Efficient Continuous-Flow Bromination of Methylsulfones and Methanesulfonates and Continuous Synthesis of Hypobromite

Abstract

An efficient continuous-flow procedure for the synthesis of tribromomethylsulfones and tribromomethanesulfonates has been developed starting from the corresponding methylsulfones or methanesulfonates and potassium hypobromite using a biphasic reaction. Two different continuous-flow systems were used and compared for the bromination reaction. Different derivatives were synthesized in excellent isolated yields in very short reaction times using a small excess of potassium hypobromite. Hypobromite can be synthesized continuously leading to the continuous production of the brominated derivates. With the optimized flow conditions, a throughput of up to 53 g/day was obtained. The bromination reaction in flow has significant advantages compared to the corresponding batch process.

Electrophilic Bromination in Flow: A Safe and Sustainable Alternative to the Use of Molecular Bromine in Batch

“…However, due to problems with the work-up, it was not possible to confirm this by obtaining pure bromothymol blue, and caution has to be taken in saying that switching from Br 2 to KOBr is a possible solution to solve solubility problems. It has been proven in literature, however, that KOBr is a valuable brominating agent, for example, in cases where an alkaline environment is necessary to activate the substrate by deprotonating the position that has to be brominated, in this case a methylsulfon(ate) [25].…”

“…The high surface over volume ratio greatly diminishes the risk of a runaway reaction and ensures a good parameter control, meaning optimal selectivities and conversions can be achieved with minimal reagent or solvent [24]. This high selectivity and efficiency of continuous flow bromination has been demonstrated in previous works [15,25,26,27,28]. Additionally, by generating the bromine in situ, as has been done in batch, the hazards associated with transport and storage can be circumvented, and the production rate can be tailored to the consumption rate.…”

The Hitchhiker’s Guide to Flow Chemistry

“…), and thus continuous flow technology can be a valuable alternative, as is the case for large-scale oxidations with H 2 O 2 or bleach, 378−380 or other industrially relevant transformations. 381,382 If a liquid−liquid reaction has to be carried out at temperatures above the boiling point of one of the respective solvents to gain a significant reduction of the reaction time, flow becomes a powerful technique for research laboratories. 93,377,383 An illustrative example is the synthesis of adipic acid 80 from cyclohexene 79 (Scheme 66a).…”

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

“…Within batch or continuous stirred tank reactors an increase in mixing intensity is achieved with optimised impellor design and speed, alongside a reactor designed to disrupt the flow and increase turbulence. Within meso-scale tubular reactors the addition of in-line aids such as split and recombination streams [ 31 – 32 ], or static mixers [ 32 – 33 ], can enhance mixing and mass transfer between phases. Phase-transfer catalysts (PTCs) can also be used to promote reactions across phase boundaries [ 31 ], their use would, however, incur additional financial costs for the reaction, and also the need for purification and removal of the catalyst from the reaction solution.…”