CN114644597B - 一种四取代吡嗪类衍生物及其制备方法和应用 - Google Patents
一种四取代吡嗪类衍生物及其制备方法和应用 Download PDFInfo
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- 150000003216 pyrazines Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 21
- 125000003277 amino group Chemical group 0.000 claims abstract description 14
- 240000008067 Cucumis sativus Species 0.000 claims abstract description 12
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- 150000001875 compounds Chemical class 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
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- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims 1
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UEEXRMUCXBPYOV-UHFFFAOYSA-N iridium;2-phenylpyridine Chemical compound [Ir].C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1 UEEXRMUCXBPYOV-UHFFFAOYSA-N 0.000 description 3
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
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- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
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- 238000004519 manufacturing process Methods 0.000 description 2
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- 239000002808 molecular sieve Substances 0.000 description 2
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
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- LCZUOKDVTBMCMX-UHFFFAOYSA-N 2,5-Dimethylpyrazine Chemical compound CC1=CN=C(C)C=N1 LCZUOKDVTBMCMX-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
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- 241000219310 Beta vulgaris subsp. vulgaris Species 0.000 description 1
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
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- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
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- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 1
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 1
- 229940114124 ferulic acid Drugs 0.000 description 1
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- 235000013305 food Nutrition 0.000 description 1
- 239000001760 fusel oil Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
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- 239000011976 maleic acid Substances 0.000 description 1
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
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- 239000012452 mother liquor Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
-
- 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
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种四取代吡嗪类衍生物及其制备方法和应用。一种具有通式(I)所示结构的一种含氰基和氨基的四取代吡嗪类衍生物,在式(I)中,所述各个基团具有如下所述的定义:R1选自芳基、烷基;R2选自芳基、C1‑5烷基。本发明对水稻纹枯病菌、黄瓜炭疽病菌、番茄早疫病菌、小麦赤霉病菌、苹果斑点病菌和草莓灰霉病菌具有较好的抑制作用,可用于防治植物真菌病害,且合成原料成本低,合成方法简便。
Description
技术领域
本发明涉及农药领域,具体来说涉及一种四取代吡嗪类衍生物及其制备方法和应用。
背景技术
植物病菌的防治抑制是农药科学研究的重要领域,化学防治依旧是防止植物病原真菌在农业上流行爆发的主要办法,杀菌剂的广泛使用使得多数植物病菌得到了有效的控制。然而随着杀菌剂使用规模不断扩大,植物病菌对传统杀菌剂产生了耐药性。与此同时,现有药剂中存在的对非靶标生物毒性较大和对环境污染严重的问题也使其在生产应用中受到了极大的限制。因此,研制具有高效、对靶标生物专一性好和环境友好型的新型杀菌剂对保障农业增产稳产和粮食安全具有重要的作用和意义。
吡嗪杂环骨架广泛存在于天然产物及活性分子中,同时被广泛应用在药物的创制工作中。1879年,从甜菜发酵的杂醇油中分离并发现了四甲基吡嗪的存在。1888年,吡嗪骨架被首次人工合成。1928年,从咖啡中发现了吡嗪、甲基吡嗪、2,5-二甲基吡嗪、2,6-二甲基吡嗪,此后,吡嗪类化合物就开始广泛应用于食用调香及有机染料领域,目前,此类化合物已成为食品香料家族成员最多的一类杂环类合成香料。除此之外,药物创制工作者发现吡嗪类化合物在医药领域具有抗结核、驱蛀虫、抗惊厥和抗菌剂等生物活性。
本发明将氰基、氨基引入到吡嗪结构中,设计了一种含氰基和氨基的四取代吡嗪类衍生物,以创制具有高效广谱活性的抑制植物病原真菌的新化合物。
发明内容
本发明的目的在于,提供一种四取代吡嗪类衍生物。
本发明的目的在于,提供一种含氰基和氨基的四取代吡嗪类衍生物。
本发明的另一目的在于提供含氰基和氨基的四取代吡嗪类衍生物的制备方法。
本发明的第4个目的在于提供上述衍生物的用途。
本发明的第一方面提供了一种具有通式(I)所示结构的一种含氰基和氨基的四取代吡嗪类衍生物或其盐,
在式(I)中,所述各个基团具有如下所述的定义:
R1选自芳基、烷基;
R2选自芳基、C1-5烷基。
在式(I)中,所述各个基团具有如下所述的优选定义:
作为本发明的一种优选,所述的R1选自苯基、卤素取代的苯基、C1-3取代的苯基;
R2选自苯基、卤素取代的苯基、C1-3取代的苯基、C1-5的烷基或C3-5的环烷基。
作为本发明的进一步优选,所述的R1选自苯基、、F或Cl取代的苯基、甲基或乙基取代的苯基;
R2选自苯基、卤素取代的苯基、甲基取代的苯基、C3-5的烷基或C3-5的环烷基;所述的卤素选自F、Cl、Br。
在本发明的一些优选实施方式中,R1选自苯基、4-氟-苯基、4-氯-苯基、3-氯-苯基、4-甲基-苯基、2-甲基-苯基中的任意一种;
R2选自苯基、4-氟-苯基、4-氯-苯基、4-溴-苯基、3-氯-苯基、2-氯-苯基、3-甲基-苯基、6-异丁基、3-丁烯基、4-戊炔基、环丙基。
作为本发明的更进一步优选,所述的四取代吡嗪类衍生物选自以下任意一种化合物:
3-氨基-5,6-二苯基吡嗪-2-甲腈;
3-氨基-6-(4-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-6-(4-溴苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-5-苯基-6-(间甲苯基)吡嗪-2-甲腈;
3-氨基-6-(3-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-5-苯基-6-(邻甲苯基)吡嗪-2-甲腈;
3-氨基-6-(2-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-6-苯基-5-(邻甲苯基)吡嗪-2-甲腈;
3-氨基-5-(4-氯苯基)-6-苯基吡嗪-2-甲腈;
3-氨基-5-(3-氯苯基)-6-苯基吡嗪-2-甲腈;
3-氨基-5,6-二对甲苯基吡嗪-2-甲腈;
3-氨基-5-(4-氟苯基)-6-(对甲苯基)吡嗪-2-甲腈;
3-氨基-6-异丁基-5-苯基吡嗪-2-甲腈;
3-氨基-6-环丙基-5-苯基吡嗪-2-甲腈;
3-氨基-6-(丁-3-烯-1-基)-5-苯基吡嗪-2-甲腈;
3-氨基-6-(戊-4-yn-1-基)-5-苯基吡嗪-2-甲腈。
本发明所述的含氰基和氨基的四取代吡嗪类衍生物的盐为该化合物的药学上可接受的盐,包括但不限于:氯化氢、溴化氢、硫酸、碳酸、草酸、柠檬酸、琥珀酸、酒石酸、磷酸、乳酸、丙酮酸、乙酸、马来酸、甲磺酸、苯磺酸、对甲苯磺酸或阿魏酸。
本发明的第二个方面提供了如通式(A)所示的一种含氰基和氨基的四取代吡嗪衍生物(I)的制备方法,在三(2-苯基吡啶)合铱(Ir(ppy)3),三氟甲磺酸铜(Cu(OTf)2)、三乙胺盐酸盐(Et3N·HCl)、分子筛和二甲亚砜(DMSO)存在下,含取代基的肟酯(II)与三甲基氰硅烷(TMSCN)在12瓦蓝光照射下反应生成一种含氰基和氨基的四取代吡嗪衍生物(I):
其中在上述各结构式中:
R1、R2均具有如前所述的相应基团的定义。
本发明的第三个方面提供了式(I)所示的一种含氰基和氨基的四取代吡嗪衍生物的应用,该类衍生物对植物病原真菌具有显著的抑制活性,可应用于抑制植物病原真菌、防治植物真菌病害。
本发明的一种含氰基和氨基的四取代吡嗪衍生物适合于抑制水稻纹枯病菌、黄瓜炭疽病菌、番茄早疫病菌、小麦赤霉病菌、苹果斑点病菌和草莓灰霉病菌,适合用于防治水稻纹枯病、黄瓜炭疽病、番茄早疫病、小麦赤霉病、苹果斑点病和草莓灰霉病。
有益效果:
本发明与现有技术相比,具有明显的有益效果,从以上技术方案可知:本发明将属于优良活性基团的氰基和氨基结构引入吡嗪杂环的结构中,设计合成了一系列含氰基和氨基的四取代吡嗪衍生物(I),该类化合物的结构具有新颖性;将该类化合物应用于抗植物病原真菌方面的研究,发现此类化合物在抗植物病原真菌方面拥有突出的抑制活性,体现出本技术方案的显著进步;其中部分化合物对黄瓜炭疽病菌和草莓灰霉病菌的抑制活性超过对照药剂多菌灵和蛇床子素,具有明显的应用价值。
具体实施方式
本发明的实质性特点可从下述实施例得以体现,但它不应视为是对本发明的任何限制。
以下实施例涉及的化合物的名称和结构见下表:
表1化合物I1-I34的名称及结构
制备实施例
实施例一:3-氨基-5,6-二苯基吡嗪-2-甲腈(I1)的合成
将1,2-二苯乙烷-1-酮-O-(4(三氟甲基)苯甲酰基)肟(II-1)(0.20mmol)、三(2-苯基吡啶)合铱(0.0020mmol),三氟甲磺酸铜(0.020mmol)、三乙胺盐酸盐(0.40mmol)和分子筛(200mg)加入到18mL试管中,置换氮气三次,加入二甲亚砜(2.0mL)和三甲基氰硅烷(0.60mmol),室温下12瓦蓝灯照射搅拌24小时后,停止反应。加入20mL水,乙酸乙酯萃取(3×10mL),碳酸氢钠饱和溶液洗涤(20mL),饱和食盐水洗涤(20mL),合并有机相,无水硫酸钠干燥,过滤并减压浓缩除去溶剂,使用硅胶柱分离纯化,即得化合物3-氨基-5,6-二苯基吡嗪-2-甲腈(I1)。
化合物I2-I34按照实施例一的方法依次合成,所合成的含氰基和氨基的四取代吡嗪衍生物(I1-I34)的结构均采用核磁共振谱(NMR)和高分辨质谱(HRMS)进行了确证,目标化合物的理化参数和光谱数据如下所示:
3-氨基-5,6-二苯基吡嗪-2-甲腈(I1):黄色固体,产率85%,熔点166-167℃;1HNMR(400MHz,CDCl3)δ7.40(d,J=6.9Hz,2H),7.36(d,J=7.0Hz,1H),7.34–7.23(m,7H),5.35(s,2H).13C NMR(100MHz,CDCl3)δ154.5,154.0,144.5,137.32,137.28,129.7,129.6,129.3,128.4,128.30,128.26,115.5,110.6;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H13N4273.1135,found 273.1138.
3-氨基-6-(4-甲氧基苯基)-5-苯基吡嗪-2-甲腈(I3):黄色固体,产率64%,熔点204-205℃;1H NMR(400MHz,CDCl3)δ7.46–7.39(m,2H),7.38–7.35(m,1H),7.34–7.29(m,2H),7.28–7.23(m,2H),6.80(d,J=8.8Hz,2H),5.27(s,2H),3.80(s,3H).13C NMR(100MHz,CDCl3)δ159.7,154.2,153.7,144.3,137.6,130.6,129.7,129.6,129.5,128.3,115.6,113.7,110.5,55.2;HRMS(ESI-TOF)m/z:[M+H]+calcd for C18H15N4O 303.1240,found303.1246.
6-([1,1'-联苯]-4-基)-3-氨基-5-苯基吡嗪-2-甲腈(I4):黄色固体,产率78%,熔点218-219℃;1H NMR(400MHz,CDCl3)δ7.59(d,J=7.3Hz,2H),7.52(d,J=8.3Hz,2H),7.50–7.37(m,6H),7.40–7.29(m,4H),5.33(s,2H).13C NMR(100MHz,CDCl3)δ154.5,153.9,144.1,141.0,140.3,137.4,136.2,129.74,129.71,129.6,128.8,128.4,127.6,127.0,126.9,115.5,110.7;HRMS(ESI-TOF)m/z:[M+H]+calcd for C23H17N4 349.1448,found349.1458.
3-氨基-6-(4-氟苯基)-5-苯基吡嗪-2-甲腈(I5):黄色固体,产率60%,熔点161-162℃;1H NMR(400MHz,CDCl3)δ7.44–7.36(m,3H),7.36–7.27(m,4H),6.96(t,J=8.5Hz,2H),5.36(s,2H).13C NMR(100MHz,CDCl3)δ162.7(d,J=248.7Hz),154.4,154.0,143.3,137.2,133.3(d,J=3.3Hz),131.2(d,J=8.3Hz),129.8,129.5,128.4,115.4,115.3(d,J=21.6Hz),110.6;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H12FN4 291.1041,found291.1042.
3-氨基-6-(4-氯苯基)-5-苯基吡嗪-2-甲腈(I6):黄色固体,产率73%,熔点195-196℃;1H NMR(400MHz,CDCl3)δ7.42–7.37(m,3H),7.36–7.31(m,2H),7.28–7.21(m,4H),5.38(s,2H).13C NMR(100MHz,CDCl3)δ154.5,154.0,143.1,137.1,135.7,134.5,130.6,129.9,129.5,128.5,115.4,110.7;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H12ClN4307.0745,found 307.0755.
3-氨基-6-(4-溴苯基)-5-苯基吡嗪-2-甲腈(I7):黄色固体,产率77%,熔点174-175℃;1H NMR(400MHz,CDCl3)δ7.40(d,J=8.3Hz,5H),7.36–7.30(m,2H),7.21(d,J=8.2Hz,2H),5.36(s,2H).13C NMR(100MHz,CDCl3)δ154.5,154.0,143.1,137.1,136.2,131.4,130.9,129.9,129.5,128.5,122.8,115.3,110.7;HRMS(ESI-TOF)m/z:[M+H]+calcdfor C17H12BrN4 351.0240,found 351.0251.
3-氨基-5-苯基-6-(4-(三氟甲基)苯基)吡嗪-2-甲腈(I8):白色固体,产率71%,熔点192-193℃;1H NMR(400MHz,CDCl3)δ7.53(d,J=8.2Hz,2H),7.46(d,J=8.2Hz,2H),7.45–7.37(m,3H),7.37–7.30(m,2H),5.44(s,2H).13C NMR(100MHz,CDCl3)δ154.8,154.2,142.6,140.8,136.8,130.2(q,J=32.4Hz),130.0,129.6,129.5,128.6,125.2(q,J=3.8Hz),123.9(q,J=270.5Hz),115.2,110.9;HRMS(ESI-TOF)m/z:[M+H]+calcd forC18H12F3N4 341.1009,found 341.1013.
3-氨基-5-苯基-6-(间甲苯基)吡嗪-2-甲腈(I9):黄色固体,产率69%,熔点148-150℃;1H NMR(400MHz,CDCl3)δ7.43–7.39(m,2H),7.38–7.34(m,1H),7.33–7.28(m,2H),7.24(s,1H),7.16–7.07(m,2H),7.04–6.98(m,1H),5.34(s,2H),2.29(s,3H).13C NMR(100MHz,CDCl3)δ154.5,153.9,144.6,138.1,137.4,137.2,129.9,129.62,129.56,129.1,128.2,128.0,126.5,115.5,110.5,21.4;HRMS(ESI-TOF)m/z:[M+H]+calcd for C18H15N4287.1291,found 287.1299.
