CN115626889B - Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound - Google Patents

Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound Download PDF

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CN115626889B
CN115626889B CN202211265495.1A CN202211265495A CN115626889B CN 115626889 B CN115626889 B CN 115626889B CN 202211265495 A CN202211265495 A CN 202211265495A CN 115626889 B CN115626889 B CN 115626889B
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nitrogen
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CN115626889A (en
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贾振华
吕永恒
张振国
罗德平
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Nanjing Yaojiayuan Biomedical Co ltd
Nanjing Tech University
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Nanjing Yaojiayuan Biomedical Co ltd
Nanjing Tech University
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Abstract

The invention provides an organic chemical conversion method for oxidative dehydrogenation of a nitrogen-containing heterocyclic compound. The catalyst required in the preparation method is a non-metal catalyst, and compared with the existing metal catalyzed synthesis method, the synthesis process is easier to purify, and the toxicity problem caused by metal residues is avoided. The preparation method has the advantages that the required reaction raw materials (the aza-cycle compound or the derivative thereof) are cheap and easy to obtain, the compound after dehydrogenation aromatization is obtained by a one-step method, the problem that the existing synthesis method is excessively complicated in reaction is solved, compared with the existing synthesis method, the method has mild conditions and the temperature of 70 ℃, only needs oxygen to participate, is simple to operate, and only needs to add 3mol% Ph 3C+[B(C6F5)4]‑ and 10mol% TEMPO additive, compared with other reactions with stoichiometric additives, the method has the advantages of low cost, high reaction efficiency and high atom economy, can effectively reduce the generation of chemical waste, and reduces environmental pollution.

Description

Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a preparation method of a metal-free catalytic nitrogen heterocyclic compound dehydrogenation aryl.
Background
Nitrogen-containing heterocycles occupy an important role in heterocyclic compounds, and in the prescription drugs on the market in 2018 all america, the total number of nitrogen-containing oxygen-containing heterocyclic compounds is 106, which accounts for more than half. The nitrogenous heterocycle is a common substance in organism metabolites, has unique activity, low toxicity and high intracellular absorbability, is commonly applied to products such as medicines, pesticides, dyes and the like, and is widely known that most of the compounds in alkaloids are nitrogenous heterocycles, are core basic skeletons of a plurality of drug molecules, have special properties, and are key structures for the curative effects of a plurality of medicaments, such as local anesthesia, antiviral, antitubercular and the like. Through decades of development, the nitrogen-containing heterocycle is not only used for medicines, pesticides and industries, but also used for multifunctional materials and dyes, and is characterized in that the structural framework is easy to modify, so that the nitrogen-containing heterocycle can be designed into substances with biological activity or organic functional materials, such as classical 1,2, 3-triazole, 1,3, 5-triazine, isothiazole and thiazole, and plays roles in medicines and pesticides, chemical materials, multifunctional lubricating oil, organic photoelectric functional materials and dye sensitized solar cells.
In recent years, conventional methods with various catalytic bodies have appeared. From the perspective of aerobic dehydrogenation, various methods of transition metal-catalyzed dehydroaromatization of nitrogen heterocyclic compounds, such as Pd, ru, ir, cu, fe, co, ni and Zn, etc., have been developed, the use of transition metals inevitably generates chemical wastes, and may introduce toxic contaminants into the target product. However, the use of stoichiometric oxidants or noble metals is not desirable from an environmental and economic standpoint. Although many excellent catalytic systems have been explored under relatively mild conditions, most of these processes are based on the use of noble metals. Therefore, the development of the nonmetal-mediated aerobic oxidation reaction process has more practical application value.
To date, few reports have been made on nonmetallic catalyzed dehydroaromatization of nitrogen heterocycles. Therefore, there is a need in the art for a method of dehydroaromatizing nitrogen heterocycles that is green, efficient, atom economical, mild in reaction conditions and wide in substrate application.
Disclosure of Invention
The invention aims to provide an organic chemical conversion method for oxidative dehydrogenation of a nitrogen-containing heterocyclic compound, which is prepared by a method with the advantages of greenness, high efficiency, high atom economy, milder reaction conditions and wider application range of a substrate.
In order to solve the technical problems of the invention, the technical proposal is as follows: an organic chemical conversion method for oxidative dehydrogenation of a nitrogen-containing heterocyclic compound, wherein the preparation route is as follows:
in the above nitrogen heterocyclic compound formula (I) and target product formula (II),
R is any one of hydrogen and methyl:
FG is any one of hydrogen, methyl, ethoxyacyl, fluorine, chlorine, bromine, iodine, methoxy, methoxyacyl, cyano, acetyl, nitro, hydroxyl, carboxyl, ortho-nitrophenyl, p-chlorophenyl, meta-nitrophenyl, 2-methoxyethoxyacyl, cinnamyl formate and isopropyl formate;
n is any one of 0 and 1;
Het is an unsaturated nitrogen-containing heterocycle;
the preparation method comprises the following specific steps:
(1) Sequentially adding an aza-cycle compound (I) and a catalyst of triphenylcarbon tetra (pentafluorophenyl) borate Ph 3C+[B(C6F5)4]- and 2, 6-tetramethylpiperidine oxide (TEMPO) into a reactor under an oxygen atmosphere, and then adding an organic solvent isopropanol to obtain a mixture, wherein the mole volume ratio of the aza-cycle compound, the triphenylcarbon tetra (pentafluorophenyl) borate (Ph 3C+[B(C6F5)4]-) and the 2, 6-tetramethylpiperidine oxide (TEMPO), and the organic solvent isopropanol is as follows: 0.2mmol to 10mmol:0.006mmol to 0.3mmol:0.02mmol to 1mmol:1 mL-20 mL;
(2) Transferring the reaction bottle to a heating device for heating reaction for 1-12 hours, and rapidly stirring for reaction, and after TLC detection reaction is completed, separating and purifying to obtain a corresponding target product formula (II).
Preferably, in the step (1), the molar volume ratio of the aza-cycle compound (I) to the catalyst triphenylcarbon tetra (pentafluorophenyl) borate Ph 3C+[B(C6F5)4]- to the 2, 6-tetramethylpiperidine oxide (TEMPO) to the solvent is added as follows: 0.2mmol:0.06mmol:0.02mmol:1mL; in step (2), the heating temperature was 70℃and the reaction time was 12 hours.
Preferably, the method comprises the steps of, in step (1), the azaheterocyclic compound is indoline, N-methylindoline, indoline-1-carboxylic acid ethyl ester, 1-methylindoline, 5-fluoroindoline, 5-chloroindoline, 5-bromoindoline, 5-methoxyindoline, indoline-5-carboxylic acid methyl ester, 5-cyanoindoline, 5-acetylindoline, 6-nitroindoline, tetrahydroquinoline, 1-tetrahydromethylquinoline, 6-methoxytetrahydroquinoline, 6-hydroxytetrahydroquinoline, 6-fluorotetrahydroquinoline, 6-chlorotetrahydroquinoline, tetrahydroquinoline-6-carboxylic acid methyl ester 6-carboxytetrahydroquinoline, 6-nitrotetrahydroquinoline, 1,2,3, 4-tetrahydroisoquinoline, 7-methyl-1, 2,3, 4-tetrahydroisoquinoline, 6-bromo-1, 2,3, 4-tetrahydroisoquinoline, diethyl 2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate, dimethyl 2, 6-dimethyl-4- (2-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, dimethyl 4- (4-chlorophenyl) -2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate, 3-cinnamyl 5- (2-methoxyethyl) 2, 6-dimethyl-4- (3-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, any one of 3-cinnamyl 5- (2-methoxyethyl) 2, 6-dimethyl-4- (3-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, 1,2,3, 4-tetrahydroquinoxaline, 9, 10-dihydroacridine, 2,3,4, 5-tetrahydro-1H-pyrido [4,3-b ] indole, 2,3,4, 9-tetrahydro-1H-pyrido [3,4-b ] indole, 2-phenyl-2, 3-dihydrobenzo [ d ] oxazole, 2-phenyl-2, 3-dihydrobenzo [ d ] thiazole.
Preferably, the nitrogen heterocyclic compound is shown as formula (II) and is any one of the following nitrogen heterocyclic compounds:
preferably, the synthesis method of the formula (II) is any one of the following indole compound synthesis methods.
The invention overcomes the defects of the prior art and provides an organic chemical conversion method for oxidative dehydrogenation of a nitrogen-containing heterocyclic compound, which has the following beneficial effects compared with the defects and the shortcomings of the prior art:
(1) The catalyst required in the preparation method is a non-metal catalyst, and compared with the existing metal catalyzed synthesis method, the synthesis process is easier to purify, and the toxicity problem caused by metal residues is avoided. The preparation method has the advantages that the required reaction raw materials (the nitrogen heterocyclic compound or the derivative thereof) are cheap and easy to obtain, the compound after dehydrogenation aromatization is obtained by a one-step method, the problem that the existing synthesis method is excessively complicated in reaction is solved, compared with the existing synthesis method, the method has mild conditions and the temperature of 70 ℃, only needs oxygen to participate, is simple to operate, and only needs to add 3mol% Ph 3C+[B(C6F5)4]- and 10mol% TEMPO additive, compared with other reactions with stoichiometric additives, the cost is low, the reaction efficiency is high, the atom economy is high, and the generation of chemical waste can be effectively reduced. Can reduce environmental pollution and meet the requirement of sustainable development.
(2) The catalyst required in the preparation method is a nonmetallic catalyst, the catalyst is economical and easy to obtain, a complex synthesis method is not needed, compared with the existing stoichiometric catalyst or heavy metal catalyst synthesis method, the catalytic amount of the nonmetallic catalyst can be used for dehydrogenating and aromatizing the nitrogen heterocyclic compound, and the catalyst has the advantages of being richer, cheaper, smaller in toxicity, high in atom economy, free of adding an additional oxidant, only needing oxygen to participate, capable of effectively reducing the generation of chemical waste and the like.
(3) In the preparation method, compared with the existing synthesis method, the compatibility of the substrate functional group has wider range of the synthesized substrate and good universality.
(4) In the step (2), the heating temperature is 70 ℃, the optimal reaction temperature is 70 ℃, and the reaction temperature is reduced, so that the smooth reaction is not facilitated, and the reaction effect is not improved any more when the reaction temperature is increased. The reaction time was 12 hours, and the comparison of the reaction time showed that the reaction was extended to 12 hours to complete the reaction. The mole volume ratio of the nitrogen heterocyclic compound, the ion pair, the additive and the solvent is as follows: 0.2mmol:0.006mmol:0.02mmol:1mL. The catalyst dosage is reduced, and the yield of the target product starts to be correspondingly reduced.
