Preparation method of P-Betti alkali compound

Abstract

The invention discloses a preparation method of a P-Betti alkali compound, and belongs to the technical field of organic synthesis. The method disclosed by the invention comprises the following steps: mixing 2-benzylidene-cyclohex-3-ene-1-ketone, diaryl phosphine oxide, alkali and an organic solvent, and carrying out a reaction on the 2-benzylidene-cyclohex-3-ene-1-ketone, the diaryl phosphine oxide, the alkali and the organic solvent; after the reaction is finished, carrying out acid washing, then drying an organic phase, and evaporating to remove a solvent to obtain a mixture containing an allyl phosphine oxide compound; then adding copper bromide and acetonitrile into the allyl phosphine oxide for reaction; and after the reaction is finished, evaporating to remove the solvent, separating and purifying residues, eluting with an eluent, evaporating the eluent to remove the solvent, and drying to obtain the P-Betti alkali compound. The P-Betti alkali synthesis method is high in innovation, mild in reaction condition, high in operation convenience and excellent in functional group compatibility, and the obtained P-Betti alkali compound with the diversified structure is an important organic synthesis intermediate and can also serve as a potential P, O-bidentate ligand to optimize the catalytic performance of transition metal.

Description

Technical Field

[0001] This invention relates to a method for preparing P-Betti base compounds, belonging to the field of organic synthesis technology. Background Technology

[0002] Betti bases are a class of α-aminomethylphenol products generated through the Betti reaction (a three-component condensation reaction of aromatic or aliphatic aldehydes, phenols, and primary or secondary amines). These compounds have attracted much attention due to their important applications in medicinal chemistry, asymmetric catalysis, and organic synthesis. Introducing phosphine structural units into the Betti base molecular skeleton to replace the amino group yields phosphorus-containing Betti base derivatives—P-Betti bases. Studies have shown that flame-retardant resins synthesized from P-Betti base monomers exhibit good heat resistance and hydrolysis resistance. As a class of multifunctional compounds, the abundant chemical transformation characteristics of the phenolic hydroxyl groups and phosphine oxygen fragments in P-Betti bases can be used to efficiently construct complex molecular systems. Simultaneously, the unique P,O-bident ligand structure of these compounds provides new insights into optimizing the coordination environment of transition metal catalysts, contributing to improved catalytic activity and selectivity.

[0003] However, the currently reported methods for synthesizing P-Betti bases have significant limitations: on the one hand, there are relatively few reported synthetic strategies for P-Betti bases, mainly including: (1) the classic Betti reaction involving phosphine nucleophiles (Tetrahedron Letters, 2015, 56, 5054-5056); (2) the Michael addition reaction involving phosphine nucleophiles (Organic Letters, 2017, 19, 5988-5991; Molecules 2018, 23, 1240; Organic Letters, 2018, 20, 7229-7233); on the other hand, the substrates are mainly limited to o-methylenebenzoquinone generated in situ from 2-hydroxybenzyl alcohol or 2-hydroxybenzyl sulfone, which leads to the need to improve the efficiency and universality of the synthetic methods. Therefore, it is necessary to find a new method for preparing P-Betti base compounds. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing P-Betti base compounds. This method, using mild reaction conditions and simple operation, prepares P-Betti base compounds with high functional group tolerance. These compounds are not only important intermediates in organic synthesis but also potential P,O-bident ligands for optimizing the catalytic performance of transition metals. The method specifically includes the following steps:

[0005] (1) Mix 2-benzyl-cyclohexyl-3-en-1-one and diarylphosphine oxide, base and organic solvent and react them; after the reaction is complete (preferably by thin-layer chromatography to detect whether the reaction of the raw materials is complete), wash the reaction solution with acid (preferably with 1 mol / L citric acid twice), then dry the organic phase (preferably anhydrous sodium sulfate as a drying agent), and evaporate the solvent to obtain a mixture containing allylphosphine oxide (preferably by vacuum evaporation).

[0006] (2) Add copper bromide and acetonitrile to the allylphosphine oxide compound and react; after the reaction is completed (preferably by thin-layer chromatography to detect whether the reaction is completed), evaporate the solvent, separate and purify the residue (preferably by silica gel column chromatography), elute with eluent, evaporate the solvent from the eluent and dry it to obtain the P-Betti base compound.

[0007] Preferably, the preparation of 2-benzylidene-cyclohexyl-3-en-1-one in step (1) of the present invention is carried out by conventional methods, using cyclohexenone-MBH alcohol (an alcohol compound prepared by the Morita-Baylis-Hillman reaction) and di-tert-butyl dicarbonate as reactants, and 4-dimethylaminopyridine as a catalyst. The structural formula of 2-benzylidene-cyclohexyl-3-en-1-one is as follows:

[0008]

[0009] Wherein, R group is a phenyl group or a mono- or di-substituted phenyl group of one of the following groups: methyl, halogen, methoxy, phenyl, cyano, 2-naphthyl, 2-thienyl, cyclohexyl.

[0010] Preferably, the structural formula of the diarylphosphine oxide in step (1) of the present invention is:

[0011]

[0012] The Ar group is either phenyl or 1-naphthyl.

[0013] Preferably, in step (1) of the present invention, the alkali is one of cesium carbonate, potassium tert-butoxide, potassium hydroxide, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0014] Preferably, in step (1) of the present invention, the organic solvent is one of the following: ethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile, methanol, toluene, trifluorotoluene, N,N-dimethylformamide, and dichloroethane.

