Wednesday, June 25, 2008 - 3:00 PM
New York (Capital Hilton)

Synthesis of Amino Functionalised 2,4,6-Triarylpyridines and 1,5-Diketones Via Process Intensification on Rotating Surfaces

Nicole M. Smith, Marck Norret, and Colin L. Raston. University of Western Australia, Crawley, Australia

Since Krohnke's original report on the synthesis of 2,4,6-triarylpyridines, there has been a plethora of research targeting their syntheses.1 Nevertheless there are no reported simple ‘one-pot' procedures for the synthesis of amino functionalised compounds, for example, 4'-aryl-2,6-bis(4-aminophenyl)pyridines. We have deemed these compounds as precursors for further elaboration en route to the synthesis of DNA binding ligands, in particular targeting G-quadruplex DNA which has recently received much attention as a possible target in cancer therapy.2 We recently reported the efficient ‘one-pot' synthesis of 4'-(pyridyl)-terpyridines in polyethylene glycol (PEG)3 and the ‘one-pot' synthesis of 4'-aryl-2,6-bis(4-aminophenyl)pyridines and their corresponding 1,5-diketone intermediates in PEG with high yield, purity and negligible waste.4 This ‘one-pot' base catalysed approach in making amino-substituted pyridines of this type is without precedent. Process intensification is another tool for green chemistry.5 It has been developed in the present study to prepare the intermediate 1,5-diketones in a single pass on a spinning disc processor (SDP) (Fig 1). This is associated with a residence time of ca 0.5 secs, whereas some reactions using traditional batch technology take several hours to go to completion. Fig 1 Spinning Disc Processor (SDP) 1. Cave, G.W.V., Raston, C.L., J. Chem. Soc., Perkin Trans 1., 2001, 1, 3258; Cave, G.W.V., Raston, C.L., Chem. Commun., 2000, 2199; Rothenberg, G, Downie, A.P., Raston, C.L., Scott, J.L., J. Am. Chem. Soc., 2001, 123, 8701. 2. Waller, Z.A.E., Shirude, P.S., Rodriguez, R., Balasubramanian, S., Chem. Commun., 2008. 3. Smith, C.B., Raston, C.L., Sobolev, A.N., Green Chem., 2005, 7, 650. 4. Smith, M.N., Raston, C.L., Smith, C.B., Sobolev, A.N., Green Chem., 2007, 9, 1185. 5. Anantachoke, N, Makha, M, Raston, C.L., Reutrakul, V, Smith, N.C., J. Am. Chem. Soc., 2006, 128, 13847-13853.