Synthesis and thermochemical study of quinoxaline-N-oxides: enthalpies of dissociation of the N–O bond Miguel L. F. Viveiros a , Vera L. S. Freitas a , Nuno Vale a , José R. B. Gomes a,b , Paula Gomes a and Maria D. M. C. Ribeiro da Silva a * The synthesis of three new quinoxaline mono-N-oxides derivatives, namely, 2-tert-butoxycarbonyl-3-methylquinoxaline- N-oxide, 2-phenylcarbamoyl-3-ethylquinoxaline-N-oxide, and 2-carbamoyl-3-methylquinoxaline-N-oxide, from their corresponding 1,4-di-N-oxides is reported. Samples of these compounds were used for a thermochemical study, which allowed derivation of their gaseous standard molar enthalpies of formation, Δ f H o m ðgÞ, from their enthalpies of formation in the condensed phase, Δ f H o m ðcrÞ, determined by static bomb combustion calorimetry, and from their enthalpies of sublimation, Δ g cr H o m , determined by Calvet microcalorimetry. Finally, combining the Δ f H o m ðgÞ for the quinoxaline-N-oxides derived in this work with literature values for the corresponding 1,4-di-N-oxides and atomic oxygen, the bond dissociation enthalpies for cleavage of the first NO bond in the di-N-oxides, DH 1 (N–O), were obtained and compared with existing data. Copyright © 2011 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper Keywords: dissociation enthalpy N–O bond; quinoxaline mono-N-oxides derivatives; synthesis; thermochemistry INTRODUCTION The interest in a large range of compounds with the N-oxide functional group has been expanded significantly over the past two decades because of their remarkable success in a broad variety of applications as oxidizing agents. Some of these compounds, particularly the quinoxaline derivatives, assumed relevant importance because of their selective biological activi- ties [1–6] related with inherent pharmacological and toxicological properties. [7,8] Energetic studies on compounds containing terminal NO bonds in different molecular environments have been developed in our research group, [9–18] with the main goal of evaluating the influence of the chemical vicinity on that bond. In this context, computational and experimental studies have been extensively developed for quinoxaline 1,4-di-N- oxides. [9–20] More recently, with the possibility of synthesizing very pure samples of two quinoxaline derivatives containing only a single dative N–O bond, the first experimental thermo- chemical study for quinoxaline-N-oxide derivatives has been reported. [13] The present work reports the experimental study of the energetics of three new quinoxaline mono-N-oxide derivatives whose structures are represented in Scheme 1, that is, 2-tert-butoxycarbonyl-3-methylquinoxaline-N-oxide (4.1), 2-phenylcarbamoyl-3-methylquinoxaline-N-oxide (4.2), and 2- carbamoyl-3-methylquinoxaline-N-oxide (4.3). Their syntheses have been performed from the corresponding 1,4-di-N-oxides (compounds 3.1–3.3, Scheme 1) by selective reduction. The standard (p o = 0.1 MPa) massic energies of combustion in oxygen of the three compounds were measured with a high precision static bomb calorimeter, from which the values of the standard molar enthalpies of formation in the crystalline phase at T = 298.15 K were derived. The enthalpies of sublimation of the three compounds were determined from high temperature Calvet microcalorimetry measurements. Combining the standard molar enthalpies of formation in the crystalline phase with the enthalpies of sublimation of each compound, the corresponding standard ( p o = 0.1 MPa) molar enthalpies of formation in the gas phase at T = 298.15 K were obtained. The latter results were used to obtain the experimental values for the first NO bond dissociation enthalpy in the parent di-N-oxide quinoxalines based on their standard molar enthalpies of formation in the gas phase that were previously reported in the literature. [11,12] EXPERIMENTAL Synthesis and purification The quinoxaline di-N-dioxides (3.1–3.3, Scheme 1) were prepared from benzofuroxan (1) and the appropriate b-ketoester/amide (2) following the method described by Robertson and Kasubick. [21] Briefly, * Correspondence to: M. D. M. C. Ribeiro da Silva, Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, R. do Campo Alegre, 687, P-4169-007 Porto, Portugal. E-mail: mdsilva@fc.up.pt a M. L. F. Viveiros, V. L. S. Freitas, N. Vale, J. R. B. Gomes, P. Gomes, M. D. M. C. R. Silva Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, R. do Campo Alegre, 687 P-4169-007 Porto, Portugal b J. R. B. Gomes CICECO, Departamento de Quıímica, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal J. Phys. Org. Chem. 2012, 25 420–426 Copyright © 2011 John Wiley & Sons, Ltd. Research Article Received: 11 March 2011, Revised: 1 August 2011, Accepted: 23 August 2011, Published online in Wiley Online Library: 2 October 2011 (wileyonlinelibrary.com) DOI: 10.1002/poc.1932 420