1-Methylcyclopropanecarboxamide was synthesized as follows:
1. In a 1-L four-neck flask equipped with a magnetic stirrer, a dosing funnel, and a nitrogen inlet connected to a water scrubber, a 77.7 wt% toluene solution of 1-methylcyclopropanecarboxylic acid (185.66 g of the solution, containing approximately 144.24 g of 1-methylcyclopropanecarboxylic acid, 1.44 mol) and additional toluene (42 mL) were added.
2. The solution was heated to 45 °C and thionyl chloride (116 mL, 1.58 mol, 1.1 eq.) was added slowly and dropwise over a period of 1 hour. Gas escape and mild heat absorption were observed during the dropwise addition.
3. After the dropwise addition was completed, the reaction mixture was warmed to 80 °C and maintained for 5 hours until GC analysis showed complete consumption of 1-methylcyclopropanecarboxylic acid.
4. In another 2-L three-necked flask equipped with a mechanical stirrer and addition funnel, 28% ammonium hydroxide solution (390 mL, 5.76 mol, 4 eq.) was added.
5. The above thionyl chloride-treated reaction mixture was transferred to a charging funnel and the original reaction flask was washed with a small amount of toluene.
6. The ammonium hydroxide solution was cooled in an ice-acetone bath and the contents of the addition funnel were slowly added over a period of 1 hr, controlling the reaction temperature to no more than 25 °C. The contents of the addition funnel were then mixed with the ammonium hydroxide solution in an ice-acetone bath.
7. After completion of the addition, the mixture was further cooled to 0-5 °C and kept in an ice-water bath for 1 hour.
8. The precipitated 1-methylcyclopropanecarboxamide was collected by filtration, washed with ice water and dried over air to give a white solid product 119.4 g (84% yield) with a melting point of 144-145°C.
1H NMR (DMSO) δ: 7.03 (bs, 1H), 6.83 (bs, 1H), 1.19 (s, 3H), 0.89 (m, 2H), 0.45 (m, 2H).
