Acetaminophen → 5-Acetamidosalicyaldehyde

HRID 2360948Notes

Reaction equation

HRID 2360948 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.FC(F)(F)[C:14](O)=[O:15].C1N2CN3CN(C2)CN1C3.C1(C)C=CC=CC=1.CO>C(OCC)(=O)C.O>[CH:14]([C:7]1[CH:6]=[C:5]([NH:8][C:9](=[O:11])[CH3:10])[CH:4]=[CH:3][C:2]=1[OH:1])=[O:15]

Participants

7

Reactant 4

HCID 1983AcetaminophenHCID 4101HexamethylenetetramineHCID 6422Trifluoroacetic acidHCID 21867641Toluene methanol

Product 1

HCID 125851785-AcetamidosalicyaldehydeYield 47.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

25 g of N-(4-hydroxyphenyl)acetamide (0.165 mol; 1 equivalent) and 92.7 g of trifluoroacetic acid (0.661 mol; 4 equivalents) are placed in a 500 ml reactor. The mixture is stirred, and 92.7 g of hexamethylenetetramine (0.661 mol; 4 equivalents) are then added portionwise. The reaction is exothermic. A temperature of 70° C. is maintained over 18 hours, while monitoring the reaction progress by thin-layer chromatography (eluent: 8/2 toluene/methanol). The reaction medium is allowed to warm to room temperature. It becomes thick, and is diluted by addition of 200 ml of water to facilitate the stirring. 100 ml of ethyl acetate are then added. Stirring is continued and the phases are allowed to separate by settling. 300 ml of water and 200 ml of ethyl acetate are added, the mixture is stirred and the phases are then allowed to separate by settling. The aqueous phase is removed first, then the organic phase. The organic phase is then washed twice with 150 ml of water in total to collect, after phase separation, a new organic phase and a new aqueous phase. This new organic phase is then concentrated on a rotary evaporator (T=45° C.; 50 mmHg). 14 g of the desired compound are thus obtained in the form of crystals recovered from an orange-red solution.

Workup

  1. temperatureto warm to room temperature
  2. stirringStirring
  3. customto separate
  4. addition300 ml of water and 200 ml of ethyl acetate are added
  5. stirringthe mixture is stirred
  6. customto separate
  7. customThe aqueous phase is removed first
  8. washThe organic phase is then washed twice with 150 ml of water in total
  9. customto collect
  10. customafter phase separation
  11. concentrationThis new organic phase is then concentrated on a rotary evaporator (T=45° C.; 50 mmHg)

Sources & evidence

ORD record
ord-9d0492c6373744a78544a506fb25318c
Source dataset
uspto-grants-2014_04
Patent number
US08686180B2

Reaction notes

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