MICROFLOW SYSTEMS FOR MECHANISTIC INVESTIGATION OF
COMPLEX REACTION SEQUENCES.
R.C.R.Wootton*1 and S.D.Brandt2
1
ETH Zürich, SWITZERLAND and
Liverpool John Moores University, UNITED KINGDOM
2
ABSTRACT
Microfluidic flow reactors coupled to an appropriate sensor can be used to gather high density information about the entire reactome of a chemical process. ESI-TOF coupled microfluidic devices were used to investigate the mechanism of oligomer formation in a chemically simple but mechanistically complex polymerisation reaction. Using detectors in-line allows
a snapshot of a single space-like trajectory through reaction space to be probed. The speed with which data can be generated
in these devices makes it possible to look at the entirety of reaction phase space rather than just a section of it for the first
time.
KEYWORDS: ESI-TOF, mass spectrometry, kinetics
INTRODUCTION
Microfluidic flow reactor/detector technology has moved from simple detectors such as UV/Visible spectrometry, which
could give only very low density information about a limited range of reactions through Raman devices and now Electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS) mass spectrometry. Each detector has its benefits and
limitations but in general the information density has increased exponentially with each generation of device.1-3 Although
coupling mass spectrometers to microfluidic devices in flow is not new, for most systems studied the range of products from
the reaction under consideration is very limited. Consequently sensing techniques with low resolution, such as UV-Visible
spectroscopy, can be used to determine reaction progress.4 When more information is required techniques such as Raman
spectroscopy may be of use 5 but suffer from relatively low sensitivity unless specialised systems are employed. ESI-TOFMS is a technique which can gather high resolution data on reaction outputs rapidly and continuously. In addition, the ability
of a TOF system to generate a large number of mass spectra at high speed (~ 20k/s) makes it ideal for studying transient systems and also systems with complex product distributions.6, 7 We chose to use a simple T-mixer coupled to a capillary reactor
to study reactions with complex interrelations between product profiles and reaction conditions.
THEORY
The properties of dimethylsiloxane polymers and oligomers vary with chain length and cross -linking. Small cyclic
oligomers are high boiling point solvents, and are named according to the number of dimethylsiloxane units present in
the ring. Thus, octamethylcyclotetrasiloxane is D4, decamethylcyclopentasiloxane is D5 and so on. Simple cyclic
oligomers are normally synthesised by the reaction of dichlorodimethylsilane (DCDMS) with water. This produces HCl
as a byproduct. The mixture of oligomers present at the end of the synthesis depends on many factors including the
amount of water present, the concentration of DCDMS, the pH of the system and indeed t he reaction time. The
mechanistic steps involved in oligomer growth are generally supposed to be as shown in Figure 1. 8
This complex system makes this reaction an ideal choice for study in order to investigate the mechanistic steps and how
they depend upon system conditions. We chose to study the formation of oligomers D3-D10 in acetonitrile solution starting
from DCDMS and water. The HCl produced would remain in solution and catalyse the typical mechanistic steps outlined
above. The product profiles from each reaction should depend on the relative dominance of the suggested mechanistic steps,
which in turn will depend upon the concentrations of water, DCDMS and HCl present in the local system. The use of a nonaqueous solvent allows for greater control over the localised water concentrations at any point in the reaction. Acetonitrile
was chosen as it will act as a solvent for all reagents and byproducts of the reaction over the desired range of concentrations
without forming emulsions or ternary phases. Although many papers use an equilibrated flow system to measure kinetics we
have previously shown this to be unnecessary and time-consuming and so we employ a system of ramped flow with backcalculation of instantaneous residence times. This generates many more data points than would otherwise be possible in the
time.
EXPERIMENTAL
Reagents were purchased from Sigma-Aldrich (Dorset, UK) and used as supplied. Reagents consisting of DCDMS (10
ppm in dry acetonitrile) and water (100 ppm in dry acetonitrile) were infused into a simple “T” mixer and delay pipe (FEP
tubing, 0.2 mm diameter) and then fed directly into the mass spectrometer. A Micromass LCT orthogonal acceleration timeof-flight mass spectrometer (Micromass, UK) equipped with an electrospray ionisation source was operated in positive mode.
978-0-9798064-4-5/µTAS 2011/$20©11CBMS-0001
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15th International Conference on
Miniaturized Systems for Chemistry and Life Sciences
October 2-6, 2011, Seattle, Washington, USA
Samples were introduced using WPI Aladdin syringe pumps (WPI, Sarasota, Florida, US). The instrument was tuned and calibrated in the mass range of 160-1000 Da using a mixture of sodium iodide and cesium iodide (50:50, v/v, isopropanolwater). Products were detected as protonated molecules [M+H]+. Operation settings were: capillary voltage: 3000 V, sample
cone voltage: 20 V, RF lens: 250 V, desolvation temperature: 150 °C, source temperature: 100 °C, acceleration: 200 V, cone
gas flow: 22 L/h, desolvation gas flow: 880 L/h. Data acquisition was carried out using MassLynx version 4.0 SP2. Data
were collected for a variety of mix ratios and reaction residence times and full scan spectra (TIC) were analysed for each oligomeric product. Traces were normalised to the TIC trace to eliminate ionisation artefacts.
Flow rates were determined so that the Fourier number of the system (calculated on DCDMS) was always greater than 1.
Figure 1: Mechanistic steps of siloxane formation
RESULTS AND DISCUSSION
Plots of oligomer concentration against residence time for a 1:1 ratio of DCDMS:water at different flow rates, as well as at
fixed reaction times for a range of flow rates, are shown in Figure 2.
Figure 2: Effect of residence time and mix ratio on oligomer formation
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Figure 3: The strong temporal relationship between d8 and d3
A wide variance of relative abundances was noted, with odd-numbered oligomers performing differently from even numbered oligomers, though generally as expected. The most striking relationship developed from the scan data was that between d8 and d3. It is clear that for a wide range of mix ratios d8 develops early on in the sequence and then is transformed
into d3. This is the reverse of the expected process and an unknown mechanistic step. The result is so striking that we postulate that d3 is in fact only formed from d8 and not via the linear trimer route proposed earlier.
CONCLUSION
ESI-TOF coupled devices and ramped scanning enabled us to identify a totally unknown mechanistic step in a complex
reaction sequence. A new route for the formation of d3 is proposed.
ACKNOWLEDGEMENTS
Thanks to Prof. de Mello (ETH Zürich) for support and advice.
REFERENCES
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[3] H. Lindstrom, R.C.R. Wootton and Alexander Iles AIChE Journal 2007, 53(3), 695-702.
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[6] C. Marquez, F. Fabbretti and J. Metzger, Angewandte Chemie International Edition, 2007, 46, 6915-6917.
[7] L. S. Santos and J. O. Metzger, Angewandte Chemie International Edition, 2006, 45, 977-981.
[8] M. Cypryk and J. Chojnowski, Macromolecules, 1991, 24, 2498-2505
CONTACT
*R.C.R.Wootton, tel: +41-4463-23339; [email protected]
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