Hydrochloric Acid → 2-Hydroxy-5-(methylsulfanyl)benzaldehyde

HRID 722280Notes

Reaction equation

HRID 722280 reaction equation
C([Mg]Br)C.[CH3:5][S:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1.CN(C)P(N(C)C)(N(C)C)=O.[CH2:25]=[O:26].Cl>C(OCC)C.C1(C)C=CC=CC=1>[CH3:5][S:6][C:7]1[CH:12]=[C:11]([CH:25]=[O:26])[C:10]([OH:13])=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 12679HexamethylphosphoramideHCID 140864-(Methylthio)phenolHCID 178418443HCID 178418443, compound

Product 1

HCID 124333972-Hydroxy-5-(methylsulfanyl)benzaldehydeYield 31.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
90 °C

Procedure

Ethyl magnesium bromide (38 mL of a 3.0 M solution in diethyl ether, 113.8 mmole) was chilled with an ice-water bath. To the chilled solution was added a solution of 4-(methylthio)phenol (15.95 g, 113.8 mmole) in diethyl ether (30 mL) over 0.15 hour during which time gas was evolved. The reaction was held at 0° C. for 0.5 hour, at room temperature for 0.5 hour, and the addition funnel replaced with a distillation head. Toluene (250 mL) and the diethyl ether were distilled out of the reactor. The reaction was cooled, toluene (250 mL) and hexamethylphosphoramide (HMPA) (19.8 mL, 20.4 g, 113.8 mmole) were added, and the resulting mixture was stirred for 0.25 hours. The distillation head was replaced with a condenser and paraformaldehyde (8.5 g, 284.4 mmole) was added. The reaction was heated to 90° C. for 3 hours. The reaction mixture was cooled to room temperature, was acidified with 1N HCl and the layers separated. The organic phase was washed with water, and with brine, dried over MgSO4, filtered, and concentrated in vacuo to yield a solid. This solid was purified by silica chromatography (hexanes-ethyl acetate, 5:1) yielding the salicylaldehyde as a yellow crystalline solid (6.01 g) of suitable purity to be used in the next reaction without further purification.

Workup

  1. distillationToluene (250 mL) and the diethyl ether were distilled out of the reactor
  2. temperatureThe reaction was cooled
  3. customThe distillation head was replaced with a condenser
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customthe layers separated
  6. washThe organic phase was washed with water
  7. dry with materialwith brine, dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a solid
  11. customThis solid was purified by silica chromatography (hexanes-ethyl acetate, 5:1)

Sources & evidence

ORD record
ord-74d1dc5ceef8437090d587ad186c722f
Source dataset
uspto-grants-2006_11
Patent number
US07138411B2

Reaction notes

Loading…