Abstract
In this study, two series of novel diacylhydrazine derivatives containing an isoxazole carboxamide or a pyridine carboxamide moiety have been synthesized and their structures confirmed by 1H and 13C NMR, and mass spectra. According to bioassay data LC50 values for the product 3-(2-chlorophenyl)-N-{2-[2-(2,6-difluorobenzoyl)hydrazinecarbonyl]-4-fluorophenyl}-5-methylisoxazole-4-carboxamide (5f) against Plutella xylostella (P. xylostella) and Empoasca vitis (E. vitis) have been determined to be 1.67 and 1.29 mg/L, respectively, that were higher than those of spinosad, chlorpyrifos, beta cypermethrin, and azadirachtin.
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INTRODUCTION
Over recent years, the damage to cruciferous plants such as cabbage, broccoli, broccoli, brussels sprouts, and radishes, and tea leaves caused by P. xylostella and E. vitis, respectively have become more and more serious and caused huge economic losses every year [1, 2]. The insecticides abuse has led to the resistance of P. xylostella and E. vitis to most of those [2–5]. Therefore, development of new insecticides for controlling P. xylostella and E. vitis is of considerable importance.
Diacylhydrazine derivatives have been used efficiently in synthesis of various new pesticides such as tebufenozide, halofenozide, methoxyfenozide, and chromafenozide [6–10]. Isoxazole carboxamide or pyridine carboxamide derivatives also demonstrated high efficiency in the synthesis of new pesticide characterized by broad activity [11–16]. Earlier our group had reported a series of isoxazole carboxamide or pyridine carboxamide derivatives (Fig. 1) with potent antiviral and insecticidal activities [13–16].
Previously reported compounds with potent antiviral and insecticidal activity.
In this study, in search of “me-better” active molecules, we replaced the carboxamide or acylhydrazone by diacylhydrazine, as shown in Fig. 2, to design and synthesize two series of novel diacylhydrazine derivatives containing the isoxazole carboxamide or pyridine carboxamide moiety. To the best of our knowledge, it is the first report on diacylhydrazine derivatives containing an isoxazole carboxamide or a pyridine carboxamide moiety with potent insecticidal activities against P. xylostella and E. vitis.
Designed approach to the target compounds.
RESULTS AND DISCUSSION
Intermediates 2–4 and 7–9 were prepared according to the previously reported methods [13–16] from 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (1) and 5-bromonicotinoyl chloride (6) (Schemes 1 and 2). The compounds 5a–5f and 10a–10i were synthesized with yields of 70–90%, and their structures were confirmed by 1H and 13C NMR, and mass spectra.
Synthetic pathway to the target compounds 5a–5f.
Synthetic approach to the target compounds 10a–10i.
The groups –CONH– and –CONHNHCO– were recorded in the 1H NMR spectra of compounds 5a–5f and 10a–10i by signals in the range of 9.08–10.98 ppm. A singlet at 171.27–174.38 ppm and three singlets at 153.17–166.79 ppm in their 13C NMR spectra indicated the presence of isoxazole ring and C=O, respectively.
Biological evaluation. The preliminary bioassay results listed in Table 1 showed that the target compounds 5a, 5b, 5e, 5f, 10g, 10h, and 10i exhibited high insecticidal activity (100%) against P. xylostella and E. vitis at 500 mg/L after 72 h. The determined LC50 values of compounds 5a–5f and 10a–10i based on the preliminary bioassay (Table 2) indicated that the products exhibited moderate to good insecticidal activity against P. xylostella and E. vitis. The compound 3-(2-chlorophenyl)-N-{2-[2-(2,6-difluorobenzoyl)hydrazinecarbonyl]-4-fluorophenyl}-5-methylisoxazole-4-carboxamide (5f) exhibited the highest insecticidal activity against P. xylostella and E. vitis with LC50 values of 1.67 and 1.29 mg/L, respectively, that were superior to those of the standards. The results indicated that the series of diacylhydrazine derivatives containing an isoxazole carboxamide or pyridine carboxamide moiety could be used in development of potential agrochemicals for controlling P. xylostella and E. vitis.
