CN113004248A - Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt - Google Patents

Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt Download PDF

Info

Publication number
CN113004248A
CN113004248A CN202110282813.4A CN202110282813A CN113004248A CN 113004248 A CN113004248 A CN 113004248A CN 202110282813 A CN202110282813 A CN 202110282813A CN 113004248 A CN113004248 A CN 113004248A
Authority
CN
China
Prior art keywords
cobalt
amination reaction
carbazole compounds
catalyzed hydrocarbon
synthesizing
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
CN202110282813.4A
Other languages
Chinese (zh)
Other versions
CN113004248B (en
Inventor
冯若昆
王朝彧
潘健
朱天阳
冉冬梅
刘伊琳
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.)
University of Shaoxing
Original Assignee
University of Shaoxing
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 University of Shaoxing filed Critical University of Shaoxing
Priority to CN202110282813.4A priority Critical patent/CN113004248B/en
Publication of CN113004248A publication Critical patent/CN113004248A/en
Application granted granted Critical
Publication of CN113004248B publication Critical patent/CN113004248B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • 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

Abstract

The invention discloses a method for synthesizing carbazole compounds by a cobalt-catalyzed hydrocarbon amination reaction, which comprises the following steps: under the catalysis of a cobalt catalyst, the pyridine amide compounds react in an organic solvent under the action of an oxidant and alkali, and after the reaction is finished, the carbazole compounds are obtained through post-treatment. The method adopts cheap cobalt metal as a catalyst to catalyze the hydrocarbon amination reaction of the pyridine amide compounds, avoids the use of a noble metal catalyst, improves the reaction yield, and has important industrial application value.

