Revisiting aromatic diazotization and aryl diazonium salts in continuous flow: highlighted research during 2001–2021

Abstract

Aryl diazonium salts play an important role in the chemical transformation, however nature of explosiveness limits their applications in batch. Continuous flow technology allows safer operation for diazotization and application...

Construction of an α-chiral pyrrolidine library with a rapid and scalable continuous flow protocol

“…Featuring precisely controlled reaction parameters, 13 fast condition screening, 14 efficient synthesis, 15 and reliable scale-up, 16 continuous flow technology has been demonstrated to be particularly suitable for the development of compound libraries. 17 Comparative to batch, the reaction of Grignard reagents in continuous flow commonly affords better yield or selectivity under mild conditions, 18 and reliable scale-up is easily realized by enhancing the flow rate, reactor volume, or processing time.…”

Catalytic Aerobic N-Nitrosation by Secondary Nitroalkanes in Water: A Tandem Diazotization of Aryl Amines and Azo Coupling

“…15 The fact that the developed o-NQ-catalyzed aerobic diazotization method permitted the in situ generation of reactive aryl diazonium species in a small quantity at any given time enabled a safe in situ consumption strategy for the hydrodeamination of aryl amines. 16 Previously, the formation of areneazo-2-(2-nitro)propane was observed under the influence of 2-nitropropane alone, even in the absence of an o-NQ catalyst (Scheme 1b).…”

“…With an aim of developing safe aryl diazonium chemistry, we disclosed the first catalytic aerobic diazotization of aryl amines in the presence of a catalytic amount of o -NQ, where the in situ -generated aryl diazonium species was dediazotized to give the hydrodeamination products (Scheme b) . The fact that the developed o -NQ-catalyzed aerobic diazotization method permitted the in situ generation of reactive aryl diazonium species in a small quantity at any given time enabled a safe in situ consumption strategy for the hydrodeamination of aryl amines . Previously, the formation of areneazo-2-(2-nitro)propane was observed under the influence of 2-nitropropane alone, even in the absence of an o -NQ catalyst (Scheme b).…”

ortho-Naphthoquinone-Catalyzed Aerobic Hydrodeamination of Aryl Amines via in Situ De-diazotization of Aryl Diazonium Species

“…While the stability of aryl diazonium salts and their surrogates largely depends on the substituents on the aryl ring, the concomitant nitrogen gas evolution from the decomposition of aryl diazonium salts remains a safety concern for the industrial application . The safe synthetic utilization of aryl diazonium salts can be achieved by the in situ generation of reactive aryl diazonium salts in small amounts at any given time, and the recent development of the continuous flow techniques can offer increased reaction temperature control, where the possibility of runaway reactions is eliminated (Scheme a) . Thus, one of the most desirable safety features of aryl diazonium chemistry is the controlled generation and in situ consumption of diazonium species, avoiding the accumulation and handling of reactive chemical species.…”

“…8 The safe synthetic utilization of aryl diazonium salts can be achieved by the in situ generation of reactive aryl diazonium salts in small amounts at any given time, and the recent development of the continuous flow techniques can offer increased reaction temperature control, where the possibility of runaway reactions is eliminated (Scheme 1a). 9 Thus, one of the most desirable safety features of aryl diazonium chemistry is the controlled generation and in situ consumption of diazonium species, avoiding the accumulation and handling of reactive chemical species. In this context, the continuous flow hydrode-diazotizations of aryl amines developed by the Su group 10 and the Baxendale group 11 demonstrated the feasibility of generating small amounts of diazonium species in continuous flow settings.…”