CN114989145B - Trifluoromethyl coumarin-containing tertiary alcohol derivative and preparation method and application thereof - Google Patents

Trifluoromethyl coumarin-containing tertiary alcohol derivative and preparation method and application thereof Download PDF

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CN114989145B
CN114989145B CN202210816286.5A CN202210816286A CN114989145B CN 114989145 B CN114989145 B CN 114989145B CN 202210816286 A CN202210816286 A CN 202210816286A CN 114989145 B CN114989145 B CN 114989145B
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tertiary alcohol
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coumarin
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CN114989145A (en
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徐翠莲
吴璐璐
江圣飞
杨国玉
史力军
樊良鑫
潘振良
王彩霞
周冰怡
常潇丹
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Henan Agricultural University
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Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a tertiary alcohol derivative containing trifluoromethyl coumarin, a preparation method and application thereof, wherein 3- (trifluoroacetyl) coumarin compounds and substituted pyrrole compounds are used as raw materials, and the tertiary alcohol derivative can be prepared through Friedel-crafts alkylation reaction at room temperature under the condition of no catalyst; the derivatives have good antibacterial effect on one or more of six common pathogenic bacteria in agricultural production, namely fusarium graminearum, fusarium oxysporum, fusarium graminearum, fusarium moniliforme, rhizoctonia solani and phytophthora nicotianae, wherein the compounds 3ad,3gd and 3hd show broad-spectrum antibacterial activity.

Description

Trifluoromethyl coumarin-containing tertiary alcohol derivative and preparation method and application thereof
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a tertiary alcohol derivative containing trifluoromethyl coumarin, and a preparation method and application thereof.
Background
Trifluoromethyl compounds have been widely studied by researchers due to their unique properties. Among them, α -trifluoromethyl tertiary alcohol structures are present in various drugs, for example, the following compounds each contain an α -trifluoromethyl tertiary alcohol structure, in which α -trifluoromethyl tertiary alcohol a and efavirenz (efavirenz) are HIV reverse transcriptase inhibitors, B1653048 and MK-0633 are glucocorticoid agonists and 5-lipoxygenase inhibitors, respectively.
For the synthesis of numerous tertiary trifluoromethyl alcohols, as shown below, each reactant is typically prepared by friedel-crafts alkylation with a trifluoromethyl ketone, e.g., trifluoromethyl ketone as acceptor (a) for the addition reaction, and when an α, β -unsaturated trifluoromethyl ketone is used as acceptor, 1, 4-addition product (b) is formed.
The existing synthesis process needs to use a catalyst, and the reaction conditions are harsh, which is unfavorable for large-scale production and application. When developing new compounds, not only attention is paid to the performance of the prepared compounds, but also the synthetic method is required to be simple and has strong operability, so that the method has the prospect of large-scale industrial production and application. For this reason, trifluoromethyl tertiary alcohols which are excellent in performance and simple in preparation method are also required to be further studied.
Disclosure of Invention
In order to solve the technical problems, the invention provides the tertiary alcohol derivative containing the trifluoromethyl coumarin, and the preparation method and application thereof, and the tertiary alcohol derivative containing the trifluoromethyl coumarin has good antibacterial effect, does not need to add a catalyst in the preparation process, has mild reaction conditions and high yield, and has a large-scale production application prospect.
The invention is realized by the following technical scheme.
The first object of the invention is to provide a tertiary alcohol derivative containing trifluoromethyl coumarin, which has a chemical structural formula shown in the following formula (3-1) or formula (3-2):
wherein R is 1 、R 2 、R 3 Are respectively and independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, halogen or aryl, R 4 、R 5 、R 6 、R 7 、R 8 Are respectively and independently hydrogen, C 1 -C 3 An alkyl group.
Preferably, the aryl is a fused ring aryl, such as naphthyl.
Preferably, the halogen is fluorine, chlorine, bromine or iodine.
Preferably, the alkyl group is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl or tert-pentyl; the alkoxy is methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, isopropoxy, isobutoxy, sec-butoxy, tert-butoxy, isopentoxy or tert-pentoxy.
The second object of the invention is to provide a preparation method of the tertiary alcohol derivative containing trifluoromethyl coumarin, which comprises the following steps:
preparing a compound shown in a formula (3-1) or a formula (3-2) by taking a 3- (trifluoroacetyl) coumarin compound and a substituted pyrrole compound as raw materials through Friedel-crafts alkylation reaction;
preferably, the reaction solvent is methylene chloride.
Preferably, the reaction is carried out at 0-45 ℃, and the reaction can be carried out within the range, so that the equipment required for controlling the reaction conditions is less and the operation is simple when the reaction is carried out at room temperature.
Preferably, the molar ratio of the 3- (trifluoroacetyl) coumarin compound to the substituted pyrrole compound is 0.5-2:1, the amount of the solvent to be used is not particularly limited as long as the raw materials for the reaction can be dissolved.
The third object of the invention is to provide the effect of the tertiary alcohol derivative containing trifluoromethyl coumarin in preparing a bacteriostatic agent.
Preferably, the bacteriostatic agent is used for inhibiting fusarium graminearum, fusarium oxysporum, fusarium graminearum (from wheat), fusarium moniliforme, rhizoctonia solani and phytophthora nicotianae.
Compared with the prior art, the invention has the following beneficial effects:
(1) In order to further explore trifluoromethyl tertiary alcohol compounds which have high performance and simple preparation method, the invention combines the advantages of coumarin compounds and alpha-trifluoromethyl tertiary alcohol compounds, and provides a novel trifluoromethyl coumarin tertiary alcohol derivative which has good antibacterial effect on one or more of fusarium graminearum (from corn), fusarium oxysporum, fusarium graminearum (from wheat), fusarium moniliforme, rhizoctonia solani and phytophthora nicotianae which are common in agricultural production; wherein the compounds 3ad,3gd,3hd exhibit a broad spectrum of bacteriostatic activity.
(2) The derivative is prepared by taking 3- (trifluoroacetyl) coumarin compounds and substituted pyrrole as raw materials under the conditions of room temperature and no catalyst, has high yield, and is suitable for large-scale production and application.
Drawings
FIG. 1 is a single crystal structure diagram of compound 3 fa;
FIG. 2 is a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum, and a nuclear magnetic fluorine spectrum of compound 3 aa;
FIG. 3 is a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum, and a nuclear magnetic fluorine spectrum of the compound 3 ec;
FIG. 4 shows the nuclear magnetic hydrogen spectrum, the nuclear magnetic carbon spectrum and the nuclear magnetic fluorine spectrum of the compound 3 ed.
Detailed Description
In order that those skilled in the art will better understand the technical solution of the present invention, the present invention will be further described with reference to the specific examples and the accompanying drawings, but the examples are not intended to be limiting. The experimental methods and the detection methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available unless otherwise specified. The sources of the strains used were all from the university of agricultural plant protection university in Henan.
Example 1
The invention provides a tertiary alcohol derivative containing trifluoromethyl coumarin, which has a structural formula shown in the following formula (3-1) or formula (3-2):
wherein R is 1 、R 2 、R 3 Are respectively and independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, halogen or aryl, R 4 、R 5 、R 6 、R 7 、R 8 Are respectively and independently hydrogen, C 1 -C 3 An alkyl group.
The invention also provides a preparation method of the tertiary alcohol derivative containing the trifluoromethyl coumarin, which is theoretically prepared by taking alpha, beta-unsaturated trifluoromethyl ketone containing the coumarin as an electrophile and performing Friedel-crafts alkylation on the alpha, beta-unsaturated trifluoromethyl ketone and pyrrole compounds, but the synthesis conditions influence the yield of the products, so that the reaction conditions are firstly explored.
R is as described above 1 、R 2 、R 3 、R 4 、R 6 、R 7 、R 8 Respectively are hydrogen, R 5 When the reaction is methyl, namely, the following compound 1a and compound 2a are used as substrate templates, the reaction conditions are screened, and the reaction equation is as follows:
the specific reaction process is as follows:
placing the compound 1a (1.0 mmol) and the compound 2a (1.0 mmol) in a solvent (10 mL), stirring and reacting for 1h, after the reaction is detected by thin layer chromatography, distilling under reduced pressure to remove the solvent, and purifying the residue by 100-200 mesh silica gel column chromatography; the eluent used in the column chromatography is petroleum ether: ethyl acetate=2 to 4:1. the reaction conditions to be screened are:
solvent species: CH (CH) 2 Cl 2 、EtOAc、CH 3 CN, tolene (toluene), THF, dioxane, clCH 2 CH 2 Cl、BrCH 2 CH 2 Br、CH 2 Cl 2 ；
Reaction temperature: room temperature 25 ℃, 0 ℃;
catalyst: when the catalyst is contained, the usage amount of the catalyst is 5%; no catalyst is contained;
the yields of the products obtained by the combination of the above different reaction conditions are shown in table 1:
TABLE 1 comparison of product yields for different reaction conditions
As can be seen from Table 1, under room temperature conditions, when AlCl catalyst was added 3 When the reaction is carried out in CH 2 Cl 2 The product was successfully prepared in 46% yield (item 1), indicating that lewis acid can promote the reaction; subsequently, a series of Lewis acids were screened, and the yield was low although the product was produced (entries 2-6); on the other hand, when no catalyst was added under the above conditions, the yield was found to be significantly improved (to 97%, item 7); subsequent counter-rotationScreening with solvent showed that the solvent had a significant effect on the product yield (entries 7-15), and the yield was drastically reduced when chloroform, ethyl acetate, acetonitrile, toluene and tetrahydrofuran were used as solvents (entries 8-12); as a comparison, methylene chloride was the best solvent, with the highest yield reaching 97%, but when the temperature was lowered to 0℃the yield was drastically reduced (entry 16).
In conclusion, the reaction can be carried out at room temperature under the condition of dichloromethane without catalyst, and the yield is higher.
Example 2
On the premise of determining the optimal reaction conditions, two types of reaction substrates with different substituents are explored, namely, under the above reaction conditions, the types of the substituents and the substitution positions of the reaction substrates are changed, and the influence on the yield is examined, wherein the reaction equation is as follows:
all compounds 1 were prepared according to the following prior art:
1.C.Xu,G.Yang,C.Wang,S.Fan,L.Xie,Y.Cao,Molecules,2013,18,11964-11977.
2.C.Wang,C.Xu,G.Yang,S.Fan,L.Xin,T.Guo,Molbank,2014,3,M830.
