喹啉-2，4-二酮类衍生物的合成及杀虫活性研究
摘要
近年来,杂环化合物在抑菌、除草以及杀虫等植物保护领域以其高效、低毒和对环境友好的特点,在新农药的开发研制领域受到极大的关注。喹啉类化合物是氮杂环中非常重要的一类化合物,在医疗保健和植物保护领域具有广泛的应用性和良好的发展前景,是抗肿瘤、抗艾滋病毒等药物的重要前体化合物,同时在新型绿色农药的创制中也占据着重要地位。
基于此,本论文设计以邻氨基苯甲酸,对氯邻氨基苯甲酸和5-甲基邻氨基苯甲酸为原料,通过酯化、酰化、环合再酯化的合成路线合成了24个喹啉-2,4-二酮类衍生物,化合物结构均经1~H-NMR、IR和ESI-MS等波谱手段予以确认,所有化合物均未见文献报道。对新化合物进行三龄粘虫的拒食活性和毒杀活性研究,希望能为高效低毒的新型杀虫剂的创制奠定一定的理论基础。
初步杀虫活性测试结果表明,在100 mg/L浓度下,24种化合物对三龄粘虫均有不同程度的拒食活性和毒杀活性。实验数据表明,喹啉环上3位取代基为2,4-二氯苯时活性要优于3位取代基为3,4-二氯苯基的化合物,例如,化合物M3b对粘虫的校正死亡率达到19.28%,而化合物M4b的校正死亡率只有10.00%;喹啉环中苯环上的取代基的类型与位置的不同对化合物杀虫活性差异并无明显影响,例如M1a、M2d和M3e三种化合物对粘虫的校正死亡率分别为17.20%、16.92%和14.96%,差别不大;对4位羟基酯化衍生后,发现使用可α-甲基丙烯酰氯进行酯化的化合物的活性要优于同中间体衍生的其他化合物,例如,化合物M1a对粘虫的校正死亡率在48 h时达到17.20%,接近吡虫啉22.86%的校对死亡率,也明显高于同一中间体衍生的其他化合物M1b(8.00%)、M1c(4.00%)、M1d(8.00%)和M1e(8.62%)。
In recent years, heterocyclic compounds are used to research and develop new pesticides because of theirs features of high efficiency, low toxicity and environmentally friendly in the areas of antibacterial, herbicidal and insecticidal plant protection.Quinoline compounds are a very important class of heterocyclic compounds, which have wide application and good prospects for development in the field of health care and plant protection. They are important precursor compounds of the drug for the anti-tumor, anti-HIV drugs and so on, while are also occupy an important position on created of new green pesticides
Based on this, the paper designed to use anthranilic acid, p-chloro anthranilic acid and 4- methyl anthranilic acid as raw materials ,we synthesized 24 quinoline-2,4-dione derivatives by esterification , acylation, cyclization and then esterification,and all the synthesized compounds were characterized by IR, NMR and ESI-MS,and the derivatives were first studied.All the compounds were studied for antifeedant activity and insecticidal activity of third M. separata, in order to find new efficiency and low toxicity pesticides
The insecticidal activity results showed as fowllows: the 24 compounds has differerntly ntifeedant activity and insecticidal activity for third M. separata at concentration of 100 mg/L. Experimental data show, the activity for the compounds of the third position of the quinoline ring are substituted by 2,4 - dichlorobenzene of is better than the compounds which substituted by the 3,4 - dichloro-phenyl, such as the mortality rate of M3b is 19.28%, higher than M4b(10.00%). The compounds that have different types and locations’substituents on the benzene ring of the quinoline ring have no significant difference in effects of insecticidal activity, for example the mortality rates of M1a, M2d and M3e are 17.20%, 16.92% and 14.96%, the difference is small; the derivatives that 4-hydroxy were esterified by a- Methacryloyl chloride , have higher insecticidal activity than other derivatives which were derived from the same intermediates but esterified by other differet acyl chloride , for example M1a which mortality rate reached 17.20% in 48 h, close to Imidacloprid (22.86%) ,and higher than the other compounds derived from the same intermediate M1b (8.00 %), M1c (4.00%), M1d (8.00%) and M1e (8.62%).
