{"title":"α-Bromination of Aldehydes by Continuous Flow Chemistry and Its Application to the Flow Synthesis of 2-Aminothiazoles","authors":"Yong Lu, Zilong Yan, Yu Jiang, Haibing He, Jian Zhou, Shuanhu Gao and Dong Xing*, ","doi":"10.1021/acs.oprd.5c00076","DOIUrl":null,"url":null,"abstract":"<p >A continuous flow protocol for the α-bromination of aldehydes with bromine is reported, demonstrating significantly improved reaction efficiency and superior mono/dibromination selectivity compared to conventional batch methods. A wide range of aldehydes, including both aryl-substituted and simple aliphatic aldehydes, exhibited excellent reactivity and selectivity under optimized flow conditions. Utilizing this α-bromination flow strategy, a two-step flow synthesis of 2-aminothiazoles, a core structural motif present in many biologically active molecules, was successfully developed, starting from aldehydes. Furthermore, by integrating the α-bromination, 2-aminothiazole formation, and subsequent condensation, a three-step flow process was established for the synthesis of a 2-aminothiazole-containing Hep3B inhibitor. This study highlights the potential of continuous flow chemistry in both bromination reactions and the downstream multistep synthesis of complex bioactive molecules.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 8","pages":"2047–2055"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.5c00076","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
A continuous flow protocol for the α-bromination of aldehydes with bromine is reported, demonstrating significantly improved reaction efficiency and superior mono/dibromination selectivity compared to conventional batch methods. A wide range of aldehydes, including both aryl-substituted and simple aliphatic aldehydes, exhibited excellent reactivity and selectivity under optimized flow conditions. Utilizing this α-bromination flow strategy, a two-step flow synthesis of 2-aminothiazoles, a core structural motif present in many biologically active molecules, was successfully developed, starting from aldehydes. Furthermore, by integrating the α-bromination, 2-aminothiazole formation, and subsequent condensation, a three-step flow process was established for the synthesis of a 2-aminothiazole-containing Hep3B inhibitor. This study highlights the potential of continuous flow chemistry in both bromination reactions and the downstream multistep synthesis of complex bioactive molecules.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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