CN113999223A - Flavone derivative containing thiazole, preparation method and application thereof - Google Patents
Flavone derivative containing thiazole, preparation method and application thereof Download PDFInfo
- Publication number
- CN113999223A CN113999223A CN202111458496.3A CN202111458496A CN113999223A CN 113999223 A CN113999223 A CN 113999223A CN 202111458496 A CN202111458496 A CN 202111458496A CN 113999223 A CN113999223 A CN 113999223A
- Authority
- CN
- China
- Prior art keywords
- chlorophenyl
- thiazole
- fluorophenyl
- preparation
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title abstract description 43
- 150000002212 flavone derivatives Chemical class 0.000 title description 2
- 150000002214 flavonoid derivatives Chemical class 0.000 claims abstract description 19
- 229930003935 flavonoid Natural products 0.000 claims abstract description 8
- 235000017173 flavonoids Nutrition 0.000 claims abstract description 8
- 150000002215 flavonoids Chemical class 0.000 claims abstract description 5
- 241000813090 Rhizoctonia solani Species 0.000 claims abstract description 4
- 239000000839 emulsion Substances 0.000 claims abstract description 4
- 239000004530 micro-emulsion Substances 0.000 claims abstract description 4
- 239000004563 wettable powder Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract 3
- -1 p-chlorophenyl tert-butyl Chemical group 0.000 claims description 46
- 239000007787 solid Substances 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical class CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 235000005513 chalcones Nutrition 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- 241000123650 Botrytis cinerea Species 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- VRMUIVKEHJSADG-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=CN=C(Cl)S1 VRMUIVKEHJSADG-UHFFFAOYSA-N 0.000 claims description 2
- 241000213004 Alternaria solani Species 0.000 claims description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 241000223195 Fusarium graminearum Species 0.000 claims 1
- 241000233791 Ustilago tritici Species 0.000 claims 1
- 239000004495 emulsifiable concentrate Substances 0.000 claims 1
- 201000004792 malaria Diseases 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 31
- 241000894006 Bacteria Species 0.000 abstract description 6
- 241000209140 Triticum Species 0.000 abstract description 6
- 235000021307 Triticum Nutrition 0.000 abstract description 6
- 244000052769 pathogen Species 0.000 abstract description 5
- 230000001717 pathogenic effect Effects 0.000 abstract description 5
- 241000223218 Fusarium Species 0.000 abstract description 3
- 235000007688 Lycopersicon esculentum Nutrition 0.000 abstract description 3
- 240000003768 Solanum lycopersicum Species 0.000 abstract description 3
- 244000000004 fungal plant pathogen Species 0.000 abstract description 3
- 239000000375 suspending agent Substances 0.000 abstract description 3
- 235000016623 Fragaria vesca Nutrition 0.000 abstract description 2
- 240000009088 Fragaria x ananassa Species 0.000 abstract description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 72
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 35
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 18
- 239000011734 sodium Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 15
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- CPMTVLFRDOBFDB-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-3-[(2-chloro-1,3-thiazol-5-yl)methoxy]chromen-4-one Chemical compound O=C1C(OCC(S2)=CN=C2Cl)=C(C(C(F)=CC=C2)=C2Cl)OC2=CC=CC=C12 CPMTVLFRDOBFDB-UHFFFAOYSA-N 0.000 description 3
- CXVIEXNADLICOC-UHFFFAOYSA-N 3-[(2-chloro-1,3-thiazol-5-yl)methoxy]-2-(4-methoxyphenyl)chromen-4-one Chemical compound COC(C=C1)=CC=C1C(OC1=CC=CC=C1C1=O)=C1OCC(S1)=CN=C1Cl CXVIEXNADLICOC-UHFFFAOYSA-N 0.000 description 3
- TZKMGJWIQRPHOI-UHFFFAOYSA-N 3-[(2-chloro-1,3-thiazol-5-yl)methoxy]-2-[4-(trifluoromethyl)phenyl]chromen-4-one Chemical compound O=C1C(OCC(S2)=CN=C2Cl)=C(C2=CC=C(C(F)(F)F)C=C2)OC2=CC=CC=C12 TZKMGJWIQRPHOI-UHFFFAOYSA-N 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- KOFFXZYMDLWRHX-UHFFFAOYSA-N 1-(5-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1O KOFFXZYMDLWRHX-UHFFFAOYSA-N 0.000 description 2
- HIKRJHFHGKZKRI-UHFFFAOYSA-N 2,4,6-trimethylbenzaldehyde Chemical compound CC1=CC(C)=C(C=O)C(C)=C1 HIKRJHFHGKZKRI-UHFFFAOYSA-N 0.000 description 2
- FSTCEOUUMMYFOF-UHFFFAOYSA-N 2-(2-bromo-4-fluorophenyl)-3-[(2-chloro-1,3-thiazol-5-yl)methoxy]chromen-4-one Chemical compound O=C1C(OCC(S2)=CN=C2Cl)=C(C(C=CC(F)=C2)=C2Br)OC2=CC=CC=C12 FSTCEOUUMMYFOF-UHFFFAOYSA-N 0.000 description 2