3.G.-Y.Yang,J.-T.Yang,C.-X.Wang,S.-F.Fan,P.-H.Xie,C.-L.Xu,J.Fluor.Chem.2014,168,1-8.
the yields of the different substrates are shown in Table 2:
TABLE 2 comparison of yields of different substrates
As can be seen from Table 2, the position 6, 7 or 8 of 3- (trifluoroacetyl) coumarinThe corresponding product was successfully obtained when the substitution (hydrogen, urgent, chlorine, bromine, naphthyl) was carried out and reacted with pyrrole substituted at the 2-position, and the yield was higher (84% -97%, entries 1-9), after which the substituents on the pyrrole were changed, and the reaction conditions were examined, and it was found that the position and electronic properties of the substituents had a significant effect on the yield of the product, and the pyrrole ring was higher in the 2-, 3-or 4-position (entries 10, 11, 21-27), but since the activity of pyrrole at the 2-position was higher than that of pyrrole at the 3-position, the reaction yield was lowered when substitution was carried out at both the 2-and 5-positions, and Sc (OTf) was added to the system 3 (5%) and after increasing the reaction temperature to 45 ℃, the yield increased (entries 12-20); when pyrrole and N-methylpyrrole are used, it is also possible to obtain a certain yield of product (entries 28-29), whereas no reaction occurs when the pyrrole ring bears electron-deficient groups (entry 30).
The spectrogram data for the above compounds are provided below:
3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 aa) A light brown solid, as shown in FIG. 2, mp 134.5-135.6 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.43(s,1H),7.87(s,1H),7.61(t,J＝7.8Hz,1H),7.52(d,J＝7.7Hz,1H),7.44-7.23(m,4H),5.92(s,1H),2.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.47,153.22,145.16,133.21,129.12,128.97,125.92,125.29,123.50,123.07,122.35,118.39,116.60,108.76,106.82,77.37,77.05,76.87,76.73,76.56,76.25,12.96. 19 F NMR(376MHz,CDCl 3 )δ-78.01.HRMS(ESI):m/z calcd for C 16 H 11 F 3 NO 3 [M-H] - 322.0691,found:322.0685.
6-methyl-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 ba) is pale yellowSolid, mp 207.9-208.7 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.41(d,J＝48.1Hz,1H),8.27(d,J＝20.8Hz,1H),7.70(d,J＝1.0Hz,1H),7.49(dd,J＝8.5,1.9Hz,1H),7.31(t,J＝14.1Hz,1H),6.02(s,1H),5.69(s,1H),2.39(s,3H),2.13(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ158.48,152.02,143.74,134.41,133.92,129.46,128.37,126.73,125.48,124.53,123.87,118.64,115.98,107.68,105.78,74.80,74.51,74.21,73.91,20.68,13.09. 19 F NMR(376MHz,DMSO-d 6 )δ-74.08.HRMS(ESI):m/z calcd for C 17 H 13 F 3 NO 3 [M-H] - 336.0848,found:336.0833.
6-chloro-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 ca) white solid, mp 235.9-236.5 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.43(s,1H),8.45(s,1H),8.13(d,J＝2.5Hz,1H),7.71(dd,J＝8.8,2.6Hz,1H),7.48(d,J＝8.9Hz,1H),7.20(s,1H),6.01(s,1H),5.69(s,1H),2.11(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ157.47,152.62,142.80,132.58,129.50,128.95,128.81,128.38,126.64,126.01,125.35,123.79,120.93,120.41,118.23,107.69,105.86,74.53,74.23,73.94,73.63,13.09. 19 F NMR(376MHz,DMSO-d 6 )δ-73.76.HRMS(ESI):m/z calcd for C 16 H 10 ClF 3 NO 3 [M-H] - 356.0301,found:356.0295.
6-bromo-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 da) cyan solid, mp 236.5-236.9 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.41(s,1H),8.43(s,1H),8.24(d,J＝2.3Hz,1H),7.81(dd,J＝8.8,2.4Hz,1H),7.40(d,J＝8.8Hz,1H),7.17(s,1H),6.01(s,1H),5.68(s,1H),2.11(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ157.41,153.01,142.70,135.33,131.94,128.36,126.63,125.94,125.34,123.77,120.90,118.50,116.58,107.67,105.84,74.22,73.92,13.09. 19 FNMR(376MHz,DMSO-d 6 )δ-73.78.HRMS(ESI):m/z calcd for C 16 H 10 BrF 3 NO 3 [M-H] - 399.9796,found:399.9782.
7-methoxy-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 ea) white solid, mp 160.5-161.8 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.45(s,1H),8.29(d,J＝16.8Hz,1H),7.82(d,J＝8.7Hz,1H),7.17-6.96(m,3H),6.01(s,1H),5.68(t,J＝2.4Hz,1H),3.88(s,3H),2.12(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ163.53,158.79,155.83,143.94,130.98,128.30,126.83,125.65,123.97,120.75,113.20,112.48,107.63,105.73,100.51,74.75,74.46,74.16,73.86,56.90,56.52,13.10. 19 F NMR(376MHz,DMSO-d 6 )δ-74.31.HRMS(ESI):m/zcalcd for C 17 H 13 F 3 NO 4 [M-H] - 352.0797,found:352.0783.
8-methoxy-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 fa) pink solid, mp 198.1-198.6 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.44(s,1H),8.36(s,1H),7.46(dd,J＝7.1,1.9Hz,1H),7.40-7.29(m,2H),7.15(d,J＝0.9Hz,1H),6.01(s,1H),5.69(s,1H),3.93(s,3H),2.11(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.02,147.08,147.06,145.28,142.86,128.91,128.75,125.90,125.17,123.46,123.05,122.50,120.22,119.05,114.72,108.69,106.77,77.36,77.24,77.04,76.85,76.83,76.72,76.52,76.22,56.35,12.93. 19 F NMR(376MHz,CDCl 3 )δ-78.04.HRMS(ESI):m/z calcd for C 17 H 13 F 3 NO 4 [M-H] - 352.0797,found:352.0791.
