Letter pubs.acs.org/JPCL Rediscovering the Wheel. Thermochemical Analysis of Energetics of the Aromatic Diazines † ‡ † § § Sergey P. Verevkin,*, , Vladimir N. Emel’yanenko, Rafael Notario, María Victoria Roux, ∥ ⊥ James S. Chickos, and Joel F. Liebman † Department of Physical Chemistry, University of Rostock, Dr-Lorenz-Weg 1, D-18059, Rostock, Germany ‡ Faculty of Interdisciplinary Research, Department of “Science and Technology of Life, Light and Matter”, University of Rostock, Germany § Instituto de Química Física “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain ∥ Department of Chemistry and Biochemistry, University of Missouri-St. Louis, St. Louis, Missouri 63121, United States ⊥ Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, United States *S Supporting Information ABSTRACT: Thermochemical properties of pyrimidine, pyrazine, and pyridazine have been measured and re-evaluated to provide benchmark quality results. A new internally Δ ° consistent data set of fHm(g) has been obtained from combustion calorimetry and vapor pressure measurements. The gas and condensed phase enthalpies of formation of the parent diazines have been re-evaluated, and the results were compared to current theoretical calculations using the highly accurate first-principles methods: G3, G4, CBS- APNO, W1(RO). Simple “corrected atomization procedures” to derive theoretical Δ ° fHm(g) directly from the enthalpies H298 have been tested and recommended as an alternative to using the bond separation and isodesmic reaction models for organic cyclic and heterocyclic compounds containing one to three nitrogen atoms. SECTION: Molecular Structure, Quantum Chemistry, and General Theory iazabenzenes are key building blocks used to develop pyrazine ring. Many other pyrimidines and pyrazines show D compounds of biological, medicinal, and chemical biological activity and have natural functions. Additionally, alkyl interest. There are three isomeric diazabenzenes or diazines: derivatives of pyrazines are also commonplace ingredients of the 1,2-, more commonly known as pyridazine; the 1,3-, more the human diet as they arise from the cooking process. By commonly known as pyrimidine, and the 1,4-, more commonly contrast, pyridazines are almost unknown in the natural setting. known as pyrazine (Figure 1). Does any of this disparity between the abundance of pyrimidines, pyrazines and pyridazines reflect differences in their inherent chemical stability? Thermodynamics is able to provide a plausible explanation, provided that reliable data are available. Physical and chemical properties of benzene and its simple heteroatom nitrogen derivatives are textbook knowl- Figure 1. The structures of pyridazine, pyrimidine, and pyrazine. edge, and their properties should be known with impeccable quality. Much to our surprise and disappointment, this is still not the case for diazabenzenes. The previous comprehensive The study of biochemistry is inseparable from that of experimental study of both the condensed and gas phase pyrimidines. The simple pyrimidine derivatives thymine, enthalpies of formation of all three diazines was reported by cytosine, and uracil are three of the five key components of Tjebbes in 1962.1 These and some recent other measure- nucleic acids. The pyrimidine ring is also found as a 1−7 ’ substructure for purines, the other two key components of ments on these species are collected in Table 1. Tjebbes nucleic acids, as well as other biomolecules such as ATP and results were then commonly accepted. In 1989, using NADP(H). The pyrimidine ring is also a substructure for theoretical calculations on all three diazines at the MP3/6- pteridines and their benzo derivatives, and therefore are ubiquitous as folic acid and flavin derivatives within the Received: September 27, 2012 biochemical context, two inherent constituents of essential Accepted: November 9, 2012 coenzymes. These latter folic and flavin species also contain a Published: November 10, 2012 © 2012 American Chemical Society 3454 dx.doi.org/10.1021/jz301524c | J. Phys. Chem. Lett. 2012, 3, 3454−3459 The Journal of Physical Chemistry Letters Letter Table 1. Compilation of Thermochemical Data for Diazines (in kJ·mol−1 at T = 298.15 K) Δ ° Δg Δg Δ ° Δ ° compounds fHm(l or cr) crHm l Hm(298 K) fHm(g) fHmcalc pyridazine (l) 224.9 ± 0.9 [1] 53.5 ± 0.4 [1] 278.3 ± 1.3[30,31] 279.5 ± 2.9 [8]e 226.9 ± 1.3a 46.5 ± 2.2 [3]b 281.5 ± 1.3a 52.7 ± 4.5 [7] 52.8 ± 3.8 [7] 60.6 [6]d (225.9 ± 1.6) 54.6 ± 0.2a 281.7 (G4)a recommendeda 225.6 ± 0.7 54.6 ± 0.2 280.2 ± 0.7 280.1g pyrimidine (l) 146.6 ± 0.8 [1] 50.0 ± 0.3 [1] 195.7 ± 1.4 [30,31] 182.8 ± 2.9 [8]e 143.2 ± 1.8 [2] 49.9 ± 0.6 [2] 187.4 ± 4.2 [9]f 144.9 ± 1.0a 41.0 ± 1.9 [3] 44.0 [6]d (145.6 ± 0.6) 58.3 ± 0.6a 44.1 ± 0.4a 189.0 ± 1.1a 187.8 (G4)a recommendeda 145.6 ± 0.6 44.1 ± 0.4 189.7 ± 0.7 187.9g pyrazine (cr) 139.8 ± 1.2 [1] 55.3 ± 1.7 [3] 40.5 ± 1.7 [3] 196.1 ± 1.3 [30,31] 200.2 ± 2.9 [8]e 56.3 ± 0.5 [1] 41.8 ± 0.7 [1]c 41.0 ± 0.1 [4] 40.2 ± 0.2 [5] 39.9 [6]d 145.7 ± 1.3a 57.5 ± 0.4a 42.0 ± 0.8a,c 203.2 ± 1.5a 206.5 (G4)a recommendeda 145.7 ± 1.3 57.5 ± 0.4 42.0 ± 0.8 203.2 ± 1.5 206.4g aThis work; values given in italics were averaged and the averaged values are given in parentheses. bThis value was measured in ref 3 but was c ff Δg Δl d e considered unreliable. From the di erence between crHm and crHm. From Monte Carlo simulations. Calculated using the MP3/6-31G(d,p) method in ref 8. fA weighted average calculated using the CBS-APNO, G3, and G3B3LYP method in ref 9. gMean values obtained from G4 and W1 calculations given in Table S9. 31G(d,p) level, Wiberg et al.8 concluded that the experimental which is indispensable for proper temperature management of gas phase enthalpy of formation of pyrimidine was in error. the highly exothermic ILs synthesis reactions.16 Using CBS-APNO, G3, and G3B3LYP methods, Da Silva et al.9 The current study investigates the energetics of diazines from later suggested that the available measured enthalpy of both calorimetric and first principle computational perspectives formation of pyrimidine is high by 4−12 kJ·mol−1. Recently, where the comparison of these archetypical heterocycles will Lipkind and Chickos3,10 presented new vaporization enthalpies help benchmark contemporary calculational protocols. More of all three diazines using the technique of correlation-gas precisely, we investigate the enthalpies of formation of chromatography, and their results cast additional doubt on the pyridazine, pyrimidine, and pyrazine in both the condensed accuracy of the literature vaporization enthalpy measured for and gaseous state where our results and accompanying analysis Δ ° has ramifications for both the biochemical and computational pyrimidine. As indicated in Table 1, the experimental fHm(g) value reported for pyrimidine were in good agreement but chemistry communities. ff · −1 Materials. All compounds were purchased from Aldrich or di ered from the calculated results by more than 10 kJ mol . − The ambiguity of the thermochemical properties of pyrimidine Acros Ltd. Gas liquid chromatography (GLC) analyses of the and perhaps the other diazines initially prompted this work. as-purchased samples gave an average mass fraction of 0.99, in agreement with specifications. Liquid compounds were frac- Our interest has been reinforced by our current activities on the tionally distilled under flowing dry N , after being dried with field of ionic liquids (ILs).11 This field is currently dominated 2 molecular sieves (0.4 nm). Solid pyrazine was sublimed under by low melting imidazolium, pyridinium, pyrrolidinium, and − reduced pressure to remove any traces of solvent. The alkyl ammonium salts.12 15 However, the ease with which the determination of purity was carried out by GLC. No impurities six-membered 1,2-, 1,3-, and 1,4- diazines undergo quaterniza- (≥0.01 mass percent) could be detected in samples used in this tion reactions significantly extends the variety of ILs with 12 study. The samples were stored cold in the dark, either at promising practical properties. Pyridazinium-, pyrimidinium-, reduced pressure or in a nitrogen atmosphere. and pyrazinium-based ILs demonstrate high thermal, radiative, Combustion Calorimetry. For measurements of the enthalpies ff and chemical stability and thus o er many opportunities for of combustion of the diazines, an isoperibolic calorimeter with a ff fl wide application as liquid crystals, dye-stu s, uoroplastics, static bomb and a stirred water bath was used. The samples 13 anesthetics, and as chemotherapeutic agents. These ILs can were placed (under an inert atmosphere in a glovebox) in also be used as industrial solvents, especially as ligands for polythene capsules and burned in oxygen at 3.04 MPa pressure. 14 efficient catalyst recycling, or heat-resistant thermally stable The detailed procedure has been described previously,11,17 and explosives. They are also suitable candidates for high-energy it is briefly given in the Supporting Information. The density materials with higher performance and/or decreased combustion procedure has been tested successfully on the sensitivity with respect to thermal, shock, and friction secondary reference material, nicotinic acid. For the reduction stability.15 Use of the three diazines as precursors for ILs of the data to standard conditions, conventional procedures18,19 raised the necessity of reliable thermochemical properties, were used. The auxiliaries are given in Table S1 (Supporting 3455 dx.doi.org/10.1021/jz301524c | J.