CN104230689A - 6,7-dihydro-5H-diphenyl[a,c]cyclohepta-5-ketone compound and preparation method thereof - Google Patents
6,7-dihydro-5H-diphenyl[a,c]cyclohepta-5-ketone compound and preparation method thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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Abstract
The invention relates to a 6,7-dihydro-5H-diphenyl[a,c]cyclohepta-5-ketone compound and a preparation method thereof. A formula of the compound is as shown in the specification. O-bromoaryl methanol, aryl ethanone, [Ir(cod)Cl]2, a palladium salt, a sliver salt, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine and alkaline are taken and added into an organic solvent, heated and refluxed in the presence of an N2 gas, filtered, evaporated and re-crystallized after the reaction is ended to obtain the 6,7-dihydro-5H-diphenyl[a,c]cyclohepta-5-ketone compound. The 6,7-dihydro-5H-diphenyl[a,c]cyclohepta-5-ketone compound is synthesized by one step, wherein the reaction substrate scope is wide, the yield is high, the reaction is economical and efficient, and the application prospect is wide.
Description
Technical field
The present invention relates to technical field of organic synthesis, be specifically related to 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds and preparation method thereof.
Background technology
Allocolchicine (
) compounds is important cancer therapy drug, have unique mechanism of action, active and to advantages such as solid tumor are evident in efficacy efficiently, enjoy the concern of people, developing this type of medicine has wide market outlook.Allocolchicine obtains from the middle separation of spending of liliaceous plant Colchicum autumnale, and its product category and limits throughput, can not meet the need of market.The synthetic method of present allocolchicine derivative has a great development, its synthesize most important intermediate be 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds (
).The synthesis of existing this intermediate of bibliographical information, but reactions steps is more, condition is harsh, and complex operation, yield is lower.Synthesizing such intermediate with metal catalytic is at present most study and a kind of the most promising method, for improving Atom economy and the combined coefficient of reaction, one kettle way cascade reaction can with succinct, highly selective and efficiently advantage synthesize complicated molecule, become the important directions that chemist endeavours researchdevelopment.In recent years, the alpha-alkyl of metal catalytic alcohol and aryl methyl ketone reacts and carbon-hydrogen bond activation reacts, become C-C generate important method and organic synthesis in indispensable means.As far as we know, with the adjacent bromine aryl methyl alcohol of many metal catalytics and aryl methyl ketone (or adjacent bromine aryl methyl ketone and aryl methyl alcohol) by alpha-alkyl reaction and carbon-hydrogen bond activation reaction one-step synthesis 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds is not also reported.We are by the cascade reaction of the adjacent bromine aryl methyl alcohol of iridium, palladium and silver-colored co-catalysis and aryl methyl ketone (or adjacent bromine aryl methyl ketone and aryl methyl alcohol), one kettle way prepares 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, used catalyst commodity can obtain, substrate spectrum is wide, productive rate is high, economical and efficient, has a extensive future.
summary of the invention
The object of the invention is the deficiency for solving the problems of the technologies described above, 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds and preparation method thereof is provided.
The present invention is the deficiency solved the problems of the technologies described above, and the technical scheme adopted is: 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, and the general formula of this compound is:
，
Wherein, R
1, R
2for-H ,-CH
3,-OCH
3,-C
2h
5,-CN ,-NO
2,-COOCH
3,-CHO ,-F ,-Cl or-Br; R
1, R
2be positioned at any position on aromatic ring 1-4 and 8-11.
The preparation method of 6,7-described dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, gets adjacent bromine aryl methyl alcohol, aryl methyl ketone, [Ir (cod) Cl]
2(cod=1,5-cyclooctadiene), palladium salt, silver salt, the two diphenyl phosphine of 1,1'-dinaphthalene-2,2'-and alkali join in organic solvent, at N
2reflux under gas shielded, reaction terminates rear filtration, evaporate to dryness, recrystallization and namely obtains 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds.Adjacent bromine aryl methyl alcohol, aryl methyl ketone, [Ir (cod) Cl]
2the mol ratio of (cod=1,5-cyclooctadiene), palladium salt, silver salt, three cyclohexyl phosphines and alkali is 1:1 ~ 2:0.01 ~ 0.1:0.05 ~ 0.2:1 ~ 3:0.05 ~ 0.2:1 ~ 3.
