CN116621906A - 表雄酮吡唑类衍生物及其合成方法和应用 - Google Patents
表雄酮吡唑类衍生物及其合成方法和应用 Download PDFInfo
- Publication number
- CN116621906A CN116621906A CN202310662333.XA CN202310662333A CN116621906A CN 116621906 A CN116621906 A CN 116621906A CN 202310662333 A CN202310662333 A CN 202310662333A CN 116621906 A CN116621906 A CN 116621906A
- Authority
- CN
- China
- Prior art keywords
- epiandrosterone
- compound
- pyrazole
- pyrazole derivative
- hours
- 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.)
- Pending
Links
- QGXBDMJGAMFCBF-UHFFFAOYSA-N Etiocholanolone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC21 QGXBDMJGAMFCBF-UHFFFAOYSA-N 0.000 title claims abstract description 52
- -1 Epiandrosterone pyrazole derivative Chemical class 0.000 title claims abstract description 51
- 238000010189 synthetic method Methods 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 241000607479 Yersinia pestis Species 0.000 claims abstract description 13
- 241001124076 Aphididae Species 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 241000500437 Plutella xylostella Species 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 238000001308 synthesis method Methods 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 6
- 241000238631 Hexapoda Species 0.000 claims abstract description 5
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 5
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 5
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
- 150000001924 cycloalkanes Chemical class 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 claims description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 claims description 6
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 5
- 239000000575 pesticide Substances 0.000 claims description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 4
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims description 4
- YUCBLVFHJWOYDN-HVLQGHBFSA-N 1,4-bis[(s)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@H](OC=3C4=CC=CC=C4C(O[C@H]([C@@H]4N5CC[C@H]([C@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-HVLQGHBFSA-N 0.000 claims description 3
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims description 3
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 3
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 claims description 3
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- 239000002917 insecticide Substances 0.000 claims description 2
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- 239000003814 drug Substances 0.000 abstract description 9
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- 241000409991 Mythimna separata Species 0.000 abstract description 4
- 230000000607 poisoning effect Effects 0.000 abstract description 4
- QGXBDMJGAMFCBF-LUJOEAJASA-N epiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-LUJOEAJASA-N 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 241000196324 Embryophyta Species 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000749 insecticidal effect Effects 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 241000258937 Hemiptera Species 0.000 description 4
