A method for synthesizing an azaxanthone compound

Abstract

Studies have shown that Marcanine A as a natural product exhibits certain inhibitory activity on a variety of human tumor cells, and the natural product has strong potential drug value for treating cancer. Therefore, how to efficiently and economically synthesize the natural product has become an important issue. The existing synthesis route has obvious defects, and has problems such as complicated steps, harsh conditions and low yield. The present application provides an efficient and economical synthesis method, which uses NHC to catalyze the [3+3] reaction of enamine and enal to construct a delta-lactam in one step, and then quickly synthesize Marcanine A. Further, the present application proposes a new synthesis method for synthesizing azaxanthone compounds by using nitrogen amino methyl carbamate naphthoquinone as a substrate.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing azanthraquinone compounds using tert-butyl carbamate naphthoquinone as a substrate. Background Technology

[0002] Natural products generally refer to secondary metabolites produced by plants, animals, fungi, and bacteria in nature. In medicine, many natural products can be used for antibacterial, anti-insect, anti-tumor, and other clinically relevant drug activities. According to existing research, Marcanine A, as a natural product, has shown certain inhibitory activity against nine types of human tumor cells, including BEL-7402, K562, SPCA-1, SGC-7409 (Journal of Natural Products, 1999, 62(10): 1390-1394.) and A-549 (Chemical and Pharmaceutical Bulletin, 2011, 59.3: 338-340.), indicating that this natural product has strong potential drug value for cancer treatment. However, there are very few reports on the artificial synthesis of this natural product. Therefore, how to synthesize this natural product efficiently and economically has become a difficult problem that chemists need to solve.

[0003] In 2008, Matthew J. Pigggott's research group at the University of Western Australia reported the artificial synthesis of Marcanine A (Journal of Natural Products, 2008, 71(5): 866-868). They synthesized the target natural product Marcanine A through a five-step reaction starting from 1,4-dimethoxynaphthalene. This was the first report of the synthesis of Marcanine A, providing an important approach for later researchers. However, the method has obvious drawbacks, namely, too many steps, requiring a total of six steps, resulting in an overall yield of only 52%. Moreover, the excessive number of steps also leads to increased time and economic costs.

[0004]

[0005] In 2015, Ulrich Groth's group reported the synthesis of Marcanine A (RSC advances, 2015, 5(72): 58561-58565). This method starts from 1,4-naphthoquinone and synthesizes Marcanine A through 10 steps. This strategy is largely consistent with the synthesis strategy of Matthew J. Pigggott's group, except for changes in reaction conditions. This greatly helps to broaden the synthetic route, but the problem of cumbersome reaction steps has not yet been solved.

[0006]

[0007] In 2020, Jon D. Rainier's research group published an article on the synthesis of Marcanine A from naphthoquinone via photoelectro-cyclization (The Journal of Organic Chemistry, 2020, 85(6):4298-4311.). In this reaction, he continued the strategy of the previous two research groups, first introducing an amino functional group at the 2-position of naphthoquinone through nitration followed by reduction, and then achieving the cyclization reaction by introducing an unsaturated group on the amino group. The difference from the previous two research groups is that this group introduced a diene group instead of a dicarbonyl group on the amino group, thus broadening the approach. Finally, they used photocatalysis to complete the cyclization reaction in one step, which greatly reduced the number of cyclization steps. However, the drawback is that there are still many steps before cyclization.

[0008]

[0009] Based on the three previously reported synthetic routes for Marcanine A, they all share a similar approach: starting with 1,4-dimethoxynaphthalene as the substrate, introducing an amino functional group at the ortho position of the methoxy group, and then introducing a suitable group onto the amino group to complete the subsequent cyclization reaction. However, their methods also have significant drawbacks: the construction of the δ-lactam is overly cumbersome and requires stringent conditions. Therefore, finding a new, cost-effective synthetic route for Marcanine A is of great importance. Summary of the Invention

[0010] To address the aforementioned shortcomings, this invention provides an efficient and economical synthetic method. Nitrogen heterocyclic carbene (NHC), as one of the most important organic catalysts currently available, has been widely used to synthesize δ-lactams from simple acyclic starting materials. This invention utilizes NHC to catalyze the [3+3] reaction of enamines and enales to construct δ-lactams in one step, thereby rapidly synthesizing Marcanine A. Based on this, this invention proposes a novel synthetic method for synthesizing xanthones using tert-butyl carbamate naphthoquinone as a substrate, achieved through the following steps:

[0011] Using naphthoquinone tert-butyl carbamate as shown in Formula 1 and an aldehyde as shown in Formula 2 as raw materials, nitrogen-containing heterocyclic carbene as catalyst, and oxidant as shown in Formula 4, the reaction is carried out under the conditions of an aprotic solvent and Cs₂CO₃ as a base to obtain the target product compound as shown in Formula 3. The reaction steps are as follows:

[0012]

[0013] Wherein, R1 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, and C4-C6 heterocyclic; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy.