The preparation method of 6,7-described dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, gets adjacent bromine aryl methyl ketone, aryl methyl alcohol, [Ir (cod) Cl]
2(cod=1,5-cyclooctadiene), palladium salt, silver salt, the two diphenyl phosphine of 1,1'-dinaphthalene-2,2'-and alkali join in organic solvent, at N
2reflux under gas shielded, reaction terminates rear filtration, evaporate to dryness, recrystallization and namely obtains 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds.Adjacent bromine aryl methyl ketone, aryl methyl alcohol, [Ir (cod) Cl]
2the mol ratio of (cod=1,5-cyclooctadiene), palladium salt, silver salt, three cyclohexyl phosphines and alkali is 1:1 ~ 2:0.005 ~ 0.1:0.02 ~ 0.2:1 ~ 3:0.05 ~ 0.2:1 ~ 5.
Above-mentioned palladium salt is palladium salt is Palladous chloride, palladium or palladium trifluoroacetate; Silver salt is silver carbonate, Silver monoacetate or trifluoroacetic acid silver.
Above-mentioned alkali is sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium phosphate or potassiumphosphate.
Above-mentioned organic solvent is dioxane, benzene, toluene, DMF or dimethyl sulfoxide (DMSO).
The above-mentioned condition stating back flow reaction is: temperature of reaction 100-160 DEG C, reaction times 6-48h.
beneficial effect
The present invention utilizes the available metal-salt of commodity, the adjacent bromine aryl methyl alcohol of co-catalysis and aryl methyl ketone (or adjacent bromine aryl methyl ketone and aryl methyl alcohol), reacted by the alpha-alkyl reaction of aryl methyl alcohol and aryl methyl ketone and carbon-hydrogen bond activation, one kettle way prepares 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, for synthesis replacement 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone derivatives provides a practical method, the method is simple to operate, and substrate spectrum is wide, productive rate is high, has important using value.
Embodiment
the preparation of embodiment 1:6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (1)
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol phenylcarbinol, 2.0mmol adjacent bromoacetophenone, 0.01mmol [Ir (cod) Cl]
2, 0.1mmol palladium, 1.0mmol silver carbonate, 0.1mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 1.0mmol cesium hydroxide and 5ml dioxane, 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, water-bath drops 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): d 7.58-7.67 (m, 2H), 7.27-7.46 (m, 6H), 2.99 (s, 4H), molecular formula is as follows:
the preparation of embodiment 2:9-methyl-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (2)
Under rare gas element (as high pure 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 2.0mmol 2-, 1.0mmol methyl phenyl ketone, 0.05mmol [Ir (cod) Cl]
2, 0.1mmol Palladous chloride, 3.0mmol Silver monoacetate, 0.12mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.0mmol potassium hydroxide and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 6 hours.Remove oil bath, water-bath drops 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 89%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.55-7.64 (m, 2H), 7.25-7.43 (m, 3H), 7.09 (s, 1H), 7.03 (d, 1H), 2.97 (s, 4H), 2.34 (s, 3H), molecular formula is as follows:
the preparation of embodiment 3:10-methoxyl group-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (5)
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol p-methoxybenzyl alcohol, 1.6mmol adjacent bromoacetophenone, 0.08mmol [Ir (cod) Cl]
2, 0.2mmol palladium trifluoroacetate, 3.0mmol trifluoroacetic acid silver, 0.2mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3mmol salt of wormwood and 5ml benzene, with nitrogen replacement reaction tubes 3 times, then 60 DEG C are heated to oil bath under magnetic stirring, reaction backflow 48 hours.Remove oil bath, water-bath drops 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
5, productive rate 90%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.52-7.61 (m, 2H), 7.21-7.40 (m, 3H), 7.07 (s, 1H), 6.82 (d, 1H), 3.84 (s, 3H), 2.96 (s, 4H), molecular formula is as follows:
the preparation of bromo-6,7-dihydro-5H-hexichol [a, the c] rings-5-in heptan ketone (7) of embodiment 4:10-
