新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

Jie LIU; Bingchun ZHU; Dan PEI; Fan ZHANG; Donglin ZHANG; Xuedong WANG; Chengxia TAN

doi:10.16801/j.issn.1008-7303.2019.0002

新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

doi: 10.16801/j.issn.1008-7303.2019.0002

刘杰^1,,
朱冰春²,
裴丹¹,
张帆¹,
张冬林¹,
王学东³,
谭成侠^1, ,

1.
浙江工业大学化学工程学院，杭州 310014
2.
浙江省化工研究院有限公司，杭州 310023
3.
温州医科大学，浙江温州 325035

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出版历程
- 收稿日期: 2018-11-16
- 录用日期: 2019-01-07
- 刊出日期: 2019-02-01

Synthesis and insecticidal activity of novel heptafluoroisopropyl substituted 2,2-difluoro-1,3-benzodioxol-5-acetamide derivatives

1.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China
2.
Zhejiang Institute of Chemical Industry Co. Ltd., Hangzhou 310023, China
3.
Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China

Funds: The National Science & Technology Pillar Program of China (No. 2011BAE06B01-20); Provincial Natural Science Fund Project (LY16B070010).

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Author Bio:
LIU jie, female, postgraduate student, E-mail: 2291431926@qq.com

Corresponding author: TAN Chengxia, author for correspondence, male, professor, engaged in new pesticide creation research, E-mail: tanchengxia@zjut.edu.cn

摘要

摘要:
为探索环境友好新型农药先导化合物，通过水相中酰胺缩合反应合成了16个未见文献报道的七氟异丙基苯基取代的2,2-二氟-1,3-苯并二氧-5-乙酰胺类目标化合物。其结构通过核磁共振氢谱、氟谱以及高分辨质谱确认。初步生物活性测定表明，部分目标化合物对蚕豆蚜虫和粘虫表现出良好的杀虫活性，初步构效关系显示苯环上取代基的种类和位置在化合物的杀虫活性中起关键作用。
- 多氟化合物 /
- 乙酰胺 /
- TPGS-750-M/H₂O /
- 杀虫活性
Abstract:
In order to discover novel and environmentally benign pesticides, a series of novel heptafluoroisopropyl substituted 2,2-difluoro-1,3-benzodioxol-5-acetamide derivatives were synthesized via amide condensation reaction in aqueous solution. All the title compouds were characterized by ¹H NMR, ¹⁹F NMR and HRMS. The bioassays showed that some of the compounds exhibited good insecticidal activities against bean aphids (Aphis craccivora) and armyworms (Mythimna separata). Preliminary structure-activity relationship studies suggested that the substituent groups played a key role in the insecticidal activities of the compounds.
- poly-fluorinated compounds /
- acetamide /
- TPGS-750-M/H₂O /
- insecticidal activity

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Figure 1. Commercial pesticides with polyfluoroalkyl groups

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Figure 2. Design of the title compounds

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Figure 3. Structural formula of TPGS-750-M

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1. General synthetic route of the title compound h1-h16

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2. Route improvement for the synthesis of the title compounds h1

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Table 1. Physical and chemical data of title compounds h1-h16

Entry	Compd.	R	Appearance	m.p./°C	Yield/%
1	h1	2-CH₃	White solid	125-127	60
2	h2	H	White solid	103-105	63
3	h3	2, 3-(CH₃)₂	White solid	135-137	60
4	h4	3-CH₃	White solid	112-114	59
5	h5	2, 5-(CH₃)₂	White solid	127-129	61
6	h6	3-OCH₃	White solid	134-136	55
7	h7	2, 6-(CH₂CH₃)₂	White solid	111-113	53
8	h8	2-CH₃-6-CH₂CH₃	White solid	118-120	56
9	h9	2-OH	White solid	130-132	43
10	h10	2, 6-(CH₃)₂	White solid	132-134	58
11	h11	2-OCH₃	White solid	114-116	56
12	h12	2-CH₂CH₃	White solid	120-122	57
13	h13	2-OCH₂CH₃	White solid	105-107	60
14	h14	3-CH₂CH₃	White solid	128-130	55
15	h15	2, 5-(OCH₃)₂	White solid	122-124	52
16	h16	2, 6-(OCH₃)₂	White solid	123-125	58

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Table 2. The ¹H NMR, ¹⁹F NMR and HRMS of the title compounds h1-h16

