Method for catalytically synthesizing N-(4-vinylidene tetrahydrofuran-2-yl) amide by lewis acid and application of N-(4-vinylidene tetrahydrofuran-2-yl) amide

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to N-(4-vinylidene tetrahydrofuran-2-yl) amide, a preparation method of the N-(4-vinylidene tetrahydrofuran-2-yl) amide, a derivative of the N-(4-vinylidene tetrahydrofuran-2-yl) amide and a preparation method of the derivative. According to the invention, the N-(4-vinylidene tetrahydrofuran-2-yl) amide compound can be prepared at normal temperature and normal pressure by taking substituted 2-butyne-1, 4-diol and an alkenyl amide reactant as raw materials and lewis acid as a catalyst. The preparation method provided by the invention is convenient to operate, simple and easily available in raw materials, mild in reaction conditions and suitable for industrial application and production. The N-(4-vinylidene tetrahydrofuran-2-yl) amide compound prepared according to the preparation method provided by the invention has relatively high yield and purity, is easy to derivatize, and has good application prospects and economic benefits in the fields of organic synthesis and drug research and development.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to an N-(4-vinylidenetetrahydrofuran-2-yl)amide compound and its preparation method, derivatives of the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound and their preparation methods. Background Technology

[0002] Allenes, as important backbones in organic synthesis, are not only widely found in various natural products and bioactive molecules, but also serve as versatile intermediates for the synthesis of natural products and high-value-added chemicals. This invention, under Lewis acid catalysis, utilizes inexpensive and readily available substituted 2-butynedi-1,4-diols and enamide compounds to directly convert them into multifunctionalized N-(4-vinylidenetetrahydrofuran-2-yl)amide products. These molecules simultaneously integrate multiple convertible functional groups, including N,O-acetal structural units, N-(tetrahydrofuran-2-yl)benzamide, and tetrasubstituted allene fragments with long-range nucleophilic amide groups, exhibiting rich reactivity and holding significant importance for organic chemistry and medicinal chemistry. Summary of the Invention

[0003] In view of this, the present invention provides an N-(4-vinylidenetetrahydrofuran-2-yl)amide compound and its preparation method, a derivative of the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound and its preparation method. The preparation method of the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound provided by the present invention is simple and easy to operate, and the yield of the prepared N-(4-vinylidenetetrahydrofuran-2-yl)amide compound is relatively high.

[0004] This invention provides a method for preparing N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds, comprising the following steps:

[0005] The substituted 2-butyn-1,4-diol, enamide, Lewis acid catalyst and organic solvent were mixed and subjected to a cyclization reaction to obtain the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound.

[0006] The substituted 2-butyn-1,4-diol has the structure shown in Formula 1 or is... The olefin amide has the structure shown in any one of formulas 2 to 4:

[0007] Formula 1, Equation 2, Formula 3, Equation 4;

[0008] When the substituted 2-butyn-1,4-diol is When the alkenamide is The N-(4-vinylidenetetrahydrofuran-2-yl)amide compound is ;

[0009] When the substituted 2-butyn-1,4-diol is When the enamide has the structure shown in any of formulas 2 to 4; when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula I, and when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula II, and when the enamide is At that time, the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula III:

[0010] Formula I, Formula II, Formula III;

[0011] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkoxy-substituted phenyl;

[0012] R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, and alkenyl;

[0013] R 4 and R 5 Independently, it is an alkyl group.

[0014] Preferably, the Including 1,1-diphenylbut-2-yne-1,4-diol, 1,1-bis(4-fluorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-chlorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-bromophenyl)but-2-yne-1,4-diol, 1,1-bis(p-tolyl)but-2-yne-1,4-diol, 1,1-bis(naphthyl-2-yl)but-2-yne-1,4-diol, and 1-(4-methoxyphenyl)-1-phenylbut-2-yne-1,4-diol.

[0015] Preferably, the Lewis acid catalyst includes indium trifluoromethanesulfonate, aluminum trifluoromethanesulfonate, tin trifluoromethanesulfonate, iron trifluoromethanesulfonate, and copper trifluoromethanesulfonate;

[0016] The molar ratio of the substituted 2-butyn-1,4-diol to the Lewis acid catalyst is 1:0.05~0.2.

[0017] Preferably, the Including N-(2-methylprop-1-en-1-yl)benzamide, 4-methyl-N-(2-methylprop-1-en-1-yl)benzamide, 4-methoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-fluoro-N-(2-methylprop-1-en-1-yl)benzamide, 4-chloro-N-(2-methylprop-1-en-1-yl)benzamide, 4-bromo-N-(2-methylprop-1-en-1-yl)benzamide, N-(2-methylprop-1-en-1-yl)-[1,1'-biphenyl]-4-carboxamide, N-(2-methylprop-1-en-1-yl)-2-naphthylcarboxamide, N-(2-methylprop-1-en-1-yl)benzo[b]thiamethoxam Pheno-3-carboxamide, N-(2-methylprop-1-en-1-yl)benzofuran-2-carboxamide, N-(2-methylprop-1-en-1-yl)acetamide, N-(2-methylprop-1-en-1-yl)butamide, N-(2-methylprop-1-en-1-yl)cyclohexylcarboxamide, N-(2-methylprop-1-en-1-yl)acrylamide, N-(2-ethylbut-1-en-1-yl)benzamide, 2-ethoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-iodo-N-(2-methylprop-1-en-1-yl)-3-nitrobenzamide, 2-methyl-N-(2-methylprop-1-en-1-yl)-3,5-dinitrobenzamide.

[0018] Preferably, the molar ratio of the substituted 2-butyn-1,4-diol to the enamide is 1:1.8~2.2.

[0019] Preferably, the cyclization reaction is carried out at a temperature of 0-45°C for 3-48 hours.

[0020] This invention also provides an N-(4-vinylidenetetrahydrofuran-2-yl)amide compound prepared according to the preparation method described above, having the structure shown in any one of formulas I to IV:

[0021] Formula I, Formula II, Formula III, Formula IV;

[0022] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkoxy-substituted phenyl;

[0023] R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, and alkenyl;

[0024] R4 and R 5 Independently, it is an alkyl group.

[0025] Preferably, it has the structure shown in any one of the formulas I-1 to I-24, II-1, III-1, and IV:

[0026] Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21

[0027] Formula I-22 Formula I-23 Formula I-24; Formula II-1; Formula III-1; Formula IV.

[0028] The present invention also provides derivatives prepared from N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds having the structure shown in Formula I in the above-described technical solutions, having the structure shown in any one of Formulas a to b:

[0029] Formula a Formula b.

[0030] The present invention also provides a method for preparing the derivatives described in the above technical solution, comprising the following steps:

[0031] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of palladium on carbon, hydrogen, and a first organic solvent undergoes a reduction reaction to obtain the desired product. ;

[0032] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of N-iodosuccinimide and a second organic solvent undergoes an electrophilic cyclization reaction to obtain the desired product. .

[0033] This invention utilizes substituted 2-butyn-1,4-diol and enamide as reactants, and a Lewis acid as a catalyst to prepare N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds under normal pressure. The preparation method provided by this invention is simple and easy to operate, with mild reaction conditions, economical and readily available raw materials, and is suitable for large-scale production. The N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds prepared according to the method provided by this invention have high yields and purity, demonstrating good economic benefits and application prospects. Detailed Implementation

[0034] This invention provides a method for preparing N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds, comprising the following steps:

[0035] The substituted 2-butyn-1,4-diol, enamide, Lewis acid catalyst and organic solvent were mixed and subjected to a cyclization reaction to obtain the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound.

[0036] The substituted 2-butyn-1,4-diol has the structure shown in Formula 1 or is... The olefin amide has the structure shown in any one of formulas 2 to 4:

[0037] Formula 1, Equation 2, Formula 3, Formula 4.

[0038] In one specific embodiment of the present invention, when the substituted 2-butyn-1,4-diol is When the alkenamide is The N-(4-vinylidenetetrahydrofuran-2-yl)amide compound is ;

[0039] When the substituted 2-butyn-1,4-diol is When the enamide has the structure shown in any of formulas 2 to 4; when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula I, and when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula II, and when the enamide is At that time, the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula III:

[0040] Formula I, Formula II, Formula III;

[0041] In this invention, R 1 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, or alkoxy-substituted phenyl. 1 The aryl group can be naphthyl, and the R 1 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, or 4-bromophenyl, wherein R 1 The alkyl-substituted phenyl group can be 4-methylphenyl, wherein R 1 The alkoxy-substituted phenyl group can be 4-methoxyphenyl; R 2 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, or alkoxy-substituted phenyl. 2 The aryl group can be naphthyl, and the R 2 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, or 4-bromophenyl, wherein R 2 The alkyl-substituted phenyl group can be 4-methylphenyl, wherein R 2 The alkoxy-substituted phenyl group can be 4-methoxyphenyl.

