A chromanone compound and its preparation method and application

Abstract

The present invention discloses a chromanone compound, and the structural formula is: wherein: X is C, NR<supgt;5< / supgt>, O or S, Y is N or C-CN, and n is 0, 1, 2 or 3; R is selected from hydrogen, halogen, hydrocarbon group, aryl group, heteroaryl group, cyano group or nitro group, and R<supgt;1< / supgt>, R<supgt;2< / supgt>, R<supgt;3< / supgt> and R<supgt;4< / supgt> are independently selected from hydrogen, halogen, hydrocarbon group, alkoxy group, alkenyl group, alkynyl group, aryl group, heteroaryl group, and the R<supgt;5 is one of an alkyl group or an acyl group.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a chromanone compound and a preparation method and application thereof. Background Art

[0002] Chromone is the core structure of many natural products and important biologically active molecules. It has a wide range of physiological activities. Its derivatives are widely distributed in nature, such as inhibiting SIRT2, anti-tobacco mosaic virus, anti-HIV, antioxidant, antibacterial, anti-angiogenesis, etc. In the process of drug discovery and design, chromone skeleton compounds are important intermediates and building blocks in the synthesis of lead compounds. Its general structural formula is as follows (IV):

[0003]

[0004] Dihydroisoflavonoids (V) are derivatives of chromanone with benzyl substitution at the 3-position, and are important components of chromanone compounds. However, the aromatic W in such chromanone compounds distributed in nature is all phenyl, that is, there are no compounds in which the aromatic W is a heteroaromatic ring in natural products. This indicates that in the natural synthesis of natural products, the relevant reaction cannot be carried out, that is, in the natural synthesis of chromanone compounds, when W is a heteroaromatic ring, the reaction is blocked and cannot be carried out, resulting in the structure that the aromatic W in chromanone compounds in nature is a benzene ring.

[0005] Therefore, developing and preparing new chromanone compounds has become a direction for technical breakthroughs for those skilled in the art. Summary of the invention

[0006] The present invention provides a chromanone compound and a preparation method and application thereof, aiming to break through the structural limitations of the chromanone compound through chemical synthesis and obtain a new type of chromanone compound.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] First, the present invention provides a chromanone compound, which is represented by structural formula (III):

[0009]

[0010] in:

[0011] X is C, NR 5 , O or S, Y is N or C-CN, and n is 0, 1, 2 or 3.

[0012] R is selected from hydrogen, halogen, hydrocarbon, aryl, heteroaryl, cyano or nitro, R 1 , R 2 , R 3 and R4 are independently selected from hydrogen, halogen, hydrocarbon, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, and the R 5 It is one of an alkyl group or an acyl group.

[0013] Furthermore, the halogen in R is one of fluorine, chlorine, and bromine, the hydrocarbon group is one of methyl, ethyl, propyl, trifluoromethyl, and methoxy, and the aryl group is one of phenyl, quinoline, isoquinoline, indole, pyrimidine, pyrazine, pyridazine, furan, thiazole, thiophene, and imidazole;

[0014] Furthermore, the R 1 , R 2 , R 3 and R 4 wherein the halogen is one of fluorine, chlorine and bromine, the alkyl is one of methyl, ethyl, propyl, trifluoromethyl, tert-butyl and methoxy, the alkenyl is one of vinyl and propenyl, the alkynyl is one of ethynyl and butynyl, and the aryl is one of phenyl, pyridine, quinoline, isoquinoline, indole, pyrimidine, pyrazine, pyridazine, pyrrole, furan, thiazole, thiophene and imidazole;

[0015] Furthermore, the R 5 It is one of methyl, ethyl, propyl, trifluoromethyl, tert-butyl, acetyl, methanesulfonyl, trifluoroacetyl and trifluoromethanesulfonyl.

[0016] Furthermore, the halogen in R is one of fluorine and chlorine, the hydrocarbon group is one of methyl, trifluoromethyl, and methoxy, and the aryl group is one of phenyl, p-methylphenyl, p-methoxyphenyl, p-tert-butylphenyl, p-fluorophenyl, quinoline, isoquinoline, indole, and pyrimidine;

[0017] Furthermore, the R 1 , R 2 , R 3 and R 4 wherein the halogen is one of fluorine and chlorine, the alkyl is one of methyl, ethyl, propyl, trifluoromethyl and tert-butyl, the alkenyl is one of vinyl and propenyl, the alkynyl is one of ethynyl and butynyl, and the aryl is one of phenyl, pyridine, quinoline, isoquinoline, indole, pyrimidine, pyridazine, pyrazine, furan, thiazole, thiophene and imidazole;

[0018] Furthermore, the R 5 It is one of methyl, ethyl, trifluoromethyl, tert-butyl, acetyl and methanesulfonyl.

[0019] Further, the chromanone structure is as follows:

[0020]

[0021] Secondly, the present invention provides a method for preparing the chromanone compounds, wherein allylbenzoic acid (I) and cyanoarene (II) are mixed with a photocatalyst and an organic phosphine, dissolved in an organic solvent, and reacted under photocatalysis.

[0022] Furthermore, the reaction is carried out under an inert gas atmosphere.

[0023] Furthermore, the photocatalysis is visible light catalysis.

[0024] Furthermore, the photocatalyst is one or more of 3DPAFIPN, 3DPA2FBN, 3CzClIPN, 3DPAClIPN, 4CzIPN, and 5CzBN.

[0025] Furthermore, the molar ratio of the allylbenzoic acid, cyanoarene, photocatalyst and organic phosphine is 1:(1-2):(0.01-0.05):(1-5), preferably 1:1.5:0.02:2.

[0026] Furthermore, the compound allylbenzoic acid is represented by the structural formula (I), and the compound cyanoarene is represented by the structural formula (II):

[0027]

[0028] Furthermore, the compound allylbenzoic acid is 1.0 equivalent, cyanoarene is 1.5 equivalent, photocatalyst is 0.02 equivalent, organic phosphine is 2.0 equivalent, organic solvent is 2 mL / equivalent, the inert gas is argon, the reaction temperature is 25° C., and the reaction time is 24 h.

[0029] Furthermore, the organic phosphine is one or more of triphenylphosphine, tri-p-tolylphosphine, diphenylmethylphosphine, dimethylphenylphosphine, tri(4-methoxyphenyl)phosphine, tri(2-methoxyphenyl)phosphine, diphenylethoxyphosphine, triethyl phosphite, and tri(pentafluorophenyl)phosphine.

[0030] Furthermore, the organic solvent is one or more of acetonitrile, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide.

[0031] Furthermore, the compound allylbenzoic acid (I) has the structural formula:

[0032]

[0033] Furthermore, the compound cyanoarene (II) has the structural formula:

[0034]

[0035] Further, the specific steps of the reaction are as follows:

[0036] Under inert gas protection conditions, allyl benzoic acid (I) and cyanoarene (II) are used as raw materials, mixed with a certain amount of photocatalyst and organic phosphine, and reacted in an organic solvent at a temperature of 0°C to 50°C under 30W blue light irradiation for 12 to 24 hours. After the reaction is completed, the solvent is removed under reduced pressure, and column chromatography is used for separation and purification to obtain a chromanone compound shown in structural formula (III); the weight proportions of allyl benzoic acid, cyanoarene, photocatalyst, organic phosphine, and organic solvent are as follows: allyl benzoic acid is 1.0 to 2.0 equivalents, cyanoarene is 1.0 to 4.0 equivalents, photocatalyst is 0.01 to 0.02 equivalents, organic phosphine is 1.0 to 4.0 equivalents, and organic solvent is 2 to 5 mL / equivalent.

[0037] Finally, the present invention provides the use of the above chromanone compounds in the preparation of pharmaceutical products and chemical raw materials, and further, in the preparation of anti-tumor pharmaceutical products and / or chemical raw materials for the preparation of anti-tumor drugs.

