Synthesis of 2,5-dimethoxybenzaldehyde from anise oil (small scale)

[HIGGS BOSSON]

Yes, but to produce 2,5-dmbenzaldehyde through the reaction you posted this could be the starting material, no?

DocXIt's impossible. If the pair position is already occupied by the methoxy group, it cannot be shifted to the position along the benzene ring in 2 or 5.

 

[summer_child]

It's impossible. If the pair position is already occupied by the methoxy group, it cannot be shifted to the position along the benzene ring in 2 or 5.

HIGGS BOSSONYou can just as the synthesis suggest , Bayer-Villiger oxidation of the aldehyde will give 4-methoxyphenol, and formylation yields 2-hydroxy-5-methoxybenzaldehyde.

 

[Joker_55555]

Step 1. Anisaldehyde from anethole via oxidative cleavage.
View attachment 1403
20 g anise oil was suspended in a mixture of 150 mL water and 30 mL conc. sulfuric acid; addition of 55 g sodium bichromate at such a rate that the temperature did not exceed 40 °C. The reaction mixture was extracted with 4 x 125 mL toluene and the solvent evaporated. The residual oil was vacuum distilled to yield 9.1 g anisaldehyde.


Step 2. O-formyl-4-methoxyphenol.
View attachment 1404
6 mL anisaldehyde was dissolved in 75 mL dichloromethane (DCM). A mixture of 12g hydrogen peroxide 60% aq.soln and 10 mL conc. formic acid was added over 30 min. The reaction mixture was gently refluxed for 21 h.


Step 3. 4-methoxyphenol.
View attachment 1405
Evaporating the solvent from reaction Step 2 and taking up the residue in 100 mL aqueous NaOH (20%) (25 mL MeOH as co-solvent) yielded 4.1 g 4-methoxyphenol as a white crystalline product after the usual work-up and purification steps.


Step 4. Reimer-Tiemann formylation of 4-methoxyphenol to 2-hydroxy-5-methoxybenzaldehyde.
View attachment 1407
124.1 g 4-methoxyphenol was dissolved in NaOH solution (320 g NaOH in 400 mL water). In total, 161 mL chloroform was added. The usual work-up and steam distillation yielded 109.8 g of a clear, yellow oil that did not solidify upon standing at room temperature.


Step 5. Methylation of 2-hydroxy-5-methoxybenzaldehyde.
View attachment 1408
The yellow oil from Step 4 was used without further purification. A 250 mL RB flask was charged with 100 mL acetone, 14 g anhydrous potassium carbonate and 10 g 2-hydroxy-5-methoxy-benzaldehyde. The mixture was brought at reflux temperature and 11 g dimethyl sulfate was added. The reaction was continued for 4 hours. The solvent is evaporated and the crude end product crystallized in cold water. Recrystallization from EtOH/water yielded 8.3 g 2,5-dimethoxybenzaldehyde.
View attachment 1410

William DampierHi frend in step 4, At this stage you did not convert the salt with dilute acid, your writing is incomplete and the yield you reported is high, is this yield real???

200g of hydroquinone monomethyl ether were dissolved in a solution of 190 g of sodium hydroxide in 550 ml of water and the resulting solution was heated to 50°C on a water bath. To the solution maintained at 50-60°C, there were added dropwise 420 g of chloroform and a solution of 560 g of sodium hydroxide in 500 ml of water from two separate dropping funnels and, thereafter, the reaction mixture was heated for 1 hour at a temperature of 50-60°C and atmospheric pressure. After cooling, the precipitated sodium salt of 2-hydroxy-5-methoxybenzaldehyde was recovered by filtration and washed with 100 ml of ethanol.The sodium salt thus obtained was dissolved in 800 ml of water, slightly acidified with dilute sulphuric acid (1200 mL of 3N dilute sulphuric acid were added at room temperature and atmospheric pressure) and then extracted with 200 ml of toluene. The extract was dried with calcium chloride, distilled to eliminate toluene and then distilled under reduced pressure to obtain 132 g of 2-hydroxy-5 methoxybenzaldehyde having a boiling point of 110°C/5mmHg.

 

[MadHatter]

Hi frend in step 4, At this stage you did not convert the salt with dilute acid, your writing is incomplete and the yield you reported is high, is this yield real???

200g of hydroquinone monomethyl ether were dissolved in a solution of 190 g of sodium hydroxide in 550 ml of water and the resulting solution was heated to 50°C on a water bath. To the solution maintained at 50-60°C, there were added dropwise 420 g of chloroform and a solution of 560 g of sodium hydroxide in 500 ml of water from two separate dropping funnels and, thereafter, the reaction mixture was heated for 1 hour at a temperature of 50-60°C and atmospheric pressure. After cooling, the precipitated sodium salt of 2-hydroxy-5-methoxybenzaldehyde was recovered by filtration and washed with 100 ml of ethanol.The sodium salt thus obtained was dissolved in 800 ml of water, slightly acidified with dilute sulphuric acid (1200 mL of 3N dilute sulphuric acid were added at room temperature and atmospheric pressure) and then extracted with 200 ml of toluene. The extract was dried with calcium chloride, distilled to eliminate toluene and then distilled under reduced pressure to obtain 132 g of 2-hydroxy-5 methoxybenzaldehyde having a boiling point of 110°C/5mmHg.

Joker_333So this is another write-up using hydroquinine as starting material? Could you please provide osurce for this? Is it a synth that you performed yourself or is it just a quote?

 

[summer_child]

So this is another write-up using hydroquinine as starting material? Could you please provide osurce for this? Is it a synth that you performed yourself or is it just a quote?

DocXIt's taken from here https://www.thevespiary.org/rhodium/Rhodium/chemistry/25-dimethoxybenzaldehyde.html

 

[Joker_55555]

source is erowid

So this is another write-up using hydroquinine as starting material? Could you please provide osurce for this? Is it a synth that you performed yourself or is it just a quote?

DocX