Visible light induced 9-acyl acridine derivative and preparation method thereof

Abstract

The preparation method comprises the following steps: under the irradiation of visible light, by taking an acridine derivative and 4-acyl substituted Hanss ester as initial raw materials and benzoic acid and potassium carbonate as acidic and alkaline additives respectively, carrying out a reaction on the acridine derivative and the 4-acyl substituted Hanss ester to obtain the visible-light-induced 9-acyl acridine derivative. 9-acridine full-carbon free radicals and acyl free radicals are generated through a single electron transfer process, then free radical-free radical cross coupling is performed to obtain the 9-acyl acridine derivative, and the 9-acyl acridine derivative contains 9-carbamoyl, aryl formyl and alkyl formyl substitution. The method is green, efficient, mild in reaction condition and wide in substrate range, transition metal and stoichiometric oxidizing agents are prevented from being used, and the method is a novel method for synthesizing the 9-acyl acridine derivative.

Description

Technical Field

[0001] The invention belongs to the technical field of photochemical organic synthesis and relates to a visible light-induced 9-acylacridine derivative and a preparation method thereof. Background Art

[0002] Acridine is an important nitrogen heterocyclic compound. Compounds containing this skeleton as a core fragment exhibit a wide range of biological activities, including anti-tumor, anti-malarial, anti-cancer, antibacterial, and leukemia therapeutic effects. Furthermore, some acridine derivatives, due to their fluorescent properties, have been used as imaging probes and DNA-binding cancer treatments. Therefore, the development of green and efficient methods to synthesize such compounds is of great significance in the field of organic synthesis. Although acridine derivatives are widely used in biochemistry, the introduction and modification of specific active substituents primarily relies on cyclization reactions to construct the acridine ring, a synthetic strategy that limits the synthetic applications of acridine derivatives. Direct selective C-H functionalization has brought opportunities for the efficient derivatization and synthesis of acridine derivatives. Among them, using organozinc reagents as substrates, transition metal rhodium catalyzed regioselective arylation of the C-H bond at the 9-position of acridine has achieved the efficient synthesis of 9-arylacridine derivatives (Chem. Commun. 2012, 48, 308). However, the synthetic strategy of achieving C-H bond functionalization of the acridine skeleton through catalytic methods still needs further development.

[0003] In recent years, visible-light-induced photocatalysis has attracted widespread attention as a powerful organic synthesis strategy due to its green, efficient, mild conditions, and strong functional group compatibility. Many methods have been successfully used for the selective functionalization of acridine at the C-9 position. Among them, regarding the free radical reaction for the preparation of 9-acyl-substituted acridine derivatives, the existing method mainly uses ketoacid, benzoylhydrazide or benzoyl chloride as acyl radical precursors, adds an excess oxidant under visible light irradiation, or generates acyl radicals under photoredox catalysis conditions, and then undergoes free radical addition with acridine, followed by oxidation to obtain 9-acyl-substituted acridine compounds (Org. Biomol. Chem. 2015, 13, 11561; Angew. Chem. Int. Ed. 2013, 52, 2082; Adv. Synth. Catal. 2018, 360, 4184; RSC Adv. 2021, 11, 38683; ACS Omega, 2019, 4, 14021). However, these methods for preparing C-9-substituted acridine derivatives also have certain limitations: for example, they only present one or two examples, lack substrate accessibility, require the addition of heavy metal compounds, use excessive amounts of dangerous peroxides as oxidants, or employ harsh reaction conditions. These limitations restrict the further development and application prospects of acridine derivative synthesis. Summary of the Invention

[0004] In response to the problems existing in the prior art, the present invention provides a visible light-induced 9-acylacridine derivative and a preparation method thereof. In the absence of a photocatalyst and an oxidant, visible light and a Brønsted acid-base synergistically promote the carbamoylation and acylation reactions at the C-9 position of acridine. Under mild reaction conditions, a class of 9-acylacridine derivatives is efficiently synthesized. This method has a broad spectrum of substrate applicability.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing a visible light-induced 9-acylacridine derivative comprises the following steps:

[0007] Acridine and its derivatives and 4-acyl substituted Hans ester are added to a reaction solvent, and a Bronsted acid and base are used as catalysts. The reaction is carried out under light conditions and in an inert atmosphere to prepare visible light-induced 9-acyl acridine derivatives.

[0008] Preferably, the acridine and its derivatives include any one of the following structural formulas:

[0009]

[0010] Preferably, the 4-acyl substituted Hans ester comprises any one of the following structural formulas:

[0011]

[0012] Here, Me represents a methyl group, and Et represents an ethyl group.

[0013] Preferably, the molar ratio of acridine and its derivatives to 4-acyl-substituted hans ester is 1:1.5;

[0014] The molar ratio of the acridine and its derivatives to the acid is 1:1.5;

[0015] The molar ratio of the acridine and its derivatives to the base is 1:2.5.

