CN113234083B - Tetrahydroquinoline pyran compound and preparation method and application thereof - Google Patents

Tetrahydroquinoline pyran compound and preparation method and application thereof Download PDF

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CN113234083B
CN113234083B CN202110408933.4A CN202110408933A CN113234083B CN 113234083 B CN113234083 B CN 113234083B CN 202110408933 A CN202110408933 A CN 202110408933A CN 113234083 B CN113234083 B CN 113234083B
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tetrahydroquinoline
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benzopyran
cyclohexanedione
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张珉
龚玲珍
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South China University of Technology SCUT
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Abstract

The invention provides a tetrahydroquinoline benzopyran compound and a preparation method and application thereof. The tetrahydroquinoline benzopyran compound has the characteristics of cheap and easily obtained preparation raw materials, wide applicability, high atom economy and high diastereoselectivity, and has better industrial application prospect. The method for preparing the tetrahydroquinoline pyran compounds utilizes iridium-catalyzed hydrogen transfer cyclization reaction of azaarene salt, paraformaldehyde and 1, 3-cyclohexanedione compounds, wherein the reacted paraformaldehyde is a hydrogen source and a coupling reagent, and the tetrahydroquinoline pyran compounds can be synthesized by a one-step method. In addition, different types of tetrahydroquinoline benzopyran compounds can be synthesized according to different structures of the azaarene salt and the 1, 3-cyclohexanedione compound. The method does not need to use an additional hydrogen source, has simple post-treatment, directly constructs a target product through one-step multicomponent reaction, and is suitable for expanded industrial production.

Description

Tetrahydroquinoline pyran compound and preparation method and application thereof
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a tetrahydroquinoline benzopyran compound, and a preparation method and application thereof.
Background
The nitrogen-oxygen heterocyclic compound is used as a chemical intermediate and widely applied to the fields of organic synthesis, coatings, medicaments, pesticides and the like. Because many drug molecular structures contain the heterocyclic units, the nitrogen-oxygen heterocyclic aromatic compound has very wide application prospect in the field of organic synthesis. With the idea of green and economic sustainable development, higher requirements are put forward for developing new synthetic reactions. The exploration of a green, efficient and easy-to-operate method for constructing the nitrogen-oxygen heterocyclic compound has become one of the most concerned fields of scientific researchers.
In recent decades, the use of pyridinium salts in organic synthesis has been implicated in a wide range of applications, such as the preparation of derivatives of pyrrole, fused heterocycles, spiropyrroles, furans and cyclopropanes, as well as various spirocycles and fused polyheterocycles. Experiments show that the pyridinium compounds have unique chemical and physical properties, such as aromaticity, alkalinity, electrophilic effect, and higher electrophilicity/nucleophilicity compared with the parent heterocyclic ring which is not activated. Therefore, the method is widely applied to the construction of various polycyclic synthesis reaction systems, and has important application value in a plurality of fields such as organic synthesis, catalytic chemistry, biology, material science and the like.
However, in the related art, when constructing these nitrogen-oxygen heterocyclic compounds, harsh reaction conditions are usually required, such as complicated reaction steps, additional additives, etc., which greatly limits the variety, abundance and synthesis speed of the nitrogen-oxygen heterocyclic compounds.
Disclosure of Invention
The present invention is directed to solving at least one of the above problems in the prior art. Therefore, the invention provides the tetrahydroquinoline benzopyran compound, which has the characteristics of cheap and easily obtained raw materials, wide applicability, high atom economy and high diastereoselectivity and has better industrial application prospect.
The invention also provides a preparation method of the tetrahydroquinoline benzopyran compound.
The invention also provides application of the tetrahydroquinoline benzopyran compound.
The invention provides tetrahydroquinoline benzopyran compounds in a first aspect, which have the following structures:
Figure BDA0003023381430000021
wherein R is1Selected from hydrogen, furan or a benzene ring;
R2selected from alkyl, substituted or unsubstituted benzene ring;
r is selected from alpha, beta-unsaturated carbonyl;
x is selected from nitrogen atom or carbon atom.
The tetrahydroquinoline pyran compound has at least the following beneficial effects:
the tetrahydroquinoline benzopyran compound has the characteristics of cheap and easily obtained preparation raw materials, wide applicability, high atom economy and high diastereoselectivity, and has better industrial application prospect.
According to some embodiments of the invention, R is selected from α, β -unsaturated carbonyl.
