C–H group acidity and the nature of C–H···N interactions: crystal structural analysis of pyrazine and methyl substituted pyrazines

Abstract

Crystal structures of methyl-, 2,3-, 2,5- and 2,6-dimethyl-, and trimethylpyrazine (2–6) have been determined by X-ray diffraction analysis. Four of these compounds (2–4 and 6) are liquids and their single crystals have been grown in situ on the diffractometer using a miniature zone melting procedure. These structures are analysed together with those of pyrazine (1) and tetramethylpyrazine (7) in the context of C–H···N interactions. Compounds 1–7 were chosen because they contain only C, H and N atoms, and also C–H groups of variable acidity. This facilitates the comparison of C–H···N geometries with respect to the C–H group acidity. Compounds 1 and 2 are dominated by sp2 C–H groups in their molecules and their supramolecular structures are generated by sp2 C–H···N. On the other hand the domination of sp3 C–H groups at the molecular level in 6 and 7 results in crystal structures that are governed by sp3 C–H···N. A balance of sp2 and sp3 C–H groups in the dimethyl derivatives 3–5 leads to a situation where both kinds of C–H groups play a structure directing role. While the sp2 C–H groups form C–H···N, the sp3 C–H groups are involved in C–H···π interactions. Thus the C–H group interactions follow a property unique to hydrogen bonds—stronger donors interact with stronger acceptors while weaker donors approaching weaker acceptors. Inter-structural comparison revealed that H···N distances decrease with increasing C–H acidity and therefore C–H···N interactions could be considered as weak hydrogen bonds.