[0014] Or the reaction steps are:

[0015]

[0016] R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro groups; R3 and R4 are substituted together to form a phenyl group, as shown in Formula 1e below; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, and C4-C6 heterocyclic groups; the substituents in "substituted or unsubstituted" are halogens, trifluoromethyl, ester groups, and C1-C3 alkoxy groups.

[0017] Wherein, C1-C5 alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, and isobutyl; C3-C6 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, and cyclopentyl; C1-C4 alkoxy groups include, but are not limited to, methoxy, ethoxy, and butoxy; C6-C10 aryl groups include, but are not limited to, phenyl and naphthyl; C4-C6 heterocyclic groups include, but are not limited to, thiophene and furan; C1-C3 alkoxy groups include, but are not limited to, methoxy; halogens include, but are not limited to, chlorine and bromine; and ester groups include, but are not limited to, methyl acetate.

[0018] Preferably, the reaction is carried out using tert-butyl carbamate naphthoquinone as shown in Formula 1 and an aldehyde as shown in Formula 2 as raw materials, a nitrogen heterocyclic carbene as a catalyst, and an oxidant as shown in Formula 4, under the conditions of an aprotic solvent and Cs2CO3 as a base, to obtain the target product compound as shown in Formula 3. The reaction steps are as follows:

[0019]

[0020] Wherein, R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, and C4-C6 heterocyclic; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy.

[0021] Or the reaction steps are:

[0022]

[0023] Wherein, R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, and C4-C6 heterocyclic; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy.

[0024] Preferably, the substituents of tert-butyl carbamate naphthoquinone as shown in Formula 1 are selected from the group consisting of hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, methoxy, hydroxy, nitro, and phenyl.

[0025] Preferably, the substituents of the aldehyde shown in Formula 2 are selected from the group consisting of: hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, phenyl, chloro-substituted phenyl, bromo-substituted phenyl, trifluoromethyl-substituted phenyl, methoxy-substituted phenyl, methyl acetate-substituted phenyl, naphthyl, thiophene, and furan.

[0026] Preferably, the tert-butyl carbamate naphthoquinone shown in Formula 1 is selected from the tert-butyl carbamate naphthoquinone shown in Formulas 1a, 1b, 1c, 1d, 1e, and 1f.

[0027]

[0028] Preferably, the aldehyde shown in Formula 2 is selected from aldehydes shown in 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q.

[0029]

[0030] Preferably, the aprotic solvent is selected from acetonitrile, dichloromethane, chloroform, toluene, or dioxane.

[0031] Further preferred, the aprotic solvent is acetonitrile.

[0032] Preferably, the nitrogen heterocyclic carbene is selected from catalysts represented by formulas NHC-A, NHC-B, NHC-C, NHC-D, and NHC-E.

[0033]

[0034] More preferably, the nitrogen heterocyclic carbene is selected from catalysts of the formula NHC-C.

[0035] Preferably, the tert-butyl carbamate naphthoquinone is selected from tert-butyl carbamate naphthoquinone as shown in 1a, the aldehyde is selected from aldehydes shown in 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q, the nitrogen heterocyclic carbene is selected from catalysts shown in NHC-C, and the aprotic solvent is selected from acetonitrile.

[0036]

[0037]

[0038] Alternatively, the tert-butyl carbamate naphthoquinone may be selected from those shown in 1a, 1b, 1c, 1d, 1e, and 1f; the aldehyde may be selected from those shown in 2a; the nitrogen heterocyclic carbene may be selected from those shown in NHC-C; and the aprotic solvent may be selected from those shown in acetonitrile.

[0039]

[0040] More preferably, the tert-butyl carbamate naphthoquinone is selected as shown in 1a, the aldehyde is selected as shown in 2a, the nitrogen heterocyclic carbene is selected as a catalyst such as NHC-C, and the aprotic solvent is selected as acetonitrile.

[0041]

[0042] Preferably, the synthesis method is carried out at 0–40°C; and / or the reaction is carried out for 10–48 hours; and / or the molar ratio of the tert-butyl carbamate naphthoquinone to the aldehyde is 5:1 to 1:5; and / or the amount of the catalyst is 10–50 mol% by mass of the tert-butyl carbamate naphthoquinone.

