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The continuous flow synthesis of carboxylic acids using CO2 in a tube-in-tube gas permeable membrane reactor

A. Polyzos, M. O’Brien, T. Pugaard-Petersen, I.R. Baxendale, S.V. Ley, Angew. Chem. Int. Ed. 2011, 50, 1190-1193.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201006618/abstract

http://onlinelibrary.wiley.com/store/10.1002/anie.201006618/asset/supinfo/anie_201006618_sm_miscellaneous_information.pdf?v=1&s=eeb1de81511ff2fac7a88009df9f45da49384532

Keep it simple: A gas–liquid flow reactor has been developed based on a gas permeable tube-in-tube configuration which effectively delivers gas to a liquid substrate stream in a safe, continuous fashion. A series of carboxylic acids were prepared from the reaction of CO₂with a range of Grignard reagents (see picture).

The gas-liquid reactor assembly is comprised of a 1 m section of Teflon AF-
2400 tubing (0.8 mm o.d.; 0.6 mm i.d.) placed within PTFE tubing (3.2 mm o.d.; 1.6
mm i.d). These tubings were coiled and each end fastened to a 1/8” stainless steel tube
fitting, which was fixed onto an aluminium base plate. One section of the Teflon AF-
2400 membrane tubing was passed through to a stainless steel T-piece (Swagelok 2 ×
1/8”, 1 × 16” fittings) that was united with PTFE tubing (1/16”), forming the liquid
inlet. The other section of the Teflon AF-2400 was passed through a 4-way stainless
steel connector (Swagelok, 3 × 1/8”, 1 × 16” fittings) and directly united with a
second piece of PTFE tubing (1/16”), forming the liquid outlet. One of the 1/8”
fittings on the 4-way connector was attached to a fine needle release valve (Swagelok)
used to purge the reactor of excess gas. The remaining connector was attached to
another stainless steel T-piece (Swagelok 3 × 1/8” fittings) that was connected to a
pressure gauge (Swagelok, 10 Bar) and a gas pressure regulator valve (10 bar
maximum) via stainless steel tubing (1/8”) (Figure S1).

Two flow streams driven by the Vapourtec R4/R2+; stream 1 containing a
solution of 1a (1.0 M in THF, 1.0 equiv, 1.0 mmol) loaded into a 2mL PEEK loop
and stream 2 containing the dry THF, were mixed at a T-piece before entering the
gas-liquid tube-in-tube reactor at room temperature. A back pressure regulator (75
psi) was placed immediately after the gas-liquid reactor to prevent out-gassing of the
dissolved CO2 from the solvent stream in the reactor. The flow stream was collected
in a flask containing a biphasic mixture of saturated ammonium chloride solution and
diethyl ether (1:1) (20 mL). The solution was acidified with HCl (1.0 M) and the
product was extracted with EtOAc (2 × 10 mL), dried (Na2SO4) and solvent removed
in vacuo to give the crude product 1b.