- VETBPKAHTIBOBG-UHFFFAOYSA-N 3-[(2-chloro-1,3-thiazol-5-yl)methoxy]-2-(2,4-dichlorophenyl)chromen-4-one Chemical compound O=C1C(OCC(S2)=CN=C2Cl)=C(C(C=CC(Cl)=C2)=C2Cl)OC2=CC=CC=C12 VETBPKAHTIBOBG-UHFFFAOYSA-N 0.000 description 2
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 2
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 2
- WJTFHWXMITZNHS-UHFFFAOYSA-N 5-bromofuran-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)O1 WJTFHWXMITZNHS-UHFFFAOYSA-N 0.000 description 2
- GPTZMNCYGHTQOF-UHFFFAOYSA-N 6-bromo-2-(4-chlorophenyl)-3-[(2-chloro-1,3-thiazol-5-yl)methoxy]chromen-4-one Chemical compound O=C(C1=C2)C(OCC(S3)=CN=C3Cl)=C(C(C=C3)=CC=C3Cl)OC1=CC=C2Br GPTZMNCYGHTQOF-UHFFFAOYSA-N 0.000 description 2
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- WHHIPMZEDGBUCC-UHFFFAOYSA-N probenazole Chemical compound C1=CC=C2C(OCC=C)=NS(=O)(=O)C2=C1 WHHIPMZEDGBUCC-UHFFFAOYSA-N 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 2
- 239000004308 thiabendazole Substances 0.000 description 2
- 229960004546 thiabendazole Drugs 0.000 description 2
- 235000010296 thiabendazole Nutrition 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- TUBQDCKAWGHZPF-UHFFFAOYSA-N 1,3-benzothiazol-2-ylsulfanylmethyl thiocyanate Chemical compound C1=CC=C2SC(SCSC#N)=NC2=C1 TUBQDCKAWGHZPF-UHFFFAOYSA-N 0.000 description 1
- LQCMMXGKEGWUIM-UHFFFAOYSA-N 1-(4-bromo-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1O LQCMMXGKEGWUIM-UHFFFAOYSA-N 0.000 description 1
- HQCCNFFIOWYINW-UHFFFAOYSA-N 1-(5-bromo-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC=C1O HQCCNFFIOWYINW-UHFFFAOYSA-N 0.000 description 1
- GGERGLKEDUUSAP-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbaldehyde Chemical compound C1=C(C=O)C=C2OC(F)(F)OC2=C1 GGERGLKEDUUSAP-UHFFFAOYSA-N 0.000 description 1
- OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 1
- OACPOWYLLGHGCR-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound FC1=CC=CC(Cl)=C1C=O OACPOWYLLGHGCR-UHFFFAOYSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- OTXINXDGSUFPNU-UHFFFAOYSA-N 4-tert-butylbenzaldehyde Chemical compound CC(C)(C)C1=CC=C(C=O)C=C1 OTXINXDGSUFPNU-UHFFFAOYSA-N 0.000 description 1
- UZAOOCPKYMGRHG-UHFFFAOYSA-N 5-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=CN=CS1 UZAOOCPKYMGRHG-UHFFFAOYSA-N 0.000 description 1
- 241000412366 Alternaria mali Species 0.000 description 1
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 241001149475 Gaeumannomyces graminis Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 229930182559 Natural dye Natural products 0.000 description 1
- 241000233679 Peronosporaceae Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 description 1
- 239000006013 carbendazim Substances 0.000 description 1
- 239000000490 cosmetic additive Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Chemical compound O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000000978 natural dye Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 244000000003 plant pathogen Species 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Abstract
The invention relates to a flavonoid derivative containing thiazole, a preparation method and application thereof in the technical field of organic synthesis chemical industry, the structural formula of the flavonoid derivative containing thiazole is shown as (I),
Description
Technical Field
The invention relates to a thiazole-containing flavonoid derivative, a preparation method and application thereof, belonging to the technical field of organic synthetic chemistry and agricultural pharmacy.
Background
The flavonoid compounds are plant secondary metabolites, have wide biological activities such as weeding, insect killing, sterilization, antioxidation, anticancer, anti-inflammatory, anti-cardiovascular disease, antivirus and other biological activities, and are applied to the fields of medicines and pesticides. In addition, flavonoids are also used as natural dyes, cosmetic additives, food additives, and the like.
Thiazole contains N, S heteroatoms, and the thiazole compound is an important heterocyclic compound and has the activities of sterilization, disinsection, weeding and the like. Thiazole and derivatives thereof have been widely used in the field of bactericides due to their broad-spectrum bactericidal activity, good compatibility and easy modification of structure. Commercial thiazole fungicides include thiabendazole (thiabendazole), probenazole (probenazole) for controlling rice blast, thiocyanobenzene (benthiazole), benzothiostrobin (benzothiostrobin) for controlling powdery mildew and downy mildew, and the like. In addition, many active compounds having antibacterial activity and containing thiazole rings have been reported and have been one of hot spots in the development of bactericides.
