CN107698604B - 3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate and its synthetic method and application - Google Patents
3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate and its synthetic method and application Download PDFInfo
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 55
- UDXDKEFITPQLCI-UHFFFAOYSA-N O1CC=CC=C1.[S] Chemical compound O1CC=CC=C1.[S] UDXDKEFITPQLCI-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 10
- 238000010189 synthetic method Methods 0.000 title abstract description 8
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 13
- 241000813090 Rhizoctonia solani Species 0.000 claims description 8
- 241001512566 Valsa mali Species 0.000 claims description 8
- -1 methoxyl group Chemical group 0.000 abstract description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 6
- 229910052794 bromium Inorganic materials 0.000 abstract description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000460 chlorine Substances 0.000 abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 abstract description 5
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000003208 petroleum Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 17
- QGNIZTZEZZJHEK-UHFFFAOYSA-N 2-sulfanylidene-1h-quinoline-3-carbaldehyde Chemical compound C1=CC=C2NC(=S)C(C=O)=CC2=C1 QGNIZTZEZZJHEK-UHFFFAOYSA-N 0.000 description 16
- SKDNDVDHYMEGNJ-UHFFFAOYSA-N (2-bromo-2-nitroethenyl)benzene Chemical compound [O-][N+](=O)C(Br)=CC1=CC=CC=C1 SKDNDVDHYMEGNJ-UHFFFAOYSA-N 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 11
- 241000894006 Bacteria Species 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 9
- 230000005311 nuclear magnetism Effects 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 239000005864 Sulphur Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 241000223195 Fusarium graminearum Species 0.000 description 4
- 241000227653 Lycopersicon Species 0.000 description 4
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000012805 post-processing Methods 0.000 description 4
- 241000233866 Fungi Species 0.000 description 3
- 235000009811 Momordica charantia Nutrition 0.000 description 3
- 244000078912 Trichosanthes cucumerina Species 0.000 description 3
- 235000008322 Trichosanthes cucumerina Nutrition 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010523 cascade reaction Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003032 phytopathogenic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000021513 Cinchona Nutrition 0.000 description 1
- 241000157855 Cinchona Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The structure such as formula (I) of the invention discloses a kind of the 3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate and its synthetic method and application, the 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate is shown, wherein R1And R2Independently selected from hydrogen, methyl, bromine, chlorine, nitro or methoxyl group.Simultaneously sulphur pyran derivate has preferable antibacterial effect to the 3- bromo -3- nitro -2- aryl quinoline, can be used as a kind of potential antibacterial agent use.
Description
Technical field
The present invention relates to the synthesis fields of heterocyclic compound, and in particular to a kind of 3- bromo -3- nitro -2- aryl quinoline
And sulphur pyran derivate and its synthetic method and application.
Background technique
Quino sulphur pyrylium compound is a kind of important nitrogen-containing hetero spiro-compound.Quino sulphur pyrans Portugal's compound tool
There are very strong pharmacology, physiology and a bioactivity, such as there is anticancer, anti-inflammatory, antibacterial, antipsychotic, analgesia and antitumor important
Physiological activity.Such compound has a wide range of applications in fields such as catalysis, materials.Therefore, synthesize and study quino sulphur
Pyrylium compound has great importance.
There is the method for several synthesis 3- bromo -3- nitro -2- aryl quinolines and sulphur pyran derivate recently:
(1) 2013 year, chemist Zhenghong Zhou was reported using cinchona alkaloid-derived ligands as catalyst, ethyl acetate
For solvent, tandem reaction occurs for 2- sulfydryl-quinoline-3-formaldehyde and nitroolefin, obtains chiral 3- bromo -3- nitro -2-
Aryl quinoline and sulphur pyran derivate (Adv.Synth. Catal.2013,355,1053-1057).
(2) 2014 years, Manish P.Patel then reported 2- sulfydryl-quinoline-3-formaldehyde under the catalysis of proline, with
Malononitrile, benzenethiol carry out one pot of tandem reaction, obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate
(RSC Adv.,2014,4,28798–28801)。
(3) 2012 years, Radhey M.Singh reported 2- sulfydryl-quinoline-3-formaldehyde and acrylonitrile and is catalyzed in triethylamine
Under, tandem reaction occurs under DMF solvent, obtains 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate
(Tetrahedron Letters 53(2012)3242–3244)。
In addition there are some other methods, but step is more cumbersome than three of the above, numerous to list herein.Although these
Method has synthesized a series of 3- bromo -3- nitro -2- aryl quinolines and sulphur pyran derivate, but does not study such chemical combination
The antibiotic property of object.Therefore, a kind of new 3- bromo -3- nitro -2- aryl quinoline is developed and sulphur pyran derivate and its new
Synthetic method simultaneously studies its bioactivity and has great importance.
Summary of the invention
The present invention provides a kind of 3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate
And its application, the 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate are with preferable antibacterial activity.
The present invention also provides a kind of raw materials to be easy to get, while easy to operate and environment amenable 3- bromo -3- nitro -
The synthetic method of 2- aryl quinoline and sulphur pyran derivate.
A kind of 3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate, structure such as formula (I)
It is shown:
In formula (I), R is selected from hydrogen, methyl, bromine, chlorine, nitro or methoxyl group.
Preferably, simultaneously sulphur pyran derivate is formula (II)~formula to the 3- bromo -3- nitro -2- aryl quinoline
One of (IV):
Wherein, R5、R2、R3And R4Independently selected from hydrogen, methyl, bromine, chlorine, nitro or methoxyl group.
The present invention also provides the synthesis of the 3- bromo -3- nitro -2- aryl quinoline described in one kind and sulphur pyran derivate
Method, comprising the following steps:
Under the catalysis of DBU, 2- sulfydryl-quinoline-3-formaldehyde reacts 5 hours in a solvent with the bromo- Nitrostyrene of 1-,
It is post-treated to obtain the 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate；
2- sulfydryl-quinoline-3-formaldehyde structural formula is one of A~E:
The structure of the bromo- Nitrostyrene of the 1- is as follows:
R2Selected from hydrogen, methyl, bromine, chlorine, nitro or methoxyl group.
The structural formula of the DBU is as follows:
The mechanism of action of the synthetic method is as follows: under the catalysis of DBU, Mike's addition reaction first occurs, then carries out hydroxyl
Aldehyde condensation and cyclization, to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate.
By taking solvent existence condition as an example, the reaction equation between the various raw materials of the present invention is as follows:
Wherein, R2、R3、R4And R5Independently selected from hydrogen, methyl, bromine, chlorine, nitro or methoxyl group.
There is no stringent for the dosage of reaction raw materials 2- sulfydryl-quinoline-3-formaldehyde and the bromo- Nitrostyrene of 1- in the present invention
Restriction, generally according to chemical reaction metering ratio reacted, be also possible to one of compound and excessively reacted.
Preferably, the solvent is acetone.There is no stringent restrictions for reaction dissolvent consumption in the present invention, can basis
The dosage of reaction raw materials adjusts: the more dosage for increasing reaction dissolvent of reaction raw materials, the less reduction reaction dissolvent of reaction raw materials
Dosage.
Preferably, the reaction temperature is 25 DEG C.
The common post-processing approach in synthesis field can be used in the post-processing, is such as mentioned using recrystallization or column chromatography
It is pure, post-processing can include: recrystallized after removing solvent with organic solvent.
One of ethyl acetate, petroleum ether or two kinds can be selected in the organic solvent.
Alternatively, the post-processing includes: solvent to be removed under reduced pressure, then chromatograph through column.The leacheate choosing of the column chromatography
With the mixed liquor of petroleum ether and ethyl acetate.
3- bromo -3- nitro -2- the aryl quinoline and sulphur pyran derivate can be used as antibacterial agent use, by water
Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, fusarium graminearum are tested, such
Compound has preferable antibacterial activity.
Final object of the present invention is to provide 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate is made
For the application of antibacterial agent.
Compared with the existing technology, the present invention has the advantage that
(1) synthetic method of 3- bromo -3- nitro -2- aryl quinoline of the present invention and sulphur pyran derivate, key problem in technology
It is 2- sulfydryl-quinoline-3-formaldehyde and the bromo- Nitrostyrene of 1- is raw material, DBU is catalyst, and selects cheap reaction
Solvent, one kettle way directly synthesize 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate；With flexible reaction time, receive
Rate is higher, and solvent is cheap and easy to get, easy to operate, and equal many merits applied widely are suitable for industrialized production.
(2) 3- bromo -3- nitro -2- aryl quinoline of the invention and sulphur pyran derivate can be used as antibacterial agent use, especially
It is that have one to Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, fusarium graminearum etc.
Fixed inhibiting effect.
Specific embodiment
Embodiment 1
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1a (38mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2a (68mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3aa (94
Mg, yield 89%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3aa are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (400MHz, DMSO) δ 8.43 (s, 1H), 8.04 (d, J=8.0Hz, 1H),
7.88 (d, J=8.4Hz, 1H), 7.77 (t, J=7.4Hz, 1H), 7.62-7.49 (m, 6H), 6.28 (s, 1H), 6.00 (d, J
=7.2Hz, 1H)13C NMR(101 MHz,DMSO)δ156.2,146.9,135.3,134.8,131.7,131.7,131.4,
131.2,131.1, 129.4,129.4,128.7,127.3,126.6,125.7,110.5,75.0,50.3.ESI-HRMS:
calcd. for C18H12BrN2O33- bromo -3- nitro -2- the virtue that S+H, 416.9903, found 416.9918. show
Base quino sulphur pyran derivate 3aa has structure shown in structural formula.
Embodiment 2
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1b (40mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2a (68mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain the 3- bromo -3- nitro -2- aryl quinoline of structural formula such as 3ba and sulphur pyrans
Derivative 3ba (97mg, yield 90%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ba are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (400MHz, DMSO) δ 8.33 (s, 1H), 7.79 (d, J=8.4Hz, 2H),
7.66-7.45 (m, 6H), 6.27 (s, 1H), 5.99 (d, J=7.1Hz, 1H), 2.50 (s, 3H)13C NMR(101MHz,
DMSO)δ155.0,145.5,136.1, 135.3,134.2,133.2,131.7,131.7,131.3,131.2,129.4,
129.4,127.3,127.1, 125.7,110.7,75.0,50.2,21.5.ESI-HRMS:calcd.for C19H15BrN2O3S+
3- bromo -3- nitro -2- aryl quinoline and sulphur the pyran derivate tool that H, 431.0060, found 431.0108. show
There is structure shown in structural formula 3ba.
Embodiment 3
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1c (40mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2a (68mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain the 3- bromo -3- nitro -2- aryl quinoline of structural formula such as 3ca and sulphur pyrans
Derivative 3ca (97mg, yield 90%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ca are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.38 (s, 1H), 7.95 (d, J=8.3Hz, 1H),
7.68 (s, 1H), 7.58 (q, J=8.6Hz, 4H), 7.49 (d, J=7.4Hz, 1H), 7.43 (d, J=8.3Hz, 1H), 6.28
(s, 1H), 5.99 (d, J=7.3Hz, 1H), 2.53 (s, 3H)13C NMR(151MHz,DMSO)δ156.0,147.1,141.3,
135.3,134.6, 131.7,131.7,131.2,130.4,129.4,129.4,128.7,128.4,126.3,123.8,
It is tied 110.7,75.0,50.2,21.9. the 3- bromo -3- nitro -2- aryl quinoline shown and sulphur pyran derivate have
Structure shown in structure formula 3ca.
Embodiment 4
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1d (54mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2a (68mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3da 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate
(89mg, yield 73%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3da are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.44 (s, 1H), 8.37 (d, J=2.0Hz, 1H),
7.87 (dd, J=9.0,2.1Hz, 1H), 7.82 (d, J=8.9 Hz, 1H), 7.61-7.53 (m, 5H), 6.28 (s, 1H), 6.01
(d, J=5.9Hz, 1H)13C NMR (151MHz,DMSO)δ157.2,145.4,135.4,134.1,134.1,132.4,
132.4,131.7, 130.9,130.7,129.5,129.5,127.1,127.1 119.3,110.2,75.0,50.3.ESI-
HRMS: calcd.for C18H12Br2N2O33- bromo -3- the nitre that S+H, 494.9008, found 494.9023. show
Simultaneously sulphur pyran derivate has structure shown in structural formula 3da to base -2- aryl quinoline.
Embodiment 5
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1e (47mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2a (68mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3ea (57
Mg, yield 89%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ea are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (400MHz, DMSO) δ 8.97 (s, 1H), 8.42 (d, J=7.7Hz, 1H),
8.29 (d, J=8.4Hz, 1H), 7.96 (t, J=8.1 Hz, 1H), 7.76 (d, J=7.2Hz, 1H), 7.62-7.49 (m, 4H),
6.36 (s, 1H), 6.08 (d, J=7.1Hz, 1H)13C NMR(101MHz,DMSO)δ158.7,146.7,145.6,135.5,
134.5,131.7,131.7,130.6,130.0,129.5,129.5,124.6,118.1,109.6,99.9,74.9, 55.3,
50.3.ESI-HRMS:calcd.for C18H12BrN2O3The 3- bromine that S+H, 416.9903, found 416.9913. show
Simultaneously sulphur pyran derivate has structure shown in structural formula 3ea to generation -3- nitro -2- aryl quinoline.
Embodiment 6
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1a (38mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2b (72mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3ab
(99mg, yield 93%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ab are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.40 (s, 1H), 8.03 (d, J=8.0Hz, 1H),
7.87 (d, J=8.4Hz, 1H), 7.76 (t, J=7.5Hz, 1H), 7.55 (t, J=7.4Hz, 1H), 7.49-7.39 (m, 3H),
7.25 (d, J=7.9Hz, 2H), 6.17 (s, 1H), 6.00 (d, J=7.2Hz, 1H), 2.32 (s, 3H)13C NMR(151MHz,
DMSO)δ156.7,146.9,140.2,134.7,131.5,131.1,129.9,129.8,129.0,128.7, 127.3,
127.3,126.5,125.7,110.9,75.1,55.3,50.8,21.2.ESI-HRMS:calcd.for C19H15BrN2O3S+H,
3- bromo -3- nitro -2- the aryl quinoline and sulphur pyran derivate that 431.0060, found 431.0071. show have
Structure shown in structural formula 3ab.
Embodiment 7
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1a (38mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene of 1- (78mg, 0.3mmol), stirs
Reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:1)
Mixed liquor be leacheate carry out column chromatograph to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3ac (43mg,
Yield 60%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ac are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.57 (d, J=24.6Hz, 1H), 7.89 (t, J=
7.3Hz, 2H), 7.78 (d, J=6.4Hz, 1H), 7.71-7.66 (m, 1H), 5.37 (d, J=6.1Hz, 1H), 4.20 (d, J=
13.2Hz, 1H), 4.10 (d, J=13.2Hz, 1H)13C NMR(151MHz,DMSO)δ156.8,148.0,136.0,132.1,
130.4,130.3,127.6,124.9,121.6,117.0,73.1,55.3,33.4.ESI-HRMS:calcd. for
C13H8BrClN23- bromo -3- nitro -2- the aryl quinoline and sulphur that OS+H, 354.9302, found 354.9332. show
Pyran derivate has structure shown in structural formula 3ac.
Embodiment 8
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1a (38mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 1d (72mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3ad
(43mg, yield 60%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ad are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.43 (s, 1H), 8.05 (d, J=8.0Hz, 1H),
7.88 (d, J=8.3Hz, 1H), 7.77 (t, J=7.5Hz, 1H), 7.60-7.54 (m, 4H), 7.52 (d, J=7.2Hz, 1H),
6.29 (s, 1H), 6.00 (d, J=7.0Hz, 1H)13C NMR(151MHz,DMSO)δ156.2,146.9,135.3,134.8,
131.7, 131.4,131.2,131.1,129.5,129.5,128.7,127.3,126.6,125.7,110.5,75.0,55.3,
50.3.ESI-HRMS:calcd.for C18H12BrClN2O3S+H, the 3- that 450.9513, found 450.9532. show
Simultaneously sulphur pyran derivate has structure shown in structural formula 3ad to bromo -3- nitro -2- aryl quinoline.
Embodiment 9
At 25 DEG C, by 2- sulfydryl-quinoline-3-formaldehyde 1a (38mg, 0.2mmol), DBU (7.0mg, 0.04mmol), 2 millis
The acetone risen sequentially adds 5 milliliters of reaction tube, is then poured into the bromo- Nitrostyrene 2e (90mg, 0.3mmol) of 1-, stirs
Mix reaction 10 minutes.Solvent then is removed under reduced pressure, with petroleum ether and ethyl acetate (petroleum ether and ethyl acetate volume ratio is 12:
1) mixed liquor is that leacheate progress column chromatographs to obtain 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate 3ae (43
Mg, yield 60%).Reaction equation is as follows:
The structure of 3- bromo -3- nitro -2- aryl quinoline obtained above and sulphur pyran derivate 3ae are total to by nuclear-magnetism
It shakes and high resolution mass spectrum is identified,1H NMR (600MHz, DMSO) δ 8.37 (s, 1H), 7.98 (d, J=8.0Hz, 1H),
7.85 (t, J=8.2Hz, 1H), 7.75 (dd, J=14.9,7.3Hz, 1H), 7.64 (d, J=8.4Hz, 2H), 7.54 (t, J=
7.4Hz, 1H), 7.49 (d, J=8.4 Hz, 2H), 6.17 (s, 1H), 5.94 (d, J=11.3Hz, 1H)13C NMR(151MHz,
DMSO) δ156.1,146.8,134.9,132.3,132.1,132.0,131.3,131.3,131.2,128.7,127.1,
127.1,126.8,125.7,124.1,110.4,75.0,50.4.ESI-HRMS:calcd.for C18H12Br2N2O3S+H,
3- bromo -3- nitro -2- the aryl quinoline and sulphur pyran derivate that 494.9008, found 494.9018. show have
Structure shown in structural formula 3ae.
