含有双酰肼结构三嗪酮衍生物及其制备方法和在杀虫、杀菌
方面的应用
技术领域
本发明涉及含有双酰肼结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用,属农药技术领域。
背景技术
上世纪八十年代瑞士诺华公司发现吡蚜酮对刺吸口器害虫具有良好的防治效果,此后二十多年引起众多科研工作者的持续关注,通过总结文献发现,前人的工作主要集中在对三嗪酮环和吡啶环部分的修饰与改造,对中间连接臂的改造报道较少。1995年Henry报道了硫代酰胺替换亚胺的化合物结构,但并没有报道此类化合物的生物活性(Henry,S.;Haukur,K.;Peter,M.WO9518123. 1995-07-06.)。1996年Uehara报道了亚胺还原之后N原子含有取代基的化合物结构,并报道了部分化合物在500ppm浓度下,对桃蚜和稻褐粉虱表现出100%的杀虫活性(Uehara,M.;Shimizu.T.;Fujioka.S.et al.EP 0987255A2. 1996-03-28.)。2012年高聪杰报道了用酰胺替换亚胺的化合物结构,并报道了化合物对黄瓜枯萎菌、苹果轮纹菌、番茄早疫菌、花生褐斑菌、小麦赤霉菌等5种病原菌的孢子萌发均有一定的抑制作用(高聪杰.现代农药.2012.11(2).16-20.)。
发明内容
本发明的目的是提供含有双酰肼结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。本专利的含有双酰肼结构三嗪酮衍生物表现出很好的杀虫活性,同时还具有杀菌活性。
本发明含有双酰肼结构三嗪酮衍生物是具有如下通式(I)所示结构的化合物:
本发明所述的含有双酰肼结构三嗪酮衍生物(I)是具有如下两种通式(Ia,Ib)所示结构的化合物:
本发明含有双酰肼结构三嗪酮衍生物Ia-1--1a-8可以按如下方法制备(路线一):氨基三嗪酮(II)与氯甲酸苯酯反应生成化合物III,化合物III与水合肼反应生成中间体氨基脲三嗪酮IV,之后化合物IV与各种异氰酸酯Va进行缩合反应生成含双酰肼结构三嗪酮化合物Ia;
路线一:
第一步反应的溶剂可以是甲醇、二氯甲烷、1,2-二氯乙烷、氯仿、乙腈;缚酸剂可以是碳酸钠、碳酸钾、碳酸铯、吡啶、三乙胺;反应温度在80℃至120℃进行。第二步反应的溶剂可以是甲醇、乙醇,二氯甲烷、1,2-二氯乙烷、乙腈;反应温度在80℃至120℃进行。第三步反应的溶剂可以是甲醇、乙醇、乙腈、N,N-二甲基甲酰胺、二甲基亚砜;反应温度在80℃至130℃进行。
本发明含有双酰肼结构三嗪酮衍生物Ia-9--1a-48可以按如下方法制备(路线二):首先含有各种取代基的苯胺Vb与固体光气反应生成对应的苯基异氰酸酯,然后此类化合物与氨基脲三嗪酮(IV)进行缩合反应生成含有双酰肼结构三嗪酮化合物Ia;
路线二:
第一步反应的溶剂可以是甲醇、1,2-二氯乙烷,氯仿、乙腈;反应温度在70℃至90℃进行。第二步反应的溶剂可以是甲醇、1,2-二氯乙烷,氯仿、乙腈;反应温度在70℃至90℃进行。
本发明含有双酰肼结构三嗪酮衍生物Ib-1--1b-21可以按如下方法制备(路线三):氨基脲三嗪酮(IV)与各种异硫氰酸酯Vc进行缩合反应生成含有双酰肼结构三嗪酮化合物Ib;
路线三:
溶剂可以是甲醇、乙醇、乙腈、N,N-二甲基甲酰胺、二甲基亚砜;反应温度在20℃至35℃进行。
以上各通式中,
X分别代表O、S;
R分别代表1-10碳烃基、3-6碳环烷基、苄基、苯乙基、萘基、取代的苯基(其中取代基可以是氢、卤素原子、羟基、硝基、氰基、三氟甲基、三氟甲氧基、酯基、1-5碳烃基、1-6碳烷氧基、以及同时含有2-3个上述取代基)。
本发明所述的含有双酰肼结构三嗪酮衍生物(I)优选如下化合物:
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-正丙基酰肼-1,2-二酰胺(Ia-3);
N1-正丁基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-4);
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-对甲基苯基酰肼-1,2-二酰胺(Ia-12);
N1-(2,4-二甲基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-二酰胺(Ia-13);
N1-(2-溴苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-二酰胺(Ia-29);
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(苯基氨基甲酰硫)氨基甲酰肼(Ib-7);
2-(苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-8);
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(邻甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-9);
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(间甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-10);
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(对甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-11);
2-(4-甲氧基苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-18);
2-(4-乙氧基苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-19)。
本发明通式(I)的化合物表现出很好的杀蚜虫活性,其中,化合物Ib-7,Ib-9,Ib-10,Ib-11,Ib-18,Ib-19在5mg/kg浓度下表现出和吡蚜酮相当的活性。同时所有化合物对棉铃虫、玉米螟、粘虫及蚊幼虫均表现出杀虫活性。尤其是化合物Ia-4,Ia-13,Ib-7在5mg/kg时对蚊幼虫分别表现出55%、70%和35%的杀虫活性。
本发明通式(I)的化合物对以下14种病原菌表现出杀菌活性,14种病原菌分别是:番茄早疫、小麦赤霉、马铃薯晚疫、辣椒疫霉、油菜菌核、黄瓜灰霉、水稻纹枯、黄瓜枯萎、花生褐斑、苹果轮纹、小麦纹枯、玉米小斑、西瓜炭疽和水稻恶苗,尤其是化合物Ia-3,Ia12,Ia-29,Ia-35,Ib-3,Ib-4和Ib-8在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。
具体实施方式
下述的实施例和生测试验结果可用来进一步说明本发明,但不意味着限制本发明。
实施例1:N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼的合成
苯基(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酸酯(III)的合成
在100mL单口瓶中,加入二氯甲烷(50mL)、氨基三嗪酮(II)(2.56g,20mmol)、碳酸钾(2.76g,20mmol),充分搅拌,室温下慢慢滴加氯甲酸苯酯(3.13g,20mmol),大约1h滴加完毕,之后加热回流6h,TLC监测反应完毕。降温至室温,过滤,溶液减压脱溶,用石油醚/乙酸乙酯(1∶1)进行常压柱层析得化合物III 4.5g,白色固体,产率91%,熔点181-182℃。1HNMR(300MHz,DMSO-d6)δ10.08(s,1H,NH),9.92(s,1H,NH),7.42(t,J=14.7,7.8Hz,2H,Ph-H),7.25(t,J=14.7,7.2Hz,1H,Ph-H),7.14(d,J=7.8Hz,2H,Ph-H),4.15(s,2H,CH2),1.88(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ154.0,151.2,150.5,145.2,129.5,125.6,121.5,51.5,19.9;ESI-HRMS(m/z):Calcd.for C11H13N4O3[M+H]+249.0982,found 249.0988
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(IV)的合成
在250mL单口瓶中,加入甲醇(120mL),化合物III(2.7g,11mmol)、水合肼(10mL),充分搅拌,之后加热回流8h,TLC监测反应完毕。降温至室温,过滤得到IV 1.56g,白色固体,收率77%,熔点229-231℃。1H NMR(300MHz,DMSO-d6)δ9.65(s,1H,NH),8.25(s,1H,NH),7.60(s,1H,NH),4.11(s,2H,NH2),4.02(s,2H,CH2),1.83(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ159.1,151.7,144.7,52.4,19.9.ESI-HRMS(m/z):Calcd.for C5H11N6O2[M+H]+187.0938;found 187.0939.
实施例2:N1-乙基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-1)的合成
在250mL单口瓶中,加入氨基脲三嗪酮(IV)(0.93g,5mmol),乙基异氰酸酯(Va-1)(0.36g,5mmol),乙腈(100mL)搅拌溶解。然后加热回流5h,TLC监测反应完毕。将反应液脱除溶剂后析出固体,常压抽滤,用乙腈洗涤得到化合物Ia-1 1.28g,白色固体,产率99%,熔点227-228℃。1H NMR(400MHz,DMSO-d6)δ9.78(s,1H,NH),8.42(s,1H,NH),7.63(s,1H,NH),6.21(t,J=4.4Hz,1H,NH),4.02(s,2H,CH2),2.99-3.06(m,2H,CH2CH3),1.83(s,3H,CH3),0.99(t,J=7.2Hz,3H,CH2CH3);13C NMR(100MHz,DMSO-d6)δ158.5,157.8,151.8,145.0,52.3,34.1,19.9,15.5.ESI-HRMS(m/z):Calcd.for C8H16N7O3[M+H]+258.1309;found258.1315.
化合物Ia-2-Ia-8通过重复上述步骤完成。
N1-异丙基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-2)
白色固体,产率69%,熔点231-233℃。1H NMR(400MHz,DMSO-d6)δ9.79(s,1H,NH),8.40(s,1H,NH),7.54(s,1H,NH),5.96(d,J=7.6Hz,1H,NH),4.02(s,2H,CH2),3.67-3.72(m,1H,CH(CH3)2),1.83(s,3H,CH3),1.04(d,J=6.0Hz,6H,CH(CH3)2);13C NMR(100MHz,DMSO-d6)δ157.9,157.8,151.7,144.9,52.4,41.1,23.0,19.9.ESI-HRMS(m/z):Calcd.forC9H11N7NaO3[M+Na]+294.1285.1466;found 294.1284.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-正丙基酰肼-1,2-二酰胺(Ia-3)
白色固体,产率92%,熔点212-213℃。1H NMR(400MHz,DMSO-d6)δ9.78(s,1H,NH),8.42(s,1H,NH),7.62(s,1H,NH),6.22(t,J=5.2Hz,1H,NH),4.02(s,2H,CH2),2.96(q,J=6.8Hz,2H,CH2CH2CH3),1.83(s,3H,CH3),1.34-1.43(m,2H,CH2CH2CH3),0.82(t,J=7.2Hz,3H,CH2CH2CH3);13C NMR(100MHz,DMSO-d6)δ159.1,158.2,152.2,145.4,52.7,41.4,23.4,20.3,11.7.ESI-HRMS(m/z):Calcd.for C9H18N7O3[M+H]+272.1466;found 272.1467.
N1-正丁基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-4)
白色固体,产率86%,熔点198-199℃。1H NMR(300MHz,DMSO-d6)δ9.77(s,1H,NH),8.40(s,1H,NH),7.59(s,1H,NH),6.18(t,J=5.7Hz,1H,NH),4.03(s,2H,CH2),3.00(q,J=6.3Hz,2H,CH2CH2CH2CH3),1.84(s,3H,CH3),1.23-1.39(m,4H,CH2CH2CH2CH3),0.86(t,J=7.2Hz,3H,CH2CH2CH2CH3);13C NMR(100MHz,DMSO-d6)δ158.7,157.8,151.8,145.0,52.4,38.9,32.0,19.9,19.5,13.8.ESI-HRMS(m/z):Calcd.for C10H20N7O3[M+H]+286.1622;found286.1627.
N1-环戊基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-5)
白色固体,产率87%,熔点228-229℃。1H NMR(300MHz,DMSO-d6)δ9.78(s,1H,NH),8.39(s,1H,NH),7.52(s,1H,NH),6.06(d,J=6.6Hz,1H,NH),4.03(s,2H,CH2),3.81-3.92(m,1H),1.83(s,3H,CH3),1.71-1.79(m,2H),1.59-1.64(m,2H),1.44-1.53(m,2H),1.33-1.41(m,2H);13C NMR(100MHz,DMSO-d6)δ158.4,157.9,151.9,145.0,52.4,51.1,32.7,23.3,19.9.ESI-HRMS(m/z):Calcd.for C11H20N7O3[M+H]+298.1622;found 298.1627.
N1-环己基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-6)
白色固体,产率92%,熔点226-227℃。1H NMR(300MHz,DMSO-d6)δ9.77(s,1H,NH),8.38(s,1H,NH),7.52(s,1H,NH),5.97(d,J=7.6Hz,1H,NH),4.02(s,2H,CH2),1.83(s,3H,CH3),1.73(d,J=7.8Hz,2H),1.65(d,J=9.6Hz,2H),1.53(d,J=8.4Hz,1H),1.08-1.29(m,6H);13C NMR(100MHz,DMSO-d6)δ157.9,157.8,151.7,144.9,52.4,48.1,33.0,25.3,24.6,19.8.ESI-HRMS(m/z):Calcd.for C12H22N7O3[M+H]+312.1779;found 312.1781.
N1-苄基-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-7)
白色固体,产率95%,熔点223-224℃。1H NMR(400MHz,DMSO-d6):δ9.76(s,1H,NH),8.46(s,1H,NH),7.78(s,1H,NH),7.29(d,J=6.0Hz,4H,Ar-H),7.22(d,J=6.0Hz,1H,Ar-H),6.80(brs,1H,NH),4.24(d,J=5.6Hz,2H,NCH2),4.03(s,2H,CH2),1.83(s,3H,CH3);13CNMR(100MHz,DMSO-d6)δ158.7,157.8,151.8,144.9,140.5,128.2,127.0,126.6,52.3,42.6,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O3[M+H]+320.1466;found 320.1469.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-苯乙酰肼-1,2-二酰胺(Ia-8)
DMSO-d6)δ9.78(s,1H,NH),8.44(s,1H,NH),7.72(s,1H,NH),7.29(t,J=7.6Hz,2H,Ar-H),7.18-7.22(m,3H,Ar-H),6.31(brs,1H,NH),4.02(s,2H,CH2),3.23(q,J=6.8Hz,2H,N-CH2CH2),2.69(t,J=7.6Hz,2H,N-CH2CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ158.6,157.8,151.8,145.0,139.6,128.7,128.4,126.1,52.3,41.1,36.0,19.9.ESI-HRMS(m/z):Calcd.for C14H20N7O3[M+H]+334.1622;found 334.1626.
实施例3:N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-苯乙酰肼-1,2-二酰胺(Ia-9)的合成
在250mL四口瓶中,加入固体光气(BTC)(0.89g,3mmol),1.2-二氯乙烷(100mL)搅拌溶解,加热升温至70℃。苯胺(0.84g,9mmol)溶于1.2-二氯乙烷(50mL),慢慢滴加到上述反应体系中,升温至83℃搅拌3h,加入氨基脲三嗪酮(IV)(1.34g,7.2mmol),继续加热回流5h。TLC监测反应完毕。脱除溶剂后析出固体,常压抽滤,用二氯甲烷洗涤,之后用甲醇重结晶得到白色固体1.71g,产率78%,熔点246-247℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.54(s,2H,NH),8.03(s,1H,NH),7.51(d,J=5.6Hz,2H,Ar-H),7.25(t,J=7.6Hz,2H,Ar-H),6.95(t,J=7.6Hz,1H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.0,151.9,145.0,139.7,128.6,121.9,118.4,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N7NaO3[M+Na]+328.1134;found 328.1130.
化合物Ia-10-Ia-48通过重复上述步骤完成。
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-邻甲基苯基酰肼-1,2-二酰胺(Ia-10)
白色固体,产率95%,熔点237℃。1H NMR(400MHz,DMSO-d6)δ9.79(s,1H,NH),8.60(s,1H,NH),8.19(s,1H,NH),7.76(s,1H,NH),7.66(brs,1H,Ar-H),7.10-7.16(m,2H,Ar-H),6.95(t,J=7.2Hz,1H,Ar-H),4.05(s,2H,CH2),2.20(s,3H,CH3),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.1,151.8,145.0,137.1,130.2,128.5,122.0,126.1,123.2,52.3,19.9,17.7.ESI-HRMS(m/z):Calcd.for C13H18N7O3[M+H]+320.1466;found 320.1472.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-间甲基苯基酰肼-1,2-二酰胺(Ia-11)
白色固体,产率89%,熔点239-240℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.54(s,1H,NH),8.41(s,1H,NH),7.99(s,1H,NH),7.35(s,1H,Ar-H),7.28(brs,1H,Ar-H),7.12(t,J=7.2Hz,1H,Ar-H),6.77(d,J=6.8Hz,1H,Ar-H),4.06(s,2H,CH2),2.25(s,3H,CH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.0,151.9,145.0,139.6,137.8,128.5,122.7,118.9,115.6,52.4,21.3,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O3[M+H]+320.1466;found 320.1466.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-对甲基苯基酰肼-1,2-二酰胺(Ia-12)
白色固体,产率87%,熔点245-246℃。1H NMR(400MHz,DMSO-d6)δ9.87(s,1H,NH),8.53(s,1H,NH),8.39(s,1H,NH),7.97(s,1H,NH),7.39(brs,2H,Ar-H),7.05(d,J=7.6Hz,2H,Ar-H),4.06(s,2H,CH2),2.23(s,3H,CH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.0,151.9,145.0,137.1,130.7,129.0,118.4,52.3,20.4,19.8.ESI-HRMS(m/z):Calcd.for C13H18N7O3[M+H]+320.1466;found 320.1470.
N1-(2,4-二甲基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-13)
白色固体,产率79%,熔点245-246℃。1H NMR(400MHz,DMSO-d6)δ9.78(s,1H,NH),8.56(s,1H,NH),8.10(s,1H,NH),7.69(s,1H,NH),7.47(brs,1H,Ar-H),6.96(s,1H,Ar-H),6.92(d,J=8.0Hz,1H,Ar-H),4.05(s,2H,CH2),2.22(s,3H,CH3),2.16(s,3H,CH3),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.3,151.8,145.0,134.5,132.2,130.7,126.5,52.3,20.4,19.9,17.6.ESI-HRMS(m/z):Calcd.for C14H20N7O3[M+H]+334.1622;found 334.1622.
N1-(2-甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-14)
白色固体,产率79%,熔点165-167℃。1H NMR(400MHz,DMSO-d6)δ9.75(s,1H,NH),8.60(s,1H,NH),8.42(s,1H,NH),8.07(d,J=8.0Hz,1H,Ar-H),8.03(s,1H,NH),7.00(d,J=7.2Hz,1H,Ar-H),6.93(t,J=7.2Hz,1H,Ar-H),6.87(t,J=8.0Hz,1H,Ar-H),4.04(s,2H,CH2),3.85(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,155.6,151.7,147.6,145.0,128.5,122.0,120.6,118.1,110.8,55.9,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O4[M+H]+336.1415;found 336.1418.
N1-(3-甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-15)
白色固体,产率77%,熔点175-176℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.55(brs,2H,NH),8.03(s,1H,NH),7.23(s,1H,Ar-H),7.14(t,J=7.6Hz,1H,Ar-H),7.05(s,1H,Ar-H),6.53(d,J=7.6Hz,1H,Ar-H),4.06(s,2H,CH2),3.71(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ159.6,157.8,155.9,151.9,145.1,140.9,129.4,110.8,107.3,104.3,55.0,52.4,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O4[M+H]+336.1415;found 336.1416.
N1-(4-甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-16)
白色固体,产率83%,熔点234-235℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.53(s,1H,NH),8.33(s,1H,NH),7.94(s,1H,NH),7.40(brs,2H,Ar-H),6.83(d,J=7.6Hz,2H,Ar-H),4.06(s,2H,CH2),3.70(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.2,154.5,151.9,145.1,132.8,120.1,113.8,55.2,52.4,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O4[M+H]+336.1415;found 336.1416.
N1-(2,5-二甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-17)
紫色固体,产率89%,熔点172-174℃。1H NMR(400MHz,DMSO-d6)δ9.75(s,1H,NH),8.61(s,1H,NH),8.47(s,1H,NH),8.05(s,1H,NH),7.77(s,1H,Ar-H),6,90(d,J=8.4Hz,1H,Ar-H),6.47(d,J=7.6Hz,1H,Ar-H),4.03(s,2H,CH2),3.79(s,3H,OCH3),3.67(s,3H,OCH3),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.9,155.7,153.5,151.8,145.2,142.0,129.5,111.6,105.5,105.2,56.5,55.4,52.4,20.0.ESI-HRMS(m/z):Calcd.for C14H20N7O5[M+H]+366.1520;found 366.1526.
N1-(3,4-二甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-18)
紫色固体,产率80%,熔点168-170℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.54(s,1H,NH),8.36(s,1H,NH),7.95(s,1H,NH),7.23(s,1H,Ar-H),6.99(brs,1H,Ar-H),6.83(d,J=8.4Hz,1H,Ar-H),4.06(s,2H,CH2),3.71(s,3H,OCH3),3.69(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ158.0,156.2,152.0,148.8,145.3,144.2,133.4,112.4,110.5,104.2,56.0,55.5,52.5,19.9.ESI-HRMS(m/z):Calcd.for C14H20N7O5[M+H]+366.1520;found 366.1518.
N1-(3,4,5-三甲氧基苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-19)
白色固体,产率85%,熔点188-189℃。1H NMR(400MHz,DMSO-d6)δ9.84(s,1H,NH),8.54(s,1H,NH),8.45(s,1H,NH),8.01(s,1H,NH),6.92(s,2H,Ar-H),4.06(s,2H,CH2),3.72(s,6H,OCH3),3.59(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.0,152.8,151.9,145.2,135.9,132.5,96.2,60.2,55.8,52.4,19.8.ESI-HRMS(m/z):Calcd.for C15H22N7O6[M+H]+396.1626;found 396.1628.