In conclusion, the flavonoid compound and the thiazole compound have broad-spectrum biological activity, but in the prior art, a technical scheme for splicing the active substructures of the flavonoid compound and the thiazole compound is not available.
Disclosure of Invention
The invention aims to provide a preparation method of a novel thiazole-containing flavonoid derivative and application of the novel thiazole-containing flavonoid derivative in plant disease control.
The thiazole-containing flavonoid derivative (I) provided by the invention has the following structural general formula:
in the formula (I), the compound is shown in the specification,
r is selected from hydrogen atom, methoxyl, bromine atom and fluorine atom;
r1 is selected from the group consisting of phenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, 2, 4-dichlorophenyl, p-methoxyphenyl, p-trifluoromethylphenyl, 2-chloro-6-fluorophenyl, 2-bromo-4-fluorophenyl, p-tert-butylphenyl, 2,4, 6-trimethylphenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, n-chlorophenyl, p-chlorophenyl, 4-fluorophenyl, 6-fluorophenyl, p-butylphenyl, p-fluorophenyl, p-butylphenyl, 4-butylphenyl, p-butylphenyl, n-fluorophenyl, n-butyl, n,
The invention provides a preparation method of the thiazole-containing flavonoid derivative, which comprises the following steps:
step 1: dissolving the different substituted o-hydroxyacetophenone A and the different substituted aromatic aldehyde in methanol, dropwise adding a sodium hydroxide aqueous solution with the mass concentration of 30%, and stirring at room temperature for 2 hours. After the reaction, concentrated hydrochloric acid was slowly added dropwise to the reaction system to adjust the pH to 3, the reaction solution was filtered, and the solid was collected and dried to obtain an intermediate chalcone B.
Step 2: dissolving chalcone B in ethanol, sequentially adding a sodium hydroxide aqueous solution with the mass concentration of 20% and hydrogen peroxide with the mass concentration of 30% dropwise at the temperature of 0 ℃, and reacting for 12 hours at room temperature. After the reaction was completed, concentrated hydrochloric acid was slowly added dropwise to the reaction system to adjust the pH to 6, and the reaction solution was filtered, and the solid was collected and dried to obtain intermediate C.
And step 3: dissolving the intermediate C, 2-chloro-5-chloromethylthiazole and potassium carbonate in acetonitrile, reacting for 5 hours at 80 ℃, adding water and ethyl acetate into reaction liquid after the reaction is finished, layering the solution, separating an organic phase, extracting a water phase with ethyl acetate, combining the organic phase, carrying out reduced pressure concentration to form a solid, adding petroleum ether into the solid, filtering, collecting the solid, and drying to obtain a final product I.
The synthesis of the flavonoid derivative containing thiazole provided by the invention has the characteristics of simple steps, high yield and easy operation.
The preferable structure of the thiazole-containing flavonoid derivative related to the invention is shown as Ia-Ir:
compared with the prior art, the invention has the beneficial effects that: according to the invention, a series of flavonoid derivatives containing thiazole are designed and synthesized by carrying out substructure splicing on the flavonoid and the thiazole structure. The compounds have novel structure, simple and convenient preparation method, easily obtained raw materials and high yield, and are all novel compounds which are not reported in documents; the research shows that the compounds can resist plant pathogenic fungi, have good inhibitory activity, can be processed into missible oil, microemulsion, emulsion in water, suspending agent or wettable powder and the like, and are used for preventing and treating plant diseases such as rice sheath blight bacteria, wheat scab bacteria, wheat take-all bacteria, tomato early blight bacteria, strawberry botrytis cinerea, apple spot bacteria and the like.
Detailed Description
Example 1
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2-phenyl-4H-chromen-4-one (Ia)
Dissolving o-hydroxyacetophenone and benzaldehyde in methanol, dropwise adding a sodium hydroxide aqueous solution with the mass concentration of 30%, and stirring at room temperature for 2 hours. After the reaction is finished, slowly dropwise adding concentrated hydrochloric acid into the reaction system to make the pH value of the concentrated hydrochloric acid equal to 3, filtering the reaction solution, collecting solids, and drying to obtain an intermediate chalcone; dissolving chalcone in ethanol, sequentially adding a sodium hydroxide aqueous solution with the mass concentration of 20% and hydrogen peroxide with the mass concentration of 30% dropwise at the temperature of 0 ℃, and reacting for 12 hours at room temperature. After the reaction is finished, slowly dropwise adding concentrated hydrochloric acid into the reaction system to ensure that the pH value is 6, filtering the reaction liquid, collecting solids, and drying to obtain an intermediate 3-hydroxy-2-phenyl-4H-chromen-4-one; dissolving it in acetonitrile and adding 2-chloroReacting 5-chloromethyl thiazole and potassium carbonate at 80 ℃ for 5 hours, adding water and ethyl acetate into reaction liquid after the reaction is finished, demixing the solution, separating out an organic phase, extracting the aqueous phase by using ethyl acetate, combining the organic phase, carrying out reduced pressure concentration to form a solid, adding petroleum ether into the solid, filtering, collecting the solid, and drying to obtain the product Ia. White solid, yield 96%;1H NMR(600MHz,CDCl3)δ8.27(d,J＝7.9Hz,1H),7.92(d,J＝7.4Hz,2H),7.70(t,J＝7.7Hz,1H),7.55–7.46(m,4H),7.43(t,J＝7.5Hz,1H),7.33(s,1H),5.27(s,2H)；13C NMR(150MHz,CDCl3)δ174.8,156.9,155.3,153.4,141.1,138.6,136.1,133.7,130.9,130.5,128.8,128.4,125.7,124.9,123.9,118.1,65.1；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H12ClNNaO3S 392.0119,found 392.0109.
