Computational study of the general base catalysed aminolysis of 2-benzoxazolinone Sonia Ilieva, Yasen Atanasov, Veneta Kalcheva, Boris Galabov * Department of Chemistry, University of Sofia, St Kliment Ohridsky, 1 Janes Bourchier Avenue, Sofia 1164, Bulgaria Received 6 March 2003; revised 7 April 2003; accepted 10 April 2003 Abstract B3LYP/6-31G* computations were applied in examining the possible mechanistic pathways for the reaction of ring opening of 2-benzoxazolinone by aminolysis with methylamine in the case of general base catalysis by a second molecule of the amine. Transition state structures and energies were determined for concerted and neutral stepwise pathways. The theoretical data show that the concerted mechanism is more favourable than the neutral stepwise pathway by 2.54 kcal/mol in the gas phase. q 2003 Elsevier B.V. All rights reserved. Keywords: 2-Benzoxazolinone; 2(3H)-Benzoxazolone; Aminolysis; Mechanism of aminolysis; Computations 1. Introduction The reaction of aminolysis of esters has been a subject of scientific interest as a model process for the formation of peptide bonds [1–10]. Recently, theor- etical quantum mechanical methods have been applied for studying the mechanism of acyl transfer reactions [11,12], aminolysis of b-lactams [13–17], ester aminolysis [18–22]. In a recent study [22], the ester aminolysis was reinvestigated by applying higher level of electronic structure theory, examining the general base catalysis by the nucleophile, and a more comprehensive study of the solvent effect. Ab initio QCISD/6-31G(d,p) and B3LYP/6-31G(d) den- sity functional theory computations were applied. The results showed that in the case of catalysed aminolysis by second ammonia molecule, the stepwise mechan- ism has distinctly lower energy. 2-Benzoxazolinone and its derivatives are widely studied for biological activity properties [23–26]. Solvolysis reactions are included in the metabolitic pathways of these derivatives [27]. The aminolysis of 2-benzoxazolinone goes through a breakage of O – CO bond and is considered to follow similar pathway as the ester aminolysis [10]. The aminolysis of 2-benzoxazolinone (BO) was studied recently by quantum mechanical methods [28]. B3LYP/6-31G* computations were applied for examining the three possible pathways for the aminolysis of BO with CH 3 NH 2 : zwitterionic, concerted and neutral step- wise. Among the three different mechanisms of this reaction, the neutral concerted mechanism is shown to be the most favourable. This mechanism proceeds via formation of a weakly bound pre-reaction molecular complex, followed by the rate-determining four-centred transition state. At this transition state 0166-1280/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0166-1280(03)00310-5 Journal of Molecular Structure (Theochem) 633 (2003) 49–55 www.elsevier.com/locate/theochem * Corresponding author. Tel.: þ359-2-6256-421; fax: þ 359-2- 9625-438. E-mail address: galabov@chem.uni-sofia.bg (B. Galabov).