A newly developed microscale ReactIR flow cell was used as a convenient and versatile inline analytical tool for Grignard formation in continuous flow chemical processing. The LiCl-mediated halogen/Mg exchange reaction was used for the preparation of functionalized arylmagnesium compounds from aryl iodides or bromides. Furthermore, inline IR monitoring was used for the analysis of conversion and possible byproduct formation, as well as a potential tool for elucidation of mechanistic details. The results described herein indicate that the continuous flow systems are effective for highly exothermic reactions such as the Grignard exchange reaction due to fast mixing and efficient heat transfer.

We report on the development of a continuous flow process for the palladium catalysed methoxycarbonylation of aryl, heteroaromatic and vinyl iodides and an aryl bromide using a Teflon AF-2400 based Tube-in-Tube reactor to mediate the selective permeation of carbon monoxide into solution at elevated pressures. The low volume of pressurised gas within the reactor (5.6 mL) offers the potential for an enhanced safety profile compared to batch processes. We also present preliminary results for the use of in situ FTIR to measure solution concentrations of carbon monoxide and demonstrate the use of a second reactor to effect the removal of carbon monoxide from the flow stream.The carbonyl group is integral to many of the key bond forming reactions of organic synthesis. 1 Its success is dependent upon the availability of methods to access carbonyl substrates, of which the transition metal-mediated insertion of carbon monoxide (CO) is one of the most efficient (Scheme 1). 2 Scheme 1 General transition metal-catalysed carbonyl insertion reaction. This atom-economical process combines the ready availability of CO, the ability to drive reactions to completion through pressurisation, and ease of workup (as the excess reagent is a gas), making this transformation particularly attractive to synthesis chemists. However, there still exists a general reluctance to use CO gas in research laboratories, and there are good reasons for this. The concerns relate to the pressurised containment, toxicity and flammable nature of this reactive gas input. As such the safe and scalable use of CO and other gases within laboratory synthesis programmes represents an unmet need. Flow chemistry (in which the substrates/reagents are continuously pumped through a relatively low volume reaction zone so that only a very small fraction of the total is exposed to the reaction conditions at any one time) has emerged as a new paradigm of chemical

A prototype continuous-flow liquid-liquid extraction system is reported. By harnessing several open-source software libraries, a computer control script was written using the Python programming language. Using a 'computer-vision' approach, this allowed the computer to monitor the interface level between the organic and aqueous phases using a simple webcam setup and (by dynamically controlling pump flow rate) to keep this interface within defined limits. The system enabled the efficient 'inline' extraction of excess reagent in hydrazone formations, dithiane formations and epoxidations. The initial results of dispersion measurement are also presented.

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A series of continuous flow chemistry processes that facilitate the palladium‐catalysed carbonylation of aryl and vinyl iodides and aryl bromides with a range of alkoxy, hydroxy and amino nucleophiles is reported. Harnessing a semipermeable Teflon® AF‐2400 Tube‐in‐Tube assembly, these reactors permit the controlled transport of carbon monoxide into solution at elevated pressure to generate homogeneous flow streams, avoiding some potential issues associated with segmented flow gas‐liquid reactors. As the volume of pressurised gas contained within the device is low, the hazards associated with this are potentially mitigated relative to comparable batch processes. We also show how the incorporation of a second in‐line gas‐flow reactor allows for the sequential introduction of two gases (carbon monoxide and a gaseous nucleophile) into the reaction stream.