More Robust and Reliable Cyanation Reactions

01 January 2008

A recent publication from workers at GSK* concerns the palladium catalysed cyanation of aromatic halides with zinc cyanide. This reaction is very sensitive to traces of oxygen, which can cause catalyst poisoning. The resulting reactions can be difficult to restart. The group at RTP have found that the addition of 1 wt% of polymethylhydrosiloxane (PMHS) to the reaction mixture avoids the problem and allows reactions to progress even when fully exposed to the atmosphere.

A typical procedure is included in which 3-bromoacetophenone is reacted with zinc cyanide in NMP, using palladium acetate and DPPF with 1 wt% PMHS open to the atmosphere, to give 3-cyanoacetophenone in 78% yield after work up and isolation.

*M.T. Martin et al., Tetrahedron Letters 2007, 48, 2555-2557