[0016] The molar ratio of the acridine and its derivatives to the acid is 1:1.5;

[0017] The molar ratio of the acridine and its derivatives to the base is 1:2.5.

[0018] Preferably, the Bronsted acid includes lithium tetrafluoroborate, boron trifluoride ethyl etherate, benzoic acid, trifluoroacetic acid and trifluoromethanesulfonic acid, with benzoic acid being the most preferred acid.

[0019] Preferably, the Bronsted base includes potassium carbonate, 4-dimethylaminopyridine, triethylamine, cesium carbonate, sodium bicarbonate and potassium hydrogen phosphate, and potassium carbonate is the best base.

[0020] Preferably, the reaction solvent includes chloroform, 1,2-dichloroethane, acetonitrile, methanol and N,N-dimethylformamide, with chloroform being the optimal solvent.

[0021] Preferably, the lighting condition is to use blue light as the reaction simulation light source, that is, two groups of 3W blue LED lights for illumination.

[0022] Preferably, the reaction conditions are: under argon atmosphere and room temperature, the carbamoylation reaction time is 32 hours, and the arylformylation and alkylformylation reaction time is 20 hours.

[0023] Preferably, the 9-acylacridine derivative includes any one of the following structural formulas:

[0024]

[0025] A visible light-induced 9-acyl acridine derivative is prepared based on the preparation method of the visible light-induced 9-acyl acridine derivative.

[0026] Compared with the prior art, the present invention has the following beneficial technical effects:

[0027] The present invention develops a method for synergistically promoting the carbamoylation and acylation reactions at the C-9 position of acridine under conditions without a photocatalyst or an oxidant, using visible light and a Brønsted acid-base reaction. This method efficiently achieves the synthesis of a class of 9-acyl acridine derivatives under mild reaction conditions, and has a broad substrate applicability. The 4-acyl-substituted Hans ester is directly excited to an excited state under visible light irradiation. The excited 4-acyl-substituted Hans ester 2 undergoes single electron transfer with protonated acridine and its derivatives to produce a 9-acridinium carbonyl free radical, while simultaneously releasing pyridine and a substituted formyl free radical through homolytic cleavage of the C-C bond. The substituted formyl free radical then couples with the 9-acridinium carbonyl free radical to produce a 9-acyl acridine derivative. This method is green and efficient, with mild conditions, a wide substrate applicability, good functional group compatibility, and avoids the addition of transition metal catalysts and stoichiometric oxidants. Furthermore, it can be effectively grafted with a variety of amino acid molecules, representing a new method for preparing 9-acyl acridine derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the application of acridine in the fields of anti-tumor, anti-malarial, anti-cancer, antibacterial and leukemia treatment in the prior art;

[0029] Figure 2 The figure is a flow chart of the synthesis of the visible light-induced 9-acylacridine derivatives of the present invention. DETAILED DESCRIPTION

[0030] The technical solution of the present invention will be described clearly and completely below. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0031] The present invention provides a method for preparing a 9-acylacridine derivative induced by visible light. Under visible light irradiation, an acridine derivative and a 4-acyl-substituted Hans ester are used as starting materials, and benzoic acid and potassium carbonate are used as acidic and basic additives, respectively. A 9-acridinium carbonyl free radical and an acyl free radical are generated through a single electron transfer process. Subsequently, free radical-free radical cross-coupling is performed to obtain a 9-acylacridine derivative containing 9-carbamoyl, arylformyl and alkylformyl substitutions.

[0032] The substrates of the method include: compound 1 is acridine and its derivatives and compound 2 is 4-acyl substituted hensyl ester;

[0033] The method comprises the following steps: adding acridine and its derivatives and 4-acyl substituted Hans ester into a reaction solvent, using Bronsted acid and base as catalysts, reacting under light conditions and in an inert atmosphere to prepare visible light-induced 9-acyl acridine derivatives.

[0034] The reaction formula of the synthesis method of the visible light induced 9-acyl acridine derivative of the present invention is as follows: Figure 1 As shown, where: R 1 represents hydrogen, methyl, methoxy, halogen; R 2 represents aryl, heteroaryl, alkyl, secondary amino, primary amino and their derivatives; Et represents ethyl.

[0035] In some embodiments, the experimental method for preparing 9-acyl acridine derivatives includes:

[0036] Using acridine and its derivatives and 4-acyl-substituted hensyl esters as starting materials, potassium carbonate and benzoic acid, chloroform as solvent, and blue LEDs as simulated sunlight light sources, 9-acyl acridine derivatives were obtained. The reaction formula is as follows:

[0037]

[0038] The ratio of the amount of the acridine and its derivatives to the amount of the 4-acyl-substituted hans ester is 1:1.5.

