CN103497193A - 具有1,2,4-三嗪骨架结构的衍生物及其合成方法 - Google Patents

具有1,2,4-三嗪骨架结构的衍生物及其合成方法 Download PDF

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CN103497193A
CN103497193A CN201310441318.9A CN201310441318A CN103497193A CN 103497193 A CN103497193 A CN 103497193A CN 201310441318 A CN201310441318 A CN 201310441318A CN 103497193 A CN103497193 A CN 103497193A
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王春江
仝敏超
陈旋
陶海燕
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Abstract

本发明公开了一种具有1,2,4-三嗪骨架结构的衍生物及其合成方法，该方法为：在有机溶剂中，在惰性气体保护下，以偶氮甲碱叶立德和甘氨酸甲酯衍生的亚胺为原料，铜盐/Ferrocenyl-basedLigand络合物为催化剂，加入碳酸盐或有机碱，在-20～25℃温度下反应，蒸去溶剂，经柱层析得到目标化合物。所得目标化合物具有杀菌活性，可作为杀菌剂的有效成分。

Description

具有1,2,4-三嗪骨架结构的衍生物及其合成方法
技术领域
本发明属于杂环化合物合成技术领域，尤其涉及一种具有1,2,4-三嗪骨架结构的衍生物及其合成方法。
背景技术
近年来由于越来越多具有生物功能活性杂环化合物的发现，使得对具有特殊结构的杂环化合物的需求随之增加，所以合成各种各样的非天然杂环化合物具有重要意义，并引起了广泛的关注。(a)X.-L.Hou,Z.Yang,K.-S.Yeung,H.N.C.Wong inProgress in Heterocyclic Chemistry,Vol.19(Eds.:G.W.Gribble,J.Joule),Pergamon:Oxford,2008.(b)I.Ojima,M.Tzamarioudaki,Z.Li,R.J.Donovan,Chem.Rev.1996,96,635;b)L.Yet,Chem.Rev.2000,100,2963;c)C.Aubert,O.Buisine,M.Malacria,Chem.Rev.2002,102,813;d)I.Nakamura,Y.Yamamoto,Chem.Rev.2004,104,2127;e)W.Zhao,Chem.Rev.2010,110,1706;f)W.Carruthers,Cycloaddition Reactions inOrganic Synthesis Pergamon:Oxford,1990,pp.1-208;g)The Alkaloids,Vol.14,J.S.Bindra,R.H.F.Manske,Eds.Academic Press:New York,1973;h)C.V.Galliford,K.A.Scheidt,Angew.Chem.2007,46,8902;Angew.Chem.Int.Ed.2007,46,8748.i)L.Hong,R.Wang,Adv.Synth.Catal.2013,355,1023.)。
具有1,2,4-三嗪骨架结构的衍生物是一类重要的化合物，主要应用在一些药物和生物活性化合物方面(a)A.S.Oganisyan,G.O.Grigoryan,A.S.Noravyan,I.A.Dzhagatspanyan,G.G.Melikyan,Pharm.Chem.J.2001,35,124;b)A.Deeb,F.El-Mariah,M.Hosny,Bioorg.Med.Chem.Lett.2004,14,5013;c)T.Ali,E.Eur.J.Med.Chem.2009,44,4539;d)D.Kaushik,S.A.Khan,G.Chawla,Eur.J.Med.Chem.2010,45,3960;e)P.Zhan,X.Li,Z.Li,X.Chen,Y.Tian,W.Chen,X.Liu,C.Pannecouque,E.D.Clercq,Bioorg.Med.Chem.Lett.2012,22,7155;f)M.Congreve,S.P.Andrews,A.S,Doré,K.Hollenstein,E.Hurrell,C.J.Langmead,J.S.Mason,I.W.Ng,B.Tehan,A.Zhukov,M.Weir,F.H.Marshall,J.Med.Chem.2012,55,1898;g)A.Bolognese,G.Correale,M.Manfra,A.Esposito,E.Novellino,A.Lavecchia,J.Med.Chem.2008,51,8148;h)E.D.Miller,C.A.Kauffman,P.R.Jensen,W.Fenical,J.Org.Chem.2006,72,323;i)W.Li,J.Gan,D.Ma,Angew.Chem.2009,121,9053.Angew.Chem.Int.Ed.2009,48,8891.)。
发明内容
本发明的目的是提供一种具有1,2,4-三嗪骨架结构的衍生物及其合成方法，本发明的具有1,2,4-三嗪骨架结构的衍生物具有高效的杀菌活性，采用本发明合成方法可合成高产率和高对映选择性的产物。
本发明提供的具有1,2,4-三嗪骨架结构的衍生物，结构式如下：
Figure BDA0000387284630000021
或
Figure BDA0000387284630000022
其中，
R1为苯基、烷基苯基、烷氧基苯基、卤苯基、三卤烷基苯基、萘基、噻吩基、吡啶基、硝基苯基、烷基或苄基；
R2为苯基、烷基苯基、烷氧基苯基、卤苯基、萘基、噻吩基、吡啶基、氰苯基、烷基或苄基。
上述R1优选为苯基、对甲基苯基、间甲基苯基、邻甲基苯基、对氯苯基、对溴苯基、间溴苯基、对三氟甲基苯基、2-萘基、对硝基苯、3-吡啶基或正丙基。
上述R2有选为苯基、对甲基苯基、邻甲基苯基、对甲氧基苯基、对氯苯基、邻氯苯基、间氯苯基、2-萘基、3-吡啶基、对氰基苯基或正戊基。
本发明还提供了上述化合物（Ⅱ）和（Ⅱ）的合成方法，具体为：