[0043] The advantages of this invention are as follows: This invention provides a novel synthetic method for synthesizing xanthones using tert-butyl carbamate naphthoquinone as a substrate. Under mild reaction conditions, this invention utilizes a nitrogen-heterocyclic carbene catalysis to activate an aldehyde and tert-butyl carbamate naphthoquinone as a substrate to undergo a [3+3] cyclization reaction, constructing the natural product xanthones in one step. The method of this invention is mild, highly efficient, and has good substrate universality, achieving efficient preparation of the natural product marcanine A through NHC catalysis. This provides a new and efficient method for the artificial synthesis of this natural product. The method of this invention achieves cyclization, oxidation, and deprotection in one step, and yields the final product in high yield, which is beneficial for constructing aromatic lactam natural products and drug molecules using NHC catalysis. Attached Figure Description

[0044] Figure 1 These are the 1H and 1C NMR spectra of reaction product 3a from Example 2.

[0045] Figure 2 These are the 1H and 1C NMR spectra of reaction product 3b from Example 3.

[0046] Figure 3 These are the 1H and 1C NMR spectra of reaction product 3c from Example 4.

[0047] Figure 4 These are the 1H and 1C NMR spectra of the reaction product from Example 5, taken 3 days prior.

[0048] Figure 5 These are the 1H and 1C NMR spectra of the reaction product 3e from Example 6.

[0049] Figure 6 These are the 1H and 1C NMR spectra of reaction product 3f from Example 7.

[0050] Figure 7 The NMR spectra of 3g of the reaction product from Example 8 are the 1H NMR and 1C NMR spectra.

[0051] Figure 8 These are the 1H and 1C NMR spectra of the reaction products from Example 9 after 3 hours.

[0052] Figure 9 These are the 1H and 1C NMR spectra of reaction product 3i from Example 10.

[0053] Figure 10 These are the 1H and 1C NMR spectra of reaction product 3j from Example 11. Detailed Implementation

[0054] All chemical reagents used were purchased from commercially available products. Solvents were purchased from commercially available ultra-dry solvents. Thin-layer chromatography (TLC) was performed using 60F254 silica gel plates under 254 nm UV light.1 H NMR and 13 C10 NMR was characterized using a Bruker 400M NMR instrument with deuterated chloroform as the solvent. The coupling constant is measured in Hz. Optical rotation was measured using a Jasco P-1030 polarimeter. Enantiomer excess was determined using a Shimadzu LC-20AD HPLC. High-resolution mass spectrometry (HRMS) was performed using a Waters Q-TOF Permier Spectrometer.

[0055] Example 1

[0056] Preparation of reaction substrates (taking 1a as an example; the preparation methods for 1b, 1c, and 1d are similar).

[0057]

[0058] Preparation of substrate 1a: 1,4-naphthoquinone (3.1632 g, 20 mmol), tert-butyl N-hydroxycarbamate (2.9293 g, 22 mmol), and 75 mL of acetonitrile were added to a 150 mL round-bottom flask. The mixture was refluxed at 70 °C for 12 hours. After the reaction was complete, excess solvent was removed by rotary evaporation, and the product was purified by column chromatography (EA / PE = 1:20) to obtain the final product, a yellow powder solid 1a (3.8225 g, 14 mmol, 70% yield).

[0059]

[0060] The determination parameters of the prepared (1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester are as follows:

[0061] 1 H NMR (400MHz, CDCl3) (400Hz, CDCl3): δ = 8.10 (d, J = 7.8Hz, 2H), 7.68-7.80 (m, 2H), 7.48 (s, 1H), 1.54 (s, 9H),. 13 C NMR(100MHz, CDCl3)(100Hz, CDCl3): δ=184.7,180.8,151.2,141.1,134.8,133.0,132.3,130.1,126.6,126.3,114.9,82.6,28.1,.HRMS(ESI)Calcd for C 15 H 15 NO4[M] + 273.1001; found 273.1005.

[0062] The determination parameters of the prepared (8-nitro-1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester are as follows:

[0063] 1 H NMR (400MHz, CDCl3) δδ = 8.78 (1H, s), 7.69-7.82 (m, 2H), 7.49 (s, 1H), 1.52 (s, 9H), 13 C NMR(100MHz, CDCl3)δ186.7,169.8,165.4,157.8,145.1,130.1,127.8,114.2,113.1,107.9,82.7,9.2.HRMS(ESI)Calcd for C 15 H 15 N2O6 + [M+Na] + 391.0925; Found: 391.0922.

