CN115626889A - 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

Info

Publication number
CN115626889A
CN115626889A CN202211265495.1A CN202211265495A CN115626889A CN 115626889 A CN115626889 A CN 115626889A CN 202211265495 A CN202211265495 A CN 202211265495A CN 115626889 A CN115626889 A CN 115626889A
Authority
CN
China
Prior art keywords
reaction
nitrogen
heterocyclic compound
nmr
tlc
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202211265495.1A
Other languages
Chinese (zh)
Other versions
CN115626889B (en
Inventor
贾振华
吕永恒
张振国
罗德平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Yaojiayuan Biomedical Co ltd
Nanjing Tech University
Original Assignee
Nanjing Yaojiayuan Biomedical Co ltd
Nanjing Tech University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanjing Yaojiayuan Biomedical Co ltd, Nanjing Tech University filed Critical Nanjing Yaojiayuan Biomedical Co ltd
Priority to CN202211265495.1A priority Critical patent/CN115626889B/en
Publication of CN115626889A publication Critical patent/CN115626889A/en
Application granted granted Critical
Publication of CN115626889B publication Critical patent/CN115626889B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/006—Catalysts comprising hydrides, coordination complexes or organic compounds comprising organic radicals, e.g. TEMPO
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
    • B01J31/0275—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 also containing elements or functional groups covered by B01J31/0201 - B01J31/0269
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/18—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D263/57—Aryl or substituted aryl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Indole Compounds (AREA)

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 nonmetal catalyst, and compared with the existing metal-catalyzed synthesis method, the method has the advantages that the synthesis process is easier to purify, and the toxicity problem caused by metal residue is avoided. In the preparation method, the required reaction raw materials (nitrogen heterocyclic compounds or derivatives thereof) are cheap and easy to obtain, the compound after dehydroaromatization is obtained by one-step method, the problem that the existing synthesis method still has complicated reaction is avoided, compared with the method that the condition is mild and the temperature is 70 ℃, oxygen is only needed to participate, the operation is simple, and only the addition of 3mol of Ph is needed 3 C + [B(C 6 F 5 ) 4 ] ‑ Compared with other reactions for adding stoichiometric additives, the reaction has the advantages of low cost, high reaction efficiency and high atom economy, and can effectively reduce the generation of chemical waste and reduce the environmental pollution.
Figure DDA0003892985080000011

