Synthesis of Macropolycyclic Ligands Based on Tetraazacycloalkanes

Abstract

A versatile synthesis of spherical macrobicyclic and cylindrical macrotricyclic ligands is described using 1,4,8,11‐tetraazacyclotetradecane (cyclam), 1,4,7,10‐tetraazacyclododecane (cyclen), or dioxo macrocycles as precursors. Macrobicycles have been obtained by allowing cyclam, cyclen, or 5,12‐dioxocyclam (1,4,8,11‐tetraazacyclotetradecane‐5,12‐dione) to react with a bis‐electrophilic spacer under high dilution conditions. A surprising selectivity has been observed for 2,6‐dioxocyclen (1,4,7,10‐tetraazacyclododecane‐2,6‐dione), which yields only macrotricycles under the same reaction conditions. Molecular modelling studies have been carried out to investigate the selectivity of the reactions, and good agreement has been observed between the theoretical predictions and experimental data. 1D‐ and 2D‐NMR studies reveal a highly rigid structure in the case of macrobicycles. The macropolycyclic ligands show very different basicities, which demonstrates the influence of the cross‐linker on the coordination properties of the ligands.

Pycup—A Bifunctional, Cage-like Ligand for 64Cu Radiolabeling

“…The high dilution intramolecular di-alkylation of cyclam with 2,6-bis(bromomethyl)pyridine was conducted as previously reported in literature by Brandes et al 22 The product (0.22 g, 0.73 mmol) was afforded in a 14 % yield starting from cyclam (1g, 5 mmol). 1 H-NMR (CD 3 OD, 400 MHz, ppm): 7.83 (m, 1H), 7.28 (d, 2H), 4.15 (d, 2H), 3.82 (d, 2H), 3.31 – 2.84 (m, 16H), 2.62 (m, 2H), 2.07 (m, 2H).…”

Palladium-catalyzed amination in the synthesis of polyazamacrocycles

“…These compounds can be regarded as tricyclic, where two tetraazamacrorings constitute structural fragment of a larger ring. Analogous compounds with shorter benzyl bridges were synthesized preciously by alkylation of protected tetraazamacrocycle derivatives with bis(bromomethyl)-benzenes [142].…”

Synthesis of Trismacrocyclic and Macrotricyclic Compounds Possessing Structural Fragments of Aza- and Diazacrown Ethers, Cyclen and Cyclam via Pd-Catalyzed Amination Reactions

“…The fixed distance between the two cations induces cations interactions leading to unique electronic properties. [1,2] Two of us previously described several convenient methods for the synthesis of macrotricycles possessing two cyclen (1,4,7,10-tetraazacyclododecane) or cyclam (1,4,8,11-tetraazacyclotetradecane) moieties linked via two xylylene bridges. These 3-step approaches utilize either N 1 ,N 8 -ditosyl-N 4 -Boc-cyclam [3] or N-Boc-substituted dioxocyclen and dioxocyclam.…”

“…These 3-step approaches utilize either N 1 ,N 8 -ditosyl-N 4 -Boc-cyclam [3] or N-Boc-substituted dioxocyclen and dioxocyclam. [4] So-called bisaminal strategy exploits protected glyoxal-cyclen and glyoxalcyclam and the synthetic scheme also comprises three steps with a reduction reaction at the last step, [5] this method was used for the synthesis of macrotricycles with two crossbridged cyclen fragments. [6] On the basis of these cryptands, mono-and bimetallic homonuclear and heteronuclear complexes were obtained with Cu(II) and Ni(II) cations.…”