[0039] The acid comprises at least one of lithium tetrafluoroborate, boron trifluoride ethyl etherate, benzoic acid, trifluoroacetic acid, and trifluoromethanesulfonic acid, preferably benzoic acid.

[0040] The molar ratio of the acridine and its derivatives to the acid is 1:1.2 to 1:1.5, preferably 1:1.5.

[0041] The base includes at least one of potassium carbonate, 4-dimethylaminopyridine, triethylamine, cesium carbonate, sodium bicarbonate, and potassium hydrogen phosphate, preferably potassium carbonate.

[0042] The molar ratio of the acridine and its derivatives to the base is 1:1.5 to 1:2.5, preferably 1:2.5.

[0043] The reaction solvent includes any one of chloroform, 1,2-dichloroethane, acetonitrile, methanol, and N,N-dimethylformamide, preferably chloroform.

[0044] The reaction time at room temperature is 20 to 32 hours, preferably 32 hours for 9-carbamoylacridine derivatives, and preferably 20 hours for 9-arylformylacridine derivatives or 9-alkylformylacridine derivatives.

[0045] The following examples are used to specifically illustrate the method for preparing the visible light-induced 9-acylacridine derivatives of the present invention. These examples are merely illustrative of the present invention and are not intended to limit the present invention.

[0046] Example 1, Preparation of 9-Acylacridine Derivative Compound 3aa

[0047]

[0048] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted hensel ester 2a (109.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic separator. The reaction was allowed to proceed at room temperature for 32 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, compound 3aa (49.7 mg, 85%).

[0049] The structural characterization data of the product compound 3aa are as follows:

[0050] 1H NMR (400MHz, CDCl3) δ8.26(d,J=8.8Hz,2H),7.92(d,J=8.6Hz,2H),7.85–7.77(m,2H),7.63 –7.56(m,2H),4.16–4.07(m,2H),3.97–3.89(m,2H),3.50–3.43(m,2H),3.08–3.00(m,2H).

[0051] 13 C NMR (100MHz, CDCl3) δ166.4,148.6,139.6,130.6,130.6,127.6,124.7,1221,67.0,47.0,42.0.

[0052] Example 2 Preparation of 9-acylacridine derivative compound 3ba

[0053]

[0054] Under argon, acridine and its derivative 1b (38.7 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2a (109.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ba (55.8 mg, 91%).

[0055] The structural characterization data of the product compound 3ba are as follows:

[0056] 1 H NMR (400MHz, CDCl3) δ8.25(d,J=8.8Hz,1H),8.17(d,J=9.3Hz,1H),7.91(d,J=8.7Hz,1H),7.79(t,J=7.7Hz,1H),7.66(d,J=7.3Hz ,2H),7.60(t,J=7.6Hz,1H),4.16(tt,J=9.7,4.4Hz,2H),3.95(t,J=4.3Hz,2H),3.49(t,J=4.5Hz,2H),3.06(s,2H),2.59(s,3H).

[0057] 13C NMR (100MHz, CDCl3) δ166.7,148.0,147.7,138.4,137.4,133.6,130.1,13 0.0,129.7,127.1,124.6,122.6,122.18,122.15,67.0,47.1,42.0,22.1.

[0058] Example 3 Preparation of 9-Acylacridine Derivative Compound 3ca

[0059]

[0060] Under argon, acridine and its derivative 1c (41.9 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2a (109.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ca (60.6 mg, 94%).

[0061] The structural characterization data of the product 9-acylacridine derivative compound 3ca are as follows:

[0062] 1 H NMR (400MHz, CDCl3) δ8.23(d,J=8.8Hz,1H),8.15(d,J=9.5Hz,1H),7.88(d,J=8.6Hz,1H),7.80–7.72(m,1H),7.60(t,J=7.6H z,1H),7.50(d,J=11.9Hz,1H),7.02(s,1H),4.21–4.05(m,2H),4.02–3.86(m,5H),3.52–3.48(m,2H),3.08(t,J=4.4Hz,2H).

[0063] 13 C NMR (100MHz, CDCl3) δ166.9,158.2,146.9,146.0,136.9,131.7,130.0,129 .4,127.3,125.9,124.2,123.1,122.4,99.6,67.2,67.1,55.6,47.0,42.1.

[0064] Example 4 Preparation of 9-Acylacridine Derivative Compound 3da

[0065]

[0066] Under argon, acridine and its derivative 1d (42.7 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2a (109.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the 9-acylacridine derivative 3da (60.1 mg, 92%).

[0067] The structural characterization data of the product 9-acyl acridine derivative compound 3da are as follows:

[0068] 1 H NMR (400MHz, CDCl3) δ8.23(dd,J=16.1,9.0Hz,2H),7.95–7.89(m,2H),7.84(ddd,J=8.7,6.6,1.3Hz,1H),7.74(dd,J=9.3,2.2Hz,1 H),7.64(ddd,J=7.9,6.7,1.0Hz,1H),4.20–4.07(m,2H),3.96(dt,J=6.7,3.2Hz,2H),3.50(t,J=4.9Hz,2H),3.06(q,J=4.5Hz,2H).

