CN115417879A - 一种n-嘧啶基环亚胺二苯并[1,5]二氮杂环辛衍生物及其制备和应用 - Google Patents
一种n-嘧啶基环亚胺二苯并[1,5]二氮杂环辛衍生物及其制备和应用 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Agronomy & Crop Science (AREA)
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Abstract
本发明公开一种N‑嘧啶基环亚胺二苯并[1,5]二氮杂环辛衍生物及其制备和应用，涉及有机合成技术领域。本发明的N‑嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其结构通式为：
；其中R1和R2为分别选自H、C1‑C4的烷基、C1‑C4烷氧基、卤素、卤代C1‑C4烷基、硝基、芳基。本发明的化合物对多种农作物细菌性病害具有明显的抑制活性。
Description
技术领域
本发明涉及一种N-嘧啶基环亚胺二苯并[1,5]二氮杂环辛衍生物及其制备和应用，涉及有机合成技术领域。
背景技术
杂环化合物结构多样、数量庞大，占已知有机化合物的一半以上。根据所含杂原子的不同，杂环化合物可以分为含氮杂环、含氧杂环、含硫杂环等，有的同时含有多种杂原子。其中，含氮杂环最为常见，应用也最广泛。比如：在天然产物方面，一系列以生物碱为代表的含氮天然产物，具有丰富的生物活性，其中包括许多处方药，如阿托品(Atropine)、毒芹碱(Coniine)、维生素B1(Vitamin B1)、吗啡(Morphine)、罂粟碱(PapaVerine)、咖啡因(Caffeine)和尼古丁(Nicotine)和血清素(5-hydroxytryptamine)等。在医药领域，含氮杂环化合物不仅作为基本骨架存在于多种有生物活性的天然产物中，而且一些合成的含氮杂环化合物或经结构修饰后的天然产物，也已成为医药市场的明星药物。在生活方面，含氮杂环化合物亦广泛存在于饮食中，如硫胺素（维生素B1）、核黄素（维生素B2）、吡哆素（维生素B6）、烟酰胺（维生素B3）等。在农药领域，大多数含氮杂环化合物具有广谱的生物活性，在植物保护中具有重要的应用。过去几十年以来，人们一直致力于开发新型、灵活、高效的含氮杂环化合物及其合成方法。
发明内容
本发明的目的之一是提供一类N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其化学名为13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物。
为实现上述目的，本发明的技术方案如下：
一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其结构通式为：
通式(I)中，R1选自H、C1-C4的烷基、C1-C4烷氧基、卤素、卤代C1-C4烷基；R2选自H、C1-C4的烷基、卤素、C1-C4烷氧基、硝基、芳基。
优选的R1选自 H、Cl、Br、CH3、OCH3；R2选自H、F、Cl、Br、CH3、OCH3、NO2、Ph。
本发明的另一目的在于：提供一种酸催化剂催化的由2-氨基-5-取代嘧啶和2-氨基-4-取代苯甲醛出发，通过一锅法反应，获得13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，包括以下步骤：
步骤一：将2-氨基-5-取代嘧啶和2-氨基-4-取代苯甲醛溶于有机溶剂，在酸催化下加热回流反应，得含有通式(I)的反应混合物；
步骤二：将所述含有通式(I)的反应混合物减压旋蒸、柱层析分离、重结晶提纯、干燥，得具有通式(I)的13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物。
由此，通过“一锅法”合成N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物。本发明的合成方法具有广泛的底物适应性、反应条件温和、原料易得、合成过程简单的特点。
优选的，步骤一中，所述酸催化的催化剂为质子酸或路易斯酸。
更优选的，所述质子酸为醋酸、五氟苯甲酸或对甲基苯磺酸，所述路易斯酸为氯化铝、氯化铁、三氟甲磺酸镱或三氟甲磺酸钪。
优选的，步骤一中，所述催化剂用量在基于所述式 (I) 化合物的 1-20 mol％的范围内。
更优选的，所述催化剂用量在 5-20 mol％的范围内。
还优选的，所述催化剂用量在5-15 mol％的范围内。
优选的，步骤一中，所述有机溶剂为质子性和非质子性溶剂。
更优选的，所述有机溶剂为无水乙醇、甲苯、二甲基亚砜、N,N-二甲基甲酰胺、正丁醇、1,2-二氯乙烷或乙腈。
优选的，步骤一中，所述加热回流温度为40~130℃，反应时间为8~40h。
更优选的，加热回流温度为70~110℃，反应时间为12~20h。
优选的，步骤一中，2-氨基-5-取代嘧啶与2-氨基-4-取代苯甲醛的物质的量之比为1:1~10。
更优选的，所述2-氨基-5-取代嘧啶与所述2-氨基-4-取代苯甲醛的物质的量之比为1:2~5。
优选的，步骤二中，所述分离为柱层析分离，使用石油醚/乙酸乙酯作为流动相=5~30/1（v/v）；所述提纯为重结晶，使用石油醚/乙酸乙酯的混合液作为溶剂。
本发明的又一目的在于提供一种上述N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物作为农作物细菌性病害杀菌剂的应用。
优选的，所述农作物细菌性病害为番茄早疫病、小麦赤霉病、油菜菌核病、水稻纹枯病、苹果轮纹病、小麦纹枯病和水稻恶苗病中的一种或几种。
本发明的有益效果
本发明提供了一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物及其制备方法和应用。本发明的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其结构通式为：
；其中R1和R2为分别选自H、C1-C4的烷基、C1-C4烷氧基、卤素、卤代C1-C4烷基、硝基、芳基。通过“一锅法”合成N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物。本发明的化合物对多种农作物细菌性病害具有明显的抑制活性，可用于植物病害防治。本发明具有反应条件简单温和、原料易得、合成过程简单的特点。
具体实施方式
为了更好地理解本发明，结合以下实施例对本发明作进一步描述，但本发明的内容并不局限于此。
实施例1：
一种13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，具体步骤如下：
具体化合物见表1。
表1 所合成的目标化合物
以No.1, R1=H, R2=H的化合物为例说明合成方法，其它化合物的合成方法类似。
(No.1) 13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛
具体合成步骤及表征如下：
