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. The method is generally inefficient.[1] The reaction is named after James Cooper Duff.[2]
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 at the para position.[3]
Examples
[edit]The modified salicylaldehyde 3,5-di-tert-butylsalicylaldehyde is prepared by the Duff reaction:[4]
![Duff reaction 3,5-di-tert-butylsalicylaldehyde](http://178.128.105.246/content-http-upload.wikimedia.org/wikipedia/commons/thumb/2/20/Duff_reaction.svg/475px-Duff_reaction.svg.png)
The natural product syringaldehyde can also be prepared by the Duff reaction. In this example, formylation occurs at the position para to the phenolic OH.[5]
![Duff reaction syringaldehyde](http://178.128.105.246/content-http-upload.wikimedia.org/wikipedia/commons/thumb/0/09/Duff_reaction_syringaldehyde.svg/400px-Duff_reaction_syringaldehyde.svg.png)
Unlike other formylation reactions the Duff reaction is able to attach multiple aldehyde groups. If both ortho positions are vacant then a diformylation is possible, as in the formation of diformylcresol from p-cresol.[6] Conversion of phenol to the corresponding 1,3,5-trialdehyde has also been reported[7]
Reaction mechanism
[edit]The reaction mechanism is related to that for the Reimer–Tiemann reaction, which uses chloroform as the formylating agent.[1] Protonated hexamine ring-opens to expose an iminium group. 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://178.128.105.246/content-http-upload.wikimedia.org/wikipedia/commons/1/15/Duff_Reaction_Mechanism3.png)
Historical references
[edit]Duff was a chemist at the College of Technology, Birmingham, around 1920–1950.[2] who
- 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.
See also
[edit]- Bouveault aldehyde synthesis
- Bodroux-Chichibabin aldehyde synthesis
- Reimer-Tiemann reaction
- Sommelet reaction
- Vilsmeier-Haack reaction
References
[edit]- ^ a b March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 3rd edition, New York: Wiley, p. 727, ISBN 9780471854722, OCLC 642506595
- ^ a b 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.
- ^ 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.
- ^ Lindoy, Leonard F. (July 1998). "Mono- and Diformylation of 4-Substituted Phenols: A New Application of the Duff Reaction". Synthesis. 1998 (7): 1029–1032. doi:10.1055/s-1998-2110.
- ^ Anderson, Andrew A.; Goetzen, Thomas; Shackelford, Scott A.; Tsank, Stella (September 2000). "A Convenient One-Step Synthesis of 2-Hydroxy-1,3,5-Benzenetricarbaldehyde". Synthetic Communications. 30 (17): 3227–3232. doi:10.1080/00397910008086933.