CN117466815A - Synthesis method of azaanthrone compound - Google Patents

Synthesis method of azaanthrone compound Download PDF

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CN117466815A
CN117466815A CN202310934429.7A CN202310934429A CN117466815A CN 117466815 A CN117466815 A CN 117466815A CN 202310934429 A CN202310934429 A CN 202310934429A CN 117466815 A CN117466815 A CN 117466815A
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unsubstituted
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butyl
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付振乾
张叶
黄维
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Northwestern Polytechnical University
Nanjing Tech University
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Northwestern Polytechnical University
Nanjing Tech University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/08—Aza-anthracenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Abstract

Research shows that Marcanine A as a natural product has certain inhibition activity on various human tumor cells, and the natural product has strong potential pharmaceutical value for treating cancers. Therefore, how to synthesize the natural product efficiently and economically becomes an important subject. The existing synthetic route has obvious defects, and has the problems of complicated steps, harsh conditions, low yield and the like. The invention provides a high-efficiency and economical synthesis method, which utilizes NHC to catalyze [3+3] reaction of enamine and enaldehyde to construct delta-lactam in one step, thereby rapidly synthesizing Marcanine A. Furthermore, the invention provides a novel synthesis method for synthesizing the azaanthrone compound by taking tert-butyl azocarbamate naphthoquinone as a substrate.

Description

Synthesis method of azaanthrone compound
Technical Field
The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method for synthesizing an azaanthrone compound by taking tert-butyl carbamate naphthoquinone as a substrate.
Background
Natural products generally refer to secondary metabolites produced by plants, animals, fungi, bacteria in nature. Many natural products are medically useful for antibacterial, anti-insect, anti-tumor and other clinically relevant pharmaceutical activities. According to the existing researches, marcanine A as a natural product shows certain inhibition activity on nine human tumor cells of BEL-7402, K562, SPCA-1, SGC-7409 (Journal of natural products,1999,62 (10): 1390-1394.) and A-549, etc. (Chemical and Pharmaceutical Bulletin,2011, 59.3:338-340.), which shows that the natural product has strong potential pharmaceutical value for treating cancers. However, few reports have been made on the artificial synthesis of such natural products. Thus, how to synthesize the natural product efficiently and economically is a problem that chemists need to solve.
The Matthew J.Piggott subject group at the university of Western Australia in 2008 reported the synthesis of Marcanine A (Journal of natural products,2008,71 (5): 866-868.). They finally synthesize the target natural product Marcanine A by five steps of reactions starting from 1, 4-dimethoxy naphthalene. This is the first report of the synthesis of Marcanine a, which provides an important idea for the latter. However, the disadvantage of this process is evident, i.e. the number of steps is excessive, which requires six steps in total, resulting in a total yield of only 52%, and the excessive steps also result in an increase in time and economic costs.
Marcanine A (RSC Advances,2015,5 (72)) was reported by Ulrich Groth topic group in 2015 (58161-58556.). According to the method, starting from 1, 4-naphthoquinone, 10 steps of reactions are carried out, and finally Marcanine A is synthesized, wherein the strategy is approximately consistent with the synthetic strategy of Matthew J.Piggott subject group, and only the reaction conditions are changed, so that the method is helpful for widening the synthetic route, and the problem of complicated reaction steps is not solved.
In 2020, the Jon D.Rainier group published an article (The Journal of organic chemistry,2020,85 (6): 4298-4311.) on the synthesis of Marcanine A from naphthoquinone by a photocyclization reaction in which he continued the strategy of the first two groups, also by introducing an amino function at the 2-position of naphthoquinone by nitration followed by reduction, and then by introducing an unsaturated group at the amino group to effect the cyclization reaction. The difference from the first two subject groups is that the subject groups introduce diene groups instead of dicarbonyl groups on the amino groups, thereby widening the idea, and finally the cyclization reaction is completed in one step using photocatalysis, thereby greatly reducing the steps of cyclization, but the disadvantage is that the steps before cyclization are still numerous.
The three previous reports of synthesizing Marcanine A are synthesized, and the three reports find that the Marcanine A has the same thought, namely, 1, 4-dimethoxy naphthalene is taken as a substrate, and then amino functional groups are introduced at the ortho position of methoxy groups, and proper groups are introduced on amino groups, so that the subsequent cyclization reaction is completed. However, they are also remarkable in that the procedure for constructing delta-lactams is too cumbersome and the conditions are severe. Therefore, the search of a new synthetic route of Marcanine A with economy and high efficiency is of great significance.
Disclosure of Invention
Aiming at the defects, the invention provides a high-efficiency and economical synthesis method. Azacyclic carbenes (NHCs) have been widely used as one of the most important organic catalysts today for the synthesis of delta-lactams from simple acyclic starting materials. The invention utilizes NHC to catalyze [3+3] reaction of enamine and enaldehyde to construct delta-lactam in one step, thereby rapidly synthesizing Marcanine A. Based on the method, the invention provides a novel synthesis method for synthesizing the azaanthrone compound by taking tert-butyl carbamate naphthoquinone as a substrate, which is realized by the following steps:
adopting tert-butyl carbanilate naphthoquinone shown in formula 1 and aldehyde shown in formula 2 as raw materials, adopting N-heterocyclic carbene as a catalyst, adopting oxidant shown in formula 4, adopting aprotic solvent as solvent, and adopting Cs 2 CO 3 The method is characterized in that the reaction is carried out under the condition of alkali to obtain a target product compound shown in a formula 3, and 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the 'substituted or unsubstituted' is halogen, trifluoromethyl, ester group and C1-C3 alkoxy;
or 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, hydroxy, nitro; r3 and R4 are jointly substituted to synthesize a phenyl group, as shown in the following formula 1 e; r2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, C4-C6 heterocyclyl; the substituent in the "substituted or unsubstituted" is halogen, trifluoromethyl, ester group, C1-C3 alkoxy.
Wherein, the C1-C5 alkyl includes but is not limited to methyl, ethyl, propyl, isopropyl, butyl and isobutyl; cycloalkyl of C3-C6 includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl; alkoxy groups of C1 to C4 include, but are not limited to, methoxy, ethoxy, butoxy; aryl groups of C6 to C10 include, but are not limited to, phenyl and naphthyl; C4-C6 heterocyclyl includes, but is not limited to, thiophene and furan; alkoxy groups of C1 to C3 include, but are not limited to methoxy; halogen includes, but is not limited to, chlorine and bromine; ester groups include, but are not limited to, methyl acetate groups.
Preferably, tert-butyl naphthoquinone nitrogen carbamate shown in formula 1 and aldehyde shown in formula 2 are used as raw materials, N-heterocyclic carbene is used as a catalyst, oxidant shown in formula 4, and Cs is an aprotic solvent 2 CO 3 The method is characterized in that the reaction is carried out under the condition of alkali to obtain a target product compound shown in a formula 3, and 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the 'substituted or unsubstituted' is halogen, trifluoromethyl, ester group and C1-C3 alkoxy;
or 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the "substituted or unsubstituted" is halogen, trifluoromethyl, ester group, C1-C3 alkoxy.
Preferably, the substituent of t-butyl-naphthoquinone-nitrogen carbamate as shown in formula 1 is selected from the group consisting of: hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, methoxy, hydroxy, nitro, phenyl.
Preferably, the substituent of the aldehyde as shown in formula 2 is 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, furan.
Preferably, the tert-butyl naphthoquinone azocarbamate represented by formula 1 is selected from tert-butyl naphthoquinone azocarbamate represented by formula 1a,1b,1c,1d,1e,1f
Preferably, the aldehyde represented by formula 2 is selected from the group consisting of aldehydes represented by 2a,2b,2c,2d,2e,2f,2g,2h,2i,2j,2k,2l,2m,2n,2o,2p,2q
Preferably, the aprotic solvent is selected from acetonitrile, dichloromethane, chloroform, toluene, or dioxane.
