Journal of Flow Chemistry

, Volume 4, Issue 3, pp 118–124 | Cite as

Efficient Continuous-Flow Bromination of Methylsulfones and Methanesulfonates and Continuous Synthesis of Hypobromite

  • Frederik E. A. Van Waes
  • Sofie Seghers
  • Wim Dermaut
  • Bart Cappuyns
  • Christian V. Stevens
Full Paper


An efficient continuous-flow procedure for the synthesis of tribromomethylsulfones and tribromomethanesulfonates has been developed starting from the corresponding methylsulfones or methanesulfonates and potassium hypobromite using a biphasic reaction. Two different continuous-flow systems were used and compared for the bromination reaction. Different derivatives were synthesized in excellent isolated yields in very short reaction times using a small excess of potassium hypobromite. Hypobromite can be synthesized continuously leading to the continuous production of the brominated derivates. With the optimized flow conditions, a throughput of up to 53 g/day was obtained. The bromination reaction in flow has significant advantages compared to the corresponding batch process.


continuous flow methylsulfones methanesulfonates bromination hypobromite 

Supplementary material

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  1. 1.
    (a) Crovetti, A. J.; Kenney, D. S.; Hasbrouck, R. B. Antimicrobial Coatings and Method Using Diiodomethyl Sulfones. U.S. Patent 3,615,745, October 26, 1971Google Scholar
  2. 1a.
    (b) Becker, F. C.; Li, J. P. N-Substituted Maleimides in Liquid Concentrates. U.S. Patent 4,247,559, January 27, 1981Google Scholar
  3. 1b.
    (c) Baum, R.; Schmidt, H.; Wunder, T.; Savides, C. Biocide Compositions Comprising 3-Methylisothia-zolin-3-one and a Haloalkyl Sulphone. U.S. Patent 0,189,811, July 29, 2010.Google Scholar
  4. 2.
  5. 3.
    Smith, A. Topical Treatment of Fungal or Yeast Infections Using p-Tolyl Diiodomethyl Sulfone. U.S. Patent 4,185,120, January 22, 1980.Google Scholar
  6. 4.
    (a) Craig, W. E.; Hester, W. F. 3,4-Dichlorophenylsulfonyl Tribromomethane. U.S. Patent 2,484,489, August 7, 1947Google Scholar
  7. 4a.
    (b) Shigematsu, S.; Yamada, Y.; Kimura, I. Herbicide Composition. Japanese Patent 58,128,305, July 30, 1983.Google Scholar
  8. 5.
    Oishi, Y.; Watanabe, T.; Kusa, K.; Kazama, M.; Konya, K. Diphenylamine Derivative and Aquatic Adhesive Life-Controlling Agent Containing Said Derivative. Japanese Patent 63,243,067, October 7, 1988.Google Scholar
  9. 6.
    (a) Kondo, S.; Higashi, T. Photopolymerizable Composition and Image Recording Material. European Patent 1,510,865, March 2, 2005Google Scholar
  10. 6a.
    (b) Barr, R. K.; O’Connor, C. Imaging Methods. U.S. Patent 0,117,042, May 24, 2007Google Scholar
  11. 6b.
    (c) Williamson, A.; Geukens, C.; Van Aert, H.; Heylen, K. Method of Making a Lithographic Printing Plate. W.O. Patent 063,024, May 22, 2009Google Scholar
  12. 6c.
    (d) Williamson, A.; Loccufier, J.; Wynants, S.; Heylen, K. A Lithographic Printing Plate. European Patent 2,186,637, October 23, 2008.Google Scholar
  13. 7.
    (a) Suda, M.; Hino, C. Tetrahedron Lett. 1981, 22, 1997–2000CrossRefGoogle Scholar
  14. 7a.
    (b) Burton, D. J.; Wiemers, D. M. J. Fluorine Chem. 1981, 18, 573–582CrossRefGoogle Scholar
  15. 7b.
    (c) Saikia, A. K.; Tsuboi, S. J. Org. Chem. 2001, 66, 643–647.CrossRefGoogle Scholar
  16. 8.
    Farrar, W. V. J. Chem. Soc. 1956, 78, 508–513.CrossRefGoogle Scholar
  17. 9.
    Ochal, Z.; Kaminski, R. Pol. J. Appl. Chem. 2005, 3, 215–225.Google Scholar
  18. 10.
    (a) Borys, K. M.; Korzynski, M. D.; Ochal, Z. Tetrahedron Lett. 2012, 53, 6606–6610CrossRefGoogle Scholar
