Method for synthesizing rutaecarpin and derivatives thereof through two-step tandem hydrogen borrowing reaction

Abstract

The rutaecarpin and the derivative thereof are synthesized by using a hydrogen borrowing reaction strategy. In an experiment, ethylene glycol is used as a solvent and an alkylating reagent, and the ethylene glycol and a substrate are subjected to a heating reaction in the presence of an iridium-based catalyst under an alkaline condition to prepare a target product. In the reaction process, two hydroxyl groups in the ethylene glycol are respectively and successively converted into formyl groups, and then a nucleophilic addition reaction of aldehyde is carried out; and the alkylation reaction is completed through the steps of dehydration, reduction and the like. In the whole reaction process, hydrogen and other reducing agents do not need to be additionally added, and only water serves as a byproduct. Therefore, from the perspective of synthetic chemistry and environmental protection, the hydrogen borrowing reaction method has the characteristics of high efficiency and greenness, and has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry, and in particular relates to a two-step tandem hydrogen-based method for synthesizing evodiamine and its derivatives. Background Technology

[0002] Quinazolinones are important nitrogen-containing heterocyclic compounds with a molecular skeleton that is a preferred structure for pharmaceuticals, widely found in natural products and synthetic drug molecules. Indoles and their derivatives possess a wide range of biological activities, including as plant growth regulators, neurotransmitter precursors, microbial signaling molecules, and anti-inflammatory and antitumor drug components. They also play key roles in gut microbiota metabolism, immune regulation, and immunotoxicity. The evodiamine prepared in this invention is a compound containing both quinazolinone and indole substructures, exhibiting various biological activities such as anticancer, anti-inflammatory, and anti-obesity activity. Furthermore, due to the large conjugated system formed by the pentacyclic structure of the evodiamine molecule, this type of molecule possesses strong fluorescence properties and can be used to prepare fluorescent molecular probes. Evodiamine was initially extracted from plants such as Evodia rutaecarpa. In recent years, various methods for the chemical synthesis of evodiamine and its derivatives have been proposed. However, these methods often suffer from drawbacks such as long reaction times, high reaction temperatures, cumbersome reaction steps, or simple derivative structures. Therefore, the development of green and simple synthetic methods is a major challenge currently facing the field of chemistry. This invention utilizes a hydrogen-borrowing reaction strategy to synthesize evodiamine and its derivatives. In the reaction process, ethylene glycol is used as the alkylating agent, where its two hydroxyl groups are sequentially converted to formyl groups, followed by a nucleophilic addition reaction of the aldehyde. The alkylation reaction is then completed through dehydration and reduction steps. No additional reducing agents such as hydrogen are required throughout the entire reaction process, and water is the only byproduct. Therefore, this hydrogen-borrowing reaction method is highly efficient and environmentally friendly, with broad application prospects. Summary of the Invention

[0003] The purpose of this invention is to provide a two-step tandem hydrogen-borrowing reaction method for synthesizing evodiamine and its derivatives. The main synthetic steps of evodiamine are as follows: 2-aminobenzamide reacts with 1H-indole-2-carboxaldehyde under p-toluenesulfonic acid catalysis. The resulting intermediate then undergoes oxidation with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to generate the key intermediate 2-(1H-indole-2-yl)quinazolin-4(3H)-one. This intermediate further undergoes a two-step tandem hydrogen-borrowing reaction with ethylene glycol under an iridium catalyst to cyclize and obtain the target compound. The synthetic route is attached. Figure 1 As shown. R1 and R2 are substituents such as F, Cl, Br, methyl, and methoxy.

[0004] Advantages of this invention:

[0005] 1. The raw materials used are readily available and the synthesis route is simple.

[0006] 2. Using ethylene glycol as the alkylating agent, the only byproduct is water, which is green and has high atom economy. Attached Figure Description

[0007] Figure 1 Schematic diagram for the preparation of evodiamine and its derivatives.

[0008] Figure 2 Hydrogen borrowing reaction using ethylene glycol as an alkylating agent Detailed Implementation

[0009] Any feature disclosed in this specification (including any appended claims and abstract) may be replaced by other equivalent or similar features, unless specifically stated otherwise. That is, unless specifically stated otherwise, each feature is merely one example of a series of equivalent or similar features.

[0010] In the following embodiments, 1 The internal standard for H NMR testing was tetramethylsilane (TMS).

