Piperazine → 1-(Thiazol-2-yl)piperazine

Participants

Reaction Steps

Piperazine (3.44 g, 40 mmol) was added to a solution of 2-bromothiazole (1.8 ml, 20 mmol) in acetonitrile (90 ml). The mixture was heated at reflux for 20 h. The reaction was cooled down at RT and the precipitate (disubstituted piperazine) was filtered off. The filtrate was evaporated, the residue was partitioned between water and ethyl acetate, the organic phase was separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were extracted with HCl (1 M). The organic phase was discarded, and the aqueous layer was neutralized by addition of NaHCO3 (solid) to pH 8, and then extracted with EtOAc. The organic extracted was dried over sodium sulfate and evaporated, providing 1-thiazol-2-ylpiperazine (intermediate IIIa, 860 mg, 25% yield) as colorless oil. H-NMR (CDCl3): 2.98 (m, 4H), 3.48 (m, 4H), 6.56 (d, 1H, J=3.63 Hz), 7.20 (d, 1H, J=3.63 Hz).

Provenance & Evidence