CN104910073A - Diaryl-azepin-5-one compound synthesis method - Google Patents
Diaryl-azepin-5-one compound synthesis method Download PDFInfo
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- CN104910073A CN104910073A CN201510269304.2A CN201510269304A CN104910073A CN 104910073 A CN104910073 A CN 104910073A CN 201510269304 A CN201510269304 A CN 201510269304A CN 104910073 A CN104910073 A CN 104910073A
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- aryl
- azatropylidene
- ketone compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
Abstract
The invention relates to a diaryl-azepin-5-one compound synthesis method. The method comprises that o-haloarylmethanol and aryl cyanide (or a mixture of aryl methanol and o-haloarylmethanol), a ruthenium catalyst, a palladium salt, azacycloimidazolium salt and an alkali are added into an organic solvent and the solution is heated in a N2 protective atmosphere so that through a hydrogen transfer reaction and a carbon-hydrogen bond activation reaction, the diaryl-azepin-5-one compound is produced. The method provides an economic and practical preparation method for synthesis of the substituted diaryl-azepin-5-one derivative with drug activity. The method has simple processes, utilizes cheap reaction substrates with a wide source scope, produces small environment pollution, has high reaction economy and efficiency and has an important application value.
Description
Technical field
The present invention relates to technical field of organic synthesis, be specifically related to di-aryl and the synthetic method of azatropylidene-5-ketone compounds.
Background technology
The basic structural unit of azatropylidene compounds is seven yuan of Zhuo Huan containing a nitrogen-atoms, aryl azatropylidene compounds has unique physiologically active and the heterogeneous ring compound of pharmacologically active, enjoys the concern of people.Some of them compound has the curative effect of the aspects such as antipsychotic disease, pain relieving and treatment cardiovascular diseases, and it has very large pharmaceutical potential and wide application prospect.Although have now very eurypalynous aryl and azatropylidene compounds is synthesized out, di-aryl azatropylidene-5-ketone compounds also rare report.Grigg in 1991 etc. report Reactive Synthesis di-aryl within dividing of two halogen aromatic hydrocarbons of palladium chtalyst special substrate phosphinylidyne-containing amine group and azatropylidene-5-ketone compounds (Tetrahedron Letters, 1991,32,3859-3862).
;
The report such as Goh in 2010 obtains di-aryl and azatropylidene-5-ketone compounds (Heterocycles, 2010,80,669-677) by Suzuki and reduction reaction two-step reaction.
;
The synthetic method of these palladium chtalyst needs to use special substrate, is not easy to obtain and limitednumber, and its preparation is comparatively loaded down with trivial details, expensive, needs with to the disadvantageous Phosphine ligands of environment in addition, and environmental pollution is large, make them receive certain restriction in the industrial production.
Summary of the invention
The object of the invention is the deficiency for solving the problems of the technologies described above, providing a kind of di-aryl and the synthetic method of azatropylidene-5-ketone compounds.