在有机溶剂中，在惰性气体保护下，以偶氮甲碱叶立德和甘氨酸甲酯衍生的亚胺为原料，铜盐/Ferrocenyl-based Ligand络合物为催化剂，加入碳酸盐或有机碱，在-20～25℃温度下反应，蒸去溶剂，经柱层析得到目标化合物（Ⅰ）或（Ⅱ）。
针对上述合成方法，可进行以下优选：
1）偶氮甲碱叶立德和甘氨酸甲酯衍生的亚胺的摩尔比为1:1.2～1:5。
2）Ferrocenyl-based Ligand为基于二茂铁骨架的手性配体。铜盐/Ferrocenyl-based Ligand络合物采用如下方法制备：
室温下，按铜盐摩尔数不大于手性配体Ferrocenyl-based Ligand摩尔数分别取铜盐和手性配体Ferrocenyl-based Ligand溶于有机溶剂中，经反应得到铜盐/Ferrocenyl-based Ligand络合物。
所述的手性配体Ferrocenyl-based Ligand为手性配体(S,Sp)-Ferrocenyl-basedLigand或手性配体(R,Rp)-Ferrocenyl-based Ligand，其中，手性配体(S,Sp)-Ferrocenyl-based Ligand的结构式为：
Figure BDA0000387284630000031
手性配体(R,Sp)-Ferrocenyl-based Ligand的结构式为
Figure BDA0000387284630000032
3）所述柱层析以硅胶为填充料，以石油醚和乙酸乙酯的混合溶剂为淋洗剂，并且：石油醚和乙酸乙酯的体积比为2:1。
对本发明制备的目标化合物（Ⅰ）和（Ⅱ）进行杀菌活性检测，发现目标化合物（Ⅰ）和（Ⅱ）具有杀菌活性，可作为杀菌剂的有效成分。
与现有技术相比，本发明具有以下特点：
1）本发明方法合成简单，成本低，产率高，所得目标化合物对应选择性好，产率67-94%，对应选择性过量≥90%。
2）采用本发明方法合成的新型的具有1,2,4-三嗪骨架结构衍生物具除草活性，可作为除草剂的有效成分。
3）本发明方法采用的催化剂铜盐/Ferrocenyl-based Ligand络合物，在反应中表现出催化反应速度快和催化剂用量低的优点。
具体实施方式
为了更好的理解本发明，下面结合实施例对本发明做进一步说明。
下列实施例中所采用的手性配体(S,Sp)-Ferrocenyl-based Ligand的结构式为
Figure BDA0000387284630000033
所采用的手性配体(R,Rp)-Ferrocenyl-based Ligand的结构式为
实施例1
Figure BDA0000387284630000041
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-20℃下，依次加入0.24mmol2-(对氯苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析（石油醚/乙酸乙酯2/1），得到白色固体，产率85%，熔点136℃，产物的对映选择性过量96%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=13.25and22.78min.)[α]25 D=-74.0(c0.79,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.44-7.37(m,9H),5.26(d,J=10.8Hz,1H),3.86-3.79(m,1H),3.52(d,J=9.3Hz,1H),3.39(s,3H),3.23-3.15(m,1H),2.70-2.59(m,1H),2.44-2.25(m,2H),2.15-2.04(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.4,170.1,135.4,135.1,133.8,128.6,128.3,128.0,73.1,71.4,63.8,51.6,48.4,30.3;IR(KBr)ν3453,2951,2847,1713,1492,1436,1381,1263,1174,1089,1014,774,710,584cm-1.HRMS计算值for C20H20ClN3O3+H+:386.1266,测量值:386.1273。
实施例2
Figure BDA0000387284630000042
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对溴苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率87%，熔点110℃，产物的对映选择性过量95%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=14.24and24.51min.)[α]25 D=-57.5(c1.10,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.52(d,J=8.1Hz,2H),7.37(m,7H),5.24(d,J=12.3Hz,1H),3.86-3.78(m,1H),3.51(d,J=9.6Hz,1H),3.39(s,3H),3.23-3.16(m,1H),2.70-2.59(m,1H),2.44-2.25(m,2H),2.14-2.04(m,1H);13CNMR(CDCl3,TMS,75MHz)δ172.7,170.3,136.0,135.2,131.5,128.8,128.5,122.4,73.4,71.8,64.0,51.8,48.7,30.5;IR(KBr)ν3297,2951,2848,1717,1490,1436,1380,1263,1070,1011,817,774,702cm-1.HRMS计算值forC20H20BrN3O3+H+:430.0761,测量值:430.0770。
实施例3
Figure BDA0000387284630000051
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(间溴苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率84%，熔点146℃，产物的对映选择性过量94%，HPLC((Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=14.40and37.25min);[α]25 D=-69.3(c0.36,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.63(m,1H),7.51-7.24(m,8H),5.24(d,J=12.0Hz,1H),3.86-3.78(m,1H),3.52(d,J=9.6Hz,1H),3.40(s,3H),3.24-3.16(m,1H),2.71-2.61(m,1H),2.45-2.29(m,2H),2.15-2.04(m,1H);13CNMR(CDCl3,TMS,75MHz)δ172.6,170.2,139.1,135.1,131.4,129.8,128.7,127.8,125.5,122.2,73.2,71.5,63.9,51.8,48.6,30.4;IR(KBr)ν3453,2925,2851,1712,1641,1435,1379,1262,1206,1174,769,702cm-1.HRMS计算值forC20H20BrN3O3+H+:430.0761,测量值:430.0773。
实施例4
Figure BDA0000387284630000052
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对硝基苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到淡黄色固体，产率96%，熔点148℃，产物的对映选择性过量96%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=24.24and43.41min;[α]25 D=-50.5(c0.46,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ8.21(d,J=8.7Hz,2H),7.79(d,J=8.4Hz,2H),7.39(m,5H),5.49(d,J=10.5Hz,1H),3.91-3.84(m,1H),3.72(d,J=10.2Hz,1H),3.34(s,3H),3.08-3.01(m,2H),2.69-2.65(m,1H),2.40(m,1H),2.24-2.20(m,1H);13C NMR(CDCl3,TMS,75MHz)δ173.2,170.3,147.8,143.7,135.1,129.0,127.9,123.7,73.2,71.3,64.1,52.0,48.7,30.4;IR(KBr)δ3300,2952,2852,1712,1520,1438,1348,1265,1207,1175,1102,856,752,701cm-1.HRMS计算值for C20H20N4O5+H+:397.1506,测量值:397.1509。
实施例5
Figure BDA0000387284630000061
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对三氟甲基苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到黄色液体，产率82%，产物的对映选择性过量95%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=8.27and15.29min;[α]25 D=-65.7(c1,28,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.71(m,4H),7.39(m,5H),5.43(d,J=10.5Hz,1H),3.90-3.83(m,1H),3.70(d,J=8.4Hz,1H),3.31(s,3H),3.03-2.91(m,2H),2.68-2.57(m,1H),2.38(m,1H),2.22(m,1H);13C NMR(DMSO-d6,100MHz)δ171.7,169.7,141.8,135.9,128.3,128.2,128.1,128.0,124.0(q,J=270.4Hz),124.41,124.37,71.0,70.8,63.6,51.3,47.6,29.8;IR(KBr)δ3468,2952,2849,1713,1510,1438,1381,1264,1224,1175,1090,1014,818,594cm-1.HRMS计算值forC21H20F3N3O3+H+:420.1530,测量值:420.1525。
实施例6
Figure BDA0000387284630000071
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率88%，熔点116℃，产物的对映选择性过量97%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=11.43and21.85min;[α]25 D=-127.0(c0.26,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.50-7.47(m,2H),7.43-7.38(m,8H),5.28(d,J=12.3Hz,1H),3.88-3.80(m,1H),3.53(d,J=9.3Hz,1H),3.39(s,3H),3,23-3.15(m,1H),2.69-2.59(m,1H),2.43-2.31(m,2H),2.21-2.12(m,1H);13CNMR(CDCl3,TMS,75MHz)δ172.4,170.4,136.9,135.3,128.7,128.4,128.3,127.6,127.1,126.7,73.6,72.4,64.0,51.7,48.7,30.5;IR(KBr)ν3454,2925,2851,1713,1454,1436,1344,1263,1174,835,753,700cm-1.HRMS计算值forC20H21N3O3+H+:352.1565,测量值:352.1566。
实施例7
