Duff reaction
Template:Short description The Duff reaction (after James Cooper Duff[1]) also known as the hexamine aromatic formylation, is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes. Hexamine acts as the formyl carbon source, while acetic acid or trifluoroacetic acid acts as both reagent and solvent. The process is generally inefficient,[2] but is unusual in that it is able to attach multiple aldehyde groups. Other formylation reactions struggle to achieve this, as aldehydes are strongly deactivating.
The reaction requires strongly electron donating substituents on the aromatic ring such as in the case of phenols. 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
The modified salicylaldehyde 3,5-di-tert-butylsalicylaldehyde is prepared by the Duff reaction:[4]
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]
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
The reaction mechanism is related to that for the Reimer–Tiemann reaction, which uses chloroform as the formylating agent.[2] 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.
Historical references
Duff was a chemist at the College of Technology, Birmingham, around 1920–1950.[1] who
- Page Module:Citation/CS1/styles.css has no content.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.
- Page Module:Citation/CS1/styles.css has no content.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.
- Page Module:Citation/CS1/styles.css has no content.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.
- Page Module:Citation/CS1/styles.css has no content.Lloyd Noel Ferguson (1946). "The Synthesis of Aromatic Aldehydes". Chem. Rev. 38 (2): 227–254. doi:10.1021/cr60120a002. PMID 21024865.
- Page Module:Citation/CS1/styles.css has no content.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
- Bouveault aldehyde synthesis
- Bodroux-Chichibabin aldehyde synthesis
- Reimer-Tiemann reaction
- Sommelet reaction
- Vilsmeier-Haack reaction
References
Page Template:Reflist/styles.css has no content.
- ^ a b Page Module:Citation/CS1/styles.css has no content.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.
- ^ a b Page Module:Citation/CS1/styles.css has no content.March, Jerry (1985). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.). New York: Wiley. p. 727. ISBN 9780471854722. OCLC 642506595.
- ^ 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.
- ^ Page Module:Citation/CS1/styles.css has no content.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; Page Module:Citation/CS1/styles.css has no content.Collected Volumes, vol. 10, p. 96.
- ^ Page Module:Citation/CS1/styles.css has no content.Allen, C. F. H.; Leubner, Gerhard W. (1951). "Syringic aldehyde". Organic Syntheses. 31: 92. doi:10.15227/orgsyn.031.0092; Page Module:Citation/CS1/styles.css has no content.Collected Volumes, vol. 4, p. 866.
- ^ Page Module:Citation/CS1/styles.css has no content.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.
- ^ Page Module:Citation/CS1/styles.css has no content.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.