Drawings
Nuclear magnetic hydrogen Spectrometry (1H NMR 400MHz,CDCl3) for Compound 1 of FIG. 1
FIG. 2 Nuclear magnetic resonance spectrum of Compound 2 (13C NMR 100MHz,CDCl3)
Detailed Description
The present invention will be further described in detail and fully illustrated in the following examples, which are set forth to facilitate an understanding of the present invention, but are not to be construed as limiting the scope of the present subject matter to the following examples, all techniques being accomplished based on the foregoing disclosure of the present invention.
General description:
abbreviations are used in the examples and have the following meanings:
Me is methyl, et is a radical, boc is t-butoxycarbonyl, ph is phenyl, 1,4-Dioxane is 1,4-Dioxane, DCM is dichloromethane, PE is petroleum ether, and EA is ethyl acetate. TLC is thin layer chromatography, NMR is nuclear magnetic resonance, HRMS is high resolution mass spectrometry.
The solvent is purified by standard method and dried before use; all reagents are commercially available or synthesized according to the prior literature methods and purified prior to use.
Example 1:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 23mg of the objective compound in 94% yield.
1H-indole(1)
TLC:Rf＝0.46(silica gel,PE/EA,50:1),(23mg,94％yield),white solid.1H NMR(400MHz,CDCl3)δ8.14(s,1H),7.67(dt,J＝7.8,1.2Hz,1H),7.46-7.37(m,1H),7.25-7.18(m,2H),7.17-7.09(m,1H),6.63-6.52(m,1H).13C NMR(101MHz,CDCl3)δ135.84,127.92,124.22,122.07,120.82,119.90,111.13,102.71.
Example 2:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 16mg of the objective compound in 61% yield.
1-methyl-1H-indole(2)
TLC:Rf＝0.45(silica gel,PE/EA,50:1),(16mg,61％yield),colorless oil.1H NMR(400MHz,CDCl3)δ7.65(dt,J＝7.9,1.0Hz,1H),7.35(dq,J＝8.2,0.9Hz,1H),7.25(ddd,J＝8.2,7.0,1.2Hz,1H),7.13(ddd,J＝8.0,7.0,1.1Hz,1H),7.07(d,J＝3.1Hz,1H),6.51(dd,J＝3.1,0.9Hz,1H),3.81(s,3H).13C NMR(101MHz,CDCl3)δ136.76,128.90,128.54,121.57,120.96,119.35,109.28,100.96,32.93.
Example 3:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound (25.5 mg, yield 67%).
ethyl 1H-indole-2-carboxylate(3)
TLC:Rf＝0.52(silica gel,PE/EA,5:1),(25.5mg,67％yield),white solid.1H NMR(400MHz,CDCl3)δ9.07(s,1H),7.70(dd,J＝8.1,1.1Hz,1H),7.44(dd,J＝8.3,1.1Hz,1H),7.33(ddd,J＝8.3,7.0,1.2Hz,1H),7.24(dd,J＝2.1,1.0Hz,1H),7.16(ddd,J＝8.0,6.9,1.0Hz,1H),4.43(q,J＝7.1Hz,2H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ162.22,136.93,128.04,127.59,125.44,122.71,120.88,111.99,108.74,61.17,14.51.
Example 4:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 24mg of the objective compound in 93% yield.
2-methyl-1H-indole(4)
TLC:Rf＝0.62(silica gel,PE/EA,20:1),(24mg,93％yield),white solid.1H NMR(400MHz,CDCl3)δ7.79(s,1H),7.54(d,J＝6.0Hz,1H),7.29(dt,J＝7.9,1.0Hz,1H),7.12(dtd,J＝17.1,7.1,1.3Hz,2H),6.24(dt,J＝2.2,1.1Hz,1H),2.45(d,J＝1.0Hz,3H).13C NMR(101MHz,CDCl3)δ136.13,135.18,129.15,121.03,119.74,110.32,100.48,13.83.
Example 5:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 21mg of the objective compound in 78% yield.
5-fluoro-1H-indole(5)
TLC:Rf＝0.45(silica gel,PE/EA,20:1),(21mg,78％yield),off-white solid.
1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.30(d,J＝2.0Hz,1H),7.29(d,J＝3.4Hz,1H),7.24(t,J＝2.8Hz,1H),6.96(td,J＝9.1,2.5Hz,1H),6.53(ddd,J＝3.1,2.0,0.9Hz,1H).13C NMR(101MHz,CDCl3)δ158.3(d,J＝274.8),132.4,128.1(d,J＝57.9),126.4,111.7(d,J＝10.1),110.5(d,J＝26.5),105.5(d,J＝23.5),102.9(d,J＝4.4).19F NMR(376MHz,CDCl3)δ-124.8.
Example 6:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 24mg of the objective compound in 80% yield.
5-chloro-1H-indole(6)
TLC:Rf＝0.40(silica gel,PE/EA,20:1),(24mg,80％yield),white solid.1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.62(d,J＝2.0Hz,1H),7.31(d,J＝8.6Hz,1H),7.23(t,J＝2.9Hz,1H),7.16(dd,J＝8.6,2.0Hz,1H),6.54-6.48(m,1H).13C NMR(101MHz,CDCl3)δ134.21,129.04,125.62,125.56,122.42,120.22,112.08,102.51.
Example 7:
a process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 36mg in 93% yield.
5-bromo-1H-indole(7)
TLC:Rf＝0.44(silica gel,PE/EA,20:1),(36mg,93％yield),brown solid.1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.81(d,J＝1.7Hz,1H),7.33-7.27(m,2H),7.22(t,J＝2.8Hz,1H),6.52(t,J＝2.6Hz,1H).13C NMR(101MHz,CDCl3)δ134.47,129.71,125.55,124.93,123.33,113.13,112.61,102.38.