[0069] 13 C NMR (100MHz, CDCl3) δ165.9,148.7,146.9,138.7,133.2,131.9,131.8,130.9,130.2,127.9,124.6,123.0,122.3,66.99,66.95,47.1,42.1.

[0070] Example 5 Preparation of 9-Acylacridine Derivative Compound 3ea

[0071]

[0072] Under argon, acridine and its derivative 1e (51.6 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2a (109.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ea (70.5 mg, 95%).

[0073] The structural characterization data of compound 3ea of ​​the 9-acylacridine derivative are as follows:

[0074] 1 H NMR (400MHz, CDCl3) δ8.25(d,J=8.7Hz,1H),8.18–8.06(m,2H),7.93(d,J=8.5Hz,1H),7.85(t,J=8.1Hz ,2H),7.64(t,J=7.5Hz,1H),4.12(t,J=9.0Hz,2H),3.95(s,2H),3.52–3.49(m,2H),3.09–2.98(m,2H).

[0075] 13 C NMR (100MHz, CDCl3) δ165.9,148.8,147.0,138.7,134.3,131.8,131.0,13 0.2,127.9,126.6,124.7,122.9,122.3,121.6,67.01,66.96,47.1,42.1.

[0076] Example 6 Preparation of 9-Acylacridine Derivative Compound 3ab

[0077]

[0078] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2b (105.1 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative, compound 3ab (47.0 mg, 85%).

[0079] The structural characterization data of the product 9-acyl acridine derivative compound 3ab are as follows:

[0080] 1 H NMR (400MHz, CDCl3) δ8.26(d,J=8.8Hz,2H),7.93(d,J=8.6Hz,2H),7.85–7.78(m,2H),7.63–7.56( m,2H),3.98(t,J=7.1Hz,2H),2.95(t,J=6.8Hz,2H),2.08(p,J=6.9Hz,2H),1.86(p,J=6.8Hz,2H).

[0081] 13 C NMR (100MHz, CDCl3)166.3,148.9,141.7,130.5,139.9,127.0,125.0,121.7,47.7,45.7,25.9,24.6.

[0082] Example 7 Preparation of 9-Acylacridine Derivative Compound 3ac

[0083]

[0084] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2c (131.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the 9-acylacridine derivative 3ac (58.1 mg, 80%).

[0085] The structural characterization data of the product 9-acylacridine derivative compound 3ac are as follows:

[0086] 1 H NMR (400MHz, CDCl3) δ8.29(d,J=8.7Hz,2H),7.91(d,J=8.6Hz,2H),7.88–7.78(m,2H),7.66–7. 55(m,2H),4.23–4.02(m,4H),3.85–3.70(m,2H),3.38–3.24(m,2H),3.04(s,2H),1.25(s,3H).

[0087] 13 C NMR (100MHz, CDCl3) δ166.6,155.2,148.6,130.7,130.0,127.3,124.7,122.0,61.9,46.5,41.5,14.6.

[0088] Example 8 Preparation of 9-Acylacridine Derivative Compound 3ad

[0089]

[0090] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2d (105.7 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ad (49.0 mg, 88%).

[0091] The structural characterization data of the product 9-acylacridine derivative compound 3ad are as follows:

[0092] 1 H NMR (400MHz, CDCl3) δ8.26(d,J=8.8Hz,2H),7.92(d,J=8.3Hz,2H),7.84–7.77(m,2H),7.61–7.54( m,2H),3.87(q,J=7.1Hz,2H),3.03(q,J=7.1Hz,2H),1.51(t,J=7.1Hz,3H),0.90(t,J=7.1Hz,3H).

[0093] 13 C NMR (100MHz, CDCl3) δ167.2,148.7,141.2,130.5,129.9,126.8,125.1,122.1,43.2,39.2,14.2,13.2.

[0094] Example 9 Preparation of 9-Acylacridine Derivative Compound 3ae

[0095]

[0096] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2e (128.6 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3ae (56.7 mg, 80%).

[0097] The structural characterization data of the product 9-acyl acridine derivative compound 3ae are as follows:

[0098] 1 H NMR (400MHz, CDCl3) δ8.28(d,J=8.8Hz,2H),7.98(d,J=8.6Hz,2H),7.82(t,J=7.7Hz,2H),7.71(d,J=7.6Hz,2H),7.58(t ,J=7.6Hz,2H),7.47(t,J=7.5Hz,2H),7.37(t,J=7.2Hz,1H),5.00(s,2H),3.58(p,J=7.2Hz,1H),0.98(d,J=6.6Hz,6H).

