HTML by Rhodium
Preparation of N-Methyl Amides1 (abbreviated)
The most generally useful method was to drop acid chloride very slowly, with constant stirring, into three moles of amine in concentrated aqueous solution. The temperature was kept at -20 to -10°C during the addition. The methyl amides were caused to separate by the addition of solid caustic potash to the mixture. The separated amide was dried over caustic potash and distilled. Yields run from 85 to 95%. Similar yields were obtained when the amine was passed into a soln of the acid chloride in dry toluene at -10°C followed by the addition of 20% sodium hydroxide solution. For comparison various other methods of preparing amides were tried. The reaction of dry methylamine on esters proved to be very slow but with an excess of the aqueous amine, 68% of the heptamine was obtained after several days. From the sodium salt of an acid and methylamine hydrochloride, a good yield was obtained but it was difficult to purify. Acetamide and its sodium salt were methylated, yields 50-60%. The N-methylamides of formic and acetic acid were obtained by passing the amine through the heated acids.
Sodium metal (1.38 g, 60 mmol) was dissolved in 100 mL of anhydrous methanol under gentle reflux. To this solution of sodium methoxide, first 3.7 mL (60 mmol) of methyl formate was added and then 4.00 g (59 mmol) of methylammonium chloride under cooling with and ice bath. The solution was stirred overnight at room temperature. The suspension was filtered over celite and the filtrate was carefully concentrated in vacuo (30°C, 20 mmHg). The residue was taken up in dichloromethane and the precipitated salts were removed by filtration. The filtrate was dried on MgSO4, filtered again and the solvent was carefully evaporated in vacuo. This resulted in 3.49 g of N-methylformamide (99% yield).