A meso-fluidic, multi-purpose continuous evaporator
Continuous solvent removal and switching is well established on a large industrial scale with falling film evaporators, cone evaporators and similar large scale devices serving the needs of the food, beverage, petroleum and other industries. On the other end of the spectrum, a number of forays have also been made into the design of microfluidic evaporator units but these have primarily been used as concentrators for specialised analytical devices. We believe there is a need to develop a general, multi-purpose evaporator for meso-fluidic processing in research laboratories which is compatible with existing flow chemistry equipment and with the typical product output from the reactors. Drawing inspiration from electrospray ionisation techniques, we envisaged a device which would expose a high surface spray of solution to a desolvation gas to remove solvent quickly and efficiently.
1 Omnifit® column 100 x 15 mm o.d.
2 Modified top end piece assembly
3 Bottom end piece assembly
4 PTFE end fitting
5 Connection cap
6 PTFE tubing 1/4” (6.35 mm) o.d. x 3/16” (4.8 mm) i.d.
7 Swagelok® Stainless steel Union tee, 1/4” (6.35 mm) tube o.d.
8 Swagelok® Stainless steel Bored-through Reducer, 1/8” (3.17mm) x 1/4” (6.35 mm) tube o.d.
9 Stainless Steel Tubing, 1/8″ (3.17mm) o.d. x 0.080″ (2.03mm) i.d.
10 Swagelok® Stainless stee Union tee, 1/8″ (3.17mm) tube o.d.
11 Swagelok® Stainless steel Bored-Through Reducer, 1/16″ (1.587mm) x 1/8” (3.17mm) tube o.d.
12 Stainless Steel Tubing, 1/16″ (1.587mm) o.d. x 1/200″ (0.127mm) i.d.
In our flow synthesis of the probe for the Neurotensin receptor-1, Meclinertant (SR48692), we reported the solvent switch from toluene to methanol in a multi-step flow sequence. For us this represented an unfortunate problem since both the previous acylation/rearrangement steps and the subsequent aromatisation/methylation were telescoped, the only break in the sequence being the necessity to remove toluene and subsequently re-dissolve 2-acetylcyclohexane-1,3-dione intermediate 1 in methanol. (Scheme 1)
Scheme 1. a) Semi-telescoped flow scheme for the synthesis of acetophenone 2 and b) graphical scheme for the solvent switch from toluene to MeOH involving intermediate 1, using our bespoke prototype.
Using our in-line evaporator prototype, a flowing solution of 1 in toluene was concentrated by the evaporator (0.13 mL/min) and enriched in MeOH (10:1 MeOH/toluene). The evaporator was run continuously for 1 hour and the resulting solution of 1 was fed directly into the subsequent steps of the flow synthesis of Meclinertant. (Scheme 1)
For a video demonstration of the Prototype In-Line Evaporator in Action, click here. (http://www.rsc.org/suppdata/gc/c3/c3gc40967h/c3gc40967h.avi)
Also see: http://www.ch.cam.ac.uk/sites/ch/files/chem_at_cam/eChem%40Cam47.pdf Page 7.
A prototype device for evaporation in batch and flow chemical processing B.J. Deadman, C. Battilocchio, E. Sliwinski, S.V. Ley, Green Chem. 2013, 15, 2050-2055.
A machine-assisted flow synthesis of SR48692: a probe for the investigation of neurotensin receptor-1 C. Battilocchio, B.J. Deadman, N. Nikbin, M.O. Kitching, I.R. Baxendale, S.V. Ley, Chem. Eur. J. 2013, 19, 7917-7930.