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对甲苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率84%，熔点116℃，产物的对映选择性过量95%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=10.72and16.80min;[α]25 D=-70.6(c0.34,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.39-7.33(m,7H),7.13(d,J=7.8Hz,2H),5.24(d,J=10.8Hz,1H),3.86-3.79(m,1H),3.64(d,J=9.3Hz,1H),3.33(s,3H),3.03-2.94(m,1H),2.63-2.55(m,2H),2,40-2.34(m,1H),2.31(s,3H),2.23-2.16(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.4,170.5,138.2,135.5,134.1,129.2,128.7,126.6,73.7,72.4,64.1,51.8,48.8,30.7.21.2;IR(KBr)ν3321,2925,2853,1720,1435,1380,1263,1206,1174,1128,772,702cm-1.HRMS计算值for C21H23N3O3+H+:366.1812,测量值:366.1807。
实施例8
Figure BDA0000387284630000081
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(邻甲基苯亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率86%，熔点102℃，产物的对映选择性过量97%，HPLC(97%ee(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=8.48and14.33min;[α]25 D=-84.8(c0.42,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.51-7.20(m,9H),5.48(d,J=11.7Hz,1H),3.89-3.81(m,1H),3.55(d,J=9.3Hz,1H),3.39(s,3H),3.22-3.14(m,1H),2.69-2.59(m,1H),2.46(s,3H),2.35-2.16(m,3H);13CNMR(CDCl3,TMS,75MHz)δ172.2,170.5,135.5,135.4,135.1,133.5,130.5,128.8,128.3,125.9,73.7,69.1,64.3,51.8,48.8,30.6,19.5;IR(KBr)ν3458,2989,2849,1713,1519,1454,1436,1275,1261,1174,1129,749,702cm-1.HRMS计算值for C21H23N3O3+H+:366.1812,测量值:366.1825。
实施例9
Figure BDA0000387284630000091
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(2-萘亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率81%，熔点148℃，产物的对映选择性过量97%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=17.53and49.12min;[α]25 D=-67.9(c0.52,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.99-7.85(m,4H),7.67-7.40(m,8H),5.48(d,J=10.8Hz,1H),3.95-3.87(m,1H),3.72(d,J=9.3Hz,1H),3.36(s,3H),3.08-3.01(m,1H),2.89-2.81(m,1H),2.69-2.62(m,1H),2.39(m,1H),2.27-2.17(m,1H);13C NMR(DMSO-d6,75MHz)δ171.7,170.1,136.3,135.3,132.8,132.7,128.6,127.9,127.5,127.2,126.0,125.9,125.8,71.8,71.5,63.9,51.6,47.9,30.2;IR(KBr)ν3327,3005,2832,1720,1453,1377,1275,1261,1174,1128,750,702cm-1.HRMS计算值for C24H23N3O3+H+:402.1812,测量值:402.1819。
实施例10
Figure BDA0000387284630000092
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(3-吡啶亚甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到淡黄色液体，产率73%，产物的对映选择性过量91%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flowrate1.0mL/min,λ=210nm);tr=17.77and39.13min;[α]25 D=-83.1(c0.44,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ8.66(s,1H),8.50(d,J=3.9Hz,1H),7.91(d,J=7.8Hz,1H),7.39-7.34(m,6H),5.38(d,J=10.8Hz,1H),3.89-3.81(m,1H),3.70(d,J=9.6Hz,1H),3.34(s,3H),3.09-2.98(m,2H),2.66-2.62(m,1H),2.37(m,1H),2.23(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.5,170.0,149.1,148.1,134.9,134.3,131.7,128.5,72.9,70.1,63.8,51.6,48.3,30.2;IR(KBr)ν3401,2924,2851,1712,1435,1384,1274,1175,1129,1096,756,750,703cm-1.HRMS计算值for C19H20N4O3+H+:353.1608,测量值:353.1611。
实施例11
