Duff reaction

The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source.^{[1][2][3][4][5][6]} It is named after James Cooper Duff, who was a chemist at the College of Technology, Birmingham, roughly 1920-1950.

The electrophilic species in this electrophilic aromatic substitution reaction is the iminium ion CH₂⁺NR₂. The initial reaction product is an iminium which is hydrolyzed to the aldehyde. See mechanism below. The reaction requires strongly activating substituents on the aromatic ring such as in a phenol.

Examples are the synthesis of 3,5-di-tert-butylsalicylaldehyde:^[7]

and the synthesis of syringaldehyde:^[8]

Reaction mechanism

The reaction mechanism displayed below ^[9] demonstrates step by step how hexamine donates a methine group to an aromatic substrate via a series of equilibria reactions, with iminium ion intermediates. Initially, addition to the aromatic ring results in an intermediate at the oxidation state of a benzylamine. An intramolecular redox reaction then ensues, raising the benzylic carbon to the oxidation state of an aldehyde. The oxygen atom is kindly provided by water on acid hydrolysis in the final step.

References

1. ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1932, 1987.
2. ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1934, 1305.
3. ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1941, 547.
4. ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1945, 276.
5. ^ Ferguson, L. N. (1946), "The Synthesis of Aromatic Aldehydes", Chem. Rev. 38: 227–254, doi:10.1021/cr60120a002, PMID 21024865 .
6. ^ Ogata, Y.; Sugiura, F. Tetrahedron 1968, 24, 5001.
7. ^ 3,5-Di-tert-butylsalicylaldehyde in Organic Syntheses Coll. Vol. 10, p.96; Vol. 75, p.1 (Article)
8. ^ C. F. H. Allen and Gerhard W. Leubner (1963), "Syringic aldehyde", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv4p0866 ; Coll. Vol. 4: 866 
9. ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7 

See also

• Bouveault aldehyde synthesis
• Bodroux-Chichibabin aldehyde synthesis
• Reimer-Tiemann reaction
• Sommelet reaction
• Vilsmeier-Haack reaction