Rapid Synthesis of Aryl Fluorides in Continuous Flow through the Balz–Schiemann Reaction

Abstract

The Balz-Schiemann reaction remains a highly utilized means for preparing aryl fluorides from anilines. However, the limitations associated with handling aryl diazonium salts often hinder both the substrate scope and scalability of this reaction. To address this, a new continuous flow protocol was developed that eliminates the need to isolate the aryl diazonium salts. The new process has enabled the fluorination of an array of aryl and heteroaryl amines.

Efficient Long‐Range Hole Transport Through G‐Quadruplexes

“…to −0.2072 a.u. Similar to the organic polymers with aromatic π‐stacking, the HOMO energy of the entire GQ bridge was enhanced with a larger number of aromatic G‐tetrads integrated into the bridge. Consequently, the energetic barriers at the conjunction of donor–bridge and bridge–acceptor would be reduced, which could facilitate the hole injection to and separation over the bridges and accelerate HT …”

Expanding the Balz–Schiemann Reaction: Organotrifluoroborates Serve as Competent Sources of Fluoride Ion for Fluoro‐Dediazoniation

“…In contrast, protic solvents such as MeOH furnished low yields (Table , entry 4), likely owing to preferential reaction of the solvent with the diazonium cation to afford both the corresponding arene (hydro‐dediazoniation) and the arylmethyl‐ether . Poor yields were also obtained in MeCN (Table , entry 5), due to arylacetamide formation upon work‐up via a Ritter‐type reaction . Not unexpectedly, DMSO gave low yields (Table , entry 6) as it is well‐known to reduce ArN 2 + s to the corresponding arenes while also producing phenols and other by‐products .…”

“…[8b] Over the past 90 years, ac onsiderable body of work on the Balz-Schiemann and the related Wallach reactions has detailed the use of different solvents including perfluorinated solvents and ionic liquids, [9] one-pot reactions, [10] and flow reactors. [11] In nearlya ll cases, high-temperature thermolysis (> 100 8C) with inorganic "-ate" salts or demanding conditions (e.g.,d ry HF) are required. While yields remainv ariable and highly dependent on specific conditions or ag iven substrate class, [12] no set of conditions has emerged to be generally applicablef or the Balz-Schiemann reaction, ap eculiarity typifying many fluorination methodologies of variable scope often accompanied by significant limitations.…”

Engineering chemistry: integrating batch and flow reactions on a single, automated reactor platform

“…This idea has been partially explored by some, [7][8][9][10] however in the vast majority of reported cases there has not been a true and free integration between the two schools of thought. Although operating a flow process which culminates in dropwise addition of the product stream into a stirred round bottom flask can be useful, it does not constitute full amalgamation.…”