Compd.	¹H NMR(CDCl₃, 400 MHz)，δ	¹⁹F NMR (CDCl₃, 564 MHz)，δ	HRMS [M+H]⁺, m/z
Compd.	¹H NMR(CDCl₃, 400 MHz)，δ	¹⁹F NMR (CDCl₃, 564 MHz)，δ	Calcd.	Found
h1	2.26 (s, 3H, -CH₃), 3.68 (s, 2H, -CH₂-), 7.02-7.07 (m, 4H, Ar-H × 3, N-H), 7.19-7.33 (m, 3H, Ar-H).	–181.70 (m, 1F, CF), –75.82 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.94 (s, 2F, CF₂).	474.074 6	474.075 0
h2	3.69 (s, 2H, -CH₂-), 7.00-7.04 (m, 3H, Ar-H), 7.51 (d, 2H, J = 9.0 Hz, Ar-H), 7.60 (d, 2 H, J = 9.0 Hz, Ar-H), 7.74 (br, 1H, N-H).	–182.32 (m, 1F, CF), –75.87 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.96 (s, 2F, C F₂).	460.059 0	460.058 7
h3	2.01 (s, 3H, -CH₃), 2.38 (d, 3 H, J = 5.4 Hz, -CH₃), 3.74 (s, 2H, -CH₂-), 7.07-7.09 (m, 3H, Ar-H), 7.17 (br, 1H, N-H), 7.34 (d, 1H, J = 7.8 Hz, Ar-H), 7.64 (d, 1H, J = 7.8 Hz, Ar-H).	–174.74 (m, 1F, CF), –74.06 (d, 6 F, J = 6.2 Hz, CF₃ × 2), –50.04 (s, 2 F, CF₂).	488.090 3	488.089 9
h4	2.46 (d, 3H, J = 8.8 Hz, -CH₃), 3.71 (s, 2H, -CH₂-), 7.04-7.08 (m, 2H, Ar-H), 7.38-7.44 (m, 2H, Ar-H × 1, N-H), 7.68-7.79 (m, 3H, Ar-H)	–175.08 (m, 1F, CF), –74.11 (d, 6F, J = 6.2 Hz, CF₃ × 2), –50.02 (s, 2F, CF₂)	474.074 6	474.074 3
h5	2.05 (s, 3H, -CH₃-), 2.46 (d, 3H, J = 9.2 Hz, -CH₃), 3.76 (s, 2H, -CH₂-), 7.00 (br, 1H, N-H), 7.05-7.10 (m, 3H, Ar-H × 3), 7.20 (s, 1H, Ar-H), 7.68-7.69 (m, 1H, Ar-H).	–174.33 (m, 1F, CF), –74.04 (d, 6F, J = 6.2 Hz, CF₃ × 2), –50.03 (s, 2F, C F₂)	488.090 3	488.091 0
h6	3.72 (s, 2H, -CH₂-), 3.81 (s, 3H, -OCH₃), 7.04-7.08 (m, 3H, Ar-H × 2, N-H × 1), 7.67-7.79 (m, 4H, Ar-H).	–173.14 (m, 1F, CF), –73.62 (d, 6F, J = 6.2 Hz, CF₃ × 2), –50.01 (s, 2F, CF₂).	490.069 5	490.069 0
h7	1.17 (t, 6H, J = 7.2 Hz, -CH₂CH₃ × 2), 2.72 (q, 4H, J = 7.2 Hz, -CH₂ CH₃ × 2), 3.74 (s, 2H, -CH₂-), 7.03-7.07 (m, 3H, Ar-H), 7.36 (s, 2H, Ar-H). 7.42 (br, 1H, N-H).	–180.52 (m, 1F, CF), –75.51 (d, 6F, J = 5.6 Hz, CF₃×2), –49.95 (s, 2F, CF₂).	516.121 6	516.122 1
h8	1.15 (t, 3H, J = 7.2 Hz, -CH₂CH₃), 2.26 (s, 3H, -CH₃), 2.72 (q, 2H, J = 7.2 Hz, -CH₂CH₃), 3.73 (s, 2H, -CH₂-), 7.00-7.05 (m, 3H, Ar-H), 7.34 (s, 1H, Ar-H), 7.38 (s, 1H, Ar-H), 7.44 (br, 1H, N-H).	–181.03 (m, 1F, CF), –75.55 (d, 6F, J = 5.6 Hz, CF₃ × 2), –50.00 (s, 2F, CF₂).	502.105 9	502.105 3
h9	3.72 (s, 2H, -CH₂-), 7.02-7.07 (m, 3H, Ar-H), 7.09 (d, 1H, J = 8.4 Hz, Ar-H), 7.14 (s, 1H, Ar-H), 7.34 (br, 1H, N-H), 8.10 (d, 1H, J = 8.4 Hz, Ar-H).	–182.45 (m, 1F, CF), –75.89 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.92 (s, 2F, CF₂).	476.053 9	476.054 3
h10	2.25 (s, 6H, -CH₃ × 2), 3.70 (s, 2H, -CH₂-), 7.01-7.06 (m, 3H, Ar-H), 7.35 (s, 2H, Ar-H), 7.46 (s, br H, N-H).	–182.30 (m, 1F, CF), –75.80 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.95 (s, 2F, CF₂).	488.090 3	488.090 7
h11	3.75 (s, 2H, -CH₂-), 3.85 (s, 3H, -OCH₃), 7.02-7.09 (m, 4H, Ar-H), 7.19 (d, J =8.4 Hz, 1H, Ar-H), 7.87 (br, 1H, N-H), 8.47 (d, J =8.4 Hz, 1H, Ar-H).	–182.50 (m, 1F, CF), –75.90 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.98 (s, 2F, CF₂).	490.069 5	490.070 1
h12	1.16 (t, 3H, J = 7.2 Hz, -CH₂CH₃), 2.72 (q, 2H, J = 7.2 Hz, -CH₂CH₃), 3.71 (s, 2H, -CH₂-), 7.01-7.05 (m, 3H, Ar-H), 7.32-7.47 (m, 4H, Ar-H × 3, NH).	–181.81 (m, 1F, CF), –75.67 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.93 (s, 2F, CF₂).	488.090 3	488.091 2
h13	1.39 (t, 3H, J = 6.8 Hz, -OCH₂CH₃), 3.74 (s, 2H, -CH₂-), 3.83 (q, 2H, J = 6.8 Hz, -OCH₂CH₃), 7.03-7.10 (m, 4H, Ar-H), 7.20 (d, J = 8.4 Hz, 1H, Ar-H), 7.88 (br, 1H, N-H), 8.49 (d, J = 8.4 Hz, 1H, Ar-H).	–182.48 (m, 1F, CF), –75.89 (d, 6F, J = 5.6 Hz, CF₃ × 2), –49.97 (s, 2F, CF₂).	504.085 2	504.084 5
h14	1.11 (t, 3H, J = 7.2 Hz, -CH₂CH₃), 2.60 (q, 2H, J = 7.2 Hz, -CH₂ CH₃), 3.72 (s, 2H, -CH₂-), 7.07-7.10 (m, 2H, Ar-H), 7.41-7.48 (m, 2H, Ar-H × 1, N-H), 7.71-7.82 (m, 3H, Ar-H).	–175.15 (m, 1F, CF), –74.17 (d, 6F, J = 6.2 Hz, CF₃ × 2), –50.00 (s, 2F, CF₂).	488.090 3	488.091 0
h15	3.74 (s, 2H, -CH₂-), 3.76 (s, 3H, -OCH₃), 3.80 (s, 3H, -OCH₃), 7.62-7.24 (m, 6H, Ar-H × 5, N-H).	–178.54 (m, 1F, CF), –75.12 (d, 6F, J = 6.0 Hz, CF₃ × 2), –50.06 (s, 2F, CF₂).	520.080 1	520.080 9
h16	3.75 (s, 2H, -CH₂-), 3.79 (s, 6H, -OCH₃ × 2), 7.68-7.33 (m, 5H, Ar-H × 5). 7.44 (br, 1H, N-H).	–180.10 (m, 1F, CF), –75.52 (d, 6F, J = 5.6 Hz, CF₃ × 2), –50.03 (s, 2F, CF₂).	520.080 1	520.080 6

