Abstract An effective route for the direct synthesis of substituted pyrazole through 3+2 annulation method was described. (E)-ethyl 2-benzylidene-3-oxobutanoate was prepared from ethyl acetoacetate and benzaldehyde via Knoevenagel approach. The cyclocondensation reaction of (E)-ethyl 2-benzylidene-3-oxobutanoate with phenylhydrazine hydrochloride in acetic acid (30%) medium under reflux conditions produced directly ethyl 1-(2,4-dimethylphenyl)-3-methyl-5-phenyl-1H-pyrazole-4-carboxylate, and was characterized using spectroscopic methods such as NMR, mass, UV-Vis, and CHN analysis. The compound obtained was crystallized using methyl alcohol solvent by slow evaporation method, and the 3D molecular structure was confirmed using single crystal X-ray diffraction studies. The crystal structure is stabilized by intermolecular hydrogen bond of the type C-H•••O and π•••π stacking interactions. Further, the calculated 1H-NMR, TD-SCF, HOMO/LUMO, MEP, Hirshfeld surface and Mulliken population analysis were compared to the experimentally analyzed data. The optimized theoretical structure parameters are in good agreement with the experimental X-ray structures. The compound was evaluated in vitro for its antioxidant susceptibilities through DPPH and hydroxyl radical scavenging methods.

中文翻译：

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新型吡唑衍生物的合成、表征、晶体结构、Hirshfeld 表面分析、抗氧化性能和 DFT 计算：乙基 1-(2,4-二甲基苯基)-3-甲基-5-苯基-1H-吡唑-4-羧酸

摘要 介绍了一种通过3+2环化法直接合成取代吡唑的有效途径。(E)-乙基 2-benzylidene-3-oxobutanoate 由乙酰乙酸乙酯和苯甲醛通过 Knoevenagel 方法制备。(E)-乙基2-亚苄基-3-氧代丁酸与苯肼盐酸盐在乙酸(30%)介质中在回流条件下的环缩合反应直接生成1-(2,4-二甲基苯基)-3-甲基-5-苯基乙基-1H-pyrazole-4-carboxylate，并使用光谱方法进行表征，例如 NMR、质量、UV-Vis 和 CHN 分析。所得化合物使用甲醇溶剂通过缓慢蒸发方法结晶，并使用单晶 X 射线衍射研究确认 3D 分子结构。晶体结构通过 CH•••O 类型的分子间氢键和 π•••π 堆积相互作用来稳定。此外，将计算出的 1H-NMR、TD-SCF、HOMO/LUMO、MEP、Hirshfeld 表面和 Mulliken 布居分析与实验分析数据进行了比较。优化后的理论结构参数与实验X射线结构吻合良好。通过 DPPH 和羟基自由基清除方法在体外评估了该化合物的抗氧化敏感性。