According to some embodiments of the invention, the tetrahydroquinopyran compound has the structure according to formula (I):
Figure BDA0003023381430000022
wherein R is3Selected from the group consisting of hydrogen, mono-or poly-substituted alkyl, phenyl and furan.
According to some embodiments of the invention, the tetrahydroquinopyran compound has the structure according to formula (II):
Figure BDA0003023381430000031
wherein R is4Selected from hydrogen, halogen, mono-or poly-substituted alkyl or methoxy.
The second aspect of the invention provides a method for preparing the tetrahydroquinoline benzopyran compound, which comprises the following steps: the catalyst, the azaarene salt compound, the 1, 3-cyclohexanedione compound, paraformaldehyde, an additive and a solvent are reacted under a protective atmosphere.
The method for preparing the tetrahydroquinoline benzopyran compound has at least the following beneficial effects:
according to the method for preparing the tetrahydroquinoline benzopyran compound, the iridium-catalyzed hydrogen transfer cyclization reaction of the azaarene salt, the paraformaldehyde and the 1, 3-cyclohexanedione compound is utilized, the paraformaldehyde used for the reaction is a hydrogen source and a coupling reagent, and the tetrahydroquinoline benzopyran compound can be synthesized by a one-step method.
The method for preparing the tetrahydroquinoline benzopyran compound can synthesize different types of tetrahydroquinoline benzopyran compounds according to different structures of the azaarene salt and the 1, 3-cyclohexanedione compound.
The method for preparing the tetrahydroquinoline pyran compound does not need to use an additional hydrogen source, has simple post-treatment, directly constructs a target product through one-step multicomponent reaction, and is suitable for expanded industrial production.
The method for preparing the tetrahydroquinoline benzopyran compound is a green synthesis method, does not need to perform pre-functionalization on a substrate, is time-saving and labor-saving, has good step economy and atom economy, and is a very good supplement for the synthesis development of nitrogen-oxygen heterocyclic compounds.
According to some embodiments of the invention, the method further comprises cooling the product, concentrating and purifying.
According to some embodiments of the invention, cooling refers to cooling to room temperature.
According to some embodiments of the invention, the concentration may be a vacuum concentration.
According to some embodiments of the invention, the purification may be column chromatography.
According to some embodiments of the present invention, the eluent used for column chromatography may be (2-10): 1 of petroleum ether and ethyl acetate.
According to some embodiments of the invention, the catalyst comprises dichlorobis (4-methylisopropylphenyl) ruthenium (II) (CAS number 52462-29-0), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (CAS number 12354-84-6), and triruthenium dodecacarbonyl (CAS number 15243-33-1).
According to some embodiments of the invention, the catalyst is dichloro (pentamethylcyclopentadienyl) iridium (III) dimer.
According to some embodiments of the invention, the azaarene salt compound is a compound having a structure as shown in formula (III):
Figure BDA0003023381430000041
according to some embodiments of the present invention, when the tetrahydroquinopyran compound has the structure of formula (I), the 1, 3-cyclohexanedione compound has the structure of formula (IV):
Figure BDA0003023381430000042
according to some embodiments of the invention, when the tetrahydroquinopyran compound has the structure of formula (I), the reaction formula is:
Figure BDA0003023381430000043
the additive comprises potassium phosphate (K)3PO4) Cesium carbonate (Cs)2CO3) Magnesium methoxide (Mg (OMe)2) Sodium tert-butoxide (t-BuONa) and 1, 5-diazabicyclo [5.4.0]-5-undecene (DBU).
The additive may be sodium tert-butoxide (t-BuONa).
The solvent comprises one of tertiary amyl alcohol, toluene, 1, 4-dioxane, methanol and ethanol.
The solvent may be methanol.
According to some embodiments of the present invention, when the tetrahydroquinopyran compound has the structure of formula (II), the 1, 3-cyclohexanedione compound has the structure of formula (V):
Figure BDA0003023381430000051
according to some embodiments of the invention, when the tetrahydroquinopyran compound has the structure of formula (II), the reaction formula is:
Figure BDA0003023381430000052
the additive comprises potassium phosphate (K)3PO4) Cesium carbonate (C)s2CO3) Magnesium methoxide (Mg (OMe)2) Sodium tert-butoxide (t-BuONa), potassium hydroxide (KOH) and sodium methoxide (NaOMe).
The additive may be potassium hydroxide (KOH).
The solvent comprises one of tertiary amyl alcohol, toluene, 1, 4-dioxane, methanol and ethanol.
The solvent may be 1, 4-dioxane.
According to some embodiments of the invention, the molar ratio of the azaarene salt compound, the 1, 3-cyclohexanedione compound and the paraformaldehyde is 1: (1.0-2.0): (5-12).
According to some embodiments of the invention, the molar ratio of the azaarene salt compound, the 1, 3-cyclohexanedione compound and the paraformaldehyde is 1: 1.5: 10.
according to some embodiments of the invention, the protective atmosphere may be nitrogen.
According to some embodiments of the invention, the protective atmosphere may be argon.
According to some embodiments of the invention, the temperature of the reaction is between 80 ℃ and 90 ℃.
According to some embodiments of the invention, the temperature of the reaction may be 85 ℃.
According to some embodiments of the invention, the reaction time is between 10h and 20 h.
According to some embodiments of the invention, the reaction time may be 16 h.
In a third aspect, the invention provides the application of the tetrahydroquinoline benzopyran compound in preparing a medicament for treating Parkinson's disease.
In a fourth aspect, the invention provides a pharmaceutical composition comprising said tetrahydroquinopyran compound or a pharmaceutically acceptable salt thereof.
Pharmaceutically acceptable salts, including pharmaceutically acceptable salts, esters, hydrates, solvates, crystalline forms, enantiomers, stereoisomers, ethers, metabolites and prodrugs thereof.
Pharmaceutically acceptable salts include, but are not limited to, at least one of inorganic acid salts, organic acid salts, alkylsulfonic acid salts, and arylsulfonic acid salts. Wherein, the inorganic acid salt includes but not limited to at least one of hydrochloride, hydrobromide, nitrate, sulfate and phosphate. The organic acid salt includes, but is not limited to, at least one of formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, and citrate. The alkyl sulfonate includes, but is not limited to, at least one of a methyl sulfonate and an ethyl sulfonate. The aryl sulfonate includes, but is not limited to, at least one of benzene sulfonate and p-toluene sulfonate.
Drawings
FIG. 1 shows the product obtained in example 1 of the present invention1H NMR spectrum.
FIG. 2 is a graph of the product obtained in example 1 of the present invention13C NMR spectrum.
FIG. 3 is a graph of the product obtained in example 2 of the present invention1H NMR spectrum.
FIG. 4 shows the product obtained in example 2 of the present invention13C NMR spectrum.
FIG. 5 shows the product obtained in example 3 of the present invention1H NMR spectrum.
FIG. 6 shows the product obtained in example 3 of the present invention13C NMR spectrum.
FIG. 7 shows the product obtained in example 4 of the present invention1H NMR spectrum.
FIG. 8 shows the product obtained in example 4 of the present invention13C NMR spectrum.
FIG. 9 shows the product obtained in example 5 of the present invention1H NMR spectrum.
FIG. 10 shows the product obtained in example 5 of the present invention13C NMR spectrum.
Detailed Description
The following are specific examples of the present invention, and the technical solutions of the present invention will be further described with reference to the examples, but the present invention is not limited to the examples.
Example 1
The embodiment prepares a tetrahydroquinoline benzopyran compound, and the specific process is as follows:
1 mol% of [ Cp IrCl ] was added to the reaction tube under a nitrogen atmosphere2]2(CAS No. 12354-84-6), 0.2mmol of N-benzyl bromide quinoline salt (CAS No. 26323-01-3), 0.3mmol of 5, 5-dimethyl-1, 3-cyclohexanedione (CAS No. 126-81-8), 2.0mmol of paraformaldehyde (CAS No. 30525-89-4), 0.4mmol of sodium tert-butoxide and 1.5mL of methanol as solvents, and reacting at 85 ℃ for 16 h;
cooling to room temperature, vacuum concentrating, and separating the crude product by column chromatography to obtain compound C1The structure of the compound is verified by organic matter characterization methods such as nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, high resolution mass spectrum and the like.