向100 mL三口瓶中加入0.2423 g (2 mmol ) 2-氨基苯甲醛，0.0951 g (1 mmol)2-氨基嘧啶，0.0172g (10 mol%)对甲苯磺酸和4mL乙腈，加热至80℃，反应16小时。反应结束后，经柱层析分离提纯(石油醚:乙酸乙酯=10:1)，得白色粉末状固体13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛，产率为49%。用核磁共振氢谱和碳谱对结构进行表征，得如下结果：1H NMR (500 MHz, DMSO-d 6): δ 8.46 (d, J = 4.7 Hz, 2H),7.20 (d, J = 7.3 Hz, 2H), 6.95 (t, J = 6.9 Hz, 4H), 6.76 (t, J = 4.7 Hz, 1H),6.66 (s, 2H), 6.61 (t, J = 7.3 Hz, 2H), 6.54 (d, J = 8.0 Hz, 2H). 13C{1H} NMR(125 MHz, DMSO-d 6): δ 159.34, 158.34, 142.27, 128.07, 128.01, 123.80, 116.80,115.08, 111.84, 59.36。高分辨质谱结果为HRMS (ESI) m/z: [M + H]+ calcd forC18H15N5 302.1400, found 302.1385。
具体的，表1中的化合物表征数据为：
No.1：13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率49%. 1H NMR (500 MHz, DMSO-d 6): δ 8.46 (d, J = 4.7 Hz, 2H), 7.20(d, J = 7.3 Hz, 2H), 6.95 (t, J = 6.9 Hz, 4H), 6.76 (t, J = 4.7 Hz, 1H), 6.66(s, 2H), 6.61 (t, J = 7.3 Hz, 2H), 6.54 (d, J = 8.0 Hz, 2H). 13C{1H} NMR (125MHz, DMSO-d 6): δ 159.34, 158.34, 142.27, 128.07, 128.01, 123.80, 116.80,115.08, 111.84, 59.36。HRMS (ESI) m/z: [M + H]+ calcd for C18H15N5 302.1400,found 302.1385。
：3,9-二氟-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率56%. 1H NMR (500 MHz, DMSO-d 6): δ 8.48 (d, J = 4.7 Hz, 2H),7.30 (d, J = 3.2 Hz, 2H), 7.23 (t, J = 7.4 Hz, 2H), 6.80 (t, J = 4.7 Hz, 1H),6.69 (d, J = 3.2 Hz, 2H), 6.45 – 6.35 (m, 2H), 6.32 (d, J = 11.1 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 162.13 (d, J = 240.7 Hz), 159.20, 158.43,143.93 (d, J = 11.8 Hz), 129.67 (d, J = 10.3 Hz), 119.65, 112.27, 103.37 (d,J = 22.0 Hz), 100.70 (d, J = 24.7 Hz), 58.57. HRMS (ESI) m/z: [M + H]+ calcdfor C18H13F2N5 338.1212; found 338.1177。
：3,9-二氯-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率53%. 1H NMR (500 MHz, DMSO-d 6): δ 8.48 (d, J = 4.7 Hz, 2H),7.32 (d, J = 2.8 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.81 (t, J = 4.7 Hz, 1H),6.70 (d, J = 3.0 Hz, 2H), 6.63 (d, J = 8.1 Hz, 2H), 6.58 (s, 2H). 13C{1H} NMR(125 MHz, DMSO-d 6): δ 159.19, 158.45, 143.68, 132.39, 129.66, 122.12, 116.41,113.96, 112.42, 58.63. HRMS (ESI) m/z: [M + H]+ calcd for C18H13Cl2N5 370.0621,found 370.0586。
：3,9-二溴-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率51%. 1H NMR (500 MHz, DMSO-d 6): δ 8.48 (d, J = 4.7 Hz, 2H),7.31 (d, J = 3.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 6.81 (t, J = 4.7 Hz, 1H),6.79 – 6.71 (m, 4H), 6.69 (d, J = 3.3 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6):δ 159.16, 158.42, 143.92, 129.90, 122.47, 120.86, 119.23, 116.84, 112.42,58.66. HRMS (ESI) m/z: [M + H]+ calcd for C18H13Br2N5 457.9610; found 457.9611。
：3,9-二硝基-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 黄色固体, 产率56%. 1H NMR (500 MHz, DMSO-d 6): δ 8.52 (d, J = 4.7 Hz, 2H),7.85 (d, J = 3.2 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 9.2 Hz, 4H),6.94 (d, J = 3.3 Hz, 2H), 6.87 (t, J = 4.7 Hz, 1H). 13C{1H} NMR (125 MHz,DMSO-d 6): δ 159.12, 158.57, 147.66, 143.06, 129.24, 113.03, 111.26, 108.99,58.70. HRMS (ESI) m/z: [M + H]+ calcd for C18H13N7O4 392.1102, found 392.1101。
