] This embodiment provides a method for synthesizing 2,3-bis(bis(4-chlorophenyl)phosphoryl)-1-phenylpropan-1-one (Compound 5), and the reaction equation is shown in Formula (8).

[0053]

[0054] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-phenylprop-2-ene-1-one (0.57 mmol), bis(4-chlorophenyl)phosphine oxide (1.25 mmol), and aluminum trioxide (1.14 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 14 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, separated, the organic layers are combined, and washed twice with saturated brine, the organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 5. In this embodiment, 356 mg of compound 5 was collected, and the yield was 93%.

[0055] The structure of compound 5 was detected by nuclear magnetic resonance, and the results are as follows:

[0056] 1 H NMR (400MHz, CDCl3) δ7.70 (dd, J=10.6, 8.5Hz, 2H), 7.63–7.49 (m, 4H), 7.49–7.36 ( m,9H),7.24–7.08(m,6H),5.20–5.06(m,1H),3.47–3.37(m,1H),2.76–2.63(m,1H). 13CNMR (101MHz, CDCl3) δ194.80 (d, J = 2.4Hz), 139.57 (d, J = 2.4Hz), 139.26 (d, J = 2.6Hz), 139.16 (d, J = 2.5Hz), 138.99 (d, J = 2 .8Hz),136.91,133.24,132.98(d,J=1.4Hz),132.90(d,J=2.1Hz),132.67(d,J=2.3Hz),132.59(d,J=2.1Hz),131.89(d,J=2 .2Hz),131.81(d,J=2.3Hz),130.94,129.83(d,J=17.1Hz),129.38,129.29,129.17,128.95(d,J=2.4Hz),128.90–128.76( m), 128.71 (d, J = 2.7Hz), 128.56, 128.28, 128.17, 128.08, 127.42 (d, J = 24.7Hz), 42.92 (d, J = 52.3Hz), 27.87 (d, J = 65.9Hz). 31 P NMR(162MHz,CDCl3)δ30.03–29.29(m).HRMS:[M+Na] + m / z calculation for C 33 H 24 O3NaP2Cl4:692.9852; found:692.9852.

[0057] The above hydrogen spectrum proves that the compound 5 synthesized in this example is the target product compound 5 in formula (8).

[0058] Example 6

[0059] This embodiment provides a method for synthesizing 1-(3,4-dimethylphenyl)-2,3-bis(diphenylphosphoryl)propan-1-one (Compound 6), and the reaction equation is shown in Formula (9).

[0060]

[0061] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(3,4-dimethylphenyl)prop-2-en-1-one (0.49 mmol), diphenylphosphine oxide (1.08 mmol), and aluminum trioxide (0.98 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is placed on a magnetic stirrer for stirring at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 16 hours. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 6. In this embodiment, 236 mg of compound 6 was collected, and the yield was 86%.

[0062] The structure of compound 6 was detected by NMR, and the results are as follows:

[0063] 1 H NMR (400MHz, CDCl3) δ7.80(dd,J=11.1,7.2Hz,2H),7.67–7.37(m,12H),7.34–7.13(m,7H),7.05(s,1H),6.85(d,J=7. 9Hz,1H),5.15(dd,J=24.0,12.3Hz,1H),3.55–3.45(m,1H),2.76(dd,J=28.0,14.3Hz,1H),2.14(s,3H),2.05(s,3H). 13C NMR (101MHz, CDCl3) δ194.83 (d, J = 3.5Hz), 142.13, 135.87, 135.45, 133.25 (d, J = 3.5Hz), 132.27 (d, J = 1.9Hz), 131.97 (d,J=2.4Hz),131.89(d,J=2.0Hz),131.77,131.69,131.58,131.44(d,J=3.5Hz),131.37,131.27,130.88(d,J=3.7Hz ),130.66,130.57,130.52(d,J=2.7Hz),130.45(d,J=3.5Hz),129.91(d,J=3.8Hz),129.55(d,J=3.2Hz),129.46,129. 02,128.78,128.67,128.29,128.23,128.17,128.11,126.18,42.98(d,J=51.5Hz),27.86(d,J=66.1Hz),19.89,19.48. 31 P NMR (162MHz, CDCl3) δ31.00 (dd, J=137.5, 42.3Hz).HRMS: [M+Na] + m / z calculation for C 35 H 32 O3NaP2:585.1724; found:585.1733.

[0064] The above hydrogen spectrum proves that the compound 6 synthesized in this example is the target product compound 6 in formula (9).

[0065] Example 7

[0066] This embodiment provides a method for synthesizing 2,3-bis(diphenylphosphoryl)-1-(3,4,5-trimethoxyphenyl)propan-1-one (Compound 7), and the reaction equation is shown in Formula (10).

