Thionyl Chloride → 1,3-Dibenzylpiperazine-2,5-dione

Participants

Reaction Steps

To a 0° C. solution of dipeptide 5 (2.18 g, 5.11 mmol) in methanol (30 mL) was slowly added excess thionyl chloride (1.9 mL). The solution stirred at ambient temperature for 2.5 h. The solvent was evaporated and the residue was triturated with ˜30 mL of ether, producing a white solid that was collected by filtration. The solid was dissolved in methanol (40 mL) and treated with ammonium hydroxide (29%, 10 mL) and then stirred for 18 h followed by concentration. The solid residue was partitioned between saturated NaHCO3 (40 mL), water (20 mL) and CHCl3:isopropyl alcohol, 4:1 (40 mL). The organic phase was separated and the aqueous phase extracted with CHCl3:isopropyl alcohol, 4:1 (3×40 mL). The combined organic phases were dried (K2CO3) and concentrated to afford 6 as a white solid (1.382 g, 92% yield). 1H NMR (400 MHz, CDCl3): δ 2.99 (d, part of AB pattern, J=17.6 Hz, 1H), 3.17 (m, AB pattern, 2H), 3.52 (d, part of AB pattern, J=17.6 Hz, 1H), 4.35 (m, 1H), 4.48 (m, AB pattern, J=14.7 Hz, 1H), 6.39 (bs, NH, 1H), 7.13-7.35 (m, 10H, overlapped with CDCl3); 13C NMR (100 MHz, CDCl3): δ 40.5, 48.2, 49.6, 56.4, 127.4, 128.1, 128.59, 128.63, 128.8, 130.0, 134.65, 134.68, 165.2, 166.3.

Provenance & Evidence