The present invention is the deficiency solved the problems of the technologies described above, the technical scheme adopted is: a kind of di-aryl the synthetic method of azatropylidene-5-ketone compounds, be specially: get adjacent halogen aryl methyl alcohol, aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali and join in organic solvent, at N
2heat under gas shielded, reaction terminates rear extraction and obtains di-aryl and azatropylidene-5-ketone compounds, and reaction formula is as follows:
；
Or get aryl methyl alcohol, adjacent halogen aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali and join in organic solvent, at N
2heat under gas shielded, reaction terminates rear extraction and obtains di-aryl and azatropylidene-5-ketone compounds, and reaction process is as follows:
；
The structural formula of described adjacent halogen aryl methyl alcohol is as follows:
；
The structural formula of described aryl cyanides is as follows:
；
The structural formula of described aryl methyl alcohol is as follows:
；
The structural formula of described adjacent halogen aryl cyanides is as follows:
；
Described di-aryl the structural formula of azatropylidene-5-ketone compounds is as follows:
；
R in described adjacent halogen aryl methyl alcohol, aryl cyanides, aryl methyl alcohol, adjacent halogen aryl cyanides structural formula
1, R
2group and di-aryl R in azatropylidene-5-ketone compounds structural formula
1, R
2group connotation is identical; R
1and R
2for-H ,-CH
3,-CF
3,-OCH
3,-C
2h
5,-OC
2h
5,-C
6h
5,-CH
2c
6h
5,-NO
2,-COCH
3,-COOCH
3,-CHO ,-F ,-Cl or-Br; R
1any position on aromatic ring 1-4, R
2on aromatic ring 8-11, any position X is-Br or-Cl.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, the add-on mol ratio of described adjacent halogen aryl methyl alcohol, aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali is 1:1 ~ 2:0.02 ~ 0.1:0.03 ~ 0.1:0.05 ~ 0.15:2 ~ 6; Or the add-on mol ratio of aryl methyl alcohol, adjacent halogen aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali is 1:1 ~ 2:0.02 ~ 0.1:0.03 ~ 0.1:0.05 ~ 0.15:2 ~ 6.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, the condition of described reacting by heating is: temperature of reaction is 100-160 DEG C, reaction times 6-48h, reaction terminates rear recrystallization and purifies to product.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, described ruthenium catalyst is RuH
2(PPh
3)
4or RuH
2(CO) (PPh
3)
3.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, described palladium salt is Palladous chloride or palladium.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, described nitrogen heterocyclic imidazole salts is 1,3-two (2,6-diisopropyl phenyl) imidazolitm chloride, 1, two (2, the 6-diisopropyl phenyl) limidazolium of 3-or 1,3-two (2,6-diisopropylbenzyl)-4,5-glyoxalidine a tetrafluoro borates.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, described alkali is sodium hydride, sodium tert-butoxide or potassium tert.-butoxide.
Above-mentioned di-aryl in the synthetic method of azatropylidene-5-ketone compounds, described organic solvent is benzene, toluene, dioxane, DMF or dimethyl sulfoxide (DMSO).
beneficial effect
The present invention utilizes the available ruthenium of commodity, palladium metal catalyst, the adjacent halogen aryl methyl alcohol of co-catalysis and aryl cyanides (or aryl methyl alcohol and adjacent halogen aryl cyanides), react a step by hydrogen transfer reactions and carbon-hydrogen bond activation and generate di-aryl azatropylidene-5-ketone compounds, for synthesis has the replacement di-aryl of pharmaceutical activity and azatropylidene-5-ketones derivant provides an economical and practical preparation method.The method is simple to operate, and the cheap scope of reaction substrate is wide, environmental pollution is little, and economical in reaction is efficient, has important using value.
Embodiment
Synthetic method of the present invention can prepare the di-aryl shown in following table and azatropylidene-5-ketone compounds:
be below the specific embodiment that the present invention synthesizes invention, the compound no in embodiment is consistent with the compound no in upper table.
embodiment 1
di-aryl the preparation of azatropylidene-5-ketone compounds (1):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds the adjacent bromobenzene methyl alcohol of 1.0mmol, 2.0mmol cyanobenzene, 0.02mmol RuH
2(PPh
3)
4, 0.03mmol palladium, 0.05mmol 1,3-two (2,6-diisopropyl phenyl) imidazolitm chloride, 2.0mmol sodium hydride and 5ml toluene, with nitrogen replacement reaction tubes 3 times, be then heated to 110 DEG C with oil bath under magnetic stirring, reaction backflow 24 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
1, productive rate 85%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): δ 8.01 (d, 1H), 7.69 – 7.56 (m, 3H), 7.53 – 7.48 (m, 1H), 7.45 (td, 1H), 7.37 (td, 1H), 7.29 (dd, 1H), 6.66 (brs, 1H), 4.25 (dd, 1H), 3.96 (dd, 1H).
