Synthesis of Aromatic Aldehydes by Oxidative Hydroxymethylation

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 paraformal- dehyde with concurrent selective oxidation of the intermediate aro- matic carbinol by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to the aldehyde product. The discovery of new methods for the preparation of chemicals is an important goal in the development of modern methods for chemical synthesis. Of special signif- icance are the use procedures that minimize amounts of waste and by-products. In this context, the preparation of rather simple aromatic aldehydes presents a surprisingly difficult challenge. Perusal of basic organic textbooks will show that many different approaches can be taken towards the synthesis of aromatic aldehydes including: (a) direct oxidation of methylaromatic substrates to aromatic alde- hydes using stoichiometric reagents such as silver(II) oxide, ceric ammonium nitrate, selenium dioxide, manga- nese dioxide, chromyl chloride and periodic acid; 1 (b) chlorination/bromination of methylaromatic substrates in the presence of peroxides and/or light as radical chain ini- tiators followed by hydrolysis to the required aldehyde; (c) oxidation of the methylaromatic substrates to the cor- responding carboxylic acids with oxidants such as nitric acid, chromic acid and derivatives and potassium permanganate 1 followed by halogenation to acyl halides and catalytic hydrogenation to the corresponding aromat- ic aldehydes using palladium-based catalysts; 2 (d) haloge- nation of arenes to the corresponding haloarenes followed by carbonylation with carbon monoxide in the presence of noble metal based catalysts (usually palladium) to yield aromatic aldehydes; 3 (e) formylation of arenes with vari- ous reagents notably (i) aluminum chloride/gaseous hy- drogen chloride/carbon monoxide (Gatterman-Koch reaction), 4 (ii) zinc cyanide/hydrogen chloride (Gatterman reaction), 5 (iii) phosphorous oxychloride disubstituted formamides (Vilsmeier-Haack reaction), 6 (iv) chloro- form/sodium hydroxide (Reimer-Tiemann reaction), 7 (v) dichloromethyl methyl ether/aluminum chloride, 8 and (vi) formylfluoride/boron trifluoride. 9 All these methods are