The synthesis of Deuterium-Labeled N-Nitrosodiethanolamine and N-Nitroso-2-hydroxymorpholine

Article abstract of DOI:10.1002/jlcr.2580341114

Two deuterated derivatives of N-nitrosodiethanolamine and two deuterated derivatives of N'-Nitroso-2-hydroxymorpholine were prepared. 1,1,1',1'-²H₄-N-Nitrosodiethanolamine 1a was prepared in 99% isotopic purity by simple base catalyzed H-D exchange. 2,2,2',2'-²H₄-N-Nitrosodiethanolamide 1b was synthesized in 98% isotopic purity by the LiAlD₄ reduction of dimethyl iminodiethanoate, followed by acid catalyzed nitrosation. 5,5-²H₂-N-Nitroso-2-hydroxymorpholine 2a was prepared in 99% isotopic purity through a series of steps involving 1) the selective base catalyzed H-D exchange of the CH₂ adjacent to the ester function of 2,2-diethoxyethylcarboethoxymethylnitrosamine, 2) its reduction with diisobutylaluminum hydride at 78°C followed by 3) acid catalyzed hydrolysis of the acetal and cyclization to the hemiacetal. 2-²H-N-Nitroso-2-hydroxymorpholine 2b (98% isotopic purity) was prepared through the LiAlD₄ reduction of 2-hydroxyethylcorboethoxymethylnitrosamine at -78°C.