Received: 8 October 2009, Revised: 9 December 2009, Accepted: 21 December 2009, Published online in Wiley Online Library: 14 April 2010 Theoretical and experimental studies on stability of the C-ON bond in new ketone functionalized N-alkoxyamines Elz ˙bieta Megiel a * , Andrzej Kaim a and Michal Ksawery Cyran ´ ski a Three new ketone functionalized N-alkoxyamines derived from 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) were prepared: N-(1-phenylpropyloxy)-2,2,6,6-tetramethylpiperidin-4-one, 1-phenyl-1-(2,2,6,6- tetramethylpiperidinoxy)- propanone, 1-phenyl-1-(4-oxo-2,2,6,6-tetramethylpiperidinoxy)propanone. The rate constants of C-ON bonds homo- lysis in the synthesized alkoxyamines were determined over a range of temperatures via nitroxide-exchange experiments using HPLC to monitor the concentration. The Arrhenius parameters of homolysis for the investigated alkoxyamines were determined (lnA, E a ). Homolytic bond dissociation energies (BDE) of the C-ON bond in the synthesized compounds were determined from quantum-mechanical calculations at the B3-LYP/6-31G(d) and BMK/ 6-311RG(3df,2p) levels. Ketone functionalization of the alkyl fragment of alkoxyamine in b position dramatically increases the rate constant of homolysis (by a factor of ca. 500 at the temperature of 363 K) suggesting that the new ketone functionalized N-alkoxyamines should be effective as C-radical precursor and unimolecular initiators in NMRP at lower temperatures than the alkoxyamines applied earlier. The analyses of natural bond, frontal orbitals and spin distribution indicated that the decrease in the strength of C-ON bonds in ketone fuctionalized alkoxyamines in the alkyl fragment predominantly originates from a substantially smaller HOMO–LUMO gap and more delocalized spin density in leaving alkyl radicals as compared with unfunctionalized alkoxyamines. Copyright ß 2010 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper Keywords: bond dissociation energy (BDE); bond homolysis; N-alkoxyamine; persistent radical effect (PRE) INTRODUCTION Stable nitroxide radicals have been used for a long time in many areas of organic chemistry. [1–6] They are mostly unreactive products of the spin trapping reactions of nitrone/nitroso reagents having the general structure R-N(O)-R 0 that can be easily studied by electron spin resonance (ESR) spectroscopy. [7–10] Nevertheless, this subject remains of interest because of the use of aminoxyls as spin probes, [11] contrast agents [12] and antioxidants in polymers [13] as well as in biological systems. [14,15] These radicals exhibit persistent radical effect [16] and enable to control radical polymerizations and create in this way new materials with promising properties. Nitroxide-mediated radical polymerization (NMRP) has become an important method of Controlled Radical Polymerization, which makes it possible to synthesize polymers of tailor-made molecular weight, architecture and low polydispersity. [17–25] The alkyl derivatives of nitroxide radicals named N-alkoxyamines with thermal labile C-ON bond could decompose on heating in the homolysis process to give C-radical as well as the nitroxide – persistent radical in 1:1 stoichiometry. N-alkoxyamines with respective thermolytically unstable C-ON bonds give, in the homolysis process, both an alkyl radical which can be used as an initiating radical and a persistent radical (Scheme 1). The equilibrium between the reactions shown in Scheme 1 is as follows: dissociation (k d ) and coupling (k c ) lie on the side of the alkoxyamine molecule. The polymer chains, obtained in the NMRP process using alkoxyamine as an initiator, are capped by nitroxyl radical from one side, and by initiating radical derived from alkoxyamine molecules from the other side. Thus, functionalized alkoxyamines can be used in synthesis of alpha, omega functional polymers, accurately designed spherical nanostructures supported on the surface [30–34] and biohybrid materials. [35,36] The functionalized alkoxyamines with carbonyl group are very promising for all these tailored materials. Particularly they are useful for the last purpose because of their high chemical reactivity and the ability of the carbonyl group introduced to the polymer chain to react under mild conditions with peptide and protein molecules bearing the amine groups during reductive amination to form covalent bonds. [35] Recently, thermal reversible N-alkoxyamines’ homolysis was used as a highly efficient method for the clean generation of C-radicals for organic synthesis e.g. cyclizations and intermolecular addition reactions and can be used to conduct environmentally benign tin-free radical reactions. [37,38] A serious limitation of these reactions is the long reaction time necessary to get high conversions and high temperature of reaction. The success of the reaction strongly depends on the C-ON bond strength of the starting alkoxyamine. It was proved that the izomerization process works well if the bond dissociation enthalpy of C-ON bond BDE is smaller than (wileyonlinelibrary.com) DOI 10.1002/poc.1685 Research Article * Correspondence to: E. Megiel, University of Warsaw, Faculty of Chemistry, Pasteura 1, 02–093 Warsaw, Poland. E-mail: emegiel@chem.uw.edu.pl a E. Megiel, A. Kaim, M. K. Cyran ´ski University of Warsaw, Faculty of Chemistry, Pasteura 1, 02–093 Warsaw, Poland J. Phys. Org. Chem. 2010, 23 1146–1154 Copyright ß 2010 John Wiley & Sons, Ltd. 1146