embodiment 2
di-aryl the preparation of azatropylidene-5-ketone compounds (3):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol phenylcarbinol, the bromo-5-chlorobenzonitrile of 1.2mmol 2-, 0.1mmol RuH
2(CO) (PPh
3)
3, 0.1mmol Palladous chloride, two (2, the 6-diisopropylbenzyl)-4 of 0.15mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 3.0mmol sodium tert-butoxide and 5ml benzene, with nitrogen replacement reaction tubes 3 times, be then heated to 100 DEG C with oil bath under magnetic stirring, reaction backflow 6 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
2, productive rate 82%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.01 (d, 1H), 7.63 – 7.49 (m, 4H), 7.43 (dd, 1H), 7.30 (d, 1H), 6.78 (brs, 1H), 4.21 (dd, 1H), 3.92 (dd, 1H).
embodiment 3
di-aryl the preparation of azatropylidene-5-ketone compounds (6):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol phenylcarbinol, 1.1mmol 2-bromo-4-methoxycarbonyl cyanobenzene, 0.05mmol RuH
2(CO) (PPh
3)
3, 0.06mmol acid chloride, 0.1mmol 1,3-two (2,6-diisopropyl phenyl) limidazolium, 6.0mmol potassium tert.-butoxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 10 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
6, productive rate 80%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 8.28 (s, 1H), 8.06 – 8.02 (m, 2H), 7.64 (d, 2H), 7.58 – 7.52 (m, 1H), 7.38 (d, 1H), 7.01 (brs, 1H), 4.26 (dd, 1H), 4.03 (dd, 1H), 3.95 (s, 3H).
embodiment 4
di-aryl the preparation of azatropylidene-5-ketone compounds (8):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol adjacent chlorobenzene methanol, 1.6mmol para-fluoroaniline, 0.1mmol RuH
2(CO) (PPh
3)
3, 0.09mmol palladium, two (2, the 6-diisopropylbenzyl)-4 of 0.13mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 5.0mmol sodium hydride and 5ml dimethyl sulfoxide (DMSO), with nitrogen replacement reaction tubes 3 times, be then heated to 160 DEG C with oil bath under magnetic stirring, reaction backflow 18 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
8, productive rate 79%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.00 (d, 1H), 7.63 – 7.48 (m, 4H), 7.15 (td, 1H), 7.02 (dd, 1H), 6.85 (brs, 1H), 4.22 (dd, 1H), 3.99 (dd, 1H).
embodiment 5
di-aryl the preparation of azatropylidene-5-ketone compounds (11):under nitrogen protection, to the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) of 10 ml add the adjacent bromobenzene methyl alcohol of 1.0mmol, the chloro-5-trifluoromethylbenzonitrile of 1.3mmol 2-, 0.1mmol RuH
2(PPh
3)
4, 0.1mmol palladium, 0.15mmol 1,3-two (2,6-diisopropylbenzyl)-4,5-glyoxalidine a tetrafluoro borate, 4.0mmol sodium hydride and 5ml N, dinethylformamide, with nitrogen replacement reaction tubes 3 times, be then heated to 160 DEG C with oil bath under magnetic stirring, reaction backflow 20 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
11, productive rate 81%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.00 (d, 1H), 7.60 – 7.48 (m, 4H), 7.41 (dd, 1H), 7.26 (d, 1H), 6.76 (brs, 1H), 4.20 (dd, 1H), 3.90 (dd, 1H).
embodiment 6
di-aryl the preparation of azatropylidene-5-ketone compounds (13):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol to bromobenzene methyl alcohol, the chloro-5-methyl benzonitrile of 1.3mmol 2-, 0.08mmol RuH
2(CO) (PPh
3)
3, 0.1mmol Palladous chloride, 0.15mmol 0.1mmol 1,3-two (2,6-diisopropyl phenyl) limidazolium, 3.0mmol sodium tert-butoxide and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 24 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
13, productive rate 87%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.02 (d, 1H), 7.86 (d, 1H), 7.65 (d, 1H), 7.35 (d, 1H), 7.12 (d, 1H), 7.03 (d, 1H), 6.73 (brs, 1H), 4.18 (dd, 1H), 3.87 (dd, 1H), 2.37 (s, 3H).
embodiment 7
di-aryl the preparation of azatropylidene-5-ketone compounds (15):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds the bromo-5-methylbenzyl alcohol of 1.0mmol 2-, 1.3mmol p-Fluorophenyl cyanide, 0.06mmol RuH
2(CO) (PPh
3)
3, 0.08mmol palladium, two (2, the 6-diisopropylbenzyl)-4 of 0.15mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 3.0mmol sodium hydride and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, be then heated to 110 DEG C with oil bath under magnetic stirring, reaction backflow 24 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
15, productive rate 78%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.01 (d, 1H), 7.88 (d, 1H), 7.67 (d, 1H), 7.42 (d, 1H), 7.20 (d, 1H), 7.12 (d, 1H), 6.87 (brs, 1H), 4.25 (dd, 1H), 4.00 (dd, 1H), 2.36 (s, 3H).
embodiment 8
di-aryl the preparation of azatropylidene-5-ketone compounds (17):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol meta-methoxy phenylcarbinol, the bromo-3-methoxy benzonitrile of 1.5mmol 2-, 0.06mmol RuH
2(PPh
3)
4, 0.1mmol palladium, two (2, the 6-diisopropylbenzyl)-4 of 0.15mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 2.0mmol potassium tert.-butoxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, be then heated to 110 DEG C with oil bath under magnetic stirring, reaction backflow 20 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
17, productive rate 91%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 7.98 (d, 1H), 7.67 (d, 1H), 7.61 (d, 1H), 7.10 (dt, 1H), 7.02 (d, 1H), 6.78 (dd, 1H), 6.71 (brs, 1H), 4.15 (dd, 1H), 3.82 (dd, 1H), 3,80 (s, 3H), 3,77 (s, 3H).
embodiment 9
di-aryl the preparation of azatropylidene-5-ketone compounds (20):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol to fluorophenyl methanol, the chloro-cyanobenzene of 1.1mmol 2-, 0.1mmol RuH
2(CO) (PPh
3)
3, 0.06mmol Palladous chloride, 0.12mmol 1,3-two (2,6-diisopropyl phenyl) imidazolitm chloride, 6.0mmol sodium tert-butoxide and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 22 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
20, productive rate 85%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.01 (d, 1H), 7.64 – 7.50 (m, 4H), 7.17 (td, 1H), 7.03 (dd, 1H), 6.87 (brs, 1H), 4.25 (dd, 1H), 4.00 (dd, 1H).
embodiment 10
di-aryl the preparation of azatropylidene-5-ketone compounds (22):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds the chloro-4-methylbenzyl alcohol of 1.0mmol 2-, 1.5mmol to trifluoromethylbenzonitrile, 0.1mmol RuH
2(PPh
3)
4, 0.1mmol palladium, two (2, the 6-diisopropylbenzyl)-4 of 0.15mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 5.0mmol sodium hydride and 5ml toluene, with nitrogen replacement reaction tubes 3 times, be then heated to 110 DEG C with oil bath under magnetic stirring, reaction backflow 18 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
22, productive rate 80%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.03 (d, 1H), 7.73 (d, 1H), 7.69 (d, 1H), 7.52 (d, 1H), 7.44 (d, 1H), 7.28 (dd, 1H), 6.96 (brs, 1H), 4.42 (dd, 1H), 4.26 (dd, 1H), 2.37 (s, 3H).