[0064] The determination parameters of the prepared (6,7-dimethyl-1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ = 7.80 (s, 2H), 7.69 (s, 1H), 7.37 (s, 1H), 2.38 (s, 3H), 2.37 (s, 3H), 1.53 (s, 9H). 13 C NMR (100MHz, CDCl3)δ=185.1,180.7,151.2,144.9,142.6,140.9,130.2,128.0,127.6,127.4,114.6,82.4,28.1,20.3,20.0.HRMS(ESI)Calcd forC 17 H 19 NNaO4 + [M+Na + ]:324.1206,found 324.1212.

[0066] The determination parameters of the prepared (8-hydroxy-1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester are as follows:

[0067] 1 H NMR (400MHz, DMSO-D6) δ = 11.00 (1H, s), 8.73 (1H, s), 7.12 (1H, s), 7.10 (1H, s), 1.50 (9H, s). 13C NMR (100MHz, CDCl3)δ=179.7,161.8,161.2,152.1,142.8,129.1,126.9,118.7,114.1,107.9,82,9.2.HRMS(ESI)Calcd for C 15 H 16 NO5 + [M+H + ]:290.1023,found290.1028.

[0068] Example 2

[0069] Preparation of reaction product 3a

[0070]

[0071] 3a was prepared using the following method:

[0072] To a dry test tube, substrate (1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester was added to synthesize 1a (0.1 mmol) containing azaxanthone compounds, cinnamaldehyde 2a (0.15 mmol), and azaxane carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0073] The product 4-phenylbenzoquinoline-2,5,10(1H)-trione was obtained with a yield of 96%. The determination parameters are as follows:

[0074] 1 H NMR (400MHz, CDCl3) δ = 9.94 (s, 1H), 8.22 (d, J = 7.6Hz, 1H), 8.10 (d, J = 7.6Hz, 1H), 7.82-7.77 (m, 2H), 7.47 (s, 3H), 7.31 (s, 1H), 6.74 (s, 1H); 13 C NMR (100MHz, CDCl3)δ=175.2,170.3,154.6,153.7,141.4,133.4,129.0,127.4,126.7,126.3,125.7,123.3,117.3,102.3; HRMS(ESI)calcd for C 24 H 24 NO6(M+H) + :422.1598,Found:422.1590.

[0075] Example 3

[0076] Preparation of reaction product 3b

[0077]

[0078] 3b was prepared using the following method:

[0079] To a dry test tube, substrate (1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate tert-butyl ester was added to synthesize 1a (0.1 mmol) containing azathanthrone compounds, o-methoxycinnamaldehyde 2b (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0080] The product 4-(2-methoxyphenyl)benzoquinoline-2,5,10(1H)-trione was obtained with a yield of 92%. The determination parameters are as follows:

[0081] 1 H NMR(400MHz,CF3COOD)δ=8.38-8.36(m,1H),8.24-8.22(m,1H),8.01-7.95(m,2H),7.58(t,J=8.0Hz ,1H),7.38(d,J=7.6Hz,1H),7.28(s,1H),7.22(t,J=7.6Hz,1H),7.10(d,J=4.4Hz,1H),3.78(s,3H); 13 C NMR(100MHz,CF3COOD)δ=183.86,178.03,155.75,153.88,139.12,136.49,135.06,132.71 ,131.81,129.87,128.10,127.52,127.30,125.50,121.85,111.22,42.95; HRMS(ESI)calcd for C 20 H 14 NO4(M+H) + :332.0917,Found:332.0911.

[0082] Example 4

[0083] Preparation of reaction product 3c

[0084]

[0085] 3C was prepared using the following method:

[0086] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), o-trifluoromethylcinnamaldehyde 2c (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0087] The product 4-(2-trifluoromethyl)phenylbenzoquinoline-2,5,10(1H)-trione was obtained with a yield of 73%. The determination parameters are as follows:

[0088] 1 H NMR(400MHz,CF3COOD)δ=8.28(d,J=7.6Hz,1H),8.13(d,J=7.6Hz,1H),7.92-7.86(m ,2H),7.77(d,J=4Hz,1H),7.61(t,J=7.6Hz,2H),7.52(d,J=7.6Hz,1H),7.08(s,1H); 13 C NMR(100MHz,CF3COOD)δ=183.61,177.38,157.15,140.46,137.10,136.68,135.27,132 .34,130.07,129.80,128.94,127.92,127.32,126.05,123.77,25.86; HRMS(ESI)calcd for C 20 H 11 F3NO3 + (M+H) + :370.0686,Found:370.0685.

