Chemical Properties
yellow crystalline solid
Uses
2,5-Dimethoxybenzaldehyde is used in the preparation of 2,5-dimethoxyphenethylamine, which is utilized to prepare psychoactive drugs such as 2,5-dimethoxy-4-bromophenethylamine, 2,5-dimethoxy-4-iodophenethylamine and 4-Chloro-2,5-dimethoxy-phenethylamine. It acts as an intermediate in organic synthesis.
Application
2,5-Dimethoxybenzaldehyde, also known as 2C-H, is an organic compound and a benzaldehyde derivative. It can be used to produce 2,5-dimethoxyphenethylamine. 2C-H is also used to produce many other substituted phenethylamines such as 2C-B, 2C-I and 2C-C.
Definition
ChEBI: 2,5-dimethoxy-Benzaldehyde is a dimethoxybenzene.
Preparation
2,5-Dimethoxybenzaldehyde synthesis: Anethole is oxidized to anisaldehyde , which after isolation is subjected to a BaeyerVilliger oxidation reaction with performic or peracetic acid. The O-formyl-4-methoxyphenol obtained this way is hydrolyzed . 4-Methoxyphenol is subsequently formylated using the Reimer-Tiemann method and the obtained 2-hydroxy-5-methoxybenzaldehyde is methylated with dimethylsulfate to 2,5-dimethoxybenzaldehyde.
Reaction
A : Anisaldehyde from anethole via oxidative cleavage: 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.
B : O-formyl-4-methoxyphenol: 6 mL anisaldehyde was dissolved in 75 mL dichloromethane (DCM). A mixture of 12 g hydrogen peroxide and 10 mL conc. formic acid was added over 30 min. The reaction mixture was gently refluxed for 21 h.
C: B 4-methoxyphenol: Evaporating the solvent from reaction mixture 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.
D : Reimer-Tiemann formylation of 4-methoxyphenol: 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 (GC/MS: 94% 2-hydroxy-5-methoxybenzaldehyde).
E: D Methylation of 2-hydroxy-5-methoxybenzaldehyde: The yellow oil from 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-methoxybenzaldehyde; 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 (GC/MS: 98%+ 2,5-dimethoxybenzaldehyde)
Synthesis
The synthesis of 2,5-dimethoxybenzaldehyde (2,5-DMBA) is mainly achieved through several well-established chemical methods, typically using readily available precursors as starting materials. A common industrial method is the formylation of 1,4-dimethoxybenzene (hydroquinone dimethyl ether), usually using the Vilsmeier-Haack reaction with reagents including N,N-dimethylformamide and phosphorus oxychloride; or using a Friedel-Crafts-type reaction, starting with 1,1-dichlorodimethyl ether, directly introducing the aldehyde group onto the activated aromatic ring. In addition, 2,5-DMBA can also be prepared by oxidizing the methyl group of 2,5-dimethoxytoluene, or through a multi-step reaction, starting with p-methoxyphenol, first undergoing a Reimer-Tiemann reaction to generate 2-hydroxy-5-methoxybenzaldehyde, and finally methoxylating it with dimethyl sulfate. These methods offer flexibility in terms of scale and precursor availability, making 2,5-DMBA a versatile intermediate for the synthesis of a wide range of fine chemicals, particularly psychoactive compounds such as 2C-H.