Example 8:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 26mg of the objective compound in 86% yield.
5-methoxy-1H-indole(8)
TLC:Rf＝0.45(silica gel,PE/EA,20:1),(26mg,86％yield),white solid.1H NMR(400MHz,CDCl3)δ8.05(s,1H),7.27(d,J＝8.8Hz,1H),7.17(t,J＝2.8Hz,1H),7.13(dd,J＝4.7,2.2Hz,1H),6.89(ddt,J＝8.8,6.6,2.5Hz,1H),6.50(tdt,J＝3.1,2.1,1.0Hz,1H),3.86(s,3H).13C NMR(101MHz,CDCl3)δ154.28,131.06,128.38,125.01,112.46,111.85,102.47,102.40,55.97.
Example 9:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 14mg of the objective compound in 40% yield.
methyl 1H-indole-5-carboxylate(9)
TLC:Rf＝0.54(silica gel,PE/EA,10:1),(14mg,40％yield),white solid.1H NMR(400MHz,CDCl3)δ8.51(s,1H),8.43(dt,J＝1.6,0.8Hz,1H),7.91(dd,J＝8.6,1.7Hz,1H),7.41(dt,J＝8.6,0.9Hz,1H),7.27(dd,J＝3.3,2.3Hz,1H),6.65(ddd,J＝3.2,2.0,0.9Hz,1H),3.94(s,3H).13C NMR(101MHz,CDCl3)δ168.43,138.50,127.56,125.65,123.89,123.47,121.98,109.94,103.50,52.00.
Example 10:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 13mg in 46% yield.
1H-indole-5-carbonitrile(10)
TLC:Rf＝0.48(silica gel,PE/EA,20:1),(13mg,46％yield),white solid.1H NMR(400MHz,CDCl3)δ8.69(s,1H),8.00(t,J＝1.2Hz,1H),7.49-7.40(m,2H),7.35(dd,J＝3.3,2.4Hz,1H),6.63(ddd,J＝3.1,2.0,0.9Hz,1H).13C NMR(101MHz,CDCl3)δ137.60,127.75,126.60,126.52,124.98,120.99,112.13,103.53,102.86.
Example 11:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 31mg of the objective compound in 98% yield.
1-(1H-indol-5-yl)ethan-1-one(11)
TLC:Rf＝0.42(silica gel,PE/EA,20:1),(31mg,98％yield),white solid.1H NMR(400MHz,CDCl3)δ8.77(s,1H),8.35-8.30(m,1H),7.87(dd,J＝8.6,1.7Hz,1H),7.41(d,J＝8.7Hz,1H),7.28(dd,J＝3.3,2.3Hz,1H),6.69-6.63(m,1H),2.67(s,3H).13C NMR(101MHz,CDCl3)δ198.91,138.62,129.93,127.49,125.98,123.26,122.31,111.19,104.31,26.83.
Example 12:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound (31 mg, yield 99%).
6-nitro-1H-indole(12)
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(31mg,99％yield),yellow solid.1H NMR(400MHz,CDCl3)δ8.88(s,1H),8.42(d,J＝2.1Hz,1H),8.02(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.52(t,J＝2.9Hz,1H),6.66(ddd,J＝3.1,1.9,1.0Hz,1H).13C NMR(101MHz,CDCl3)δ143.23,134.36,132.98,130.37,120.71,115.45,107.78,103.66.
Example 13:
a process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 18mg of the objective compound in 70% yield.
Quinoline(13)
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(18mg,70％yield),pale purple oil.1H NMR(400MHz,CDCl3)δ8.91(dd,J＝4.2,1.8Hz,1H),8.15(dd,J＝8.3,1.7Hz,1H),8.10(d,J＝8.5Hz,1H),7.81(dd,J＝8.1,1.4Hz,1H),7.71(ddd,J＝8.5,6.8,1.5Hz,1H),7.54(ddd,J＝8.2,6.9,1.3Hz,1H),7.39(dd,J＝8.3,4.1Hz,1H).13C NMR(101MHz,CDCl3)δ150.54,148.36,136.18,131.26,129.57,128.38,127.90,126.65,121.19.
Example 14:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound (25.5 mg, yield 67%).
Example 15:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound (23 mg, yield 79%).
2-methylquinoline(15)
TLC:Rf＝0.42(silica gel,PE/EA,5:1),(23mg,79％yield),yellow oil.1H NMR(400MHz,CDCl3)δ8.03(dd,J＝11.5,8.3Hz,2H),7.76(dd,J＝8.3,1.5Hz,1H),7.67(ddd,J＝8.5,6.9,1.5Hz,1H),7.47(ddd,J＝8.1,6.9,1.2Hz,1H),7.28(d,J＝8.3Hz,1H),2.74(s,3H).13C NMR(101MHz,CDCl3)δ159.10,147.85,136.37,129.59,128.63,127.60,126.57,125.80,122.13,25.47.
Example 16:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 29mg of the objective compound in 91% yield.
6-methoxyquinoline(16)
TLC:Rf＝0.50(silica gel,PE/EA,5:1),(29mg,91％yield),white powder.1H NMR(400MHz,CDCl3)δ8.75(dd,J＝4.3,1.8Hz,1H),8.04(d,J＝8.2Hz,1H),7.99(d,J＝9.2Hz,1H),7.40-7.30(m,2H),7.05(d,J＝2.7Hz,1H),3.92(s,3H).13C NMR(101MHz,CDCl3)δ157.79,148.01,144.44,134.94,130.91,129.38,122.43,121.48,105.13,55.64.