EXPERIMENTAL
The uncorrected melting points were determined on an XT-4 binocular microscope (Beijing Tech Instrument Co., Beijing, China). 1H and 13C NMR spectra were measured on a JEOL ECX 500 NMR (JEOL, Tokyo, Japan) spectrometer using DMSO-d6 as a solvent. Elemental analysis was carried out on an Elemental Vario-III CHN analyzer (Elementar, Hanau, German). Mass spectra were measured on an Agilent mass spectrometer, model 5973, Agilent Technologies (Palo Alto, Canada). Microwave experiments were carried out in a 300 W CEM Discover Labmate Microwave Reactor (Matthews, NC, USA).
Preparation of intermediates 2–4 and 7–9. Intermediates 2–4 and 7–9 were prepared according to the previously reported methods [13–16]. As showed in Schemes 1 and 2, 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride 1 or 5-bromonicotinoyl chloride 6 (0.02 mol) was added dropwise to a solution of substituted 2-aminobenzoic acid (0.02 mol) in anhydrous pyridine (100 mL), and the reaction mixture was stirred for 2 h, then it was poured into a cool 5% HCl solution (200 mL). The residues were filtered, dried and crystallized from ethanol to give the corresponding intermediate 2 or 7.
2-[3-(2-Chlorophenyl)-5-methylisoxazole-4-carboxamido]-5-fluorobenzoic acid (2). White solid, yield 86%, mp 229–231°C. 1Н NMR spectrum, δ, ppm: 2.77 s (3H, CH3), 7.34–7.67 m (7H, Ar-H), 8.45 s (1H, isoxazole-CONH), 11.56 s (1H, COOH).
2-(5-Bromonicotinamido)-3-methylbenzoic acid (7). White solid, mp 269–271°C, yield 87%. 1Н NMR spectrum, δ, ppm: 2.89 s (3H, CH3), 7.24–7.87 m (3H, Ar-H), 8.64 s (1H, pyridine-H), 8.78 s (1H, pyridine-H), 8.95 s (1H, pyridine-H), 9.06 s (1H, pyridine-CONH), 11.56 s (1H, Ar-COOH). An intermediate 2 or 7 (0.02 mmol) and acetic anhydride (150 mL) were added to a 250 mL round-bottom flask which was sealed and placed in a synthesizer irradiated at 145°C and 150 W for 10 min. Upon completion of the reaction, the residue was filtered off, washed with water, dried, and crystallized from anhydrous ethanol to give the corresponding compound 3 or 8.
2-[3-(2-Chlorophenyl)-5-methylisoxazol-4-yl]-6-fluoro-4H-benzo[d][1,3]oxazin-4-one (3). White solid, yield 90%, mp 148–149°C. 1Н NMR spectrum, δ, ppm: 2.91 s (3H, CH3), 7.42–7.64 m (5H, Ar-H), 7.76–7.85 m (2H, Ar-H).
2-(5-Bromopyridin-3-yl)-8-methyl-4H-benzo[d][1,3]oxazin-4-one (8). White solid, mp 267–268°C, yield 93%. 1Н NMR spectrum, δ, ppm: 2.91 s (3H, CH3), 7.38 d. d (1H, J = 2.25, 4.50 Hz, Ar-H), 7.52 t (1H, J = 14.30 Hz, Ar-H), 7.57 s (1H, Ar-H), 7.64 s (1H, pyridine-H), 7.93 d (1H, J = 8.60 Hz, pyridine-H), 8.04 s (1H, pyridine-H). To a solution of an intermediate 3 or 8 (0.02 mol) in THF (100 mL), 80% hydrazine hydrate (6 mL) was added, and the reaction mixture was reacted at room temperature for 2 h. Then the residue was filtered off, washed with water, anhydrous ethanol and crystallized from ethanol to give the corresponding intermediate 4 or 9.
3-(2-Chlorophenyl)-N-[4-fluoro-2-(hydrazinecarbonyl)phenyl]-5-methylisoxazole-4-carboxamide (4). White solid, yield 91%, mp 186–188°C. 1Н NMR spectrum, δ, ppm: 2.77 s (3H, CH3), 4.51 s (2H, NH2), 7.35–7.60 m (6H, Ar-H), 8.35 q (1H, J = 14.30 Hz, Ar-H), 10.07 s (1H, Ar-CONH), 11.22 s (1H, isoxazole-CONH).
