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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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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| Organocatalytic Domino Michael/cyclization for the synthesis of highly substituted 4, 5-dihydrothiophenes;Chen-Hao Ding,et al.,;《Chinese Chemical Letters》;20170830;第29卷;第517-520页 * |
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