CN103755715B - Cumarone is [2,3-c] pyridine compounds and synthetic method thereof also - Google Patents

Cumarone is [2,3-c] pyridine compounds and synthetic method thereof also Download PDF

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CN103755715B
CN103755715B CN201310728861.7A CN201310728861A CN103755715B CN 103755715 B CN103755715 B CN 103755715B CN 201310728861 A CN201310728861 A CN 201310728861A CN 103755715 B CN103755715 B CN 103755715B
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phenyl
butene
cumarone
bromo
methyl
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CN103755715A (en
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郑化
胡佳兴
张方林
徐文刚
陈小清
李青翠
张津甫
武博
王宝龙
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Wuhan University of Technology WUT
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The present invention relates to cumarone also [2,3-c] pyridine compounds and synthetic method thereof, cumarone also [2,3-c] pyridine compounds has following general formula: wherein R 1for phenyl, the bromo-phenyl of 3-, the bromo-phenyl of 4-, the chloro-phenyl of 4-, 4-methoxyl group-phenyl, 3-methylphenyl or 4-methylphenyl; R 2for hydrogen or 5-chlorine, 5-bromine, the 5-tertiary butyl, 3,5-di-t-butyls, 4-methoxyl group, 5-methoxyl group, 5-methyl, 3,5-dimethyl, 4,5-dimethyl; R 3for methyl or phenyl, the bromo-phenyl of 4-, the bromo-phenyl of 3-, the chloro-phenyl of 2-, the chloro-phenyl of 4-, 4-methoxyl group-phenyl, 4-methylphenyl.The present invention is with alpha-brominated methyl phenyl ketone or derivatives thereof, 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof for reactant, adopt cumarone also [2,3-c] pyridine compounds described in one pot process.This synthetic method step is easy, and mild condition, productive rate is higher.

Description

Cumarone is [2,3-c] pyridine compounds and synthetic method thereof also
Technical field
The invention belongs to orgnnic comopounds synthesis technical field, particularly cumarone also [2,3-c] pyridine compounds and synthetic method thereof.
Background technology
Cumarone also [2,3-c] pyridines organic heterocyclic molecule is widely used in organic synthesis, medicine and other fields, is important pharmaceutical intermediate.This is external manyly to has in the molecule of physiologically active also containing this kind of structural unit, the people such as such as D.G.Wishka synthesize a kind of cumarone also [2,3-c] pyridine compounds and their (I), this compound is the medicine (WO02/100857A1) with central nervous system activity; The people such as L.A.Gharat synthesize cumarone also [2,3-c] pyridine compounds and their (II), and this compound is a kind of inhibitor (WO2011/132051A2) of phosphodiesterase-10.The method steps of above-mentioned synthesis cumarone also [2,3-c] pyridine compounds and their is complicated, and severe reaction conditions, such as, need carry out at anhydrous and oxygen-free reaction conditions.The people such as Wen adopt 3-chloropyridine to react with tributyltin chloride under-78 DEG C of conditions, products therefrom reacts with phenol o-iodine again and generates intermediate 2-(3-chloropyridine-4-base under the condition of Palladous chloride) phenol, this intermediate becomes ring under the catalysis of tertiary butyl sodium, obtain cumarone also [2, 3-c] pyridine, reaction overall yield about about 27% (WenSongYueandJieJackLi, AConciseSynthesisofAllFourPossibleBenzo [4, 5] furopyridinesviaPalladium-MediatedReactions.Org.Lett., Vol.4, No.13, 2002), this reaction is not only harsh to temperature requirement, complex process, and have employed transition-metal catalyst, cause cost intensive.Synthetic route reaction conditions known at present is in a word all harsher, greatly limit the industrial application of this compounds.
Summary of the invention
Technical problem to be solved by this invention is for above shortcomings in prior art, and provide cumarone also [2,3-c] pyridine compounds and synthetic method thereof, synthesis step is easy, and reaction conditions is gentle, is easy to realize.
Solve technical scheme that the technology of the present invention problem adopts be this cumarone also [2,3-c] pyridine compounds there is following general structure:
Wherein
R 1for phenyl, the bromo-phenyl of 3-, the bromo-phenyl of 4-, the chloro-phenyl of 4-, 4-methoxyl group-phenyl, 3-methylphenyl or 4-methylphenyl;
R 2for hydrogen or 5-chlorine, 5-bromine, the 5-tertiary butyl, 3,5-di-t-butyls, 4-methoxyl group, 5-methoxyl group, 5-methyl, 3,5-dimethyl, 4,5-dimethyl;
R 3for methyl or phenyl, the bromo-phenyl of 4-, the bromo-phenyl of 3-, the chloro-phenyl of 2-, the chloro-phenyl of 4-, 4-methoxyl group-phenyl, 4-methylphenyl.
The present invention adopts the above-mentioned cumarone of one pot process also [2,3-c] pyridine compounds, and one kettle way does not do refining and is separated between each elementary reaction, is the process of enforcement continuously, has that energy consumption is low, productive rate advantages of higher.