5-Bromo-N-[2-(hydrazinecarbonyl)-3-methylphenyl]nicotinamide (9). White solid, mp 248–249°C, yield 94%. 1Н NMR spectrum, δ, ppm: 2.91 s (3H, CH3), 4.87 s (2H, NH2), 7.33 d. d (1H, J = 1.70), 2.85 Hz, Ar-H), 7.84 d (1H, J = 8.60 Hz, Ar-H), 8.45 t (1H, J = 4.55 Hz, Ar-H), 8.64 d (1H, J = 1.75 Hz, pyridine-H), 8.98 d (1H, J = 2.30 Hz, pyridine-H), 9.07 d (1H, J = 1.70 Hz, pyridine-H), 10.30 s (1H, Ar-CONH), 12.79 s (1H, pyridine-CONH).
Synthesis of compounds 5a–5f and 10a–10i. To the desired intermediate 4 or 9 (1 mmol), anhydrous THF (10 mL) and anhydrous potassium carbonate (1.5 mmol) were added. Then substituted benzoyl chloride (1 mmol) was added dropwise to the reaction mixture, and it was stirred for 4 h. Upon completion of the process, the mixture was poured into 50 mL of water, the residue was filtered off and recrystallized from anhydrous ethanol to give the corresponding compounds 5a–5f and 10a–10i as white solids.
3-(2-Chlorophenyl)-N-(4-fluoro-2-{2-[3-(trifluoromethyl)benzoyl]hydrazinecarbonyl}phenyl)-5-methylisoxazole-4-carboxamide (5a). mp 147–148°C, yield 85%. 1Н NMR spectrum, δ, ppm: 2.75 s (3H, CH3), 7.22–7.26 m (2H, Ar-H), 7.44–7.64 m (8H, Ar-H), 8.25 q (1H, J = 14.30 Hz, Ar-H), 10.83 s (1H, Ar-CONH), 10.85 s (1H, Ar-CONH), 10.97 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 12.46, 112.08, 112.27, 113.12, 113.78, 115.06, 119.47, 122.22, 124.02, 127.33, 127.51, 129.70, 131.64, 131.74, 132.59, 132.71, 134.62, 156.52, 158.18, 158.44, 159.08, 160.04, 160.22, 165.81, 171.82. Found, %: C 55.95, H 3.42, N 10.26. C26H17ClF4N4O4. Calculated, %: C 55.68, H 3.05, N 9.99. MS: m/z: 561.7 [M + H]+.
3-(2-Chlorophenyl)-N-{2-[2-(2,4-dichlorobenzoyl)hydrazinecarbonyl]-4-fluorophenyl}-5-methylisoxazole-4-carboxamide (5b). mp 265–267°C, yield 88%. 1Н NMR spectrum, δ, ppm: 2.75 s (3H, CH3), 7.46–7.65 m (8H, Ar-H), 7.79 s (1H, Ar-H), 8.29 q (1H, J = 14.30 Hz, Ar-H), 10.62 s (1H, Ar-CONH), 10.90 s (1H, Ar-CONH), 10.94 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 13.00, 114.14, 115.29, 119.83, 122.37, 124.36, 127.69, 127.99, 128.10, 130.10, 130.19, 131.31, 132.17, 132.26, 133.04, 133.65, 135.18, 136.03, 156.91, 158.84, 159.54, 160.36, 165.29, 166.54, 171.55. Found, %: C 53.67, H 2.83, N 10.25. C25H16Cl3FN4O4. Calculated, %: C 53.45, H 2.87, N 9.97. MS: m/z: 562.7 [M + H]+.
3-(2-Chlorophenyl)-N-[2-(2-benzoylhydrazinecarbonyl)-4-fluorophenyl]-5-methylisoxazole-4-carboxamide (5c). mp 153–155°C, yield 76%. 1Н NMR spectrum, δ, ppm: 2.71 s (3H, CH3), 7.39–7.54 m (5H, Ar-H), 7.61–7.64 d. d (1H, J= 2.85, 5.70 Hz, Ar-H), 8.12 s (1H, Ar-H), 8.13 s (1H, Ar-H), 8.21–8.24 q (1H, J = 14.30 Hz, Ar-H), 8.37 s (2H, Ar-H), 8.39 s (1H, Ar-H), 10.78 s (1H, Ar-CONH), 10.87 s (1H, Ar-CONH), 10.96 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 13.81, 109.50, 113.83, 114.02, 118.45, 118.52, 125.43, 125.62, 127.74, 127.79, 128.33, 129.78, 129.84, 129.90, 131.88, 131.96, 132.18, 133.36, 143.26, 151.24, 157.81, 157.84, 160.26, 162.24, 174.38. Found, %: C 60.99, H 3.70, N 11.48. C25H18ClFN4O4. Calculated, %: C 60.92, H 3.68, N 11.37. MS: m/z: 493.8 [M + H]+.