基于此,本论文设计以邻氨基苯甲酸,对氯邻氨基苯甲酸和5-甲基邻氨基苯甲酸为原料,通过酯化、酰化、环合再酯化的合成路线合成了24个喹啉-2,4-二酮类衍生物,化合物结构均经1~H-NMR、IR和ESI-MS等波谱手段予以确认,所有化合物均未见文献报道。对新化合物进行三龄粘虫的拒食活性和毒杀活性研究,希望能为高效低毒的新型杀虫剂的创制奠定一定的理论基础。
初步杀虫活性测试结果表明,在100 mg/L浓度下,24种化合物对三龄粘虫均有不同程度的拒食活性和毒杀活性。实验数据表明,喹啉环上3位取代基为2,4-二氯苯时活性要优于3位取代基为3,4-二氯苯基的化合物,例如,化合物M3b对粘虫的校正死亡率达到19.28%,而化合物M4b的校正死亡率只有10.00%;喹啉环中苯环上的取代基的类型与位置的不同对化合物杀虫活性差异并无明显影响,例如M1a、M2d和M3e三种化合物对粘虫的校正死亡率分别为17.20%、16.92%和14.96%,差别不大;对4位羟基酯化衍生后,发现使用可α-甲基丙烯酰氯进行酯化的化合物的活性要优于同中间体衍生的其他化合物,例如,化合物M1a对粘虫的校正死亡率在48 h时达到17.20%,接近吡虫啉22.86%的校对死亡率,也明显高于同一中间体衍生的其他化合物M1b(8.00%)、M1c(4.00%)、M1d(8.00%)和M1e(8.62%)。
In recent years, heterocyclic compounds are used to research and develop new pesticides because of theirs features of high efficiency, low toxicity and environmentally friendly in the areas of antibacterial, herbicidal and insecticidal plant protection.Quinoline compounds are a very important class of heterocyclic compounds, which have wide application and good prospects for development in the field of health care and plant protection. They are important precursor compounds of the drug for the anti-tumor, anti-HIV drugs and so on, while are also occupy an important position on created of new green pesticides
Based on this, the paper designed to use anthranilic acid, p-chloro anthranilic acid and 4- methyl anthranilic acid as raw materials ,we synthesized 24 quinoline-2,4-dione derivatives by esterification , acylation, cyclization and then esterification,and all the synthesized compounds were characterized by IR, NMR and ESI-MS,and the derivatives were first studied.All the compounds were studied for antifeedant activity and insecticidal activity of third M. separata, in order to find new efficiency and low toxicity pesticides
The insecticidal activity results showed as fowllows: the 24 compounds has differerntly ntifeedant activity and insecticidal activity for third M. separata at concentration of 100 mg/L. Experimental data show, the activity for the compounds of the third position of the quinoline ring are substituted by 2,4 - dichlorobenzene of is better than the compounds which substituted by the 3,4 - dichloro-phenyl, such as the mortality rate of M3b is 19.28%, higher than M4b(10.00%). The compounds that have different types and locations’substituents on the benzene ring of the quinoline ring have no significant difference in effects of insecticidal activity, for example the mortality rates of M1a, M2d and M3e are 17.20%, 16.92% and 14.96%, the difference is small; the derivatives that 4-hydroxy were esterified by a- Methacryloyl chloride , have higher insecticidal activity than other derivatives which were derived from the same intermediates but esterified by other differet acyl chloride , for example M1a which mortality rate reached 17.20% in 48 h, close to Imidacloprid (22.86%) ,and higher than the other compounds derived from the same intermediate M1b (8.00 %), M1c (4.00%), M1d (8.00%) and M1e (8.62%).
引文
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邵柏,李西标,韩喜东. 2008.简述杀虫剂研究进展[J].口岸卫生控制. 13(3): 9~10
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陈万义,薛振祥,王能武. 1995.新农药研究与开发[M].北京:化学工业出版社: 26~65.
陈旭艳,葛宝坤,常春燕. 2010.咪唑啉酮类除草剂环境行为研究进展[J].精细化工中间体. 40(2): 1-6
姜志宽,王以燕. 2006.我国的卫生杀虫剂发展概括[J].中华卫生杀虫药械. 12(6): 413~418
刘莹. 2001.顺耳宁[J].中国新药杂志. 10(2): 136~137
陆一夫,徐旭辉,孙楠,赵金浩. 2009.新型杀螨剂螺螨酯的合成[J].精细化工中间体. 39(2):19~21
吕芬,杨定乔,汪朝阳. 2003. Friedlander反应研究进展[J].合成化学. 11(6): 472~478.
邵柏,李西标,韩喜东. 2008.简述杀虫剂研究进展[J].口岸卫生控制. 13(3): 9~10
师文娟,廖道华,杨芳,刘少春,杜梦. 2010.螺虫乙酯的合成[J].农药. 49(4): 250~263
施顺发. 1995.除草剂-克稗灵[J].上海化工, 20(2): 24~26.
舒思清,王兴汉. 1988. 5-乙酰基-8-羟基喹啉硫酸盐和磷酸二氢盐增效杀菌剂的成研究[J].徐洲师范学院学报(自然科学版). 2(2): 66~71
王正权,王大翔. 1999.新世纪农药发展趋势[J].农药. 38(10): 9~11
夏澄,冯化成. 2002.一系列新颖芳氧基对甲基喹啉化合物的合成和杀菌活性[J].世界农药. 24(1): 9
徐峰,杨定乔,李文辉,韩英锋,蒋凯龄. 2004.喹啉类药物研究进展[J].广东药学. 14(6): 6~8
杨蕾,王鹏,蒋益林,王虹. 2003.氯喹酸酯类衍生物的合成及QSAR分析[J].哈尔滨工业大学学报. 35(9): 1128~1130
易思齐,张旭泉译. 1991.农药译丛[M]. 13(1): 15~19
张庆宽. 2009.双向内吸性新杀虫剂螺虫乙酯的开发[J].农药. 48(6): 445~447
张文升,李安良. 1999.药物化学[M].高等教育出版社.北京: 528
张兴,赵善欢. 1983.楝科植物对几种害虫的拒食和忌避作用[J].华南农学院学报. 4(3): 1~7
张一宾,张怿,伍贤英. 2010.世界农药新进展[M].化学工业出版社.北京
张一宾,张怿. 2007.世界农药新进展.化学工业出版社.北京
张应年,冯亚非. 1993. N-甲基氨基甲酸-8-喹啉醋农药的研制[J].甘肃农业大学学报. 28(3): 269~271
赵善欢,张兴. 1982.植物质杀虫剂对水稻三化螟的拒食及内吸毒力试验[J].中国农业科学. 2:55~62.
朱淬砺. 1999.药物合成化学[M].化学工业出版社: 395
Adnan A Bekhita, Ola A El-Sayeda, Talal A K Al-Allafb, Hassan Y Aboul-Eneinc, Muhammed Kunhic, Subramanian Manogaran Pulicatc, Khalid Al-Hussainc, Fahad Al-Khodairyc, Jamal Arif. 2004. Synthesis, characterization and cytotoxicity evaluation of some new platinum(II) complexes of tetrazolo[1,5-a]quinolines[J]. Eur. J. Med. Chem. 39(6): 499~505
Camps R. 1899. Synthesis of 2 - and 4 -hydroxyquinolines[J]. Berichte der Deutschen ChemischenGesellschaft. 32: 3228~3234
Churl Min Seong, Woo Kyu Park, Chul Min Park, Jae Yang Kong,No Sang Park. 2007. Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists[J]. Bioorganic & Medicinal Chemistry Letters. 18(2): 738~743
Dale L B, Chen J H. 1995. A modified Ffiedlander Condensation for the Synthesis of 3-Hydroxyquinoline-2-Carboxylates[J].The Journal of Organic Chemistry. 60(22): 7369~7371
Foley M, Tilley L. 1998. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents[J]. Pharmacol. Ther. 79(1):55~87
Hadjeri M, Peiller E L, Beney C, Deka N, Lawson M A, Dumontet C, Boumendjel A. 2004.
Antimitotic activity of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones[J]. J.Med.Chem. 47(20): 4964~4970
Hewawasam P, Fan W, Knipe J, Moon S L, Boissard C G, Gribkoff V K, Starett J E. 2002. The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection[J]. Bioorg. Med. Chem.Lett. 12(13): 1779~1783
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