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

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 ZnI 2 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 1 H NMR, 13 C 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 cyanocontaining biological heterocycles.

Hierarchical Self‐Assembly of Curved Aromatics: From Donor–Acceptor Porphyrins to Triply Periodic Minimal Surfaces

“…To date, cubic lattices with dimensions exceeding 60 Å have mostly been observed for highly porous MOF families, such as MIL‐100 , [58,59] ZIF‐100 , [60] NU‐109 / 110 , [61] COZ‐1 , [62] or Fujita's capsule networks [63] . Among non‐polymeric materials, such large lattices have been reported in ionic solids containing charged cage complexes [64–66] or polyoxometalate ions, [67,68] and in some chargeless cages capable of intermolecular hydrogen bonding [69,70] …”