Further preferably, the aprotic solvent is acetonitrile.
Preferably, the N-heterocyclic carbene is selected from the group consisting of catalysts represented by the formulas NHC-A, NHC-B, NHC-C, NHC-D and NHC-E
Further preferably, the N-heterocyclic carbene is selected from the group consisting of catalysts of the formula NHC-C.
Preferably, the tert-butyl carbazepine is selected from tert-butyl carbazepine 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
Or the tert-butyl carbanilate naphthoquinone is selected from tert-butyl carbanilate naphthoquinone shown as 1a,1b,1C,1d,1e and 1f, the aldehyde is selected from aldehyde shown as 2a, the N-heterocyclic carbene is selected from catalyst shown as NHC-C, and the aprotic solvent is selected from acetonitrile
Further preferably, the tert-butyl naphthoquinone nitrogen carbamate is selected from tert-butyl naphthoquinone nitrogen carbamate shown in 1a, the aldehyde is selected from aldehyde shown in 2a, the N-heterocyclic carbene is selected from catalyst shown in NHC-C, and the aprotic solvent is selected from acetonitrile
Preferably, the synthesis method is carried out at 0-40 ℃; and/or the reaction is carried out for 10 to 48 hours; and/or the molar ratio of said t-butyl carbanilate naphthoquinone to said aldehyde is 5:1 to 1:5, a step of; and/or the catalyst is used in an amount of 10 to 50mol% based on the mass ratio of the tert-butyl azodicarbonate naphthoquinone.
The invention has the advantages that: the invention provides a novel synthesis method for synthesizing a aza-anthrone compound by taking tert-butyl carbamate naphthoquinone as a substrate. Under mild reaction conditions, the invention uses N-heterocyclic carbene to catalyze and activate aldehyde and tert-butyl carbamate naphthoquinone as substrates to carry out [3+3] cyclization reaction, thus constructing the natural product of the aza-anthrone compound in one step. The method has mild conditions, high reaction efficiency and good substrate universality, and realizes the efficient preparation of the natural product marcanine A through NHC catalysis. This provides a new and efficient method for the artificial synthesis of the natural product. The method realizes three processes of cyclization, oxidation and deprotection in one step, can obtain a final product with high yield, and is favorable for constructing aromatic lactam natural products and drug molecules by using NHC catalysis.
Drawings
FIG. 1 is a nuclear magnetic hydrogen and carbon spectrum of reaction product 3a of example 2.
FIG. 2 is a nuclear magnetic hydrogen and carbon spectrum of reaction product 3b of example 3.
FIG. 3 is a nuclear magnetic hydrogen and carbon spectrum of reaction product 3c of example 4.
FIG. 4 is a nuclear magnetic hydrogen and carbon spectrum of the reaction product 3d of example 5.
FIG. 5 is a nuclear magnetic hydrogen and carbon spectrum of reaction product 3e of example 6.
FIG. 6 is a nuclear magnetic hydrogen and carbon spectrum of the reaction product 3f of example 7.
FIG. 7 is a nuclear magnetic hydrogen spectrum and a carbon spectrum of 3g of the reaction product of example 8.
FIG. 8 is a nuclear magnetic hydrogen and carbon spectra of the reaction product 3h of example 9.
FIG. 9 is a nuclear magnetic hydrogen and carbon spectrum of the reaction product 3i of example 10.
FIG. 10 is a nuclear magnetic hydrogen and carbon spectrum of the reaction product 3j of example 11.
Detailed Description
The following chemicals were all purchased from commercial products. The solvent is a super dry solvent commercially available. Thin Layer Chromatography (TLC) was performed using 60F254 silica gel plates and developed under UV light at 254 nm. 1 H NMR 13 C NMR was characterized using a Bruker 400M NMR instrument with deuterated chloroform as the solvent. The unit of coupling constant is Hz.. Optical rotation was measured using a Jasco P-1030 polarimeter. Enantiomeric excess was determined using Shimadzu LC-20AD HPLC High Resolution Mass Spectrometry (HRMS) using Waters Q-TOF Permier Spectrometer.
