4-(Diethylamino)butan-2-one
4-(Diethylamino)butan-2-one
The Mannich Reaction remains a popular tool in organic synthesis. It performs a one-carbon homologation and an amination in a single step and is involved in the biosynthetic pathways in the synthesis of many alkaloid natural products.
A very simple example of the reaction is the synthesis of 4-(diethylamino)butan-2-one. A solution of diethylamine hydrochloride (88.0 g, 0.80 mol), paraformaldehyde (34.0 g, 1.13 mol), acetone (300 mL, 4.1 mol), 40 mL of methanol, and 0.1 mL of concentrated hydrochloric acid is stirred at reflux using an oil bath for 12 hours. The reaction mixture is then allowed to cool to ambient temperature. A solution of sodium hydroxide (32.5 g) in 150 mL is then cooled to 0 °C and added to the reaction mixture. The resulting solution is extracted with diethyl ether (3X100 mL) and the combined organic fractions are washed with brine. The combined aqueous layers are then washed with diethyl ether (2X75 mL).
The combined organic fractions are dried over magnesium sulfate, filtered, and purified via vacuum distillation. The title compound is collected in fractions at approximately 63-67 °C at 15 mm of pressure.