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用于合成2H-吲唑衍生物的创新级联反应。

Innovative cascade reaction for 2H-indazole derivative synthesis.

作者信息

Choudhary Annu, Patel Rohit, Goswami Dweipayan, Chikhalia Kishor H

机构信息

Department of Chemistry, Veer Narmad South Gujarat University, Surat, Gujarat, 395007, India.

Department of Microbiology and Biotechnology, University School of Sciences, Gujarat University Ahmedabad, Gujarat, 781014, India.

出版信息

Mol Divers. 2025 Feb;29(1):551-559. doi: 10.1007/s11030-024-10874-0. Epub 2024 May 26.

Abstract

In the realm of synthetic organic chemistry, by using a one-pot sequential combination of MCR, it is possible to manufacture chemical commodities (fine chemicals, agrochemicals, and pharmaceutical substances) that enhance our quality of life while generating less waste materials and increasing economic advantages. With this motivation, using a "one-pot" method with multiple components, we present a relatively simple way to make stereoselective substitute 2H-indazole analogues for this study. Firstly, functionalised 3-bromo-4-((methylthio)methyl) derivatives were produced using DMSO as both a carbon source and a solvent, in conjunction with TMSOTf as the Lewis acid promoter. These derivatives were then utilised in the synthesis of 2-H-indazole derivatives with an up to 80% yield using t-BuPHBF as the ligand and CsCO as the base, in the presence of a Pd catalyst at 100°C in an airtight tube. The phenyl ring is endowed with an electron-releasing group situated at position C-6, which efficiently synthesises several 2-H-indazol derivatives with cost-efficient and noteworthy yields by using this method. A comparative analysis of a number of halogen derivatives was also undertaken, using a variety of solvents that were classified according to their halogen group. To confirm the structures of the synthesised target compounds, spectrometric analysis (H NMR, C NMR, and LCMS) was performed.

摘要

在合成有机化学领域,通过一锅法连续组合多组分反应(MCR),可以制造出提高我们生活质量的化学商品(精细化学品、农用化学品和药物物质),同时产生更少的废料并增加经济优势。出于这个动机,我们采用多组分“一锅法”,提出了一种相对简单的方法来制备立体选择性取代的2H-吲唑类似物用于本研究。首先,以二甲基亚砜(DMSO)作为碳源和溶剂,与三氟甲磺酸三甲基硅酯(TMSOTf)作为路易斯酸促进剂,制备官能化的3-溴-4-((甲硫基)甲基)衍生物。然后,在100°C的密闭管中,以叔丁基膦四氟硼酸盐(t-BuPHBF)作为配体,碳酸铯(CsCO)作为碱,在钯催化剂存在下,利用这些衍生物合成2-H-吲唑衍生物,产率高达80%。苯环在C-6位带有一个供电子基团,通过这种方法可以高效地合成几种2-H-吲唑衍生物,产率具有成本效益且值得关注。还使用根据卤素基团分类的多种溶剂,对一些卤素衍生物进行了对比分析。为了确认合成的目标化合物的结构,进行了光谱分析(1H NMR、13C NMR和LCMS)。

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