[0089] Example 5

[0090] Preparation of reaction product 3e

[0091]

[0092] 3e was prepared using the following method:

[0093] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), m-chlorocinnamaldehyde 2e (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0094] The product 4-(3-chlorophenyl)benzoquinoline-2,5,10(1H)-trione (3e) was obtained with a yield of 84%. The determination parameters are as follows:

[0095] 1 H NMR (400MHz, CF3COOD) δ = 8.38-8.36 (m, 1H), 8.24-8.22 (m, 1H), 8.02-8.00 (m, 2H), 7. 56(d,J=8Hz,1H),7.51-7.46(m,1H),7.39(s,1H),7.29(d,J=7.2Hz,1H),7.23(s,1H); 13 C NMR(100MHz,CF3COOD)δ=181.11,175.86,154.61,139.93,137.87,136.68,135.27,134 .78,131.49,129.82,129.66,129.50,127.94,127.34,126.89,124.88.HRMS(ESI)calcd for C 19 H 10 CINO3 + (M+H) + :336.0422,Found:336.0415.

[0096] Example 6

[0097] Preparation of reaction product 3f

[0098]

[0099] The following preparation method was used to prepare 3f:

[0100] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), p-methoxycinnamaldehyde 2f (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0101] The product 4-(4-methoxyphenyl)benzoquinoline-2,5,10(1H)-trione (3f) was obtained: 96% yield. The determination parameters are as follows:

[0102] 1 HNMR (400MHz, CF3COOD) δ = 8.31-8.26 (m, 1H), 8.14 (d, J = 6.8Hz, 1H), 7.92-7.85 (m, 2H), 7.27 (d, J = 8Hz, 2H), 7.19 (t, J = 5.6Hz, 3H), 2.4 (s, 3H); 13 CNMR(100MHz,CF3COOD)δ=183.25,178.30,141.05,140.20,136.63,135.15,133.77,131.91 ,129.76,129.44,129.06,127.94,127.23,126.96,125.17,119.17,19.97; HRMS(ESI)calcd for C 20 H 14 NO4 + (M+H) + :332.0917,Found:332.0922.

[0103] Example 7

[0104] Preparation of 3g of reaction product

[0105]

[0106] 3g was prepared using the following method:

[0107] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), o-bromocinnamaldehyde 2 g (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0108] The product 4-(2-bromophenyl)benzoquinoline-2,5,10(1H)-trione (3g) was obtained: 84% yield. The determination parameters are as follows:

[0109] 1 H NMR (400MHz, CF3COOD) δ = 8.38-8.36 (m, 1H), 8.24-8.22 (m, 1H), 8.02-8.00 (m, 2H), 7. 56(d,J=8Hz,1H),7.51-7.46(m,1H),7.39(s,1H),7.29(d,J=7.2Hz,1H),7.23(s,1H); 13 C NMR(100MHz,CF3COOD)δ=181.11,175.86,154.61,139.93,137.87,136.68,135.27,134 .78,131.49,129.82,129.66,129.50,127.94,127.34,126.89,124.88.HRMS(ESI)calcd for C 19 H 10 BrNO3 + (M+H) + :378.9844,Found:378.9849.

[0110] Example 8

[0111] Preparation of reaction products over 3 hours

[0112]

[0113] The following preparation method was used for 3 hours:

[0114] To a dry test tube, tert-butyl carbamate (1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), m-trifluorocinnamaldehyde 2h (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0115] The product 4-(4-trifluoromethyl)phenylbenzoquinoline-2,5,10(1H)-trione was obtained (3h): 84% yield. The determination parameters are as follows:

[0116] 1 H NMR (400MHz, CF3COOD) δ = 8.37 (dd, J = 5.6, 1.6Hz, 1H), 8.21 (d, J = 8Hz, 1H), 8.01-7.95 (m, 2H), 7.83 (d, J = 7.6Hz, 2H), 7.53 (d, J = 8Hz, 2H), 7.22 (s, 1H); 13 C NMR(100MHz,CF3COOD)δ=181.92,178.23,156.72,136.67,134.53,132.30,129.79,127.88,127.32,127.18,125.27.HRMS(ESI)calcd for C 20 H 10 F3NO3 + (M+H) + :369.0613,Found:369.0619.

[0117] Example 9

[0118] Preparation of reaction product 3i

[0119]

[0120] 3i was prepared using the following method:

[0121] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), p-chlorocinnamaldehyde 2i (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0122] The product 4-(4-chlorophenyl)benzoquinoline-2,5,10(1H)-trione (3i) was obtained: 95% yield. The determination parameters are as follows:

[0123] 1 H NMR(400MHz,CF3COOD)δ=8.38-8.36(m,1H),8.24-8.22(m,1H),8.02-8.00(m,2H),7.5 6(d,J=8.0Hz,1H),7.51-7.46(m,1H),7.39(s,1H),7.29(d,J=7.2Hz,1H),7.23(s,1H); 13 C NMR(100MHz,CF3COOD)δ=181.11,175.86,154.61,139.93,137.87,136.68,135.27,134 .78,131.49,129.82,129.66,129.50,127.94,127.34,126.89,124.88.HRMS(ESI)calcd for C 19 H 10 CINO3 + (M+H) + :336.0422,Found:336.0415.

