2-Propynamide

Waxy Yellow Solid

Propynamide is a ynamide, a terminal acetylenic compound and a primary carboxamide. It derives from a propynoic acid.

N-Isoxazol-5-yl-4-(4-phenyl-1, 3-thiazol-2-yl)piperazine-1-carboxamide; (1) Propiolamide; Methyl propiolate (25 ml, 281 mmol) was added dropwise to conc. aqueous ammonia (25 ml, 281 mmol) at 30°C and the mixture was stirred at -30°C for 20 minutes. The solvent was distilled off under reduced pressure, ether (200 ml) was added to the residue, the mixture was filtered and the filtrate was concentrated to obtain the desired product (18.5 g, 95.4percent) as a solid. Propiolamide (3): Methyl propiolate (2.0 mL, 22.5 mmol) was added to liquid ammonia at -78 °C and stirred for 2 hours. Evaporation at room temperature yielded compound 3 as white crystals (1.46 g, 94percent). mp 58-61°C (lit.[5], 61-62°C); 1H NMR (D2O) δ 3.50 (s, 1H), 4.43 (bs, 2H).Example 1.1: Propiolamide; o'NHExample 1.1: Propiolamide; Methyl propioate (5 mL, 55 mmol) was added to ammonium hydroxide (15 ml_) at -50 to -60° C over 20 min. The reaction mixture was stirred at this temperature for 1 hour. The solvent was evaporated and the residue dried under vacuum to give the product (3.7 g, 92percent). Example 5Synthesis of Compound (IV)Propiolamide; Methyl propiolate (IV) (72 g, 0.86 mol) is slowly dropped into a 33percent ammonia aqueous solution (240 ml) cooled at -30° C. The reaction mixture is kept under stirring at the same temperature for 1 hour, then slowly brought again to about 25° C. The reaction is concentrated under reduced pressure to a residue, which is then taken up with methyl tert-butyl ether (350 ml) and the solution is dried over NaSynthesis of compound (IV): Propiolamide Methyl propiolate (IV) (72 g, 0.86 mol) is slowly dropped into a 33percent ammonia aqueous solution (240 ml) cooled at -30°C. The reaction mixture is kept under stirring at the same temperature for 1 hour, then slowly brought again to about 25°C. The reaction is concentrated under reduced pressure to a residue, which is then taken up with methyl tert-butyl ether (350 ml) and the solution is dried over NaPropynamide: To a solution of 30 mL of water and 7.15 g (105 mmol) ammonia (25-28 wt percent in water) is added dropwise 8.4 g (100 mmol) methyl propiolate at 0° C. for 30 minutes. The mixture was stirred for 2 h at 0° C., then acetic acid (2 mL) was added. The mixture was stirred for another 10 minutes and saturated with NaCl, followed by extraction with ethyl acetate (3*40 mL). The combined organic phase was washed with saturated aqueous solution of NaH-COTo a solution of 30 mL of water and 7.15 g (105 mmol) ammonia (25-28 wt percent in water) is added dropwise 8.4 g (100 mmol) methyl propiolate at 0 °C for 30 mins. The mixture was stirred for 2 h at 0 °C, then acetic acid (2 mL) was added. The mixture was stirred for another 10 mins and saturated with NaCI, followed by extraction with ethyl acetate (3 χ 40 mL). The combined organic phase was washed with saturated aqueous solution of NaHC03 (20 mL), dried over Na2S04, and removed by rotary evaporation to give product (5.0 g, yield 72percent, purity 99percent by GC).1H NMR (400 MHz, DMSO-d6) δ 8.07 (1 H, s), 7.61 (1 H, s), 4.05 (1 H, s).To a solution of liquid NHEthyl propiolate (4.0 mL, 40 mmol) was added to aqueous ammonia (25percent w/w; 130 mL) at −10 °C and the reaction was stirred at −10 °C (1 h). The reaction mixture was poured onto ethyl acetate (100 mL) and the layers were separated. The aqueous phase was extracted with ethyl acetate (4 x 100 mL) and the combined organic extracts were dried over MgSO4. The solvent and unreacted ethyl propiolate were removed in vacuo to give the crude title compound (2.02 g, 74percent) as an off-white solid, which was used without further purification.Propynamide: To a solution of 30 mL of water and 9.19 g (135 mmol) ammonia (25-28 wt percent) is added dropwise 9.81 g (100 mmol) ethyl propiolate at 0° C. for 30 minutes. The mixture was stirred for 5 h at 0° C., then acetic acid (3 mL) was added. The mixture was stirred for another 10 minutes and saturated with NaCl, followed by extraction with ethyl acetate (3×40 mL). The combined organic phase was washed with saturated aqueous solution of NaHCOTo a solution of 30 mL of water and 9.19 g (135 mmol) ammonia (25-28 wt percent) is added dropwise 9.81 g (100 mmol) ethyl propiolate at 0 °C for 30 mins. The mixture was stirred for 5 h at 0 °C, then acetic acid (3 mL) was added. The mixture was stirred for another 10 mins and saturated with NaCI, followed by extraction with ethyl acetate (3 χ 40 mL). The combined organic phase was washed with saturated aqueous solution of NaHC03 (20 mL), dried over Na2S04, and removed by rotary evaporation to give product (5.0 g, yield 72percent, purity 99percent by GC).1H NMR (400 MHz, DMSO-d6) δ 8.07 (1 H, s), 7.61 (1 H, s), 4.05 (1 H, s).

Molecular Weight:69.06
XLogP3:-0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:69.021463719
Monoisotopic Mass:69.021463719
Topological Polar Surface Area:43.1
Heavy Atom Count:5
Complexity:86.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes