PMGB

Case 1: Amidation using DCC and DMAP: 

A mixture of aromatic carboxylic acid (0.025 mol), amine (0.025 mol), dicyclohexylcarbodiimide (DCC) (0.025 mmol), 4-(dimethylamino) pyridine (DMAP) (0.025 mmol) in 200 mL dichloromethane was stirred at room temperature for 1 h. The clear solution became turbid after 5 minutes. The solid (dicyclohexyl urea) precipitated was filtered and washed with dichloromethane; the combined filtrate and washings was washed with saturated aqueous citric acid solution (to remove amine and DMAP) and water, dried (MgSO₄) and evaporated to give the corresponding amide which was purified by triturating with ethyl acetate (white solid, 76%).

Case 2: Amidation using NHS/DCC:

To a solution of the aliphatic carboxylic acid (0.012 mol) and N-hydroxysuccinimide (NHS) (0.013 mol) in 20 mL THF was added dicyclohexylcarbodiimide (DCC) (0.013 mol) and stirred at room temperature for overnight (12 h). The clear solution became turbid after 10 minutes. The reaction mixture was filtered to remove the white precipitate (dicyclohexylurea), washed the precipitate with 50 mL THF. To the combined filtrate and washings was added the amine HCl salt (0.01 mol) followed by sodium bicarbonate (0.07 mol). Then 20 mL of water was added and the heterogeneous mixture was stirred vigorously at room temperature for 4 h. The reaction mixture was concentrated, the residue was diluted with dichloromethane, washed with water and dried (MgSO₄) to give the corresponding amide which was purified by silica gel column chromatography using a gradient of hexanes and ethyl acetate (oil, 85%).

Case 3: Carboxamide

A mixture of the aromatic ethyl ester (0.05 mol) and ammonia (7N solution in methanol, 0.25 mol) in a sealed tube was heated to 50 ^oC for overnight (12 h). The solvent was evaporated to give the corresponding carboxamide which was purified by triturating with ether (orange solid, 84%).

Case 4: from acid chlorides

To a stirred suspension of the aliphatic amine hydrochloride salt (0.02 mol) in 25 mL DCM cooled by ice bath was added aliphatic acid chloride (0.02 mol) followed by triethylamine (0.03 mol) drop wise. The resulting mixture was stirred at room temperature for overnight (12 h). The reaction mixture was diluted with 50 mL water, extracted with 50 mL dichloromethane, washed with saturated NaHCO₃ solution, dried (MgSO₄) and evaporated to give the corresponding amide which was purified by silica gel column chromatography using a  gradient of hexane and ethyl acetate (colorless oil, 22%).