Duff reaction

Examples

The modified salicylaldehyde 3,5-di-tert-butylsalicylaldehyde is prepared by the Duff reaction:

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.

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. Conversion of phenol to the corresponding 1,3,5-trialdehyde has also been reported

Reaction mechanism

The reaction mechanism is related to that for the Reimer–Tiemann reaction, which uses chloroform as the formylating agent. 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Historical references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. who

References

References

1. 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.
2. (1998). "(''R'',''R'')-''N'',''N'''-Bis(3,5-di-''tert''-butylsalicylaldehyde)-1,2-cyclohexanediamino Manganese(III) Chloride, a Highly Enantioselective Epoxidation Catalyst".
3. (1951). "Syringic aldehyde".
4. Lindoy, Leonard F.. (July 1998). "Mono- and Diformylation of 4-Substituted Phenols: A New Application of the Duff Reaction". Synthesis.
5. (September 2000). "A Convenient One-Step Synthesis of 2-Hydroxy-1,3,5-Benzenetricarbaldehyde". Synthetic Communications.
6. {{JerryMarch
7. (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.]].