CN115304543A - 含降冰片烯基芳磺酰胺的制备方法和产品及其应用 - Google Patents
含降冰片烯基芳磺酰胺的制备方法和产品及其应用 Download PDFInfo
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- CN115304543A CN115304543A CN202210770634.XA CN202210770634A CN115304543A CN 115304543 A CN115304543 A CN 115304543A CN 202210770634 A CN202210770634 A CN 202210770634A CN 115304543 A CN115304543 A CN 115304543A
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- Prior art keywords
- norbornenyl
- sulfonyl chloride
- arylsulfonamide
- norbornene
- producing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 title claims abstract description 35
- 125000004421 aryl sulphonamide group Chemical group 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- -1 aromatic sulfonamide Chemical class 0.000 claims abstract description 14
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- 241000233866 Fungi Species 0.000 claims abstract description 10
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 102
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 48
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 23
- XLBALIGLOMYEKN-UHFFFAOYSA-N 5-bicyclo[2.2.1]hept-2-enylmethanamine Chemical compound C1C2C(CN)CC1C=C2 XLBALIGLOMYEKN-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
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- A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
- A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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- A—HUMAN NECESSITIES
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
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Abstract
本发明公开了含降冰片烯基芳磺酰胺的制备方法和产品及其应用，所述含降冰片烯基芳磺酰胺结构式如下所示：
所述含降冰片烯基芳磺酰胺在防治农业或林业的植物真菌的应用，活性结果表明：本发明所提供的化合物对油菜菌核病菌，葡萄座腔病菌和辣椒疫霉病菌有较好的防治效果。
Description
技术领域
本发明属于农药合成技术领域，具体涉及到含降冰片烯基芳磺酰胺的制备方法和产品及其应用。
背景技术
作为一种重要的化工中间体，降冰片烯(Norbornene)是降莰烯(norcamphene)的桥环烃，化学式为C7H10。是一种白色固体，有刺激性酸味。该分子由环己烯环和亚甲基桥(C-3和C-6之间)组成。分子带有一个双键引起显著的环张力和明显的反应。降冰片烯的合成有多种方法，如环戊二烯和乙烯进行Diels-Alder反应。与bicylic相似的还有norbornadiene,它与没有双键完全饱和的norbornane有一样的结构，但它多了两个双键。降冰片烯进行酸催化水合反应，与水形成降冰片。
目前，降冰片烯主要用于过渡金属催化去影响亲电子的过渡金属的迁移。例如在环烯烃ROMP研究领域，降冰片烯及其衍生物是研究最多和应用最广的一类单体,这是因为它们的反应活性较高,来源丰富，价格也不昂贵。除研究拓展ROMP适用单体外，研究者主要从降冰片烯基单体的空间位阻、化学构型、侧基极性以及与其他环烯烃或降冰片烯基单体共聚改性等方面不断进行尝试，同时充分发挥环烯烃ROMP优势，与其他聚合方法联用，不断改善所得聚合物的性能并将其应用于不同研究领域。降冰片烯及其衍生物ROMP在阻燃材料、交换膜、纳米材料、生物医药等领域已取得一系列研究成果，其中在阻燃材料领域研究最早且许多产品已经工业化。在交换膜领域，由于降冰片烯基聚合物膜的热稳定性、耐酸碱性和电导率均较好，目前的研究主要是探索如何在燃料电池中获得应用。纳米材料是近年来最热门的研究领域之一，降冰片烯基纳米金属聚合物材料和纳米磁性聚合物材料等已有初步应用。在生物医药领域，降冰片烯及其衍生物极具发展前景，目前的研究主要集中在药物传输材料，已有初步的研究成果，但要实现工业化尚待进一步研究，但整体而言，在医药或者农药方面的应用，报道较少。