[0011] Example 1: Synthesis of compound 2a

[0012] The reaction steps are as follows:

[0013]

[0014] In a 100 mL round-bottom flask, 2-aminobenzamide (0.2723 g, 2 mmol), 1H-indole-2-carboxaldehyde (0.4354 g, 3 mmol), anhydrous magnesium sulfate (0.7944 g, 6.6 mmol), p-toluenesulfonic acid monohydrate (0.114 g, 0.6 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ, 0.5448 g, 2.4 mmol) was added under ice-water bath conditions. The reaction was continued for 0.5 h, followed by another 4 h at room temperature. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.4589 g of yellowish-brown powder as compound 1a (yield 87%).

[0015] Compound 1a (0.1044 g, 0.4 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer ([Cp*IrCl2]2, 0.0318 g, 0.04 mmol), potassium phosphate (0.1697 g, 0.8 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask, and the mixture was reacted at 160 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried, and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane (V... 石油醚 :V 二氯甲烷 =1:3), yielding 0.0941 g of pale yellow powder, which was compound 2a (yield 82%). 1 H NMR(500 MHz, DMSO) δ 11.87 (s, 1H), 8.16 (d, J = 5 Hz, 1H), 7.81 (t, J = 7.5 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.48 (d, J = 2.5 Hz,2H), 7.26 (t, J = 9.2 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.44 (d, J = 5 Hz,2H), 3.17 (t, J = 5 Hz, 2H).

[0016] Example 2: Synthesis of compound 2b

[0017] The reaction steps are as follows:

[0018]

[0019] In a 100 mL round-bottom flask, 2-amino-3-fluorobenzamide (0.2310 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇= 200:1), yielding 0.2032 g of brown powder as compound 1b (yield 48%).

[0020] Compound 1b (0.0976 g, 0.35 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer (0.0278 g, 0.035 mmol), potassium acetate (0.0687 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 170 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0772 g of pale yellow powder, which was compound 2b (yield 72%). 1 H NMR (500MHz, DMSO) δ 11.81 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.70 – 7.64 (m, 2H), 7.52 (d, J = 4.2 Hz, 1H), 7.47 – 7.42 (m, 1H), 7.28 (t, J = 7.7 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 4.45 (t, J = 6.7 Hz, 2H), 3.19 (t, J = 7.0 Hz, 2H).

[0021] Example 3: Synthesis of compound 2c

[0022] The reaction steps are as follows:

[0023]

[0024] In a 100 mL round-bottom flask, 2-amino-4-fluorobenzamide (0.2310 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇= 200:1), yielding 0.2813 g of light yellow powder, which was compound 1c (yield 67%).

[0025] Compound 1c (0.0976 g, 0.35 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer (0.0278 g, 0.035 mmol), potassium carbonate (0.0967 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 170 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0520 g of white powder as compound 2c (yield 49%). 1 H NMR (500 MHz, DMSO) δ 11.92 (s, 1H), 8.22 (t, J = 7.5 Hz, 1H), 7.66 (d, J = 4.0 Hz, 1H), 7.48 (d, J = 4.2 Hz, 1H), 7.37 – 7.32 (m, 2H), 7.28 (t, J = 7.2 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 4.44 (t, J = 6.7 Hz, 2H), 3.18 (t, J = 6.7 Hz, 2H).

[0026] Example 4: Synthesis of compound 2d

[0027] The reaction steps are as follows:

[0028]

[0029] In a 100 mL round-bottom flask, 2-amino-5-fluorobenzamide (0.2310 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued for 0.5 h, followed by another 4 h at room temperature. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V甲醇 = 200:1), yielding 0.2813 g of yellowish-brown powder as compound 1d (yield 67%).

[0030] Compound 1d (0.0976 g, 0.35 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer (0.0278 g, 0.035 mmol), sodium carbonate (0.0742 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0773 g of pale yellow powder as compound 2d (yield 73%). 1 H NMR (500MHz, DMSO) δ 11.87 (s, 1H), 7.82 (d, J = 4.5 Hz, 1H), 7.74 – 7.68 (m, 2H), 7.64 (d, J = 4.0 Hz, 1H), 7.47 (d, J = 4.2 Hz, 1H), 7.26 (t, J = 7.7 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.44 (t, J = 7.0 Hz, 2H), 3.17 (t, J = 7.0 Hz, 2H).

[0031] Example 5: Synthesis of compound 2e

[0032] The reaction steps are as follows:

[0033]

[0034] In a 100 mL round-bottom flask, 2-amino-6-fluorobenzamide (0.2310 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued for 0.5 h, followed by another 4 h at room temperature. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents.二氯甲烷 :V 甲醇 = 200:1), yielding 0.2878 g of yellow powder as compound 1e (yield 68%).

[0035] Compound 1e (0.0976 g, 0.35 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer (0.0278 g, 0.035 mmol), sodium bicarbonate (0.0588 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 20 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0593 g of pale yellow powder, which was compound 2e (yield 56%). 1 H NMR (500MHz, DMSO) δ 11.89 (s, 1H), 7.77 (m, 1H), 7.65 (d, J = 4.0 Hz, 1H), 7.48 (d,J = 4.2 Hz, 2H), 7.27 (t, J = 7.7 Hz, 1H), 7.21 (t, J = 9.7 Hz, 1H), 7.09 (t,J = 7.5 Hz, 1H), 4.39 (t, J = 7.0 Hz, 2H), 3.17 (t, J = 7.0 Hz, 2H).

[0036] Example 6: Synthesis of compound 2f

[0037] The reaction steps are as follows:

[0038]

[0039] In a 100 mL round-bottom flask, 2-amino-4-chlorobenzamide (0.2550 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents.二氯甲烷 :V 甲醇 = 200:1), yielding 0.2836 g of yellowish-brown powder as compound 1f (yield 64%).

[0040] Compound 1f (0.0118 g, 0.4 mmol), dichloro(pentamethylcyclopentadienyl)iridium dimer (0.0318 g, 0.04 mmol), sodium hydroxide (0.032 g, 0.8 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 20 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0791 g of pale yellow powder as compound 2f (yield 62%). 1 H NMR (500MHz, DMSO) δ 11.88 (s, 1H), 8.14 (d, J = 4.2 Hz, 1H), 7.68 – 7.60 (m, 2H), 7.49 (d, J = 4.0 Hz, 2H), 7.28 (t, J = 7.7 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.43 (t, J = 7.0 Hz, 2H), 3.18 (t, J = 6.7 Hz, 2H).

[0041] Example 7: Synthesis of 2g of compound

[0042] The reaction steps are as follows:

[0043]

[0044] In a 100 mL round-bottom flask, 2-amino-5-chlorobenzamide (0.2550 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V甲醇 = 200:1), yielding 0.2751 g of yellow powder, which was 1 g of compound (yield 62%).

[0045] 1 g (0.1032 g, 0.35 mmol) of compound, 0.0278 g (0.035 mmol) of dichloro(pentamethylcyclopentadienyl)iridium dimer, 0.0701 g (0.7 mmol) of potassium bicarbonate, and 2.5 mL of ethylene glycol were added sequentially to a sealed reaction flask. The mixture was then reacted at 170 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0722 g of pale yellow powder, which was 2 g of compound (yield 64%). 1 H NMR (500MHz, DMSO) δ 11.89 (s, 1H), 8.07 (s, 1H), 7.82 (d, J = 4.2 Hz, 1H), 7.66 (d,J =8.5 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), , 7.48 (d, J = 4.2 Hz, 1H), 7.27 (t,J = 7.5 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.44 (t, J = 7.0 Hz, 2H), 3.18 (t,J = 7.0 Hz, 2H).

[0046] Example 8: Synthesis of compound 2h

[0047] The reaction steps are as follows:

[0048]

[0049] In a 100 mL round-bottom flask, 2-amino-3-methylbenzamide (0.1501 g, 1 mmol), 1H-indole-2-carboxaldehyde (0.2177 g, 1.5 mmol), anhydrous magnesium sulfate (0.3972 g, 3.3 mmol), p-toluenesulfonic acid monohydrate (0.057 g, 0.3 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.2724 g, 1.2 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.216 g of brown powder as compound 1h (yield 84%).

[0050] Compound 1h (0.0907 g, 0.33 mmol), carbonyl di(triphenylphosphine)iridium chloride (IrCl(CO)(PPh3)2, 0.0257 g, 0.033 mmol), sodium phosphate (0.1082 g, 0.66 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0690 g of light brown powder as compound 2h (yield 68%). 1 H NMR(500 MHz, DMSO) δ 11.67 (s, 1H), 7.99 (d, J = 4.0 Hz, 1H), 7.66 (d, J = 4.0Hz, 2H), 7.54 (d, J = 4.0 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.28 (t, J = 7.7Hz, 1H), 7.10 (t, J = 7.2 Hz, 1H), 4.44 (t, J = 7.0 Hz, 2H), 3.18 (t, J = 7.0Hz, 2H), 2.68 (s, 3H).

[0051] Example 9: Synthesis of Compound 2i

[0052] The reaction steps are as follows:

[0053]

[0054] In a 100 mL round-bottom flask, 2-amino-4-methylbenzamide (0.2251 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.335 g of light yellow powder as compound 1i (yield 80%).

[0055] Compound 1i (0.0962 g, 0.35 mmol), carbonyl bis(triphenylphosphine)iridium chloride (0.0273 g, 0.035 mmol), dipotassium hydrogen phosphate (0.1219 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 170 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0784 g of pale yellow powder, which was compound 2i (yield 74%). 1 H NMR (500 MHz, DMSO)δ 11.84 (s, 1H), 8.05 (d, J = 4.2 Hz, 1H), 7.65 (d, J = 4.0 Hz, 1H), 7.51 –7.46 (m, 2H), 7.30 – 7.25 (m, 2H), 7.09 (t, J = 7.2 Hz, 1H), 4.43 (t, J = 6.7Hz, 2H), 3.17 (t, J = 6.7 Hz, 2H), 2.48 (s, 3H).

[0056] Example 10: Synthesis of Compound 2j

[0057] The reaction steps are as follows:

[0058]

[0059] In a 100 mL round-bottom flask, 2-amino-5-methylbenzamide (0.2251 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued for 0.5 h, followed by another 4 h at room temperature. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.295 g of light yellow powder as compound 1j (yield 71%).

[0060] Compound 1j (0.0962 g, 0.35 mmol), carbonyl bis(triphenylphosphine)iridium chloride (0.0273 g, 0.035 mmol), lithium phosphate (0.0811 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.076 g of pale yellow powder, which was compound 2j (yield 72%). 1 H NMR (500 MHz, DMSO) δ11.84 (s, 1H), 7.96 (s, 1H), 7.67 – 7.61 (m, 2H), 7.59 (d, J = 4.0 Hz, 1H), 7.48 (d, J = 4.0 Hz, 1H), 7.26 (t, J = 7.5 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.44 (t, J = 7.0 Hz, 2H), 3.16 (t, J = 6.7 Hz, 2H), 2.45 (s, 3H).

[0061] Example 11: Synthesis of compound 2k

[0062] The reaction steps are as follows:

[0063]

[0064] In a 100 mL round-bottom flask, 2-amino-5-methoxybenzamide (0.2491 g, 1.5 mmol), 1H-indole-2-carboxaldehyde (0.3266 g, 2.25 mmol), anhydrous magnesium sulfate (0.5958 g, 4.95 mmol), p-toluenesulfonic acid monohydrate (0.0855 g, 0.45 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.4086 g, 1.8 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.3510 g of brown powder as compound 1k (yield 80%).

[0065] Compound 1k (0.1047 g, 0.36 mmol), carbonyl bis(triphenylphosphine)iridium chloride (0.0281 g, 0.036 mmol), sodium acetate (0.0590 g, 0.72 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0554 g of white powder as compound 2k (yield 49%). 1 H NMR (500 MHz, DMSO) δ11.83 (s, 1H), 7.64 (d, J = 4.5 Hz, 2H), 7.56 (s, 1H), 7.45 (d, J = 8.7 Hz,1H), 7.43 (t, J = 8.7 Hz, 1H), 7.25 (t, J = 7.5 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 4.46 (t, J = 6.7 Hz, 2H), 3.89 (s, 3H), 3.17 (t, J = 6.7 Hz, 2H).

[0066] Example 12: Synthesis of compound 2l

[0067] The reaction steps are as follows:

[0068]

[0069] In a 100 mL round-bottom flask, 2-aminobenzamide (0.1326 g, 0.975 mmol), 5-methyl-1H-indole-2-carboxaldehyde (0.1034 g, 0.65 mmol), anhydrous magnesium sulfate (0.2581 g, 2.145 mmol), p-toluenesulfonic acid monohydrate (0.037 g, 0.195 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1771 g, 0.78 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.1035 g of white powder as compound 1l (yield 57%).