embodiment 11
di-aryl the preparation of azatropylidene-5-ketone compounds (25):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds fluorobenzonitrile, 0.05mmol RuH between the bromo-5-methylbenzyl alcohol of 1.0mmol 2-, 1.3mmol
2(CO) (PPh
3)
3, 0.1mmol Palladous chloride, 0.12mmol 1,3-two (2,6-diisopropyl phenyl) limidazolium, 5.0mmoll sodium tert-butoxide and 5ml benzene, with nitrogen replacement reaction tubes 3 times, be then heated to 100 DEG C with oil bath under magnetic stirring, reaction backflow 16 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
25, productive rate 77%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.00 (d, 1H), 7.70 (d, 1H), 7.67 (d, 1H), 7.50 (d, 1H), 7.42 (d, 1H), 7.24 (dd, 1H), 6.92 (brs, 1H), 4.40 (dd, 1H), 4.25 (dd, 1H), 2.35 (s, 3H).
embodiment 12
di-aryl the preparation of azatropylidene-5-ketone compounds (27):under nitrogen protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol to methylbenzyl alcohol, 1.2mmol 2-chloro-4-methoxy cyanobenzene, 0.08mmol RuH
2(CO) (PPh
3)
3, 0.1mmol palladium, two (2, the 6-diisopropylbenzyl)-4 of 0.12mmol 1,3-, 5-glyoxalidine a tetrafluoro borate, 3.0mmol sodium hydride and 5ml toluene, with nitrogen replacement reaction tubes 3 times, be then heated to 110 DEG C with oil bath under magnetic stirring, reaction backflow 18 hours.Remove oil bath, drop to room temperature; Add 3ml water to reaction solution, with the dichloromethane extraction three times of 5ml, merge organic phase and also use anhydrous MgSO
4dry 30 minutes, filter; Filtrate concentrates with rotatory evaporator, and the solid after concentrated is solvent with methylene dichloride, and recrystallization obtains straight product
27, productive rate 88%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 8.00 (d, 1H), 7.71 (d, 1H), 7.67 (d, 1H), 7.50 (d, 1H), 7.41 (d, 1H), 7.25 (dd, 1H), 6.92 (brs, 1H), 4.17 (dd, 1H), 3.84 (dd, 1H), 3,76 (s, 3H), 2.35 (s, 3H).
Claims (8)
1. di-aryl the synthetic method of azatropylidene-5-ketone compounds, is characterized in that:
Getting adjacent halogen aryl methyl alcohol, aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali joins in organic solvent, at N
2heat under gas shielded, reaction terminates rear extraction and obtains di-aryl and azatropylidene-5-ketone compounds;
Or get aryl methyl alcohol, adjacent halogen aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali and join in organic solvent, at N
2heat under gas shielded, reaction terminates rear extraction and obtains di-aryl and azatropylidene-5-ketone compounds;
The structural formula of described adjacent halogen aryl methyl alcohol is as follows:
；
The structural formula of described aryl cyanides is as follows:
；
The structural formula of described aryl methyl alcohol is as follows:
；
The structural formula of described adjacent halogen aryl cyanides is as follows:
；
Described di-aryl the structural formula of azatropylidene-5-ketone compounds is as follows:
；
R in described adjacent halogen aryl methyl alcohol, aryl cyanides, aryl methyl alcohol, adjacent halogen aryl cyanides structural formula
1, R
2group and di-aryl R in azatropylidene-5-ketone compounds structural formula
1, R
2group connotation is identical; R
1and R
2for-H ,-CH
3,-CF
3,-OCH
3,-C
2h
5,-OC
2h
5,-C
6h
5,-CH
2c
6h
5,-NO
2,-COCH
3,-COOCH
3,-CHO ,-F ,-Cl or-Br; R
1any position on aromatic ring 1-4, R
2on aromatic ring 8-11, any position X is-Br or-Cl.
