Note Number 1
Examples of FRX Applications for
Demonstration
application notes
Examples of FRX Applications for Demonstration
1 Summary
FRX as a product offers a wide range of applications in a number of areas. To try and increase the
exposure of the product to a wider audience, two standard demonstrations are detailed here. The
first is a Wittig reaction showing the operation of an FRX200 system. The second is a separation of
water and ethyl acetate demonstrating the operation of the FLLEX (Flow Liquid Liquid EXtraction
module), for FRX300 or FRX400.
2 Wittig Reaction - Materials
For the Wittig reaction the following chemicals are needed:
•
2-(nitrobenzyl) triphenylphosphonium bromide, monohydrate (CAS: 23308-83-0) – Note this
is available from Lancaster
•
Methyl-4-formylbenzoate (CAS: 67-56-1)
•
0.5M Sodium Methoxide (CAS: 124-41-4)
•
Dry Methanol (CAS: 67-56-1)
Note: The phosphonium bromide is usually on a long lead time.
3 Experimental
The FRX used for the Wittig reaction was a standard FRX200 system configured as shown below
in figure 1.
Figure 1. System schematic of FRX200 for Wittig reaction
The reagent loops should be connected to a two input 250µl microreactor using the header and the
output of this to the pressurisation module. The microreactor should be clipped onto the reactor
adaptor (mounted on the hotplate) with the thermocouple measuring temperature at the back of the
microreactor. Initially the hotplate should be left off and the pressurisation module set to 2 bar.
The final system should resemble that shown in figure 2.
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Figure 2. The full FRX200 system ready for operation
Both pumps should be primed as per the user guide and set to pre-flush the system with solvent
(dry methanol) at a rate of 0.15ml/min (total flow rate of 0.3ml/min). Reagent 1 (a solution of
596mg of 2-(nitrobenzyl) triphenylphosphonium bromide, monohydrate in 12ml of methanol) should
be loaded into reagent loop 1 whilst reagent 2 (a solution of 216mg of methyl-formylbenzoate and
2.64ml of 0.5M sodium methoxide in 9.36ml of methanol) should be loaded in reagent loop 2 (note:
these solutions will be sufficient for two runs of the three set conditions). The sample loops should
be left in the load position until the reaction is ready to start.
The reaction expected is shown below in figure 3. Note that the phosphorous ylide formed in this
reaction is strongly coloured (pink/purple) – this colouration should be visible in the waste bottle
when loading the sample loops. If this is not seen then there may be a problem with the solutions
being used - it may be for example that the methanol is too wet.
NO2
PPh3 Br
CO2Me
+
NO2
CO2Me
NaOMe
MeOH
O
Figure 3. Reaction scheme for Wittig reaction.
The reaction is started by changing both reagent loops to the inject position with both pumps
pumping at a rate of 0.15ml/min. At this point the contents of the reagent loops flow through the
microreactor and after a brief pause (caused by the time taken to flow from the reagent loop to the
visible portion of the microreactor) a pink colouration should be seen gradually filling the reactor
from the bottom. In this reaction the rate limiting step is the reaction of the ylide intermediate with
the methyl-formylbenzoate, the pink colour should therefore fade as the reactants reach the top of
the reactor. Eventually the reaction should reach equilibrium where the pink colour is strongest at
the bottom of the reactor and completely clear at the top. With normal tube lengths, it should take
1-2 min to reach this stable state.
This rate-limited reaction can be used to demonstrate the ability of the FRX system to rapidly
change conditions. If the flow rate of both reagents is increased the colouration should rise within
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© 2007 Syrris Ltd
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the reactor (as the residence time decreases) and vice versa. If the temperature of the reactor is
increased the rate of the reaction will increase and therefore the colouration should fall. The
equivalence of the reactants can also be investigated by changing the flow rate of the individual
reagents. In all cases it may take several minutes (more in the case of changing temperature) for
a final equilibrium to be established.
4 FLLEX Separation - Materials
For the FLLEX separation experiment the following chemicals are needed:
•
Water
•
Blue food colouring
•
Ethyl acetate (CAS: 141-78-6)
5 Experimental
Normally the 2 phase mixing is performed inside the FLLEX separator. However, in order to show
the formation of stable slug flow of the two immiscible liquids, they can be injected into a 250µl
microreactor mounted on the reactor adaptor. Note that this configuration (shown below) also
mimics a temperature controlled biphasic reaction with on-line separation.
Pump 1 should be set-up to pump water whilst reagent 2 (ethylacetate) should be loaded in pump
2. Ensure that both pumps are correctly primed as detailed in the user guide. The system
pressure (on the left hand regulator/gauge of the FLLEX) may be set to ~2 bar and the cross
membrane pressure on the right hand regulator/gauge of the FLLEX should be set to 150mbar). A
solution of the blue food dye should then be loaded into the reagent loop (“Reagent 1” in diagram
above). The pumps can then be set to a flow rate of around 0.1ml/min and allowed to stabilise for
a few minutes (until materials are seen coming from both the aqueous and organic channels). The
reagent loop can now be moved to the inject position, after a brief delay the blue colour should be
seen. It should be possible to see the immiscibility of the two liquids with “slugs” of one liquid
within the other (at high flow rates this may simply appear as a flickering effect in the microreactor
due to strobing effects with artificial lighting). The slug flow can also be seen in the tube leading
from the reactor to the FLLEX.
The PTFE membrane is hydrophobic, so if slugs of clear ethyl acetate are seen in the blue
aqueous stream coming from the lower FLLEX output tube, the not all of the organic liquid is
passing though the membrane, and the cross membrane pressure should be increased to assist
organic stream flow. Conversely, if blue slugs are seen in the upper clear organic stream, then the
transmembrane pressure should be reduced to prevent unwanted aqueous material passing
through the membrane.
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© 2007 Syrris Ltd
All Rights reserved