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

引用本文

刘杰, 朱冰春, 裴丹, 张帆, 张冬林, 王学东, 谭成侠. 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[J]. 农药学学报, 2019, 21(1): 12-18, doi: 10.16801/j.issn.1008-7303.2019.0002

LIU Jie, ZHU Bingchun, PEI Dan, ZHANG Fan, ZHANG Donglin, WANG Xuedong, TAN Chengxia. Synthesis and insecticidal activity of novel heptafluoroisopropyl substituted 2,2-difluoro-1,3-benzodioxol-5-acetamide derivatives[J]. Chinese Journal of Pesticide Science, 2019, 21(1): 12-18, 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

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

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。

关键词: 多氟化合物乙酰胺 TPGS-750-M/H₂O 杀虫活性

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

LIU Jie¹, ZHU Bingchun², PEI Dan¹, ZHANG Fan¹, ZHANG Donglin¹, WANG Xuedong³, TAN Chengxia¹

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

Received: Nov 16, 2018 Accepted: Jan 7, 2019

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

Biography: LIU jie, female, postgraduate student, E-mail: 2291431926@qq.com ^* TAN Chengxia, author for correspondence, male, professor, engaged in new pesticide creation research, E-mail: tanchengxia@zjut.edu.cn

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.

Key words: poly-fluorinated compounds acetamide TPGS-750-M/H₂O insecticidal activity

The highly fluorinated groups have become an important bio-functional moiety in many bioactive compounds, mainly because of its high lipophilicity for crust penetration^[1]. The introduction of fluorine atoms into organic molecules has been demonstrated in several widely used pesticides^[2-3]. Flubendiamide, the first artificially synthesized insecticide targeting ryanodine receptors (RyRs), has shown extremely high activity against a broad spectrum of lepidopterous insects^[4-5]. Since its discovery by Nihon Nohyaku and development with Bayer company in 1998, a series of pesticides containing polyfluorinated groups with high activities was reported, such as pyrifluquinazon^[6-7] and pyflubumide^[8](Fig. 1).

Fig. 1 Commercial pesticides with polyfluoroalkyl groups

Fludioxonil^[9-11], a non-systemic fungicide, is the world's biggest seed treatment agent in terms of current unit sales. As a cereal seed treatment, it controls seed- and soil-borne diseases and gives particularly good control of Fusarium roseum and Gerlachia nivalis in small-grain cereals. The key moiety of the fungicide is 2,2-difluoro-1,3-benzodioxole.

In order to find some compounds with high biological activities and new action mode, herein we designed and synthesized a series of novel 2,2-difluoro-1,3-benzodioxol-5-acetamide compounds containing multi-fluorine atoms. As showed in Fig. 2, 2,2-difluoro-1,3-benzodioxole moiety from fludioxonil and heptafluoroisopropyl aniline moiety from flubendiamide were linked with amide group. These new 2,2-difluoro-1,3-benzodioxol-5-acetamide compounds are expected to exhibit desirable biological activities.

Fig. 2 Design of the title compounds

In addition, organic solvents represent the vast majority of mass consumption and waste generated by the chemical industry. Since most of chemical reactions are conducted in traditional organic solvents, a green protocol with reduced organic waste would be desirable^[12-13]. The nanomicelle-forming amphiphile TPGS-750-M (Fig. 3) was reported recently, which can facilitate many reactions under mild conditions in water^[14]. Encouraged by this, we have successfully improved the last key step of amidation using HATU as the coupling agent in 2 wt.% TPGS-750-M/H₂O under mild conditions^[15-22]. Furthmore, a series of novel poly fluorinated 1,3-benzodioxol-5-acetamides (h1-h16) was designed and synthesized (Scheme 1). And the insecticidal activities were evaluated.