3-氨基-6-(3-氯苯基)-5-苯基吡嗪-2-甲腈(I10):黄色固体,产率74%,熔点157-158℃;1H NMR(400MHz,CDCl3)δ7.44–7.37(m,4H),7.37–7.30(m,2H),7.27(d,J=7.4Hz,1H),7.16(t,J=7.7Hz,1H),7.11(d,J=8.1Hz,1H),5.40(s,2H).13C NMR(100MHz,CDCl3)δ154.6,154.1,142.8,139.0,136.9,134.3,130.0,129.5,129.33,129.30,128.5,127.5,115.3,110.7;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H12ClN4 307.0745,found307.0756.
3-氨基-5-苯基-6-(邻甲苯基)吡嗪-2-甲腈(I11):黄色固体,产率76%,熔点147-148℃;1H NMR(400MHz,CDCl3)δ7.39–7.34(m,2H),7.33–7.29(m,1H),7.27–7.20(m,3H),7.19–7.11(m,3H),5.39(s,2H),1.97(s,3H).13C NMR(100MHz,CDCl3)δ154.6,154.4,144.6,137.1,136.8,136.1,130.5,130.1,129.7,129.3,128.7,128.1,126.0,115.5,110.4,19.6;HRMS(ESI-TOF)m/z:[M+H]+calcd for C18H15N4 287.1291,found 287.1282.
3-氨基-6-(2-氯苯基)-5-苯基吡嗪-2-甲腈(I12):黄色固体,产率62%,熔点161-162℃;1H NMR(400MHz,CDCl3)δ7.40–7.33(m,4H),7.32–7.29(m,3H),7.27–7.22(m,2H),5.45(s,2H).13C NMR(100MHz,CDCl3)δ155.3,154.7,142.3,136.74,136.69,133.2,131.6,130.0,129.8,129.1,128.1,127.1,115.3,110.4;HRMS(ESI-TOF)m/z:[M+H]+calcd forC17H12ClN4 307.0745,found 307.0756.
3-氨基-6-苯基-5-(间甲苯基)吡嗪-2-甲腈(I13):黄色固体,产率87%,熔点145-146℃;1H NMR(400MHz,CDCl3)δ7.33(dd,J=7.5,2.1Hz,2H),7.31–7.23(m,4H),7.20–7.14(m,2H),7.13–7.08(m,1H),5.39(s,2H),2.30(s,3H).13C NMR(100MHz,CDCl3)δ154.7,154.0,144.4,138.1,137.3,137.2,130.4,130.1,129.3,128.3,128.2,128.0,126.7,115.5,110.5,21.3;HRMS(ESI-TOF)m/z:[M+H]+calcd for C18H15N4 287.1291,found287.1285.
3-氨基-6-苯基-5-(邻甲苯基)吡嗪-2-甲腈(I14):黄色固体,产率65%,熔点143-144℃;1H NMR(400MHz,CDCl3)δ7.33–7.17(m,8H),7.15(d,J=7.6Hz,1H),5.40(s,2H),1.98(s,3H).13C NMR(100MHz,CDCl3)δ155.6,153.9,144.7,137.4,136.7,135.5,130.7,129.3,128.7,128.3,128.1,126.1,115.4,111.4,19.5;HRMS(ESI-TOF)m/z:[M+H]+calcd forC18H15N4 287.1291,found 287.1283.
3-氨基-5-(4-氯苯基)-6-苯基吡嗪-2-甲腈(I15):黄色固体,产率77%,熔点145-147℃;1H NMR(400MHz,CDCl3)δ7.38–7.34(m,2H),7.34–7.24(m,7H),5.34(s,2H).13C NMR(100MHz,CDCl3)δ153.9,153.1,144.3,137.0,136.0,135.7,131.0,129.3,128.6,128.4,115.4,110.9;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H12ClN4 307.0745,found307.0742.
3-氨基-5-(3-氯苯基)-6-苯基吡嗪-2-腈(I16):黄色固体,产率71%),熔点187-188℃;1H NMR(400MHz,CDCl3)δ7.52(s,1H),7.37–7.23(m,6H),7.22–7.14(m,2H),5.32(s,2H).13C NMR(100MHz,CDCl3)δ153.9,152.8,144.4,139.1,136.8,134.5,129.72,129.67,129.4,129.3,128.7,128.4,127.9,115.3,111.2;HRMS(ESI-TOF)m/z:[M+H]+calcd forC17H12ClN4 307.0745,found 307.0752.
3-氨基-5-(2-氯苯基)-6-苯基吡嗪-2-腈(I17):黄色固体,产率76%,熔点184-185℃;1H NMR(400MHz,CDCl3)δ7.37–7.33(m,2H),7.33–7.29(m,3H),7.28(d,J=2.0Hz,1H),7.27–7.19(m,3H),5.42(s,2H).13C NMR(100MHz,CDCl3)δ153.8,153.0,145.0,136.9,136.5,132.4,130.8,130.5,130.0,128.7,128.4,128.1,127.0,115.2,112.0;HRMS(ESI-TOF)m/z:[M+H]+calcd for C17H12ClN4 307.0745,found 307.0754.
3-氨基-5-(4-甲氧基苯基)-6-(对甲苯基)吡嗪-2-腈(I18):黄色固体,产率65%,熔点213-214℃;1H NMR(400MHz,CDCl3)δ7.38(d,J=8.6Hz,2H),7.24(d,J=7.9Hz,2H),7.09(d,J=7.9Hz,2H),6.81(d,J=8.7Hz,2H),5.29(s,2H),3.81(s,3H),2.34(s,3H).13CNMR(100MHz,CDCl3)δ160.8,153.9,153.8,144.3,138.2,134.8,131.3,129.7,129.1,129.0,115.8,113.7,109.8,55.3,21.2;HRMS(ESI-TOF)m/z:[M+H]+calcd for C19H17N4O317.1397,found 317.1392.
3-氨基-5,6-二对甲苯基吡嗪-2-甲腈(I19):黄色固体,产率78%,熔点166-167℃;1H NMR(400MHz,CDCl3)δ7.32(d,J=8.2Hz,2H),7.26–7.20(m,2H),7.14–7.04(m,4H),5.31(s,2H),2.36(s,3H),2.34(s,3H).13C NMR(100MHz,CDCl3)δ154.4,153.9,144.4,139.9,138.2,134.61,134.56,129.5,129.1,128.98,128.95,115.7,110.1,21.4,21.2;HRMS(ESI-TOF)m/z:[M+H]+calcd for C19H17N4 301.1448,found 301.1452.
3-氨基-5-(4-氟苯基)-6-(对甲苯基)吡嗪-2-甲腈(I20):黄色固体,产率88%,熔点174-175℃;1H NMR(400MHz,CDCl3)δ7.46–7.38(m,2H),7.21(d,J=7.8Hz,2H),7.09(d,J=7.8Hz,2H),6.99(t,J=8.6Hz,2H),5.31(s,2H),2.34(s,3H).13C NMR(100MHz,CDCl3)δ163.5(d,J=250.9Hz),153.8,153.1,144.4,138.5,134.3,133.5(d,J=3.4Hz),131.7(d,J=8.0Hz),129.11,129.09,115.5,115.4(d,J=21.7Hz),110.6,21.2;HRMS(ESI-TOF)m/z:[M+H]+calcd for C18H14FN4 305.1197,found 305.1189.
3-氨基-5-甲基-6-苯基吡嗪-2-甲腈(I21):黄色固体,产率56%,熔点117-118℃;1H NMR(400MHz,CDCl3)δ7.55–7.40(m,5H),5.19(s,2H),2.53(s,3H).13C NMR(100MHz,CDCl3)δ155.1,154.1,145.6,137.2,128.8,128.6,128.5,115.5,109.9,23.5;HRMS(ESI-TOF)m/z:[M+H]+calcd for C12H11N4 211.0978,found 211.0983.
3-氨基-6-苯乙基-5-苯基吡嗪-2-甲腈(I22):黄色固体,产率67%,熔点121-122℃;1H NMR(400MHz,CDCl3)δ7.50–7.40(m,3H),7.40–7.34(m,2H),7.25–7.19(m,2H),7.18–7.13(m,1H),7.03(dd,J=6.7,1.6Hz,2H),5.15(s,2H),3.11–3.02(m,2H),2.94(dd,J=9.2,5.7Hz,2H).13C NMR(100MHz,CDCl3)δ155.9,153.8,145.2,141.0,137.2,129.5,128.50,128.47,128.39,128.36,126.0,115.7,110.9,35.5,34.9;HRMS(ESI-TOF)m/z:[M+H]+calcd for C19H17N4 301.1448,found 301.1451.
3-氨基-6-苯乙基-5-(对甲苯基)吡嗪-2-甲腈(I23):黄色固体,产率66%,熔点123-124℃;1H NMR(400MHz,CDCl3)δ7.30–7.19(m,6H),7.18–7.13(m,1H),7.05(d,J=6.9Hz,2H),5.19(s,2H),3.06(dd,J=9.4,5.5Hz,2H),2.95(dd,J=9.3,5.8Hz,2H),2.41(s,3H).13C NMR(100MHz,CDCl3)δ155.9,153.8,145.2,141.1,139.7,134.3,129.2,128.5,128.4,128.3,126.0,115.8,110.5,35.6,34.8,21.3;HRMS(ESI-TOF)m/z:[M+H]+calcd forC20H19N4 315.1604,found 315.1609.
3-氨基-5-(4-氟苯基)-6-苯乙基吡嗪-2-甲腈(I24):黄色固体,产率51%,熔点120-121℃;1H NMR(400MHz,CDCl3)δ7.38–7.30(m,2H),7.25–7.20(m,2H),7.18(d,J=7.0Hz,1H),7.16–7.09(m,2H),7.02(d,J=7.0Hz,2H),5.20(s,2H),3.10–3.01(m,2H),3.00–2.92(m,2H).13C NMR(100MHz,CDCl3)δ163.3(d,J=250.2Hz),154.8,153.8,145.0,140.8,133.3(d,J=3.3Hz),130.6(d,J=8.4Hz),128.40,128.38,126.1,115.60(d,J=21.7Hz),115.56,111.0,35.5,34.9;HRMS(ESI-TOF)m/z:[M+H]+calcd for C19H16FN4319.1354,found 319.1361.
