Isobenzofuran aggregation-induced emission molecule containing phosphine oxide structure and synthesis method thereof

Abstract

The invention discloses an isobenzofuran aggregation-induced emission molecule containing a phosphine oxide structure and a synthesis method of the isobenzofuran aggregation-induced emission molecule, and belongs to the technical field of organic synthesis. According to the method, o-propargyl alcohol benzaldehyde and a diaryl phosphine oxide compound are adopted as raw materials, and a series of isobenzofuran compounds containing the phosphine oxide structure are synthesized through a Pudovik addition / cyclization / aromatization reaction, so that the preparation of the isobenzofuran compounds containing the phosphine oxide structure is simple and convenient to operate, mild in reaction environment, low in cost and atom-economical; and the method is high in reaction efficiency and environment-friendly, and is the most direct and efficient method for the isobenzofuran aggregation-induced emission molecule containing the phosphine oxide structure reported at present. Besides, the isobenzofuran compound containing the phosphine oxide structure provided by the invention is a series of compounds with diversified structures and potential application value, full-wave-band cell lipid droplet imaging from blue light to red light can be realized, and experiments prove that the molecule has important biological activity.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to an aggregation-induced luminescence molecule of an isobenzofuran compound containing a phosphine oxygen structure and a synthesis method thereof. Background Art

[0002] Organophosphine oxide compounds characterized by heterocyclic rings are a class of molecules with unique structures and biological properties. They have important applications in synthetic chemistry, pharmaceutical development, pesticide chemistry, and materials chemistry (Chemical Review 2017, 117, 5704-5783.). Functionalized isobenzofuran compounds containing phosphine oxide structures are also an important class of oxygen-containing heterocyclic compounds, which have important applications in the synthesis of a variety of molecules with physiological functions and pharmaceutical activities (Advanced Synthesis & Catalysis 2008, 350, 2733-2739. The Journal of Organic Chemistry, 2024, DOI: 10.1021 / acs.joc.4c00877.). However, the existing synthesis methods of isobenzofuran compounds containing phosphine oxide structures require the use of acids and bases as catalysts, or the use of precious metal palladium catalysts, and the reaction conditions are harsh, thereby causing potential environmental pollution and causing troubles for subsequent purification processes. On the other hand, through searching the published literature, there are relatively few reports on isobenzofuran-type aggregation-induced emission molecules. Therefore, the optical properties of this type of fluorescent molecules have not been systematically studied. Summary of the invention

[0003] In view of the shortcomings of the prior art, the inventors have established a simple and practical method for preparing isobenzofuran compounds containing a phosphine oxide structure through a large number of experimental studies and unremitting exploration. That is, o-propargyl alcohol benzaldehyde and diaryl phosphine oxide compounds are used as raw materials, and a series of isobenzofuran compounds containing a phosphine oxide structure are synthesized through Pudovik addition / cyclization / aromatization reaction.

[0004] Based on the above research results of the inventors, the first object of the present invention is to provide a series of isobenzofuran compounds containing phosphine oxide structures, the general structural formula of which is as follows:

[0005]

[0006] Where R 1 is hydrogen or methyl or methoxy or halogen, R 2 It is a phenyl group having 0 to 2 substituents, and Ar is an aryl group.

[0007] Further preferably, the isobenzofuran compound containing a phosphine oxygen structure as described above has R 1The halogen mentioned in the above may be fluorine, chlorine or bromine.

[0008] Further preferably, the isobenzofuran compound containing a phosphine oxygen structure as described above has R 2 The substituent in is C 1 ~C 2 Alkyl, C 1 ~C 2 Alkoxy or halogen.

[0009] In a preferred embodiment of the present invention, the isobenzofuran compound containing a phosphine oxide structure as described above has R 2 The substituent is methyl, methoxy or halogen.

[0010] Further preferably, in the above-mentioned isobenzofuran compound containing a phosphine oxide structure, the aromatic group is selected from any one of the following: a phenyl group, a thienyl group, and a dibenzocyclic substituent group containing 0 to 2 substituents.

[0011] Still more preferably, in the above-mentioned isobenzofuran compound containing a phosphine oxide structure, the aryl group is a phenyl group containing 1 to 2 substituents, and the substituents are methyl, methoxy or halogen.