example 2
Preparation of 2- (2-chlorophenyl) -3- (2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Ib)
The preparation method is the same as example 1, and the benzaldehyde is changed into 2-chlorobenzaldehyde to obtain a compound product Ib. White solid, yield 89%;1H NMR(400MHz,CDCl3)δ8.32(d,J＝7.9Hz,1H),7.71(t,J＝7.8Hz,1H),7.55–7.43(m,4H),7.42–7.34(m,2H),7.26(s,1H),5.27(s,2H)；13C NMR(100MHz,CDCl3)δ174.7,156.3,155.6,153.5,141.0,139.1,136.2,133.9,133.7,131.6,131.5,130.0,129.7,126.6,125.8,125.1,124.3,118.3,65.3；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H11Cl2NNaO3S 425.9729,found 425.9728.
example 3
Preparation of 2- (3-chlorophenyl) -3- (2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Ic)
The preparation method is the same as example 1, and the benzaldehyde is changed into 3-chlorobenzaldehyde, so that the compound product Ic is obtained. White solid, yield 93%;1H NMR(400MHz,CDCl3)δ8.27(d,J＝7.9Hz,1H),7.94(s,1H),7.84(d,J＝7.7Hz,1H),7.72(t,J＝7.7Hz,1H),7.55(d,J＝8.4Hz,1H),7.51–7.40(m,3H),7.36(s,1H),5.32(s,2H)；13C NMR(100MHz,CDCl3)δ174.7,155.2,155.0,153.6,141.4,138.9,135.8,134.6,134.0,132.2,130.8,129.8,128.7,126.9,125.8,125.2,123.9,118.1,65.2；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H11Cl2NNaO3S 425.9729,found 425.9721.
example 4
Preparation of 2- (4-chlorophenyl) -3- (2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Id)
The preparation method is the same as example 1, and the benzaldehyde is changed into 4-chlorobenzaldehyde to obtain the compound product Id. White solid, yield 83%;1H NMR(400MHz,CDCl3)δ8.26(dd,J＝8.0,1.5Hz,1H),7.94–7.87(m,2H),7.71(ddd,J＝8.6,7.1,1.6Hz,1H),7.53(d,J＝8.2Hz,1H),7.49–7.40(m,3H),7.35(s,1H),5.30(s,2H)；13C NMR(100MHz,CDCl3)δ174.7,155.5,155.2,153.6,141.3,138.7,137.1,135.9,133.9,130.1,129.0,128.8,125.8,125.1,123.9,118.0,65.1；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H11Cl2NNaO3S 425.9729,found 425.9733.
example 5
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2- (2, 4-dichlorophenyl) -4H-chromen-4-one (Ie)
The preparation method is the same as example 1, and benzaldehyde is changed into 2, 4-dichlorobenzaldehydeTo obtain a compound product Ie. White solid, yield 81%;1H NMR(400MHz,CDCl3)δ8.33–8.27(m,1H),7.75–7.67(m,1H),7.53(d,J＝1.8Hz,1H),7.46(t,J＝8.2Hz,2H),7.36(dd,J＝8.3,1.8Hz,1H),7.32(d,J＝8.3Hz,1H),7.27(s,1H),5.28(s,2H)；13C NMR(100MHz,CDCl3)δ174.5,155.5,155.2,153.7,141.2,139.0,137.3,136.0,134.7,134.0,132.4,130.0,128.2,127.1,125.8,125.2,124.3,118.2,65.2；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H10Cl3NNaO3S 459.9339,found 459.9340.
example 6
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2- (4-methoxyphenyl) -4H-chromen-4-one (If)
The preparation method is the same as example 1, and the benzaldehyde is changed into 4-methoxybenzaldehyde, so that the compound product If is obtained. White solid, yield 74%;1H NMR(400MHz,CDCl3)δ8.26(dd,J＝8.0,1.5Hz,1H),7.96(d,J＝8.9Hz,2H),7.73–7.64(m,1H),7.52(d,J＝8.4Hz,1H),7.41(t,J＝7.4Hz,1H),7.36(s,1H),7.00(d,J＝8.9Hz,2H),5.27(s,2H),3.90(s,3H)；13C NMR(100MHz,CDCl3)δ174.6,161.7,156.8,155.2,153.3,141.1,138.1,136.3,133.5,130.5,125.7,124.8,123.9,122.8,118.0,113.9,65.0,55.4.
example 7
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2- (4- (trifluoromethyl) phenyl) -4H-chromen-4-one (Ig)
The preparation method is the same as example 1, and the benzaldehyde is changed into 4-trifluoromethyl benzaldehyde, so that the compound product Ig is obtained. White solid, yield 87%;1H NMR(600MHz,CDCl3)δ8.28(dd,J＝8.0,1.7Hz,1H),8.05(d,J＝8.2Hz,2H),7.77–7.70(m,3H),7.55(d,J＝8.5Hz,1H),7.46(t,J＝7.5Hz,1H),7.33(s,1H),5.32(s,2H)；13C NMR(150MHz,CDCl3)δ174.7,155.3,155.0,153.7,141.5,139.1,135.7,134.1,133.9,132.4(q,J＝32.9Hz),129.2,125.8,125.4(q,J＝3.3Hz),125.3,123.9,123.6(q,J＝270.9Hz),118.1,65.2；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C20H14ClNNaO4S 422.0224,found 422.0231.
example 8
Preparation of 2- (2-chloro-6-fluorophenyl) -3- ((2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Ih)
The preparation was carried out as in example 1, substituting benzaldehyde for 2-chloro-6-fluorobenzaldehyde, and the final product was purified by column chromatography (petroleum ether: ethyl acetate: 3:1) to give compound Ih. White solid, yield 77%;1H NMR(400MHz,CDCl3)δ8.31(dd,J＝8.0,1.6Hz,1H),7.75–7.67(m,1H),7.52–7.42(m,3H),7.32(d,J＝8.3Hz,2H),7.13(t,J＝8.5Hz,1H),5.39(d,J＝12.8Hz,1H),5.28(d,J＝12.8Hz,1H)；13C NMR(100MHz,CDCl3)δ174.4,160.4(d,J＝253.9Hz),155.8,153.4,150.4,141.0,140.6,136.3,135.2(d,J＝3.5Hz),134.0,132.5(d,J＝9.5Hz),125.8,125.6(d,J＝3.5Hz),125.2,124.4,118.9(d,J＝18.8Hz),118.3,114.4(d,J＝21.7Hz),65.4；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H10Cl2FNNaO3S 443.9635,found 443.9642.
example 9
Preparation of 2- (2-bromo-4-fluorophenyl) -3- ((2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Ii)
The preparation method is the same as example 1, benzaldehyde is changed into 2-bromo-4-fluorobenzaldehyde, and the final product is purified by column chromatography (petroleum ether: ethyl acetate: 3:1)Compound Ii. White solid, yield 71%;1H NMR(400MHz,CDCl3)δ8.30(dd,J＝8.0,1.6Hz,1H),7.75–7.68(m,1H),7.52–7.41(m,3H),7.37(dd,J＝8.6,5.8Hz,1H),7.28(s,1H),7.15(td,J＝8.2,2.4Hz,1H),5.29(s,2H)；13C NMR(100MHz,CDCl3)δ174.6,163.3(d,J＝255.8Hz),156.4,155.5,153.6,141.2,138.9,136.1,134.0,133.1(d,J＝9.0Hz),128.0(d,J＝3.7Hz),125.8,125.2,124.3,123.7(d,J＝9.8Hz),120.7(d,J＝24.8Hz),118.2,114.7(d,J＝21.7Hz),65.2；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H10BrClFNNaO3S 487.9130,found 487.9135.
example 10
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2- (2, 2-difluorobenzo [ d ] [1,3] dioxy-5-yl) -4H-chromen-4-one (Ij)
The preparation method is the same as example 1, and the benzaldehyde is changed into 2, 2-difluoro-1, 3-benzodioxole-5-formaldehyde, so that the compound product Ij is obtained. White solid, yield 79%;1H NMR(600MHz,CDCl3)δ8.25(dd,J＝8.0,1.3Hz,1H),7.77(dd,J＝8.5,1.8Hz,1H),7.74–7.69(m,2H),7.52(d,J＝8.4Hz,1H),7.44(t,J＝7.5Hz,1H),7.35(s,1H),7.18(d,J＝8.5Hz,1H),5.32(s,2H)；13C NMR(150MHz,CDCl3)δ174.6,155.1,154.9,153.7,145.2,143.8,141.4,138.5,135.8,134.0,131.6(t,J＝257.2Hz),126.5,125.8,125.3,125.2,123.8,118.0,110.1,109.4,65.1；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C20H10ClF2NNaO5S 471.9828,found 471.9823.
example 11
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -2- (thiophen-2-yl) -4H-chromen-4-one (Ik)
Preparation methodThe procedure is as in example 1 except that benzaldehyde is replaced by 2-thiophenecarboxaldehyde to obtain compound Ik. White solid, yield 76%;1H NMR(600MHz,CDCl3)δ8.23(d,J＝7.9Hz,1H),7.94(d,J＝3.6Hz,1H),7.68(t,J＝7.4Hz,1H),7.63(d,J＝4.8Hz,1H),7.56(s,1H),7.52(d,J＝8.3Hz,1H),7.41(t,J＝7.5Hz,1H),7.21(t,J＝4.1Hz,1H),5.54(s,2H)；13C NMR(150MHz,CDCl3)δ173.9,154.7,153.6,151.8,141.7,136.1,135.8,133.7,131.8,131.3,130.1,127.6,125.6,124.9,123.9,117.8,64.5；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C17H10ClNNaO3S2 397.9683,found397.9686.
example 12
Preparation of 2- (5-bromofuran-2-yl) -3- (2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Il)
The preparation method is the same as example 1, and benzaldehyde is changed into 5-bromo-2-furaldehyde, so that a compound product Il is obtained. White solid, yield 95%;1H NMR(400MHz,CDCl3)δ8.22(d,J＝7.6Hz,1H),7.69(t,J＝7.8Hz,1H),7.56(d,J＝8.4Hz,1H),7.53(s,1H),7.41(t,J＝7.5Hz,1H),7.21(d,J＝3.5Hz,1H),6.55(d,J＝3.5Hz,1H),5.50(s,2H)；13C NMR(100MHz,CDCl3)δ173.9,154.6,153.5,146.8,145.9,141.4,136.5,136.0,133.8,126.7,125.6,125.1,124.0,118.9,118.1,114.5,64.9；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C17H9BrClNNaO4S 459.9016,found 459.9012.
example 13
Preparation of 2- (4- (tert-butyl) phenyl) -3- (2-chlorothiazol-5-yl) methoxy) -7-methoxy-4H-chromen-4-one (Im)
The preparation method is the same as example 1, the o-hydroxyacetophenone is changed to 2' -hydroxy-4-Methoxy acetophenone and benzaldehyde are changed into 4-tert-butyl benzaldehyde, and a compound product Im is obtained. White solid, yield 72%;1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.9Hz,1H),7.83(d,J＝8.6Hz,2H),7.49(d,J＝8.6Hz,2H),7.33(s,1H),6.99(dd,J＝8.9,2.4Hz,1H),6.89(d,J＝2.4Hz,1H),5.24(s,2H),3.91(s,3H),1.38(s,9H)；13CNMR(100MHz,CDCl3)δ174.1,164.2,157.1,156.7,154.3,153.3,141.1,138.3,136.3,128.4,127.7,127.0,125.4,117.8,114.6,100.0,65.2,55.8,34.9,31.1；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C24H22ClNNaO4S 478.0850,found 478.0857.
example 14
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -7-methoxy-2- (4-methoxyphenyl) -4H-chromen-4-one (In)
The preparation method was the same as example 1, and the compound product In was obtained by replacing o-hydroxyacetophenone with 2 '-hydroxy-4' -methoxyacetophenone and replacing benzaldehyde with 4-methoxybenzaldehyde. White solid, yield 82%;1H NMR(600MHz,CDCl3)δ8.15(d,J＝8.9Hz,1H),7.93(d,J＝9.0Hz,2H),7.36(s,1H),6.99(d,J＝8.9Hz,3H),6.90(d,J＝2.4Hz,1H),5.26(s,2H),3.92(s,3H),3.90(s,3H)；13C NMR(150MHz,CDCl3)δ174.1,164.1,161.5,157.0,156.4,153.4,141.1,137.9,136.4,130.4,127.0,123.0,117.8,114.6,113.9,100.0,65.1,55.9,55.5；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C21H16ClNNaO5S 452.0330,found 452.0336.
example 15
Preparation of 7-bromo-3- ((2-chlorothiazol-5-yl) methoxy) -2-trimethyl-4H-chromen-4-one (Io)
The preparation method is the same as example 1, andthe hydroxyacetophenone is changed into 2 '-hydroxy-4' -bromoacetophenone, and the benzaldehyde is changed into 2,4, 6-trimethylbenzaldehyde, so as to obtain a compound product Io. White solid, yield 83%;1H NMR(400MHz,CDCl3)δ8.17(d,J＝8.6Hz,1H),7.63(d,J＝1.8Hz,1H),7.56(dd,J＝8.6,1.8Hz,1H),7.21(s,1H),6.95(s,2H),5.18(s,2H),2.37(s,3H),2.08(s,6H)；13C NMR(100MHz,CDCl3)δ173.9,159.0,155.7,153.6,140.6,140.5,139.5,137.3,136.8,128.7,128.4,128.1,127.2,126.5,123.2,121.3,65.4,21.3,19.6；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C22H17BrClNNaO3S 511.9693,found511.9686.
