Jozef Hodyl PhD Thesis - Theses - Flinders University

75Figure 2.5 Structure of (S)-(-)-propylene oxide, 75.Studies relating to N-alkylation of cyclen with propylene oxide are few innumber 100, 118, 181-183 and most relate to substitution on all four nitrogen atoms of thecyclen framework. 181-183 The only recorded procedure leading to hetero-N-alkylationof cyclen specifically at one nitrogen atom alkylates the fourth nitrogen atom of the118, 181tri-N-substituted cyclen adducts DOTA and DOTEP, which are water soluble.However, this method could not be used here as, the tri-N-alkylated cyclen adduct 46is not water soluble. In the absence of catalysis, direct reaction of (S)-(-)-propyleneoxide with 46 was prohibitively slow. Lithium bromide was chosen to catalyse theepoxide ring-opening reaction as there are examples of successful syntheticprocedures in the literature for the aforesaid reaction with amines. 184, 185 Previousstudies have discovered that Li +has the ability to activate oxygen-bearingelectrophiles, due to its high oxophilic capacity, enabling attack by a nucleophile at184, 185the α carbon, Figure 2.6. Successfulregioselective ring-opening reactionsadhering exclusively to S N 2 nucleophilic attack at the terminal carbon of propyleneoxide by aliphatic amines, utilising lithium bromide as catalyst have been reportedwith good yields. 185Figure 2.6Proposed mechanism for the LiBr catalysed ring-opening reaction of (S)-(-)-propyleneoxide, 75, by cyclen.48