6, 8-dichloro-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 ga) as a pale yellow solid, mp 168.5-169.1 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.45(s,1H),7.76(s,1H),7.63(d,J＝2.3Hz,1H),7.43(d,J＝2.3Hz,1H),6.88(s,1H),6.22(s,1H),5.91(s,1H),2.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ160.77,147.55,143.78,132.98,130.53,129.39,128.53,126.86,125.68,124.71,122.83,122.72,122.63,120.13,119.98,77.39,77.21,77.07,76.90,76.75,76.58,76.27,12.92. 19 FNMR(376MHz,CDCl 3 )δ-77.71.HRMS(ESI):m/z calcd for C 16 H 9 Cl 2 F 3 NO 3 [M-H] - 389.9912,found:389.9903.
6, 8-dibromo-3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 ha.) cyan solid, mp 162.1-163.2 ℃. 1 HNMR(400MHz,CDCl 3 )δ8.47(s,1H),7.92(d,J＝2.2Hz,1H),7.74(s,1H),7.61(d,J＝2.2Hz,1H),6.87(s,1H),6.23(t,J＝3.1Hz,1H),5.91(t,J＝3.2Hz,1H),2.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ160.85,149.06,143.75,138.01,130.57,129.38,126.10,124.64,122.84,122.74,120.53,119.32,117.88,111.52,108.96,106.95,76.86,76.54,76.23,12.95. 19 FNMR(376MHz,CDCl 3 )δ-77.71.HRMS(ESI):m/z calcd for C 16 H 9 Br 2 F 3 NO 3 [M-H] - 479.8881,found:479.8868.
3- (2, 2-trifluoro-1-hydroxy-1- (5-methyl-1H-pyrrol-2-yl) ethyl) -2H benzo [ H ]]Chrome-2-one (3 ia) yellow brown solid, mp 192.0-192.9 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.68(s,1H),8.54(s,1H),8.12-8.00(m,2H),7.91(d,J＝8.1Hz,1H),7.71(t,J＝7.6Hz,1H),7.60(t,J＝7.5Hz,1H),7.51-7.40(m,2H),7.26(s,1H),6.39(s,1H),6.01(s,1H),2.28(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.56,153.31,141.04,134.78,130.47,129.16,129.01,128.97,128.90,126.70,126.09,123.60,123.24,121.48,121.04,116.24,112.91,108.65,107.03,77.38,77.27,77.12,77.07,76.81,76.75,76.50,12.97. 19 FNMR(376MHz,CDCl 3 )δ-78.07.HRMS(ESI):m/z calcd for C 20 H 13 F 3 NO 3 [M-H] - 372.0848,found:372.0838.
3- (1- (3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 ab) pink solid, mp.131.7-132.8 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.19(s,1H),7.79(s,1H),7.58-7.49(m,2H),7.30(dd,J＝14.1,7.7Hz,2H),6.28(s,1H),5.63(d,J＝2.7Hz,1H),2.16(s,3H),1.79(s,3H). 13 C NMR(101MHz,CDCl 3 )δ161.74,153.09,142.52,133.01,129.11,128.81,127.25,125.96,125.31,123.10,118.92,118.19,118.01,116.66,110.71,76.66,76.35,76.04,12.91,12.48. 19 F NMR(376MHz,CDCl 3 )δ-75.55.HRMS(ESI):m/z calcd for C 17 H 13 F 3 NO 3 [M-H] - 336.0848,found:336.0833.
3- (1- (3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -8-methoxy-2H-chrome-2-one (3 fb) orange solid, mp 67.1-68.5 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.17(s,1H),7.76(s,1H),7.21(d,J＝6.3Hz,1H),7.10-7.04(m,2H),6.33(s,1H),5.62(d,J＝2.9Hz,1H),3.91(s,3H),2.15(s,3H),1.79(s,3H). 13 C NMR(101MHz,CDCl 3 )δ161.34,147.08,142.74,128.87,127.28,126.02,125.25,123.27,123.17,120.33,120.24,118.91,118.86,118.05,114.62,110.69,77.44,77.32,77.12,77.02,76.80,76.71,76.40,76.09,56.31,12.87,12.50. 19 F NMR(376MHz,CDCl 3 )δ-75.57.HRMS(ESI):m/z calcd for C 18 H 15 F 3 NO 3 [M-OH] + 350.0999,found:350.1008.
3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 ac) cyan solid, mp 109.7-110.8 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.86(s,1H),7.73(s,1H),7.59(t,J＝8.5Hz,1H),7.50(d,J＝7.7Hz,1H),7.40-7.28(m,2H),6.59(s,1H),5.90(s,1H),2.21(s,3H),2.15(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.19,153.26,144.34,132.76,128.94,126.79,125.92,125.22,125.10,124.76,123.93,121.07,78.45,78.16,77.86,77.56,77.40,77.29,77.09,76.77,12.96,12.80. 19 FNMR(376MHz,CDCl 3 )δ-76.82.HRMS(ESI):m/z calcd for C 17 H 13 F 3 NO 2 [M-OH] + 320.0893,found:320.0917.
3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -6-methyl-2H-chrome-2-one (3 bc) white solid, mp 161.2-162.0 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.75(s,1H),7.67(s,1H),7.39(dd,J＝8.5,1.3Hz,1H),7.29(d,J＝7.1Hz,1H),6.61(s,1H),5.89(s,1H),2.39(s,1H),2.21(s,1H),2.17(s,1H). 13 C NMR(101MHz,CDCl 3 )δ162.34,151.42,144.19,134.87,133.75,129.63,128.62,126.78,125.84,125.03,124.63,123.92,118.35,116.24,115.17,106.54,78.40,78.11,77.81,77.51,20.71,12.99,12.82. 19 F NMR(376MHz,CDCl 3 )δ-76.88.HRMS(ESI):m/z calcd for C 18 H 15 F 3 NO 3 [M-H] - 350.1004,found:350.0989.
6-chloro-3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 cc) yellow solid, mp 145.2-146.5 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.25(s,1H),8.45(s,1H),8.13(d,J＝2.5Hz,1H),7.71(dd,J＝8.8,2.6Hz,1H),7.47(s,1H),7.20(s,1H),6.00(s,1H),5.69(s,1H),2.11(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ157.47,152.62,142.80,132.58,129.50,128.95,128.81,128.38,126.64,126.01,125.35,123.79,120.93,120.41,118.23,107.69,105.86,74.53,74.23,73.94,73.63,13.09. 19 F NMR(376MHz,DMSO-d 6 )δ-76.72.HRMS(ESI):m/z calcd for C 17 H 12 ClF 3 NO 3 [M-H] - 370.0458,found:370.0449.
6-bromo-3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 dc) brown solid, mp 168.6-170.4 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.74(s,1H),7.65(dd,J＝6.7,2.9Hz,3H),7.24(s,1H),6.32(s,1H),5.85(s,1H),2.19(s,3H),2.15(s,3H). 13 C NMR(101MHz,CDCl 3 )δ161.34,152.10,142.81,135.42,131.12,126.64,125.86,124.88,123.75,120.07,118.28,117.68,114.78,106.45,78.13,77.84,13.02,12.82. 19 F NMR(376MHz,CDCl 3 )δ-76.70.HRMS(ESI):m/z calcd for C 17 H 12 BrF 3 NO 3 [M-H] - 413.9953,found:413.9936.
3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -7-methoxy-2H-chrome-2-one (3 ec) a yellow solid, as shown in FIG. 3, mp 80.1-81.7 ℃. 1 HNMR(400MHz,CDCl 3 )δ8.22(s,1H),7.75(s,1H),7.22-7.14(m,1H),7.02(s,1H),6.32(s,1H),5.60(s,1H),3.86(s,3H),2.12(s,3H),1.78(s,3H). 13 C NMR(101MHz,CDCl 3 )δ161.59,147.06,144.21,126.74,125.88,125.51,124.90,124.61,123.89,120.06,119.27,115.11,114.29,106.53,78.08,77.79,56.33,13.00,12.82. 19 F NMR(376MHz,CDCl 3 )δ-76.86.HRMS(ESI):m/z calcd for C 18 H 15 F 3 NO 4 [M-H] - 366.0953,found:366.0941.
3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -8-methoxy-2H-chrome-2-one (3 fc) cyan solid, mp 79.8-81.1 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.69(s,1H),7.23(d,J＝7.9Hz,1H),7.12(d,J＝8.1Hz,1H),7.06(d,J＝7.8Hz,1H),6.55(s,1H),5.78(d,J＝82.7Hz,1H),4.02-3.88(m,1H),2.21(s,1H),2.17(s,1H). 13 C NMR(101MHz,CDCl 3 )δ161.59,147.06,144.21,126.74,125.88,125.51,124.90,124.61,123.89,120.06,119.27,115.11,114.29,106.53,78.08,77.79,56.33,13.00,12.82. 19 F NMR(376MHz,CDCl 3 )δ-76.86.HRMS(ESI):m/z calcd for C 18 H 15 F 3 NO 4 [M-H] - 366.0953,found:366.0941.
6, 8-dichloro-3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 gc) a tan solid, mp 119.1-120.3 ℃. 1 HNMR(400MHz,CDCl 3 )δ7.81(s,1H),7.68-7.60(m,2H),7.42(d,J＝2.3Hz,1H),6.16(s,1H),5.86(s,1H),2.21(s,3H),2.17(s,3H). 13 C NMR(101MHz,CDCl 3 )δ160.74,150.72,143.67,133.55,130.24,127.58,126.66,125.91,124.67,123.64,122.56,120.36,115.05,108.26,78.12,77.82,12.98,12.78. 19 F NMR(376MHz,CDCl 3 )δ-76.73.HRMS(ESI):m/z calcd for C 17 H 11 Cl 2 F 3 NO 3 [M-H] - 404.0068,found:404.0052.
6, 8-dibromo-3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 hc.) yellow solid, mp 172.6-174.3 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.84(d,J＝2.1Hz,1H),7.73(s,1H),7.57-7.49(m,2H),6.11(s,1H),5.78(s,1H),2.13(s,3H),2.08(s,3H). 13 C NMR(101MHz,CDCl 3 )δ160.40,149.16,142.67,138.06,130.36,129.36,127.48,126.50,125.90,125.00,123.64,120.79,120.16,117.60,114.46,111.06,106.34,78.38,78.08,77.78,77.48,13.00,12.80. 19 F NMR(376MHz,CDCl 3 )δ-77.71.HRMS(ESI):m/z calcd for C 17 H 11 Br 2 F 3 NO 2 [M-OH] + 477.9083,found:477.9106.
3- (1- (2, 5-dimethyl-1H-pyrrol-3-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H benzo [ H ]]Chrome-2-one (3 ic) Carbonic solid, mp 168.6-170.4 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ10.69(s,1H),9.38(s,1H),8.67(d,J＝8.5Hz,1H),8.49(d,J＝9.1Hz,1H),8.35(d,J＝8.1Hz,1H),8.05(t,J＝7.7Hz,1H),7.97-7.83(m,2H),6.16(s,1H),2.47(s,3H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.13,153.25,139.80,134.20,133.03,130.48,130.36,129.16,129.11,128.63,128.29,126.51,126.13,125.94,124.84,124.26,121.52,116.44,115.18,112.99,106.55,78.32,78.02,77.72,13.11,12.90. 19 F NMR(376MHz,CDCl 3 )δ-76.70.HRMS(ESI):m/z calcd for C 21 H 15 F 3 NO 3 [M-H] - 386.1004,found:386.0996.
