Synthesis and Bioactivity of 2-Benzoyl Pyrimidine Derivatives

doi:10.6023/cjoc201412032

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (6): 1260-1269.DOI: 10.6023/cjoc201412032 Previous Articles Next Articles

Articles

2-苯甲酰基嘧啶类化合物的合成与生物活性

吕强^a,b, 芦昕婷^b, 戴明^b, 刘世梦^b, 朱为宏^a, 杜葩^c, 吕龙^b

a 华东理工大学化学与分子工程学院上海 200237;
b 中国科学院上海有机化学研究所有机氟化学重点实验室上海 200032;
c 上海应用技术学院化学与环境工程学院上海 201418

收稿日期:2015-12-18 修回日期:2015-02-17 发布日期:2015-02-18
通讯作者: 杜葩 E-mail:dupa@sit.edu.cn
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

Lü Qiang^a,b, Lu Xinting^b, Dai Ming^b, Liu Shimeng^b, Zhu Weihong^a, Du Pa^c, Lü Long^b

a School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237;
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032;
c School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418

Received:2015-12-18 Revised:2015-02-17 Published:2015-02-18
Supported by:
Project supported by the National Key Technologies R&D Program (No. 2011BAE06B02).

1. Synthesis and Bioactivity of 2-Benzoyl Pyrimidine Derivatives.PDF(3074KB)

Abstract

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.

Key words: 2-benzoyl pyrimidine, synthesis, structral optimization, biological activity

Cite this article

Lü Qiang, Lu Xinting, Dai Ming, Liu Shimeng, Zhu Weihong, Du Pa, Lü Long. Synthesis and Bioactivity of 2-Benzoyl Pyrimidine Derivatives[J]. Chin. J. Org. Chem., 2015, 35(6): 1260-1269.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] (a) Lamberth, C. Heterocycles 2006, 68, 561. (b) Ren, W.-J.; Wang, L.-Z.; Li, Y. Agrochemicals 2013, 52, 1 (in Chinese). (任玮静, 王立增, 李云, 农药, 2013, 52, 1.) (c) Liu, W.; Zou, X.-M.; Wang, Y.-F.; Hu, F.-Z.; Wan, Y.-Q.; Yang, H.-Z. Chem. J. Chin. Univ. 2000, 21, 237 (in Chinese). (刘卫敏, 邹小毛, 汪义丰, 胡方中, 朱有全, 杨华铮, 高等学校化学学报, 2000, 21, 237.) (d) Yang, Z.-J.; Yin, C.; Zhang, L.-P.; Zhong, Y.; Xu, H.; Mao, Z.-P. Chin. J. Org. Chem.2013, 33, 2607 (in Chinese). (杨梓君, 尹冲, 张琳萍, 钟毅, 徐红, 毛志平, 有机化学, 2013, 33, 2607.) (e) Deng, L.-Q.; Zhong, H.; Wang, S. Chin. J. Org. Chem. 2014, 34, 414 (in Chinese). (邓兰青, 钟宏, 王帅, 有机化学, 2014, 34, 414.) (f) Lin, X.-F.; Tan, Z.; Liu, Y.; He, J.-P.; Bao, X.-P. Chin. J. Org. Chem. 2013, 33, 353 (in Chinese). (林选福, 谭赞, 刘勇, 贺银菊, 鲍小平, 有机化学, 2013, 33, 353.) (g) Bao, X.-P.; Lin, X.-F.; Jian, J.-Y.; Zhang, F.; Zou, L.-B. Chin. J. Org. Chem. 2013, 33, 995 (in Chinese). (鲍小平, 林选福, 蹇军友, 张峰, 邹林波, 有机化学, 2013, 33, 995.)
[2] (a) Feng, X.; Yao, J.-H.; Lu, L.; Tanq, Q. H.; Fan, B.-T. Acta Chim. Sinica 2006, 64, 1097. (b) Tai, W.-J.; Chen, J.; Xu X.-Y.; Liu, Y.-J.; Xu, Y.-H.; Tang, Q.-H., Chin. J. Pestic. Sci. 2009, 11, 87 (in Chinese). (台文俊, 陈杰, 徐小燕, 刘燕君, 许勇华, 唐庆红, 农药学学报, 2009, 11, 87.) (c) Xu, Y.-H.; Lue, Q; Tai, W.-J.; Tang, Q.-H., Chen, J. Chin. J. Pestic. Sci. 2009, 11, 279 (in Chinese). (许勇华, 吕强, 台文俊, 唐庆红, 陈杰, 农药学学报, 2009, 11, 279.)
[3] (a) Yoshimura, T.; Ikeuchi, T.; Ohno, S.; Asakura, S.; Hamada, Y. J. Pestic. Sci. 2013, 38, 171. (b) Yoshimura, T.; Nakatani, M.; Asakura, S.; Hanai, R.; Hiraoka, M.; Kuwahara, S. J. Pestic. Sci. 2011, 36, 212.
[4] Lu, L.; Lu, Q.; Tang, Q.-H.; Dai, M.; Yang, B.; Xu, K.; Fu, Q.-M.; Lu, X.-T. CN 101381347, 2009 [Chem. Abstr. 2009, 310916].
[5] (a) Kawazoe, K. WO 2011024429, 2011 [Chem. Abstr. 2011, 261861]. (b) Donetti, A.; Boniardi, O.; Ezhaya, A. Synthesis 1980, 1009. (c) Kulp, S. S.; McGee, M. J. J. Org. Chem. 1983, 48, 4097. (d) Sauter, F.; Stanetty, P.; Mesbah, A. J. Chem. Res., Synop. 1977, 186.
[6] (a) Curtze, J.; Morschhaeuser, G.; Stumm, K.; Albert, G.; Reichert, G.; Simon, W.; Waldeck, A.; Van Tuyl Cotter, H.; Rehnig, A. E. E.; Stumm, K. O.; Cotter, H. V. T.; Morschlaeuser, G.; Rehning, A. E. E.; Stumm, A. K.; Van Tuyl, C. H.; Edi, A.; Kertz, Y.; Moschhouizer, G.; Schtum, K.; Werner, S.; Ketz, J.; Moshhoyizel, G.; Schtum, K. O.; Curtze, J.; Morschhaeuser, G.; Stumm, K.; Albert, G.; Reichert, G.; Simon, W.; Waldeck, A.; Van Tuyl Cotter, H.; Rehnig, A. E. E.; Stumm, K. O.; Cotter, H. V. T.; Morschlaeuser, G.; Rehning, A. E. E.; Stumm, A. K.; Van Tuyl, C. H.; Edi, A.; Kertz, Y.; Moschhouizer, G.; Schtum, K.; Werner, S.; Ketz, J.; Moshhoyizel, G.; Schtum, K. O. EP 897904, 1999 [Chem. Abstr. 1999, 139752]. (b) Kameswaran, V. WO 2001051440, 2001 [Chem. Abstr. 2001, 526037]. (c) Maywald, V.; Hoffmann, N.; Keil, M.; Vogelbacher, U. J.; Wevers, J. H. WO 2004054953, 2004 [Chem. Abstr. 2004, 534158].
[7] (a) Coates, R. M.; Firsan, S. J. J. Org. Chem. 1986, 51, 5198. (b) Kozlov, M. V.; Kleymenova, A. A.; Romanova, L. I.; Konduktorov, K. A.; Smirnova, O. A.; Prasolov, V. S.; Kochetkov, S. N. Bioorg. Med. Chem. Lett. 2013, 23, 5936. (c) Punta, C.; Rector, C. L.; Porter, N. A. Chem. Res. Toxicol. 2005, 18, 349.

[1]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[2]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[3]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[4]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[5]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[6]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[7]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[8]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[9]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[10]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[11]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[12]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[13]	Yang Li, Jinding Yuan, Di Zhao. Deep Eutectic Solvent of 1,3-Dimethylurea/L-(+)-Tartaric Acid for the Green Synthesis of (E)-2-Styrylquinoline-3-carboxylic Acid Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3268-3276.
[14]	Dandan Sui, Nannan Cen, Ruoqu Gong, Yang Chen, Wenbo Chen. Supporting-Electrolyte-Free Electrochemical Synthesis of Trifluoromethylated Oxindoles in Continuous Flow [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3239-3245.
[15]	Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.

2-苯甲酰基嘧啶类化合物的合成与生物活性

Synthesis and Bioactivity of 2-Benzoyl Pyrimidine Derivatives

PDF

Supporting Info.

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments