A photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds

Abstract

The invention discloses a photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds, and belongs to the technical field of organic synthesis. The technical scheme of the invention is as follows: using isocyanide compounds and diphenylphosphine oxide compounds as starting raw materials, under the action of additives and catalysts, using acetonitrile and water as mixed solvents, and reacting under blue light at room temperature under air conditions to obtain the target product ((alkylamino)methyl)diphenylphosphine oxide compounds. The preparation method of the invention is simple and safe to operate, and the reaction conditions are mild. The light source used in the preparation method is visible light, which is green and pollution-free. The catalyst and the reaction medium are also relatively friendly to the environment. The yield of the synthesized target product of the invention is relatively high.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of substituted phosphine oxide compounds, and specifically relates to a photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds. Background Art

[0002] Organophosphorus compounds are widely used in the pharmaceutical industry (Chem. Rev. 2006, 106, 3868), pesticides (Plants 2019, 8, 341) and functional materials, so the construction of carbon-phosphorus bonds has important research value. α-Aminomethylphosphoryl compounds, as electronic isosteres of α-amino acids, are used in inhibitors of various proteases (J. Med. Chem. 1986, 29, 29).

[0003] The Kabachnik-Fieds reaction is currently the most commonly used method for constructing α-aminomethylphosphoryl compounds. This method obtains the target compound through a three-component reaction of a molecule of amine, polyformaldehyde and a phosphoryl compound (Synthetic Communications, 2019, 49, 1047; Molecules 2019, 24, 1640). However, the reaction requires high temperature heating. Therefore, it is of great significance to develop a method for preparing ((alkylamino)methyl)diphenylphosphine oxide compounds under mild conditions. Summary of the invention

[0004] The technical problem solved by the present invention is to provide a photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds with a simple synthesis process and mild reaction conditions. The method can effectively solve the problem that high-temperature heating is required in the original technology, and provides a new method for synthesizing ((alkylamino)methyl)diphenylphosphine oxide compounds.

[0005] The present invention adopts the following technical scheme to solve the above technical problems: a photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds, characterized in that the specific process is: using isocyanide compounds and diphenylphosphine oxide compounds as starting raw materials, in the presence of additives and catalysts, using acetonitrile and water as a mixed solvent, reacting under blue light illumination at room temperature under air conditions, evaporating the solvent after the reaction, extracting the reaction solution with ethyl acetate, drying, rotating to remove the organic phase, and separating the residue by column chromatography to obtain the target product ((alkylamino)methyl)diphenylphosphine oxide compounds, wherein the additive is one or more of triethylamine, N,N-diisopropylethylamine DIPEA, 1,8-diazabicycloundec-7-ene DBU or tetramethylethylenediamine TMEDA, the catalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4-CzIPN, the structural formula of the isocyanide compound is shown in formula A, the structural formula of the diphenylphosphine oxide compound is shown in formula B, and the structural formula of the ((alkylamino)methyl)diphenylphosphine oxide compound is shown in formula C:

[0006]

[0007] Where R 1 is tert-butyl, benzyl or ester-containing alkyl, R 2 For halogen, C 1-5 Alkyl or C 1-5 Alkoxy.

[0008] It is further defined that the specific structural formula of the ((alkylamino)methyl)diphenylphosphine oxide compound is:

[0009]

[0010] It is further defined that the molar ratio of the isocyanate compound, the diphenylphosphine oxide compound, the catalyst and the additive is 1:1-3:1%-10%:1-3.

[0011] It is further defined that the volume ratio of acetonitrile to water in the mixed solvent is 200:1-50:1, preferably 100:1.

[0012] It is further defined that the reaction equation in the preparation process of the ((alkylamino)methyl)diphenylphosphine oxide compound is:

[0013]

[0014] The structural formula of the catalyst 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4-CzIPN is:

[0015]

[0016] It is further defined that the light source of the blue light during the reaction process is a blue LED lamp with a wavelength of 405nm and a power of 10W.

[0017] Compared with the prior art, the present invention has the following advantages and beneficial effects: the present invention provides a photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds. Compared with the prior art, the preparation method of the present invention does not require high-temperature heating, uses an organic photosensitizer as a catalyst under the catalytic action of visible light, and synthesizes the target product ((alkylamino)methyl)diphenylphosphine oxide compounds through a one-pot reaction. The preparation method of the present invention is simple and safe to operate, and the reaction conditions are mild. The light source used in the preparation method is visible light, which is green and pollution-free. The catalyst and the reaction medium are also environmentally friendly, and the yield of the synthesized target product of the present invention is relatively high. DETAILED DESCRIPTION

[0018] The technical scheme of the present invention is specifically described below by way of examples. It is necessary to point out here that the following examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by professionals and technicians in this field based on the content of the present invention above still belong to the scope of protection of the present invention. In addition, if there is no other explanation, the raw materials used are all commercially available.

[0019] Example 1

[0020] 2-isocyano-2-methylpropane (0.2mmol), diphenylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 85% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0021] The structural formula of the target product is as follows:

[0022] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0023] 1H NMR (400MHz, CDCl3) δ 7.83-7.78 (m, 4H), 7.55-7.51 (m, 2H), 7.48-7.44 (m, 4H), 3.40 (d, J = 9.8Hz, 2H), 1.07 (s, 9H).

[0024] 13 C NMR (100MHz, CDCl3) δ 132.2 (d, J = 98.0Hz), 132.0 (d, J = 3.0Hz), 131.4 (d, J = 9.0Hz), 128.6 (d, J = 11.0Hz), 51.3 (d, J = 13.0Hz), 42.8 (d, J = 84.0Hz), 28.6.

[0025] 31 P NMR (162 MHz, CDCl3) δ 30.6.

[0026] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 23 NOP + 288.1512,Found:288.1512.

[0027] Example 2

[0028] To a 10mL reaction tube equipped with a magnetic device, (isocyanomethyl)benzene (0.2mmol), diphenylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added in sequence, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added for dilution, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 50% based on the molar amount of (isocyanomethyl)benzene as 100%.

[0029] The structural formula of the target product is as follows:

[0030] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0031] 1H NMR (600MHz, CDCl3) δ7.77-7.74(m,4H),7.55-7.52(m,2H),7.47-7.44(m,4H),7.30-7.23(m,5H),3.87(s,2H),3.42(d,J=7.9Hz,2H).

[0032] 13 C NMR (100MHz, CDCl3) δ139.2, 132.1 (d, J = 3.0Hz), 132.0 (d, J = 97.0Hz), 131.3 (d, J = 9.0H z), 128.8, 128.7, 128.5 (d, J = 14.0Hz), 127.4, 55.2 (d, J = 14.0Hz), 48.2 (d, J = 80.0Hz).

[0033] 31 P NMR (162 MHz, CDCl3) δ 29.5.

[0034] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 21 NOP + 322.1355,Found:322.1352.

[0035] Example 3

[0036] 2-isocyano-2-methylpropane (0.2mmol), di(naphthalene-1-yl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 40% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0037] The structural formula of the target product is as follows:

[0038] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0039] 1H NMR (400MHz, CDCl3) δ8.74(d,J=8.1Hz,2H),8.01(dd,J=13.9Hz,6.1Hz4H),7.88(d,J=7.7Hz,2H),7.50-7.43(m,6H),3.71(d,J=10.0Hz,2H),1.07(s,9H).

[0040] 13 C NMR (100MHz, CDCl3) δ133.9 (q, J = 8.0Hz), 133.2 (d, J = 3Hz), 132.8, 132.7, 129.1, 128.9 (d, J = 95.0Hz), 127.4, 126.9 (d, J = 5.0Hz), 126.5, 124.7 (d, J = 14.0Hz), 51.4 (d, J = 14.0Hz), 43.8 (d, J = 83.0Hz), 28.6.

[0041] 31 P NMR (162 MHz, CDCl3) δ 36.6.

[0042] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 25 H 27 NOP + 388.1825,Found:388.1844.

[0043] Example 4

[0044] 2-isocyano-2-methylpropane (0.2mmol), bis(4-fluorophenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a light yellow solid. The yield of the target product was 78% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0045] The structural formula of the target product is as follows:

[0046] The above light yellow solid was subjected to nuclear magnetic spectrum and mass spectrum analysis, and the data were as follows:

[0047] 1H NMR (600MHz, CDCl3) δ7.83-7.79 (m, 4H), 7.18-7.15 (m, 4H), 3.36 (d, J = 10.0Hz, 2H), 1.06 (s, 9H).

[0048] 13 C NMR (150MHz, CDCl3) δ165.2 (dd, J1=252.0Hz, J2=3.0Hz), 134.0 (t, J=9.0Hz), 128.0 (dd, J1=102.0 Hz, J2=3.0Hz), 116.1 (dd, J1=21.0Hz, J2=12.0Hz), 51.4 (d, J=13.5Hz), 43.2 (d, J=87.0Hz), 29.1.

[0049] 19 F NMR (564MHz, CDCl3) δ-106.5.

[0050] 31 P NMR (243 MHz, CDCl3) δ 29.1.

[0051] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 21 F2NOP + 324.1323,Found:324.1323.

[0052] Example 5

[0053] 2-isocyano-2-methylpropane (0.2mmol), bis(3-methoxyphenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the reaction solution was diluted with water, extracted with ethyl acetate, and the organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was removed by rotation, and the residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 38% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0054] The structural formula of the target product is as follows:

[0055] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0056] 1 H NMR (400MHz, CDCl3) δ7.45-7.41(m,2H),7.39-7.34(m,2H),7.32-7.28(m,2H),7.06-7.03(m,2H),3.82(s,6H),3.38(d,J=9.8Hz,2H),1.08(s,9H).

[0057] 13 C NMR (100MHz, CDCl3) δ159.7(d,J=14.0Hz), 133.5(d,J=97.0Hz), 129.8(d,J=14.0Hz), 123.5(d,J=9 .0Hz), 118.4 (d, J = 2.0Hz), 116.2 (d, J = 9.0Hz), 55.6, 51.3 (d, J = 14.0Hz), 43.0 (d, J = 84.0Hz), 28.6.

[0058] 31 P NMR (162 MHz, CDCl3) δ 30.7.

[0059] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 27 NO3P + 348.1723,Found:348.1723.

[0060] Example 6

[0061] 2-isocyano-2-methylpropane (0.2mmol), di-p-methylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 56% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0062] The structural formula of the target product is as follows:

[0063] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0064] 1H NMR (600MHz, CDCl3) δ7.68 (dd, J1=11.1Hz, J2=8.0Hz, 4H), 7.27-7.25 (m, 4H), 3.35 (d, J=9.9Hz, 2H), 2.39 (s, 6H), 1.06 (s, 9H).

[0065] 13 C NMR (100MHz, CDCl3) δ142.3 (d, J = 3.0Hz), 131.5 (d, J = 9.0Hz), 129.4 (d, J = 12.0 Hz), 129.2 (d, J = 101.0Hz), 51.3 (d, J = 14.0Hz), 43.0 (d, J = 84.0Hz), 28.6, 21.7.

[0066] 31 P NMR (162 MHz, CDCl3) δ 30.7.

[0067] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 27 NOP + 316.1825,Found:316.1808.

[0068] Example 7

[0069] 2-isocyano-2-methylpropane (0.2mmol), dibenzylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a light red solid. The yield of the target product was 45% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0070] The structural formula of the target product is as follows:

[0071] The above light red solid was subjected to nuclear magnetic spectrum and mass spectrum analysis, and the data are as follows:

[0072] 1H NMR (400MHz, CDCl3) δ7.34-7.26 (m, 10H), 3.28-3.12 (m, 4H), 2.72 (d, J = 9.3Hz, 2H), 1.02 (s, 9H).

[0073] 13 C NMR (100MHz, CDCl3) δ 132.0 (d, J = 6.0Hz), 130.0 (d, J = 6.0Hz), 129.0 (d, J = 3.0Hz), 127.1 (d, J = 3.0Hz), 34.7, 34.1, 29.9, 28.5.

[0074] 31 P NMR (243 MHz, CDCl3) δ 44.6.

[0075] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 27 NOP + 316.1825,Found:316.1826.

[0076] Example 8

[0077] 2-isocyano-2-methylpropane (0.2mmol), bis(3-fluorophenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 72% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0078] The structural formula of the target product is as follows:

[0079] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0080] 1 H NMR (400MHz, CDCl3) δ7.60-7.52 (m, 4H), 7.50-7.44 (m, 2H), 7.26-7.22 (m, 2H), 3.40 (d, J = 9.8Hz, 2H), 1.08 (s, 9H).

[0081] 13 C NMR (150MHz, CDCl3) δ 162.7 (dd, J1 = 249.0Hz, J2 = 16.5Hz), 134.4 (dd, J1 = 97.5Hz, J2 = 6.0Hz), 130.8 (dd, J1 = 13.5Hz, J2 = 7.5Hz), 127.1 (dd, J1=7.5Hz, J2=3.0Hz), 119.5 (dd, J1=21.0Hz, J2=1.5Hz), 118.4 (dd, J1=22.5Hz, J2=10.5Hz), 51.5 (d, J=13.5Hz), 42.8 (d, J=87.0Hz), 28.5.

[0082] 19 F NMR (564MHz, CDCl3) δ-110.8.

[0083] 31 P NMR (243 MHz, CDCl3) δ 28.4.

[0084] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 21 F2NOP + 324.1323,Found:324.1323.

[0085] Example 9

[0086] 2-isocyano-2-methylpropane (0.2mmol), bis(4-methoxyphenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 65% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0087] The structural formula of the target product is as follows:

[0088] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0089] 1H NMR (400MHz, CDCl3) δ 7.74-7.68 (m, 4H), 6.97-6.94 (m, 4H), 3.83 (s, 6H), 3.32 (d, J = 10.1Hz, 2H), 1.06 (s, 9H).

[0090] 13 C NMR (100MHz, CDCl3) δ162.5 (d, J = 3.0Hz), 133.3 (d, J = 10.0Hz), 123.7 (d, J = 105 .0Hz), 114.1 (d, J = 13Hz), 55.4, 51.3 (d, J = 14.0Hz), 43.2 (d, J = 85.0Hz), 28.6.

[0091] 31 P NMR (162 MHz, CDCl3) δ 30.4.

[0092] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 27 NO3P + 348.1723,Found:348.1723.

[0093] Example 10

[0094] 2-isocyano-2-methylpropane (0.2mmol), dimethylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 81% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0095] The structural formula of the target product is as follows:

[0096] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0097] 1H NMR (400MHz, CDCl3) δ7.66 (d, J = 11.8 Hz, 2H), 7.55-7.52 (m, 2H), 7.35-7.31 (m, 4H), 3.37 (d, J = 9.6 Hz, 2H), 2.37 (s, 6H), 1.07 (s, 9H).

[0098] 13 C NMR (100MHz, CDCl3) δ138.5 (d, J = 12.0Hz), 132.7 (d, J = 3.0Hz), 132.1 (d, J = 98.0Hz), 131.9 (d, J = 8. 0Hz), 128.5 (d, J = 12.0Hz), 128.3 (d, J = 9.0Hz), 51.4 (d, J = 13.0Hz), 42.8 (d, J = 84.0Hz), 28.5, 21.5.

[0099] 31 P NMR (162 MHz, CDCl3) δ 30.6.

[0100] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 27 NOP + 316.1825,Found:316.1825.

[0101] Embodiment 11

[0102] 2-isocyano-2-methylpropane (0.2mmol), bis(4-chlorophenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 51% based on the molar amount of 2-isocyano-2-methylpropane as 100%.

[0103] The structural formula of the target product is as follows:

[0104] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0105] 1H NMR (400MHz, CDCl3) δ7.73 (dd, J1 = 10.8Hz, J2 = 2.4Hz, 4H), 7.45 (dd, J1 = 8.5Hz, J2 = 2.2Hz, 4H), 3.36 (d, J = 9.9Hz, 2H), 1.06 (s, 9H).