：3,9-二甲基-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率35% . 1H NMR (500 MHz, DMSO-d 6): δ 8.45 (d, J = 4.5 Hz, 2H),7.08 (d, J = 7.6 Hz, 2H), 6.80 (s, 2H), 6.73 (t, J = 4.4 Hz, 1H), 6.61 (s,2H), 6.43 (d, J = 7.4 Hz, 2H), 6.34 (s, 2H), 2.11 (s, 6H). 13C{1H} NMR (125MHz, DMSO-d 6): δ 159.40, 158.27, 142.23, 137.07, 127.88, 121.27, 117.80,115.37, 111.70, 59.29, 20.91. HRMS (ESI) m/z: [M + H]+ calcd for C20H19N5330.1713, found 330.1399。
：3,9-二甲氧基-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率27%. 1H NMR (500 MHz, DMSO-d 6): δ 8.45 (d, J = 4.5 Hz,2H), 7.10 (d, J = 8.3 Hz, 2H), 6.98 – 6.85 (m, 2H), 6.74 (t, J = 4.5 Hz, 1H),6.65 – 6.53 (m, 2H), 6.21 (d, J = 8.2 Hz, 2H), 6.15 – 6.04 (m, 2H), 3.61 (s,6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 159.33, 159.27, 158.29, 143.45, 128.86,116.68, 111.74, 103.61, 99.30, 58.98, 54.71. HRMS (ESI) m/z: [M + H]+ calcdfor C20H19N5O2 362.1612, found 362.1221。
：3,9-二苯基-13-(嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 36% yield. 1H NMR (500 MHz, DMSO-d 6): δ 8.50 (d, J = 4.7 Hz,2H), 7.51 (d, J = 7.6 Hz, 4H), 7.40 (t, J = 7.6 Hz, 4H), 7.32 (dd, J = 12.7,7.7 Hz, 4H), 7.13 (d, J = 3.1 Hz, 2H), 6.91 (d, J = 7.9 Hz, 2H), 6.86 – 6.71(m, 5H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 159.40, 158.37, 142.69, 140.51,140.31, 128.72, 128.66, 127.17, 126.44, 123.07, 115.65, 113.16, 111.99,59.29. HRMS (ESI) m/z: [M + H]+ calcd for C30H23N5 454.2026, found 454.2030。
：13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率33%. 1H NMR (500 MHz, DMSO-d 6): δ 8.55 (s, 2H), 7.21 (d, J = 7.4Hz, 2H), 7.08 – 6.88 (m, 4H), 6.72 – 6.58 (m, 4H), 6.55 (d, J = 8.0 Hz, 2H).13C{1H} NMR (125 MHz, DMSO-d 6): δ 157.65, 156.52, 142.05, 128.11, 128.06,123.48, 119.33, 116.95, 115.14, 59.77. HRMS (ESI) m/z: [M + H]+ calcd forC18H14ClN5 336.1010, found 336.1866。
：3, 9-二氟-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率36%. 1H NMR (500 MHz, DMSO-d 6): δ 8.56 (s, 2H), 7.34 (d,J = 3.0 Hz, 2H), 7.24 (t, J = 7.4 Hz, 2H), 6.63 (d, J = 3.1 Hz, 2H), 6.41 (t,J = 8.6 Hz, 2H), 6.33 (d, J = 10.8 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ162.16 (d, J = 240.9 Hz), 157.51, 156.64, 143.75 (d, J = 11.7 Hz), 129.72 (d,J = 10.3 Hz), 119.84, 119.37, 103.56 (d, J = 22.1 Hz), 100.78 (d, J = 24.6Hz), 58.96. HRMS (ESI) m/z: [M + H]+ calcd for C18H12ClF2N5 372.0822; found,372.0778。
：3,9-二氯-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率50%. 1H NMR (500 MHz, DMSO-d 6): δ 8.58 (s, 2H), 7.36 (d, J= 3.4 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H), 6.64 (dd, J = 5.0, 2.9 Hz, 4H), 6.59(d, J = 1.8 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 157.50, 156.64, 143.47,132.49, 129.67, 121.83, 120.00, 116.57, 114.03, 59.00. HRMS (ESI) m/z: [M +H]+ calcd for C18H12Cl3N5 404.0231, found 404.0241。
：3,9-二溴-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率46%. 1H NMR (500 MHz, DMSO-d6): δ8.57 (s, 2H), 7.35 (d, J =3.1 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 6.83 – 6.70 (m, 4H), 6.63 (d, J = 3.2Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 157.49, 156.62, 143.72, 129.93,122.19, 120.98, 120.01, 119.40, 116.93, 59.05. HRMS (ESI) m/z: [M + H]+ calcdfor C18H12Br2ClN5 491.9221, found 491.9242。
