Structures, Stability, and Safety of Diazonium Salts

Upscaling and Risk Evaluation of the Synthesis of the 3-5-Diamino-1H-Pyrazole, Disperazol

“…Ensuring low temperature (< 5°C) [8] is crucial for the safety of this step, which can be difficult in a large-scale production. Historically, most incidents with diazo coupling reactions have resulted from isolation and/or accumulation of a diazonium species where decomposition can be caused by shock, friction, heat, light and a number of other factors [8][9][10][11][12][13]. One of the main reasons for the limited stability is the low bond strength between the diazo group and the aromatic ring [9], therefore both the substitution pattern and counterion will affect the stability [14].…”

“…Historically, most incidents with diazo coupling reactions have resulted from isolation and/or accumulation of a diazonium species where decomposition can be caused by shock, friction, heat, light and a number of other factors [8][9][10][11][12][13]. One of the main reasons for the limited stability is the low bond strength between the diazo group and the aromatic ring [9], therefore both the substitution pattern and counterion will affect the stability [14]. In general, smaller counterions like chlorides and acetates has a low stability whereas larger counterions like tetrafluoroborates and tosylates provide higher stability [15].…”

A Halogen-Atom Transfer (XAT)-Based Approach to Indole Synthesis Using Aryl Diazonium Salts and Alkyl Iodides

“…Although diazonium salts can be unstable and must be handled with care (see the Supporting Information), the use of BF 4 − as a nonnucleophilic counteranion helps to mitigate safety risks. 10,11 Building on the work of Citterio and Minisci, 12,13 we envisioned a strategy in which SET (single-electron transfer) reduction of aryl diazonium salt (A) would deliver the corresponding aryl radical (B), which can in turn engage the alkyl iodide (C) in a XAT step (via collinear transition state TS1) (Scheme 2A). This would generate the corresponding alkyl radical (E) that could add across the N�N bond of another molecule of diazonium (A), thus yielding a transient azo radical cation (F).…”

“…The key radical C–N bond formation step occurs at room temperature in the absence of acid and carbonyl electrophiles, which allows circumvention of some of the limitations associated with condensation between carbonyls and hydrazines. Although diazonium salts can be unstable and must be handled with care (see the Supporting Information), the use of BF 4 – as a non-nucleophilic counteranion helps to mitigate safety risks. , …”

“…Although diazonium salts can be unstable and must be handled with care (see the Supporting Information ), the use of BF 4 – as a non-nucleophilic counteranion helps to mitigate safety risks. 10 , 11 …”