[0038] Due to the adoption of the above technical solution, the present invention has the following advantages:

[0039] 1. The products prepared in the present invention are all chromanone compounds with novel structures, which break through the limitation that the aromatic ring structure of chromanone compounds in nature must be a benzene ring, and obtain chromanone compounds with heteroaromatic ring structures. The obtained compounds are confirmed by nuclear magnetic resonance spectrometer detection.

[0040] 2. The present invention realizes the chemical preparation of the above-mentioned chromanone compounds through chemical synthesis, and obtains a reliable preparation method that can be used for industrial production.

[0041] 3. The chemical preparation method of the present invention uses allylbenzoic acid and cyanoarene as raw materials, is easy to operate, has mild reaction conditions, stable process conditions, easy product purification, a wide substrate range, good functional group tolerance, low production cost, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The accompanying drawings of the present invention are as follows:

[0043] Figure 1 The synthetic flow chart of this application;

[0044] Figure 2 This is the nuclear magnetic resonance image of the compound prepared in Example 1 of the present invention;

[0045] Figure 3 This is the nuclear magnetic resonance image of the compound prepared in Example 2 of the present invention;

[0046] Figure 4This is the nuclear magnetic resonance image of the compound prepared in Example 3 of the present invention;

[0047] Figure 5 This is the nuclear magnetic resonance image of the compound prepared in Example 4 of the present invention;

[0048] Figure 6 This is the nuclear magnetic resonance image of the compound prepared in Example 5 of the present invention;

[0049] Figure 7 This is the nuclear magnetic resonance image of the compound prepared in Example 6 of the present invention;

[0050] Figure 8 This is the nuclear magnetic resonance image of the compound prepared in Example 7 of the present invention;

[0051] Fig. 9 This is the nuclear magnetic resonance image of the compound prepared in Example 8 of the present invention;

[0052] Fig.10 This is the nuclear magnetic resonance image of the compound prepared in Example 9 of the present invention;

[0053] Fig.11 This is the nuclear magnetic resonance image of the compound prepared in Example 10 of the present invention;

[0054] Fig.12 This is the nuclear magnetic resonance image of the compound prepared in Example 11 of the present invention;

[0055] Fig.13 This is the nuclear magnetic resonance image of the compound prepared in Example 12 of the present invention;

[0056] Fig.14 This is the nuclear magnetic resonance image of the compound prepared in Example 13 of the present invention;

[0057] Fig.15 This is the nuclear magnetic resonance image of the compound prepared in Example 14 of the present invention;

[0058] Fig.16 This is the nuclear magnetic resonance image of the compound prepared in Example 15 of the present invention;

[0059] Fig.17 This is the nuclear magnetic resonance image of the compound prepared in Example 16 of the present invention;

[0060] Fig.18 This is the nuclear magnetic resonance image of the compound prepared in Example 17 of the present invention. DETAILED DESCRIPTION

[0061] The present invention is further described below in conjunction with the accompanying drawings and embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments, and all technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0062] Preparation of chromanone compounds, such as Figure 1 As shown, the general synthesis steps are as follows:

[0063] Under the protection of argon, 1.0 equivalent of allylbenzoic acid (I), 1.5 equivalent of cyanoarene (II), 0.02 equivalent of 3DPAFIPN, and 2.0 equivalent of tri-p-tolylphosphine were mixed in sequence, and reacted in 2 mL / equivalent of acetonitrile at 25°C for 24 h. After the reaction, the solvent was removed under reduced pressure, and the mixture was separated and purified by column chromatography to obtain chromanone compounds.

[0064] Example 1: Preparation of 3-(2-(pyridin-4-yl)propan-2-yl)chroman-4-one

[0065]

[0066] (1) Experimental methods

[0067] Under argon conditions, 2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (61.8 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0068] (2) Experimental results

[0069] Depend on Figure 2 It can be seen that Figure 2 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B NMR 13 C spectrum, the obtained product is a yellow oily liquid with a yield of 72%;

[0070] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.62–8.50(m,2H),7.87(d,J=7.8Hz,1H),7.44(t,J=7.6Hz,1H),7.33–7.27(m,2H),7.01(t,J=7.3Hz,1H),6.8 7(d,J=8.2Hz,1H),4.37–4.30(m,1H),4.23(dd,J=12.0,5.3Hz,1H),2.91–2.82(m,1H),1.53(s,3H),1.43(s,3H). 13 CNMR (101MHz, CDCl 3 )δ192.5,161.2,156.4,150.0,136.0,127.2,122.0,121.5,121.3,117.6,68.9,54.4,39.8,27.8,24.0.

