CN115181090B - 二氢吲哚3,4并萘环骨架化合物的新用途及一种植物杀菌剂 - Google Patents

二氢吲哚3,4并萘环骨架化合物的新用途及一种植物杀菌剂 Download PDF

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CN115181090B
CN115181090B CN202210966742.4A CN202210966742A CN115181090B CN 115181090 B CN115181090 B CN 115181090B CN 202210966742 A CN202210966742 A CN 202210966742A CN 115181090 B CN115181090 B CN 115181090B
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邱斌
肖建
时亚飞
安孝德
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Qingdao Agricultural University
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Abstract

本发明公开了二氢吲哚3,4并萘环骨架化合物的新用途及一种植物杀菌剂，属于有机农药技术领域。本发明所述的二氢吲哚3,4并萘环骨架化合物可被作为有效成分用于制备植物杀菌剂，所制备的植物杀菌剂具有较好的杀菌活性，尤其对柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌以及小麦全蚀病菌等植物病害真菌，其杀菌效果非常优异，应用前景广阔。

Description

二氢吲哚3,4并萘环骨架化合物的新用途及一种植物杀菌剂
技术领域
本发明属于有机农药技术领域，具体涉及二氢吲哚3,4并萘环骨架化合物的新用途及一种植物杀菌剂。
背景技术
植物真菌性病害是指植物在生长发育过程中，由于真菌的入侵，使植物正常的生理功能受到损害甚至造成死亡。常见的植物病害真菌有柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌和小麦全蚀病菌等。每年由植物真菌病害造成的农作物损失占农业总产量的10～15％。因此，及时控制植物真菌病害可以有效减少经济损失。化学杀菌剂由于其效率高、速度快、可操作性强等特点，是防治植物病害最经济有效的方法。
发明内容
本发明在二氢吲哚3,4并萘环骨架化合物的合成研究中发现，该类化合物具有较好的杀菌活性，尤其对于柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌和小麦全蚀病菌等植物病害真菌具有优异的抑制活性。
为此，本发明提供了如下技术方案：
二氢吲哚3,4并萘环骨架化合物的用途，用于制备植物杀菌剂。
上述技术方案中，二氢吲哚3,4并萘环骨架化合物的结构如下所示：
Figure BDA0003795171730000011
其中：
R1选自甲基、苄基、丙烯基、甲基环丙基或3,5-二甲氧基苄基；R2选自氟或氯；R3选自氟、氯、甲氧基或苄氧基；R4与R5成环，环选自四氢异喹啉、哌啶、吗啉或硫代吗啉；或者，R4选自甲基，R5选自苄基。
在具体实施方案中，上述二氢吲哚3,4并萘环骨架化合物可选自如下具体结构：
Figure BDA0003795171730000021
上述技术方案中，所述植物杀菌剂的作用菌为柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌和/或小麦全蚀病菌。
本发明提供了一种植物杀菌剂，其有效成分为上述二氢吲哚3,4并萘环骨架化合物中的一种或几种。
上述技术方案中，植物杀菌剂还包含农药上可接受的助剂、添加剂、稳定剂、芳香剂、乳化剂或增效剂。
上述技术方案中，植物杀菌剂的有效浓度为50～100mg/L。优选地，该浓度为上述有效成分的总浓度。
上述技术方案中，植物杀菌剂的剂型为粉剂、悬浮剂、可湿性粉剂、乳剂、乳油、乳膏、糊剂、胶体剂、熏蒸剂、熏烟剂、烟雾剂、颗粒剂、微粒剂或油剂。
本发明的有益效果为：
本发明所述的二氢吲哚3,4并萘环骨架化合物可被作为有效成分用于制备植物杀菌剂，所制备的植物杀菌剂具有较好的杀菌活性，尤其对柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌以及小麦全蚀病菌等植物病害真菌，其杀菌效果非常优异，应用前景广阔。
附图说明
图1为苹果腐烂病菌的抑制效果图；
图2为柑橘炭疽病菌的抑制效果图；
图3为番茄灰霉病菌的抑制效果图；
图4为小麦全蚀病菌的抑制效果图；
图5为黄瓜枯萎病菌的抑制效果图。
具体实施方式
在本发明中所使用的术语，除非有另外说明，一般具有本领域普通技术人员通常理解的含义。下面结合具体实施例，并参照数据进一步详细的描述本发明。以下实施例只是为了举例说明本发明，而非以任何方式限制本发明的范围。