：3,9-二硝基-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 红色固体, 产率55%. 1H NMR (500 MHz, DMSO-d 6): δ 8.61 (s, 2H), 7.88 (d,J = 3.4 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 9.5 Hz, 4H), 6.88 (d,J = 3.4 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 157.42, 156.78, 147.69,142.88, 129.29, 128.94, 120.69, 111.38, 109.08, 59.03. HRMS (ESI) m/z: [M +H]+ calcd for C18H12ClN7O4 426.0712, found 426.0715。
：3,9-二甲基-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率34%. 1H NMR (500 MHz, DMSO-d 6): δ 8.53 (s, 2H), 7.07 (d,J = 7.7 Hz, 2H), 6.84 (d, J = 2.6 Hz, 2H), 6.52 (d, J = 2.8 Hz, 2H), 6.43 (d,J = 7.7 Hz, 2H), 6.33 (s, 2H), 2.10 (s, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ157.72, 156.48, 142.04, 137.24, 127.90, 120.97, 119.21, 117.98, 115.43,59.72, 20.91. HRMS (ESI) m/z: [M + H]+ calcd for C20H18ClN5 364.1323, found364.1212。
：3,9-二甲氧基-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率26%. 1H NMR (500 MHz, DMSO-d 6): 1H NMR (500 MHz, DMSO-d 6): δ 8.53 (s, 2H), 7.09 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 3.5 Hz, 2H), 6.51(d, J = 3.5 Hz, 2H), 6.21 (dd, J = 8.4, 2.5 Hz, 2H), 6.08 (d, J = 2.4 Hz,2H), 3.61 (s, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 191.67, 164.77, 153.06,137.67, 112.96, 104.36, 97.69, 55.20. HRMS (ESI) m/z: [M + H]+ calcd forC20H18ClN5O2 396.1222, found 396.0887。
：3,9-二苯基-13-(5-氯嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率29%. 1H NMR (500 MHz, DMSO-d 6): δ 8.58 (s, 2H), 7.78 –7.46 (m, 4H), 7.46 – 7.25 (m, 8H), 7.19 (s, 2H), 7.05 – 6.52 (m, 6H). 13C{1H}NMR (125 MHz, DMSO-d 6): δ 158.22, 157.08, 143.00, 140.94, 140.92, 129.23,129.20, 127.71, 126.95, 123.26, 120.03, 116.31, 113.71, 60.20. HRMS (ESI) m/z: [M + H]+ calcd for C30H22ClN5 488.1636, found 488.1636。
：13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率27%. 1H NMR (500 MHz, DMSO-d 6): δ 8.59 (s, 2H), 7.21 (d, J = 7.4Hz, 2H), 7.10–6.88 (m, 4H), 6.73–6.47 (m, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6):δ 158.52, 157.75, 142.05, 128.12, 128.06, 123.47, 116.96, 115.14, 107.42,59.69. HRMS (ESI) m/z: [M + H]+ calcd for C18H14BrN5 380.0505, found 380.0487。
：3,9-二氟-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率40%. 1H NMR (500 MHz, DMSO-d 6): δ8.61 (s, 2H), 7.34 (d, J =3.0 Hz, 2H), 7.24 (t, J = 7.4 Hz, 2H), 6.62 (d, J = 3.1 Hz, 2H), 6.41 (t, J =8.5 Hz, 2H), 6.33 (d, J = 10.9 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6) δ162.15 (d, J = 240.7 Hz), 158.64, 157.63, 143.74 (d, J = 11.7 Hz), 129.72 (d,J = 10.3 Hz), 119.35, 107.95, 103.56 (d, J = 22.1 Hz), 100.77 (d, J = 24.7Hz), 58.88. HRMS (ESI) m/z: [M + H]+ calcd for C18H12BrF2N5 416.0317, found416.0309。
：3,9-二氯-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率53%. 1H NMR (500 MHz, DMSO-d 6): δ 8.62 (s, 2H), 7.36 (d, J= 3.1 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 6.64 (d, J = 8.2 Hz, 4H), 6.60 (s,2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.65, 157.63, 143.48, 132.50, 129.68,121.82, 116.58, 114.04, 108.14, 58.93, 54.91. HRMS (ESI) m/z: [M + H]+ calcdfor C18H12BrCl2N5 447.9726, found 447.9763。