[0124] Example 10

[0125] Preparation of reaction product 3j

[0126]

[0127] The following preparation method was used to prepare 3j:

[0128] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), (E)-4-(3-oxopropyl-1-enyl)phenylacetate 2j (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0129] The product methyl 4-(2,5,10-trioxo-1,2,5,10-tetrahydrobenzo[g]quinoline-4-yl)benzoate (3j) was obtained, with a yield of 84%. The determination parameters are as follows:

[0130] 1 HNMR (400MHz, CF3COOD) δ = 8.28 (d, J = 7.4, 1H), 8.18 (d, J = 7.6Hz, 2H), 8.11 (d, J = 7.2Hz, 2H), 7.92-7.86 (m, 2H), 7.14 (s, 1H), 4.08 (s, 3H); 13 CNMR(100MHz,CF3COOD)δ=183.86,178.03,155.75,153.88,139.12,136.49,135.06,132.71 ,131.81,129.87,128.10,127.52,127.30,125.50,121.85,111.22,42.95; HRMS(ESI)calcd for C 21 H 14 NO5 + (M+H) + :360.0866,Found:360.0875.

[0131] Example 11

[0132] Preparation of reaction product 3k

[0133]

[0134] 3k was prepared using the following method:

[0135] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), 3-(3,5-dichlorophenyl)propenal 2k (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0136] The product 4-(3,4-dichlorophenyl)benzoquinoline-2,5,10(1H)-trione (3k) was obtained with a yield of 93%. The determination parameters are as follows:

[0137] 1 H NMR(400MHz,CF3COOD)δ=8.28-8.11(m,1H),8.12(d,J=8.4Hz,1H),7.90-7.84(m,2 H),7.47(d,J=10Hz,1H),7.40(d,J=9.6Hz,1H),7.21(d,J=8.0Hz,1H),7.08(s,1H); 13 C NMR(100MHz,CF3COOD)δ=181.50,177.49,153.87,136.62,135.24,133.87,132.02,130.49,129.28,128.68,127.86,127.52,127.34; HRMS(ESI)calcd for C 19 H 10 CI2NO3 + (M+H) + :370.0032,Found:370.0035.

[0138] Example 12

[0139] Preparation of reaction product 3l

[0140]

[0141] The following preparation method was used to prepare 3l:

[0142] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), thiophene cinnamaldehyde 2l (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0143] The product 4-(thiophen-2-yl)benzo[g]quinoline-2,5,10(1H)-trione (3l) was obtained: 97% yield. The determination parameters are as follows:

[0144] 1 H NMR (400MHz, CDCl3) δ = 9.89 (s, 1H), 8.20 (dd, J = 7.6, 6.0Hz, 1H), 8.14 (dd, J = 7.6, 1.6Hz, 1H), 7. 86-7.81(m,1H),7.79-7.75(m,1H),7.48(dd,J=4.8,1.2Hz,1H),7.16-7.11(m,2H),6.87(s,1H); 13 C NMR (100MHz, CDCl3)δ=181.50,177.49,153.87,136.62,135.24,133.87,132.02,130.49,129.28,128.68,127.86,127.52,127.34; HRMS(ESI)calcdfor C 17 H9NO3S + (M+H) + :370.0032,Found:307.0039.

[0145] Example 13

[0146] Preparation of reaction product 3m

[0147]

[0148] The following preparation method was used to prepare 3m:

[0149] To a dry test tube, tert-butyl carbamate (1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize compound 1a (0.1 mmol), furanocinnamaldehyde 2m (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0150] The product 4-(furan-2-yl)benzo[g]quinoline-2,5,10(1H)-trione (3m) was obtained with a yield of 90%. The determination parameters are as follows:

[0151] 1 H NMR (400MHz, CDCl3) δ = 8.20 (dd, J = 7.6, 6.0Hz, 1H), 8.14 (dd, J = 7.6, 1.6Hz, 1H), 7.86-7.8 1(m,1H),7.79-7.75(m,1H),7.48(dd,J=4.8,1.2Hz,1H),7.16-7.11(m,2H),6.87(s,1H); 13 C NMR (100MHz, CDCl3)δ=181.50,177.49,153.87,136.62,135.24,133.87,132.02,130.49,129.28,128.68,127.86,127.52,127.34; HRMS(ESI)calcd for C 17 H9NO4 + (M+H) + :291.0532,Found:291.0537.