N1-(2-氟苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-20)
白色固体,产率87%,熔点257-258℃。1H NMR(400MHz,DMSO-d6)δ9.76(s,1H,NH),8.59(s,1H,NH),8.35(s,1H,NH),8.24(s,1H,Ar-H),8.01(s,1H,NH),7.21(t,J=9.6Hz,1H,Ar-H),6.93(t,J=7.6Hz,1H,Ar-H),7.00(brs,1H,Ar-H),4.04(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.5,152.3(d,J=238.7Hz),151.7,145.0,127.4(d,J=9.8Hz),124.5,122.9,121.1,115.1(d,J=18.7Hz),52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15FN7O3[M+H]+324.1215;found 324.1214.
N1-(4-氟苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-21)
白色固体,产率98%,熔点247-248℃。1H NMR(400MHz,DMSO-d6)δ9.87(s,1H,NH),8.55(brs,2H,NH),8.07(s,1H,NH),7.53(brs,2H,Ar-H),7.09(t,J=8.0Hz,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ158.6,157.8,156.2,152.0,145.1,136.1,120.1,115.1(d,J=21.8Hz),52.4,19.9.ESI-HRMS(m/z):Calcd.forC12H15FN7O3[M+H]+324.1215;found 324.1220.
N1-(2,4-二氟苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-22)白色固体,产率90%,熔点252℃。1H NMR(400MHz,DMSO-d6)δ9.77(s,1H,NH),8.57(s,1H,NH),8.33(s,1H,NH),8.21(s,1H,Ar-H),7.91(s,1H,NH),7.29(t,J=11.2Hz,1H,Ar-H),7.03(d,J=7.6Hz,1H,Ar-H),4.04(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ158.5,157.8,155.8,154.0,151.8,145.1,123.9(d,J=6.0Hz),122.8,111.1(d,J=21.5Hz),103.9(t,J=24.1Hz),52.4,19.9.ESI-HRMS(m/z):Calcd.forC12H14F2N7O3[M+H]+342.1121;found 342.1122.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(2,4,5-三氟苯基)酰肼-1,2-二酰胺(Ia-23)
白色固体,产率78%,熔点229-230℃。1H NMR(400MHz,DMSO-d6)δ9.77(s,1H,NH),8.59(brs,2H,NH),8.29(s,1H,Ar-H),8.05(s,1H,NH),7.58-7.65(m,1H,Ar-H),4.03(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,155.4,151.9,145.6(dd,J=241.1,242.8Hz),145.5(dd,J=10.1,12.8Hz),145.2,124.5,109.0,105.7(t,J=22.9Hz),52.4,19.9.ESI-HRMS(m/z):Calcd.for C12H13F3N7O3[M+H]+360.1026;found 360.1025.
N1-(2-氯苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-24)
白色固体,产率86%,熔点245-246℃。1H NMR(400MHz,DMSO-d6)δ9.76(s,1H,NH),8.60(brs,2H,NH),8.10(brs,2H,NH,Ar-H),7.44(d,J=7.6Hz,1H,Ar-H),7.28(t,J=7.6Hz,1H,Ar-H),7.02(t,J=7.6Hz,1H,Ar-H),4.04(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.6,155.3,151.6,144.9,135.8,129.2,127.7,123.4,121.9,120.9,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15ClN7O3[M+H]+340.0919;found 340.0923.
N1-(3-氯苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-25)
白色固体,产率88%,熔点238-239℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.73(s,1H,NH),8.58(s,1H,NH),8.20(s,1H,NH),7.75(s,1H,Ar-H),7.40(brs,1H,Ar-H),7.27(t,J=7.6Hz,1H,Ar-H),7.00(d,J=7.6Hz,1H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.0,152.0,145.2,141.3,133.1,130.3,121.6,117.8,116.9,52.4,19.9.ESI-HRMS(m/z):Calcd.for C12H15ClN7O3[M+H]+340.0919;found340.0919.
N1-(4-氯苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-26)
白色固体,产率77%,熔点176-178℃。1H NMR(400MHz,DMSO-d6)δ9.87(s,1H,NH),8.70(s,1H,NH),8.57(s,1H,NH),8.14(s,1H,NH),7.55(brs,2H,Ar-H),7.30(d,J=7.6Hz,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.9,156.1,152.0,145.3,138.8,128.6,125.6,120.1,52.4,20.0.ESI-HRMS(m/z):Calcd.forC12H15ClN7O3[M+H]+340.0919;found 340.0919.
N1-(2,3-二氯苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-27)
白色固体,产率91%,熔点213-214℃。1H NMR(400MHz,DMSO-d6)δ9.77(s,1H,NH),8.69(brs,2H,NH),8.27(s,1H,NH),8.10(d,J=5.6Hz,1H,Ar-H),7.25-7.35(m,2H,Ar-H),4.04(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.3,151.7,145.0,137.9,131.7,128.3,123.8,120.4,119.4,52.3,19.9.ESI-HRMS(m/z):Calcd.forC12H14Cl2N7O3[M+H]+374.0530;found 374.052.
N1-(3,4-二氯苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-28)
白色固体,产率90%,熔点236℃。1H NMR(400MHz,DMSO-d6)δ9.84(s,1H,NH),8.90(s,1H,NH),8.59(s,1H,NH),8.30(s,1H,NH),7.92(s,1H,Ar-H),7.49(brs,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.1,140.0,130.9,130.5,123.3,119.5,118.5,52.3,19.9.ESI-HRMS(m/z):Calcd.forC12H14Cl2N7O3[M+H]+374.0530;found 374.0527.
N1-(2-溴苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-29)
白色固体,产率75%,熔点173-175℃。1H NMR(300MHz,DMSO-d6)δ9.75(s,1H,NH),8.66(brs,2H,NH),8.08(d,J=7.8Hz,1H,Ar-H),7.98(s,1H,NH),7.60(d,J=8.1Hz,1H,Ar-H),7.33(t,J=8.1Hz,1H,Ar-H),6.96(t,J=8.1Hz,1H,Ar-H),4.05(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.6,155.4,151.6,144.9,136.9,132.5,128.2,124.0,121.4,112.8,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15BrN7O3[M+H]+384.0414;found 384.0408.
N1-(3-溴苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-30)
白色固体,产率89%,熔点239-240℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),8.72(s,1H,NH),8.58(s,1H,NH),8.20(s,1H,NH),7.89(s,1H,Ar-H),7.43(s,1H,Ar-H),7.21(t,J=7.6Hz,1H,Ar-H),7.13(d,J=7.6Hz,1H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.1,141.4,130.6,124.5,121.6,120.6,117.3,52.4,19.9.ESI-HRMS(m/z):Calcd.for C12H15BrN7O3[M+H]+384.0414;found384.0410.
N1-(4-溴苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-31)
白色固体,产率82%,熔点250-251℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.67(s,1H,NH),8.57(s,1H,NH),8.14(s,1H,NH),7.50(brs,2H,Ar-H),7.42(d,J=7.6Hz,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.1,139.2,131.4,120.4,113.4,52.4,19.9.ESI-HRMS(m/z):Calcd.forC12H15BfN7O3[M+H]+384.0414;found 384.0408.
