Comprehensive Thermochemical Study of Cyclic Five- and Six- Membered N,N′‑Thioureas Ana L. R. Silva and Maria D. M. C. Ribeiro da Silva* Centro de Investigaç ã o em Química, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal * S Supporting Information ABSTRACT: An experimental and computational study of the thermochemical and structural properties of ethylenethiourea (ETU) has been carried out. The enthalpies of combustion and sublimation, measured respectively by rotating-bomb combustion calorimetry and Calvet microcalorimetry, yielded the gas-phase enthalpy of formation of ETU at T = 298.15 K. This latter parameter was also derived from high-level molecular orbital calculations at the G3(MP2)//B3LYP level of theory, leading to a value in excellent agreement with the one obtained from experimental data. With the purpose of evaluating the influence of the ring size in the enthalpy of formation of cyclic N,N′- thiourea derivatives, the calculation of the enthalpy of formation of N,N′-trimethylenethiourea (MTU) was performed using the G3- (MP2)//B3LYP approach. The effects of substituents (carbonyl and thiocarbonyl) on the molecular stability of several N-alkyl (cyclic) ureas/thioureas were also studied. ■ INTRODUCTION Ethylenebisdithiocarbamate and propylenebisdithiocarbamate have been two of the species most widely used as fungicides in agriculture. 1 These fungicides are considered to have low toxicity, but their derivatives ethylenethiourea (imidazolidine-2- thione, ETU) and other degradation products are a toxicologically serious problem. 2-4 The teratogenicity and molecular structure of compounds related to ETU have been assessed, 5 via modifications of the ring size and the substituents, in order to evaluate the structural effects on the characteristics of the compounds. The results indicated a teratogenic activity and molecular structure correlation that was closely linked to the imidazolidinethione structure, and although there is interest in the energetic vs structural effects for the prediction of the chemical behavior of ETU derivatives, such studies are scarce but are important to carry out. Ethylenethiourea (ETU) and N,N′-trimethylenethiourea (MTU), whose structures contain a thioamide group (Figure 1), are well known as ligands for the synthesis of coordination compounds, 6 appearing in the literature as extensively studied inherent metal-biological species interactions. 7 As an extension of our previous studies on the structural and energy properties of cyclic ureas, specifically ethyleneurea and N,N′-trimethyle- neurea, 8 parabanic acid, 9 barbital, 10 hydantoin, and 2- thiohydantoin 11 and other heterocycles with a benzene ring fused to a five-membered ring containing two nitrogen heteroatoms, namely, 2-mercaptoimidazole 12 and 2-mercapto- benzimidazole, 13 this article reports an experimental and computational thermochemical study of ETU. The standard (p° = 0.1 MPa) molar energy of combustion in the condensed phase at T = 298.15 K for the compound studied was measured by rotating bomb combustion calorimetry. The standard molar enthalpy of sublimation at T = 298.15 K was obtained by the vacuum sublimation drop microcalorimetric technique using a high-temperature Calvet microcalorimeter. These experimental results enabled the derivation of the standard molar enthalpy of formation of ETU in the gaseous state at T = 298.15 K. The gas-phase enthalpy of formation for ETU was also calculated from high-level molecular orbital calculations at the G3- (MP2)//B3LYP level of theory. In addition, we have also calculated the gas-phase enthalpy of formation of N,N′- trimethylenethiourea (MTU) from the same high-level molecular orbital calculations to develop a possible relation between the ring size and the enthalpy of formation. The main purpose of these studies is to provide reliable data for these key Special Issue: Memorial Issue in Honor of Ken Marsh Received: January 25, 2017 Accepted: March 30, 2017 Figure 1. Structural formula of ethylenethiourea (ETU) and N,N′- trimethylenethiourea (MTU) studied experimentally and computa- tionally, respectively. Article pubs.acs.org/jced © XXXX American Chemical Society A DOI: 10.1021/acs.jced.7b00083 J. Chem. Eng. Data XXXX, XXX, XXX-XXX