[0042] As a specific embodiment of the present invention, R 1 and R 2 It can be simultaneously naphthyl, phenyl, 4-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, and 4-methylphenyl; when R 1 When R is phenyl 2 It can also be 4-methoxyphenyl.

[0043] As a specific embodiment of the present invention, the It may include 1,1-diphenylbut-2-yne-1,4-diol, 1,1-bis(4-fluorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-chlorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-bromophenyl)but-2-yne-1,4-diol, 1,1-bis(p-tolyl)but-2-yne-1,4-diol, 1,1-bis(naphthyl-2-yl)but-2-yne-1,4-diol, and 1-(4-methoxyphenyl)-1-phenylbut-2-yne-1,4-diol.

[0044] In this invention, R 3 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, or alkenyl group. 3The aryl groups include 2-naphthyl, 4-phenylphenyl, 2-benzofuranyl, and 3-benzothiophenyl, wherein R 3 The halogenated phenyl groups include 4-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, and 4-iodo-3-nitrophenyl, wherein R 3 The alkyl-substituted phenyl groups include 4-methylphenyl, wherein R 3 The alkoxy-substituted phenyl groups include 4-methoxyphenyl and 2-ethoxyphenyl, wherein R 3 The mixed substituted phenyl groups include 2-methyl-3,5-dinitrophenyl, wherein R 3 The alkyl groups include methyl, n-propyl, and cyclohexyl, wherein R 3 The alkenyl group includes vinyl; R 4 The R is an alkyl group. 4 Alkyl groups include methyl and ethyl; R 5 The R is an alkyl group. 5 Alkyl groups include methyl and ethyl.

[0045] As a specific embodiment of the present invention, R 4 and R 5 It can be either methyl or ethyl.

[0046] As a specific embodiment of the present invention, the Including N-(2-methylprop-1-en-1-yl)benzamide, 4-methyl-N-(2-methylprop-1-en-1-yl)benzamide, 4-methoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-fluoro-N-(2-methylprop-1-en-1-yl)benzamide, 4-chloro-N-(2-methylprop-1-en-1-yl)benzamide, 4-bromo-N-(2-methylprop-1-en-1-yl)benzamide, N-(2-methylprop-1-en-1-yl)-[1,1'-biphenyl]-4-carboxamide, N-(2-methylprop-1-en-1-yl)-2-naphthylcarboxamide, N-(2-methylprop-1-en-1-yl)benzo[b]thiamethoxam Pheno-3-carboxamide, N-(2-methylprop-1-en-1-yl)benzofuran-2-carboxamide, N-(2-methylprop-1-en-1-yl)acetamide, N-(2-methylprop-1-en-1-yl)butamide, N-(2-methylprop-1-en-1-yl)cyclohexylcarboxamide, N-(2-methylprop-1-en-1-yl)acrylamide, N-(2-ethylbut-1-en-1-yl)benzamide, 2-ethoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-iodo-N-(2-methylprop-1-en-1-yl)-3-nitrobenzamide, 2-methyl-N-(2-methylprop-1-en-1-yl)-3,5-dinitrobenzamide.

[0047] In one specific embodiment of the present invention, the Lewis acid catalyst may include indium trifluoromethanesulfonate, aluminum trifluoromethanesulfonate, tin trifluoromethanesulfonate, iron trifluoromethanesulfonate, or copper trifluoromethanesulfonate. In this invention, the Lewis catalyst possesses multiple activation functions to promote the efficient and highly selective synthesis of the product, enabling the synthesis of N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds under ambient pressure, without the need for prior activation of the reactants during the reaction.

[0048] In one specific embodiment of the present invention, the molar ratio of the substituted 2-butyn-1,4-diol to the Lewis acid catalyst can be 1:0.05~0.2. Reducing the amount of Lewis acid will result in a longer reaction time and a significantly lower yield.

[0049] In one specific embodiment of the present invention, the organic solvent may be acetonitrile or dichloromethane; the molar concentration of the substituted 2-butyn-1,4-diol in the reaction solution system of the cyclization reaction may be 0.08~0.12 mol / L, specifically 0.1 mol / L.

[0050] In one specific embodiment of the present invention, the molar ratio of the substituted 2-butyn-1,4-diol and the enamide can be 1:1.8 to 2.2, specifically 1:2.

[0051] In one specific embodiment of the present invention, the temperature of the cyclization reaction can be 0~45℃. o C; The cyclization reaction can take 3-48 hours.

[0052] As a specific embodiment of the present invention, preparation The reaction equation is: .

[0053] 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 N-(4-vinylidenetetrahydrofuran-2-yl)amide compound. This invention does not have special requirements for the concentration and silica gel column chromatography; conventional methods in the art can be used.

[0054] The present invention also provides an N-(4-vinylidenetetrahydrofuran-2-yl)amide compound prepared according to the preparation method described above, having the structure shown in any one of formulas I to IV:

[0055] Formula I, Formula II, Formula III, Formula IV;

[0056] Among them, R 1 and R2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkoxy-substituted phenyl;

[0057] R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, and alkenyl;

[0058] R 4 and R 5 Independently, it is an alkyl group.

[0059] As a specific embodiment of the present invention, the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound may have any of the structures shown in Formula I-1 to I-24, Formula II-1, Formula III-1, and Formula IV:

[0060] Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21

[0061] Formula I-22 Formula I-23 Formula I-24; Formula II-1; Formula III-1; Formula IV.

[0062] The present invention also provides derivatives prepared from N-(4-vinylidenetetrahydrofuran-2-yl)amide compounds having the structure shown in Formula I in the above-described technical solutions, having the structure shown in any one of Formulas a to b:

[0063] Formula a Formula b.

[0064] As a specific embodiment of the present invention, the It can be The It can be .

[0065] The present invention also provides a method for preparing the derivatives described in the above technical solution, comprising the following steps:

[0066] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Palladium on carbon, hydrogen, and the first organic solvent are mixed and then reduced to obtain... As stated above;

[0067] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of N-iodosuccinimide and a second organic solvent undergoes an electrophilic cyclization reaction to obtain the desired product. .

[0068] In this invention, the The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Palladium on carbon and a first organic solvent are mixed and then reduced by hydrogen gas to obtain the desired product. As a specific embodiment of the present invention, the first organic solvent may be methanol; The molar ratio of palladium to carbon can be 1:0.1~0.3, specifically 1:0.2; the amount of the first organic solvent is not particularly limited in this invention, as long as it can dissolve completely. In one specific embodiment of this invention, the reduction reaction temperature can be room temperature, specifically 20~35℃; the reduction reaction time can be 47~49 hours. In another specific embodiment of this invention, the reduction reaction can be accompanied by stirring; the stirring is not particularly limited in this invention, as long as the reaction is complete.

[0069] In this invention, the equation for the reduction reaction is: .

[0070] In this invention, the The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of N-iodosuccinimide and a second organic solvent undergoes an electrophilic cyclization reaction to obtain the desired product. In one specific embodiment of the present invention, the second organic solvent may be dichloromethane; the dichloromethane may be dried dichloromethane, and the water content of the dried dichloromethane is less than or equal to 50 ppm; The molar ratio of the second organic solvent to N-iodosuccinimide (NIS) can be 1:1.0 to 1.4, specifically 1:1.2. The amount of the second organic solvent used is not particularly limited in this invention, as long as it can dissolve completely. In one specific embodiment of this invention, the electrophilic cyclization reaction can be carried out at room temperature, specifically 20-35°C; the electrophilic substitution reaction can take 23-25 ​​hours. In another specific embodiment of this invention, the electrophilic substitution reaction can be accompanied by stirring; the stirring is not particularly limited in this invention, as long as the reaction is complete.

[0071] In this invention, the equation for the electrophilic cyclization reaction is: .

[0072] This invention is based on The method for preparing derivatives from raw materials is simple, easy to operate, has mild reaction conditions, and produces high-purity products.

[0073] 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.

[0074] 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.

[0075] Example 1

[0076] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0077] 1,1-Diphenylbut-2-yn-1,4-diol (95.7 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.8 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0078]

[0079] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 134.9 mg, with a calculated yield of 85%.

[0080] The analysis of the test is as follows:

[0081] 1. Proton and carbon NMR spectra:

[0082] 1 H NMR (300 MHz, CDCl3) δ 7.80-7.70 (m, 2H), 7.55-7.47 (m, 1H), 7.46-7.39 (m, 2H), 7.38-7.26 (m, 10H), 6.50 (d, J = 9.6 Hz, 1H), 5.77 (d, J = 9.5Hz, 1H), 4.74-4.59 (m, 2H), 1.37 (s, 3H), 1.26 (s, 3H) ppm.