2. di-aryl as claimed in claim 1 the synthetic method of azatropylidene-5-ketone compounds, is characterized in that: the add-on mol ratio of described adjacent halogen aryl methyl alcohol, aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali is 1:1 ~ 2:0.02 ~ 0.1:0.03 ~ 0.1:0.05 ~ 0.15:2 ~ 6; Or the add-on mol ratio of aryl methyl alcohol, adjacent halogen aryl cyanides, ruthenium catalyst, palladium salt, nitrogen heterocyclic imidazole salts and alkali is 1:1 ~ 2:0.02 ~ 0.1:0.03 ~ 0.1:0.05 ~ 0.15:2 ~ 6.
3. di-aryl as claimed in claim 1 the synthetic method of azatropylidene-5-ketone compounds, it is characterized in that: the condition of described reacting by heating is: temperature of reaction is 100-160 DEG C, reaction times 6-48h, reaction terminates rear recrystallization and purifies to product.
4. the di-aryl as described in claim as arbitrary in claim 1-3 the synthetic method of azatropylidene-5-ketone compounds, is characterized in that: described ruthenium catalyst is RuH
2(PPh
3)
4or RuH
2(CO) (PPh
3)
3.
5. the di-aryl as described in claim as arbitrary in claim 1-3 the synthetic method of azatropylidene-5-ketone compounds, is characterized in that: described palladium salt is Palladous chloride or palladium.
6. the di-aryl as described in claim as arbitrary in claim 1-3 azatropylidene-5-ketone chemical combination
The synthetic method of thing, is characterized in that: described nitrogen heterocyclic imidazole salts is two (2, the 6-of 1,3-
Diisopropyl phenyl) imidazolitm chloride, 1,3-two (2,6-diisopropyl phenyl) limidazolium or 1,3-two (2,6-diisopropylbenzyl)-4,5-glyoxalidine a tetrafluoro borate.
7. the di-aryl as described in claim as arbitrary in claim 1-3 the synthetic method of azatropylidene-5-ketone compounds, is characterized in that: described alkali is sodium hydride, sodium tert-butoxide or potassium tert.-butoxide.
8. the di-aryl as described in claim as arbitrary in claim 1-3 the synthetic method of azatropylidene-5-ketone compounds, is characterized in that: described organic solvent is benzene, toluene, dioxane, DMF or dimethyl sulfoxide (DMSO).
Priority Applications (1)
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| CN106699661A (en) * | 2016-11-22 | 2017-05-24 | 大连理工大学 | Preparation method of dibenzo [c, e] aza-5, 7 (6H)-dione compound |
| CN108586342A (en) * | 2017-12-27 | 2018-09-28 | 连云港笃翔化工有限公司 | Condensed biaryl azatropylidene -5- ketone compounds and its synthetic method |
| CN113214157A (en) * | 2021-04-25 | 2021-08-06 | 广西壮族自治区花红药业集团股份公司 | Application of pyrrolidone compound in preparation of medicine for treating inflammatory diseases |
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| BYUNGJOON KANG, ET AL.: "Ruthenium-catalyzed redox-neutral and single-step amide synthesis from alcohol and nitrile with complete atom economy", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| GUAN-WU WANG,ET AL.: "One-pot formation of C-C and C-N bonds through Palladium-catalyzed dual C-H activation: synthesis of phenanthridinones", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION》 * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106699661A (en) * | 2016-11-22 | 2017-05-24 | 大连理工大学 | Preparation method of dibenzo [c, e] aza-5, 7 (6H)-dione compound |
| CN106699661B (en) * | 2016-11-22 | 2019-04-09 | 大连理工大学 | A kind of preparation method of dibenzo [c, e] azepine -5,7 (6H)-dione compounds |
| CN108586342A (en) * | 2017-12-27 | 2018-09-28 | 连云港笃翔化工有限公司 | Condensed biaryl azatropylidene -5- ketone compounds and its synthetic method |
| CN113214157A (en) * | 2021-04-25 | 2021-08-06 | 广西壮族自治区花红药业集团股份公司 | Application of pyrrolidone compound in preparation of medicine for treating inflammatory diseases |
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