The structure of the product is as follows:
Figure BDA0003023381430000071
compound characterization data: a yellow solid, m.p. 141.5-142.5 ℃;1H NMR(400MHz,Chloroform-d)δ7.44–7.33(m,4H),7.31–7.27(m,1H),7.04(d,J＝8.0Hz,2H),6.78(d,J＝8.0Hz,1H),6.63(d,J＝8.0Hz,1H),5.18(s,1H),4.83–4.64(m,2H),3.75(d,J＝8.0Hz,1H),3.56(d,J＝8.0Hz,1H),2.82(d,J＝16.0Hz,1H),2.59(d,J＝16.0Hz,1H),2.43(d,J＝20.0Hz,1H),2.38–2.24(m,4H),2.19(d,J＝20.0Hz,1H),1.10(s,3H),1.05(s,3H).13C NMR(101MHz,CDCl3)δ198.58,167.32,141.06,138.59,129.77,128.79,127.26,127.20,126.56,120.84,119.08,112.77,108.25,90.93,66.11,55.02,50.58,41.94,34.20,32.37,29.56,29.50,27.33,26.64.HRMS(ESI):Calcd.for C26H30NO3[M+H]+:404.2220；found:404.2219。
FIG. 1 shows the product obtained in the example of the present invention1H NMR spectrum.
FIG. 2 shows the product obtained in the example of the present invention13C NMR spectrum.
Example 2
The embodiment prepares a tetrahydroquinoline benzopyran compound, and the specific process is as follows:
1 mol% of [ Cp IrCl ] was added to the reaction tube under a nitrogen atmosphere2]20.2mmol of N-benzyl bromide-2-phenyl naphthyridine salt (CAS number is 2414110-24-8), 0.3mmol of 5, 5-dimethyl-1, 3-cyclohexanedione, 2.0mmol of paraformaldehyde, 0.4mmol of sodium tert-butoxide and 1.5mL of methanol as solvents, and reacting for 16h at 85 ℃;
cooling to room temperature, vacuum concentrating, and separating the crude product by column chromatography to obtain compound C2The structure of the compound is verified by organic matter characterization methods such as nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, high resolution mass spectrum and the like.
Figure BDA0003023381430000081
Compound characterization data: a yellow solid, m.p. 165.9-166.9 ℃;1H NMR(500MHz,Chloroform-d)δ7.96(d,J＝10.0Hz,2H),7.43(d,J＝5.0Hz,2H),7.41–7.37(m,2H),7.36–7.29(m,4H),7.28(d,J＝5.0Hz,1H),7.18(d,J＝5.0Hz,1H),5.92(d,J＝15.0Hz,1H),5.11(s,1H),4.45(d,J＝15.0Hz,1H),3.47(d,J＝10.0Hz,1H),3.35(d,J＝10.0Hz,1H),2.73(d,J＝15.0Hz,1H),2.49–2.37(m,2H),2.30–2.18(m,4H),2.15(d,J＝20.0Hz,1H),1.51(s,1H),1.07(s,3H),1.02(s,3H).13C NMR(126MHz,CDCl3)δ198.3,166.8,153.3,151.9,139.6,139.4,138.0,128.7,128.5,128.1,127.4,126.5,114.3,111.3,108.3,88.2,65.9,50.6,49.9,41.8,33.7,32.4,29.5,28.9,27.3,26.3HRMS(ESI):Calcd.for C31H33N2O3[M+H]+:481.2486；found:481.2477。
FIG. 3 shows the product obtained in the example of the present invention1H NMR spectrum.
FIG. 4 shows a product obtained by an example of the present invention13C NMR spectrum.
Example 3
The embodiment prepares a tetrahydroquinoline benzopyran compound, and the specific process is as follows:
1 mol% of [ Cp IrCl ] was added to the reaction tube under a nitrogen atmosphere2]20.2mmol of N-benzyl bromoquinoline salt, 0.3mmol of 5- (2-furyl) -1, 3-cyclohexanedione (CAS number 1774-11-4), 2.0mmol of paraformaldehyde, 0.4mmol of sodium tert-butoxide and 1.5mL of methanol as solvents, and reacting for 16h at 85 ℃;
cooling to room temperature, vacuum concentrating, and separating the crude product by column chromatography to obtain compound C3The structure of the compound is verified by organic matter characterization methods such as nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, high resolution mass spectrum and the like.