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 metal-free catalytic dehydroaromatization of nitrogen heterocyclic compounds.
Background
The nitrogen-containing heterocyclic ring occupies an important position in heterocyclic compounds, and through years of development, in the prescription medicine which is sold in the whole U.S. in 2018, 106 nitrogen-containing oxygen-containing heterocyclic compounds account for more than half. The nitrogenous heterocyclic ring is a common substance in biological metabolites, has unique activity, low toxicity and high intracellular systemic property, is usually applied to products such as medicines, pesticides, dyes and the like, and as is known, most compounds in alkaloid are nitrogenous heterocyclic rings, are the core basic skeletons of a plurality of drug molecules, have special properties, and are key structures for playing curative effects of a plurality of medicaments, such as local anesthesia, antivirus, antituberculosis and other diseases. After decades of development, nitrogen-containing heterocycles are used not only in medicine, pesticides and industry, but also in multifunctional materials and dyes, and are characterized in that the structural framework is easily modified, so that the nitrogen-containing heterocycles can be designed into bioactive substances or organic functional materials, such as classical 1,2, 3-triazole, 1,3, 5-triazine, isothiazole and thiazole, and play a role in medicine, pesticide, chemical materials, multifunctional lubricating oil, organic photoelectric functional materials and dye-sensitized solar cells.
Conventional methods with various catalysts have emerged in recent years. From the viewpoint of aerobic dehydrogenation, various methods for catalyzing the dehydroaromatization of nitrogen heterocyclic compounds by transition metals, such as Pd, ru, ir, cu, fe, co, ni, zn and the like, are developed, the use of the transition metals inevitably generates chemical wastes, and toxic pollutants can be introduced into target products. However, the use of stoichiometric oxidants or precious metals is undesirable from an environmental and economic standpoint. Although many excellent catalytic systems have been explored under relatively mild conditions, most of these methods 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, there have been few reports of non-metal catalyzed dehydroaromatization of nitrogen heterocycles. Therefore, there is a need in the art for a method for dehydroaromatization of nitrogen heterocyclic compounds, which is green, efficient, and has high atom economy, mild reaction conditions, and wide substrate application range.
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, mild reaction conditions and wide substrate application range.
In order to solve the technical problem of the invention, the technical scheme is as follows: the organic chemical conversion process for the oxidative dehydrogenation of nitrogen-containing heterocyclic compound includes the following steps:
Figure BDA0003892985060000011
in the nitrogen heterocyclic compound formula (I) and the 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, para-chlorophenyl, meta-nitrophenyl, 2-methoxyethoxyacyl, cinnamyl formate and isopropyl formate;
n is 0 or 1;
het is an unsaturated nitrogen-containing heterocycle;
the preparation method comprises the following specific steps:
(1) Under oxygen atmosphere, nitrogen heterocyclic compound (I) and catalyst triphenylcarbenium tetrakis (pentafluorophenyl) borate Ph 3 C + [B(C 6 F 5 ) 4 ] - And 2, 6-tetramethylpiperidine oxide (TEMPO) were sequentially added to the reactor, followed by the addition of an organic solvent, isopropanol, to give a mixture, wherein the nitrogen heterocycle compound, triphenylcarbetetrakis (pentafluorophenyl) borate (Ph) 3 C + [B(C 6 F 5 ) 4 ] - ) And 2, 6-tetramethylpiperidine oxide (TEMPO), and the organic solvent isopropanol in a molar volume ratio of: 0.2 mmol-10 mmol:0.006 mmol-0.3 mmol:0.02 mmol-1 mmol:1 mL-20 mL;
(2) And transferring the reaction bottle to a heating device for heating reaction for 1-12 hours, quickly stirring for reaction, and after TLC detection reaction is finished, separating and purifying to obtain a corresponding target product shown in formula (II).
Preferably, in step (1), the nitrogen heterocyclic compound (I) is addedAnd the catalyst triphenylcarbenium tetrakis (pentafluorophenyl) borate Ph 3 C + [B(C 6 F 5 ) 4 ] - And 2, 6-tetramethylpiperidine oxide (TEMPO) and a solvent in a molar volume ratio of: 0.2mmol; in the step (2), the heating temperature is 70 ℃, and the reaction time is 12 hours.
Preferably, the first and second liquid crystal materials are, in the step (1), the nitrogen heterocyclic 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-tetramethylquinoline, 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, 3-cinnamyl 5- (2-methoxyethyl) 2, 6-dimethyl-4- (3-nitroethyl) 2, 6-dimethyl-4- (3-nitroisoquinoline, 4-dicarboxylate Any one of phenyl) -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 and 2-phenyl-2, 3-dihydrobenzo [ d ] thiazole.
