CN115626904A - 3-enamide substituted benzodihydrofuran compound and preparation method thereof - Google Patents

Abstract

The invention discloses a 3-enamide substituted benzodihydrofuran compound and a preparation method thereof. The preparation method comprises the following steps: stirring and reacting 1, 6-eneyne compounds connected with phenol, alkyl nitrile, lewis acid, protonic acid and a solvent at the temperature of 30-80 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the 3-enamide substituted benzodihydrofuran compounds. The 3-enamide substituted benzodihydrofuranes prepared by the invention are further hydrolyzed to form C3-acylated benzofuran which is widely used as basic skeleton of antiarrhythmic and anti-inflammatory drugs. The preparation method develops Lewis acid to promote the series/cyclization reaction of 1, 6-eneyne and alkyl nitrile to construct a series of highly functionalized 3-enamide substituted dihydrobenzofuran compounds, has no transition metal participation in the reaction, has mild reaction conditions, and meets the development requirement of green organic chemistry.

Description

3-enamide substituted benzodihydrofuran compound and preparation method thereof

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-enamide substituted benzodihydrofuran compound and a preparation method thereof.

Background

Benzofuran compounds widely exist in nature as an important oxygen-containing heterocyclic compound, special chemical properties and biological activity of the benzofuran compounds are attracted in the fields of medicines, dyes, foods and the like, wherein different substituted functional groups are introduced into C2 and C3 positions of a chroman skeleton structure, so that the benzofuran compounds have the functions of resisting AIDS virus, malaria, cancer, pain, inflammation, fungi and bacteria, and therefore, the synthesis and modification of the heterocyclic compounds have important significance in organic chemical research. By introducing different functional groups into the C2 and C3 positions of the benzofuran, the diversification of the performances of the benzofuran can be realized. Enamides are important components of biologically active natural products and drug candidates as important sources for the synthesis of nitrogen-containing molecules. The incorporation of an enamide into the benzofuran skeleton will further expand their range of applications in the fields of medicinal chemistry, materials and organic synthesis.

In recent years, the synthesis of functionalized benzofuran compounds by using phenol-linked 1, 6-enynes has received much attention. <xnotran> (Skiyama, N.; noguchi, K.; tanaka, K.Angew.Chem.Int.Ed.2012,51,5976-5980;Wu,W.; yi, S.; huang, W.; luo, D.; jiang, H.Org.Lett.2017,19,2825-2828;Wang,L.; qi, C.; cheng, R.; liu, H.; xiong, W.; jiang, H.Org.Lett.2019,21,7386-7389;) (Jana, S.; verma, A.; kadu, R.; kumar, S.Chem.Sci.2017,8,6633-6644;Chen,F.; huang, X.; yang, C.; jiang, H.; zeng, W.J.Org.Chem.2021,86,14572-14585;) / , C2 C3 , 1,6- / . </xnotran> Since vinyl ether in the phenol-linked 1, 6-eneyne belongs to electron-rich olefin and is easily attacked by electrophilic reagent, the alkynyl is activated by the electrophilic intermediate, and the formed alkenyl cation intermediate can be attacked by nucleophilic reagent to construct the polysubstituted alkenyl benzofuran derivative. Therefore, the development of a novel high-efficiency metal-free catalytic reaction is beneficial to widening the adaptability of the reaction and accords with the concept of environmental protection.

Conventional methods for the synthesis of enamides include imidization, condensation of amides with aldehydes, curtius rearrangement of unsaturated acyl azides (Evano, g.; gaumont, a. -c.; alayrac, c.; wro, i.e.; giguere, j.r.; delaroix, o.; bayer, a.; jouvin, k.; theunissen, c.; gatignol j.; silveranus, a.c. tetrahedron,2014,70, 9-1616), direct amide dehydrogenation, etc. (Trost, b.m.; cregg j.j.; quach, N.j.am.Chem. Soc.2017,139, 5115233-5139, spie β, P.; berger, M.; kaiser, D.n.J.am.g. Chem.10524, R.143, R.29, R.g.), lewis acids, R.143, R.g., G., G., J., D.

Acid-promoted Ritter-type reaction is an effective method for constructing an amide framework, simple nitrile which is cheap and easy to obtain is used as a nucleophilic reagent to react with a corresponding cationic intermediate, and then the nitrile intermediate is captured by water to realize amidation. In recent years, the construction of polysubstituted enamide compounds by the reaction of unactivated alkynes with nitriles using lewis acids or electrophiles has also been reported, but the present research for the construction of tetra-substituted enamides with heterocyclic backbones is relatively rare and generally requires the participation of transition metals. In combination with the previously reported heterocyclic skeleton with different functionalities at C2 and C3 positions, which is achieved mainly by radical concatenation/cyclization, the alkenyloxy, carbamate and aryl substitution of the alkenyl group can be achieved by the participation of transition metals after the formation of the alkenyl intermediate at C3 position, while the heterocyclic skeleton with enamide substitution can be constructed by the reaction of the nitrile onium intermediate formed by trapping the nucleophilic nitrile with water after the formation of the alkenyl cationic intermediate by the cyclization of the alkenylene, using the mode of electrophilic addition, without the participation of transition metals, and the conversion can be achieved by lewis acid promotion under acidic conditions. In conclusion, the Lewis acid without the participation of transition metal is developed to promote the electrophilic addition/cyclization reaction of the eneyne, the nitrile and the electrophilic protonic acid, the heterocyclic ring and the carbon-nitrogen bond can be constructed in one step, the 3-enamide substituted benzofuran ring construction is realized, the atom economy is high, and the application prospect is expected besides the methodological novelty.

Disclosure of Invention

In view of the shortcomings and drawbacks of the prior art, the present invention is directed to 3-enamide substituted chromans and a method for preparing the same. The method selectively constructs the 3-enamide substituted benzodihydrofuran derivative by taking a simple and easily obtained phenol-connected 1, 6-eneyne compound and alkyl nitrile as raw materials, taking common boron compounds and the like as Lewis acid, taking fatty acid and the like as protonic acid, taking 1, 2-dichloroethane and the like as a solvent and adopting a Lewis acid-promoted strategy, has the advantages of high atom economy, no participation of transition metal, simple and safe operation, wide substrate applicability and the like, and has good application prospect in actual production and research.

The purpose of the invention is realized by the following technical scheme.

A method for preparing 3-enamide substituted benzodihydrofuran compounds, which comprises the following steps:

stirring and reacting 1, 6-eneyne compounds connected with phenol, alkyl nitrile, lewis acid, protonic acid and a solvent at the temperature of 30-80 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the 3-enamide substituted benzodihydrofuran compounds.

Further, the chemical reaction equation of the synthesis process is as follows:

wherein R is ¹ Is a substituent on the alkynylphenyl and is at least one of hydrogen, 4-methyl, 4-chlorine, 4-bromine, 4-fluorine, 4-tertiary butyl, 4-methyl formate, 4-trifluoromethyl, 4-cyano, 3-methyl, 3-fluorine, 3-chlorine and 3-bromine;

R ² a substituent on the phenol-linked 1, 6-enynylphenol, R ² Is at least one of hydrogen, 4-fluorine, 4-chlorine, 4-bromine, 4-trifluoromethyl and 5-chlorine;

R ³ is methyl.

Further, the phenol-linked 1, 6-enyne compound is 1- (phenylethynyl) -2- (ethyleneoxy) benzene; the alkyl nitrile is acetonitrile.

Further, the Lewis acid is one or more than two of boron trifluoride diethyl etherate, boron trichloride, stannic chloride and aluminum trichloride.

Further, the molar ratio of the added Lewis acid to the phenol-linked 1, 6-eneyne compound is 1.0-3.0.

Further, the molar ratio of the alkyl nitrile added to the phenol-linked 1, 6-enyne compound is 5.0 to 10.0.

Further, the protonic acid is one or more than two of acetic acid, propionic acid, trifluoroacetic acid, trimethylacetic acid, benzoic acid and p-toluenesulfonic acid.

Further, the molar ratio of the added protonic acid to the 1, 6-eneyne compound linked to the phenol is 1.0-2.5.

Further, the solvent is one or more than two of dichloromethane, 1, 2-dichloroethane and tetrahydrofuran.

Further, the volume mol ratio of the solvent to the phenol-linked 1, 6-eneyne compound is 5-15mL:1mmoL.

Further, the stirring reaction time is 6-18 hours; preferably 10 to 18 hours.

Further, the stirring rate of the stirring reaction is 500 to 1000rpm.

Further, the separation and purification operations are as follows: extracting the reaction liquid with ethyl acetate, combining organic phases, drying with anhydrous magnesium sulfate, filtering, decompressing, steaming and removing the organic solvent to obtain a crude product, and purifying by column chromatography to obtain the 3-enamide substituted benzodihydrofuran compound.

Furthermore, the eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1-8, preferably a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1-5.

The reaction principle of the synthetic method is that under the promotion of Lewis acid, hydrogen positive ions of protonic acid (carboxylic acid) are added to alkenyl of eneyne to form alkyl positive ions, then the alkyl positive ions are added to the alkyne to form alkenyl positive ions, and nitrile is captured as a nucleophilic reagent and then hydrolyzed to obtain the final 3-enamide substituted benzodihydrofuran compound.

The 3-enamide substituted benzodihydrofuran compound is prepared by the preparation method, and the structural formula of the 3-enamide substituted benzodihydrofuran compound is as follows:

wherein R is ¹ Is at least one of hydrogen, 4-methyl, 4-chlorine, 4-bromine, 4-fluorine, 4-tertiary butyl, 4-methyl formate, 4-trifluoromethyl, 4-cyano, 3-methyl, 3-fluorine, 3-chlorine and 3-bromine;

R ² is at least one of hydrogen, 4-chlorine, 4-fluorine, 4-bromine, 4-trifluoromethyl and 5-chlorine;

R ³ is methyl.

The 3-enamide substituted benzodihydrofuranes prepared by the invention are further hydrolyzed to form C3-acylated benzofuran which is widely used as basic skeleton of antiarrhythmic and anti-inflammatory drugs.

Compared with the prior art, the invention has the following advantages and beneficial effects:

(1) The invention develops a synthetic method for constructing the 3-enamide substituted benzodihydrofuran compound by electrophilic addition/cyclization of the 1, 6-eneyne compound connected with phenol such as 1- (phenylethynyl) -2- (ethyleneoxy) benzene and the like and alkyl nitrile under the promotion of Lewis acid and the participation of protonic acid, and the 1, 6-eneyne compound connected with phenol such as 1- (phenylethynyl) -2- (ethyleneoxy) benzene and the like serving as a basic raw material can be synthesized by cheap o-iodophenol, 1, 2-dibromoethane and phenylacetylene, so that the method has the characteristics of simple and easily obtained raw materials, safe and simple operation, mild conditions, high atom economy and wide substrate applicability;

(2) The synthesis method is convenient and fast to operate, free of transition metal participation, green and environment-friendly, good in tolerance to functional groups, high in atom economy and good in substrate applicability, and is the main characteristics of reaction, a carbon-carbon bond and a carbon-nitrogen bond are constructed in one step of reaction, so that the method is expected to be applied to actual industrial production and further derivatization.

Drawings

FIGS. 1 and 2 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 1, respectively;

FIGS. 3 and 4 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 2;

FIGS. 5 and 6 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 3, respectively;

FIGS. 7 and 8 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 4;

FIGS. 9 and 10 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 5;

FIGS. 11 and 12 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 6;

FIGS. 13 and 14 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 7;

FIGS. 15 and 16 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 8;

FIGS. 17 and 18 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 9;

FIGS. 19 and 20 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 10;

FIGS. 21 and 22 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 11;

FIGS. 23 and 24 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 12;

FIGS. 25 and 26 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 13;

FIGS. 27 and 28 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 14;

FIGS. 29 and 30 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 15;

FIGS. 31 and 32 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 16;

FIG. 33 and FIG. 34 are a hydrogen spectrum and a carbon spectrum, respectively, of the objective product obtained in example 17.

Detailed Description

The technical solutions of the present invention are further described in detail below with reference to specific examples and drawings, but the scope and implementation of the present invention are not limited thereto.

Example 1

0.1 mmol of 1- (phenylethynyl) -2- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl etherate and 0.8 ml of 1, 2-dichloroethane as solvents were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 1 and fig. 2, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.41(s,1H),7.47-7.41(m,3H),7.37(dt,J＝7.7,2.0Hz,2H),7.10-7.02(m,1H),6.78(d,J＝8.0Hz,1H),6.53(t,J＝7.6Hz,1H),6.37(d,J＝8.0Hz,1H),5.56(q,J＝6.4Hz,1H),1.94(s,3H),1.42(d,J＝6.0Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.5,162.5,138.2,133.6,130.3 129.5,129.2,129.0,126.5,124.4,122.9,120.4,110.6,82.4,23.4,19.2；

IR(KBr)ν _max 2922,2833,1607,1459,1362,1269,1069,760cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₆ NO ₂ [M-H] ^- :278.1187,Found 278.1187。

the structure of the target product is deduced from the above data as follows:

example 2

0.1 mmol of 1- (p-tolylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 4.

The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 3 and 4, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.35(s,1H),7.25(s,4H),7.08-7.04(m,1H),6.77(d,J＝8.0Hz,1H),6.54(t,J＝7.6Hz,1H),6.46(d,J＝8.0Hz,1H),5.54(q,J＝6.4Hz,1H),2.35(s,3H),1.93(s,3H),1.40(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.5,162.4,138.4,135.2,133.2,130.2,129.7,129.4,126.5,124.5,122.9,120.4,110.5,82.4,23.4,21.5,19.3；

IR(KBr)ν _max 2924,2833,1608,1361,772cm ^-1 ；

HRMS(ESI)Calcd for C ₁₉ H ₁₈ NO ₂ [M-H] ^- :292.1343,Found 292.1343。

the structure of the target product is deduced from the above data as follows:

example 3

0.1 mmol of 1- (4-chlorophenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 3.

The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 5 and 6, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.41(s,1H),7.50-7.48(m,2H),7.40-7.38(m,2H),7.10(t,J＝8.0Hz,1H),6.80(d,J＝8.0Hz,1H),6.59(t,J＝7.6Hz,1H),6.46(d,J＝7.6Hz,1H),5.57(q,J＝6.4Hz,1H),1.93(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.9,162.6,137.0,134.2,133.4,131.4,130.6,129.2,125.4,123.9,122.9,120.6,110.7,82.3,23.4,19.3；

IR(KBr)ν _max 2903,1635,1506,1311,741cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ ClNO ₂ [M-H] ^- :312.0797,Found 312.0797。

the structure of the target product is deduced from the above data as follows:

example 4

0.1 mmol of 1- (4-bromophenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl etherate, and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 7 and fig. 8, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.40(s,1H),7.65-7.62(m,2H),7.33(d,J＝8.0Hz,2H),7.12-7.08(m,1H),6.80(d,J＝8.0Hz,1H),6.60(t,J＝7.6Hz,1H),6.47(d,J＝8.0Hz,1H),5.56(q,J＝6.4Hz,1H),1.93(s,3H),1.41(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.9,162.6,137.3,134.1,132.1,131.7,130.6,125.5,123.9,122.8,122.0,120.6,110.7,82.3,23.3,19.3；

IR(KBr)ν _max 2926,2832,1602,1362,769cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ BrNO ₂ [M-H] ^- :356.0292,Found 356.0292。

the structure of the target product is deduced from the above data as follows:

example 5

0.1 mmol of 1- (4-fluorophenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 9 and fig. 10, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.41(s,1H),7.43-7.39(m,2H),7.29-7.24(m,2H),7.08(t,J＝7.6Hz,1H),6.79(d,J＝8.0Hz,1H),6.57(t,J＝7.6Hz,1H),6.38(d,J＝8.0Hz,1H),5.56(q,J＝6.4Hz,1H),1.94(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.7,162.5(d,J＝143.8Hz,1C),162.5,134.5(d,J＝3.0Hz,1C),133.8,131.7(d,J＝8.0Hz,1C),130.4,125.5,124.2,122.8,120.5,116.1(d,J＝21.3Hz,1C),110.6,82.3,23.4,19.2；

