Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

Abstract

SummaryThe continuous flow synthesis of a range of organic solutions of N,N-dialkyl-N-chloramines is described using either a bespoke meso-scale tubular reactor with static mixers or a continuous stirred tank reactor. Both reactors promote the efficient mixing of a biphasic solution of N,N-dialkylamine in organic solvent, and aqueous sodium hypochlorite to achieve near quantitative conversions, in 72–100% in situ yields, and useful productivities of around 0.05 mol/h with residence times from 3 to 20 minutes. Initial calorimetric studies have been carried out to inform on reaction exotherms, rates and safe operation. Amines which partition mainly in the organic phase require longer reaction times, provided by the CSTR, to compensate for low mass transfer rates in the biphasic system. The green metrics of the reaction have been assessed and compared to existing procedures and have shown the continuous process is improved over previous procedures. The organic solutions of N,N-dialkyl-N-chloramines produced continuously will enable their use in tandem flow reactions with a range of nucleophilic substrates.

Simple and Versatile Laboratory Scale CSTR for Multiphasic Continuous-Flow Chemistry and Long Residence Times

“…30 We have previously reported a continuous-flow synthesis of various N,N-dialkyl-N-chloroamines using either a bespoke mesoscale tubular reactor with static mixers or a 50 mL single-stage CSTR (Table 1, entries 1 and 2, respectively). 31 Taking N-chloro-N-methylbenzylamine as an example, we decided to compare these reactor types to our CSTR (see subsequent entries of Table 1).…”

“…All data are consistent with those reported in the literature. 31 Electrocyclization Reaction. A four-stage CSTR was connected to two input feeds.…”

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

“…N -(Di)alkyl- N -chloramines have been prepared in continuous organic–aqueous biphasic flow using either static mixers or a single-stage CSTR [ 26 ]. The choice of reactor and definition of t res for this reaction is governed by both the thermodynamic phase partition parameter of reactants and mixing efficiency which control mass transfer between each phase (and thus, reaction rate).…”

“…A continuous-flow process for the oxidation of alcohols using NaOCl as a phase-transfer catalyst was recently reported [ 25 ]. We have published a communication that describes the continuous mixing of aqueous NaOCl and an organic solution of secondary amine, using either a tubular reactor with in-line static mixers or a single stage CSTR [ 26 ]. The reactor was selected to provide a t res for optimal conversion.…”

Continuous Flow for the Photochemical C‐H Amination of Arenes

“…We then turned our attention to the production of the N ‐chloroamine in flow. This transformation has previously been reported using biphasic conditions with aqueous bleach as the chlorinating agent, with efficient reactions delivered through the use of static‐flow mixers, but we wished to remain in a solely organic reaction medium. We therefore modified our reaction conditions from the batch process.…”