Figure BDA0000387284630000101
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(正丙基甲基氨基)乙酸甲酯、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率80%，熔点82℃，产物的对映选择性过量90%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate0.5mL/min,λ=220nm);tr=18.56and40.13min;[α]25 D=-80.2(c0.17,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.33(m,5H),4.35(m,1H),3.74(d,J=9.6Hz,1H),3.47-3.43(m,1H),3.40(s,3H),3.23-3.13(m,1H),2.76-2.67(m,1H),2.61-2.49(m,2H),2.40-2.28(m,1H),2.06-1.91(m,2H),1.67-1.50(m,4H),0.99(t,J=7.2Hz,3H);13C NMR(DMSO-d6,75MHz)δ171.5,170.2,136.9,128.5,128.3,128.1,70.7,70.5,64.5,51.5,46.6,33.1,30.6,18.7,13.9;IR(KBr)ν3347,2958,2836,1737,1693,1483,1462,1440,1402,1276,1171,764,702cm-1..HRMS计算值for C17H23N3O3+Na+:340.1632,测量值:340.1637。
实施例12
Figure BDA0000387284630000111
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(苯亚甲氨基)二氢呋喃-2(3H)-酮、0.20mmol2-(苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率82%，熔点146℃，产物的对映选择性过量94%，HPLC(Chiralcel OD-H,i-propanol/hexane=40/60,flow rate1.0mL/min,λ=220nm);tr=11.57and21.58min;[α]25 D=-39.5(c0.85,CH2Cl2)1H NMR(CDCl3,TMS,400MHz)δ7.63-7.32(m,10H),5.14(d,J=13.2Hz,1H),4.07-4.02(m,1H),3.87(s,1H),3.53-3.49(m,1H),2.94-2.78(m,2H),2.67-2.56(m,1H),2.46-2.31(m,4H);13C NMR(CDCl3,TMS,75MHz)δ176.5,172.1,136.7,133.6,129.6,129.2,128.9,128.5,126.6,73.9,69.9,66.4,63.6,49.2,30.5,29.3;IR(KBr)ν3296,2922,2850,1767,1710,1454,1384,1265,1110,1025,741,702cm-1.HRMS计算值for C21H21N3O3+Na+:386.1475,测量值:386.1480。
实施例13
Figure BDA0000387284630000112
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(对甲基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率86%，熔点130℃，产物的对映选择性过量95%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=11.75and22.64min;[α]25 D=-46.5(c0.56,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.45(d,J=8.4Hz,2H),7.33(d,J=8.4Hz,2H),7.21-7.11(m,4H),5.25(d,J=10.8Hz,1H),3.75(t,J=9.9Hz,1H),3.57(d,J=9.3Hz,1H),3.30(s,3H),2.96-2.89(m,1H),2.78-2.70(m,1H),2.57-2.53(m,1H),2.35-2.29(m,1H),2.25(s,3H),2.14-2.08(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.7,170.4,138.6,135.6,134.2,132.2,129.5,128.6,128.2,73.2,71.8,64.0,51.9,48.6,30.6,21.2;IR(KBr)ν3302,2925,2821,1712,1493,1381,1262,1174,1089,1015,809,765,750cm-1.HRMS计算值for C21H22ClN3O3+H+:400.1422,测量值:400.1423。
实施例14
Figure BDA0000387284630000121
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(间甲基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到黄色液体，产率83%，产物的对映选择性过量97%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=10.51and16.18min;[α]25 D=-61.8(c0.84,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.44-7.14(m,8H),5.25(m,1H),3.80(m,1H),3.48(d,J=9.3Hz,1H),3.40(s,3H),3.25-3.16(m,1H),2.70-2.59(m,1H),2.44-2.29(m,5H),2.10(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.6,170.4,135.5,135.1,134.1,129.5,129.3,128.5,128.1,73.3,71.7,64.0,51.8,48.6,30.5,21.3;IR(KBr)ν3299,2951,2821,1720,1493,1437,1380,1263,1200,1174,1089,1014,824,787,704cm-1.HRMS计算值for C21H22ClN3O3+H+:400.1422,测量值:400.1430。