[0099] 13 C NMR (100MHz, CDCl3) δ168.4,148.7,139.6,130.6,129.8,128.7,127.4,126.8,125.1,122.2,51.4,44.2,21.7.

[0100] Example 10 Preparation of 9-Acylacridine Derivative Compound 3af

[0101]

[0102] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2f (143.0 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3af (63.6 mg, 79%).

[0103] The structural characterization data of the product 9-acyl acridine derivative compound 3af are as follows:

[0104] 1 H NMR (400MHz, CDCl3) δ8.26–8.22(m,2H),7.98–7.94(m,2H),7.82–7.76(m,2H),7. 55(s,4H),7.51–7.41(m,3H),7.19(s,3H),6.91(s,2H),4.94(s,2H),4.07(s,2H).

[0105] 13 C NMR (100MHz, CDCl3) δ168.4,148.7,140.0,136.6,134.8,130.5,130.0,12 9.5,128.9,128.7,128.1,128.0,127.96,127.0,125.0,122.4,51.4,46.6.

[0106] Example 11 Preparation of 9-Acylacridine Derivative Compound 3ag

[0107]

[0108] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 2 g of a 4-acyl-substituted Hans ester (105.7 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3ag (48.4 mg, 87%).

[0109] The structural characterization data of the product 9-acyl acridine derivative compound 3ag are as follows:

[0110] 1 H NMR (400MHz, CDCl3) δ8.11(d,J=8.8Hz,2H),7.95(d,J=8.7Hz,2H),7.74–7.66(m,2H),7.52–7.45(m,2H ),6.69(s,1H),3.72(q,J=7.0Hz,2H),1.79(p,J=7.5Hz,2H),1.58–1.49(m,2H),1.04(t,J=7.4Hz,3H)..

[0111] 13 C NMR (100MHz, CDCl3) δ166.9,148.2,141.3,130.4,129.2,126.8,125.2,122.1,40.q,31.7,20.3,13.8.

[0112] Example 12 Preparation of 9-Acylacridine Derivative Compound 3ah

[0113]

[0114] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted hensyl ester 2h (110.5 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the product, 9-acylacridine derivative 3ah (48.9 mg, 83%).

[0115] The structural characterization data of the product 9-acyl acridine derivative compound 3ah are as follows:

[0116] 1 H NMR (400MHz, CDCl3) δ8.14(dd,J=12.7,8.8Hz,4H),7.77–7.70(m,2H),7.57–7.50(m,2H),7.10(s,1H),4.51(d,J=5.7Hz,2H),3.89(s,3H).

[0117] 13 C NMR (101MHz, CDCl3) δ170.0,167.5,148.0,130.6,129.2,127.0,125.3,122.1,52.7,41.5.

[0118] Example 13 Preparation of 9-Acylacridine Derivative Compound 3ai

[0119]

[0120] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2i (115.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the 9-acylacridine derivative 3ai (49.4 mg, 79%).

[0121] The structural characterization data of the product 9-acyl acridine derivative compound 3ai are as follows:

[0122] 1 H NMR(400MHz, CDCl3)δ8.12(d,J=8.8Hz,2H),7.99(d,J=8.7Hz,2H),7.76–7.69(m,2H),7.54–7 .47(m,4H),7.42(t,J=7.6Hz,2H),7.35(t,J=7.8Hz,1H),6.68(s,1H),4.91(d,J=5.8Hz,2H).

[0123] 13C NMR (100MHz, CDCl3) δ166.9,148.3,137.5,130.4,129.4,129.0,128.2,128.0,126.8,125.1,122.1,44.3.

[0124] Example 14 Preparation of 9-Acylacridine Derivative Compound 3aj

[0125]

[0126] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2j (100.9 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3aj (47.7 mg, 91%).

[0127] The structural characterization data of the product 9-acyl acridine derivative compound 3aj are as follows:

[0128] 1 H NMR (400MHz, CDCl3) δ8.12(d,J=8.8Hz,2H),7.96(d,J=8.7Hz,2H),7.76–7.69(m,2H),7.55–7.48( m,2H),6.67(s,1H),3.23(dq,J=7.2,3.6Hz,1H),1.05(q,J=7.0Hz,2H),0.84(q,J=6.9,5.5Hz,2H).

[0129] 13 C NMR (100MHz, CDCl3) δ168.4,148.3,130.5,129.4,127.0,126.9,125.1,122.1,23.3,6.9.

[0130] Example 15 Preparation of 9-Acylacridine Derivative Compound 3ak

[0131]

[0132] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2k (113.5 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ak (56.6 mg, 93%).

[0133] The structural characterization data of the product 9-acylacridine derivative compound 3ak are as follows:

[0134] 1 H NMR (400MHz, CDCl3) δ8.23–8.16(m,2H),8.07–8.01(m,2H),7.76(ddt,J=8.9,6.6,1.2Hz,2H),7.54(ddt,J=8.6,6.5,1.0Hz,2H),6.12 (s,1H),4.38–4.29(m,1H),2.27–2.23(m,2H),1.83(dt,J=13.6,3.9Hz,2H),1.73–1.68(m,1H),1.52–1.48(m,1H),1.42–1.18(m,4H).

