Stereochemistry of the intermediates in the synthesis of 1,4,7,10-tetraazacyclododecane from triethylenetetramine, glyoxal and diethyl oxalate

The equilibrium and rearrangement phenomena encountered in two steps for the synthesis of 1,4,7,10-tetraazacyclododecane from triethylenetetramine, glyoxal and diethyl oxalate were studied and elucidated after the development of two micellar electrokinetic chromatographic (MEKC) methods. The latter were able to separate: (i) the four bis-aminals (2–5) obtained from the condensation of triethylenetetramine with glyoxal; (ii) the four diones (6–9) derived from the reaction of the bis-aminals with diethyl oxalate, whose solid state structures were determined by single crystal X-ray diffraction. The three not yet reported diones (6, 7 and 9) were synthesised by taking advantage of both the reaction conditions and the use of a particular catalyst (MeONa). A plausible reaction mechanism, as well as a discussion of the solid state structures, is presented.