[0083] 13 C NMR (75 MHz, CDCl3) δ 195.4, 167.2, 137.0, 136.4, 133.9, 131.9,128.6, 128.5, 128.4, 128.3, 128.2, 127.6, 127.5, 127.0, 115.9, 112.0, 88.0,65.7, 45.9, 24.8, 21.6 ppm.

[0084] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 25 NNaO2 [M + +Na]: 418.1778, Found: 418.1779.

[0085] The results show that the theoretical mass is 418.1778, while the observed peak value in the actual mass spectrum is 418.1779. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0086] This is a product of this embodiment.

[0087] Example 2

[0088] Using R 1 =R 2 1,1-bis(4-fluorophenyl)but-2-yne-1,4-diol, R 3 It is a phenyl group, R 4 =R 5The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0089] 1,1-Bis(4-fluorophenyl)but-2-yn-1,4-diol (109.5 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.4 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0090]

[0091] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 138.7 mg, with a calculated yield of 81%.

[0092] The analysis of the test is as follows:

[0093] 1. Proton and carbon NMR spectra:

[0094] 1 H NMR (300 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.58-7.39 (m, 3H), 7.36-7.22 (m, 4H), 7.16-6.97 (m, 4H), 6.48 (d, J = 9.6 Hz, 1H), 5.77 (d, J =9.5 Hz, 1H), 4.79-4.53 (m, 2H), 1.35 (s, 3H), 1.26 (s, 3H) ppm.

[0095] 13 C NMR (75 MHz, CDCl3) δ 195.0, 167.3, 162.4 (d, J = 246.0 Hz), 162.3(d, J = 246.0 Hz) 133.9, 132.8 (d, J = 3.8 Hz), 132.3 (d, J = 3.8 Hz), 132.0,129.8 (d, J = 8.3 Hz), 129.7 (d, J = 7.5 Hz), 128.7, 127.0, 115.5 (d, J =21.0 Hz), 114.2, 112.6, 88.0, 65.6, 45.9, 24.7, 21.7ppm.

[0096] 2. High-resolution mass spectrometry: HRMS (ESI) C27 H 23 F2NNaO2 [M + +Na]: 454.1589, Found: 454.1585.

[0097] The results show that the theoretical mass is 454.1589, while the observed value of the peak found in the actual mass spectrum is 454.1585. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0098] This is a product of this embodiment.

[0099] Example 3

[0100] Using R 1 =R 2 1,1-bis(4-chlorophenyl)but-2-yne-1,4-diol, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0101] 1,1-Bis(4-chlorophenyl)but-2-yn-1,4-diol (122.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.4 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 45 °C for 3 h. The reaction equation is as follows:

[0102]

[0103] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 108.7 mg, with a calculated yield of 59%.

[0104] The analysis of the test is as follows:

[0105] 1. Proton and carbon NMR spectra:

[0106] 1H NMR (300 MHz, CDCl3) δ 7.79-7.72 (m, 2H), 7.57-7.49 (m, 1H), 7.48-7.40 (m, 2H), 7.36-7.29 (m, 4H), 7.28-7.21 (m, 4H), 6.49 (d, J = 9.5 Hz, 1H), 5.76 (d, J = 9.5 Hz, 1H), 4.69 (d, J = 12.5 Hz, 1H), 4.63 (d, J = 12.5 Hz, 1H), 1.35 (s, 3H), 1.25 (s, 3H) ppm.

[0107] 13 C NMR (75 MHz, CDCl3) δ 195.2, 167.3, 135.1, 134.6, 133.8, 133.61,133.56, 132.0, 129.5, 129.3, 128.77, 128.75, 128.6, 127.0, 114.1, 113.0,88.0, 65.5, 46.1, 24.7, 21.7 ppm.

[0108] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 23 Cl2NNaO2 [M + +Na]: 486.0998, Found: 486.0997.

[0109] The results show that the theoretical mass is 486.0998, while the observed peak value in the actual mass spectrum is 486.0997. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0110] This is a product of this embodiment.

[0111] Example 4

[0112] Using R 1 =R 2 1,1-bis(4-bromophenyl)but-2-yne-1,4-diol, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0113] 1,1-Bis(4-bromophenyl)but-2-yn-1,4-diol (158.8 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.6 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 45 °C for 12 h. The reaction equation is as follows:

[0114]

[0115] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 149.6 mg, with a calculated yield of 68%.

[0116] The analysis of the test is as follows:

[0117] 1. Proton and carbon NMR spectra:

[0118] 1 H NMR (300 MHz, CDCl3) δ 7.80-7.71 (m, 2H), 7.56-7.42 (m, 7H), 7.20-7.16 (m, 4H), 6.45 (d, J = 9.5 Hz, 1H), 5.76 (d, J = 9.5 Hz, 1H), 4.71-4.61(m, 2H), 1.35 (s, 3H), 1.24 (s, 3H) ppm.

[0119] 13 C NMR (75 MHz, CDCl3) δ 195.2, 167.3, 135.5, 135.0, 133.9, 132.0,131.8, 131.7, 129.8, 129.6, 128.7, 127.0, 121.81, 121.75, 114.3, 113.2, 88.1,65.4, 46.1, 24.7, 21.7 ppm.

[0120] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 23 Br2NNaO2 [M + +Na]: 573.9988, Found:573.9985.

[0121] The results show that the theoretical mass is 573.9988, while the observed value of the peak found in the actual mass spectrum is 573.9985. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0122] This is a product of this embodiment.

[0123] Example 5

[0124] Using R 1 =R 2 It is 1,1-di(p-tolyl)but-2-yne-1,4-diol of 4-methylphenyl, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0125] 1,1-Di(p-tolyl)but-2-yn-1,4-diol (106.2 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (23.0 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0126]

[0127] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 119.3 mg, with a calculated yield of 70%.

[0128] The analysis of the test is as follows:

[0129] 1. Proton and carbon NMR spectra:

[0130] 1 H NMR (300 MHz, CDCl3) δ 7.81-7.72 (m, 2H), 7.56-7.48 (m, 1H), 7.47-7.37 (m, 2H), 7.27-7.21 (m, 4H), 7.20-7.11 (m, 4H), 6.51 (d, J = 9.6 Hz, 1H), 5.76 (d, J = 9.5 Hz, 1H), 4.72-4.59 (m, 2H), 2.38 (s, 3H), 2.37 (s, 3H), 1.36 (s, 3H), 1.25 (s, 3H) ppm.

[0131] 13C NMR (75 MHz, CDCl3) δ 195.1, 167.2, 137.4, 137.3, 134.1, 133.9,133.5, 131.9, 129.12, 129.09, 128.6, 128.2, 128.0, 127.0, 115.6, 111.5, 87.9,65.7, 45.8, 24.8, 21.5, 21.14, 21.11 ppm.

[0132] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 29 NNaO2 [M + +Na]: 446.2091, Found: 446.2093.

[0133] The results show that the theoretical mass is 446.2091, while the observed value of the peak found in the actual mass spectrum is 446.2093. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0134] This is a product of this embodiment.

[0135] Example 6

[0136] Using R 1 =R 2 It is 1,1-di(naphthyl-2-yl)but-2-yn-1,4-diol, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0137] 1,1-Di(naphthyl-2-yl)but-2-yn-1,4-diol (135.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.3 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.5 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0138]

[0139] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 159.9 mg, with a calculated yield of 81%.

[0140] The analysis of the test is as follows:

[0141] 1. Proton and carbon NMR spectra:

[0142] 1 H NMR (300 MHz, CDCl3) δ 7.88-7.80 (m, 5H), 7.79-7.70 (m, 5H), 7.60-7.53 (m, 2H), 7.49-7.42 (m, 5H), 7.38-7.29 (m, 2H), 6.58 (d, J = 9.5 Hz, 1H), 5.83 (d, J = 9.5 Hz, 1H), 4.81-4.67 (m, 2H), 1.43 (s, 3H), 1.31 (s, 3H) ppm.

[0143] 13 C NMR (75 MHz, CDCl3) δ 196.3, 167.2, 134.4, 133.8, 133.4, 133.3,132.80, 132.78, 131.8, 128.5, 128.2, 128.00, 127.97, 127.60, 127.58, 127.2,127.1, 127.0, 126.5, 126.33, 126.27, 126.13, 126.10, 116.1, 112.3, 88.1,65.7, 46.1, 24.9, 21.6 ppm.

[0144] 2. High-resolution mass spectrometry: HRMS (ESI) C 35 H 29 NNaO2 [M + +Na]: 518.2091, Found: 518.2092.

