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 consistent data set of Δ f H m ° (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 f H m ° (g) directly from the enthalpies H 298 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 D iazabenzenes are key building blocks used to develop compounds of biological, medicinal, and chemical interest. There are three isomeric diazabenzenes or diazines: the 1,2-, more commonly known as pyridazine; the 1,3-, more commonly known as pyrimidine, and the 1,4-, more commonly known as pyrazine (Figure 1). The study of biochemistry is inseparable from that of pyrimidines. The simple pyrimidine derivatives thymine, cytosine, and uracil are three of the five key components of nucleic acids. The pyrimidine ring is also found as a substructure for purines, the other two key components of nucleic acids, as well as other biomolecules such as ATP and NADP(H). The pyrimidine ring is also a substructure for pteridines and their benzo derivatives, and therefore are ubiquitous as folic acid and flavin derivatives within the biochemical context, two inherent constituents of essential coenzymes. These latter folic and flavin species also contain a pyrazine ring. Many other pyrimidines and pyrazines show biological activity and have natural functions. Additionally, alkyl derivatives of pyrazines are also commonplace ingredients of the human diet as they arise from the cooking process. By contrast, pyridazines are almost unknown in the natural setting. 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- 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 experimental study of both the condensed and gas phase enthalpies of formation of all three diazines was reported by Tjebbes in 1962. 1 These and some recent other measure- ments 1−7 on these species are collected in Table 1. Tjebbes’ results were then commonly accepted. In 1989, using theoretical calculations on all three diazines at the MP3/6- Received: September 27, 2012 Accepted: November 9, 2012 Published: November 10, 2012 Figure 1. The structures of pyridazine, pyrimidine, and pyrazine. Letter pubs.acs.org/JPCL © 2012 American Chemical Society 3454 dx.doi.org/10.1021/jz301524c | J. Phys. Chem. Lett. 2012, 3, 3454−3459