Description

Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing carbazole compounds through a cobalt-catalyzed hydrocarbon amination reaction.
Background
Carbazole is an important nitrogen-containing heteroatom compound, and the carbazole is used as an intermediate of fine chemicals and has wide application in the fields of medicines, organic photoelectric materials, fluorescent probes and the like, as shown in the figure, researches show that a compound I has anticancer activity, a compound II has anti-HIV activity, a compound III shows anti-malaria activity, a compound IV is a bipolar blue light material, a compound V is an OLED material with high glass transition temperature (210 ℃), and a compound VI can be used for detecting copper ions and the like. In recent years, the synthesis and design of carbazole derivatives with novel structures and excellent performance are favored by researchers, so that the search for efficient and simple synthesis methods is helpful for exerting the application value of carbazole compounds.
Figure BDA0002979263700000011
Transition metal rhodium catalyzed bisaryl azide synthesis of carbazole via nitrogen carbene insertion was reported by Brankica Jovanovic et al in 2009. In addition to using expensive rhodium as a catalyst, the article also needs to add a ligand to reduce the regioselectivity of the reaction, which greatly increases the cost of the reaction, as shown in the following formula:
Figure BDA0002979263700000021
in 2011, So Won Youn task group reports that transition metal palladium-catalyzed intramolecular cyclization reaction of N-p-toluenesulfonyl o-aminobiphenyl is used for synthesizing carbazole compounds, and the synthesis method is specifically shown as follows:
Figure BDA0002979263700000022
huiying Zeng et al reported that palladium-catalyzed diphenol compounds synthesize carbazoles by dearomatization-re-aromatization in 2020. In the reaction, carbazole is synthesized by taking sodium formate as a hydrogen source, palladium-carbon as a catalyst, trifluoroethanol as an additive, toluene as a solvent and ammonia water as an ammoniation reagent. However, the synthesis of diphenol compounds is difficult, which greatly limits the wide application of the method, as shown in the following formula:
Figure BDA0002979263700000023
in summary, the carbazole synthesis methods developed at the present stage are all implemented by using ortho-aminobiphenyl as a raw material and constructing an intramolecular carbon-nitrogen bond through transition metal catalysis, but expensive catalysts are mostly used in the reaction, and the reaction yield still has room for improvement, so that the development of a hydrocarbon amination reaction catalyzed by cheap metals to prepare carbazole and derivatives thereof has very important research significance.
Disclosure of Invention
The invention provides a method for synthesizing carbazole compounds by a cobalt-catalyzed hydrocarbon amination reaction, which avoids the use of expensive catalysts and improves the reaction yield.
A method for synthesizing carbazole compounds by a cobalt-catalyzed hydrocarbon amination reaction comprises the following steps:
under the catalysis of a cobalt catalyst, reacting a pyridine amide compound in an organic solvent under the action of an oxidant and alkali, and performing post-treatment after the reaction to obtain the carbazole compound;
the reaction formula is as follows:
Figure BDA0002979263700000031
wherein R is1Is H, C1～C4Alkyl or halogen;
R2is H or C1～C4An alkyl group.
Preferably, R1Is H, methyl or chlorine;
R2is H, methyl or propyl.
Preferably, the cobalt catalyst is one or more of cobalt chloride, cobalt bromide, cobalt acetate hydroxide, cobalt carbonate hydroxide, cobalt oxide and cobalt acetylacetonate.
Preferably, the oxidant is one or more of silver carbonate, silver sulfate, silver oxide, manganese oxide and manganese acetate.
Preferably, the alkali is one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium acetate and potassium phosphate.
Preferably, the organic solvent is one or more of toluene, dichloroethane, tetrahydrofuran, fluorobenzene and chlorobenzene.
Preferably, the reaction temperature is 110-130 ℃ and the reaction time is 10-20 hours.
Preferably, the pyridine amide compound is: cobalt catalyst: oxidizing agent: base 1: 0.1-0.2: 1.5-2.5: 1.5 to 2.5.
Compared with the prior art, the invention has the beneficial effects that:
the invention adopts cheap cobalt metal as a catalyst to catalyze the hydrocarbon amination reaction of the pyridine amide compounds, avoids the use of a noble metal catalyst, improves the reaction yield, and has important industrial application value.
Drawings
FIG. 1 is a hydrogen spectrum of the product obtained in example 5 of the present invention;
FIG. 2 is a hydrogen spectrum of a product obtained in example 24 of the present invention;
FIG. 3 is a hydrogen spectrum of the product obtained in example 25 of the present invention;
FIG. 4 is a hydrogen spectrum of a product obtained in example 27 of the present invention;
FIG. 5 is a hydrogen spectrum of the product obtained in example 28 of the present invention.
Detailed Description
Examples 1 to 23
0.2mmol of N- (2-phenylphenyl) pyridinecarboxamide and 0.02mmol of cobalt catalyst were added to a sealed tube with 0.4mmol of the oxidizing agent, 0.4mmol of the base and 4mL of the solvent, and then the sealed tube was tightened, after which it was placed in a heat-collecting heating stirrer and reacted at 120 ℃ for 12 hours. After the reaction is finished, transferring the reaction liquid into a round-bottom flask, drying the solvent by using a rotary evaporator, and separating and purifying by using a column chromatography method to obtain a product, wherein the hydrogen spectrum of the obtained product is shown in figure 1, the result is shown in table 1, and the reaction formula is as follows:
Figure BDA0002979263700000041
TABLE 1 reaction results of examples 1 to 8
Figure BDA0002979263700000042
Examples 24 to 28
To a sealed tube containing 0.4mmol of silver carbonate, 0.02mmol of basic cobalt carbonate, 0.4mmol of silver carbonate and 0.4mmol of sodium carbonate were added 0.2mmol of picolinamide and 4mL of toluene, and then the sealed tube was tightened, after which it was placed in a heat-collecting heating stirrer and reacted at 120 ℃ for 12 hours. After the reaction is finished, the reaction solution is transferred to a round-bottom flask, the solvent is dried by a rotary evaporator, and then separation and purification are carried out by a column chromatography method, so as to obtain the following carbazole compound (shown below).
Figure BDA0002979263700000051
The characterization data of the partial products obtained are as follows:
(9H-carbazol-9-yl)(pyridin-2-yl)methanone:yellow soild；δH(400MHz, Chloroform-d)8.75(dd,1H,J＝8.0,4.0Hz),8.04–8.00(m,3H),7.92(dd, 1H,J＝8.0,4.0Hz),7.62–7.59(m,1H),7.41–7.31(m,6H).13C NMR(100 MHz,CDCl3)δ167.76,153.40,149.66,138.89,137.66,126.83,126.46, 126.36,124.17,123.79,119.87,115.88.
(9H-carbazol-9-yl)(3-methylpyridin-2-yl)methanone:white soild；δH(400MHz,Chloroform-d)8.59(dd,1H,J＝8.0,4.0Hz),8.04–7.97(m,2H), 7.78–7.73(m,1H),7.46(dd,1H,J＝8.0,4.0Hz),7.48–7.32(m,7H),2.40 (s,3H).13C NMR(100MHz,CDCl3)δ167.4,153.2,147.4,139.4,138.5, 131.7,127.3,126.7,125.5,124.1,119.9,115.8,17.7..
(9H-carbazol-9-yl)(3-chloropyridin-2-yl)methanone:white soild；δH(400MHz,Chloroform-d)8.64(dd,1H,J＝8.0,4.0Hz),7.97(d,3H,J＝8.0 Hz),7.89(dd,1H,J＝8.0,4.0Hz),7.49(dd,1H,J＝8.0,4.0Hz),7.38–7.29 (m,5H).13C NMR(100MHz,CDCl3)δ164.6,152.3,148.1,138.4,138.3, 129.5,127.4,126.8,126.3,124.4,120.0,115.7.
(2-methyl-9H-carbazol-9-yl)(pyridin-2-yl)methanone:white soild；δH(400 MHz,Chloroform-d)8.77(d,1H,J＝4.0 Hz),8.04(t,1H,J＝8.0 Hz), 7.98(dd,1H,J＝8.0,4.0 Hz),7.91(dd,2H,J＝8.0,4.0 Hz),7.62(dd,1H,J＝ 8.0,4.0 Hz),7.40–7.32(m,2H,),7.27(dd,1H,J＝8.0,4.0 Hz),7.22(t,2H,J ＝8.0 Hz),2.45(s,3H).13C NMR(100 MHz,CDCl3)δ167.8,153.5,149.6, 139.3,138.8,137.6,137.1,126.6,126.2,126.2,125.1,124.1,124.1,123.7, 119.6,119.4,116.4,115.8,22.2.
(2-propyl-9H-carbazol-9-yl)(pyridin-2-yl)methanone:yellow liquid；δH(400 MHz,Chloroform-d)8.70(dt,1H,J＝8.0,4.0 Hz),8.00–7.90(m,2H), 7.85(dd,2H,J＝8.0,4.0 Hz),7.56–7.53(m,1H),7.35–7.21(m,4H),7.20– 7.14(m,2H),2.60(t,2H,J＝8.0 Hz),1.58(t,2H,J＝8.0 Hz),0.89(t,3H,J＝ 8.0 Hz).13C NMR(100 MHz,CDCl3)δ167.7,153.6,149.6,141.9,139.6, 139.2,138.9,137.6,126.6,126.3,126.2,124.6,124.3,124.1,123.7,119.6, 119.5,115.8,38.6,24.7,13.8.