(一)二氢吲哚3,4并萘环骨架化合物的制备
取0.1mmol的2-吲哚基苯甲醛类化合物于反应瓶中，再加入0.1mmol仲胺类化合物，加入1.0mL溶剂乙醇，5mol％催化剂醋酸。控制体系温度为室温，空气气氛，持续搅拌，通过薄层色谱板点样跟踪反应至原料反应完全，待反应完成后，通过过滤、洗涤即可获得目标产物。
其中：
上述2-吲哚基苯甲醛类化合物选自如下结构：
Figure BDA0003795171730000031
其中，R1选自甲基、苄基、丙烯基、甲基环丙基或3,5-二甲氧基苄基；R2选自氟或氯；R3选自氟、氯、甲氧基或苄氧基。
上述仲胺类化合物选自如下结构：
Figure BDA0003795171730000032
其中，
R4与R5成环，环选自四氢异喹啉、哌啶、吗啉或硫代吗啉；或者，R4选自甲基，R5选自苄基。
在上述反应条件下，通过替换不同的反应底物——例如在实施例1中，反应底物为2-(1-甲基-1H-吲哚-4-基)苯甲醛和四氢异喹啉——共获得16种二氢吲哚3,4并萘环骨架化合物，具体如实施例1～16所示。
(二)二氢吲哚3,4并萘环骨架化合物抑菌活性测试
抑菌活性试验，如下所示：
选取柑橘炭疽病菌(C.gloeosporioides)、苹果腐烂病菌(V.mali)、黄瓜枯萎病菌(F.oxysporum)、番茄灰霉病菌(B.cinerea)和小麦全蚀病菌(G.graminis)等五种常见的菌株，采用菌丝生长率法(Irzykowska，2008)测定化合物的抑菌活性。上述供试菌株，均由山东省生物农药工程技术研究中心提供。
首先称取一定量的PDA(马铃薯葡萄糖琼脂)于广口烧瓶中，加入蒸馏水配置成培养基并放入120℃的高压灭菌锅中灭菌半小时。称取1mg待测药品溶于10mL的丙酮中配置成100mg/L的药剂，再取其中一半药剂用丙酮稀释到10mL配置成50mg/L的药剂。取其中5mL药剂倒入50mL马铃薯葡萄糖琼脂中混匀，再分别倒入5个高温灭菌的培养基中。待其冷却后用接种环分别接种上述五种病菌，用封口膜密封后转移到适宜温度下进行观察。当不加药剂的对照组中菌落达到80％时，采用十字交叉法对实验组菌落进行测量，公式如下：
抑制率＝(对照组菌落直径—实验组菌落直径)/对照组菌落直径×100％
试验结果如表1所示：
表1目标化合物的抑菌活性(抑制率％)
Figure BDA0003795171730000041
由表1可知，本发明合成的二氢吲哚3,4并萘环骨架化合物，对柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌和小麦全蚀病菌均展现了非常优异的抑制活性(除了个别病菌外)。因此，在实际应用过程中，可将上述二氢吲哚3,4并萘环骨架化合物制备成植物杀菌剂，应用前景可观。
实施例1-16的反应产物，其结构以及核磁共振数据如下所示：
实施例1
Figure BDA0003795171730000051
5-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-4,5-dihydronaphtho[3,2,1-cd]indole(3a):According to general procedure(for 24h),1a(23.5mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3a(30.8mg,88％)as a yellowsolid by filtering and washing with EtOH,mp 152–154℃.1H NMR(500MHz,CDCl3)δ8.52(d,J＝10.0Hz,1H),7.85(d,J＝5.0Hz,1H),7.66(d,J＝10.0Hz,1H),7.58(d,J＝5.0Hz,2H),7.53(t,J＝10.0Hz,1H),7.49(t,J＝10.0Hz,1H),7.09(s,2H),7.06(s,1H),6.90(d,J＝10.0Hz,1H),6.47(d,J＝5.0Hz,1H),5.70(s,1H),3.84(dd,J＝125.0,15.0Hz,2H),3.18–3.16(m,1H),3.14(s,3H),2.98(t,J＝10.0Hz,2H),2.90–2.85(m,1H).13C NMR(126MHz,DMSO)δ151.58,136.79,135.36,134.86,134.07,130.73,129.77,129.27,129.08,128.21,127.03,126.92,126.42,126.33,126.17,125.88,123.70,118.92,109.24,100.09,87.06,48.82,46.39,33.40,30.04.HRMS(ESI-TOF)m/z calcd for C25H23N2[M+H]+:351.1856；found:351.1856.