N1-(2-碘苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-32)
白色固体,产率79%,熔点238-239℃。1H NMR(400MHz,DMSO-d6)δ9.75(s,1H,NH),8.64(brs,2H,NH),7.92(s,1H,NH),7.81(d,J=8.0Hz,2H,Ar-H),7.33(t,J=6.8Hz,1H,Ar-H),6.81(t,J=6.8Hz,1H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.6,155.6,151.7,145.0,139.6,138.9,128.8,124.9,121.5,90.6,52.3,20.0.ESI-HRMS(m/z):Calcd.for C12H15IN7O3[M+H]+432.0276;found 432.0267.
N1-(3-碘苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-33)
白色固体,产率87%,熔点235-236℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),8.57(brs,2H,NH),8.17(brs,1H,Ar-H),8.05(s,1H,NH),7.45(brs,1H,Ar-H),7.30(d,J=6.8Hz,1H,Ar-H),7.05(t,J=7.6Hz,1H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.1,141.2,130.7,130.5,126.5,117.8,94.6,52.4,19.9.ESI-HRMS(m/z):Calcd.for C12H15IN7O3[M+H]+432.0276;found 432.0272.
N1-(4-碘苯基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-34)
白色固体,产率92%,熔点242-244℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),8.56(brs,2H,NH),8.12(s,1H,NH),7.57(d,J=8.4Hz,2H,Ar-H),7.38(brs,2H,Ar-H),4.06(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.1,139.7,137.2,120.7,84.9,52.4,19.9.ESI-HRMS(m/z):Calcd.for C12H15IN7O3[M+H]+432.0276;found 432.0267.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(2-(三氟甲基)苯基)酰肼-1,2-二酰胺(Ia-35)
白色固体,产率77%,熔点166-167℃。1H NMR(400MHz,DMSO-d6)δ9.76(s,1H,NH),8.61(brs,2H,NH),7.97(brs,1H,Ar-H),7.91(s,1H,NH),7.60-7.66(m,2H,Ar-H),7.25(t,J=6.8Hz,1H,Ar-H),4.03(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.7,151.7,145.0,136.5,133.1,126.1(q,J=4.9Hz),124.6,124.1(q,J=271.4Hz),123.6,119.6,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O3[M+H]+374.1183;found374.1186
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(3-(三氟甲基)苯基)酰肼-1,2-二酰胺(Ia-36)
白色固体,产率76%,熔点170-171℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),8.94(s,1H,NH),8.61(s,1H,NH),8.27(brs,1H,Ar-H),8.05(s,1H,NH),7.71(brs,1H,Ar-H),7.48(t,J=7.6Hz,1H,Ar-H),7.29(d,J=7.6Hz,1H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.1,152.0,145.3,140.7,129.9,129.5(q,J=31.1Hz),124.3(q,J=270.6Hz),122.2,118.3,114.5,52.4,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O3[M+H]+374.1183;found 374.1186.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(4-(三氟甲基)苯基)酰肼-1,2-二酰胺(Ia-37)
白色固体,产率77%,熔点232-234℃。1H NMR(400MHz,DMSO-d6)δ9.84(s,1H,NH),8.97(s,1H,NH),8.59(s,1H,NH),8.24(s,1H,NH),7.73(brs,2H,Ar-H),7.61(d,J=8.4Hz,2H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.9,156.0,152.1,145.4,143.6,128.8,126.1,124.7(q,J=269.4Hz),122.2(q,J=31.4Hz),118.3,52.4,20.0.ESI-HRMS(m/z):Calcd.for C13H15F3N7O3[M+H]+374.1183;found 374.1181.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(2-(三氟甲氧基)苯基)酰肼-1,2-二酰胺(Ia-38)
白色固体,产率76%,熔点163-165℃。1H NMR(400MHz,DMSO-d6)δ9.75(s,1H,NH),8.58(s,1H,NH),8.50(s,1H,NH),8.27(s,1H,NH),8.19(d,J=8.0Hz,1H,Ar-H),7.35(d,J=9.2Hz,1H,Ar-H),7.31(d,J=8.0Hz,1H,Ar-H),7.07(t,J=8.0Hz,1H,Ar-H),4.04(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.4,151.7,145.0,137.3,132.2,127.9,122.7,121.2,120.9,120.3(q,J=256.1Hz),52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O4[M+H]+390.1132;found 390.1133.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(3-(三氟甲氧基)苯基)酰肼-1,2-二酰胺(Ia-39)
白色固体,产率78%,熔点188-190℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),8.87(s,1H,NH),8.59(s,1H,NH),8.22(s,1H,NH),7.72(s,1H,Ar-H),7.43(s,1H,Ar-H),7.37(t,J=7.6Hz,1H,Ar-H),6.93(d,J=6.4Hz,1H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,155.9,152.0,148.7,145.2,141.6,130.3,120.2(q,J=254.4Hz),117.1,113.8,110.5,52.4,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O4[M+H]+390.1132;found 390.1138.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(4-(三氟甲氧基)苯基)酰肼-1,2-二酰胺(Ia-40)
白色固体,产率89%,熔点235-237℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),8.73(s,1H,NH),8.57(s,1H,NH),8.16(s,1H,NH),7.62(brs,2H,Ar-H),7.27(d,J=8.8Hz,2H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.1,152.0,145.2,142.8,139.1,121.6,120.3(q,J=253.4Hz),119.7,52.4,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O4[M+H]+390.1132;found 390.1130.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(3-硝基苯基)酰肼-1,2-二酰胺(Ia-41)
淡黄色固体,产率91%,熔点231-232℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),9.15(s,1H,Ar-H),8.61(brs,2H,NH),8.36(s,1H,NH),7.85(s,1H,Ar-H),7.81(d,J=8.0Hz,1H,Ar-H),7.54(t,J=8.0Hz,1H,Ar-H),4.08(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,156.0,151.9,148.1,145.1,141.1,129.9,124.6,116.4,112.4,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N8O5[M+H]+351.1160;found 351.1159.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(4-硝基苯基)酰肼-1,2-二酰胺(Ia-42)
淡黄色固体,产率77%,熔点242-243℃。1H NMR(400MHz,DMSO-d6)δ9.80(s,1H,NH),9.42(s,1H,NH),8.62(brs,2H,NH),8.17(d,J=9.2Hz,2H,Ar-H),7.78(brs,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.6,155.5,151.9,146.4,145.2,141.2,125.0,117.8,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N8O5[M+H]+351.1160;found 351.1164.
N1-(3-氰基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-43)
粉红色固体,产率75%,熔点243-245℃。1H NMR(400MHz,DMSO-d6)δ9.89(s,1H,NH),8.93(s,1H,Ar-H),8.59(s,1H,NH),8.32(s,1H,Ar-H),8.01(s,1H,NH),7.80(s,1H,Ar-H),7.48(t,J=8.0Hz,1H,Ar-H),7.41(d,J=8.0Hz,1H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.9,151.9,145.2,140.7,130.1,125.4,123.1,120.9,118.9,111.5,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H15N8O3[M+H]+331.1262;found 331.1268.
N1-(4-氰基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-44)
白色固体,产率81%,熔点229-231℃。1H NMR(400MHz,DMSO-d6)δ9.83(s,1H,NH),9.12(s,1H,NH),8.60(s,1H,NH),8.32(s,1H,NH),7.72(brs,4H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.7,155.6,151.9,145.2,144.2,133.2,119.4,118.3,103.5,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H15N8O3[M+H]+331.1262;found 331.1262.
N1-(4-乙氧基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-45)
白色固体,产率87%,熔点245-246℃。1H NMR(400MHz,DMSO-d6)δ9.87(s,1H,NH),8.53(s,1H,NH),8.31(s,1H,NH),7.93(s,1H,NH),7.39(d,J=7.6Hz,2H,Ar-H),6.81(d,J=9.2Hz,2H,Ar-H),4.06(s,2H,CH2),3.95(q,J=6.8Hz,2H,CH2CH3),1.85(s,3H,CH3),1.29(t,J=6.8Hz,3H,CH2CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.2,153.8,151.9,145.1,132.7,120.1,114.4,63.1,52.4,19.9,14.8.ESI-HRMS(m/z):Calcd.for C14H20N7O4[M+H]+350.1571;found 350.1575.
N1-(4-叔丁基)-N2-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)酰肼-1,2-二酰胺(Ia-46)
白色固体,产率73%,熔点187-188℃。1H NMR(400MHz,DMSO-d6)δ9.84(s,1H,NH),8.53(s,1H,NH),8.42(s,1H,NH),7.96(s,1H,NH),7.40(brs,2H,Ar-H),7.26(d,J=8.0Hz,2H,Ar-H),4.06(s,2H,CH2),1.85(s,3H,CH3),1.25(s,9H,C(CH3)3);13C NMR(100MHz,DMSO-d6)δ157.8,156.1,151.9,145.1,144.2,137.0,125.2,118.3,52.4,33.9,31.3,19.9.ESI-HRMS(m/z):Calcd.for C16H24N7O3[M+H]+362.1935;found 362.1934.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(萘-1-y1)酰肼-1,2-二酰胺(Ia-47)
白色固体,产率78%,熔点186-187℃。1H NMR(400MHz,DMSO-d6)δ9.80(s,1H,NH),8.59(brs,2H,NH),8.25(s,1H,NH),8.09(d,J=6.8Hz,1H,Ar-H),7.92(d,J=5.6Hz,1H,Ar-H),7.80(brs,1H,Ar-H),7.66(d,J=7.2Hz,1H,Ar-H),7.54(brs,2H,Ar-H),7.46(d,J=7.6Hz,1H,Ar-H),4.08(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.9,156.6,151.9,145.1,134.2,133.8,128.3,126.0,125.8,125.8,123.7,122.1,52.4,19.9.ESI-HRMS(m/z):Calcd.for C16H18N7O3[M+H]+356.1466;found 356.1465.
N1-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N2-(萘-2-yl)酰肼-1,2-二酰胺(Ia-48)
白色固体,产率94%,熔点258-259℃。1H NMR(400MHz,DMSO-d6)δ9.90(s,1H,NH),8.73(s,1H,NH),8.60(s,1H,NH),8.15(brs,2H,NH),7.81(d,J=2.8Hz,1H,Ar-H),7.80(s,1H,Ar-H),7.76(d,J=8.0Hz,1H,Ar-H),7.61(brs,1H,Ar-H),7.44(t,J=7.2Hz,1H,Ar-H),7.35(t,J=7.2Hz,1H,Ar-H),4.09(s,2H,CH2),1.86(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ157.8,156.1,152.0,145.1,137.4,133.7,129.2,128.3,127.5,127.0,126.4,124.0,119.9,113.7,52.4,19.9.ESI-HRMS(m/z):Calcd.for C16H18N7O3[M+H]+356.1466;found356.1463.
实施例4:N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(甲基氨基甲酰硫)氨基甲酰肼(Ib-1)的合成
在250mL单口瓶中,加入氨基脲三嗪酮(IV)(0.93g,5mmol),乙腈(100mL)搅拌溶解,甲基异硫氰酸酯(0.36g,5mmol)溶于乙腈(20mL),加入上述体系中。然后加热回流5h,TLC监测反应完毕。将反应液脱除溶剂后析出固体,常压抽滤,用乙腈洗涤得到化合物Ib-10.88g,白色固体,产率68%,熔点236-237℃。1H NMR(400MHz,DMSO-d6)δ9.86(s,1H,NH),9.17(s,1H,NH),8.48(s,1H,NH),7.78(s,1H,NH),4.04(s,2H,CH2),2.88(d,J=4.4Hz,3H,CH3),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ183.0,156.8,151.9,145.1,52.2,30.9,19.9.ESI-HRMS(m/z):Calcd.for C7H14N7O2S[M+H]+260.0924;found 260.0922.
化合物Ib-2--Ib-21通过重复上述步骤完成。
2-(乙基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-2)
白色固体,产率74%,熔点209-210℃。1H NMR(400MHz,DMSO-d6)δ9.89(s,1H,NH),9.13(s,1H,NH),8.48(s,1H,NH),7.68(s,1H,NH),4.04(s,2H,CH2),3.41-3.47(m,2H,CH2CH3),1.84(s,3H,CH3),1.07(t,J=7.2Hz,3H,CH2CH3);13C NMR(100MHz,DMSO-d6)δ181.8,156.9,152.0,145.2,52.3,38.6,19.9,14.4.ESI-HRMS(m/z):Calcd.for C8H16N7O2S[M+H]+274.1081;found 274.1086.
2-(异丙基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-3)
白色固体,产率77%,熔点165-166℃。1H NMR(300MHz,DMSO-d6)δ9.90(s,1H,NH),9.07(s,1H,NH),8.47(s,1H,NH),7.40(d,J=7.8Hz,1H,NH),4.31-4.42(m,1H,CH(CH3)2),4.05(s,2H,CH2),1.84(s,3H,CH3),1.12(d,J=6.6Hz,6H,CH(CH3)2);13C NMR(100MHz,DMSO-d6)δ180.9,157.0,152.0,145.3,52.5,45.7,22.1,20.0.ESI-HRMS(m/z):Calcd.forC9H18N7O2S[M+H]+288.1237;found 288.1237.
2-(正丁基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-4)
白色固体,产率:86%,熔点194-196℃。1H NMR(300MHz,DMSO-d6)δ9.86(s,1H,NH),9.10(s,1H,NH),8.47(s,1H,NH),7.62(s,1H,NH),4.04(s,2H,CH2),3.38-3.48(m,2H,CH2CH2CH2CH3),1.84(s,3H,CH3),1.44-1.53(m,2H,CH2CH2CH2CH3),1.22-1.34(m,2H,CH2CH2CH2CH3),0.88(t,J=7.5Hz,3H,CH2CH2CH2CH3);13C NMR(100MHz,DMSO-d6)δ182.0,156.9,151.9,145.1,52.3,43.4,30.7,19.9,19.5,13.8.ESI-HRMS(m/z):Calcd.forC10H20N7O2S[M+H]+302.1394;found 302.1400.
2-(环戊基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-5)
白色固体,产率87%,熔点164-165℃。1H NMR(400MHz,DMSO-d6)δ9.90(s,1H,NH),9.10(s,1H,NH),8.47(s,1H,NH),7.36(s,1H,NH),4.47(brs,1H),4.04(s,2H,CH2),1.83(brs,5H),1.65(brs,2H),1.48(brs,4H);13C NMR(100MHz,DMSO-d6)δ181.5,156.9,151.8,145.0,55.3,52.4,31.9,23.4,19.8.ESI-HRMS(m/z):Calcd.for C11H20N7O2S[M+H]+314.1394;found 314.1400.
2-(环己基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-6)
白色固体,产率75%,熔点170-171℃。1H NMR(400MHz,DMSO-d6)δ9.91(s,1H,NH),9.09(s,1H,NH),8.47(s,1H,NH),7.29(s,1H,NH),4.04(s,3H),1.83(brs,5H),1.68(brs,2H),1.57(d,J=11.2Hz,1H),1.24(brs,4H),1.10(brs,1H);13C NMR(100MHz,DMSO-d6)δ180.8,156.9,151.8,145.1,52.6,52.4,32.0,25.2,24.8,19.9.ESI-HRMS(m/z):Calcd.forC12H22N7O2S[M+H]+328.1550;found 328.1558.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(苯基氨基甲酰硫)氨基甲酰肼(Ib-7)
白色固体,产率66%,熔点175-177℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.58(s,1H,NH),9.34(s,1H,NH),8.60(s,1H,NH),7.63(brs,2H,Ar-H),7.32(t,J=8.0Hz,2H,Ar-H),7.14(t,J=7.2Hz,1H,Ar-H),4.09(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.9,156.9,152.1,145.3,139.1,128.1,124.8,124.0,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N7NaO2S[M+Na]+344.0906;found 344.0905.
2-(苄基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-8)
白色固体,产率93%,熔点223-224℃。1H NMR(300MHz,DMSO-d6)δ9.84(s,1H,NH),9.29(s,1H,NH),8.52(s,1H,NH),8.27(s,1H,NH),7.31(brs,2H,Ar-H),7.29(brs,2H,Ar-H),7.18-7.24(m,1H,Ar-H),4.73(d,J=5.1Hz,2H,N-CH2),4.04(s,2H,CH2),1.83(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ182.7,156.9,151.9,145.1,139.2,128.1,127.1,126.7,52.2,46.7,20.0.ESI-HRMS(m/z):Calcd.for C13H18N7O2S[M+H]+336.1237;found336.1243.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(邻甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-9)
白色固体,产率68%,熔点179-180℃。1H NMR(400MHz,DMSO-d6)δ9.90(s,1H,NH),9.52(s,1H,NH),9.06(s,1H,NH),8.55(s,1H,NH),7.19-7.24(m,2H,Ar-H),7.12-7.18(m,2H,Ar-H),4.08(s,2H,CH2),2.18(s,3H,CH3),1.83(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ182.2,156.8,152.0,145.2,137.7,135.1,130.1,128.6,126.5,125.7,52.3,19.9,17.7.ESI-HRMS(m/z):Calcd.for C13H18N7O2S[M+H]+336.1237;found 336.1234.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(间甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-10)
白色固体,产率74%,熔点152-154℃。1H NMR(400MHz,DMSO-d6)δ9.99(s,1H,NH),9.57(s,1H,NH),9.26(s,1H,NH),8.62(s,1H,NH),7.42(brs,2H,Ar-H),7.20(t,J=7.6Hz,1H,Ar-H),7.21(d,J=7.6Hz,1H,Ar-H),4.09(s,2H,CH2),2.30(s,3H,CH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ181.0,156.9,152.1,145.3,139.0,137.4,128.0,125.5,124.7,121.5,52.3,21.1,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O2S[M+H]+336.1237;found 336.1235.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(对甲基苯基氨基甲酰硫)氨基甲酰肼(Ib-11)
白色固体,产率87%,熔点187-189℃。1H NMR(300MHz,DMSO-d6)δ9.95(s,1H,NH),9.51(s,1H,NH),9.29(s,1H,NH),8.59(s,1H,NH),7.48(d,J=7.8Hz,2H,Ar-H),7.12(d,J=7.8Hz,2H,Ar-H),4.09(s,2H,CH2),2.28(s,3H,CH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ181.0,156.9,152.1,145.3,136.5,134.0,128.6,124.2,52.3,20.6,20.0.ESI-HRMS(m/z):Calcd.for C13H18N7O2S[M+H]+336.1237;found 336.1237.
2-(2-氯苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-12)
白色固体,产率74%,熔点207-209℃。1H NMR(300MHz,DMSO-d6)δ9.84(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),8.62(s,1H,NH),7.69(s,1H,Ar-H),7.49(d,J=7.8Hz,1H,Ar-H),7.34(t,J=7.5Hz,1H,Ar-H),7.25(t,J=7.5Hz,1H,Ar-H),4.07(s,2H,CH2),1.84(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ182.5,157.2,152.3,145.5,136.7,130.0,129.7,128.0,127.4,52.6,20.3.ESI-HRMS(m/z):Calcd.for C12H15ClN7O2S[M+H]+356.0691;found356.0697.
2-(3-氯苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-13)
白色固体,产率84%,熔点163-165℃。1H NMR(400MHz,DMSO-d6)δ10.03(s,1H,NH),9.77(s,1H,NH),9.46(s,1H,NH),8.66(s,1H,NH),7.91(s,1H,Ar-H),7.57(brs,1H,Ar-H),7.35(t,J=7.6Hz,1H,Ar-H),7.20(d,J=7.6Hz,1H,Ar-H),4.09(s,2H,CH2),1.83(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.9,156.8,152.1,145.3,140.6,132.2,129.8,124.4,123.3,122.4,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15ClN7O2S[M+H]+356.0691;found356.0699.
2-(4-氯苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-14)
白色固体,产率87%,熔点199-201℃。1H NMR(400MHz,DMSO-d6)δ9.97(s,1H,NH),9.70(s,1H,NH),9.43(s,1H,NH),8.63(s,1H,NH),7.67(brs,2H,Ar-H),7.38(d,J=7.6Hz,2H,Ar-H),4.08(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.9,156.8,152.1,145.3,138.1,128.7,128.0,125.7,52.3,19.9.ESI-HRMS(m/z):Calcd.forC12H15ClN7O2S[M+H]+356.0691;found 356.0694.
2-(4-氟苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-15)
白色固体,产率86%,熔点207-208℃。1H NMR(400MHz,DMSO-d6)δ9.97(s,1H,NH),9.63(s,1H,NH),9.39(s,1H,NH),8.61(s,1H,NH),7.59(brs,2H,Ar-H),7.16(t,J=8.8Hz,2H,Ar-H),4.07(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ181.3,160.5,158.1,156.9,152.1,145.4,135.4(d,J=2.6Hz),126.5,114.9(d,J=22.4Hz),52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15FN7O2S[M+H]+340.0986;found 340.0983.
2-(4-溴苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-16)
白色固体,产率69%,熔点199-200℃。1H NMR(400MHz,DMSO-d6)δ9.98(s,1H,NH),9.71(s,1H,NH),9.42(s,1H,NH),8.64(s,1H,NH),7.63(brs,2H,Ar-H),7.51(d,J=8.0Hz,2H,Ar-H),4.08(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.9,156.8,152.1,145.3,138.5,131.0,126.0,116.9,52.3,20.0.ESI-HRMS(m/z):Calcd.forC12H15BrN7O2S[M+H]+400.0186;found 400.0189.
2-(4-碘苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-17)
白色固体,产率76%,熔点208-209℃。1H NMR(400MHz,DMSO-d6)δ9.98(s,1H,NH),9.70(s,1H,NH),9.39(s,1H,NH),8.64(s,1H,NH),7.67(d,J=8.8Hz,2H,Ar-H),7.50(brs,2H,Ar-H),4.08(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.7,156.9,152.1,145.4,139.0,136.9,126.3,89.3,52.3,20.0.ESI-HRMS(m/z):Calcd.forC12H15IN7O2S[M+H]+448.0047;found 448.0047.
2-(4-甲氧基苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-18)
白色固体,产率77%,熔点189-190℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.48(s,1H,NH),9.25(s,1H,NH),8.58(s,1H,NH),7.43(d,J=6.8Hz,2H,Ar-H),6.88(d,J=8.8Hz,2H,Ar-H),4.08(s,2H,CH2),3.74(s,3H,OCH3),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ181.2,156.9,156.6,152.1,145.3,132.0,126.1,113.3,55.3,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H18N7O3S[M+H]+352.1186;found 352.1187.
2-(4-乙氧基苯基氨基甲酰硫)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-19)
白色固体,产率77%,熔点200-201℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.47(s,1H,NH),9.25(s,1H,NH),8.58(s,1H,NH),7.43(brs,2H,Ar-H),6.87(d,J=7.2Hz,2H,Ar-H),4.08(s,2H,CH2),4.00(q,J=6.8Hz,2H,CH2CH3),1.85(s,3H,CH3),1.32(t,J=6.8Hz,3H,CH2CH3);13C NMR(100MHz,DMSO-d6)δ181.1,156.9,155.8,152.1,145.2,131.8,126.0,113.8,63.2,52.3,19.9,14.8.ESI-HRMS(m/z):Calcd.for C14H20N7O3S[M+H]+366.1343;found 366.1349.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-(三氟甲基)苯基氨基甲酰硫)氨基甲酰肼(Ib-20)
白色固体,产率87%,熔点231-233℃。1H NMR(400MHz,DMSO-d6)δ10.03(s,1H,NH),9.86(s,1H,NH),9.59(s,1H,NH),8.67(s,1H,NH),7.95(brs,2H,Ar-H),7.69(d,J=8.0Hz,2H,Ar-H),4.09(s,2H,CH2),1.85(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ181.0,156.9,152.2,145.4,142.9,124.4(q,J=269.5Hz),125.3,123.1,52.3,19.9.ESI-HRMS(m/z):Calcd.for C13H15F3N7O2S[M+H]+390.0955;found 390.0961.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-硝基苯基氨基甲酰硫)氨基甲酰肼(Ib-21)
黄色固体,产率87%,熔点235-236℃。1H NMR(400MHz,DMSO-d6)δ10.04(s,2H,NH),9.72(s,1H,NH),8.71(s,1H,NH),8.21(d,J=8.0Hz,2H,Ar-H),8.11(brs,2H,Ar-H),4.09(s,2H,CH2),1.86(s,3H,CH3);13C NMR(100MHz,DMSO-d6)δ180.7,156.7,152.2,145.4,143.1,124.0,122.9,122.7,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N8O4S[M+H]+367.0931;found 367.0941.
实施例5:杀蚜虫的测定,测定程序如下:
蚜虫的活性测试
杀蚜虫活性测定步骤如下:试虫为豆蚜(Aphis laburni Kaltenbach),实验室蚕豆叶饲养的正常群体。称取药品,加1mL DMF溶解,加两滴吐温-20乳化剂,加入一定量的蒸馏水,搅拌均匀,配成所需浓度的药液。将带蚜虫(约60只)蚕豆叶片浸入药剂中5秒钟,拿出轻轻甩干,用滤纸吸干多余药剂,然后将蚕豆枝***吸水海绵中,并用玻璃罩罩住枝条,用纱布封口,96小时检查结果,每个化合物重复3次。对照只向蒸馏水中加入乳化剂和溶剂,搅拌均匀。
表1含有双酰肼结构三嗪酮衍生物(I)的杀蚜虫活性测试结果:
a-未测.
从表1中可见,在600mg/kg浓度时,大部含有双酰肼结构三嗪酮衍生物表现出很好的杀蚜虫活性。在5mg/kg浓度时,Ib-7,Ib-9,Ib-10,Ib-11,Ib-18,Ib-19表现出和吡蚜酮相当的活性。
实施例6:杀棉铃虫、玉米螟、粘虫、蚊幼虫活性的测定,测定程序如下:
棉铃虫的活性测试
棉铃虫的实验方法:饲料混药法,从配置好的溶液中移取3mL加入约27g的刚配置好的饲料中,从而得到稀释十倍的所需浓度。药剂混匀后均匀地倒入干净的24孔板中,晾凉后接入24头三龄棉铃虫,观察3-4天后检查结果。
玉米螟的活性测试
玉米螟的试验方法:浸叶法,配置后所需浓度后,把直径约为5-6cm的叶片浸入药液中5-6秒,取出,放在吸水纸上晾干,放在指定的培养皿中,接入10头3龄幼虫,放入27±1℃的养虫室中观察3-4天后检查结果。
粘虫的活性测试
粘虫的实验方法:浸叶法,配置后所需浓度后,把直径约为5-6cm的叶片浸入药液中5-6秒,取出,放在吸水纸上晾干,放在指定的培养皿中,接入10头3龄幼虫,放入27±1℃的养虫室中观察3-4天后检查结果。
蚊幼虫的活性测试
杀蚊幼虫的实验方法:尖音库蚊淡色亚种,室内饲养的正常群体。称取供试化合物约5mg于盘尼西林药瓶中,加5mL丙酮(或适宜溶剂),振荡溶解,即为1000ppm母液。移取0.5mL母液,加入盛有89.9mL水的100mL烧杯中,选取10头4龄初蚊子幼虫,连同10mL饲养液一并倒入烧杯中,其药液的浓度即为5ppm。放入标准处理室内,24h检查结果。以含有0.5mL试验溶剂的水溶液为空白对照。
表2含有双酰肼结构三嗪酮衍生物(I)的杀棉铃虫、玉米螟、粘虫、蚊幼虫活性测试结果:
a5mg/kg下死亡率
从表2中可见,大多数含有双酰肼结构三嗪酮衍生物对棉铃虫、玉米螟、粘虫和蚊幼虫均表现出杀虫活性。尤其是化合物Ia-4,Ia-13,Ib-7在5mg/kg时对蚊幼虫分别表现出55%、70%和35%的杀虫活性。
实施例7:杀真菌活性的测定,测定程序如下:
以番茄早疫病菌为例,可以换成其他菌
离体测试方法:将番茄早疫病菌接到PDA培养基上培养7天,用打孔器在菌落边缘制取直径4cm的菌碟接种到含有50ug/ml和不含药剂的PDA培养基上培养4天,量取菌落直径,与对照比较计算出药剂的抑制百分率。
表3含有双酰肼结构三嗪酮衍衍生物(I)的杀菌活性测试结果:
从表4中可见,大多数含有双酰肼结构三嗪酮衍衍生物对14种病原菌表现出较好的杀菌活性,尤其是化合物Ia-3,Ia12,Ia-29,Ia-35,Ib-3,Ib-4和Ib-8在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。