Particularly, preferred cumarone provided by the invention also [2, 3-c] synthetic method of pyridine compounds, concrete steps are: under room temperature, with the alpha-brominated methyl phenyl ketone or derivatives thereof of 9-15mmol and 4-(2-hydroxy phenyl) ratio of-3-butene-2-one or derivatives thereof 1:1-2:1 in molar ratio feeds intake, with 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof molar weight 1.25-1.8 potassium hydroxide doubly and/or sodium hydroxide is catalyzer, 20-60mL tetrahydrofuran (THF) and/or acetonitrile are solvent, reaction 1-5h, thin-layer chromatography monitoring reaction, 60-100mmol ammonium acetate and 60-100mL dehydrated alcohol is added after reaction terminates, within back flow reaction 3-6 hour, product is obtained in 90-120 DEG C, reaction equation is as follows:
Product obtains cumarone also [2,3-c] pyridine compounds through separation, purifying.
Preferably, described alpha-brominated methyl phenyl ketone or derivatives thereof comprises alpha-brominated methyl phenyl ketone, 2,3'-dibromobenzene ethyl ketone, 2,4'-dibromobenzene ethyl ketones, 2-bromo-4'-chloro-acetophenone, 2-bromo-4'-methoxyacetophenone, 2-bromo-3'-methyl acetophenone or the bromo-4'-methyl acetophenone of 2-.
Preferably, described 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof comprises 4-(2-hydroxy phenyl)-3-butene-2-one, 4-(5-chlorine-2-hydroxyl phenyl)-3-butene-2-one, the bromo-2-hydroxy phenyl of 4-(5-)-3-butene-2-one, the 4-(5-tertiary butyl-2-hydroxy phenyl)-3-butene-2-one, 4-(3, 5-di-t-butyl-2-hydroxy phenyl)-3-butene-2-one, 4-(2-hydroxy-4-methoxyphenyl)-3-butene-2-one, 4-(2-hydroxy-5-methyl oxygen phenyl)-3-butene-2-one, 4-(2-hydroxy-5-methyl phenyl)-3-butene-2-one, 4-(2-hydroxyl-3, 5-3,5-dimethylphenyl)-3-butene-2-one or 4-(2-hydroxyl-4, 5-xylyl)-3-butene-2-one.
Preferably, described separation, purifying adopt vacuum distillation method except desolventizing, adopts silica column purification product.
It should be noted that, room temperature of the present invention is 10-30 DEG C.
The present invention also provides the purposes of above-mentioned cumarone also [2,3-c] pyridine compounds, and it is used as pharmaceutical intermediate, can be used for preparing neural medicine.
The invention has the beneficial effects as follows: to efficiently solve in prior art cumarone also [2,3-c] pyridine compounds preparation procedure is complicated, cost is high, productive rate is low problem, cumarone also [2 is obtained by easy technique, 3-c] pyridine compounds, productive rate can reach 11-83%, and with low cost, little to environmental influence.
Accompanying drawing explanation
Fig. 1 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention one 1hNMR spectrogram;
Fig. 2 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention one 13cNMR spectrogram;
Fig. 3 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention three 1hNMR spectrogram;
Fig. 4 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention three 13cNMR spectrogram;
Fig. 5 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention 18 1hNMR spectrogram;
Fig. 6 is gained cumarone also [2,3-c] pyridine compounds in the embodiment of the present invention 18 13cNMR spectrogram.
Embodiment
For making those skilled in the art understand technical scheme of the present invention better, below in conjunction with embodiment, the present invention is described in further detail.
Embodiment one
Synthesis 3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine:
Take the alpha-brominated methyl phenyl ketone of 2g (10mmol), 1.21g4-(2-hydroxy phenyl)-3-butene-2-one (7.5mmol) and 630mg potassium hydroxide (11.25mmol), add in 40mL tetrahydrofuran (THF), and at 25 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 1h, 6.1g ammonium acetate (80mmol) and 80mL dehydrated alcohol is added in this system, continue return stirring and react 3 hours, reflux temperature is 100 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain faint yellow solid product, heavy 1.37g, productive rate is 74%.
Adopt the method for nucleus magnetic resonance (NMR) to test the product prepared by the present embodiment, as Fig. 1 and Fig. 2, be respectively the present embodiment products therefrom 1hNMR spectrogram and 13cNMR spectrogram, its 1hNMR(400MHz, CDCl 3) data are: δ 8.51 – 8.44 (m, 2H), 8.01 (dd, J=7.8,0.4Hz, 1H), 7.68 (s, 2H), 7.63 – 7.57 (m, 3H), 7.52 – 7.47 (m, 1H), 7.44 – 7.38 (m, 1H), 2.81 (s, 3H); 13cNMR(400MHz, CDCl 3) data are: δ 156.9,151.4,149.0,141.3,136.4,132.8,129.6,129.1,128.7,128.6,123.2,122.4,121.9,113.2,112.5,24.5.Adopting high resolution mass spectrum to measure compound molecular weight is 259.30.
Can judge that product is 3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 18h 13nO).