3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 ad) as a yellow solid, mp 162.9-163.5 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.10(s,1H),7.85(s,1H),7.65-7.56(m,2H),7.38(dd,J＝14.8,7.6Hz,2H),6.35(s,1H),2.34(q,J＝7.4Hz,2H),2.19(s,3H),1.83(s,3H),1.02(t,J＝7.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ161.74,153.14,142.61,132.95,129.10,126.09,125.27,123.39,123.26,122.46,118.28,118.08,116.68,77.37,77.25,77.05,76.84,76.73,76.54,76.23,17.51,15.56,11.19,10.08. 19 F NMR(376MHz,CDCl 3 )δ-75.42.HRMS(ESI):m/z calcd for C 19 H 17 F 3 NO 3 [M-H] - 364.1161,found:364.1150.
3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -6-methyl-2H-chrome-2-one (3 bd) yellow solid, mp 160.8-161.9 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.10(s,1H),7.81(s,1H),7.49-7.37(m,2H),7.29(d,J＝4.1Hz,1H),6.44(s,1H),2.46(d,J＝10.9Hz,3H),2.36(q,J＝7.5Hz,2H),2.20(s,3H),1.84(s,3H),1.04(t,J＝7.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ162.01,151.29,142.67,135.15,134.03,128.97,128.82,126.12,123.27,123.18,123.13,122.43,118.17,118.04,116.62,116.35,77.37,77.25,77.05,76.85,76.73,76.55,76.24,20.75,17.51,15.57,11.19,10.06. 19 F NMR(376MHz,CDCl 3 )δ-75.46.HRMS(ESI):m/z calcd for C 20 H 19 F 3 NO 3 [M-H] - 378.1317,found:378.1299.
6-chloro-3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 cd) pale yellow solid, mp 169.4-170.1 ℃. 1 H NMR(400MHz,DMSO-d 6 )δ9.76(s,1H),8.26(s,1H),8.10(d,J＝2.3Hz,1H),7.68(d,J＝2.4Hz,1H),7.44(d,J＝8.9Hz,1H),6.97(s,1H),2.20(q,J＝7.3Hz,2H),2.04(s,3H),1.74(s,3H),0.91(d,J＝7.5Hz,3H). 13 C NMR(101MHz,DMSO-d 6 )δ157.32,152.24,140.16,132.55,129.72,129.04,128.94,126.86,126.11,124.00,122.89,121.14,120.69,120.03,118.87,118.26,75.44,75.14,74.84,74.55,17.43,16.19,11.09,10.04. 19 FNMR(376MHz,DMSO-d 6 )δ-73.50.HRMS(ESI):m/z calcd for C 19 H 16 ClF 3 NO 3 [M-H] - 398.0771,found:398.0751.
6-bromo-3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 dd) yellow solid, mp 168.6-169.2 ℃. 1 H NMR(400MHz,CDCl 3 )δ9.78(s,1H),8.18(s,1H),7.86(d,J＝8.6Hz,1H),7.05-6.94(m,2H),6.80(s,1H),3.87(s,3H),2.22(q,J＝7.4Hz,2H),2.07(s,3H),1.75(s,3H),0.94(t,J＝7.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ160.99,151.97,141.31,135.69,131.29,128.80,125.95,124.67,123.48,123.10,122.54,120.25,119.76,118.36,117.90,117.71,116.77,77.37,77.25,77.05,76.82,76.73,76.51,76.21,17.49,15.55,11.20,10.08. 19 F NMR(376MHz,CDCl 3 )δ-75.34.HRMS(ESI):m/z calcd for C 19 H 16 BrF 3 NO 3 [M-H] - 442.0266,found:442.0243.
3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -7-methoxy-2H-chrome-2-one (3 ed) cyan solid, as shown in FIG. 4, mp 160.4-161.1 ℃. 1 H NMR(400MHz,CDCl 3 )δ9.77(s,1H),8.18(s,1H),7.86(d,J＝8.6Hz,1H),7.03–6.97(m,2H),6.79(s,1H),3.86(s,3H),2.25-2.19(m,2H),2.06(s,3H),1.74(s,3H),0.93(t,J＝7.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ161.74,153.14,142.63,133.99,132.95,129.52,129.10,128.94,126.09,125.27,123.39,123.26,122.46,120.39,118.28,118.08,116.68,77.37,77.25,77.05,76.84,76.73,76.54,76.23,17.51,15.56,11.19,10.08. 19 F NMR(376MHz,CDCl 3 )δ-75.42.HRMS(ESI):m/z calcd for C 20 H 19 F 3 NO 4 [M-H] - 394.1266,found:394.1247.
6, 8-dichloro-3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 gd) a dark yellow solid, mp 145.8-146.5 ℃. 1 HNMR(400MHz,DMSO-d 6 )δ9.77(s,1H),8.33(s,1H),8.17(d,J＝2.3Hz,1H),8.00(d,J＝2.3Hz,1H),7.04(s,1H),2.23(q,J＝7.4Hz,2H),2.06(s,3H),1.80(s,3H),0.93(d,J＝7.5Hz,3H). 13 C NMR(101MHz,DMSO-d 6 )δ156.23,148.16,140.16,131.95,128.85,128.31,126.98,126.81,123.95,122.98,121.15,120.88,120.68,118.73,115.10,75.10,74.81,74.51,17.45,16.20,11.13,11.09,10.14. 19 F NMR(376MHz,DMSO-d 6 )δ-73.30.HRMS(ESI):m/z calcd for C 19 H 15 Cl 2 F 3 NO 3 [M-H] - 432.0381,found:432.0357.