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Table 3. Insecticidal activity of title compounds h1 to h16

Compd.	Concentration/(mg/L)	Mortality/%
Compd.	Concentration/(mg/L)	A. craccivora	M. separata
h1	500	80	0
h2	500	0	100
h3	500	70	0
h4	500	20	100
h5	500	100	0
h6	500	0	80
h7	500	90	0
h8	500	100	0
h9	500	0	0
h10	500	100	0
h11	500	60	0
h12	500	90	0
h13	500	70	0
h14	500	0	90
h15	500	80	0
h16	500	100	0
flubendiamide	500	0	100
abamectin	50	100	100

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参考文献(27)

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新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

doi: 10.16801/j.issn.1008-7303.2019.0002

计量

Synthesis and insecticidal activity of novel heptafluoroisopropyl substituted 2,2-difluoro-1,3-benzodioxol-5-acetamide derivatives

Author Bio:
LIU jie, female, postgraduate student, E-mail: 2291431926@qq.com

Corresponding author: TAN Chengxia, author for correspondence, male, professor, engaged in new pesticide creation research, E-mail: tanchengxia@zjut.edu.cn

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留言板

新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

doi: 10.16801/j.issn.1008-7303.2019.0002

计量

出版历程

Synthesis and insecticidal activity of novel heptafluoroisopropyl substituted 2,2-difluoro-1,3-benzodioxol-5-acetamide derivatives

Author Bio: LIU jie, female, postgraduate student, E-mail: 2291431926@qq.com

Corresponding author: TAN Chengxia, author for correspondence, male, professor, engaged in new pesticide creation research, E-mail: tanchengxia@zjut.edu.cn

计量

出版历程

目录

Author Bio:
LIU jie, female, postgraduate student, E-mail: 2291431926@qq.com