[0015] Preferably, in step (1) of the present invention, the molar ratio of 2-benzyl-cyclohexyl-3-en-1-one, diarylphosphine oxygen and base is 1:(1.2~2.5):(1.2~2.5), wherein the concentration of 2-benzyl-cyclohexyl-3-en-1-one is 0.05~0.2mol / L.

[0016] Preferably, the reaction conditions in step (1) of the present invention are: reacting at 0 to 40°C for 0.5 to 2 hours.

[0017] Preferably, the theoretical molar ratio of allylphosphine oxide and copper bromide in step (2) of the present invention is 1:2 (since the mixture containing allylphosphine oxide obtained in step (1) is not a pure substance, the theoretical value of the allylphosphine oxide content is used when adding drugs in the subsequent process, and the actual allylphosphine oxide content is lower than the theoretical value).

[0018] Preferably, the theoretical concentration of allylphosphine oxide in step (2) of the present invention is 0.05 mol / L.

[0019] Preferably, the reaction temperature in step (2) of the present invention is 80°C and the reaction time is 2h.

[0020] Preferably, the eluent in step (2) of the present invention is prepared in a volume ratio of petroleum ether to ethyl acetate of 1:1.

[0021] Mechanism of the invention:

[0022] Diarylphosphine oxide (III) first loses a proton to a basic reagent, and the resulting p-nucleophile undergoes p-Micheal addition with 2-benzyl-cyclohex-3-en-1-one (II), followed by intracyclic double bond migration to generate allylphosphine oxide (IV). This intermediate undergoes α-bromination of the cyclohexenone fragment, HBr elimination, and keto-enol tautomerism in the presence of copper bromide to generate a p-Betti base (I). The reaction equation is as follows:

[0023]

[0024] The beneficial effects of this invention are:

[0025] Unlike the reaction materials reported in current related technologies, this invention uses 2-benzyl-cyclohexyl-3-en-1-one as the reactant to synthesize P-Betti base compounds through a two-step reaction of base-mediated P-Michael addition and copper bromide oxidation-phenolization. This not only serves as an important organic synthesis intermediate but also as a potential P,O-bident ligand to optimize the catalytic performance of transition metals. The synthetic method uses readily synthesized raw materials, has mild reaction conditions, and exhibits excellent functional group tolerance, providing a novel synthetic method for P-Betti base compounds. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited to the content described.

[0027] Example 1

[0028] Preparation of [(2-hydroxyphenyl)(phenyl)methyl]diphenylphosphine oxide (Ia):

[0029]

[0030] (1) 2-Benzylene-cyclohexyl-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-benzylene-cyclohexyl-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture containing 0.2 mmol of allylphosphine oxide compound IV-a.

[0031] (2) Allylphosphine oxide compound IV-a was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-a 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ia). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ia) showed that the invention successfully prepared P-Betti base compound (Ia). The reaction yield, product appearance and melting point were tested and characterized. White solid; 56.9 mg, 74% total yield; mp 260-263℃; 1 H NMR (400MHz, CDCl3) δ10.57(s,1H),7.74(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,1H),7.58(d,J=8.0Hz,1H),7.55(d,J=4.0Hz,1H),7.48-7 .43(m,2H),7.40-7.33(m,6H),7.17-7.13(m,3H),7.10-7.05(m,2H),6.90(d,J=8.0Hz,1H),6.71-6.68(m,1H),4.82(d,J=12.0Hz,1H);13 C NMR (100MHz, Methanol-d4) δ155.7(d,Jc-p=8.0Hz), 137.9(d,Jc-p=5.0Hz), 133.9(d,Jc-p=29.0Hz), 132.9(d,J c-p=29.0Hz), 132.9(d,Jc-p=9.0Hz), 132.8(d,Jc-p=3.0Hz), 132.2(d,Jc-p=9.0Hz), 132.1(d,Jc-p=9.0Hz), 13 1.6(d,Jc-p=5.0Hz), 131.3(d,Jc-p=7.0Hz), 129.5(d,Jc-p=1.0Hz), 129.4(d,Jc-p=2.0Hz), 129.3(d,Jc-p=1.0 Hz), 129.2 (d, Jc-p = 2.0Hz), 127.9 (d, Jc-p = 2.0Hz), 125.3 (d, Jc-p = 4.0Hz), 120.6, 116.1, 44.8 (d, Jc-p = 69Hz); 31 P NMR(162MHz,Methanol-d4)δ35.5(s).IR(KBr):ν3062,2926,1486,1436,1154,1096,718,691,528cm -1 .HRMS(ESI,m / z):calcd.for C 25 H 21 O₂P + Na [M + Na] + 407.1177, found 407.1183.

[0032] Example 2

[0033] Preparation of [(2-hydroxyphenyl)(o-tolyl)methyl]diphenylphosphine oxide (Ib):

[0034]

[0035] (1) 2-(2-methylbenzyl)cyclohexane-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(2-methylbenzyl)cyclohexane-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture containing 0.2 mmol of allylphosphine oxide compound IV-b.