Under rare gas element (as high pure 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, 1.2mmol adjacent bromoacetophenone, 0.08mmol [Ir (cod) Cl]
2, 0.07mmol palladium, 2.0mmol Silver monoacetate, the two diphenyl phosphines of 0.16mmol 1,1'-dinaphthalene-2,2'-and 2.5mmol potassiumphosphate 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 36 hours.Remove oil bath, water-bath drops 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
7, productive rate 78%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.86 (s, 1H), 7.59-7.67 (m, 2H), 7.33-7.52 (m, 4H), 3.02 (s, 4H), molecular formula is as follows:
the preparation of embodiment 5:10-ethyl-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (8)
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.0mmol to ethylbenzene methyl alcohol, 1.4mmol adjacent bromoacetophenone, 0.06mmol [Ir (cod) Cl]
2, 0.08mmol palladium, 2.5mmol silver carbonate, 0.12mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3.0mmol cesium carbonate and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 130 DEG C are heated to oil bath under magnetic stirring, reaction backflow 30 hours.Remove oil bath, water-bath drops 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 87%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.53-7.64 (m, 3H), 7.25-7.43 (m, 2H), 7.23 (m, 1H), 7.12 (d, 1H), 2.97 (s, 4H), 2.53 (q, 2H), 1.25 (t, 3H), molecular formula is as follows:
the preparation of chloro-6,7-dihydro-5H-hexichol [a, the c] rings-5-in heptan ketone (10) of embodiment 6:9-
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds chlorobenzene methanol between 1.0mmol, 1.9mmol adjacent bromoacetophenone, 0.04mmol [Ir (cod) Cl]
2, 0.06mmol palladium, 3.6mmol silver carbonate, 0.15mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3.0mmol sodium hydroxide and 5ml dimethyl sulfoxide (DMSO), with nitrogen replacement reaction tubes 3 times, then 150 DEG C are heated to oil bath under magnetic stirring, reaction backflow 40 hours.Remove oil bath, water-bath drops 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
10, productive rate 78%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.63-7.72 (m, 2H), 7.34-7.49 (m, 3H), 7.29 (s, 1H), 7.07 (d, 1H), 3.05 (s, 4H), molecular formula is as follows:
the preparation of embodiment 7:3-methyl-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (12)
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds methyl acetophenone, 0.07mmol [Ir (cod) Cl] between the adjacent bromobenzene methyl alcohol of 1.7mmol, 1.0mmol
2, 0.13mmol Palladous chloride, 3.0mmol silver carbonate, 0.2mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.2mmol cesium hydroxide and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 100 DEG C are heated to oil bath under magnetic stirring, reaction backflow 28 hours.Remove oil bath, water-bath drops 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
12, productive rate 84%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.56-7.65 (m, 2H), 7.52 (s, 1H), 7.25-7.44 (m, 4H), 2.98 (s, 4H), 2.34 (s, 3H), molecular formula is as follows:
the preparation of embodiment 8:2-cyano group-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (14)
Under rare gas element (as high pure 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 1.8mmol, 1.0mmol 4-Acetylbenzonitrile, 0.05mmol [Ir (cod) Cl]
2, 0.16mmol palladium, 2.7mmol trifluoroacetic acid silver, 0.17mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.0mmol potassium hydroxide and 5ml benzene, with nitrogen replacement reaction tubes 3 times, then 130 DEG C are heated to oil bath under magnetic stirring, reaction backflow 28 hours.Remove oil bath, water-bath drops 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
14, productive rate 72%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.95 (s, 1H), 7.79-7.83 (d, 2H), 7.26-7.51 (m, 4H), 3.01 (s, 4H), molecular formula is as follows:
the preparation of embodiment 9:2-aldehyde radical-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (16)
Under rare gas element (as high pure 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 to aldehyde radical methyl phenyl ketone, 0.1mmol [Ir (cod) Cl]
