Maitland-Japp reaction

The Maitland-Japp reaction , named after the chemists Francis Robert Japp (1848–1925) and William Maitland , is a name reaction from the field of organic chemistry and was first described in 1904. The Maitland-Japp reaction enables the preparation of tetrahydropyranone derivatives from ketones and aldehydes .

Overview reaction

The Maitland-Japp reaction is a condensation reaction in which a ketone ( 3-pentanone in the example ) is reacted with two equivalents of aldehyde ( benzaldehyde in the example ) to form tetrahydropyran-4-one derivatives. The reaction takes place in a basic medium.

The use of asymmetrical ketones enables the synthesis of tetrahydropyranone derivatives with different substituents at position 2 and 6.

Reaction mechanism

The following reaction mechanism is described in the literature and is illustrated using 3-pentanone and benzaldehyde as an example :

3-Pentanone ( 1 ) is first deprotonated by the added base. It forms the enolate 2 , which reacts with benzaldehyde. Compound 3 is formed by intra-molecular proton rearrangement and subsequent elimination of water . Compound 3 reacts with another benzaldehyde to form compound 4 . A ring closure occurs. By protonation with water, 3,5-dimethyl-2,6-diphenyl-tetrahydropyran-4-one ( 5 ) is finally formed .

further reading

• PA Clarke and S. Santos: Strategies for the Formation of Tetrahydropyran Rings in the Synthesis of Natural Products In: Eur. J. Org. Chem. 2006, pp. 2045-2053, doi: 10.1002 / ejoc.200500964 .

Individual evidence

1. ^ Francis Robert Japp and William Maitland: CXLVIII. — Reduction products of αβ-dimethylanhydracetonebenzil, and condensation products of benzaldehyde with ketones In: J. Chem. Soc., Trans. 85, 1904, pp. 1473–1489, doi: 10.1039 / CT9048501473 .
2. ↑ Entry on Maitland-Japp reaction. In: Römpp Online . Georg Thieme Verlag, accessed on June 4, 2020.
3. ^ PA Clarke, WHC Martin, JM Hargreaves, C. Wilson and AJ Blake: The one-pot, multi-component construction of highly substituted tetrahydropyran-4-ones using the Maitland – Japp reaction In: Org. Biomol. Chem. 3, 2005, pp. 3551-3563, doi: 10.1039 / B508252H .
4. ^ PA Clarke, WHC Martin, JM Hargreaves, C. Wilson and AJ Blake: Revisiting the Maitland – Japp reaction. Concise construction of highly functionalized tetrahydropyran-4-ones In: Chem. Commun. 3, 2005, pp. 1061-1063, doi: 10.1039 / B416247A .
5. ^ PA Clarke and WHC Martin: Diastereoselective Synthesis of Highly Substituted Tetrahydropyran-4-ones In: Org. Lett. 4, 2002, pp. 4527-4529, doi: 10.1021 / ol027081j .
6. ^ Zerong Wang: Comprehensive Organic Name Reactions and Reagents , Wiley, 2009, ISBN 978-0-471-70450-8 , pp. 1800-1802.