3,4,5-Trimethoxybenzaldehyde Synthesis

by Hest


Add 15,2g vanilin and 17,6g Br2 to 75ml AcOH, let the solution stir 1 h. Pour out the solution in 250mL ice-water. filter off the product. Dry and recrystallise from ethanol. mp. 162°C. TLC Rf 0,47 EtOAC:P 1:1

3,5-Dimethoxy-4-Hydroxybenzaldehyde (Syringaldehyde)

In a two-necked round-bottomed flask equipped with a Claisen, and a thermomether into the solution, is dissolved 4.9g Na in 100mL dry methanol. After distilling off 30ml methanol, a solution of 17,9g bromovanilin and 3g Cu(I)Br in 50mL DMF is added in one portion. The distillation is continued until the reaction mixture reaches 100°C (takes app. 1-1.5 h. total methanol distilled off is 80mL). The reaction mixture is poured into 200mL 3M HCL/ice, extracted with 2*75mL EtOAc, the EtOAc is washed with 2*50mL water, dried with MgSO4 and evaporated. Mp.108°C (rec. from ethanol) TLC Rf 0,35 EtOAc:P 1:1


10g 3,5-dimethoxy-4-hydroxy-benzaldehyde, 13.5g K2CO3 and 8.3g dimethylsulfate is dissolved in 80mL dry DMF, the solution is stirred for 2h and then poured into 800mL ice/water, the product is filtered off and xtalised from cyclohexane.

None of these reactions gives below 80% yield after the xtalisation.

The condensation with MeNO2 and Ethylenediammonium diacetate gives ~30% yield.

Reference: Synthesis 308 (1983)