2, 0.2mmol palladium trifluoroacetate, 2.6mmol silver carbonate, 0.2mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.2mmol cesium hydroxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 18 hours.Remove oil bath, water-bath drops 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
16, productive rate 71%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 9.92 (s, 1H), 7.93 (s, 1H), 7.76-7.80 (d, 2H), 7.24-7.46 (m, 4H), 3.00 (s, 4H), molecular formula is as follows:
the preparation of embodiment 10:4-methyl-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (19)
Under rare gas element (as high pure 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 1.3mmol, 1.0mmol o-methyl-benzene ethyl ketone, 0.09mmol [Ir (cod) Cl]
2, 0.16mmol palladium, 2.3mmol trifluoroacetic acid silver, 0.15mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.3mmol sodium phosphate and 5ml benzene, with nitrogen replacement reaction tubes 3 times, then 120 DEG C are heated to oil bath under magnetic stirring, reaction backflow 30 hours.Remove oil bath, water-bath drops 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
19, productive rate 86%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.55-7.63 (m, 2H), 7.32-7.56 (m, 5H), 3.00 (s, 4H), 2.39 (s, 3H), molecular formula is as follows:
the preparation of chloro-6,7-dihydro-5H-hexichol [a, the c] rings-5-in heptan ketone (21) of embodiment 11:3-
Under rare gas element (as high pure 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 1.6mmol, 1.0mmol m bromoacetophenone, 0.07mmol [Ir (cod) Cl]
2, 0.12mmol palladium, 1.7mmol silver carbonate, 0.17mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 2.5mmol sodium hydroxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 26 hours.Remove oil bath, water-bath drops 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
21, productive rate 87%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.87 (s, 1H), 7.59-7.73 (m, 2H), 7.23-7.42 (m, 4H), 3.02 (s, 4H), molecular formula is as follows:
the preparation of embodiment 12:3-methoxyl group-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (23)
Under rare gas element (as high pure 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 1.2mmol, 1.0mmol meta-methoxy methyl phenyl ketone, 0.07mmol [Ir (cod) Cl]
2, 0.18mmol palladium trifluoroacetate, 1.8mmol Silver monoacetate, 0.18mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3.0mmol salt of wormwood and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 12 hours.Remove oil bath, water-bath drops 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
23, productive rate 88%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): 7.53-7.62 (m, 2H), 7.49 (s, 1H), 7.23-7.41 (m, 4H), 3.83 (s, 3H), 2.97 (s, 4H), molecular formula is as follows:
the preparation of embodiment 13:2-bromo-10-methyl-6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone (25)
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 1.5mmol 2-bromobenzene methyl alcohol, 1.0mmol parabromoacetophenone, 0.08mmol [Ir (cod) Cl]
2, 0.16mmol Palladous chloride, 2.5mmol silver carbonate, 0.15mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3.0mmol potassium hydroxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 16 hours.Remove oil bath, water-bath drops 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 89%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.85 (s, 1H), 7.57-7.71 (m, 2H), 7.43 (s, 1H), 7.14-7.36 (m, 2H), 2.98 (s, 4H), 2.36 (s, 3H), molecular formula is as follows:
the preparation of bromo-6,7-dihydro-5H-hexichol [a, the c] rings-5-in heptan ketone (28) of embodiment 14:3-methyl acetate base-10-
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds 2.0mmol to bromobenzene methyl alcohol, 1.0mmol 2-bromo-5-methyl acetate benzoylformaldoxime, 0.07mmol [Ir (cod) Cl]
2, 0.15mmol palladium, 1.5mmol trifluoroacetic acid silver, 0.18mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 1.5mmol cesium hydroxide and 5ml toluene, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 15 hours.Remove oil bath, water-bath drops 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
28, productive rate 75%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 8.25 (s, 1H), 7.76-7.81 (m, 2H), 7.72 (s, 1H), 7.21-7.47 (m, 2H), 3.89 (s, 3H), 3.01 (s, 4H), molecular formula is as follows:
the preparation of bromo-6,7-dihydro-5H-hexichol [a, the c] rings-5-in heptan ketone (30) of embodiment 16:3-methyl-9-
Under rare gas element (as high pure nitrogen) protection, the Schlek reaction tubes (a kind of glassware conventional during anhydrous and oxygen-free operation) to 10 ml adds bromobenzene methyl alcohol between 1.5mmol, the bromo-5-methyl acetophenone of 1.0mmol 2-, 0.1mmol [Ir (cod) Cl]
2, 0.2mmol palladium, 3.0mmol silver carbonate, 0.2mmol 1, the two diphenyl phosphines of 1'-dinaphthalene-2,2'-and 3.0mmol cesium hydroxide and 5ml dioxane, with nitrogen replacement reaction tubes 3 times, then 110 DEG C are heated to oil bath under magnetic stirring, reaction backflow 48 hours.Remove oil bath, water-bath drops 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
30, productive rate 87%.The nmr analysis data of this product are as follows:
1h NMR. (400 MHz, CDCl
3): d 7.81 (s, 1H), 7.59-7.73 (m, 2H), 7.39 (s, 1H), 7.12-7.30 (m, 2H), 3.02 (s, 4H), 2.34 (s, 3H), molecular formula is as follows:
。
Claims (9)
1.6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds, is characterized in that: the general formula of this compound is:
，
Wherein, R
1, R
2for-H ,-CH
3,-OCH
3,-C
2h
5,-CN ,-NO
2,-COOCH
3,-CHO ,-F ,-Cl or-Br; R
1, R
2be positioned at any position on aromatic ring 1-4 and 8-11.
2. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 1, is characterized in that: get adjacent bromine aryl methyl alcohol, aryl methyl ketone, [Ir (cod) Cl]
2(cod=1,5-cyclooctadiene), palladium salt, silver salt, the two diphenyl phosphine of 1,1'-dinaphthalene-2,2'-and alkali join in organic solvent, at N
2reflux under gas shielded, reaction terminates rear filtration, evaporate to dryness, recrystallization and namely obtains 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds.
3. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 1, is characterized in that: get adjacent bromine aryl methyl ketone, aryl methyl alcohol, [Ir (cod) Cl]
2(cod=1,5-cyclooctadiene), palladium salt, silver salt, the two diphenyl phosphine of 1,1'-dinaphthalene-2,2'-and alkali join in organic solvent, at N
2reflux under gas shielded, reaction terminates rear filtration, evaporate to dryness, recrystallization and namely obtains 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds.
4. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 2 or claim 3, is characterized in that: described palladium salt is palladium salt is Palladous chloride, palladium or palladium trifluoroacetate; Silver salt is silver carbonate, Silver monoacetate or trifluoroacetic acid silver.
5. as claimed in claim 2 or claim 36,7-dihydro-5H-hexichol [a, c] preparation method of ring-5-in heptan ketone compounds, it is characterized in that: described alkali is sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium phosphate or potassiumphosphate.
6. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 2 or claim 3, is characterized in that: described organic solvent is dioxane, benzene, toluene, DMF or dimethyl sulfoxide (DMSO).
7. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 2 or claim 3, is characterized in that: the condition of described back flow reaction is: temperature of reaction 100-160 DEG C, reaction times 6-48h.
8. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 2, is characterized in that: adjacent bromine aryl methyl alcohol, aryl methyl ketone, [Ir (cod) Cl]
2the mol ratio of (cod=1,5-cyclooctadiene), palladium salt, silver salt, three cyclohexyl phosphines and alkali is 1:1 ~ 2:0.01 ~ 0.1:0.05 ~ 0.2:1 ~ 3:0.05 ~ 0.2:1 ~ 3.
9. the preparation method of 6,7-dihydro-5H-hexichol [a, c] ring-5-in heptan ketone compounds as claimed in claim 3, is characterized in that: adjacent bromine aryl methyl ketone, aryl methyl alcohol, [Ir (cod) Cl]
2the mol ratio of (cod=1,5-cyclooctadiene), palladium salt, silver salt, three cyclohexyl phosphines and alkali is 1:1 ~ 2:0.005 ~ 0.1:0.02 ~ 0.2:1 ~ 3:0.05 ~ 0.2:1 ~ 5.
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| 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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Cited By (2)
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| 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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