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

Temperature

0 °C

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.

1. customIn a 5-L 4-necked round bottom flask equipped with a stirrer
2. stirringthe reaction mixture was stirred for 1 hour at 10° C
3. customreaction completion
4. washeluted on silica-gel
5. customAfter the 1 hour reaction period, 500 mL of dichloromethane
6. additionwas added
7. filtrationThe zinc acetate salts were filtered off (≃1 kg)
8. washwashed with 200-300 mL of dichloromethane
9. customto remove any remaining product
10. customwere stripped to a mush under aspirator vacuum to a pot temperature of 57° C
11. temperatureThe green mush was cooled to 25° C.
12. addition1000 ml of dichloromethane and 1000 mL of distilled water were added to the flask
13. stirringThe mixture was stirred vigorously
14. dissolutionto dissolve all product and salts
15. additionpoured into a separatory funnel
16. customThe product layer was removed
17. washwashed a second time with 1000 mL
18. distillationof fresh distilled water
19. customhad been removed
20. stirringWhile still hot, with vigorous stirring 2500-3000 mL of heptane
21. additionwas added
22. temperaturecooled to 20°-25° C.
23. stirringstirred 1-2 hours
24. customThe greenish white product was collected
25. washwashed with heptane
26. customdried in a warm air oven overnight

ORD record

ord-5feeefb41a1a4825985579aaa9e078c8

Source dataset

uspto-grants-1993_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05214194