反応 #567394

反応方程式

ammonia

artemisinin

2,6-di-tert-butyl-4-methylphenol

sulphuric acid

→

11-azaartemisinin

収率 45.0%

溶媒

dichloromethane

反応条件

後処理

1. 1
   濃縮concentrated under reduced pressure
2. 2
   その他to give a light yellow solid
3. 3
   workup.STIRRINGAfter stirring overnight at room temperature
4. 4
   ろ過the reaction mixture was filtered
5. 5
   洗浄the silica gel washed with dichloromethane
6. 6
   濃縮The combined organic solution and washes were concentrated under reduced pressure

実験手順

To a saturated solution of methanolic ammonia (12 ml) at room temperature was added artemisinin (1.128 g, 4 mmol). The solution was stirred for 1.5 hours and concentrated under reduced pressure to give a light yellow solid. The solid was dissolved in dichloromethane (180 ml), and 2,6-di-tert-butyl-4-methylphenol (BHT) (80 mg, 0.36 mmol), 15% sulphuric acid (0.8 ml), and silica gel (8.0 g) were added in succession. After stirring overnight at room temperature, the reaction mixture was filtered and the silica gel washed with dichloromethane. The combined organic solution and washes were concentrated under reduced pressure. Column chromatography of the residue on silica gel with acetone:dichloromethane (8:92) gave crystalline solid 11-azaartemisinin (510 mg, 45%): mp 143-145° C.; Rf=0.40 (acetone:CH2Cl2, 15:85); [α]25D=−40.9° (c 0.127, CH2Cl2); IR 3313, 3223, 2928, 2873, 1668 cm−1; CIMS (NH3) 299 (M+NH4+, 76), 282 (M+1,100); 1H NMR δ 0.93-1.01 (2H, m), 0.93 (3H, d, J=5.5 Hz), 1.07 (3H, d, J=7.2 Hz), 1.30 (3H, s), 1.25-1.42 (3H, m), 1.61-1.70 (2H, m), 1.71-1.77 (1H, m), 1.92 (2H, dm, J=10.2 Hz), 2.34 (1H, m), 3.17 (1H, pent, J=6.8 Hz), 5.33 (1H, s), 5.93 (1H, bs).

出典