[0135] 13 C NMR (100MHz, CDCl3) δ166.1,148.5,141.1,130.4,129.6,126.8,125.2,122.1,49.3,33.3,25.4,24.9.

[0136] Example 16 Preparation of 9-Acylacridine Derivative Compound 3a1

[0137]

[0138] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2l (114.7 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the 9-acylacridine derivative 3a1 (57.4 mg, 93%).

[0139] The structural characterization data of the product 9-acyl acridine derivative compound 3a1 are as follows:

[0140] 1 H NMR (400MHz, CDCl3) δ8.32–8.11(m,4H),7.80–7.74(m,2H),7.58(q,J=7.0H z,2H),6.99(s,1H),5.14–5.04(m,1H),3.89(s,3H),1.72(d,J=7.2Hz,3H).

[0141] 13 C NMR (100MHz, CDCl3) δ173.0,166.8,148.4,140.0,130.5,129.5,127.0,125.1,122.2,52.8,48.8,18.2.

[0142] Example 17 Preparation of 9-Acylacridine Derivative Compound 3am

[0143]

[0144] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2m (137.6 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the 9-acylacridine derivative 3am (60.0 mg, 78%).

[0145] The structural characterization data of the product 9-acyl acridine derivative compound 3am are as follows:

[0146] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=8.8Hz,2H),7.73(t,J=7.3Hz,2H),7.46(s,2H),7.33(d,J=5.0Hz,3H),7.26–7.20 (m,4H),6.52(s,1H),5.55–5.41(m,1H),3.89(s,3H),3.52(dd,J=14.3,4.7Hz,1H),3.12(dd,J=13.9,9.6Hz,1H).

[0147] 13 C NMR (100MHz, CDCl3) δ171.8,167.0,148.4,139.9,135.8,130.4,129.5,129.2,129.0,127.4,126.8,125.1,122.1,53.4,52.8,37.9.

[0148] Example 18 Preparation of 9-Acylacridine Derivative Compound 3an

[0149]

[0150] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2n (132.8 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3an (54.5 mg, 74%).

[0151] The structural characterization data of the product 9-acyl acridine derivative compound 3an are as follows:

[0152] 1H NMR (400MHz, CDCl3) δ8.22(d,J=8.8Hz,2H),8.15–8.08(m,2H),7.78(t,J=8.3Hz,2H),7.65–7.54(m,2H),6.98(d,J=8 .0Hz,1H),5.27–5.22(m,1H),3.90(s,3H),2.73(t,J=7.3Hz,2H),2.51–2.40(m,1H),2.29–2.20(m,1H),2.16(s,3H).

[0153] 13 C NMR (100MHz, CDCl3) δ172.0,167.2,148.5,140.0,130.5,129.6,127.1,125.1,122.3,52.9,52.1,31.0,30.2,15.5.

[0154] Example 19 Preparation of 9-Acylacridine Derivative Compound 3ao

[0155]

[0156] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2o (129.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3ao (67.0 mg, 94%).

[0157] The structural characterization data of the product 9-acyl acridine derivative compound 3ao are as follows:

[0158] 1 H NMR(400MHz, CDCl3)δ8.20(d,J=8.8Hz,2H),8.10(d,J=8.7Hz,2H),7.82–7.73(m,2H ),7.60–7.53(m,2H),5.86(s,1H),2.33(s,6H),2.22(s,3H),1.78(d,J=15.8Hz,6H).

[0159] 13C NMR (100MHz, CDCl3) δ166.1,148.7,141.5,130.3,129.6,126.7,125.3,122.0,54.0,41.8,36.3,29.5.

[0160] Example 20 Preparation of 9-Acylacridine Derivative Compound 3ap

[0161]

[0162] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2p (105.7 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 32 hours under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ap (48.4 mg, 87%).

[0163] The structural characterization data of the product 9-acyl acridine derivative compound 3ap are as follows:

[0164] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=10.6Hz,2H),8.04(d,J=8.7Hz,2H),7.75(t,J=8.8Hz,2H),7.54(t,J=8.2Hz,2H),6.18(s,1H),1.67(s,9H).

[0165] 13 C NMR (100MHz, CDCl3) δ166.4,148.6,141.5,130.3,129.6,126.8,125.2,122.0,53.2,29.0.

[0166] Example 21 Preparation of 9-Acylacridine Derivative Compound 3aq

[0167]

[0168] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2q (107.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3aq (43.6 mg, 77%).

