Regioselective Chlorination of Quinoline Derivatives via Fluorine Mediation in a Microfluidic Reactor

Abstract

A novel green and efficient reaction route for the synthesis of 2‐chloroquinoline via N‐fluoride fluorinated by 1‐Chloromethyl‐4‐fluoro‐1,4‐diazoniabicyclo [2.2.2] octane bis(tetrafluoroborate) (Selectfluor) with 1,3‐Dichloro‐5,5‐dimethylhydantoin (DCDMH) in Vapourtec reactor has been developed. In addition, a series of C2 heterocyclic derivative products are obtained in moderate to good yields under no metal conditions.

Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

“…Over the past two decades, continuous flow processes have been highlighted as a powerful tool to synthesize natural products, active pharmaceutical ingredients (APIs), − and fragrances . Indeed, a number of quinoline derivatives have been obtained under flow conditions through chlorination, trihalomethylation, and Suzuki–Miyaura arylation . Moreover, microreactor technology has proved its value for the functionalization of several heteroarenes using organometallic intermediates. − …”

One-step synthesis of favipiravir from Selectfluor® and 3-hydroxy-2-pyrazinecarboxamide in an ionic liquid

“…With the introduction of ILs, we found that Cl-BMIM and PF 6 -BMIM displayed poor yields, less than 6% (entries 10 and 11). The Cl-BMIM decomposed the Selectfluor® by an apparent exchange between the IL chloride anion with the fluorine atom of Selectfluor®, [31][32][33] whereas the PF 6 -BMIM showed a poor ability to dissolve the starting materials. Meanwhile, a significant improvement was achieved by using BF 4 -BMIM (50%, entry 12), being sufficiently stable in appearance and favoring the solubilization of the starting 3-hydroxy-2-pyrazinecarboxamide.…”

Selectfluor as “Fluorine-Free” Functional Reagent Applied to Organic Synthesis under Transition Metal-Free Conditions

“…2019 年, 杨科等 [101] 以 N-取代 3-甲硫基丙酰胺为原 料, 研究了 Selectfluor 促进 C-S 键断裂合成丙烯酰胺 衍生物和 N-取代 β-氨基丙酰胺的反应(Eqs. 60,61…”