[0070] Compound 1L (0.0962 g, 0.35 mmol), iridium carbonyl bis(triphenylphosphine)chloride (0.0273 g, 0.035 mmol), lithium acetate (0.0462 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0906 g of white powder as compound 2l (yield 83%). 1 H NMR (500 MHz, DMSO) δ11.76 (s, 1H), 8.16 (d, J = 4.2 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.67 (d, J= 4.0 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.41 (s, 1H), 7.37 (d, J = 4.2 Hz,1H), 7.10 (d, J = 4.2 Hz, 1H), 4.44 (t, J = 6.7 Hz, 2H), 3.14 (t, J = 7.0 Hz,2H), 2.39 (s, 3H).

[0071] Example 13: Synthesis of compound 2m

[0072] The reaction steps are as follows:

[0073]

[0074] In a 100 mL round-bottom flask, 2-aminobenzamide (0.0816 g, 0.6 mmol), 4-methoxy-1H-indole-2-carboxaldehyde (0.1702 g, 0.9 mmol), anhydrous magnesium sulfate (0.2383 g, 1.98 mmol), p-toluenesulfonic acid monohydrate (0.0342 g, 0.18 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1634 g, 0.72 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.1633 g of light yellow powder as compound 1m (yield 91%).

[0075] Compound 1M (0.1047 g, 0.36 mmol), iridium carbonyl bis(triphenylphosphine)chloride (0.0281 g, 0.036 mmol), ammonium phosphate (0.1073 g, 0.72 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 170 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried, and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0893 g of white powder as compound 2m (yield 78%). 1H NMR (500 MHz, DMSO) δ11.86 (s, 1H), 8.15 (d, J = 4.0 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.67 (d, J= 4.2 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 8.0 Hz, 1H), 7.05 (d, J= 4.0 Hz, 1H), 6.53 (d, J = 4.0 Hz, 1H), 4.41 (t, J = 6.7 Hz, 2H), 3.88 (s,3H), 3.30 (t, J = 6.7 Hz, 2H).

[0076] Example 14: Synthesis of compound 2n

[0077] The reaction steps are as follows:

[0078]

[0079] In a 100 mL round-bottom flask, 2-amino-5-methylbenzamide (0.0924 g, 0.6 mmol), 5-methyl-1H-indole-2-carboxaldehyde (0.1432 g, 0.9 mmol), anhydrous magnesium sulfate (0.2383 g, 1.98 mmol), p-toluenesulfonic acid monohydrate (0.0342 g, 0.18 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1634 g, 0.72 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.1534 g of grayish-white powder as compound 1n (yield 88%).

[0080] Compound 1n (0.1011 g, 0.35 mmol), (1,5-cyclooctadienyl)iridium chloride dimer ([Ir(COD)Cl]2, 0.0253 g, 0.035 mmol), potassium phosphate (0.1485 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 160 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents.石油醚 :V 二氯甲烷 =1:3), yielding 0.0616 g of white powder as compound 2n (yield 56%). 1 H NMR(500 MHz, DMSO) δ 11.72 (s, 1H), 7.95 (s, 1H), 7.63 (d, J = 4.2 Hz, 1H), 7.58(d, J = 4.2 Hz, 1H), 7.41 (s, 1H), 7.36 (d, J = 4.0 Hz, 1H), 7.09 (d, J = 4.2Hz, 1H), 4.43 (t, J = 6.7 Hz, 2H), 3.13 (t, J = 7.0 Hz, 2H), 2.45 (s, 3H), 2.39 (s, 3H).

[0081] Example 15: Synthesis of Compound 2o

[0082] The reaction steps are as follows:

[0083]

[0084] In a 100 mL round-bottom flask, 2-amino-5-methoxybenzamide (0.0830 g, 0.5 mmol), 5-methyl-1H-indole-2-carboxaldehyde (0.1193 g, 0.75 mmol), anhydrous magnesium sulfate (0.1986 g, 1.65 mmol), p-toluenesulfonic acid monohydrate (0.0285 g, 0.15 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1362 g, 0.6 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.1324 g of grayish-white powder as compound 1o (yield 86%).