3-(2-Chlorophenyl)-N-{4-fluoro-2-[2-(4-nitrobenzoyl)hydrazinecarbonyl]phenyl}-5-methylisoxazole-4-carboxamide (5d). mp 266–268°C, yield 87%. 1Н NMR spectrum, δ, ppm: 2.74 s (3H, CH3), 7.42–7.56 m (5H, Ar-H), 7.66 d. d (1H, J = 2.85, 5.70 Hz, Ar-H), 8.14 s (1H, Ar-H), 8.16 s (1H, Ar-H), 8.27 q (1H, J = 14.30 Hz, Ar-H), 8.39 s (1H, Ar-H), 8.41 s (1H, Ar-H), 10.81 s (1H, Ar-CONH), 10.90 s (1H, Ar-CONH), 10.98 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 12.94, 114.13, 115.25, 115.45, 119.81, 119.97, 122.71, 124.39, 127.68, 127.96, 129.62, 130.17, 132.14, 132.23, 133.03, 135.07, 138.28, 150.07, 156.98, 158.91, 159.60, 160.31, 164.74, 166.69, 171.52. Found, %: C 55.87, H 3.34, N 13.40. C25H17ClFN5O6. Calculated, %: C 55.82, H 3.19, N 13.02. MS: m/z: 538.8 [M + H]+.
3-(2-Chlorophenyl)-N-{2-[2-(4-chlorobenzoyl)hydrazinecarbonyl]-4-fluorophenyl}-5-methylisoxazole-4-carboxamide (5e). mp 255–257°C, yield 84%. 1Н NMR spectrum, δ, ppm: 2.73 s (3H, CH3), 7.41–7.65 m (8H, Ar-H), 7.93 s (1H, Ar-H), 7.95 s (1H, Ar-H), 8.27 q (1H, J = 14.30 Hz, Ar-H), 10.73 s (1H, Ar-CONH), 10.80 s (1H, Ar-CONH), 10.82 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 12.93, 114.15, 115.38, 119.71, 119.90, 122.74, 124.39, 127.70, 127.95, 129.30, 129.99, 130.16, 131.40, 132.12, 132.22, 133.03, 135.08, 137.50, 156.95, 158.88, 159.58, 160.33, 165.26, 166.79, 171.46. Found, %: C 56.97, H 3.36, N 10.75. C25H17Cl2FN4O4. Calculated, %: C 56.94, H 3.25, N 10.62. MS: m/z: 528.2 [M + H]+.
3-(2-Chlorophenyl)-N-{2-[2-(2,6-difluorobenzoyl)hydrazinecarbonyl]-4-fluorophenyl}-5-methylisoxazole-4-carboxamide (5f). mp 236–237°C, yield 87%. 1Н NMR spectrum, δ, ppm: 2.75 s (3H, CH3), 7.27 t (2H, J = 15.45 Hz, Ar-H), 7.45–7.65 m (7H, Ar-H), 8.25 q (1H, J = 13.75 Hz, Ar-H), 10.84 s (1H, Ar-CONH), 10.86 s (1H, Ar-CONH), 10.97 s (1H, isoxazole-CONH). 13C NMR spectrum, δC, ppm: 12.91, 112.53, 112.72, 113.57, 114.23, 115.52, 119.92, 122.67, 124.47, 127.78, 127.96, 130.15, 132.09, 132.19, 133.04, 133.16, 135.07, 156.97, 158.63, 158.90, 159.54, 160.49, 160.67, 166.26, 171.27. Found, %: C 56.87, H 3.42, N 10.58. C25H16ClF3N4O4. Calculated, %: C 56.78, H 3.05, N 10.59. MS: m/z: 529.8 [M + H]+.
