CN104817483A - Bis carbonyl indole compound and synthesis method - Google Patents

Bis carbonyl indole compound and synthesis method Download PDF

Info

Publication number
CN104817483A
CN104817483A CN201510103250.2A CN201510103250A CN104817483A CN 104817483 A CN104817483 A CN 104817483A CN 201510103250 A CN201510103250 A CN 201510103250A CN 104817483 A CN104817483 A CN 104817483A
Authority
CN
China
Prior art keywords
reaction
carbonyl
cdcl
benzazole compounds
nmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201510103250.2A
Other languages
Chinese (zh)
Other versions
CN104817483B (en
Inventor
姜雪峰
张泽光
代志洪
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
East China Normal University
Original Assignee
East China Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by East China Normal University filed Critical East China Normal University
Priority to CN201510103250.2A priority Critical patent/CN104817483B/en
Publication of CN104817483A publication Critical patent/CN104817483A/en
Application granted granted Critical
Publication of CN104817483B publication Critical patent/CN104817483B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom

Abstract

The present invention discloses a method for double carbonylation of indole, wherein alpha-hydroxyketone and indole are adopted as reaction raw materials, oxygen is adopted as an oxidizing agent, and a reaction is performed in benzene at a temperature of 80 DEG C under the effect of a copper catalyst to obtain the bis carbonyl indole compound represented by a formula (III). According to the present invention, advantages of high efficiency of the reaction, high yield, application of the oxygen as the oxidizing agent, mild reaction conditions, no requirement of strong acid and strong alkali, catalysis with the cheap metal, easy reaction substrate preparation, and reaction amplification achieving are provided.

