Synthesis of N-acylalkylpyrazoles and the influence of their structure on cytotoxicity properties
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DOI:
https://doi.org/10.32523/2616-6771-2025-152-3-43-57Keywords:
pyrazole, N-acylalkylation, α-bromoketones, NMR, X-ray structural analysis, cytotoxicity, Artemia SalinaAbstract
Pyrazole and its derivatives are π-electron-excess aromatic heterocyclic compounds, the ring structure of which contains two bonded nitrogen atoms. Pyrazoles are attracting increasing attention of scientists due to their extensive and diverse range of biologically active properties. In this study a series of N-(acylalkyl)pyrazole derivatives were synthesized by reactions of aliphatic and aromatic α-bromideketones with pyrazole and its 3,5-dimethyl- and 3,5-diphenyl- derivatives via a two-stage one-pot reaction, in the presence of the K2CO3 base. Thus, new, previously undescribed N-pinacolopyrazoles with yields of 65–92% and N-phenacylpyrazoles with yields of 38–91% were obtained. The structures of the products were characterized by NMR, IR, X-ray diffraction and GC-mass spectrometry. According to the X-ray diffraction results, N-(acylalkyl)pyrazoles are conjugated π-systems, in the formation of crystals of which carbonyl groups participate. The cytotoxicity of the studied N-acylalkylpyrazoles towards Artemia Salina crustaceans has been determined, and the toxicity depends on the type of substituents. Thus, N-phenacylpyrazole has a cytotoxicity 6 times higher than the cytotoxicity of N-pinacolonpyrazole, and the cytotoxicity of N-phenacylpyrazoles varies depending on the substituents in the benzene ring, and decreases in the presence of acceptors. The results of the cytotoxicity study can be used to develop drugs with their further modification.
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Copyright (c) 2025 N. Alzhapparova, S. Panshina, M. Ibrayev, A. Zhumina, A. Orazbai (Author)
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