Palladium-mediated organic synthesis using porous polymer monolith formed in situ as a continuous catalyst support structure for application in microfluidic devices
Graphical abstract
Introduction
Microreactors have the potential to revolutionise the fields of chemistry and biotechnology by replacing conventional glassware with small flow-through devices.1, 2, 3, 4, 5, 6, 7, 8 Excellent performance can be achieved by taking advantage of microchannel system features such as rapid heat and mass transfer. Reactions can be carried out under isothermal conditions with well-defined residence times, so that undesirable side reactions and fragmentations are limited. The small dimensions of microreactors also allow the use of minimal amounts of reagents and solvents under precisely controlled conditions, which reduces potential hazards and thus reduces environmental impacts.
Major issues encountered in the development of narrow bore flow-through microreactors [typical Internal Diameter (ID)<ca. 1 mm] for heterogeneous or polymer-supported catalysis are the packing and retention of the supported catalyst inside the microreactor, as well as the high back pressure over the capillary caused either by the densely packed small particle bed or swelling.9, 9(a), 9(b), 9(c)
In chromatography, silica and polymer based monolithic columns have been developed to overcome these difficulties. Monoliths can be synthesised in situ, eliminating the need for packing, and can be designed to have pore sizes in the order of 1 μm ensuring good flow-through properties.10 A polymer monolith can be formed by polymerisation in the presence of a high proportion of cross-linking monomer and a porogen. The physical properties (pore size and surface area) of the monolith are predominantly determined by the solubility of the forming polymer and the nature of the porogen,11 whereas its chemical properties are determined predominantly by the monomer.11, 12, 12(a), 12(b)
Catalytic reactions in microreactors have been explored,1, 2, 3, 4, 5, 6, 7 including for palladium catalysis with ID<ca. 1 mm for hydrogenation (ID 200–530 μm),13, 13(a), 13(b) Suzuki–Miyaura (ID 200–1500 μm),14, 14(a), 14(b), 14(c), 14(d), 14(e), 14(f), 14(g) Stille (ID 75 μm),15 carbonylative cross-coupling (ID 200 μm),16 and sequential aryl amination/Heck coupling.17 We have recently reported results for the Suzuki–Miyaura cross-coupling of p-tolylboronic acid with iodobenzene using poly(glycidyl-co-ethylene dimethacrylate) monolith (GMA/EDMA),18, 19 but see considerable advantage in developing this system for poly(chloromethylstyrene-co-divinylbenzene) monolith as it has a structure similar to widely used conventional chloromethylpolystyrene beads and does not have functional groups present in GMA/EDMA that could potentially interfere with catalysis. The Suzuki–Miyaura and Sonogashira systems were chosen for the work reported here, as established model reactions for metal complexes anchored onto conventional organic polymers in large scale catalysis.20 Microreactors were constructed using fused silica capillaries with an internal diameter of 250 μm. Polymeric monoliths were synthesised in situ and used as a pre-catalyst support. The performance of capillary microreactors was compared with that of batch reactions using bulk monolith, and bulk monolith was used to estimate catalyst loadings for capillaries.
Section snippets
Results and discussion
The polymer monolith was prepared inside the capillaries after modifying the surface of the inner wall of the capillaries21 to ensure anchoring of the monolith. A mixture containing 60% porogens (1-dodecanol and toluene), 24% monovinyl monomer and 16% cross-linking monomer was used, in accord with the recommended 6:4 porogen/monomer ratio,21, 22, 22(a), 22(b) in order to achieve a suitable porosity and void volume fraction of ca. 60% 23 consistent with good flow-through and high surface area
Conclusion
Polymer monoliths, present as a continuous phase filling capillaries and bonded to the internal surface, are promising new materials for solid supported catalysis in 250 μm internal diameter narrow bore microreactors. The performance of the flow-through microreactors included quantitative yields for the conversion of iodobenzene in the Suzuki–Miyaura reaction, and quantitative yields for Sonagashira coupling of p-iodoacetophenone with phenylacetylene. No significant differences were observed in
Materials
Commercially available chloromethylstyrene (CMS), divinylbenzene (DVB), 1-methylimidazole, 5-amino-1,10-phenanthroline and solvents were purchased from Sigma–Aldrich Pty. Ltd (Castle Hill, Australia). Divinylbenzene was purchased as a mixture of different isomers and the wanted isomer (1,4-divinylbenzene) was purified by distillation. 2,2-Azobis-(2-isobutyronitrile) (AIBN) was purchased from MP Biomedicals Australasia Pty. Limited (Seven Hills, Australia) and recrystallised before usage. All
Acknowledgements
This research was supported under the Australian Research Council's Discovery Projects funding scheme (DP0663416) and the University of Tasmania Research College Board. Dr. R.M.G. is the recipient of ARC APD fellowship (DO0557803). We thank Dr. E.F. Hilder for useful discussions. Dr. N.W. Davies (GC–MS), Mr. P. Dove (mechanical workshop), Dr. K. Gömann (SEM), and Dr. A.T. Townsend (ICP-MS analysis), of the Central Science Laboratory, University of Tasmania, are acknowledged for technical
References and notes (26)
- et al.
Tetrahedron Lett.
(2006) - et al.
Aust. J. Chem.
(2008) - et al.
Macromolecules
(2003) - et al.
Microreactors: New Technology for Modern Chemistry
(2000) - et al.
Angew. Chem., Int. Ed.
(2004) - et al.
Chem.—Eur. J.
(2006) - et al.
Lab Chip
(2006) - et al.
Chem. Asian J.
(2006) - et al.
Chem. Commun.
(2007) - et al.
Chem. Rev.
(2007)
Lab Chip
Org. Process Res. Dev.
Green Chem.
Org. Biomol. Chem.
Anal. Chem.
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