2-苯甲酰基嘧啶类化合物的合成与生物活性
收稿日期: 2015-12-18
修回日期: 2015-02-17
网络出版日期: 2015-02-18
基金资助
"十二五"国家科技支撑计划(No. 2011BAE06B02)资助项目.
Synthesis and Bioactivity of 2-Benzoyl Pyrimidine Derivatives
Received date: 2015-12-18
Revised date: 2015-02-17
Online published: 2015-02-18
Supported by
Project supported by the National Key Technologies R&D Program (No. 2011BAE06B02).
2-嘧啶氧基-N-芳基苄胺类化合物结构经过两次骨架结构优化后得到2-苯甲酰基嘧啶类化合物二次先导结构. 在二次先导结构基础上, 共设计并合成了36个化合物, 所有化合物结构经1H NMR、13C NMR、HRMS确认, 并进行了室内杀菌活性筛选, 对各部位取代基进行了逐次优化. 结果表明2-苯甲酰基嘧啶类化合物中R1取代基以2位卤素或烷基取代的苯环或杂环活性最好; 中间苯环6位引入氟原子活性保持; 嘧啶环4,6位甲氧基取代活性较好, 5位甲基取代活性大大降低; 羰基被还原为羟基后活性消失. 其中2,3-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHl)、2,5-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHn)及N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)-3-氟苯氧基]-N,2-二甲基苯甲酰胺(4AFd)对黄瓜白粉病的杀菌活性与对照样苯菌酮相当.
吕强, 芦昕婷, 戴明, 刘世梦, 朱为宏, 杜葩, 吕龙 . 2-苯甲酰基嘧啶类化合物的合成与生物活性[J]. 有机化学, 2015 , 35(6) : 1260 -1269 . DOI: 10.6023/cjoc201412032
2-Benzoyl pyrimidine as a secondary leading structure is developed by twice optimization of 2-pyrimidinoxy-N- aryl benzylamine. Based on this structure, thirty six 2-benzoyl pyrimidine derivatives have been designed and synthesized. All compounds are determined by 1H NMR, 13C NMR and HRMS. Their interior fungicidal activities show that R1 substituent prefers phenyl or heterocyclic group with 2-halo or 2-alkyl group. When introducing fluoride to 6-position on benzene ring, the fungicidal activity is maintained at a similar level. 4,6-Dimethoxy group on pyrimidine ring was recognized as a best substituent by far. The activity is seriously decreased when methyl group is fixed on 5-position of pyrimidine. Even the fungicidal activities become completely disappeared when the ketone group is reduced to hydroxyl group. Among them, three compounds 2,3-dichloro-N-(2-(4,6-dimethoxypyrimidine-2-carbonyl)phenoxy)-N-methylbenzamide (4AHl), 2,5-dichloro-N-(2-(4,6-dime- thoxypyrimidine-2-carbonyl)phenoxy)-N-methylbenzamide (4AHn) and N-(2-(4,6-dimethoxypyrimidine-2-carbonyl)-3-fluoro- phenoxy)-N,2-dimethylbenzamide (4AFd) exhibit comparable fungicidal activity against cucumber powdery mildew to the reference metrafenone.
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