本发明所提供的含降冰片烯基芳磺酰胺的制备方法及其在农用杀菌剂方面的应用尚未报道。
发明内容
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。
鉴于上述和/或现有技术中存在的问题，提出了本发明。
因此，本发明的目的是，克服现有技术中的不足，提供含降冰片烯基芳磺酰胺。
为解决上述技术问题，本发明提供了如下技术方案：含降冰片烯基芳磺酰胺，所述含降冰片烯基芳磺酰胺结构式如下所示：
本发明的再一个目的是，克服现有技术中的不足，提供含降冰片烯基芳磺酰胺类化合物的制备方法。
为解决上述技术问题，本发明提供了如下技术方案：含降冰片烯基芳磺酰胺的制备方法，包括，芳磺酰氯中间体与5-降冰片烯-2-甲胺、三乙胺和4-二甲氨基吡啶反应，合成含降冰片烯基芳磺酰胺I-1～I-8。
作为本发明所述含降冰片烯基芳磺酰胺的制备方法的一种优选方案，其中：
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入芳磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应1-5h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-1～I-8。
作为本发明所述含降冰片烯基芳磺酰胺的制备方法的一种优选方案，其中：中间体芳磺酰氯与5-降冰片烯-2-甲胺的投料摩尔比为1.1:0。
作为本发明所述含降冰片烯基芳磺酰胺的制备方法的一种优选方案，其中：5-降冰片烯-2-甲胺与三乙胺投料摩尔比为1:1.0。
作为本发明所述含降冰片烯基芳磺酰胺的制备方法的一种优选方案，其中：芳磺酰氯中间体与4-二甲氨基吡啶的摩尔比为1.0:0.1。
作为本发明所述含降冰片烯基芳磺酰胺的制备方法的一种优选方案，其中：合成含降冰片烯基芳磺酰胺I-1～I-8，其中，合成反应温度为25℃，反应时间为1-5h。
本发明的另一个目的是，克服现有技术中的不足，提供含降冰片烯基芳磺酰胺在防治农业或林业的植物真菌的应用，所述植物真菌包括油菜菌核病菌，葡萄座腔病菌和辣椒疫霉病菌。
本发明有益效果：
(1)本发明所述含降冰片烯基芳磺酰胺，分子结构新颖，均为新化合物；化学结构特征鲜明，结构式中含有降冰片烯，其中多种芳香基团与降冰片烯通过酰胺键相连接；所述的化合物的制备方法简便，原料易得，反应条件易控，尤其在合成含降冰片烯基芳磺酰胺这步反应中，产物经柱层析即可得到。
(2)本发明所述的化合物是一种在农业或林业领域的防治植物真菌的药剂，这种药剂对于油菜菌核病菌，葡萄座腔病菌和辣椒疫霉病菌有较好的防治效果。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其它的附图。其中：
图1为本发明实施例中含降冰片烯基芳磺酰胺I-1～I-8制备方法示意图。
图2为本发明实施例中化合物I-5对辣椒疫霉病菌的平板实验(从左到右药液浓度依次为12.5mg/L,3.125mg/L,0.781mg/L,0.195mg/L,0.049mg/L和0mg/L)
图3为本发明实施例中化合物I-1对油菜菌核病菌活体实验示意图(叶片法)。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书实施例对本发明的具体实施方式做详细的说明。
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入芳磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应1-5h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-1～I-8。含降冰片烯基芳磺酰胺I-1～I-8制备方法示意图，见图1。
各种芳磺酰氯，4-二甲氨基吡啶，三乙胺，氯化钠和5-降冰片烯-2-甲胺均购自上海毕得科技有限公司；二氯甲烷和甲醇购自南京晚晴有限公司；硅胶板和硅胶粉购自烟台海洋精细化工有限公司。
实施例1
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入8-喹啉磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应1h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-1。
I-1,白色粉末,收率90％,m.p.125.8-126.4℃；1H NMR(600MHz,CDCl3)δ9.08–9.05(m,1H),8.46–8.42(m,1H),8.32(dd,J＝8.3,1.6Hz,1H),8.07(dd,J＝8.2,1.2Hz,1H),7.69–7.66(m,1H),7.61–7.59(m,1H),6.39(s,1H),5.98–5.50(m,2H),2.78(s,1H),2.70–2.67(m,2H),2.46–2.42(m,1H),2.22–2.17(m,1H),1.73–1.68(m,1H),1.36(dd,J＝8.3,1.9Hz,1H),1.17–1.09(m,1H),0.37–0.34(m,1H)；13C NMR(150MHz,CDCl3)δ151.03,143.02,137.74,137.33,135.75,133.15,131.49,131.45,128.73,125.88,122.26,49.36,47.54,43.97,42.27,38.75,30.03.