example 16
Preparation of 6-bromo-2- (4-chlorophenyl) -3- ((2-chlorothiazol-5-yl) methoxy) -4H-chromen-4-one (Ip)
The preparation method is the same as example 1, the o-hydroxyacetophenone is changed into 2 '-hydroxy-5' -bromoacetophenone, and the benzaldehyde is changed into 4-chlorobenzaldehyde, so as to obtain a compound product Ip. Yellow solid, yield 76%;1H NMR(600MHz,CDCl3)δ8.38(d,J＝2.4Hz,1H),7.89(d,J＝8.6Hz,2H),7.78(dd,J＝8.9,2.5Hz,1H),7.47(d,J＝8.6Hz,2H),7.43(d,J＝8.9Hz,1H),7.34(s,1H),5.30(s,2H)；13C NMR(150MHz,CDCl3)δ173.4,155.8,153.9,153.7,141.5,138.7,137.4,136.9,135.6,130.1,128.9,128.6,128.3,125.2,120.0,118.6,65.1；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C19H10BrCl2NNaO3S 503.8834,found503.8830.
example 17
Preparation of 3- ((2-chlorothiazol-5-yl) methoxy) -6-fluoro-2- (4-methoxyphenyl) -4H-chromen-4-one (Iq)
The preparation method is the same as example 1, and the o-hydroxybenzene isThe ethyl ketone is changed into 2 '-hydroxy-5' -fluoro acetophenone, and the benzaldehyde is changed into 4-methoxy benzaldehyde, so that a compound product Iq is obtained. White solid, yield 94%;1H NMR(600MHz,CDCl3)δ7.95(d,J＝8.9Hz,2H),7.89(dd,J＝8.2,3.1Hz,1H),7.53(dd,J＝9.1,4.1Hz,1H),7.44–7.39(m,1H),7.36(s,1H),7.01(d,J＝9.0Hz,2H),5.27(s,2H),3.91(s,3H)；13C NMR(150MHz,CDCl3)δ173.9,161.8,159.3(d,J＝247.1Hz),157.1,153.5,151.5,141.2,137.7,136.1,130.6,125.1(d,J＝7.8Hz),122.6,121.9(d,J＝26.0Hz),120.1(d,J＝7.7Hz),114.0,110.4(d,J＝24.0Hz),65.0,55.5；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C20H13ClFNNaO4S 440.0130,found 440.0132.
example 18
Preparation of 2- (5-bromofuran-2-yl) -3- (2-chlorothiazol-5-yl) methoxy) -6-fluoro-4H-chromen-4-one (Ir)
The preparation method is the same as that of example 1, the o-hydroxyacetophenone is changed to 2 '-hydroxy-5' -fluoroacetophenone, and the benzaldehyde is changed to 5-bromo-2-furfural, so as to obtain the compound product Ir. Yellow solid, yield 91%;1H NMR(400MHz,CDCl3)δ7.85(dd,J＝8.2,3.1Hz,1H),7.58(dd,J＝9.2,4.1Hz,1H),7.52(s,1H),7.45–7.37(m,1H),7.22(d,J＝3.6Hz,1H),6.56(d,J＝3.5Hz,1H),5.51(s,2H)；13C NMR(100MHz,CDCl3)δ173.1(d,J＝2.2Hz),159.5(d,J＝247.2Hz),153.6,150.9(d,J＝1.6Hz),147.0,145.7,141.6,136.1,135.8,127.0,125.2(d,J＝7.6Hz),122.1(d,J＝25.7Hz),120.3(d,J＝8.2Hz),119.3,114.6,110.4(d,J＝24.1Hz),64.9；HRMS(ESI-TOF)m/z:[M+Na]+calcd for C17H8BrClFNNaO4S477.8922,found 477.8928.
example 19
Method for determining bacteriostatic activity of thiazole-containing flavonoid derivative (Ia-Ir)
Selecting the tested fungi as Rhizoctonia solani (Rhizoctonia solani) and Fusarium graminis (Fusarium gramini)earum), wheat take-all (gaeumannomyces graminis), tomato early blight (Alternaria solani), Botrytis cinerea (Botrytis cinerea) and apple spot (Alternaria mali), the test fungi were activated on PDA plates. Preparing a PDA drug-containing flat plate with a drug-containing concentration of 50 mug/mL by using the compound, punching the activated mushroom cake along the outermost ring by using a puncher with the inner diameter of 5mm, picking the prepared mushroom cake by using an inoculating needle, inoculating into the center of a drug-containing culture dish, and culturing in a constant temperature incubator at 25 ℃. Wait for CKWhen colonies grew to 3/4 medium, the results were measured by the cross method (measuring the diameter of each colony twice to the nearest mm), each group was run in parallel 3 times, the colony size was represented by the average value, and the inhibition ratio was calculated as follows:
table 1: inhibition rate (%), at 50. mu.g/mL, of compound Ia-Ir against six plant pathogensa
aThree replicates were taken and averaged.b"-" has no antibacterial activity.
The data in table 1 show that the target compound I has a certain degree of inhibition effect on the growth of six plant pathogenic fungi. The 5 compounds with the inhibition rate of more than 50 percent on the rice sheath blight germ are Ia, Ib, Ic, Id and If respectively, wherein Ia is 89.7 percent at most. The inhibition rate of the compound Ib on the wheat take-all pathogen is 91.8%, and the inhibition rate of the compound Ih on the wheat take-all pathogen is 51.9%. The activity of partial compounds is superior to that of flavonoid natural product quercetin, even equivalent to that of positive control carbendazim. The series of compounds are proved to have potential of being used as novel agricultural bactericides for development and application. The thiazole-containing flavonoid derivative can be processed into missible oil, microemulsion, aqueous emulsion, suspending agent or wettable powder.
The present invention is not limited to the above-mentioned embodiments, and based on the technical solutions disclosed in the present invention, those skilled in the art can make some substitutions and modifications to some technical features without creative efforts according to the disclosed technical contents, and these substitutions and modifications are all within the protection scope of the present invention.
Claims (6)
1. A thiazole-containing flavonoid derivative is characterized by being shown in a structural formula (I):
wherein the content of the first and second substances,
r is selected from hydrogen atom, methoxyl, bromine atom and fluorine atom;
R1selected from phenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl tert-butyl, 2, 4-dichlorophenyl, p-methoxyphenyl, p-trifluoromethylphenyl, 2-chloro-6-fluorophenyl, 2-bromo-4-fluorophenyl, p-butylphenyl, 2,4, 6-trimethylphenyl, p-methoxyphenyl, p-chlorophenyl, m-chlorophenyl, p-chlorophenyl, n-chlorophenyl, p-chlorophenyl, n-chlorophenyl, p-chlorophenyl, n-fluorophenyl, n-methoxyphenyl, p-fluorophenyl, n-butyl, n-,
、
、 
。
2. The method for preparing flavonoid derivative containing thiazole according to claim 1, which is characterized by comprising the following steps:
wherein the content of the first and second substances,
r is selected from hydrogen atom, methoxyl, bromine atom and fluorine atom;
R1selected from phenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, 2, 4-dichlorophenyl, p-methoxyphenyl, p-trifluoromethylphenyl, 2-chloro-6-fluorophenyl, 2-bromo-4-fluorophenyl, p-tert-butylphenyl, 2,4, 6-trimethylphenyl, p-methoxyphenyl, p-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-chlorophenyl, p-chlorophenyl, o-chlorophenyl, p-chlorophenyl, n-chlorophenyl, p-fluorophenyl, p-methoxyphenyl, p-fluorophenyl, n-fluorophenyl, p-fluorophenyl, n-butyl, p-butyl, n-,
、
、 
。
3. The method for preparing flavonoid derivative containing thiazole according to claim 2, comprising the steps of:
step 1: the R-substituted o-hydroxyacetophenone A and R1Dissolving substituted aromatic aldehyde in methanol, dropwise adding a sodium hydroxide aqueous solution with the mass concentration of 30%, and stirring at room temperature for reaction for 2 hours; after the reaction is finished, slowly dropwise adding concentrated hydrochloric acid into the reaction system to enable the pH of the reaction system to be = 3, filtering the reaction liquid, collecting solids, and drying to obtain an intermediate chalcone B;
step 2: dissolving intermediate chalcone B in ethanol, 0oC, sequentially dropwise adding a sodium hydroxide aqueous solution with the mass concentration of 20% and hydrogen peroxide with the mass concentration of 30%, and reacting at room temperature for 12 hours; after the reaction is finished, slowly dropwise adding concentrated hydrochloric acid into the reaction system to enable the pH of the reaction system to be = 6, filtering the reaction liquid, collecting solids, and drying to obtain an intermediate C;
and step 3: dissolving intermediate C, 2-chloro-5-chloromethylthiazole and potassium carbonate in acetonitrile at 80%oAnd C, reacting for 5 hours, after the reaction is finished, adding water and ethyl acetate into the reaction liquid, layering the solution, separating out an organic phase, extracting a water phase by using ethyl acetate, combining the organic phase, concentrating under reduced pressure to form a solid, adding petroleum ether into the solid, filtering, collecting the solid, and drying to obtain a final product I.
4. Use of a thiazole-containing flavonoid derivative according to claim 1 for controlling agricultural plant diseases.
5. The use of flavonoid thiazole-containing derivatives according to claim 4, wherein said agricultural diseases are Rhizoctonia solani, Fusarium graminearum, Ustilago tritici, Alternaria solani, Botrytis cinerea and Malaria pumila.
6. The use of the thiazole-containing flavonoid derivative according to claim 5, wherein the thiazole-containing flavonoid derivative is processed into emulsifiable concentrate, microemulsion, aqueous emulsion, suspension or wettable powder in the control of agricultural diseases.
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