The Duff Reaction: Researching A Modification

Abstract

Formylation reactions are used to synthesize aldehydes. The Duff reaction is a formylation reaction that uses phenol derivatives, hexamethylenetetramine, acetic acid, and acid to synthesis ortho substituted aromatic aldehydes. The Duff reaction is known for its low percent yield. In a previous project it was found that dimethyldichlorosilane increased the yield of 2-hydroxy-1-naphthaldehyde. This project verified that, but also determined that trimethylsilyl chloride achieved better yields. The modified Duff reaction was studied on 2-naphthol, 4-tert-butylphenol, 8-hydroxyquinoline, and butylated hydroxyanisole. 2-hydroxy-1-naphthaldehyde was synthesized relatively purely with an increased yield over the traditional Duff reaction. Attempted synthesis of 5-tert-butylsalicylaldehyde resulted in slightly higher percent yields over the traditional Duff reaction, but 1H NMR indicated that the yields for both, modified and traditional Duff reactions, were a mixture of 5-tert-butylsalicylaldehyde and starting material. Synthesis of 8-hydroxy-7-quinolinecarboxaldehyde was attempted. The yields were higher for the traditional Duff reaction than the modified reaction. 1H NMR indicated that the modified and traditional Duff reaction produced products that were so impure it was not possible to determine the desired product from the impurities. Synthesis of 3-(1,1-dimethylethyl)-2-hydroxy-5-methoxy-benzaldehyde resulted in relatively high yields for both the modified and traditional Duff reactions with the modified having a slightly higher yield. 1H NMR showed that the product was not entirely pure. The impure product and p-anisidine were used to synthesize 2-(1,1-dimethylethyl)-4-methoxy-6-[[(4-methoxyphenyl)imino]methyl]-phenol. The yields of the imine were higher for the reactions that originated from the modified reaction. 1H NMR showed that the imine formed was pure. Trimethylsilyl chloride was able to increase the yield for some of the compounds. The reason for the modest and variable yield improvement is unknown.