实施例2
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入6-甲基-8-喹啉磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应1h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-2。
I-2,白色粉末,收率80％,m.p.133-135℃；1H NMR(600MHz,CDCl3)δ8.90(s,1H),8.36–8.32(m,1H),8.05(s,1H),7.98(d,J＝8.2Hz,1H),7.61(td,J＝7.7,1.8Hz,1H),6.34(t,J＝5.3Hz,1H),5.98–5.51(m,2H),2.78(s,1H),2.72-2.64(m,2H),2.58(s,3H),2.46–2.41(m,1H),2.21–2.18(m,1H),1.73–1.68(m,1H),1.36(d,J＝8.1Hz,1H),1.17–1.10(m,1H),0.37–0.34(m,1H)；13C NMR(150MHz,CDCl3)δ153.01,141.43,137.70,136.07,135.65,132.51,132.05,131.53,130.25,128.62,125.75,49.35,47.54,43.98,42.27,38.77,30.04,18.75.
实施例3
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入1-萘磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应3h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-3。
I-3,白色粉末,收率82％,m.p 99.1-100.0℃；1H NMR(600MHz,CDCl3)δ8.44(d,J＝13.1Hz,1H),7.98–7.91(m,3H),7.85–7.82(m,1H),7.66–7.60(m,2H),6.08–5.75(m,2H),4.57(s,1H),2.82–2.75(m,3H),2.66–2.59(m,1H),2.21–2.16(m,1H),1.80–1.76(m,1H),1.25–1.18(m,1H),0.46–0.43(m,1H)；13C NMR(150MHz,CDCl3)δ137.97,132.14,131.56,129.47,129.22,128.74,128.44,127.91,127.53,122.30,47.20,43.96,42.30,38.96,30.00.
实施例4
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入4-联苯磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应2h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-4。
I-4,白色固体，收率92％,m.p 161.5-162.7℃；1H NMR(600MHz,CDCl3)δ7.94–7.91(m,2H),7.73–7.72(m,2H),7.62–7.60(m,2H),7.48(t,J＝7.7Hz,2H),7.42(t,J＝7.3Hz,1H),6.12–5.79(m,2H),4.58(s,1H),2.84(s,1H),2.80–2.75(m,2H),2.67–2.62(m,1H),2.23–2.17(m,1H),1.83–1.78(m,1H),1.43–1.41(m,1H),1.27–1.20(m,1H),0.49–0.47(m,1H)；13C NMR(150MHz,CDCl3)δ145.48,139.31,138.48,137.98,131.59,129.04,128.45,127.68,126.57,127.29,49.44,47.20,43.97,42.33,38.96,30.03.
实施例5
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入2-噻吩磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应1h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-5。
I-5,无色油状物,收率60％；1H NMR(600MHz,CDCl3)δ7.64–7.58(m,2H),7.10–7.08(m,1H),6.12–5.80(m,2H),5.17(s,1H),2.85–2.77(m,3H),2.68–2.63(m,1H),2.24–2.18(m,1H),1.83–1.79(m,1H),1.42(dd,J＝8.3,1.9Hz,1H),1.27–1.20(m,1H),0.49–0.46(m,1H)；13C NMR(150MHz,CDCl3)δ140.79,137.79,136.78,136.03,131.94,131.61,127.29,49.34,47.29,43.89,42.25,38.58,29.96.
