P-Anisidine → N-(4-Methoxyphenyl)Acetamide

Temperature

30 °C

A 2.5 liter flask is charged with 800 g of chlorobenzene. With stirring, 123.2 g of 100% p-anisidine (preferably as melt) are then added. Then 102 g of acetic anhydride are added dropwise in the course of about 15 minutes, whereupon the temperature rises to 65° C. After stirring for 15 minutes at 65° C., the mixture is cooled to about 30° C. within about 10 minutes using a cooling bath, whereupon beige-coloured crystals of the acetanisidide begin to precipitate in the temperature range from about 45° C. The resultant suspension is slightly viscous, but readily stirrable. The addition of 800 g of 92% sulfuric acid is then commenced, with care being taken that the temperature does not much exceed 30°-40° C. The addition takes about 10 minutes. With further cooling, the addition of 101.2 g of 62.3% HNO3 is commenced immediately at a maximum temperature of 25° C. During the addition, the temperature can be allowed to rise to 20°-25° C. With the first few drops of HNO3 the emulsion starts becoming fluid immediately and the original blue colour changes to brown. The addition is complete after about 10 minutes and the batch is stirred for 20 minutes at 20° to 25° C. until the reaction is complete. Volume of the solution: about 1450 ml. The reaction mixture is then charged into a 2 liter separating funnel, whereupon a lower, dark-brown layer separates immediately. The upper, chlorobenzene layer is largely colourless or only a pale yellow colour. The lower layer is then passed slowly into a glass beaker, into which a mixture of 300 g of ice and water is stirred. The temperature is kept at around +5° C. by the constant addition of altogether about 1500 g of ice (duration c. 30 minutes). A thick yellow suspension is finally obtained. The suspension is stirred and then filtered. The filter cake is washed with 350 ml of ice-water, well pressed and, if desired, dried. Mother liquor and wash water are combined. The amount of chlorobenzene remaining in the separating funnel is about 760 g and, after replenishment to the original amount, can be re-used in the next batch. Yield: about 193 to 195 g of 4-acetamido-2-nitro-anisole in 99% purity. Melting point: about 150°-151° C.

1. customrises to 65° C
2. stirringAfter stirring for 15 minutes at 65° C.
3. customto precipitate in the temperature range from about 45° C
4. additionThe addition of 800 g of 92% sulfuric acid
5. customdoes not much exceed 30°-40° C
6. additionThe addition
7. additionWith further cooling, the addition of 101.2 g of 62.3% HNO3
8. customis commenced immediately at a maximum temperature of 25° C
9. additionDuring the addition
10. customto rise to 20°-25° C
11. additionThe addition
12. waitis complete after about 10 minutes
13. stirringthe batch is stirred for 20 minutes at 20° to 25° C. until the reaction
14. additionThe reaction mixture is then charged into a 2 liter
15. customseparating funnel
16. additiona mixture of 300 g of ice and water
17. stirringis stirred
18. additionThe temperature is kept at around +5° C. by the constant addition of altogether about 1500 g of ice (duration c. 30 minutes)
19. customA thick yellow suspension is finally obtained
20. stirringThe suspension is stirred
21. filtrationfiltered
22. washThe filter cake is washed with 350 ml of ice-water
23. customdried
24. washMother liquor and wash water

ORD record

ord-cdff9530d26d436aa177f8f54aa24dda

Source dataset

uspto-grants-1982_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04339618