[0067]

[0068] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (0.38 mmol), diphenylphosphine (0.84 mmol), and aluminum trioxide (0.76 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 14 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, separated, the organic layers are combined, and washed twice with saturated brine, the organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 7. In this embodiment, 248 mg of compound 7 was collected, and the yield was 92%.

[0069] The structure of compound 7 was detected by NMR, and the results are as follows:

[0070] 1 H NMR (400MHz, CDCl3) δ7.82–7.74(m,2H),7.71–7.61(m,4H),7.61–7.54(m,2H),7.53–7.46(m,2H),7.46–7.38(m,4H),7.38 –7.20(m,6H),6.71(s,2H),5.15–5.04(m,1H),3.80(s,3H),3.74(s,6H),3.52–3.42(m,1H),2.78(dd,J=26.8,11.7Hz,1H). 13C NMR (101MHz, CDCl3) δ194.33(d,J=2.8Hz),152.20,141.97,133.08,132.46(d,J=2.1Hz),132.21(d,J=2.6Hz ),132.13(d,J=2.1Hz),131.97(d,J=2.5Hz),131.71,131.65,131.62,131.57,131.30,131.21,130.64,130.5 6,130.40(d,J=11.7Hz),129.72(d,J=12.9Hz),129.39(d,J=12.6Hz),128.88,128.77,128.45,128.39,128. 34,128.28,105.91,60.81(d,J=2.7Hz),56.09(d,J=2.5Hz),43.66(d,J=48.9Hz),27.94(dd,J=61.0,4.1Hz). 31 P NMR (162MHz, CDCl3) δ31.00 (dd, J=71.3, 42.5Hz).HRMS: [M+Na] + m / z calculation for C 36 H 34 O6NaP2:647.1728; found:647.1731.

[0071] The above hydrogen spectrum proves that the compound 7 synthesized in this example is the target product compound 7 in formula (10).

[0072] Example 8

[0073] This embodiment provides a method for synthesizing 2,3-bis(diphenylphosphoryl)-1-(naphthalen-2-yl)propan-1-one (Compound 8), and the reaction equation is shown in Formula (11).

[0074]

[0075] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(naphthalene-2-yl)prop-2-en-1-one (0.44 mmol), diphenylphosphine oxide (0.97 mmol), and aluminum trioxide (0.88 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 24 hours. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, separated, the organic layers are combined, and washed twice with saturated brine, the organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. After the eluate was concentrated under reduced pressure, pure compound 8 was obtained. In this embodiment, 226 mg of compound 8 was collected, and the yield was 88%.

[0076] The structure of compound 8 was detected by nuclear magnetic resonance, and the results are as follows:

[0077] 1 H NMR(400MHz, CDCl3)δ7.93(s,1H),7.91–7.82(m,2H),7.76–7.52(m,9H),7.52–7.39(m,9H),7.1 9–7.05(m,6H),5.35(dd,J=23.9,12.1Hz,1H),3.64–3.53(m,1H),2.84(dd,J=28.2,14.1Hz,1H). 13 C NMR(101MHz, CDCl3)δ195.00(d,J=2.7Hz),135.07,134.85,132.40(d,J=2.9Hz),132.07(d,J =2.8Hz),132.03(d,J=3.1Hz),131.87(d,J=2.8Hz),131.79,131.70,131.60,131.50,131.39 ,131.30,130.67,130.57,130.44,129.66,128.86(d,J=2.4Hz),128.75(d,J=2.3Hz),128.37 ,128.25,128.14,127.64,127.42,126.36,123.87,43.19(d,J=51.9Hz),28.04(d,J=65.6Hz). 31P NMR (162MHz, CDCl3) δ31.01 (dd, J=124.7, 41.9Hz).HRMS: [M+Na] + m / z calculation for C 37 H 30 O3NaP2:607.1568; found:607.1573.

[0078] The above hydrogen spectrum proves that the compound 8 synthesized in this example is the target product compound 8 in formula (11).

[0079] Example 9

[0080] The embodiment provides a method for synthesizing 1-(3-bromophenyl)-2,3-bis(diphenylphosphoryl)propan-1-one (Compound 9), and the reaction equation is shown in Formula (12).

[0081]

[0082] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-1-(3-bromophenyl)-3-(dimethylamino)prop-2-en-1-one (0.40 mmol), diphenylphosphine oxide (0.88 mmol), and aluminum oxide (0.80 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 15 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. After the eluate was concentrated under reduced pressure, pure compound 9 was obtained. In this embodiment, 223 mg of compound 9 was collected, and the yield was 91%.

