The use of solid-phase supported 1-N-piperazine-4-N-carboxaldehyde in Vilsmeier reactions

A Vilsmeier salt supported on solid phase was prepared using piperazine bound to Merrifield resin. Piperazine was selected because it contains two secondary amines: one of the amines is protected upon binding to the resin, and the second was formylated to give resin-1-N-piperazine-4-N-carboxaldehyde (9). Activation of the formamide with either bis(trichloromethyl)carbonate (BTC) or POCl(3) afforded the Vilsmeier salt 10. Several olefins were used to test the supported Vilsmeier reagent. The in-solution activation with BTC and POCl(3) of various secondary amides was also evaluated: dimethylformamide (1), N-methyformanilide (4), 4-formylmorpholine (5), and 1,4-dicarboxylpiperazine (6), which showed that amides with one additional heteroatom increase the yields in the Vilsmeier salt formation.