title: Mono- and Bis-Alkylation of Glyoxal-Bridged Tetraazamacrocycles Using Mechanochemistry.
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.
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Bassim H
authors.initials: BH
authors.lastname: Abdulwahaab
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Burke
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Juozas
authors.initials: J
authors.lastname: Domarkas
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Silversides
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Prior
authors.affiliation: Department of Chemistry and ‡Positron Emission Tomography Research Centre, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Archibald