：3,9-二溴-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率47%. 1H NMR (500 MHz, DMSO-d 6): δ 8.61 (s, 2H), 7.35 (d, J= 3.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 6.83 – 6.69 (m, 4H), 6.62 (d, J =3.2 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.62, 157.61, 143.72, 129.92,122.17, 120.98, 119.41, 116.93, 108.14, 58.97. HRMS (ESI) m/z: [M + H]+ calcdfor C18H12Br3N5 535.8716, found 535.8773。
：3,9-二硝基-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.红色固体, 产率55%. 1H NMR (500 MHz, DMSO-d 6): δ 8.66 (s, 2H), 7.89 (d,J = 3.3 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 9.5 Hz, 4H), 6.87 (d,J = 3.3 Hz, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.86, 157.62, 147.71,142.94, 129.36, 128.97, 111.44, 109.12, 108.92, 58.98. HRMS (ESI) m/z: [M +H]+ calcd for C18H12BrN7O4 470.0207, found 470.0206。
：3,9-二甲基-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率31%. 1H NMR (500 MHz, DMSO-d 6): δ 8.58 (s, 2H), 7.07 (d,J = 7.7 Hz, 2H), 6.88 – 6.82 (m, 2H), 6.51 (s, 2H), 6.43 (d, J = 7.7 Hz, 2H),6.33 (s, 2H), 2.10 (s, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.48, 157.81,142.02, 137.24, 127.89, 120.94, 117.98, 115.42, 107.29, 20.91. HRMS (ESI) m/z: [M+H]+ calcd for C20H18BrN5 408.0818, found 408.0703。
：3,9-二甲氧基-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率27%. 1H NMR (500 MHz, DMSO-d 6): δ 8.58 (s, 2H), 7.09(d, J = 8.4 Hz, 2H), 6.94 (d, J = 3.1 Hz, 2H), 6.50 (d, J = 3.2 Hz, 2H), 6.21(dd, J = 8.4, 2.2 Hz, 2H), 6.08 (d, J = 2.1 Hz, 2H), 3.61 (s, 6H). 13C{1H} NMR(125 MHz, DMSO-d 6): δ 159.33, 158.49, 157.73, 143.25, 128.88, 116.33, 107.32,103.81, 99.34, 59.32, 54.73. HRMS (ESI) m/z: [M + H]+ calcd for C20H18BrN5O2440.0717, found 440.0574。
：3,9-二苯基-13-(5-溴嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率33%. 1H NMR (500 MHz, DMSO-d 6): δ 8.63 (s, 2H), 7.51 (d,J = 7.5 Hz, 4H), 7.45 – 7.25 (m, 8H), 7.19 (s, 2H), 6.92 (d, J = 7.7 Hz, 2H),6.83 (s, 2H), 6.77 – 6.66 (m, 2H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.59,157.84, 142.50, 140.44, 140.43, 128.74, 128.70, 127.22, 126.46, 122.75,115.82, 113.22, 107.65, 59.64. HRMS (ESI) m/z: [M + H]+ calcd for C30H22BrN5532.1131, found 532.1039。
：13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率29%. 1H NMR (500 MHz, DMSO-d 6): δ 8.31 (s, 2H), 7.20 (d, J = 7.2Hz, 2H), 6.99 – 6.90 (m, 4H), 6.66 – 6.57 (m, 4H), 6.53 (d, J = 7.9 Hz, 2H),2.08 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.29, 158.12, 142.36, 128.15,128.01, 123.93, 120.36, 115.05, 59.69, 14.14. HRMS (ESI) m/z: [M + H]+ calcd forC19H17N5 316.1557, found 316.1376。
：3,9-二氟-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率49%. 1H NMR (500 MHz, DMSO-d 6): δ 8.33 (s, 2H), 7.27 (d,J = 2.9 Hz, 2H), 7.22 (t, J = 7.4 Hz, 2H), 6.64 (d, J = 2.9 Hz, 2H), 6.39 (t,J = 8.4 Hz, 2H), 6.30 (d, J = 10.7 Hz, 2H), 2.09 (s, 3H). 13C{1H} NMR (125MHz, DMSO-d 6): δ 162.09 (d, J = 240.4 Hz), 158.13, 158.03, 143.94 (d, J =11.8 Hz), 129.65 (d, J = 10.3 Hz), 120.75, 119.73, 103.20 (d, J = 22.0 Hz),100.58 (d, J = 24.5 Hz), 58.83, 14.09. HRMS (ESI) m/z: [M + H]+ calcd forC19H15F2N5 352.1368; found 352.1289。
