ORIGINAL PAPER Theoretical investigations on the mechanistic pathway of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines Youssef Arfaoui & Mohamed Lotfi Efrit & Néji Besbes Received: 27 May 2013 /Accepted: 24 July 2013 /Published online: 25 August 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determined and reaction identified by IRC calculations. The results show that thermal rearrange- ments occur in three ways. Firstly, the transition state TS 1 in which a hydrogen atom of methyl groups migrates from pri- mary carbon to oxygen of amid group to give the N- methallylamide 2. The second is via the transition state TS 2 in which the attack of oxygen to the tertiary carbon yields the oxazoline 3. The third is via the transition state TS 3 in which a hydrogen migrate from the secondary carbon to oxygen to give the vinylamide 4. In order to get insights into the factors determining the exact nature of its interactions with electro- philes, the application of reactivity parameters derived from density functional theory in a local sense, in particular the softness and Fukui function, to interpret and predict the mech- anisms of the thermal decomposition of the N-acyl-2,2- dimethylaziridines 1, has been discussed. Keywords Density functional theory . Intrinsic reaction coordinate . N-acyl-2,2-dimethylaziridines . Theoretical mechanism . Thermolysis . Fukui functions (FF) Introduction Aziridines are strained three-membered nitrogen-containing heterocycles that have been closely studied due to their great synthetic utility [1–3]. As well numerous synthetic aziridines have found biological applications as antitumor agents, antibi- otics and as enzyme inhibitors [4, 5]. The strain energy of aziridine is similar to that of cyclopropane (27 kcal mol −1 ), reflecting high bond-angle strain [6]. A large number of aziridines reactions involve opening of the ring and thus a release of strain energy but it has been suggested that lowering activation energy in these reactions is not solely due to the release of strain. Significantly, activation of aziridine, due to an electron withdrawing group on the nitrogen atom such as the acyl moiety, is necessary to readily achieve regioselective nu- cleophilic ring-opening. N-acyl-2,2-dimethylaziridines react with ethanol, water and sodium iodide, to provide products resulting from nucleophilic selective attack on the more substituted carbon atom of the aziridine ring [7–9]. Such het- erocycles are also unstable in the presence of Bronsted acids (concentrated and aqueous sulfuric acid) and azaphilic Lewis acids, e.g., [BF 3. Et 2 O], Zn(II) triflate, silica gel, alumina and acid activated clays), which coordinate to nitrogen atom instead of oxygen one, yielding a mixture of amidoalcohols, allylamides and oxazolines, via aziridinium and tertiary aliphat- ic carbocation intermediates where heterolytic cleavage of the C-N bond of the aziridine ring can occur [10–16]. In contrast, heating N-p-nitrobenzoyl-2-benzylaziridine in toluene, leads to trans-(N-cinnamyl)-p-nitrobenzamide [17], which could be explained by the low polarity of toluene that favors intramo- lecular reaction mechanism, involving a concerted cis- elimination of proton followed by the opening of the aziridine ring. It has also been observed that the thermolysis of N-p- nitrobenzoyl-2-vinylaziridine in toluene gave the N-p- nitrophenyldihydro-1,3-oxazepine through ring formation Y. Arfaoui (*) : M. L. Efrit Laboratoire de Synthèse Organique et Hétérocyclique, Département de Chimie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092 El Manar, Tunisie e-mail: arfaoui.youssef@gmail.com N. Besbes Laboratoire Physico-Chimie des Matériaux Minéraux et leurs Applications, Centre National des Recherches en Sciences des Matériaux, Technopole de Bordj Cédria, Soliman 8027, Tunisie J Mol Model (2013) 19:4603–4612 DOI 10.1007/s00894-013-1959-9