Description

A kind of two carbonyl Benzazole compounds and synthetic method thereof
Technical field
The invention belongs to organic compound process application technical field, be specifically related to the two carbonyl Benzazole compounds of a class and synthetic method thereof.
Background technology
Double carbonyl compound is not only present among a series of natural product with unique activity widely, and can transform to multiple fluorescent material as important synthon.The Kui quinoline structure of such as fragrant heterocyclic substituted can be convenient obtained by double carbonyl compound, and this class formation has many application as light trigger and fluoride ions detector.Although traditional acyl chlorides reagent was once used to build some two carbonyl structures, but due to its toxicity and susceptibility, there are some and hinder in the application of this kind of strategy.Meanwhile, due to outstanding fluorescent characteristic and be easy to the features such as functionalization, the fluorescent material containing indoles skeleton more and more caused the concern of people in recent years.
Containing natural product and the derivatize application of two carbonyl structure
So, find a kind of simple, green, high efficiency low cost, the novel method of compatible good, environmental friendliness, mild condition and economic and practical structure pair carbonyl indoles just seem and be even more important.The present inventor finds that α hydroxyketone is the compound of a class uniqueness after deliberation, the oxidative coupling reaction of free radical and then generation and indoles is very easily formed in the α position of carbonyl, based on this, the present invention proposes the reaction being the two carbonyl indoles of raw material preparation with α hydroxyketone and indoles of copper oxygen catalytic oxidation.
Summary of the invention
Instant invention overcomes the shortcomings of traditional acyl chlorides linked reaction, realize the method for the two carbonyl indoles of a kind of efficient structure innovatively.The present invention uses cheap α-benzoinoxime catalyzer, with α hydroxyketone, indoles for raw material, is oxygenant, in reaction solvent, have effectively achieved corresponding conversion at 80 DEG C with oxygen, prepares such as formula the two carbonyl indoles shown in (III).
Wherein, described reaction process is as shown in following reaction formula.
In above reaction formula,
Ar is phenyl ring, heterocycle or substituted benzene ring; R is electron rich base, electron-deficient base or halogen atom; R ' is alkyl, allyl group, benzyl or substituted benzyl.
Preferably, Ar is phenyl, 4-fluorophenyl, 4-p-methoxy-phenyl, 4-chloro-phenyl-, 4-bromophenyl, 2-naphthyl, 2-benzothienyl, 2-benzofuryl, 2-thienyl, 3-thienyl; R is 4-methyl-formiate base, 5-oxyethyl group, 5-methoxyl group, 6-methoxyl group, 7-benzyloxy, 4-chlorine, 5-chlorine, 6-chlorine, 5-bromine; R ' is methyl, allyl group, benzyl or to methoxy-benzyl.
In the present invention, Ar, R, R ' include but are not limited to above-mentioned group.
As above reaction formula, the present invention utilizes the indoles shown in the α hydroxyketone shown in formula (I) and formula (II) as starting raw material, using oxygen as oxidising agent, under the effect of α-benzoinoxime catalyzer, react in reaction solvent, synthesize such as formula the two carbonyl benzazolyl compounds shown in (III).
In the present invention, described starting raw material is 1:1-1:15 such as formula the mole dosage ratio of the indoles shown in the α hydroxyketone shown in (I) and formula (II).Preferably, both usage ratio are 1:3.
In the present invention, take oxygen as oxidising agent.
In the present invention, described copper catalyst is CuSO 4, CuSO 4 .5H 2o, Cu (OAc) 2, Cu (NO 3) 2, Cu (TFA) 2, Cu (OTf) 2, CuCl 2, CuBr 2, Cu (acac) 2, CuO, CuOAc, CuI, CuBr, CuCl, CuTc, Cu etc.Preferably, described copper catalyst is CuTc.Wherein, the consumption of described catalyzer is the 1-10mol% such as formula the raw material α hydroxyacetone compounds shown in (I).Preferably, described catalyst levels is the 10mol% such as formula the raw material α hydroxyacetone compounds shown in (I).
In the present invention, described reaction solvent is any one or arbitrary combination of methyl alcohol, ethanol, Virahol, the trimethyl carbinol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, benzene, methylene dichloride, 1,2-ethylene dichloride, chloroform.Preferably, described solvent is benzene.
Building-up reactions of the present invention comprises the following steps: in reaction vessel, add α hydroxyketone, indoles, copper catalyst, solvent, in oxygen atmosphere, react to stirred at reflux condition in room temperature, obtain the two carbonyl Benzazole compounds shown in formula (III).Preferably, reactions steps is reacted at 80 DEG C of temperature.
In a specific examples, building-up reactions of the present invention is in reaction flask A, add α hydroxyacetone compounds (X mmol), indoles (Y mmol) Catalysts Cu TC (Z mmol), solvent (V mL), reaction system, in oxygen atmosphere, stirs 6 hours at 80 DEG C, stirs 4-24 hour.Monitoring reaction process.After completion of the reaction, directly the two carbonyl benzazolyl compounds shown in target product formula (III) are obtained through column chromatography for separation.
The invention allows for according to the above-mentioned synthetic method of the present invention prepare such as formula the two carbonyl benzazolyl compounds shown in (III),
Ar is phenyl ring, heterocycle or substituted benzene ring; R is electron rich base, electron-deficient base or halogen atom; R ' is alkyl, allyl group, benzyl or substituted benzyl.
Preferably, Ar is phenyl, 4-fluorophenyl, 4-p-methoxy-phenyl, 4-chloro-phenyl-, 4-bromophenyl, 2-naphthyl, 2-benzothienyl, 2-benzofuryl, 2-thienyl, 3-thienyl; R is 4-methyl-formiate base, 5-oxyethyl group, 5-methoxyl group, 6-methoxyl group, 7-benzyloxy, 4-chlorine, 5-chlorine, 6-chlorine, 5-bromine; R ' is methyl, allyl group, benzyl or to methoxy-benzyl.
The invention allows for new two carbonyl benzazolyl compounds, its structural formula such as formula shown in (III),
Wherein, Ar is phenyl, 4-fluorophenyl, 4-p-methoxy-phenyl, 4-chloro-phenyl-, 4-bromophenyl, 2-naphthyl, 2-benzothienyl, 2-benzofuryl, 2-thienyl, 3-thienyl; R is 4-methyl-formiate base, 5-oxyethyl group, 5-methoxyl group, 6-methoxyl group, 7-benzyloxy, 4-chlorine, 5-chlorine, 6-chlorine, 5-bromine; R ' is methyl, allyl group, benzyl or to methoxy-benzyl.
