SITE-SELECTIVE OXIDATIVE N-DEALKYLATION IN A COBALT(III) POLYAMINE HYDROLYTIC AGENT

Site-selective and quantitative C-N bond cleavage occurs at one of the C-N(tertiary) bonds of half the [Co(III)(trpn)(H20)2]3+ complex (trpn = tris(3-aminopropyl)amine) dissolved in D2O under acidic conditions. The cleavage leads to 100% consumption of [Co(trpn)(H2O)2]3+ and 100% formation of Co2+ quantified by assessing solution paramagnetism with t-BuOH (tert-butyl alcohol) as an internal and external H-1 NMR stand ard as well as by direct measurement with optical spectroscopy. In con trast, the analogous tren complex (tren = tris(2-aminoethyl)amine) doe s not exhibit C-N bond cleavage. The major organic products produced b y [Co(trpn)(H20)2]3+, trpn and bpn (3,3'-iminobis(propylamine)), forme d in a 1:1 ratio, were identified and characterized using H-1 NMR spec troscopy as well as modern 2D NMR methods (COSY, HOHAHA, HMBC, HMQC). bpn was presumably formed by an oxidative N-dealkylation of half the t rpn at the tertiary amine, since an essentially identical H-1 NMR spec trum was obtained on treatment of trpn with 1 equiv of Br2. This oxida nt is known to cleave C-N bonds by oxidative N-dealkylation. In additi on, two identifiable minor byproducts were formed in the two types of trpn N-dealkylation reactions. The major byproduct was unstable but wa s identified as the hydrated form of beta-aminopropionaldehyde, the me tabolite of spermine produced by mammalian polyamine oxidases. Also fo rmed was beta-alanine, an oxidation product of beta-aminopropionaldehy de. Furthermore, Br2 accelerated the C-N cleavage reaction for [Co(trp n)(H20)2]3+, but even under these conditions [Co(tren)(H20)2]3+ was st able. The tren ligand was readily cleaved by Br2 to form initially die thylenetriamine and hydrated aminoacetaldehyde; these products were ev entually oxidized to ethylenediamine and glycine. Co(III) coordination does not prevent trpn oxidation by Br2 but does prevent such oxidatio n of tren. We speculate that an intramolecular one-electron oxidation of the tertiary N of coordinated trpn by Co(III) initiates the oxidati on process. Ironically, factors that favor hydrolytic efficiency in Co (III) polyamine complexes produce electron-deficient Co(III) centers; such centers facilitate the initial electron transfer and hence oxidat ive N-dealkylation.