6, 8-dibromo-3- (1- (4-ethyl-3, 5-dimethyl-1H-pyrrol-2-yl) -2, 2-trifluoro-1-hydroxyethyl) -2H-chrome-2-one (3 hd) -dark yellow solid, mp:142.2-142.9 DEG C. 1 H NMR(400MHz,DMSO-d 6 )δ7.97(s,1H),7.88(d,J＝2.2Hz,1H),7.65(s,1H),7.60(d,J＝2.2Hz,1H),5.88(s,1H),2.29-2.23(m,2H),2.11(s,3H),1.74(s,3H),0.95(t,J＝7.5Hz,3H). 13 CNMR(101MHz,DMSO-d 6 )δ156.40,149.64,140.11,137.24,131.84,129.69,126.84,123.97,122.97,121.57,120.69,118.75,116.78,115.09,110.16,75.38,75.09,74.79,74.47,17.46,16.21,11.13,11.09,10.15. 19 F NMR(376MHz,DMSO-d 6 )δ-73.32.HRMS(ESI):m/z calcd for C 19 H 15 Br 2 F 3 NO 3 [M-H] - 521.9350,found:521.9319.
3- (2, 2-trifluoro-1-hydroxy-1- (1H-pyrrol-2-yl) -ethyl) -2H-chrome-2-one (3 ae) white solid, mp 153.5-154.3 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.80(s,1H),7.84(s,1H),7.62(t,J＝7.9Hz,1H),7.50(s,1H),7.44-7.34(m,3H),7.26(s,1H),6.86(s,1H),6.40(s,1H),6.27(s,1H). 13 C NMR(101MHz,CDCl 3 )δ76.54,76.86,108.40,109.06,110.00,116.62,118.33,118.81,122.14,123.04,125.20,125.34,125.89,129.13,135.26,146.88,154.19,162.44. 19 F NMR(376MHz,CDCl 3 )δ-78.07.HRMS(ESI):m/z Calcd for C 15 H 9 F 3 NO 2 [M-OH] + 292.0580,found:292.0607.
3- (2, 2-trifluoro-1-hydroxy-1- (1-methyl-1H-pyrrol-2-yl) ethyl) -2H-chrome-2-one (3 af) white solid, mp 129.3-131.1 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.66-7.60(m,1H),7.46-7.40(m,2H),7.36-7.31(m,2H),7.21(s,1H),6.70-6.64(m,1H),6.46(s,1H),6.17-6.10(m,1H),3.55(s,3H). 13 C NMR(101MHz,CDCl 3 )δ162.22,153.42,146.17,133.39,129.06,126.14,125.76,125.35,124.87,123.28,122.31,118.39,116.69,111.43,106.56,78.30,78.00,77.69,36.14. 19 F NMR(376MHz,CDCl 3 )δ-77.07.HRMS(ESI):m/z calcd for C 16 H 11 F 3 NO 2 [M-OH] + 306.0737,found:306.0762.
In addition, single crystals of compound 3fa (as shown in fig. 1) are provided, and the crystal data of the compound are shown in table 3, and the configuration of other products can be determined by analogy.
TABLE 3 Crystal data of Compound 3fa
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Example 3
The compound synthesized in example 2 was subjected to activity performance test.
Bacteriostasis experiment: according to the agricultural industry standard of the people's republic of China (NY/T1156.2-2006), the compound is subjected to sterilization or bacteriostasis activity determination by adopting a hypha growth rate method, and the specific process is as follows:
the obtained pathogenic bacteria are subjected to activation culture a few days before the experiment, and the codes and names of the tested strains are as follows:
a: fusarium graminearum (from corn), B: fusarium oxysporum, C: fusarium graminearum (from wheat), D: fusarium moniliforme, E: rhizoctonia solani, F: phytophthora nicotianae.
Preparation of PDA Medium
Weighing 200 g of potatoes, cutting into small pieces, adding 1000mL of distilled water, boiling and steaming for 30 minutes; weighing 20 g of glucose and 18 g of agar; filtering the steamed potato with absorbent gauze, adding water to approximately 1000mL, adding glucose for dissolution, pouring into a pot, boiling, adding agar, heating and stirring uniformly; pouring into a beaker, adding water to 1000mL, stirring uniformly, subpackaging into 30mL conical flask, and sealing in double.
Sterilizing, transplanting and treating
Wrapping the inoculating loop and the inoculating needle with newspaper, and simultaneously placing the prepared PDA culture medium in a sterilizing box, and sterilizing the PDA culture medium by raising the temperature to 120 ℃ for 30 minutes; weighing 16.6mg of the medicine in an conical flask, adding 0.66mL of DMSO to dissolve the medicine, placing the medicine in an aseptic operation box for ultraviolet sterilization, and inoculating for later use; the temperature of the sterilization box is reduced to about 50 ℃ for post treatment, 2.65mL of Tween is added into a 250mL conical flask to prepare warm water for spitting, and the warm water is uniformly mixed for later use; mixing 2.65mL of warm water and medicines, packaging in culture dishes, transplanting fungi in triplicate after the culture medium is solidified, sealing the culture medium by a sealing film after the transplanting is completed, and placing the culture medium in an incubator to determine that the fungi grow according to blank control. Measuring data, calculating the bacteriostasis rate, wherein the calculation formula is as follows: antibacterial ratio i= (D) 0 -Dt)/D 0 *100％；
Wherein D is 0 For the average diameter of hyphae of the control disc, dt is the average diameter of hyphae of the sample disc; the comparison of the bacteriostatic effects of the different compounds on six pathogenic bacteria is shown in table 4.
