Nitric Acid → N-(5-Chloro-2-hydroxy-3-nitrophenyl)acetamide

HRID 2114597Notes

Reaction equation

HRID 2114597 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([OH:17])=[C:11]([NH:13][C:14](=[O:16])[CH3:15])[CH:12]=1.[N+:18]([O-])([OH:20])=[O:19]>O>[Cl:6][C:7]1[CH:8]=[C:9]([N+:18]([O-:20])=[O:19])[C:10]([OH:17])=[C:11]([NH:13][C:14](=[O:16])[CH3:15])[CH:12]=1

Participants

5

Reactant 3

HCID 944Nitric Acid2×HCID 1118Sulfuric Acid2×HCID 952582-Acetylamino-4-chlorophenol

Product 1

HCID 22142329N-(5-Chloro-2-hydroxy-3-nitrophenyl)acetamideYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

224.5 g of sulphuric acid (50% w/w) was dissolved in 300 ml of water and cooled to 25° C. while stirring under a mild nitrogen purge. 185.1 g (1 mole) of N-(5-chloro-2-hydroxyphenyl) acetamide prepared according to Example 1a was added to the diluted sulphuric acid and mixed intensively. 4 ml of nitric acid 65% w/w was added to the foam formed on top of the reaction mixture at low stirring speed. The stirring speed was increased and 75 ml of nitric acid 65% w/w was added in 45 minutes, while maintaining the temperature between 23 and 26° C. The mixture was stirred vigorously for an additional 1 hour at 23-26° C. Then the mixture was cooled to 0-5° C. and vigorously stirred at this temperature for 1 hour. The solid was filtered off quickly, washed three times with 300 ml of cold water, sucked for at least 30 minutes and dried at 50° C. and 100 mbar under a gentle nitrogen stream till dry. The crude product was suspended in 2000 ml 96% ethanol, heated till reflux and refluxed under stirring for about 15 minutes until a clear solution was obtained. The solution was cooled to 25-30° C. in about 1 hour, while stirring slowly, further cooled to 0-5° C. and stirred at this temperature for an additional hour. The solid was filtered off, washed twice with 250 ml of cold 96% ethanol, and dried at 50° C. and 100 mbar under a gentle nitrogen stream till dry. Yield about 78%.

Workup

  1. custompurge
  2. additionmixed intensively
  3. customformed on top of the reaction mixture at low stirring speed
  4. temperatureThe stirring speed was increased
  5. temperaturewhile maintaining the temperature between 23 and 26° C
  6. stirringThe mixture was stirred vigorously for an additional 1 hour at 23-26° C
  7. temperatureThen the mixture was cooled to 0-5° C.
  8. stirringvigorously stirred at this temperature for 1 hour
  9. filtrationThe solid was filtered off quickly
  10. washwashed three times with 300 ml of cold water
  11. waitsucked for at least 30 minutes
  12. customdried at 50° C.
  13. customtill dry
  14. temperatureheated
  15. temperaturetill reflux
  16. temperaturerefluxed
  17. stirringunder stirring for about 15 minutes until a clear solution
  18. customwas obtained
  19. temperatureThe solution was cooled to 25-30° C. in about 1 hour
  20. stirringwhile stirring slowly
  21. temperaturefurther cooled to 0-5° C.
  22. stirringstirred at this temperature for an additional hour
  23. filtrationThe solid was filtered off
  24. washwashed twice with 250 ml of cold 96% ethanol
  25. customdried at 50° C.
  26. customtill dry

Sources & evidence

ORD record
ord-25e1b243648d4a4bb1dfe557461d912b
Source dataset
uspto-grants-2008_10
Patent number
US07435738B2

Reaction notes

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