实施例2
Figure BDA0003795171730000052
4-benzyl-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4,5-dihydronaphtho[3,2,1-cd]indole(3b):According to general procedure(for 24h),1b(31.1mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3b(28.7mg,67％)as a yellowsolid by filtering and washing with EtOH,mp 120–122℃.1H NMR(500MHz,CDCl3)δ8.53(d,J＝10.0Hz,1H),7.85(d,J＝5.0Hz,1H),7.68(d,J＝10.0Hz,1H),7.60–7.57(m,2H),7.55–7.52(m,1H),7.45(t,J＝10.0Hz,1H),7.33–7.32(m,2H),7.29–7.26(m,2H),7.23–7.21(m,2H),7.10–7.04(m,3H),6.91(d,J＝5.0Hz,1H),6.47(d,J＝5.0Hz,1H),5.87(d,J＝1.5Hz,1H),4.73(dd,J＝40.0,20.0Hz,2H),3.86(dd,J＝155.0,15.0Hz,2H),3.15–3.11(m,1H),2.95–2.83(m,3H).13C NMR(126MHz,CDCl3)δ150.80,138.76,136.23,135.25,134.78,133.91,130.12,129.55,129.31,128.92,128.67(s,2C),128.61,127.51(s,2C),127.07,126.77,126.46,126.28,126.02,125.94,125.60,123.34,119.01,109.35,99.85,85.33,49.12,49.08,45.92,30.16.HRMS(ESI-TOF)m/z calcd for C31H27N2[M+H]+:427.2169；found:427.2166.
实施例3
Figure BDA0003795171730000061
4-allyl-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4,5-dihydronaphtho[3,2,1-cd]indole(3c):According to general procedure(for 24h),1c(26.1mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3c(29.5mg,78％)as a yellowsolid by filtering and washing with EtOH,mp 121–124℃.1H NMR(500MHz,CDCl3)δ8.53(d,J＝5.0Hz,1H),7.85(d,J＝10.0Hz,1H),7.68(d,J＝10.0Hz,1H),7.60(d,J＝5.0Hz,1H),7.59–7.57(m,1H),7.55–7.52(m,1H),7.49–7.46(m,1H),7.10–7.08(m,2H),7.08–7.05(m,1H),6.91(d,J＝10.0Hz,1H),6.51(d,J＝5.0Hz,1H),5.96–5.89(m,1H),5.88(d,J＝1.0Hz,1H),5.29–5.26(m,1H),5.19–5.17(m,1H),4.18–4.08(m,2H),3.88(dd,J＝140.0,15.0Hz,2H),3.18–3.13(m,1H),2.98–2.92(m,2H),2.89–2.82(m,1H).13C NMR(126MHz,CDCl3)δ150.56,136.42,135.30,134.78,134.20,133.95,130.04,129.56,129.31,128.93,128.50,126.76,126.47,126.41,126.01,125.89,125.61,123.32,118.97,116.78,109.32,100.10,85.64,49.07,48.61,46.04,30.20.HRMS(ESI-TOF)m/z calcd forC27H25N2[M+H]+:377.2012；found:377.2010.
