Poster Presentation RACI Biomolecular Division Conference 2013

The influence of ionic liquids on the Knoevenagel condensation of pyrrole with phenyl acetonitriles (#50)

Ahmed Abdullah Alotaibi 1 , Adam McCluskey 1
  1. Chemistry, Centre for Chemical Biology, School of Environmental & Life Sciences, The University of Newcastle, University Dr, Callaghan, NSW, Australia

Our group has invested significant effort into the development of focused compound libraries in the search for new biologically active molecules. Of recent particular note has been synthesis of a range of 2-phenylacrylonitrile moieties with both anti-parasitic and anti-cancer activity using PhCH2N(CH3)3(OH) as a phase transfer catalyst (PTC) facilitating a biphasic Knoevenagel condensation.1,2

This application of the Knoevenagel condensation has been a cornerstone in our efforts towards a wide range of key precursors.3,4,5  Coincident with this we have had an active interest in developing green medicinal chemistry approaches to focused compound libraries of biologically active compounds.  This interest has led us to examine the use of room temperature ionic liquids (RTILs) to enhance and/or modify reaction outcomes.

Herein report our most recent efforts evaluating Knoevenagel approaches to cytotoxic compounds RTILs, and the emerging sub-classes of protic and basic ionic liquids. The Knoevenagel condensation of pyrrole-2-carboxaldehyde with a range of substituted benzyl nitriles afforded rapid access to a family of α,β-unsaturated nitriles (Scheme 1) in low yield to good yields (33-98%). The influence of RTIL, basic and protic ionic liquids on reaction outcome will be discussed.

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Scheme 1: Synthesis of 2-phenylacrylonitriles

  1. Tarleton, M.; Gilbert, J.; Robertson, M. J.; McCluskey, A.; Sakoff, J. A. MedChemCommun 2011, 2, 31.
  2. Tarleton, M.; Gilbert, J.; Sakoff, J. A.; McCluskey, A. Eur. J. Med. Chem. 2012, 57, 65.
  3. Hill, T.; Odell, L. R.; Edwards, J. K.; Graham, M. E.; McGeachie, A. B.; Rusak, J.; Quan, A.; Abagyan, R.; Scott, J. L.; Robinson, P. J.; McCluskey, A. Small molecule inhibitors of dynamin I GTPase activity: development of dimeric tyrphostins. J. Med. Chem., 2005, 48, 7781.
  4. Hill, T. A.; Gordon, C. P.; McGeachie, A. B.; Venn-Brown, B.; Odell, L. R.; Chau, N.; Quan, A.; Mariana, A.; Sakoff, J. A.; Chircop, M.; Robinson, P. J.; McCluskey, A. J. Med. Chem., 2009, 52, 3762.
  5. Gordon, C.P.; Venn-Brown, B.; Robertson, M.J.; Young, K.A.; Chau, N.; Quan, A.; Robinson, P.J.; McCluskey, A. J. Med. Chem., 2013, 56, 46.