Piperonal from Ethylvanillin

The aim of this work was to develop a simple yet reproducible method for the synthesis of piperonal using readily available, only slightly toxic or untoxic chemicals. The synthesis takes place in two steps, each carried out in a home-built autoclave at comparatively low temperatures (70–85 °C) in a water bath. The setup is simple: just add the reagents to the reactor, seal it, and leave it in the water bath for a calculated amount of time - minimal workup required.

1. Ethyl vanillin (32.2 g, 200 mmol) was added with stirring to concentrated sulfuric acid (196.6 g, 106 mL, 2000 mmol) in a PVDF-lined stainless steel autoclave. The autoclave was purged with argon, sealed, and placed in a water bath at 70 °C for 4 hours under continuous stirring. After completion of the reaction, the mixture was cooled to room temperature and poured onto 420 g of crushed ice in a 1000 mL Erlenmeyer flask. Stirring was continued until a solid precipitate formed. The supernatant was decanted, and the solids were collected by filtration. The crude product was obtained as a light gray crystalline mass. It was recrystallized twice from hot water (approximately 80 mL at 60 °C). During the second recrystallization, the still-hot saturated aqueous solution was subsequently washed with 30 mL of xylene. After separation and cooling, pure protocatechualdehyde crystallized from the aqueous phase. Yield after drying: 17.4 g, 65%; melting point: 152 °C. This product was used in the subsequent step without further purification.

2. Protocatechualdehyde (11.7 g, 85 mmol) and tetrabutylammonium bromide (2.7 g) were added to a cooled solution of sodium hydroxide (10.2 g, 225 mmol) in water (85 mL) in the autoclave. After complete dissolution, dichloromethane (85 mL) was added. The autoclave was filled with argon, sealed, and kept in a water bath at 85 °C for 6 hours with continuous stirring. After this period, the reaction mixture was cooled to room temperature, and the excess dichloromethane was recovered by simple distillation.
The product was isolated by steam distillation; a total of 500 mL was collected. The distillate was saturated with NaCl and extracted with a total of 40 mL of dichloromethane. 3.8 g of crude piperonal was obtained after evaporation (30% yield).

Production of protocatechualdehyde, Patent JPH10265428A
High Selectivity in the Oxidation of Mandelic Acid Derivatives and in O-Methylation of Protocatechualdehyde


the autoclave and crude protocatechualdehyde settled down in the ice water


crude and twice recrystallized protocatechualdehyde

steam distillate and crude piperonal after dichloromethane evaporation

[Edited on 30-9-2025 by beeology]

Quote: Originally posted by Mateo_swe

Have you tried with plain vanillin as starting material and if so what was the yield of the first stage?

Quote: Originally posted by FableP

Presumably if its just a PTC, others (more easily sourced or cheaper) could be substituted.

Interesting, maybe i can do some experiments during Christmas/new year when i have some time.
I do have some 48% HBr.

I wonder if this would work on ethyl vanillin.






[Edited on 2025-11-28 by Mateo_swe]

Quote: Originally posted by Mateo_swe

Yes i agree, if he didn´t buy the 5-Hydroxyeugenol it it would be interesting to know how it was prepared. He probably bought it online though if i were to guess. The DBM also, it´s a better methylating agent than DCM but its not easily commonly available so if it was prepared it would be interesting info.

DBM was bought.

the hydroxyeugenol was made by duff reaction from eugenol

i can write a writeup in an new topic for u guys.

so my research wont go to waste.. for some years, eventually everything ll go to waste sooner or later