实施例4
Figure BDA0003795171730000062
4-(cyclopropylmethyl)-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4,5-dihydronap-htho[3,2,1-cd]indole(3d):According to general procedure(for 24h),1d(27.5mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3d(34.9mg,89％)as a yellow solid by filtering and washing with EtOH,mp 174–178℃.1H NMR(500MHz,CDCl3)δ8.52(d,J＝10.0Hz,1H),7.84(d,J＝10.0Hz,1H),7.63(d,J＝10.0Hz,1H),7.60(s,1H),7.58–7.56(m,1H),7.55–7.51(m,1H),7.49–7.46(m,1H),7.10–7.09(m,2H),7.08–7.05(m,1H),6.92(d,J＝10.0Hz,1H),6.51(d,J＝5.0Hz,1H),6.04(d,J＝5.0Hz,1H),3.86(dd,J＝170.0,15.0Hz,2H),3.60(dd,J＝15.0,5.0Hz,1H),3.19(dd,J＝15.0,5.0Hz,1H),3.16–3.13(m,1H),2.95–2.85(m,3H),1.18–1.10(m,1H),0.58–0.53(m,1H),0.48–0.43(m,1H),0.38(td,J＝10.0,5.0Hz,1H),0.23(td,J＝10.0,5.0Hz,1H).13CNMR(126MHz,CDCl3)δ150.49,136.44,135.30,134.77,133.84,130.09,129.49,129.23,128.88,128.63,126.74,126.35(s,2C),125.97,125.79,125.58,123.31,118.73,108.57,99.16,84.73,49.28,48.90,45.65,30.11,9.76,4.74,2.72.HRMS(ESI-TOF)m/z calcd forC28H27N2[M+H]+:391.2169；found:391.2163.
实施例5
Figure BDA0003795171730000071
5-(3,4-dihydroisoquinolin-2(1H)-yl)-4-(3,5-dimethoxybenzyl)-4,5-dihydrona-phtho[3,2,1-cd]indole(3e):According to general procedure(for 24h),1e(37.1mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3e(36.4mg,75％)as a brown solid by filtering and washing with EtOH,mp 147–149℃.1H NMR(500MHz,CDCl3)δ8.54(d,J＝10.0Hz,1H),7.86(d,J＝10Hz,1H),7.69(d,J＝10.0Hz,1H),7.61–7.58(m,2H),7.56–7.53(m,1H),7.46(t,J＝10.0Hz,1H),7.11–7.09(m,2H),7.08–7.05(m,1H),6.91(d,J＝10.0Hz,1H),6.51–6.488(m,3H),6.33(t,J＝5.0Hz,1H),5.90(s,1H),4.67(dd,J＝35.0,15.0Hz,2H),4.02(d,J＝15.0Hz,1H),3.72(d,J＝15.0Hz,1H),3.67(s,6H),3.19–3.14(m,1H),2.96–2.86(m,3H).13C NMR(126MHz,CDCl3)δ161.09(s,2C),150.78,141.38,136.15,135.21,134.73,133.89,130.08,129.55,129.26,128.86,128.56,126.70,126.39,126.25,125.97,125.87,125.56,123.28,118.92,109.41,105.41(s,2C),99.97,98.94,85.64,55.24(s,2C),49.50,49.06,45.96,30.17.HRMS(ESI-TOF)m/z calcd for C33H31N2O2[M+H]+:487.2380；found:487.2383.
实施例6
Figure BDA0003795171730000081
5-(3,4-dihydroisoquinolin-2(1H)-yl)-8-methoxy-4-methyl-4,5-dihydronapht-ho[3,2,1-cd]in dole(3f):According to general procedure(for 24h),1f(26.5mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3f(27.0mg,71％)as a yellow solid by filtering and washing with EtOH,mp 164–166℃.1H NMR(500MHz,CDCl3)δ8.42(d,J＝10.0Hz,1H),7.58(d,J＝10.0Hz,1H),7.54(d,J＝1.0Hz,1H),7.49–7.46(m,1H),7.25–7.23(m,2H),7.11(d,J＝4.0Hz,2H),7.09–7.05(m,1H),6.92(d,J＝10.0Hz,1H),6.43(d,J＝5.0Hz,1H),5.72(d,J＝1.5Hz,1H),3.98(d,J＝15.0Hz,1H),3.92(s,3H),3.74(d,J＝15.0Hz,1H),3.22–3.19(m,1H),3.16(s,3H),3.03–2.96(m,2H),2.92–2.87(m,1H).13C NMR(126MHz,CDCl3)δ158.10,151.43,137.23,135.46,135.28,134.72,130.21,128.88,128.47,126.74,125.95,125.58,125.46,124.70,123.94,118.33,116.45,109.30,108.65,98.56,87.67,55.37,48.93,46.47,33.30,30.24.HRMS(ESI-TOF)m/z calcd for C26H25N2O[M+H]+:381.1961；found:381.1959.
实施例7
Figure BDA0003795171730000082
8-(benzyloxy)-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-4,5-dihydronap-htho[3,2,1-cd]indole(3g):According to general procedure(for 24h),1g(34.1mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3g(31.0mg,68％)as a yellow solid by filtering and washing with EtOH,mp 158–160℃.1H NMR(500MHz,CDCl3)δ8.42(d,J＝10.0Hz,1H),7.57(d,J＝10.0Hz,1H),7.50(s,1H),7.48(s,1H),7.46-7.45(m,2H),7.38(t,J＝10.0Hz,2H),7.33–7.29(m,3H),7.10-7.09(m,2H),7.08–7.04(m,1H),6.91(d,J＝5.0Hz,1H),6.42(d,J＝5.0Hz,1H),5.68(s,1H),5.17(s,2H),3.85(dd,J＝120.0,15.0Hz,2H),3.19–3.16(m,1H),3.14(s,3H),3.01–2.94(m,2H),2.90–2.86(m,1H).13C NMR(126MHz,CDCl3)δ157.38,151.44,137.27,137.07,135.46,135.31,134.74,130.23,128.87,128.64(s,2C),128.49,128.01,127.55(s,2C),126.73,125.95,125.58,125.54,124.75,124.19,118.32,116.93,110.80,108.70,98.63,87.68,70.21,49.02,46.42,33.25,30.25.HRMS(ESI-TOF)m/z calcd for C32H29N2O[M+H]+:457.2274；found:457.2274.
实施例8
Figure BDA0003795171730000091
9-chloro-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-4,5-dihydronaphtho
[3,2,1-cd]indole(3h):According to general procedure(for 24h),1h(27.0mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3h(30.7mg,80％)as a yellow solid by filtering and washing with EtOH,mp 141–143℃.1H NMR(500MHz,CDCl3)δ8.47(d,J＝5.0Hz,1H),7.75(d,J＝10.0Hz,1H),7.57(d,J＝10.0Hz,1H),7.53(s,1H),7.51(d,J＝5.0Hz,1H),7.48–7.46(m,1H),7.11–7.09(m,2H),7.08–7.05(m,1H),6.91(d,J＝5.0Hz,1H),6.48(d,J＝10.0Hz,1H),5.69(s,1H),3.84(dd,J＝130.0,15.0Hz,2H),3.19–3.17(m,1H),3.15(s,3H),3.00–2.95(m,2H),2.91–2.84(m,1H).13C NMR(126MHz,CDCl3)δ151.31,136.98,135.12,134.66,132.22,131.76,130.55(s,2C),130.47,128.91,127.50,126.87,126.73,126.62,126.04,125.64,122.90,118.30,108.92,99.82,87.54,48.95,46.43,33.16,30.21.HRMS(ESI-TOF)m/zcalcd for C25H22ClN2[M+H]+:385.1466；found:385.1467.
实施例9
Figure BDA0003795171730000092
8-chloro-5-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-4,5-dihydronaphtho
[3,2,1-cd]indole(3i):According to general procedure(for 24h),1i(27.0mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3i(32.5mg,84％)as a yellow solid by filtering and washing with EtOH,mp 160–162℃.1H NMR(500MHz,CDCl3)δ8.42(d,J＝10.0Hz,1H),7.81(d,J＝5.0Hz,1H),7.59(d,J＝5.0Hz,1H),7.52–7.50(m,2H),7.48-7.47(m,1H),7.11–7.09(m,2H),7.08–7.05(m,1H),6.91(d,J＝5.0Hz,1H),6.47(d,J＝10.0Hz,1H),5.69(s,1H),3.84(dd,J＝125.0,15.0Hz,2H),3.18–3.16(m,1H),3.15(s,3H),3.00–2.95(m,2H),2.91–2.86(m,1H).13C NMR(126MHz,CDCl3)δ151.40,138.01,135.10,135.06,134.65,132.07,130.63,128.88,128.15,128.09,127.88,126.69,126.30,126.26,126.03,125.62,124.79,117.77,108.83,99.60,87.52,49.05,46.36,33.10,30.19.HRMS(ESI-TOF)m/z calcd for C25H22ClN2[M+H]+:385.1466；found:385.1463.
实施例10
Figure BDA0003795171730000101
5-(3,4-dihydroisoquinolin-2(1H)-yl)-8-fluoro-4-methyl-4,5-dihydronaphtho
[3,2,1-cd]indole(3j):According to general procedure(for 24h),1j(25.3mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3j(26.7mg,72％)as a yellow solid by filtering and washing with EtOH,mp 180–182℃.1H NMR(500MHz,CDCl3)δ8.48(dd,J＝10.0,5.0Hz,1H),7.59(d,J＝5.0Hz,1H),7.51(s,1H),7.50–7.46(m,2H),7.34–7.30(m,1H),7.11-7.10(m,2H),7.08–7.05(m,1H),6.91(d,J＝10.0Hz,1H),6.46(d,J＝10.0Hz,1H),5.70(s,1H),3.84(dd,J＝125.0,15.0Hz,2H),3.20–3.16(m,1H),3.15(s,3H),3.01–2.95(m,2H),2.91–2.86(m,1H).13C NMR(126MHz,CDCl3)δ161.19(d,J＝245.7Hz),151.44,138.03,135.41(d,J＝8.8Hz),135.13,134.66,130.61,128.92,128.26,126.73,126.14(d,J＝1.3Hz),126.04,125.94,125.64,125.36(d,J＝10.1Hz),118.09(d,J＝3.8Hz),114.82(d,J＝23.9Hz),113.21(d,J＝21.4Hz),108.75,99.25,87.52,48.97,46.45,33.20,30.21.HRMS(ESI-TOF)m/z calcd for C25H22FN2[M+H]+:369.1762；found:369.1761.
实施例11
Figure BDA0003795171730000102
5-(3,4-dihydroisoquinolin-2(1H)-yl)-9-fluoro-4-methyl-4,5-dihydronaphtho
[3,2,1-cd]indole(3k):According to general procedure(for 24h),1k(25.3mg,0.1mmol),2a(13.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3k(26.4mg,72％)as a yellow solid by filtering and washing with EtOH,mp 140–143℃.1H NMR(500MHz,CDCl3)δ8.12(dd,J＝10.0,5.0Hz,1H),7.81(dd,J＝8.5,5.5Hz,1H),7.56(s,1H),7.54(d,J＝10.0Hz,1H),7.49(t,J＝5.0Hz,1H),7.29(td,J＝10.0,5.0Hz,1H),7.11(d,J＝5.0Hz,2H),7.08–7.05(m,1H),6.91(d,J＝10.0Hz,1H),6.48(d,J＝10.0Hz,1H),5.71(s,1H),3.84(dd,J＝125.0,15.0Hz,2H),3.19–3.17(m,1H),3.15(s,3H),3.01–2.95(m,2H),2.91–2.86(m,1H).13C NMR(126MHz,CDCl3)δ161.13(d,J＝245.7Hz),151.35,135.83(d,J＝2.5Hz),135.18,134.69,131.10(d,J＝8.8Hz),130.91(d,J＝8.8Hz),130.62,130.15,128.88,127.89(d,J＝3.8Hz),126.71,126.61,126.00,125.61,118.40,115.44(d,J＝23.9Hz),109.06,108.14(d,J＝21.4Hz),99.71,87.56,48.99,46.37,33.11,30.21.HRMS(ESI-TOF)m/z calcd for C25H22FN2[M+H]+:369.1762；found:369.1763.
实施例12
Figure BDA0003795171730000111
4-(4-(3,5-dimethoxybenzyl)-4,5-dihydronaphtho[3,2,1-cd]indol-5-yl)morpho-line(3l):According to general procedure(for 24h),1e(37.1mg,0.1mmol),2l(8.7mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3l(34.5mg,78％)as a brownsolid by filtering and washing with EtOH,mp 162–164℃.1H NMR(500MHz,CDCl3)δ8.53(d,J＝5.0Hz,1H),7.91–7.89(m,1H),7.66(d,J＝10.0Hz,1H),7.62–7.56(m,3H),7.42(t,J＝10.0Hz,1H),6.52(d,J＝5.0Hz,2H),6.46(d,J＝10.0Hz,1H),6.36(t,J＝5.0Hz,1H),5.64(s,1H),4.65(dd,J＝25.0,15.0Hz,2H),3.73(s,6H),3.71–3.65(m,4H),2.86–2.83(m,2H),2.60–2.56(m,2H).13C NMR(126MHz,CDCl3)δ161.13(s,2C),150.65,141.32,135.79,133.81,130.02,129.52,129.28,128.52,126.42,126.11,125.92,123.27,119.01,109.46,105.51(s,2C),99.87,98.81,85.57,67.44(s,2C),55.29(s,2C),49.37,47.60(s,2C).HRMS(ESI-TOF)m/z calcd for C28H29N2O3[M+H]+:441.2173；found:441.2171.
实施例13
Figure BDA0003795171730000121
N-benzyl-N,4-dimethyl-4,5-dihydronaphtho[3,2,1-cd]indol-5-amine(3m):According to general procedure(for 24h),1a(23.5mg,0.1mmol),2m(12.1mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3m(21.0mg,62％)as a yellow solid byfiltering and washing with EtOH,mp 101–103℃.1H NMR(500MHz,CDCl3)δ8.53–8.52(m,1H),7.94–7.93(m,1H),7.64–7.63(m,2H),7.60–7.56(m,2H),7.47(t,J＝10.0Hz,2H),7.40(d,J＝10.0Hz,2H),7.33(t,J＝10.0Hz,2H),7.26–7.23(m,1H),6.44(d,J＝5.0Hz,1H),5.67(d,J＝1.5Hz,1H),3.77(dd,J＝80.0,10.0Hz,2H),3.20(s,3H),2.33(s,3H).13C NMR(126MHz,CDCl3)δ151.15,139.68,136.96,133.98,130.06,129.52,129.28,128.54(s,2C),128.38,128.33(s,2C),126.96,126.31(s,2C),125.76,123.34,118.56,108.86,99.04,87.09,56.25,36.37,32.59.HRMS(ESI-TOF)m/zcalcd for C24H23N2[M+H]+:339.1856；found:339.1857.
实施例14
Figure BDA0003795171730000122
4-methyl-5-(piperidin-1-yl)-4,5-dihydronaphtho[3,2,1-cd]indole(3n):According to general procedure(for 24h),1a(23.5mg,0.1mmol),2n(8.5mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3n(21.8mg,73％)as a yellow solid by filteringand washing with EtOH,mp 165–168℃.1H NMR(500MHz,CDCl3)δ8.51–8.49(m,1H),7.90–7.89(m,1H),7.60(d,J＝10.0Hz,1H),7.59–7.53(m,3H),7.45(t,J＝10.0Hz,1H),6.41(d,J＝5.0Hz,1H),5.46(d,J＝1.5Hz,1H),3.11(s,3H),2.76–2.72(m,2H),2.56–2.52(m,2H),1.58–1.53(m,4H),1.47–1.43(m,2H).13C NMR(126MHz,CDCl3)δ151.41,137.11,133.97,129.98,129.45,129.24,128.28,126.39,126.22,125.61,123.32,118.58,108.64,98.82,88.01,48.54(s,2C),32.75,26.52(s,2C),24.99.HRMS(ESI-TOF)m/z calcd for C21H23N2[M+H]+:303.1856；found:303.1855.
实施例15
Figure BDA0003795171730000131
4-(4-methyl-4,5-dihydronaphtho[3,2,1-cd]indol-5-yl)morpholine(3o):According to general procedure(for 24h),1a(23.5mg,0.1mmol),2o(8.7mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3o(25.1mg,84％)as a yellow solid by filteringand washing with EtOH,mp 165–167℃.1H NMR(500MHz,CDCl3)δ8.51–8.50(m,1H),7.90–7.88(m,1H),7.63(d,J＝10.0Hz,1H),7.60–7.54(m,3H),7.46(t,J＝10.0Hz,1H),6.43(d,J＝10.0Hz,1H),5.45(d,J＝1.5Hz,1H),3.74–3.67(m,4H),3.13(s,3H),2.83–2.79(m,2H),2.63–2.59(m,2H).13C NMR(126MHz,CDCl3)δ151.23,136.18,133.89,130.05,129.51,129.31,128.33,126.39,126.22,125.89,123.31,118.98,109.10,99.28,87.55,67.51(s,2C),47.74(s,2C),33.09.HRMS(ESI-TOF)m/z calcd for C20H21N2O[M+H]+:305.1648；found:305.1649.
实施例16
Figure BDA0003795171730000132
4-(4-methyl-4,5-dihydronaphtho[3,2,1-cd]indol-5-yl)thiomorpholine(3p):According to general procedure(for 24h),1a(23.5mg,0.1mmol),2p(10.3mg,0.1mmol),AcOH(0.3mg,0.005mmol),afforded 3o(21.5mg,67％)as a yellow solid byfiltering and washing with EtOH,mp145–147℃.1H NMR(500MHz,CDCl3)δ8.51–8.49(m,1H),7.90–7.88(m,1H),7.62(d,J＝1.0Hz,1H),7.60–7.54(m,3H),7.45(t,J＝10.0Hz,1H),6.41(d,J＝10.0Hz,1H),5.39(d,J＝1.5Hz,1H),3.09(s,3H),3.08–3.05(m,2H),2.9–2.87(m,2H),2.69–2.61(m,4H).13C NMR(126MHz,CDCl3)δ151.03,136.37,133.92,130.05,129.48,129.30,128.34,126.38,126.15,125.86,123.32,118.70,109.01,99.07,88.70,50.18(s,2C),32.49,28.68(s,2C).HRMS(ESI-TOF)m/z calcd for C20H21N2S[M+H]+:321.1420；found:321.1420.
以上所述，仅是本发明的较佳实施例而已，并非是对本发明作其它形式的限制，任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是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作的任何简单修改、等同变化与改型，仍属于本发明技术方案的保护范围。

Claims (7)

1.二氢吲哚3,4并萘环骨架化合物在制备植物杀菌剂中的应用；
所述二氢吲哚3,4并萘环骨架化合物的结构如下所示：
Figure FDA0004127224730000011
其中：
R1选自甲基；R2选自氯；R3选自甲氧基；R4与R5形成四氢异喹啉环。
2.二氢吲哚3,4并萘环骨架化合物在制备植物杀菌剂中的应用，其特征在于，所述二氢吲哚3,4并萘环骨架化合物具体选自如下结构式的化合物：
Figure FDA0004127224730000012
3.根据权利要求1所述的应用，其特征在于，所述植物杀菌剂的作用菌为柑橘炭疽病菌、苹果腐烂病菌、黄瓜枯萎病菌、番茄灰霉病菌和/或小麦全蚀病菌。
4.一种植物杀菌剂，其特征在于，其有效成分为权利要求1或2中所述二氢吲哚3,4并萘环骨架化合物中的一种或几种。
5.根据权利要求4所述的植物杀菌剂，其特征在于，所述植物杀菌剂还包含农药上可接受的助剂、添加剂、稳定剂、芳香剂、乳化剂或增效剂。
6.根据权利要求4所述的植物杀菌剂，其特征在于，所述植物杀菌剂的有效浓度为50～100mg/L。
7.根据权利要求4所述的植物杀菌剂，其特征在于，所述植物杀菌剂的剂型为粉剂、悬浮剂、可湿性粉剂、乳剂、乳油、乳膏、糊剂、胶体剂、熏蒸剂、熏烟剂、烟雾剂、颗粒剂、微粒剂或油剂。
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