Continuous, on-demand generation and separation of diphenylphosphoryl azide

Development of a Telescoped Flow Process for the Safe and Effective Generation of Propargylic Amines

“…As mentioned earlier, this was driven by the desire to streamline the synthesis effort avoiding time consuming isolation and purification stages for the potentially hazardous azide intermediate 5 as well as the release of nitrogen gas during the Staudinger reduction step, that could lead to a dangerous run-away process. To accomplish this, we opted to utilize diphenylphosphoryl azide ( 8 , DPPA) as a readily available and bench stable azide donor that we [24] and others [25,26] had exploited previously in flow-based azide transformations. This rendered the opportunity to subsequently treat the resulting propargylic azide with triphenylphosphine in a suitable solvent system to affect the formation of the desired propargylic amines via a telescoped Staudinger reduction [27] sequence (Scheme 4).…”

Cutting edge of diphenyl phosphorazidate (DPPA) as a synthetic reagent – A fifty-year odyssey

“…Recently, Jensen and colleagues developed a continuous flow preparation of DPPA in a pilot plant scale. 6 They used a Corning's low flow reactor system which was coupled to a membrane separator and in line Fourier transform infrared (FTIR). By this system, DPPA was safely produced at a rate of 1 mol h −1 as a 2 M anhydrous toluene stream.…”

Continuous Flow Organophosphorus Chemistry

“…To the best of our knowledge, only one report details the continuous flow preparation of DPPA: Jensen and colleagues developed a continuous flow system for the generation of DPPA featuring an enhanced safety. [175] The process included an in-line IR spectrometer for reaction monitoring for an improved safety. The procedure relied on a biphasic mixture of diphenylphosphoryl chloride (DPPCl) in toluene mixed with an aqueous solution of NaN 3 with a phase-transfer catalyst (Figure 80).…”