Preferably, the nitrogen heterocyclic compound of formula (ii) is any one of the following nitrogen heterocyclic compounds:
Figure BDA0003892985060000031
preferably, the synthesis method of the formula (II) is any one of the following synthesis methods of indole compounds.
Figure BDA0003892985060000041
Figure BDA0003892985060000051
Figure BDA0003892985060000061
Compared with the defects and shortcomings of the prior art, the organic chemical conversion method for oxidative dehydrogenation of the nitrogenous heterocyclic compound has the following beneficial effects:
(1) The catalyst required in the preparation method is a nonmetal catalyst, and compared with the existing metal-catalyzed synthesis method, the preparation method has the advantages that the synthesis process is easier to purify, and the toxicity problem caused by metal residue is avoided. The reaction raw materials (the nitrogen heterocyclic compound or the derivatives thereof) required in the preparation method are cheap and easy to obtain, the compound after dehydroaromatization is obtained by one step, the problem that the reaction is too complicated in the existing synthesis method is avoided, compared with the method, the used condition is mild, the temperature is 70 ℃, only oxygen is needed to participate, the operation is simple, and only 3mol% of Ph is needed to be added 3 C + [B(C 6 F 5 ) 4 ] - And 10mol% TEMPO additive, compared with other reactions for adding stoichiometric additive, the method has the advantages of low cost, high reaction efficiency and high atom economy, and can effectively reduce the generation of chemical waste. Can reduce environmental pollution and meet the requirement of sustainable development.
(2) The catalyst required in the preparation method is a nonmetal catalyst, the catalyst is economical and easy to obtain, a complex synthesis method is not required, and compared with the existing synthesis method of a stoichiometric catalyst or a heavy metal catalyst, the catalyst can ensure that the nitrogen heterocyclic compound is dehydroaromatized by the nonmetal catalyst with a catalytic amount, and has the advantages of being richer, cheaper, less 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 materials and the like.
(3) Compared with the existing synthetic method, the preparation method of the invention has wider range of synthetic substrates and good universality for the compatibility of the substrate functional groups.
(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, the reaction temperature is increased, and the reaction effect is not improved. The reaction time is 12 hours, and the comparison result of the reaction time shows that the reaction is prolonged to 12 hours, and the complete reaction is achieved. The molar volume ratio of the nitrogen heterocyclic compound to the ion pair to the additive to the solvent is as follows: 0.2mmol. By reducing the amount of catalyst used, the yield of the desired product also begins to decrease.
Drawings
FIG. 1 nuclear magnetic hydrogen spectrum of Compound 1: ( 1 H NMR 400MHz,CDCl 3 )
FIG. 2 nuclear magnetic carbon spectrum of Compound 2: ( 13 C NMR 100MHz,CDCl 3 )
Detailed Description
The present invention will be described more fully hereinafter with reference to the following examples, which are set forth to provide an understanding of the present invention, but it should not be construed that the scope of the present invention is limited to the examples set forth below, and that all techniques described in the present invention are within the scope of the present invention.
Figure BDA0003892985060000081
General description:
abbreviations are used in the examples and have the following meanings:
me is methyl, et is the radical, boc is t-butyloxycarbonyl, ph is phenyl, 1,4-Dioxane is 1,4-Dioxane, DCM is dichloromethane, PE is petroleum ether, EA is ethyl acetate. TLC is thin layer chromatography, NMR is nuclear magnetic resonance, and HRMS is high resolution mass spectrometry.
The solvent is purified by standard method before use, and dried; the reagents used are either commercially available or synthesized according to established literature methods and purified before use.
Example 1:
Figure BDA0003892985060000082
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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)
Figure BDA0003892985060000091
TLC:Rf＝0.46(silica gel,PE/EA,50:1),(23mg,94％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ135.84,127.92,124.22,122.07,120.82,119.90,111.13,102.71.
Example 2:
Figure BDA0003892985060000092
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, TEMPO 3.1mg, indoline 02mmol, replacing oxygen for 3 times by the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and stirring vigorously for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 16mg in 61% yield.
1-methyl-1H-indole(2)
Figure BDA0003892985060000093
TLC:Rf＝0.45(silica gel,PE/EA,50:1),(16mg,61％yield),colorless oil. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ136.76,128.90,128.54,121.57,120.96,119.35,109.28,100.96,32.93.
Example 3:
Figure BDA0003892985060000094
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 25.5mg of the objective compound in 67% yield.
