Revisiting the Balz–Schiemann Reaction of Aryldiazonium Tetrafluoroborate in Different Solvents under Catalyst- and Additive-Free Conditions

Abstract

The thermal and photochemical Balz–Schiemann reaction in commonly used solvents was revisited under catalyst- and additive-free conditions. The study showed that using low- or non-polar solvents could improve the pyrolysis and photolysis of aryldiazonium tetrafluoroborates, enabling effective fluorination at a low temperature or under visible-light irradiation. PhCl and hexane were exemplified as cheap and reliable solvents for both reactions, providing good to excellent yields of aryl fluorides from the corresponding diazonium tetrafluoroborates. The combination of slight heating with visible-light irradiation was beneficial for the transformation of stable aryldiazonium tetrafluoroborates. Nevertheless, the electronic and steric nature of aryldiazonium tetrafluoroborates still had a pivotal effect on both fluorinations even in these solvents.

Indole-Based and Cyclopentenylindole-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers

“…However, it is limited by several factors: (1) substrate scope, restricted to primary aromatic amines, (2) low specific activity caused by competing incorporation of non-radioactive fluoride from monolabeled BF 4 − , (3) a maximum theoretical RCY of 25% due to isotopic exchange, (4) byproducts, as a significant amount of potentially toxic waste may be produced, (5) reaction conditions, as stringent anhydrous conditions and high temperatures are required [ 117 ].…”

Catalyst-free photoarylation reactions promoted by visible light

“…39,40 Diazonium salts were developed by Peter Griefs in 1858, 41 and despite the potential dangers of handling, they present great versatility in organic synthesis and are applied as important synthetic intermediates. 38 Classic reactions such as Balz-Schiemann fluorination, 42 Meerwein arylation, 43 Sandmeyer reaction, 44 Pschorr cyclization 45 and coupling reactions 46 utilize diazonium salts as precursors.…”

Total Synthesis of Dragmacidins G and H

“…The order of introducing substituents is important, because the sulfide unit can affect the reactivity of transition-metal catalysts by poisoning them. We expected that the introduction of a fluoride group onto the pyrazine ring could be realized by a Balz–Schiemann reaction using 3 . Generally, the Balz–Schiemann reaction is not a high-yield process with electron-deficient substrates; therefore, optimization of the reaction conditions is crucial for this transformation.…”