[0106] 13 C NMR (100MHz, CDCl3) δ 138.9 (d, J = 3.0Hz), 132.8 (d, J = 10.0Hz), 130.3 (d, J = 99.0Hz), 129.1 (d, J = 12.0Hz), 51.4 (d, J = 15.0Hz), 42.9 (d, J = 86.0Hz), 28.6.

[0107] 31 P NMR (162 MHz, CDCl3) δ 29.2.

[0108] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 21 Cl2NOP + 356.0732,Found:356.0767.

[0109] Example 12

[0110] In a 10mL reaction tube equipped with a magnetic device, 2-methyl isocyanate (0.2mmol), diphenylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added in sequence, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added for dilution, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 68% based on the molar amount of 2-methyl isocyanate as 100%.

[0111] The structural formula of the target product is as follows:

[0112] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0113] 1H NMR (600MHz, CDCl3) δ7.82-7.79(m,4H),7.56-7.53(m,2H),7.50-7.47(m,4H),3.70(s,3H),3.55(d,J=7.8Hz,2H),3.51(s,2H).

[0114] 13 C NMR (100MHz, CDCl3) δ172.4, 132.2 (d, J = 2.0Hz), 131.7 (d, J = 98.0Hz), 131.3 (d , J=9.0Hz), 128.9 (d, J=12.0Hz), 52.0, 51.8 (d, J=13.0Hz), 49.0 (d, J=82.0Hz).

[0115] 31 P NMR (162 MHz, CDCl3) δ 29.1.

[0116] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 16 H 19 NO3P + 304.1097,Found:304.1095.

[0117] Example 13

[0118] To a 10mL reaction tube equipped with a magnetic electron, ethyl 2-isocyanate (0.2mmol), diphenylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added in sequence, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a light yellow oil. The yield of the target product was 74% based on the molar amount of ethyl 2-isocyanate as 100%.

[0119] The structural formula of the target product is as follows:

[0120] The above light yellow oil was subjected to NMR and mass spectrometry analysis, and the data are as follows:

[0121] 1H NMR (400MHz, CDCl3) δ7.83-7.78(m,4H),7.55-7.51(m,2H),7.49-7.45(m,4H),4 .15(q,J=7.1Hz,2H),3.55(d,J=7.8Hz,2H),3.48(s,2H),1.24(t,J=7.1Hz,3H).

[0122] 13 C NMR (100MHz, CDCl3) δ 171.9, 132.21, 132.18, 131.3, (d, J = 9.0Hz), 131.2, 128.8 (d, J = 11.0Hz), 61.0, 52.0 (d, J = 13.0Hz), 49.0 (d, J = 82.0Hz), 14.3.

[0123] 31 P NMR (162 MHz, CDCl3) δ 29.0.

[0124] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 21 NO3P + 318.1254,Found:318.1254.

[0125] Embodiment 14

[0126] 2-isocyano-3-phenylpropionic acid benzyl ester (0.2mmol), diphenylphosphine oxide (0.4mmol), N, N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added for dilution, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 48% based on the molar amount of 2-isocyano-3-phenylpropionic acid benzyl ester as 100%.

[0127] The structural formula of the target product is as follows:

[0128] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0129] 11H NMR (600 MHz, CDCl3) δ 7.71 - 7.65 (m, 4H), 7.53 - 7.50 (m, 2H), 7.42 - 7.38 (m, 4H), 7.35 - 7.32 (m, 3H), 7.2 (dd, J1 = 7.6 Hz, J2 = 2.8 Hz, 2H), 7.21 - 7.20 (m, 3H), 7.05 - 7.04 (m, 2H), 5.11 - 5.07 (m, 2H), 3.63 - 3.61 (m, 1H), 3.55 (q, J = 7.1 Hz, 1H), 3.25 (dd, J1 = 14.2 Hz, J2 = 11.2 Hz, 1H), 2.97 (dd, J1 = 13.7 Hz, J2 = 6.0 Hz, 1H), 2.84 (dd, J1 = 13.7 Hz, J2 = 7.7 Hz, 1H).