：3,9-二氯-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率74%. 1H NMR (500 MHz, DMSO-d 6): δ 8.34 (s, 2H), 7.29 (d,J = 3.4 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 6.62 (dd, J = 14.0, 5.8 Hz, 4H),6.56 (s, 2H), 2.10 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.15, 158.03,143.72, 132.35, 129.67, 122.21, 120.95, 116.29, 113.87, 58.91, 14.12. HRMS(ESI) m/z: [M + H]+ calcd for C19H15Cl2N5 384.0777, found 384.0674。
：3,9-二溴-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率55%. 1H NMR (500 MHz, DMSO-d 6): δ 8.34 (s, 2H), 7.29 (d,J = 3.5 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 6.74 (d, J = 8.1 Hz, 2H), 6.70 (s,2H), 6.62 (d, J = 3.5 Hz, 2H), 2.10 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ158.15, 158.01, 143.97, 129.94, 122.55, 120.97, 120.82, 119.11, 116.74,58.94, 14.12. HRMS (ESI) m/z: [M + H]+ calcd for C19H15Br2N5 471.9767, found471.9787。
：3,9-二硝基-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 红色固体, 产率90%. 1H NMR (500 MHz, DMSO-d 6): δ 8.38 (s, 2H), 7.84(s, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.47 – 7.28 (m, 4H), 6.87 (s, 2H), 2.11(s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 158.32, 157.90, 147.63, 143.11,129.36, 129.29, 121.71, 111.19, 58.98, 14.16. HRMS (ESI) m/z: [M + H]+ calcdfor C19H15N7O4 406.1258, found 406.1217。
：3,9-二甲基-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率40%. 1H NMR (500 MHz, DMSO-d 6): δ 8.30 (s, 2H), 7.05(d, J = 7.7 Hz, 2H), 6.76 (d, J = 3.0 Hz, 2H), 6.52 (d, J = 3.1 Hz, 2H), 6.41(d, J = 7.7 Hz, 2H), 6.31 (s, 2H), 2.09 (d, J = 5.3 Hz, 9H). 13C{1H} NMR (125MHz, DMSO-d 6): δ 158.31, 158.00, 142.27, 136.99, 127.90, 120.12, 117.68,115.29, 59.55, 14.09. HRMS (ESI) m/z: [M + H]+ calcd for C21H21N5 344.1870,found 344.1576。
：3,9-二甲氧基-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率31%. 1H NMR (500 MHz, DMSO-d 6): δ 8.30 (s, 2H), 7.09(d, J = 8.4 Hz, 2H), 6.87 (d, J = 3.2 Hz, 2H), 6.53 (d, J = 3.2 Hz, 2H), 6.19(dd, J = 8.4, 2.3 Hz, 2H), 6.07 (d, J = 2.2 Hz, 2H), 3.60 (s, 6H), 2.08 (s,3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 159.28, 158.28, 158.07, 143.54, 128.93,120.24, 103.54, 99.26, 59.30, 54.76, 14.13. HRMS (ESI) m/z: [M + H]+ calcdfor C21H21N5O2 376.1768, found 376.1272。
：3,9-二苯基-13-(5-甲基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率53%. 1H NMR (500 MHz, DMSO-d 6): δ 8.35 (s, 2H), 7.57 –7.46 (m, 4H), 7.39 (t, J = 7.7 Hz, 4H), 7.35 – 7.25 (m, 4H), 7.10 (d, J = 3.7Hz, 2H), 6.89 (dd, J = 7.8, 1.8 Hz, 2H), 6.80 (d, J = 1.9 Hz, 2H), 6.71 (d, J= 3.6 Hz, 2H), 2.11 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ158.29, 158.10,142.73, 140.56, 140.25, 128.73, 128.69, 127.16, 126.45, 123.17, 120.46,115.54, 113.08, 59.57, 14.10. HRMS (ESI) m/z: [M + H]+ calcd for C31H25N5468.2183, found 468.2183。
：13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛.白色固体, 产率50%. 1H NMR (500 MHz, DMSO-d 6): δ 8.29 (s, 2H), 7.20 (d, J = 7.3Hz, 2H), 6.94 (dd, J = 15.5, 7.8 Hz, 4H), 6.60 (t, J = 7.2 Hz, 2H), 6.54 (dd,J = 12.8, 5.3 Hz, 4H), 3.77 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 155.00,147.10, 144.99, 142.27, 128.10, 127.90, 123.89, 116.63, 114.94, 60.11, 56.44.HRMS (ESI) m/z: [M + H]+ calcd for C19H17N5O 332.1506, found 332.1455。
：3,9-二氟-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率59%. 1H NMR (500 MHz, DMSO-d 6): δ8.29 (s, 2H), 7.25(s, 2H), 7.21 (t, J = 7.4 Hz, 2H), 6.56 (s, 2H), 6.38 (t, J = 8.5 Hz, 2H),6.29 (d, J = 11.0 Hz, 2H), 3.78 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ162.09 (d, J = 240.4 Hz), 154.70, 147.36, 143.91 (d, J = 11.7 Hz), 129.67 (d,J = 10.3 Hz), 119.74, 103.16 (d, J = 21.8 Hz), 100.54 (d, J = 24.6 Hz),59.32, 56.43. HRMS (ESI) m/z: [M + H]+ calcd for C19H15F2N5O 368.1317, found368.1138。
：3,9-二氯-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率82%. 1H NMR (500 MHz, DMSO-d 6): δ 8.30 (s, 2H), 7.28(d, J = 2.7 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 6.61 (d, J = 8.1 Hz, 2H), 6.56(d, J = 6.3 Hz, 4H), 3.78 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 154.63,147.45, 144.99, 143.66, 132.28, 129.67, 122.20, 116.22, 113.80, 59.37, 56.43.HRMS (ESI) m/z: [M + H]+ calcd for C19H15Cl2N5O 400.0726, found 400.0612。
：3,9-二溴-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率62%. 1H NMR (500 MHz, DMSO-d 6): δ 8.30 (s, 2H), 7.28(d, J = 3.1 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 6.74 (d, J = 8.1 Hz, 2H), 6.70(s, 2H), 6.55 (d, J = 3.2 Hz, 2H), 3.78 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 154.62, 147.46, 144.99, 143.93, 129.96, 122.56, 120.79, 119.07,116.69, 59.42, 56.43. HRMS (ESI) m/z: [M + H]+ calcd for C19H15Br2N5O 487.9716,found 487.9696。
：3,9-二硝基-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 红色固体, 产率95%. 1H NMR (500 MHz, DMSO-d 6): δ 8.33 (s, 2H), 7.80(d, J = 3.3 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.47 – 7.33 (m, 4H), 6.80 (d,J = 3.4 Hz, 2H), 3.79 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 154.32,147.81, 147.59, 145.04, 143.01, 129.34, 129.22, 111.09, 108.79, 59.43, 56.41.HRMS (ESI) m/z: [M + H]+ calcd for C19H15N7O5 422.1207, found 422.1205。
：3,9-二甲基-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率46%. 1H NMR (500 MHz, DMSO-d 6): δ 8.27 (s, 2H), 7.06(d, J = 7.5 Hz, 2H), 6.75 (s, 2H), 6.47 (s, 2H), 6.41 (d, J = 7.3 Hz, 2H),6.31 (s, 2H), 3.77 (s, 3H), 2.10 (s, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ147.02, 144.94, 142.23, 136.93, 127.91, 121.36, 117.63, 115.24, 60.03, 56.45,20.91. HRMS (ESI) m/z: [M + H]+ calcd for C21H21N5O 360.1819, found 360.1377。
：3,9-二甲氧基-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率35%. 1H NMR (500 MHz, DMSO-d 6): δ 8.27 (s, 2H),7.08 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 3.1 Hz, 2H), 6.46 (d, J = 3.1 Hz, 2H),6.19 (dd, J = 8.4, 2.2 Hz, 2H), 6.06 (d, J = 2.1 Hz, 2H), 3.77 (s, 3H), 3.61(s, 6H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 159.20, 155.02, 147.05, 144.96,143.45, 128.89, 116.78, 103.43, 99.18, 59.72, 56.45, 54.70. HRMS (ESI) m/z:[M + H]+ calcd for C21H21N5O3 392.1717, found 392.1290。
：3,9-二苯基-13-(5-甲氧基嘧啶-2-基)-6H,12H-6,12-环亚胺二苯并[b,f][1,5]二氮杂环辛. 白色固体, 产率69%. 1H NMR (500 MHz, DMSO-d 6): δ 8.32 (s, 2H), 7.51(d, J = 7.4 Hz, 4H), 7.39 (t, J = 7.3 Hz, 4H), 7.31 (dt, J = 14.7, 7.4 Hz,4H), 7.10 (s, 2H), 6.90 (d, J = 7.7 Hz, 2H), 6.81 (s, 2H), 6.66 (s, 2H), 3.79(s, 3H). 13C{1H} NMR (125 MHz, DMSO-d 6): δ 155.02, 147.22, 145.02, 142.71,140.57, 140.22, 128.74, 127.16, 126.45, 123.18, 115.50, 113.03, 60.05, 56.45.HRMS (ESI) m/z: [M + H]+ calcd for C31H25N5O 484.2132, found 484.2132。
实施例2：
对实施例1中的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物进行杀菌活性测试。测试化合物对番茄早疫病、小麦赤霉病、油菜菌核病、水稻纹枯病、苹果轮纹病、小麦纹枯病和水稻恶苗病的防治。
实验方法：
(1) 称取化合物3mg，溶于100μL的DMSO中，配成30000ppm的母液，用1‰的吐温水稀释至500ppm的化合物溶液；
(2) 用移液枪吸取1mL的溶液放入已灭菌的平皿中，再用移液管吸取9mL的PDA培养基放入平皿中混匀，配成相应浓度的含药平板；
(3)用灭菌打孔器(直径为4 mm)切取病原菌落(培养好的)边缘，从而获得菌饼。待培养基凝固后，分别接入不同的菌种(空白对照为含等体积无菌水的培养基)。放入培养箱中培养72小时后观察并量取菌落直径；
以上操作均在无菌条件下进行，PDA培养基等均是无菌的。
实验结果：
用式(1)来计算杀菌活性，也即抑菌效率；
注：式(1)中4的单位为毫米，为接入菌饼的直径。
N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的杀菌活性列于表2。
表2 N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的杀菌活性
由表2可见，本实施例的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物中的部分化合物对油菜菌核病菌、苹果轮纹病菌和小麦纹枯病菌表现出较好的杀菌活性，尤其是对苹果轮纹病菌的杀菌活性非常显著。40个化合物中，有11个化合物(No. 1, 9, 10,12, 17, 18, 21, 22, 25, 26, 35)对苹果轮纹病菌的抑制率超过90%，其中抑制率最高的是No. 10，达98.4%，明显高出同浓度下对照药百菌清的抑菌率(89.3%)。
由表2可见，本实施例的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物中对油菜菌核病菌抑制率最高的是No. 39，抑菌率达85.7%，另有6个化合物(No. 5, 13, 18,26, 29, 34)的抑菌率超过70%。
由表2可见，本实施例的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物中对小麦纹枯病菌的抑菌率最高的是No.3，为80.5%，另有5个化合物(No. 9, 10, 14, 26,30)的抑菌率超过70%。
最后应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，对本发明的技术方案进行修改或者等同替换，不脱离本发明技术方案的实质和范围。
Claims (10)
1.一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其结构通式为：
通式(I)中，R1选自H、C1-C4的烷基、C1-C4烷氧基、卤素、卤代C1-C4烷基；R2选自H、C1-C4的烷基、卤素、C1-C4烷氧基、硝基、芳基。
2.根据权利要求1所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物，其特征在于：R1 选自 H、Cl、Br、CH3、OCH3；R2 选自H、F、Cl、Br、CH3、OCH3、NO2、Ph。
3.一种根据权利要求1所述的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，通式(I)的化合物制备包括以下步骤：
步骤一：将2-氨基-5-取代嘧啶和2-氨基-4-取代苯甲醛溶于有机溶剂，酸催化下加热回流反应，得含有通式(I)的反应混合物，
步骤二：将所述具有通式(I)的反应混合物分离，提纯，干燥，得具有通式(I)的N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物。
4.根据权利要求3所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：步骤一中，2-氨基-5-取代嘧啶与2-氨基-4-取代苯甲醛的物质的量之比为1:2~10。
5.根据权利要求3所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：步骤一中，所述有机溶剂为无水乙醇、甲苯、二甲基亚砜、N,N-二甲基甲酰胺、正丁醇、1,2-二氯乙烷或乙腈。
6.根据权利要求3所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：步骤一中，所述酸催化剂为质子酸或路易斯酸，所述质子酸为醋酸、对甲基苯甲酸、五氟苯甲酸或对甲苯磺酸，所述路易斯酸为氯化铝、氯化铁、三氟甲磺酸镱或三氟甲磺酸钪。
7.根据权利要求6所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：所述催化剂的用量为1~20 mol%。
8.根据权利要求3所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：步骤一中，所述反应温度为40~130℃，所述反应时间为8~40h。
9.根据权利要求3所述的一种N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物的制备方法，其特征在于：步骤二中，所述分离为以石油醚/乙酸乙酯作为流动相或以石油醚/二氯甲烷作为流动相进行柱层析分离；所述提纯为以石油醚/乙酸乙酯的混合液作为溶剂进行重结晶。
10.一种根据权利要求1~9任意一项所述N-嘧啶基环亚胺二苯并[b,f][1,5]二氮杂环辛衍生物作为农作物细菌性病害杀菌剂的应用，其特征在于：所述农作物细菌性病害为番茄早疫病、小麦赤霉病、油菜菌核病、水稻纹枯病、苹果轮纹病、小麦纹枯病和水稻恶苗病中的一种或几种。
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