5-Bromo-N-(2-methyl-6-{2-[3-(trifluoromethyl)benzoyl]hydrazinecarbonyl}phenyl)nicotinamide (10a). mp 234–236°C, yield 82%. 1Н NMR spectrum, δ, ppm: 2.31 s (3H, CH3), 7.44 t (1H, J = 15.50 Hz, Ar-H), 7.53–7.83 m (5H, Ar-H), 7.87 d. d (1H, J = 8.05 Hz, Ar-H), 8.59 s (1H, pyridine-H), 8.94 s (1H, pyridine-H), 8.95 s (1H, pyridine-H), 9.13 s (1H, Ar-CONH), 10.36 s (1H, Ar-CONH), 10.51 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.58, 120.55, 123.39, 124.56, 126.76, 127.34, 128.77, 129.84, 130.37, 132.06, 132.32, 133.02, 133.18, 134.19, 134.49, 137.14, 138.44, 147.96, 153.19, 163.21, 164.31, 166.77. Found, %: C 50.85, H 3.34, N 10.92. C22H16BrF3N4O3. Calculated, %: C 50.69, H 3.09, N 10.75. MS: m/z: 528.2 [M + H]+.
5-Bromo-N-{2-[2-(2-chloro-4-fluorobenzoyl)hydrazinecarbonyl]-6-methylphenyl}nicotinamide (10b). mp 242–244°C, yield 75.4%. 1Н NMR spectrum, δ, ppm: 2.26 s (3H, CH3), 7.31–7.57 m (6H, Ar-H), 8.56 s (1H, pyridine-H), 8.90–8.94 m (2H, pyridine-H), 9.10 s (1H, Ar-CONH), 10.46 s (2H, pyridine-CONH, Ar-CONH). 13C NMR spectrum, δC, ppm: 18.58, 114.82, 114.99, 115.09, 117.79, 117.98, 120.56, 126.89, 127.32, 131.73, 131.80, 132.29, 132.49, 132.57, 133.03, 137.15, 138.40, 148.00, 153.16, 161.93, 163.20, 166.66. Found, %: C 49.98, H 3.15, N 11.24. C21H15BrClFN4O3. Calculated, %: C 49.87, H 2.99, N 11.08. MS: m/z: 506.6 [M + H]+.
5-Bromo-N-{2-[2-(2,4-difluorobenzoyl)hydrazinecarbonyl]-6-methylphenyl}nicotinamide (10c). mp 259–261°C, yield 77%. 1Н NMR spectrum, δ, ppm: 2.26 s (3H, CH3), 7.19–7.54 m (5H, Ar-H), 7.71 q (1H, J = 24.65 Hz, Ar-H), 8.53 t (1H, J = 4.00 Hz, pyridine-H), 8.91 d (1H, J = 2.30 Hz, pyridine-H), 9.07 d (1H, J = 1.70 Hz, pyridine-H), 10.20 s (1H, Ar-CONH), 10.35 s (1H, Ar-CONH), 10.37 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.50, 105.12, 105.33, 105.54, 112.33, 120.56, 126.78, 127.44, 132.28, 132.39, 132.44, 133.01, 133.16, 134.35, 137.30, 138.36, 147.94, 153.21, 162.98, 163.23, 166.86. Found, %: C 51.73, H 3.45, N 11.59. C21H15BrF2N4O3. Calculated, %: C 51.55, H 3.09, N 11.45. MS: m/z: 490.1 [M + H]+.
5-Bromo-N-(2-methyl-6-{2-[2-(trifluoromethyl)benzoyl]hydrazinecarbonyl}phenyl)nicotinamide (10d). mp 253–255°C, yield 90%. 1Н NMR spectrum, δ, ppm: 2.26 s (3H, CH3), 7.36–7.78 m (6H, Ar-H), 7.82 d (1H, J = 8.05 Hz, Ar-H), 8.54 s (1H, pyridine-H), 8.89–8.95 m (2H, pyridine-H), 9.08 s (1H, Ar-CONH), 10.31 s (1H, Ar-CONH), 10.47 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.53, 116.20, 120.55, 122.94, 125.16, 126.89, 126.92, 127.14, 127.39, 129.72, 130.97, 132.28, 132.96, 133.11, 134.35, 134.61, 137.27, 138.37, 147.95, 153.17, 163.24, 166.88. Found, %: C 50.87, H 3.18, N 11.06. C22H16BrF3N4O3. Calculated, %: C 50.69, H 3.09, N 10.75. MS: m/z: 522.2 [M + H]+.
5-Bromo-N-{2-methyl-6-[2-(2-methylbenzoyl)hydrazinecarbonyl]phenyl}nicotinamide (10e). mp 222–224°C, yield 72%. 1Н NMR spectrum, δ, ppm: 2.25 s (3H, CH3), 2.36 s (3H, CH3), 7.10–7.44 m (7H, Ar-H), 7.59 d (1H, J = 8.05 Hz, pyridine-H), 8.56 s (1H, pyridine-H), 8.89 d (1H, J = 2.30 Hz, pyridine-H), 9.11 s (1H, Ar-CONH), 10.30 s (1H, Ar-CONH), 10.46 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.84, 19.90, 105.35, 106.46, 111.76, 114.85, 120.59, 126.03, 126.72, 127.82, 130.24, 131.05, 132.59, 132.71, 135.57, 136.46, 138.37, 148.00, 158.74, 162.58, 163.82, 166.35. Found, %: C 56.76, H 4.12, N 12.27. C22H19BrN4O3. Calculated, %: C 56.54, H 4.10, N 11.99. MS: m/z: 468.3 [M + H]+.
5-Bromo-N-{2-[2-(2-methoxybenzoyl)hydrazinecarbonyl]-6-methylphenyl}nicotinamide (10f). mp 258–260°C, yield 70%. 1Н NMR spectrum, δ, ppm: 2.26 s (3H, CH3), 3.88 s (3H, OCH3), 7.08 t (1H, J = 14.85 Hz, Ar-H), 7.17 (d, 1H, J = 8.00 Hz, Ar-H), 7.39 t (1H, J = 15.50 Hz, Ar-H), 7.48–7.55 m (3H, Ar-H), 7.74 d (1H, J = 6.90 Hz, Ar-H), 8.54 s (1H, pyridine-H), 8.91 d (1H, J = 2.30 Hz, pyridine-H), 9.07 s (1H, pyridine-H), 10.01 s (1H, Ar-CONH), 10.21 s (1H, Ar-CONH), 10.44 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.57, 56.42, 112.63, 120.56, 121.06, 121.87, 126.76, 127.36, 131.05, 132.34, 132.77, 133.12, 133.38, 134.36, 137.24, 138.41, 147.94, 153.20, 157.57, 163.28, 164.72, 166.55. Found, %: C 54.82, H 4.06, N 11.66. C22H19BrN4O4. Calculated, %: C 54.67, H 3.96, N 11.59. MS: m/z: 484.4 [M + H]+.
5-Bromo-N-(4-chloro-2-methyl-6-{2-[3-(trifluoromethyl)benzoyl]hydrazinecarbonyl}phenyl)nicotinamide (10g). mp 216–218°C, yield 88%. 1Н NMR spectrum, δ, ppm: 2.27 s (3H, CH3), 7.20–7.71 m (6H, Ar-H), 8.52 t (1H, J = 4.60 Hz, pyridine-H), 8.92 d (1H, J = 2.25 Hz, pyridine-H), 9.06 d (1H, J = 2.30 Hz, pyridine-H), 10.25 s (1H, Ar-CONH), 10.44 s (1H, Ar-CONH), 10.50 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.72, 116.39, 120.74, 123.12, 125.35, 127.08, 127.11, 127.33, 127.58, 129.91, 131.16, 132.46, 133.15, 133.29, 134.53, 134.80, 137.46, 138.56, 148.13, 153.36, 163.42, 167.07. Found, %: C 47.95, H 2.78, N 10.31. C22H15BrClF3N4O3. Calculated, %: C 47.55, H 2.72, N 10.08. MS: m/z: 556.6 [M + H]+.
5-Bromo-N-{4-chloro-2-[2-(2,4-difluorobenzoyl)hydrazinecarbonyl]-6-methylphenyl}nicotinamide (10h). mp 274–276°C, yield 85%. 1Н NMR spectrum, δ, ppm: 2.27 s (3H, CH3), 7.23 t (1H, J = 16.60 Hz, Ar-H), 7.42 t (1H, J = 20.00 Hz, Ar-H), 7.54–7.71 m (3H, Ar-H), 8.52 t (1H, J = 4.55 Hz, pyridine-H), 8.92 d (1H, J = 2.30 Hz, pyridine-H), 9.06 d (1H, J = 2.30 Hz, pyridine-H), 10.25 s (1H, Ar-CONH), 10.43 s (1H, Ar-CONH), 10.50 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 18.26, 105.36, 105.57, 112.36, 112.53, 120.55, 126.44, 131.44, 132.00, 132.36, 132.48, 132.58, 133.51, 134.71, 138.38, 139.94, 147.96, 153.34, 163.01, 163.37, 165.55. Found, %: C 48.31, H 2.79, N 11.05. C21H14BrClF2N4O3. Calculated, %: C 48.16, H 2.69, N 10.70. MS: m/z: 524.6 [M + H]+.
5-Bromo-N-{4-chloro-2-[2-(2,6-difluorobenzoyl)hydrazinecarbonyl]-6-methylphenyl}nicotinamide (10i). mp 254–256°C, yield 80%. 1Н NMR spectrum, δ, ppm: 2.25 s (3H, CH3), 7.17–7.68 m (5H, Ar-H), 8.49 t (1H, J = 4.55 Hz, pyridine-H), 8.89 d (1H, J = 2.30 Hz, pyridine-H), 9.03 d (1H, J = 2.30 Hz, pyridine-H), 10.22 s (1H, Ar-CONH), 10.41 s (1H, Ar-CONH), 10.47 s (1H, pyridine-CONH). 13C NMR spectrum, δC, ppm: 17.59, 104.69, 104.90, 111.69, 111.86, 119.88, 125.77, 130.77, 131.33, 131.69, 131.81, 131.91, 132.84, 134.04, 137.71, 139.27, 147.29, 152.67, 162.34, 162.70, 164.88. Found, %: C 48.24, H 2.88, N 10.83. C21H14BrClF2N4O3. Calculated, %: C 48.16, H 2.69, N 10.70. MS: m/z: 524.6 [M + H]+.
Insecticidal activity. Insecticidal activity of the compounds 5a–5f and 10a–10i against P. xylostella and E. vitis was evaluated using the previously reported methods with some modifications [17, 18]. Mortality rates were corrected using Abbott’s formula based on the percentage scale (0 = no activity and 100% = complete eradication). The commercial insecticidal agents spinosad, chlorpyrifos, beta cypermethrin, and azadirachtin were used as positive controls, and water solvent was used as a blank control. All experiments were performed in triplicates.
Insecticidal activity against P. xylostella. Fresh cabbage discs (diameter 2 cm) were dipped into the prepared solutions containing the desired compound among 5a–5f and 10a–10i for 10 s, then dried in the air and placed in a petri dish (diameter 9 cm) lined with filter paper. Thirty second-instar larvae of P. xylostella were transferred to the petri dish, sealed with a fresh keeping film with some holes, and placed in a growth chamber (25 ± 1°C and 75%) with a light–dark period of 14 : 10 h.
Insecticidal activity against E. vitis. Fresh tea shoots (length 13 cm) dipped into the prepared solutions containing a compound 5a–5f and 10a–10i for 10 s were dried in the air, wrapped with wet cotton and parafilm, and packed in a test tube (3 × 20 cm). Thirty second-third-instar larvae of E. vitis were transferred into the tube. Finally, opening of the tube was wrapped with gauze and placed in the growth chamber (25 ± 1°C and 75%) with a light–dark period of 14 : 10 h.
CONCLUSIONS
In this study, two series of novel diacylhydrazine derivatives containing an isoxazole carboxamide or a pyridine carboxamide moiety have been designed and synthesized. The compound 5f has been determined to be the most active against P. xylostella and E. vitis. This study provides the practical tool for the design and synthesis of novel promising insecticides for controlling P. xylostella and E. vitis.
REFERENCES
Arora, R., Battu, G.S., and Bath, D.S., Indian J. Ecol., 2000, vol. 27, p. 156.
Talekar, N.S., and Shelton, A.M., Annu. Rev. Entomol., 1993, vol. 38, p. 275. https://doi.org/10.1146/annurev.en.38.010193.001423
Shelton, A.M., Tang, J.D., Roush, R.T., Metz, T.D., and Earle, E.D., Nat. Biotechnol., 2000, vol. 18, p. 339. https://doi.org/10.1038/73804
Cheng, E.Y., Pestic. Sci., 1988, vol. 23, p. 177. https://doi.org/10.1002/ps.2780230211
Perez, C.J., Alvarado, P., Miranda, F., Narváez, C., Hernández, L., Vanegas, H., Hruska, A., and Shelton, A.M., J. Econ. Entomol., 2000, vol. 93, p. 1779. https://doi.org/10.1603/0022-0493-93.6.1779
Wing, K.D., Science, 1988, vol. 241, p. 467. https://doi.org/10.1126/science.3393913
Sun, R.F., Zhang, Y.L., Chen, L., Li, Y.Q., Li, Q.S., Song, H.B., Huang, R.Q., Bi, F.C., and Wang, Q.M., J. Agric. Food Chem., 2009, vol. 57, p. 3661. https://doi.org/10.1021/jf900324a
Wang, H., Yang, Z.K., Fan, Z.J., Wu, Q.J., Zhang, Y.J., Mi, N., Wang, S.X., Zhang, Z.C., Song, H.B., and Liu, F., J. Agric. Food Chem., 2011, vol. 59, p. 628. https://doi.org/10.1021/jf104004q
Yanagi, M., Tsukamoto, Y., Watanabe, T., and Kawagishi, A., J. Pestic. Sci., 2006, vol. 31, p. 163. https://doi.org/10.1584/jpestics.31.182
Aguirre, O.U., Martínez, A.M., Campos-García, J., Hernández, L., Figueroa, J.I., Lobit, P., Viñuela, E., Chavarrieta, J.M., Smagghe, G., and Pinedal, S., Insect Sci., 2013, vol. 20, p. 734. https://doi.org/10.1111/j.1744-7917.2012.01576.x
Wang, M.M., Zhang, Q.Q., Yue, K., Li, Q.S., and Xsu, F.B., Chin. J. Org. Chem., 2017, vol. 37, p. 1774. https://doi.org/10.6023/cjoc201612030
Ye, F., Zhai, Y., Kang, T., Wu, S.L., Li, J.J., Hao, S., Zhao, L.X., and Yu, Y., Pestic. Biochem. Phys., 2019, vol. 157, p. 60. https://doi.org/10.1016/j.pestbp.2019.03.003
Yang, Z.B., Li, P., and Gan, X.H., Molecules, 2018, vol. 23, p. 1798. https://doi.org/10.3390/molecules23071798
Yang, Z.B., Zhao, Y., Li, P., and He, Y.J., J. Heterocycl. Chem., 2019, vol. 56, p. 3042. https://doi.org/10.1002/jhet.3699
Yang, Z.B., Li, P., and He, Y.J., Molecules, 2019, vol. 24, p. 3766. https://doi.org/10.3390/molecules24203766
Yang, Z.B., Hu, D.Y., Zeng, S., and Song, B.A., Bioorg. Med. Chem. Lett., 2016, vol. 26, p. 1161. https://doi.org/10.1016/j.bmcl.2016.01.047
Zhang, X.Y., Li, Y.S., Weng, J.Q., and Tan, C.X., Chin. J. Org. Chem., 2011, vol. 31, p. 1295.
Feng, Q., Liu, Z.L., Xiong, L.X., Wang, M.Z., Li, Y.Q., and Li, Z.M., J. Agric. Food Chem., 2010, vol. 58, p. 12327.
ACKNOWLEDGMENTS
This research was funded by the Science and Technology Foundation of Guizhou Province, grant number ZK[2021]137; 2018 Annual Special Project of Cultivation and Innovation of Academic Young Seedlings of Guizhou Provincial Department of Science and Technology, grant number [2019]QNSYXM02; Kaili University Doctoral Program, grant number BS201811; National Torch Base Project of Qiandongnan Miao-Dong Medicine Characteristic Industrial, grant number J [2018]007; Science and Technology Platform and Talent Team Project of Guizhou Province, grant number [2018]5251; Talent Base of Fermentation Engineering and Liquor Making in Guizhou Province, grant number [2018]3; Zunyi City Innovative Talent Team Program Project, sgrant number [2020]9; Excellent Young Scientific and Technological Talent Program, grant number [2019]5645.
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Li, P., Yang, Z. & Wang, X. Design, Synthesis, and Insecticidal Activity of Novel Diacylhydrazine Derivatives Containing an Isoxazole Carboxamide or a Pyridine Carboxamide Moiety. Russ J Gen Chem 92, 132–140 (2022). https://doi.org/10.1134/S1070363222010182
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DOI: https://doi.org/10.1134/S1070363222010182