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Use of Raman spectroscopy as a tool for in situ monitoring of microwave-promoted reactions

Nature Protocols volume 3, pages 1–7 (2008)Cite this article

Abstract

The progress of microwave-promoted reactions can be monitored by interfacing a Raman spectrometer with a scientific microwave unit. The apparatus is assembled from commercially available components. It is used in this protocol to follow the base-catalyzed reaction of salicylaldehyde with ethylacetoacetate to yield 3-acetylcoumarin. It is possible to watch the reaction spectroscopically in real time, determine when it reaches completion and thus use it as a tool for rapid reaction optimization.

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Figure 6: Screenshots of the real time Raman monitoring.
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Figure 9: Interfacing the Raman and microwave modules.
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References

  1. Loupy, A. (ed.) Microwaves in Organic Synthesis (Wiley-VCH, Weinheim, 2006).

    Book  Google Scholar 

  2. Kappe, C.O. & Stadler, A. Microwaves in Organic and Medicinal Chemistry (Wiley-VCH, Weinhiem, 2005).

    Book  Google Scholar 

  3. Lidström, P. & Tierney, J.P. (eds.) Microwave-assisted Organic Synthesis (Blackwell, Oxford, 2005).

    Google Scholar 

  4. Hayes, B.L. Microwave Synthesis: Chemistry at the Speed of Light (CEM Publishing, Matthews, NC, 2002).

    Google Scholar 

  5. Kappe, C.O. Controlled microwave heating in organic and medicinal chemistry. Angew. Chem. Int. Ed. Engl. 43, 6250–6284 (2004).

    Article  CAS  Google Scholar 

  6. Larhed, M., Moberg, C. & Hallberg, A. Microwave-accelerated homogeneous catalysis in organic chemistry. Acc. Chem. Res. 35, 717–727 (2002).

    Article  CAS  Google Scholar 

  7. Lew, A., Krutzik, P.O., Hart, M.E. & Chamberlain, A.R. Increasing rates of reaction: Microwave-assisted organic synthesis for combinatorial chemistry. J. Comb. Chem. 4, 95–105 (2002).

    Article  CAS  Google Scholar 

  8. Tompsett, G.A., Conner, W.C. & Yngvesson, K.S. Microwave synthesis of nanoporous materials. ChemPhysChem 7, 296–319 (2006).

    Article  CAS  Google Scholar 

  9. Robb, G.R., Harrison, A. & Whittaker, A.G. Temperature-resolved, in-situ powder X-ray diffraction of silver iodide under microwave irradiation. PhysChemComm 135–137 (2002).

  10. Pivonka, D.E. & Empfield, J.R. Real-time in situ Raman analysis of microwave-assisted organic reactions. Appl. Spectrosc. 58, 41–46 (2004).

    Article  CAS  Google Scholar 

  11. Barnard, T.M. & Leadbeater, N.E. Real-time monitoring of microwave-promoted organometallic ligand-substitution reactions using in-situ Raman spectroscopy. Chem. Commun. 3615–3616 (2006).

  12. Leadbeater, N.E. & Smith, R.J. Real-time monitoring of microwave-promoted Suzuki coupling reactions using in situ Raman spectroscopy. Org. Lett. 8, 4588–4591 (2006).

    Article  Google Scholar 

  13. Leadbeater, N.E., Smith, R.J. & Barnard, T.M. Using in situ Raman monitoring as a tool for rapid optimisation and scale-up of microwave-promoted organic synthesis: esterification as an example. Org. Biomol. Chem. 5, 822–825 (2007).

    Article  CAS  Google Scholar 

  14. Leadbeater, N.E. & Smith R.J. In-situ Raman spectroscopy as a probe for the effect of power on microwave-promoted Suzuki coupling reactions. Org. Biomol. Chem. 5, 2770–2775 (2007).

    Article  CAS  Google Scholar 

  15. Kulkarni, M.V. & Kulkarni, G.M. Lin C.H. & Sun, C.M. Recent advances in coumarins and 1-azacoumarins as versatile biodynamic agents. Curr. Med. Chem. 13, 2795–2818 (2006).

    Article  CAS  Google Scholar 

  16. Jachak, S.M. & Saklani, A. Challenges and opportunities in drug discovery from plants. Curr. Sci. 92, 1251–1257 (2007).

    CAS  Google Scholar 

  17. Kostovam, I. Challenges and opportunities in drug discovery from plants. Curr. HIV Res. 4, 347–363 (2006).

    Article  Google Scholar 

  18. Fylaktakidou, K.C., Hadjipavlou-Litina, D.J., Litinas, K.E. & Nicolaides, D.N. Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr. Pharm. Des. 10, 3813–3833 (2004).

    Article  CAS  Google Scholar 

  19. Hepworth, J.D., Gabbut, C.D. & Heron, B.M. Pyrans and benzo derivatives: synthesis. In Comprehensive Heterocyclic Chemistry II Vol. 5 (eds. Katritzky, A.R., Rees, C.W., Scriven, E.F.V. & McKillop, A.) 1–55 (Pergamon, Oxford, 1996).

    Google Scholar 

  20. de la Hoz, A., Moreno, A. & Vazquez, E. Use of microwave irradiation and solid acid catalysts in an enhanced and environmentally friendly synthesis of coumarin derivatives. Synlett 608–610 (1999).

  21. Frere, S., Thiery, V. & Besson, T. Microwave acceleration of the Pechmann reaction on graphite/montmorillonite K10: application to the preparation of 4-substituted 7-aminocoumarins. Tetrahedron Lett. 42, 2791–2794 (2001).

    Article  CAS  Google Scholar 

  22. Rong, L.C., Li, X.Y., Shi, D.Q., Tu, S.J. & Zhuang, Q.Y. Efficient green procedure for the synthesis of coumarin derivatives by a one-pot, three-component reaction under Solvent Free conditions. Synth. Commun. 37, 183–189 (2007).

    Article  CAS  Google Scholar 

  23. Rajitha, B., Kumar, V.N., Someshwar, P., Madhav, J.V., Reddy, P.N. & Reddy, Y.T. Dipyridine copper chloride catalyzed coumarin synthesis via Pechmann condensation under conventional heating and microwave irradiation. ARKIVOC 23–27 (2006).

  24. Al-Zaydi, K.M. Microwave accelerated preparation of [bmim][HSO4] ionic liquid: an acid catalyst for improved synthesis of coumarins. Molecules 8, 541–555 (2003).

    Article  CAS  Google Scholar 

  25. Bogdal, D. Coumarins: Fast synthesis by Knoevenagel condensation under microwave irradiation. J. Chem. Res. 468–469 (1998).

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Acknowledgements

We thank the University of Connecticut for research funding. We acknowledge technical support from CEM Corporation (in particular T. Michael Barnard) and Enwave Optronics (in particular Eric Wu and Kevin Pan).

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  1. Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, 06269-3060, Connecticut, USA

    Nicholas E Leadbeater & Jason R Schmink

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  1. Nicholas E Leadbeater
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Correspondence to Nicholas E Leadbeater.

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Leadbeater, N., Schmink, J. Use of Raman spectroscopy as a tool for in situ monitoring of microwave-promoted reactions. Nat Protoc 3, 1–7 (2008). https://doi.org/10.1038/nprot.2007.453

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