实施例15
Figure BDA0000387284630000122
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(邻甲基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率81%，熔点130℃，产物的对映选择性过量95%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=10.79and47.53min;[α]25 D=-56.3(c0.33,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.56-7.50(m,3H),7.41-7.37(m,2H),7.23-7.19(m,3H),5.31(d,J=11.1Hz,1H),4.00(d,J=9.6Hz,1H),3.89-3.81(m,1H),3.36(s,3H),2.97-2.83(m,2H),2.63-2.55(m,1H),2.33(s,3H),2.26-2.13(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.8,170.6,136.2,135.5,134.3,133.6,130.5,129.1,128.6,128.2,127.3,126.7,71.9,67.9,63.9,52.0,48.2,30.7,19.7;IR(KBr)ν3302,2952,2926,1721,1493,1379,1261,1202,1174,1089,1015,820,773,724cm-1.HRMS计算值for C21H22ClN3O3+H+:400.1422,测量值:400.1426。
实施例16
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(对甲氧基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率79%，熔点166℃，产物的对映选择性过量97%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=16.61and36.58min;[α]25 D=-57.5(c0.37,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.44-7.34(m,6H),6.90(d,J=7.5Hz,2H),5.24(d,J=8.1Hz,1H),3.83-3.77(m,4H),3.49-3.45(m,1H),3.42(s,3H),3.21-3.13(m,1H),2.69-2.58(m,1H),2.39-2.34(m,2H),2.09(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.6,170.4,159.7,135.5,134.1,128.5,128.1,127.1,114.0,72.6,71.6,63.9,55.1,51.8,48.5,30.5;IR(KBr)ν3451,2924,2839,1732,1714,1514,1380,1252,1175,1085,1032,813,769cm-1.HRMS计算值for C21H22ClN3O4+H+:416.1372,测量值:416.1383。
实施例17
Figure BDA0000387284630000141
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(对氯苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率89%，熔点138℃，产物的对映选择性过量97%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=14.33and33.41min;[α]25 D=-53.0(c0.56,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.43-7.35(m,8H),5.23(d,J=12.0Hz,1H),3.82-3.74(m,1H),3.50(d,J=9.3Hz,1H),3.44(s,3H),3.17-3.13(m,1H),2.64-2.57(m,1H),2.39-2.31(m,2H),2.13-2.04(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.5,170.1,135.3,134.6,134.3,133.8,129.0,128.6,128.2,72.5,71.7,63.9,52.0,48.7,30.4;IR(KBr)ν3301,2926,2851,1716,1492,1380,1262,1174,1090,854,812,588cm-1.HRMS计算值forC20H19Cl2N3O3+H+:420.0876,测量值:420.0880。
实施例18
Figure BDA0000387284630000142
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(间氯苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到黄色液体，产率93%，产物的对映选择性过量96%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=12.93and22.05min;[α]25 D=-61.9(c1.46,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.43-7.33(m,8H),5.24(d,J=11.7Hz,1H),3.82-3.74(m,1H),3.50(d,J=9.6Hz,1H),3.44(s,3H),3.26-3.18(m,1H),2.69-2.58(m,1H),2.40-2.33(m,2H),2.14-2.05(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.4,170.0,137.4,135.3,134.1,130.0,128.9,128.5,128.1,72.5,71.6,63.8,51.8,48.6,30.4;IR(KBr)ν3300,2952,2849,1716,1597,1493,1436,1380,1262,1176,1090,1015,822,789,697cm-1.HRMS计算值for C20H19Cl2N3O3+H+:420.0876,测量值:420.0891。