[0145] The results show that the theoretical mass is 518.2091, while the observed value of the peak found in the actual mass spectrum is 518.2092. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0146] This is a product of this embodiment.

[0147] Example 7

[0148] use (5-(3-hydroxyprop-1-yn-1-yl)-5H-dibenzo[a,d][7]cyclohepten-5-ol), R 3 It is a phenyl group, R 4 =R 5The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0149] 5-(3-hydroxyprop-1-yn-1-yl)-5H-dibenzo[a,d][7]cyclohepten-5-ol (104.8 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.2 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.5 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 17 h. The reaction equation is as follows:

[0150]

[0151] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 111.2 mg of solid product, with a calculated yield of 66%.

[0152] The analysis of the test is as follows:

[0153] 1. Proton and carbon NMR spectra:

[0154] 1 H NMR (300 MHz, CDCl3) δ 7.77-7.66 (m, 2H), 7.51-7.46 (m, 1H), 7.42-7.22 (m, 10H), 6.83-6.74 (m, 2H), 6.43 (d, J = 9.5, 0.0 Hz, 1H), 5.73 (d, J =9.4 Hz, 1H), 4.61-4.53 (m, 2H), 1.39 (s, 3H), 1.29 (s, 3H) ppm.

[0155] 13 C NMR (75 MHz, CDCl3) δ 198.4, 167.1, 136.8, 136.5, 134.5, 134.3,133.9, 131.8, 131.4, 131.0, 129.32, 129.28, 128.9, 128.8, 128.7, 128.5,127.6, 127.5, 127.0, 116.5, 108.9, 88.1, 66.0, 45.1, 24.9, 21.4 ppm.

[0156] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 25 NNaO2 [M ++Na]: 442.1778, Found: 442.1778.

[0157] The results show that the theoretical mass is 442.1778, and the observed value of the peak found in the actual mass spectrum is also 442.1778. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0158] This is a product of this embodiment.

[0159] Example 8

[0160] Using R 1 It is a phenyl group, R 2 1-(4-methoxyphenyl)-1-phenylbut-2-yne-1,4-diol, R 3 It is a phenyl group, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0161] 1-(4-methoxyphenyl)-1-phenylbut-2-yn-1,4-diol (107.3 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzamide (140.7 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.6 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 0 °C for 3 h. The reaction equation is as follows:

[0162]

[0163] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 90.4 mg of solid product, with a calculated yield of 53% and dr = 1 / 1.

[0164] The analysis of the test is as follows:

[0165] 1. Proton and carbon NMR spectra:

[0166] 1H NMR (300 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.57-7.49 (m, 1H), 7.48-7.40 (m, 2H), 7.37-7.23 (m, 7H), 6.89 (d, J = 8.4 Hz, 2H), 6.48 (d, J =9.6 Hz, 1H), 5.76 (d, J = 9.5 Hz, 1H), 4.72-7.60 (m, 2H), 3.83 (s, 3H), 1.37(s, 3H), 1.25 (s, 3H) ppm.

[0167] 13 C NMR (75 MHz, CDCl3) δ 195.10, 195.05, 167.2, 159.2, 159.1, 137.3,136.7, 133.9, 131.9, 129.4, 129.3, 129.1, 128.62, 128.56, 128.43, 128.40,128.3, 128.1, 127.53, 127.48, 127.0, 115.44, 115.42, 113.89, 113.87, 111.7,87.9, 65.8, 55.3, 45.8, 24.82, 24.77, 21.6, 21.5 ppm.

[0168] 2. High-resolution mass spectrometry: HRMS (ESI) C 28 H 27 NNaO3 [M + +Na]: 448.1883, Found: 448.1886.

[0169] The results show that the theoretical mass is 448.1883, while the observed value of the peak found in the actual mass spectrum is 448.1886. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0170] This is a product of this embodiment.

[0171] Example 9

[0172] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-methylphenyl, R 4 =R 5Using 4-methyl-N-(2-methylprop-1-en-1-yl)benzamide as a reactant and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0173] 1,1-Diphenylbut-2-yn-1,4-diol (95.4 mg, 0.4 mmol), 4-methyl-N-(2-methylprop-1-en-1-yl)benzamide (151.3 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.6 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0174]

[0175] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 132.2 mg, with a calculated yield of 81%.

[0176] The analysis of the test is as follows:

[0177] 1. Proton and carbon NMR spectra:

[0178] 1 H NMR (300 MHz, CDCl3) δ 7.66 (d, J = 7.8 Hz, 2H), 7.39-7.29 (m,10H), 7.23 (d, J = 7.7 Hz, 2H), 6.45 (d, J = 9.7 Hz, 1H), 5.76 (d, J = 9.5Hz, 1H), 4.72-4.63 (m, 2H), 2.40 (s, 3H), 1.37 (s, 3H), 1.26 (s, 3H) ppm.

[0179] 13 C NMR (75 MHz, CDCl3) δ 195.4, 167.2, 142.5, 137.0, 136.4, 131.0,129.3, 128.5, 128.4, 128.3, 128.2, 127.6, 127.5, 127.0, 115.8, 112.0, 87.9,65.6, 45.9, 24.8, 21.6, 21.5 ppm.

[0180] 2. High-resolution mass spectrometry: HRMS (ESI) C 28 H 27 NNaO2 [M + +Na]: 432.1934, Found: 432.1934.

[0181] The results show that the theoretical mass is 432.1934, and the observed value of the peak found in the actual mass spectrum is also 432.1934. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0182] This is a product of this embodiment.

[0183] Example 10

[0184] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-methoxyphenyl, R 4 =R 5 Using methyl-4-methoxy-N-(2-methylprop-1-en-1-yl)benzamide as a reactant, and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0185] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), 4-methoxy-N-(2-methylprop-1-en-1-yl)benzamide (163.9 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.1 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0186]

[0187] The reaction solution was concentrated and purified by silica gel column chromatography to obtain an oily product of 139.6 mg, with a calculated yield of 82%.

[0188] The analysis of the test is as follows:

[0189] 1. Proton and carbon NMR spectra:

[0190] 1 H NMR (300 MHz, CDCl3) δ 7.76-7.68 (m, 2H), 7.40-7.28 (m, 10H), 6.96-6.88 (m, 2H), 6.39 (d, J = 9.6 Hz, 1H), 5.75 (d, J = 9.6 Hz, 1H), 4.73-4.60(m, 2H), 3.85 (s, 3H), 1.36 (s, 3H), 1.25 (s, 3H) ppm.

[0191] 13C NMR (75 MHz, CDCl3) δ 195.4, 166.7, 162.5, 137.0, 136.5, 128.9,128.5, 128.4, 128.3, 128.2, 127.6, 127.5, 126.2, 115.8, 113.8, 112.1, 88.0,65.6, 55.4, 45.9, 24.7, 21.6 ppm.

[0192] 2. High-resolution mass spectrometry: HRMS (ESI) C 28 H 27 NNaO3 [M + +Na]: 448.1883, Found: 448.1886.

[0193] The results show that the theoretical mass is 448.1883, while the observed value of the peak found in the actual mass spectrum is 448.1886. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0194] This is a product of this embodiment.

[0195] Example 11

[0196] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-fluorophenyl, R 4 =R 5 Using methyl-4-fluoro-N-(2-methylprop-1-en-1-yl)benzamide as a reactant, and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0197] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), 4-fluoro-N-(2-methylprop-1-en-1-yl)benzamide (154.9 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.8 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0198]

[0199] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 148.7 mg, with a calculated yield of 90%.

[0200] The analysis of the test is as follows:

[0201] 1. Proton and carbon NMR spectra:

[0202] 1 H NMR (300 MHz, CDCl3) δ 7.84-7.68 (m, 2H), 7.43-7.26 (m, 10H), 7.17-7.04 (m, 2H), 6.38 (d, J = 9.5 Hz, 1H), 5.74 (d, J = 9.5 Hz, 1H), 4.75-4.59(m, 2H), 1.37 (s, 3H), 1.25 (s, 3H) ppm.

[0203] 13 C NMR (75 MHz, CDCl3) δ 195.5, 166.1, 165.0 (d, J = 251.3 Hz), 137.0, 136.4, 130.1 (d, J = 3.8 Hz), 129.4 (d, J = 8.3 Hz), 128.50, 128.48,128.4, 128.2, 127.7, 127.6, 115.9, 115.7 (d, J = 21.8 Hz), 111.9, 88.1, 65.8,45.9, 24.8, 21.6 ppm.

[0204] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 24 FNNaO2 [M + +Na]: 436.1683, Found: 436.1686.

