Induction Periods in Reactions of N-Halogenimides

A Detailed Study of Irradiation Requirements Towards an Efficient Photochemical Wohl‐Ziegler Procedure in Flow

“…This was most notable in the reaction run using 30 mA current (giving the lowest possible output power), which appeared to have an initiation period of approximately 2 minutes. Initiation periods have been studied previously in halogenation reactions which use a radical initiator [23] but, to our knowledge, never within the photochemically-initiated variant. Substantially shorter initiation periods were exhibited at higher light intensities, until no significant rate difference was observed, between 200 mA, 300 mA and 400 mA currents [24] .…”

Benzylic Photobromination for the Synthesis of Belzutifan: Elucidation of Reaction Mechanisms Using In Situ LED-NMR

“…We next sought to identify how Br 2 may be formed. It has been reported in photochemical bromination using NBS that a low, steady-state concentration of bromine is formed due to reaction with traces of impurities (e.g., water) . We hypothesized our photobromination conditions using DBDMH could similarly lead to the formation of Br 2 , where the induction period is associated with the delayed onset formation of Br 2 via the following pathway: DBDMH reacts with water to generate HBr and upon reaction with a second molecule of DBDMH leads to the formation of the requisite Br 2 (Figure ).…”

Kinetic Investigations To Enable Development of a Robust Radical Benzylic Bromination for Commercial Manufacturing of AMG 423 Dihydrochloride Hydrate

“…Goldfinger later challenged this mechanism proposing that NBS simply generates and maintains a low concentration of molecular bromine which was the active brominating reagent and that the bromine radical acts as the radical chain carrying species (Scheme ). , Subsequent demonstration that the N–Br bond dissociation energy is higher than Br–Br, , along with several kinetic studies in the 1950s, led to the Goldfinger mechanism becoming widely accepted. − However, since these early reports, in-depth mechanistic studies of this widely utilized reaction have remained notably absent from investigations using modern analytical techniques.…”

“…Given the plethora of kinetic data acquired during RPKA/VTNA studies, a kinetic model could be rapidly developed to fit the experimental data using DynoChem (Figure ). The Goldfinger radical propagation mechanism , was employed using Br 2 as the active brominating agent (Scheme ). As determined by VTNA, the reaction order was fixed with respect to nitrotoluene 1 ( n = 1.3) and benzoyl peroxide ( n = 0.6).…”