[0130] 13 13C NMR (150 MHz, CDCl3) δ 173.5, 137.1, 135.5, 132.1, 131.48 (d, J = 99.0 Hz), 131.45 (d, J = 4.5 Hz), 131.4 (d, J = 3.0 Hz), 129.4, 128.7 (d, J = 1.5 Hz), 128.62, 128.55, 128.53, 126.8, 66.8, 64.37 (d, J = 13.5 Hz), 47.9 (d, J = 82.5 Hz), 39.4.

[0131] 31 31P NMR (243 MHz, CDCl3) δ 28.7.

[0132] HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 29 H 29 NO3P + 470.1880, Found: 470.1876.

[0133] Example 15

[0134] 2-isocyano-4-methylpentanoic acid methyl ester (0.2mmol), diphenylphosphine oxide (0.4mmol), N, N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, the reaction solution was extracted with ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, the organic phase was removed by rotation, and the residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 48% based on the molar amount of 2-isocyano-4-methylpentanoic acid methyl ester as 100%.

[0135] The structural formula of the target product is as follows:

[0136] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0137] 1 H NMR (600MHz, CDCl3) δ7.84-7.73(m,4H),7.56-7.50(m,2H),7.49-7.43(m,4H),3.68(s,3H),3.57(dd,J1=14.2Hz, J2=6.7Hz,1H),3.34-3.23(m,2H),1.70-1.60(m,1H),1.41(t,J=7.1Hz,2H),0.82(dd,J1=13.4Hz, J2=6.8Hz,6H).

[0138] 13 C NMR (100MHz, CDCl3) δ 175.4, 132.1 (dd, J1 = 8.0Hz, J2 = 3.0Hz), 131.8 (d, J = 122Hz), 131.4 (dd, J1 = 8.0Hz, J2 = 2.0Hz), 128.7 (dd, J1 = 11.0Hz, J2 = 2.0Hz), 61.4 (d, J = 14Hz), 51.9, 47.8 (d, J = 11Hz), 42.3, 24.8, 23.0, 21.9.

[0139] 31 P NMR (162 MHz, CDCl3) δ 29.1.

[0140] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 27 NO3P +360.1723,Found:360.1723.

[0141] Example 16

[0142] 2-isocyano-3-phenylpropionic acid benzyl ester (0.2mmol), dimethylphosphine oxide (0.4mmol), N, N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a colorless oil. The yield of the target product was 51% based on the molar amount of 2-isocyano-3-phenylpropionic acid benzyl ester as 100%.

[0143] The structural formula of the target product is as follows:

[0144] The colorless oil was analyzed by NMR and mass spectrometry, and the data are as follows:

[0145] 1 H NMR (600MHz, CDCl3) δ7.58 (dd, J1=27.5Hz, J2=11.8Hz, 2H), 7.44-7.41 (m, 2H), 7.32-7.27 (m,7H),7.23-7.22(m,2H),7.19-7.18(m,3H),7.04-7.03(m,2H),5.10-5.06(m,2H),3.63 (t, J=6.8Hz, 1H), 3.53 (dd, J1=14.2Hz, J2=6.8Hz, 1H), 3.25 (dd, J1=14.0Hz, J2=11.0Hz, 1 H), 2.95 (dd, J1 = 13.6Hz, J2 = 6.2Hz, 1H), 2.87 (dd, J1 = 13.6Hz, J2 = 7.3Hz, 1H), 2.35 (s, 6H).

[0146] 13C NMR (150MHz, CDCl3) δ173.5,138.6 (dd, J1=12Hz, J2=3.0Hz),137.1,135.6,1 32.9(t,J=3.0Hz),132.0-131.9(m),131.6(dd,J1=97.5Hz, J2=34.5Hz),129. 3,128.7,128.6(d,J=3.0Hz),128.52,128.50,128.47,128.3(dd,J1=18.0Hz, J2=9.0Hz), 126.8, 66.8, 64.3 (d, J=13.5Hz), 47.9 (d, J=82.5Hz), 39.4, 21.6.

