The Duff Reaction: Researching A Modification

Aldehydes are compounds that are commonly used and synthesized in chemistry. Most reactions that form aromatic aldehydes, such as Gattermann and Koch, and Reimer-Tiemann reactions place the aldehyde in the para position in relation to an electron donating group present on the ring or, produce a mixture of para and ortho products. The Duff reaction allows for the formation of aromatic aldehydes almost exclusively in the ortho position in relation to an electron donating group present on the ring using hexamethylenetetramine (HMTA). The down side is that the yields obtained using this method are low, usually ranging from 15-20%.1 Even though the yields are low, the reaction is still useful. Chartterjee and Biswas used the Duff reaction to form indole-3-carboxaldehydes and compared it to the Vilsmeirer-Haack formylation. While the Duff reaction did not have as high a yield it was an easier reaction to conduct.2 Lindoy, Meehan, and Svenstrup used a modified version of the Duff reaction for the mono and diformylation of 4-substituted phenols. Acetic acid was replaced with anhydrous trifluoroacetic acid. The selectivity was able to be controlled by the amount of time the solution was heated at reflux.3 Masurier determined that the Duff reaction was able to produce formyl amido-IP compounds, unless they were substituted at position 5 which caused peri-annelation. IP compounds are also known as imidazo[1,2-a]pyridinic compounds. 4 1 This topic was of interest due to the need for 2-hydroxy-1-naphthaldehyde as part of a previous project. The Duff conducted using typical reaction conditions produced a low yield of the desired product, but the reaction was attempted again with dimethydichlorosilane and the yield was significantly increased. It was then wondered if this result was reproducible and if it could then be applied to other compounds. This then formed the thesis of my project