[0012] In a preferred embodiment of the present invention, in the above-mentioned isobenzofuran compound containing a phosphine oxide structure, the dibenzocyclic substituent is a dibenzo five-membered ring, a dibenzo six-membered ring or a dibenzo seven-membered ring.

[0013] In addition, the second object of the present invention is to provide a method for synthesizing the above-mentioned isobenzofuran compounds containing a phosphine oxide structure, which comprises the following steps: using o-propargyl alcohol benzaldehyde and a diarylphosphine oxide compound as raw materials, using 1,2-dichloroethane (DCE) as a solvent, reacting in an oil bath at 78 to 82° C. for 12 to 24 hours without adding a metal or acid-base catalyst, to obtain a crude product of the isobenzofuran compound containing a phosphine oxide structure, and the specific reaction formula is as follows:

[0014]

[0015] Furthermore, the present invention also provides a method for purifying a crude isobenzofuran compound containing a phosphine oxide structure, the method comprising: taking the crude isobenzofuran compound containing a phosphine oxide structure obtained by the above-mentioned synthesis method, directly performing rotary evaporation on a rotary evaporator, adding silica gel, dry loading, and purifying by silica gel column chromatography, wherein the eluent is dichloromethane-ethyl acetate in a volume ratio of (10-25):1. Preferably, the volume ratio of dichloromethane:ethyl acetate in the eluent is 20:1.

[0016] Compared with the prior art, the isobenzofuran compounds containing phosphine oxide structures and the synthesis method thereof provided by the present invention have the following advantages and significant progress:

[0017] (1) The present invention creatively uses o-propargyl alcohol benzaldehyde and diarylphosphine oxide compounds as raw materials to synthesize a series of isobenzofuran compounds containing phosphine oxide structures through Pudovik addition / cyclization / aromatization reactions, so that the preparation of isobenzofuran compounds containing phosphine oxide structures is simple, low in cost, high in reaction efficiency, and less in environmental pollution, achieving relatively ideal results. It is one of the most direct and efficient methods for synthesizing isobenzofuran compounds containing phosphine oxide structures reported so far.

[0018] (2) The isobenzofuran compounds containing phosphine oxygen structures provided by the present invention are a series of compounds with diverse structures and potential application value, which can realize cell lipid droplet imaging in the full band from blue light to red light. Experiments have confirmed that this type of molecule has important biological activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3a prepared in Example 1 at different wavelengths.

[0020] Figure 2 Fluorescence spectra of compound 3a prepared in Example 1 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 412 nm, [3a] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0021] Figure 3 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3b prepared in Example 2 at different wavelengths.

[0022] Figure 4 Fluorescence spectra of compound 3b prepared in Example 2 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 415 nm, [3b] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0023] Figure 5 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3c prepared in Example 3 at different wavelengths.

[0024] Figure 6Fluorescence spectra of compound 3c prepared in Example 3 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 414 nm, [3c] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0025] Figure 7 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3d prepared in Example 4 at different wavelengths.

[0026] Figure 8 Fluorescence spectra of compound 3d prepared in Example 4 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 412 nm, [3d] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0027] Fig. 9 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3e prepared in Example 5 at different wavelengths.

[0028] Fig.10 Fluorescence spectra of compound 3e prepared in Example 5 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 414 nm, [3e] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0029] Fig.11 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3f prepared in Example 6 at different wavelengths.

[0030] Fig.12 Fluorescence spectra of compound 3f prepared in Example 6 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 414 nm, [3f] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0031] Fig.13 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3g prepared in Example 7 at different wavelengths.

[0032] Fig.14Fluorescence spectra of compound 3g prepared in Example 7 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 415 nm, [3g] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0033] Fig.15 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3h prepared in Example 8 at different wavelengths.

[0034] Fig.16 Fluorescence spectra of compound 3h prepared in Example 8 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 413 nm, [3h] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0035] Fig.17 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3i prepared in Example 9 at different wavelengths.

[0036] Fig.18 Fluorescence spectra of compound 3i prepared in Example 9 in different n-hexane components in dichloromethane and dichloromethane / toluene mixture. Excitation wavelength: 426 nm, [3i] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / toluene mixtures 0 The fluorescence intensity ratio of (B).

[0037] Fig.19 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3j prepared in Example 10 at different wavelengths.