The invention allows for the application of two carbonyl Benzazole compounds shown in formula (III) in synthesis Kui quinoline class fluorescent material.
The present invention has the following advantages: reaction substrate is easily prepared; Reaction is efficient, and yield is high; Oxygen is as oxygenant, cheap, green, environmentally friendly; Reaction conditions is gentle, without the need to strong acid and strong base: catalyzer is cheap metal, economical; Reaction also can realize after amplifying; Reaction substrate is easily prepared.The present invention for reaction raw materials with the α hydroxyacetone compounds easily prepared, with oxygen as sulfiding reagent, under cheap α-benzoinoxime catalyst action, carries out oxidative coupling reaction with indoles and obtains two carbonyl benzazolyl compounds.Operation is simple, and reaction conditions is gentle, is applicable to large-scale industrial production.
Accompanying drawing explanation
Fig. 1 shows the ultra-violet absorption spectrum of the compound 1ac-7ac in the embodiment of the present invention.
Fig. 2 shows the fluorescence emission spectrum of the compound 1ac-7ac in the embodiment of the present invention.
Fig. 3 shows the ultra-violet absorption spectrum of compound 1ac in opposed polarity solvent in the embodiment of the present invention.
Fig. 4 shows the fluorescence emission spectrum of compound 1ac in opposed polarity solvent in the embodiment of the present invention.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and are protection domain with appending claims.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.Data given by following examples comprise concrete operations and reaction conditions and product.Product purity is identified by nuclear-magnetism.
The building-up reactions of the two carbonyl benzazolyl compounds of the present invention, comprise the following steps: (1) adds α hydroxyketone, indoles, copper catalyst, solvent in reaction vessel, in oxygen atmosphere, react to stirred at reflux condition in room temperature, obtain the two carbonyl Benzazole compounds shown in formula (III).Object product is obtained again through column chromatography for separation.
Wherein, two carbonyl benzazolyl compounds as shown in table 1, are and synthesize by the inventive method the product obtained, and there is not yet open source literature and disclose these compounds.
Two carbonyl benzazolyl compounds in table 1 can change into quinoxaline compound, comprise the following steps: in reaction vessel, add two carbonyl indoles, O-Phenylene Diamine, solvent, react under room temperature to reflux conditions, obtain the quinoxaline compound shown in formula (IV).Object product is obtained again through column chromatography for separation.This series of Kui quinoline structure all has good photoluminescent property and solvatochromism effect.
Table 1 two carbonyl benzazolyl compounds newly of the present invention
Embodiment 1
The synthesis of compound 1ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 1-skatole 1b (0.6mmol, 78.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 1ab (43.4mg) yield after direct column chromatography for separation: 83%; 1hNMR (400MHz, CDCl 3) δ 8.53 – 8.42 (m, 1H), 8.10 (dd, J=5.1,3.4Hz, 2H), 7.80 (s, 1H), 7.67 – 7.58 (m, 1H), 7.49 (t, J=7.7Hz, 2H), 7.43 – 7.36 (m, 3H), 3.83 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.7,187.5,139.5,137.7,134.2,133.5,130.3,128.7,126.4,124.2,123.5,122.7,112.9,109.9,33.7.MS (EI) m/z 263 (M +).
Embodiment 2
The synthesis of compound 2ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 1-allyl group indoles 2b (0.6mmol, 94.8mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 2ab (39.6mg) yield after direct column chromatography for separation: 69%; 1hNMR (400MHz, CDCl 3) δ 8.55 – 8.45 (m, 1H), 8.16 – 8.07 (m, 2H), 7.85 (s, 1H), 7.67 – 7.59 (m, 1H), 7.49 (dd, J=10.6,4.8Hz, 2H), 7.42 – 7.33 (m, 3H), 6.05 – 5.91 (m, 1H), 5.25 (ddd, J=17.8,13.7,0.8Hz, 2H), 4.75 (dt, J=5.6,1.4Hz, 2H); 13c NMR (100MHz, CDCl 3) δ 193.6,187.6,138.5,137.1,134.2,133.4,131.4,130.3,128.7,126.5,124.2,123.5,122.7,119.3,113.1,110.4,49.7.HRMS (EI) Calcd for C 19h 15nO 2289.1103, Found289.1102.
Embodiment 3
The synthesis of compound 3ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 1-benzylindole 3b (0.6mmol, 124.2mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 3ab (47.8mg) yield after direct column chromatography for separation: 71%; 1hNMR (400MHz, CDCl 3) δ 8.51 (d, J=7.8Hz, 1H), 8.18 – 8.06 (m, 2H), 7.92 (s, 1H), 7.67 – 7.59 (m, 1H), 7.50 (t, J=7.7Hz, 2H), 7.38 (m, 1H), 7.36 – 7.27 (m, 5H), 7.20 – 7.13 (m, 2H), 5.33 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 193.5,187.6,138.8,137.2,135.1,134.2,133.4,130.3,129.1,128.7,128.3,127.0,126.6,124.3,123.5,122.8,113.3,110.6,51.1.HRMS (EI) Calcd for C 23h 17nO 2339.1259, Found 339.1262.
Embodiment 4
The synthesis of compound 4ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 1-to methyl-benzyl indoles 4b (0.6mmol, 142.2mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 4ab (45.1mg) yield after direct column chromatography for separation: 63%; 1h NMR (400MHz, CDCl 3) δ 8.49 (d, J=7.6Hz, 1H), 8.17 – 8.04 (m, 2H), 7.88 (s, 1H), 7.62 (t, J=7.4Hz, 1H), 7.49 (t, J=7.7Hz, 2H), 7.43 – 7.28 (m, 3H), 7.11 (d, J=8.6Hz, 2H), 6.89 – 6.78 (m, 2H), 5.25 (s, 2H), 3.77 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.5,187.6,159.6,138.6,137.2,134.2,133.4,130.3,128.7,128.6,126.9,126.7,124.2,123.5,122.7,114.4,113.2,110.6,55.3,50.7.HRMS (EI) Calcd for C 24h 19nO 3369.1365, Found369.1369.
Embodiment 5
The synthesis of compound 5ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 4-methyl-formiate base indoles 5b (0.6mmol, 105.1mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 5ab (47.3mg) yield after direct column chromatography for separation: 77%; 1h NMR (400MHz, CDCl 3) δ 10.20 (s, 1H), 8.03 – 7.95 (m, 2H), 7.69 (d, J=3.3Hz, 1H), 7.60 – 7.53 (m, 1H), 7.49 (dd, J=7.4,0.8Hz, 1H), 7.42 (ddd, J=7.5,4.0,3.2Hz, 3H), 7.25 – 7.19 (m, 1H), 3.92 (s, 3H); 13cNMR (100MHz, CDCl 3) δ 193.4,188.0,170.4,137.4,137.2,134.4,133.3,130.3,128.7,126.8,123.7,123.1,121.2,115.1,114.3,52.5.HRMS (EI) Calcd for C 18h 13nO 4307.0845, Found 307.0848.
Embodiment 6