[0169] The structural characterization data of the product 9-acylacridine derivative compound 3aq are as follows:

[0170] 1 H NMR (400MHz, CDCl3) δ8.30(d,J=8.8Hz,2H),7.79(t,J=6.9Hz,4H),7.72(d,J=8.7Hz,2H),7.63(t,J=6.9Hz,1H),7.46(q,J=8.4Hz,4H).

[0171] 13 C NMR (100MHz, CDCl3) δ197.8,148.6,143.5,137.0,134.7,130.4,130.0,129.9,129.1,126.8,125.4,122.9.

[0172] Example 22 Preparation of 9-Acylacridine Derivative Compound 3ar

[0173]

[0174] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2r (111.4 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ar (48.2 mg, 81%).

[0175] The structural characterization data of the product 9-acylacridine derivative compound 3ar are as follows:

[0176] 1 H NMR (400MHz, CDCl3) δ8.30(d,J=8.8Hz,2H),7.84–7.77(m,2H),7.72(dd,J=12.3,8.3Hz,4H),7.52–7.44(m,2H),7.25(d,J=8.4Hz,2H),2.42(s,3H).

[0177] 13 C NMR (100MHz, CDCl3) δ197.2,148.6,146.0,143.8,134.7,130.4,130.2,130.0,129.9,129.8,126.7,125.4,122.9,21.9.

[0178] Example 23 Preparation of 9-Acylacridine Derivative Compound 3as

[0179]

[0180] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2s (116.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3as (52.6 mg, 84%).

[0181] The structural characterization data of the product 9-acyl acridine derivative compound 3as are as follows:

[0182] 1 H NMR (400MHz, CDCl3) δ8.31(d,J=8.8Hz,2H),7.86–7.72(m,6H),7.51–7.44(m,2H),6.91(d,J=9.0Hz,2H),3.86(s,3H).

[0183] 13 C NMR (100MHz, CDCl3) δ195.9,164.8,148.5,144.0,132.6,130.4,129.8,126.6,125.5,123.0,114.3,55.6.

[0184] Example 24 Preparation of 9-Acylacridine Derivative Compound 3at

[0185]

[0186] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2t (117.6 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3at (54.7 mg, 86%).

[0187] The structural characterization data of the product 9-acyl acridine derivative compound 3at are as follows:

[0188] 1 H NMR (400MHz, CDCl3) δ8.32(d,J=8.8Hz,2H),7.86–7.78(m,2H),7.74(d,J=8.3Hz,2H),7.69(d,J=8.6Hz,2H),7.53–7.46(m,2H),7.43(d,J=8.8Hz,2H).

[0189] 13 C NMR (100MHz, CDCl3) δ196.5,148.6,142.8,141.4,135.4,131.3,130.5,130.0,129.5,127.0,125.1,122.8.

[0190] Example 25 Preparation of 9-Acylacridine Derivative Compound 3au

[0191]

[0192] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2u (130.1 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to yield the product, 9-acylacridine derivative 3au (58.9 mg, 82%).

[0193] The structural characterization data of the product 9-acyl acridine derivative compound 3au are as follows:

[0194] 1 H NMR (400MHz, CDCl3) δ8.32(d,J=8.8Hz,2H),7.88(d,J=7.8Hz,2H),7.84–7.77(m,4H),7.66(d,J=7.5Hz,2H),7.60(d,J=8.2Hz,2H),7.52–7.38(m,5H).

[0195] 13 C NMR (100MHz, CDCl3) δ197.2,148.6,147.4,143.6,139.4,135.8,130.6,130.5,130.0,129.0,128.6,127.7,127.3,126.8,125.4,123.0.

[0196] Example 26 Preparation of 9-Acylacridine Derivative Compound 3av

[0197]

[0198] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2v (116.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3av (51.4 mg, 82%).

[0199] The structural characterization data of the product 9-acylacridine derivative compound 3av are as follows:

[0200] 1 H NMR(400MHz, CDCl3)δ8.32(d,J=8.7Hz,2H),7.86–7.78(m,2H),7.74(d,J=8.7Hz,2H), 7.56(s,1H),7.52–7.45(m,2H),7.30(d,J=7.7Hz,1H),7.21–7.13(m,2H),3.85(s,3H).

[0201] 13 C NMR (100MHz, CDCl3) δ197.6,160.1,148.5,143.6,138.4,130.4,130.1,139.9,126.8,125.8,125.4,123.7,123.0,121.4,112.9,55.5.

[0202] Example 27 Preparation of 9-Acylacridine Derivative Compound 3aw

[0203]

[0204] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2w (122.2 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3aw (54.0 mg, 81%).

[0205] The structural characterization data of the product 9-acylacridine derivative compound 3aw are as follows:

[0206] 1 H NMR (400MHz, CDCl3) δ9.62–9.59(m,1H),8.34–8.31(m,2H),8.12–8.08(m, 1H),8.09–7.97(m,1H),7.91–7.69(m,7H),7.50–7.43(m,3H),7.47(s,2H).