Fig. 3 Structural formula of TPGS-750-M

Scheme1 General synthetic route of the title compound h1-h16

1 Materials and Methods 1.1 Instruments and reagents

All starting materials and reagents used were commercially available and were utilized without further purification (except as indicated). TPGS-750-M was synthesized according to the published procedure^[14]. All the melting points were determined with an X-4 melting point apparatus while the thermometer was uncorrected. NMR spectra were recorded on a Varian INOVA spectrometer (400 MHz for ¹H NMR), or a Bruker Avance spectrometer (600 MHz for ¹H NMR, and 564 MHz for ¹⁹F NMR spectroscopy). HRMS (ESI) were performed on an Agilent 6 210 TOF LC/MS instrument. Mass spectra were recorded on a Bruker Esquire 6 000 mass spectrometer (ESI).

1.2 Synthetic procedures 1.2.1 Synthesis of 5-methyl-1,3-benzodioxole (a)

Methylene chloride (300.0 g, 3.56 mol) and dimethylsulphoxide (1 000.0 g, 12.80 mol) were added to a flask and stirred under reflux at 90 °C to 100 °C for 1 h. A solution of sodium hydroxide (144.0 g, 3.60 mol) and 4-methylbenzene-1, 2-diol (195.2 g, 1.57 mol) in water (300 mL) were added dropwise in 1 h. At the end of the addition, the mixture was subsequently stirred for a further 2 h under reflux. Then 500 mL of water was added to the reaction solution and steam distillation was conducted. The distillation fractions at 110 °C was collected and separated. Aqueous phase was extracted with dichloromethane (200 mL). The combined organic phases were dried, concentrated and 5-methyl-1,3-benzodioxole (a) was obtained as a colorlesstaine oil, yield: 149.7 g (70%). ¹H NMR (400 MHz, CDCl₃), δ: 2.30 (s, 3H, -CH₃), 6.05 (s, 2H, -CH₂-), 6.90-7.05 (m, 3H, Ar-H).

1.2.2 Synthesis of 2,2-dichloro-5-methyl-1,3-benzodioxole (b)

5-Methyl-1,3-benzodioxole (13.6 g, 0.10 mol) was added dropwise to phosphorus pentachloride (25.0 g, 0.12 mol) in toluene (50 mL) with stirring. Vigorous evolution of hydrogen chloride started immediately. The mixture was then heated under reflux for 3 h. After distillation, phosphorus trichloride, phosphorus pentachloride and toluene were recovered and 2,2-dichloro-5-methyl-1,3-benzodioxole (b) was obtained as a pale-yellow oil at boiling point: 98-99 °C (2 200 Pa), yield: 17.0 g (82%). ¹H NMR (400 MHz, CDCl₃), δ: 2.28 (s, 3H, -CH₃), 6.70-6.80 (m, 3H, Ar-H).

1.2.3 Synthesis of 2,2-difluoro-5-methyl-1,3-benzodioxole (c)

A mixture of 2,2-dichloro-5-methyl-1,3-benzodioxole (16.4 g, 0.08 mol) and triethylamine tris (hydrogen fluoride) (9.6 g, 0.06 mol) was stirred under nitrogen at room temperature. The progress was monitored by TLC (V(ethyl acetate) :V(hexane) = 1 : 20). At the end of the reaction, the mixture was filtered. The filtrate was distilled under reduced pressure to yield 2,2-difluoro-5-methyl-1,3-benzodioxole (c) as a colorless oil at boiling point：60-62 °C(1 600 Pa), yield: 11.7 g (85%). ¹H NMR (400 MHz, CDCl₃), δ: 2.28 (s, 3H, -CH₃), 6.70-6.80 (m, 3H, Ar-H).