Example 1
Preparation of reaction substrates (in the case of 1a,1b,1c and 1d, the preparation is analogous)
Preparation of substrate 1 a: to a 150mL round bottom flask was added 1, 4-naphthoquinone (3.1632 g,20 mmol), tert-butyl N-hydroxycarbamate (2.9293 g,22 mmol), acetonitrile 75mL. After the reaction was completed, the excess solvent was removed by rotary evaporator under reflux at 70 degrees celsius for 12 hours, and purified by chromatography (EA/pe=1:20) to give the final product as yellow powdery solid 1a (3.8225 g,14mmol,70% yield).
The measurement parameters of the prepared (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester are as follows:
1 H NMR(400MHz,CDCl 3 )(400Hz,CDCl 3 ):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,CDCl 3 )(100Hz,CDCl 3 ):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 NO 4 [M] + 273.1001；found 273.1005.
the measurement parameters of the prepared (8-nitro-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester are as follows:
1 H NMR(400MHz,CDCl 3 )δδ＝8.78(1H,s),7.69-7.82(m,2H),7.49(s,1H),1.52(s,9H), 13 C NMR(100MHz,CDCl 3 )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 N 2 O 6 + [M+Na] + 391.0925；Found:391.0922.
the measurement parameters of the prepared (6, 7-dimethyl-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester are as follows:
1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 for C 17 H 19 NNaO 4 + [M+Na + ]:324.1206,found 324.1212.
the measurement parameters of the prepared (8-hydroxy-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester are as follows:
1 H NMR(400MHz,DMSO-D 6 )δ＝11.00(1H,s),8.73(1H,s),7.12(1H,s),7.10(1H,s),1.50(9H,s). 13 C NMR(100MHz,CDCl 3 )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 NO 5 + [M+H + ]:290.1023,found290.1028.
example 2
Preparation of reaction product 3a
The following preparation method is adopted for preparing 3a:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester to synthesize 1a (0.1 mmol) with azaanthrone compound, cinnamaldehyde 2a (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) and then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4-phenylbenzoquinoline-2, 5,10 (1H) -trione, 96% yield, was obtained as follows:
1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 NO 6 (M+H) + :422.1598,Found:422.1590.
example 3
Preparation of reaction product 3b
The following preparation method is adopted for preparing 3b:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester to synthesize 1a (0.1 mmol) with azaxanthones, o-methoxycinnamaldehyde 2b (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added to the mixture as solvent, the reaction system was stirred at room temperature for 10 hours, after TLC monitoring the reaction was complete, the reaction mixture was separated and purified using silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (2-methoxyphenyl) benzoquinoline-2, 5,10 (1H) -trione, 92% yield, was obtained with the following parameters:
1 H NMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 NO 4 (M+H) + :332.0917,Found:332.0911.
example 4
Preparation of reaction product 3c
The following preparation method is adopted for preparing 3c:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, o-trifluoromethyl cinnamaldehyde 2c (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluting with methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (2-trifluoromethyl) phenylbenzoquinoline-2, 5,10 (1H) -trione, 73% yield, was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 F 3 NO 3 + (M+H) + :370.0686,Found:370.0685.
example 5
Preparation of reaction product 3e
The following preparation method is adopted for preparing 3e:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, m-chlorocinnamaldehyde 2e (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (3-chlorophenyl) benzoquinoline-2, 5,10 (1H) -trione (3 e): 84% yield was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 CINO 3 + (M+H) + :336.0422,Found:336.0415.
example 6
Preparation of reaction product 3f
The following preparation method is adopted for preparing 3f:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, p-methoxycinnamaldehyde 2f (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (4-methoxyphenyl) benzoquinoline-2, 5,10 (1H) -trione (3 f): 96% yield was obtained with the following parameters:
1 HNMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 NO 4 + (M+H) + :332.0917,Found:332.0922.
example 7
Preparation of reaction product 3g
The following preparation method is adopted to prepare 3g:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, 2g (0.15 mmol) of o-bromocinnamaldehyde, and azacyclo-carbene (6.2 mg,20 mol%), then 3mL of acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent of methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (2-bromophenyl) benzoquinoline-2, 5,10 (1H) -trione (3 g): 84% yield was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 BrNO 3 + (M+H) + :378.9844,Found:378.9849.