3-氨基-6-苯乙基-5-(噻吩-2-基)吡嗪-2-甲腈(I25):黄色固体,产率60%,熔点125-126℃;1H NMR(400MHz,CDCl3)δ7.60(d,J=3.8Hz,1H),7.55(d,J=5.1Hz,1H),7.35–7.26(m,2H),7.28–7.17(m,3H),7.18–7.11(m,1H),5.11(s,2H),3.35–3.26(m,2H),3.13–3.06(m,2H).13C NMR(100MHz,CDCl3)δ153.3,148.1,143.2,141.2,141.1,130.8,129.6,128.50,128.45,128.4,126.2,115.8,109.5,36.6,33.7;HRMS(ESI-TOF)m/z:[M+H]+calcdfor C17H15N4S 307.1012,found 307.1007.
3-氨基-6-(4-甲氧基苯乙基)-5-苯基吡嗪-2-甲腈(I26):黄色固体,产率68%,熔点142-144℃;1H NMR(400MHz,CDCl3)δ7.49–7.42(m,3H),7.40–7.34(m,2H),6.94(d,J=8.6Hz,2H),6.76(d,J=8.6Hz,2H),5.24(s,2H),3.76(s,3H),3.03(dd,J=9.6,6.4Hz,2H),2.88(dd,J=9.6,6.4Hz,2H).13C NMR(100MHz,CDCl3)δ157.9,155.8,153.8,145.2,137.2,133.0,129.4,129.3,128.47,128.46,115.7,113.7,110.9,55.2,35.8,34.0;HRMS(ESI-TOF)m/z:[M+H]+calcd for C20H19N4O 331.1553,found 331.1558.
3-氨基-6-(4-溴苯乙基)-5-苯基吡嗪-2-甲腈(I27):黄色固体,产率71%,熔点132-133℃;1H NMR(400MHz,CDCl3)δ7.50–7.41(m,3H),7.38–7.33(m,2H),7.31(d,J=8.2Hz,2H),6.87(d,J=8.2Hz,2H),5.23(s,2H),3.04(dd,J=9.2,6.4Hz,2H),2.89(dd,J=9.2,6.4Hz,2H).13C NMR(100MHz,CDCl3)δ155.9,153.8,144.6,139.9,137.1,131.4,130.1,129.5,128.52,128.45,119.8,115.6,110.9,35.2,34.2;HRMS(ESI-TOF)m/z:[M+H]+calcdfor C19H16BrN4 379.0553,found 379.0564.
3-氨基-6-异丁基-5-苯基吡嗪-2-甲腈(I28):黄色固体,产率65%,熔点131-132℃;1H NMR(400MHz,CDCl3)δ7.60–7.40(s,5H),5.14(s,2H),2.66(d,J=7.2Hz,2H),2.01(hept,J=6.8Hz,1H),0.78(d,J=6.8Hz,6H).13C NMR(100MHz,CDCl3)δ156.1,153.6,145.9,137.7,129.4,128.7,128.5,115.7,110.9,42.3,28.4,22.2;HRMS(ESI-TOF)m/z:[M+H]+calcd for C15H17N4 253.1448,found 253.1452.
3-氨基-6-环丙基-5-苯基吡嗪-2-甲腈(I29):黄色固体,产率75%,熔点124-125℃;1H NMR(400MHz,CDCl3)δ7.73–7.66(m,2H),7.54–7.45(m,3H),5.11(s,2H),2.12–2.04(m,1H),1.11–1.05(m,2H),0.94–0.87(m,2H).13C NMR(100MHz,CDCl3)δ154.9,153.3,146.8,137.2,129.6,129.2,128.4,115.9,110.5,13.8,10.1;HRMS(ESI-TOF)m/z:[M+H]+calcd for C14H13N4 237.1135,found 237.1141.
3-氨基-6-(甲氧基甲基)-5-苯基吡嗪-2-甲腈(I30):黄色固体,产率49%,熔点133-134℃;1H NMR(400MHz,CDCl3)δ7.77–7.70(m,2H),7.58–7.45(m,3H),5.34(s,2H),4.39(s,2H),3.45(s,3H).13C NMR(100MHz,CDCl3)δ157.0,154.7,141.0,136.6,130.1,129.0,128.5,115.3,110.9,72.4,58.4;HRMS(ESI-TOF)m/z:[M+H]+calcd for C13H13N4O241.1084,found 241.1089.
3-(5-氨基-6-氰基-3-苯基吡嗪-2-基)丙酸甲酯(I31):黄色固体,产率61%,熔点136-137℃;1H NMR(400MHz,CDCl3)δ7.57–7.45(m,5H),5.22(s,2H),3.65(s,3H),3.08(t,J=7.1Hz,2H),2.74(t,J=7.1Hz,2H).13C NMR(100MHz,CDCl3)δ173.4,155.8,154.0,143.7,137.0,129.7,128.63,128.59,115.6,110.4,51.7,31.6,28.5;HRMS(ESI-TOF)m/z:[M+H]+calcd for C15H15N4O2 283.1190,found 283.1186.
3-氨基-6-(丁-3-烯-1-基)-5-苯基吡嗪-2-腈(I32):黄色固体,产率80%,熔点121-122℃;1H NMR(400MHz,CDCl3)δ7.49(s,5H),5.78–5.66(m,1H),5.35(s,2H),5.02–4.83(m,2H),3.04–2.69(m,2H),2.51–2.29(m,2H).13C NMR(100MHz,CDCl3)δ155.6,153.8,145.2,137.2,137.1,129.5,128.54,128.50,115.6,115.3,110.9,32.9,32.6;HRMS(ESI-TOF)m/z:[M+H]+calcd for C15H15N4 251.1291,found 251.1295.
3-氨基-6-(戊-4-yn-1-基)-5-苯基吡嗪-2-腈(I33):黄色固体,产率67%,熔点117-118℃;1H NMR(400MHz,CDCl3)δ7.56–7.44(m,5H),5.19(s,2H),2.88(t,J=7.7Hz,2H),2.24–2.12(m,2H),1.94–1.84(m,3H).13C NMR(100MHz,CDCl3)δ155.8,153.8,145.2,137.2,129.6,128.6,128.5,115.6,110.8,83.6,68.8,32.5,27.4,17.9;HRMS(ESI-TOF)m/z:[M+H]+calcd for C16H15N4 263.1291,found 263.1297.
6-((1H-吡唑-1-基)甲基)-3-氨基-5-苯基吡嗪-2-腈(I34):黄色固体,产率68%,熔点194-195℃;1H NMR(400MHz,CDCl3)δ7.59(dd,J=6.7,2.9Hz,2H),7.55–7.47(m,4H),7.42(d,J=2.3Hz,1H),6.23(t,J=2.1Hz,1H),5.35(s,4H,overlap).13C NMR(100MHz,CDCl3)δ156.3,154.6,139.8,139.5,136.2,131.1,130.1,128.9,128.8,115.1,111.4,105.8,53.6;HRMS(ESI-TOF)m/z:[M+H]+calcd for C15H13N6277.1196,found 277.1192.
用途实施例
实施例二:本发明式(I)的一种含氰基和氨基的四取代吡嗪类衍生物I1-I34的杀
菌活性
采用菌丝生长法测定了一种含氰基和氨基的四取代吡嗪类衍生物I1-I34对番茄早疫病菌(Alternaria solani)、小麦赤霉病菌(Gibberella zeae)、水稻纹枯病菌(Rhizoctoriza solani)、苹果斑点病菌(Alternaria leaf spot)、草莓灰霉病菌(Botrytis cinerea)和黄瓜炭疽病菌(Cucumber anthrax)6种供试植物病原菌生物活性的测定,具体操作步骤如下:
1.称取15mg的原药溶于0.6mL DMF中,配置成母液;
2.取0.1mL母液加入到50mL无菌马铃薯葡萄糖琼脂培养基(PDA培养基)中摇匀,得到50mg/L的含药培养基;
3.将上述含药培养基趁热等量倒入三个直径为9厘米的无菌培养皿中,冷却凝固,在培养基中央接入直径0.5cm的菌饼;
4.设不含供试药剂的空白对照,每个处理3次重复;
5.将上述培养皿置于25±1℃恒温培养箱中黑暗培养,培养至菌落直径约为7.0至7.5厘米后,测定菌落直径,计算各药剂的抑制率。
6.化合物对真菌抑制率计算公式如下:抑菌率=(空白对照菌落直径-测试药剂菌落直径)÷(空白对照菌落直径-5mm)×100%。
化合物I1-I34对番茄早疫病菌、小麦赤霉病菌、水稻纹枯病菌、苹果斑点病菌、草莓灰霉病菌和黄瓜炭疽病菌的抑制活性测定结果如表2所示:
表2化合物I1-I34对6种病菌的抑制结果
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a三次重复,取其平均值;b以商品药剂多菌灵为对照药剂;c以商品药剂蛇床子素为对照药剂。
表2数据显示,目标化合物I对六种病菌都具有一定程度的抗菌活性,尤其是对水稻纹枯病菌、草莓灰霉病菌和黄瓜炭疽病菌。共有10个化合物对水稻纹枯病菌的抑制率超过50%,分别是I5、I9、I10、I11、I12、I14、I15、I28、I29、I32,其中I15、I29的抑制率超过60%,其中A29的抑制率超过70%;共有10个化合物对草莓灰霉病菌的抑制率超过50%,分别是I5、I9、I15、I16、I19、I28、I29、I32、I33,其中I15、I16、I28、I29、I32、I33的抑制率超过60%;化合物I28、I32和I33的抑制率更是高于90%;对黄瓜炭疽病菌抑制率超过50%的12个化合物分别是I1、I5、I6、I7、I9、I10、I20、I28、I29、I32、I33,其中I5、I7、I28、I29、I32、I33的抑制率超过80%,化合物I7、I32和I33表现出100%的抗菌活性;对小麦赤霉病菌的抑制率超过50%的有I11、I12、I29、I32;I15对番茄早疫病菌的抑制率超过50%;值得注意的是,化合物I5、I9、I15、I28、I29、I32可以对六种病菌中的三种表现出高于50%的抑菌率。
通过对初筛所得抑制率数据分析,对抑制率大于60%的化合物分别对相应的病菌进行进一步的EC50毒力测定,具体测定方法如下:
称取一定量的待测化合物配成一定浓度的母液,逐步稀释配制梯度浓度的溶液,制成含药平板,以多菌灵作为对照药,余下操作按活性初筛方法,分别计算各浓度下的抑制率,通过DPS统计软件,可以得到线性回归方程、有效抑制中浓度(EC50)以及95%置信区间。