[0083] The structure of compound 9 was detected by NMR, and the results are as follows:

[0084] 1H NMR(400MHz, CDCl3)δ7.85–7.76(m,2H),7.70–7.37(m,14H),7.37–7.17(m,7H),7.00(t, J=7.9Hz,1H),5.15–5.02(m,1H),3.50(ddd,J=15.6,11.1,4.7Hz,1H),2.82–2.69(m,1H). 13 C NMR (101MHz, CDCl3) δ194.16 (d, J = 3.2Hz), 139.20, 135.28, 132.84 (d, J = 16.5Hz), 132.57 (d, J = 2.3Hz), 132.35 (d, J = 2.5Hz), 132.15 (d, J = 2.4H z),132.00(d,J=2.4Hz),131.72,131.64,131.52,131.43,131.39,131. 29,131.26,131.06,130.65(d,J=0.7Hz),130.60,130.56(d,J=0.8Hz), 130.35(d,J=16.7Hz),129.97(d,J=17.1Hz),129.68(d,J=17.3Hz),129.34,129.14(d,J=17.0Hz),128.96,128.90(d,J=1.0Hz),128.84(d,J=1 .0Hz), 128.79, 128.62 (d, J = 11.9Hz), 128.52, 128.41, 128.37, 128.25, 126.89, 122.12, 43.45 (dd, J = 45.0, 4.4Hz), 28.08 (dd, J = 58.6, 6.5Hz). 31 P NMR (162MHz, CDCl3) δ30.92 (dd, J=60.2, 41.4Hz).HRMS: [M+Na] + m / z calculation for C 33 H 27 O3NaP2Br:635.0517; found:635.0521.

[0085] The above hydrogen spectrum proves that the compound 9 synthesized in this example is the target product compound 9 in formula (12).

[0086] Example 10

[0087] The embodiment provides a method for synthesizing 1-(2-bromophenyl)-2,3-bis(diphenylphosphoryl)propan-1-one (Compound 10), and the reaction equation is shown in Formula (13).

[0088]

[0089] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-1-(3-bromophenyl)-3-(dimethylamino)prop-2-en-1-one (0.40 mmol), diphenylphosphine (0.88 mmol), and aluminum trioxide (0.80 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 16 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 10. In this embodiment, 213 mg of compound 10 was collected, and the yield was 87%.

[0090] The structure of compound 10 was detected by NMR, and the results are as follows:

[0091] 1 H NMR (400MHz, CDCl3) δ7.83–7.66(m,6H),7.66–7.56(m,3H),7.54–7.28(m,10H),7.24–7.11(m,4 H),7.00(t,J=7.6Hz,1H),5.37–5.24(m,1H),3.69–3.56(m,1H),2.68(dd,J=27.3,14.8Hz,1H). 13C NMR (101MHz, CDCl3) δ194.90 (d, J = 3.1Hz), 139.51, 133.91, 132.22 (d, J = 2.3Hz), 132.0 6(d,J=2.7Hz),131.94(d,J=2.2Hz),131.91,131.53,131.44,131.39,131.30,131.26,1 31.16,130.70,130.58,130.49,130.09,128.82(d,J=2.0Hz),128.70(d,J=2.3Hz),128. 58,128.46,128.32,128.21,126.83,120.39,47.33(d,J=51.0Hz),26.00(d,J=64.7Hz). 31 P NMR (162MHz, CDCl3) δ30.77 (dd, J=102.9, 38.1Hz).HRMS: [M+Na] + m / z calculation for C 33 H 27 O3NaP2Br:635.0517; found:635.0521.

[0092] The above hydrogen spectrum proves that the compound 10 synthesized in this example is the target product compound 10 in formula (13).

[0093] Embodiment 11

[0094] The embodiment provides a method for synthesizing 2,3-bis(diphenylphosphoryl)-1-(thiophen-2-yl)propan-1-one (Compound 11), and the reaction equation is shown in Formula (13).

[0095]

[0096] The synthesis process is as follows: in a pressure tube with a volume of 20 mL, (E)-3-(dimethylamino)-1-(thiophen-2-yl)prop-2-en-1-one (0.55 mmol), diphenylphosphine oxide (1.21 mmol), and aluminum trioxide (1.1 mmol) are added in sequence, and then 4 mL of THF is added under ice bath conditions, and a magnetic stirrer is placed, and the mixture is stirred on a magnetic stirrer at a stirring speed of 200 rpm. The reaction is carried out at 50° C. for 15 h. When no imine is left after the reaction is monitored by TLC, 10 mL of ice water is added to the reaction system to quench the reaction, and the reaction solution is extracted three times with 20 mL×3 ethyl acetate, the liquids are separated, the organic layers are combined, and the mixture is washed twice with saturated brine. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is distilled under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography. Specifically, the crude product was dissolved in dichloromethane, and the dichloromethane solution of the crude product was loaded into a 30 cm long silica gel column. A mixed solution of methanol and dichloromethane (the volume ratio of methanol to dichloromethane was 1:100) was used as an eluent to elute the silica gel column, and the eluate was collected. The eluate was concentrated under reduced pressure to obtain pure compound 10. In this embodiment, 276 mg of compound 11 was collected, and the yield was 93%.

[0097] The structure of compound 11 was detected by nuclear magnetic resonance, and the results are as follows:

[0098] 1 H NMR (400MHz, CDCl3) δ7.87–7.79(m,2H),7.73–7.62(m,4H),7.59–7.47(m,4H),7.47–7.39(m,4H),7.38–7.32(m,2H),7.31–7.24 (m,4H),7.22–7.14(m,2H),6.79–6.73(m,1H),4.91(dd,J=24.2,12.3Hz,1H),3.49–3.39(m,1H),2.77(dd,J=28.4,14.2Hz,1H). 13CNMR (101MHz, CDCl3) δ186.78 (d, J = 3.5Hz), 144.48, 134.58, 133.32, 132.44 (d, J = 2. 9Hz),132.20(d,J=2.9Hz),132.05(d,J=2.6Hz),131.87(d,J=2.7Hz),131.81,131.72 ,131.64,131.42,131.32,130.67,130.58,128.84(d,J=3.7Hz),128.73(d,J=3.5Hz) ,128.47,128.35,128.21,128.09,127.51,44.67(d,J=53.8Hz),27.74(d,J=67.4Hz). 31 PNMR(162MHz,CDCl3)δ30.82(dd,J=103.6,42.0Hz).HRMS:[M+Na] + m / z calculation for C 31 H 26 O3NaP2S:563.0976; found:563.0981.

[0099] The above hydrogen spectrum proves that the compound 11 synthesized in this example is the target product compound 11 in formula (13).

[0100] The above are only embodiments of the present invention. The invention is not limited to the fields involved in this implementation case. The common sense such as the known specific structures and characteristics in the scheme is not described in detail here. The ordinary technicians in the relevant field know all the common technical knowledge in the technical field to which the invention belongs before the application date or priority date, can obtain all the existing technologies in the field, and have the ability to apply the conventional experimental means before that date. The ordinary technicians in the relevant field can improve and implement this scheme in combination with their own abilities under the enlightenment given by this application. Some typical known structures or known methods should not become obstacles for ordinary technicians in the relevant field to implement this application. It should be pointed out that for those skilled in the art, without departing from the structure of the present invention, several deformations and improvements can be made, which should also be regarded as the protection scope of the present invention, which will not affect the effect of the implementation of the present invention and the practicality of the present invention. The protection scope required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to explain the content of the claims.

Claims

1. A method for synthesizing α,β-diphosphine oxide, characterized in that: The method comprises a synthesis reaction: the raw materials are an imine as shown in formula (2) and a diphenylphosphine oxide as shown in formula (3), the catalyst is aluminum chloride, and the solvent is tetrahydrofuran; the product is an α,β-diphosphine oxide compound as shown in formula (1); Wherein, R is selected from one of aromatic groups, furan and thiophene; R1 is independently selected from one of hydrogen groups, alkyl groups and halogen groups.

2. The synthesis method according to claim 1, characterized in that: The molar ratio of the imine to diphenylphosphine oxide is 1:2 to 1:

3.

3. The synthesis method according to claim 1, characterized in that: The molar ratio of the imine to aluminum chloride is 1:2 to 1:

3.

4. The synthesis method according to claim 1, characterized in that: The duration of the synthesis reaction is 6 to 24 hours.

5. The synthesis method according to claim 1, characterized in that: The temperature of the synthesis reaction is 50°C.

6. The synthesis method according to claim 1, characterized in that: The molar ratio of the imine to the diphenyl is 1:2.2, the molar ratio of the imine to the aluminum chloride is 1:2, the temperature of the synthesis reaction is 50° C., and the duration of the synthesis reaction is 16 hours.

7. The synthesis method according to claim 1, characterized in that: The synthesis reaction further includes a purification step: after the synthesis reaction, a mixed solution containing α, β-diphosphine oxide is obtained, and after extraction with ethyl acetate, an organic layer is taken, and a crude product is obtained after removing the solvent; The crude product was purified by silica gel column chromatography to obtain the pure product.

8. The synthesis method according to claim 7, characterized in that: The method of purifying the crude product by silica gel column chromatography is as follows: dissolve the crude product with dichloromethane, load the dichloromethane solution of the crude product into a 30 cm long silica gel column, elute the silica gel column with an eluent and collect the eluate, and obtain a pure product after the eluate is concentrated under reduced pressure.

9. The synthesis method according to claim 8, characterized in that: The eluent is a mixed solution of methanol and dichloromethane, and the volume ratio of methanol to dichloromethane is 1:100.

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