Design, synthesis and evaluation of insecticidal activity of phenylthiazole derivative containing primary amide and cyanogroup

Objective Thiazole is a class of five-membered heterocyclic compounds with a wide range of biological activities, which are widely used in the fields of medicine and agrochemicals. In this paper, we designed and synthesized a series of phenyl thiazole derivatives containing primary amide and cyanogroup to further explore the potential of thiazole scaffold in controlling Lepidoptera pests.

Method The new thiazole derivatives containing primary amide and cyanogroup were synthesized from benzoic acid with different substituent, and the structures were confirmed by ¹H NMR, ¹³C NMR and ESI-MS. The biological activities of target products against Plutella xylostella were determined by the leaf immersion method. The density functional theory (DFT) calculation was used to explain the reason and difference of insecticidal activity of this skeleton at the molecular orbital level.

Result The results of structural verification showed 22 thiazole derivatives containing primary amide and cyanogroup were synthesized. Six compounds (6d, 7d, 13a, 13b, 14a and 14b) showed good insecticidal activities (mortality > 50%) against P. xylostella, especially the compounds of 6d and 7d with LC₅₀ of 23.94 and 30.37 mg/L respectively. The structure-activity relationship showed the optimal insecticidal activity was demonstrated for benzene ring monosubstituted 4-CF₃ and 5-position thiazole unsubstituted. The results of DFT calculation showed that 4-(trifluoromethyl) phenyl thiazole both delivered and received electrons, and the compound 6d has a smaller HOMO−LUMO gap (ΔE) than 7d.

Conclusion The compound 6d can be further developed as a lead compound. This research provides a valuable clue for molecule design and optimization of insecticide containing thiazole scaffold.