- 241000209140 Triticum Species 0.000 description 4
- 235000021307 Triticum Nutrition 0.000 description 4
- 238000004166 bioassay Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 241001600408 Aphis gossypii Species 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- 239000005660 Abamectin Substances 0.000 description 2
- 241000256593 Brachycaudus schwartzi Species 0.000 description 2
- 241000982105 Brevicoryne brassicae Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000005941 Thiamethoxam Substances 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- RZWDOHOQSSGFOR-UHFFFAOYSA-N bromo-ethyl-triphenyl-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(CC)C1=CC=CC=C1 RZWDOHOQSSGFOR-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
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- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- 208000009091 myxoma Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- NWWZPOKUUAIXIW-FLIBITNWSA-N thiamethoxam Chemical compound [O-][N+](=O)\N=C/1N(C)COCN\1CC1=CN=C(Cl)S1 NWWZPOKUUAIXIW-FLIBITNWSA-N 0.000 description 2
- WCXDHFDTOYPNIE-RIYZIHGNSA-N (E)-acetamiprid Chemical compound N#C/N=C(\C)N(C)CC1=CC=C(Cl)N=C1 WCXDHFDTOYPNIE-RIYZIHGNSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 239000005875 Acetamiprid Substances 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
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- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
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- 229940123457 Free radical scavenger Drugs 0.000 description 1
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- 241000220225 Malus Species 0.000 description 1
- 241001477931 Mythimna unipuncta Species 0.000 description 1
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- 206010037660 Pyrexia Diseases 0.000 description 1
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
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- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
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- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical group CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 229950009041 edaravone Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- RLQJEEJISHYWON-UHFFFAOYSA-N flonicamid Chemical compound FC(F)(F)C1=CC=NC=C1C(=O)NCC#N RLQJEEJISHYWON-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
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- 239000004615 ingredient Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
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- 238000012216 screening Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
-
- 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
- A01N45/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds having three or more carbocyclic rings condensed among themselves, at least one ring not being a six-membered ring
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Environmental Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Agronomy & Crop Science (AREA)
- Insects & Arthropods (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明属于药物合成技术领域,具体涉及表雄酮吡唑类衍生物及其合成方法和应用,所述表雄酮吡唑类衍生物具有如通式(1)表示的化学结构,其中,R为烷基或含芳香环的基团,所述烷基为脂肪链或环烷烃,所述含芳香环的基团为苯基或取代苯基。所述表雄酮吡唑类衍生物的合成方法,其使用表雄酮为基础原料,通过一系列不同的反应得到本发明的表雄酮吡唑类衍生物。本发明公开的表雄酮吡唑类衍生物为一系列全新的化合物,属首次提出。所述合成方法制备产率高,所得产物易于分离。经生物测定证实,所述表雄酮吡唑类衍生物对蚜虫、东方黏虫、小菜蛾以及粉虱等害虫表现出良好的毒杀活性,可应用在植物虫害防治。
Description
技术领域
本发明属于药物合成技术领域,具体涉及表雄酮吡唑类衍生物及其合成方法和应用。
背景技术
杂环化合物是以含有一个或多个杂原子(O、N或S)的五元或六元环系或稠环系为主的一类化合物。自从1857年Anderson从骨焦油中分离出吡咯,1870年Scheele制出呋喃和1882年Meyer发现噻吩至今也不过一个多世纪,被研究的杂环化合物已发展到惊人的数量。本世纪三十年代拜耳斯坦有机化学手册记载的杂环化合物数目,约占当时已知的数十万种有机化合物的1/3。而在这些化合物中,含有氮原子的杂环化合物,又尤为重要。
吡唑是一类五元环芳香杂环有机化合物,其在制药工业中具有广泛的应用。吡唑母核是众多药物中的基本结构之一,如解热镇痛药安替比林、自由基清除剂依达拉奉和COX-2抑制剂塞来昔布等。经过不断研究,人们发现吡唑及其衍生物具有多种生物活性作用,如止痛、消炎、退烧、镇静、松弛肌肉、精神兴奋、抗痉挛等,而且低毒、结构新颖、可改造的空间大,在农药和医药方面有着广泛的应用,是重要的农药和医药的中间体。
刺吸式口器害虫是园林植物害虫中较大的一个类群。它们个体小,发生初期往往受害状不明显,易被人们忽视,但数量极多,常群居于嫩枝、叶、芽、花蕾、果上,汲取植物汁液,掠夺其营养,造成枝叶及花卷曲,甚至整株枯萎或死亡。同时诱发煤污病,有时害虫本身是病毒病的传播媒介。这些害虫可以为害大多数农作物,对其产量和质量造成了严重的损失,但目前有效的防治药剂经过长期使用,大多数都对刺吸式口器害虫产生了较严重的抗药性。咀嚼式口器害虫危害植物的特点是造成各种形式的机械损伤,例如,取食叶片造成缺刻、孔洞,严重时将叶肉吃光,仅留网状叶脉,甚至全部被吃光。因此,迫切需要筛选出新的防治药剂。
发明内容
本发明的目的在于克服现有技术的缺点,提供一系列新的表雄酮吡唑类衍生物;
本发明的第二目的在于提供表雄酮吡唑类衍生物的合成方法。
本发明的第三目的在于提供表雄酮吡唑类衍生物的应用。
本发明的目的通过以下技术方案来实现:表雄酮吡唑类衍生物,具有如通式(1)表示的化学结构:
其中,R为烷基或含芳香环的基团,所述烷基为脂肪链或环烷烃,所述含芳香环的基团为苯基或取代苯基。
进一步地,所述烷基为:
进一步地,所述含芳香环的基团为(a)~(g)中的任意一种:
进一步地,所述表雄酮吡唑类衍生物具有以下化学结构式:
表雄酮吡唑类衍生物的合成方法,合成路线为:
其中,步骤a的反应条件为:向溶有化合物(2)的二氯甲烷中,分别加入4-二甲氨基吡啶、三乙胺和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐以及化合物(3),常温反应10~15h,优选为12h;
步骤b的反应条件为:以四氢呋喃为溶剂,加入四丁基氟化铵三水合物,回流反应3~6h,优选为4h。
进一步地,化合物(2)和化合物(3)的合成路线分别为:
其中,步骤c的反应条件为:化合物(5)溶于N,N-二甲基甲酰胺,加入咪唑和叔丁基二甲基氯硅烷,室温反应10~14h,优选为12h;
步骤d的反应条件为:以四氢呋喃为溶剂,密封,加入叔丁醇钾和乙基三苯基溴化磷,反应50~70min,优选为60min;将化合物(6)溶于四氢呋喃,加入反应体系中,反应22~26h,优选为24h;
步骤e的反应条件为:以二氯甲烷为溶剂,加入化合物(7)、水/叔丁醇(1:1)、甲基磺酰胺和AD-mix-β,0℃反应46~50h,室温反应70~74h;0℃反应优选为48h,室温反应优选为72h;
步骤f的反应条件为:以丙酮为溶剂,加入吡唑-4-甲酸乙酯、碳酸钾和含有不同取代基的溴代烃,50℃反应5~7h,优选为6h;
步骤g的反应条件为:以乙醇为溶剂,加入氢氧化钠,50℃反应5~7h,优选为6h。
上述的表雄酮吡唑类衍生物的在植物虫害防治中的应用。
进一步地,所述的植物虫害为蚜虫、东方黏虫、小菜蛾和粉虱。
一种杀虫剂,含有上述的表雄酮吡唑类衍生物。
进一步地,所述表雄酮吡唑类衍生物的有效质量百分含量为0.01%-99.99%。
为了在农业和植保领域施用所述表雄酮吡唑类衍生物,本领域普通技术人员可以将所述表雄酮吡唑类衍生物中的一种或几种作为杀虫活性成分,与农药学上可接受的载体,或者是其他的农用活性成分组合使用,制备成便于施用的制剂,比如水分散粒剂、可湿性粉剂或可分散油悬浮剂等多种剂型。在配制上述不同剂型时,对本领域的普通技术人员来说,除需要使用含有供选的杀菌活性成分外,还需要选用多种助剂,可以根据需要选择使用不同的农药制剂辅助成分(助剂)。所述辅助成分可以为分散介质、分散剂、乳化剂、润湿剂、增稠剂、消泡剂、防冻剂、崩解剂、粘结剂、填料等中的一种或几种。关于含所述表雄酮吡唑类衍生物的单剂或组合物制剂的配制方法,为现有技术常规方法。
本发明具有以下优点:
(1)本发明公开的表雄酮吡唑类衍生物为一系列全新的化合物,属首次提出。另外,本发明还给出所述表雄酮吡唑类衍生物的合成方法,其使用表雄酮为基础原料,通过一系列不同的反应得到本发明的表雄酮吡唑类衍生物。所述合成方法制备产率高,所得产物易于分离。
(2)经生物测定证实,所述表雄酮吡唑类衍生物对蚜虫、东方黏虫、小菜蛾以及粉虱等害虫表现出良好的毒杀活性,可用于制备农用杀虫剂单剂或含所述表雄酮吡唑类衍生物的混合制剂。
附图说明
图1为目标化合物(1)-8的单晶衍射图。
具体实施方式
下面结合附图及实施例对本发明做进一步的描述,本发明的保护范围不局限于以下所述:
表雄酮吡唑类衍生物,具有如通式(1)表示的化学结构:
其中,R为烷基或含芳香环的基团,所述烷基为脂肪链或环烷烃,所述含芳香环的基团为苯基或取代苯基。
所述的表雄酮吡唑类衍生物的合成方法,合成路线为:
其中,化合物(2)合成路线为:
化合物(3)合成路线为:
上述合成路线中各步骤的反应试剂与条件为:
步骤a:二氯甲烷,EDC,DMAP;
步骤b:TBAF,DMF,rt;
步骤c:DMF,TBSCl,imidazole,rt;
步骤d:THF,t-BuOK,EtPh3BrP;
步骤e:t-BuOH,H2O,二氯甲烷,Methanesulfonamide,AD-mix-β;
步骤f:Acetone,K2CO3,X-R;
步骤g:EtOH,H2O,NaOH,HCl.
具体操作为:
先将表雄酮化合物(5)溶于N,N-二甲基甲酰胺,加入咪唑和叔丁基二甲基氯硅烷反应,得到化合物(6);之后,以四氢呋喃为溶剂,密封,加入叔丁醇钾和乙基三苯基溴化磷,反应1h;将化合物(6)溶于四氢呋喃反应得到化合物(7),然后将化合物(7)溶于二氯甲烷,加入水/叔丁醇(1:1)、甲基磺酰胺和AD-mix-β反应得到化合物(2);化合物(8)溶于丙酮,加入碳酸钾和含有不同取代基的溴代烃反应,得到化合物(9),最后以乙醇为溶剂,加入氢氧化钠反应的得到化合物(3)。
将化合物(2)和化合物(3)溶于二氯甲烷,加入4-二甲氨基吡啶、三乙胺和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐得到化合物(4),最后,将化合物(4)溶于四氢呋喃,加入四丁基氟化铵三水合物得到化合物(1)。
实施例1:表雄酮吡唑类衍生物的合成步骤为:
(1)将4.36g表雄酮(15mmol)溶于N,N-二甲基甲酰胺(60mL),加入3.7g咪唑(45mmol)和2.71g,叔丁基二甲基氯硅烷(18mmol),室温反应12h,乙酸乙酯和1mol/L盐酸水溶液萃取,无水硫酸钠干燥,减压浓缩得到5.89g白色固体化合物(6);将反应瓶加入7.42g乙基三苯基溴化磷(20mmol)和2.24g,密封,抽真空1h,将2.02g化合物(6)(5mmol)溶于四氢呋喃,常温反应12h,乙酸乙酯和1mol/L盐酸水溶液萃取,无水硫酸钠干燥,减压浓缩得到7.71g白色固体化合物(7);将反应瓶中加入1.42g甲基磺酰胺(15mmol)、7.79gAD-mix-β和水/叔丁醇(20mL/20mL),冰浴10min,将2.08g化合物(7)(5mmol)溶于10mL二氯甲烷中,加入反应瓶,冰浴反应48h,室温反应72h,之后加入无水亚硫酸钠应1h,乙酸乙酯、KOH(1M)和饱和氯化钠溶液萃取,无水硫酸钠干燥,减压浓缩,得到1.48g白色固体化合物(2)。
(2)将0.5g吡唑-4-甲酸乙酯(3.6mmol)、含有不同取代基的溴代烃(3.6mmol)、0.59g碳酸钾(4.32mmol)溶于丙酮,加入反应瓶,65℃反应6h,二氯甲烷和1mol/L盐酸水溶液萃取,无水硫酸钠干燥,减压浓缩,得到化合物(9)。将化合物(9)(5mmol)溶解于乙醇(15ml),加入0.42g氢氧化钠(7.5mmol),50℃反应6h,减压蒸馏,加入冰水30mL,在冰浴中滴加1mol/L盐酸调节pH至3~5有沉淀析出,将混合物抽滤得到滤渣,用蒸馏水洗涤,晾干可得化合物(3)。
(3)将0.315g化合物(2)(0.7mmol)和化合物(3)(3.5mmol)溶于二氯甲烷,加入0.63gEDCl(3.5mmol)和0.085gDMAP(0.7mmol),室温反应12h,二氯甲烷和盐酸水溶液(1M)萃取,无水硫酸钠干燥,减压浓缩,得到化合物(4);将化合物(4)(0.3mmol)溶于四氢呋喃(15mL),加入0.16g四丁基氟化铵三水合物(0.6mmol),室温反应4h,乙酸乙酯和水萃取,无水硫酸钠干燥,减压浓缩。用硅胶柱层析(石油醚/乙酸乙酯,1:1,v/v)纯化,得到最终目标化合物(1)。
将通过上述方法制得的所述表雄酮吡唑类衍生物通过1H-NMR、13C-NMR进行确认,其中化合物(1)-8的结构通过单晶衍射的方法予以确认,如图1所示,具体结果如下:
1.化合物(1)-1
1HNMR(500MHz,CDCl3)δ=7.87(d,J=2.4Hz,2H),5.26(q,J=6.3Hz,1H),4.10(t,J=7.2Hz,2H),3.58(tt,J=10.7,4.8Hz,1H),1.96(ddd,J=14.7,11.5,2.9Hz,1H),1.85(p,J=7.4Hz,2H),1.79(dt,J=11.6,5.7Hz,2H),1.69(dd,J=24.8,12.5,9.0,3.7Hz,6H),1.60–1.48(m,4H),1.39(d,J=11.2,4.3Hz,2H),1.29(t,J=5.5Hz,8H),1.25(d,J=14.4Hz,9H),1.12(qq,J=11.8,5.7Hz,2H),0.95(dd,J=17.6,13.4,10.0,4.5Hz,2H),0.86(t,J=6.9Hz,3H),0.80(d,J=5.7Hz,6H),0.73–0.65(m,1H).
13C NMR(125MHz,CDCl3)δ=162.39,140.93,132.48,114.90,85.06,75.64,71.38,53.96,52.87,51.01,46.46,44.96,38.29,37.91,37.13,35.59,35.52,32.18,31.92,31.62,31.42,30.19,29.47,29.29,29.17,28.79,26.60,23.41,22.75,20.86,15.82,14.88,14.20,12.42.
2.化合物(1)-2
1H NMR(500MHz,CDCl3)δ=7.94(s,1H),7.92(s,1H),7.63(d,J=8.2Hz,2H),7.35(d,J=8.0Hz,2H),5.38(d,J=7.6Hz,2H),5.28(q,J=6.4Hz,1H),3.60(s,1H),1.96(ddd,J=14.7,11.6,3.0Hz,1H),1.82–1.77(m,2H),1.73(t,J=3.7Hz,1H),1.70(t,J=4.4Hz,2H),1.68(d,J=3.3Hz,1H),1.65(d,J=3.5Hz,1H),1.61–1.49(m,5H),1.45–1.35(m,2H),1.30(d,J=6.4Hz,3H),1.28–1.27(m,2H),1.14(ddt,J=18.3,12.2,6.0Hz,2H),1.01–0.91(m,2H),0.80(d,J=7.0Hz,6H),0.70(ddd,J=12.3,10.4,3.9Hz,1H).
13C NMR(125MHz,CDCl3)δ=161.97,141.56,139.30,132.89,130.97,128.13,128.08,126.06,115.94,84.95,77.04,75.81,71.33,55.87,53.83,50.91,46.40,44.84,38.17,37.80,37.01,35.49,35.41,32.08,31.51,31.31,28.67,23.30,20.75,15.71,14.80,12.32.
3.化合物(1)-3
1H NMR(400MHz,CDCl3)δ=7.92(s,1H),7.91(s,0H),7.87(s,1H),7.40–7.33(m,3H),7.31(s,0H),7.29(d,J=3.6Hz,0H),7.27–7.22(m,2H),5.30(s,2H),5.26(d,J=6.3Hz,1H),3.59(tt,J=10.6,4.8Hz,1H),1.99–1.89(m,1H),1.78(dq,J=11.8,7.7,6.4Hz,4H),1.75(s,0H),1.74–1.62(m,4H),1.59–1.47(m,2H),1.41(ddd,J=14.5,11.9,4.0Hz,2H),1.28(dd,J=10.9,5.5Hz,7H),1.13(qd,J=12.0,5.8Hz,2H),1.03–0.83(m,2H),0.80(d,J=6.9Hz,6H),0.69(dd,J=12.4,10.5,4.0Hz,1H).
13C NMR(100MHz,CDCl3)δ=162.15,141.18,135.19,132.66,129.05,128.58,128.03,115.49,84.92,77.25,77.05,75.66,71.28,56.53,53.82,50.88,46.34,44.82,38.14,37.77,36.99,35.46,35.38,32.06,31.48,31.28,28.66,23.29,20.73,15.69,14.76,12.31,0.01.