IR(KBr)ν _max 2926,2832,1601,1510,1461,1363,1227,1151,1064,839,766cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ FNO ₂ [M-H] ^- ,296.1092,found 296.1092。

the structure of the target product is deduced from the above data as follows:

example 6

0.1 mmol of 1- (4-tert-butylphenyl ethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl etherate, and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 11 and fig. 12, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.36(s,1H),7.46(d,J＝8.4Hz,2H),7.30(d,J＝8.0Hz,2H),7.08-7.04(m,1H),6.78(d,J＝8.0Hz,1H),6.53(t,J＝7.2Hz,1H),6.47(d,J＝7.6Hz,1H),5.54(q,J＝6.4Hz,1H),1.93(s,3H),1.40(d,J＝6.4Hz,3H),1.32(s,9H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.3,162.4,151.6,135.2,133.2,130.2,129.2,126.3,125.9,124.5,122.9,120.4,110.5,82.5,35.0,31.6,23.4,19.2；

IR(KBr)ν _max 2957,2857,1609,1517,1462,1361,1279,834,753cm ^-1 ；

HRMS(ESI)Calcd for C ₂₂ H ₂₄ NO ₂ [M-H] ^- :334.1813,Found 334.1813。

the structure of the target product is deduced from the above data as follows:

example 7

0.1 mmol of methyl 4- ((2- (vinyloxy) phenyl) ethynyl) benzoate, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 13 and fig. 14, and the structural characterization data are as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.48(s,1H),8.02(d,J＝8.4Hz,2H),7.53(d,J＝8.0Hz,2H),7.13-7.08(m,1H),6.81(d,J＝8.1Hz,1H),6.57(t,J＝7.6Hz,1H),6.45(d,J＝7.6Hz,1H),5.59(q,J＝6.4Hz,1H),3.87(s,3H),1.94(s,3H),1.44(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝168.1,166.5,162.8,142.9,134.9,130.9,130.1,129.9,129.8,125.6,123.7,123.0,120.7,110.8,82.4,52.8,23.4,19.3；

IR(KBr)ν _max 2921,2837,1720,1600,1457,1365,1278,1104,750cm ^-1 ；

HRMS(ESI)Calcd for C ₂₀ H ₁₈ NO ₄ [M-H] ^- :336.1241,Found 336.1241。

the structure of the target product is deduced from the above data as follows:

example 8

0.1 mmol of 1- (4-trifluoromethylphenylethynyl) -2- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl etherate and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 4.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 15 and fig. 16, and the structural characterization data are as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.47(s,1H),7.80(d,J＝8.0Hz,2H),7.61(d,J＝7.6Hz,2H),7.12(t,J＝7.6Hz,1H),6.82(d,J＝8.0Hz,1H),6.59(t,J＝7.6Hz,1H),6.44(d,J＝7.6Hz,1H),5.61(q,J＝6.4Hz,1H),1.94(s,3H),1.44(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝168.2,162.8,142.3,135.0,130.9,130.4,129.1(q,J＝31.5Hz,1C),126.1(q,J＝3.6Hz,1C),125.3,123.6,123.4,122.8,120.7,110.9,82.3,23.3,19.3；

IR(KBr)ν _max 2922,2830,1612,1461,1360,1124,1068,763cm ^-1 ；

HRMS(ESI)Calcd for:C ₁₉ H ₁₅ F ₃ NO ₂ [M-H] ^- :346.1060,Found 346.1060。

the structure of the target product is deduced from the above data as follows:

example 9

0.1 mmol of 4- ((2- (vinyloxy) phenyl) ethynyl) benzonitrile, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl etherate, and 0.8 ml of 1, 2-dichloroethane as a solvent were added to a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 2.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 17 and fig. 18, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.48(s,1H),7.89(d,J＝8.0Hz,2H),7.58(d,J＝8.1Hz,2H),7.15-7.11(m,1H),6.82(d,J＝8.4Hz,1H),6.60(t,J＝7.6Hz,1H),6.48(d,J＝7.6Hz,1H),5.61(q,J＝6.4Hz,1H),1.94(s,3H),1.44(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝168.3,162.9,142.9,135.4,133.1,131.1,130.5,125.1,123.4,122.9,120.8,119.3,111.2,110.9,82.3,23.3,19.3；