[0071] Example 2: Preparation of 7-methyl-3-(2-(pyridin-4-yl)propan-2-yl)chroman-4-one

[0072]

[0073] (1) Experimental methods

[0074] Under argon conditions, 4-methyl-2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (66.1 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0075] (2) Experimental results

[0076] Depend on Figure 3 It can be seen that Figure 3 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B NMR 13 C spectrum, the obtained product is a yellow oily liquid with a yield of 65%;

[0077] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.56(d,J=4.8Hz,2H),7.76(d,J=8.0Hz,1H),7.34–7.26(m,2H),6.82(d,J=8.0Hz,1H),6.67(s,1H),4.30(d d,J=12.0,4.0Hz,1H),4.18(dd,J=12.0,5.1Hz,1H),2.86–2.77(m,1H),2.33(s,3H),1.52(s,3H),1.42(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ192.2,161.2,156.6,149.9,147.5,127.1,122.9,121.4,119.8,117.6,69.0,54.4,39.9,27.9,23.9,21.9.

[0078] Example 3: Preparation of 7-methoxy-3-(2-(pyridin-4-yl)propane-2-yl)chroman-4-one

[0079]

[0080] (1) Experimental methods

[0081] Under argon conditions, 4-methoxy-2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (70.9 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0082] (2) Experimental results

[0083] Depend on Figure 4 It can be seen that Figure 4 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B NMR 13 C spectrum, the obtained product is a white solid, melting point 112.1-113.5℃, yield 48%;

[0084] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.55(d,J=4.5,2H),7.81(d,J=8.8,1H),7.29(d,J=4.7,2H),6.56(d,J=8.8,1H),6.29(s,1H),4.30(dd ,J=12.0,4.0,1H),4.18(dd,J=12.0,4.7,1H),3.81(s,3H),2.80–2.72(m,1H),1.51(s,3H),1.41(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ191.0,166.0,163.1,156.6,149.9,128.9,121.4,115.9,110.1,100.4,69.3,55.6,54.2,40.0,28.1,23.9.

[0085] Example 4: Preparation of 7-chloro-3-(2-(pyridin-4-yl)propane-2-yl)chroman-4-one

[0086]

[0087] (1) Experimental methods

[0088] Under argon conditions, 4-chloro-2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (72.2 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0089] (2) Experimental results

[0090] Depend on Figure 5 It can be seen that Figure 5 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B NMR 13 C spectrum, the product is a yellow oily liquid, the yield is 54%;

[0091] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.56(d,J=4.1,2H),7.80(d,J=8.4,1H),7.28(d,J=4.6,2H),6.98(d,J=8.4Hz,1H),6.90(s,1H), 4.32(dd,J=12.1,4.1,1H),4.21(dd,J=12.2,5.3,1H),2.87–2.80(m,1H),1.51(s,3H),1.41(s,3H).

[0092] 13 C NMR (101 MHz, CDCl 3 )δ191.4,161.5,156.1,150.1,141.8,128.5,122.4,121.3,120.5,117.7,69.3,54.3,39.9,27.8,23.9.

[0093] Example 5: Preparation of 7-fluoro-3-(2-(pyridin-4-yl)propan-2-yl)chroman-4-one

[0094]

[0095] (1) Experimental methods

[0096] Under argon conditions, 4-fluoro-2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (67.3 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 5:1).

