Synthesis of Tris[2‐(dimethylamino)ethyl]amine with Regiospecific Deuterium Labels. Issue 5 (1st February 2023)

• Record Type: Journal Article
• Authors: Sobieski, Julian; Ruzhylo, Illia; Szczepaniak, Grzegorz; Gorczyński, Adam; Matyjaszewski, Krzysztof; Manoury, Eric; Poli, Rinaldo
• Is Part Of: ChemistrySelect. Volume 8:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-01
• Subjects: Deuterium labels -- Regioselective deuteration -- Tripodal ligand -- Tris[2-(dimethylamino)ethyl]amine; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202300053
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Simple synthetic routes to regioselectively deuterated tris[2‐(dimethylamino)ethyl]amine (Me6 TREN) variants are described. Imine formation with formaldehyde‐ d2 from tris(2‐aminoethyl)amine (TREN) and subsequent reductions with NaBD4 afforded N[CH2 CH2 N(CD3 )2 ]3 or d 18 ‐Me6 TREN in 79 % yield. A trisubstitution protocol from 2‐bromo‐ N, N ‐dimethylacetamide and ammonium carbonate and subsequent reduction of the N(CH2 CONMe2 )3 intermediate by lithium aluminum deuteride has afforded N[CH2 CD2 N(CH3 )2 ]3 or ( d 6 ‐arm)‐Me6 TREN in three steps and 52 % overall yield. A similar protocol from 2‐bromo‐ N, N ‐dimethyl‐ d 2 ‐ acetamide, obtained in two steps from d 4 ‐acetic acid, with reduction of the N(CD2 CONMe2 )3 intermediate by lithium aluminum hydride has afforded N[CD2 CH2 N(CH3 )2 ]3 or ( d 6 ‐cap)‐Me6 TREN in four steps and 13 % overall yield from CD3 COOD. Abstract : Simple synthetic routes to regioselectively deuterated variants of the common tris[2‐(dimethylamino)ethyl]amine (Me6 TREN) ligand are described, where the deuterium labels are located either on the six methyl groups, on the three methylene groups adjecent to the NMe2 arms or on the three methylene groups adjacent to the capping N atom.