IR(KBr)ν _max 2924,2834,1611,1461,1361,772cm ^-1 ；

HRMS(ESI)Calcd for C ₁₉ H ₁₅ N ₂ O ₂ [M-H] ^- :303.1139,Found 303.1139。

the structure of the target product is deduced from the above data as follows:

example 10

0.1 mmol of 1- (m-methylphenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged in a reaction tube and stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The hydrogen spectrogram and the carbon spectrogram of the obtained target product are respectively shown in fig. 19 and fig. 20, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.38(s,1H),7.33(t,J＝7.6Hz,1H),7.22(d,J＝7.6Hz,1H),7.16(d,J＝9.6Hz,1H),7.08-7.04(m,1H),6.78(d,J＝8.0Hz,1H),6.53(t,J＝7.2Hz,1H),6.39(d,J＝7.6Hz,1H),5.55(q,J＝6.4Hz,1H),2.33(s,3H),1.94(s,3H),1.41(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.4,162.4,138.4,138.1,133.3,130.2,129.8,129.6,129.1,126.6,126.5,124.5,123.0,120.4,110.5,82.4,23.4,21.4,19.2；

IR(KBr)ν _max 2922,1647,1523,1313,748cm ^-1 ；

HRMS(ESI)Calcd for C ₁₉ H ₁₈ NO ₂ [M-H] ^- :292.1343,Found 292.1343。

the structure of the target product is deduced from the above data as follows:

example 11

0.1 mmol of 1- (3-fluorophenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 21 and 22, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.43(s,1H),7.49-7.46(m,1H),7.27-7.22(m,2H),7.17-7.14(m,1H),7.12-7.08(m,1H),6.81(d,J＝8.0Hz,1H),6.58(t,J＝7.6Hz,1H),6.43(d,J＝7.6Hz,1H),5.57(q,J＝6.4Hz,1H),1.94(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝165.2(d,J＝502.4Hz,1C),162.8(d,J＝242.9Hz,1C)140.5(d,J＝7.6Hz,1C),134.3,131.2(d,J＝8.4Hz,1C),130.6,125.8(d,J＝2.7Hz,1C),125.2(d,J＝2,2Hz,1C),123.9,122.9,120.6,116.2,115.9(d,J＝8.4Hz,1C),115.7,110.7,82.3,23.4,19.2；

IR(KBr)ν _max 2924,2831,1598,1459,1364,769cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ FNO ₂ [M-H] ^- :296.1092,Found 296.1092。

the structure of the target product is deduced from the above data as follows:

example 12

0.1 mmol of 1- (3-chlorophenylethynyl) -2- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 23 and 24, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.44(s,1H),7.48-7.46(m,2H),7.38-7.34(m,2H),7.13-7.08(m,1H),6.81(d,J＝8.0Hz,1H),6.59(t,J＝7.6Hz,1H),6.41(d,J＝7.6Hz,1H),5.58(q,J＝6.4Hz,1H),1.94(s,3H),1.42(d,J＝6.4Hz,3H).

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.9,162.7,140.3,134.5,133.7,131.1,130.7,129.1,128.8,128.3,125.1,123.8,122.8,120.6,110.8,82.3,23.3,19.2；

IR(KBr)ν _max 2924,2830,1601,1362,770cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ ClNO ₂ [M-H] ^- :312.0797,Found 312.0797。

the structure of the target product is deduced from the above data as follows:

example 13

0.1 mmol of 1- (3-bromophenylethynyl) -2- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged in a reaction tube and stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 3.

The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 25 and 26, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.43(s,1H),7.62-7.59(m,1H),7.51(s,1H),7.43-7.39(m,2H),7.11(t,J＝7.6Hz,1H),6.81(d,J＝8.4Hz,1H),6.59(t,J＝7.6Hz,1H),6.40(d,J＝8.0Hz,1H),5.57(q,J＝6.4Hz,1H),1.94(s,3H),1.42(d,J＝6.4Hz,3H)..

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.9,162.7,140.5,134.6,131.9,131.7,131.4,130.7,128.7,125.0,123.8,122.8,122.2,120.6,110.8,82.3,23.3,19.2；

IR(KBr)ν _max 2925,2831,1598,1364,1070,765cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ BrNO ₂ [M-H] ^- :356.0292,Found 356.0291。

the structure of the target product is deduced from the above data as follows:

example 14

0.1 mmol of 4-fluoro-2- (phenylethynyl) -1- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 27 and 28, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.50(s,1H),7.48-7.44(m,3H),7.38-7.36(m,2H),6.92-6.87(m,1H),6.79-6.76(m,1H),5.90(d,J＝8.8Hz,1H),5.62(q,J＝6.4Hz,1H),1.95(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝163.0(d,J＝883.6Hz,1C),156.4(d,J＝232.2Hz,1C),137.6,132.4,129.5,129.4,129.3,128.0,125.8(d,J＝9.5Hz,1C),116.5(d,J＝24.5Hz,1C),111.0(d,J＝8.9Hz,1C),109.1,108.9,83.3,23.4,19.0；

IR(KBr)ν _max 2928,2828,1612,1472,1360,771,529cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ FNO ₂ [M-H] ^- :296.1092,found 296.1092。

the structure of the target product is deduced from the above data as follows:

example 15

0.1 mmol of 4-chloro-2- (phenylethynyl) -1- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the reaction was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 29 and fig. 30, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.48(s,1H),7.51-7.45(m,3H),7.38-7.36(m,2H),7.10-7.07(m,1H),6.80(d,J＝8.4Hz,1H),6.16(s,1H),5.63(q,J＝6.3Hz,1H),1.95(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.4,161.1,137.6,131.6,129.5,129.4(2C),129.4,128.3,126.7,124.0,122.3,111.8,83.4,23.4,19.0；

IR(KBr)ν _max 2923,2833,1624,1532,1363,773,699cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ ClNO ₂ [M-H] ^- :312.0797,found 312.0797。

the structure of the target product is deduced from the above data as follows:

example 16

0.1 mmol of 4-bromo-2- (phenylethynyl) -1- (vinyloxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 31 and 32, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.50(s,1H),7.49-7.46(m,3H),7.38-7.36(m,2H),7.21-7.18(m,1H),6.76(d,J＝8.4Hz,1H),6.30(s,1H),5.63(q,J＝6.4Hz,1H),1.95(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.4,161.4,137.6,132.3,131.4,129.4,129.4(2C),128.3,127.3,125.3,112.4,111.6,83.3,23.4,19.0；

IR(KBr)ν _max 2925,2831,1607,1457,1362,1065,772cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₅ BrNO ₂ [M-H] ^- :356.0292,found 356.0292。

the structure of the target product is deduced from the above data as follows:

example 17

0.1 mmol of 4-trifluoromethyl-2- (phenylethynyl) -1- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride ethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The obtained hydrogen spectrogram and carbon spectrogram of the target product are respectively shown in fig. 33 and fig. 34, and the structural characterization data are shown as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.57(s,1H),7.50-7.46(m,3H),7.40-7.38(m,3H),6.95(d,J＝8.4Hz,1H),6.42(s,1H),5.71(q,J＝6.4Hz,1H),1.97(s,3H),1.45(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝166.1(d,J＝270.4Hz,1C),137.4(d,J＝5.8Hz,1C),130.6,129.5,129.5,129.4,128.9,127.3(d,J＝2.9Hz,1C),126.1,125.8,123.4,121.3(q,J＝31.5Hz,1C),119.8(q,J＝4.1Hz,1C),111.0,84.0,23.5,18.8；

IR(KBr)ν _max 3237,3023,2918,1648,1500,1449,1333,1277,1159,1107,1001,901,822,764,708cm ^-1 ；

HRMS(ESI)Calcd for C ₁₉ H ₁₅ F ₃ NO ₂ [M-H] ^- :346.1060,found 346.1060。

the structure of the target product is deduced from the above data as follows:

example 18

0.1 mmol of 4-chloro-1- (phenylethynyl) -2- (ethyleneoxy) benzene, 0.1 mmol of propionic acid, 1mmol of acetonitrile, 0.2 mmol of boron trifluoride diethyl ether and 0.8 ml of 1, 2-dichloroethane as a solvent were charged into a reaction tube, and the mixture was stirred at a rotation speed of 700rpm at 50 ℃ for 12 hours; stopping stirring, adding 5mL of saturated sodium bicarbonate solution, extracting with ethyl acetate for 3 times, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and separating and purifying by column chromatography, wherein the used eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3.

The structural characterization data of the obtained target product are as follows:

¹ H NMR(400MHz,DMSO-d ₆ )δ＝9.46(s,1H),7.47-7.42(m 3H),7.37-7.35(m,2H),6.90(d,J＝2.0Hz,1H),6.61-6.59(m,1H),6.29(d,J＝8.4Hz,1H),5.62(q,J＝6.3Hz,1H),1.94(s,3H),1.42(d,J＝6.4Hz,3H)；

¹³ C NMR(100MHz,DMSO-d ₆ )δ＝167.5,163.1,137.8,134.1,131.7,129.5,129.4,129.3,127.4,123.9,123.6,120.6,110.8,83.7,23.4,19.0；

IR(KBr)ν _max 2924,2832,1599,1363,1070,770cm ^-1 ；

HRMS(ESI)Calcd for C ₁₈ H ₁₇ ClNO ₂ [M-H] ^- :312.0797,found 312.0797。

the structure of the target product is deduced from the above data as follows:

the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A preparation method of 3-enamide substituted benzodihydrofuran compounds is characterized by comprising the following steps:

stirring and reacting 1, 6-eneyne compounds connected with phenol, alkyl nitrile, lewis acid, protonic acid and a solvent at the temperature of 30-80 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the 3-enamide substituted benzodihydrofuran compounds.

2. The method of claim 1, wherein the chemical reaction equation is as follows:

wherein R is ¹ Is at least one of hydrogen, 4-methyl, 4-chlorine, 4-bromine, 4-fluorine, 4-tertiary butyl, 4-methyl formate, 4-trifluoromethyl, 4-cyano, 3-methyl, 3-fluorine, 3-chlorine and 3-bromine;

R ² is at least one of hydrogen, 4-chlorine, 4-fluorine, 4-bromine, 4-trifluoromethyl and 5-chlorine;

R ³ is methyl.

3. The method of claim 1, wherein the phenol-linked 1, 6-enyne compound is 1- (phenylethynyl) -2- (ethyleneoxy) benzene; the alkyl nitrile is acetonitrile.

4. The preparation method according to claim 1 or 2, characterized in that the lewis acid is one or more of boron trifluoride diethyl etherate, boron trichloride, stannic chloride and aluminum trichloride;

the molar ratio of the Lewis acid to the phenol-linked 1, 6-eneyne compound is 1.0-3.0.

5. The synthesis process according to claim 1 or 2, characterized in that the molar ratio of the alkylnitrile to the phenol-linked 1, 6-enyne compound is from 5.0 to 10.0.

6. The synthesis method according to claim 1 or 2, wherein the protonic acid is one or more of acetic acid, propionic acid, trifluoroacetic acid, trimethylacetic acid, benzoic acid and p-toluenesulfonic acid;

the mol ratio of the protonic acid to the 1, 6-eneyne compound connected with the phenol is 1.0-2.5.

7. The production method according to claim 1 or 2, wherein the solvent is one or more of dichloromethane, 1, 2-dichloroethane, and tetrahydrofuran; the volume mol ratio of the solvent to the phenol-linked 1, 6-eneyne compound is 5-15mL:1mmoL.

8. The production method according to claim 1 or 2, wherein the stirring reaction time is 6 to 18 hours.

9. The method according to claim 1 or 2, characterized in that the separation and purification operation is: extracting the reaction liquid with ethyl acetate, combining organic phases, drying with anhydrous magnesium sulfate, filtering, decompressing, steaming and removing the organic solvent to obtain a crude product, and purifying by column chromatography to obtain the 3-enamide substituted benzodihydrofuran compound.

10. A 3-enamide-substituted chroman compound, which is obtained by the production method according to any one of claims 1 to 9, and the structural formula of the 3-enamide-substituted chroman compound is:

wherein R is ¹ Is at least one of hydrogen, 4-methyl, 4-chlorine, 4-bromine, 4-fluorine, 4-tertiary butyl, 4-methyl formate, 4-trifluoromethyl, 4-cyano, 3-methyl, 3-fluorine, 3-chlorine and 3-bromine;

R ² is at least one of hydrogen, 4-chlorine, 4-fluorine, 4-bromine, 4-trifluoromethyl and 5-chlorine;

R ³ is methyl.

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