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

doi:10.6023/cjoc202307029

摘要/Abstract

为发现具有优异杀菌活性的新型嘧啶类化合物, 采用活性亚结构拼接法设计合成了13种N-(取代苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺及3种不含环丙基的类似物, 其结构经核磁共振氢谱(¹H NMR)、核磁共振碳谱(¹³C NMR)、红外光谱(IR)和高分辨质谱(HRMS)鉴定. 利用菌丝生长速率法测定了化合物对植物病原菌的杀菌活性, 在浓度为100 mg/L时, 部分化合物显示出较高的杀菌活性, 其中N-(4-氯苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4e)、N-(4-溴苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4h)和N-(3,4-二氯苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4k)对灰霉菌的抑制率分别为87.9%、84.4%和85.2%, 4k对菌核菌的抑制率为84.6%. 进一步试验显示4k对灰霉菌的抑制中浓度为4.67 mg/L, 其活性与对照药剂嘧菌环胺相当且高于啶酰菌胺. 与不含环丙基的4-甲基嘧啶-5-甲酰胺的比较揭示了嘧啶环上引入环丙基有利于提高化合物的杀菌活性.

关键词: 嘧啶, 环丙基, 酰胺, 合成, 杀菌活性

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

引用此文

李鹏辉, 谢青洋, 万福贤, 张元红, 姜林. 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[J]. 有机化学, 2024, 44(2): 650-656.

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)