Flow Chemistry Syntheses of Styrenes, Unsymmetrical Stilbenes and Branched Aldehydes

Abstract

Two tandem flow chemistry processes have been developed. A single palladium‐catalysed Heck reaction with ethylene gas provides an efficient synthesis for functionalised styrenes. Through further elaboration the catalyst becomes multi‐functional and performs a second Heck reaction providing a single continuous process for the synthesis of unsymmetrical stilbenes. In addition, the continuous, rhodium‐catalysed, hydroformylation of styrene derivatives with syngas affords branched aldehydes with good selectivity. Incorporation of an in‐line aqueous wash and liquid–liquid separation allowed for the ethylene Heck reaction to be telescoped into the hydroformylation step such that a single flow synthesis of branched aldehydes directly from aryl iodides was achieved. The tube‐in‐tube semi‐permeable membrane‐based gas reactor and liquid–liquid separator both play an essential role in enabling these telescoped flow processes.

Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow chemistry

“…The latter sensibly improved selectivity at quantitative conversion [36]. Styrenes were also synthesized in flow by the same group from different aryl iodides and ethylene [37], as well as unsymmetrical stylbenes [38]. A tube-in-tube reactor configuration was proposed, allowing gas permeation from the shell to the inner pipe, where the liquid reactants are 6 flowing.…”

Flow Technology for Organometallic-Mediated Synthesis

“…Ley reported a fast, safe, and practical approach for the preparation of functionalized styrenes 55 via a MizorokiHeck-type cross-coupling of aryl iodides and ethylene gas (Scheme 48) [71]. The safety concerns, regarding the use of pressurized ethylene gas, were faced by employing the continuous-flow tube-in-tube gas-liquid reactor equipped with a semipermeable membrane to administer the gas in a controlled manner.…”

Recent Advances in Continuous Rhodium-Catalyzed Hydroformylation

“…However, the gas-liquid flow reactor can safely and easily allow for higher overall pressure, which eases material handling and in-line optimization [14]. Ley recently developed a continuous-flow hydroformylation process facilitated by a tube-in-tube gas-liquid reactor, which is based on the semipermeable polymer Teflon AF-2400 [15,16]. Similar to typical batch hydroformylation that employs homogeneous Rh catalyst, styrene derivatives were dissolved in an organic solvent that also contains Rh(CO) 2 (acac) and the ligand Ph 3 P. Reaction of all styrene-type substrates could be completed in 58 min with isolated yields of branched aldehyde from 69% to 94% (conditions: CO/H 2 = 1:1, 25 bar, 65°C, MeOH/PhCH 3 = 1:1).…”