CN113880780A - 苯甲脒类衍生物、制备方法及应用 - Google Patents
苯甲脒类衍生物、制备方法及应用 Download PDFInfo
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- CN113880780A CN113880780A CN202111111946.1A CN202111111946A CN113880780A CN 113880780 A CN113880780 A CN 113880780A CN 202111111946 A CN202111111946 A CN 202111111946A CN 113880780 A CN113880780 A CN 113880780A
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- benzamidine derivative
- benzamidine
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- 238000006243 chemical reaction Methods 0.000 claims description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 35
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- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
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Abstract
本发明公开了苯甲脒类衍生物、制备方法及应用。涉及的苯甲脒衍生物包括含1,2,4‑三唑甲基的苯甲脒衍生物和非杂环取代的苯甲脒衍生物。本发明公开了这些化合物的合成方法以及用于防治农业真菌和细菌病害的用途。
Description
技术领域
本发明属于农药化学领域,特别涉及苯甲脒类衍生物、制备方法及应用。
背景技术
目前,以及在可预见的将来,植物病害的防治方式主要是采用化学杀菌剂。农用杀菌剂已经有有几十年的研发应用的历史。由于单一或有限品种的农用杀菌剂的持续使用,很多病原菌已经逐渐对应用最广的几种农药产生抗药性,这需要研究人员不断开发高效、安全、与当前主要商品药剂无交互抗性的农药品种,以满足植物保护、服务于农业生产的需要。
脒是氮取代的羧酸类似物,具有强碱性。相当数量的药物和农药分子含有脒类结构。在医药上,其抗微生物、抗炎抗生素、利尿、驱虫等活性被广泛研究。脒类化合物被研究的最多的,是具有对称结构的二苯甲脒类化合物。早期的临床试验证明,芳香二脒类化合物对早期非洲锥形虫症和利什曼原虫症有一定的治疗作用。芳香二脒类化合物不仅具有抗原虫活性,而且表现出杀虫、抗细菌、真菌、病毒、及肿瘤活性。而脒类化合物的农药活性没有引起足够的重视。特定结构的苯甲脒衍生物对活化凝血第X因子具有优异的抑制作用,可用作与血凝固有关的疾病的治疗剂和预防剂。苯甲脒和苯磺酰以酰二胺连接后形成的化合物具有优良的抗疟原虫活性。
2000年以来,西北农林科技大学一直在研究苯基脒化合物的农用活性,初步研究表明,芳基二脒类化合物对多种植物病原菌有独特的预防和治疗作用,特别是对由灰霉病菌引起的蔬菜、果树等经济作物上的病害,具有显著的防治效果。为了对于非对称结构的、仅含有单个苯甲脒单元的化合物的农药活性,我们也进行了持续的研究。研究发现,单苯甲脒类化合物的抑菌、抗病毒活性受苯环以及脒官能团上取代基的影响很大,合适的取代基能赋予该类化合物良好的抗菌、抗病毒活性。我们通过系统研究,发现了具有良好抑菌活性的苯甲脒类化合物。与已登记的农用杀菌剂活性化合物相比,该类化合物具有结构新颖的特点。
参考文献:[1]高柳大,鹭和之,中川忠清,等.苯甲脒衍生物:CN 2000;[2]斯蒂凡诺·彼格拉罗.作为抗疟剂的氨磺酰基-苯基-脲基苯甲脒衍生物:2011。
发明内容
本发明的目的在于提供苯甲脒类衍生物、制备方法及应用。
本发明的技术方案如下:
苯甲脒类衍生物,所述的苯甲脒类衍生物的结构如式I或式II所示:
其中R1、R2、R3、R4和R5选自:
氢,氨基,卤素,硝基,苄基,未取代或经卤素、C1-2烷氧基中选出1~2个取代基取代的未取代或经卤素、硝基、C1-2烷氧基中选出1~3个取代基取代的C1-4烷基,未取代或经卤素、硝基、C1-2烷氧基中选出1~2个取代基取代的C1-3烷氧基,未取代或经卤素、羟基、C1-2烷氧基取代的苄基;
R6和R7各自独立为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;R6和R7其中一个为氢时,另外一个为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;
n=0、1、2、3或4。
苯甲脒类衍生物,所述的苯甲脒类衍生物的结构如式III、式IV、式V或式VI所示:
苯甲脒类衍生物,结构式如式5a~5h所示:
苯甲脒类衍生物,结构式如式8a~8j所示:
本发明所述的苯甲脒类衍生物的合成方法,包括如下步骤:
步骤一、苄基1,2,4-三氮唑衍生物的合成:以三氮唑钾盐和对氰基卤代苄为原料,三氮唑钾盐溶于N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入对氰基卤代苄,后使其缓慢升温到25~60℃,继续反应8~24h后达到反应终点;
步骤二、苯甲基脒类衍生物的合成:将相应的取代苯甲腈在无水条件下与醇发生Pinner反应生成亚胺酯,然后再与相应的含有伯胺或仲胺的化合物反应得到相应的苯甲脒衍生物。
可选的,所述的对氰基卤代苄为4-氰基氯化苄;
具体反应过程为:先将1,2,4-三氮唑和氢氧化钾溶于甲醇或乙醇中生成三唑钾,减压蒸出溶剂,再加入N,N-二甲基甲酰胺溶解产物后减压蒸出以除去残余的少量水分,再将其溶于干燥N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入4-氰基氯化苄后使其缓慢升温到25~60℃,继续反应8~24h后达到反应终点;
反应物的物质的量配比为:KOH:1,2,4-三氮唑:4-氰基氯化苄=2.0~3.5:1.2~1.5:1。
可选的,所述的步骤二中,氮气气氛下,取代苯甲腈、四氢呋喃和乙醇混合均匀,-5℃低温反应;然后向混合物中通入干燥的氯化氢气体至饱和,保持通气温度不高于-2℃并防止空气进入反应体系,0℃下反应5h后使温度自然升温到室温反应4天;反应完毕后蒸除溶剂及重结晶后得到亚胺酯;
步骤二中与相应的含有伯胺或仲胺的化合物反应的有机溶媒为质量百分含量为99.9%的乙醇或者质量百分含量为99.9%的乙醇与无水甲苯、无水四氢呋喃或无水氯仿形成的混合溶剂;
具体的:将相应的含有伯胺或仲胺的化合物溶于有机溶媒中形成反应溶液,在隔绝湿气的条件下将制备得到的亚胺酯溶于有机溶媒中,然后向其中滴加制备的反应溶液;滴加完毕后,于室温搅拌6h反应。
本发明任一所述的苯甲脒类衍生物用于制备植物杀菌剂的应用。
本发明所述的苯甲脒类衍生物用于制备抑制玉米大斑病菌、苹果腐烂病菌、番茄灰霉病菌、油菜菌核病菌、烟草黑胫病菌、辣椒疫霉病菌、烟草青枯病菌、猕猴桃溃疡病菌和/或水稻白叶枯病菌引起的植物病害农药的应用。
一种植物杀菌剂,有效成分为本发明任一所述的苯甲脒类衍生物,质量百分含量为2%~60%。
本发明具有如下优点:
本发明利用常规化工原料为起始物,经过2-4步不等的化学反应,得到了系列苯甲脒类衍生物,经离体以及活体活性测试验证,该类化合物对三种农业病原真菌具有良好的抑制活性,对于猕猴桃溃疡病具有良好的防效,为相应病害的防治提供了一类全新的解决方案。在农业病害防治领域,该类化合物具有结构新颖、结构简单以及合成步骤短的特点,为农业病害防治提供了新思路。
具体实施方式
通过以下实施例有助于进一步理解本发明,所阐述的实施例系举例说明,而非被解释为对本发明的限定。
本发明提供的苯甲脒类衍生物,在现有技术中未见相关化合物的报道,且经试验证明该类化合物对农业病原真菌、细菌等病原菌均具有良好的抑制活性,为相应病害的防治提供了一类全新的解决方案。
本发明所述的农业病原真菌包含但不限于:藻菌纲中绵霉菌(Achlya)引起的水稻烂秧,腐霉菌(Pythium)引起的幼苗猝倒和瓜果腐烂,疫霉菌(Phytophthora)引起的烟草黑胫病和马铃薯晚疫病,白锈菌(Albugo)引起的白锈病,霜霉菌(Peronospora)引起的霜霉病;子囊菌纲中白粉菌(Erysiphe)引起的白粉病,囊壳菌(Gibberella)引起的水稻恶苗病、麦类赤霉病,黑星菌(Venturia)引起的苹果和梨的黑星病,核盘菌(Sclerotinia)引起的菌核病;担子菌纲中锈菌引起的锈病,黑粉菌(Ustilago)引起的黑粉病,半知菌类引起的稻瘟病、稻胡麻斑病、玉米大斑病、小斑病等。
本发明所述的农业病原细菌包含但不限于:假单胞杆菌属(Pseudomonas)、黄单胞杆菌属(Xanthomonas)、欧氏杆菌属(Erwinia)、野杆菌属(A□robacterium)和棒杆菌属(Corynebacterium)。其中除棒杆菌属外都为格兰氏阴性。
苯甲脒类衍生物,可由如下化学结构通式表达:
其中R1、R2、R3、R4和R5各自独立为氢,氨基,卤素,硝基,苄基,未取代或经卤素、C1-2烷氧基中选出1~2个取代基取代的未取代或经卤素、硝基、C1-2烷氧基中选出1~3个取代基取代的C1-4烷基,未取代或经卤素、硝基、C1-2烷氧基中选出1~2个取代基取代的C1-3烷氧基,未取代或经卤素、羟基、C1-2烷氧基取代的苄基的一种;
R6和R7各自独立为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;R6和R7其中一个为氢时,另外一个为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;
n=0、1、2、3或4。
本发明公开了一类4-((1H-1,2,4-三唑-1-基)甲基)-苯甲脒类衍生物,结构通式如式III和IV所示:
n=0、1、2、3或4;
表1本发明中合成的部分4-((1H-1,2,4-三唑-1-基)甲基)-苯甲脒类衍生物
本发明中合成的取代苯甲脒类衍生物的化学结构
本发明公开了一类苯甲脒类衍生物,结构通式如式V和VI所示:
其中:
R1=H,Me,Cl,F,Cl
R2=H,Me,Cl,F,Cl,Br
n=0,1,2或3;
表2本发明中合成的部分取代苯甲脒类衍生物
本发明的一种苯甲脒类衍生物的合成方法,如下:
步骤一、苄基1,2,4-三氮唑衍生物的合成:以三氮唑钾盐和对氰基卤代苄为原料,三氮唑钾盐溶于N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入对氰基卤代苄,后使其缓慢升温到25~60℃,继续反应8~24h后达到反应终点;
比如4-((1H-1,2,4-三氮唑-1-基)甲基)苯腈:以1,2,4-三氮唑和对氰基氯化苄为原料,首先将1,2,4-三氮唑制备成三氮唑钾盐,再与对氰基氯化苄反应得到产物。此反应过程中需不断调整优化反应条件与合成路线。
以对氰基卤代苄为4-氰基氯化苄为例;
具体反应过程为:先将1,2,4-三氮唑和氢氧化钾溶于甲醇或乙醇中生成三唑钾,减压蒸出溶剂,再加入N,N-二甲基甲酰胺溶解产物后减压蒸出以除去残余的少量水分,再将其溶于干燥N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入4-氰基氯化苄后使其缓慢升温到25~60℃,继续反应8~24h后达到反应终点;反应物的物质的量配比为:KOH:1,2,4-三氮唑:4-氰基氯化苄=2.0~3.5:1.2~1.5:1。
另外,步骤一得到的产物的纯化方式为萃取,优选的萃取剂为苯、甲苯或二氯甲烷。产物直接在有机相内利用干燥剂干燥,干燥剂优选为无水硫酸镁、3A或4A分子筛,干燥时间大于8h。
步骤二、苯甲基脒类衍生物的合成:将相应的取代苯甲腈在无水条件下与醇发生Pinner反应生成亚胺酯,比如(4-((1H-1,2,4-三唑-1-基)甲基)-苯甲基乙亚胺酯的合成:取代苯甲腈中加入无水醇,进行Pinner反应后得到产物;然后再与相应的含有伯胺或仲胺的化合物反应得到相应的苯甲脒衍生物,比如4-((1H-1,2,4-三唑-1-基)甲基)-苯甲脒类衍生物的合成:将相应的胺溶于无水溶剂后加入到亚胺酯的溶液中,经过胺解反应得到目的产物。具体包括,氮气气氛下,取代苯甲腈、四氢呋喃和乙醇混合均匀,-5℃低温反应;然后向混合物中通入干燥的氯化氢气体至饱和,保持通气温度不高于-2℃并防止空气进入反应体系,0℃下反应5h后使温度自然升温到室温反应4天;反应完毕后蒸除溶剂及重结晶后得到亚胺酯;
