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

TY - JOUR

T1 - Mono- and bis-alkylation of glyoxal-bridged tetraazamacrocycles using mechanochemistry

AU - Abdulwahaab, Bassim H.

AU - Burke, Benjamin P.

AU - Domarkas, Juozas

AU - Silversides, Jon D.

AU - Prior, Timothy J.

AU - Archibald, Stephen J.

N1 - Publisher Copyright: © 2015 American Chemical Society.

PY - 2016/2/5

Y1 - 2016/2/5

N2 - 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 64Cu, 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.

AB - 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 64Cu, 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.

UR - https://www.scopus.com/pages/publications/84957577009

U2 - 10.1021/acs.joc.5b02464

DO - 10.1021/acs.joc.5b02464

M3 - Article

AN - SCOPUS:84957577009

SN - 0022-3263

VL - 81

SP - 890

EP - 898

JO - JOURNAL OF ORGANIC CHEMISTRY

JF - JOURNAL OF ORGANIC CHEMISTRY

IS - 3

ER -