[0036] (2) Allylphosphine oxide compound IV-b and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-b 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ib). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ib) showed that the invention successfully prepared P-Betti base compound (Ib). The reaction yield, product appearance and melting point were tested and characterized. White solid; 25.5 mg, 32% total yield; mp 285-288℃; 1 H NMR (400MHz, CDCl3) δ8.04(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,1H),7.67(d,J=8.0Hz,1H),7.49-7.35(m,6H),7.32-7.26(m,2H),7.16- 7.12(m,2H),7.10-7.03(m,2H),6.97(d,J=8.0Hz,1H),6.89(d,J=8.0Hz,1H),6.71-6.67(m,1H),5.17(d,J=12.0Hz,1H),2.05(s,3H); 13 C NMR (100MHz, Pyridine-d5) δ155.7(d,Jc-p=7.0Hz), 137.4(d,Jc-p=8.0Hz), 137.0(d,Jc-p=4.0Hz ),134.5(d,Jc-p=72.0Hz), 133.6(d,Jc-p=74.0Hz), 131.9(d,Jc-p=6.0Hz), 131.7(d,Jc-p=9.0Hz ),131.4(d,Jc-p=12.0Hz),131.4,131.2(d,Jc-p=5.0Hz),130.3,128.3(d,Jc-p=7.0Hz),128.2(d ,Jc-p=8.0Hz),126.9,126.1,125.1(d,Jc-p=4.0Hz),119.6,115.4,39.4(d,Jc-p=68.0Hz),20.0; 31 P NMR(162MHz, CDCl3)δ38.8(s).IR(KBr):ν3039,2954,1456,1438,1157,1112,746,697cm -1.HRMS(ESI,m / z):calcd.for C 26 H 23 O₂P + Na [M + Na] + 421.1333, found 421.1339.

[0037] Example 3

[0038] Preparation of [(2-hydroxyphenyl)(m-chlorophenyl)methyl]diphenylphosphine oxide (Ic):

[0039]

[0040] (1) 2-(3-chlorobenzyl)cyclohexyl-3-en-1-one, diphenylphosphine oxide, and potassium tert-butoxide were mixed in a molar ratio of 1:2:2.5. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(3-chlorobenzyl)cyclohexyl-3-en-1-one was added and the mixture was reacted at 30 °C for 0.5 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-c containing a theoretical amount of 0.2 mmol.

[0041] (2) Allylphosphine oxide compound IV-c and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-c 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ic). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ic) showed that the invention successfully prepared P-Betti base compound (Ic). The reaction yield, product appearance and melting point were tested and characterized. White solid; 48.6 mg, 58% total yield; mp 256-261℃; 1H NMR (400MHz, CDCl3) δ10.36(s,1H),7.74(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,1H),7.60(d,J=4.0Hz,1H),7.58(d,J=8.0Hz,1H),7.52 -7.44(m,2H),7.41-7.34(m,5H),7.23(s,1H),7.13-7.06(m,4H),6.91(d,J=8.0Hz,1H),6.73-6.69(m,1H),4.78(d,J=12.0Hz,1H); 13 C NMR (100MHz, Pyridine-d5) δ156.5(d,Jc-p=8.0Hz), 141.3(d,Jc-p=4.0Hz), 134.9(d,Jc-p=12.0Hz), 134.6,133.9(d,Jc-p=13.0Hz), 132.3(d,Jc-p=3.0Hz), 132.1(d,Jc-p=8.0Hz), 132.0(d,Jc-p=7.0Hz) ,131.8(d,Jc-p=5.0Hz),131.2(d,Jc-p=6.0Hz),130.6,129.8(d,Jc-p=6.0Hz),129.4,129.3(d,Jc-p =5.0Hz),129.2(d,Jc-p=5.0Hz),127.7,125.8(d,Jc-p=3.0Hz),120.5,116.5,44.3(d,Jc-p=68.0Hz); 31 P NMR(162MHz, CDCl3)δ38.0(s).IR(KBr):ν3054,2928,1591,1457,1437,1155,1106,753,719,691,570cm -1 .HRMS(ESI,m / z):calcd.for C 25 H 20 ClO₂P + Na [M + Na] + 441.0787, found 441.0782.

[0042] Example 4

[0043] Preparation of [(2-hydroxyphenyl)(p-methoxyphenyl)methyl]diphenylphosphine oxide (Id):

[0044]

[0045] (1) 2-(4-methoxybenzyl)cyclohexyl-3-en-1-one, diphenylphosphine oxide, and tetramethylguanidine were mixed in a molar ratio of 1:1.5:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.05 mol / L based on the concentration of 2-(4-methoxybenzyl)cyclohexyl-3-en-1-one was added and the mixture was reacted at 30 °C for 2 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-d containing a theoretical amount of 0.2 mmol.

[0046] (2) Allylphosphine oxide compound IV-d was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-d 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Id). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Id) showed that the invention successfully prepared P-Betti base compound (Id). The reaction yield, product appearance and melting point were tested and characterized. White solid; 34.8 mg, 42% total yield; mp 225-228℃; 1 H NMR (400MHz, CDCl3) δ10.48(s,1H),7.73(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,1H),7. 60(d,J=8.0Hz,1H),7.57(d,J=8.0Hz,1H),7.48-7.41(m,2H),7.38-7.33(m,4H),7. 29(d,J=8.0Hz,2H),7.11(d,J=4.0Hz,1H),7.07-7.03(m,1H),6.90(d,J=8.0Hz,1H) ,6.70(d,J=8.0Hz,1H),6.68(d,J=8.0Hz,2H),4.82(d,J=12.0Hz,1H),3.69(s,3H); 13C NMR (100MHz, CDCl3) δ158.7(d,Jc-p=2.0Hz), 155.7(d,Jc-p=4.0Hz), 132.3, 132.2(d,Jc-p=3.0Hz), 132.2(d,Jc-p=4.0Hz), 131.5(d,Jc-p=9.0Hz), 131.3(d,Jc-p=9.0Hz), 131.1(d,Jc-p=21.0Hz), 131 .0(d,Jc-p=6.0Hz),130.2(d,Jc-p=22.0Hz),129.2,128.6(d,Jc-p=20.0Hz),128.6(d,Jc-p=20.0Hz ), 127.8 (d, Jc-p = 4.0Hz), 124.0 (d, Jc-p = 4.0Hz), 120.4, 119.7, 114.0, 55.3, 52.2 (d, Jc-p = 65.0Hz); 31 P NMR(162MHz, CDCl3)δ38.4(s).IR(KBr):ν3066,3014,1508,1456,1439,1244,1151,1027,744,699,560cm -1 .HRMS(ESI,m / z):calcd.for C 26 H 23 O3P + Na [M + Na] + 437.1283, found 437.1288.

[0047] Example 5

[0048] [(1,1'-Biphenyl)-4-yl(2-hydroxyphenyl)methyl]diphenylphosphine oxide (Ie):

[0049]

[0050] (1) 2-[(1,1'-biphenyl)-4-ylmethylene]cyclohex-3-en-1-one, diphenylphosphine oxide, and 1,8-diazabicyclo[5.4.0]undec-7-ene were mixed in a molar ratio of 1:2:1.2. Then, tetrahydrofuran with a concentration of 0.1 mol / L based on the concentration of 2-[(1,1'-biphenyl)-4-ylmethylene]cyclohex-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the tetrahydrofuran was removed by vacuum distillation to obtain a mixture of allylphosphine oxides IV-e containing a theoretical amount of 0.2 mmol.

[0051] (2) Allylphosphine oxide IV-e and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide IV-e 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ie). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ie) showed that the invention successfully prepared P-Betti base compound (Ie). The reaction yield, product appearance and melting point were tested and characterized. White solid; 48.8 mg, 53% total yield; mp 282-284℃; 1 H NMR (400MHz, CDCl3) δ10.56(s,1H),7.77(d,J=8.0Hz,1H),7.74(d,J=8.0Hz,1H),7.64(d,J=8.0Hz,1H),7.61(d,J=12.0Hz,1H),7.50-7.43(m,6H) ,7.40-7.34(m,8H),7.32-7.28(m,1H),7.14(d,J=8.0Hz,1H),7.10-7.06 (m,1H),6.93(d,J=8.0Hz,1H),6.73-6.70(m,1H),4.90(d,J=12.0Hz,1H); 13 C NMR (100MHz, CDCl3) δ 155.8 (d, Jc-p = 5.0Hz), 140.5, 139.9 (d, Jc-p = 2.0Hz), 134.7 (d, Jc-p = 4.0Hz), 132.4 (d, J c-p=8.0Hz),132.2(d,Jc-p=8.0Hz),132.2(d,Jc-p=2.0Hz),131.5(d,Jc-p=9.0Hz),131.3(d,Jc-p=8.0Hz),130 .9(d,Jc-p=30.0Hz),130.1(d,Jc-p=6.0Hz),129.9(d,Jc-p=30.0Hz),129.4,128.7,128.7(d,Jc-p=3.0Hz),12 8.6(d,Jc-p=2.0Hz),128.5,127.3,127.1,127.0,123.5(d,Jc-p=4.0Hz),120.3,119.8,53.1(d,Jc-p=65.0Hz); 31P NMR(162MHz,CDCl3)δ37.9(s).IR(KBr):ν3059,2920,1486,1437,1142,1119,1095,751,696,564cm -1 .HRMS(ESI,m / z):calcd.for C 31 H 25 O₂P + Na [M + Na] + 483.1490, found 483.1495.

[0052] Example 6

[0053] Preparation of [(2-hydroxyphenyl)(p-chlorophenyl)methyl]diphenylphosphine oxide (If):

[0054]

[0055] (1) 2-(4-chlorobenzyl)cyclohexyl-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, toluene with a concentration of 0.05 mol / L based on the concentration of 2-(4-chlorobenzyl)cyclohexyl-3-en-1-one was added and the mixture was reacted at 40 °C for 2 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the toluene was removed by vacuum distillation to obtain a mixture of allylphosphine oxides IV-f containing a theoretical amount of 0.2 mmol.

[0056] (2) Allylphosphine oxide compound IV-f and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-f 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (If). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (If) showed that the invention successfully prepared P-Betti base compound (If). The reaction yield, product appearance and melting point were tested and characterized. White solid; 71.2 mg, 85% total yield; mp 239-242℃; 1H NMR (400MHz, CDCl3) δ10.18(s,1H),7.74(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,1H),7.61(d,J=8.0Hz,1H),7.58(d,J=8.0Hz,1H), 7.49-7.28(m,9H),7.09(d,J=8.0Hz,2H),7.06-7.02(m,1H),6.89(d,J=8.0Hz,1H),6.72-6.68(m,1H),4.97(d,J=12.0Hz,1H); 13 C NMR (100MHz, Methanol-d4) δ155.8(d,Jc-p=8.0Hz), 136.7(d,Jc-p=5.0Hz), 133.9(d,Jc-p= 2.0Hz), 133.6(d,Jc-p=36.0Hz), 133.0(d,Jc-p=2.0Hz), 132.8(d,Jc-p=6.0Hz), 132.4, 132. 1(d,Jc-p=20.0Hz), 132.1(d,Jc-p=2.0Hz), 131.4(d,Jc-p=6.0Hz), 129.6(d,Jc-p=19.0Hz), 129.5(d,Jc-p=4.0Hz), 129.2, 124.9(d,Jc-p=3.0Hz), 120.6, 116.1, 44.2(d,Jc-p=69.0Hz); 31 P NMR(162MHz, CDCl3)δ37.5(s).IR(KBr):ν3060,2926,1488,1455,1437,1169,1152,1095,750,724,691,559cm -1 .HRMS(ESI,m / z):calcd.for C 25 H 20 ClO₂P + Na [M + Na] + 441.0787, found 441.0783.

[0057] Example 7

[0058] Preparation of [(2-hydroxyphenyl)(p-bromophenyl)methyl]diphenylphosphine oxide (Ig):

[0059]

[0060] (1) 2-(4-bromobenzylidene)cyclohexane-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2.5:2. Then, 0.1 mol / L of dichloroethane (based on the concentration of 2-(4-bromobenzylidene)cyclohexane-3-en-1-one) was added and the mixture was reacted at 30 °C for 1 h. After the reaction was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the dichloroethane was removed by vacuum distillation to obtain a mixture of IV-g of allylphosphine oxide compound containing 0.2 mmol of theoretical substance.

[0061] (2) Allylphosphine oxide compound IV-g and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-g 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ig). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ig) showed that the invention successfully prepared P-Betti base compound (Ig). The reaction yield, product appearance and melting point were tested and characterized. White solid; 67.6 mg, 73% total yield; mp 234-236℃; 1 H NMR (400MHz, Methanol-d4) δ7.92(d,J=8.0Hz,1H),7.76(d,J=8.0Hz,1H),7.73(d,J=8.0Hz,1H),7.64(d,J=8.0Hz,1H),7.61(d,J=8. 0Hz,1H),7.49-7.35(m,6H),7.33-7.27(m,4H),7.01-6.97(m,1H),6.75-6.71(m,1H),6.69(d,J=8.0Hz,1H),5.60(d,J=12.0Hz,1H); 13C NMR (100MHz, Methanol-d4) δ155.8(d,Jc-p=8.0Hz), 137.2(d,Jc-p=5.0Hz), 133.6(d,Jc-p= 34.0Hz), 133.1(d,Jc-p=7.0Hz), 133.0(d,Jc-p=3.0Hz), 132.6(d,Jc-p=35.0Hz), 132.2(d,J c-p=9.0Hz),132.2,132.1(d,Jc-p=9.0Hz), 131.4(d,Jc-p=6.0Hz), 129.6(d,Jc-p=20.0Hz), 129.6(d,Jc-p=2.0Hz), 124.8(d,Jc-p=4.0Hz), 121.9,120.6,116.1,44.3(d,Jc-p=69.0Hz); 31 P NMR(162MHz, CDCl3)δ37.7(s).IR(KBr):ν3060,2925,2248,1486,1454,1438,1168,1155,1119,746,724,692,559cm -1 .HRMS(ESI,m / z):calcd.for C 25 H 20 BrO₂P + H[M + H] + 463.0463, found 463.0467.

[0062] Example 8

[0063] Preparation of [(2-hydroxyphenyl)(p-cyanophenyl)methyl]diphenylphosphine oxide (Ih):

[0064]

[0065] (1) 2-(4-cyanobenzylidene)cyclohexane-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.5. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(4-cyanobenzylidene)cyclohexane-3-en-1-one was added and the mixture was reacted at 0 °C for 2 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxides IV-h containing a theoretical amount of 0.2 mmol.

[0066] (2) Allylphosphine oxide compound IV-h was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-h 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ih). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ih) showed that the invention successfully prepared P-Betti base compound (Ih). The reaction yield, product appearance and melting point were tested and characterized. White solid; 26.2 mg, 32% total yield; mp 250-252℃; 1 H NMR(400MHz, CDCl3) δ7.96(d,J=4.0Hz,1H),7.79-7.75(m,2H),7.65-7.60(m,2H),7.57(d,J =8.0Hz,2H),7.50-7.35(m,8H),7.04-6.98(m,1H),6.77-6.70(m,2H),5.71(d,J=8.0Hz,1H). 13 CNMR(100MHz,Methanol-d4)δ155.9(d,Jc-p=8.0Hz),143.8(d,Jc-p=4.0Hz),133.3(d,Jc-p=39 .0Hz),133.2(d,Jc-p=2.0Hz),132.9,132.5,132.3(d,Jc-p=6.0Hz),132.1(d,Jc-p=9.0Hz),132 .0(d,Jc-p=9.0Hz),131.3(d,Jc-p=6.0Hz),129.9,129.7(d,Jc-p=7.0Hz),129.6(d,Jc-p=8.0H z), 124.2 (d, Jc-p = 4.0Hz), 120.7, 119.5, 116.2, 111.6 (d, Jc-p = 2.0Hz), 45.1 (d, Jc-p = 67.0Hz); 31 P NMR(162MHz, CDCl3)δ38.6(s).IR(KBr):ν3062,2923,2231,1560,1502,1455,1438,1159,1118,759,722,696,566cm -1 .HRMS(ESI,m / z):calcd.for C 26 H 20NO₂P + Na [M + Na] + 432.1129, found 432.1124.

