Duff reaction

What is Duff reaction?

The Duff reaction, also known as the Duff formylation or Duff synthesis, was reported by Duff and Bills in 1932. It involves the formylation of phenols or aromatic amines in a mixture of hexamethylenetetramine (HMT), boric acid H3BO3, and glycerol (see list of acronyms).

Duff reaction - general reaction scheme
Duff Reaction

The Duff reaction typically proceeds very quickly and produces only ortho-formylated products (or occasionally small amounts of ortho, para-disubstituted products) in the case of phenols.

Duff reaction - general reaction scheme
Duff Reaction

However, anilines yield para-products using this procedure. It has been observed that electron-withdrawing groups can hinder or prevent the reaction from occurring, which means that hydroxypyridines and hydroxyquinolines are not suitable for formylation using this method.

Mechanism of reaction

Duff reaction mechanism
Duff reaction mechanism

References

Duff, J. C.; Bills, E. J. “Reactions between hexamethylenetetramine and phenolic compounds. Part I. A new method for the preparation of 3- and 5-aldehydosalicylic acidsJ. Chem. Soc., 1932, 1987-1988
DOI: 10.1039/JR9320001987

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