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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

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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
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cobalt
amination reaction
carbazole compounds
catalyzed hydrocarbon
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CN113004248B (en
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冯若昆
王朝彧
潘健
朱天阳
冉冬梅
刘伊琳
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University of Shaoxing
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    • 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
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Abstract

本发明公开了一种钴催化碳氢胺化反应合成咔唑类化合物的方法，包括：在钴催化剂的催化下，吡啶酰胺类化合物在氧化剂和碱的作用下于有机溶剂中进行反应，反应结束后经过后处理得到所述的咔唑类化合物。该采用了廉价的钴金属作为催化剂，催化吡啶酰胺类化合物的碳氢胺化反应，避免了贵金属催化剂的使用，同时，提高了反应收率，具有重要的工业应用价值。The invention discloses a method for synthesizing carbazole compounds by cobalt-catalyzed hydrocarbon amination reaction. After post-treatment, the carbazole compound is obtained. The cheap cobalt metal is used as a catalyst to catalyze the hydrocarbon amination reaction of pyridine amide compounds, avoiding the use of precious metal catalysts, and at the same time, the reaction yield is improved, 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.
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Cited By (1)

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* 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

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