example 8
Preparation of the reaction product 3h
The preparation is carried out for 3 hours by adopting the following preparation method:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, m-trifluorocinnamaldehyde 2h (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (4-trifluoromethyl) phenylbenzoquinoline-2, 5,10 (1H) -trione (3H): 84% yield was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 F 3 NO 3 + (M+H) + :369.0613,Found:369.0619.
example 9
Preparation of reaction product 3i
The following preparation method is adopted for preparing 3i:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, p-chlorocinnamaldehyde 2i (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (4-chlorophenyl) benzoquinoline-2, 5,10 (1H) -trione (3 i): 95% yield was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)δ＝8.38-8.36(m,1H),8.24-8.22(m,1H),8.02-8.00(m,2H),7.56(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,CF 3 COOD)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 CINO 3 + (M+H) + :336.0422,Found:336.0415.
example 10
Preparation of reaction product 3j
The following preparation method is adopted for preparing 3j:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaanthrone compound, (E) -4- (3-oxoprop-1-enyl) phenylacetate 2j (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added to the mixture as solvent, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product methyl 4- (2, 5, 10-trioxo-1, 2,5, 10-tetrahydrobenzo [ g ] quinolin-4-yl) benzoate (3 j): 84% yield, measured parameters are as follows:
1 HNMR(400MHz,CF 3 COOD)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,CF 3 COOD)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 NO 5 + (M+H) + :360.0866,Found:360.0875.
example 11
Preparation of reaction product 3k
The following preparation method is adopted for preparing 3k:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, 3- (3, 5-dichlorophenyl) acrolein 2k (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (3, 4-dichlorophenyl) benzoquinoline-2, 5,10 (1H) -trione (3 k): 93% yield was obtained as follows:
1 H NMR(400MHz,CF 3 COOD)δ＝8.28-8.11(m,1H),8.12(d,J＝8.4Hz,1H),7.90-7.84(m,2H),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,CF 3 COOD)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 CI 2 NO 3 + (M+H) + :370.0032,Found:370.0035.
example 12
Preparation of reaction product 3l
The following preparation method was used to prepare 3l:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, 2l (0.15 mmol) thiophenecarboxamide (6.2 mg,20 mol%) and then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (thiophen-2-yl) benzo [ g ] quinoline-2, 5,10 (1H) -trione (3 l): 97% yield was obtained, the following parameters were determined:
1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 H 9 NO 3 S + (M+H) + :370.0032,Found:307.0039.
example 13
Preparation of reaction product 3m
The preparation is carried out by the following preparation method for 3m:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a complex 1a (0.1 mmol) with azaxanthones, 2m (0.15 mmol) of cinnamaldehyde, and azacarbene (6.2 mg,20 mol%), then 3mL of acetonitrile was added as a solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent of methanol/dichloromethane=1: 20, the product was a yellow solid.
The product 4- (furan-2-yl) benzo [ g ] quinoline-2, 5,10 (1H) -trione (3 m): 90% yield was obtained, the following parameters were determined:
1 H NMR(400MHz,CDCl 3 )δ＝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,CDCl 3 )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 H 9 NO 4 + (M+H) + :291.0532,Found:291.0537.
example 14
Preparation of reaction product 3o
The following preparation method is adopted for preparing 3o:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize a solution with azaxanthone compound 1a (0.1 mmol), crotonaldehyde 2o (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluting with methanol/dichloromethane=1: 20, the product was a yellow solid.
4-methylbenzoquinoline-2, 5,10 (1H) -trione 67% yield, the following parameters were measured:
1 HNMR(400MHz,CF 3 COOD)δ＝8.05-8.03(m,2H),7.64(t,J＝5.2Hz,2H),2.32(s,3H)； 13 C NMR(100MHz,CF 3 COOD)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 NO 3 + (M+H) + :240.0655,Found:240.0658
example 15
Preparation of reaction product 3p
The following preparation method is adopted for preparing 3p:
to a dry test tube was added the substrate (8-ethyl-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize the product with azaanthrone 1c (0.1 mmol), crotonaldehyde 2a (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 16
Preparation of reaction product 3q
The following preparation method is adopted for preparing 3q:
to a dry test tube was added substrate (tert-butyl 6-cyclopropyl-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamate as substrate to synthesize 1d (0.1 mmol) with azaanthrone, cinnamaldehyde 2a (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) and then 3mL acetonitrile as solvent, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid. .
Example 17
Preparation of reaction product 3r
The following preparation method is adopted for preparing 3r:
to a dry test tube was added substrate (5, 8-dimethoxy-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1f (0.1 mmol) with azaanthrone compound, cinnamaldehyde 2a (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) and then 3mL acetonitrile as solvent, the reaction system was stirred at room temperature for 10 hours, after TLC monitoring the reaction completion, the reaction mixture was separated and purified using silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 18
Preparation of reaction product 3s
The following preparation method is adopted for preparation for 3s:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydroanthracene-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1e (0.1 mmol), 3-cyclopropylacrylaldehyde 2p (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) with azaanthrone type compound, then 3mL acetonitrile was added as solvent to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 19
Preparation of reaction product 3t
The following preparation method is adopted for preparing 3t:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydroanthracen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1e (0.1 mmol), 3-furan-2-propenal 2m (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) with azaxanthone, then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 20
Preparation of reaction product 3u
The following preparation method is adopted for preparing 3u:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1a (0.1 mmol) with azaanthrone compound, crotonaldehyde 2o (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 21
Preparation of reaction product 3v
The following preparation method is adopted for preparing 3v:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1a (0.1 mmol), 3-naphthalen-1-propenal 2n (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%) with azaxanthone, then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluting with methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 22
Preparation of reaction product 3w
The following preparation method is adopted for preparing 3w:
to a dry test tube was added substrate (1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize 1a (0.1 mmol) with azaanthrone compound, cinnamaldehyde 2a (0.15 mmol), azacyclo-carbene (6.2 mg,20 mol%), then 3mL acetonitrile as solvent was added to the mixture, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column, eluent methanol/dichloromethane=1: 20, the product was a yellow solid.
Example 23
Preparation of reaction product 3x
The preparation method is adopted for preparing 3x:
to a dry test tube was added the substrate (8-methoxy-1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) carbamic acid tert-butyl ester as substrate to synthesize the product with azaanthrone 1f (0.1 mmol), o-bromocinnamaldehyde (0.15 mmol), azacyclocarbene (6.2 mg,20 mol%) and then 3mL acetonitrile as solvent, the reaction system was stirred at room temperature for 10 hours, and after TLC monitoring the reaction was completed, the reaction mixture was separated and purified using a silica gel column with eluent methanol/dichloromethane=1: 20, the product was a yellow solid.

Claims (10)

1. A synthesis method of an azaanthrone compound is characterized in that tert-butyl naphthoquinone of nitrogen carbamate shown in a formula 1 and aldehyde shown in a formula 2 are adopted as raw materials, N-heterocyclic carbene is used as a catalyst, an oxidant shown in a formula 4, and a solvent is an aprotic solvent, cs 2 CO 3 The method is characterized in that the reaction is carried out under the condition of alkali to obtain a target product compound shown in a formula 3, and 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the 'substituted or unsubstituted' is halogen, trifluoromethyl, ester group and C1-C3 alkoxy;
or 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, hydroxy, nitro; r3 and R4 are jointly substituted to synthesize a phenyl group; r2 is independently selected from hydrogen, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C10 aryl, C4-C6 heterocyclyl; the substituent in the "substituted or unsubstituted" is halogen, trifluoromethyl, ester group, C1-C3 alkoxy.
2. The process according to claim 1, wherein the amino nitrogen group represented by formula 1 is usedTert-butyl naphthoquinone formate and aldehyde shown in formula 2 are used as raw materials, N-heterocyclic carbene is used as a catalyst, oxidant shown in formula 4, and Cs is prepared from aprotic solvent 2 CO 3 The method is characterized in that the reaction is carried out under the condition of alkali to obtain a target product compound shown in a formula 3, and 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the 'substituted or unsubstituted' is halogen, trifluoromethyl, ester group and C1-C3 alkoxy;
or 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, hydroxy, 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, C4-C6 heterocyclyl; the substituent in the "substituted or unsubstituted" is halogen, trifluoromethyl, ester group, C1-C3 alkoxy.
3. The preparation method according to claim 1, wherein the substituent of t-butyl naphthoquinone azocarbamate represented by formula 1 is selected from the group consisting of: hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, pentyl, methoxy, hydroxy, nitro, phenyl.
4. The method of claim 1, wherein the aldehyde substituent of formula 2 is 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, furan.
5. The process according to claim 1, wherein the t-butyl-naphthoquinone-N-carbamate represented by formula 1 is selected from the group consisting of t-butyl-naphthoquinone-N-carbamate represented by formula 1a,1b,1c,1d,1e,1f
6. The process according to claim 1, wherein the aldehyde represented by formula 2 is selected from the group consisting of aldehydes represented by 2a,2b,2c,2d,2e,2f,2g,2h,2i,2j,2k,2l,2m,2n,2o,2p,2q
7. The method of claim 1, wherein the aprotic solvent is selected from acetonitrile, dichloromethane, chloroform, toluene, and dioxane; the N-heterocyclic carbene is selected from catalysts shown as NHC-A, NHC-B, NHC-C, NHC-D and NHC-E
8. The process of claim 1, wherein the t-butylnaphthoquinone azocarbamate is selected from the group consisting of t-butylnaphthoquinone azocarbamate as shown in FIG. 1a, the aldehyde is selected from the group consisting of aldehydes as shown in FIG. 2a,2b,2C,2d,2e,2f,2g,2h,2i,2j,2k,2l,2m,2n,2o,2p,2q, the N-heterocyclic carbene is selected from the group consisting of aldehydes as shown in FIG. 2a,2b,2C,2d,2e,2f,2g,2h, 2j, 2n,2o,2p,2q, the N-heterocyclic carbene is selected from the group consisting of catalysts as shown in NHC-C, and the aprotic solvent is selected from the group consisting of acetonitrile
Or the tert-butyl carbanilate naphthoquinone is selected from tert-butyl carbanilate naphthoquinone shown as 1a,1b,1C,1d,1e and 1f, the aldehyde is selected from aldehyde shown as 2a, the N-heterocyclic carbene is selected from catalyst shown as NHC-C, and the aprotic solvent is selected from acetonitrile
9. The process of claim 1 wherein the t-butyl-naphthoquinone-nitrogen-carbamate is selected from the group consisting of t-butyl-naphthoquinone-nitrogen-carbamate as shown in FIG. 1a, the aldehyde is selected from the group consisting of aldehyde as shown in FIG. 2a, the N-heterocyclic carbene is selected from the group consisting of NHC-C catalyst, and the aprotic solvent is selected from the group consisting of acetonitrile
10. The process according to claim 1, wherein the synthesis is carried out at a temperature of 0 to 40 ℃; and/or the reaction is carried out for 10 to 48 hours; and/or the molar ratio of said t-butyl carbanilate naphthoquinone to said aldehyde is 5:1 to 1:5, a step of; and/or the catalyst is used in an amount of 10 to 50mol% based on the mass ratio of the tert-butyl azodicarbonate naphthoquinone.
CN202310934429.7A 2023-07-27 2023-07-28 Synthesis method of azaanthrone compound Pending CN117466815A (en)

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