  19. 10a.
    (b) Borys, K. M.; Korzynski, M. D.; Ochal, Z. Beilstein J. Org. Chem. 2012 8, 259–265CrossRefGoogle Scholar
  20. 11.
    (a) Acke, D. R. J.; Stevens, C. V. Green Chem. 2007, 9, 386–390CrossRefGoogle Scholar
  21. 11a.
    (b) Heugebaert, T. S. A.; Roman, B. I.; De Blieck, A.; Stevens, C. V. Tetrahedron Lett. 2010, 51, 4189–4191CrossRefGoogle Scholar
  22. 11b.
    (c) Monbaliu, J.-C. M.; Winter, M.; Chevalier, B.; Schmidt, F.; Jiang, Y.; Hoogendoorn, R.; Kousemaker, M. A.; Stevens, C. V. Bioresour Technol. 2011, 102, 9304–9307CrossRefGoogle Scholar
  23. 11c.
    (d) Van Waes, F. E. A.; Drabowicz, J.; Cukalovic, A.; Stevens, C. V. Green Chem. 2012, 14, 2776–2779.CrossRefGoogle Scholar
  24. 12.
    (a) Sinkovec, E.; Pohar, A.; Krajnc, M. Microfluid. Nanofluid. 2013, 14, 489–498CrossRefGoogle Scholar
  25. 12a.
    (b) De Zani, D.; Colombo, M. J. Flow Chem. 2012 2, 5–7CrossRefGoogle Scholar
  26. 12b.
    (c) Jovanovic, J.; Hengeveld, W.; Rebrov, E. V.; Nijhuis, T. A.; Hessel, V.; Schouten, J. C. Chem. Eng. Technol. 2011, 34, 1691–1699CrossRefGoogle Scholar
  27. 12c.
    (d) Brasholz, M.; von Kanel, V.; Hornung, C. H.; Saubern, S.; Tsanaktsidis, J. Green Chem. 2011, 13, 1114–1117CrossRefGoogle Scholar
  28. 12d.
    (e) Kashid, M. N.; Gupta, A.; Renken, A.; Kiwi-Minsker, L. Chem. Eng. Sci. 2010, 158, 233–240CrossRefGoogle Scholar
  29. 12e.
    (f) Kashid, M. N.; Kiwi-Minsker, L. Ind. Eng. Chem. Res. 2009, 48, 6465–6485CrossRefGoogle Scholar
  30. 12f.
    (g) Dessimoz, A. L.; Cavin, L.; Renken, A.; Kiwi-Minsker, L. Chem. Eng. Sci. 2008, 63, 4035–4044.CrossRefGoogle Scholar
  31. 13.
    Caygill, G.; Zanfir, M.; Gavriilidis, A. Org. Process Res. Dev. 2006, 10, 539–552.CrossRefGoogle Scholar
  32. 14.
    For example: (a) Babaouglu, K.; Boojamra, C.; Eisenberg, E.; Hui, H. C.; Mackman, R. L.; Parrish, J. P.; Sangi, M.; Saunders, O. L.; Siegel, D.; Sperandio, D.; Yang, H. Pyrazolo [1, 5-a] Pyrimidines as Antiviral Agents. W.O. Patent 2,011,163,518, December 29, 2011Google Scholar
  33. 14a.
    (b) Al-Khafaji, S.; Cardinale, N.; Hanson, J. R. J. Chem. Res., Synop. 2003, 7, 383CrossRefGoogle Scholar
  34. 14b.
    (c) Bedair, A. H.; Aly, F. M.; Elassy, R. K. M. Indian J. Chem., Sect. B. 1987 26, 91–94.Google Scholar
  35. 15.
    (a) Methylsulfones: Borys, K. M.; Korzynski, M. D.; Ochal, Z. Beilstein J. Org. Chem. 2012, 8, 259–265CrossRefGoogle Scholar
  36. 15a.
    (b) Methanesulfonamides: Jafarpour, M.; Rezaeifard, A.; Golshani, T. Phosphorus, Sulfur Silicon Relat. Elem. 2011, 186, 140–148.CrossRefGoogle Scholar
  37. 16.
    (a) Methylsulfones: Peyronneau, M.; Boisdon, M.; Roques, N.; Mazières, S.; Le Roux, C. Eur. J. Org. Chem. 2014, 22, 4636–4640Google Scholar
  38. 16a.
    (b) Phenyl methanesulfonate, 4-chlorophenyl methanesulfonate: Kaboudin, B.; Abedi, Y. Synthesis 2009, 12, 2025–2028CrossRefGoogle Scholar
  39. 16b.
    (c) 3-Methoxyphenyl methanesulfonate: Barbero, M.; Degani, I.; Dughera, S.; Fochi, R.; Perracino, P. Synthesis 1999, 1, 90–93CrossRefGoogle Scholar
  40. 16c.
    (d) Methanesulfonamides: Jayalakshmi, K. L.; Gowda, B. T. Z. Naturforsch., A 2004, 59, 491–500.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó 2014

Authors and Affiliations

  • Frederik E. A. Van Waes
    • 1
  • Sofie Seghers
    • 1
  • Wim Dermaut
    • 2
  • Bart Cappuyns
    • 2
  • Christian V. Stevens
    • 1
  1. 1.SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience EngineeringGhent UniversityGentBelgium
  2. 2.Chemical Process Development, Agfa Gevaert NVMortselBelgium

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