[0067] Example 9

[0068] Preparation of [(2-hydroxyphenyl)(2-naphthyl)methyl]diphenylphosphine oxide (Ii):

[0069]

[0070] (1) 2-(naphthyl-2-methylene)cyclohexane-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:1.2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.2 mol / L based on the concentration of 2-(naphthyl-2-methylene)cyclohexane-3-en-1-one was added and the mixture was reacted at 30 °C for 0.5 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-i containing a theoretical amount of 0.2 mmol.

[0071] (2) Allylphosphine oxide compound IV-i was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-i 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ii). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ii) showed that the invention successfully prepared P-Betti base compound (Ii). The reaction yield, product appearance and melting point were tested and characterized. White solid; 56.5 mg, 65% total yield; mp 264-266℃; 1H NMR (400MHz, Methanol-d4) δ8.04 (d, J = 8.0 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J = 8. 0Hz,1H),7.76(d,J=8.0Hz,1H),7.71-7.68(m,1H),7.66-7.58(m,4H),7.53(d ,J=8.0Hz,1H),7.46-7.42(m,1H),7.39-7.34(m,5H),7.30-7.25(m,2H),7.01 -6.97(m,1H),6.79-6.74(m,1H),6.71(d,J=8.0Hz,1H),5.81(d,J=8.0Hz,1H); 13 C NMR(100MHz, Methanol-d4)δ155.8(d,Jc-p=7.0Hz),135.4(d,Jc-p=5.0Hz),134.6,133.9,133.7,133.0(d ,Jc-p=3.0Hz),132.9(d,Jc-p=3.0Hz),132.9(d,Jc-p=3.0Hz),132.2(d,Jc-p=6.0Hz),132.1(d,Jc-p=4.0H z),131.7(d,Jc-p=6.0Hz),130.2(d,Jc-p=7.0Hz),129.5(d,Jc-p=11.0Hz),129.4,129.3(d,Jc-p=6.0Hz), 128.7(d,Jc-p=8.0Hz),128.5,127.0,126.8,125.1(d,Jc-p=3.0Hz), 120.6,116.1,44.8(d,Jc-p=69.0Hz); 31 P NMR(162MHz,Methanol-d4)δ35.6(s).IR(KBr):νy2920,1436,1423,1156,1119,1097,719,690,560cm -1 .HRMS(ESI,m / z):calcd.forC 29 H 23 O₂P + Na [M + Na] + 457.1333, found 457.1338.

[0072] Example 10

[0073] Preparation of [(2-hydroxyphenyl)(2-thienyl)methyl]diphenylphosphine oxide (Ij):

[0074]

[0075] (1) 2-(thiophene-2-ylmethylene)cyclohexane-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(thiophene-2-ylmethylene)cyclohexane-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-j containing a theoretical amount of 0.2 mmol.

[0076] (2) Allylphosphine oxide compound IV-j was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-j 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ij). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ij) showed that the invention successfully prepared P-Betti base compound (Ij). The reaction yield, product appearance and melting point were tested and characterized. Brown solid; 35.1 mg, 45% total yield; mp 219-222℃; 1 H NMR(400MHz, CDCl3)δ10.33(s,1H),7.74-7.66(m,4H),7.55-7.50(m,1H),7.46-7.41(m,3H),7.39-7.34(m, 2H),7.11-7.03(m,4H),6.94(d,J=8.0Hz,1H),6.83-6.81(m,1H),6.72-6.68(m,1H),5.15(d,J=12.0Hz,1H); 13C NMR (100MHz, Pyridine-d5) δ156.2(d,Jc-p=6.0Hz), 140.8(d,Jc-p=5.0Hz), 134.7(d,Jc-p=24.0Hz ),133.8(d,Jc-p=24.0Hz),132.3(d,Jc-p=3.0Hz),132.3,132.2(d,Jc-p=6.0Hz),132.0(d,Jc-p=9 .0Hz), 129.4, 129.3 (d, Jc-p = 12.0Hz), 129.0 (d, Jc-p = 12.0Hz), 128.5 (d, Jc-p = 6.0Hz), 127.6 (d, J c-p=2.0Hz),125.9(d,Jc-p=2.0Hz), 125.7(d,Jc-p=3.0Hz), 120.4,116.5,40.1(d,Jc-p=68.0Hz); 31 P NMR(162MHz, CDCl3)δ37.7(s).IR(KBr):ν3065,1455,1435,1278,1176,1155,712,692,522cm - 1 .HRMS(ESI,m / z):calcd.for C 23 H 19 O2PS + Na [M + Na] + 413.0741, found 413.0747.

[0077] Example 11

[0078] Preparation of [(2-hydroxyphenyl)(2-cyclohexyl)methyl]diphenylphosphine oxide (Ik):

[0079]

[0080] (1) 2-(cyclohexylmethylene)cyclohex-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(cyclohexylmethylene)cyclohex-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-k containing a theoretical amount of 0.2 mmol.