部分化合物的EC50毒力测定结果如表3所示:
表3部分化合物的EC50毒力测定a
a三次重复,取其平均值;b以商品药剂多菌灵为对照药剂。
从表3中可以看出,化合物I15、I29对水稻纹枯病菌的EC50分别为9.52μg/mL、12.42μg/mL;化合物I15、I16、I28、I29、I32、I33对草莓灰霉病菌的EC50分别为10.35μg/mL、26.17μg/mL、13.68μg/mL、25.19μg/mL、4.46μg/mL、3.38μg/mL、20.38μg/mL;化合物I5、I6、I7、I9、I10、I20、I28、I29、I32、I33对黄瓜炭疽病菌的EC50分别为10.76μg/mL、2.02μg/mL、0.56μg/mL、17.19μg/mL、21.30μg/mL、2.02μg/mL、5.56μg/mL、10.54μg/mL、1.87μg/mL、1.50μg/mL、6.47μg/mL。其中化合物I6、I7、I20、I32、I33对黄瓜炭疽病菌表现出了良好的抗菌活性(EC50分别为2.02μg/mL、0.56μg/mL、2.02μg/mL、1.87μg/mL、1.50μg/mL),优于对照药多菌灵。
以上所述,仅是本发明的较佳实施案例而已,并非对本发明作任何形式上的限制,任何未脱离本发明技术方案内容,依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化与修饰,均属于本发明技术方案的范畴。
Claims (8)
1.式(I)所示的一种含氰基和氨基基团的四取代吡嗪类衍生物或其盐,
(I)
其中,所述的R1选自苯基、卤素取代的苯基、C1-3的烷基取代的苯基;
R2选自卤素取代的苯基、C1-3的烷基取代的苯基、C1-5的烷基或C3-5的环烷基。
2.根据权利要求1所述的四取代吡嗪类衍生物或其盐,其特征在于,所述的R1选自苯基、F或Cl取代的苯基、甲基或乙基取代的苯基;
R2选自卤素取代的苯基、甲基取代的苯基、C3-5的烷基或C3-5的环烷基;所述的卤素选自F、Cl、Br。
3.根据权利要求1所述的四取代吡嗪类衍生物或其盐,其特征在于,R1选自苯基、4-氟-苯基、4-氯-苯基、3-氯-苯基、4-甲基-苯基、2-甲基-苯基中的任意一种;
R2选自4-氟-苯基、4-氯-苯基、4-溴-苯基、3-氯-苯基、2-氯-苯基、3-甲基-苯基、6-异丁基、环丙基。
4.一种含氰基和氨基基团的四取代吡嗪类衍生物或其盐,其特征在于,所述的一种含氰基和氨基基团的四取代吡嗪类衍生物选自以下任意一种化合物:
3-氨基-6-(4-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-6-(4-溴苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-5-苯基-6-(间甲苯基)吡嗪-2-甲腈;
3-氨基-6-(3-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-5-苯基-6-(邻甲苯基)吡嗪-2-甲腈;
3-氨基-6-(2-氯苯基)-5-苯基吡嗪-2-甲腈;
3-氨基-6-苯基-5 -(邻甲苯基)吡嗪-2-甲腈;
3-氨基-5-(4-氯苯基)-6-苯基吡嗪-2-甲腈;
3-氨基-5-(3-氯苯基)-6-苯基吡嗪-2-甲腈;
3-氨基 -5,6-二对甲苯基吡嗪-2-甲腈;
3-氨基-5-(4-氟苯基)-6-(对甲苯基)吡嗪-2-甲腈;
3-氨基-6-异丁基-5-苯基吡嗪-2-甲腈;
3 -氨基-6-环丙基-5-苯基吡嗪-2-甲腈;
3-氨基-6-(丁-3-烯-1-基)-5-苯基吡嗪-2-腈;
3-氨基-6-(戊-4-炔-1-基)-5-苯基吡嗪-2-腈。
5.一种制备权利要求1-4中任一项所述的一种含氰基和氨基基团的四取代吡嗪类衍生物的方法,其特征在于按通式(A)表示的方法制备:
,
(A)
在Ir(ppy)3,Cu(OTf)2、Et3N·HCl、4Å MS和DMSO存在下,含取代基的肟酯(II)与三甲基氰硅烷在12瓦蓝光照射下反应生成一种含氰基和氨基的四取代吡嗪衍生物(I)。
6.权利要求1-4中任一项所述的一种含氰基和氨基基团的四取代吡嗪类衍生物或其盐在抑制水稻纹枯病菌、黄瓜炭疽病菌、番茄早疫、小麦赤霉病菌、苹果斑点病菌或草莓灰霉病菌方面的应用。
7.权利要求1-4中任一项所述的一种含氰基和氨基基团的四取代吡嗪类衍生物在防治水稻纹枯病、黄瓜炭疽病、番茄早疫病、小麦赤霉病、苹果斑点病或草莓灰霉病方面的应用。
8.权利要求1-4中任一项所述的一种含氰基和氨基基团的四取代吡嗪类衍生物在制备防治水稻纹枯病、黄瓜炭疽病、番茄早疫病、小麦赤霉病、苹果斑点病或草莓灰霉病的制剂中的应用。
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