1.2.4 Synthesis of 2,2-difluoro-5-bromomethyl-1,3-benzodioxole (d)

To a solution of 2,2-difluoro-5-methyl-1,3-benzodioxole (11.5 g, 0.07 mol) in carbon tetrachloride (50 mL) was added N-bromosuccinimide (NBS) (12.3 g, 0.07 mol) and a catalytic amount of benzoyl peroxide (0.2 g, 0.001 mol). After stirred at refluxed for 3 h, the reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to give 2,2-difluoro-5-bromomethyl-1,3-benzodioxole (d) as a brown oil, yield: 16.0 g (95%). ¹H NMR (400 MHz, CDCl₃), δ: 4.38 (s, 2H, -CH₂-), 6.80-7.40 (m, 3H, Ar-H). The product was used without purification in the next step.

1.2.5 Synthesis of 2-(2,2-difluoro-1,3-benzodioxole-5-yl) acetonitrile (e)

A solution of 2,2-difluoro-5-bromomethyl-1,3-benzodioxole ( 12.6 g, 0.05 mol) and potassium cyanide (3.9 g, 0.06 mol) in 80% aqueous ethanol (60 mL) was heated under reflux for 6 h and then cooled to room temperature. After the addition of water (20 mL), the organic product was extracted with ethyl acetate (3 × 25 mL). The combined organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford 2-(2,2-difluoro-1,3-benzodioxole-5-yl) acetonitrile (e) as a pale-yellow liquid that was used directly in the next step, yield: 4.0 g (40%). ¹H NMR (400 MHz, CDCl₃), δ: 3.78 (s, 2H, -CH₂-), 7.01-7.03 (m, 3H, Ar-H).

1.2.6 Synthesis of 2- (2,2-difluoro-1,3-benzodioxole-5-yl) acetic acid (f)

A mixture of 2-(2,2-difluoro-1,3-benzodioxole-5-yl) acetonitrile (4.0 g, 0.02 mol), potassium hydroxide pellets (3.4 g, 0.06 mol) in ethanol (20 mL) and water (10 mL) was heated under reflux for 3 h. After cooling, the reaction mixture was poured into ice-water, acidified with dilute hydrochloric acid and extracted with ethyl acetate (3 × 20 mL). The combined extracts were washed with water (2 × 20 mL), dried over sodium sulfate and evaporated under vacuum. Recrystallization of the solid residue from heptane affords 2-(2,2-difluoro-1,3-benzodioxole-5-yl)acetic acid (f) as a pale yellow solid, yield: 8.8 g (82%), m.p. 94-96 °C. ¹H NMR (400 MHz, CDCl₃), δ: 3.65 (s, 2H, -CH₂-), 6.97-7.04 (m, 3H, Ar-H).

1.2.7 General synthetic procedure for 2-(2,2-difluoro-1,3-benzodioxole-5-yl)-N-(2-methyl-4-(perfluoropropan-2-yl) phenyl) acetamide (h1)

To a dried 5 mL reaction vial was added a mixture of 2,2-difluoro-1,3-benzodioxole-5-acetic acid (f) (0.2 g, 0.001 mol), 2, 6-lutidine (0.3 g, 0.003 mol) in 2 wt.% TPGS-750-M/H₂O (2 mL), HATU (0.418 g, 0.001 mol) and 2-methyl-4-(perfluoropropan-2-yl) aniline (0.5 g, 0.001 mol). The reaction was allowed to stir for 24 hours at 45 °C. The reaction progress was monitored by HPLC. The aqueous reaction mixture was extracted with EtOAc (3 × 2 mL). The organic extracts were then washed with 1 mol/L HCl (3 × 2 mL) and Na₂CO₃ (3 × 6 mL) saturated solution in water^[25]. The organic phase was concentrated under reduced pressure to give a crude product. The product was purified by column chromatography on silica gel (V (ethyl acetate) : V(hexane) = 1 : 1) to give compound h1. The synthetic procedure for compounds h2-h16 is the same as the synthesis of compound h1.