[0038] Fig. 20 Fluorescence spectra of compound 3j prepared in Example 10 in different n-hexane components in dichloromethane and dichloromethane / toluene mixture. Excitation wavelength: 442 nm, [3j] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / toluene mixtures 0 The fluorescence intensity ratio of (B).

[0039] Fig.21 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3k prepared in Example 11 at different wavelengths.

[0040] Fig. 22Fluorescence spectra of compound 3k prepared in Example 11 in different n-hexane components in tetrahydrofuran and tetrahydrofuran / water mixture. Excitation wavelength: 446 nm, [3k] = 1.0 × 10 -5 M(A) and different tetrahydrofuran / water mixtures I / I 0 The fluorescence intensity ratio of (B).

[0041] Fig.23 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 31 prepared in Example 12 at different wavelengths.

[0042] Fig.24 Fluorescence spectra of compound 31 prepared in Example 12 in tetrahydrofuran and tetrahydrofuran / water mixture with different n-hexane components. Excitation wavelength: 399 nm,

[31] = 1.0 × 10 -5 M(A) and different tetrahydrofuran / water mixtures I / I 0 The fluorescence intensity ratio of (B).

[0043] Fig.25 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3m prepared in Example 13 at different wavelengths.

[0044] Fig.26 Fluorescence spectra of compound 3m prepared in Example 13 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 415 nm, [3m] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B).

[0045] Fig. 27 The ultraviolet absorption curve (A) and fluorescence intensity curve (B) of compound 3n prepared in Example 14 at different wavelengths.

[0046] Fig.28 Fluorescence spectra of compound 3n prepared in Example 14 in dichloromethane and dichloromethane / n-hexane mixture with different n-hexane components. Excitation wavelength: 412 nm, [3n] = 1.0 × 10 -5 M(A) and I / I in different dichloromethane / n-hexane mixtures 0 The fluorescence intensity ratio of (B). DETAILED DESCRIPTION

[0047] The following are specific embodiments of the present invention, which further describe the technical solution of the present invention, but the protection scope of the present invention is not limited to these embodiments. Any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0048] Example 1: Synthesis of isobenzofuran (3a) containing a phosphine oxide structure, the structural formula of which is as follows:

[0049]

[0050] 0.2 mmol o-propargyl alcohol benzaldehyde (1a), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), and 90 mg of the product was obtained, with a calculated yield of 91%.

[0051] Its main physical and chemical properties are as follows: yellow solid, melting point 196-198°C; 1 H NMR (400 MHz, CDCl 3 )δ7.96(d,J=8.8Hz,1H),7.54-7.45(m,3H),7.43-7.36(m,8H),7.34-7.28(m,5 H),7.21-7.17(m,2H),7.15-7.10(m,2H),7.10-7.04(m,1H),7.04-6.96(m,3H). 13 C{ 1 H}NMR (101 MHz, CDCl 3 )δppm150.8(d,J=5.6Hz),142.8,142.3(d,J=1.4Hz),140.4,136.7,135.3,135.2,135.0,133.4,132.3,131.9(dd,J=8.9,6.8Hz),130.2, 128.5(d,J=4.1Hz),128.3,128.2,128.1,128.0,127.8,127.3(d,J=1.3Hz),125.1,124.5,124.4,119.6(d,J=137Hz),112.4(d,J=1.7Hz). 31 P NMR (162 MHz, CDCl 3 )δ=18.0.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 26 O 2 P497.1665;Found:497.1665.

[0052] Example 2: Synthesis of isobenzofuran (3b) containing a phosphine oxide structure, the structural formula of which is as follows:

[0053]

[0054] 0.2 mmol 5-chloro-o-propargyl alcohol benzaldehyde (1b), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 24 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 92 mg of the product, with a calculated yield of 87%.

[0055] Its main physical and chemical properties are as follows: yellow solid, melting point 250-252°C; 1 H NMR (400 MHz, CDCl 3 )δ8.00(s,1H),7.56-7.49(m,2H),7.44-7.34(m,9H),7.34-7.27(m,5H),7.20 -7.11(m,3H),7.08(s,1H),7.03(t,J=7.6Hz,2H),6.90(dd,J=9.2,1.6Hz,1H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm151.31(d,J=5.4Hz),143.5,142.6,140.2,139.8,135.2,135.1,133.5,133.1,132.1(d,J=2.8Hz),132.0, 131.9, 131.8, 130.1, 128.3 (d, J = 19.0Hz), 128.0 (d, J = 2.8Hz), 126.8, 122.5 (d, J = 7.3Hz), 120.6, 118.7, 112.1. 31 P NMR (162 MHz, CDCl 3 )δ=18.0.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 25 C1O 2 P 531.1275;Found:531.1261.

[0056] Example 3: Synthesis of isobenzofuran (3c) containing a phosphine oxide structure, the structural formula of which is as follows:

[0057]

[0058] 0.2 mmol 5-bromo-o-propargyl alcohol benzaldehyde (1c), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 24 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 96 mg of the product, with a calculated yield of 84%.

[0059] Its main physical and chemical properties are as follows: yellow solid, melting point: 265-267℃; 1 HNMR (400MHz, CDCl 3 )δ8.21(s,1H),7.57-7.49(m,2H),7.45-7.34(m,8H),7.33-7.27(m,6H),7.20-7.12(m,3H),7.08(s,1H),7.06-6.99(m,3H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 151.4(d,J=5.5Hz),143.5(d,J=1.3Hz),142.5,140.2,136.23,135.8,135.6,134.85,133.1,132.1(d,J=2.9Hz),132.0,131.8(d,J=10.8Hz) ,130.1,129.0,128.5,128.4,128.2,128.0(d,J=2.8Hz),122.5(d,J=7.2Hz),122.1(d,J=1.7Hz),121.4(d,J=163.4Hz),112.1(d,J=1.5Hz). 31 P NMR (162 MHz, CDCl 3 )δ=18.1.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 25 B O 2 P 575.0770; Found: 575.0774.

[0060] Example 4: Synthesis of isobenzofuran (3d) containing a phosphine oxide structure, the structural formula of which is as follows:

[0061]

[0062] 0.2 mmol 5-fluoro-o-propargyl alcohol benzaldehyde (1d), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 83 mg of the product, with a calculated yield of 81%.

[0063] Its main physical and chemical properties are as follows: yellow solid, melting point: 204-206℃; 1 HNMR (400MHz, CDCl 3 )δ7.56-7.47(m,3H),7.47-7.35(m,9H),7.34-7.27(m,5H),7.20-7.16(m, 2H),7.15-7.10(m,1H),7.06-7.01(s,1H),7.03(m,2H),6.83-6.72(m,1H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 162.7 (d, J = 1.4Hz), 160.2 (d, J = 1.4Hz), 151.3 (dd, J = 5.5, 1.8Hz) 143.6, 142.6, 140.2, 132.7 (d, J = 110.8Hz), 132.1 (d, J = 2.8Hz), 131.8 (d, J=10.8Hz),130.1,128.51(d,J=2.4Hz),128.4,128.2,128.0(d,J=3.8Hz),122.1,122.0,121.8,121.7,118.0,117.7,112.1,102.3,102.0. 31 P NMR (162 MHz, CDCl 3 )δ=17.8.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 25 FO 2 P515.1571; Found:515.1566.

[0064] Example 5: Synthesis of isobenzofuran (3e) containing a phosphine oxide structure, the structural formula of which is as follows:

[0065]

[0066] 0.2 mmol 5-methyl-o-propargyl alcohol benzaldehyde (1d), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 87 mg of the product, with a calculated yield of 85%.

[0067] Its main physical and chemical properties are as follows: yellow solid, melting point: 216-218°C; 1 HNMR (400MHz, CDCl 3 )δ7.76(d,J=1.2Hz,1H),7.56-7.48(m,2H),7.42-7.36(m,9H),7.32-7.27(m,5H),7.21-7. 17(m,2H),7.16-7.10(m,2H),7.04-6.99(m,2H),6.84(dd,J=9.2,1.2Hz,1H),2.32(s,3H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 150.6(d,J=5.7Hz),142.9,142.0(d,J=1.4Hz),140.4,137.2(d,J=1.2Hz),135.9,135.7,135.2,133.8,133.0(d,J=110.3Hz),131.9(d,J=1.6 Hz),131.8,130.2,128.5,128.4(d,J=5.9Hz),128.3,128.2,128.1,127 .9,127.7,123.6(d,J=7.6Hz),118.6,117.8,112.5(d,J=1.6Hz),22.1. 31 P NMR (162 MHz, CDCl 3 )δ=18.3.HRMS(ESI)m / z:[M+H]+Calcd for C 35 H 28 O 2 P 511.1821;Found:511.1829.

[0068] Example 6: Synthesis of isobenzofuran (3f) containing a phosphine oxide structure, the structural formula of which is as follows:

[0069]

[0070] 0.2 mmol 5-methoxy-o-propargyl alcohol benzaldehyde (1f), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =15:1), to obtain 88 mg of the product, with a calculated yield of 83%.

[0071] Its main physical and chemical properties are as follows: yellow solid, melting point: 238-240℃; 1 HNMR (400MHz, CDCl 3 )δ7.53-7.48(m,2H),7.45-7.36(m,8H),7.34(dd,J=9.6,0.78Hz,1H),7.31-7.28(m,5H),7.21-7.17( m,2H),7.15-7.09(m,2H),7.07(s,1H),7.02(t,J=7.6Hz,1H),6.69(dd,J=9.2,2Hz,2H),3.81(s,3H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 158.7(d,J=1.2Hz),150.7(d,J=6.0Hz),142.8,142.6(d,J=1.3Hz),140.3 ,136.4(d,J=16.1Hz),134.2,133.2(d,J=110.2Hz),132.8,131.8(d,J=1. 8Hz),131.7,130.2,128.4(d,J=5.2Hz),128.3(d,J=3.1Hz),128.0,127.9 ,127.8,121.7,121.6(d,J=7.6Hz),120.3,112.4(d,J=1.5Hz),94.5,55.5. 31 P NMR (162 MHz, CDCl 3 )δ=18.4.HRMS(ESI)m / z:[M+H] + Calcd for C 35 H 28 O 3 P527.1771; Found:527.1772.

[0072] Example 7: Synthesis of isobenzofuran (3 g) containing a phosphine oxide structure, the structural formula of which is as follows:

[0073]

[0074] 0.2 mmol 3-methylmethyl-o-propargyl alcohol benzaldehyde (1 g), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 58 mg of the product, with a calculated yield of 62%.

[0075] Its main physical and chemical properties are as follows: yellow solid, melting point: 208-210℃; 1 HNMR (400MHz, CDCl 3 )δ77.89(d,J=8.8Hz,1H),7.49(t,J=7.2Hz,2H),7.40-7.33(m,7H),7.32-7.23(m,7H),7.13( d,J=7.2Hz,2H),7.05(t,J=7.4Hz,1H),6.97-6.91(m,3H),6.76(d,J=6.4Hz,1H),2.67(s,3H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 151.2(d,J=5.5Hz),143.3,142.6,140.6,136.4,136.0(d,J=15.9Hz),135.0,132.7(d,J=110.5Hz),131.9(d,J=10.8Hz),131.8(d,J=2.5Hz) ,130.1,130.0,128.4(d,J=11.9Hz),128.2,128.1,128.0,127.9,127.6,127.3,125.9,124.6(d,J=7.3Hz),118.3,114.7(d,J=1.4Hz),21.5. 31 P NMR (162 MHz, CDCl 3 )δ=18.2.HRMS(ESI)m / z:[M+H] + Calcd for C 35 H 28 O 2 P 511.1821; Found: 511.1833.

[0076] Example 8: Synthesis of isobenzofuran (3h) containing a phosphine oxide structure, the structural formula of which is as follows:

[0077]

[0078] 0.2 mmol 3-fluoro-o-propargyl alcohol benzaldehyde (1h), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 88 mg of the product, with a calculated yield of 86%.

[0079] Its main physical and chemical properties are as follows: yellow solid, melting point: 190-192°C; 1 HNMR (400MHz, CDCl 3 )δ7.79(d,J=8.8Hz,1H),7.55-7.50(m,2H),7.43-7.37(m,5H),7.36-7.27(m,9H),7. 18-7.14(m,2H),7.13-7.08(m,1H),7.02-6.94(m,3H),6.63(dd,J=11.6,7.2Hz,1H). 13 C{ 1 H}NMR (101 MHz, CDCl 3 )δppm 157.5,155.0,149.6(dd,J=7.9,5.7Hz),143.5,142.5,140.3,137.1(dd,J=16.1,4.5H z), 136.9 (dd, J = 139.0, 2.4Hz), 132.9, 132.1 (d, J = 2.8Hz), 131.9, 131.8, 130.0, 128. 5,128.4(d,J=4.0Hz),128.1,128.0,127.8,127.5(d,J=5.7Hz),116.6(d,J=5.2Hz),1 16.4(d,J=7.5Hz), 116.2(d,J=7.6Hz), 113.8(dd,J=6.5,1.4Hz), 107.6(d,J=18.3Hz). 31 PNMR (162MHz, CDCl 3 )δ=18.1.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 25 FO 2 P515.1571; Found:515.1572.

