Jozef Hodyl PhD Thesis - Theses - Flinders University

is that the electron withdrawing capability of the formyl groups causes the fourthnitrogen atom to become less basic thus augmenting its inability to act as an effectivenucleophile.2.3.2 Preparation of mono-carboxybenzyl (cbz) protected cyclenProtection of the fourth nitrogen atom of tri-formylated cyclen, 52, to obtain triformyl-cbz-protectedcyclen, 53, was achieved by treatment of 52 with an excess ofbenzyl chloroformate, 54, in de-ionised water at room temperature overnight,Scheme 2.3.5452 53Scheme 2.3 Protection of the fourth N-position with a carboxybenzyl group.Since the HCl generated during the reaction may hydrolytically remove some or allof the formyl protecting groups and also cleave the cbz protecting group the pH ofthe reaction was maintained between 4 and 10 with the addition of saturated sodiumcarbonate solution. 131, 166, 167 The tetra-N-protected product 53 was extracted intodichloromethane and following evaporation of the solvent was used without addedpurification. 109 For the purpose of characterisation, a pure sample of the tri-formylcbz-protectedcyclen derivative was obtained by trituration with diethyl ether over aone week period and used to obtain 1 H NMR and 13 C NMR spectral data which41