Method for synthesizing polysubstituted 2, 7-dioxo-bicyclo [3.2. 1] octane compound under catalysis of haloid acid

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a polysubstituted 2, 7-dioxicyclo [3.2. 1] octane compound and a preparation method thereof. According to the invention, gamma-hydroxy-alpha, beta-unsaturated ketene and a compound 1 are taken as reaction raw materials, halogen acid is taken as a catalyst, and the polysubstituted 2, 7-dioxo-bicyclo [3.2. 1] octane compound can be prepared at normal temperature and normal pressure. The preparation method provided by the invention has the advantages of simple operation, cheap and easily available raw materials and catalyst, mild reaction conditions and easy industrial production. The polysubstituted 2, 7-dioxicyclo [3.2. 1] octane compound prepared by the preparation method provided by the invention has high yield and purity, and has good application prospects and economic benefits in the fields of synthesis and drug research and development.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound and a preparation method thereof. BACKGROUND

[0002] 2,7-dioxabicyclo[3.2.1]octane is the core skeleton of many natural products and bioactive molecules, and some of the compounds exhibit significant biological activity. However, the currently reported methods for synthesizing the skeleton are limited by reaction mode, rely on stoichiometric acid, require low or high temperature control, and have poor reaction efficiency and chemical selectivity. Therefore, developing an economical, universal and efficient method for synthesizing polysubstituted 2,7-dioxabicyclo[3.2.1]octane compounds is of great significance to organic chemistry and medicinal chemistry. SUMMARY

[0003] Therefore, the application provides a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound and a preparation method thereof. The preparation method of the 2,7-dioxabicyclo[3.2.1]octane compound provided by the application is simple and easy to operate, and the yield of the prepared 2,7-dioxabicyclo[3.2.1]octane compound is high.

[0004] The application provides a preparation method of a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound, comprising the following steps:

[0005] The gamma-hydroxy-alpha, beta-unsaturated enone, compound 1, a hydrogen halide acid catalyst and an organic solvent are mixed to perform a ring-forming reaction, so as to obtain the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound;

[0006] The gamma-hydroxy-alpha, beta-unsaturated enone has a structure shown in formula 1 or is The compound 1 has a structure shown in any one of formulae 2 to 10:

[0007]

[0008] When the gamma-hydroxy-alpha, beta-unsaturated enone is , the compound 1 is The polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound is

[0009] When the gamma-hydroxy-alpha, beta-unsaturated enone is , the compound 1 is The polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound is

[0010] when the γ-hydroxy-α,β-unsaturated ketone is then the compound 1 is of the structure of any one of formulas 2-10; when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula I, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula II, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula III, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula IV, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula V, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula VI, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula VII, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula VIII, when the compound 1 is then the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound has the structure of formula IX:

[0011]

[0012] wherein R 1 and R 2 are independently aryl, phenyl, halogen-substituted phenyl, alkyl;

[0013] R 3 are independently aryl, phenyl, halogen-substituted phenyl, alkoxy-substituted phenyl;

[0014] R 4 are independently hydrogen, halogen, alkoxy.

[0015] Preferably, the (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4-hydroxy-4,4-di(naphthalen-2-yl)-1-phenyl-2-buten-1-one, (E)-3-(9-hydroxy-9H-fluoren-9-yl)-1-phenyl-2-propen-1-one, (E)-4-hydroxy-4-methyl-1-phenyl-2-penten-1-one, (E)-3-(1-hydroxycyclopentyl)-1-phenyl-2-propen-1-one, (E)-4-hydroxy-1,4-diphenyl-2-penten-1-one, (E)-4-hydroxy-1-(4-methoxyphenyl)-4,4-diphenyl-2-buten-1-one, (E)-4-hydroxy-1-(2-methoxyphenyl)-4,4-diphenyl-2-buten-1-one, (E)-1-(4-bromophenyl)-4-hydroxy-4,4-diphenyl-2-buten-1-one, (E)-4-hydroxy-1-(naphthalen-2-yl)-4,4-diphenyl-2-buten-1-one.

[0016] Preferably, the hydrohalic acid catalyst comprises an aqueous solution of hydrogen chloride (4 mol / L), a 1,4-dioxane solution of hydrogen chloride (4 mol / L) or an aqueous solution of hydrogen bromide (48%);

[0017] The molar ratio of the γ-hydroxy-α,β-unsaturated enone and the hydrohalic acid catalyst is 1:0.05-0.2.

[0018] Preferably, the γ-hydroxy-α,β-unsaturated enone and the compound 1 are in a molar ratio of 1:1.3-2.2. The compound 1 comprises 2-naphthol, 6-bromo-2-naphthol, 7-bromo-2-naphthol, 6-methoxy-2-naphthol, 7-methoxy-2-naphthol.

[0019] The molar ratio of the γ-hydroxy-α,β-unsaturated enone and the compound 1 is 1:1.3-2.2.

[0020] Preferably, the temperature of the ring-forming reaction is 25-45°C and the time is 24-48 h.

[0021] The present application also provides a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound prepared by the preparation method described in the above technical solution, which has any one of the structures shown in Formulas I-IX:

[0022]

[0023] wherein, R 1 and R 2independently aryl, phenyl, halogen-substituted phenyl, alkyl;

[0024] R 3 independently aryl, phenyl, halogen-substituted phenyl, alkyl;

[0025] R 4 independently hydrogen, halogen, alkoxy.

[0026] Preferably, the compound has any one of the structures shown in Formulae I-1 to I-17, Formula II-1, Formula III-1, Formula IV-1, Formula V-1, Formula VI-1, Formula VII-1, VIII-1, IX-1:

[0027]

[0028]

[0029] The present application uses γ-hydroxy-α, β-unsaturated enone and compound 1 as raw materials, and uses hydrohalic acid as a catalyst to prepare a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound at normal temperature and pressure. The preparation method provided by the present application is simple to operate, and the raw materials and catalysts are cheap and easy to obtain. The reaction conditions are mild, and the method is easy to industrialize. The polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound prepared by the preparation method provided by the present application has high yield and purity, and has good application prospect and economic benefit in the fields of synthesis and drug research and development. DETAILED DESCRIPTION

[0030] The present application provides a preparation method of a polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound, comprising the following steps:

[0031] Mixing γ-hydroxy-α, β-unsaturated enone, compound 1, hydrohalic acid catalyst and organic solvent to carry out ring formation reaction to obtain the polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound;

[0032] The γ-hydroxy-α, β-unsaturated enone has a structure shown in Formula 1 or is The compound 1 has any one of the structures shown in Formulae 2 to 10:

[0033]

[0034] As a specific embodiment of the present application, when the γ-hydroxy-α, β-unsaturated enone is , the compound 1 is The polysubstituted 2,7-dioxabicyclo[3.2.1]octane compound is

[0035] In one specific embodiment of the present invention, when the γ-hydroxy-α,β-unsaturated enone is When, compound 1 is The polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound is

[0036] When the γ-hydroxy-α,β-unsaturated enone is When compound 1 has the structure shown in any of formulas 2 to 10; when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula I, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula II, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula III, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula IV, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula V, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula VI, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula VII, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula VIII, when compound 1 is At that time, the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula IX:

[0037]

[0038] In this invention, R 1 The R is an aryl, phenyl, halogen-substituted phenyl, or alkyl group. 1 The aryl group can be naphthyl, and the R 1 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, or 3-chlorophenyl, wherein R 1 The alkyl group can be methyl; R 2 The R is an aryl, phenyl, halogen-substituted phenyl, or alkyl group. 2 The aryl group can be naphthyl, and the R 2The halogen-substituted phenyl group of R 2 The alkyl group of R

[0039] As a specific embodiment of the present application, R 1 and R 2 may be simultaneously 2-naphthyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, or methyl; R 1 and R 2 may be different, and when R 1 is phenyl, R 2 may be methyl.