实施例6
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入5-氯-2-噻吩磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应3h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-6。
I-6白色固体,收率80％,m.p 116.3-118.2℃；1H NMR(600MHz,CDCl3)δ7.38(d,J＝4.0Hz,1H),6.92(d,J＝4.0Hz,1H),6.16–5.84(m,2H),4.69(t,J＝5.3Hz,1H),2.85–2.78(m,3H),2.72-2.67(m,1H),2.25–2.19(m,1H),1.86–1.82(m,1H),1.46–1.45(m,1H),1.30–1.23(m,1H),0.52-0.49(m,1H)；13C NMR(150MHz,CDCl3)δ138.88,138.13,137.05,136.00,131.53,131.41,126.66,49.49,47.41,44.02,42.35,38.79,30.03.
实施例7
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入吡啶-3-磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应2h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-7。
I-7,白色固体,收率66％,m.p 113-115℃；1H NMR(600MHz,CDCl3)δ9.11(d,J＝12.7Hz,1H),8.82(d,J＝4.1Hz,1H),8.19(t,J＝9.5Hz,1H),7.50(dd,J＝7.8,4.8Hz,1H),6.14–5.80(m,2H),4.79(d,J＝5.3Hz,1H),2.82–2.75(m,2H),2.70–2.60(m,1H),2.39(s,1H),2.23–2.17(m,1H),1.83–1.79(m,1H),1.44(d,J＝8.1Hz,1H),1.26–1.21(m,1H),0.49–0.46(m,1H)；13C NMR(150MHz,CDCl3)δ152.89,147.80,138.12,136.85,134.86,131.48,123.82,49.45,47.18,43.93,42.31,38.94,30.01.
实施例8
将5-降冰片烯-2-甲胺(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.0mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入2-氯吡啶-5-磺酰氯(1.0mol)的5mL无水二氯甲烷溶液，升至25℃反应5h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1，体积比)得目标化合物I-8。
I-8,白色固体，收率63％,m.p 133.0-133.7℃；1H NMR(600MHz,CDCl3)δ8.84(d,J＝2.3Hz,1H),8.08(dd,J＝8.4,2.5Hz,1H),7.49(d,J＝8.4Hz,1H),6.16–5.82(m,2H),4.84(t,J＝5.7Hz,1H),2.83–2.74(m,3H),2.71–2.66(m,1H),2.23–2.17(m,1H),1.84–1.80(m,1H),1.46–1.44(m,1H),1.28–1.21(m,1H),0.49–0.46(m,1H)；13C NMR(150MHz,CDCl3)δ155.32,148.30,138.23,137.23,135.69,131.38,124.71,77.21,77.00,76.79,49.46,48.45,47.21,44.91,43.93,42.31,41.66,38.93,30.85,30.00.
实施例9
杀菌活性(离体)实验
本实验中所用的植物真菌为实验室4℃保存的菌种，为番茄灰霉病菌、小麦赤霉病菌、马铃薯晚疫病菌、辣椒疫霉病菌、葡萄座腔病菌、甘蔗凤梨病菌和油菜菌核病菌。采用的培养基为马铃薯琼脂葡萄糖培养基(简称PDA)。PDA培养基配方:马铃薯(去皮)200g，葡萄糖20g，琼脂15g，蒸馏水1000mL，配制方法：将马铃薯洗净去皮，称200g切成小块，加水煮烂(煮沸20-30分钟，能被玻璃棒戳破即可)，用八层纱布过滤于烧杯中，根据实验需要加20g琼脂，加入20g葡萄糖，搅拌均匀，充分溶解后稍冷却，补足水至1000mL，分装后121℃灭菌15分钟，冷却后备用。
实验方法：采用生长速率法。
(1)先将7种植物真菌在PDA平板上25℃培养3-6d左右待用；
(2)将PDA培养基加热溶化，冷却至45–50℃，加入250μL的10g/L浓度的待测化合物制成含50mg/L药液的培养基，并分别倒入培养皿中冷却，氟唑菌酰羟胺作为阳性对照；
(3)以无菌操作，用打孔器在培养6d的各菌株菌丝边缘(生长状况尽量一致)打取圆形菌饼(直径0.50cm)，再用接种针挑至含药平板中央，然后将培养皿倒置于培养箱(28℃)中培养；
(4)于处理后不同时间观察测定菌丝的生长情况，并采用十字交叉法测得直径并处理数据，计算抑制率；
(5)抑制率(％)＝(对照菌丝直径-处理菌丝直径)/(对照菌丝直径-0.5cm)×100；
(6)每个处理重复3次。
表1含降冰片烯基芳磺酰胺对七种农业致病真菌的抑制活性试验结果
a注:试验中每个处理设三次重复，表中数据为三次重复的平均值。
表2部分化合物的EC50值
实验组I-1～I-8以及对照药剂氟唑菌酰羟胺的杀菌活性测定结果见表1和表2。由表1和表2的结果可见，50mg/L浓度时，化合物I-1～I-8对7种植物真菌显示出不同程度的杀菌活性，部分化合物对油菜菌核病菌有较好的抑制活性，其中，化合物I-1在50mg/L浓度下对油菜菌核病菌的抑制率达88.4％；此外，I-5对番茄灰霉病菌抑制率为72.9％；I-6对葡萄座腔病菌抑制率为89.8％；I-5对辣椒疫霉病菌抑制率达93.7％，与氟唑菌酰羟胺相当。此外，该系列化合物对马铃薯晚疫病菌和甘蔗凤梨病菌有中等抑制活性。鉴于I-5对辣椒疫霉病菌有较好的杀菌活性，测试了其EC50，为4.18mg/L。从平板实验(图2)可以看出，相对于空白对照(0mg/L)，在12.5mg/L浓度时I-5对辣椒疫霉菌丝的生长有一定抑制作用，对辣椒疫霉病菌的菌丝较好的抑制效果。该系列化合物对辣椒疫霉病菌均有较好的抑制活性，具有开发杀菌剂的潜力。
实施例10
漆酶的抑制活性测定(离体)
本实验采用ChemeGen Kuma有限公司(上海)生产的云芝漆酶进行离体酶抑制活性测定。半胱氨酸为阳性对照，DMSO为阴性对照。依次于96孔板加入含有120μL柠檬酸-磷酸缓冲液(2％的柠檬酸三钠的15mmol和100mL 150mmol单磷酸,pH值4.5),10mL漆酶底物ABTS(2,20-Azino-bis(3-ethylbenzothiazoline-6-sulfonic)联胺盐)，供试化合物药液10μL和40μL纯漆酶。通过监测ABTS在420nm处的氧化反应来检测酶活性。最后用SPSS统计软件23.0计算吸光度斜率(OD/h)的IC50值。
表3化合物I-5的漆酶抑制活性
化合物I-5在离体条件下对漆酶有较好的抑制活性，IC50值为5.409μM，优于阳性对照半胱氨酸(IC50＝35.501μM)。
实施例11
油菜菌核病菌活体实验(叶片法)
于南京林业大学校园内摘取大小均一，新鲜的油菜叶片，以灭菌水洗涤后，再以75％乙醇洗涤，室温阴干。称取适量化合物I-1和阳性对照为氟唑菌酰羟胺(pydiflumetofen)，以DMSO溶解后并以0.2％Tween-80水溶液溶解配置成200mg/L浓度。然后对每个油菜叶片表面进行喷雾(喷雾量为5mL，1个浓度),喷雾均匀，后自然阴干。待叶片表面无液体后，以接种针刺穿叶片表皮，接油菜菌核菌饼(0.5cm直径)，每个叶片接种2-4个菌饼，空白对照为不含药剂的DMSO和0.2％Tween-80混合水溶液。设置组内平行和组外平行。两个平行组置于(25±2℃和95％相对湿度)培养5天。测量病斑直径并计算抑制率。
保护活性抑制率(％)的计算公式：(空白对照病斑直径-测试化合物的病斑直径)/空白对照病斑直径-0.5)×100。
表4化合物I-1对油菜菌核病菌的活体生物活性
a该实验每个浓度做9次重复
在200mg/L浓度下，化合物I-1对油菜菌核病菌的抑制率为75.8％，接近氟唑菌酰羟胺的抑制率(90.3％)。该化合物对油菜叶的活体保护活性与阳性对照氟唑菌酰羟胺相当。从图3可以看出，经I-1药液处理的油菜叶，油菜菌核菌丝生长受到一定抑制，其病斑直径接近于氟唑菌酰羟胺药液处理的叶片的病斑直径，此说明化合物I-1对油菜菌核病菌有较强的抑制效果。
本发明所述含降冰片烯基芳磺酰胺类化合物，结构区别明显，化学结构特征鲜明，对于防治油菜菌核病菌，葡萄座腔病菌和辣椒疫霉病菌有较好的效果。可用于防治农业或林业植物真菌病害。所述化合物的制备方法简便，收率较高，产物性质稳定。
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (10)
1.含降冰片烯基芳磺酰胺类化合物，其特征在于：所述含降冰片烯基芳磺酰胺结构式如下所示：
2.如权利要求1所述含降冰片烯基芳磺酰胺类化合物的制备方法，其特征在于：包括，芳磺酰氯与5-降冰片烯-2-甲胺、三乙胺和4-二甲氨基吡啶反应，合成含降冰片烯基芳磺酰胺类化合物I-1～I-8。
3.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：
将5-降冰片烯-2-甲胺、4-二甲氨基吡啶、三乙胺溶解于无水二氯甲烷中，降温至0℃，分批加入芳磺酰氯的无水二氯甲烷溶液，升温反应；
TLC监测原料反应完全，有机层以水洗涤3次，饱和食盐水洗涤3次，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析得目标化合物I-1～I-8。
4.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：中间体芳磺酰氯与5-降冰片烯-2-甲胺的投料摩尔比为1.0:1。
5.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：5-降冰片烯-2-甲胺与三乙胺投料摩尔比为1:1.0。
6.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：芳磺酰氯中间体与4-二甲氨基吡啶的摩尔比为1.0:0.1。
7.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：合成含降冰片烯基芳磺酰胺I-1～I-8，其中，合成反应温度为25℃，反应时间为1～5h。
8.如权利要求2所述含降冰片烯基芳磺酰胺的制备方法，其特征在于：所述芳磺酰氯，包括，8-喹啉磺酰氯、6-甲基-8-喹啉磺酰氯、1-萘磺酰氯、4-联苯磺酰氯、2-噻吩磺酰氯、5-氯-2-噻吩磺酰氯、吡啶-3-磺酰氯、2-氯吡啶-5-磺酰氯。
9.如权利要求1所述含降冰片烯基芳磺酰胺在防治农业或林业的植物真菌的应用。
10.如权利要求9所述应用，其特征在于：所述植物真菌包括油菜菌核病菌，葡萄座腔病菌和辣椒疫霉病菌。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3052703A (en) * | 1957-12-30 | 1962-09-04 | Shell Oil Co | N-acylated-amino derivatives of halogenated bicyclo (2, 2, 1) hept-5-en-2-yl compounds |
| US3184501A (en) * | 1961-04-03 | 1965-05-18 | Velsicol Chemical Corp | Hexachlorobicyclic sulfonamides |
| CN105007732A (zh) * | 2012-12-31 | 2015-10-28 | 美国陶氏益农公司 | 作为杀真菌剂的大环吡啶酰胺 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3052703A (en) * | 1957-12-30 | 1962-09-04 | Shell Oil Co | N-acylated-amino derivatives of halogenated bicyclo (2, 2, 1) hept-5-en-2-yl compounds |
| US3184501A (en) * | 1961-04-03 | 1965-05-18 | Velsicol Chemical Corp | Hexachlorobicyclic sulfonamides |
| CN105007732A (zh) * | 2012-12-31 | 2015-10-28 | 美国陶氏益农公司 | 作为杀真菌剂的大环吡啶酰胺 |
Non-Patent Citations (1)
| Title |
|---|
| 孙继国等: ""4 - 二甲氨基吡啶(DMAP) 在医药合成中的应用"", 《沧州师范学院学报》, vol. 30, no. 1, pages 49 - 53 * |
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