[0152] Example 14

[0153] Preparation of reaction product 3o

[0154]

[0155] 3o was prepared using the following method:

[0156] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize a nitrogen-containing anthraquinone compound 1a (0.1 mmol), crotonaldehyde 2o (0.15 mmol), and a nitrogen-containing heterocyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0157] 4-Methylbenzoquinoline-2,5,10(1H)-trione: 67% yield, assay parameters are as follows:

[0158] 1 HNMR (400MHz, CF3COOD) δ = 8.05-8.03 (m, 2H), 7.64 (t, J = 5.2Hz, 2H), 2.32 (s, 3H); 13 C NMR(100MHz,CF3COOD)δ=183.86,178.03,155.75,153.88,139.12,136.49,135.06,132.71 ,131.81,129.87,128.10,127.52,127.30,125.50,121.85,111.22,42.95; HRMS(ESI)calcd for C 14 H 10 NO3 + (M+H) + :240.0655,Found:240.0658

[0159] Example 15

[0160] Preparation of reaction product 3p

[0161]

[0162] 3p was prepared using the following method:

[0163] To a dry test tube, tert-butyl carbamate (8-ethyl-1,4-dioxo-1,4-dihydronaphthyl-2-yl) was added as a substrate to synthesize a nitrogen-containing anthraquinone compound 1c (0.1 mmol), crotonaldehyde 2a (0.15 mmol), and a nitrogen-containing heterocyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0164] Example 16

[0165] Preparation of reaction product 3q

[0166]

[0167] 3q was prepared using the following method:

[0168] To a dry test tube, tert-butyl 6-cyclopropyl-1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize 1d (0.1 mmol), cinnamaldehyde 2a (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%) containing azathanthrone compounds. Then, 3 mL of acetonitrile was added as a solvent. The reaction mixture was stirred at room temperature for 10 hours. After the reaction was complete as monitored by TLC, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane (1:20) as the eluent. The product was a yellow solid.

[0169] Example 17

[0170] Preparation of reaction product 3r

[0171]

[0172] 3r was prepared using the following method:

[0173] To a dry test tube, tert-butyl carbamate (5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthyl-2-yl) was added as a substrate to synthesize 1f (0.1 mmol) containing a nitrogen-containing anthraquinone compound, cinnamaldehyde 2a (0.15 mmol), and a nitrogen-containing heterocyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0174] Example 18

[0175] Preparation of reaction product 3s

[0176]

[0177] The following preparation method was used to prepare 3s:

[0178] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydroanthracene-2-yl)carbamate was added as a substrate to synthesize 1e (0.1 mmol) of a nitrogen-containing anthraquinone compound, 2p (0.15 mmol) of 3-cyclopropyl acrolein, and 6.2 mg (20 mol%) of a nitrogen-containing carbene. Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0179] Example 19

[0180] Preparation of reaction product 3t

[0181]

[0182] The following preparation method was used to prepare 3t:

[0183] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydroanthracene-2-yl)carbamate was added as a substrate to synthesize 1e (0.1 mmol) of a nitrogen-containing anthraquinone compound, 2m (0.15 mmol) of 3-furan-2-propenal, and 6.2 mg (20 mol%) of a nitrogen-containing carbene. Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0184] Example 20

[0185] Preparation of reaction product 3u

[0186]

[0187] 3u was prepared using the following method:

[0188] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize 1a (0.1 mmol), crotonaldehyde 2o (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added as a solvent to the mixture. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0189] Example 21

[0190] Preparation of reaction product 3v

[0191]

[0192] 3V was prepared using the following method:

[0193] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphthyl-2-yl)carbamate was added as a substrate to synthesize 1a (0.1 mmol), 3-naphthyl-1-propenal 2n (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0194] Example 22

[0195] Preparation of reaction product 3w

[0196]

[0197] The following preparation method was used to prepare 3w:

[0198] To a dry test tube, tert-butyl 1,4-dioxo-1,4-dihydronaphth-2-yl)carbamate was added as a substrate to synthesize 1a (0.1 mmol), cinnamaldehyde 2a (0.15 mmol), and azahexacyclic carbene (6.2 mg, 20 mol%) containing azathanthrone compounds. Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography with methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

[0199] Example 23

[0200] Preparation of reaction product 3x

[0201]

[0202] The following preparation method was used to prepare 3x:

[0203] To a dry test tube, tert-butyl carbamate (8-methoxy-1,4-dioxo-1,4-dihydronaphthyl-2-yl) was added as a substrate to synthesize a nitrogen-containing xanthone compound 1f (0.1 mmol), o-bromocinnamaldehyde (0.15 mmol), and a nitrogen-containing heterocyclic carbene (6.2 mg, 20 mol%). Then, 3 mL of acetonitrile was added to the mixture as a solvent. The reaction system was stirred at room temperature for 10 hours. After the reaction was completed by TLC monitoring, the reaction mixture was purified by silica gel column chromatography using methanol / dichloromethane = 1:20 as the eluent. The product was a yellow solid.