[0081] (2) Allylphosphine oxide compound IV-k and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-k 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Ik). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Ik) showed that the invention successfully prepared P-Betti base compound (Ik). The reaction yield, product appearance and melting point were tested and characterized. White solid; 29.7 mg, 38% total yield; mp 253-256℃; 1 H NMR (400MHz, CDCl3) δ10.44(s,1H),7.96-7.91(m,2H),7.62-7.48(m,5H),7.35-7.19(m,3H),7.04-7.00(m,1H),6.86(d,J=8.0Hz,1H),6 .72(d,J=8.0Hz,1H),6.61-6.55(m,1H),3.32-3.28(m,1H),2.43-2.24(m,1H),1.86-1.84(m,1H),1.61-1.42(m,4H),1.16-0.81(m,5H); 13 C NMR(100MHz, CDCl3)δ156.5,134.2(d,Jc-p=9.0Hz),132.4,132.3,131.6,131.5 ,130.8(d,Jc-p=9.0Hz),130.5(d,Jc-p=9.0Hz),129.1(d,Jc-p=12.0Hz),129.1 ,128.4(d,Jc-p=11.0Hz),121.5,119.6(d,Jc-p=5.0Hz),53.7(d,Jc-p=65.0Hz) ,38.0,34.0(d,Jc-p=7.0Hz),32.0(d,Jc-p=6.0Hz),26.5(d,Jc-p=7.0Hz),25.9; 31 P NMR(162MHz, CDCl3)δ39.0(s).IR(KBr):ν3055,2925,2849,1454,1436,1171,1152,1118,748,721,692cm -1 .HRMS(ESI,m / z):calcd.for C 25H 27 O₂P + Na [M + Na] + 413.1646, found 413.1641.

[0082] Example 12

[0083] Preparation of [(2-hydroxyphenyl)(3,4-dichlorophenyl)methyl]diphenylphosphine oxide (Il):

[0084]

[0085] (1) 2-(3,4-dichlorobenzyl)cyclohexyl-3-en-1-one, diphenylphosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-(3,4-dichlorobenzyl)cyclohexyl-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-1 containing a theoretical amount of 0.2 mmol.

[0086] (2) Allylphosphine oxide compound IV-l and copper bromide were mixed in a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-l 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Il). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Il) showed that the invention successfully prepared P-Betti base compound (Il). The reaction yield, product appearance and melting point were tested and characterized. White solid; 47.1 mg, 52% total yield; mp 258-261℃; 1 H NMR (400MHz, CDCl3) δ10.01(s,1H),7.75(d,J=8.0Hz,1H),7.72(d,J=8.0Hz,1H),7.62(d,J=4.0Hz,1H),7.59(d,J=8.0Hz,1H), 7.50-7.30(m,9H),7.17(d,J=8.0Hz,1H),7.06-7.02(m,1H),6.91(d,J=8.0Hz,1H),6.72-6.68(m,1H),5.08(d,J=12.0Hz,1H);13 C NMR (100MHz, Pyridine-d5) δ156.5(d,Jc-p=7.0Hz), 139.8(d,Jc-p=4.0Hz), 134.7(d,Jc-p=15.0Hz), 133.7(d,J c-p=17.0Hz), 133.1(d,Jc-p=6.0Hz), 132.6, 132.4(d,Jc-p=3.0Hz), 132.4(d,Jc-p=3.0Hz), 132.1(d,Jc-p=9.0H z),131.9(d,Jc-p=9.0Hz),131.7(d,Jc-p=6.0Hz),131.3(d,Jc-p=2.0Hz),131.1(d,Jc-p=6.0Hz),131.1,129.6 ,129.4(d,Jc-p=11.0Hz), 129.2(d,Jc-p=12.0Hz), 125.6(d,Jc-p=3.0Hz), 120.5,116.5,43.7(d,Jc-p=68.0Hz); 31 P NMR(162MHz, CDCl3)δ36.4(s).IR(KBr):ν3064,2920,1467,1453,1436,1171,1153,1118,1104,721,688,581cm -1 .HRMS(ESI,m / z):calcd.for C 25 H 19 Cl₂O₂P + Na [M + Na] + 475.0397, found 475.0391.

[0087] Example 13

[0088] Preparation of [(2-hydroxyphenyl)(phenyl)methyl]di(1-naphthyl)phosphine oxide (Im):

[0089]

[0090] (1) 2-Benzylene-cyclohexyl-3-en-1-one, di(1-naphthyl)phosphine oxide, and cesium carbonate were mixed in a molar ratio of 1:2:1.2. Then, ethylene glycol dimethyl ether with a concentration of 0.1 mol / L based on the concentration of 2-benzylidene-cyclohexyl-3-en-1-one was added and the mixture was reacted at 30 °C for 1 h. After the reaction of the raw materials was completed by thin-layer chromatography, the reaction solution was washed twice with 1 mol / L citric acid. The organic phase was dried with anhydrous sodium sulfate and the ethylene glycol dimethyl ether was removed by vacuum distillation to obtain a mixture of allylphosphine oxide compound IV-m containing a theoretical amount of 0.2 mmol.

[0091] (2) Allylphosphine oxide compound IV-m was mixed with copper bromide at a theoretical molar ratio of 1:2. Acetonitrile was added to make the theoretical concentration of allylphosphine oxide compound IV-m 0.05 mol / L. The mixture was reacted at 80℃ for 2 h. After the reaction of the raw materials was monitored by thin-layer chromatography, the acetonitrile was removed by vacuum distillation. The residue was purified by silica gel column chromatography. An eluent was prepared by a volume ratio of petroleum ether and ethyl acetate of 1:1 to collect the target compound. The solvent was removed from the eluent and the eluent was dried to obtain P-Betti base compound (Im). The analysis results of nuclear magnetic resonance spectrum, infrared spectrum and high-resolution mass spectrometry of P-Betti base compound (Im) showed that the invention successfully prepared P-Betti base compound (Im). The reaction yield, product appearance and melting point were tested and characterized. White solid; 31.0 mg, 32% total yield; mp 279-282℃; 1 H NMR (400MHz, CDCl3) δ10.94(s,1H),8.47(d,J=4.0Hz,1H),8.45(d,J=4.0Hz,1H),8.13(dd,J=16.0,8.0Hz,1H),7.95-7.91(m,2H),7.8 3-7.74(m,3H),7.43-7.37(m,3H),7.34-7.24(m,5H),7.12-7.05(m,2H),7.01-6.91(m,4H),6.70-6.66(m,1H),5.18(d,J=12.0Hz,1H); 13C NMR (100MHz, Pyridine-d5) δ156.3(d,Jc-p=8.0Hz), 138.9(d,Jc-p=4.0Hz), 135.5(d,Jc-p=7.0Hz), 135.2(d,Jc-p=7.0Hz), 134.7(d,Jc-p= 9.0Hz),133.5(d,Jc-p=2.0Hz),133.4(d,Jc-p=2.0Hz),133.1(d,Jc-p=11.0Hz),132.8(d,Jc-p=6.0Hz),132.7,131.8(d,Jc-p=7.0Hz),131 .6(d,Jc-p=6.0Hz), 130.9(d,Jc-p=7.0Hz), 129.5(d,Jc-p=14.0Hz), 129.2, 128.9, 128.3(d,Jc-p=4.0Hz), 127.8(d,Jc-p=4.0Hz), 127.6(d ,Jc-p=2.0Hz),127.4(d,Jc-p=2.0Hz),127.2(d,Jc-p=3.0Hz),126.9(d,Jc-p=11.0Hz),125.3,125.2,120.5,116.5,46.5(d,Jc-p=68.0Hz); 31 P NMR(162MHz,CDCl3)δ43.2(s).IR(KBr):ν3056,1506,1452,1148,1130,800,772,755,692,568cm -1 .HRMS(ESI,m / z):calcd.for C 33 H 25 O₂P + Na [M + Na] + 507.1490, found 507.1493.

[0092] The various embodiments of the present invention have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or improvement of the technology in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A method for preparing a P-Betti base compound, characterized by, The method comprises the following steps: (1) mixing 2-benzylidene-cyclohex-3-en-1-one, diaryl phosphine oxide, base and organic solvent and reacting; after the reaction is completed, the organic phase is washed with acid, then dried, and the solvent is removed to obtain a mixture containing allyl phosphine oxide compound; (2) adding copper bromide and acetonitrile to the allyl phosphine oxide compound and reacting; after the reaction is completed, the solvent is removed, the residue is separated and purified, eluted with an eluent, and the eluent is dried and the solvent is removed to obtain a P-Betti base compound.

2. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: The structural formula of the 2-benzylidene-cyclohex-3-en-1-one in step (1) is as follows: wherein, R is a phenyl group or a mono-substituted or di-substituted phenyl group of one of the following groups: methyl, halogen, methoxy, phenyl, cyano, 2-naphthyl, 2-thienyl, cyclohexyl.

3. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: The structural formula of the diaryl phosphine oxide in step (1) is as follows: wherein, Ar is a phenyl group or a 1-naphthyl group.

4. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein, The base in step (1) is one of cesium carbonate, potassium tert-butoxide, potassium hydroxide, tetramethyl guanidine and 1,8-diazabicyclo[5.4.0]undec-7-ene.

5. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein, The organic solvent in step (1) is one of ethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile, methanol, toluene, trifluorotoluene, N,N-dimethylformamide and dichloroethane.

6. The method for preparing the P-Betti base compound according to claim 1, characterized in that, The molar ratio of 2-benzylidene-cyclohex-3-en-1-one, diaryl phosphine oxide and base added in step (1) is 1:(1.2-2.5):(1.2-2.5), wherein the concentration of 2-benzylidene-cyclohex-3-en-1-one is 0.05-0.2 mol / L.

7. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: The reaction temperature in step (1) is 0-40°C, and the reaction time is 0.5-2 h.

8. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: The acid washing condition in step (1) is that the reaction solution is washed with 1 mol / L citric acid twice.

9. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: In step (2), the allyl phosphine oxide compound and copper bromide are mixed in a theoretical molar ratio of 1:2; the theoretical concentration of the allyl phosphine oxide compound is 0.05 mol / L; the reaction temperature is 80°C, and the reaction time is 2 h.

10. The process for the preparation of P-Betti base compound as claimed in claim 1, wherein: The eluent in step (2) is prepared in a volume ratio of petroleum ether to ethyl acetate of 1:1.

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