Secondary amide-based linkers for solid phase organic synthesis

Article abstract of DOI:10.1016/S0040-4039(97)10281-7

The electron rich benzaldehyde derivatives 4-hydroxybenzaldehyde and 2-methoxy-4-hydroxybenzaldehyde have been investigated for use as linkers for solid phase organic synthesis. Reductive amination of these aldehydes attached to ArgoGel resins with a model primary amine gave the corresponding benzylic secondary amines. These compounds were then converted to the corresponding ureas, sulfonamides, aryl amides, and alkyl amides by derivatization with an appropriate electrophile. The desired secondary amide derivative was then cleaved from the support by treatment with trifluoroacetic acid to provide essentially quantitative yields of products in high purity.