Correia Catarina M, Silva Artur M S, Silva Vera L M
Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
Molecules. 2025 Apr 2;30(7):1582. doi: 10.3390/molecules30071582.
Nitrogen-containing heterocycles are fundamental scaffolds in organic chemistry, particularly due to their prevalence in pharmaceuticals, agrochemicals and materials science. Among them, five-membered rings, containing two nitrogen atoms in adjacent positions-such as pyrazoles, pyrazolines and indazoles-are especially significant due to their versatile biological activities and structural properties, which led to the search for greener, faster and more efficient methods for their synthesis. Conventional batch synthesis methods, while effective, often face challenges related to reaction efficiency, scalability and safety. Flow chemistry has emerged as a powerful alternative, offering enhanced control over reaction parameters, improved safety profiles and opportunities for scaling up synthesis processes efficiently. This review explores the impact of flow chemistry on the synthesis of these pivotal heterocycles, highlighting its advantages over the conventional batch methods. Although indazoles have a five-membered ring fused with a benzene ring, they will also be considered in this review due to their biological relevance.
含氮杂环是有机化学中的基本骨架，特别是因为它们在药物、农用化学品和材料科学中普遍存在。其中，在相邻位置含有两个氮原子的五元环——如吡唑、吡唑啉和吲唑——因其多样的生物活性和结构特性而尤为重要，这促使人们寻找更绿色、更快且更高效的合成方法。传统的间歇合成方法虽然有效，但常常面临与反应效率、可扩展性和安全性相关的挑战。流动化学已成为一种强大的替代方法，它能增强对反应参数的控制，改善安全状况，并为高效扩大合成过程提供机会。本综述探讨了流动化学对这些关键杂环合成的影响，突出了其相对于传统间歇方法的优势。尽管吲唑有一个与苯环稠合的五元环，但由于它们与生物学的相关性，本综述也将对其进行讨论。