实施例19
Figure BDA0000387284630000151
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(邻氯苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率88%，熔点172℃，产物的对映选择性过量98%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=12.95and35.12min;[α]25 D=-70.8(c0.41,CH2Cl2)1H NMR(DMSO-d6,300MHz)δ7.69(d,J=7.2Hz,1H),7.56-7.37(m,7H),5.32(d,J=11.1Hz,1H),4.25(d,J=9.3Hz,1H),3.93-3.89(m,1H),3.40(s,3H),3.06-2.92(m,2H),2.64-2.54(m,1H),2.40-2.18(m,2H);13C NMR(CDCl3,TMS,75MHz)δ172.6,169.5,135.2,134.2,133.3,129.5,129.4,128.9,128.5,128.1,127.5,71.4,67.3,63.3,52.2,48.1,30.5;IR(KBr)ν3308,2926,2823,1740,1716,1437,1379,1262,1176,1133,1090,1015,817,771cm-1.HRMS计算值for C20H19Cl2N3O3+H+:420.0876,测量值:420.0881。
实施例20
Figure BDA0000387284630000161
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(对氰基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率90%，熔点132℃，产物的对映选择性过量96%，HPLC(Chiralpak IA-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=16.71and17.94min;[α]25 D=-57.2(c0.81,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.72-7.63(m,2H),7.53-7.33(m,6H),5.24(d,J=12.0Hz,1H),3.83-3.75(m,1H),3.59(d,J=9.3Hz,1H),3.43(s,3H),3.16-3.14(m,1H),2.67-2.57(m,1H),2.41-2.33(m,2H),2.16-2.07(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.4,169.8,140.8,135.1,134.4,132.6,132.0,128.7,128.2,118.2,112.8,72.8,71.8,63.8,52.1,48.9,30.4;IR(KBr)ν3300,2926,2852,2228,1716,1493,1382,1264,1175,1090,1014,855,817,735cm-1.HRMS计算值for C21H19ClN4O3+H+:411.1218,测量值:411.1226。
实施例21
Figure BDA0000387284630000162
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(2-萘基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率87%，熔点154℃，产物的对映选择性过量96%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate1.0mL/min,λ=220nm);tr=14.84and24.69min;[α]25 D=-61.0(c0.29,CH2Cl2)1H NMR(DMSO-d6,400MHz)δ7.96-7.92(m,4H),7.56-7.53(m,5H),7.41(d,J=8.4Hz,2H),5.38(d,J=10.8Hz,1H),4.01-3.95(m,1H),3.85(d,J=9.6Hz,1H),3.28(s,3H),3.01-2.94(m,2H),2.72-2.64(m,1H),2.42-2.37(m,1H),2.26-2.18(m,1H);13C NMR(DMSO-d6,75MHz)δ171.5,169.7,136.3,133.6,132.7,132.2,129.1,128.0,127.5,127.4,126.1,71.2,70.8,63.4,51.3,47.7,29.9;IR(KBr)ν3297,2925,2852,1716,1492,1378,1317,1262,1172,1088,1014,815,746cm-1.HRMS计算值for C24H22ClN3O3+H+:436.1422,测量值:436.1435。
实施例22