[0085] Compound 1O (0.1011 g, 0.35 mmol), (1,5-cyclooctadienyl)iridium chloride dimer (0.0235 g, 0.035 mmol), sodium carbonate (0.0742 g, 0.7 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0835 g of pale yellow powder as compound 2o (yield 72%). 1 H NMR (500MHz, DMSO) δ 11.69 (s, 1H), 7.62 (d, J = 4.2 Hz, 1H), 7.54 (s, 1H), 7.42 –7.34 (m, 3H), 7.07 (d, J = 4.2 Hz, 1H), 4.43 (t, J = 6.7 Hz, 2H), 3.88 (s,3H), 3.12 (t, J = 6.7 Hz, 2H), 2.38 (s, 3H).

[0086] Example 16: Synthesis of compound 2p

[0087] The reaction steps are as follows:

[0088]

[0089] In a 100 mL round-bottom flask, 2-aminobenzamide (0.0816 g, 0.6 mmol), 5-methoxy-1H-indole-2-carboxaldehyde (0.1702 g, 0.9 mmol), anhydrous magnesium sulfate (0.2383 g, 1.98 mmol), p-toluenesulfonic acid monohydrate (0.0342 g, 0.18 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1634 g, 0.72 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇 = 200:1), yielding 0.1093 g of white powder as compound 1p (yield 62%).

[0090] Compound 1p (0.1047 g, 0.36 mmol), (1,5-cyclooctadienyl)iridium chloride dimer (0.0235 g, 0.036 mmol), potassium carbonate (0.0995 g, 0.72 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0405 g of pale yellow powder as compound 2p (yield 35%). 1 H NMR (500MHz, DMSO) δ 11.72 (s, 1H), 8.16 (d, J = 3.7 Hz, 1H), 7.81 (t, J = 7.7 Hz, 1H), 7.67 (d, J = 4.2 Hz, 1H), 7.47 (t, J = 8.2 Hz, 1H), 7.37 (d, J = 4.5 Hz, 1H), 7.12 (s, 1H), 6.92 (d, J = 4.2 Hz, 1H), 4.45 (t, J = 7.0 Hz, 2H), 3.79 (s, 3H), 3.15 (t, J = 7.0 Hz, 2H).

[0091] Example 17: Synthesis of compound 2q

[0092] The reaction steps are as follows:

[0093]

[0094] In a 100 mL round-bottom flask, 2-aminobenzamide (0.1361 g, 1.0 mmol), 5-chloro-1H-indole-2-carboxaldehyde (0.2694 g, 1.5 mmol), anhydrous magnesium sulfate (0.3972 g, 3.3 mmol), p-toluenesulfonic acid monohydrate (0.057 g, 0.3 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.2724 g, 1.2 mmol) was added under ice-water bath conditions. The reaction was continued for 0.5 h, followed by another 4 h at room temperature. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇= 200:1), yielding 0.1416 g of orange-red powder as compound 1q (yield 48%).

[0095] Compound 1q (0.0885 g, 0.3 mmol), (1,5-cyclooctadienyl)iridium chloride dimer (0.0208 g, 0.03 mmol), potassium acetate (0.0589 g, 0.6 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0418 g of brown powder as compound 2q (yield 43%). 1 H NMR (500 MHz, DMSO) δ12.08 (s, 1H), 8.17 (d, J = 3.7 Hz, 1H), 7.82 (t, J = 7.7 Hz, 1H), 7.75 (s,1H), 7.69 (d, J = 4.0 Hz, 1H), 7.48 (t, J = 9.0 Hz, 2H), 7.26 (d, J = 4.5 Hz, 1H), 4.45 (t, J = 6.7 Hz, 2H), 3.17 (t, J = 7.2 Hz, 2H).

[0096] Example 18: Synthesis of compound 2r

[0097] The reaction steps are as follows:

[0098]

[0099] In a 100 mL round-bottom flask, 2-amino-4-methylbenzamide (0.09 g, 0.6 mmol), 6-chloro-1H-indole-2-carboxaldehyde (0.1616 g, 0.9 mmol), anhydrous magnesium sulfate (0.2383 g, 1.98 mmol), p-toluenesulfonic acid monohydrate (0.0342 g, 0.18 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.1634 g, 0.72 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇= 200:1), yielding 0.124 g of light gray powder as compound 1r (yield 66%).

