Author Topic: 2,5-DMBA from 1,4-DMB in 89% yield  (Read 1375 times)

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  • Guest
2,5-DMBA from 1,4-DMB in 89% yield
« on: August 15, 2004, 08:08:00 AM »
Hey bees, check out this interesting article. You were wrong if you thought that 2,5-dimethoxybenzaldehyde can't be made directly from 1,4-dimethoxybenzene in good yield.  The reaction is called oxidative hydroxymethylation and they use 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the oxidant. The experimental procedure is simple IMO, the only drawbacks are the use of flash chromatography for the purification of the end product and the price of DDQ.

Synthesis of Aromatic Aldehydes by Oxidative Hydroxymethylation
Olena Branytska, Ronny Neumann
Synlett 1575-1576 (2004)

Abstract: A new high yield method for the synthesis of aromatic aldehydes has been developed. The procedure is based on an acid catalyzed hydroxymethylation of an arene substrate by paraformaldehyde with concurrent selective oxidation of the intermediate aromatic carbinol by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to the aldehyde product.

Typical Procedure

In a typical oxidative hydroxymethylation procedure (Table 1) 10 mmol arene substrate, 3 g (100 mmol) paraformaldehyde, 0.25 mg (0.0025 mmol) H2SO4 and 4.54 g (20 mmol) DDQ were stirred in 10 mL MeCN for 5 h at 80°C. The reaction mixtures were then cooled and the precipitate containing the DDHQ product was filtered and washed twice with EtOAc. The filtrate containing the aryl aldehyde products was purified by flash chromatography and the product was analyzed by 1H NMR and GC. The GLC were carried out with both FID and MS detectors using a Restek Rtx-5MS column (5% phenymethylsilicone, 30 m, 0.32 mm ID, 0.25 mm coating). The determination of the regioselectivity of the reactions and the confirmation of the GC analysis was carried out by 1H NMR.


  • Guest
An Alternative to DDQ?
« Reply #1 on: September 15, 2004, 12:21:00 AM »
DDQ is pricey and by the look of it the synthesis does not seem very easy, personally I'd have no idea where to begin.

According to the article the benzyl alcohol is produced via the reaction of paraformaldahyde and sulfuric acid.

Would it not be possible to substitute anther oxidizing agent (DMSO/SIBX) for DDQ and then oxidize the alcohol to the benzaldehyde.
The good thing about this proceedure is that the DDHQ can be recovered and reoxidized to DDQ however mechanic loss always plays a part in such reactions :(.