The synthesis of compound 6ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 5-oxyethyl group-1-skatole 6b (0.6mmol, 105.2mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 6ab (55.8mg) yield after direct column chromatography for separation: 91%; 1h NMR (400MHz, CDCl 3) δ 8.15 – 8.06 (m, 2H), 7.96 (d, J=2.3Hz, 1H), 7.72 (s, 1H), 7.66 – 7.56 (m, 1H), 7.49 (t, J=7.7Hz, 2H), 7.25 (d, J=8.7Hz, 1H), 7.00 (dd, J=8.9,2.5Hz, 1H), 4.17 (q, J=7.0Hz, 2H), 3.78 (s, 3H), 1.47 (t, J=7.0Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 193.8,187.4,156.4,139.3,134.2,133.5,132.5,130.3,128.7,127.3,114.9,112.5,110.8,104.9,64.1,33.9,14.9.HRMS (EI) Calcd for C 19h 17nO 3307.1208, Found 307.1205.
Embodiment 7
The synthesis of compound 7ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 5-methoxyl group-1-skatole 7b (0.6mmol, 96.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 7ab (41.3mg) yield after direct column chromatography for separation: 71%; 1h NMR (400MHz, CDCl 3) δ 8.09 (dd, J=8.3,1.2Hz, 2H), 7.97 (d, J=2.4Hz, 1H), 7.72 (s, 1H), 7.61 (dd, J=10.6,4.2Hz, 1H), 7.49 (t, J=7.8Hz, 2H), 7.25 (d, J=8.9Hz, 1H), 6.99 (dd, J=8.9,2.5Hz, 1H), 3.93 (s, 3H), 3.78 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.7,187.4,157.1,139.3,134.2,133.5,132.5,130.2,128.7,127.2,114.5,112.5,110.8,103.9,55.8,33.9.HRMS (EI) Calcd for C 18h 15nO 3293.1052, Found 293.1053.
Embodiment 8
The synthesis of compound 8ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 6-methoxyl group-1-skatole 8b (0.6mmol, 96.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 8ab (37.7mg) yield after direct column chromatography for separation: 65%; 1h NMR (400MHz, CDCl 3) δ 8.33 (d, J=8.7Hz, 1H), 8.14 – 8.06 (m, 2H), 7.70 (s, 1H), 7.64 – 7.59 (m, 1H), 7.49 (t, J=7.7Hz, 2H), 7.03 (dd, J=8.7,2.2Hz, 1H), 6.82 (d, J=2.2Hz, 1H), 3.90 (s, 3H), 3.78 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.7,187.5,157.8,138.9,138.7,134.2,133.5,130.3,128.7,123.4,120.2,113.0,112.5,93.9,55.7,33.7.HRMS (EI) Calcd for C 18h 15nO 3293.1052, Found 293.1051.
Embodiment 9
The synthesis of compound 9ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 7-benzyloxy-1-skatole 9b (0.6mmol, 142.4mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 9ab (62.1mg) yield after direct column chromatography for separation: 85%; 1h NMR (400MHz, CDCl 3) δ 8.16 – 8.05 (m, 3H), 7.73 (s, 1H), 7.62 (dd, J=10.5,4.3Hz, 1H), 7.56 – 7.46 (m, 4H), 7.41 (dd, J=10.1,4.6Hz, 2H), 7.37 – 7.32 (m, 1H), 7.29 – 7.24 (m, 1H), 7.09 (dd, J=8.9,2.5Hz, 1H), 5.20 (s, 2H), 3.77 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.7,187.4,156.2,139.4,137.1,134.2,133.5,132.7,130.2,128.7,128.5,127.9,127.7,127.3,115.0,112.6,110.9,105.4,70.6,33.8.HRMS (EI) Calcd for C 24h 19nO 3369.1365, Found 369.1362.
Embodiment 10
The synthesis of compound 10ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 4-chlorine 1-skatole 10b (0.6mmol, 99.0mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 10ab (35.2mg) yield after direct column chromatography for separation: 60%; 1h NMR (400MHz, CDCl 3) δ 8.14 – 8.04 (m, 2H), 7.85 (s, 1H), 7.62 (t, J=7.4Hz, 1H), 7.49 (t, J=7.7Hz, 2H), 7.33 (dd, J=4.9,3.8Hz, 1H), 7.26 (m, 2H), 3.82 (s, 3H). 13c NMR (100MHz, CDCl 3) δ 193.9,187.4,140.7,139.5,134.2,133.4,130.3,128.7,127.6,124.6,124.6,123.8,113.2,108.7,34.0.HRMS (EI) Calcd forC 17h 12clNO 2297.0557, Found 297.0560.
Embodiment 11
The synthesis of compound 11ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 5-chloro-1-skatole 11b (0.6mmol, 99.0mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 11ab (36.7mg) yield after direct column chromatography for separation: 62%; 1h NMR (400MHz, CDCl 3) δ 8.48 (d, J=1.8Hz, 1H), 8.14 – 8.05 (m, 2H), 7.83 (s, 1H), 7.64 (t, J=7.4Hz, 1H), 7.50 (t, J=7.7Hz, 2H), 7.32 (dt, J=17.4,5.3Hz, 2H), 3.83 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.3,187.1,140.1,136.1,134.4,133.3,130.3,129.6,128.8,127.4,124.6,122.3,112.4,111.0,34.0.HRMS (EI) Calcd forC 17h 12clNO 2297.0557, Found 297.0559.
Embodiment 12
The synthesis of compound 12ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 6-chloro-1-skatole 12b (0.6mmol, 99.0mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 12ab (52.8mg) yield after direct column chromatography for separation: 88%; 1h NMR (400MHz, CDCl 3) δ 8.38 (d, J=8.5Hz, 1H), 8.08 (dd, J=5.1,3.3Hz, 2H), 7.80 (s, 1H), 7.67 – 7.59 (m, 1H), 7.49 (dd, J=10.7,4.7Hz, 2H), 7.40 – 7.31 (m, 2H), 3.80 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.4,187.3,139.9,138.1,134.4,133.2,130.3,130.2,128.8,124.8,124.0,123.6,112.9,110.2,33.8.HRMS (EI) Calcdfor C 17h 12clNO 2297.0557, Found 297.0558.
Embodiment 13
The synthesis of compound 13ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with α hydroxy acetophenone 1a (0.2mmol, 1equiv., 27.2mg) and 5-bromo-1-skatole 13b (0.6mmol, 126.0mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 13ab (41.9mg) yield after direct column chromatography for separation: 62%; 1h NMR (400MHz, CDCl 3) δ 8.65 (s, 1H), 8.10 (d, J=7.7Hz, 2H), 7.81 (s, 1H), 7.65 (t, J=7.3Hz, 1H), 7.50 (dd, J=17.4,9.0Hz, 3H), 7.30 – 7.20 (m, 1H), 3.83 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.3,187.1,140.0,136.3,134.4,133.3,130.3,128.7,127.9,127.2,125.3,117.3,112.3,111.4,33.9.HRMS (EI) Calcd forC 17h 12brNO 2341.0051, Found 341.0054.
Embodiment 14
The synthesis of compound 14ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with 4-fluoro-(α hydroxy acetophenone) 2a (0.2mmol, 1equiv., 30.8mg) and 1-skatole 7b (0.6mmol, 96.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 14ab (44.5mg) yield after direct column chromatography for separation: 72%; 1h NMR (400MHz, CDCl 3) δ 8.22 – 8.07 (m, 2H), 7.95 (d, J=2.2Hz, 1H), 7.74 (s, 1H), 7.25 (d, J=7.9Hz, 1H), 7.15 (t, J=8.6Hz, 2H), 6.99 (dd, J=8.9,2.4Hz, 1H), 3.92 (s, 3H), 3.79 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 192.0,186.9,167.7,165.1,157.2,139.4,133.1 (d, J=9.6Hz), 132.6,130.0 (d, J=2.8Hz), 127.3,116.0,115.8,114.5,112.4,110.9,104.0,55.8 (d, J=1.9Hz), 33.9; 19f NMR (376MHz, CDCl 3) δ-102.64 (s, 1F) .HRMS (EI) Calcd for C 18h 14fNO 3311.0958, Found 311.0956.
Embodiment 15
The synthesis of compound 15ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with 4-methoxyl group-(α hydroxy acetophenone) 3a (0.2mmol, 1equiv., 33.3mg) and 1-skatole 1b (0.6mmol, 78.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 15ab (35.6mg) yield after direct column chromatography for separation: 61%; 1h NMR (400MHz, CDCl 3) δ 8.54 – 8.40 (m, 1H), 8.13 – 8.04 (m, 2H), 7.80 (s, 1H), 7.44 – 7.33 (m, 3H), 7.00 – 6.90 (m, 2H), 3.87 (s, 3H), 3.82 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 192.5,188.1,164.5,139.5,137.6,132.7,126.4,126.3,124.1,123.4,122.6,114.0,112.9,109.9,55.6,33.7.HRMS (EI) Calcd for C 18h 15nO 3293.1052, Found 293.1050.
Embodiment 16
The synthesis of compound 16ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with 4-chloro-(α hydroxy acetophenone) 4a (0.2mmol, 1equiv., 34.0mg) and 1-skatole 1b (0.6mmol, 78.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 16ab (40.1mg) yield after direct column chromatography for separation: 68%; 1h NMR (400MHz, CDCl 3) δ 8.46 (d, J=2.5Hz, 1H), 8.09 – 8.00 (m, 2H), 7.83 (s, 1H), 7.50 – 7.44 (m, 2H), 7.42 – 7.37 (m, 3H), 3.84 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 192.2,186.7,140.8,139.7,137.7,131.8,131.7,129.1,126.3,124.3,123.6,122.6,112.7,110.0,33.8.HRMS (EI) Calcd for C 17h 12clNO 2297.0557, Found297.0556.
Embodiment 17
The synthesis of compound 17ab:
By Catalysts Cu TC (0.02mmol, 10mol%) with 4-bromo-(α hydroxy acetophenone) 5a (0.2mmol, 1equiv., 43.0mg) and 1-skatole 1b (0.6mmol, 78.7mg) join in reaction tubes, then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 17ab (49.0mg) yield after direct column chromatography for separation: 72%; 1h NMR (400MHz, CDCl 3) δ 8.50 – 8.41 (m, 1H), 8.02 – 7.94 (m, 2H), 7.82 (s, 1H), 7.67 – 7.60 (m, 2H), 7.40 (m, 3H), 3.84 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 192.4,186.6,139.6,137.7,132.3,132.1,131.7,129.7,126.4,124.3,123.6,122.7,112.7,110.0,33.8.HRMS (EI) Calcd for C 17h 12brNO 2341.0051, Found 341.0053.
Embodiment 18
The synthesis of compound 18ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) naphthalene 6a (0.2mmol; 1equiv.; 37.3mg) and 1-skatole 1b (0.6mmol; 78.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 18ab (51.3mg) yield after direct column chromatography for separation: 82%; 1h NMR (400MHz, CDCl 3) δ 8.63 (s, 1H), 8.54 (dd, J=5.0,2.7Hz, 1H), 8.16 (dd, J=8.6,1.7Hz, 1H), 7.94 (dd, J=8.5,3.0Hz, 2H), 7.88 (d, J=8.1Hz, 1H), 7.84 (s, 1H), 7.65 – 7.59 (m, 1H), 7.57 – 7.51 (m, 1H), 7.46 – 7.37 (m, 3H), 3.83 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 193.8,187.7,139.6,137.7,136.2,133.7,132.4,130.7,130.0,129.1,128.7,127.8,126.9,126.4,124.4,124.2,123.5,122.7,113.0,110.0,33.7.HRMS (EI) Calcd forC 21h 15nO 2313.1103, Found 313.1100.
Embodiment 19
The synthesis of compound 19ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) cumarone 7a (0.2mmol; 1equiv.; 35.3mg) and 1-skatole 1b (0.6mmol; 78.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 19ab (49.7mg) yield after direct column chromatography for separation: 82%; 1h NMR (400MHz, CDCl 3) δ 8.55 – 8.47 (m, 1H), 8.16 (s, 1H), 8.02 (d, J=0.9Hz, 1H), 7.74 (d, J=7.9Hz, 1H), 7.63 (dd, J=8.5,0.7Hz, 1H), 7.52 (ddd, J=8.4,7.2,1.2Hz, 1H), 7.44 – 7.36 (m, 3H), 7.36 – 7.29 (m, 1H), 3.85 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 183.6,181.9,156.3,150.0,140.3,137.5,129.3,127.2,126.9,124.2,124.1,124.0,123.6,122.7,120.0,112.5,112.1,110.0,33.8.HRMS (EI) Calcd for C 19h 13nO 3303.0895, Found 303.0898.
Embodiment 20
The synthesis of compound 20ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) thionaphthene 8a (0.2mmol; 1equiv.; 38.4mg) and 1-skatole 1b (0.6mmol; 78.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 20ab (50.0mg) yield after direct column chromatography for separation: 78%; 1h NMR (400MHz, CDCl 3) δ 8.57 – 8.48 (m, 1H), 8.39 (s, 1H), 8.11 (s, 1H), 7.90 (d, J=8.8Hz, 2H), 7.53 – 7.46 (m, 1H), 7.44 – 7.36 (m, 4H), 3.84 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 186.5,184.2,143.6,140.3,139.5,139.1,137.5,134.7,128.1,126.8,126.6,125.1,124.2,123.5,122.8,122.6,112.1,110.0,33.7.HRMS (EI) Calcd for C 19h 13nO 2s319.0667, Found 319.0666.
Embodiment 21
The synthesis of compound 21ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) cumarone 7a (0.2mmol; 1equiv.; 35.2mg) and 5-methoxyl group-1-skatole 7b (0.6mmol; 96.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 21ab (51.8mg) yield after direct column chromatography for separation: 78%; 1h NMR (400MHz, CDCl 3) δ 8.08 (s, 1H), 8.01 (d, J=0.9Hz, 1H), 7.97 (d, J=2.5Hz, 1H), 7.72 (d, J=7.9Hz, 1H), 7.61 (dd, J=8.5,0.7Hz, 1H), 7.50 (ddd, J=8.4,7.2,1.2Hz, 1H), 7.34 – 7.27 (m, 1H), 7.24 (d, J=1.9Hz, 1H), 6.98 (dd, J=8.9,2.5Hz, 1H), 3.92 (s, 3H), 3.82 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 183.6,182.0,157.3,156.3,150.0,140.1,132.4,129.3,127.9,127.2,124.1,124.0,120.0,114.5,112.6,111.8,110.9,104.1,55.8,34.0.HRMS (EI) Calcd for C 20h 15nO 4333.1001, Found 333.0999.
Embodiment 22
The synthesis of compound 22ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) thionaphthene 8a (0.2mmol; 1equiv.; 38.4mg) and 5-methoxyl group-1-skatole 7b (0.6mmol; 96.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 22ab (55.3mg) yield after direct column chromatography for separation: 80%; 1h NMR (400MHz, CDCl 3) δ 8.40 (s, 1H), 8.06 (s, 1H), 8.01 (d, J=2.4Hz, 1H), 7.90 (d, J=8.5Hz, 2H), 7.49 (t, J=7.7Hz, 1H), 7.40 (t, J=7.5Hz, 1H), 7.30 – 7.23 (m, 1H), 7.00 (dd, J=8.9,2.4Hz, 1H), 3.95 (s, 3H), 3.82 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 186.6,184.1,157.2,143.6,140.1,139.5,139.1,134.6,132.4,128.1,127.9,126.6,125.1,122.9,114.5,111.9,110.9,104.1,55.8,34.0.HRMS (EI) Calcd forC 20h 15nO 3s349.0773, Found 349.0775.
Embodiment 23
The synthesis of compound 23ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 2-(2-hydroxyacetyl) thiophene 9a (0.2mmol; 1equiv.; 28.4mg) and 5-methoxyl group-1-skatole 7b (0.6mmol; 96.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 23ab (51.5mg) yield after direct column chromatography for separation: 86%; 1h NMR (400MHz, CDCl 3) δ 8.11 (d, J=3.8Hz, 1H), 8.09 (s, 1H), 7.98 (d, J=2.4Hz, 1H), 7.79 (d, J=4.9Hz, 1H), 7.25 (d, J=8.9Hz, 1H), 7.21 – 7.14 (m, 1H), 6.98 (dd, J=8.9,2.5Hz, 1H), 3.93 (s, 3H), 3.81 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 184.5,184.3,157.1,140.1,139.3,136.6,132.3,128.3,127.9,114.3,111.7,110.8,104.1,55.8,33.9.HRMS (EI) Calcd for C 16h 13nO 3s299.0616, Found 299.0617.
Embodiment 24
The synthesis of compound 24ab:
By Catalysts Cu TC (0.02mmol; 10mol%) with 3-(2-hydroxyacetyl) thiophene 10a (0.2mmol; 1equiv.; 28.4mg) and 5-methoxyl group-1-skatole 7b (0.6mmol; 96.7mg) join in reaction tubes; then after adding reaction solvent benzene (4mL), in oxygen atmosphere, stirring reaction 6 hours under 80 DEG C of temperature of reaction.After being terminated by thin-layer chromatography monitoring reaction, obtain product 24ab (49.6mg) yield after direct column chromatography for separation: 83%; 1h NMR (400MHz, CDCl 3) δ 8.49 (dd, J=2.9,1.1Hz, 1H), 7.97 (d, J=2.5Hz, 1H), 7.92 (s, 1H), 7.73 (dd, J=5.1,1.1Hz, 1H), 7.35 (dd, J=5.1,2.9Hz, 1H), 7.25 (d, J=8.9Hz, 1H), 6.99 (dd, J=8.9,2.5Hz, 1H), 3.93 (s, 3H), 3.80 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 186.7,186.2,157.1,139.8,138.3,137.1,132.5,127.9,127.7,126.3,114.4,112.1,110.9,104.1,55.9,33.9.HRMS (EI) Calcd for C 16h 13nO 3s299.0616, Found299.0617.
Embodiment 25
The synthesis of compound 1ac:
By compound 1ab (0.2mmol, 52.7mg), O-Phenylene Diamine (0.3mmol, 32.5mg) joins in reaction tubes, then add reaction solvent MeOH (2.5mL) and AcOH (2.5mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 1ac (65.5mg).Yield: 98%; 1h NMR (400MHz, CDCl 3) δ 8.59 – 8.45 (m, 1H), 8.16 (dd, J=8.2,1.0Hz, 1H), 8.09 (dd, J=8.2,1.1Hz, 1H), 7.77 – 7.58 (m, 4H), 7.43 (t, J=6.3Hz, 3H), 7.31 – 7.22 (m, 3H), 6.58 (s, 1H), 3.60 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 153.6,149.4,141.6,140.3,139.5,137.0,132.2,129.6,129.2,128.9,128.8,128.6,128.5,127.2,122.6,122.4,121.0,113.3,109.2,33.0.HRMS (EI) Calcd for C 23h 17n 3335.1422, Found 335.1419.
Embodiment 26
The synthesis of compound 2ac:
By compound 16ab (0.2mmol, 59.6mg), O-Phenylene Diamine (0.3mmol, 32.5mg) joins in reaction tubes, then add reaction solvent MeOH (2.5mL) and AcOH (2.5mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 2ac (76.7mg).Yield: 99%; 1h NMR (400MHz, CDCl 3) δ 8.35 (d, J=7.7Hz, 1H), 8.13 (d, J=8.3Hz, 1H), 8.06 (d, J=8.1Hz, 1H), 7.72 (t, J=7.5Hz, 1H), 7.65 (t, J=7.5Hz, 1H), 7.60 (d, J=8.3Hz, 2H), 7.36 (d, J=8.3Hz, 2H), 7.30 – 7.20 (m, 3H), 6.72 (s, 1H), 3.66 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 152.3,149.1,141.6,139.6,138.6,137.1,135.0,131.8,130.8,129.8,128.9,128.8,128.7,128.7,127.0,122.7,122.1,121.1,113.2,109.4,33.1.HRMS (EI) Calcd for C 23h 17n 3335.1422, Found 335.1419.HRMS (EI) Calcd for C 23h 16clN 3369.1033, Found 369.1031.
Embodiment 27
The synthesis of compound 3ac:
By compound 17ab (0.2mmol, 68.5mg), O-Phenylene Diamine (0.3mmol, 32.5mg) joins in reaction tubes, then add reaction solvent MeOH (2.5mL) and AcOH (2.5mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 3ac (82.9mg).Yield: 99%; 1h NMR (400MHz, CDCl 3) δ 8.35 (d, J=7.8Hz, 1H), 8.13 (d, J=8.2Hz, 1H), 8.05 (d, J=8.1Hz, 1H), 7.72 (t, J=7.5Hz, 1H), 7.65 (t, J=7.5Hz, 1H), 7.58 – 7.47 (m, 4H), 7.33 – 7.18 (m, 3H), 6.72 (s, 1H), 3.66 (s, 3H); 13c NMR (101MHz, CDCl 3) δ 152.3,149.0,141.6,139.6,139.1,137.1,131.8,131.7,131.0,129.9,128.9,128.8,128.7,127.0,123.3,122.8,122.1,121.1,113.2,109.4,33.2.HRMS (EI) Calcd for C 23h 16brN 3413.0531, Found 413.0528.
Embodiment 28
The synthesis of compound 4ac:
By compound 20ab (0.1mmol, 32.0mg), O-Phenylene Diamine (0.15mmol, 16.8mg) joins in reaction tubes, then add reaction solvent MeOH (1.2mL) and AcOH (1.2mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 4ac (33.6mg).Yield: 86%; 1h NMR (400MHz, CDCl 3) δ 8.17 – 8.05 (m, 2H), 7.94 (d, J=8.0Hz, 1H), 7.84 (d, J=7.9Hz, 1H), 7.75 – 7.64 (m, 2H), 7.54 (d, J=10.8Hz, 2H), 7.42 – 7.23 (m, 5H), 7.15 (t, J=7.5Hz, 1H), 3.79 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 148.3,147.4,142.8,141.2,140.9,140.0,139.9,137.1,130.9,130.0,129.2,128.9,128.7,126.8,126.0,125.3,124.4,124.3,122.5,122.2,121.4,120.9,113.6,109.5,33.2.HRMS (EI) Calcd for C 25h 17n 3s391.1143, Found 391.1141.
Embodiment 29
The synthesis of compound 5ac:
By compound 19ab (0.07mmol, 21.3mg), O-Phenylene Diamine (0.1mmol, 10.9mg) joins in reaction tubes, then add reaction solvent MeOH (1mL) and AcOH (1mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 5ac (22.6mg).Yield: 89%; 1h NMR (400MHz, CDCl 3) δ 8.26 – 8.18 (m, 1H), 8.17 – 8.10 (m, 1H), 8.01 (d, J=8.0Hz, 1H), 7.80 – 7.68 (m, 2H), 7.58 (dd, J=8.3,0.6Hz, 1H), 7.51 (d, J=7.7Hz, 1H), 7.40 (d, J=8.2Hz, 1H), 7.38 – 7.32 (m, 1H), 7.32 – 7.27 (m, 2H), 7.26 – 7.20 (m, 1H), 7.20 – 7.14 (m, 1H), 7.05 (d, J=0.8Hz, 1H), 3.81 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 155.1,153.2,148.7,143.7,141.4,139.9,137.1,130.7,130.4,129.3,129.2,128.8,128.2,126.8,125.7,123.2,122.6,121.8,121.4,121.0,113.5,111.9,109.8,109.5,33.2.HRMS (EI) Calcd for C 25h 17n 3o375.1372, Found 375.1374.
Embodiment 30
The synthesis of compound 6ac:
By compound 22ab (0.2mmol, 69.8mg), O-Phenylene Diamine (0.3mmol, 32.5mg) joins in reaction tubes, then add reaction solvent MeOH (2.5mL) and AcOH (2.5mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 6ac (74.8mg).Yield: 89%; 1h NMR (400MHz, CDCl 3) δ 8.09 – 7.98 (m, 2H), 7.78 (d, J=8.1Hz, 1H), 7.69 – 7.59 (m, 2H), 7.57 – 7.43 (m, 2H), 7.35 (s, 1H), 7.30 – 7.24 (m, 2H), 7.24 – 7.15 (m, 3H), 6.83 (dd, J=8.9,2.4Hz, 1H), 3.72 (s, 3H), 3.59 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 155.1,148.6,147.4,142.7,141.3,140.9,140.0,132.4,131.4,130.0,129.1,128.9,128.6,127.2,126.0,125.3,124.4,124.4,122.2,113.3,113.2,110.4,102.8,55.6,33.4.HRMS (EI) Calcd for C 26h 19n 3oS421.1249, Found 421.1253.
Embodiment 31
The synthesis of compound 7ac:
By compound 21ab (0.2mmol, 66.6mg), O-Phenylene Diamine (0.3mmol, 32.5mg) joins in reaction tubes, then add reaction solvent MeOH (2.5mL) and AcOH (2.5mL), stir 2 hours at 60 DEG C.After being terminated by thin-layer chromatography monitoring reaction, after direct column chromatography for separation, obtain product 7ac (75.9mg).Yield: 94%; 1h NMR (400MHz, CDCl 3) δ 8.22 (dd, J=8.1,1.5Hz, 1H), 8.13 (dd, J=8.2,1.3Hz, 1H), 7.75 (pd, J=6.9,1.6Hz, 2H), 7.59 (d, J=8.3Hz, 1H), 7.53 (d, J=7.7Hz, 1H), 7.41 (d, J=2.4Hz, 1H), 7.38 – 7.30 (m, 2H), 7.30 – 7.21 (m, 2H), 7.09 (s, 1H), 6.93 (dd, J=8.9,2.4Hz, 1H), 3.78 (s, 3H), 3.67 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 155.2,155.1,153.4,148.9,143.6,141.5,139.8,132.4,131.2,130.4,129.2,129.2,128.7,128.2,127.2,125.7,123.2,121.8,113.1,111.8,110.3,109.6,102.8,55.6,33.4.HRMS (EI) Calcd for C 26h 19n 3o 2405.1477, Found 405.1474.
The ultra-violet absorption spectrum of the compound 1ac-7ac in the embodiment of the present invention as shown in Figure 1, the fluorescence emission spectrum of compound 1ac-7ac as shown in Figure 2, as shown in Figure 3, the fluorescence emission spectrum of compound 1ac in opposed polarity solvent as shown in Figure 4 for the ultra-violet absorption spectrum of compound 1ac in opposed polarity solvent.

Claims (9)

1. the synthetic method of a two carbonyl Benzazole compounds, it is characterized in that, with alpha-alcohol ketone and indoles for reaction raw materials, take oxygen as oxygenant, under the effect of copper catalyst, be obtained by reacting such as formula the two carbonyl Benzazole compounds shown in (III) in reaction solvent; Described reaction process is as shown in reaction formula:
Wherein, Ar is phenyl ring, heterocycle or substituted benzene ring; R is electron rich base, electron-deficient base or halogen atom; R ' is alkyl, allyl group, benzyl or substituted benzyl.
2. the synthetic method of two carbonyl Benzazole compounds as claimed in claim 1, it is characterized in that, described copper catalyst is CuSO 4, CuSO 45H 2o, Cu (OAc) 2, Cu (NO 3) 2, Cu (TFA) 2, Cu (OTf) 2, CuCl 2, CuBr 2, Cu (acac) 2, CuO, CuOAc, CuI, CuBr, CuCl, CuTc, or Cu; The consumption of described copper catalyst is the 1-10% of α hydroxyketone.
3. the synthetic method of two carbonyl Benzazole compounds as claimed in claim 1, it is characterized in that, described reaction solvent is any one or arbitrary combination of water, methyl alcohol, ethanol, Virahol, the trimethyl carbinol, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran (THF), toluene, benzene, methylene dichloride, 1,2-ethylene dichloride, chloroform.
4. the synthetic method of two carbonyl Benzazole compounds as claimed in claim 1, it is characterized in that, in described reaction, the mole dosage ratio of described α hydroxyketone and indoles is 1:1-1:15.
5. the synthetic method of two carbonyl Benzazole compounds as claimed in claim 1, is characterized in that, said method comprising the steps of:
In reaction vessel, add α hydroxyketone, indoles, copper catalyst, reaction solvent, in oxygen atmosphere, react to stirred at reflux condition in room temperature, obtain the two carbonyl Benzazole compounds shown in formula (II).
6. the synthetic method of two carbonyl Benzazole compounds as claimed in claim 1, it is characterized in that, described reaction is carried out under 80 DEG C of conditions.
7. two carbonyl Benzazole compounds of method synthesis as described in any one of claim 1 ~ 6, it is characterized in that, its structure is such as formula shown in (III):
Wherein, Ar is phenyl ring, heterocycle or substituted benzene ring; R is electron rich base, electron-deficient base or halogen atom; R ' is alkyl, allyl group, benzyl or substituted benzyl.
8. a two carbonyl Benzazole compounds, it is characterized in that, its structure is such as formula shown in (III):
Wherein, Ar is phenyl, 4-fluorophenyl, 4-p-methoxy-phenyl, 4-chloro-phenyl-, 4-bromophenyl, 2-naphthyl, 2-benzothienyl, 2-benzofuryl, 2-thienyl, 3-thienyl; R is 4-methyl-formiate base, 5-oxyethyl group, 5-methoxyl group, 6-methoxyl group, 7-benzyloxy, 4-chlorine, 5-chlorine, 6-chlorine, 5-bromine; R ' is methyl, allyl group, benzyl or to methoxy-benzyl.
9. the application of the two carbonyl Benzazole compounds shown in formula (III) in synthesis Kui quinoline class fluorescent material.
CN201510103250.2A 2015-03-10 2015-03-10 A kind of pair of carbonyl Benzazole compounds and its synthetic method Active CN104817483B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510103250.2A CN104817483B (en) 2015-03-10 2015-03-10 A kind of pair of carbonyl Benzazole compounds and its synthetic method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510103250.2A CN104817483B (en) 2015-03-10 2015-03-10 A kind of pair of carbonyl Benzazole compounds and its synthetic method

Publications (2)

Publication Number Publication Date
CN104817483A true CN104817483A (en) 2015-08-05
CN104817483B CN104817483B (en) 2017-10-31

Family

ID=53727988

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510103250.2A Active CN104817483B (en) 2015-03-10 2015-03-10 A kind of pair of carbonyl Benzazole compounds and its synthetic method

Country Status (1)

Country Link
CN (1) CN104817483B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105566198A (en) * 2016-02-22 2016-05-11 新乡医学院 3-dicarbonyl substitution indole compound and preparation method thereof
CN106478483A (en) * 2016-10-14 2017-03-08 方美兰 A kind of diaryl replaces the synthetic method of dicarbonyl compound

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02188579A (en) * 1989-01-13 1990-07-24 Taisho Pharmaceut Co Ltd Indolylimidazole derivative

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02188579A (en) * 1989-01-13 1990-07-24 Taisho Pharmaceut Co Ltd Indolylimidazole derivative

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JI CHENG WU,等: "Copper-Catalyzed C-H Oxidation/Cross-Coupling of a-Amino Carbonyl Compounds", 《ANGEW. CHEM. INT. ED.》 *
JONATHAN L. SESSLER，等: "Diindolylquinoxalines: Effective Indole-Based Receptors for Phosphate Anion", 《J. AM. CHEM. SOC.》 *
K. SHIVA KUMAR，等: "AlCl3 induced (hetero)arylation of 2,3-dichloroquinoxaline: A one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents", 《BIOORGANIC & MEDICINAL CHEMISTRY》 *
QINGHE GAO,等: "Direct Regioselective Oxidative Cross-Coupling of Indoles with Methyl Ketones: A Novel Route to C3-Dicarbonylation of Indoles", 《ORG. LETT.》 *
SABRINA TALIANI，等: "Modulation of A2B adenosine receptor by 1-Benzyl-3-ketoindole derivatives", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105566198A (en) * 2016-02-22 2016-05-11 新乡医学院 3-dicarbonyl substitution indole compound and preparation method thereof
CN105566198B (en) * 2016-02-22 2018-04-20 新乡医学院 A kind of 3 dicarbapentaborane substituent indole compounds and preparation method thereof
CN106478483A (en) * 2016-10-14 2017-03-08 方美兰 A kind of diaryl replaces the synthetic method of dicarbonyl compound

Also Published As

Publication number Publication date
CN104817483B (en) 2017-10-31

Similar Documents

Publication Publication Date Title
Tang et al. Gold nanoparticles supported on titanium dioxide: An efficient catalyst for highly selective synthesis of benzoxazoles and benzimidazoles
CN108033922B (en) Preparation method of 3-acyl quinoxalinone derivative
Jhulki et al. Facile organocatalytic domino oxidation of diols to lactones by in situ-generated TetMe-IBX
Rong et al. Synthesis of benzofuro-and benzothieno [2, 3-c] pyridines via copper-catalyzed [4+ 2] annulation of ketoxime acetates with acetoacetanilide
CN104177241A (en) Alkynyl diketone compound and synthetic method thereof
CN109320489A (en) A kind of color alkyl compound and preparation method thereof
CN108250124A (en) A kind of method of carbazyl conjugation microporous polymer photocatalysis Benzazole compounds formylation reaction
CN112794782B (en) Fluorine-containing carboxylic acid compound and preparation method thereof
CN102775288A (en) Synthetic method of chalcone compounds
CN104817483A (en) Bis carbonyl indole compound and synthesis method
CN111808023B (en) Method for preparing 3-aryl isoquinoline derivative
CN101265231B (en) Method for preparing isoquinoline-N-oxide
CN112442008A (en) Method for preparing 1, 4-dithiine and thiophene compounds by regulating elemental sulfur and active internal alkyne at temperature and conversion reaction of compound
Huang et al. Preparation of a resin-bound cyclic malonic ester and a facile solid-phase synthesis of 4 (1H) quinolones
CN113651788B (en) 3-aminoalkylchromone compound and preparation method thereof
CN109651344B (en) Benzofuran triarylmethane compounds and green catalytic synthesis method thereof
CN111484436A (en) Method for introducing isopentenyl group to C3 position of indole
CN109942432B (en) Triaryl methanol compound and synthetic method thereof
CN113214134A (en) Synthesis method of quaternary carbon oxoindole skeleton
CN109232282B (en) Synthetic method of 2-aminobenzophenone compound
Cui et al. Palladium-catalyzed direct construction of oxazoline-containing polycyclic scaffolds via tandem addition/cyclization of nitriles and arylboronic acids
CN108276268B (en) Preparation method of 1, 3-diaryl propine ketone
CN108863895B (en) Synthetic method of dicarbonyl indole compound
CN109833908A (en) A kind of chirality high price iodine catalyst and its preparation method and application
CN104478799A (en) Preparation method of 1,4-diallyl isoquinoline

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
EXSB Decision made by sipo to initiate substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant