Preparation of 3,4,5-Trimethoxybenzaldehyde from Vanillin via 5-Bromovanillin

The overall conversion from vanillin to 3,4,5-trimethoxybenzalde-hyde is depicted in the following reaction scheme  

The bromination of vanillin to afford 5-bromovanillin is performed by contacting vanillin with bromine in an acidic solvent medium. The bromination is generally carried out using at least one mole of bromine for each mole of vanillin. It is preferred to utilize a slight excess, most preferably about 10% excess, bromine in the bromination step. 

Suitable acidic solvent media include, for example, concentrated aqueous mineral acids, e.g., concentrated aqueous hydrobromic acid, preferably 48% aqueous hydrobromic acid glacial acetic acid, and forth. 

The hydrolysis of 5-bromovanillin to 5-hydroxyvanillin is accomplished by contacting the 5-bromovanillin with an alkali metal hydroxide in the presence of copper metal in an aqueous medium. 

Any alkali metal hydroxide is suitable for the present reaction. However, sodium hydroxide is preferred. Generally, at least one mole of alkali metal hydroxide is employed for each mole of 5-bromovanillin. Preferably an excess of alkali metal hydroxide, most preferably a 5 to 10 molar excess is employed. 

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