Hydrochloric Acid → (R)-N-hydroxy-N-(3-butyn-2-yl)urea

Participants

Reaction Steps

To a solution of (S)-O-p-toluenesulfonyl-3-butyn-2-ol (11.2 g, 50.0 mmol), prepared by addition of p-toluenesulfonyl chloride and triethylamine to (S)-3-butyn-2-ol, in methanol (100 mL), was added 55% aqueous hydroxylamine (30 mL, 0.50 mol) and the reaction mixture was stirred at ambient temperature for 40 hours. The reaction mixture was cooled to 10° C. and concentrated HCl (50 mL) was added dropwise. The reaction mixture was concentrated in vacuo and the residue was partitioned between H2O (50 mL) and ethyl acetate (200 mL). The 2-phase mixture was cooled to 10° C. and taken to pH 8 with 50% aqueous NaOH solution (60 mL). After stirring for 15 min the layers were separated and the aqueous phase was extracted twice with 200 mL of ethyl acetate. The combined ethyl acetate extracts were cooled to 10° C. and a solution of KOCN (8.1 g, 0.10 mmol) in H2O (30 mL) was added, followed by dropwise addition of 11 mL of concentrated HCl, and the reaction mixture was stirred for 30 min. The ethyl acetate layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give 5.9 g (92% yield) of (R)-N-hydroxy-N-(3-butyn-2-yl)urea. mp 129° C. [α]D24 =+53.3° (c=0.58, CH3OH). 1H NMR (DMSO-d6, 300 MHz) δ1.25 (d, 3H, J=7 Hz), 3.05 (d, 1H, J=2.5 Hz), 4.85 (dq, 1H, J=2.5, 7 Hz), 6.50 (br s, 2H), 9.24 (s, 1H). 13CNMR (DMSO-d6, 75 MHz) d 18.43, 45.14, 72.81, 83.87, 161.51. IR (KBr) 3455, 3330, 3290, 3215, 1658, 1637, 1585 cm-1. MS (DCI/NH3) m/e 146 (M+NH4)+, 163 (M+NH4.NH3)+. Anal. Calc for C5H8N2O2 : C, 46.87; H, 6.29; N, 21.86. Found: C, 46.78; H, 6.34; N, 21.72.

Provenance & Evidence