[0040] In the present application, R 3 is aryl, phenyl, halogen-substituted phenyl, alkoxy-substituted phenyl, R 3 The aryl group of R 3 The halogen-substituted phenyl group of R 3 The alkoxy-substituted phenyl group of R

[0041] As a specific embodiment of the present application, the include (E)-4-hydroxy-l,4,4-triphenyl-2-buten-l-one, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-l-phenyl-2-buten-l-one, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-l-phenyl-2-buten-l-one, (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-l-phenyl-2-buten-l-one, (E)-4-hydroxy-4,4-di(naphthalen-2-yl)-l-phenyl-2-buten-l-one, (E)-3-(9-hydroxy-9H-fluoren-9-yl)-l-phenyl-2-propen-l-one, (E)-4-hydroxy-4-methyl-l-phenyl-2-penten-l-one, (E)-3-(l-hydroxycyclopentyl)-l-phenyl-2-propen-l-one, (E)-4-hydroxy-l,4-diphenyl-2-penten-l-one, (E)-4-hydroxy-l-(4-methoxyphenyl)-4,4-diphenyl-2-buten-l-one, (E)-4-hydroxy-l-(2-methoxyphenyl)-4,4-diphenyl-2-buten-l-one, (E)-l-(4-bromophenyl)-4-hydroxy-4,4-diphenyl-2-buten-l-one, (E)-4-hydroxy-l-(naphthalen-2-yl)-4,4-diphenyl-2-buten-l-one.

[0042] In the present application, R 4 is hydrogen, halogen, alkoxy, R 4 The halogen of R 4The alkoxy group of the alkoxy group can be methoxy.

[0043] As a specific embodiment of the present application, the may include 2-naphthol, 6-bromo-2-naphthol, 7-bromo-2-naphthol, 6-methoxy-2-naphthol, 7-methoxy-2-naphthol;

[0044] As a specific embodiment of the present application, the hydrogen halide catalyst can include an aqueous solution of hydrogen chloride (4 mol / L), a 1,4-dioxane solution of hydrogen chloride (4 mol / L), or an aqueous solution of hydrogen bromide (48%). In the present application, the hydrogen halide has a dual role: its acidic proton activates the γ-hydroxy-α,β-unsaturated enone carbonyl, while the halide ion performs a nucleophilic 1,4-addition to the γ-hydroxy-α,β-unsaturated enone to generate the key 2-hydroxy-2,5-dihydrofuran intermediate, thereby facilitating the efficient and selective synthesis of the product, and the synthesis of polysubstituted 2,7-dioxabicyclo[3.2.1]octane compounds can be achieved at normal temperature and pressure without the need for prior activation of the reactants.

[0045] As a specific embodiment of the present application, the molar ratio of the γ-hydroxy-α,β-unsaturated enone and the hydrogen halide catalyst can be 1:0.05-0.2. If the amount of hydrogen halide is reduced, the reaction time will be prolonged and the yield will also be reduced.

[0046] As a specific embodiment of the present application, the organic solvent can be dichloromethane, 1,2-dichloroethane, ethyl acetate, chloroform, toluene, nitromethane, chlorobenzene, or acetonitrile; the molar concentration of the γ-hydroxy-α,β-unsaturated enone in the reaction solution system of the ring-closing reaction can be 0.08-0.12 mol / L, and can be specifically 0.1 mol / L.

[0047] As a specific embodiment of the present application, the molar ratio of the γ-hydroxy-α,β-unsaturated enone and compound 1 can be 1:1.3-2.2, and can be specifically 1:1.5 or 1:2.

[0048] As a specific embodiment of the present application, the temperature of the ring-closing reaction can be 25-45°C; the time of the ring-closing reaction can be 24-48 h.

[0049] As a specific embodiment of the present application, the preparation The reaction equation is:

[0050] In this invention, the cyclization reaction further includes: concentrating the cyclization reaction system and then separating and purifying it using silica gel column chromatography to obtain the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound. This invention does not have special requirements for the concentration and silica gel column chromatography; conventional methods in the art can be used.

[0051] The present invention also provides a polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound prepared according to the preparation method described above, having the structure shown in any of formulas I to IX:

[0052]

[0053] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, or alkyl;

[0054] R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, and alkoxy-substituted phenyl;

[0055] R 4 The independent components are hydrogen, halogen, and alkoxy.

[0056] In one specific embodiment of the present invention, the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound may have any of the structures shown in Formula I-1 to I-17, Formula II-1, Formula III-1, Formula IV-1, Formula V-1, Formula VI-1, Formula VII-1, Formula VIII-1, and Formula IX-1:

[0057]

[0058] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0059] After the preparation of each embodiment was completed, in order to further verify that the purified compound was indeed the target product to be prepared in this embodiment, the obtained solid product was analyzed. The analytical methods used were nuclear magnetic resonance and high-resolution mass spectrometry, and the detection results are listed in each embodiment.

[0060] Example 1

[0061] Using R 1 =R 2 It is a phenyl group, R 3 Using (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 2-naphthol as reactants and hydrochloric acid as a catalyst, the specific process is as follows:

[0062] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (126.4 mg, 0.40 mmol), 2-naphthol (99.19%, 87.2 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μί, 0.04 mmol, 10 mol%, 4.0 min H20), 25 °C, 24 h. The reaction equation is as follows:

[0063]

[0064] After the reaction solution was concentrated, the solid product was obtained by silica gel column chromatography 160.5 mg, the calculated yield was 91 %.

[0065] The analysis of the test is as follows:

[0066] 1. Hydrogen spectrum of nuclear magnetic resonance analysis, carbon spectrum:

[0067] 1 H NMR (300 MHz, CDCI3) δ 7.84 - 7.66 (m, 5H), 7.55 (d, J = 8.6 Hz, 2H), 7.48 - 7.11 (m, 11H), 6.79 - 6.58 (m, 3H), 4.93 (d, J = 3.8 Hz, 1H), 2.70 (dd, Ji = 11.6 Hz, J2= 3.9 Hz, 1H), 2.58 (d, J = 11.6 Hz, 1H) ppm.

[0068] 13 C NMR (75 MHz, CDCI3) δ 150.6, 144.8, 142.5, 139.3, 131.1, 128.9, 128.69, 128.65, 128.5, 128.2, 128.1, 127.4, 126.8, 126.2, 126.0, 125.7, 125.6, 122.9, 121.8, 117.7, 117.5, 107.2, 98.3, 41.2, 39.5 ppm.

[0069] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 25 O2[M + + H]: 441.1849, Found: 441.1847.

[0070] From the results, it can be seen that the theoretical mass is 441.1849, and the observed value of the peak found in the actual mass spectrum is 441.1847; combined with nuclear magnetic resonance, the structure of the product can be determined as follows:

[0071] From the results, it can be seen that the theoretical mass is 441.1849, and the observed value of the peak found in the actual mass spectrum is 441.1847; combined with nuclear magnetic resonance, the structure of the product can be determined as follows: To the product of this example.

[0072] Example 2

[0073] R = R 1 = R 2 = 4-fluorophenyl, R 3 (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one and 2-naphthol as the starting materials, with hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0074] (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one (139.8 mg, 0.40 mmol), 2-naphthol (99.19%, 85.8 mg, 0.59 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), 25 °C for 48 h. The reaction equation is as follows:

[0075]

[0076] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 133.3 mg, the calculated yield was 70%.

[0077] The analysis of the test is as follows:

[0078] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0079] 1 H NMR (300 MHz, CDC13) δ 7.74-7.63 (m, 5H), 7.58 (d, J = 8.6 Hz, 2H), 7.45-7.36 (m, 3H), 7.35-7.26 (m, 1H), 7.23-7.06 (m, 6H), 6.48-6.36 (m, 2H), 4.85 (d, J = 3.6 Hz, 1H), 2.69 (dd, J1 = 11.7 Hz, J2 = 3.8 Hz, 1H), 2.60 (d, J = 11.7 Hz, 1H) ppm.

[0080] 13C NMR (75 MHz, CDC13) δ 162.0 (d, J = 245.3 Hz), 161.2 (d, J = 244.5 Hz), 150.4, 140.5 (d, J = 3.0 Hz), 139.0, 138.3 (d, J = 3.0 Hz), 130.9, 129.2, 128.81, 128.78, 128.4, 128.3, 127.7 (d, J = 7.5 Hz), 127.4 (d, J = 8.3 Hz), 126.03, 125.96, 123.2, 121.4, 117.6, 117.1, 115.5 (d, J = 21.0 Hz), 113.7 (d, J = 21.8 Hz), 107.3, 97.4, 41.4, 39.4 ppm.

[0081] 19 F NMR (282 MHz, CDC13) δ -114.7, -116.4 ppm.

[0082] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 23 F2O2[M + + H]: 477.1661, Found: 477.1668.

[0083] From this result, it can be seen that the theoretical mass is 477.1661, and the observed value of the peak found in the actual mass spectrum is 477.1668; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0084] Product of this example.

[0085] Example 3

[0086] R 1 = R 2 is 4-chlorophenyl, and R 3 is phenyl, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one and 2-naphthol are used as reaction raw materials, and hydrochloric acid is used as a catalyst for reaction, and the specific implementation process is as follows:

[0087] (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one (152.6 mg, 0.40 mmol), 2-naphthol (99.19%, 86.8 mg, 0.6 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0088]

[0089] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 185.0 mg of solid product, with a calculated yield of 91%.

[0090] The analysis of the test is as follows:

[0091] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0092] 1 H NMR (300 MHz, CDC13) δ 7.77-7.57 (m, 7H), 7.48-7.29 (m, 6H), 7.27-7.09 (m, 4H), 6.77-6.66 (m, 2H), 4.87 (d, J = 3.5 Hz, 1H), 2.68 (dd, Ji = 11.8 Hz, J2 = 3.7 Hz, 1H), 2.61 (d, J = 11.6 Hz, 1H) ppm.

[0093] 13 C NMR (75 MHz, CDC13) δ 150.4, 143.0, 140.8, 138.8, 133.5, 132.2, 130.8, 129.3, 128.84, 128.80, 128.77, 128.4, 128.3, 127.3, 127.1, 127.0, 126.1, 126.0, 123.2, 121.3, 117.6, 116.8, 107.2, 97.3, 41.1, 39.3 ppm.

[0094] 2. High-resolution mass spectrum: HRMS (ESI) C 32 H 23 Cl2O2[M + + H]: 509.1070, Found: 509.1077.

[0095] As can be seen from the result, the theoretical mass is 509.1070, and the observed value of the peak found in the actual mass spectrum is 509.1077; in combination with nuclear magnetic resonance, the product structure can be determined as follows:

[0096] The product of this example.

[0097] Example 4

[0098] R 1 = R 2 is 3-chlorophenyl, and R 3 is phenyl, (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one and 2-naphthol are used as the reaction raw materials, and hydrochloric acid is used as the catalyst, and the specific implementation process is as follows:

[0099] (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one (153.8 mg, 0.40 mmol), 2-naphthol (99.19%, 87.9 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O) was added, and the reaction was allowed to proceed at 25 °C for 40 h. The reaction equation is as follows:

[0100]

[0101] After the reaction solution was concentrated, silica gel column chromatography was used to obtain 176.4 mg of solid product, with a calculated yield of 87%.

[0102] The analysis of the test is as follows:

[0103] 1. Hydrogen spectrum of nuclear magnetic resonance analysis, carbon spectrum:

[0104] 1 H NMR (300 MHz, CDC13) δ 7.79 - 7.64 (m, 4H), 7.63 - 7.51 (m, 3H), 7.45 - 7.26 (m, 6H), 7.23 - 7.07 (m, 4H), 6.67 - 6.56 (m, 2H), 4.84 (d, J = 3.5 Hz, 1H), 2.64 (dd, Ji = 11.8 Hz, J2= 3.6 Hz, 1H), 2.58 (d, J = 11.8 Hz, 1H) ppm.

[0105] 13 C NMR (75 MHz, CDC13) δ 150.4, 146.1, 144.1, 138.7, 134.7, 133.0, 130.8, 130.0, 129.4, 128.9, 128.8, 128.4, 128.3, 128.2, 127.9, 126.6, 126.1, 126.01, 125.95, 125.8, 124.3, 123.6, 123.2, 121.4, 117.6, 116.6, 107.3, 97.1, 41.1, 39.1 ppm.

[0106] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 23 Cl2O2[M + + H]: 509.1070, Found: 509.1077.

[0107] From the results, the theoretical mass is 509.1070, while the observed value of the peak found in the actual mass spectrum is 509.1077; in combination with nuclear magnetic resonance, the product structure can be determined as follows:

[0108] The product of this example.

[0109] Example 5

[0110] R 1 = R 2 is 2-naphthyl, and R 3 is phenyl, (E)-4-hydroxy-4,4-di(naphthalen-2-yl)-1-phenyl-2-buten-1-one and 2-naphthol are used as the reaction raw materials, and hydrochloric acid is used as the catalyst, and the specific implementation process is as follows:

[0111] (E)-4-hydroxy-4,4-di(naphthalen-2-yl)-1-phenyl-2-buten-1-one (166.4 mg, 0.40 mmol), 2-naphthol (99.19%, 87.3 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0112]

[0113] After the reaction solution is concentrated, silica gel column chromatography is used to obtain 148.0 mg of solid product, and the calculated yield is 68%.

[0114] The analysis of the test is as follows:

[0115] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0116] 1 H NMR (300 MHz, CDCI3) δ 8.34 (s, 1 H), 8.05-7.68 (m, 8H), 7.58-7.22 (m, 11 H), 7.20-7.01 (m, 5H), 5.23 (d, J = 3.8 Hz, 1 H), 2.87 (dd, J1 = 11.7 Hz, J2 = 3.9 Hz, 1 H), 2.66 (d, J = 11.7 Hz, 1 H) ppm.

[0117] 13C NMR (75 MHz, CDC13) δ 150.6, 142.1, 140.0, 139.2, 132.9, 132.6, 132.4, 131.8, 131.0, 129.1, 128.7, 128.3, 128.2, 127.9, 127.7, 127.0, 126.5, 126.4, 126.3, 126.2, 125.7, 125.3, 125.2, 124.4, 124.3, 123.1, 122.9, 121.7, 117.6, 117.4, 107.3, 98.6, 40.9, 39.9 ppm.

[0118] 2. High resolution mass spectrum: HRMS (ESI) C 40 H 29 O2[M + +H]: 541.2162, Found: 541.2162.

[0119] From the results, it can be seen that the theoretical mass is 541.2162, and the observed value of the peak found in the actual mass spectrum is 541.2162; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0120] Product of the present example.

[0121] Example 6

[0122] (E)-3-(9-hydroxy-9H-fluoren-9-yl)-1-phenyl-2-propen-1-one and 2-naphthol were used as reaction raw materials, and hydrobromic acid was used as a catalyst to carry out the reaction, and the specific implementation process was as follows:

[0123] (E)-3-(9-hydroxy-9H-fluoren-9-yl)-1-phenyl-2-propen-1-one (129.4 mg, 0.40 mmol), 2-naphthol (99.19%, 118.5 mg, 0.82 mmol), dissolved in dichloromethane (4.0 mL), added hydrobromic acid (9.1 μL, 0.08 mmol, 20 mol%, 48% in water), reacted at 25°C for 26h. The reaction equation is as follows:

[0124]

[0125] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 106.3 mg, and the calculated yield was 61%.

[0126] The test analysis is as follows:

[0127] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0128] 1 H NMR (300 MHz, CDC13) δ 7.94 - 7.85 (m, 2H), 7.77 (d, J = 8.9 Hz, 1H), 7.73 - 7.61 (m, 3H), 7.51 - 7.36 (m, 5H), 7.34 - 7.23 (m, 2H), 7.20 - 7.11 (m, 1H), 7.10 - 7.02 (m, 2H), 6.98 (td, J1= 7.5 Hz, J2= 1.1 Hz, 1H), 6.40 (td, J1= 7.6 Hz, J2= 1.1 Hz, 1H), 6.03 (d, J = 7.7 Hz, 1H), 3.99 (d, J = 4.2 Hz, 1H), 3.54 (dd, J1= 12.2 Hz, J2= 4.3 Hz, 1H), 2.84 (d, J = 12.2 Hz, 1H) ppm.

[0129] 13 C NMR (75 MHz, CDC13) δ 150.5, 147.6, 144.0, 139.5, 139.3, 139.1, 131.7, 129.34, 129.29, 128.9, 128.8, 128.7, 128.4, 128.2, 127.4, 126.7, 126.4, 126.2, 124.7, 123.7, 123.2, 121.3, 120.2, 119.8, 119.2, 117.7, 108.5, 100.1, 43.6, 38.9 ppm.

[0130] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 23 O2[M + +H]: 439.1693, Found: 439.1701.

[0131] From the results, it can be seen that the theoretical mass is 439.1693, while the observed value of the peak found in the actual mass spectrum is 439.1701; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0132] is the product of this example.

[0133] Example 7

[0134] R 1 = R 2 is methyl, R 3 is phenyl, (E)-4-hydroxy-4-methyl-1-phenyl-2-penten-1-one and 2-naphthol are used as reaction raw materials, and hydrochloric acid is used as a catalyst for the reaction, and the specific implementation process is as follows:

[0135] (E)-4-hydroxy-4-methyl-1-phenyl-2-penten-1-one (78.1 mg, 0.41 mmol), 2-naphthol (99.19%, 88.2 mg, 0.61 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 Min H2O), 25 °C for 24 h. The reaction equation is as follows:

[0136]

[0137] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 68.0 mg, and the calculated yield was 54%.

[0138] The analysis of the test is as follows:

[0139] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0140] 1 H NMR (300 MHz, CDC13) δ 7.88-7.66 (m, 5H), 7.54-7.31 (m, 5H), 7.19 (d, J = 8.8 Hz, 1H), 3.76 (d, J = 4.3 Hz, 1H), 2.85 (dd, J1 = 11.9 Hz, J2 = 4.3 Hz, 1H), 2.44 (d, J = 11.9 Hz, 1H), 1.57 (s, 3H), 1.12 (s, 3H) ppm.

[0141] 13 C NMR (75 MHz, CDC13) δ 150.3, 139.6, 131.6, 128.9, 128.7, 128.53, 128.46, 128.2, 126.5, 125.9, 123.2, 121.6, 119.2, 118.4, 106.7, 91.0, 42.1, 38.7, 27.4, 25.6 ppm.

[0142] 2. High resolution mass spectrum: HRMS (ESI) C 22 H 21 O2[M + +H]: 317.1536, Found: 317.1545.

[0143] From the results, it can be seen that the theoretical mass is 317.1536, and the observed value of the peak found in the actual mass spectrum is 317.1545; combined with nuclear magnetic resonance, the structure of the product can be determined as follows:

[0144] The product of this example.

[0145] Example 8

[0146] (E)-3-(1-hydroxycyclopentyl)-1-phenyl-2-propen-1-one and 2-naphthol were used as the raw materials for the reaction, hydrochloric acid was used as the catalyst, and the specific implementation process was as follows:

[0147] (E)-3-(1-hydroxycyclopentyl)-1-phenyl-2-propen-1-one (87.3 mg, 0.40 mmol), 2-naphthol (99.19%, 87.8 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 Min H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0148]

[0149] After the reaction solution was concentrated, silica gel column chromatography was used to obtain an oily product 85.8 mg, and the calculated yield was 63%.

[0150] The analysis of the test is as follows:

[0151] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0152] 1 H NMR (300 MHz, CDCl3) δ 7.90-7.65 (m, 5H), 7.54-7.29 (m, 5H), 7.18 (d, J = 8.9 Hz, 1H), 3.81 (d, J = 4.1 Hz, 1H), 2.70 (dd, J1 = 11.6 Hz, J2 = 4.1 Hz, 1H), 2.47 (d, J = 11.6 Hz, 1H), 2.11-1.82 (m, 3H), 1.82-1.62 (m, 2H), 1.62-1.45 (m, 3H) ppm.

[0153] 13 C NMR (75 MHz, CDCl3) δ 150.4, 139.8, 131.6, 128.9, 128.7, 128.5, 128.4, 128.2, 126.5, 126.0, 123.1, 121.6, 119.3, 118.5, 106.3, 102.6, 41.4, 39.3, 38.7, 35.6, 24.7, 23.9 ppm.

[0154] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 23 O2[M + +H]: 343.1693, Found: 343.1695.

[0155] The results show that the theoretical mass is 343.1693, while the observed value of the peak found in the actual mass spectrum is 343.1695. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0156] This is a product of this embodiment.

[0157] Example 9

[0158] Using R 1 It is a phenyl group, R 2 For methyl, R 3 Using (E)-4-hydroxy-1,4-diphenyl-2-penten-1-one and 2-naphthol as reactants and hydrochloric acid as a catalyst, the specific process is as follows:

[0159] (E)-4-hydroxy-1,4-diphenyl-2-penten-1-one (100.0 mg, 0.40 mmol) and 2-naphthol (99.19%, 87.1 mg, 0.60 mmol) were dissolved in dichloromethane (4.0 mL), and hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 min H2O) was added. The reaction was carried out at 25 °C for 24 h. The reaction equation is as follows:

[0160]

[0161] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 118.8 mg, with a calculated yield of 79%.

[0162] The analysis of the test is as follows:

[0163] 1. Proton and carbon NMR spectra:

[0164] 1H NMR (300 MHz, CDC13) δ 8.05 (d, J = 8.5 Hz, 0.34H), 7.89 - 7.78 (m, 2H), 7.75 - 7.64 (m, 1H), 7.62 - 7.53 (m, 1H), 7.52 - 7.25 (m, 8H), 7.22 - 7.09 (m, 1H), 7.03 (d, J = 8.8 Hz, 0.72H), [6.84 - 6.75 (m, 1.38H), 6.74 - 6.66 (m, 0.70H), 2H], [4.24 (d, J = 3.9 Hz, 0.33H), 4.11 (d, J = 4.3 Hz, 0.67H), 1H], 2.98 (dd, Ji = 11.9 Hz, J2= 4.4 Hz, 0.70H), 2.63 - 2.49 (m, 1H), 2.40 (d, J = 11.6 Hz, 0.33H), [1.89 (s, 2H), 1.34 (s, 1H), 3H] ppm.

[0165] 13 C NMR (75 MHz, CDC13) δ 150.5, 150.1, 146.7, 143.7, 139.5, 138.9, 132.0, 130.6, 129.0, 128.88, 128.86, 128.8, 128.7, 128.5, 128.41, 128.35, 128.3, 128.1, 126.94, 126.91, 126.8, 126.2, 126.1, 126.0, 125.5, 124.69, 124.66, 123.4, 122.8, 122.0, 121.4, 119.1, 118.4, 117.9, 117.5, 107.0, 106.9, 95.2, 95.0, 43.4, 42.5, 39.3, 35.8, 27.8, 27.1 ppm.

[0166] 2High resolution mass spectrum: HRMS (ESI) C 27 H 23 O2[M + +H]: 379.1693, Found: 379.1697.

[0167] From this result, it can be seen that the theoretical mass is 379.1693, while the observed value of the peak found in the actual mass spectrum is 379.1697; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0168] Product of the present example.

[0169] Example 10

[0170] R 1 = R2 is phenyl, R 3 (E)-4-hydroxy-1-(4-methoxyphenyl)-4,4-diphenyl-2-buten-1-one and 2-naphthol as the raw materials for reaction, hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0171] (E)-4-hydroxy-1-(4-methoxyphenyl)-4,4-diphenyl-2-buten-1-one (138.9 mg, 0.40 mmol), 2-naphthol (99.19%, 86.9 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0172]

[0173] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 173.8 mg, the calculated yield was 92%.

[0174] The analysis of the test is as follows:

[0175] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0176] 1 H NMR (300 MHz, CDCI3) δ 7.81-7.71 (m, 3H), 7.68-7.51 (m, 4H), 7.43 (t, J = 7.6 Hz, 2H), 7.34-7.11 (m, 6H), 6.92 (d, J = 8.4 Hz, 2H), 6.80-6.59 (m, 3H), 4.92 (d, J = 3.8 Hz, 1H), 3.80 (s, 3H), 2.69 (dd, J1 = 11.7 Hz, J2 = 3.9 Hz, 1H), 2.57 (d, J = 11.6 Hz, 1H) ppm.

[0177] 13 C NMR (75 MHz, CDCI3) δ 159.8, 150.6, 144.9, 142.5, 131.6, 131.1, 128.9, 128.7, 128.5, 128.1, 127.5, 127.3, 126.8, 126.1, 126.0, 125.7, 125.6, 122.9, 121.8, 117.7, 117.5, 113.6, 107.2, 98.1, 55.3, 41.3, 39.4 ppm.

[0178] 2. High resolution mass spectrum: HRMS (ESI) C 33 H27 O3[M + +H]: 471.1955, Found: 471.1948.

[0179] From the results, it can be seen that the theoretical mass is 471.1955, while the observed value of the peak found in the actual mass spectrum is 471.1948; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0180] is the product of this example.

[0181] Example 11

[0182] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1-(2-methoxyphenyl)-4,4-diphenyl-2-buten-1-one and 2-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0183] (E)-4-hydroxy-1-(2-methoxyphenyl)-4,4-diphenyl-2-buten-1-one (138.0 mg, 0.40 mmol), 2-naphthol (99.19%, 86.4 mg, 0.59 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0M in H2O), reacted at 25°C for 24h. The reaction equation is as follows:

[0184]

[0185] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 162.0 mg, the calculated yield was 86%.

[0186] The test analysis is as follows:

[0187] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0188] 1H NMR (300 MHz, CDC13) δ 8.19 (d, J = 7.2 Hz, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 7.7 Hz, 2H), 7.53 (t, J = 8.0 Hz, 2H), 7.39 - 7.03 (m, 10H), 6.90 (d, J = 8.2 Hz, 1H), 6.81 - 6.61 (m, 3H), 4.88 (d, J = 3.9 Hz, 1H), 3.62 (s, 3H), 3.08 (d, J = 11.9 Hz, 1H), 2.77 (dd, J1= 11.9 Hz, J2= 4.0 Hz, 1H) ppm.

[0189] 13 C NMR (75 MHz, CDC13) δ 157.2, 150.8, 145.3, 142.9, 131.2, 130.2, 128.7, 128.52, 128.48, 128.2, 128.1, 127.3, 127.0, 126.8, 126.1, 126.0, 125.7, 125.6, 122.7, 121.7, 120.4, 117.84, 117.77, 111.7, 106.0, 97.2, 55.4, 41.0, 36.3 ppm.

[0190] 2. High resolution mass spectrum: HRMS (ESI) C 33 H 27 O3[M + +H]: 471.1955, Found: 471.1958.

[0191] From the results, it can be seen that the theoretical mass is 471.1955, and the observed value of the peak found in the actual mass spectrum is 471.1958; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0192] is the product of the present example.

[0193] Example 12

[0194] R 1 = R 2 is phenyl, R 3 (E)-1-(4-bromophenyl)-4-hydroxy-4,4-diphenyl-2-buten-1-one and 2-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0195] (E)-1-(4-bromophenyl)-4-hydroxy-4,4-diphenyl-2-buten-1-one (158.9 mg, 0.40 mmol), 2-naphthol (99.19%, 86.9 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O) was added, and the reaction was allowed to proceed at 25 °C for 24 h. The reaction equation is as follows:

[0196]

[0197] After the reaction solution was concentrated, silica gel column chromatography was used to obtain 187.7 mg of solid product, with a calculated yield of 90%.

[0198] The analysis of the test is as follows:

[0199] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0200] 1 H NMR (300 MHz, CDC13) δ 7.80-7.66 (m, 3H), 7.62-7.47 (m, 6H), 7.46-7.37 (m, 2H), 7.36-7.24 (m, 2H), 7.22-7.10 (m, 4H), 6.78-6.59 (m, 3H), 4.92 (d, J = 3.7 Hz, 1H), 2.66 (dd, Ji = 11.6 Hz, J2= 3.8 Hz, 1H), 2.55 (d, J = 11.6 Hz, 1H) ppm.

[0201] 13 C NMR (75 MHz, CDC13) δ 150.4, 144.7, 142.4, 138.5, 131.5, 131.1, 129.2, 128.8, 128.7, 128.3, 128.1, 127.6, 127.0, 126.4, 126.1, 125.9, 125.6, 123.1, 122.9, 121.8, 117.6, 117.5, 106.8, 98.6, 41.3, 39.6 ppm.

[0202] 2. High-resolution mass spectrum: HRMS (ESI) C 32 H 24 BrO2[M + + H]: 519.0954, Found: 519.0945.

[0203] From the results, it can be seen that the theoretical mass is 519.0954, and the observed value of the peak found in the actual mass spectrum is 519.0945; combined with nuclear magnetic resonance, the structure of the product can be determined as follows:

[0204] To the product of this example.

[0205] Example 13

[0206] R 1 = R 2 phenyl, R 3 (E)-4-hydroxy-l-(naphthalen-2-yl)-4,4-diphenyl-2-buten-l-one and 2-naphthalenol as the starting materials, and hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0207] (E)-4-hydroxy-l-(naphthalen-2-yl)-4,4-diphenyl-2-buten-l-one (145.4 mg, 0.40 mmol), 2-naphthalenol (99.19%, 86.8 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0208]

[0209] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 186.2 mg, and the calculated yield was 95%.

[0210] The analysis of the test is as follows:

[0211] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0212] 1 H NMR (300 MHz, CDC13) δ 8.29 (s, 1H), 7.92-7.74 (m, 6H), 7.71 (dd, J1= 8.6 Hz, J2= 1.8 Hz, 1H), 7.61-7.53 (m, 2H), 7.51-7.39 (m, 4H), 7.35-7.24 (m, 4H), 7.22-7.13 (m, 2H), 6.82-6.59 (m, 3H), 4.96 (d, J = 3.8 Hz, 1H), 2.79 (dd, J1= 11.7 Hz, J2= 3.9 Hz, 1H), 2.65 (d, J = 11.6 Hz, 1H) ppm.

[0213] 13C NMR (75 MHz, CDC13) δ 150.6, 144.8, 142.5, 136.6, 133.4, 132.9, 131.1, 129.0, 128.7, 128.5, 128.2, 128.1, 127.6, 127.4, 126.9, 126.4, 126.2, 126.14, 126.08, 125.7, 125.6, 125.5, 124.0, 123.0, 121.8, 117.7, 117.6, 107.3, 98.4, 41.3, 39.4 ppm.

[0214] 2. High resolution mass spectrum: HRMS (ESI) C 36 H 27 O2[M + +H]: 491.2006, Found: 491.2000.

[0215] From the results, it can be seen that the theoretical mass is 491.2006, and the observed value of the peak found in the actual mass spectrum is 491.2000; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0216] The product of this example.

[0217] Example 14

[0218] R 1 = R 2 is phenyl, and R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 6-bromo-2-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0219] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.7 mg, 0.40 mmol), 6-bromo-2-naphthol (98%, 135.5 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 Min H2O), reacted at 25°C for 24h. The reaction equation is as follows:

[0220]

[0221] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 150.9 mg, the calculated yield was 73%.

[0222] The test analysis is as follows:

[0223] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0224] 1 H NMR (300 MHz, CDC13) δ 7.78 - 7.64 (m, 5H), 7.61 (d, J = 9.1 Hz, 1H), 7.50 - 7.26 (m, 8H), 7.24 - 7.10 (m, 3H), 6.83 - 6.62 (m, 3H), 4.85 (d, J = 3.8 Hz, 1H), 2.71 (dd, Ji = 11.7 Hz, J2= 3.9 Hz, 1H), 2.57 (d, J = 11.7 Hz, 1H) ppm.

[0225] 13 C NMR (75 MHz, CDC13) δ 151.0, 144.6, 142.4, 139.1, 130.2, 129.9, 129.7, 128.9, 128.8, 128.6, 128.4, 128.2, 127.6, 127.1, 126.5, 126.2, 126.1, 125.6, 123.7, 119.0, 117.9, 116.7, 107.4, 98.4, 41.4, 39.5 ppm.

[0226] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 24 BrO2[M + +H]: 519.0954, Found: 519.0954.

[0227] From the results, it can be seen that the theoretical mass is 519.0954, and the observed value of the peak found in the actual mass spectrum is 519.0954; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0228] is the product of this example.

[0229] Example 15

[0230] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 7-bromo-2-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0231] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.9 mg, 0.40 mmol) and 7-bromo-2-naphthol (99%, 133.6 mg, 0.59 mmol) were dissolved in dichloromethane (4.0 mL), and hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 min H₂O) was added. The reaction was carried out at 25 °C for 24 h. The reaction equation is as follows:

[0232]

[0233] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 174.7 mg, with a calculated yield of 84%.

[0234] The analysis of the test is as follows:

[0235] 1. Proton and carbon NMR spectra:

[0236] 1 H NMR (300MHz, CDCl3) δ7.85 (d, J = 1.9Hz, 1H), 7.78-7.64 (m, 4H), 7.54-7.27 (m, 8H), 7.23-7.13 (m, 4H), 6.82-6.73 ( m,2H),6.71-6.63(m,1H),4.80(d,J=3.8Hz,1H),2.72(dd,J1=11.7Hz,J2=3.9Hz,1H),2.57(d,J=11.7Hz,1H)ppm.

[0237] 13 C NMR (75MHz, CDCl3) δ151.4,144.3,142.3,139.0,132.4,129.7,128.9,128.8,128.6,128.3,127.5,127. 0,126.9,126.4,126.2,126.11,126.07,125.5,124.3,120.2,118.2,116.9,107.3,98.4,41.3,39.3ppm.

[0238] 2. High-resolution mass spectrometry: HRMS(ESI)C 32 H 24 BrO2[M + +H]:519.0954,Found:519.0960.

[0239] The results show that the theoretical mass is 519.0954, while the observed value of the peak in the actual mass spectrum is 519.0960. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0240] To the product of this example.

[0241] Example 16

[0242] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 6-methoxy-2-naphthol as the starting materials, with hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0243] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.0 mg, 0.40 mmol), 6-methoxy-2-naphthol (97%, 105.4 mg, 0.59 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), 25°C for 24 h. The reaction equation is as follows:

[0244]

[0245] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 179.7 mg, the calculated yield was 96%.

[0246] The analysis of the test is as follows:

[0247] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0248] 1 H NMR (300 MHz, CDC13) δ 7.79-7.61 (m, 5H), 7.47-7.18 (m, 9H), 7.12 (d, J = 8.8 Hz, 1H), 6.98 (dd, J1= 9.2 Hz, J2= 2.6 Hz, 1H), 6.86 (d, J = 2.6 Hz, 1H), 6.78-6.60 (m, 3H), 4.86 (d, J = 3.7 Hz, 1H), 3.75 (s, 3H), 2.67 (dd, J1= 11.6 Hz, J2= 3.8 Hz, 1H), 2.55 (d, J = 11.6 Hz, 1H) ppm.

[0249] 13C NMR (75 MHz, CDC13) δ 155.3, 149.0, 144.8, 142.6, 139.4, 129.6, 128.6, 128.5, 128.2, 127.5, 127.3, 126.8, 126.4, 126.2, 126.1, 126.0, 125.5, 123.3, 118.2, 118.0, 117.8, 107.0, 106.3, 98.1, 55.0, 41.4, 39.5 ppm.

[0250] 2. High resolution mass spectrum: HRMS (ESI) C 33 H 27 O3[M + +H]: 471.1955, Found: 471.1956.

[0251] From the results, it can be seen that the theoretical mass is 471.1955, and the observed value of the peak found in the actual mass spectrum is 471.1956; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0252] is the product of the present example.

[0253] Example 17

[0254] R 1 = R 2 is phenyl, and R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 7-methoxy-2-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0255] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.8 mg, 0.40 mmol), 7-methoxy-2-naphthol (98%, 103.9 mg, 0.58 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0M in H2O), reacted at 25°C for 24h. The reaction equation is as follows:

[0256]

[0257] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 167.4 mg, and the calculated yield was 89%.

[0258] The test analysis is as follows:

[0259] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0260] 1 H NMR (300 MHz, CDC13) δ 7.80 - 7.62 (m, 4H), 7.51 - 7.26 (m, 8H), 7.24 - 7.16 (m, 2H), 7.06 - 6.97 (m, 2H), 6.88 - 6.62 (m, 4H), 4.81 (d, J = 3.8 Hz, 1H), 3.88 (s, 3H), 2.71 (dd, Ji = 11.7 Hz, J2= 3.8 Hz, 1H), 2.58 (d, J = 11.6 Hz, 1H) ppm.

[0261] 13 C NMR (75 MHz, CDC13) δ 157.5, 151.2, 144.7, 142.4, 139.3, 132.4, 129.7, 128.7, 128.6, 128.5, 128.2, 127.4, 126.8, 126.3, 126.14, 126.10, 125.7, 124.1, 116.5, 115.3, 114.7, 107.1, 101.6, 98.1, 55.2, 41.5, 39.7 ppm.

[0262] 2. High resolution mass spectrum: HRMS (ESI) C 33 H 27 O3[M + +H]: 471.1955, Found: 471.1952.

[0263] From this result, it can be seen that the theoretical mass is 471.1955, and the observed value of the peak found in the actual mass spectrum is 471.1952; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0264] is the product of this example.

[0265] Example 18

[0266] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 1-naphthol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0267] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (126.9 mg, 0.40 mmol), 1 -naphthol (99%, 87.7 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μί, 0.04 mmol, 10 mol%, 4.0 min H20), 25 °C, 24 h. The reaction equation is as follows:

[0268]

[0269] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 108.6 mg, the calculated yield was 62%.

[0270] The analysis of the test is as follows:

[0271] 1. Hydrogen spectrum of nuclear magnetic resonance analysis, carbon spectrum:

[0272] 1 H NMR (300 MHz, CDCI3) δ 8.27 (d, J = 8.0 Hz, 1 H), 7.83 - 7.72 (m, 2H), 7.70 - 7.58 (m, 3H), 7.47 - 7.32 (m, 7H), 7.31 - 7.15 (m, 3H), 7.05 (d, J = 8.3 Hz, 1 H), 6.97 - 6.82 (m, 3H), 6.74 (d, J = 8.3 Hz, 1 H), 4.24 (d, J = 3.3 Hz, 1 H), 2.68 (dd, J1= 11.6 Hz, J2= 3.5 Hz, 1 H), 2.59 (d, J = 11.6 Hz, 1 H) ppm.

[0273] 13 C NMR (75 MHz, CDCI3) δ 147.7, 144.8, 143.3, 139.6, 133.7, 128.6, 128.5, 128.2, 127.5, 127.4, 127.3, 126.5, 126.23, 126.19, 125.8, 125.4, 125.1, 124.1, 121.7, 119.5, 119.2, 107.6, 98.4, 46.8, 39.8 ppm.

[0274] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 25 O2[M + + H]: 441.1849, Found: 441.1850.

[0275] From the result, it can be seen that the theoretical mass is 441.1849, while the observed value of the peak found in the actual mass spectrum is 441.1850; in combination with nuclear magnetic resonance, the product structure can be determined as follows:

[0276] The product of this example.

[0277] Example 19

[0278] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and sesamol as the reaction raw material, using hydrochloric acid as the catalyst for the reaction, the specific implementation process is as follows:

[0279] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.9 mg, 0.40 mmol), sesamol (99.9%, 82.1 mg, 0.59 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 min H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0280]

[0281] After the reaction solution was concentrated, silica gel column chromatography was used to obtain 170.5 mg of solid product, with a calculated yield of 88%.

[0282] The test analysis is as follows:

[0283] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0284] 1 H NMR (300 MHz, CDCI3) δ 7.71-7.52 (m, 4H), 7.39-7.17 (m, 8H), 7.13-6.91 (m, 3H), 6.43 (s, 1H), 6.10 (s, 1H), 5.70 (dd, J1= 14.1 Hz, J2= 1.4 Hz, 2H), 3.99 (d, J = 1.8 Hz, 1H), 2.60-2.41 (m, 2H) ppm.