[0205] The results show that the theoretical mass is 436.1683, while the observed value of the peak found in the actual mass spectrum is 436.1686. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0206] This is a product of this embodiment.

[0207] Example 12

[0208] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-chlorophenyl, R 4 =R 5 Using methyl-4-chloro-N-(2-methylprop-1-en-1-yl)benzamide as a reactant, and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0209] 1,1-Diphenylbut-2-yn-1,4-diol (95.2 mg, 0.4 mmol), 4-chloro-N-(2-methylprop-1-en-1-yl)benzamide (168.0 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.3 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0210]

[0211] The reaction solution was concentrated and purified by silica gel column chromatography to obtain a solid product of 151.3 mg, with a calculated yield of 88%.

[0212] The analysis of the test is as follows:

[0213] 1. Proton and carbon NMR spectra:

[0214] 1 H NMR (300 MHz, CDCl3) δ 7.71-7.62 (m, 2H), 7.39-7.26 (m, 12H), 6.60(d, J = 9.4 Hz, 1H), 5.74 (d, J = 9.4 Hz, 1H), 4.73-4.58 (m, 2H), 1.36 (s,3H), 1.25 (s,3H) ppm.

[0215] 13 C NMR (75 MHz, CDCl3) δ 195.3, 166.2, 138.0, 136.9, 136.3, 132.2,128.7, 128.5, 128.39, 128.37, 128.2, 128.1, 127.54, 127.49, 115.8, 111.8,88.1, 65.7, 45.9, 24.8, 21.5 ppm.

[0216] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 24 ClNNaO2 [M + +Na]: 452.1388, Found: 452.1390.

[0217] The results show that the theoretical mass is 452.1388, while the observed value of the peak in the actual mass spectrum is 452.1390. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0218] This is a product of this embodiment.

[0219] Example 13

[0220] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-bromophenyl, R 4 =R 5 Using methyl-4-bromo-N-(2-methylprop-1-en-1-yl)benzamide as a reactant, and with indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0221] 1,1-Diphenylbut-2-yn-1,4-diol (95.5 mg, 0.4 mmol), 4-bromo-N-(2-methylprop-1-en-1-yl)benzamide (203.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.4 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0222]

[0223] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 176.7 mg, with a calculated yield of 93%.

[0224] The analysis of the test is as follows:

[0225] 1. Proton and carbon NMR spectra:

[0226] 1 H NMR (300 MHz, CDCl3) δ 7.66-7.51 (m, 4H), 7.35-7.27 (m, 10H), 6.45(d, J = 9.5 Hz, 1H), 5.74 (d, J = 9.4 Hz, 1H), 4.75-4.59 (m, 2H), 1.37 (s,3H), 1.25 (s,3H) ppm.

[0227] 13 C NMR (75 MHz, CDCl3) δ 195.4, 166.2, 137.0, 136.4, 132.7, 131.8,128.6, 128.48, 128.45, 128.3, 128.2, 127.62, 127.58, 126.7, 115.9, 111.8,88.1, 65.8, 46.0, 24.8, 21.5 ppm.

[0228] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 24 BrNNaO2 [M + +Na]: 496.0883, Found: 496.0886.

[0229] The results show that the theoretical mass is 496.0883, while the observed peak value in the actual mass spectrum is 496.0886. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0230] This is a product of this embodiment.

[0231] Example 14

[0232] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-phenylphenyl, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)-[1,1'-biphenyl]-4-carboxamide as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0233] 1,1-Diphenylbut-2-yn-1,4-diol (95.3 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)-[1,1'-biphenyl]-4-carboxamide (201.4 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0234]

[0235] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 148.8 mg, with a calculated yield of 79%.

[0236] The analysis of the test is as follows:

[0237] 1. Proton and carbon NMR spectra:

[0238] 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.66-7.58 (m, 4H), 7.48-7.29 (m, 13H), 6.58-6.53 (m, 1H), 5.80 (d, J = 9.3 Hz, 1H), 4.73-4.64(m, 2H), 1.38 (s, 3H), 1.28 (s, 3H) ppm.

[0239] 13 C NMR (75 MHz, CDCl3) δ 195.4, 166.9, 144.7, 139.8, 136.9, 136.4,132.5, 128.9, 128.5, 128.4, 128.3, 128.2, 128.0, 127.6, 127.5, 127.24,127.15, 115.8, 111.9, 88.0, 65.7, 45.9, 24.8, 21.6 ppm.

[0240] 2. High-resolution mass spectrometry: HRMS (ESI) C 33 H 29 NNaO2 [M + +Na]: 494.2091, Found: 494.2092.

[0241] The results show that the theoretical mass is 494.2091, while the observed value of the peak found in the actual mass spectrum is 494.2092. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0242] This is a product of this embodiment.

[0243] Example 15

[0244] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 2-naphthyl, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)-2-naphthylcarboxamide as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0245] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)-2-naphthylcarboxamide (180.7 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.3 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0246]

[0247] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 145.8 mg, with a calculated yield of 82%.

[0248] The analysis of the test is as follows:

[0249] 1. Proton and carbon NMR spectra:

[0250] 1 H NMR (300 MHz, CDCl3) δ 8.27 (s, 1H), 7.92-7.77 (m, 4H), 7.61-7.51(m, 2H), 7.40-7.28 (m, 10H), 6.63 (d, J = 9.5 Hz, 1H), 5.84 (d, J = 9.5 Hz,1H), 4.78-4.62 (m, 2H), 1.40 (s, 3H), 1.31 (s, 3H) ppm.

[0251] 13 C NMR (75 MHz, CDCl3) δ 195.5, 167.3, 137.0, 136.5, 134.9, 132.5,131.1, 129.0, 128.6, 128.49, 128.46, 128.3, 128.2, 127.9, 127.74, 127.67,127.61, 127.57, 126.8, 123.4, 115.9, 112.0, 88.2, 65.8, 46.0, 24.8, 21.7 ppm.

[0252] 2. High-resolution mass spectrometry: HRMS (ESI) C 31 H 27 NNaO2 [M + +Na]: 468.1934, Found: 468.1939.

[0253] The results show that the theoretical mass is 468.1934, while the observed peak value in the actual mass spectrum is 468.1939. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0254] This is a product of this embodiment.

[0255] Example 16

[0256] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 3-benzothiophene, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzo[b]thiophene-3-carboxamide as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0257] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzo[b]thiophene-3-carboxamide (185.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.9 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0258]

[0259] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 146.9 mg, with a calculated yield of 81%.

[0260] The analysis of the test is as follows:

[0261] 1. Proton and carbon NMR spectra:

[0262] 1 H NMR (300 MHz, CDCl3) δ 7.88-7.80 (m, 2H), 7.74 (s, 1H), 7.47-7.29(m, 12H), 6.44 (d, J = 9.6 Hz, 1H), 5.75 (d, J = 9.6 Hz, 1H), 4.75-4.62 (m,2H), 1.38 (s, 3H), 1.28 (s, 3H) ppm.

[0263] 13C NMR (75 MHz, CDCl3) δ 195.5, 162.0, 141.0, 138.9, 137.7, 137.0,136.4, 128.53, 128.47, 128.3, 128.2, 127.7, 127.6, 126.6, 125.8, 125.1,125.0, 122.7, 116.0, 111.8, 88.1, 65.8, 46.0, 24.8, 21.5 ppm.

[0264] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 25 NNaO2S [M + +Na]: 474.1498, Found: 474.1503.

[0265] The results show that the theoretical mass is 474.1498, while the observed value of the peak found in the actual mass spectrum is 474.1503. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0266] This is a product of this embodiment.

[0267] Example 17

[0268] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 2-benzofuranyl, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)benzofuran-2-carboxamide (methyl) as the reactant and indium trifluoromethanesulfonate as the catalyst. The specific implementation process is as follows:

[0269] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)benzofuran-2-carboxamide (172.6 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0270]

[0271] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 161.0 mg, with a calculated yield of 92%.

[0272] The analysis of the test is as follows:

[0273] 1. Proton and carbon NMR spectra:

[0274] 1 H NMR (300 MHz, CDCl3) δ 7.66 (d, J = 7.8 Hz, 1H), 7.56-7.47 (m, 2H), 7.46-7.25 (m, 12H), 7.00 (d, J = 9.8 Hz, 1H), 5.79 (d, J = 9.7 Hz, 1H), 4.75(d, J = 12.4 Hz, 1H), 4.68 (d, J = 12.4 Hz, 1H), 1.38 (s, 3H), 1.32 (s, 3H)ppm.

[0275] 13 C NMR (75 MHz, CDCl3) δ 195.4, 158.6, 154.7, 147.9, 136.8, 136.4,128.43, 128.40, 128.3, 128.2, 127.6, 127.5, 127.4, 127.1, 123.7, 122.8,115.9, 111.83, 111.76, 111.4, 87.3, 65.7, 45.9, 24.8, 21.6 ppm.