[0147] 31 P NMR (243 MHz, CDCl3) δ 27.3.

[0148] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 31 H 33 NO3P + 498.2193,Found:498.2178.

[0149] Embodiment 17

[0150] 2-isocyano-4-methylpentanoic acid methyl ester (0.2mmol), dimethylphosphine oxide (0.4mmol), N, N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic electron, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, the mixture was diluted with water, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a white solid. The yield of the target product was 48% based on the molar amount of 2-isocyano-4-methylpentanoic acid methyl ester as 100%.

[0151] The structural formula of the target product is as follows:

[0152] The white solid was subjected to NMR and mass spectrometry analysis, and the data were as follows:

[0153] 11H NMR (600 MHz, CDCl3) δ 7.65 (dd, J1 = 23.2 Hz, J2 = 11.8 Hz, 2H), 7.58 - 7.55 (m, 1H), 7.50 - 7.47 (m, 1H), 7.37 - 7.33 (m, 4H), 3.69 (s, 3H), 3.55 (dd, J1 = 14.2 Hz, J2 = 6.6 Hz, 1H), 3.33 (t, J = 7.2 Hz, 1H), 3.25 (dd, J1 = 14.2 Hz, J2 = 10.5 Hz, 1H), 2.38 (d, J = 5.3 Hz, 6H), 1.71 - 1.64 (m, 1H), 1.42 (t, J = 7.1 Hz, 2H), 0.88 (dd, J1 = 18.0 Hz, J2 = 6.7 Hz, 6H).

[0154] 13 13C NMR (150 MHz, CDCl3) δ 175.5, 138.6 (q, J = 6 Hz), 132.9 (dd, J1 = 13.5 Hz, J2 = 3 Hz,), 132.0 (d, J = 7.5 Hz), 131.7 (dd, J1 = 97.5 Hz, J2 = 42.0 Hz), 128.5 (q, J = 6.0 Hz), 128.3 (dd, J1 = 9.0 Hz, J2 = 1.5 Hz), 61.4 (d, J = 15.0 Hz), 51.9, 47.8 (d, J = 84.0 Hz), 42.3, 24.8, 23.0, 21.9, 21.5.

[0155] 31 31P NMR (243 MHz, CDCl3) δ 29.3.

[0156] HRMS (ESI - TOF) m / z: [M + H] + Calcd for C 22 H 31 NO3P + 388.2036, Found: 388.2034.

[0157] Example 18

[0158] To a 10mL reaction tube equipped with a magnetic electron, ethyl 2-isocyanate (0.2mmol), di-p-methylphosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added in sequence, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a colorless oil. The yield of the target product was 46% based on the molar amount of ethyl 2-isocyanate as 100%.

[0159] The structural formula of the target product is as follows:

[0160] The colorless oil was analyzed by NMR and mass spectrometry, and the data are as follows:

[0161] 1 H NMR (400MHz, CDCl3) δ7.68 (dd, J=11.2Hz, 8.1Hz, 4H), 7.29-7.26 (m, 4H), 4.16 (q, J= 7.1Hz, 2H), 3.50 (d, J = 7.9Hz, 2H), 3.48 (s, 2H), 2.39 (s, 6H), 1.25 (t, J = 7.1Hz, 3H).

[0162] 13 C NMR (100MHz, CDCl3) δ172.0, 142.6 (d, J = 2.0Hz), 131.4, (d, J = 9.0Hz), 129.6 (d, J = 12. 0Hz), 128.6 (d, J = 101.0Hz), 61.0, 52.1 (d, J = 13.0Hz), 49.1 (d, J = 81.0Hz), 21.8, 14.4.

[0163] 31 P NMR (162 MHz, CDCl3) δ 29.4.

[0164] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 25 NO3P + 346.1567,Found:346.1567.