步骤二中与相应的含有伯胺或仲胺的化合物反应的有机溶媒为质量百分含量为99.9%的乙醇或者质量百分含量为99.9%的乙醇与无水甲苯、无水四氢呋喃或无水氯仿形成的混合溶剂;具体的:将相应的含有伯胺或仲胺的化合物溶于有机溶媒中形成反应溶液,在隔绝湿气的条件下将制备得到的亚胺酯溶于有机溶媒中,然后向其中滴加制备的反应溶液;滴加完毕后,于室温搅拌6h反应。
另外,步骤二中使用的醇类溶剂为含水量不超过0.01%(质量百分含量)的绝对乙醇或绝对甲醇。Pinner反应条件为:在冰浴条件下,通入干燥的氯化氢气体至饱和。反应混合物在室温条件下搅拌3~7天后,在无水条件下将溶剂蒸出,利用乙醚重结晶得到中间体,无需进一步纯化,可直接用于下一步反应。
步骤二中,与相应的含有伯胺或仲胺的化合物反应的反应温度为室温,反应时间根据胺的种类不同,为2~10h。
步骤二中反应产物的分离纯化具体方法为柱层析,用洗脱剂二氯甲烷/甲醇或氯仿/甲醇以等比例或梯度洗脱,柱层析填料为中性或碱性氧化铝。
本发明的苯甲脒类衍生物及其农药制剂上可接受的盐与常见农药辅料和载体结合,制备抗农业病原菌的组合物,可达到保护和治疗农业病害的效果。上述化合物可根据实际需要选择合适的剂型,如悬浮剂、水乳剂、可溶性液剂等。即本发明的苯甲脒类衍生物用于制备植物杀菌剂的应用。特别是用于制备抑制玉米大斑病菌、苹果腐烂病菌、番茄灰霉病菌、油菜菌核病菌、烟草黑胫病菌、辣椒疫霉病菌、烟草青枯病菌、猕猴桃溃疡病菌和/或水稻白叶枯病菌引起的植物病害农药的应用。
选取农业上6种重要的植物病原真菌:油菜菌核病菌(Sclerotiniasclerotiorum)、番茄灰霉病菌(Botrytis cinerea)、玉米大斑病菌(Exserohilumturcicum(Pass.)Leonay et Suggs),烟草黑胫病菌(Phytophthoraparasiticavar.nicotianae(Breda de hean)Tuker,辣椒疫霉病菌(PhytophthoracapsiciLeonian)和苹果腐烂病菌(Valsa maliMiyabe et Yamada.)作为供试菌种,在50mg/L的浓度下,用含药培养基法测量了4-((1H-1,2,4-三唑-1-基)甲基)-苯甲脒类衍生物和取代苯甲脒类衍生物对这些菌的离体抑制活性;选取3中农业病原细菌:丁香假单胞杆菌(Pseudomonas syringae)及烟草青枯病菌(Ralstonia solanacearum(E.F.Smith)Yabuuhi et al.)和水稻白叶枯病菌(Xanthomonas oryzae(Uyeda et Ishiyama)Dowson)作为供试细菌,用浑浊度法测试了标题化合物对细菌的抑制活性;结果表明该系列化合物普遍具有显著的抗菌活性,可以用作新型农用杀菌剂的候选化合物。
实施例中使用的测定仪器:高分辨率质谱用美国LC-30A–Triple TOF5600+高分辨液质联用仪;核磁共振用瑞士Bruker AV-500核磁共振仪;反应试剂均为常规市售试剂,试剂均为分析纯或化学纯;氘代试剂购自美国剑桥CIL试剂公司。
以下实验中如无特殊说明,使用的相关溶剂的百分含量浓度均为质量百分含量。以下实验中如无特殊说明,所用的实验方法均为本领域常规实验方法。
实施例1:4-((1H-1,2,4-三唑-1-基)甲基)-N-丙基苯甲脒(5a)的合成
实施例中的目标化合物5a-5h的通用合成步骤如下所示:
步骤1,中间体4-((1H-1,2,4-三唑-1-基)甲基)苯腈(3)的合成:向100mL圆底烧瓶中加入如下底物:1H-1,2,4-三唑2.75g(0.04mol),KOH 2.63g(0.047mol),甲醇15mL,加热至60℃使之溶解。将上述混合物减压浓缩,得到三唑钾的结晶状物质。再向上述烧瓶中加入二甲基甲酰胺(DMF)15mL,继续浓缩除去残留的甲醇和水。再向其中加入40mL DMF,降温至-10℃,分批加入6.25g(0.032mol)4-(溴甲基)苯腈(对氰基溴苄),在加入过程中保持体系温度不高于5℃。反应混合物在50℃下搅拌45分钟后,将其减压浓缩(85℃,真空度:0.095MPa)到无溶剂蒸出为止,再加入饱和食盐水20mL、甲苯60mL,于室温搅拌30min,分离出油相,水相用甲苯(20mL×3)提取,合并油相,向其中加入3g无水硫酸镁干燥,过滤,浓缩至无溶剂蒸出,加入石油醚25mL,室温搅拌1h后过滤,滤去石油醚,之后在110℃干燥4小时,得到白色晶体4.81g,产率:82%。
步骤2,中间体4-((1H-1,2,4-三唑-1-基)甲基)苯亚胺酸乙酯(4)的合成:在250mL装有磁力搅拌和温度计的三口烧瓶中,将2.0g(0.011mol)化合物3溶于15mL绝对乙醇。用低温浴槽降温至5℃以下后通入干燥的氯化氢气体,控制通气速率,保持温度不超过5℃。通气至饱和后隔绝湿气密封,在0℃中搅拌3hr后自然升温至室温搅拌4天,在无水条件下减压蒸发至浓稠状。加入无水乙醚重结晶,在干燥的条件下过滤,重复三遍得白色晶体2.22g(0.0091mol),收率:84%。
步骤3,目标化合物4-((1H-1,2,4-三唑-1-基)甲基)-N-丙基苯甲脒(5a)的合成:用10mL绝对甲醇将所得白色晶体溶解,置于50mL圆底烧瓶内,加入正丙胺20mmol(1.18g),隔绝湿气搅拌10小时,减压蒸馏(70℃,真空度:0.09MPa)除去溶剂及一部分胺直至无液体蒸出,加入30%的NaOH水溶液2mL,乙醚20mL,搅拌后混合物分为三层,分液除去上部分乙醚相以及下部分水相,中间粘稠物用柱层析(CH2Cl2/MeOH梯度或CH2Cl2:MeOH=15:1等比洗脱),得到白色晶体0.685g(2.8mmol),收率:31%。
波谱信息:1H NMR(500MHz,DMSO)δ8.72(s,1H),8.05(s,1H),7.97(d,J=8.3Hz,2H),7.40(d,J=8.3Hz,2H),5.55(s,2H),4.33(q,J=7.1Hz,2H),2.57–2.49(m,1H),1.33(t,J=7.1Hz,3H).13C NMR(126MHz,DMSO)δ165.87,152.44,145.07,142.01,129.95,129.91,128.44,61.27,52.10,14.62.HR-MS(ESI)m/z:found 244.1559[M+H]+,calcd.forC13H18N5 244.1559.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5a的化学式为C13H18N5,结构式如下:
实施例2:2-(4-((1H-1,2,4-三唑-1-基)甲基)苯基)-4,5,6,7,8,9-六氢-1H-1,3-二偶氮宁(5b)的合成
化合物5b的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以己二胺;
白色晶体,收率:36%。合成产物的波谱数据如下:1H NMR(500MHz,DMSO)δ8.73(d,J=5.2Hz,2H),8.02(s,2H),7.74(d,J=8.0Hz,2H),7.38(d,J=8.0Hz,2H),5.52(s,2H),3.22(m,4H),1.69–1.57(m,4H),0.96(m,4H).HR-MS(ESI)m/z:found 284.1877[M+H]+,calcd.for C16H22N5284.1875.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物5b的化学式为C16H21N5,结构式如下:
实施例3:4-((1H-1,2,4-三唑-1-基)甲基)-N-仲丁基苯甲脒(5c)的合成
化合物5c的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以仲丁胺;
淡黄色晶体,收率:29%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ9.17(s,3H),8.74(s,1H),8.01(s,1H),7.76(d,J=8.2Hz,3H),7.49(d,J=8.0Hz,3H),5.57(s,3H),3.98(s,2H),2.53(s,1H),1.68(td,J=14.3,7.3Hz,1H),1.60(dt,J=13.6,6.7Hz,1H),1.25(d,J=6.4Hz,4H),0.95(t,J=7.3Hz,4H).HR-MS(ESI)m/z:found 258.1722[M+H]+,calcd.for C14H20N5 258.1719.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物5b的化学式为C14H19N5,结构式如下:
实施例4:4-((1H-1,2,4-三唑-1-基)甲基)-N-正己基苯甲脒(5d)的合成
化合物5d的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以正己胺;
白色晶体,收率:41%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ8.71(s,1H),8.02(s,1H),7.72(d,J=8.1Hz,2H),7.34(d,J=8.1Hz,2H),5.49(s,2H),3.18(t,J=7.0Hz,3H),1.58(dd,J=14.5,7.2Hz,3H),1.30(dd,J=12.6,9.6Hz,7H),0.90(t,J=6.2Hz,3H).HR-MS(ESI)m/z:found 286.2036[M+H]+,calcd.for C16H24N5 286.2032.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5b的化学式为C16H23N5,结构式如下:
实施例5:4-((1H-1,2,4-三唑-1-基)甲基)-N,N-二乙基苯甲脒(5e)的合成
化合物5e的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以二乙胺;
淡黄色晶体,收率:22%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ8.72(s,1H),8.04(s,1H),7.97(d,J=8.2Hz,2H),7.40(d,J=8.1Hz,2H),5.55(s,2H),4.33(q,J=7.1Hz,2H),2.53(s,2H),1.33(t,J=7.1Hz,3H).HR-MS(ESI)m/z:found 258.1720[M+H]+,calcd.for C16H24N5 258.1719.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5e的化学式为C14H19N5,结构式如下:
实施例6:4-((1H-1,2,4-三唑-1-基)甲基)-1,4,5,6-四氢嘧啶(5f)的合成
化合物5f的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以丙二胺;
淡黄色晶体,收率:43%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ8.78(s,1H),8.04(s,1H),7.80(d,J=8.2Hz,2H),7.46(d,J=8.3Hz,2H),5.57(s,2H),3.48(t,J=5.7Hz,4H),2.01–1.88(m,2H).HR-MS(ESI)m/z:found 242.1404[M+H]+,calcd.for C13H16N5 242.1406.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5f的化学式为C13H15N5,结构式如下:
实施例7:4-((1H-1,2,4-三唑-1-基)甲基)-4,5-二氢咪唑(5g)的合成
化合物5g的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以乙二胺;
淡黄色晶体,收率:30%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ8.73(s,0H),8.04(s,0H),7.90(d,J=8.3Hz,1H),7.72(d,J=18.9Hz,0H),7.39(d,J=8.3Hz,1H),5.52(d,J=10.3Hz,1H),3.75(s,2H),2.57–2.49(m,1H).HR-MS(ESI)m/z:found 228.1246[M+H]+,calcd.for C16H24N5 228.1249.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5f的化学式为C12H14N5,结构式如下:
实施例8:4-((1H-1,2,4-三唑-1-基)甲基)-N-(2-羟乙基)苯甲脒(5h)的合成
化合物5h的合成步骤参照实施例1中的通用合成步骤,将实施例1中步骤3的正丙胺更代之以乙醇胺;
淡黄色晶体,收率:36%。产物的波谱数据如下:1H NMR(500MHz,DMSO)δ8.72(s,0H),8.35(s,0H),8.04(s,0H),7.88(d,J=8.3Hz,2H),7.36(d,J=8.4Hz,1H),5.51(d,J=8.1Hz,1H),4.42(t,J=9.5Hz,1H),3.97(t,J=9.5Hz,1H),3.38(s,2H),2.57–2.49(m,0H).HR-MS(ESI)m/z:found 245.1279[M+H]+,calcd.for C16H24N5 245.1277.根据以上高分辨质谱及核磁谱信息,可鉴定化合物5h的化学式为C12H15N5O,结构式如下:
实施例9:N-丁基-4-氟苯甲脒(8a)的合成
实施例中的目标化合物8a-8f的通用合成步骤如下所示:
步骤1,中间体乙基4-氟苯亚胺酸乙酯(7)的合成:用99.999的高纯氮气将装有磁力搅拌和温度计的100mL三口烧瓶中中的空气置换三遍,然后向其中加入4-氟苯甲腈(2.42g,0.02mol)、无水四氢呋喃(20ml)绝对乙醇(20ml),室温搅拌30分钟混合均匀。然后在氮气保护下,用低温反应槽将混合物的温度降低至-5℃,然后用鼓泡法向混合物中通入干燥的氯化氢气体,保持通气温度不高于-2℃并防止空气进入反应体系。带体系内氯化氢气体饱和后,停止通气,密封反应装置。在0℃下反应5小时后使温度自然升温到室温反应四天。反应完毕后将反应混合物在无水条件下蒸除溶剂,然后用无水乙醚重结晶得到产物,可不经进一步处理直接用于下一步反应。
步骤2,N-丁基-4-氟苯甲脒(8a)的合成:将正丁胺(5.8g,0.08mol)溶于15ml绝对乙醇中。在隔绝湿气的条件下将步骤1中制备的中间体(7)溶于20ml绝对乙醇中,然后像其中滴加制备的正丁胺乙醇溶液。滴加完毕后,于室温搅拌6小时。蒸除溶剂后加入2N NaOH水溶液10ml,用二氯甲烷(20ml×3)萃取后将有机相合并,用柱层析法(CH2Cl2/MeOH梯度或CH2Cl2:MeOH=20:1等比洗脱)分离得到白色晶体2.02g,收率,54%。
波谱数据如下:1H NMR(500MHz,DMSO)δ7.75(d,J=7.4Hz,2H),7.64(d,J=7.9Hz,2H),2.98(d,J=6.6Hz,2H),2.53(s,1H),1.91(m,2H),0.97(t,J=6.6Hz,3H).3.22(d,J=7.1Hz,3H),3.20(s,1H),2.53(s,0H),1.69–1.57(m,2H),0.96(t,J=7.3Hz,1H).HR-MS(ESI)m/z:found 195.1296[M+H]+,calcd.for C11H15FN2 195.1298.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8a的化学式为C11H14FN2,结构式如下:
实施例10:2-(4-氟苯基)-4,5-二氢-1H-咪唑(8b)的合成
化合物8b的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤2中的正丁胺更换为乙二胺;
淡黄色晶体,收率:40%。产物的波谱数据如下:
1H NMR(500MHz,DMSO)δ7.89(dd,J=8.6,5.7Hz,1H),7.29(t,J=8.9Hz,1H),3.62(s,2H).13C NMR(126MHz,DMSO)δ164.70,163.09,129.91,129.84,127.72,115.69,115.52.HR-MS(ESI)m/z:found 165.0829[M+H]+,calcd.for C9H11FN2165.0828.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8b的化学式为C8H10FN2,结构式如下:
实施例11:4-溴-N-十四烷基苯甲脒(8c)的合成
化合物8c的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为4-溴苯甲腈,步骤2中的正丁胺更换为十四胺;
淡黄色晶体,收率:51%,m.p.49.1-52℃。产物的波谱数据:
1H NMR(500MHz,DMSO)δ7.59(d,J=8.4Hz,2H),7.43(d,J=8.4Hz,2H),2.67–2.47(m,2H),1.48–1.31(m,2H),1.01(s,22H),0.64(s,3H).13C NMR(126MHz,DMSO)δ165.26,131.97,129.49,128.44,126.56,31.54,29.26,29.19,29.11,28.96,28.80,28.48,26.35,22.30,13.78.HR-MS(ESI)m/z:found[M+H]+395.2046,calcd.for C21H36BrN2 395.2062,结构式如下:
实施例12:2-(4-溴苯基)-4,5,6,7,8,9-六氢-1H-1,3-二偶氮宁(8d)的合成
化合物8d的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为4-溴苯甲腈,步骤2中的正丁胺更换为己二胺;
淡黄色晶体,收率:51%。产物的波谱数据:1H NMR(500MHz,DMSO)δ7.72(d,J=7.7Hz,2H),7.47(d,J=7.3Hz,2H),3.53(m,4H),1.61(m,4H),0.92(m,4H).HR-MS(ESI)m/z:found 280.0577[M+H]+,calcd.for C13H17BrN2280.0575.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8d的化学式为C13H16BrN2,结构式如下:
实施例13:2-(4-溴苯基)-1,4,5,6-四氢嘧啶(8e)的合成
化合物8e的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为4-溴苯甲腈,步骤2中的正丁胺更换为丙二胺;
淡黄色固体,收率:47%。产物的波谱数据:1H NMR(500MHz,DMSO)δ7.82(d,J=8.2Hz,2H),7.69(d,J=8.2Hz,2H),4.31(s,2H),3.50–3.13(m,1H),2.42-2.76(m,2H),1.71–1.27(m,2H).HR-MS(ESI)m/z:found 239.0185[M+H]+,calcd.for C10H12BrN2239.0184.
实施例14:4-溴-N-异丁基苯甲脒(8f)的合成
化合物8f的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为4-溴苯甲腈,步骤2中的正丁胺更换为异丁胺;
淡灰色固体,收率:39%。产物的波谱数据:1H NMR(500MHz,DMSO-d6)δ7.75(d,J=8.4Hz,2H),7.64(d,J=8.0Hz,2H),2.98(d,J=6.6Hz,2H),1.91(dt,J=13.3,6.6Hz,1H),0.97(d,J=6.6Hz,6H).13C NMR(126MHz,DMSO)δ167.39,156.35,135.43,131.46,129.42,123.88,53.30,29.04,21.13.HR-MS(ESI)m/z:found 255.0499[M+H]+,calcd.forC11H16BrN2 255.0497.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8f的化学式为C11H15BrN2,结构式如下:
实施例15:4-溴-N-正辛基苯甲脒(8g)的合成
化合物8g的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为4-溴苯甲腈,步骤2中的正丁胺更换为正辛胺;
白色粉末(C15H23BrN2),产率55.1%,m.p.76.7-77.8℃。1H NMR(500MHz,DMSO)δ8.04(s,1H),7.81(d,J=7.9Hz,2H),7.66(d,J=7.9Hz,2H),7.45(s,1H),2.88(s,1H),2.54(s,1H),1.34(s,2H),1.23(s,10H),0.85(s,3H).13C NMR(126MHz,DMSO)δ166.86,133.38,131.15,131.15,129.54,129.54,124.92,31.19,28.79,28.64,28.64,26.31,26.31,22.02,13.86.HR-MS(ESI)m/z:found311.1129[M+H]+,calcd.for C15H24BrN2 311.1123.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8g的化学式为C10H11N2,结构式如下:
实施例16:2-邻甲基-4,5-二氢-1H-咪唑(8h)的合成
化合物8h的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为2-甲基苯腈,步骤2中的正丁胺更换为乙二胺;
淡灰色固体,收率:39%。产物的波谱数据:
M9:1H NMR(500MHz,DMSO-d6)δ7.49(d,J=7.6Hz,1H),7.33(t,J=7.4Hz,1H),7.30–7.21(m,2H),3.61(s,5H),2.47(s,3H).13C NMR(126MHz,DMSO)δ165.41,137.12,132.00,131.11,129.56,128.88,125.86,50.24,21.07.HR-MS(ESI)m/z:found 161.1077[M+H]+,calcd.for C10H12N2 161.1079.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8h的化学式为C10H11N2,结构式如下:
实施例17:2-邻甲基-N-正辛基苯甲脒(8i)的合成
化合物8i的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为2-甲基苯腈,步骤2中的正丁胺更换为正辛胺;
淡黄色固体,收率:39%。产物的波谱数据:
1H NMR(500MHz,DMSO)δ8.07(s,2H),7.25–7.20(m,1H),7.17–7.12(m,1H),3.19(s,2H),2.43–2.11(m,3H),1.55(s,2H),1.30(dd,J=49.8,14.1Hz,10H),0.84(t,J=6.6Hz,3H).13C NMR(126MHz,DMSO)δ163.12,134.13,129.73,129.73,128.23,126.80,125.10,41.49,31.10,28.66,28.55,28.55,26.58,21.91,18.74,13.62.ESI-MS:MS(ESI)m/z:found,247.2156[M+H]+,calculated for C16H27N2:247.2174;
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8i的化学式为C10H11N2,结构式如下:
实施例18:N-(2-羟乙基)-2-甲基苯甲脒(8j)的合成
化合物8j的合成步骤参照实施例9中的通用合成步骤,将实施例9中步骤1中的4-氟苯甲腈更换为2-甲基苯腈,步骤2中的正丁胺更换为乙醇胺;
淡黄色固体,收率:44%。产物的波谱数据:1H NMR(500MHz,MeOD)δ7.69(d,J=7.6Hz,0H),7.53(dd,J=11.4,4.5Hz,1H),7.48(t,J=7.2Hz,1H),7.45–7.37(m,2H),4.94(s,8H),3.86(t,J=5.2Hz,2H),3.61(t,J=5.2Hz,2H),2.46(s,3H).HR-MS(ESI)m/z:found179.1187[M+H]+,calcd.for C10H15N2O 179.1184.
根据以上高分辨质谱及核磁谱信息,可鉴定化合物8j的化学式为C10H14N2O,结构式如下:
实施例19所制备化合物对6种代表性植物病害病原真菌的抑制活性的测定
抑菌活性测定方法如下:
(1)病原真菌的培养:将病原菌接种于PDA培养基上,置于25±0.1℃恒温培养箱中培养3-6天,菌丝长好后备用。
(2)测定方法:离体抑制活性采用菌丝生长速率法测定。
将供试化合物和对照药剂用DMSO(二甲基亚砜)配制成20000mg/L的药液,再继续用1%的吐温80水溶液稀释到4000mg/L的药液。随后将计算量的药液与PDA(马铃薯-葡萄糖-琼脂)培养基配制成测试浓度。以DMSO作为空白对照,多菌灵为阳性对照。将培养基在9cm培养皿中制备成平板、每个处理三个重复,接种5mm菌饼后置于26±1℃的恒温培养箱中。待空白对照培养皿中的菌落直径7.5-8cm后用十字交叉法测量各处理及对照的菌落直径。
(3)抑菌率的计算:
菌落增长直径(mm)=菌落测量直径(mm)-菌饼直径(mm);
菌丝生长抑制率(%)=[对照菌落增长直径(mm)-含药培养基上菌落增长直径(mm)]对照菌落增长直径(mm)×100;
按照上述方法,在50mg/L浓度下测试实施例1-18所制备化合物对6种代表性植物病原的抑制效果,测定结果见表4(表中数据为各化合物在测试浓度下对病原菌的生长抑制百分率)。
表3部分苯甲脒类衍生物对6种农业病原真菌的抑制率(50mg/L)
试验结果表明:在50mg/L的测试浓度下,多个化合物对多数供试病原真菌都有不同程度的抑制作用。对于不同的菌株,化合物5e、8b、8g、8i皆表现出了优异的抑菌活性。化合物5e对番茄灰霉病菌和油菜菌核病菌的抑制活性分别达到93.48%和96.10%。化合物8b同样也对番茄灰霉病菌表现出了达92%的抑制率。8g对四株病原菌菌显示出了优异的抑制活性,其对玉米大斑病菌、苹果腐烂病菌、番茄灰霉病菌、油菜菌核病菌、烟草黑胫病菌的抑制活性分别为94.55%、100%、95.33%、100%、99.03%。以上数据表明了示例化合物对常见农业病原真菌具有优异的抑制活性。
制细菌活性测定:
参照文献(NY/T 1156.16-2008农药室内生物测定试验准则杀菌剂第16部分:抑制细菌生长量试验浑浊度法)报道的方法测试化合物对三种植物病原细菌的离体抑制活性。先将化合物溶于DMSO配成高浓度的母液,然后用0.1的PEG400水溶液将待化合物稀释到待测浓度。将待测药液与对数生长期的细菌悬浮液(OD 600nm=0.1~0.2)以体积比为1:1混合后加入到孔板内,并设置溶剂对照。然后将孔板置于28℃的培养箱中培养36-48h。在600nm波长下测量细菌悬浮液的OD值。由式3计算抑制率:
其中ODCK为空白对照组细菌校正浊度值(OD 600nm),ODT为处理组细菌校正浊度值(OD 600nm)。
表4部分苯甲脒类衍生物对3种农业病原细菌的抑制率
由以上数据可以看出,大多数示例化合物对供试植物病原细菌表现出了一定的抑制活性。尤其是8c,其在50mg/L的浓度下对烟草青枯病菌、猕猴桃溃疡病菌、水稻白叶枯病菌的抑制率分别达到了85.66%、90.38%和78.41%。
实施例20:有效成分浓度为60%的4-溴-N-正辛基苯甲脒悬浮剂;
处方组成以100g样品为例:4-溴-N-正辛基苯甲脒60.0g、分散剂木质素磺酸钠4.0g、润湿剂Atlars G-2242 2.5g、防冻剂乙二醇6g、硅酮消泡剂1g、增稠剂黄原胶0.15g,软水补足到100g。
制备工艺:将计量数的4-溴-N-正辛基苯甲脒、木质素磺酸钠、润湿剂Atlars G-2242、乙二醇、软水加入到胶体磨中研磨10分中进行预混合,过程中利用硅酮消泡剂消除过程中产生的泡沫;利用砂磨机研磨预混合物料50分钟后,将物料过滤放出,加入含有5%的黄原胶水溶液3g后利用剪切分散机混合15分钟得到成品,检测合格后包装。
实施例21:有效成分浓度为40%的4-溴-N-正辛基苯甲脒可溶性液剂:
将4-溴-N-正辛基苯甲脒化合物8g与10g农乳1601#表面活性剂混合后,用乙醇稀释到100mL混合均匀,即可制成本发明所述的可溶性液剂产品。
实施例22:有效成分浓度为2%的4-溴-N-正辛基苯甲脒水剂:
将4-溴-N-正辛基苯甲脒化合物2g溶于5mL95%乙醇后,加入润湿剂Atlas G-263、5g,农乳1601#表面活性剂乳化后,用去离子水稀释到100mL混合均匀,即可制成。
以上详细描述了本公开的优选实施方式,但是,本公开并不限于上述实施方式中的具体细节,在本公开的技术构思范围内,可以对本公开的技术方案进行多种简单变型,这些简单变型均属于本公开的保护范围。
另外需要说明的是,在上述具体实施方式中所描述的各个具体技术特征,在不矛盾的情况下,可以通过任何合适的方式进行组合,为了避免不必要的重复,本公开对各种可能的组合方式不再另行说明。
此外,本公开的各种不同的实施方式之间也可以进行任意组合,只要其不违背本公开的思想,其同样应当视为本公开所公开的内容。
Claims (10)
1.苯甲脒类衍生物,其特征在于,所述的苯甲脒类衍生物的结构如式I或式II所示:
其中R1、R2、R3、R4和R5选自:
氢,氨基,卤素,硝基,苄基,未取代或经卤素、C1-2烷氧基中选出1~2个取代基取代的未取代或经卤素、硝基、C1-2烷氧基中选出1~3个取代基取代的C1-4烷基,未取代或经卤素、硝基、C1-2烷氧基中选出1~2个取代基取代的C1-3烷氧基,未取代或经卤素、羟基、C1-2烷氧基取代的苄基;
R6和R7各自独立为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;R6和R7其中一个为氢时,另外一个为未取代或经卤素、羟基、C1-2烷氧基选出一个取代的直链或支链C1-18烷基;
n=0、1、2、3或4。
5.权利要求1-4任一所述的苯甲脒类衍生物的合成方法,其特征在于,包括如下步骤:
步骤一、苄基1,2,4-三氮唑衍生物的合成:以三氮唑钾盐和对氰基卤代苄为原料,三氮唑钾盐溶于N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入对氰基卤代苄,后使其缓慢升温到25~60℃,继续反应8~24h后达到反应终点;
步骤二、苯甲基脒类衍生物的合成:将相应的取代苯甲腈在无水条件下与醇发生Pinner反应生成亚胺酯,然后再与相应的含有伯胺或仲胺的化合物反应得到相应的苯甲脒衍生物。
6.根据权利要求5所属的苯甲脒类衍生物的合成方法,其特征在于,所述的对氰基卤代苄为4-氰基氯化苄;
具体反应过程为:先将1,2,4-三氮唑和氢氧化钾溶于甲醇或乙醇中生成三唑钾,减压蒸出溶剂,再加入N,N-二甲基甲酰胺溶解产物后减压蒸出以除去残余的少量水分,再将其溶于干燥N,N-二甲基甲酰胺后,先在0~15℃的范围内分批或一次性加入4-氰基氯化苄后使其缓慢升温到25~60℃,继续反应8-24小时后达到反应终点;
反应物的物质的量配比为:KOH:1,2,4-三氮唑:4-氰基氯化苄=2.0~3.5:1.2~1.5:1。
7.根据权利要求5所属的苯甲脒类衍生物的合成方法,其特征在于,
所述的步骤二中,氮气气氛下,取代苯甲腈、四氢呋喃和乙醇混合均匀,-5℃低温反应;然后向混合物中通入干燥的氯化氢气体至饱和,保持通气温度不高于-2℃并防止空气进入反应体系,0℃下反应5h后使温度自然升温到室温反应4天;反应完毕后蒸除溶剂及重结晶后得到亚胺酯;
步骤二中与相应的含有伯胺或仲胺的化合物反应的有机溶媒为质量百分含量为99.9%的乙醇或者质量百分含量为99.9%的乙醇与无水甲苯、无水四氢呋喃或无水氯仿形成的混合溶剂;
具体的:将相应的含有伯胺或仲胺的化合物溶于有机溶媒中形成反应溶液,在隔绝湿气的条件下将制备得到的亚胺酯溶于有机溶媒中,然后向其中滴加制备的反应溶液;滴加完毕后,于室温搅拌6h反应。
8.权利要求1~4任一所述的苯甲脒类衍生物用于制备植物杀菌剂的应用。
9.权利要求1~4任一所述的苯甲脒类衍生物用于制备抑制玉米大斑病菌、苹果腐烂病菌、番茄灰霉病菌、油菜菌核病菌、烟草黑胫病菌、辣椒疫霉病菌、烟草青枯病菌、猕猴桃溃疡病菌和/或水稻白叶枯病菌引起的植物病害农药的应用。
10.一种植物杀菌剂,其特征在于,有效成分为权利要求1~4任一所述的苯甲脒类衍生物,质量百分含量为2%~60%。
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CN117586546A (zh) * | 2024-01-18 | 2024-02-23 | 常州六次方纳米科技有限公司 | 一种单壁碳纳米管改性抗静电涂层的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2042528A (en) * | 1979-02-08 | 1980-09-24 | Ube Industries | Benzamidine derivatives, process for preparing the same and fungicidal compositions containing the same |
CN103664875A (zh) * | 2013-12-21 | 2014-03-26 | 西北大学 | 1,4,5,6-四氢嘧啶衍生物的合成新方法 |
-
2021
- 2021-09-18 CN CN202111111946.1A patent/CN113880780A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2042528A (en) * | 1979-02-08 | 1980-09-24 | Ube Industries | Benzamidine derivatives, process for preparing the same and fungicidal compositions containing the same |
CN103664875A (zh) * | 2013-12-21 | 2014-03-26 | 西北大学 | 1,4,5,6-四氢嘧啶衍生物的合成新方法 |
Non-Patent Citations (5)
Title |
---|
AMERICAN CHEMICAL SOCIETY (ACS): "STNext, Registry 数据库", HTTP://WWW.STN.ORG, 11 February 2002 (2002-02-11), pages 391220 - 3 * |
AMERICAN CHEMICAL SOCIETY (ACS): "STNext,Registry数据库", HTTP://WWW.STN.ORG, pages 391220 - 33 * |
SHENGBO XU等: "Rhodium-catalyzed C-H activation/annulation of amidines with 4-diazoisochroman-3-imines toward isochromeno[3, 4-c]isoquinolines", 《ORG. BIOMOL. CHEM.》, vol. 17, no. 36, 30 August 2019 (2019-08-30), pages 8417 - 8424 * |
陈光友: "芳基脒类化合物 的合成与农用抑菌活性 研究", 《中国博士学位论文全文数 据库农业科技辑》, vol. 2016, 15 June 2016 (2016-06-15), pages 046 - 22 * |
陈光友: "芳基脒类化合物的合成与农用抑菌活性研究", 《中国博士学位论文全文数据库农业科技辑》, no. 2016, pages 046 - 22 * |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117586546A (zh) * | 2024-01-18 | 2024-02-23 | 常州六次方纳米科技有限公司 | 一种单壁碳纳米管改性抗静电涂层的制备方法 |
CN117586546B (zh) * | 2024-01-18 | 2024-04-12 | 常州六次方纳米科技有限公司 | 一种单壁碳纳米管改性抗静电涂层的制备方法 |
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