CN108218888B - A kind of simultaneously dihydro-thiophene derivative and its synthetic method and application of the 2- aryl chromene with antibacterial activity - Google Patents
A kind of simultaneously dihydro-thiophene derivative and its synthetic method and application of the 2- aryl chromene with antibacterial activity Download PDFInfo
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- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical class C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 238000010189 synthetic method Methods 0.000 title claims abstract description 13
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 9
- -1 methoxyl group Chemical group 0.000 claims abstract description 21
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 239000000460 chlorine Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- 238000006243 chemical reaction Methods 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 19
- PNXCGUHRJZGVPT-UHFFFAOYSA-N 3-nitro-2h-chromene Chemical compound C1=CC=C2OCC([N+](=O)[O-])=CC2=C1 PNXCGUHRJZGVPT-UHFFFAOYSA-N 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 14
- 235000019441 ethanol Nutrition 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 241000223195 Fusarium graminearum Species 0.000 claims description 6
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 5
- 241000588724 Escherichia coli Species 0.000 claims description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000012805 post-processing Methods 0.000 claims description 5
- 239000012973 diazabicyclooctane Substances 0.000 claims description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 4
- 125000005909 ethyl alcohol group Chemical group 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 1
- 229910052731 fluorine Inorganic materials 0.000 abstract 1
- 239000011737 fluorine Substances 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- 229940093499 ethyl acetate Drugs 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 22
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 10
- 238000010517 secondary reaction Methods 0.000 description 10
- 239000002994 raw material Substances 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 2
- 240000008067 Cucumis sativus Species 0.000 description 2
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 241000123650 Botrytis cinerea Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 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
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229930192474 thiophene Natural products 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The structure such as formula (I) of the invention discloses a kind of the 2- aryl chromene with antibacterial activity and dihydro-thiophene derivative and its synthetic method and application, the 2- aryl chromene and dihydro-thiophene derivative is shown, wherein R1、R2It is independently selected from hydrogen, fluorine, chlorine, bromine, methoxyl group, methyl or nitro.Simultaneously dihydro-thiophene derivative has preferable antibacterial effect to the 2- aryl chromene, 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 2- aryl chromene and dihydro-thiophene spreads out
Biology and its synthetic method and application.
Background technique
2- aryl chromene and dihydro-thiophene do not have also at present as a kind of very unique sulfur heterocyclic compound
There is the synthetic method of such compound of document report, bioactivity of such compound etc. is not also carried out studying.
Therefore, develop a kind of new method and construct 2- aryl chromene and dihydro-thiophene derivative have it is important
Meaning.
Summary of the invention
The present invention provides a kind of the 2- aryl chromene with antibacterial activity and dihydro-thiophene derivative and its application,
Simultaneously dihydro-thiophene derivative has preferable antibacterial activity to the 2- aryl chromene.
The present invention also provides a kind of raw materials to be easy to get, while easy to operate and environment amenable 2- aryl chromene is simultaneously
The synthetic method of dihydro-thiophene derivative.
A kind of 2- aryl chromene with antibacterial activity and dihydro-thiophene derivative, shown in structure such as formula (I):
In formula (I), R1、R2、R3、R4、R5It is independently selected from hydrogen, chlorine, bromine, methoxyl group or methyl.
The present invention also provides the synthetic methods of the 2- aryl chromene described in one kind and dihydro-thiophene derivative, including
Following steps:
Substituted thioamides ethyl acetate is catalyzed down through DABCO in a solvent with 3- nitro chromene to be reacted,
It is post-treated to obtain the 2- aryl chromene and dihydro-thiophene derivative;
The structure of the substituted thioamides ethyl acetate is shown below:
Wherein, R3、R4、R5Definition it is described above.
The structure of the 3- nitro chromene is shown below:
Wherein, R1、R2It is as defined above described in text.
The structure of the DABCO is shown below:
The mechanism of action of the synthetic method is as follows: Mike's addition first occurs for the reaction, and then addition reaction occurs for intramolecular
And cyclization, to obtain 2- aryl chromene and dihydro-thiophene derivative.
By taking solvent existence condition as an example, the reaction equation between the various raw materials of the present invention is as follows:
Wherein, R1、R2、R3、R4、R5It is independently selected from hydrogen, chlorine, bromine, methoxyl group or methyl.
There is no tight for the dosage of the thioamides ethyl acetate with 3- nitro chromene of reaction raw materials substitution in the present invention
The restriction of lattice is reacted generally according to chemical reaction metering ratio, is also possible to one of compound and is excessively reacted.
