새로운 pyrazole oxime ether 유도체의 살충활성 연구

The pyrazole family was discovered as effective insecticides/acaricides, and fenpyroximate and tebufenpyrad were introduced in the market. In this study, new series of pyrazole oxime ethers were designed and synthesized. The pyrazolone 1 was prepared by the condensation of ethyl acetoacetate with methylhydrazine, and then subsequently subjected to the Vilsmeier-Haack chloroformylation yielding 4-formyl-5-chloro-pyrazole 2. The nucleophilic aromatic substitution of 2 generally allowed the introduction of a wide range of heterocycles into the pyrazole ring. The resulting pyrazole aldehydes 3a-i were readily converted to the corresponding pyrazole oxime derivatives 4a-i, and subsequently to 5-substituted pyrazole oxime ether derivatives 6a-i. The screening assay results clearly show that the activities of 6d were comparable to those of fenpyroximate (6a) against BPH, DBM, and TSSM. It indicates that 6d has a potential to be developed as an insecticidal agent. 효과적인 살충제로 pyrazole 계통의 화합물이 널리 알려졌으며, 이중에 fenpyroximate와 tebufenpyrad는 시판되고 있다. 본 연구에서는 fenpyroximate의 새로운 유도체로써 5-번 위치가 치환된 pyrazole oxime ether를 합성하였다. 본 연구의 핵심 중간체인 4-formyl-5-chloro-pyrazole 2는 ethyl acetoacetate와 methylhyazine의 축합반응으로 얻은 pyrazolone 1을 Vilsmeier-Haack chloroformylation을 통하여 합성하였다. 2에 nucleophilic aromatic substitution 반응을 하여 질소고리화합물이 5-번 위치에 도입된 pyrazole aldehyde 3a-i를 만든 후, 차레로 oxime 화합물 4a-i 그리고 oxime ether 화합물 6a-i를 각각 합성하였다. 합성된 화합물 중에서 6d는 벼멸구 (Brown Planthopper, BPH), 배추좀나방 (Diamondback Moth, DBM), 점박이응애 (Two Spotted Spider Mite, TSSM)에서 높은 활성을 보여주고 있으며, 이는 fenpyroximate의 살충활성과 비슷하였다. 본 결과는 6d가 다양한 곤충 및 응애에 대하여 효과가 우월하여 살충, 살비제로써 개발 가능성을 보여주고 있다.