4.化合物(1)-4
1H NMR(500MHz,CDCl3)δ=7.93(d,J=2.9Hz,1H),7.89(s,1H),7.33–7.25(m,3H),7.12(dd,J=6.5,2.1Hz,1H),5.28(d,J=6.8Hz,3H),3.59(tt,J=10.6,4.7Hz,1H),1.95(ddd,J=14.6,11.5,2.9Hz,1H),1.79(td,J=11.9,11.5,6.8Hz,2H),1.73–1.63(m,4H),1.55(dtd,J=16.0,12.4,11.0,7.7Hz,4H),1.44–1.36(m,2H),1.31–1.24(m,7H),1.19–1.07(m,2H),0.96(ddt,J=18.0,10.0,4.6Hz,2H),0.80(d,J=6.7Hz,6H),0.73–0.65(m,1H).
13C NMR(125MHz,CDCl3)δ=162.13,141.54,137.34,135.04,132.91,130.43,128.89,128.11,126.10,115.91,85.05,75.87,71.42,55.92,53.93,51.00,46.48,44.93,38.25,37.89,37.11,35.58,35.50,32.17,31.59,31.40,28.77,23.40,20.85,15.81,14.89,12.42.
5.化合物(1)-5
1H NMR(500MHz,MeOD)δ=7.73(s,1H),7.49(s,1H),6.97(d,J=7.9Hz,2H),6.65(d,J=7.9Hz,2H),4.79(s,2H),4.73(q,J=6.4Hz,1H),3.02(tt,J=10.6,4.8Hz,1H),1.37(t,J=11.9Hz,1H),1.33–1.11(m,7H),1.11–1.05(m,1H),1.04–0.98(m,2H),0.90(td,J=11.5,4.9Hz,2H),0.76(dd,J=15.0,7.9Hz,7H),0.66–0.56(m,2H),0.46(tt,J=12.2,6.1Hz,2H),0.30(d,J=15.2Hz,6H),0.16(ddd,J=13.5,10.7,3.8Hz,1H).
13C NMR(125MHz,MeOD)δ=163.72,142.29,135.74,134.58,132.69,130.32,123.01,116.40,85.44,76.40,71.44,56.00,54.84,51.47,47.31,45.70,38.38,37.80,37.24,36.28,36.19,32.92,32.09,31.67,29.48,23.96,21.51,15.94,15.38,12.68.
6.化合物(1)-6
1HNMR(400MHz,CDCl3)δ=8.07(s,1H),7.97(s,1H),7.82–7.73(m,1H),7.65–7.48(m,1H),7.09–6.89(m,2H),5.73(d,J=4.7Hz,2H),5.28(q,J=6.3Hz,1H),3.59(tt,J=10.7,4.8Hz,1H),1.97(ddd,J=14.5,11.5,2.7Hz,1H),1.80(td,J=11.6,7.4Hz,3H),1.68(ddd,J=18.7,10.7,3.6Hz,4H),1.62–1.50(m,4H),1.45–1.37(m,2H),1.32(d,J=6.4Hz,3H),1.26(d,J=4.6Hz,2H),1.17(d,J=6.3Hz,1H),1.10(ddd,J=15.4,12.1,6.6Hz,2H),0.96(dt,J=14.9,10.2,5.3Hz,2H),0.80(d,J=2.4Hz,6H),0.72–0.66(m,1H).
13CNMR(125MHz,CDCl3)δ=164.43,161.58,141.02,138.02,132.10,126.85,125.86,119.05,118.11,115.55,85.23,76.36,73.45,53.28,52.92,50.27,46.83,43.2539.68,37.85,37.10,35.63,35.35,32.23,31.76,31.27,28.57,26.10,23.42,20.82,18.19,15.63,14.59,12.41.
7.化合物(1)-7
1HNMR(500MHz,CDCl3)δ=7.96(s,1H),7.90(s,1H),7.70(d,J=7.7Hz,1H),7.51(t,J=7.6Hz,1H),7.43(t,J=7.6Hz,1H),7.09(d,J=7.9Hz,1H),5.52(s,2H),5.26(q,J=6.2Hz,1H),3.59(tt,J=10.9,5.2Hz,1H),1.95(t,J=13.0Hz,1H),1.79(dd,J=12.5,6.8Hz,2H),1.68(dt,J=20.6,7.8Hz,4H),1.61–1.44(m,4H),1.45–1.32(m,2H),1.32–1.19(m,7H),1.18–1.02(m,2H),1.01–0.86(m,2H),0.79(d,J=5.8Hz,6H),0.68(t,J=10.3Hz,1H).