Preferably, the solvent is ethyl alcohol.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 15-35 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.
The 2- aryl chromene and dihydro-thiophene derivative can be used as antibacterial agent use, by Escherichia coli,
Hay bacillus, fusarium graminearum and cucumber grey mold are tested, such compound has certain antibacterial activity.
Final object of the present invention is to provide 2- aryl chromene and dihydro-thiophene derivative as antibacterial agent
Application.
Preferably, simultaneously dihydro-thiophene derivative is preparing the application in antibacterial agent, institute to the 2- aryl chromene
The compound 4ac, 4ca stated is for inhibiting Escherichia coli;
The compound 4ba, 4ac is for inhibiting hay bacillus;
The compound 4af is for inhibiting fusarium graminearum.
These compounds have preferable inhibitory activity to specific strain.
Compared with the existing technology, the present invention has the advantage that
(1) synthetic method of 2- aryl chromene of the present invention and dihydro-thiophene derivative, key problem in technology are to replace
Thioamides ethyl acetate and 3- nitro chromene are raw material, and select cheap reaction dissolvent, and one kettle way directly synthesizes
2- aryl chromene and dihydro-thiophene derivative;With flexible reaction time, yield is higher, and solvent is cheap and easy to get, operation letter
Just, equal many merits applied widely, are suitable for industrialized production.
(2) 2- aryl chromene of the invention and dihydro-thiophene derivative can be used as antibacterial agent use, especially to big
Enterobacteria, hay bacillus, fusarium graminearum and cucumber grey mold etc. have certain inhibiting effect.
Specific embodiment
Embodiment 1
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3a (25mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4aa and dihydro-thiophene derivative 4aa (42mg, yield
92%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4aa are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.67 (s, 1H), 7.43 (d, J=7.7Hz, 1H), 7.36 (t, J=
7.9Hz, 2H), 7.29-7.18 (m, 5H), 7.12 (d, J=7.7Hz, 2H), 7.08-7.03 (m, 2H), 7.00 (d, J=
7.1Hz, 2H), 6.91 (s, 1H), 4.33 (dq, J=10.9,7.1Hz, 1H), 4.29 (s, 1H), 4.23 (dq, J=10.9,
7.1Hz, 1H), 1.31 (t, J=7.1Hz, 3H)13C NMR(151MHz,DMSO)δ165.6,156.5,152.3,140.1,
136.1,129.8,129.5,129.2,129.1,127.0,126.1,123.4,123.1,123.0,117.3,109.1,95.8,
73.7,60.1,38.7,15.0.ESI-HRMS:calcd for C26H22N2O4S+H 459.1373, found 459.1370. table
Simultaneously dihydro-thiophene derivative has structure shown in structural formula 4aa to bright obtained 2- aryl chromene.
Embodiment 2
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3b (33mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ab and dihydro-thiophene derivative 4ab (50mg, yield
94%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ab are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.69 (s, 1H), 7.61 (dd, J=2.5,0.9Hz, 1H), 7.44
(ddd, J=8.7,2.5,0.6Hz, 1H), 7.37 (dd, J=8.3,7.5Hz, 2H), 7.29-7.20 (m, 4H), 7.14 (d, J=
7.5Hz, 2H), 7.03 (d, J=8.7Hz, 1H), 6.99 (s, 2H), 6.98 (s, 1H), 4.43 (dq, J=10.9,7.1Hz,
1H), 4.31 (s, 1H), 4.18 (dq, J=10.9,7.1Hz, 1H), 1.34 (t, J=7.1Hz, 3H)13C NMR(151MHz,
DMSO)δ165.28(s),157.0,151.6,140.0,135.7,131.9,131.6,129.8,129.7,129.3,127.1,
126.4,126.1,123.4,119.8,114.0,108.1,95.0,73.6,60.1,38.6,15.0.ESI-HRMS:calcd
for C26H21BrN2O4The 2- aryl chromene and dihydro-thiophene that S+H 537.0478, found 537.0478. show
Derivative has structure shown in structural formula 4ab.
Embodiment 3
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3c (4mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ac and dihydro-thiophene Derivatives-4ac (44mg, yield
90%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene Derivatives-4ac is passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR(600MHz,CDCl3) δ 9.68 (s, 1H), 7.47 (dd, J=2.6,0.9Hz, 1H), 7.37
(dd, J=8.3,7.5Hz, 2H), 7.33 (ddd, J=8.7,2.6,0.6Hz, 1H), 7.29-7.20 (m, 4H), 7.14 (d, J=
7.5Hz, 2H), 7.09 (d, J=8.7Hz, 1H), 6.99 (s, 1H), 6.98 (s, 2H), 4.42 (dq, J=10.9,7.1Hz,
1H), 4.31 (s, 1H), 4.20 (dq, J=10.9,7.1Hz, 1H), 1.33 (t, J=7.1Hz, 3H)13C NMR(151MHz,
DMSO)δ165.3,157.0,151.1,140.0,135.7,129.8,129.7,129.3,129.1,128.7,127.1,
126.4,126.3,125.6,123.4,119.3,108.2,95.0,73.6,60.1,38.7,15.0.ESI-HRMS:calcd
for C26H21ClN2O4The 2- aryl chromene and dihydro-thiophene that S+H 493.0983, found 493.0985. show
Derivative has structure shown in structural formula 4ac.
Embodiment 4
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3d (27mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ad and dihydro-thiophene derivative 4ad (37mg, yield
79%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ad are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.69 (s, 1H), 7.36 (dd, J=8.4,7.5Hz, 2H), 7.26-
7.18 (m, 5H), 7.15-7.11 (m, 2H), 7.09-7.05 (m, 1H), 6.99 (dd, J=8.2,1.3Hz, 2H), 6.93 (d, J
=8.3Hz, 1H), 6.84 (s, 1H), 4.41 (dq, J=10.9,7.1Hz, 1H), 4.25 (s, 1H), 4.19 (dq, J=10.9,
7.1Hz, 1H), 2.25 (s, 3H), 1.33 (t, J=7.1Hz, 3H)13C NMR(151MHz,DMSO)δ165.6,156.6,
150.2,140.1,136.1,131.6,129.8,129.7,129.5,129.3,129.1,127.0,126.1,123.1,
117.1,109.3,95.7,73.8,60.0,38.7,20.9,15.0. the 2- aryl chromene and dihydro-thiophene shown
Derivative has structure shown in structural formula 4ad.
Embodiment 5
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3e (33mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ae and dihydro-thiophene derivative 4ae (47mg, yield
87%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ae are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR(600MHz,CDCl3) δ 9.68 (s, 1H), 7.47 (d, J=8.6Hz, 2H), 7.43 (d, J=
7.7Hz, 1H), 7.36 (dd, J=8.3,7.6Hz, 2H), 7.27 (ddd, J=8.1,7.5,0.9Hz, 1H), 7.20 (t, J=
7.4Hz, 1H), 7.13 (d, J=7.6Hz, 2H), 7.09-7.04 (m, 2H), 6.96 (d, J=8.6Hz, 2H), 6.90 (s, 1H),
4.33 (dq, J=10.9,7.1Hz, 1H), 4.28 (s, 1H), 4.23 (dq, J=10.9,7.1Hz, 1H), 1.31 (t, J=
7.1Hz,3H).13C NMR(151MHz,DMSO)δ165.5,156.5,152.1,140.1,135.4,132.2,129.8,
129.3,129.2,129.1,126.2,123.4,123.1,122.9,117.3,109.1,95.5,73.2,60.1,38.7,
15.0.ESI-HRMS:calcd for C26H21BrN2O4The 2- aryl that S+H537.0478, found 537.0475. show
Simultaneously dihydro-thiophene derivative has structure shown in structural formula 4ae to chromene.
Embodiment 6
At 25 DEG C, by substituted thioamides ethylacetate derivative 2a (27mg, 0.12mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3f (27mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4af and dihydro-thiophene derivative 4af (41mg, yield
86%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4af are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.66 (s, 1H), 7.43 (d, J=7.7Hz, 1H), 7.35 (t, J=
7.9Hz, 2H), 7.26 (t, J=7.5Hz, 1H), 7.19 (t, J=7.4Hz, 1H), 7.11 (d, J=7.8Hz, 2H), 7.04
(dd, J=17.2,7.8Hz, 4H), 6.89-6.85 (m, 3H), 4.33 (dq, J=10.9,7.1Hz, 1H), 4.28 (s, 1H),
4.24 (dq, J=10.9,7.1Hz, 1H), 2.18 (s, 3H), 1.32 (t, J=7.1Hz, 3H)13C NMR(151MHz,DMSO)δ
165.6,156.4,152.3,140.1,139.1,133.1,129.8,129.7,129.2,129.1,126.9,126.1,
123.4,123.0,122.9,117.3,108.9,95.9,73.4,60.1,38.6,21.1,15.0.ESI-HRMS:calcd
for C27H24N2O4The 2- aryl chromene and dihydro-thiophene that S+H 473.1530, found 473.1533. show spread out
Biology has structure shown in structural formula 4af.
Embodiment 7
At 25 DEG C, by substituted thioamides ethylacetate derivative 2b (22mg, 0.1mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3a (25mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ba and dihydro-thiophene derivative 4ba (47mg, yield
96%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ba are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 10.16 (s, 1H), 7.45 (d, J=7.8Hz, 1H), 7.38-7.33
(m, 2H), 7.29 (dd, J=18.7,7.4Hz, 1H), 7.21 (ddd, J=21.9,11.2,5.1Hz, 4H), 7.10-7.02 (m,
5H), 6.38 (s, 1H), 4.45 (s, 1H), 4.42 (ddd, J=14.2,9.0,5.4Hz, 1H), 4.31 (tt, J=14.3,
5.4Hz, 1H), 1.40 (t, J=7.1Hz, 3H)13C NMR(151MHz,CDCl3)δ166.4,152.9,136.7,135.1,
130.0,129.1,129.0,128.6,128.5,127.4,126.7,125.5,123.5,122.6,121.3,117.1,
109.7,97.3,82.0,76.3,60.3,38.9,14.7.ESI-HRMS:calcd for C26H21ClN2O4S+H
The 2- aryl chromene and dihydro-thiophene derivative that 493.0983, found 493.0987. show have structural formula 4ba
Shown in structure.
Embodiment 8
At 25 DEG C, by substituted thioamides ethylacetate derivative 2c (22mg, 0.1mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3a (25mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ca and dihydro-thiophene derivative 4ca (45mg, yield
92%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ca are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.65 (s, 1H), 7.42 (d, J=7.7Hz, 1H), 7.37 (t, J=
8.1Hz, 1H), 7.29-7.20 (m, 6H), 7.10-7.03 (m, 3H), 7.00 (d, J=7.1Hz, 2H), 6.97 (s, 1H), 4.32
(dq, J=10.9,7.1Hz, 1H), 4.29 (s, 1H), 4.23 (dq, J=10.9,7.1Hz, 1H), 1.30 (t, J=7.1Hz,
3H).13C NMR(151MHz,DMSO)δ165.2,155.1,152.3,141.7,136.1,133.9,131.3,129.6,
129.2,129.1,127.0,125.6,123.1,123.0,122.5,121.3,117.3,109.0,97.7,73.4,60.3,
38.8,14.9.ESI-HRMS:calcd for C26H21ClN2O4S+H 493.0983, found 493.0986. show
Simultaneously dihydro-thiophene derivative has structure shown in structural formula 4ca to 2- aryl chromene.
Embodiment 9
At 25 DEG C, by substituted thioamides ethylacetate derivative 2d (22mg, 0.1mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3a (25mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4da and dihydro-thiophene derivative 4da (41mg, yield
84%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4da are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR(600MHz,DMSO)δ9.65(s,1H),7.44–7.38(m,3H),7.29–7.21(m,
4H), 7.15 (d, J=8.8Hz, 2H), 7.05 (ddd, J=9.8,7.8,1.8Hz, 2H), 7.00 (d, J=7.1Hz, 2H),
6.91 (s, 1H), 4.35-4.30 (m, 1H), 4.30 (s, 1H), 4.22 (dq, J=10.9,7.1Hz, 1H), 1.30 (t, J=
7.1Hz,3H).13C NMR(151MHz,DMSO)δ165.3,155.8,152.3,139.1,136.0,130.1,129.6,
129.5,129.2,127.0,124.8,123.3,123.0,117.3,109.1,96.7,73. 6,60.2,38.8,14.9. shows
Obtained 2- aryl chromene and dihydro-thiophene derivative has structure shown in structural formula 4da.
Embodiment 10
At 25 DEG C, by substituted thioamides ethylacetate derivative 2e (22mg, 0.1mmol), 1 milliliter of ethyl alcohol according to
In the secondary reaction flask for being added 5 milliliters, it is subsequently added into 3- nitro chromene 3a (25mg, 0.1mmol), is stirred 1 hour at room temperature.
Solvent then is removed under reduced pressure, the mixed liquor with petroleum ether and ethyl acetate (petroleum ether is with ethyl acetate volume ratio for 100:1) is
Leacheate carries out column and chromatographs to obtain the 2- aryl chromene of structural formula such as 4ea and dihydro-thiophene derivative 4ea (37mg, yield
76%).Reaction equation is as follows:
The structure of 2- aryl chromene obtained above and dihydro-thiophene derivative 4ea are passed through into nuclear magnetic resonance and high score
Distinguish that mass spectrum is identified,1H NMR (600MHz, DMSO) δ 9.68 (s, 1H), 7.43 (d, J=7.6Hz, 1H), 7.29-7.21
(m, 5H), 7.05 (t, J=7.7Hz, 2H), 7.00 (d, J=7.0Hz, 2H), 6.92 (s, 1H), 6.76 (dd, J=7.4,
1.7Hz, 1H), 6.69 (dd, J=8.5,1.4Hz, 2H), 4.33 (dq, J=10.9,7.1Hz, 1H), 4.28 (s, 1H), 4.23
(dq, J=10.9,7.1Hz, 1H), 3.74 (s, 3H), 1.31 (t, J=7.1Hz, 3H)13C NMR(151MHz,DMSO)δ
165.6,160.4,156.2,152.3,141.2,136.1,130.6,129.5,129.2,129.1,127.0,123.4,
122.9,117.3,114.6,111.8,109.0,108.3,96.1,73.6,60.2,55.7,38.6,15.0.ESI-HRMS:
calcd for C27H24N2O5The 2- aryl chromene and dihydro that S+H 489.1479, found 489.1477. show
Thiophene derivant has structure shown in structural formula 4ea.
The anti-microbial property of 11 sample of embodiment is evaluated
With cup disk cultivation Preliminary Determination compound 3 when mass concentration is 100 μ g/mL to Escherichia coli, withered grass bar
Bacterium, fusarium graminearum and botrytis cinerea pers bacteriostatic activity, as shown in table 1.
1 antifungal activity of tablea
aAntibacterial circle diameter: < 10mm (-), drug resistance;10~12mm (+), muting sensitive;13~15mm (++), medium sensitivity;16
~20mm (+++), it is highly sensitive.
By all there is certain inhibitory activity to four kinds of bacterium in the visible all test compounds of the result of table 1.Wherein chemical combination
Object 4ac, 4ca are respectively highly sensitive to the function and effect of Escherichia coli;Compound 4ba, 4ac are respectively to the effect of hay bacillus
Effect is highly sensitive;Compound 4af is highly sensitive to the function and effect of fusarium graminearum.
Claims (6)
1. a kind of 2- aryl chromene with antibacterial activity and dihydro-thiophene derivative, which is characterized in that structure such as formula (I)
It is shown:
In formula (I), R1、R2、R3、R4、R5It is independently selected from hydrogen, chlorine, bromine, methoxyl group or methyl.
2. the synthetic method of a kind of 2- aryl chromene as described in claim 1 and dihydro-thiophene derivative, feature exist
In, comprising the following steps:
Substituted thioamides ethyl acetate is catalyzed down through DABCO in a solvent with 3- nitro chromene to be reacted, reaction
After post-treated obtain the 2- aryl chromene and dihydro-thiophene derivative;
The structure of the substituted thioamides ethyl acetate is shown below:
Wherein, R3、R4、R5Definition it is as described in claim 1;
The structure of the 3- nitro chromene is shown below:
Wherein, R1、R2Definition it is as described in claim 1;
The structure of the DABCO is shown below:
3. the synthetic method of 2- aryl chromene according to claim 2 and dihydro-thiophene derivative, which is characterized in that
The solvent is ethyl alcohol.
4. the synthetic method of 2- aryl chromene according to claim 2 and dihydro-thiophene derivative, which is characterized in that
Reaction temperature is 15-35 DEG C.
5. the synthetic method of 2- aryl chromene according to claim 2 and dihydro-thiophene derivative, which is characterized in that
The post-processing includes: solvent to be removed under reduced pressure, then chromatograph to obtain the 2- aryl chromene through column and dihydro-thiophene spreads out
Biology.
6. simultaneously dihydro-thiophene derivative is preparing answering in antibacterial agent to a kind of 2- aryl chromene as described in claim 1
With, which is characterized in that the compound 4ac, 4ca is for inhibiting Escherichia coli;
The compound 4ba, 4ac is for inhibiting hay bacillus;
The compound 4af is for inhibiting fusarium graminearum;
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手性伯胺催化麦克尔/烷基化串联反应:螺靛红环丙烷衍生物的高效合成;谢建武,等;《浙江师范大学学报(自然科学版)》;20170228;第40卷(第1期);第51-57页 * |
绿色合成苯并吡喃并四氢噻吩衍生物;丁晨浩;《浙江化工》;20171231;第48卷(第10期);第27-30页 * |
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