ethyl 1H-indole-2-carboxylate(3)
Figure BDA0003892985060000095
TLC:Rf＝0.52(silica gel,PE/EA,5:1),(25.5mg,67％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ162.22,136.93,128.04,127.59,125.44,122.71,120.88,111.99,108.74,61.17,14.51.
Example 4:
Figure BDA0003892985060000101
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 24mg in 93% yield.
2-methyl-1H-indole(4)
Figure BDA0003892985060000102
TLC:Rf＝0.62(silica gel,PE/EA,20:1),(24mg,93％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ136.13,135.18,129.15,121.03,119.74,110.32,100.48,13.83.
Example 5:
Figure BDA0003892985060000103
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 21mg in 78% yield.
5-fluoro-1H-indole(5)
Figure BDA0003892985060000104
TLC:Rf＝0.45(silica gel,PE/EA,20:1),(21mg,78％yield),off-white solid.
1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-124.8.
Example 6:
Figure BDA0003892985060000111
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 desired compound in an amount of 24mg at a yield of 80%.
5-chloro-1H-indole(6)
Figure BDA0003892985060000112
TLC:Rf＝0.40(silica gel,PE/EA,20:1),(24mg,80％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ134.21,129.04,125.62,125.56,122.42,120.22,112.08,102.51.
Example 7:
Figure BDA0003892985060000113
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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)
Figure BDA0003892985060000121
TLC:Rf＝0.44(silica gel,PE/EA,20:1),(36mg,93％yield),brown solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ134.47,129.71,125.55,124.93,123.33,113.13,112.61,102.38.
Example 8:
Figure BDA0003892985060000122
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 26mg in 86% yield.
5-methoxy-1H-indole(8)
Figure BDA0003892985060000123
TLC:Rf＝0.45(silica gel,PE/EA,20:1),(26mg,86％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ154.28,131.06,128.38,125.01,112.46,111.85,102.47,102.40,55.97.
Example 9:
Figure BDA0003892985060000124
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing and placingHeating at 70 deg.C, stirring vigorously for 12 hr to complete reaction, and detecting by TLC. After completion of the reaction, 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 with a yield of 40%.
methyl 1H-indole-5-carboxylate(9)
Figure BDA0003892985060000131
TLC:Rf＝0.54(silica gel,PE/EA,10:1),(14mg,40％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ168.43,138.50,127.56,125.65,123.89,123.47,121.98,109.94,103.50,52.00.
Example 10:
Figure BDA0003892985060000132
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 desired compound 13mg in 46% yield.
1H-indole-5-carbonitrile(10)
Figure BDA0003892985060000133
TLC:Rf＝0.48(silica gel,PE/EA,20:1),(13mg,46％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ137.60,127.75,126.60,126.52,124.98,120.99,112.13,103.53,102.86.
Example 11:
Figure BDA0003892985060000134
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound in 98% yield.
1-(1H-indol-5-yl)ethan-1-one(11)
Figure BDA0003892985060000141
TLC:Rf＝0.42(silica gel,PE/EA,20:1),(31mg,98％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ198.91,138.62,129.93,127.49,125.98,123.26,122.31,111.19,104.31,26.83.
Example 12:
Figure BDA0003892985060000142
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing stirring magnetons with proper sizes, and sequentially carrying outAccurate weighing of Ph 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 target compound in 99% yield.
6-nitro-1H-indole(12)
Figure BDA0003892985060000143
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(31mg,99％yield),yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ143.23,134.36,132.98,130.37,120.71,115.45,107.78,103.66.
Example 13:
Figure BDA0003892985060000144
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 18mg in 70% yield.
Quinoline(13)
Figure BDA0003892985060000151
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(18mg,70％yield),pale purple oil. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ150.54,148.36,136.18,131.26,129.57,128.38,127.90,126.65,121.19.
Example 14:
Figure BDA0003892985060000152
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 25.5mg of the objective compound in 67% yield.
Example 15:
Figure BDA0003892985060000153
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 79% yield.
2-methylquinoline(15)
Figure BDA0003892985060000154
TLC:Rf＝0.42(silica gel,PE/EA,5:1),(23mg,79％yield),yellow oil. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ159.10,147.85,136.37,129.59,128.63,127.60,126.57,125.80,122.13,25.47.
Example 16:
Figure BDA0003892985060000161
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 desired compound in a yield of 91 mg.
6-methoxyquinoline(16)
Figure BDA0003892985060000162
TLC:Rf＝0.50(silica gel,PE/EA,5:1),(29mg,91％yield),white powder. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ157.79,148.01,144.44,134.94,130.91,129.38,122.43,121.48,105.13,55.64.
Example 17:
Figure BDA0003892985060000163
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 title compound 26mg in 87% yield.
6-fluoroquinoline(17)
Figure BDA0003892985060000164
TLC:Rf＝0.38(silica gel,PE/EA,10:1),(26mg,87％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-113.1.
