Mono- and bis-alkylation of glyoxal-bridged tetraazamacrocycles using mechanochemistry

Abdulwahaab, Bassim H.; Burke, Benjamin P.; Domarkas, Juozas; Silversides, Jon D.; Prior, Timothy J.; Archibald, Stephen J.

Abstract

Glyoxal-bridged bisaminal tetraazamacrocyclic derivatives of 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) can be N-functionalized to incorporate coordinating groups or for conjugation to biomolecules. Herein, we present an improved N-functionalization methodology using mechanochemistry which reduces reaction times in comparison with conventional synthetic routes. A range of six alkyl halides were reacted with cyclen and cyclam bisaminal derivatives in various ratios to form mono- and bis-functionalized quaternary ammonium salts. Cross-bridged cyclam, a key intermediate for CB-TE2A, a commonly used chelator in positron emission tomography medical imaging with 64 Cu, has been synthesized using nonconventional synthetic methodologies (grinding and microwave heating) with intermediates characterized by 2D NMR and single crystal XRD. The overall synthesis time of CB-TE2A from cyclam could be shortened to 5 days from the 35 days required for the conventional synthesis.

Citation

Abdulwahaab, B. H., Burke, B. P., Domarkas, J., Silversides, J. D., Prior, T. J., & Archibald, S. J. (2016). Mono- and bis-alkylation of glyoxal-bridged tetraazamacrocycles using mechanochemistry. Journal of Organic Chemistry, 81(3), 890-898. https://doi.org/10.1021/acs.joc.5b02464

• Journal Article Type: Article
• Online Publication Date: Jan 21, 2016
• Publication Date: Feb 5, 2016
• Deposit Date: Dec 11, 2020
• Journal: Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 81
• Issue: 3
• Pages: 890-898
• DOI: https://doi.org/10.1021/acs.joc.5b02464
• Public URL: https://hull-repository.worktribe.com/output/518322