[0100] Compound 1r (0.0927 g, 0.3 mmol), (1,5-cyclooctadienyl)iridium chloride dimer (0.0202 g, 0.03 mmol), potassium hydroxide (0.0336 g, 0.6 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0494 g of pale yellow powder as compound 2r (yield 49%). 1 H NMR (500 MHz, DMSO) δ11.96 (s, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.48 (t, J= 8 Hz, 2H), 7.31 (d, J = 8.9 Hz, 1H), 7.10 (s, 1H), 4.43 (t, J = 6.9 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 2.48 (s, 3H).

[0101] Example 19: Synthesis of compound 2s

[0102] The reaction steps are as follows:

[0103]

[0104] In a 100 mL round-bottom flask, 2-amino-4-trifluoromethylbenzamide (0.2041 g, 1.0 mmol), 1H-indole-2-carboxaldehyde (0.2177 g, 1.5 mmol), anhydrous magnesium sulfate (0.3977 g, 3.3 mmol), p-toluenesulfonic acid monohydrate (0.057 g, 0.3 mmol), and tetrahydrofuran (20 mL) were added sequentially. The mixture was reacted at room temperature for 4 h under nitrogen protection. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (0.2724 g, 1.2 mmol) was added under ice-water bath conditions. The reaction was continued at room temperature for 4 h after 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane and methanol as eluents. 二氯甲烷 :V 甲醇= 200:1), yielding 0.1970 g of pale yellow powder as compound 1s (yield 59%).

[0105] Compound 1S (0.0987 g, 0.3 mmol), (1,5-cyclooctadienyl)iridium chloride dimer (0.0202 g, 0.03 mmol), cesium carbonate (0.1955 g, 0.6 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask. The mixture was then reacted at 180 °C under vacuum for 30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents. 石油醚 :V 二氯甲烷 =1:3), yielding 0.0844 g of pale yellow powder as compound 2s (yield 79%). 1 H NMR (500 MHz, DMSO)δ 11.87 (s, 1H), 8.33 (d, J = 4.2 Hz, 1H), 7.86 (s, 1H), 7.74 (d, J = 4.0 Hz, 1H), 7.66 (d, J = 4.0 Hz, 1H), 7.50 (d, J = 4.0 Hz, 1H), 7.29 (t, J = 7.7 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 4.46 (t, J = 7.0 Hz, 2H), 3.20 (t, J = 6.7 Hz, 2H).

[0106] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A method for synthesizing evodiamine and its derivative (II) by heating a reaction of compound (I) and ethylene glycol under iridium-based catalyst and alkaline conditions. Its characteristics are, The specific steps are as follows: Compound I (0.4 mmol), iridium-based catalyst (0.04 mmol), base (0.8 mmol), and ethylene glycol (2.5 mL) were added sequentially to a sealed reaction flask, and the mixture was reacted at 160-180 °C for 20-30 h. After the reaction was complete, the reaction solution was extracted with water and dichloromethane. The organic phase was dried and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether and dichloromethane as eluents to obtain the target product II. In target product II, R 1 or R 2 The following are the compounds: H, methoxy, ethoxy, methyl, ethyl, phenyl, benzyl, nitro, fluorine, chlorine, bromine, trifluoromethyl, and difluoromethyl.

2. The method according to claim 1, characterized in that, The characteristic of target product II is R 1 Or R 2 Preferably, it contains H, methoxy, ethoxy, methyl, ethyl, fluorine, chlorine, and trifluoromethyl.

3. The method according to claim 1, characterized in that, The characteristic of target product II is R 1 Preferably, H, methoxy, methyl, fluorine, chlorine, and trifluoromethyl; R 2 Preferably, it contains H, methoxy, methyl, and chlorine.

4. The method according to claim 1, characterized in that, The preferred iridium-based catalysts are dichloro(pentamethylcyclopentadienyl)iridium dimer, carbonyl di(triphenylphosphine)iridium chloride, and (1,5-cyclooctadienyl)iridium chloride dimer.

5. The method according to claim 1, characterized in that, The preferred alkalis are sodium acetate, potassium acetate, sodium carbonate, potassium carbonate, cesium carbonate, lithium phosphate, sodium phosphate, potassium phosphate, ammonium phosphate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, and potassium hydroxide.

6. The method according to claim 1, characterized in that, The preferred alkalis are sodium acetate, potassium acetate, sodium carbonate, potassium carbonate, sodium phosphate, potassium phosphate, and ammonium phosphate.

7. The method according to claim 1, characterized in that, The preferred reaction conditions are vacuum reaction at 160-180 ℃.

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