[0080] Example 9: Synthesis of isobenzofuran (3i) containing a phosphine oxide structure, the structural formula of which is as follows:

[0081]

[0082] 0.2 mmol 2-(3-hydroxy-3,3-di(thiophen-2-yl)prop-1-yn-1-yl)benzaldehyde (1i), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), and 92 mg of the product was obtained, with a calculated yield of 91%.

[0083] Its main physical and chemical properties are as follows: yellow solid, melting point: 234-236℃; 1 HNMR (400MHz, CDCl 3 )δ7.92(d,J=8.8Hz,1H),7.57-7.46(m,7H),7.45-7.37(m,4H),7.27-7.23(m ,1H),7.20(s,1H),7.13-7.04(m,2H),7.03-6.94(m,4H),6.74-6.69(m,1H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 149.9(d,J=5.6Hz),147.1,139.9,137.7,136.3,135.0(d,J=15.8Hz),133.3,132.2,132.0(d,J=2.8Hz),131.9(d,J=10.8Hz),128. 6,128.5,128.3,128.0,127.8,127.4,127.0(d,J=37.1Hz),126.4,126.2,125.4,125.0(d,J=7.5Hz),119.6(d,J=142.3Hz),112.6. 31 P NMR (162 MHz, CDCl 3 )δ=17.9.HRMS(ESI)m / z:[M+H] + Calcd for C 30 H 22 O 2 PS 2 509.0793;Found:509.0799.

[0084] Example 10: Synthesis of isobenzofuran (3j) containing a phosphine oxide structure, the structural formula of which is as follows:

[0085]

[0086] 0.2 mmol 2-((9-hydroxy-9H-fluoren-9-yl)ethynyl)benzaldehyde (1j), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 86 mg of the product, with a calculated yield of 87%.

[0087] Its main physical and chemical properties are as follows: yellow solid, melting point: 197-199°C; 1 HNMR (400MHz, CDCl 3 )δ8.17(d,J=8.0Hz,1H),7.92(ddd,J=12.8,8.2,1.2Hz,4H),7.82-7.74(m,2H),7.72-7.68(m,1H),7.68-7.58(m,5H ),7.56-7.49(m,4H),7.35-7.27(m,2H),7.23(dd,J=7.2,0.8Hz,1H),7.17-7.11(m,2H),6.66(td,J=8.0,1.2Hz,1H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 150.0(d,J=5.6Hz),141.2,140.4,140.1,139.3,139.1,135.8,135.0,134.9,132.8,132.7(d,J=2.8Hz),132.0,131.9,131.7,129.1,1 28.94,128.89,128.6,127.9,127.3,127.2,127.1,126.2,125.8,120.2,119.8(d,J=16.2Hz),119.7(d,J=88.0Hz),107.9(d,J=1.6Hz). 31 PNMR (162MHz, CDCl 3 )δ=17.2.HRMS(ESI)m / z:[M+H] + Calcd for C 34 H 24 O 2P 495.1508; Found: 495.1531.

[0088] Example 11: Synthesis of isobenzofuran (3k) containing a phosphine oxide structure, the structural formula of which is as follows:

[0089]

[0090] 0.2 mmol 2-((9-hydroxy-10,10-dimethyl-9,10-dihydroanthracen-9-yl)ethynyl)benzaldehyde (1k), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 94 mg of the product, with a calculated yield of 88%.

[0091] Its main physical and chemical properties are as follows: yellow solid, melting point: 209-211°C; 1 HNMR (400MHz, CDCl 3 )δ7.93(d,J=8.8Hz,1H),7.77-7.73(m,1H),7.57-7.49(m,10H),7.40-7.34(m,4H),7.33-7.28(m,2H), 7.17-7.09(m,2H),7.08(s,1H),7.02(dd,J=8.4,6.4Hz,1H),6.33(td,J=7.6,0.8Hz,1H),1.61(s,6H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 150.33(d,J=5.6Hz),146.4,144.5,139.1,137.7,136.5,135.2,135.1 ,135.0,134.9,133.1(d,J=110.6Hz),132.0,131.9(d,J=10.7Hz),128. 5,128.4(d,J=12.8Hz),128.1,127.6,127.4,126.6,125.2,125.1,124 .4(d,J=7.4Hz),123.5,123.4,122.7,120.2,119.2,110.1,40.0,28.9. 31 PNMR (162MHz, CDCl 3 )δ=17.8.HRMS(ESI)m / z:[M+H] +Calcd for C 37 H 30 O 2 P537.1978.Found:537.1975.

[0092] Example 12: Synthesis of isobenzofuran (31) containing a phosphine oxide structure, the structural formula of which is as follows:

[0093]

[0094] 0.2 mmol 2-((5-hydroxy-10,11-dihydro-5H-dibenzo[a,d][7]cyclo-5-yl)ethynyl)benzaldehyde (1l), 0.3 mmol diphenylphosphine oxide (2a) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 95 mg of the product, with a calculated yield of 91%.

[0095] Its main physical and chemical properties are as follows: yellow solid, melting point: 170-172°C; 1 HNMR (400MHz, CDCl 3 )δ7.99(d,J=8.8Hz,1H),7.64-7.27(m,12H),7.25-7.17(m,3H),7.11-7.05(m,3H),7 .04-6.96(m,3H),6.41(td,J=7.6,1.2Hz,1H),3.48-3.26(m,2H),3.06-2.77(m,2H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 150.28(d,J=5.5Hz),144.0,141.4,140.7,138.4,137.8,136.4,135.1,135.04,134.97,131.8,130.6,128.3,128.23(dd,J=3 5.9, 1.8Hz), 128.0, 127.6, 127.3, 126.4, 126.0, 125.1, 124.3, 124.2, 119.53 (d, J = 149.2Hz), 115.0 (d, J = 1.5Hz), 33.8, 32.1. 31 P NMR (162 MHz, CDCl 3 )δ=18.1.HRMS(ESI)m / z:[M+H] +Calcd for C 36 H 28 O 2 P523.1821.Found:523.1831.

[0096] Example 13: Synthesis of isobenzofuran (3m) containing a phosphine oxide structure, the structural formula of which is as follows:

[0097]

[0098] 0.2 mmol of o-propargyl alcohol benzaldehyde (1a), 0.3 mmol of bis(4-methoxyphenyl)phosphine oxide (2m) and 5 mL of 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 84 mg of the product, with a calculated yield of 76%.

[0099] Its main physical and chemical properties are as follows: yellow solid, melting point: 168-170℃; 1 HNMR (400MHz, CDCl 3 )δ7.92(d,J=8.8Hz,1H),7.47-7.41(m,1H),7.38-7.28(m,9H),7.22-7.12(m,4H),7. 09-7.01(m,3H),6.96(ddd,J=8.6,6.4,0.64Hz,1H),6.91-6.86(m,4H),3.85(s,6H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 162.5(d,J=3.0Hz),150.3(d,J=5.6Hz),142.9,141.9(d,J=1.4Hz),140.4,137. 2(d,J=140.2Hz),134.5,134.4,133.7(d,J=12.2Hz),130.2,128.4,128.0(d,J= 10.6Hz),127.9(d,J=40.2Hz),127.0(d,J=1.0Hz),125.0(d,J=3.4Hz),124.4(d ,J=7.3Hz),123.9,120.4,118.9,113.9(d,J=13.9Hz),112.5(d,J=1.5Hz),55.5. 31 P NMR (162 MHz, CDCl 3)δ=17.7.HRMS(ESI)m / z:[M+H] + Calcd for C 36 H 30 O 4 P 557.1876;Found:557.1846.