Example 18:
Figure BDA0003892985060000171
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, TEMPO 3.1mg, indoline compound0.2mmol, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 20mg in 61% yield.
6-chloroquinoline(18)
Figure BDA0003892985060000172
TLC:Rf＝0.52(silica gel,PE/EA,5:1),(20mg,61％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ149.83,145.73,135.24,132.39,131.22,130.52,128.93,126.52,122.02.
Example 19:
Figure BDA0003892985060000173
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 30mg in 78% yield.
methyl quinoline-6-carboxylate(26)
Figure BDA0003892985060000174
TLC:Rf＝0.48(silica gel,PE/EA,5:1),(30mg,78％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ163.62,152.62,146.78,136.08,131.11,129.90,129.05,128.18,126.35,121.95,52.01.
Example 20:
Figure BDA0003892985060000181
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 28mg of the objective compound in 81% yield.
quinoline-6-carboxylic acid(20)
Figure BDA0003892985060000182
TLC:Rf＝0.32(silica gel,PE/EA,1:1),(28mg,81％yield),beige powder. 1 H NMR(400MHz,DMSO-d 6 )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). 13 C NMR(101MHz,DMSO-d 6 )δ167.52,153.25,149.85,138.06,131.52,129.85,129.30,129.06,127.71,122.78.
Example 21:
Figure BDA0003892985060000183
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 target compound 18mg in 51% yield.
6-nitroquinoline(21)
Figure BDA0003892985060000184
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(18mg,51％yield),pale yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ153.22,150.31,137.26,131.53,127.14,124.09,123.04.
Example 22:
Figure BDA0003892985060000191
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 26mg in 61% yield.
6-bromo-3,4-dihydroisoquinoline(22)
Figure BDA0003892985060000192
TLC:Rf＝0.46(silica gel,PE/EA,1:1),(26mg,61％yield),brown solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ159.51,137.96,130.70,130.41,128.72,127.23,125.28,46.49,24.83.
Example 23:
Figure BDA0003892985060000193
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 target compound 21mg in 80% yield.
3,4-dihydroisoquinoline(23)
Figure BDA0003892985060000194
TLC:Rf＝0.50(silica gel,PE/EA,1:1),(21mg,80％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ160.51,136.44,131.18,128.58,127.53,127.33,127.19,47.01,25.66.
Example 24:
Figure BDA0003892985060000201
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 a yield of 76%.
7-methyl-3,4-dihydroisoquinoline(24)
Figure BDA0003892985060000202
TLC:Rf＝0.54(silica gel,PE/EA,1:1),(22mg,76％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ162.69,138.68,134.84,131.85,129.08,128.02,126.27,46.05,29.35,22.04.
Example 25:
Figure BDA0003892985060000203
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, the mixture was diluted with EA (2 mL). Concentrating the organic matter under reduced pressureAnd purifying the solvent by silica gel column chromatography to obtain 48mg of the target compound with the yield of 96%.
diethyl 2,6-dimethylpyridine-3,5-dicarboxylate(25)
Figure BDA0003892985060000204
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(48mg,96％yield),white solid. 1 H NMR(400MHz,CDCl 3 )δ8.67(s,1H),4.39(q,J＝7.2Hz,4H),2.84(s,6H),1.41(t,J＝7.2Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ166.06,162.35,141.04,123.12,61.53,25.11,14.38.
Example 26:
Figure BDA0003892985060000211
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 42mg in 61% yield.
dimethyl 2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylate(26)
Figure BDA0003892985060000212
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(42mg,61％yield),yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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:
Figure BDA0003892985060000213
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 desired compound 51mg in 78% yield.
dimethyl 4-(4-chlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate(27)
Figure BDA0003892985060000221
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(51mg,78％yield),white solid. 1 H NMR(400MHz,CDCl 3 )δ7.35(dd,J＝8.7,2.3Hz,2H),7.20-7.11(m,2H),3.56(s,6H),2.58(s,6H). 13 C NMR(101MHz,CDCl 3 )δ165.05,152.60,143.75,136.24,129.33,128.62,124.30,49.26,21.18.
Example 28:
Figure BDA0003892985060000222
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, TEMPO 3.1mg, indoline compound 0.2mmol, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, heating at 70 deg.CVigorously stirred for 12 hours until the reaction was complete, and checked by TLC. After completion of the reaction, 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 target compound 77mg, in 79% yield.
3-cinnamyl 5-(2-methoxyethyl)2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate(28)
Figure BDA0003892985060000223
TLC:Rf＝0.40(silica gel,PE/EA,5:1),(77mg,79％yield),pale yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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:
Figure BDA0003892985060000231
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 57mg in 69% yield.
3-isopropyl 5-(2-methoxyethyl)2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate(29)
Figure BDA0003892985060000232
TLC:Rf＝0.38(silica gel,PE/EA,5:1),(57mg,69％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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:
Figure BDA0003892985060000233
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, 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 target compound 21mg in 82% yield.
Quinoxaline(30)
Figure BDA0003892985060000234
TLC:Rf＝0.45(silica gel,PE/EA,10:1),(21mg,82％yield),brown solid. 1 H NMR(400MHz,CDCl 3 )δ8.85(s,2H),8.16-8.07(m,2H),7.83-7.74(m,2H). 13 C NMR(101MHz,CDCl 3 )δ145.10,143.13,132.85,128.78.
Example 31:
Figure BDA0003892985060000241
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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)
Figure BDA0003892985060000242
TLC:Rf＝0.54(silica gel,PE/EA,5:1),(32mg,89％yield),yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ149.13,136.24,130.46,129.45,128.33,126.69,125.81.
Example 32:
Figure BDA0003892985060000243
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen for 3 times in the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours to completely react, and detecting by TLC. After completion of the reaction, the mixture was diluted with EA (2 mL). Concentrating the organic solvent under reduced pressure, byPurification by silica gel column chromatography gave the objective compound in 26mg, yield 76%.
9H-pyrido[3,4-b]indole(32)
Figure BDA0003892985060000244
TLC:Rf＝0.40(silica gel,PE/EA,2:1),(26mg,76％yield),yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ140.54,139.18,135.72,133.67,129.14,128.71,121.93,121.55,120.31,114.89,112.43.
Example 33:
Figure BDA0003892985060000251
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 target compound 16mg in 47% yield.
5H-pyrido[4,3-b]indole(33)
Figure BDA0003892985060000252
TLC:Rf＝0.46(silica gel,PE/EA,1:1),(16mg,47％yield),yellow solid.
1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ144.30,143.84,141.97,139.66,127.40,121.46,121.22,120.85,120.56,111.45,106.57.
Example 34:
Figure BDA0003892985060000253
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, preparing a stirring magneton with a proper size, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, 3.1mg of TEMPO and 0.2mmol of indoline compound, replacing oxygen in the reaction system for 3 times, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and violently stirring for 12 hours until complete reaction, and detecting by TLC. After completion of the reaction, 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 desired compound 29mg in 74% yield.
2-phenylbenzo[d]oxazole(34)
Figure BDA0003892985060000254
TLC:Rf＝0.54(silica gel,PE/EA,5:1),(29mg,74％yield),white solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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:
Figure BDA0003892985060000261
the preparation method of the nitrogen heterocyclic compound comprises the following steps: taking a 25mL Schlenk tube, configuring stirring magnetons with proper sizes, and accurately weighing Ph in sequence 3 C + [B(C 6 F 5 ) 4 ] - 5.6mg, TEMPO 3.1mg, indolinizationAnd (3) replacing oxygen for 3 times by the reaction system, adding 1mL of isopropanol, sealing, placing at 70 ℃, heating and stirring vigorously for 12 hours until complete reaction, and detecting by TLC (thin layer chromatography). After completion of the reaction, 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 target compound 67mg in 67% yield.
2-phenylbenzo[d]thiazole(35)
Figure BDA0003892985060000262
TLC:Rf＝0.46(silica gel,PE/EA,5:1),(28mg,67％yield),pale yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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
Figure BDA0003892985060000263
Figure BDA0003892985060000271
Other ion pairs are selected to replace the ion pair catalyst Ph 3 C + [B(C 6 F 5 ) 4 ] - The reaction effect is greatly reduced, which shows that the ion pair catalyst Ph 3 C + [B(C 6 F 5 ) 4 ] - The reaction effect is best under the catalytic system.
Comparative example two: comparison of reaction temperatures
Figure BDA0003892985060000272
The optimal reaction temperature is 80 ℃, the reaction temperature is reduced, the smooth proceeding of the reaction is not facilitated, the reaction temperature is increased, and the reaction effect is not improved.
Comparative example three: comparison of catalyst amounts
Figure BDA0003892985060000273
In order to fully exert ion on the catalyst Ph 3 C + [B(C 6 F 5 ) 4 ] - The amount of the catalyst used may be reduced to 3mol%.
Comparative example four: comparison of reaction time
Figure BDA0003892985060000281
The reaction time comparison results show that the reaction is prolonged to 12 hours and complete reaction is achieved.
Comparative example five: comparison of additives
Figure BDA0003892985060000282
Other additives replace TEMPO as reaction additives, and the yield of the target product is reduced to different degrees and even the catalytic activity of the catalyst is lost.
Comparative example six: comparison of reaction solvents
Figure BDA0003892985060000291
Other solvents replace isopropanol as reaction solvents, and the yield of the target product is reduced to different degrees and even the catalytic activity of the catalyst is lost.

Claims (4)

1. The organic chemical conversion method for the oxidative dehydrogenation of the nitrogenous heterocyclic compound is characterized by comprising the following preparation route:
Figure FDA0003892985050000011
in the nitrogen heterocyclic compound formula (I) and the 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, para-chlorophenyl, meta-nitrophenyl, 2-methoxyethoxyacyl, cinnamyl formate and isopropyl formate;
n is 0 or 1;
het is an unsaturated nitrogen-containing heterocycle;
the preparation method comprises the following specific steps:
(1) Under oxygen atmosphere, nitrogen heterocyclic compound formula (I) and catalyst triphenylcarbenium tetrakis (pentafluorophenyl) borate Ph 3 C + [B(C 6 F 5 ) 4 ] - And 2, 6-tetramethylpiperidine oxide (TEMPO) were sequentially added to the reactor, followed by the addition of the organic solvent isopropanol to give a mixture, wherein the nitrogen heterocycle compound, triphenylcarbetetrakis (pentafluorophenyl) borate (Ph) 3 C + [B(C 6 F 5 ) 4 ] - ) And 2, 6-tetramethylpiperidine oxide (TEMPO), and the organic solvent isopropanol in a molar volume ratio of: 0.2 mmol-10 mmol:0.006 mmol-0.3 mmol:0.02 mmol-1 mmol:1 mL-20 mL;
(2) And transferring the reaction bottle to a heating device for heating reaction for 1-12 hours, quickly stirring for reaction, and after TLC detection reaction is finished, separating and purifying to obtain a corresponding target product shown in formula (II).
2. The process for the organic chemical conversion of the oxidative dehydrogenation of a nitrogen-containing heterocyclic compound according to claim 1, wherein the nitrogen-containing heterocyclic compound of formula (I) and the catalyst triphenylcarbetetrakis (pentafluorophenyl) borate Ph are added in step (1) 3 C + [B(C 6 F 5 ) 4 ] - And 2, 6-tetramethylpiperidine oxide (TEMPO) and a solvent in a molar volume ratio of: 0.2mmol; in the step (2), the heating temperature is 70 ℃, and the reaction time is 12 hours.
3. <xnotran> 1 , , (1) , N- , -1- , 1- ,5- ,5- ,5- ,5- , -5- ,5- ,5- ,6- , , 1- ,6- ,6- ,6- ,6- , -6- ,6- ,6- ,1,2,3,4- , 7- -1,2,3,4- ,6- -1,2,3,4- ,2,6- -1,4- -3,5- ,2,6- -4- (2- ) -1,4- -3,5- ,4- (4- ) -2,6- -1,4- -3,5- ,3- 5- (2- ) 2,6- -4- (3- ) -1,4- -3,5- , </xnotran> 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.
4. The process for the oxidative dehydrogenation of an organic chemical conversion compound containing a nitrogen-containing heterocyclic compound according to claim 1, wherein the compound of formula (ii) is any one of the following compounds:
Figure FDA0003892985050000021
the synthesis method of the formula (II) is any one of the following synthesis methods:
Figure FDA0003892985050000031
Figure FDA0003892985050000041
Figure FDA0003892985050000051
CN202211265495.1A 2022-10-17 2022-10-17 Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound Active CN115626889B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211265495.1A CN115626889B (en) 2022-10-17 2022-10-17 Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211265495.1A CN115626889B (en) 2022-10-17 2022-10-17 Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound

Publications (2)

Publication Number Publication Date
CN115626889A true CN115626889A (en) 2023-01-20
CN115626889B CN115626889B (en) 2024-04-30

Family

ID=84904966

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211265495.1A Active CN115626889B (en) 2022-10-17 2022-10-17 Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound

Country Status (1)

Country Link
CN (1) CN115626889B (en)

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
JING-JIANG LIU，等: "A biomass-derived N-doped porous carbon catalyst for the aerobic dehydrogenation of nitrogen heterocycles", 《NEW J. CHEM》, pages 1791 *
LEVY L. CAO，等: "Homolytic Cleavage Reactions of a Neutral Doubly Base Stabilized Diborane(4)", 《ORGANOMETALLICS》, pages 3163 *
NARMINA O. BALAYEVA，等: "Visible-Light-Mediated Photocatalytic Aerobic Dehydrogenation of N‑heterocycles by Surface-Grafted TiO2 and 4‑amino-TEMPO", 《ACS CATAL》, pages 10694 *

Also Published As

Publication number Publication date
CN115626889B (en) 2024-04-30

Similar Documents

Publication Publication Date Title
Letessier et al. First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline
MXPA05000893A (en) Preparation of 1h-imidazo[4,5-c]quinolin-4-amines via1h-imidazo [4,5-c]quinolin-4-phthalimide intermediates.
CN115093410B (en) Preparation method of beta-carboline compound
Nandi et al. One‐Pot Multicomponent Reaction: A Highly Versatile Strategy for the Construction of Valuable Nitrogen‐Containing Heterocycles
Sridharan et al. New findings on the cerium (IV) ammonium nitrate catalyzed Povarov reaction: Stereoselective synthesis of 4-alkoxy-2-aryl-1, 2, 3, 4-tetrahydroquinoline derivatives
Xu-Xu et al. Enantioselective synthesis of 4-Silyl-1, 2, 3, 4-tetrahydroquinolines via copper (I) hydride catalyzed asymmetric hydrosilylation of 1, 2-dihydroquinolines
Zhao et al. Asymmetric Allylic Amination of Morita–Baylis–Hillman Adducts with Simple Aromatic Amines by Nucleophilic Amine Catalysis
Yan et al. Copper acetate aerobic oxidative synthesis of pyrido [1, 2-a] benzimidazoles from aminopyridines and phenylboronic acids
CN113185555B (en) Pincer-shaped manganese complex and preparation method thereof, related ligand and preparation method thereof, catalyst composition and application
CN115626889B (en) Organic chemical conversion method for oxidative dehydrogenation of nitrogen-containing heterocyclic compound
CN109608394A (en) The synthetic method and azepine aromatic amine compounds of azepine aromatic amine compounds
CN111848508A (en) Method for preparing quinoline compound
Wang et al. Transition-metal-free access to 7-azaindoles
CN115710281A (en) Isoxazolo [5,4-b ] pyridine FLT 3inhibitor and preparation method and application thereof
CN113845509B (en) Synthetic method of indolyl-substituted spiro [ cyclobutane-1,1&#39; -indene ] compound
Zhang et al. Cobalt-Catalyzed Oxidative [4+ 2] Annulation of Benzamides with Dihydrofuran: A Facile Route to Tetrahydrofuro [2, 3-c] isoquinolinones
CN113264876B (en) Method for selectively catalyzing and hydrogenating aromatic heterocyclic compounds by non-hydrogen participation
CN109897039B (en) Method for preparing pyrrolo [3,2,1-ij ] quinolinone compound
CN108191834A (en) A kind of preparation method of benzo-fused N- heterocyclic compounds
CN110862347B (en) Preparation method of 2-aryl substituted quinoline nitroxide compound
Laborde et al. Novel 7‐substituted quinolone antibacterial agents. Synthesis of 7‐alkenyl, cycloalkenyl, and 1, 2, 3, 6‐tetrahydro‐4‐pyridinyl‐1, 8‐naphthyridines
Han et al. One-Pot Synthesis of 2-Arylquinolines via in situ Acid Catalysis
Komori et al. Synthetic studies on plakinidines
CN114807987B (en) Electrochemical method for preparing fused polycyclic quinazolinone derivative
CN116396211B (en) Method for preparing meta-chiral allyl substituted pyridine compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant