Duff reaction
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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].
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 synthesis of 3,5-Di-tert-butylsalicylaldehyde [7]
or the synthesis of syringaldehyde [8]
[edit] 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.
[edit] References
- ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1932, 1987.
- ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1934, 1305.
- ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1941, 547.
- ^ Duff, J. C.; Bills, E. J. J. Chem. Soc. 1945, 276.
- ^ Ferguson, L. N. Chem. Rev. 1946, 38, 227.
- ^ Ogata, Y.; Sugiura, F. Tetrahedron 1968, 24, 5001.
- ^ 3,5-Di-tert-butylsalicylaldehyde in Organic Syntheses Coll. Vol. 10, p.96; Vol. 75, p.1 (Article)
- ^ Syringaldehyde in Organic Syntheses Coll. Vol. 4, p.866; Vol. 31, p.92 (Article)
- ^ March, Jerry (1985). Advanced Organic Chemistry, Reactions, Mechanisms and Structure, third Edition, John Wiley & Sons. ISBN 0-471-85472-7.