13CNMR(125MHz,CDCl3)δ=162.13,141.57,134.04,133.51,132.67,129.77,128.58,126.34,115.95,85.04,75.91,71.41,53.92,52.69,50.99,46.47,44.93,38.22,37.87,37.10,35.57,35.49,32.16,31.55,31.40,28.76,23.40,20.84,15.79,14.87,12.41.
8.化合物(1)-8
1HNMR(400MHz,CDCl3)δ=7.94(s,1H),7.92(s,1H),7.16(dt,J=10.0,8.2Hz,1H),7.07(dd,J=10.4,7.4,2.2Hz,1H),6.99(dt,J=8.1,3.9,1.7Hz,1H),5.27(d,J=11.0Hz,3H),3.59(tt,J=11.0,4.8Hz,1H),1.95(dd,J=14.5,11.5,2.8Hz,1H),1.82–1.78(m,2H),1.75–1.63(m,4H),1.61–1.49(m,4H),1.40(qd,J=13.0,11.2,3.8Hz,2H),1.34–1.24(m,7H),1.18–1.07(m,2H),1.02–0.89(m,2H),0.80(d,J=5.0Hz,6H),0.69(dd,J=12.3,10.4,4.0Hz,1H).
13CNMR(100MHz,CDCl3)δ=162.07,151.76,149.28,141.61,132.84,132.40,124.08,117.96,117.12,115.96,84.98,75.88,71.32,55.42,53.91,50.96,46.46,44.91,38.24,37.81,37.09,35.55,35.47,32.15,31.56,31.38,28.75,23.37,20.82,15.78,14.86,12.39.
实施例2:
采用玻片浸渍法测定表1所列的表雄酮吡唑类衍生物对麦二叉蚜(Schizaphisgraminum)、甘蓝蚜(BrevicorynebrassicaeLinn)、棉蚜(Aphisgossypii)、苹果黄蚜(AphiscitricolavanderGoot)、桃蚜(Myzuspersicae)的死亡率。具体方法:准确称量一定量待测化合物,以丙酮为溶剂,将化合物溶解,用0.1%Tween-80水溶液配制成浓度100μg/mL的溶液,室温下静置半小时待样品完全溶解后保存待用。将待测蚜虫粘贴到含有双面胶的载玻片上,然后将含有蚜虫的玻片在配置的药液中浸渍5s取出,用吸水纸吸干残余的药液,阳性对照为啶虫脒,阴性对照为0.1%Tween-80水溶液。在培养皿中保湿48h后观察其死亡率,结果见表1。
表1本发明式(1)的表雄酮吡唑类衍生物对五种蚜虫的死亡率
表1室内生物测定结果表明,测试化合物对麦二叉蚜、甘蓝蚜、棉蚜、苹果黄蚜、桃蚜具有较好的生物活性,部分化合物与氟啶虫酰胺具有相似的杀虫效果。
实施例3:
采用浸叶法测定表2所列的表雄酮吡唑类衍生物对东方黏虫和小菜蛾的死亡率,具体方法:准确称量一定量待测化合物,以丙酮为溶剂,将化合物溶解,用0.1%Tween-80水溶液配制成浓度1000μg/mL和200μg/mL的溶液,室温下静置半小时待样品完全溶解后保存待用。将新鲜小麦叶片剪切成0.5×0.5cm大小,每个叶片放入配置好的溶液中3-5s取出,待溶液晾干;将东方粘虫3龄幼虫放入24孔板中,并分别喂养晾干的小麦叶片;阳性对照为阿维菌素,阴性对照为0.1%Tween-80水溶液。72h后观察其死亡率,结果见表2。
表2本发明式(1)的表雄酮吡唑类衍生物对东方黏虫的死亡率
注:虫螨腈浓度分别为50μg/mL和10μg/mL
表2室内生物测定结果表明,测试化合物对东方黏虫具有较好的生物活性,部分化合物与阿维菌素具有相似的杀虫效果。