Claims

1. A method for synthesizing azathanthrone compounds, characterized in that, Using naphthoquinone tert-butyl carbamate as shown in Formula 1 and an aldehyde as shown in Formula 2 as raw materials, nitrogen-containing heterocyclic carbene as catalyst, and oxidant as shown in Formula 4, the reaction is carried out under the conditions of an aprotic solvent and Cs₂CO₃ as a base to obtain the target product compound as shown in Formula 3. The reaction steps are as follows: Wherein, R1 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy. Or the reaction steps are: Wherein, R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R3 and R4 are combined to form a phenyl group after substitution; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy. The nitrogen heterocyclic carbene is selected from catalysts represented by NHC-A, NHC-B, NHC-C, NHC-D, or NHC-E. The synthesis method is carried out at 0–40°C; and / or the reaction is carried out for 10–48 hours.

2. The synthesis method according to claim 1, characterized in that, Using naphthoquinone tert-butyl carbamate as shown in Formula 1 and an aldehyde as shown in Formula 2 as raw materials, nitrogen-containing heterocyclic carbene as catalyst, and oxidant as shown in Formula 4, the reaction is carried out under the conditions of an aprotic solvent and Cs₂CO₃ as a base to obtain the target product compound as shown in Formula 3. The reaction steps are as follows: Wherein, R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy. Or the reaction steps are: Wherein, R3 and R4 are independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C4 alkoxy, hydroxyl, and nitro; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; the substituent in "substituted or unsubstituted" is halogen, trifluoromethyl, ester, or C1-C3 alkoxy.

3. The synthesis method as described in claim 1, characterized in that, The substituents of the tert-butyl carbamate naphthoquinone as shown in Formula 1 are selected from the group consisting of hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, methoxy, hydroxy, nitro, and phenyl.

4. The synthesis method according to claim 1, characterized in that, The substituents of the aldehyde as shown in Formula 2 are selected from the group consisting of: hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, phenyl, chloro-substituted phenyl, bromo-substituted phenyl, trifluoromethyl-substituted phenyl, methoxy-substituted phenyl, methyl acetate-substituted phenyl, naphthyl, thiophene, and furan.

5. The synthesis method according to claim 1, characterized in that, The tert-butyl carbamate naphthoquinone shown in Formula 1 is selected from the tert-butyl carbamate naphthoquinone shown in Formulas 1a, 1b, 1c, 1d, 1e, and 1f.

6. The synthesis method according to claim 1, characterized in that, The aldehydes represented by Formula 2 are selected from aldehydes represented as 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q.

7. The synthesis method according to claim 1, characterized in that, The aprotic solvent is selected from acetonitrile, dichloromethane, trichloromethane, toluene, or dioxane.

8. The synthesis method according to claim 1, characterized in that, The tert-butyl carbamate naphthoquinone is selected as shown in 1a; the aldehyde is selected as shown in 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q; the nitrogen heterocyclic carbene is selected as shown in NHC-C; and the aprotic solvent is selected as acetonitrile. Alternatively, the tert-butyl carbamate naphthoquinone may be selected from those shown in 1a, 1b, 1c, 1d, 1e, and 1f; the aldehyde may be selected from those shown in 2a; the nitrogen heterocyclic carbene may be selected from those shown in NHC-C; and the aprotic solvent may be selected from those shown in acetonitrile.

9. The synthesis method according to claim 1, characterized in that, The tert-butyl carbamate naphthoquinone is selected as shown in 1a, the aldehyde is selected as shown in 2a, the nitrogen heterocyclic carbene is selected as a catalyst as shown in NHC-C, and the aprotic solvent is selected as acetonitrile.

10. The synthesis method according to claim 1, characterized in that, The molar ratio of the tert-butyl carbamate naphthoquinone to the aldehyde is 5:1 to 1:5; and / or the amount of the catalyst is 10 to 50 mol by mass of the tert-butyl carbamate naphthoquinone.

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