Embodiment 10: the anti-microbial property evaluation of sample segment
1. antifungal activity continuous mode: containing different compounds preparation of culture medium: by the different compounds of synthesis point
It is not dissolved in acetone, is made into the mother liquor of various concentration.1mL mother liquor and 9mL MEA culture medium (20g malt, 20g sugarcane are drawn respectively
Sugar, 1g peptone, 1L water, 18g agar) in sterile test tube, it is poured into sterile petri dish after shake well, makes to change in culture medium
The final mass concentration for closing object is respectively 100,50,10 and 1 μ g/mL, using equivalent acetone as blank control.By the plant of activation
Pathomycete breaks into the fungus block that diameter is 5mm with aseptic card punch, is placed in above-mentioned culture medium, every processing is repeated 3 times, in 28 DEG C of perseverances
Under temperature, after culture 3~7 days, using crossing method measurement for trying bacterium colony diameter.Inhibiting rate is calculated as follows: inhibiting
Rate=(control colony diameter-processing colony diameter)/(control colony diameter -5mm) × 100%.
2. anti-microbial property
Known by table 1, all compound 3aa-3ae to Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium,
Five kinds of Valsa mali, fusarium graminearum fungies have certain inhibitory activity, wherein compound 3da, 3ea, 3ad, 3ae
It is fine to Rhizoctonia solani Kuhn, Valsa mali inhibiting rate.
Inhibiting effect of the different compounds to 5 kinds of phytopathogenic fungis under the concentration of the same race of table 1. (concentration is 50 μ g/mL)
Then, based on two kinds of Rhizoctonia solani Kuhn, Valsa mali bacterium, all compounds are configured to various concentration
It does, and has obtained IC50(minimum inhibitory concentration) value.Two IC in table 250It is worth less than 100, wherein 3da, 3ea, 3ad is to water
Rhizoctonia solani Kuhn has preferable inhibitory activity, and 3da, 3ad, 3ae then have preferable inhibitory activity to Valsa mali.
The specific inhibitory effect of 2. 2 kinds of phytopathogenic fungis of table
Above it is demonstrated experimentally that 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate are to Rhizoctonia solani Kuhn, hardship
Five kinds of cucurbit wilt bacterium, tomato early blight bacterium, Valsa mali, fusarium graminearum fungies have certain inhibiting effect.
Claims (3)
1. a kind of 3- bromo -3- nitro -2- aryl quinoline with antibacterial activity and sulphur pyran derivate, which is characterized in that be
Compound 3da, one of 3ea, 3ad and 3da；Wherein the structural formula of 3da, 3ea, 3ad and 3da are as follows:
2. simultaneously sulphur pyran derivate is preparing antibacterial agent to a kind of 3- bromo -3- nitro -2- aryl quinoline as described in claim 1
In application, which is characterized in that the 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate is compound 3da,
At least one of 3ea and 3ad, the antibacterial agent is for preventing and treating Rhizoctonia solani Kuhn.
3. simultaneously sulphur pyran derivate is preparing antibacterial agent to a kind of 3- bromo -3- nitro -2- aryl quinoline as described in claim 1
In application, which is characterized in that the 3- bromo -3- nitro -2- aryl quinoline and sulphur pyran derivate is compound 3da,
At least one of 3ad and 3ae, the antibacterial agent is for preventing and treating Valsa mali.
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| Facile "on water" domino reactions for the expedient synthesis of 2H-thiopyrano[2,3-b]quinolines;Sundaravel Vivek Kumar，等;《RSC Adv.》;20150323;第5卷;30826-30832页 |
| Synthesis of Optically Active 2H-ThiopyranoACHTUNGTRENUNG[2,3-b]quinolines with Three Contiguous Stereocenters via an Organocatalytic Asymmetric Tandem Michael–Henry Reaction;Lulu Wu,等;《Adv. Synth. Catal》;20130408;第355卷;1053-1057页 |
| Xin-Ni Ping，等.Catalyst-Controlled Switch in Diastereoselectivities: Enantioselective Construction of Functionalized 3,4-Dihydro‑2H‑thiopyrano[2,3‑b]quinolines with Three Contiguous Stereocenters.《J. Org. Chem.》.2017,第82卷2205-2210页. |
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