Example 17:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 26mg of the objective compound in 87% yield.
6-fluoroquinoline(17)
TLC:Rf＝0.38(silica gel,PE/EA,10:1),(26mg,87％yield),white solid.1H NMR(400MHz,CDCl3)δ8.86(dd,J＝4.2,1.7Hz,1H),8.08(dd,J＝9.0,5.4Hz,2H),7.51-7.43(m,1H),7.39(ddd,J＝8.8,5.5,3.4Hz,2H).13C NMR(101MHz,CDCl3)δ160.46(d,J＝248.2Hz),149.79(d,J＝2.8Hz),145.46,135.52(d,J＝5.4Hz),132.07(d,J＝9.2Hz),128.96(d,J＝10.0Hz),121.87,119.85(d,J＝25.7Hz),110.79(d,J＝21.6Hz).19F NMR(376MHz,CDCl3)δ-113.1.
Example 18:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound (20 mg, yield 61%).
6-chloroquinoline(18)
TLC:Rf＝0.52(silica gel,PE/EA,5:1),(20mg,61％yield),white solid.1H NMR(400MHz,CDCl3)δ8.90(dd,J＝4.3,1.7Hz,1H),8.09-8.05(m,1H),8.04(d,J＝9.3Hz,1H),7.79(d,J＝2.3Hz,1H),7.64(dd,J＝8.9,2.3Hz,1H),7.41(dd,J＝8.3,4.2Hz,1H).13C NMR(101MHz,CDCl3)δ149.83,145.73,135.24,132.39,131.22,130.52,128.93,126.52,122.02.
Example 19:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 30mg in 78% yield.
methyl quinoline-6-carboxylate(26)
TLC:Rf＝0.48(silica gel,PE/EA,5:1),(30mg,78％yield),white solid.1H NMR(400MHz,CDCl3)δ8.98(dd,J＝4.2,1.7Hz,1H),8.56(d,J＝1.9Hz,1H),8.26(ddd,J＝15.4,8.5,2.1Hz,2H),8.12(d,J＝8.8Hz,1H),7.45(dd,J＝8.3,4.3Hz,1H),3.97(s,3H).13C NMR(101MHz,CDCl3)δ163.62,152.62,146.78,136.08,131.11,129.90,129.05,128.18,126.35,121.95,52.01.
Example 20:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 28mg in 81% yield.
quinoline-6-carboxylic acid(20)
TLC:Rf＝0.32(silica gel,PE/EA,1:1),(28mg,81％yield),beige powder.1H NMR(400MHz,DMSO-d6)δ8.98(dd,J＝4.3,1.8Hz,1H),8.65(d,J＝1.9Hz,1H),8.54(dd,J＝8.5,1.8Hz,1H),8.18(dd,J＝8.8,2.0Hz,1H),8.06(d,J＝8.8Hz,1H),7.59(dd,J＝8.4,4.2Hz,1H).13C NMR(101MHz,DMSO-d6)δ167.52,153.25,149.85,138.06,131.52,129.85,129.30,129.06,127.71,122.78.
Example 21:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 18mg of the objective compound in 51% yield.
6-nitroquinoline(21)
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(18mg,51％yield),pale yellow solid.1H NMR(400MHz,CDCl3)δ9.10(dd,J＝4.3,1.8Hz,1H),8.81(d,J＝2.5Hz,1H),8.49(dd,J＝9.2,2.5Hz,1H),8.37(dd,J＝8.2,1.7Hz,1H),8.24(d,J＝9.2Hz,1H),7.59(dd,J＝8.3,4.2Hz,1H).13C NMR(101MHz,CDCl3)δ153.22,150.31,137.26,131.53,127.14,124.09,123.04.
Example 22:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 26mg of the objective compound in 61% yield.
6-bromo-3,4-dihydroisoquinoline(22)
TLC:Rf＝0.46(silica gel,PE/EA,1:1),(26mg,61％yield),brown solid.1H NMR(400MHz,CDCl3)δ8.29(s,1H),7.43(dd,J＝8.0,1.9Hz,1H),7.31(d,J＝1.0Hz,1H),7.13(d,J＝8.1Hz,1H),3.75(ddd,J＝10.0,6.3,2.2Hz,2H),2.76-2.68(m,2H).13C NMR(101MHz,CDCl3)δ159.51,137.96,130.70,130.41,128.72,127.23,125.28,46.49,24.83.
Example 23:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 21mg of the objective compound in 80% yield.
3,4-dihydroisoquinoline(23)
TLC:Rf＝0.50(silica gel,PE/EA,1:1),(21mg,80％yield),white solid.1H NMR(400MHz,CDCl3)δ8.33(t,J＝2.2Hz,1H),7.34(dd,J＝7.1,2.1Hz,1H),7.28(dd,J＝7.5,1.5Hz,2H),7.15(d,J＝8.3Hz,1H),3.81-3.69(m,2H),2.79-2.70(m,2H).13C NMR(101MHz,CDCl3)δ160.51,136.44,131.18,128.58,127.53,127.33,127.19,47.01,25.66.
Example 24:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 22mg of the objective compound in 76% yield.