With the product 3-methyl isophthalic acid-phenylbenzofuran prepared by this enforcement also [2, 3-c] pyridine (compound 1) is pharmaceutical intermediate, take potassium permanganate as oxygenant, when methylene dichloride is solvent, back flow reaction and oxidablely obtain compound 2, condensation dehydration reaction is carried out with 3-amino quinine compounds by 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC) and/or dicyclohexylcarbodiimide (DCC), skeleton structure and N-(3R can be obtained)-1-azabicyclo [2, 2, 2] oct-3-yl-[1] cumarone also [2, 3-c] pyridine-3-carboxamide (N-(3R)-1-azabicyclo [2, 2, 2] oct-3-yl-[1] benzofuro [2, 3-c] pyridine-3-carboxamide) identical compound 3(1-phenyl-N-(rubane-3-base) cumarone also [2, 3-c] pyridine-3-carboxamide), this compound has stronger central nervous system activity, can be used as neural medicine.Its reaction formula is as follows:
Embodiment two
Synthesis 3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine: adopt the method identical with embodiment one, difference is to adopt acetonitrile to substitute tetrahydrofuran (THF), and acquired results is substantially identical with embodiment one.
Embodiment three
Synthesis 1-(3-bromophenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Take 2.77g2, 3'-dibromobenzene ethyl ketone (10mmol), 1.21g4-(2-hydroxy phenyl)-3-butene-2-one (7.5mmol) and 630mg potassium hydroxide (11.25mmol), add in 40mL tetrahydrofuran (THF), and at 25 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 2.5h, 6.1g ammonium acetate (80mmol) and 100mL dehydrated alcohol is added in this system, continue return stirring and react 3 hours, reflux temperature is 100 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain faint yellow solid product, heavy 1.17g, productive rate is 46%.
Adopt the method identical with embodiment one to test the product prepared by the present embodiment, as Fig. 3 and Fig. 4, be respectively the present embodiment products therefrom 1hNMR spectrogram and 13cNMR spectrogram, its 1hNMR(400MHz, CDCl 3) data are: δ 8.63 (s, 1H), 8.44 (d, J=7.7Hz, 1H), 8.00 (d, J=7.7Hz, 1H), 7.70 (d, J=8.2Hz, 2H), 7.62 (t, J=7.9Hz, 2H), 7.48 – 7.40 (m, 2H), 2.79 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.9,151.5,148.8,139.3,138.2,133.0,131.9,131.4,130.0,129.8,127.1,123.3,122.7,122.2,121.9,113.8,112.4,24.4; Adopting high resolution mass spectrum to measure compound molecular weight is 328.20.
Can judge that product is 1-(3-bromophenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 18h 12nOBr).
Embodiment four
Synthesis 1-(3-bromophenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Take 4.15g2, 3'-dibromobenzene ethyl ketone (15mmol), 1.21g4-(2-hydroxy phenyl)-3-butene-2-one (7.5mmol) and 657mg potassium hydroxide (13.5mmol), add in 60mL tetrahydrofuran (THF), and at 30 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 5h, 7.7g ammonium acetate (100mmol) and 100mL dehydrated alcohol is added in this system, continue return stirring and react 6 hours, reflux temperature is 120 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain faint yellow solid product, heavy 1.27g, productive rate is 50%.Acquired results is substantially identical with embodiment three.
Embodiment five
Synthesis 1-(4-bromophenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment three, difference is to substitute 2.77g2,3'-dibromobenzene ethyl ketone (10mmol) with 2.77g2,4'-dibromobenzene ethyl ketone (10mmol), and obtain white solid product, weigh 1.06g, productive rate 42%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.37 (d, J=8.6Hz, 2H), 7.99 (d, J=7.9Hz, 1H), 7.68 (dd, J=13.8,8.2Hz, 4H), 7.64 – 7.58 (m, 1H), 7.41 (t, J=7.4Hz, 1H), 2.77 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.8,151.5,148.8,139.7,135.1,132.7,131.6,130.2,129.8,123.5,123.3,122.2,121.9,113.6,112.3,24.1; Adopting high resolution mass spectrum to measure compound molecular weight is 338.20.
Can judge that product is 1-(4-bromophenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 18h 12nOBr).
Embodiment six
Synthesis 1-(4-chloro-phenyl-)-3-methl-benzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment three, difference is to substitute 2.77g2,3'-dibromobenzene ethyl ketone (10mmol) with the bromo-4'-chloro-acetophenone (10mmol) of 2.33g2-, and obtain yellow solid product, weigh 0.68g, productive rate 31%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.45 (d, J=8.7Hz, 2H), 8.02 (d, J=7.8Hz, 1H), 7.69 (t, J=4.1Hz, 2H), 7.65 – 7.59 (m, 1H), 7.56 (d, J=8.6Hz, 2H), 7.43 (dd, J=11.4,4.3Hz, 1H), 2.79 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.9,151.4,148.8,139.9,135.1,134.8,133.0,129.9,129.8,129.7,128.7,123.3,122.3,121.9,113.5,112.5,24.5; Adopting high resolution mass spectrum to measure compound molecular weight is 293.75.
Can judge that product is 1-(4-chloro-phenyl-according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 18h 12nOCl).
Embodiment seven
Synthesis 1-(4-p-methoxy-phenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment three, difference is to substitute 2.77g2,3'-dibromobenzene ethyl ketone (10mmol) with the bromo-4'-methoxyacetophenone (10mmol) of 2.29g2-, and obtain yellow solid product, weigh 1.19g, productive rate 55%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.50 – 8.43 (m, 2H), 7.92 (d; J=7.7Hz, 1H), 7.63 (d; J=8.3Hz, 1H), 7.59 – 7.50 (m; 2H), 7.40 – 7.31 (m, 1H); 7.16 – 7.06 (m, 2H), 3.92 (s; 3H), 2.77 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 160.4,156.7,151.2,148.7,141.0,132.4,130.1,129.4,129.1,123.1,122.5,121.8,114.0,112.4,112.3,55.1,24.4; Adopting high resolution mass spectrum to measure compound molecular weight is 289.33.
Can judge that product is 1-(4-p-methoxy-phenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 19h 15nO 2).
Embodiment eight
Synthesis 1-(3-aminomethyl phenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment three, difference is to substitute 2.77g2,3'-dibromobenzene ethyl ketone (10mmol) with the bromo-3'-methyl acetophenone (10mmol) of 2.13g2-, and obtain yellow solid product, weigh 1.21g, productive rate 59%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.29 (d, J=9.8Hz, 2H), 7.97 (d; J=7.7Hz, 1H), 7.67 (d, J=8.3Hz; 1H), 7.60 (dd, J=14.1,6.6Hz; 2H), 7.51 (t, J=7.6Hz, 1H); 7.42 – 7.32 (m, 2H), 2.81 (s; 3H), 2.56 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.9,151.3,150.0,141.6,138.2,136.3,132.7,130.0,129.6,129.2,128.8,128.4,128.4,126.0,123.1,122.4,121.8,113.1,112.4,24.5,21.7; Adopting high resolution mass spectrum to measure compound molecular weight is 273.33.
Can judge that product is 1-(3-aminomethyl phenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 19h 15nO).
Embodiment nine
Synthesis 1-(4-aminomethyl phenyl)-3-methl-benzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment three, difference is to substitute 2.77g2,3'-dibromobenzene ethyl ketone (10mmol) with the bromo-4'-methyl acetophenone (10mmol) of 2.13g2-, and obtain yellow solid product, weigh 1.39g, productive rate 68%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.41 (d, J=8.2Hz, 2H), 7.91 (dd; J=16.5,6.8Hz, 1H), 7.64 (d; J=8.3Hz, 1H), 7.60 – 7.54 (m, 2H); 7.43 (d, J=8.0Hz, 2H); 7.40 – 7.35 (m, 1H), 2.80 (s; 3H), 2.51 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.8,151.2,148.8,141.4,139.1,133.6132.6,129.5,129.3,128.7,123.1,122.4,121.8,112.9,112.4,24.5,21.5; Adopting high resolution mass spectrum to measure compound molecular weight is 273.33.
Can judge that product is 1-(4-aminomethyl phenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data)-3-methl-benzofuran also [2,3-c] pyridine (C 19h 15nO).
Embodiment ten
The synthesis chloro-3-methyl isophthalic acid-phenylbenzofuran of 6-also [2,3-c] pyridine:
Take the alpha-brominated methyl phenyl ketone of 2g (10mmol), 1.47g4-(5-chlorine-2-hydroxyl phenyl)-3-butene-2-one (7.5mmol) and 630mg potassium hydroxide (11.25mmol), add in 40mL tetrahydrofuran (THF), and at 25 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 1h, 6.1g ammonium acetate (80mmol) and 80mL dehydrated alcohol is added in this system, continue return stirring and react 3 hours, reflux temperature is 100 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain faint yellow solid product, heavy 1.01g, productive rate is 46%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.44 – 8.40 (m, 2H), 7.88 (d, J=1.3Hz, 1H), 7.60 (d, J=7.2Hz, 2H), 7.53 – 7.50 (m, 4H), 2.77 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 155.0,151.7,149.4,141.5,136.0,131.7,129.7,129.3,128.7,128.6,128.6,123.8,121.5,113.5,113.1,24.5; Adopting high resolution mass spectrum to measure compound molecular weight is 293.75.
Can judge that product is the chloro-3-methyl isophthalic acid-phenylbenzofuran of 6-also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 18h 12nOCl).
Embodiment 11
The synthesis bromo-3-methyl isophthalic acid-phenylbenzofuran of 6-also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with the bromo-2-hydroxy phenyl of 1.81g4-(5-) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow solid product, weigh 1.12g, productive rate 44%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.41 (d, J=7.3Hz, 2H), 8.03 (d, J=1.8Hz, 1H), 7.62 (m, 3H), 7.49 (dd, J=13.9,7.3Hz, 3H), 2.76 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 155.3,151.7,149.2,141.3,136.0,132.3,131.5,129.3,128.6,128.6,128.4,124.6,116.0,113.9,113.1,24.5; Adopting high resolution mass spectrum to measure compound molecular weight is 338.20.
Can judge that product is the bromo-3-methyl isophthalic acid-phenylbenzofuran of 6-also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 18h 12nOBr).
Embodiment 12
The synthesis 6-tertiary butyl-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with the 1.64g4-(5-tertiary butyl-2-hydroxy phenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow solid product, weigh 1.68g, productive rate 71%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.49 (t, J=7.0Hz, 2H); 8.02 (d, J=1.7Hz, 1H); 7.71 – 7.65 (m, 2H), 7.64 – 7.58 (m; 3H), 7.55 – 7.47 (m, 1H); 2.82 (s; 3H), 1.49 (s, 9H); 13cNMR(100MHz, CDCl 3) data are: δ 155.1,151.2,146.4,141.1,136.4,133.1,129.1,128.7,128.5,128.5,127.6,122.0,117.8,113.2,111.8,34.9,31.8,24.5.Adopting high resolution mass spectrum to measure compound molecular weight is 315.41.
Can judge that product is the 6-tertiary butyl-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 22h 21nO).
Embodiment 13
Synthesis 6,8-di-t-butyl-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with 2.06g4-(3,5-di-t-butyl-2-hydroxy phenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow solid product, weigh 2.17g, productive rate 78%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.55 (d, J=7.4Hz, 2H), 7.90 (d; J=1.7Hz, 1H), 7.73 (s, 1H); 7.62 (dd, J=7.1,4.9Hz, 3H); 7.51 (t, J=7.4Hz, 1H); 2.83 (s, 3H), 1.67 (s; 9H), 1.50 (s, 9H); 13cNMR(100MHz, CDCl 3) data are: δ 153.3,150.9,148.9,146.2,140.6,136.7,134.9,133.2,128.9,128.5,128.4,124.2,122.3,115.6,113.1,35.1,34.7,31.9,29.9,24.6.Adopting high resolution mass spectrum to measure compound molecular weight is 371.51.
Can judge that product is 6,8-di-t-butyl-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 26h 29nO).
Embodiment 14
Synthesis 7-methoxyl group-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with 1.44g4-(4-methoxyl group-2-hydroxy phenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow solid product, weigh 0.24g, productive rate 11%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.50 – 8.37 (m, 2H), 7.86 (d, J=8.6Hz; 1H), 7.58 (dd, J=10.7,4.4Hz; 3H), 7.52 – 7.42 (m, 1H), 7.18 (d; J=2.2Hz, 1H), 7.01 (dd, J=8.6; 2.2Hz, 1H), 3.94 (s; 3H), 2.78 (s, 3H); 13cNMR(400MHz, CDCl 3) data are: δ 161.8,158.5,151.5,149.2,140.7,136.5,133.0,129.0,128.6,128.5,128.5,122.2,115.4,112.6,112.2,96.6,55.8,24.5.Adopting high resolution mass spectrum to measure compound molecular weight is 289.33.
Can judge that product is 7-methoxyl group-3-methyl isophthalic acid-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 19h 15nO 2).
Embodiment 15
Synthesis 3,6-dimethyl-1-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with 1.32g4-(2-hydroxy-5-methyl base phenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow solid product, weigh 0.66g, productive rate 32%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 7.55 – 7.51 (m, 2H), 7.12 (s, 1H); 7.04 (s, 1H), 6.84 (d, J=8.5Hz; 1H), 6.73 (t, J=7.5Hz; 2H), 6.64 (dd, J=11.6; 4.3Hz, 2H), 1.82 (s; 3H), 1.62 (s, 3H); 13cNMR(400MHz, CDCl 3) data are: δ 159.7,156.0,153.7,144.8,140.9,138.1,137.6,136.5,134.4,133.7,133.4,127.2,126.8,118.9,117.1,29.3,26.0.Adopting high resolution mass spectrum to measure compound molecular weight is 273.33.
Can judge that product is 3,6-dimethyl-1-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 19h 15nO).
Embodiment 16
Synthesis 3,6,8 – trimethylammonium-1-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with 1.43g4-(2-hydroxyl-3,5-3,5-dimethylphenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain white solid product, weigh 1.23g, productive rate 57%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.56 – 8.49 (m, 2H), 7.66 – 7.59 (m, 2H), 7.55 – 7.46 (m; 3H), 7.14 (s, 1H), 2.79 (s, 3H); 2.56 (s, 3H), 2.46 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 154.2,150.9,149.0,140.8,136.6,133.1,132.6,131.7,129.0,128.6,128.5,121.9,121.6,118.8,113.2,24.5,21.3,15.2.Adopting high resolution mass spectrum to measure compound molecular weight is 287.35.
Can judge that product is 3,6,8 – trimethylammonium-1-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 20h 17nO).
Embodiment 17
Synthesis 3,6,7 – trimethylammonium-1-phenylbenzofuran also [2,3-c] pyridine:
Adopt the method identical with embodiment nine, difference is with 1.43g4-(2-hydroxyl-4,5-3,5-dimethylphenyl) the alternative 1.47g4-(5-chlorine-2-hydroxyl phenyl of-3-butene-2-one (7.5mmol))-3-butene-2-one (7.5mmol), obtain yellow oil product, weigh 1.36g, productive rate 63%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.48 (dd, J=8.3,1.0Hz; 2H), 7.62 (dd, J=10.4; 4.7Hz, 3H), 7.55 – 7.48 (m; 2H), 7.37 (s, 1H); 2.78 (s, 3H), 2.40 (s; 3H), 2.38 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 155.8,151.0,148.9,140.8,139.3,136.6,132.9,131.8,128.9,128.7,128.5,121.7,119.9,112.9,112.7,24.5,20.9,19.9.Adopting high resolution mass spectrum to measure compound molecular weight is 287.35.
Can judge that product is 3,6,7 – trimethylammonium-1-phenylbenzofuran also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 20h 17nO).
Embodiment 18
Synthesis 1,3-phenylbenzene-cumarone also [2,3-c] pyridine:
Take the alpha-brominated methyl phenyl ketone of 2g (10mmol), 1.68g2-hydroxylated chalcone (7.5mmol) and 630mg potassium hydroxide (11.25mmol), add in 40mL tetrahydrofuran (THF), and at 25 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 1h, 6.1g ammonium acetate (80mmol) and 100mL dehydrated alcohol is added in this system, continue return stirring and react 6 hours, reflux temperature is 110 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain white solid product, heavy 0.77g, productive rate is 32%.
Adopt the method identical with embodiment one to test the product prepared by the present embodiment, as Fig. 5 and Fig. 6, be respectively the present embodiment products therefrom 1hNMR spectrogram and 13cNMR spectrogram, its 1hNMR(400MHz, CDCl 3) data are: δ 8.66 (d, J=7.3Hz, 2H), 8.27 (t; J=3.6Hz, 3H), 8.10 (d, J=7.8Hz; 1H), 7.73 (d, J=8.4Hz; 1H), 7.67 – 7.62 (m, 3H); 7.59 – 7.53 (m, 3H), 7.47 (dd; J=7.4,2.6Hz, 2H); 13cNMR(100MHz, CDCl 3) data are: δ 157.0,150.8,149.7,141.3,139.8,136.4,133.2,129.8,129.3,128.8,128.7,128.6,128.4,127.1,123.3,122.6,121.9,112.6,110.6; Adopting high resolution mass spectrum to measure compound molecular weight is 321.37.
Can judge that product is 1,3-phenylbenzene-cumarone also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 23h 15nO).
Embodiment 19
Synthesis 1,3-phenylbenzene-cumarone also [2,3-c] pyridine:
Take the alpha-brominated methyl phenyl ketone of 1.8g (9mmol), 2.02g2-hydroxylated chalcone (9mmol) and 630mg potassium hydroxide (11.25mmol), add in 20mL tetrahydrofuran (THF), and at 10 DEG C stirring reaction, thin-layer chromatography is adopted to follow the tracks of reaction, after reaction 1h, 6.1g ammonium acetate (60mmol) and 60mL dehydrated alcohol is added in this system, continue return stirring and react 3 hours, reflux temperature is 90 DEG C, gained reaction mixture adopts vacuum distillation method except desolventizing, recycle silicon glue post carries out purifying to remaining material, obtain white solid product, heavy 0.98g, productive rate is 34%.
Adopt the method identical with embodiment one to test the product prepared by the present embodiment, as Fig. 5 and Fig. 6, be respectively the present embodiment products therefrom 1hNMR spectrogram and 13cNMR spectrogram, its 1hNMR(400MHz, CDCl 3) data are: δ 8.66 (d, J=7.3Hz, 2H), 8.27 (t; J=3.6Hz, 3H), 8.10 (d, J=7.8Hz; 1H), 7.73 (d, J=8.4Hz; 1H), 7.67 – 7.62 (m, 3H); 7.59 – 7.53 (m, 3H), 7.47 (dd; J=7.4,2.6Hz, 2H); 13cNMR(100MHz, CDCl 3) data are: δ 157.0,150.8,149.7,141.3,139.8,136.4,133.2,129.8,129.3,128.8,128.7,128.6,128.4,127.1,123.3,122.6,121.9,112.6,110.6; Adopting high resolution mass spectrum to measure compound molecular weight is 321.37.
Can judge that product is 1,3-phenylbenzene-cumarone also [2,3-c] pyridine (C according to hydrogen spectrum, carbon spectrum and mass-spectrometric data 23h 15nO).
Embodiment 20
Synthesis 1-phenyl-3-(p-methylphenyl) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 1.79g3-(2-hydroxy phenyl)-1-(4-aminomethyl phenyl) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain faint yellow solid product, weigh 2.09g, productive rate 83%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.74 – 8.58 (m, 2H), 8.18 (d, J=8.1Hz; 2H), 8.13 (d, J=5.9Hz, 1H); 8.00 (d, J=7.7Hz, 1H); 7.72 – 7.64 (m, 3H), 7.62 – 7.56 (m; 2H), 7.40 (t, J=7.1Hz; 3H), 2.52 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 156.9,150.7,149.7,141.0,138.3,137.0,136.6,133.2,129.7,129.5,129.3,128.9,128.7,128.6,126.9,123.3,122.7,121.8,112.4,110.2,21.1.Adopting high resolution mass spectrum to measure compound molecular weight is 335.40.
