Gram-Scale Synthesis of N-Aryl- and N-Aryl-N′-methylpiperazines on a Novel­, Water-Swellable, Oxethane-Linked Poly(ethylene glycol) High-Loading Resin

Abstract

A new methodology for the synthesis of N-arylpiperazines was developed using a poly(ethylene glycol)-derived solid support. The reactions proceeded in up to 60% overall yield over four steps. The scope and limitations of the method are discussed, as well as the utility of ¹³C gel-phase NMR spectroscopy for reaction monitoring.

Key words

N-arylpiperazines - solid-phase synthesis - heterocycles - cleavage - ¹³C gel-phase NMR spectroscopy

References

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2

Price for 100 g of Versabeads™ VO400 loading 2 mol·kg^-1 (as used in this article): e 739 equal to e 370 per mol. Price for 100 g of Rapp Polymere hydroxymethyl polystyrene loading 1.5 mol·kg^-1: e 360 equal to e 240 per mol (price for 100 g of Rapp Polymere TentaGel Standard (water compatible), loading 0.3 mol·kg^-1: e 1010 equal to e 33667 per mol)

16

Compound 3h was only sparingly soluble in the NMR solvent, so quaternary carbon peaks were not visible.

17

Gentle magnetic stirring did not appear to damage the resin. Vigorous magnetic stirring, however, caused significant damage due to grinding.