Vanillin → 4-Ethoxy-3-methoxybenzaldehyde

HRID 1175207Notes

Reaction equation

HRID 1175207 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH3:11].[CH:12](O)(C)[CH3:13].[OH-].[Na+].C(Br)C>C1OCCOCCOCCOCCOCCOC1.O>[CH2:12]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH3:11])[CH3:13]

Participants

7

Reactant 4

HCID 1183VanillinHCID 3776IsopropanolHCID 6332Ethyl BromideHCID 14798Sodium Hydroxide

Product 1

HCID 671164-Ethoxy-3-methoxybenzaldehydeYield 91%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

A 1-liter four-necked flask fitted with thermometer, mechanical stirrer, and reflux condenser was charged with 62 g 4-hydroxy-3-methoxybenzaldehyde (0.41 mol) and 400 ml isopropyl alcohol. The mixture was stirred for 20 min, and then a 120 ml water solution containing 5 g 18-crown-6 ether and 106.3 g sodium hydroxide (2.66 mol) was gradually dropped thereto using a constant pressure funnel. After dropping, the mixture was stirred for 30 min, and then heated to 60° C. At this temperature, 67.3 g ethyl bromide (0.62 mol) was introduced within 5-6 hours and the reaction was monitored with TLC. After the reaction finished, the mixture was cooled to 15° C., and 400 ml water was then added to quench the reaction. The resulting mixture was extracted three times with ether (300 ml×3). The organic layer was washed with water to pH=7, and dried with anhydrous magnesium sulfate. Part of the ether was removed by flash distillation and then large amount of petroleum ether was added to precipitate crude product. The crude product was recrystallized from diethyl ether/petroleum ether to give 67 g 4-ethoxy-3-methoxybenzaldehyde in a yield of 91%. 1H-NMR (ppm) δ: 9.87 (1H, s; —CHO); 7.31 (1H, m; 2-ArH); 7.26 (1H, m; 6-ArH); 6.86 (1H, m; 5-ArH); 3.98 (2H, q; —CH2); 3.73 (3H, s; —OCH3); 1.42 (3H, t; —CH3). MS (m/Z): 180 (M+).

Workup

  1. customA 1-liter four-necked flask fitted with thermometer, mechanical stirrer
  2. temperaturereflux condenser
  3. additionwas gradually dropped
  4. stirringthe mixture was stirred for 30 min
  5. temperaturethe mixture was cooled to 15° C.
  6. customto quench
  7. customthe reaction
  8. extractionThe resulting mixture was extracted three times with ether (300 ml×3)
  9. washThe organic layer was washed with water to pH=7
  10. dry with materialdried with anhydrous magnesium sulfate
  11. customPart of the ether was removed by flash distillation
  12. additionlarge amount of petroleum ether was added
  13. customto precipitate crude product
  14. customThe crude product was recrystallized from diethyl ether/petroleum ether

Sources & evidence

ORD record
ord-8cd27b305c6c4fecbebaa003f3e4460d
Source dataset
uspto-grants-2010_11
Patent number
US07838706B2

Reaction notes

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