[0285] 13C NMR (75 MHz, CDC13) δ 147.4, 147.0, 144.7, 143.4, 140.9, 139.4, 128.6, 128.4, 128.2, 127.6, 127.2, 126.3, 126.0, 125.7, 125.4, 116.8, 108.0, 107.1, 100.7, 98.1, 97.7, 46.6, 39.5 ppm.

[0286] 2. High resolution mass spectrum: HRMS (ESI) C 29 H 23 O4[M + +H]: 435.1591, Found: 435.1589.

[0287] From the results, it can be seen that the theoretical mass is 435.1591, and the observed value of the peak found in the actual mass spectrum is 435.1589; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0288] The product of this example.

[0289] Example 20

[0290] R 1 = R 2 is phenyl, and R 3 is phenyl, (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and phenanthrene-9-ol as the reaction raw material, using hydrochloric acid as the catalyst for the reaction, the specific implementation process is as follows:

[0291] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (126.0 mg, 0.40 mmol), phenanthrene-9-ol (98%, 115.8 mg, 0.58 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 Min H2O), reacted at 25°C for 24h. The reaction equation is as follows:

[0292]

[0293] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 179.2 mg, the calculated yield was 91%.

[0294] The analysis of the test is as follows:

[0295] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0296] 1H NMR (300 MHz, CDC13) δ 8.59 - 8.36 (m, 3H), 7.91 - 7.71 (m, 5H), 7.67 - 7.54 (m, 2H), 7.52 - 7.27 (m, 8H), 7.27 - 7.15 (m, 2H), 6.72 - 6.54 (m, 3H), 4.98 (d, J = 3.8 Hz, 1H), 2.77 (dd, Ji = 11.6 Hz, J2= 3.9 Hz, 1H), 2.62 (d, J = 11.6 Hz, 1H) ppm.

[0297] 13 C NMR (75 MHz, CDC13) δ 146.1, 144.8, 142.3, 139.5, 130.7, 130.2, 128.7, 128.5, 128.3, 127.4, 126.83, 126.79, 126.4, 126.3, 126.2, 126.14, 126.09, 125.8, 125.0, 123.7, 122.6, 122.4, 122.3, 113.9, 107.2, 98.5, 41.3, 40.3 ppm.

[0298] 2. High resolution mass spectrum: HRMS (ESI) C 36 H 27 O2[M + +H]: 491.2006, Found: 491.2010.

[0299] From the results, it can be seen that the theoretical mass is 491.2006, while the observed value of the peak found in the actual mass spectrum is 491.2010; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0300] is the product of this example.

[0301] Example 21

[0302] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and anthracene-2-ol as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0303] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (126.6 mg, 0.40 mmol), anthranol (98%, 119.0 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 Min H2O), 45 °C for 24 h. The reaction equation is as follows:

[0304]

[0305] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 187.8 mg, the calculated yield was 96%.

[0306] The analysis of the test is as follows:

[0307] 1. Hydrogen spectrum of nuclear magnetic resonance analysis, carbon spectrum:

[0308] 1 H NMR (300 MHz, CDCI3) δ 8.21 (s, 1 H), 8.1 1 (s, 1 H), 7.93 (d, J = 8.4 Hz, 1 H), 7.86 - 7.67 (m, 6H), 7.52 - 7.23 (m, 10H), 7.17 (d, J = 9.0 Hz, 1 H), 6.69 - 6.65 (m, 2H), 6.52 - 6.41 (m, 1 H), 5.03 (d, J = 3.7 Hz, 1 H), 2.75 (dd, J1= 1 1.7 Hz, J2= 3.8 Hz, 1 H), 2.61 (d, J = 1 1.6 Hz, 1 H) ppm.

[0309] 13 C NMR (75 MHz, CDCI3) δ 150.0, 144.8, 142.4, 139.2, 131.5, 129.6, 129.5, 128.7, 128.5, 128.3, 128.0, 127.9, 127.8, 127.4, 126.72, 126.65, 126.2, 126.1, 125.6, 125.4, 124.4, 1 19.7, 1 19.0, 1 15.7, 107.3, 98.6, 41.3, 39.5 ppm.

[0310] 2. High resolution mass spectrum: HRMS (ESI) C 36 H 27 O2[M + + H]: 491.2006, Found: 491.2000.

[0311] From the results, it can be seen that the theoretical mass is 491.2006, while the observed value of the peak found in the actual mass spectrum is 491.2000; in combination with nuclear magnetic resonance, the product structure can be determined as follows:

[0312] The product of this example.

[0313] Example 22

[0314] R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 2-hydroxy-1,4-naphthoquinone as the reaction raw material, using hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0315] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.2 mg, 0.40 mmol), 2-hydroxy-1,4-naphthoquinone (98%, 106.9 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0M in H2O), reacted at 45°C for 24h. The reaction equation is as follows:

[0316]

[0317] After the reaction solution was concentrated, silica gel column chromatography was used to obtain 135.9 mg of solid product, and the calculated yield was 72%.

[0318] The test analysis is as follows:

[0319] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0320] 1 H NMR (300 MHz, CDC13) δ 8.06-7.95 (m, 1H), 7.93-7.84 (m, 1H), 7.77-7.54 (m, 6H), 7.54-7.31 (m, 7H), 7.31-7.19 (m, 1H), 7.13-7.00 (m, 2H), 7.00-6.89 (m, 1H), 4.81 (d, J = 3.5 Hz, 1H), 2.67 (dd, J1 = 12.2 Hz, J2 = 3.7 Hz, 1H), 2.46 (d, J = 12.1 Hz, 1H) ppm.

[0321] 13C NMR (75 MHz, CDC13) δ 182.1, 179.0, 153.9, 143.9, 142.2, 137.1, 133.9, 133.0, 131.3, 130.9, 129.2, 128.6, 128.4, 127.7, 127.5, 126.9, 126.2, 126.1, 126.0, 125.6, 125.2, 124.4, 109.2, 99.3, 38.6, 38.0 ppm.

[0322] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 23 O4[M + +H]: 471.1591, Found: 471.1588.

[0323] From the results, it can be seen that the theoretical mass is 471.1591, and the observed value of the peak found in the actual mass spectrum is 471.1588; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0324] The product of this example.

[0325] Example 23

[0326] R 1 = R 2 is phenyl, and R 3 is phenyl, (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 4-hydroxy-6-methyl-2H-pyran-2-one are used as reaction raw materials, and hydrochloric acid is used as a catalyst for the reaction, and the specific implementation process is as follows:

[0327] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.3 mg, 0.40 mmol), 4-hydroxy-6-methyl-2H-pyran-2-one (98%, 77.6 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 45°C for 24 h. The reaction equation is as follows:

[0328]

[0329] After the reaction solution is concentrated, silica gel column chromatography is used to obtain 164.8 mg of solid product, and the calculated yield is 98%.

[0330] The analysis of the test is as follows:

[0331] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0332] 1 H NMR (300 MHz, CDC13) δ 7.69 - 7.52 (m, 6 H), 7.46 - 7.36 (m, 3 H), 7.34 - 7.24 (m, 2 H), 7.23 - 7.13 (m, 3 H), 7.12 - 7.02 (m, 1 H), 5.72 (s, 1 H), 4.47 (d, J = 3.6 Hz, 1 H), 2.56 (dd, Ji = 12.0 Hz, J2= 3.8 Hz, 1 H), 2.39 (d, J = 12.1 Hz, 1 H), 2.03 (s, 3 H) ppm.

[0333] 13 C NMR (75 MHz, CDC13) δ 163.9, 163.1, 162.1, 144.1, 142.6, 137.4, 129.2, 128.4, 128.3, 127.7, 127.2, 126.8, 125.9, 125.3, 125.0, 108.9, 101.8, 99.4, 99.3, 39.4, 38.2, 19.8 ppm.

[0334] 2. High resolution mass spectrum: HRMS (ESI) C 28 H 22 Na04[M + + Na]: 445.1410, Found: 445.1420.

[0335] From this result, it can be seen that the theoretical mass is 445.1410, while the observed value of the peak found in the actual mass spectrum is 445.1420; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0336] The product of this example.