[0276] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 25 NNaO3 [M + +Na]: 458.1727, Found: 458.1728.

[0277] The results show that the theoretical mass is 458.1727, while the observed peak value in the actual mass spectrum is 458.1728. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0278] This is a product of this embodiment.

[0279] Example 18

[0280] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 For methyl, R 4 =R 5The reaction was carried out using N-(2-methylprop-1-en-1-yl)acetamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0281] 1,1-Diphenylbut-2-yn-1,4-diol (95.8 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)acetamide (90.6 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.8 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 48 h. The reaction equation is as follows:

[0282]

[0283] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 79.9 mg, with a calculated yield of 60%.

[0284] The analysis of the test is as follows:

[0285] 1. Proton and carbon NMR spectra:

[0286] 1 H NMR (300 MHz, CDCl3) δ 7.37-7.27 (m, 10H), 6.07 (d, J = 9.8 Hz, 1H), 5.56 (d, J = 9.8 Hz, 1H), 4.68-4.53 (m, 2H), 2.04 (s, 3H), 1.28 (s, 3H),1.19 (s, 3H) ppm.

[0287] 13 C NMR (75 MHz, CDCl3) δ 195.2, 170.4, 136.8, 136.5, 128.4, 128.3,128.0, 127.49, 127.47, 115.8, 112.1, 87.4, 65.3, 45.2, 24.4, 23.5, 21.7 ppm.

[0288] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 23 NNaO2 [M + +Na]: 356.1621, Found: 356.1622.

[0289] The results show that the theoretical mass is 356.1621, while the observed value of the peak found in the actual mass spectrum is 356.1622. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0290] This is a product of this embodiment.

[0291] Example 19

[0292] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is n-propyl, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)butyramide (methyl) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0293] 1,1-Diphenylbut-2-yn-1,4-diol (95.5 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)butyramide (113.1 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 4 h. The reaction equation is as follows:

[0294]

[0295] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 96.7 mg, with a calculated yield of 67%.

[0296] The analysis of the test is as follows:

[0297] 1. Proton and carbon NMR spectra:

[0298] 1 H NMR (300 MHz, CDCl3) δ 7.38-7.26 (m, 10H), 5.91 (d, J = 9.8 Hz, 1H), 5.58 (d, J = 9.8 Hz, 1H), 4.68-4.52 (m, 2H), 2.27-2.16 (m, 2H), 1.76-1.60 (m, 2H), 1.28 (s, 3H), 1.18 (s, 3H), 0.96 (t, J = 7.4 Hz, 3H) ppm.

[0299] 13C NMR (75 MHz, CDCl3) δ 195.2, 173.1, 136.9, 136.5, 128.4, 128.3,128.1, 127.50, 127.47, 115.7, 112.1, 87.3, 65.4, 45.3, 38.8, 24.5, 21.6,18.9, 13.6 ppm.

[0300] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 27 NNaO2 [M + +Na]: 384.1934, Found: 384.1934.

[0301] The results show that the theoretical mass is 384.1934, and the observed value of the peak found in the actual mass spectrum is also 384.1934. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0302] This is a product of this embodiment.

[0303] Example 20

[0304] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 For cyclohexyl, R 4 =R 5 The reaction was carried out using N-(2-methylprop-1-en-1-yl)cyclohexanecarboxamide (methyl group) as a reactant and indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0305] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)cyclohexanecarboxamide (145.5 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.8 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0306]

[0307] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 114.1 mg, with a calculated yield of 71%.

[0308] The analysis of the test is as follows:

[0309] 1. Proton and carbon NMR spectra:

[0310] 1 H NMR (300 MHz, CDCl3) δ 7.39-7.26 (m, 10H), 5.81 (d, J = 9.7 Hz,1H), 5.56 (d, J = 9.7 Hz, 1H), 4.67-4.53 (m, 2H), 2.12 (tt, J1 = 11.5 Hz, J2 =3.5 Hz, 1H), 1.96-1.72 (m, 4H), 1.72-1.59 (m, 1H), 1.52-1.36 (m, 2H), 1.34-1.20 (m, 6H), 1.16 (s, 3H) ppm.

[0311] 13 C NMR (75 MHz, CDCl3) δ 195.3, 175.9, 137.0, 136.5, 128.4, 128.3,128.1, 127.52, 127.48, 115.7, 112.1, 87.3, 65.5, 45.6, 29.8, 29.2, 25.7,25.5, 24.6, 21.6 ppm.

[0312] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 31 NNaO2 [M + +Na]: 424.2247, Found: 424.2246.

[0313] The results show that the theoretical mass is 424.2247, while the observed value of the peak in the actual mass spectrum is 424.2246. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0314] This is a product of this embodiment.

[0315] Example 21

[0316] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 For vinyl, R 4 =R 5 N-(2-methylprop-1-en-1-yl)acrylamide, which is methyl, was used as a reactant and reacted with indium trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0317] 1,1-Diphenylbut-2-yn-1,4-diol (95.1 mg, 0.4 mmol), N-(2-methylprop-1-en-1-yl)acrylamide (100.3 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.9 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0318]

[0319] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 97.9 mg, with a calculated yield of 71%.

[0320] The analysis of the test is as follows:

[0321] 1. Proton and carbon NMR spectra:

[0322] 1 H NMR (300 MHz, CDCl3) δ 7.40-7.24 (m, 10H), 6.32 (dd, J1 = 17.9 Hz, J2 = 13.1 Hz, 2H), 6.15 (dd, J1 = 17.0 Hz, J2 = 10.1 Hz, 1H), 5.69 (d, J = 9.3Hz, 1H), 5.66 (d, J = 9.1 Hz, 1H), 4.71-4.53 (m, 2H), 1.30 (s, 3H), 1.20 (s,3H) ppm.

[0323] 13 C NMR (75 MHz, CDCl3) δ 195.2, 165.4, 136.8, 136.4, 130.4, 128.4,128.3, 128.1, 127.8, 127.48, 127.45, 115.8, 112.1, 87.7, 65.5, 45.6, 24.5,21.6 ppm.

[0324] 2. High-resolution mass spectrometry: HRMS (ESI) C 23 H 23 NNaO2 [M + +Na]: 368.1621, Found: 368.1622.

[0325] The results show that the theoretical mass is 368.1621, while the observed value of the peak found in the actual mass spectrum is 368.1622. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0326] This is a product of this embodiment.

[0327] Example 22

[0328] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is a phenyl group, R 4 =R 5 Using N-(2-ethylbut-1-en-1-yl)benzamide as a reactant and indium trifluoromethanesulfonate as a catalyst, the specific process is as follows:

[0329] 1,1-Diphenylbut-2-yn-1,4-diol (95.5 mg, 0.4 mmol), N-(2-ethylbut-1-en-1-yl)benzamide (162.8 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0330]

[0331] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 122.5 mg, with a calculated yield of 72%.

[0332] The analysis of the test is as follows:

[0333] 1. Proton and carbon NMR spectra:

[0334] 1 H NMR (300 MHz, CDCl3) 6.63 (d, J = 9.8 Hz, 1H), 5.89 (d, J = 9.9Hz, 1H), 4.62 (s, 2H), 1.85-1.70 (m, 3H), 1.63-1.49 (m, 1H), 0.90 (t, J = 7.5Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H) ppm.

[0335] 13C NMR (75 MHz, CDCl3) δ 196.8, 166.8, 137.3, 136.5, 134.0, 131.8,128.5, 128.4, 128.3, 128.23, 128.15, 127.5, 127.4, 126.9, 114.9, 109.3, 86.6,66.1, 53.0, 26.7, 23.8, 8.5, 8.4 ppm.

[0336] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 29 NNaO2 [M + +Na]: 446.2091, Found: 446.2091.

[0337] The results show that the theoretical mass is 446.2091, and the observed value of the peak found in the actual mass spectrum is also 446.2091. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0338] This is a product of this embodiment.

[0339] Example 23

[0340] Using R 1 =R 2 It is a phenyl 1,1-diphenylbut-2-yne-1,4-diol. (N-(cyclopentylmethyl)benzamide) was used as a reactant and indium trifluoromethanesulfonate was used as a catalyst. The specific implementation process is as follows:

[0341] 1,1-Diphenylbut-2-yne-1,4-diol (95.3 mg, 0.4 mmol), N-(cyclopentylmethyl)benzamide (161.3 mg, 0.8 mmol), and indium trifluoromethanesulfonate (23.0 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0342]

[0343] The reaction solution was concentrated and purified by silica gel column chromatography to obtain a solid product of 127.8 mg, with a calculated yield of 76%.

