Formaldehyde → 2-Hydroxy-5-methyl-3-(2-phenylpropan-2-yl)benzaldehyde

HRID 1062520Notes

Reaction equation

HRID 1062520 reaction equation
C([Mg]Br)C.[C:5]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[OH:21])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:7])[CH3:6].[CH2:22]=[O:23].C(N(CC)CC)C>C1COCC1.C1(C)C=CC=CC=1>[C:5]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH:22]=[O:23])[C:15]=1[OH:21])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 948562-Cumyl-4-methylphenolHCID 178418443HCID 178418443, compound

Product 1

HCID 219514192-Hydroxy-5-methyl-3-(2-phenylpropan-2-yl)benzaldehydeYield 92.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Into a 500 ml reactor thoroughly purged with nitrogen, 21.0 ml of an ether solution containing 63.1 mmol of ethylmagnesium bromide and 40 ml of THF were introduced. To the reactor, a solution containing 13.61 g (60.1 mmol) of 2-cumyl-4-methylphenol diluted with 20 ml of a THF was dropwise added at 0° C. over a period of 1 hour, then the temperature of the system was slowly raised to room temperature, and the reaction solution was stirred at room temperature for 30 minutes. Then, 220 ml of toluene was added, and the system was heated to 100° C. to distill off about 50 ml of a mixed solution of ether and THF, whereby an opaque white slurry was obtained. After the slurry was cooled to 24° C., 4.37 g (145.5 mmol) of paraformaldehyde and 12.0 ml (86.0 mmol) of triethylamine were added, followed by stirring at 90° C. for 1 hour. The reaction solution was allowed to cool to room temperature and then quenched with 42 ml of 18% hydrochloric acid. The organic layer was concentrated, and the resulting liquid was purified by silica gel column chromatography to obtain 14.13 g (yield: 92%) of 3-cumyl-5-methylsalicylaldehyde.

Workup

  1. customInto a 500 ml reactor thoroughly purged with nitrogen, 21.0 ml of an ether solution
  2. additionwere introduced
  3. additionwas dropwise added at 0° C. over a period of 1 hour
  4. temperaturethe system was heated to 100° C.
  5. distillationto distill off about 50 ml of a mixed solution of ether and THF, whereby an opaque white slurry
  6. customwas obtained
  7. temperatureAfter the slurry was cooled to 24° C.
  8. stirringby stirring at 90° C. for 1 hour
  9. temperatureto cool to room temperature
  10. customquenched with 42 ml of 18% hydrochloric acid
  11. concentrationThe organic layer was concentrated
  12. customthe resulting liquid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-40804a8118114aeeb14265f15e46fe02
Source dataset
uspto-grants-2005_11
Patent number
US06962890B2

Reaction notes

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