[0100] Example 14: Synthesis of isobenzofuran (3n) containing a phosphine oxide structure, the structural formula of which is as follows:

[0101]

[0102] 0.2 mmol o-propargyl alcohol benzaldehyde (1a), 0.3 mmol bis(4-methylphenyl)phosphine oxide (2n) and 5 mL 1,2-dichloroethane solvent were added to the reaction tube in sequence. Then, the mixture was stirred at 80°C in an oil bath for 12 h. After the reaction was completed, the mixture was concentrated under reduced pressure, silica gel was added, and the sample was loaded by dry method. The crude product was subjected to rapid silica gel column chromatography (V 二氯甲烷 :V 乙酸乙酯 =20:1), to obtain 83 mg of the product, with a calculated yield of 79%.

[0103] Its main physical and chemical properties are as follows: yellow solid, melting point: 248-250℃; 1 HNMR (400MHz, CDCl 3 )δ7.94(d,J=8.8Hz,1H),7.44(d,J=8.8Hz,1H),7.36-7.26(m,9H),7.22-7.17(m,6 H),7.16-7.12(m,2H),7.08-7.01(m,3H),6.96(dd,J=8.6,6.4Hz,1H),2.41(s,6H). 13 C{ 1 H}NMR (100MHz, CDCl 3 )δppm 150.5(d,J=5.4Hz),142.9,142.3(d,J=2.9Hz),142.0(d,J=1.2Hz),140.4, 136.8(d,J=139.6Hz),134.7(d,J=15.8Hz),131.9(d,J=11.1Hz),130.3,13 0.2,129.2,129.1,129.0,128.4,128.1,128.0,127.9,127.7,127.1,125.0 ,124.4(d,J=7.4Hz),120.36,118.9,112.5(d,J=1.5Hz),21.8(d,J=1.3Hz). 31 P NMR (162 MHz, CDCl3 )δ=18.1.HRMS(ESI)m / z:[M+H] + Calcd for C 36 H 30 O 2 P 525.1972;Found:525.1957。

Claims

1. An isobenzofuran compound containing a phosphine oxygen structure, the general structural formula of which is as follows: Where R 1 is hydrogen or methyl or methoxy or halogen, R 2 It is a phenyl group having 0 to 2 substituents, and Ar is an aryl group.

2. The isobenzofuran compound containing a phosphine oxygen structure according to claim 1, characterized in that: The halogen is fluorine, chlorine or bromine.

3. The isobenzofuran compound containing a phosphine oxygen structure according to claim 1, characterized in that: R 2 The substituent is C1~C2 alkyl, C1~C2 alkoxy or halogen.

4. The isobenzofuran compound containing a phosphine oxygen structure according to claim 3, characterized in that: R 2 The substituent is methyl, methoxy or halogen.

5. The isobenzofuran compound containing a phosphine oxygen structure according to claim 1, characterized in that: The aryl group is selected from any one of the following: phenyl, thienyl, and dibenzocyclic substituents containing 0 to 2 substituents.

6. The isobenzofuran compound containing a phosphine oxygen structure according to claim 5, characterized in that: The aryl group is a phenyl group containing 1 to 2 substituents, and the substituents are methyl, methoxy or halogen.

7. The isobenzofuran compound containing a phosphine oxygen structure according to claim 5, characterized in that: The dibenzocyclic substituent is a dibenzo five-membered ring, a dibenzo six-membered ring or a dibenzo seven-membered ring.

8. A method for synthesizing the isobenzofuran compound containing a phosphine oxide structure according to any one of claims 1 to 7, characterized in that: The synthetic route of this method is as follows: The method comprises the following steps: using o-propargyl alcohol benzaldehyde compounds and diaryl phosphine oxide compounds as reaction raw materials, using 1,2-dichloroethane as reaction solvent, reacting in an oil bath at 78 to 82° C. for 12 to 24 hours without adding metal or acid-base catalysts, and obtaining a crude product of isobenzofuran compounds containing a phosphine oxide structure.

9. The method for synthesizing the isobenzofuran compound containing a phosphine oxide structure according to claim 8, characterized in that: The method also includes the following purification steps: taking a crude product of an isobenzofuran compound containing a phosphine oxygen structure, directly concentrating it under reduced pressure on a rotary evaporator, adding silica gel, loading the sample by dry method, and purifying it by silica gel column chromatography, wherein the eluent is dichloromethane-ethyl acetate in a volume ratio of (10-25):

1.

10. The method for synthesizing isobenzofuran compounds containing phosphine oxide structures according to claim 8, characterized in that: The eluent is dichloromethane-ethyl acetate in a volume ratio of 20:1.

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