Theoretical investigation of the regioselective ring opening of 2-methylaziridine. Lewis acid effect
- 22 Downloads
The formation of substituted 1,2-diamines via the regiospecific nucleophilic ring opening of 2-methylaziridine with methylamine was performed by nucleophilic attack at aziridine carbon atoms. A detailed theoretical study was investigated by density functional theory (DFT) at the B3LYP level and second order Moller Plesset perturbation theory (MP2) by using the 6-311G(d,p) basis set. The third Grimme correction term (D3) was used to take into account weak interactions. Solvent effects were computed in methanol and dimethylsulfoxide using the polarizable continuum model (PCM). Emphasis was placed on the ring opening mechanisms of neutral aziridines and aziridinium ions obtained through N-complexation with the BF3 Lewis acid. Moreover, the effect of substituent groups on the regioselectivity of the ring opening was investigated. The nucleophilic attack was carried out via two pathways (frontside attack M1 and backside attack M2) where activation barriers proved the preference for ring opening through the backside attack at the C3 aziridine carbon atom. The obtained results showed that the frontside attack with methylamine takes place along a concerted mechanism that leads to formation of products through one transition state. However, the backside attack is carried via a stepwise process in which the methylamine attack takes place in an SN2 fashion where the leaving group is the ring nitrogen. It first conduces a ring opening considered as the rate-determining step followed by formation of a zwitterionic intermediate. This latter undergoes a rotation to allow the proton transfer step and finally leads to formation of the thermodynamic products.
KeywordsAziridine Ring opening Nitrogen inversion Activation energy
The authors gratefully acknowledge the support provided by the Tunisian Ministry of Higher Education and Scientific Research and would like to thank Professor Bahoueddine Tangour for valuable insights and recommendations.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
- 3.Budzisz E, Bobka R, Hauss A, Roedel JN, Wirth S, Lorenz IP, Rozalska B, WięckowskaSzakiel M, Krajewska U, Rozalski M (2012) Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper (II) and palladium (II). Dalton Trans 41:5925–5933CrossRefGoogle Scholar
- 7.Phung C, Tantillo DJ, Hein J, Pinha AR (2017) The mechanism of the reaction between an aziridine and carbon dioxide with no added catalyst. J Phys Org Chem 31:1–7Google Scholar
- 13.Bosschieter J, Nieuwenhuijzen JA, Van Ginkel T, Vis AN, Witte B, Newling D, Beckers GMA, Moorselaar RJAV (2017) Value of an immediate Intravesical instillation of mitomycin C in patients with non–muscle-invasive bladder cancer: a prospective multicentre randomised study in 2243 patients. Eur Urol 73(2):226–232CrossRefGoogle Scholar
- 37.Gaussian 09, Revision A.02, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) Gaussian Inc., WallingfordGoogle Scholar
- 40.Stamm H, Assithianakis P, Weiss R, Bentz G, Buchholz B (1984) Electron attachment to N-benzoylaziridines followed by C–N homolysis of the aziridine ring. J Chem Soc Chem Commun:753–754Google Scholar
- 45.Catak S, Dhooghe M, Verstraelen T, Hemelsoet K, Nieuwenhove AV, Ha HJ, Waoquier M, De Kimpe N, Van Speybroeck V (2010) Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization. J Og Chem 75:4530–4541CrossRefGoogle Scholar
- 46.Pearson WH, Lian BW, Bergmeier SC (1996) Aziridines and azirines monocyclic. In: Padwa A (ed) Comprehensive heterocyclic chemistry II. Pergamon, Oxford, p 1Google Scholar