Design, Synthesis, Characterization, and Insecticidal BioefficacyScreening of Some New Pyridine DerivativesAdel M. Kamal El-Dean,† Aly A. Abd-Ella,‡ Reda Hassanien,§ Mohamed E. A. El-Sayed,∥

and Shaban A. A. Abdel-Raheem*,∥

†Chemistry Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt‡Plant Protection Department, Faculty of Agriculture, Assiut University, 71526 Assiut, Egypt§Chemistry Department, Faculty of Science, New Valley University, 72511 El-Kharja, Egypt∥Soil, Water, and Environment Research Institute, Agriculture Research Center, 12112 Giza, Egypt

*S Supporting Information

ABSTRACT: A lot of insecticides are found nowadays, but neonicotinoids areconsidered the most famous. So, a series of pyridine derivatives neonicotinoidsanalogues, namely, 3-cyano-4,6-dimethylpyridine-2(1H)-one (1), 2-chloro-3-cyano-4,6-dimethylpyridine (2), 3-cyano-4,6-dimethylpyridine-2(1H)-thione (3), 3-cyano-4,6-distyrylpyridine-2(1H)-thione (4), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-phenyl-acetamide (5), 3-amino-N-phenyl-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (6),2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(p-tolyl)acetamide (7), 3-amino-4,6-distyr-yl-N-(p-tolyl)thieno[2,3-b]pyridine-2-carboxamide (8), 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(4-methoxyphenyl)acetamide (9), and 3-amino-N-(4-methoxyphenyl)-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (10), have been designed and synthesized inpure state, and their agricultural bioefficacy as insecticides against cowpea aphid Aphiscraccivora Koch was screened. The structures of the synthesized compounds were verifiedby means of spectroscopic and elemental analyses. Insecticidal bioefficacy data illustratedthat some compounds are excellent against cowpea aphid, and the bioefficacy of the rest of the tested compounds ranged fromgood to moderate against the same insects.

■ INTRODUCTION

Pyridine derivatives exist widely in the nature and havedifferent biological activities such as antimicrobial, anticancer,antioxidant, insecticidal, etc.1−6 As a result, these compoundshave become an attractive target for chemists around theworld. Pyridine moiety constitutes a part of the neonicotinoidsstructure, and nowadays, neonicotinoid insecticides are mostcommonly used in the world for insect control because of theiradvantages in protecting a great variety of crops, as well as highefficacy without cross-resistance to other insecticides, lowmammalian toxicity, a novel mode of action specific fornAChRs, and broad insecticidal spectra.7−14

In contrast, there is a clear evidence for the need of synthesisof some new organic compounds neonicotinoids analoguesalthough the advantages of neonicotinoids. This evidenceshows that some recent studies monitoring the human andanimal exposure to imidacloprid as neonicotinoid insecticidefound that DNA damage, oxidative stress, genotoxic effect, andclastogenic effect can be produced after long-term exposure ofrabbits to that insecticide.15−18

Pyridine derivatives that contain styryl group attached to thepyridine moiety were synthesized, and some of them with asignificant biological activity.19−22 The data in our previouswork encouraged us to continue the search for newheterocycles containing pyridine moiety with agricultural

bioactivity.1−3 In view of these findings, we reported hereinthe synthesis of some new heterocyclic pyridine derivatives andstudied their insecticidal bioefficacy against cowpea Aphid,Aphis craccivora Koch.

■ RESULTS AND DISCUSSION

The synthesis of the target compounds started frommalononitrile, which on reaction with acetylacetone affordedcompound 1 that undergoes chlorination with POCl3 to givecompound 2. Compound 3 was obtained by reaction of chlorocompound 2 with thiourea. Condensation of compound 3 withbenzaldehyde in the presence of few drops of piperidineresulted in the formation of distyryl derivative 4 (Scheme 1).All characterization data of compounds 1−4 were in agreementwith those reported before.23−25

Compound 4 was reacted with α-halogenated carbonylcompounds (chloroacetanilide, p-methylchloroacetanilide, andp-methoxychloroacetanilide) to afford 3-cyano-4,6-distyryl-2-substituted mercaptopyridines 5, 7, and 9. The chemicalstructures of compounds 5, 7, and 9 were confirmed byspectral and elemental analyses. Compounds 5, 7, and 9

Received: April 2, 2019Accepted: May 6, 2019Published: May 13, 2019

Article

http://pubs.acs.org/journal/acsodfCite This: ACS Omega 2019, 4, 8406−8412

© 2019 American Chemical Society 8406 DOI: 10.1021/acsomega.9b00932ACS Omega 2019, 4, 8406−8412

This is an open access article published under an ACS AuthorChoice License, which permitscopying and redistribution of the article or any adaptations for non-commercial purposes.

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underwent the Thorpe−Ziegler cyclization upon heating inethanolic sodium ethoxide solution affording the correspond-ing thieno[2,3-b]pyridines 6, 8, and 10. The mechanism of theThorpe−Ziegler cyclization can be represented by Scheme 2.26

Spectroscopic data and elemental analyses of compounds 6, 8,and 10 are in agreement with their proposed structures.IR spectrum of compound 5 showed absorption bands at

3290, 2209, and 1663 cm−1 characteristics for (NH), (CN),and (CO) groups, respectively. The absorption band of(CN) of compound 5 disappeared when cyclized to givethienopyridine 6 and was replaced by bands at 3413 and 3303cm−1 for NH2.

1H NMR spectrum (DMSO-d6, 400 MHz) ofcompound 5 illustrated singlet signals at 10.38 and 4.28 for(NH) and (CH2) groups, respectively. The signal of the (CH2)group of compound 5 disappeared when cyclized to givecompound 6. DEPT 135 (DMSO-d6, 100 MHz) spectrum ofcompound 5 showed a characteristic signal at 35.68 for the(CH2) group, which disappeared when cyclized to givecompound 6.IR spectrum of compound 7 showed absorption bands at

3279, 2207, and 1664 cm−1 characteristics for (NH), (CN),and (CO) groups, respectively. The absorption band of

Scheme 1

Scheme 2

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(CN) of compound 7 disappeared when cyclized to give thethienopyridine compound 8 and was replaced by 3416 and3301 cm−1 for NH2.

1H NMR spectrum (DMSO-d6, 400MHz) of compound 7 illustrated singlet signals at 10.32, 4.25,and 2.24 for (NH), (CH2), and (CH3) groups, respectively.The signal of the (CH2) group of compound 7 disappearedwhen cyclized to give compound 8. DEPT 135 (DMSO-d6,100 MHz) spectrum of compound 7 showed characteristicsignal at 35.64 for the (CH2) group, which disappeared whencyclized to give compound 8.IR spectrum of compound 9 showed absorption bands at

3281, 2215, and 1658 cm−1 characteristics for (NH), (CN),and (CO) groups, respectively. The absorption band of(CN) of compound 9 disappeared when cyclized to givethienopyridine 10 and was replaced by 3480 and 3299 cm−1

for NH2.1H NMR spectrum (DMSO-d6, 400 MHz) of

compound 9 showed singlet signals at 10.12, 4.24, and 3.73 for(NH), (CH2), and (CH3 anilide) groups, respectively. Thesignal of (CH2) group of compound 9 disappeared whencyclized to give compound 10. DEPT 135 (DMSO-d6, 100MHz) spectrum of compound 9 showed a characteristic signalat 35.37 for the (CH2) group, which disappeared whencyclized to give compound 10.

■ CONCLUSIONS

A new series of pyridine derivatives neonicotinoid analogueshave been synthesized in our lab, and their structures wereproved by elemental and spectroscopic analyses. Thebioefficacy of all compounds as potential insecticides againstcowpea Aphid, A. craccivora Koch, was evaluated. The presenceof different functional groups in the structure of thecompounds gave a variety of insecticidal activities as potentialinsecticides. This study illustrated that the synthesized pyridinederivatives have valuable agricultural bioactivities.

■ EXPERIMENTAL SECTION

A Fisher-Johns apparatus was used to record the melting pointsof all synthesized compounds. Infrared spectra and elementalanalyses (C, H, N, and S) were accomplished via a Pye-Unicam SP3-100 spectrophotometer using the KBr disktechnique and a Vario EL C, H, N, S analyzer, respectively.A Bruker 400 MHz spectrometer was used to measure DEPT135 spectra and the 1H and 13C NMR spectra in the presenceof tetramethylsilane as an internal standard. Chemical shiftswere measured in ppm. Reaction progress and purity of thesynthesized compounds were monitored by thin-layerchromatography.Compounds 1−4 were prepared according to the reported

methods.23−25 The reference insecticide, acetamiprid neon-icotinoid insecticide, was obtained from Sigma-Aldrich(France). Cowpea aphid batches were compiled from fababean, Vicia faba L., fields of the experimental farm of AssiutUniversity. The insecticidal activity of the reference neon-icotinoid insecticide (acetamiprid) plus the synthesizedcompounds was checked against adults and nymphs of thegathered aphids.Synthetic Procedure for 3-Cyano-4,6-dimethylpyri-

dine-2(1H)-thione (3). In addition to the procedure found inref 25, compound 3 was synthesized here by reaction ofcompound 2 with thiourea as follows: a mixture ofchloropyridine derivative 2 (7 g, 0.04 mol) and thiourea (9g, 0.12 mol) in ethanol was refluxed for 4 h. The solid

precipitate that formed on hot was filtrated off andrecrystallized from dioxane to give pale green crystals of 3.Yield: 92%; melting point (mp): 277−279 °C. IR (ν) (KBr)cm−1: 3180 (NH), 2913, 2880 (C−H aliphatic), 2218 (CN); 1H NMR (DMSO-d6): δ 2.35 (s. 3H, CH3), 3.4 (s, 3H,CH3), 6.7 (s, 1H, Ar−H), 13.8 (br. s, 1H, NH). Elementalanalysis calculated for C8H8N2S (%): C, 58.51; H, 4.91; N,17.06; S, 19.52. Found (%): C, 58.45; H, 4.8; N, 17.00; S,19.45.

Synthetic Procedure for 3-Cyano-4,6-distyrylpyri-dine-2(1H)-thione (4). Fusion of the dimethyl mercaptopyr-idine compound 3 (1 g, 0.006 mol) with benzaldehyde (2 mL,0.019 mol) for 5 min in the presence of few drops ofpiperidine, then adding ethanol (25 mL) followed by reflux for2 h gave a solid precipitate. The precipitate was filtrated off andrecrystallized from ethanol−dioxane mixture (1:2) as pale redcrystals of compound 4. Yield: 90%; melting point (mp): 178−180 °C. IR (ν) (KBr) cm−1: 3166 (NH), 2972, 2921, 2854(C−H aliphatic), 2217 (CN), 1611 (CN). 1H NMR(DMSO-d6, 400 MHz): δ 13.72 (br. s, 1H, NH), 7.19−7.99(m, 15H, 2CHCH and Ar−H). 13C NMR (DMSO-d6, 100MHz): δ 178.91, 152.62, 151.39, 141.19, 135.57, 130.77,130.54, 129.65, 128.30, 128.03, 122.25, 116.49, 111.52, 105.73.DEPT 135 (DMSO-d6, 100 MHz): δ 135.57 (CH), 130.77(CH), 130.54 (CH), 129.65 (CH), 128.30 (CH), 128.03(CH), 122.25 (CH), 111.52 (CH). Elemental analysiscalculated for C22H16N2S (%): C, 77.62; H, 4.74; N, 8.23; S,9.42. Found (%): C, 77.64; H, 4.77; N, 8.25; S, 9.40.

Synthetic Procedure for 3-Cyano-4,6-distyryl-2-sub-stituted Mercaptopyridines (5, 7, and 9) via Reaction of4 with N-Substituted Chloroacetamides. General Proce-dure. A mixture of distyryl compound 4 (2 g, 0.006 mol), therespective halocompound (chloroacetanilide, p-methylchlor-oacetanilide, p-methoxychloroacetanilide) (0.006 mol), andfused sodium acetate (0.6 g, 0.007 mol) in ethanol (25 mL)was heated under reflux for 30 min. The formed precipitatewas collected and recrystallized from ethanol−dioxane mixture(1:2) to afford compounds 5, 7, and 9.

2-((3-Cyano-4,6-distyrylpyridin-2-yl)thio)-N-phenylaceta-mide (5). Pale orange crystals in 83% yield, mp 222−224 °C.IR (ν) (KBr) cm−1: 3290 (NH), 3058 (C−H aromatic), 2920,2851 (C−H aliphatic), 2209 (CN), 1663 (CO), 1633(CN). 1H NMR (DMSO-d6, 400 MHz): δ 10.38 (s, 1H,NH), 7.03−7.88 (m, 20H, 2CHCH and Ar−H), 4.28 (s,2H, CH2).

13C NMR (DMSO-d6, 100 MHz): δ 166.32,162.33, 157.39, 149.62, 139.58, 138.70, 136.88, 136.16, 135.73,130.33, 129.60, 129.24, 128.10, 127.86, 126.94, 123.81, 122.10,119.61, 115.61, 114.71, 101.85, 35.68. DEPT 135 (DMSO-d6,100 MHz): δ 138.70 (CH), 136.88 (CH), 130.33 (CH),129.59 (CH), 129.23 (CH), 128.10 (CH), 127.86 (CH),126.94 (CH), 123.81 (CH), 122.10 (CH), 119.61 (CH),114.71 (CH), 35.68 (CH2). Elemental analysis calculated forC30H23N3OS (%): C, 76.08; H, 4.90; N, 8.87; S, 6.77. Found(%): C, 76.11; H, 4.93; N, 8.84; S, 6.81.

2-((3-Cyano-4,6-distyrylpyridin-2-yl)thio)-N-(p-tolyl)-acetamide (7). Pale yellow crystals in 86% yield, mp 207−208°C. IR (ν) (KBr) cm−1: 3279 (NH), 3035 (C−H aromatic),2917 (C−H aliphatic), 2207 (CN), 1664 (CO), 1633(CN). 1H NMR (DMSO-d6, 400 MHz): δ 10.32 (s, 1H,NH), 7.08−7.87 (m, 19H, 2CHCH and Ar−H), 4.25 (s,2H, CH2), 2.24 (s, 3H, CH3).

13C NMR (DMSO-d6, 100MHz): δ 166.09, 162.35, 157.36, 149.57, 138.66, 137.11,136.85, 136.15, 135.70, 132.77, 130.33, 129.60, 129.21, 128.10,

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127.88, 126.91, 122.05, 119.58, 115.62, 114.67, 101.82, 35.64,20.85. DEPT 135 (DMSO-d6, 100 MHz): δ 138.66 (CH),136.85 (CH), 130.33 (CH), 129.61 (CH), 129.58 (CH),129.21 (CH), 128.10 (CH), 127.88 (CH), 126.91 (CH),122.05 (CH), 119.57 (CH), 114.67 (CH), 35.64 (CH2), 20.85(CH3). Elemental analysis calculated for C31H25N3OS (%): C,76.36; H, 5.17; N, 8.62; S, 6.57. Found (%): C, 76.39; H, 5.15;N, 8.67; S, 6.59.2-( (3-Cyano-4,6-distyry lpyr idin-2-y l ) thio)-N-(4-

methoxyphenyl)acetamide (9). Yellowish crystals in 87%yield, mp 191−193 °C. IR (ν) (KBr) cm−1: 3281 (NH), 2922,2851 (C−H aliphatic), 2215 (CN), 1658 (CO), 1612(CN). 1H NMR (DMSO-d6, 400 MHz): δ 10.12 (s, 1H,NH), 6.88−7.79 (m, 19H, 2CHCH and Ar−H), 4.24 (s,2H, CH2), 3.73 (s, 3H, OCH3).

13C NMR (DMSO-d6, 100MHz): δ 165.89, 161.84, 157.35, 155.84, 149.57, 136.16,135.70, 132.79, 130.77, 129.54, 129.24, 128.04, 127.89, 126.92,122.20, 115.44, 114.65, 114.41, 101.82, 55.66, 35.37. DEPT135 (DMSO-d6, 100 MHz): δ 135.70 (CH), 132.79 (CH),129.54 (CH), 129.24 (CH), 128.04 (CH), 127.88 (CH),126.91 (CH), 122.20 (CH), 114.65 (CH), 114.40 (CH),55.66 (OCH3), 35.37 (CH2). Elemental analysis calculated forC31H25N3O2S (%): C, 73.93; H, 5.00; N, 8.34; S, 6.37. Found(%): C, 73.97; H, 5.05; N, 8.32; S, 6.40.Synthetic Procedure for 3-Amino-4,6-distyryl-2-sub-

stituted Thieno[2, 3-b]pyridines (6, 8 and 10). GeneralProcedure. Compounds 5, 7, and 9 (0.005 mol) weresuspended in sodium ethoxide solution (0.5 g of sodium in31 mL of absolute ethanol) and heated for 5 min under reflux.The formed product after cooling was collected and recrystal-lized from ethanol−dioxane mixture (1:2) to afford com-pounds 6, 8, and 10.3-Amino-N-phenyl-4,6-distyrylthieno[2,3-b]pyridine-2-

carboxamide (6). Yellow crystals in 83% yield, mp 263−264°C. IR (ν) (KBr) cm−1: 3413, 3303 (NH, NH2), 3023 (C−Haromatic), 2891 (C−H aliphatic), 1647 (CO), 1633 (CN). 1H NMR (DMSO-d6, 400 MHz): δ 9.53 (s, 1H, NH),6.95−8.06 (m, 22H, 2CHCH, NH2 and Ar−H). 13C NMR(DMSO-d6, 100 MHz): δ 164.51, 160.65, 155.96, 149.18,144.38, 139.21, 136.75, 136.48, 134.42, 129.37, 129.26, 128.89,128.12, 127.75, 124.17, 123.74, 122.31, 122.00, 117.64, 116.71,100.17. DEPT 135 (DMSO-d6, 100 MHz): δ 136.75 (CH),134.42 (CH), 129.37 (CH), 129.26 (CH), 128.89 (CH),128.12 (CH), 127.75 (CH), 124.17 (CH), 123.73 (CH),122.31 (CH), 117.64 (CH), 116.69 (CH). Elemental analysis

calculated for C30H23N3OS (%): C, 76.08; H, 4.90; N, 8.87; S,6.77. Found (%): C, 76.13; H, 4.92; N, 8.82; S, 6.79.

3-Amino-4,6-distyryl-N-(p-tolyl)thieno[2,3-b]pyridine-2-carboxamide (8). Orange crystals in 84% yield, mp 251−253°C. IR (ν) (KBr) cm−1: 3416, 3301 (NH, NH2), 2918 (C−Haliphatic), 1645 (CO). 1H NMR (DMSO-d6, 400 MHz): δ9.45 (s, 1H, NH), 6.93−8.05 (m, 19H, 2CHCH and Ar−H), 2.62 (s, 2H, NH2), 2.29 (s, 3H, CH3).

13C NMR (DMSO-d6, 100 MHz): δ 164.38, 160.02, 155.86, 148.99, 144.31,136.70, 136.40, 134.34, 133.18, 133.08, 129.28, 128.09, 127.73,123.76, 123.67, 122.37, 122.05, 121.96, 121.44, 117.60, 20.95.DEPT 135 (DMSO-d6, 100 MHz): δ 134.34 (CH), 133.18(CH), 129.28 (CH), 123.76 (CH), 123.66 (CH), 122.37(CH), 122.05 (CH), 121.95 (CH), 121.44 (CH), 117.60(CH), 20.95 (CH3). Elemental analysis calculated forC31H25N3OS (%): C, 76.36; H, 5.17; N, 8.62; S, 6.58.Found (%): C, 76.38; H, 5.21; N, 8.65; S, 6.52.

3-Amino-N-(4-methoxyphenyl)-4,6-distyrylthieno[2,3-b]-pyridine-2-carboxamide (10). Pale orange crystals in 82%yield, mp 222−223 °C. IR (ν) (KBr) cm−1: 3480, 3299 (NH,NH2), 3024 (C−H aromatic), 2916, 2848 (C−H aliphatic),1624 (CO). 1H NMR (DMSO-d6, 400 MHz): δ 9.43 (s,1H, NH), 6.92−8.06 (m, 21H, 2CHCH, NH2 and Ar−H),3.77 (s, 3H, OCH3).

13C NMR (DMSO-d6, 100 MHz): δ164.29, 160.58, 156.26, 155.79, 148.82, 144.26, 136.71, 134.30,132.08, 129.35, 129.24, 128.80, 128.33, 128.09, 127.95, 127.73,123.82, 122.40, 116.65, 114.11, 55.69. DEPT 135 (DMSO-d6,100 MHz): δ 134.30 (CH), 132.08 (CH), 128.80 (CH),128.09 (CH), 127.95 (CH), 127.73 (CH), 123.82 (CH),122.40 (CH), 116.65 (CH), 114.11 (CH), 55.69 (OCH3).Elemental analysis calculated for C31H25N3O2S (%): C, 73.93;H, 5.00; N, 8.34; S, 6.37. Found (%): C, 73.91; H, 5.03; N,8.37; S, 6.33.

Laboratory Bioassay. The insecticidal bioefficacy of allsynthesized pyridine derivatives was evaluated via the leaf dipbioassay method.27 Laboratory screening results are reportedhere for the title compounds to find out the concentrationsthat are required to kill 50% (LC50) of the gathered insects. Inthis work, six concentrations of each synthesized pyridinederivative plus 0.1% Triton X-100 (surfactant) were used. Atotal of 20 adults and 20 nymphs of cowpea aphids, almost ofthe same size, were dipped three times in every concentrationfor 10 s. Tested cowpea aphids were dried at roomtemperature for 0.5 h. Cowpea aphids control batches werealso used. Batches of aphids after drying were transported to

Table 1. Insecticidal Bioefficacy of Acetamiprid and Compounds 1−10 against the Nymphs of Cowpea Aphid, A. craccivora,after 24 and 48 h of Treatmenta

24 h after treatment 48 h after treatment

compd slope ± SE LC50 (ppm) toxic ratio slope ± SE LC50 (ppm) toxicity ratio

acetamiprid 0.34 ± 0.02 0.045 1 0.42 ± 0.03 0.006 11 0.39 ± 0.03 2.341 0.019 0.37 ± 0.03 0.151 0.0402 0.44 ± 0.02 0.175 0.257 0.46 ± 0.03 0.017 0.3533 0.32 ± 0.03 1.382 0.033 0.38± 0.03 0.101 0.0604 0.32 ± 0.03 0.787 0.057 0.30± 0.02 0.091 0.0665 0.36 ± 0.02 0.573 0.079 0.40 ± 0.03 0.054 0.1116 0.37 ± 0.03 1.138 0.040 0.35 ± 0.03 0.068 0.0887 0.34 ± 0.02 0.421 0.107 0.40 ± 0.03 0.039 0.1548 0.35± 0.02 0.551 0.082 0.40 ± 0.03 0.053 0.1139 0.34 ± 0.02 0.284 0.158 0.31 ± 0.03 0.021 0.28610 0.39 ± 0.03 0.334 0.135 0.47 ± 0.03 0.031 0.194

aToxic ratio is defined as the ratio of the LC50 values of acetamiprid for baseline toxicity and the compound.

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Petri dishes (9 cm diameter) and grasped for 24 and 48 h at aphotoperiod of 12:12 light/dark cycle, 22 ± 2 °C, and 60 ± 5%relative humidity. Mortality of the aphids was counted after 24and 48 h of test by means of a binocular microscope. Theaphids that are not capable of coordinating forward movementwere considered dead. Bioefficacy check of the synthesizedcompounds was iterated twice, and the results of this checkwere corrected using Abbott’s formula.28 Slope values andmedian lethal concentrations (LC50) of the title compoundswere calculated through a computerized Probit regressionanalysis program and recorded in (ppm).29

■ INSECTICIDAL BIOEFFICACY SCREENINGThe synthesized compounds have been screened for theirinsecticidal bioefficacy, as described below:Insecticidal Bioefficacy Test for the Nymphs of

Cowpea Aphid. Compounds 1−10 were tested against thenymphs of the collected aphids for their insecticidalbioefficacy, and the results are presented in Table 1. After 24h of treatment, bioefficacy results indicated that all of thesecompounds exhibit high to low insecticidal activity against thecowpea aphid nymphs and the LC50 values ranged from 0.175to 2.341 ppm, whereas the LC50 value of acetamiprid was 0.045ppm. After 48 h of treatment, it is found that the insecticidalbioefficacy of all compounds against cowpea aphid nymphsvaried from strong to weak with LC50 values assorted from0.017 to 0.151 ppm, while the LC50 value of acetamiprid was0.006 ppm, which indicates that a number of them haveinsecticidal bioefficacy close to that of acetamiprid insecticideafter 48 h of test. For example, compounds 2 and 9 haveexcellent insecticidal activities against nymphs of cowpea aphidbecause their LC50 values were 0.017 and 0.021, respectively,and the LC50 value of acetamiprid was 0.006 ppm after 48 h oftreatment.Insecticidal Bioefficacy Test for the Adults of Cowpea

Aphid. Compounds 1−10 were tested also against the adultsof the collected aphids for their insecticidal bioefficacy, and theresults are presented in Table 2. The results indicated that after24 h of insecticidal bioefficacy test, the compounds own strongto weak bioefficacy and LC50 values assorted from 0.887 to9.431 ppm, while 0.225 ppm was the LC50 value ofacetamiprid. Compounds 2, 4, 5, 6, 7, 8, 9, and 10 possess ahigh insecticidal bioefficacy, and their LC50 values are 1.660,0.887, 2.612, 1.482, 1.265, 2.262, 2.623, and 2.101 ppm,respectively. The insecticidal activities of the tested com-

pounds strongly increased against cowpea aphid adults after 48h of bioefficacy test, and the values of LC50 assorted from 0.103to 1.172 ppm. Thus, compound 2 showed a high insecticidalbioefficacy close to that of acetamiprid because the value ofLC50 of compound 2 is 0.103 ppm, while the LC50 value ofacetamiprid is 0.023 ppm. Compounds 1 and 3 showed areasonable insecticidal bioefficacy with LC50 values of 1.172and 0.472 ppm, respectively.

■ STRUCTURE−ACTION RELATIONSHIP

It appears from the general framework structure of thesynthesized pyridine moiety-containing compounds that thecompounds 2-chloro-3-cyano-4,6-dimethylpyridine 2 and 2-( ( 3 - c y a n o - 4 , 6 - d i s t y r y l p y r i d i n - 2 - y l ) t h i o ) -N - ( 4 -methoxyphenyl)acetamide 9 are more active against cowpeaaphid than the rest of tested compounds. It also appears thatcompounds that contain a distyrylpyridine part in the structureown a high insecticidal bioefficacy than compounds 1 and 3that contain a dimethylpyridine part in the structure. So,compounds 4, 5, 6, 7, 8, 9, and 10 have insecticidal activitymore than that of compounds 1 and 3. Compounds 5, 7, and 9are more active than compounds 6, 8, and 10, which may bedue to the presence of cyano group in the former and itsabsence in the latter. Compound 9 has more activity thancompounds 5 and 7, which may be due to the presence of 4-methoxyphenyl moiety in its structure and the absence of thismoiety in compounds 5 and 7. Also, compound 10 is moreactive against cowpea aphid than compounds 6 and 8, whichmay be due to the presence of 4-methoxyphenyl moiety in itsstructure. Although compounds 1 and 3 that contain adimethylpyridine part have a reasonable insecticidal bioeffi-cacy, compound 2 which contain this part in its structure isconsidered more active than all synthesized compounds, whichmay be due to the presence of chlorine atom attached to thepyridine ring. Finally, the insecticidal bioefficacy of compound3-cyano-4,6-dimethylpyridine-2(1H)-thione 3 is more thanthat of compound 3-cyano-4,6-dimethylpyridine-2(1H)-one 1,which may be due to the presence of thiol group in itsstructure.

Table 2. Insecticidal Bioefficacy of Acetamiprid and Compounds 1−10 against the Adults of Cowpea Aphid, A. craccivora, after24 and 48 h of Treatmenta

24 h after treatment 48 h after treatment

compd slope ± SE LC50 (ppm) toxic ratio slope ± SE LC50 (ppm) toxicity ratio

acetamiprid 0.24 ± 0.02 0.225 1 0.32 ± 0.03 0.023 11 0.42 ± 0.03 9.431 0.024 0.30 ± 0.02 1.172 0.0192 0.37 ± 0.02 1.660 0.136 0.35 ± 0.03 0.103 0.2233 0.34 ± 0.02 6.541 0.034 0.39 ± 0.03 0.472 0.0494 0.32 ± 0.02 0.887 0.253 0.33 ± 0.03 0.276 0.0835 0.35 ± 0.03 2.612 0.086 0.40 ± 0.03 0.201 0.1146 0.44 ± 0.03 1.482 0.152 0.39 ± 0.03 0.153 0.1507 0.42 ± 0.03 1.265 0.178 0.38 ± 0.03 0.137 0.1688 0.36 ± 0.02 2.262 0.099 0.38 ± 0.02 0.151 0.1529 0.37 ± 0.03 2.623 0.086 0.35 ± 0.03 0.213 0.10810 0.36 ± 0.02 2.101 0.107 0.40 ± 0.03 0.151 0.152

aToxic ratio is defined as the ratio of the LC50 values of acetamiprid for baseline toxicity and the compound.

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■ ASSOCIATED CONTENT*S Supporting InformationThe Supporting Information is available free of charge on theACS Publications website at DOI: 10.1021/acsome-ga.9b00932.

IR spectra, 1H NMR spectra, 13C NMR spectra, andDEPT 135 spectra of compounds 4−10 (PDF)

(PDF)

■ AUTHOR INFORMATIONCorresponding Author*E-mail: mrshaban2000@gmail.com.NotesThe authors declare no competing financial interest.

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