7-methyl-3,4-dihydroisoquinoline(24)
TLC:Rf＝0.54(silica gel,PE/EA,1:1),(22mg,76％yield),white solid.1H NMR(400MHz,CDCl3)δ8.28(t,J＝2.2Hz,1H),7.16(dd,J＝7.7,1.8Hz,1H),7.08(d,J＝1.9Hz,1H),7.04(d,J＝7.6Hz,1H),3.78-3.69(m,2H),2.74-2.65(m,2H),2.34(s,3H).13C NMR(101MHz,CDCl3)δ162.69,138.68,134.84,131.85,129.08,128.02,126.27,46.05,29.35,22.04.
Example 25:
a process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 48mg of the objective compound in 96% yield.
diethyl 2,6-dimethylpyridine-3,5-dicarboxylate(25)
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(48mg,96％yield),white solid.1H NMR(400MHz,CDCl3)δ8.67(s,1H),4.39(q,J＝7.2Hz,4H),2.84(s,6H),1.41(t,J＝7.2Hz,6H).13C NMR(101MHz,CDCl3)δ166.06,162.35,141.04,123.12,61.53,25.11,14.38.
Example 26:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 42mg of the objective compound in 61% yield.
dimethyl 2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylate(26)
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(42mg,61％yield),yellow solid.1H NMR(400MHz,CDCl3)δ8.20(dd,J＝8.2,1.3Hz,1H),7.67-7.52(m,2H),7.19(dd,J＝7.6,1.5Hz,1H),3.49(s,6H),2.64(s,6H).13C NMR(101MHz,CDCl3)δ167.39,157.20,147.65,145.20,133.08,132.07,130.69,129.70,124.80,124.44,52.33,23.82.
Example 27:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 51mg in 78% yield.
dimethyl 4-(4-chlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate(27)
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(51mg,78％yield),white solid.1H NMR(400MHz,CDCl3)δ7.35(dd,J＝8.7,2.3Hz,2H),7.20-7.11(m,2H),3.56(s,6H),2.58(s,6H).13C NMR(101MHz,CDCl3)δ165.05,152.60,143.75,136.24,129.33,128.62,124.30,49.26,21.18.
Example 28:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 77mg of the target compound in 79% yield.
3-cinnamyl 5-(2-methoxyethyl)2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate(28)
TLC:Rf＝0.40(silica gel,PE/EA,5:1),(77mg,79％yield),pale yellow solid.1H NMR(400MHz,CDCl3)δ8.15(t,J＝2.0Hz,1H),7.98(ddd,J＝8.3,2.3,1.1Hz,1H),7.56(ddd,J＝7.6,1.8,1.1Hz,1H),7.40(t,J＝7.9Hz,1H),7.35-7.28(m,3H),7.24-7.21(m,2H),6.44(d,J＝15.8Hz,1H),5.84(dt,J＝15.8,7.0Hz,1H),4.62(dd,J＝7.0,1.2Hz,2H),4.10(s,2H),3.31(t,J＝4.6Hz,2H),3.20(s,3H),2.63(d,J＝3.1Hz,6H).13C NMR(101MHz,CDCl3)δ167.24,167.07,156.47,156.37,147.85,143.85,137.75,136.01,135.73,134.39,129.21,128.79,128.58,126.68,126.39,126.37,123.50,123.47,121.16,69.86,66.32,64.45,58.83,29.79,23.24.
Example 29:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 57mg of the objective compound in 69% yield.
3-isopropyl 5-(2-methoxyethyl)2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate(29)
TLC:Rf＝0.38(silica gel,PE/EA,5:1),(57mg,69％yield),white solid.1H NMR(400MHz,CDCl3)δ8.29-8.22(m,1H),8.19(q,J＝2.1Hz,1H),7.63-7.53(m,2H),4.93(ddd,J＝10.3,7.3,5.2Hz,1H),4.12(s,2H),3.33(t,J＝4.6Hz,2H),3.22(s,3H),2.63(s,3H),2.62(s,3H),1.03-0.99(m,6H).13C NMR(101MHz,CDCl3)δ167.29,166.75,156.17,156.10,147.94,143.51,138.06,134.55,129.72,126.99,126.32,124.07,123.44,69.88,69.69,64.43,58.84,23.22,23.10,21.37.
Example 30:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 21mg of the objective compound in 82% yield.
Quinoxaline(30)
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(21mg,82％yield),brown solid.1H NMR(400MHz,CDCl3)δ8.85(s,2H),8.16-8.07(m,2H),7.83-7.74(m,2H).13C NMR(101MHz,CDCl3)δ145.10,143.13,132.85,128.78.
Example 31:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give the objective compound 32mg in 89% yield.
Acridine(31)
TLC:Rf＝0.54(silica gel,PE/EA,5:1),(32mg,89％yield),yellow solid.1H NMR(400MHz,CDCl3)δ8.77(s,1H),8.24(dq,J＝8.8,0.9Hz,2H),8.00(dt,J＝8.6,1.0Hz,2H),7.78(ddd,J＝8.8,6.6,1.5Hz,2H),7.53(ddd,J＝8.1,6.6,1.1Hz,2H).13C NMR(101MHz,CDCl3)δ149.13,136.24,130.46,129.45,128.33,126.69,125.81.
Example 32:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 26mg of the objective compound in 76% yield.
9H-pyrido[3,4-b]indole(32)
TLC:Rf＝0.40(silica gel,PE/EA,2:1),(26mg,76％yield),yellow solid.1H NMR(400MHz,CDCl3)δ8.92(s,1H),8.68(s,1H),8.46(d,J＝5.3Hz,1H),8.14(d,J＝7.9Hz,1H),7.97(d,J＝5.2Hz,1H),7.60-7.49(m,2H),7.30(ddd,J＝8.0,6.6,1.5Hz,1H).13C NMR(101MHz,CDCl3)δ140.54,139.18,135.72,133.67,129.14,128.71,121.93,121.55,120.31,114.89,112.43.
