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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.

Authors

Bassim H. Abdulwahaab

Benjamin P. Burke

Juozas Domarkas

Jon D. Silversides



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
Electronic ISSN 1520-6904
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