[0344] The analysis of the test is as follows:

[0345] 1. Proton and carbon NMR spectra:

[0346] 1H NMR (300 MHz, CDCl3) δ 7.72-7.65 (m, 2H), 7.56-7.47 (m, 1H), 7.45-7.30 (m, 12H), 6.47 (d, J = 9.3 Hz, 1H), 5.85 (d, J = 9.4 Hz, 1H), 4.71 (d, J= 12.0 Hz, 1H), 4.64 (d, J = 12.1 Hz, 1H), 2.09-1.86 (m, 2H), 1.85-1.66 (m,6H) ppm.

[0347] 13 C NMR (75 MHz, CDCl3) δ 195.6, 167.0, 137.4, 136.3, 134.0, 131.9,128.7, 128.6, 128.3, 128.2, 127.70, 127.67, 127.0, 115.6, 111.1, 87.4, 66.5,57.7, 38.1, 31.5, 25.2, 25.1 ppm.

[0348] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 27 NNaO2 [M + +Na]: 444.1934, Found: 444.1938.

[0349] The results show that the theoretical mass is 444.1934, while the observed value of the peak found in the actual mass spectrum is 444.1938. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0350] This is a product of this embodiment.

[0351] Example 24

[0352] Using R 1 =R 2 It is a phenyl 1,1-diphenylbut-2-yne-1,4-diol. (N-(cyclohexylmethyl)benzamide) was used as a reactant and indium trifluoromethanesulfonate was used as a catalyst. The specific implementation process is as follows:

[0353] 1,1-Diphenylbut-2-yne-1,4-diol (95.8 mg, 0.4 mmol), N-(cyclohexylmethyl)benzamide (172.0 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.3 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0354]

[0355] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 150.4 mg, with a calculated yield of 86%.

[0356] The analysis of the test is as follows:

[0357] 1. Proton and carbon NMR spectra: 1 H NMR (300 MHz, CDCl3) δ 7.74-7.67 (m, 2H), 7.55-7.46 (m, 1H), 7.44-7.28 (m, 12H), 6.54 (d, J = 9.6 Hz, 1H), 5.98 (d, J =9.6 Hz, 1H), 4.71 (d, J = 12.1 Hz, 1H), 4.61 (d, J = 12.1 Hz, 1H), 1.94-1.83(m, 1H), 1.78-1.54 (m, 6H), 1.51-1.33 (m, 3H) ppm.

[0358] 13 C NMR (75 MHz, CDCl3) δ 196.9, 166.9, 137.4, 136.4, 134.0, 131.8,128.6, 128.5, 128.4, 128.2, 128.1, 127.52, 127.50, 126.9, 114.6, 110.1, 86.3,66.3, 50.5, 34.9, 30.5, 25.5, 22.8, 22.7 ppm.

[0359] 2. High-resolution mass spectrometry: HRMS (ESI) C 30 H 29 NNaO2 [M + +Na]: 458.2091, Found: 458.2089.

[0360] The results show that the theoretical mass is 458.2091, while the observed peak value in the actual mass spectrum is 458.2089. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0361] This is a product of this embodiment.

[0362] Example 25

[0363] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 2-ethoxyphenyl, R 4 =R 5 Using methyl-2-ethoxy-N-(2-methylprop-1-en-1-yl)benzamide as a reactant, and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0364] 1,1-Diphenylbut-2-yn-1,4-diol (95.6 mg, 0.4 mmol), 2-ethoxy-N-(2-methylprop-1-en-1-yl)benzamide (175.4 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.6 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0365]

[0366] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 167.7 mg, with a calculated yield of 95%.

[0367] The analysis of the test is as follows:

[0368] 1. Proton and carbon NMR spectra:

[0369] 1 H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 9.4 Hz, 1H), 8.26 (dd, J1 = 7.8Hz, J2 = 1.9 Hz, 1H), 7.47-7.25 (m, 11H), 7.05 (t, J = 7.3 Hz, 1H), 6.93 (d,J = 8.4 Hz, 1H), 5.86 (d, J = 9.4 Hz, 1H), 4.68 (s, 2H), 4.16-3.99 (m, 2H),1.37 (s, 3H), 1.34-1.24 (m, 6H) ppm.

[0370] 13C NMR (75 MHz, CDCl3) δ 195.0, 165.4, 157.0, 136.9, 136.6, 133.1,132.5, 128.4, 128.32, 128.27, 128.0, 127.4, 127.3, 121.1, 120.8, 115.7,112.5, 112.1, 88.0, 65.5, 64.6, 45.9, 25.1, 22.0, 14.6 ppm.

[0371] 2. High-resolution mass spectrometry: HRMS (ESI) C 29 H 29 NNaO3 [M + +Na]: 462.2040, Found: 462.2041.

[0372] The results show that the theoretical mass is 462.2040, while the observed value of the peak found in the actual mass spectrum is 462.2041. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0373] This is a product of this embodiment.

[0374] Example 26

[0375] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 4-iodo-3-nitrophenyl, R 4 =R 5 Using methyl-4-iodo-N-(2-methylprop-1-en-1-yl)-3-nitrobenzamide as the reactant, and indium trifluoromethanesulfonate as the catalyst, the specific implementation process is as follows:

[0376] 1,1-Diphenylbut-2-yn-1,4-diol (95.2 mg, 0.4 mmol), 4-iodo-N-(2-methylprop-1-en-1-yl)-3-nitrobenzamide (276.6 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0377]

[0378] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 208.7 mg, with a calculated yield of 92%.

[0379] The analysis of the test is as follows:

[0380] 1. Proton and carbon NMR spectra:

[0381] 1 H NMR (300 MHz, CDCl3) δ 8.18 (d, J = 2.0 Hz, 1H), 8.11 (d, J = 8.2Hz, 1H), 7.61 (dd, J1 = 8.2 Hz, J2 = 2.1 Hz, 1H), 7.40-7.28 (m, 10H), 6.59 (d,J = 9.3 Hz, 1H), 5.74 (d, J = 9.2 Hz, 1H), 4.74-4.63 (m, 2H), 1.38 (s, 3H),1.26 (s, 3H) ppm.

[0382] 13 C NMR (75 MHz, CDCl3) δ 195.4, 164.3, 153.0, 142.5, 136.8, 136.3,135.1, 131.3, 128.52, 128.48, 128.3, 128.2, 127.7, 123.7, 116.1, 111.5, 90.7,88.4, 66.0, 46.0, 25.0, 21.6 ppm.

[0383] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 23 IN2NaO4 [M + +Na]: 589.0595, Found:589.0594.

[0384] The results show that the theoretical mass is 589.0595, while the observed value of the peak found in the actual mass spectrum is 589.0594. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0385] This is a product of this embodiment.

[0386] Example 27

[0387] Using R 1 =R 2 1,1-Diphenylbut-2-yne-1,4-diol of phenyl group, R 3 It is 2-methyl-3,5-dinitrophenyl, R 4 =R 5Using 2-methyl-N-(2-methylprop-1-en-1-yl)-3,5-dinitrobenzamide as a reactant, and indium trifluoromethanesulfonate as a catalyst, the specific implementation process is as follows:

[0388] 1,1-Diphenylbut-2-yn-1,4-diol (95.5 mg, 0.4 mmol), 2-methyl-N-(2-methylprop-1-en-1-yl)-3,5-dinitrobenzamide (223.4 mg, 0.8 mmol), and indium trifluoromethanesulfonate (22.7 mg, 0.04 mmol) were dissolved in acetonitrile (4 mL) and reacted at 25 °C for 3 h. The reaction equation is as follows:

[0389]

[0390] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 106.1 mg, with a calculated yield of 53%.

[0391] The analysis of the test is as follows:

[0392] 1. Proton and carbon NMR spectra:

[0393] 1 H NMR (300 MHz, CDCl3) δ 8.67 (d, J = 2.3 Hz, 1H), 8.38 (d, J = 2.4Hz, 1H), 7.39-7.27 (m, 10H), 6.38 (d, J = 9.4 Hz, 1H), 5.73 (d, J = 9.4 Hz,1H), 4.76-4.63 (m, 2H), 2.64 (s, 3H), 1.42 (s, 3H), 1.26 (s, 3H) ppm.

[0394] 13 C NMR (75 MHz, CDCl3) δ 195.2, 165.7, 150.7, 145.6, 140.6, 137.8,136.6, 136.2, 128.49, 128.45, 128.4, 128.1, 127.74, 127.69, 124.6, 120.5,116.3, 111.2, 88.2, 66.2, 46.0, 25.2, 21.6, 16.7 ppm.