Claims (8)

1. a method for synthesizing carbazole compounds by a cobalt-catalyzed hydrocarbon amination reaction is characterized by comprising the following steps:
under the catalysis of a cobalt catalyst, reacting a pyridine amide compound in an organic solvent under the action of an oxidant and alkali, and performing post-treatment after the reaction to obtain the carbazole compound;
the reaction formula is as follows:
Figure FDA0002979263690000011
wherein R is1Is H, C1～C4Alkyl or halogen;
R2is H or C1～C4An alkyl group.
2. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein R is1Is H, methyl or chlorine;
R2is H, methyl or propyl.
3. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the cobalt catalyst is one or more of cobalt chloride, cobalt bromide, cobalt acetate, cobalt subacetate, cobalt hydroxycarbonate, cobalt oxide and cobalt acetylacetonate.
4. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the oxidant is one or more of silver carbonate, silver sulfate, silver oxide, manganese oxide and manganese acetate.
5. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the base is one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium acetate and potassium phosphate.
6. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the organic solvent is one or more of toluene, dichloroethane, tetrahydrofuran, fluorobenzene and chlorobenzene.
7. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the reaction temperature is 110-130 ℃ and the reaction time is 10-20 hours.
8. The method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction according to claim 1, wherein the molar amount of the picolinamide compound: cobalt catalyst: oxidizing agent: base 1: 0.1-0.2: 1.5-2.5: 1.5 to 2.5.
CN202110282813.4A 2021-03-16 2021-03-16 Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt Active CN113004248B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110282813.4A CN113004248B (en) 2021-03-16 2021-03-16 Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110282813.4A CN113004248B (en) 2021-03-16 2021-03-16 Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt

Publications (2)

Publication Number Publication Date
CN113004248A true CN113004248A (en) 2021-06-22
CN113004248B CN113004248B (en) 2022-11-18

Family

ID=76408590

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110282813.4A Active CN113004248B (en) 2021-03-16 2021-03-16 Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt

Country Status (1)

Country Link
CN (1) CN113004248B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117024354A (en) * 2023-10-08 2023-11-10 天津凯莱英制药有限公司 Preparation method of Rui Mi Buti Ni

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108707111A (en) * 2018-07-23 2018-10-26 浙江工业大学 A kind of green synthesis method of 6 (5H)-phenanthridines ketone derivatives
CN111004176A (en) * 2019-10-21 2020-04-14 绍兴文理学院 Synthesis method of 2-aryloxy ethanol compound
US20200317615A1 (en) * 2019-04-03 2020-10-08 Council Of Scientific & Industrial Research PALLADIUM (II)-CATALYZED gammaC(SP3)-H ALKYNYLATION OF AMINE2