[0097] (2) Experimental results

[0098] Depend on Figure 6 It can be seen that Figure 6 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, C is nuclear magnetic resonance 19 Spectrum F, the product is a yellow oily liquid, the yield is 60%;

[0099] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.56(d,J=4.4,2H),7.96–7.82(m,1H),7.29(d,J=5.7,2H),6.78–6.68(m,1H),6.60–6.50(m,1H), 4.34(dd,J=12.1,4.2,1H),4.24(dd,J=12.1,5.2,1H),2.89–2.81(m,1H),1.53(s,3H),1.42(s,3H). 13 CNMR (101MHz, CDCl 3 )δ191.1,167.4(d,J=256.4),162.8(d,J=13.6),156.2,150.0,129.8(d,J=11.4),121. 3,118.9(d,J=2.4),110.0(d,J=22.7),104.3(d,J=24.5),69.5,54.2,39.9,27.8,24.0. 19 FNMR (376MHz, CDCl 3 )δ-100.36.

[0100] Example 6: Preparation of 6-methoxy-3-(2-(pyridin-4-yl)propan-2-yl)chroman-4-one

[0101]

[0102] (1) Experimental methods

[0103] Under argon conditions, 5-methoxy-2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (70.9 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0104] (2) Experimental results

[0105] Depend on Figure 7 It can be seen that Figure 7 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a white solid, melting point 80.6-82.6℃, yield 58%;

[0106] Product characterization: 1 H NMR (400 MHz, CDCl 3 )δ8.55(d,J=4.8,2H),7.33–7.27(m,3H),7.05(dd,J=9.0,2.6Hz,1H),6.80(d,J=9.0Hz,1H),4.29(dd, J=12.1,4.2,1H),4.17(dd,J=12.0,5.4,1H),3.78(s,3H),2.85–2.79(m,1H),1.51(s,3H),1.41(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ192.6,156.5,155.9,154.1,149.9,125.2,121.7,121.3,118.9,107.4,69.1,55.8,54.4,39.9,27.7,24.1.

[0107] Example 7: Preparation of 5-fluoro-3-(2-(pyridin-4-yl)propan-2-yl)chroman-4-one

[0108]

[0109] (1) Experimental methods

[0110] Under argon conditions, 2-fluoro-6-((3-methylbut-2-en-1-yl)oxy)benzoic acid (67.3 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0111] (2) Experimental results

[0112] Depend on Figure 8 It can be seen that Figure 8 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, C is nuclear magnetic resonance 19 F spectrum, the obtained product is a yellow solid, melting point 109.9-110.9℃, yield 24%;

[0113] Product characterization:1 H NMR (400 MHz, CDCl 3 )δ8.55(d,J=4.5,2H),7.40–7.32(m,1H),7.32–7.26(m,2H),6.73–6.63(m,2H),4.33(dd, J=12.0,3.9,1H),4.24(dd,J=12.1,5.7,1H),2.88–2.81(m,1H),1.54(s,3H),1.46(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ190.3,162.0(d,J=3.0),161.7(d,J=265.8),156.1,149.9,135.9(d,J=11.9),121. 3,113.3(d,J=3.9),112.0(d,J=8.6),109.0(d,J=21.4),68.7,55.0,39.8,27.6,24.1. 19 F NMR (376 MHz, CDCl 3 )δ-111.01.

[0114] Example 8: Preparation of 3-(pyridin-4-ylmethyl)chroman-4-one

[0115]

[0116] (1) Experimental methods

[0117] Under argon conditions, 2-(allyloxy)benzoic acid (53.5 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL), and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0118] (2) Experimental results

[0119] Depend on Fig. 9 It can be seen that Fig. 9 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a white solid, melting point 75.1-77.4 ° C, yield 25%;

[0120] Product characterization: 1 H NMR (400 MHz, CDCl 3 )δ8.55(d,J=4.3,2H),7.92(d,J=7.8,1H),7.50(t,J=7.7,1H),7.19(d,J=4.8,2H),7.05(t,J=7.5,1H),6.97(d,J =8.3,1H),4.39(dd,J=11.5,4.4,1H),4.21–4.10(m,1H),3.33–3.24(m,1H),3.06–2.94(m,1H),2.77–2.67(m,1H). 13 C NMR (101 MHz, CDCl 3 )δ192.9,161.5,150.0,147.6,136.2,127.5,124.4,121.7,120.4,117.9,69.4,46.7,31.7.

[0121] Example 9: Preparation of 3-(2-(pyridin-4-yl)propane-2-yl)thiochroman-4-one

[0122]

[0123] (1) Experimental methods

[0124] Under argon conditions, 2-((3-methylbut-2-en-1-yl)thio)benzoic acid (66.7 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL), and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0125] (2) Experimental results

[0126] Depend on Fig.10 It can be seen that Fig.10 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow oily liquid with a yield of 52%;

[0127] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.55(d,J=4.5,2H),7.96(d,J=7.9,1H),7.38–7.32(m,1H),7.31(d,J=4.9,2H),7.20(d,J=7.9,1H), 7.14(t,J=7.5,1H),3.37–3.29(m,1H),3.21–3.12(m,1H),2.99–2.91(m,1H),1.55(s,3H),1.47(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ194.3,158.0,149.9,141.1,133.0,132.2,129.5,127.1,124.9,121.0,55.9,40.5,28.3,25.6,25.0.

[0128] Example 10: Preparation of 1-butyryl-3-(2-(pyridin-4-yl)propyl-2-yl)-2,3-dihydroquinolin-4(1H)-one

[0129]

[0130] (1) Experimental methods

[0131] Under argon conditions, 2-(N-(3-methylbut-2-en-1-yl)butyramide)benzoic acid (82.6 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, dichloromethane: methanol = 30:1).

[0132] (2) Experimental results

[0133] Depend on Fig.11 It can be seen that Fig.11 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow oily liquid with a yield of 60%;

[0134] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.57(d,J=4.0,2H),7.94(d,J=7.7,1H),7.51(t,J=7.5,1H),7.48–7.39(m,1H),7.31–7.26(m,2H),7.26–7.20(m,1H),4.60–4.26( m,1H),3.66–3.54(m,1H),3.08(dd,J=10.5,4.1,1H),2.37–2.22(m,2H),1.67(m,2H),1.56(s,3H),1.43(s,3H),0.92(t,J=7.3,3H). 13 C NMR (101 MHz, CDCl 3 )δ195.1,172.2,157.1,150.0,143.4,133.9,127.9,127.0,125.4,123.5,121.1,56.9,46.0,40.1,36.4,26.7,25.1,18.9,13.8.

[0135] Example 11: Preparation of 2-(2-(pyridin-4-yl)propan-2-yl)-3,4-dihydronaphthalen-1(2H)-one

[0136]

[0137] (1) Experimental methods

[0138] Under argon conditions, 2-(4-methylpent-3-en-1-yl)benzoic acid (61.3 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 3:1).

[0139] (2) Experimental results

[0140] Depend on Fig.12 It can be seen that Fig.12 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow solid, melting point 108.4-109.4℃, yield 60%;

[0141] Product characterization: 1H NMR (400 MHz, CDCl 3 )δ8.68–8.42(m,2H),7.89(d,J=7.6,1H),7.44(t,J=7.2,1H),7.35–7.24(m,3H),7.20(d,J= 7.4,1H),3.11–2.88(m,3H),2.13–2.02(m,1H),2.01–1.85(m,1H),1.55(s,3H),1.39(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ198.2,159.3,149.7,143.2,133.8,133.1,128.5,127.3,126.6,121.1,56.6,40.0,29.9,25.7,25.7,25.1.

[0142] Example 12: Preparation of 2-(2-(pyridin-4-yl)propane-2-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-one

[0143]

[0144] (1) Experimental methods

[0145] Under argon conditions, 1-(3-methylbut-2-ene-1-yl)-1H-indole-2-carboxylic acid (68.8 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 1:1).

[0146] (2) Experimental results

[0147] Depend on Fig.13 It can be seen that Fig.13 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow solid, melting point 205.4-206.3℃, yield 42%;

[0148] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.60(d,J=5.2Hz,2H),7.74(d,J=8.2Hz,1H),7.35–7.27(m,4H),7.20–7.14(m,1H),6.99(s,1H),4.22(d d,J=11.5,8.2Hz,1H),3.80(dd,J=11.5,4.5Hz,1H),3.59(dd,J=8.1,4.5Hz,1H),1.66(s,3H),1.39(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ193.5,156.4,150.2,136.3,135.0,132.0,125.2,124.2,121.6,121.1,110.5,99.2,58.5,44.0,41.1,28.0,21.8.

[0149] Example 13: Preparation of 8-(2-(pyridin-4-yl)propan-2-yl)-7,8-dihydropyrido[1,2-a]indol-9(6H)-one

[0150]

[0151] (1) Experimental methods

[0152] Under argon conditions, 1-(4-methylpent-3-en-1-yl)-1H-indole-2-carboxylic acid (73.0 mg, 0.3 mmol), 4-cyanopyridine (46.8 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 1:1).

[0153] (2) Experimental results

[0154] Depend on Fig.14 It can be seen that Fig.14 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow solid, melting point 200.5-201.7℃, yield 54%;

[0155] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.56(d,J=5.3Hz,2H),7.70(d,J=8.1Hz,1H),7.39–7.27(m,4H),7.22(s,1H),7.15(t,J=7.4Hz,1H), 4.41–4.28(m,1H),4.09–3.95(m,1H),3.14–2.99(m,1H),2.25–2.14(m,2H),1.63(s,3H),1.45(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ190.1,158.5,149.9,136.9,134.5,126.9,125.6,123.4,121.2,121.1,110.2,105.7,54.9,41.6,40.2,26.4,25.8,24.8.

[0156] Example 14: Preparation of 3-(2-(2-(p-tolyl)pyridin-4-yl)propan-2-yl)chroman-4-one

[0157]

[0158] (1) Experimental methods

[0159] Under argon conditions, 2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (61.8 mg, 0.3 mmol), 2-(p-tolyl)isonicotinonitrile (87.4 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 10:1).

[0160] (2) Experimental results

[0161] Depend on Fig.15 It can be seen that Fig.15 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a colorless oily liquid with a yield of 71%;

[0162] Product characterization: 1 H NMR (400 MHz, CDCl 3)δ8.61(d,J=5.0Hz,1H),7.92–7.82(m,3H),7.69(s,1H),7.43(t,J=7.6Hz,1H),7.31–7.26(m,2H),7.23(d,J=4.6Hz,1H),7.00(t,J =7.4Hz,1H),6.86(d,J=8.3Hz,1H),4.38–4.32(m,1H),4.31–4.24(m,1H),2.94–2.83(m,1H),2.41(s,3H),1.58(s,3H),1.48(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ192.7,161.2,157.8,157.0,149.8,139.0,136.8,136.0,129.5,127.2,12 6.9,122.0,121.5,119.6,118.0,117.6,69.0,54.5,40.1,28.2,23.9,21.3.

[0163] Example 15: Preparation of 3-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)propan-2-ylchroman-4-one

[0164]

[0165] (1) Experimental methods

[0166] Under argon conditions, 2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (61.8 mg, 0.3 mmol), 3-chloro-5-(trifluoromethyl)pyridinecarbonitrile (93.0 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 60:1).

[0167] (2) Experimental results

[0168] Depend on Fig.16 It can be seen that Fig.16 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, C is nuclear magnetic resonance 19F spectrum, the obtained product is a white solid, melting point 112.9-113.8℃, yield 38%; product characterization: 1 H NMR (400 MHz, CDCl 3 )δ8.67(s,1H),7.87(s,1H),7.82(d,J=7.8Hz,1H),7.46(t,J=7.7Hz,1H),7.00(t,J=7.5Hz, 1H), 6.95 (d, J = 8.3Hz, 1H), 4.63–4.51 (m, 2H), 3.98–3.90 (m, 1H), 1.68 (s, 3H), 1.64 (s, 3H). 13 C NMR (101 MHz, CDCl 3 )δ192.9,165.3,161.4,142.5(q,J=4.0Hz),136.4(q,J=3.5Hz),135.6,130.2,127.4,125. 5(q,J=33.4Hz),122.7(q,J=272.7Hz),122.1,121.5,117.6,69.0,52.2,44.5,25.2,24.2. 19 F NMR (376 MHz, CDCl 3 )δ-62.23.

