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, around 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 electron donating substituents on the aromatic ring such as in a phenol. Formylation occurs ortho to the electron donating substituent preferentially, unless the ortho positions are blocked, in which case the formylation occurs para.[7]
Examples are the synthesis of 3,5-di-tert-butylsalicylaldehyde:[8]
![Duff reaction 3,5-di-tert-butylsalicylaldehyde](http://upload.wikimedia.org/wikipedia/commons/a/a0/Duff_reaction.png)
and the synthesis of syringaldehyde:[9]
![Duff reaction syringaldehyde](http://upload.wikimedia.org/wikipedia/commons/4/4b/Duff_reaction2.png)
Reaction mechanism
The reaction mechanism displayed below [10] 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 provided by water on acid hydrolysis in the final step.
![Duff reaction mechanism](http://upload.wikimedia.org/wikipedia/commons/1/15/Duff_Reaction_Mechanism3.png)
See also
- Bouveault aldehyde synthesis
- Bodroux-Chichibabin aldehyde synthesis
- Reimer-Tiemann reaction
- Sommelet reaction
- Vilsmeier-Haack reaction
References
- ^ Duff, J. C.; Bills, E. J. (1932). "273. Reactions between hexamethylenetetramine and phenolic compounds. Part I. A new method for the preparation of 3- and 5-aldehydosalicylic acids". J. Chem. Soc.: 1987. doi:10.1039/jr9320001987.
- ^ Duff, J. C.; Bills, E. J. (1934). "282. Reactions between hexamethylenetetramine and phenolic compounds. Part II. Formation of phenolic aldehydes. Distinctive behaviour of p-nitrophenol". J. Chem. Soc.: 1305. doi:10.1039/jr9340001305.
- ^ Duff, J. C.; Bills, E. J. (1941). "96. A new general method for the preparation of o-hydroxyaldehydes from phenols and hexamethylenetetramine". J. Chem. Soc.: 547. doi:10.1039/jr9410000547.
- ^ Duff, J. C.; Bills, E. J. (1945). "71. A new method for the preparation of p-dialkylaminobenzaldehydes". J. Chem. Soc.: 276. doi:10.1039/jr9450000276.
- ^ Lloyd Noel Ferguson (1946). "The Synthesis of Aromatic Aldehydes". Chem. Rev. 38 (2): 227–254. doi:10.1021/cr60120a002. PMID 21024865.
- ^ Ogata, Y.; Sugiura, F. (1968). "Kinetics and mechanism of the Duff reaction". Tetrahedron. 24 (14): 5001. doi:10.1016/S0040-4020(01)88408-8.
- ^ Mundy, Bradford P.; Ellerd, Michael G.; Favaloro, Frank G. (2005). Name Reactions and Reagents in Organic Synthesis, 2nd Edition, John Wiley & Sons, pp. 222 – 223.
- ^ Larrow, Jay F.; Jacobsen, Eric N. (1998). "(R,R)-N,N'-Bis(3,5-di-tert-butylsalicylaldehyde)-1,2-cyclohexanediamino Manganese(III) Chloride, a Highly Enantioselective Epoxidation Catalyst". Organic Syntheses. 75: 1. doi:10.15227/orgsyn.075.0001; Collected Volumes, vol. 10, p. 96.
- ^ Allen, C. F. H.; Leubner, Gerhard W. (1951). "Syringic aldehyde". Organic Syntheses. 31: 92. doi:10.15227/orgsyn.031.0092; Collected Volumes, vol. 4, p. 866.
- ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 3rd edition, New York: Wiley, ISBN 9780471854722, OCLC 642506595