Design, Synthesis and Biological Activity of 5-Pyrazole Carboxamides †

doi:10.7503/cjcu20190504

Abstract

Abstract:

Twenty-three novel 5-pyrazole carboxamides were prepared by condensing two kinds of 5-pyrazolecarboxylic acids with thiazolamides and benzofuranamines. The chemical structures were confirmed by nuclear magnetic resonance(NMR) and mass spectrometry, etc. Quantum chemical calculations, frontier molecular orbitals and molecular van der Waals surface electrostatic potentials were analyzed for compounds B1 and B3. Biological activity screening test results showed that some compounds had excellent Insecticidal activity against Armyworm and Aphis fabae at 500 mg/L concentration, and the lethal rate of compound A1 and B1 against Armyworm was 100%, while compound B3, B4 and C9 showed excellent inhibitory activity towards Aphis fabae with the inhibition rate of 100%, 100% and 95.54%, correspondingly. At a concentration of 25 mg/L, the growth inhibition rates of compound A3 against Alternaria alternata, compound C7 against Gibberella zeae, compounds A1 and A4 against Sclerotonia sclerotiorum were over 50%.

Key words: 5-Pyrazolecarboxamide, Bactericidal activity, Insecticidal activity, Quantum chemical calculation

CLC Number:

O626
O641

TrendMD:

LI Kangming, LI Yansai, YI Yangjie, XU Leitao, YE Jiao, OU Xiaoming, LI Jianming, HU Aixi. Design, Synthesis and Biological Activity of 5-Pyrazole Carboxamides ^†[J]. Chem. J. Chinese Universities, 2020, 41(4): 716.

Figures/Tables 10

Scheme 1 Design strategy and general synthetic routes of the novel 5-pyrazole carboxamide derivatives

Compd.	Reaction time/h	Feature	m. p./℃	Yield(%)	HRMS(calcd.), m/z^*
A1	4.0	Grey solid	148—149	68.8	364.1012(364.1310)
A2	1.0	White solid	149—150	66.0	378.1209(378.1507)
A3	1.0	White solid	157—158	59.5	392.1405(392.1707)
A4	0.5	Yellow solid	138—139	61.4	440.0810(440.1714)
A5	0.5	White solid	173—174	32.7	522.1002(522.0701)
A6	8.0	Yellow solid	250—252	48.2	491.0907(491.0421)

Compd.	Reaction time/h	Feature	m. p./℃	Yield(%)	HRMS(calcd.), m/z^*
B1	4	White solid	177—179	28.1	447.0534(447.1229)
B2	10	White solid	185—187	30.9	461.0247(461.1349)
B3	10	White solid	135—138	31.6	560.0925(560.0139)
B4	10	White solid	218—220	52.4	574.0826(574.0229)

Compd.	Reaction time/h	Feature	m. p./℃	Yield(%)	HRMS(calcd.), m/z^*
C1	8	White solid	126—128	43.6	327.1037(327.0640)
C2	16	White solid	151—152	69.4	356.0103(356.0902)
C3	4	White solid	126—128	62.0	357.0416(357.0717)
C4	4	Grey solid	164—166	44.2	394.0312(394.1113)
C5	4	Grey solid	177—179	33.5	432.0509(432.9812)
C6	5	White solid	92—94	58.6	357.0615(357.0718)
C7	4	Yellow solid	166—168	35.6	447.0609(447.1213)
C8	10	White solid	174—176	42.6	461.0913(461.1319)
C9	4	White solid	220—222	57.3	470.0309(469.9612)
C10	6	White solid	222—224	52.1	507.0629(507.0031)
C11	4	White solid	147—150	40.7	470.0425(469.9617)
C12	10	White solid	158—160	50.2	560.0523(560.0121)
C13	10	White solid	131—133	63.4	574.0009(574.0213)

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
A1	8.28(s, 1H, NH), 7.05(s, 1H, benzofuran-H), 7.00(s, 1H, benzofuran-H), 4.16(s, 3H, NCH₃), 3.89(s, 3H, OCH₃), 3.04(s, 2H, CH₂), 2.67(q, J=7.6 Hz, 2H, CH₂), 1.51(s, 6H, 2CH₃), 1.26(t, J=7.6 Hz, 3H, CH₃)	156.42, 149.64, 144.90, 144.30, 131.29, 129.89, 128.13, 110.45, 107.36, 104.92, 87.94, 56.02, 43.41, 40.78, 28.19, 19.29, 12.82
A2	8.25(s, 1H, NH), 7.02(s, 2H, benzofuran-H), 4.14(d, J=6.8 Hz, 2H, CH₂), 4.16(s, 3H, CH₃), 3.03(s, 2H, CH₂), 2.67(q, J=7.5 Hz, 2H, CH₂), 1.51(s, 6H, 2CH₃), 1.44(t, J=7.0 Hz, 3H, CH₃), 1.27(t, J=7.5 Hz, 3H, CH₃)	156.38, 149.62, 145.28, 143.50, 131.33, 129.78, 128.42, 110.45, 107.33, 106.51, 87.74, 64.66, 43.47, 40.77, 28.18, 19.30, 14.85, 12.83
A3	8.25(s, 1H, NH), 7.01(s, 2H, benzofuran-H), 4.17(s, 3H, NCH₃), 4.03(t, J=6.9 Hz, 2H, OCH₂), 3.02(s, 2H, CH₂), 2.67(q, J=7.6 Hz, 2H, CH₂), 1.90—1.80(m, 2H, CH₂), 1.51(s, 6H, 2 CH₃), 1.27(t, J=7.6 Hz, 3H, CH₃), 1.02(t, J=7.4 Hz, 3H, CH₃)
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
A4	8.19(s, 1H, NH), 7.45(d, J=7.5 Hz, 2H, Ph-H), 7.38—7.27(m, 3H, Ph-H), 7.08(s, 1H, benzofuran-H), 6.99(s, 1H, benzofuran-H), 5.19(s, 2H, OCH₂), 4.15(s, 3H, NCH₃), 3.03(s, 2H, CH₂), 2.66(q, J=7.6 Hz, 2H, CH₂), 1.52(s, 6H, 2CH₃), 1.26(t, J=7.6 Hz, 3H, CH₃)	156.45, 149.72, 145.69, 143.24, 137.13, 131.42, 129.88, 128.92, 128.59, 128.01, 127.73, 111.25, 107.99, 107.45, 87.99, 71.43, 43.49, 40.84, 28.29, 19.40, 12.95
A5	8.32(s, 1H, NH), 8.07(d, J=8.4 Hz, 1H, C₆H₃), 7.54(s, 1H, benzofuran-H), 7.37(d, J=8.4 Hz, 2H, C₆H₃), 7.26(s, 1H, benzofuran-H), 4.16(s, 3H, NCH₃), 3.09(s, 2H, CH₂), 2.67(q, J=7.5 Hz, 2H, CH₂), 1.49(s, 6H, 2CH₃), 1.26(t, J=7.5 Hz, 3H, CH₃)	162.03, 156.55, 149.80, 147.93, 136.04, 133.67, 133.47, 131.39, 130.52, 129.67, 127.24, 116.42, 114.81, 107.62, 89.30, 43.36, 40.97, 28.18, 19.42, 12.96
A6	8.47—7.39(m, 3H, pyridine-H), 6.91(s, 1H, benzofuran-H), 6.83(s, 1H, pyrazole-H), 6.78(s, 1H, benzofuran-H), 4.01(q, J=7.0 Hz, 2H, CH₂), 2.94(s, 2H, CH₂), 1.47(s, 6H, 2CH₃), 1.37(t, J=7.0 Hz, 3H, CH₃)	155.50, 148.85, 146.66, 145.22, 143.34, 139.99, 139.52, 129.40, 129.20, 128.27, 127.98, 125.80, 110.66, 110.14, 106.42, 87.80, 64.49, 43.38, 28.15, 14.79
B1	10.11(s, 1H, NH), 7.27—7.03(m, 3H, benzofuran-H+thiazole-H), 4.21(s, 3H, NCH₃), 3.95(s, 3H, OCH₃), 3.07(s, 2H, CH₂), 2.68(q, J=7.6 Hz, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.27(t, J=7.5 Hz, 3H, CH₃)	156.08, 155.58, 150.89, 150.07, 147.58, 144.54, 129.15, 128.41, 127.39, 115.47, 109.30, 108.94, 106.20, 88.18, 55.95, 43.26, 41.14, 28.25, 19.22, 12.71
B2	10.38(s, 1H, NH), 7.30(s, 1H, benzofuran-H), 7.28(s, 1H, benzofuran-H), 7.02(s, 1H, thiazole-H), 4.22(t, 2H, J=7.2 Hz, CH₂), 4.21(s, 3H, CH₃), 3.06(s, 2H, CH₂), 2.69(q, J=7.6 Hz, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.47(t, J=7.0 Hz, 3H, CH₃), 1.28(t, J=7.6 Hz, 3H, CH₃)	156.10, 155.62, 154.05, 150.97, 150.12, 148.07, 143.79, 129.23, 128.74, 127.29, 115.55, 111.16, 106.14, 88.02, 64.59, 43.36, 41.17, 28.28, 19.21, 14.95, 12.69
B3	8.54—7.44(m, 3H, pyridine-H), 6.98(s, 1H, pyrazole-H), 7.19—6.86(m, 3H, benzofuran-H+thiazole-H), 3.90(s, 3H, CH₃), 3.06(s, 2H, CH₂), 1.52(s, 6H, 2CH₃)	157.53, 154.97, 150.65, 148.37, 147.80, 146.87, 144.58, 139.56, 137.26, 128.86, 128.51, 128.05, 126.92, 125.89, 115.56, 111.40, 109.32, 106.60, 88.27, 55.83, 43.17, 28.23
B4	10.83(s, 1H, NH), 8.55—7.43(m, 3H, pyridine-H), 6.97(s, 1H, pyrazole-H), 7.18—6.76(m, 3H, benzofuran-H+ thiazole-H), 4.14(q, J=7.0 Hz, 2H, CH₂), 3.04(s, 2H, CH₂), 1.50(s, 6H, 2CH₃), 1.43(t, J=7.0 Hz, 3H, CH₃)	157.61, 155.02, 150.71, 148.41, 148.16, 146.90, 143.80, 139.54, 137.24, 128.87, 128.77, 128.02, 126.87, 125.88, 115.55, 111.38, 111.06, 106.54, 88.08, 64.45, 43.22, 28.22, 14.92