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108707111A (en) * 2018-07-23 2018-10-26 浙江工业大学 A kind of green synthesis method of 6 (5H)-phenanthridines ketone derivatives
US20200317615A1 (en) * 2019-04-03 2020-10-08 Council Of Scientific & Industrial Research PALLADIUM (II)-CATALYZED gammaC(SP3)-H ALKYNYLATION OF AMINE2
CN111004176A (en) * 2019-10-21 2020-04-14 绍兴文理学院 Synthesis method of 2-aryloxy ethanol compound

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
DAQIAN ZHU 等: "synthesis of Carbazoles via One-Pot Copper-Catalyzed Amine Insertion into Cyclic Diphenyleneiodoniums as a Strategy to Generate a Drug-Like Chemical Library", 《ADV. SYNTH. CATAL.》 *
GANG HE 等: "Highly Efficient Syntheses of Azetidines, Pyrrolidines, and Indolines via Palladium Catalyzed Intramolecular Amination of C(sp3)−H and C(sp2)−H Bonds at γ and δ Positions", 《JOURNAL OF AMERICAN CHEMICAL SOCIETY》 *
HONGWEI SUN 等: "Cascade double isocyanide insertion and C–N coupling of 2-iodo-2’-isocyano-1,1’-biphenyls", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *
KAZUTAKA TAKAMATSU 等: "Synthesis of Carbazoles by Copper-Catalyzed Intramolecular C−H/N−H Coupling", 《ORGANIC LETTERS》 *
KAZUTAKA TAKAMATSU 等: "Synthesis of Indolines by Copper-Mediated Intramolecular Aromatic C−H Amination", 《THE JOURNAL OF ORGANIC CHEMISTRY》 *
TINGFANG ZHANG 等: "Cobalt(II)ecatalyzed C8-H alkoxylation of 1-naphthylamine derivatives with alcohols", 《TETRAHEDRON》 *
XINMOU WANG 等: "Construction of 2-(2-Arylphenyl)azoles via Cobalt-Catalyzed C-H/C-H Cross-Coupling Reactions and Evaluation of Their Antifungal Activity", 《ORGANIC LETTERS》 *
王鹏 等: "《有机波谱》", 31 January 2012 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117024354A (en) * 2023-10-08 2023-11-10 天津凯莱英制药有限公司 Preparation method of Rui Mi Buti Ni
CN117024354B (en) * 2023-10-08 2023-12-08 天津凯莱英制药有限公司 Preparation method of Rui Mi Buti Ni

Also Published As

Publication number Publication date
CN113004248B (en) 2022-11-18

Similar Documents

Publication Publication Date Title
CN107235923B (en) Preparation method of 3-aryl quinoxalinone derivatives
CN107880079B (en) Cyclic N-heterocyclic bis-carbene-palladium complex and preparation method and application thereof
CN109369545B (en) Synthesis process of 2-methyl-5-pyrazine formate
CN102977017B (en) Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component
CN113004248B (en) Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt
CN113416150A (en) Novel synthesis method of lobaplatin intermediate
CN109776407B (en) Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof
CN112390696B (en) Method for preparing alpha-aminonitrile, product and application thereof
CN113045496B (en) Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds
CN113735752B (en) Method for preparing isothiourea compound based on substituted iodobenzene
CN105924390B (en) A kind of synthetic method of Mei Tafeini
CN112694489B (en) Preparation method of N-heterocyclic carbene copper catalyst
US8729303B2 (en) 2,2′,6,6′-tetrasubstituted aminophosphine ligand and its synthesis method
CN111039767B (en) Method for preparing deuterated aldehyde by using triazole carbene as catalyst
CN113072470A (en) N-acetonitrile bis-benzenesulfonylimine derivative and preparation method and application thereof
CN109438349A (en) 6- (alpha-cyano imines) base phenanthridines class compound and its synthetic method
CN113999239B (en) Method for synthesizing diaza-bridge compound
CN109021002B (en) Preparation method of naphthalene-1, 8-diamino aryl boron amide
CN112300059B (en) Preparation method of PF-06651600 intermediate
CN108299236B (en) Synthetic method of alpha-cyanoacrylate compound
CN112441921B (en) Method for synthesizing 9-acetoxyl-9, 10-dihydrophenanthrene compound by virtue of iridium photocatalysis
CN102241590B (en) Synthetic method of spirocyclic tetronic acid compound key intermediate
CN108586331B (en) Intermediate for synthesizing nitrogen-containing heterocyclic compound and preparation method thereof
CN112778198A (en) Synthesis method of dihydroquinolinone compound
CN113173949A (en) Method for synthesizing trisubstituted aryl phosphine oxide species by taking diphenyl tert-butyl phosphine as substrate

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