[0395] 2. High-resolution mass spectrometry: HRMS (ESI) C 28 H 26 N3O6 [M ++H]: 500.1816, Found: 500.1800.

[0396] The results show that the theoretical mass is 500.1816, while the observed value of the peak in the actual mass spectrum is 500.1800. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0397] This is a product of this embodiment.

[0398] Example 28

[0399] The reaction was carried out using N-[4-(2,2-diphenylvinylene)-3,3-dimethyltetrahydrofuran-2-yl]benzamide from Example 1, with palladium on carbon as the reactant. The specific implementation process is as follows:

[0400] N-[4-(2,2-diphenylvinylene)-3,3-dimethyltetrahydrofuran-2-yl]benzamide (79.0 mg, 0.2 mmol) and palladium on carbon (10% palladium on carbon, 42.5 mg, 0.02 mmol) were dissolved in methanol (2 mL), and hydrogen gas was introduced. 25 o The reaction was carried out at C for 48 hours. The reaction equation is as follows:

[0401]

[0402] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 48.2 mg of solid product, with a calculated yield of 60%.

[0403] The analysis of the test is as follows:

[0404] 1. Proton and carbon NMR spectra:

[0405] 1 H NMR (300 MHz, CDCl3) δ 7.82-7.70 (m, 2H), 7.53-7.37 (m, 3H), 7.35-7.14 (m, 10H), 6.31 (d, J = 9.9 Hz, 1H), 5.47 (d, J = 9.8 Hz, 1H), 3.89-3.73(m, 2H), 3.51 (dd, J = 10.1, 8.0 Hz, 1H), 2.37-2.11 (m, 1H), 2.10-1.82 (m,2H), 1.00 (s, 3H), 0.91 (s, 3H) ppm.

[0406] 13C NMR (75 MHz, CDCl3) δ 167.4, 144.9, 143.4, 134.1, 131.8, 128.7,128.5, 127.6, 127.4, 127.0, 126.6, 126.4, 88.0, 70.0, 49.9, 46.0, 42.1, 33.8,22.5, 14.8 ppm.

[0407] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 30 NO2 [M + +H]: 400.2271, Found: 400.2271.

[0408] The results show that the theoretical mass is 400.2271, and the observed value of the peak found in the actual mass spectrum is also 400.2271. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0409] This is a product of this embodiment.

[0410] Example 29

[0411] The reaction was carried out using N-[4-(2,2-diphenylvinylene)-3,3-dimethyltetrahydrofuran-2-yl]benzamide and N-iodosuccinimide from Example 1 as reactants. The specific implementation process is as follows:

[0412] Under argon protection, N-[4-(2,2-diphenylvinylene)-3,3-dimethyltetrahydrofuran-2-yl]benzamide (79.0 mg, 0.2 mmol) and N-iodosuccinimide (54.4 mg, 0.24 mmol) were dissolved in ultra-dry dichloromethane (2 mL) with a water content ≤50 ppm. o The reaction proceeds at C for 24 hours. The reaction equation is as follows:

[0413]

[0414] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 96.3 mg of solid product, with a calculated yield of 92%.

[0415] The analysis of the test is as follows:

[0416] 1. Proton and carbon NMR spectra:

[0417] 1H NMR (300 MHz, Acetone-d6) δ 8.16 (d, J = 7.5 Hz, 2H), 7.62-7.46 (m,4H), 7.46-7.25 (m, 9H), 4.70 (s, 1H), 3.93-3.80 (m, 2H), 1.38 (s, 6H) ppm.

[0418] 13 C NMR (75 MHz, Acetone-d6) δ 158.5, 157.7, 151.1, 142.2, 132.9,132.1, 129.4, 129.0, 128.6, 128.4, 128.3, 100.4, 92.5, 90.9, 79.0, 44.2,21.9, 21.4 ppm.

[0419] 2. High-resolution mass spectrometry: HRMS (ESI) C 27 H 25 INO2 [M + +H]: 522.0924, Found: 522.0905.

[0420] The results show that the theoretical mass is 522.0924, while the observed value of the peak in the actual mass spectrum is 522.0905. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0421] This is a product of this embodiment.

[0422] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing and using an N-(4-vinylidenetetrahydrofuran-2-yl)amide compound, characterized in that, Includes the following steps: The substituted 2-butyn-1,4-diol, enamide, Lewis acid catalyst and organic solvent were mixed and subjected to a cyclization reaction to obtain the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound. The substituted 2-butyn-1,4-diol has the structure shown in Formula 1 or is... The olefin amide has the structure shown in any one of formulas 2 to 4: Formula 1, Equation 2, Formula 3, Equation 4; When the substituted 2-butyn-1,4-diol is When, the alkenamide is The N-(4-vinylidenetetrahydrofuran-2-yl)amide compound is ; When the substituted 2-butyn-1,4-diol is When the enamide has the structure shown in any of formulas 2 to 4; when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula I, and when the enamide is When the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula II, and when the enamide is At that time, the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound has the structure shown in Formula III: Formula I, Formula II, Formula III; Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkoxy-substituted phenyl; R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, and alkenyl; R 4 and R 5 Independently, it is an alkyl group.

2. The preparation method according to claim 1, characterized in that, The Including 1,1-diphenylbut-2-yne-1,4-diol, 1,1-bis(4-fluorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-chlorophenyl)but-2-yne-1,4-diol, 1,1-bis(4-bromophenyl)but-2-yne-1,4-diol, 1,1-bis(p-tolyl)but-2-yne-1,4-diol, 1,1-bis(naphthyl-2-yl)but-2-yne-1,4-diol, and 1-(4-methoxyphenyl)-1-phenylbut-2-yne-1,4-diol.

3. The preparation method according to claim 1 or 2, characterized in that, The Lewis acid catalyst includes indium trifluoromethanesulfonate, aluminum trifluoromethanesulfonate, tin trifluoromethanesulfonate, iron trifluoromethanesulfonate, and copper trifluoromethanesulfonate; The molar ratio of the substituted 2-butyn-1,4-diol to the Lewis acid catalyst is 1:0.05~0.

2.

4. The preparation method according to claim 1, characterized in that, The Including N-(2-methylprop-1-en-1-yl)benzamide, 4-methyl-N-(2-methylprop-1-en-1-yl)benzamide, 4-methoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-fluoro-N-(2-methylprop-1-en-1-yl)benzamide, 4-chloro-N-(2-methylprop-1-en-1-yl)benzamide, 4-bromo-N-(2-methylprop-1-en-1-yl)benzamide, N-(2-methylprop-1-en-1-yl)-[1,1'-biphenyl]-4-carboxamide, N-(2-methylprop-1-en-1-yl)-2-naphthylcarboxamide, N-(2-methylprop-1-en-1-yl)benzo[b]thiamethoxam Pheno-3-carboxamide, N-(2-methylprop-1-en-1-yl)benzofuran-2-carboxamide, N-(2-methylprop-1-en-1-yl)acetamide, N-(2-methylprop-1-en-1-yl)butamide, N-(2-methylprop-1-en-1-yl)cyclohexylcarboxamide, N-(2-methylprop-1-en-1-yl)acrylamide, N-(2-ethylbut-1-en-1-yl)benzamide, 2-ethoxy-N-(2-methylprop-1-en-1-yl)benzamide, 4-iodo-N-(2-methylprop-1-en-1-yl)-3-nitrobenzamide, 2-methyl-N-(2-methylprop-1-en-1-yl)-3,5-dinitrobenzamide.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of the substituted 2-butyn-1,4-diol and the enamide is 1:1.8~2.

2.

6. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out at a temperature of 0-45℃ for 3-48 hours.

7. The N-(4-vinylidenetetrahydrofuran-2-yl)amide 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 IV: Formula I, Formula II, Formula III, Formula IV; Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkoxy-substituted phenyl; R 3 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, mixed polysubstituted phenyl, alkyl, and alkenyl; R 4 and R 5 Independently, it is an alkyl group.

8. The N-(4-vinylidenetetrahydrofuran-2-yl)amide compound according to claim 7, characterized in that, It has any of the structures shown in Equations I-1 to I-24, II-1, III-1, and IV: Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21 Formula I-22 Formula I-23 Formula I-24; Formula II-1; Formula III-1; Formula IV.

9. A derivative prepared from the N-(4-vinylidenetetrahydrofuran-2-yl)amide compound having the structure shown in Formula I of claim 7, characterized in that, It has the structure shown in any of the equations a to b: Formula a Formula b.

10. A method for preparing the derivative of claim 9, comprising the following steps: The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of palladium on carbon, hydrogen, and a first organic solvent undergoes a reduction reaction to obtain the desired product. ; The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of N-iodosuccinimide and a second organic solvent undergoes an electrophilic cyclization reaction to obtain the desired product. .

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