Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety

doi:10.6023/cjoc202307029

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (2): 650-656.DOI: 10.6023/cjoc202307029 Previous Articles Next Articles

含环丙基的新型取代嘧啶-5-甲酰胺的合成及杀菌活性研究

李鹏辉, 谢青洋, 万福贤, 张元红, 姜林^*()

山东农业大学化学与材料科学学院山东泰安 271018

收稿日期:2023-07-31 修回日期:2022-09-17 发布日期:2023-10-12
作者简介:
^†共同第一作者
基金资助:
山东省自然科学基金(ZR2020MB110)

Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety

Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang()

College of Chemistry and Material Science, Shandong Agricultural University, Tai'an, Shandong 271018

Received:2023-07-31 Revised:2022-09-17 Published:2023-10-12
Contact: * E-mail: jiangl@sdau.edu.cn
About author:
^†These authors contributed equally to this work.
Supported by:
Natural Science Foundation of Shandong Province(ZR2020MB110)

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Abstract

In order to develop novel pyrimidine compounds with excellent fungicidal activity, thirteen N-substituted phenyl-2- cyclopropyl-4-methylpyrimidine-5-carboxamides and three analogues without cyclopropyl moiety were designed and synthesized by means of the active substructure splicing method. The structures of target compounds were characterized by¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C NMR), infrared spectrometry (IR) and high-resolution mass spectra (HRMS). The preliminary fungicidal activities against plant fungi were evaluated, and the result revealed that some compounds exhibited high activity at a concentration of 100 mg/L. For example, N-(4-chlorophenyl)- 2-cyclopropyl-4-methylpyrimidine-5-carboxamide(4e), N-(4-brorophenyl)-2-cyclopropyl-4-methylpyrimidine-5-carboxamide (4h) and N-(3,4-dichlorophenyl)-2-cyclopropyl-4-methylpyrimidine-5-carboxamide(4k) showed inhibitory rates of 87.9%, 84.4% and 85.2% against Botrytis cinerea, respectively, and 4k showed inhibitory rate of 84.6% against Sclerotinia sclerotiorum. Further bioassay indicated that 4k possessed a lower effective concentration value of 4.67 mg/L, which meant that its activity was comparable to that of cyprodimol and was higher than that of boscalid. A bioactivity comparison between target compounds and the analogues without cyclopropyl moiety, demonstrated that the intrduction of cyclopropyl to the pyrimidine ring is beneficial for improving the fungicidal activity.

Key words: pyrimidine, cyclopropyl, amide, synthesis, fungicidal activity

Cite this article

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.

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Compd.	R	Botrytis cinerea		Sclerotinia sclerotiorum
Compd.	R	50 mg/L	100 mg/L	50 mg/L	100 mg/L
4a	H	11.4	44.7	17.7	33.3
4b	4-F	40.7	56.6	25.0	38.6
4c	2-Cl	16.3	33.7	46.5	56.6
4d	3-Cl	49.6	71.9	52.1	59.5
4e	4-Cl	70.2	87.9	58.3	67.0
4f	2-Br	15.1	38.9	11.5	31.8
4g	3-Br	59.6	79.2	47.5	66.9
4h	4-Br	80.9	84.4	67.6	73.6
4i	4-CH₃	47.7	65.9	35.5	47.7
4j	4-OCH₃	15.1	25.9	19.7	30.3
4k	3,4-Cl₂	76.4	85.2	77.5	84.6
4l	3-F-4-CH₃	57.0	80.3	41.2	62.4
4m	2-Cl-4-CH₃	15.1	18.7	12.7	31.9
5a	4-Cl	13.2	36.8	10.1	14.9
5b	4-Br	28.2	48.3	8.3	29.5
5c	3,4-Cl₂	45.9	60.3	55.7	80.2
Cypro- dimil		86.3	94.8	92.1	97.8
Boscalid		75.5	90.5	97.8	100

Compd.	R	Botrytis cinerea		Sclerotinia sclerotiorum
Compd.	R	50 mg/L	100 mg/L	50 mg/L	100 mg/L
4a	H	11.4	44.7	17.7	33.3
4b	4-F	40.7	56.6	25.0	38.6
4c	2-Cl	16.3	33.7	46.5	56.6
4d	3-Cl	49.6	71.9	52.1	59.5
4e	4-Cl	70.2	87.9	58.3	67.0
4f	2-Br	15.1	38.9	11.5	31.8
4g	3-Br	59.6	79.2	47.5	66.9
4h	4-Br	80.9	84.4	67.6	73.6
4i	4-CH₃	47.7	65.9	35.5	47.7
4j	4-OCH₃	15.1	25.9	19.7	30.3
4k	3,4-Cl₂	76.4	85.2	77.5	84.6
4l	3-F-4-CH₃	57.0	80.3	41.2	62.4
4m	2-Cl-4-CH₃	15.1	18.7	12.7	31.9
5a	4-Cl	13.2	36.8	10.1	14.9
5b	4-Br	28.2	48.3	8.3	29.5
5c	3,4-Cl₂	45.9	60.3	55.7	80.2
Cypro- dimil		86.3	94.8	92.1	97.8
Boscalid		75.5	90.5	97.8	100

化合物	n	EC₅₀ (95%置信限)/(mg•L^—1)
化合物	n	草莓灰霉菌	茄子菌核菌
4e	0	24.75 (23.19~27.62)	NT^a
4h	0	22.68 (19.96~26.52)	NT
4k		4.67 (2.97~6.76)	22.65 (20.66~25.23)
Cyprodimil	—	4.35 (2.84~7.14)	1.24 (0.51~2.92)
Boscalid		9.68 (7.63~12.75)	1.91 (1.31~2.72)

化合物	n	EC₅₀ (95%置信限)/(mg•L^—1)
化合物	n	草莓灰霉菌	茄子菌核菌
4e	0	24.75 (23.19~27.62)	NT^a
4h	0	22.68 (19.96~26.52)	NT
4k		4.67 (2.97~6.76)	22.65 (20.66~25.23)
Cyprodimil	—	4.35 (2.84~7.14)	1.24 (0.51~2.92)
Boscalid		9.68 (7.63~12.75)	1.91 (1.31~2.72)

含环丙基的新型取代嘧啶-5-甲酰胺的合成及杀菌活性研究

Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety

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