Received: 26 November 2010, Revised: 5 January 2011, Accepted: 10 January 2011, Published online in Wiley Online Library: 23 February 2011 Reactivity of phenyl N-phenylcarbamates in the alkaline hydrolysis reaction Didi Nalbantova a , Diana Cheshmedzhieva a , Boriana Hadjieva a , Sonia Ilieva a * and Boris Galabov a * In the present study, we explore the application of several theoretically estimated indices that characterize the reactivity of a series of phenyl N-phenylcarbamates in the alkaline hydrolysis reaction. The rate constants (at 25 -C) for the hydrolysis of several derivatives were spectrophotometrically determined. The obtained kinetic data in this study, combined with literature data for other derivatives, were then correlated with theoretically estimated reactivity indices: Hirshfeld and NBO atomic charges, the Parr electrophilicity index (v), and the electrostatic potential at the carbon and oxygen atoms of the reaction centre (V C , V O ). The predictive ability of these quantities is discussed in a comparative context. Copyright ß 2011 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this article. Keywords: alkaline hydrolysis; phenyl N-phenyl substituted carbamates; reactivity indices; reactivity of organic compounds INTRODUCTION The principal aim of the present study is to assess the quality of reactivity predictions coming from alternative theoretical approaches for the alkaline hydrolysis of substituted phenyl N-phenylcarbamates. Carbamates are well-known class of compounds that can be synthesized by various methods. [1–4] The interest for studying their properties is determined mostly by the biological activities of carbamate derivatives. [1–11] Various carbamates find application in the agrochemical industry [5–9] as herbicides, fungicides and pesticides, in the pharmaceuticals industry [5,6,10] as drug intermediates, and in the polymer industry [5,6,11] for the synthesis of polyurethane and peptides. In the course of studying the biological activity of carbamates it was established that for some representatives the mode of decomposition during hydrolysis is a factor influencing their effects. [3] Therefore, the detailed understanding of the chemistry of the hydrolysis process, the theoretical prediction of kinetic parameters as well as the achievement of quantitative compliance with experimental reactivity trends is of particular importance. These objectives provided the motivation for carrying out theoretical evaluation of reactivity descriptors as well as experimental kinetic studies on the hydrolysis of a series of phenyl N-phenylcarbamates. The bulk of experimental kinetic data for the studied reaction was taken from the work of Williams, [12] who reported carefully determined kinetic constants for the alkaline hydrolysis of twelve compounds from the series examined. The series was expanded in the present study with four more derivatives, following the kinetic procedure of Williams. [12] We determined experimentally the rate constants for the following derivatives: m-CH 3 , p-NO 2 , m-N(CH 3 ) 2 , and p-C(CH 3 ) 3 phenyl N-phenylcarbamates substituted in the O-phenyl ring. The series of compounds studied is presented in Scheme 1. These derivatives contain both electron donating and electron withdrawing groups, thus allowing to reflect alternative polar influence of the substituents. Experimental kinetic data for such a representative series of derivatives provided a solid basis for a reliable assessment of the factors governing reactivity. The experimental kinetic constants were rationalized in terms of global and local reactivity indices derived from density functional theory. Thus the predictive power of the theoretically evaluated reactivity descriptors was assessed by direct compari- son with experimental results. KINETIC EXPERIMENTS AND THEORETICAL COMPUTATIONS Kinetic experiments Substituted carbamates were obtained through condensation of the corresponding phenols with equivalent amount of phenyl isocyanate in the presence of small amount of triethylamine as catalyst. [13] The kinetic measurements on the alkaline hydrolysis of a series of phenyl N-phenylcarbamates were carried out using UV spectroscopy. We strictly followed the kinetic procedure used by Williams [12] in his study on the alkaline hydrolysis of phenyl N-phenylcarbamates. Thus, it was possible to combine his experimental data with the kinetic constants determined in the present study for several additional derivatives. In his work Williams has provided a detailed justification of the adopted kinetic procedure. For three of the molecules studied in the present work the rate of hydrolysis was measured at the (wileyonlinelibrary.com) DOI 10.1002/poc.1841 Research Article * Correspondence to: B. Galabov, Department of Chemistry, University of Sofia, 1 James Bourchier Ave., 1164 Sofia, Bulgaria. E-mail: silieva@chem.uni-sofia.bg; E-mail: galabov@chem.uni-sofia.bg a D. Nalbantova, D. Cheshmedzhieva, B. Hadjieva, S. Ilieva, B. Galabov Department of Chemistry, University of Sofia, 1 James Bourchier Ave., 1164 Sofia, Bulgaria J. Phys. Org. Chem. 2011, 24 1166–1171 Copyright ß 2011 John Wiley & Sons, Ltd. 1166