[0165] Embodiment 19

[0166] 2-isocyano-3-phenylpropionic acid benzyl ester (0.2mmol), bis(4-methoxyphenyl)phosphine oxide (0.4mmol), N,N-diisopropylethylamine (0.4mmol) and 4-CzIPN (5mol% equivalent) were added to a 10mL reaction tube equipped with a magnetic device, followed by the addition of solvent acetonitrile (2mL) and water (20μL). The reaction was carried out at room temperature for 12 hours under air conditions and irradiation of a 405nm blue LED lamp. After the reaction was completed, water was added to dilute the mixture, and the reaction solution was extracted with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate, and the organic phase was removed by rotation. The residue was separated by column chromatography to obtain the target product, which was a colorless oil. The yield of the target product was 40% based on the molar amount of 2-isocyano-3-phenylpropionic acid benzyl ester as 100%.

[0167] The structural formula of the target product is as follows:

[0168] The colorless oil was analyzed by NMR and mass spectrometry, and the data are as follows:

[0169] 1 H NMR (600MHz, CDCl3) δ7.62-7.55(m,4H),7.35-7.31(m,3H),7.24-7.23(m,2H),7 .21-7.20(m,3H),7.05-7.04(m,2H),6.90-6.87(m,4H),5.09(t,J=12.6,2H),3.8 4(s,6H),3.59(t,J=6.8,1H),3.50-3.46(m,1H),3.17(dd,J1=13.7Hz, J2=11.8H z, 1H), 2.96 (dd, J1 = 13.6Hz, J2 = 6.0Hz, 1H), 2.83 (dd, J1 = 13.6Hz, J2 = 7.7Hz, 1H).

[0170] 13 C NMR (150MHz, CDCl3) δ173.6,162.5,137.2,135.6,133.3(d,J=10.5Hz),129.4,128.7,128.6,128.5,126.8,123.1(dd,J1=10 5Hz, J2=58.5Hz), 114.2 (dd, J1=12.0Hz, J2=3.0Hz), 66.8, 64.4 (d, J=13.5Hz), 55.4 (d, J=1.5Hz), 48.3 (d, J=84.0Hz), 39.4.

[0171] 31 P NMR (243 MHz, CDCl3) δ 28.6.

[0172] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 31 H 33 NO5P + 530.2091,Found:530.2069.

[0173] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for illustrating the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds, characterized in that The specific process is: using isocyanide compounds and diphenylphosphine oxide compounds as starting materials, in the presence of additives and catalysts, using acetonitrile and water as a mixed solvent, reacting under blue light illumination at room temperature under air conditions, evaporating the solvent after the reaction, extracting the reaction solution with ethyl acetate, drying, and spinning off the organic phase, and separating the residue by column chromatography to obtain the target product ((alkylamino)methyl)diphenylphosphine oxide compounds, wherein the additive is one or more of triethylamine, N,N-diisopropylethylamine DIPEA, 1,8-diazabicycloundec-7-ene DBU or tetramethylethylenediamine TMEDA, the catalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4-CzIPN, the structural formula of the isocyanide compound is shown in Formula A, the structural formula of the diphenylphosphine oxide compound is shown in Formula B, and the structural formula of the ((alkylamino)methyl)diphenylphosphine oxide compound is shown in Formula C: The specific structural formula of formula C is: The substituent R1 in formula A and the substituent R2 in formula B are defined the same as the substituent R1 and R2 in formula C.

2. The photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds according to claim 1, characterized in that: The molar ratio of the isocyanate compound, the diphenylphosphine oxide compound, the catalyst and the additive is 1:1-3:1%-10%:1-3.

3. The photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds according to claim 1, characterized in that: The volume ratio of acetonitrile to water in the mixed solvent is 200:1-50:

1.

4. The photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds according to claim 1, characterized in that The reaction equation in the preparation process of the ((alkylamino)methyl)diphenylphosphine oxide compounds is: The structural formula of the catalyst 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4-CzIPN is:

5. The photocatalytic preparation method of ((alkylamino)methyl)diphenylphosphine oxide compounds according to claim 1, characterized in that: The blue light source during the reaction is a blue LED lamp with a wavelength of 405nm and a power of 10W.

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