Figure BDA0003023381430000091
Compound characterization data: a yellow solid; m.p. 155.3-156.3 ℃;1H NMR(500MHz,Chloroform-d)δ7.38–7.29(m,5H),7.27–7.24(m,1H),7.04–6.97(m,2H),6.79–6.72(m,1H),6.65–6.59(m,1H),6.32–6.28(m,0.6H),6.28–6.25(m,0.4H),6.03(d,J＝5.0Hz,0.6H),6.00(d,J＝5.0Hz,0.4H),5.19(s,0.4H),5.15(s,0.6H),4.76–4.64(m,2H),3.73(d,J＝10.0Hz,0.4H),3.71(d,J＝10.0Hz,0.6H),3.53(d,J＝10.0Hz,0.6H),3.51(d,J＝10.0Hz,0.4H),3.49–3.43(m,0.4H),3.41–3.35(m,0.6H),2.85(d,J＝15.0Hz,0.6H),2.78–2.75(m,0.4H),2.74–2.72(m,0.6H),2.71–2.68(m,0.4H),2.67–2.64(m,1H),2.64–2.57(m,2H),2.57–2.54(m,0.6H),2.54–2.52(m,0.4H),2.49–2.36(m,1H),2.34–2.28(m,1H),2.10(s,1H).13C NMR(126MHz,CDCl3)δ197.0,196.7,167.4,167.1,156.0,141.6,141.5,141.0,140.9,138.6,138.5,129.8,128.8,127.3,127.3,126.6,126.5,120.8,120.7,119.3,119.2,112.8,112.8,110.1,109.5,109.4,104.8,104.5,91.1,66.2,55.0,54.9,41.1,40.8,34.4,34.2,33.1,32.8,32.7,32.5,29.5,29.4,26.9,26.6.HRMS(ESI):Calcd.for C28H28NO4[M+H]+:442.2013；found:442.2005。
FIG. 5 shows a product obtained by an example of the present invention1H NMR spectrum.
FIG. 6 shows a product obtained by an example of the present invention13C NMR spectrum.
Example 4
The embodiment prepares a tetrahydroquinoline benzopyran compound, and the specific process is as follows:
1 mol% of [ Cp IrCl ] was added to the reaction tube under a nitrogen atmosphere2]20.2mmol of N-benzyl bromide quinoline salt, 0.3mmol of 4-hydroxycoumarin (CAS number 1076-38-6), 2.0mmol of paraformaldehyde, 0.2mmol of potassium hydroxide and 1.5mL of 1, 4-dioxane as a solvent, and reacting for 16h at 85 ℃;
cooling to room temperature, vacuum concentrating, and separating the crude product by column chromatography to obtain compound C4The structure of the compound is verified by organic matter characterization methods such as nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, high resolution mass spectrum and the like.
Figure BDA0003023381430000101
Compound characterization data: yellow solid, m.p. 117.1-118.1 ℃;1H NMR(400MHz,Chloroform-d)δ7.66(d,J＝8.0Hz,1H),7.52–7.45(m,3H),7.39(t,J＝8.0Hz,2H),7.34–7.28(m,3H),7.23(t,J＝8.0Hz,1H),7.11–7.02(m,2H),6.80(t,J＝8.0Hz,1H),6.75(d,J＝8.0Hz,1H),5.48(d,J＝1.6Hz,1H),4.94(d,J＝16.0Hz,1H),4.86(d,J＝16.0Hz,1H),3.86(d,J＝8.0Hz,1H),3.65(d,J＝12.0Hz,1H),3.06(d,J＝20.0Hz,1H),2.96(d,J＝16.0Hz,1H),2.59(d,J＝16.0Hz,1H),2.51(d,J＝20.0Hz,1H).13C NMR(126MHz,CDCl3)δ163.4,157.6,152.8,140.7,138.4,131.5,129.9,128.8,127.4,127.4,126.7,123.8,122.8,120.5,119.5,116.6,115.5,112.9,99.40,92.0,65.9,55.0,34.5,29.79,28.5.HRMS(ESI):Calcd.for C27H24NO4[M+H]+:426.1700；found:426.1697。
FIG. 7 shows a product obtained by an example of the present invention1H NMR spectrum.
FIG. 8 shows a product obtained by an example of the present invention13C NMR spectrum.
Example 5
The embodiment prepares a tetrahydroquinoline benzopyran compound, and the specific process is as follows:
under nitrogen atmosphere, 1m of the solution was added to the reaction tubeol% of [ Cp IrCl2]20.2mmol of N-benzyl bromide-2- (2-furyl) naphthyridine salt (CAS number is 2414110-30-6), 0.3mmol of 4-hydroxycoumarin, 2.0mmol of paraformaldehyde, 0.2mmol of potassium hydroxide and 1.5mL of 1, 4-dioxane as a solvent, and reacting for 16h at 85 ℃;
cooling to room temperature, vacuum concentrating, and separating the crude product by column chromatography to obtain compound C4The structure of the compound is verified by organic matter characterization methods such as nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, high resolution mass spectrum and the like.