1.3 Insecticidal activity

The preliminary bioactivity tests were performed on representative test organisms reared in the laboratory. All compounds were dissolved in N, N-dimethylformamide (DMF) and diluted with distilled water containing 0.1% tween-80 to achieve the testing solution with the desired concentration. For insecticidal activity test, flubendiamide and abamectin were tested under the same conditions as the control.

1.3.1 Insecticidal activity against Homoptera pest—Aphis craccivora

The foliar contact activity against bean aphid (A. craccivora) was tested. Tender shoots of soybean with 60 insects of each species were dipped in the diluted solutions of the chemicals for 5 s. Then the superfluous liquor was removed, and they were kept in the conditioned room for normal cultivation. The mortality was evaluated by the number of live larvae in the treated bottles relative to that in the untreated controls after 48 h. Controls were performed under the same conditions.

1.3.2 Insecticidal activity against Lepidopteran pest—Mythimna separata

The insecticidal activity against armyworms (M. separata) was also tested by foliar application. Individual corn leaves were placed on moistened pieces of filter paper in petri-dishes. The leaves were then sprayed with the testing solution and exposed to dry. The dishes were infested with 10 third-instar larvae and maintained in the conditioned room. The mortality rates were evaluated 48 h after treatment.

2 Results and Discussion 2.1 Synthesis of the title compounds

As shown in Scheme 1, 2,2-difluoro-5-methyl-1,3-benzodioxole (c) is the key intermediate for the synthesis of title compounds and was prepared starting from 4-methylbenzene-1, 2-diol by cyclization, chlorination and fluorination reaction ^[23-26]. During the fluorination reaction, triethylamine trihydrogenfluoride was employed as the fluorinating agent and high yields were obtained under ambient reaction conditions. Then the intermediate c was converted to another key intermediate 2,2-difluoro-1,3-benzodioxole-5-acetic acid (f) by bromination, cyanation and hydrolysis. In traditional synthetic procedure, the intermediate f was converted to compound h1 by acylchlorination and acylation reaction in 45% total yield^[27](Scheme 2, Route A). In the improved route, compound h1 was prepared in 60% yield by coupling intermediate f and 2-methyl-4-heptafluoroisopropyl aniline using TPGS-750-M in water (Scheme 2, Route B). With the above mentioned environment-friendly and easy operative method, title compounds h2-h16 were synthesized with moderate yields. Physical and chemical data of the title compounds h1-h16 were listed in Table 1. ¹H NMR, ¹⁹F NMR and HRMS spectra were listed in Table 2.

Scheme2 Route improvement for the synthesis of the title compounds h1

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

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

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, -O CH₂CH₃), 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

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

2.2 Insecticidal activity

The insecticidal activity of the above compounds against bean aphids (A. craccivora) and armyworms (M. separata) in vivo was evaluated. The results were listed in Table 3. h5, h8, h10 and h16 exhibited 100% mortality against A. craccivora at the concentration of 500 mg/L. h1, h7, h12 and h15 also showed high activities, and displayed mortalities higher than 80%. As for the insecticidal activities against M. separata, compounds h2, h4 and h14 exhibited mortalities higher than 80% at the concentration of 500 mg/L.

Table 3 Insecticidal activity of title compounds h1 to h16

Preliminary structure-activity relationship studies suggested that the insecticidal activities were significantly influenced by the substituent on the benzene ring of p-heptafluoroisopropyl aniline. For example, alkyl and alkoxy substituted compounds (h1-h8, h10-h16) showed good insecticidal activities, whereas hydroxyl substituted compound h9 exhibited no insecticidal activity. The target compounds displayed high selectivity between A. craccivora and M. separate, and compounds with substituent on 2-position of heptafluoroisopropyl aniline exhibited obvious insecticidal effect against A. craccivora. Whereas 3-position substituted compounds (h4 and h6) and unsubstituted compound h2 showed insecticidal activities against M. separata. Further studies on structure optimization are currently in progress.

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农药学学报 2019, Vol. 21 Issue (1): 12-18	PDF