Example 33:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 16mg of the objective compound in 47% yield.
5H-pyrido[4,3-b]indole(33)
TLC:Rf＝0.46(silica gel,PE/EA,1:1),(16mg,47％yield),yellow solid.
1H NMR(400MHz,CDCl3)δ9.33(s,1H),8.50(d,J＝5.6Hz,1H),8.14(d,J＝7.8Hz,1H),7.58-7.48(m,2H),7.42(d,J＝5.8Hz,1H),7.34(ddd,J＝8.0,5.5,2.6Hz,1H).13C NMR(101MHz,CDCl3)δ144.30,143.84,141.97,139.66,127.40,121.46,121.22,120.85,120.56,111.45,106.57.
Example 34:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 29mg of the target compound in 74% yield.
2-phenylbenzo[d]oxazole(34)
TLC:Rf＝0.54(silica gel,PE/EA,5:1),(29mg,74％yield),white solid.1H NMR(400MHz,CDCl3)δ8.30-8.21(m,2H),7.82-7.73(m,1H),7.63-7.54(m,1H),7.53(dd,J＝5.1,2.0Hz,3H),7.40-7.31(m,2H).13C NMR(101MHz,CDCl3)δ163.15,150.86,142.20,131.64,129.03,127.72,127.26,125.22,124.69,120.12,110.71,1.13.
Example 35:
A process for the preparation of an azacyclic compound: 25mL Schlenk tube is taken, stirring magnetic seeds with proper size are prepared, ph 3C+[B(C6F5)4]- 5.6.6 mg, TEMPO 3.1mg, indoline compound 0.2mmol are accurately weighed in sequence, the reaction system is substituted for oxygen for 3 times, isopropanol 1mL is added, the mixture is sealed and placed at 70 ℃, and the mixture is heated and vigorously stirred for 12 hours until complete reaction is achieved, and TLC detection is carried out. After the reaction was completed, the mixture was diluted with EA (2 mL). The organic solvent was concentrated under reduced pressure and purified by silica gel column chromatography to give 67mg of the objective compound in 67% yield.
2-phenylbenzo[d]thiazole(35)
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(28mg,67％yield),pale yellow solid.1H NMR(400MHz,CDCl3)δ8.14-8.04(m,3H),7.90(dt,J＝7.9,0.9Hz,1H),7.55-7.45(m,4H),7.38(ddd,J＝8.3,7.2,1.2Hz,1H).13C NMR(101MHz,CDCl3)δ168.20,154.24,135.16,133.71,131.10,129.14,127.67,126.44,125.31,123.34,121.74.
Comparative example one: comparison of catalysts
Other ion pairs are selected to replace the ion pair catalyst Ph 3C+[B(C6F5)4]-, the reaction effect is greatly reduced, and the ion pair catalyst Ph 3C+[B(C6F5)4]- has the best reaction effect under the catalytic system.
Comparative example two: comparison of reaction temperatures
The optimal reaction temperature is 80 ℃, and the smooth reaction is not facilitated when the reaction temperature is reduced, and the reaction effect is not improved any more when the reaction temperature is increased.
Comparative example three: comparative catalyst usage
In order to fully exert the catalytic efficiency of the ion to the catalyst Ph 3C+[B(C6F5)4]-, the catalyst amount can be reduced to 3mol%.
Comparative example four: comparison of reaction time
Comparison of the reaction times shows that the reaction is extended to 12 hours to complete the reaction.
Comparative example five: comparison of additives
Other additives replace TEMPO as a reaction additive, and the yield of target products is reduced to different degrees, so that the catalyst loses catalytic activity.
Comparative example six: comparison of reaction solvents
Other solvents replace isopropanol as a reaction solvent, so that the yield of target products is reduced to different degrees and even the catalyst loses catalytic activity.