[0207] 13C NMR (100MHz, CDCl3) δ199.7,148.7,135.6,135.4,134.2,133.1,130.6,130.4,129.9,129.7,128.9,127.1,126.8,126.2,125.5,124.6,123.2.

[0208] Example 28 Preparation of 9-Acylacridine Derivative Compound 3ax

[0209]

[0210] Under argon, acridine and its derivative 1a (35.8 mg, 0.2 mmol), 4-acyl-substituted Hans ester 2x (124.7 mg, 0.3 mmol), K2CO3 (69.1 mg, 0.5 mmol), PhCO2H (36.6 mg, 0.3 mmol), and 2.0 mL of CHCl3 were added to a dry Schlenk reaction tube equipped with a magnetic field. The reaction was allowed to proceed at room temperature for 20 h under blue LED illumination. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography using hexane / ethyl acetate or CH2Cl2 / MeOH as eluents to obtain the 9-acylacridine derivative 3ax (57.4 mg, 84%).

[0211] The structural characterization data of the product 9-acyl acridine derivative compound 3ax are as follows:

[0212] 1 H NMR (400MHz, CDCl3) δ8.26(d,J=8.8Hz,2H),7.80(t,J=8.0Hz,2H),7.72(d,J=8.6 Hz,2H),7.55(m,J=8.0Hz,2H),2.01(s,3H),1.98(s,6H),1.67(q,J=12.3Hz,6H).

[0213] 13 C NMR (100MHz, CDCl3) δ215.2,148.5,145.7,130.3,130.0,126.3,125.8,122.1,48.0,38.9,36.2,27.9.

[0214] The present invention shows that benzoic acid is the optimal acid, potassium carbonate is the optimal base, and chloroform is the optimal solvent, which is the most preferred experimental formula for preparing 9-acylacridine derivatives of the present invention. The specific test data are shown in Table 1. By comparing the experimental test data, the reaction process conditions are the same as those in Example 1. By adding different types of acids and bases, as well as solvents, the formula of benzoic acid, potassium carbonate and chloroform is characterized as the most preferred experimental formula for preparing 9-acylacridine derivatives of the present invention, with a yield of up to 95%;

[0215] Table 1 shows the test data for the preparation of 9-acylacridine derivatives by adding different types of acids, bases, and solvents.

[0216]

[0217] The examples provided above demonstrate that the present invention provides a method for preparing 9-acylacridine derivatives. The reaction is green and efficient, the reaction conditions are mild, the yield is as high as 95%, the substrate range is wide, the functional group compatibility is good, and the use of transition metals and stoichiometric oxidants is avoided. At the same time, it can be effectively grafted with a variety of amino acid molecules.

Claims

1. A method for preparing a visible light-induced 9-acylacridine derivative, characterized in that: The following steps are involved: Acridine and its derivatives and 4-acyl substituted Hans ester are added into a reaction solvent, and a Bronsted acid and base are used as catalysts to react under light conditions and in an inert atmosphere to prepare 9-acyl acridine derivatives.

2. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, characterized in that: The acridine and its derivatives include any one of the following structural formulas:

3. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, characterized in that: The 4-acyl substituted Hans ester includes any of the following structural formulas: Here, Me represents a methyl group, and Et represents an ethyl group.

4. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, wherein: The molar ratio of acridine and its derivatives to 4-acyl-substituted hans ester is 1:1.5; The molar ratio of the acridine and its derivatives to the acid is 1:1.5; The molar ratio of the acridine and its derivatives to the base is 1:2.

5.

5. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, wherein: The Bronsted acid includes any one of lithium tetrafluoroborate, boron trifluoride ethyl etherate, benzoic acid, trifluoroacetic acid and trifluoromethanesulfonic acid; The Bronsted base includes any one of potassium carbonate, 4-dimethylaminopyridine, triethylamine, cesium carbonate, sodium bicarbonate and potassium hydrogen phosphate; The reaction solvent includes any one of chloroform, 1,2-dichloroethane, acetonitrile, methanol and N,N-dimethylformamide.

6. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, characterized in that: The Bronsted acid is benzoic acid; the Bronsted base is potassium carbonate; and the reaction solvent is chloroform.

7. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, wherein: The illumination condition is to use blue light as the reaction simulation light source, that is, two groups of 3W blue LED lights are used for illumination.

8. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, characterized in that: The reaction conditions are: under argon atmosphere and room temperature, the carbamoylation reaction time is 32 hours, and the arylformylation and alkylformylation reaction time is 20 hours.

9. The method for preparing a visible light-induced 9-acylacridine derivative according to claim 1, wherein: The 9-acyl acridine derivative includes any one of the following structural formulas:

10. A visible light-induced 9-acylacridine derivative, obtained by the preparation method of a visible light-induced 9-acylacridine derivative according to any one of claims 1 to 9.

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