Can judge that product is 1-phenyl-3-(p-methylphenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 24h 17nO).
Embodiment 21
Synthesis 1-phenyl-3-(p-methoxyphenyl) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 1.91g3-(2-hydroxy phenyl)-1-(4-p-methoxy-phenyl) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain faint yellow oil product, weigh 1.71g, productive rate 65%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1h-NMR (400MHz, CDCl 3) δ 8.65 (d, J=7.4Hz, 2H), 8.21 (d, J=8.9Hz; 3H), 8.10 (d, J=7.7Hz, 1H); 7.73 (d, J=8.3Hz, 1H), 7.67 – 7.60 (m; 3H), 7.54 (d, J=7.2Hz, 1H); 7.46 (t, J=7.5Hz, 1H), 7.09 (d; J=8.8Hz, 2H), 3.93 (s, 3H); 13cNMR(100MHz, CDCl 3) data are: δ 160.0,156.9,150.6,149.5,141.2,136.6,133.1,132.5,129.7,129.3,128.8,128.5,128.3,123.3,122.5,121.7,114.0,112.6,109.8,29.4.Adopting high resolution mass spectrum to measure compound molecular weight is 351.39.
Can judge that product is 1-phenyl-3-(p-methoxyphenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 24h 17nO 2).
Embodiment 22
Synthesis 1-phenyl-3-(rubigan) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 1.94g3-(2-hydroxy phenyl)-1-(4-chloro phenyl) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain faint yellow solid product, weigh 1.68g, productive rate 63%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: 8.66 – 8.59 (m, 2H), 8.23 – 8.15 (m, 3H), 8.08 (d; J=7.7Hz, 1H), 7.73 (d, J=8.3Hz, 1H); 7.68 – 7.60 (m, 3H), 7.55 – 7.44 (m, 4H); 13cNMR(100MHz, CDCl 3) data are: δ 157.1,149.9,149.5,141.5,138.2,136.2,134.5,133.3,129.9,129.5,128.8,128.8,128.6,128.3,123.5,122.5,121.9,112.6,110.4.Adopting high resolution mass spectrum to measure compound molecular weight is 355.81.
Can judge that product is 1-phenyl-3-(rubigan according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 23h 14nOCl).
Embodiment 23
Synthesis 1-phenyl-3-(2-chloro-phenyl-) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 1.94g3-(2-hydroxy phenyl)-1-(2-chloro-phenyl-) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain pale yellow oily liquid body, weigh 1.47g, productive rate 55%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.64 – 8.58 (m, 2H), 8.19 (s, 1H); 8.07 (d, J=7.7Hz, 1H), 7.85 (dd; J=7.5,1.8Hz, 1H), 7.74 (d; J=8.3Hz, 1H), 7.66 – 7.59 (m; 4H), 7.54 (d, J=7.3Hz; 1H), 7.48 – 7.40 (m, 3H); 13cNMR(100MHz, CDCl 3) data are: 13c-NMR (100MHz, CDCl 3) δ 157.0,150.0,149.7,141.7,139.6,136.2,132.5,132.4,132.2,130.2,129.9,129.4,129.3,128.9,128.6,127.1,123.4,122.4,122.0,115.3,112.5.Adopting high resolution mass spectrum to measure compound molecular weight is 355.81.
Can judge that product is 1-phenyl-3-(2 chloro-phenyl-according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 23h 14nOCl).
Embodiment 24
Synthesis 1-phenyl-3-(3-bromophenyl) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 2.27g3-(2-hydroxy phenyl)-1-(3-bromophenyl) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain weak yellow liquid, weigh 2.43g, productive rate 81%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.57 (d, J=7.7Hz, 2H); 8.34 (s, 1H), 8.08 (d; J=7.8Hz, 1H), 8.02 (s; 1H), 7.95 (d, J=7.7Hz; 1H), 7.64 – 7.55 (m, 6H); 7.42 – 7.35 (m, 2H); 13cNMR(100MHz, CDCl 3) data are: δ 156.9,149.9,148.7,141.6,141.3,136.1,133.1,131.2,130.1,130., 129.9,129.5,128.7,128.6,125.5,123.5,123.0,122.3,121.8,112.5,110.6.Adopting high resolution mass spectrum to measure compound molecular weight is 400.27.
Can judge that product is 1-phenyl-3-(3-bromophenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 23h 14nOBr).
Embodiment 25
Synthesis 1-phenyl-3-(is to bromophenyl) cumarone also [2,3-c] pyridine:
Adopt the method identical with embodiment 18, difference is with 2.27g3-(2-hydroxy phenyl)-1-(4-bromophenyl) the alternative 1.68g2-hydroxylated chalcone (7.5mmol) of-2-propylene-1-ketone (7.5mmol), obtain faint yellow solid product, weigh 2.25g, productive rate 75%.