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(3-吡啶基苯亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到黄色油状液体，产率85%，熔点136℃，产物的对映选择性过量96%，HPLC(Chiralpak AS-H,i-propanol/hexane=40/60,flow rate0.5mL/min,λ=220nm);tr=26.37and37.82min;[α]25 D=-68.1(c0.51,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ8.64-8.58(m,2H),7.75(m,1H),7.44-7.33(m,5H),5.26(d,J=11.7Hz,1H),3.87-3.79(m,1H),3.57(d,J=9.6Hz,1H),3.44(s,3H),3.21-3.13(m,1H),2.70-2.60(m,1H),2.40-2.27(m,2H),2.18-2.09(m,1H);13C NMR(CDCl3,TMS,75MHz)δ172.5,169.8,150.3,149.3,135.2,134.3,131.2,128.6,128.2,123.7,70.7,63.7,52.0,48.8,33.4,30.4;IR(KBr)ν3303,2927,2852,1717,1492,1437,1381,1263,1173,1089,1014,805,716cm-1.HRMS计算值for C19H19ClN4O3+H+:387.1218,测量值:387.1224。
实施例23
Figure BDA0000387284630000181
的制备
在25mL反应管中加入0.01mmol Cu(CH3CN)4BF4与0.011mmol(S,Sp)-Ferrocenyl-based Ligand，在氮气保护下，加入1mL二氯甲烷，室温下搅拌1小时，然后在-10℃下，依次加入0.24mmol2-(对氯苯甲基氨基)乙酸甲酯、0.20mmol2-(正戊基亚甲基)吡唑烷3-酮叶立德和0.03mmol碳酸铯，搅拌24h后，蒸去溶剂，产物经硅胶柱层析(石油醚/乙酸乙酯2/1)，得到白色固体，产率67%，熔点74℃，产物的对映选择性过量74%，HPLC(Chiralpak AS-H,i-propanol/hexane=30/70,flow rate0.5mL/min,λ=220nm);tr=24.45and29.60min;[α]25 D=-71.5(c0.50,CH2Cl2)1H NMR(CDCl3,TMS,300MHz)δ7.34(m,4H),5.09(m,1H),3.71-3.55(m,4H),3.55-3.43(m,1H),2.78(m,1H),2.60(m,1H),2.46-2.40(m,2H),1.71-1.63(m,1H),1.50-1.25(m,7H),0.91(t,J=6.9Hz,3H);13CNMR(CDCl3,TMS,75MHz)δ172.4,171.0,136.0,134.1,128.5,128.2,71.4,67.3,60.0,52.1,48.2,32.1,30.8,28.0,23.5,22.2,13.9;IR(KBr)ν3448,2953,2870,1740,1491,1437,1379,1263,1199,1088,1014,824,763cm-1.HRMS计算值forC19H26ClN3O3+Na+:402.1555,测量值:402.1557。
上述实施例1-23中，Cu(CH3CN)4BF4可由Cu(OTf)2、CuOTf、CuI、CuBr、CuCl、Cu(ClO)4、CuOAc、Cu(OAc)等替换,，碳酸铯可由Na2CO3、K2CO3、三乙胺等替换，作为溶剂的二氯甲烷可由乙醚、乙酸乙酯、四氢呋喃、甲醇、氯仿等替换，N2可由其他惰性气体替换。
实施例1-23所得化合物的产率和对应选择性过量见表1所示。
表1实施例所得化合物的产率和对映体过量
Figure BDA0000387284630000191
实施例24
杀菌活性检测
药液浓度50ppm，用5mm打空器取所制的琼脂片，分挑入各培养皿，设空白对照，将其在恒温培养箱27℃培养48-72小时，检查菌斑直径，抑制率=(对照菌斑直径－样品菌斑直径)/对照菌斑直径×100%，同时做一重复。测定结果见表2。
助溶剂：二甲基甲酞胺；乳化剂：吐温-80；配制溶液：无菌水。其中，二甲基甲酞胺/H2O=1/1000；乳化剂/H2O=5/1000(重量百分比)。
表2本发明目标化合物的抑菌率
Figure BDA0000387284630000192
Figure BDA0000387284630000201
Figure BDA0000387284630000211
Figure BDA0000387284630000221

Claims (7)

1.具有1,2,4-三嗪骨架结构的衍生物，其特征在于，结构式为：
Figure FDA0000387284620000011
或
Figure FDA0000387284620000012
其中，
R1为苯基、烷基苯基、烷氧基苯基、卤苯基、三卤烷基苯基、萘基、噻吩基、吡啶基、硝基苯基、烷基或苄基；
R2为苯基、烷基苯基、烷氧基苯基、卤苯基、萘基、噻吩基、吡啶基、氰苯基、烷基或苄基。
2.如权利要求1所述的具有1,2,4-三嗪骨架结构的衍生物，其特征在于：
所述的R1为苯基、对甲基苯基、间甲基苯基、邻甲基苯基、对氯苯基、对溴苯基、间溴苯基、对三氟甲基苯基、2-萘基、对硝基苯、3-吡啶基或正丙基。
3.如权利要求1所述的具有1,2,4-三嗪骨架结构的衍生物，其特征在于：
所述的R2为苯基、对甲基苯基、邻甲基苯基、对甲氧基苯基、对氯苯基、邻氯苯基、间氯苯基、2-萘基、3-吡啶基、对氰基苯基或正戊基。
4.权利要求1所述的具有1,2,4-三嗪骨架结构的衍生物的合成方法，其特征在于：
在有机溶剂中，在惰性气体保护下，以偶氮甲碱叶立德和甘氨酸甲酯衍生的亚胺为原料，铜盐/Ferrocenyl-based Ligand络合物为催化剂，加入碳酸盐或有机碱，在-20～25℃温度下反应，蒸去溶剂，经柱层析得到目标化合物（Ⅰ）或（Ⅱ）。
5.如权利要求1所述的合成方法，其特征在于：
所述的偶氮甲碱叶立德和甘氨酸甲酯衍生的亚胺的摩尔比为1:1.2～1:5。
6.如权利要求1所述的合成方法，其特征在于：
所述的铜盐/Ferrocenyl-based Ligand络合物采用如下方法制备：
室温下，按铜盐摩尔数不大于手性配体Ferrocenyl-based Ligand摩尔数分别取铜盐和手性配体Ferrocenyl-based Ligand溶于有机溶剂中，经反应得到铜盐/Ferrocenyl-based Ligand络合物。
7.权利要求1～3中任一项所述的化合物作为杀菌剂的有效成分的应用。
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