Exploring the synthesis and functionalisation of methano[10]annulene

Within medicinal chemistry, there is always effort to strive for more effective drug molecules. One method to achieve this is through bioisosteres. Bioisosteres are “groups or molecules which have chemical and physical similarities producing broadly similar biological effects”. For this thesis, the proposed bioisostere of naphthalene, methano[10]annulene was investigated. Methono[10]annulene differs from naphthalene as it contains an additional bridging methylene which affords it 3D character while retaining its aromaticity. Methano[10]annulene was first described by Vogel and Bӧll. However, their synthesis uses harsh chemicals, and over the past 50 years there have been new method development that could be applicable to the synthesis of methano[10]annulene. Importantly, these new methods use milder and safer reagents but have note been applied to the synthesis of methano[10]annulene. This thesis details attempts to modernise the synthesis of methano[10]annulene while also looking at procedures to functionalise this molecule. In addition, work was done to include methano[10]annulene into a biologically relevant molecule. This thesis details the improve the synthesis of methano[10]annulene from Vogel’s reported 28% yield over 4 steps to 34% yield over 3 steps. However, the final methano[10]annulene could not be separated from CH2I2. Similar procedures were also investigated to create an amino acid naphthalene analogue. A range of functional groups were successfully incorporated onto methano[10]annulene, with a novel nitrile, amide and sulfonyl amide being reported. Methano[10]annulene and a bromo substituted derivative underwent Diels-Alder reactions to form the relevant Diels-Alder adducts.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2026

Author dc:creator

• Buckley, Zoë

• Chemistry
• Organic Chemistry
• Aromatic compounds
• anzsrc-for: 340503 Organic chemical synthesis

Statement dc:rights

• open access
• CC BY 4.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

en

Identifier

https://doi.org/10.26190/unsworks/32430

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/108120