Claims (3)

1. An organic chemical conversion method for oxidative dehydrogenation of a nitrogen-containing heterocyclic compound is characterized by comprising the following preparation routes:
The azaheterocyclic compound in the preparation route has the formula (I) indoline, N-methylindoline, indoline-1-carboxylic acid ethyl ester, 1-methylindoline, 5-fluoroindoline, 5-chloroindoline, 5-bromoindoline, 5-methoxyindoline, indoline-5-carboxylic acid methyl ester, 5-cyanoindoline, 5-acetylindoline, 6-nitroindoline, tetrahydroquinoline, 1-tetrahydromethylquinoline, 6-methoxytetrahydroquinoline, 6-hydroxytetrahydroquinoline, 6-fluorotetrahydroquinoline, 6-chlorotetrahydroquinoline, tetrahydroquinoline-6-carboxylic acid methyl ester 6-carboxytetrahydroquinoline, 6-nitrotetrahydroquinoline, 1,2,3, 4-tetrahydroisoquinoline, 7-methyl-1, 2,3, 4-tetrahydroisoquinoline, 6-bromo-1, 2,3, 4-tetrahydroisoquinoline, diethyl 2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate, dimethyl 2, 6-dimethyl-4- (2-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, dimethyl 4- (4-chlorophenyl) -2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate, 3-cinnamyl 5- (2-methoxyethyl) 2, 6-dimethyl-4- (3-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, any one of 3-cinnamyl 5- (2-methoxyethyl) 2, 6-dimethyl-4- (3-nitrophenyl) -1, 4-dihydropyridine-3, 5-dicarboxylate, 1,2,3, 4-tetrahydroquinoxaline, 9, 10-dihydroacridine, 2,3,4, 5-tetrahydro-1H-pyrido [4,3-b ] indole, 2,3,4, 9-tetrahydro-1H-pyrido [3,4-b ] indole, 2-phenyl-2, 3-dihydrobenzo [ d ] oxazole, 2-phenyl-2, 3-dihydrobenzo [ d ] thiazole;
The compound formula (II) is any one of the following compounds:
the preparation method comprises the following specific steps:
(1) Sequentially adding an aza-cycle compound shown in formula (I) and a catalyst of triphenylcarbon tetra (pentafluorophenyl) borate Ph 3C+[B(C6F5)4]- and 2, 6-tetramethylpiperidine oxide TEMPO into a reactor under an oxygen atmosphere, and then adding an organic solvent isopropanol to obtain a mixture, wherein the mole volume ratio of the aza-cycle compound, the triphenylcarbon tetra (pentafluorophenyl) borate (Ph 3C+[B(C6F5)4]-) and the 2, 6-tetramethylpiperidine oxide TEMPO, and the organic solvent isopropanol is as follows: 0.2mmol to 10mmol:0.006mmol to 0.3mmol:0.02mmol to 1mmol:1 mL-20 mL;
(2) Transferring the reaction bottle to a heating device for heating reaction for 1-12 hours, and rapidly stirring for reaction, and after TLC detection reaction is completed, separating and purifying to obtain a corresponding target product formula (II).
2. The organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compounds according to claim 1, wherein the molar volume ratio of nitrogen-containing heterocyclic compounds of formula (i) to the catalyst triphenylcarbon tetra (pentafluorophenyl) borate Ph 3C+[B(C6F5)4]- to 2, 6-tetramethylpiperidine oxide (TEMPO) to solvent is added in step (1): 0.2mmol:0.06mmol:0.02mmol:1mL; in step (2), the heating temperature was 70℃and the reaction time was 12 hours.
3. The method for organic chemical conversion of oxidative dehydrogenation of a nitrogen-containing heterocyclic compound according to claim 1, wherein the nitrogen-containing heterocyclic compound is a nitrogen-containing heterocyclic compound,
The synthesis method of the formula (II) is any one of the following synthesis methods:
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107162968A (en) * 2017-05-25 2017-09-15 陕西师范大学 A kind of method of visible light catalytic Tetrahydroquinolinesas oxidative dehydrogenation synthesis of quinoline class compound
CN109053567A (en) * 2018-10-25 2018-12-21 西南石油大学 A kind of method of hydrogen transfer reduction nitrogen-containing heterocycle compound
CN109134362A (en) * 2018-09-26 2019-01-04 中国科学技术大学 A kind of method that the nonmetal catalyzed active carboxylic acid's ester decarboxylation of photoinduction introduces azacyclo-
CN111848508A (en) * 2020-07-31 2020-10-30 宁波大学 Method for preparing quinoline compound
CN111909074A (en) * 2020-07-31 2020-11-10 宁波大学 Method for preparing indole compound by air oxidation catalyzed by N-hydroxyphthalimide
CN112209915A (en) * 2020-09-08 2021-01-12 宁波大学 Method for air oxidation of N-pyridine indoline compounds
CN115073351A (en) * 2022-07-06 2022-09-20 南京工业大学 Preparation method of 3,3' -bis-indolyl methane
CN115093410A (en) * 2022-07-06 2022-09-23 南京工业大学 Preparation method of beta-carboline compound

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107162968A (en) * 2017-05-25 2017-09-15 陕西师范大学 A kind of method of visible light catalytic Tetrahydroquinolinesas oxidative dehydrogenation synthesis of quinoline class compound
CN109134362A (en) * 2018-09-26 2019-01-04 中国科学技术大学 A kind of method that the nonmetal catalyzed active carboxylic acid's ester decarboxylation of photoinduction introduces azacyclo-
CN109053567A (en) * 2018-10-25 2018-12-21 西南石油大学 A kind of method of hydrogen transfer reduction nitrogen-containing heterocycle compound
CN111848508A (en) * 2020-07-31 2020-10-30 宁波大学 Method for preparing quinoline compound
CN111909074A (en) * 2020-07-31 2020-11-10 宁波大学 Method for preparing indole compound by air oxidation catalyzed by N-hydroxyphthalimide
CN112209915A (en) * 2020-09-08 2021-01-12 宁波大学 Method for air oxidation of N-pyridine indoline compounds
CN115073351A (en) * 2022-07-06 2022-09-20 南京工业大学 Preparation method of 3,3' -bis-indolyl methane
CN115093410A (en) * 2022-07-06 2022-09-23 南京工业大学 Preparation method of beta-carboline compound

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A biomass-derived N-doped porous carbon catalyst for the aerobic dehydrogenation of nitrogen heterocycles;Jing-Jiang Liu，等;《New J. Chem》;1791–1799 *
Homolytic Cleavage Reactions of a Neutral Doubly Base Stabilized Diborane(4);Levy L. Cao，等;《Organometallics》;3163−3170 *
Visible-Light-Mediated Photocatalytic Aerobic Dehydrogenation of N‑heterocycles by Surface-Grafted TiO2 and 4‑amino-TEMPO;Narmina O. Balayeva，等;《ACS Catal》;10694−10704 *

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