Synthesis and Biological Activity Study of Novel Cyano-containing Multi-substituted Pyrazoles Obtained via Strecker Reaction

doi:10.6023/cjoc201812019

Abstract

In order to study the Strecker reaction of multi-substituted amino armorotic heterocycles and the biological activity of the target compounds, the reaction of 3,5-disubstituted pyrazole-4-amine, TMSCN and aldehydes was realized for the first time by the catalysis of anhydrous ZnI₂ with 4Å molecular seive. The reaction condition was preliminarily optimized and the substrate scop of aldehydes was studied. 20 target compounds of cyano-containing multi-substituted pyrazoles were obtained with the highest yield of 93.5%, and the sturctures of the compounds were confirmed via ¹H NMR, ¹³C NMR and HRMS methods. Priliminary bioassay of the target compounds showed that 13 target compounds possessed 100% larvicidal activity against mosquito at a concentration of 10×10^-3 g/L, and four compounds possessed over 40% larvicidal activity at 5×10^-3 g/L, and 10 compounds poccessed weak larvicidal activity against army worm at 500×10^-3 g/L with the highest activity of 40%; five compounds were confirmed poccessed good inactivation activity against tobacco mosaic virus (TMV) in vivo with the highest inhibition rate of 31.8%, and four compounds possessed moderate host-protection activity against TMV in vivo with the highest rate of 28.3%; in addition, at a concentration of 50×10^-3 g/L, three compounds showed moderate fungicidal activity against Pythium aphanidermatum, Phomopsis asparagi, Phytophora capsic and Rhizoctonia solani in vitro. 4-((1-cyanododecyl)amino)-5-ethyl-N-methyl-1H-pyrazole-3-carboxamide (3t) possessed the highest activity against Phytophora capsic of 62.3%. All the results showed that 3,5-disubstitued pyrazole-4-amine could undergo Strecker reaction smoothly, and this study gave a useful example to explore the Strecker reaction of other multi-substituted aromatic hetreocyclic amines. Additionally, the larvicidal and anti-TMV activity of the target compounds gave some clues in design cyano-containing biological heterocycles.

Key words: multi-substituted pyrazole-4-amine, Strecker reaction, anhydrous ZnI₂, cyano-containing pyrazoles, larvicidal activity, anti-TMV activity, fungicidal activity

Cite this article

Su Shimiao, Zhu Mo, Zhang Daqiang, Yuan Dekai. Synthesis and Biological Activity Study of Novel Cyano-containing Multi-substituted Pyrazoles Obtained via Strecker Reaction[J]. Chin. J. Org. Chem., 2019, 39(7): 2026-2034.

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