The method of nucleus magnetic resonance (NMR) is adopted to test the product prepared by the present embodiment, its 1hNMR(400MHz, CDCl 3) data are: δ 8.59 (d, J=7.4Hz, 2H), 8.10 (s, 1H), 8.06 (d; J=8.4Hz, 2H), 8.00 (d, J=7.6Hz, 1H), 7.63 (dd; J=17.1,8.6Hz, 7H), 7.45 – 7.40 (m, 1H); 13cNMR(100MHz, CDCl 3) data are: δ 157.0,149.8,149.2,141.3,138.4,136.1,133.2,131.8,129.9,129.4,128.7,128.6,128.5,123.5,122.7,122.4,121.8,112.6,110.2.Adopting high resolution mass spectrum to measure compound molecular weight is 400.27.
Can judge that product is that 1-phenyl-3-(is to bromophenyl according to hydrogen spectrum, carbon spectrum and mass-spectrometric data) cumarone also [2,3-c] pyridine (C 23h 14nOBr).
By the above detailed description to the embodiment of the present invention, can understand and the invention solves ordinary method and prepare cumarone also [2,3-c] pyridine compounds cost is high, the difficult situation of complex process, the cumarone simultaneously prepared also [2,3-c] pyridine compounds purity is higher, is suitable for industrial application.
Be understandable that, the illustrative embodiments that above embodiment is only used to principle of the present invention is described and adopts, but the present invention is not limited thereto.For those skilled in the art, without departing from the spirit and substance in the present invention, can make various modification and improvement, these modification and improvement are also considered as protection scope of the present invention.

Claims (5)

1. cumarone also [2,3-c] pyridine compounds, is characterized in that having following general structure:
Wherein
R 1for phenyl, the bromo-phenyl of 3-, the bromo-phenyl of 4-, the chloro-phenyl of 4-, 4-methoxyl group-phenyl, 3-methylphenyl or 4-methylphenyl;
R 2for hydrogen or 5-chlorine, 5-bromine, the 5-tertiary butyl, 3,5-di-t-butyls, 4-methoxyl group, 5-methoxyl group, 5-methyl, 3,5-dimethyl, 4,5-dimethyl;
R 3for methyl.
2. cumarone according to claim 1 also [2, 3-c] synthetic method of pyridine compounds, concrete steps are: at 10-30 DEG C, feed intake with the ratio of the alpha-brominated methyl phenyl ketone or derivatives thereof of 9-15mmol and 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof 1:1-2:1 in molar ratio, with 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof molar weight 1.25-1.8 potassium hydroxide doubly and/or sodium hydroxide for catalyzer, 20-60mL tetrahydrofuran (THF) and/or acetonitrile are solvent, reaction 1-5h, thin-layer chromatography monitoring reaction, 60-100mmol ammonium acetate and 60-100mL dehydrated alcohol is added after reaction terminates, within back flow reaction 3-6 hour, product is obtained in 90-120 DEG C, product is through being separated, purifying obtains cumarone also [2, 3-c] pyridine compounds.
3. cumarone according to claim 2 also [2,3-c] synthetic method of pyridine compounds, it is characterized in that: described alpha-brominated methyl phenyl ketone or derivatives thereof comprises alpha-brominated methyl phenyl ketone, 2,3'-dibromobenzene ethyl ketone, 2,4'-dibromobenzene ethyl ketones, 2-bromo-4'-chloro-acetophenone, 2-bromo-4'-methoxyacetophenone, 2-bromo-3'-methyl acetophenone or the bromo-4'-methyl acetophenone of 2-.
4. cumarone according to claim 2 also [2, 3-c] synthetic method of pyridine compounds, it is characterized in that: described 4-(2-hydroxy phenyl)-3-butene-2-one or derivatives thereof comprises 4-(2-hydroxy phenyl)-3-butene-2-one, 4-(5-chlorine-2-hydroxyl phenyl)-3-butene-2-one, 4-(the bromo-2-hydroxy phenyl of 5-)-3-butene-2-one, 4-(the 5-tertiary butyl-2-hydroxy phenyl)-3-butene-2-one, 4-(3, 5-di-t-butyl-2-hydroxy phenyl)-3-butene-2-one, 4-(2-hydroxy-4-methoxyphenyl)-3-butene-2-one, 4-(2-hydroxy-5-methyl oxygen phenyl)-3-butene-2-one, 4-(2-hydroxy-5-methyl phenyl)-3-butene-2-one, 4-(2-hydroxyl-3, 5-3,5-dimethylphenyl)-3-butene-2-one or 4-(2-hydroxyl-4, 5-xylyl)-3-butene-2-one.
5. the synthetic method of cumarone according to claim 2 also [2,3-c] pyridine compounds, is characterized in that: described separation, purifying adopt vacuum distillation method except desolventizing, then adopt silica column purification product.
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CN109912610A (en) * 2019-04-04 2019-06-21 北京诚志永华显示科技有限公司 Organic compound and its preparing the application in organic electroluminescent device

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