[0169] Example 16: Preparation of 3-(2-(quinolin-2-yl)propane-2-ylchroman-4-one

[0170]

[0171] (1) Experimental methods

[0172] Under argon conditions, 2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (61.8 mg, 0.3 mmol), quinoline-2-carbonitrile (69.4 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 10:1).

[0173] (2) Experimental results

[0174] Depend on Fig.17 It can be seen that Fig.17 A in the figure stands for nuclear magnetic resonance 1H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow oily liquid with a yield of 49%;

[0175] Product characterization: 1 H NMR (400 MHz, CDCl 3 )δ8.13(d,J=8.6Hz,1H),7.92(d,J=8.4Hz,1H),7.84(d,J=7.3Hz,1H),7. 78(d,J=8.0Hz,1H),7.63(t,J=7.5Hz,1H),7.57(d,J=8.6Hz,1H),7.47(t, J=7.4Hz,1H),7.41(t,J=7.3Hz,1H),6.97(t,J=7.4Hz,1H),6.90(d,J=8. 3Hz,1H),4.64–4.56(m,2H),3.78–3.68(m,1H),1.62(s,3H),1.61(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ193.7,166.5,161.5,147.3,136.3,135.4,129.3,129.1,127.3,127.2 ,126.5,125.9,122.4,121.2,118.1,117.5,69.5,54.2,42.8,26.6,26.3.

[0176] Example 17: Preparation of 4-(2-(7-methoxy-4-oxochroman-3-yl)propane-2-yl)benzonitrile

[0177]

[0178] (1) Experimental methods

[0179] Under argon conditions, 2-((3-methylbut-2-en-1-yl)oxy)benzoic acid (61.8 mg, 0.3 mmol), terephthalonitrile (57.6 mg, 0.45 mmol), 3DPAFIPN (3.9 mg, 0.006 mmol), tri-p-tolylphosphine (182.6 mg, 0.6 mmol) and acetonitrile (6 mL) were added to a dry Schlenk tube (10 mL) in sequence, and the reaction tube was placed in a 30 W blue LEDs light source (about 2 cm from the light source) and reacted at room temperature for 24 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compound was separated by column chromatography (100-200 mesh, petroleum ether: ethyl acetate = 10:1).

[0180] (2) Experimental results

[0181] Depend on Fig.18 It can be seen that Fig.18 A in the figure stands for nuclear magnetic resonance 1 H spectrum, B is NMR 13 C spectrum, the obtained product is a yellow solid, melting point 117.7-119.1℃, yield 63%;

[0182] Product characterization: 1 H NMR (400 MHz, CDCl 3 )δ7.77(d,J=8.9Hz,1H),7.60(d,J=8.6Hz,2H),7.49(d,J=8.6Hz,2H),6.54(dd,J=8.9,2.4Hz,1H),6.26(d,J=2.4Hz,1H ),4.30(dd,J=12.1,4.4Hz,1H),4.18(dd,J=12.1,4.9Hz,1H),3.80(s,3H),2.79–2.72(m,1H),1.52(s,3H),1.42(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ191.0,166.0,163.1,153.1,132.1,128.9,127.0,118.9,115.9,110.1,100.4,69.3,55.7,54.5,40.5,28.0,24.8.

Claims

1. A method for preparing a chromanone compound, Features: Allylbenzoic acid and cyanoaromatic hydrocarbon are mixed with a photocatalyst and an organic phosphine, dissolved in an organic solvent, and reacted under photocatalysis; Wherein, the structural formula of the allyl benzoic acid is as follows: The structural formula of the cyano aromatic hydrocarbon is as follows: The photocatalyst is 3DPAFIPN.

2. The method for preparing the chromanone compound according to claim 1, Features: The reaction is carried out under an inert gas atmosphere.

3. The method for preparing the chromanone compound according to claim 1, Features: The molar ratio of the allylbenzoic acid, cyanoarene, photocatalyst and organic phosphine is 1:(1-2):(0.01-0.05):(1-5).

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