Synthesis and Biological Activity of 1,3,4-Oxadiazole Mannich Bases Containing Pyrimidine Rings†

doi:10.7503/cjcu20131254

Abstract

Abstract:

1,3,4-Oxadiazole derivatives were reported to possess a broad spectrum of biological activities, such as antifungal, antibacterial, antiviral and antitubercular. Mannich bases had also been reported as potential biological agents, they were applicated in the fields of synthetic study and medicinal chemistry. In recent years, Mannich bases containing 1,3,4-oxadiazole ring had attracted a lot of attention and many Mannich bases of 1,3,4-oxadiazole bearing heterocycle scaffold were reported to have special bioactivity. Nevertheless, literature revealed that there were no reports of a molecular scaffold that Mannich base of 1,3,4-oxadiazole bearing pyrimidine. Prompted by these observations, a series of 1,3,4-oxadiazole derivatives containing pyrimidine(E1—E15) was synthesized from 5-aryl-1,3,4-oxadiazole-2-thione(C1—C3), formaldehyde and substituted aminopyrimidine(D1—D5) by Mannich reaction. 5-Aryl-1,3,4-oxadiazole-2-thione derivatives(C1—C3) were prepared from aromatic acids as the starting material via esterification, hydrazinolysis and cyclization. The structures of all title compounds were confirmed by elemental analysis, IR, ¹H NMR techniques. Furthermore, their biological activities to four vegetable pathogens containing Gibberll nicotiancola, Gibberlla saubinetii, Fusarium oxysporium f. sp. niveum, Pythium solani had been tested. The preliminary results indicated that most of the compounds exhibit relatively good fungicidal activities, especially compounds E3 and E8 showed better biological activity than triazolone.

Key words: 1, 3, 4-Oxadiazole, 2-Aminopyrimidine, Mannich reaction, Biological activity

CLC Number:

O626.27

TrendMD:

SHEN Shengqiang, SUN Xiaohong, LIU Yuanfa, CHEN Bang, JIN Ruyi, MA Haixia. Synthesis and Biological Activity of 1,3,4-Oxadiazole Mannich Bases Containing Pyrimidine Rings^†[J]. Chem. J. Chinese Universities, 2014, 35(7): 1427.

Figures/Tables 4

Scheme 1 Synthetic routes of compounds E1—E15

Table 1 Physical data and elemental analysis results of the compounds E1—E15

Compd.	Appearance	m.p./℃	Yield(%)	Elemental analysis(%, calcd.)
Compd.	Appearance	m.p./℃	Yield(%)	C	H	N
E1	White solid	196.1—197.9	81.3	63.21(63.14)	4.09(4.18)	19.55(19.38)
E2	White solid	197.1—198.8	78.6	57.41(57.29)	3.59(3.68)	15.66(15.72)
E3	White solid	191.8—193.6	84.5	57.61(57.49)	4.59(4.82)	22.44(22.35)
E4	Light yellow solid	168.5—170.3	51.6	48.28(48.07)	3.21(3.46)	19.98(20.09)
E5	White solid	167.1—169.1	69.4	52.43(52.16)	4.22(4.38)	20.47(20.28)
E6	White solid	194.3—195.8	79.8	53.21(53.03)	2.89(3.05)	16.45(16.28)
E7	White solid	205.7—207.2	82.1	50.23(50.13)	2.71(2.80)	19.66(19.49)
E8	White solid	204.8—206.2	78.4	47.19(47.13)	3.39(3.43)	18.51(18.32)
E9	White solid	195.4—197.1	50.1	40.32(40.16)	2.26(2.41)	16.89(16.73)
E10	Light yellow solid	163.7—165.2	73.3	43.77(43.49)	3.08(3.16)	16.22(16.19)
E11	White solid	189.7—191.1	85.7	63.21(63.14)	4.09(4.18)	19.55(19.38)
E12	White solid	223.1—224.9	82.4	56.32(56.19)	3.51(3.61)	27.11(26.98)
E13	White solid	198.7—199.6	84.1	53.41(53.49)	4.15(4.49)	26.98(26.73)
E14	White solid	200.1—201.5	68.8	44.71(44.51)	3.02(3.16)	24.15(23.96)
E15	White solid	151.3—153.1	56.9	48.71(48.55)	3.96(4.07)	24.29(24.26)

Table 2 IR and 1H NMR data of the compounds E1—E15

Table 3 Biological test results of compounds E1—E15 to four vegetable pathogens

Compd.	EC₅₀/(g·L^-1)				EC₉₅/(g·L^-1)
Compd.	Gibberll nicotiancola	Gibberlla saubinetii	F.o.f.sp. niveum^a	Pythium solani	Gibberll nicotiancola	Gibberlla saubinetii	F.o.f.sp. niveum	Pythium solani
E1	0.01	0.03	0.04	0.10	2.53	0.72	1.92	1.70
E2	0.04	0.11	0.00	0.11	0.54	0.35	4.25	2.45
E3	0.02	0.09	0.03	0.01	0.12	0.21	0.88	0.65
E4	28.68	4.77	28.02	6.79	$b$			285.23
E5	0.18	0.43	0.40	0.65	0.80	1.40	2.50	1.63
E6	0.36	0.18	0.26	0.87	6.35	2.01	3.37	20.87
E7	0.12	0.13	0.16	0.37	0.91	0.65	1.36	1.14
E8	0.01	0.15	0.12	0.21	0.56	0.46	2.15	1.08
E9	0.02	0.18	0.07	0.10	1.21	6.60	1.12	1.33
E10	0.03	0.23	0.16	0.16	1.31	1.43	2.73	0.91
E11	0.41	0.19	0.36	0.95	4.29	9.01	6.21	5.11
E12	0.28	0.19	0.28	0.51	2.58	1.21	9.19	1.81
E13	0.52	0.66	0.82	0.49	4.86	5.42	5.90	1.66
E14	1.35	1.72	2.79	118.64	40.10	25.91	203.17	-
E15	2.60	160.19	-	125.70
Triazolone	0.11	0.00	0.03	0.00	1.93	0.38	19.97	2.43

Table 3 Biological test results of compounds E1—E15 to four vegetable pathogens

Compd.	EC₅₀/(g·L^-1)				EC₉₅/(g·L^-1)
Compd.	Gibberll nicotiancola	Gibberlla saubinetii	F.o.f.sp. niveum^a	Pythium solani	Gibberll nicotiancola	Gibberlla saubinetii	F.o.f.sp. niveum	Pythium solani
E1	0.01	0.03	0.04	0.10	2.53	0.72	1.92	1.70
E2	0.04	0.11	0.00	0.11	0.54	0.35	4.25	2.45
E3	0.02	0.09	0.03	0.01	0.12	0.21	0.88	0.65
E4	28.68	4.77	28.02	6.79	$b$			285.23
E5	0.18	0.43	0.40	0.65	0.80	1.40	2.50	1.63
E6	0.36	0.18	0.26	0.87	6.35	2.01	3.37	20.87
E7	0.12	0.13	0.16	0.37	0.91	0.65	1.36	1.14
E8	0.01	0.15	0.12	0.21	0.56	0.46	2.15	1.08
E9	0.02	0.18	0.07	0.10	1.21	6.60	1.12	1.33
E10	0.03	0.23	0.16	0.16	1.31	1.43	2.73	0.91
E11	0.41	0.19	0.36	0.95	4.29	9.01	6.21	5.11
E12	0.28	0.19	0.28	0.51	2.58	1.21	9.19	1.81
E13	0.52	0.66	0.82	0.49	4.86	5.42	5.90	1.66
E14	1.35	1.72	2.79	118.64	40.10	25.91	203.17	-
E15	2.60	160.19	-	125.70
Triazolone	0.11	0.00	0.03	0.00	1.93	0.38	19.97	2.43

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