实施例4:
采用浸叶法测定表3所列的表雄酮吡唑类衍生物对小菜蛾的毒杀活性。阳性对照为虫螨腈,阴性对照为丙酮。观察其在72h后的死亡数并计算校正死亡率,结果见表3:
表3本发明式(1)的表雄酮吡唑类衍生物对小菜蛾的死亡率
注:虫螨腈浓度分别为50μg/mL和10μg/mL
表3室内生物测定结果表明,测试化合物对小菜蛾具有较好的生物活性,部分化合物与虫螨腈具有相似的杀虫效果。
实施例5:
采用叶面喷雾法测定表4所列的表雄酮吡唑类衍生物对粉虱的毒杀活性。具体方法:准确称量一定量待测化合物,以丙酮溶解,用0.1%吐温80水溶液配制成浓度为100和50μg/mL的溶液保存待用。将药液喷施于黄瓜叶片的背面,待其自然晾干将待测粉虱放入植株叶片上。阳性对照为噻虫嗪,阴性对照为丙酮。观察其在7d后的死亡数并计算校正死亡率,结果见表4。
表4本发明式(1)的表雄酮吡唑类衍生物对粉虱的死亡率
表4室内生物测定结果表明,测试化合物对粉虱具有较好的生物活性,部分化合物与噻虫嗪具有相似的杀虫效果。
以上所述,仅为本发明较佳的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,根据本发明的技术方案及其发明构思加以等同替换或改变,都涵盖在本发明的保护范围之内。
Claims (10)
1.表雄酮吡唑类衍生物,其特征在于,具有如通式(1)表示的化学结构:
其中,R为烷基或含芳香环的基团,所述烷基为脂肪链或环烷烃,所述含芳香环的基团为苯基或取代苯基。
2.根据权利要求1所述的表雄酮吡唑类衍生物,其特征在于,所述烷基为:
3.根据权利要求1所述的表雄酮吡唑类衍生物,其特征在于,所述含芳香环的基团为(a)~(g)中的任意一种:
4.根据权利要求1所述的表雄酮吡唑类衍生物,其特征在于,所述表雄酮吡唑类衍生物具有以下化学结构式:
5.根据权利要求1所述的表雄酮吡唑类衍生物的合成方法,其特征在于,合成路线为:
其中,步骤a的反应条件为:向溶有化合物(2)的二氯甲烷中,分别加入4-二甲氨基吡啶、三乙胺和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐以及化合物(3),常温反应10~15h;
步骤b的反应条件为:以四氢呋喃为溶剂,加入四丁基氟化铵三水合物,回流反应3~6h。
6.根据权利要求5所述的表雄酮吡唑类衍生物的合成方法,其特征在于,化合物(2)和化合物(3)的合成路线分别为:
其中,步骤c的反应条件为:化合物(5)溶于N,N-二甲基甲酰胺,加入咪唑和叔丁基二甲基氯硅烷,室温反应10~14h;
步骤d的反应条件为:以四氢呋喃为溶剂,密封,加入叔丁醇钾和乙基三苯基溴化磷,反应50~70min;将化合物(6)溶于四氢呋喃,加入反应体系中,反应22~26h;
步骤e的反应条件为:以二氯甲烷为溶剂,加入化合物(7)、水/叔丁醇(1:1)、甲基磺酰胺和AD-mix-β,0℃反应46~50h,室温反应70~74h;
步骤f的反应条件为:以丙酮为溶剂,加入吡唑-4-甲酸乙酯、碳酸钾和含有不同取代基的溴代烃,50℃反应5~7h;
步骤g的反应条件为:以乙醇为溶剂,加入氢氧化钠,50℃反应5~7h。
7.权利要求1-4中任意一项所述的表雄酮吡唑类衍生物,权利要求5或6合成的表雄酮吡唑类衍生物的在植物虫害防治中的应用。
8.根据权利要求7所述的应用,其特征在于,所述的植物虫害为蚜虫、东方黏虫、小菜蛾和粉虱。
9.一种杀虫剂,其特征在于,含有权利要求1-4中任意一项所述的表雄酮吡唑类衍生物。
10.根据权利要求9所述的杀虫剂,其特征在于,所述表雄酮吡唑类衍生物的有效质量百分含量为0.01%-99.99%。
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