Methanol → 4-Ethyl-N-(4-methylbenzylidene)benzeneamine N-oxide

Participants

Reaction Conditions

Reaction Steps

In a 5-L 4-necked round bottom flask equipped with a stirrer, thermometer, dropping funnel and ice-acetone bath was placed 2800 mL of methanol, 300 mL of distilled water, 400 g (2.64 moles, 1.0 equiv.) of 4-ethyl-1-nitrobenzene (11), 349.7 g (2.9 moles, 1.1 equiv.) of p-tolualdehyde, and 367.5 g (5.62 moles, 2.13 equiv.) of zinc powder. The reaction mixture was cooled to 0° C., then with vigorous stirring the dropwise addition of 792.0 g (13.2 moles, 5.0 equiv.) of acetic acid was started. There was a 3-5 minute induction period before the exotherm began. When the acetic acid addition was complete, the reaction mixture was stirred for 1 hour at 10° C. The reaction mixture changes from gray opaque to greenish white, which signifies reaction completion. The reaction mixture was checked for reaction completion by TLC (1 BuOAc, 2 PhCH3, 4 CHCl3) eluted on silica-gel and viewed under short-wave UV light. After the 1 hour reaction period, 500 mL of dichloromethane was added to solubilize any undissolved product. The zinc acetate salts were filtered off (≃1 kg) and washed with 200-300 mL of dichloromethane. (Salts may also be slurried in dichloromethane to remove any remaining product.) The filtrates were stripped to a mush under aspirator vacuum to a pot temperature of 57° C. The green mush was cooled to 25° C. and 1000 ml of dichloromethane and 1000 mL of distilled water were added to the flask. The mixture was stirred vigorously to dissolve all product and salts, then poured into a separatory funnel. The product layer was removed and washed a second time with 1000 mL of fresh distilled water. The product layer was stripped under aspirator vacuum on a steam pot until most of the dichloromethane had been removed. While still hot, with vigorous stirring 2500-3000 mL of heptane was added, then cooled to 20°-25° C. and stirred 1-2 hours. The greenish white product was collected, washed with heptane and dried in a warm air oven overnight. The yield of green-white crystals was 467.9 g (74%): MP 97°-99° C.; IR (KBr) (>C=N) 6.33μ, (N→O) 8.65μ; NMR (CCl4, Me4Si) δ1.3 (T, 3H), 2.4 (S, 3H), 2.7 (Q, 2H), 7.2 (D, 4H), 7.7 (Q, 2H), 7.8 (S, 1H), 8.2 (D, 2H); TLC (1 BuOAc, 2 PhCH3, 4 CHCl3, 4 CHCl3), silica-gel coated plates, viewed under short-wave UV light, major spot for the desired nitrone, Rf=0.50.

Provenance & Evidence