[0337] Example 24

[0338] R 1 = R 2 is phenyl, and R 3 is phenyl, (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 4-hydroxy-2H- benzopyran-2-one are used as reaction raw materials, and hydrochloric acid is used as a catalyst for reaction, and the specific implementation process is as follows:

[0339] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (125.5 mg, 0.40 mmol), 4-hydroxy-2H-chromen-2-one (98%, 97.4 mg, 0.59 mmol), dissolved in dichloromethane (4.0 mL), hydrochloric acid (10.0 μί, 0.04 mmol, 10 mol%, 4.0 M in H20), 45 °C for 24 h. The reaction equation is as follows:

[0340]

[0341] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 170.1 mg, calculated yield was 93%.

[0342] The analysis of the test is as follows:

[0343] 1. Hydrogen spectrum of nuclear magnetic resonance analysis, carbon spectrum:

[0344] 1 H NMR (300 MHz, CDC13) δ 7.81 - 7.69 (m, 3H), 7.64 (d, J = 7.7 Hz, 2H), 7.54 (d, J = 7.5 Hz, 2H), 7.51 - 7.38 (m, 4H), 7.34 (t, J = 7.6 Hz, 2H), 7.27 - 6.96 (m, 6H), 4.65 (d, J = 3.6 Hz, 1H), 2.67 (dd, Ji = 12.1 Hz, J2= 3.8 Hz, 1H), 2.50 (d, J = 12.1 Hz, 1H) ppm.

[0345] 13 C NMR (75 MHz, CDC13) δ 161.5, 159.4, 153.2, 144.2, 142.5, 137.6, 132.0, 129.4, 128.7, 128.6, 127.9, 127.5, 127.1, 126.2, 125.4, 125.3, 123.9, 122.8, 116.7, 114.8, 109.4, 104.7, 99.8, 40.1, 38.7 ppm.

[0346] 2. High resolution mass spectrum: HRMS (ESI) C 31 H 23 O4[M + + H]: 459.1591, Found: 459.1588.

[0347] From the results, it can be seen that the theoretical mass is 459.1591, and the observed value of the peak found in the actual mass spectrum is 459.1588; combined with nuclear magnetic resonance, the structure of the product can be determined as follows:

[0348] To the product of this example.

[0349] Example 25

[0350] Using R 1 = R 2 is phenyl, R 3 (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one and 2-phenyl-5-(trifluoromethyl)-2,4-dihydro-3H-pyrazol-3-one as the starting materials, with hydrochloric acid as the catalyst, the specific implementation process is as follows:

[0351] (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one (126.7 mg, 0.40 mmol), 2-phenyl-5-(trifluoromethyl)-2,4-dihydro-3H-pyrazol-3-one (99%, 138.2 mg, 0.60 mmol), dissolved in dichloromethane (4.0 mL), added hydrochloric acid (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in H2O), reacted at 25°C for 24 h. The reaction equation is as follows:

[0352]

[0353] After the reaction solution was concentrated, silica gel column chromatography was used to obtain solid product 156.6 mg, and the calculated yield was 87%.

[0354] The analysis of the test is as follows:

[0355] 1. Hydrogen spectrum and carbon spectrum of nuclear magnetic resonance analysis:

[0356] 1 H NMR (300 MHz, CDCl3) δ 7.84-7.77 (m, 2H), 7.65-7.56 (m, 4H), 7.48-7.34 (m, 7H), 7.33-7.23 (m, 4H), 7.17-7.04 (m, 3H), 4.46 (t, J = 2.6 Hz, 1H), 2.74-2.61 (m, 2H) ppm.

[0357] 13 C NMR (75 MHz, CDCl3) δ 149.7, 143.5, 142.3, 137.8, 137.7 (q, J = 37.5 Hz), 137.6, 129.3, 129.1, 128.6, 128.4, 127.9, 127.6, 127.0, 126.0, 125.7, 125.2, 121.1 (q, J = 268.3 Hz), 120.8, 112.2, 100.5, 41.2, 40.1 ppm.

[0358] 19 F NMR (282 MHz, CDC13) δ -61.1 ppm.

[0359] 2. High resolution mass spectrum: HRMS (ESI) C 32 H 24 F3N2O2[M + +H]: 525.1784, Found: 525.1779.

[0360] From the results, it can be seen that the theoretical mass is 525.1784, while the observed value of the peak found in the actual mass spectrum is 525.1779; combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0361] is the product of the present example.

[0362] Although the above examples make a detailed description of the present application, it is only a part of the embodiments of the present application, not all the embodiments, and people can also obtain other embodiments according to the present example without creativity, which all belong to the protection scope of the present application.

Claims

1. A method for preparing a polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound, characterized in that, Includes the following steps: The γ-hydroxy-α,β-unsaturated enone, compound 1, hydrohalic acid catalyst and organic solvent were mixed and subjected to a cyclization reaction to obtain the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound; The γ-hydroxy-α,β-unsaturated enone has the structure shown in Formula 1 or is... Compound 1 has the structure shown in any one of Formulas 2 to 10: When the γ-hydroxy-α,β-unsaturated enone is When, compound 1 is The polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound is When the γ-hydroxy-α,β-unsaturated enone is When, compound 1 is The polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound is When the γ-hydroxy-α,β-unsaturated enone is When compound 1 has the structure shown in any of formulas 2 to 10; when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula I, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula II, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula III, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula IV, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula V, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula VI, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula VII, when compound 1 is When the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in formula VIII, when compound 1 is At that time, the polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound has the structure shown in Formula IX: Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, or alkyl; R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, and alkoxy-substituted phenyl; R 4 The independent components are hydrogen, halogen, and alkoxy.

2. The preparation method according to claim 1, characterized in that, The Including (E)-4-hydroxy-1,4,4-triphenyl-2-buten-1-one, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-1-phenyl-2-buten-1-one, (E)-4-hydroxy-4,4-di(naphthyl-2-yl)-1-phenyl-2-buten-1-one, (E)-3-(9-hydroxy-9H-fluoren-9-yl)-1-phenyl-2-propen-1-one, (E)-4-hydroxy-4- Methyl-1-phenyl-2-penten-1-one, (E)-3-(1-hydroxycyclopentyl)-1-phenyl-2-propen-1-one, (E)-4-hydroxy-1,4-diphenyl-2-penten-1-one, (E)-4-hydroxy-1-(4-methoxyphenyl)-4,4-diphenyl-2-buten-1-one, (E)-4-hydroxy-1-(2-methoxyphenyl)-4,4-diphenyl-2-buten-1-one, (E)-1-(4-bromophenyl)-4-hydroxy-4,4-diphenyl-2-buten-1-one, (E)-4-hydroxy-1-(naphth-2-yl)-4,4-diphenyl-2-buten-1-one.

3. The preparation method according to claim 1 or 2, characterized in that, The hydrogen halide catalyst comprises an aqueous solution of hydrogen chloride (4 mol / L), a 1,4-dioxane solution of hydrogen chloride (4 mol / L), or an aqueous solution of hydrobromic acid (48%). The molar ratio of the γ-hydroxy-α,β-unsaturated ketone to the hydrohalic acid catalyst is 1:0.05 to 0.

2.

4. The preparation method according to claim 1, characterized in that, The Including 2-naphthol, 6-bromo-2-naphthol, 7-bromo-2-naphthol, 6-methoxy-2-naphthol, and 7-methoxy-2-naphthol.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of the γ-hydroxy-α,β-unsaturated enone to compound 1 is 1:1.3 to 2.

2.

6. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out at a temperature of 25–45°C for 24–48 hours.

7. A polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound prepared according to the preparation method of any one of claims 1 to 6, characterized in that, It has the structure shown in any of Equations I to IX: Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, or alkyl; R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, and alkoxy-substituted phenyl; R 4 The independent components are hydrogen, halogen, and alkoxy.

8. The polysubstituted 2,7-dioxobicyclo[3.2.1]octane compound according to claim 7, characterized in that, It has any of the structures shown in Formulas I-1 to I-17, II-1, III-1, IV-1, V-1, VI-1, VII-1, VIII-1, and IX-1:

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