Figure BDA0003023381430000111
Compound characterization data: a yellow solid, m.p. 129.5-130.5 ℃;1H NMR(500MHz,Chloroform-d)δ7.51–7.43(m,5H),7.36–7.32(m,2H),7.31–7.26(m,3H),7.19–7.13(m,2H),6.96(d,J＝5.0Hz,1H),6.52–6.46(m,1H),5.61(d,J＝15.0Hz,1H),5.44(s,1H),4.89(d,J＝15.0Hz,1H),3.59(d,J＝15.0Hz,1H),3.45(d,J＝10.0Hz,1H),2.95(d,J＝15.0Hz,1H),2.85(d,J＝15.0Hz,1H),2.51(d,J＝20.0Hz,1H),2.45(d,J＝15.0Hz,1H).13C NMR(126MHz,CDCl3)δ163.2,157.3,154.3,152.7,151.6,145.9,142.7,139.5,138.0,131.6,128.8,128.5,127.5,123.8,122.8,116.5,115.3,114.0,111.9,110.0,107.8,99.3,89.3,65.7,50.4,34.0,29.1,28.1.HRMS(ESI):Calcd.for C30H25N2O5[M+H]+:493.1758；found:493.1749。
FIG. 9 shows a product obtained by an example of the present invention1H NMR spectrum.
FIG. 10 shows a product obtained by the example of the present invention13C NMR spectrum.
The tetrahydroquinoline benzopyran compound can be used for preparing medicaments for treating Parkinson diseases.
Example 6
The embodiment provides a pharmaceutical composition, which comprises the tetrahydroquinoline benzopyran compound or the pharmaceutically acceptable salt thereof.
Pharmaceutically acceptable salts, including pharmaceutically acceptable salts, esters, hydrates, solvates, crystalline forms, enantiomers, stereoisomers, ethers, metabolites and prodrugs thereof.
Pharmaceutically acceptable salts include, but are not limited to, at least one of inorganic acid salts, organic acid salts, alkylsulfonic acid salts, and arylsulfonic acid salts. Wherein, the inorganic acid salt includes but not limited to at least one of hydrochloride, hydrobromide, nitrate, sulfate and phosphate. The organic acid salt includes, but is not limited to, at least one of formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, and citrate. The alkylsulfonic acid salt includes, but is not limited to, at least one of a methylsulfonic acid salt and an ethylsulfonic acid salt. The aryl sulfonate includes, but is not limited to, at least one of benzene sulfonate and p-toluene sulfonate.
The present invention has been described in detail with reference to the embodiments, but the present invention is not limited to the embodiments described above, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present invention.

Claims (2)

1. The preparation method of the tetrahydroquinoline pyran compound is characterized by comprising the following steps: reacting a catalyst, a nitrogen heteroaromatic salt compound, a 1, 3-cyclohexanedione compound, paraformaldehyde, an additive and a solvent under a protective atmosphere;
the structure of the tetrahydroquinoline pyran compound is shown as the formula (I) or the formula (II):
Figure FDA0003573592100000011
wherein R is1Selected from hydrogen, furan or a benzene ring;
R2selected from alkyl, substituted or unsubstituted benzene ring;
R3selected from hydrogen, phenyl, furan, mono-or polysubstituted alkyl;
R4selected from hydrogen;
x is selected from nitrogen atom or carbon atom;
the catalyst is dichloro (pentamethylcyclopentadienyl) iridium (III) dimer;
the azaarene salt compound has a structure shown as a formula (III):
Figure FDA0003573592100000012
Figure FDA0003573592100000021
when the structure of the tetrahydroquinoline benzopyran compound is shown as a formula (I), the 1, 3-cyclohexanedione compound has a structure shown as a formula (IV):
Figure FDA0003573592100000022
when the structure of the tetrahydroquinoline benzopyran compound is shown as a formula (II), the 1, 3-cyclohexanedione compound has a structure shown as a formula (V):
Figure FDA0003573592100000023
the additive is potassium phosphate, cesium carbonate, magnesium methoxide, sodium tert-butoxide, potassium hydroxide or sodium methoxide.
2. The method according to claim 1, further comprising cooling the obtained product, and concentrating and purifying the cooled product.
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