C1	10.00(s, 1H, NH), 4.22(s, 3H, NCH₃), 2.69(t, 2H, J=7.6 Hz, CH₂), 2.67(s, 3H, CH₃), 2.54(s, 3H, COCH₃), 1.27(t, J=7.6 Hz, 3H, CH₃)	190.46, 157.35, 155.72, 155.51, 150.25, 128.64, 126.17, 109.39, 41.26, 30.43, 19.17, 18.09, 12.65
C2	4.21(s, 3H, NCH₃), 3.96—3.97[2s, (2.25+0.75)H, OCH₃], 2.69(t, 2H, J=7.6 Hz, CH₂), 2.46—2.51[2s, (0.75+2.25)H, CH₃], 2.25, 2.31[2s, (2.25+0.75) H, CH₃], 1.27(t, J=7.6 Hz, 3H, CH₃)
C3	10.06(s, 1H, NH), 4.32(q, J=6.9 Hz, 2H, OCH₂), 4.20(s, 3H, NCH₃), 2.69—2.65(m, 5H, CH₃+CH₂), 1.36(t, J=7.0 Hz, 3H, CH₃), 1.26(t, J=7.4 Hz, 3H, CH₃)	162.52, 157.92, 156.72, 155.70, 150.22, 128.72, 116.74, 109.31, 60.96, 41.25, 19.18, 17.10, 14.34, 12.67
C4	9.88(s, 1H, NH), 8.27(s, 1H, 1,2,4-triazole-H), 8.11(s, 1H, 1,2,4-triazole-H), 4.18(s, 3H, NCH₃), 2.69(q, J=7.5 Hz, 2H, CH₂), 1.27(t, J=7.6 Hz, 3H, CH₃), 1.16(s, 9H, 3CH₃)	156.73, 155.70, 152.53, 152.48, 150.22, 147.36, 128.68, 119.78, 109.18, 41.19, 35.95, 29.58, 19.20, 12.70
C5	10.16(s, 1H, NH), 7.82(d, 1H, C₆H₂), 7.50(d, 1H, C₆H₂), 7.26(s, 1H, thiazole-H), 4.20(s, 3H, NCH₃), 2.68(q, J=7.6 Hz, 2H, CH₂), 1.27(t, J=7.6 Hz, 3H, CH₃)	158.02, 155.64(d), 155.55, 150.17, 144.75, 132.77(d), 131.91, 128.90, 126.87(d), 120.87(d), 12.67, 19.21, 41.15, 109.14, 114.53, 118.55(d)
C6	9.98(s, 1H, NH), 6.89(s, 1H, thiazole-H), 4.20(s, 5H, COCH₂+NCH₃), 3.73—3.70(m, 2H, CH₂), 2.71—2.61(m, 2H, CH₂), 1.32—1.22(m, 6H, CH₃+CH₃)	170.17, 156.39, 155.51, 150.10, 144.01, 129.08, 111.54, 109.03, 61.13, 41.12, 37.01, 19.1, 14.18, 12.68
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
C7	10.06(s, 1H, NH), 7.89(d, J=8.5 Hz, 1H, benzofuran-H), 7.57(s, 1H, thiazole-H), 6.48(d, J=8.5 Hz, 1H, benzofuran-H), 4.22(s, 3H, NCH₃), 3.86(s, 3H, OCH₃), 3.00(s, 2H, CH₂), 2.68(q, J=7.3 Hz, 2H, CH₂), 1.55(s, 6H, 2CH₃), 1.27(t, J=7.4 Hz, 3H, CH₃)	157.30, 156.15, 155.52, 155.15, 150.04, 146.24, 129.31, 127.67, 114.18, 111.09, 109.72, 108.87, 102.80, 88.27, 55.41, 41.14, 40.08, 28.67, 19.23, 12.73
C8	10.02(s, 1H, NH), 7.88(d, J=8.6 Hz, 1H, benzofuran-H), 7.57(s, 1H, thiazole-H), 6.47(d, J=8.7 Hz, 1H, benzofuran-H), 4.22(s, 3H, CH₃), 4.09(q, J=7.0 Hz, 2H, CH₂), 3.01(s, 2H, CH₃), 2.69(q, J=7.6 Hz, 2H, CH₂), 1.55(s, 6H, 2CH₃), 1.41(t, J=7.0 Hz, 3H, CH₃), 1.28(t, J=7.6 Hz, 3H, CH₃)	157.33, 155.59, 155.56, 155.20, 150.04, 146.31, 129.38, 127.57, 114.4, 110.86, 109.61, 108.88, 103.77, 88.19, 63.59, 41.10, 40.19, 28.69, 19.23, 14.96, 12.72
C9	8.58—7.48(m, 3H, pyridine-H), 6.95(s, 1H, pyrazole-H), 4.27(q, J=7.0 Hz, 2H, CH₂), 2.61(s, 3H, CH₃), 1.31(t, J=7.1 Hz, 3H, CH₃)	162.25, 158.79, 155.90, 155.24, 148.22, 147.00, 140.00, 137.25, 128.98, 128.35, 126.08, 116.73, 111.84, 61.02, 16.92, 14.27
C10	8.47(s, 1H, 1,2,4-triazole-H), 8.09(s, 1H, 1,2,4-triazole-H), 8.77—7.52(m, 3H, pyridine-H), 6.86(s, 1H, pyrazole-H), 1.10(s, 9H, 3CH₃)
C11	8.54—7.45(m, 3H, pyridine-H), 6.91(s, 1H, pyrazole-H), 6.82(s, 1H, thiazole-H), 4.18(q, J=7.1 Hz, 2H, CH₂), 3.67(s, 2H, CH₂), 1.26(t, J=7.0 Hz, 3H, CH₃)	170.21, 157.07, 154.83, 148.35, 146.99, 143.50, 139.67, 137.67, 128.91, 128.23, 126.02, 111.72, 111.44, 61.25, 36.90, 14.15
C12	7.69(d, J=8.6 Hz, 1H, benzofuran), 8.55—7.43(m, 3H, pyridine-H), 7.40(s, 1H, thiazole-H), 6.92(s, 1H, pyrazole-H), 6.47(d, J=8.7 Hz, 1H, benzofuran-H), 3.84(s, 3H, OCH₃), 2.98(s, 2H, CH₂), 1.54(s, 6H, 2CH₃)	157.71, 157.13, 156.37, 155.90, 148.62, 146.87, 144.74, 139.49, 138.17, 129.00, 128.08, 127.23, 125.84, 114.38, 111.49, 110.02, 109.05, 103.08, 88.55, 55.42, 40.02, 28.64
C13	10.74(s, 1H, NH), 7.65(d, J=8.6 Hz, 1H, benzofuran-H), 8.55—7.43(m, 3H, pyridine-H), 7.39(s, 1H, thiazole-H), 6.85(s, 1H, pyrazole-H), 6.43(d, J=8.7 Hz, 1H, benzofuran-H), 4.07(q, J=7.0 Hz, 2H, CH₂), 2.99(s, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.40(t, J=7.0 Hz, 3H, CH₃)	157.85, 157.10, 156.09, 155.85, 148.65, 146.85, 146.48, 139.49, 138.45, 129.03, 128.12, 127.10, 125.83, 114.62, 111.51, 109.66, 108.69, 104.05, 88.54, 63.63, 40.12, 28.66, 14.93

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
A1	8.28(s, 1H, NH), 7.05(s, 1H, benzofuran-H), 7.00(s, 1H, benzofuran-H), 4.16(s, 3H, NCH₃), 3.89(s, 3H, OCH₃), 3.04(s, 2H, CH₂), 2.67(q, J=7.6 Hz, 2H, CH₂), 1.51(s, 6H, 2CH₃), 1.26(t, J=7.6 Hz, 3H, CH₃)	156.42, 149.64, 144.90, 144.30, 131.29, 129.89, 128.13, 110.45, 107.36, 104.92, 87.94, 56.02, 43.41, 40.78, 28.19, 19.29, 12.82
A2	8.25(s, 1H, NH), 7.02(s, 2H, benzofuran-H), 4.14(d, J=6.8 Hz, 2H, CH₂), 4.16(s, 3H, CH₃), 3.03(s, 2H, CH₂), 2.67(q, J=7.5 Hz, 2H, CH₂), 1.51(s, 6H, 2CH₃), 1.44(t, J=7.0 Hz, 3H, CH₃), 1.27(t, J=7.5 Hz, 3H, CH₃)	156.38, 149.62, 145.28, 143.50, 131.33, 129.78, 128.42, 110.45, 107.33, 106.51, 87.74, 64.66, 43.47, 40.77, 28.18, 19.30, 14.85, 12.83
A3	8.25(s, 1H, NH), 7.01(s, 2H, benzofuran-H), 4.17(s, 3H, NCH₃), 4.03(t, J=6.9 Hz, 2H, OCH₂), 3.02(s, 2H, CH₂), 2.67(q, J=7.6 Hz, 2H, CH₂), 1.90—1.80(m, 2H, CH₂), 1.51(s, 6H, 2 CH₃), 1.27(t, J=7.6 Hz, 3H, CH₃), 1.02(t, J=7.4 Hz, 3H, CH₃)
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
A4	8.19(s, 1H, NH), 7.45(d, J=7.5 Hz, 2H, Ph-H), 7.38—7.27(m, 3H, Ph-H), 7.08(s, 1H, benzofuran-H), 6.99(s, 1H, benzofuran-H), 5.19(s, 2H, OCH₂), 4.15(s, 3H, NCH₃), 3.03(s, 2H, CH₂), 2.66(q, J=7.6 Hz, 2H, CH₂), 1.52(s, 6H, 2CH₃), 1.26(t, J=7.6 Hz, 3H, CH₃)	156.45, 149.72, 145.69, 143.24, 137.13, 131.42, 129.88, 128.92, 128.59, 128.01, 127.73, 111.25, 107.99, 107.45, 87.99, 71.43, 43.49, 40.84, 28.29, 19.40, 12.95
A5	8.32(s, 1H, NH), 8.07(d, J=8.4 Hz, 1H, C₆H₃), 7.54(s, 1H, benzofuran-H), 7.37(d, J=8.4 Hz, 2H, C₆H₃), 7.26(s, 1H, benzofuran-H), 4.16(s, 3H, NCH₃), 3.09(s, 2H, CH₂), 2.67(q, J=7.5 Hz, 2H, CH₂), 1.49(s, 6H, 2CH₃), 1.26(t, J=7.5 Hz, 3H, CH₃)	162.03, 156.55, 149.80, 147.93, 136.04, 133.67, 133.47, 131.39, 130.52, 129.67, 127.24, 116.42, 114.81, 107.62, 89.30, 43.36, 40.97, 28.18, 19.42, 12.96
A6	8.47—7.39(m, 3H, pyridine-H), 6.91(s, 1H, benzofuran-H), 6.83(s, 1H, pyrazole-H), 6.78(s, 1H, benzofuran-H), 4.01(q, J=7.0 Hz, 2H, CH₂), 2.94(s, 2H, CH₂), 1.47(s, 6H, 2CH₃), 1.37(t, J=7.0 Hz, 3H, CH₃)	155.50, 148.85, 146.66, 145.22, 143.34, 139.99, 139.52, 129.40, 129.20, 128.27, 127.98, 125.80, 110.66, 110.14, 106.42, 87.80, 64.49, 43.38, 28.15, 14.79
B1	10.11(s, 1H, NH), 7.27—7.03(m, 3H, benzofuran-H+thiazole-H), 4.21(s, 3H, NCH₃), 3.95(s, 3H, OCH₃), 3.07(s, 2H, CH₂), 2.68(q, J=7.6 Hz, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.27(t, J=7.5 Hz, 3H, CH₃)	156.08, 155.58, 150.89, 150.07, 147.58, 144.54, 129.15, 128.41, 127.39, 115.47, 109.30, 108.94, 106.20, 88.18, 55.95, 43.26, 41.14, 28.25, 19.22, 12.71
B2	10.38(s, 1H, NH), 7.30(s, 1H, benzofuran-H), 7.28(s, 1H, benzofuran-H), 7.02(s, 1H, thiazole-H), 4.22(t, 2H, J=7.2 Hz, CH₂), 4.21(s, 3H, CH₃), 3.06(s, 2H, CH₂), 2.69(q, J=7.6 Hz, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.47(t, J=7.0 Hz, 3H, CH₃), 1.28(t, J=7.6 Hz, 3H, CH₃)	156.10, 155.62, 154.05, 150.97, 150.12, 148.07, 143.79, 129.23, 128.74, 127.29, 115.55, 111.16, 106.14, 88.02, 64.59, 43.36, 41.17, 28.28, 19.21, 14.95, 12.69
B3	8.54—7.44(m, 3H, pyridine-H), 6.98(s, 1H, pyrazole-H), 7.19—6.86(m, 3H, benzofuran-H+thiazole-H), 3.90(s, 3H, CH₃), 3.06(s, 2H, CH₂), 1.52(s, 6H, 2CH₃)	157.53, 154.97, 150.65, 148.37, 147.80, 146.87, 144.58, 139.56, 137.26, 128.86, 128.51, 128.05, 126.92, 125.89, 115.56, 111.40, 109.32, 106.60, 88.27, 55.83, 43.17, 28.23
B4	10.83(s, 1H, NH), 8.55—7.43(m, 3H, pyridine-H), 6.97(s, 1H, pyrazole-H), 7.18—6.76(m, 3H, benzofuran-H+ thiazole-H), 4.14(q, J=7.0 Hz, 2H, CH₂), 3.04(s, 2H, CH₂), 1.50(s, 6H, 2CH₃), 1.43(t, J=7.0 Hz, 3H, CH₃)	157.61, 155.02, 150.71, 148.41, 148.16, 146.90, 143.80, 139.54, 137.24, 128.87, 128.77, 128.02, 126.87, 125.88, 115.55, 111.38, 111.06, 106.54, 88.08, 64.45, 43.22, 28.22, 14.92
C1	10.00(s, 1H, NH), 4.22(s, 3H, NCH₃), 2.69(t, 2H, J=7.6 Hz, CH₂), 2.67(s, 3H, CH₃), 2.54(s, 3H, COCH₃), 1.27(t, J=7.6 Hz, 3H, CH₃)	190.46, 157.35, 155.72, 155.51, 150.25, 128.64, 126.17, 109.39, 41.26, 30.43, 19.17, 18.09, 12.65
C2	4.21(s, 3H, NCH₃), 3.96—3.97[2s, (2.25+0.75)H, OCH₃], 2.69(t, 2H, J=7.6 Hz, CH₂), 2.46—2.51[2s, (0.75+2.25)H, CH₃], 2.25, 2.31[2s, (2.25+0.75) H, CH₃], 1.27(t, J=7.6 Hz, 3H, CH₃)
C3	10.06(s, 1H, NH), 4.32(q, J=6.9 Hz, 2H, OCH₂), 4.20(s, 3H, NCH₃), 2.69—2.65(m, 5H, CH₃+CH₂), 1.36(t, J=7.0 Hz, 3H, CH₃), 1.26(t, J=7.4 Hz, 3H, CH₃)	162.52, 157.92, 156.72, 155.70, 150.22, 128.72, 116.74, 109.31, 60.96, 41.25, 19.18, 17.10, 14.34, 12.67
C4	9.88(s, 1H, NH), 8.27(s, 1H, 1,2,4-triazole-H), 8.11(s, 1H, 1,2,4-triazole-H), 4.18(s, 3H, NCH₃), 2.69(q, J=7.5 Hz, 2H, CH₂), 1.27(t, J=7.6 Hz, 3H, CH₃), 1.16(s, 9H, 3CH₃)	156.73, 155.70, 152.53, 152.48, 150.22, 147.36, 128.68, 119.78, 109.18, 41.19, 35.95, 29.58, 19.20, 12.70
C5	10.16(s, 1H, NH), 7.82(d, 1H, C₆H₂), 7.50(d, 1H, C₆H₂), 7.26(s, 1H, thiazole-H), 4.20(s, 3H, NCH₃), 2.68(q, J=7.6 Hz, 2H, CH₂), 1.27(t, J=7.6 Hz, 3H, CH₃)	158.02, 155.64(d), 155.55, 150.17, 144.75, 132.77(d), 131.91, 128.90, 126.87(d), 120.87(d), 12.67, 19.21, 41.15, 109.14, 114.53, 118.55(d)
C6	9.98(s, 1H, NH), 6.89(s, 1H, thiazole-H), 4.20(s, 5H, COCH₂+NCH₃), 3.73—3.70(m, 2H, CH₂), 2.71—2.61(m, 2H, CH₂), 1.32—1.22(m, 6H, CH₃+CH₃)	170.17, 156.39, 155.51, 150.10, 144.01, 129.08, 111.54, 109.03, 61.13, 41.12, 37.01, 19.1, 14.18, 12.68
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
C7	10.06(s, 1H, NH), 7.89(d, J=8.5 Hz, 1H, benzofuran-H), 7.57(s, 1H, thiazole-H), 6.48(d, J=8.5 Hz, 1H, benzofuran-H), 4.22(s, 3H, NCH₃), 3.86(s, 3H, OCH₃), 3.00(s, 2H, CH₂), 2.68(q, J=7.3 Hz, 2H, CH₂), 1.55(s, 6H, 2CH₃), 1.27(t, J=7.4 Hz, 3H, CH₃)	157.30, 156.15, 155.52, 155.15, 150.04, 146.24, 129.31, 127.67, 114.18, 111.09, 109.72, 108.87, 102.80, 88.27, 55.41, 41.14, 40.08, 28.67, 19.23, 12.73
C8	10.02(s, 1H, NH), 7.88(d, J=8.6 Hz, 1H, benzofuran-H), 7.57(s, 1H, thiazole-H), 6.47(d, J=8.7 Hz, 1H, benzofuran-H), 4.22(s, 3H, CH₃), 4.09(q, J=7.0 Hz, 2H, CH₂), 3.01(s, 2H, CH₃), 2.69(q, J=7.6 Hz, 2H, CH₂), 1.55(s, 6H, 2CH₃), 1.41(t, J=7.0 Hz, 3H, CH₃), 1.28(t, J=7.6 Hz, 3H, CH₃)	157.33, 155.59, 155.56, 155.20, 150.04, 146.31, 129.38, 127.57, 114.4, 110.86, 109.61, 108.88, 103.77, 88.19, 63.59, 41.10, 40.19, 28.69, 19.23, 14.96, 12.72
C9	8.58—7.48(m, 3H, pyridine-H), 6.95(s, 1H, pyrazole-H), 4.27(q, J=7.0 Hz, 2H, CH₂), 2.61(s, 3H, CH₃), 1.31(t, J=7.1 Hz, 3H, CH₃)	162.25, 158.79, 155.90, 155.24, 148.22, 147.00, 140.00, 137.25, 128.98, 128.35, 126.08, 116.73, 111.84, 61.02, 16.92, 14.27
C10	8.47(s, 1H, 1,2,4-triazole-H), 8.09(s, 1H, 1,2,4-triazole-H), 8.77—7.52(m, 3H, pyridine-H), 6.86(s, 1H, pyrazole-H), 1.10(s, 9H, 3CH₃)
C11	8.54—7.45(m, 3H, pyridine-H), 6.91(s, 1H, pyrazole-H), 6.82(s, 1H, thiazole-H), 4.18(q, J=7.1 Hz, 2H, CH₂), 3.67(s, 2H, CH₂), 1.26(t, J=7.0 Hz, 3H, CH₃)	170.21, 157.07, 154.83, 148.35, 146.99, 143.50, 139.67, 137.67, 128.91, 128.23, 126.02, 111.72, 111.44, 61.25, 36.90, 14.15
C12	7.69(d, J=8.6 Hz, 1H, benzofuran), 8.55—7.43(m, 3H, pyridine-H), 7.40(s, 1H, thiazole-H), 6.92(s, 1H, pyrazole-H), 6.47(d, J=8.7 Hz, 1H, benzofuran-H), 3.84(s, 3H, OCH₃), 2.98(s, 2H, CH₂), 1.54(s, 6H, 2CH₃)	157.71, 157.13, 156.37, 155.90, 148.62, 146.87, 144.74, 139.49, 138.17, 129.00, 128.08, 127.23, 125.84, 114.38, 111.49, 110.02, 109.05, 103.08, 88.55, 55.42, 40.02, 28.64
C13	10.74(s, 1H, NH), 7.65(d, J=8.6 Hz, 1H, benzofuran-H), 8.55—7.43(m, 3H, pyridine-H), 7.39(s, 1H, thiazole-H), 6.85(s, 1H, pyrazole-H), 6.43(d, J=8.7 Hz, 1H, benzofuran-H), 4.07(q, J=7.0 Hz, 2H, CH₂), 2.99(s, 2H, CH₂), 1.54(s, 6H, 2CH₃), 1.40(t, J=7.0 Hz, 3H, CH₃)	157.85, 157.10, 156.09, 155.85, 148.65, 146.85, 146.48, 139.49, 138.45, 129.03, 128.12, 127.10, 125.83, 114.62, 111.51, 109.66, 108.69, 104.05, 88.54, 63.63, 40.12, 28.66, 14.93

Compd.	Inhibition rate(%)			Mortality rate(%)
Compd.	Aa	Gz	Ss	Ms	Af
A1	45.00	40.00	56.30	100	50.68
A2	30.00	14.30	45.80	0	22.93
A3	50.00	17.10	33.30	0	49.69
A4	30.00	11.40	54.20	0	19.64
A5	45.00	22.90	31.30	0	58.91
A6	0	0		0	54.16
B1	6.82	40.58	12.98	100	18.21
B2	0.00	5.80		0	62.32
B3	7.50	23.19		0	100
B4	0.00	0		0	100
C1	6.82	14.49	9.87	0	41.85
C2
C3	22.50	28.99		0	18.27
C4	13.64	40.58	42.36	4.55	12.66
C5	0.00	47.83	25.41	5.56	19.93
C6	15.91	33.33	42.81	0	36.09
C7	0.00	53.62	37.68	3.85	16.90
C8	0.00	8.70		0	47.00
C9	0.00	11.59		0	95.54
C10	5.00	10.14		0	67.21
C11	7.50	0		0	56.04
C12
C13
Boscalid		37.00	100
Azoxystrobin			93.50
Dimethachlon	100
Chlorantraniliprole				100
Imidacloprid					100

Scheme 2 Molecular structure optimization diagrams of compound imidacloprid(A), B3(B) and B1(C)

Fig.1 LUMO(A, C, E) and LUMO(B, D, F) maps for imidacloprid(A, B), B3(C, D) and B1(E, F) The green parts represent positive molecular orbital, and the red parts represent negative molecular orbital.

DFT	Δ $E Total a$ /Hartree	ΔE_LUMO/Hartree	ΔE_HOMO/Hartree	ΔE^b/Hartree	Mortality rate(%)
Imidacloprid	-4613.41817	-0.06741	-0.23952	0.17211	100
B1	-2117.50553782	-0.06094	-0.19678	0.13584	18.21
B4	-4859.53075761	-0.06146	-0.20170	0.14024	100
B3	-4820.20321025	-0.06211	-0.20260	0.14049	100

DFT	Δ $E Total a$ /Hartree	ΔE_LUMO/Hartree	ΔE_HOMO/Hartree	ΔE^b/Hartree	Mortality rate(%)
Imidacloprid	-4613.41817	-0.06741	-0.23952	0.17211	100
B1	-2117.50553782	-0.06094	-0.19678	0.13584	18.21
B4	-4859.53075761	-0.06146	-0.20170	0.14024	100
B3	-4820.20321025	-0.06211	-0.20260	0.14049	100

Fig.2 ESP-mapped molecular vdW surface of compoud B1(A), B3(B) and imidacloprid(C)

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