TABLE 4 antibacterial effect of the above compounds
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Using triazolone at a concentration of 10mg/L as a positive control, it can be seen from the results of Table 4 that most of the compounds had a degree of bactericidal activity, wherein the inhibition rate of the compounds 3ad, 3bd and 3cd against F.zeae was over 90%, the inhibition rate of the compounds 3ad, 3bd, 3gd and 3hd against F.oxysporum was over 80%, the inhibition rate of the compounds 3ad and 3bd against F.cereus was over 80%, and especially 3ad,3gd and 3hd showed excellent activity against F.subtilis (> 98%), and the compounds 3ac, 3ad, 3bd, 3gd and 3hd had higher antifungal activity against tobacco parasitic bacteria (> 80%). Furthermore, it is notable that 3ad,3gd and 3hd have broad-spectrum bactericidal activity.
In summary, substituents have a great influence on the activity, and in general, 3-ethyl-2, 4-dimethyl-1H-pyrrole derivatives (3 ad, 3bd, 3cd, 3gd and 3 hd) have a generally higher bactericidal activity against the fungi tested than other substituted pyrrole derivatives.
Further, several compounds having high antifungal activity at a concentration of 500mg/L were selected, and the half-effective concentration (EC 50 ) Values, results are shown in table 5:
TABLE 5 EC of the above compounds 50 Value of
As shown in Table 5, the compounds have good bactericidal activity against Rhizoctonia solani. Of these, compound 3cd is the most potent, EC 50 The value was 10.88mg/L.
In summary, the invention provides a novel trifluoromethyl coumarin tertiary alcohol derivative, which combines the advantages of coumarin compounds and alpha-trifluoromethyl tertiary alcohol compounds, takes 3- (trifluoroacetyl) coumarin and pyrrole as raw materials, can be prepared at room temperature under the condition of no catalyst, and has high yield; the derivatives have good antibacterial effect on one or more of six common pathogenic bacteria in agricultural production, namely fusarium graminearum (from corn), fusarium oxysporum, fusarium graminearum (from wheat), fusarium moniliforme, rhizoctonia solani and phytophthora nicotianae. Wherein the compounds 3ad,3gd,3hd exhibit a broad spectrum of bacteriostatic activity.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that such modifications and variations be included herein within the scope of the appended claims and their equivalents.

Claims (9)

1. The trifluoromethyl coumarin tertiary alcohol derivative is characterized in that the chemical structure is shown as a formula (3-1) or a formula (3-2):
wherein R is 1 、R 2 、R 3 Are respectively and independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, halogen or naphthyl, R 4 、R 5 、R 6 、R 7 、R 8 Are respectively and independently hydrogen, C 1 -C 6 An alkyl group.
2. The tertiary alcohol derivative of trifluoromethyl coumarin according to claim 1, wherein the halogen is fluorine, chlorine, bromine or iodine.
3. The tertiary alcohol derivative of trifluoromethyl coumarin according to claim 1, wherein the alkyl group is methyl, ethyl, propyl, butyl, pentyl or hexyl; the alkoxy is methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy.
4. A tertiary alcohol derivative of trifluoromethyl coumarin according to claim 3, wherein the alkyl group is isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl or tert-pentyl; the alkoxy is isopropoxy, isobutoxy, sec-butoxy, tert-butoxy, isopentyloxy or tert-pentyloxy.
5. The process for producing a tertiary alcohol derivative containing trifluoromethylcoumarin according to any one of claims 1 to 4, comprising the steps of:
preparing a compound shown in a formula (3-1) or a formula (3-2) by taking a 3- (trifluoroacetyl) coumarin compound and a substituted pyrrole compound as raw materials through Friedel-crafts alkylation reaction;
6. the process according to claim 5, wherein the reaction solvent is methylene chloride.
7. The process according to claim 5, wherein the reaction is carried out at 0 to 45 ℃.
8. The method according to claim 5, wherein the molar ratio of the 3- (trifluoroacetyl) coumarin compound to the substituted pyrrole compound is 0.5-2:1.
9. the use of a tertiary alcohol derivative containing trifluoromethyl coumarin according to claim 1 for preparing a bacteriostatic agent, wherein the bacteriostatic agent is used for inhibiting fusarium graminearum, fusarium oxysporum, fusarium graminearum, fusarium moniliforme, rhizoctonia solani and phytophthora nicotianae.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5624951A (en) * 1992-09-01 1997-04-29 Pfizer Inc. 4-hydroxy coumarin derivatives with antibacterial activity
CN107674055A (en) * 2017-10-30 2018-02-09 南京农业大学 Hydroxycoumarin derivatives of 4 trifluoromethyl 7 and its preparation method and application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5624951A (en) * 1992-09-01 1997-04-29 Pfizer Inc. 4-hydroxy coumarin derivatives with antibacterial activity
CN107674055A (en) * 2017-10-30 2018-02-09 南京农业大学 Hydroxycoumarin derivatives of 4 trifluoromethyl 7 and its preparation method and application

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Title
Synthesis of 1-(b-coumarinyl)-1-(b-indolyl) trifluoroethanols through regioselective Friedel– Crafts alkylation of indoles with b-(trifluoroacetyl) coumarins catalyzed by Sc(OTf)3;Lijun Shi等;《RSC Adv》;第10卷;第13929-13935页 *
新型香豆素类衍生物的合成及其抗菌活性;杨国玉等;《合成化学》;第19卷(第3期);第337-340页 *

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