Synthesis and Biological Activity of Novel Dicyano-containning Cyclopropane-1-carboxamides†

doi:10.7503/cjcu20150729

Abstract

Abstract:

A series of novel dicyano-contained cyclopropanecarboxamide derivatives were designed and synthesized using fungicides containing cyano or cyclopropyl as leading structures. Intermediates 2-amino-2-(substituted) phenylacetonitriles or propionitriles 1a—1n were prepared via Strecker reaction. 1-Cyano-cyclopro-pyl-1-carboxylic(3) was obtained from ethyl cyanacetate and 1,2-dibrimoethane via cyclization and hydrolysis. 14 title compounds were obtained via the condensation of intermediates 1 and 3. The structures of all title compounds were confirmed by ¹H NMR and HRMS. Compound 4f showed good fungicidal activity against Pythium aphanidermatum and Pyricularia oryzae with inhibiton rates of 55.3% and 67.1% at 50 μg/mL in vitro and against Pseudoperonospora cubensis and Erysiphe graminis with inhibiton rates of 50% and 85% at 400 μg/mL in vivo. Compound 4m could give total control against Puccinia sorghi at 400 μg/mL in vivo. In addition, compounds 4c, 4d, 4g, 4j and 4m showed good larvicidal activity against mosquitoes(Culex pipiens pallens) at 5 μg/mL with the lethal rate above 60%; compounds 4h and 4j possessed larvicidal activity against armyworms(Mythimna separata) at 600 μg/mL with the lethal rate of 66.7% and 50%.

Key words: Dicyano-containning cyclopropane-1-carboxamide, Strecker reaction, Condensation, Biological activity

CLC Number:

TrendMD:

XU Gaofei, LIU Yanhong, YANG Xinling, WANG Daoquan, YUAN Dekai. Synthesis and Biological Activity of Novel Dicyano-containning Cyclopropane-1-carboxamides^†[J]. Chem. J. Chinese Universities, 2016, 37(3): 486.

Figures/Tables 7

References 43

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Compd.	Appearance	Yield(%)	m.p./℃	HRMS(Calcd.), m/z
4a	White solid	50.0	99—101	248.0791(248.0800)[M+Na]⁺
4b	White solid	47.9	138—140	266.0706(266.0706)[M+Na]⁺
4c	Yellow solid	43.6	91—93	258.0434(258.0436)[M-H]^-
4d	Yellow solid	29.3	124—126	301.9929(301.9931)[M-H]^-
4e	White solid	69.8	135—137	238.0980(238.0983)[M-H]^-
4f	White solid	67.5	100—102	304.1426(304.1416)[M+Na]⁺
4g	White solid	60.9	84—86	254.0930(254.0936)[M-H]^-
4h	White solid	23.8	148—150	268.0722(268.0728)[M-H]^-
4i	White solid	58.9	112—114	238.0980(238.0989)[M-H]^-
4j	Yellow solid	54.5	136—138	296.0567(296.0560)[M+Na]⁺
4k	White solid	45.3	116—118	316.0086(316.0092)[M-H]^-
4l	White solid	46.5	150—152	316.0086(316.0090)[M-H]^-
4m	White solid	33.1	184—186	276.1113(276.1112)[M+Na]⁺
4n	Yellow solid	43.0	122—124	292.1062(292.1058)[M+Na]⁺

Compd.	Appearance	Yield(%)	m.p./℃	HRMS(Calcd.), m/z
4a	White solid	50.0	99—101	248.0791(248.0800)[M+Na]⁺
4b	White solid	47.9	138—140	266.0706(266.0706)[M+Na]⁺
4c	Yellow solid	43.6	91—93	258.0434(258.0436)[M-H]^-
4d	Yellow solid	29.3	124—126	301.9929(301.9931)[M-H]^-
4e	White solid	69.8	135—137	238.0980(238.0983)[M-H]^-
4f	White solid	67.5	100—102	304.1426(304.1416)[M+Na]⁺
4g	White solid	60.9	84—86	254.0930(254.0936)[M-H]^-
4h	White solid	23.8	148—150	268.0722(268.0728)[M-H]^-
4i	White solid	58.9	112—114	238.0980(238.0989)[M-H]^-
4j	Yellow solid	54.5	136—138	296.0567(296.0560)[M+Na]⁺
4k	White solid	45.3	116—118	316.0086(316.0092)[M-H]^-
4l	White solid	46.5	150—152	316.0086(316.0090)[M-H]^-
4m	White solid	33.1	184—186	276.1113(276.1112)[M+Na]⁺
4n	Yellow solid	43.0	122—124	292.1062(292.1058)[M+Na]⁺

Compd.	¹H NMR(300 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
4a	1.57—1.64, 1.76—1.85(dm, 4H, CH₂CH₂), 6.03, 6.06[d, 1H, (CN)CH], 6.88, 6.91(d, 1H, CONH), 7.46—7.52(m, 5H, Ar—H)	13.62, 18.72, 18.97, 45.02, 116.73, 119.20, 127.22, 129.50, 129.88, 132.33, 165.25
4b	1.58—1.65, 1.75—1.83(dm, 4H, CH₂CH₂), 6.02, 6.05[d, 1H, (CN)CH], 6.98—7.01(m, 1H, CONH), 7.13—7.52(m, 4H, Ar—H)	13.59, 18.79, 19.02, 44.32, 116.41, 116.63, 119.17, 128.40, 128.43, 129.28, 129.37, 162.11, 164.60, 165.27
4c	1.62—1.66, 1.78—1.83(dm, 4H, CH₂CH₂), 6.04, 6.07[d, 1H, (CN)CH], 7.12, 7.15(d, 1H, CONH), 7.40—7.50(m, 4H, Ar—H)	13.61, 18.94, 19.15, 44.36, 116.25, 119.14, 125.45, 127.51, 130.05, 130.72, 134.35, 135.33, 165.36
4d	1.57—1.67, 1.75—1.84(dm, 4H, CH₂CH₂), 6.01, 6.04[d, 1H, (CN)CH], 7.06, 7.08(d, 1H, NH), 7.35—7.63(m, 4H, Ar—H )	13.60, 18.86, 19.09, 44.43, 116.32, 119.12, 124.17, 128.91, 131.50, 132.64, 165.31
4e	1.55—1.64, 1.75—1.84(dm, 4H, CH₂CH₂), 2.40(s, 3H, CH₃), 5.96, 5.99[d, 1H, (CN)CH], 6.82, 6.85(d, 1H, CONH), 7.26—7.39(m, 4 H, Ar—H)	13.62, 18.65, 18.92, 21.22, 44.85, 116.86, 119.23, 127.14, 129.33,130.15, 140.06, 165.16
4f	1.34[s, 9 H, C(CH₃)₃], 1.56—1.66, 1.70—1.85(dm, 4H, CH₂CH₂), 5.97, 5.99[d, 1H, (CN)CH], 6.88,6.90(d, 1H, CONH), 7.40—7.50(m, 4H, Ar—H)	13.62, 18.64, 18.92, 26.18, 30.96, 31.20, 34.80, 44.85, 116.83, 119.25, 126.54, 127.01, 129.17, 153.30, 165.13
Compd.	¹H NMR(300 MHz, CDCl₃), δ		¹³C NMR(100 MHz, CDCl₃), δ
4g	1.58—1.63, 1.77—1.83(dm, 4H, CH₂CH₂), 3.85(s, 3H, OCH₃), 5.94, 5.96[d, 1H, (CN)CH], 6.78, 6.80(d, 1H, CONH), 6.95—7.44(m, 4 H, Ar—H)		13.61, 18.64, 18.90, 44.59, 55.47, 114.79, 116.98, 119.24, 124.29, 128.73, 160.66, 165.14
4h	1.56—1.64, 1.75—1.82(dm, 4H, CH₂CH₂), 5.90, 5.93[d, 1H, (CN)CH], 6.04(s, 2H, OCH₂O), 6.85—7.02(m, 4 H, Ar—H)		13.63, 18.66, 18.96, 44.80, 101.93, 107.58, 108.88, 116.60, 119.17, 121.24, 125.63, 148.73, 149.11, 164.98
4i	1.55—1.68, 1.70—1.80(dm, 4H, CH₂CH₂), 2.03[s, 3H, (CN)C(CH₃)], 6.82(s, 1H, CONH), 7.25—7.58(m, 5H, Ar—H)		13.58, 18.48, 18.56, 29.33, 54.76, 118.86, 119.61, 124.50, 129.14, 129.33, 138.45, 164.55
4j	1.55—1.78(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.91(s, 1H, CONH), 7.26—7.50(m, 4H, Ar—H)		13.53, 18.59, 18.74, 29.51, 54.30, 118.53, 119.52, 125.98, 129.46, 135.03, 137.15, 164.64
4k	1.57—1.80(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.91(s, 1H, CONH), 7.26—7.66(m, 4H, Ar—H)		13.54, 18.70, 18.82, 29.61, 54.26, 118.39, 119.51, 123.29, 127.57, 130.80, 132.21, 140.84, 164.68
4l	1.54—1.79(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.85(s, 1H, CONH), 7.40—7.58(m, 4H, Ar—H)		13.52, 18.60, 18.75, 29.49, 54.36, 118.47, 119.51, 123.15, 126.24, 132.41, 137.71, 164.63
4m	1.54—1.58, 1.67—1.75(dm, 4H, CH₂CH₂), 2.01[s, 3H, (CN)C(CH₃)], 2.37(s, 3H, Ar—CH₃), 5.79(s, 1H, CONH), 7.23—7.45(m, 4H, Ar—H)		19.26, 22.04, 22.09, 25.74, 34.78, 59.01, 124.90, 125.14, 129.23, 134.49, 142.50, 142.64, 170.29
4n	1.54—1.57, 1.71—1.76(dm, 4H, CH₂CH₂), 2.05[s, 3H, (CN)C(CH₃)], 3.83(s, 3H, OCH₃), 6.74(s, 1H, CONH), 6.94—7.50(m, 4H, Ar—H)		13.62, 18.41, 18.48, 28.84, 54.23, 55.43, 114.63, 118.98, 119.63, 126.08, 130.20, 160.09, 164.47

Compd.	¹H NMR(300 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
4a	1.57—1.64, 1.76—1.85(dm, 4H, CH₂CH₂), 6.03, 6.06[d, 1H, (CN)CH], 6.88, 6.91(d, 1H, CONH), 7.46—7.52(m, 5H, Ar—H)	13.62, 18.72, 18.97, 45.02, 116.73, 119.20, 127.22, 129.50, 129.88, 132.33, 165.25
4b	1.58—1.65, 1.75—1.83(dm, 4H, CH₂CH₂), 6.02, 6.05[d, 1H, (CN)CH], 6.98—7.01(m, 1H, CONH), 7.13—7.52(m, 4H, Ar—H)	13.59, 18.79, 19.02, 44.32, 116.41, 116.63, 119.17, 128.40, 128.43, 129.28, 129.37, 162.11, 164.60, 165.27
4c	1.62—1.66, 1.78—1.83(dm, 4H, CH₂CH₂), 6.04, 6.07[d, 1H, (CN)CH], 7.12, 7.15(d, 1H, CONH), 7.40—7.50(m, 4H, Ar—H)	13.61, 18.94, 19.15, 44.36, 116.25, 119.14, 125.45, 127.51, 130.05, 130.72, 134.35, 135.33, 165.36
4d	1.57—1.67, 1.75—1.84(dm, 4H, CH₂CH₂), 6.01, 6.04[d, 1H, (CN)CH], 7.06, 7.08(d, 1H, NH), 7.35—7.63(m, 4H, Ar—H )	13.60, 18.86, 19.09, 44.43, 116.32, 119.12, 124.17, 128.91, 131.50, 132.64, 165.31
4e	1.55—1.64, 1.75—1.84(dm, 4H, CH₂CH₂), 2.40(s, 3H, CH₃), 5.96, 5.99[d, 1H, (CN)CH], 6.82, 6.85(d, 1H, CONH), 7.26—7.39(m, 4 H, Ar—H)	13.62, 18.65, 18.92, 21.22, 44.85, 116.86, 119.23, 127.14, 129.33,130.15, 140.06, 165.16
4f	1.34[s, 9 H, C(CH₃)₃], 1.56—1.66, 1.70—1.85(dm, 4H, CH₂CH₂), 5.97, 5.99[d, 1H, (CN)CH], 6.88,6.90(d, 1H, CONH), 7.40—7.50(m, 4H, Ar—H)	13.62, 18.64, 18.92, 26.18, 30.96, 31.20, 34.80, 44.85, 116.83, 119.25, 126.54, 127.01, 129.17, 153.30, 165.13
Compd.	¹H NMR(300 MHz, CDCl₃), δ		¹³C NMR(100 MHz, CDCl₃), δ
4g	1.58—1.63, 1.77—1.83(dm, 4H, CH₂CH₂), 3.85(s, 3H, OCH₃), 5.94, 5.96[d, 1H, (CN)CH], 6.78, 6.80(d, 1H, CONH), 6.95—7.44(m, 4 H, Ar—H)		13.61, 18.64, 18.90, 44.59, 55.47, 114.79, 116.98, 119.24, 124.29, 128.73, 160.66, 165.14
4h	1.56—1.64, 1.75—1.82(dm, 4H, CH₂CH₂), 5.90, 5.93[d, 1H, (CN)CH], 6.04(s, 2H, OCH₂O), 6.85—7.02(m, 4 H, Ar—H)		13.63, 18.66, 18.96, 44.80, 101.93, 107.58, 108.88, 116.60, 119.17, 121.24, 125.63, 148.73, 149.11, 164.98
4i	1.55—1.68, 1.70—1.80(dm, 4H, CH₂CH₂), 2.03[s, 3H, (CN)C(CH₃)], 6.82(s, 1H, CONH), 7.25—7.58(m, 5H, Ar—H)		13.58, 18.48, 18.56, 29.33, 54.76, 118.86, 119.61, 124.50, 129.14, 129.33, 138.45, 164.55
4j	1.55—1.78(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.91(s, 1H, CONH), 7.26—7.50(m, 4H, Ar—H)		13.53, 18.59, 18.74, 29.51, 54.30, 118.53, 119.52, 125.98, 129.46, 135.03, 137.15, 164.64
4k	1.57—1.80(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.91(s, 1H, CONH), 7.26—7.66(m, 4H, Ar—H)		13.54, 18.70, 18.82, 29.61, 54.26, 118.39, 119.51, 123.29, 127.57, 130.80, 132.21, 140.84, 164.68
4l	1.54—1.79(dm, 4H, CH₂CH₂), 1.99[s, 3H, (CN)C(CH₃)], 6.85(s, 1H, CONH), 7.40—7.58(m, 4H, Ar—H)		13.52, 18.60, 18.75, 29.49, 54.36, 118.47, 119.51, 123.15, 126.24, 132.41, 137.71, 164.63
4m	1.54—1.58, 1.67—1.75(dm, 4H, CH₂CH₂), 2.01[s, 3H, (CN)C(CH₃)], 2.37(s, 3H, Ar—CH₃), 5.79(s, 1H, CONH), 7.23—7.45(m, 4H, Ar—H)		19.26, 22.04, 22.09, 25.74, 34.78, 59.01, 124.90, 125.14, 129.23, 134.49, 142.50, 142.64, 170.29
4n	1.54—1.57, 1.71—1.76(dm, 4H, CH₂CH₂), 2.05[s, 3H, (CN)C(CH₃)], 3.83(s, 3H, OCH₃), 6.74(s, 1H, CONH), 6.94—7.50(m, 4H, Ar—H)		13.62, 18.41, 18.48, 28.84, 54.23, 55.43, 114.63, 118.98, 119.63, 126.08, 130.20, 160.09, 164.47

Compd.^a	SS^b	BC^b	PA^b	PO^b	PAS^b	RS^b
4a	22.4	13.7	13.4	30.2	18.3	8.4
4b	16.1	4.3	30.8	44.3	33.3	6.3
4c	11.5	14.3	16.5	20.1	41.7	10.2
4d	17.3	22.6	33.5	32.9	28.2	10.0
4e	8.5	21.0	26.7	26.9	15.6	17.0
4f	19.4	36.8	55.3	67.1	40.9	29.6
4g	9.9	15.1	23.5	25.5	20.2	11.2
4h	6.8	19.4	28.4	19.5	22.0	6.3
4i	32.8	55.7	10.29	0.05	0.05	7.51
4j	47.5	47.5	7.84	0.83	0.83	3.62
4k	37.7	45.9	5.64	17.36	17.36	5.45
4l	49.2	65.6	4.66	0.31	0.31	12.32
4m	41.0	49.2	0.49	2.89	2.89	7.28
4n	44.3	39.3	32.35	1.86	1.86	8.42
Carbendazim	94.1	83.1	41.0	40.9	91.9	93.0
Chlorothalonil	71.6	78.0	55.8	70.5	91.9	77.0
Tricyclazole	15.7	28.8	26.7	25.5	64.5	41.9