FULL PAPER DOI: 10.1002/ejoc.200700809 A Combined Experimental and Theoretical Study of Anion–π Interactions in Bis(pyrimidine) Salts Angel Garcia-Raso,* [a] Francisca M. Albertí, [a] Juan J. Fiol, [a] Andrés Tasada, [a] Miquel Barceló-Oliver, [a] Elies Molins, [b] Daniel Escudero, [a] Antonio Frontera,* [a] David Quiñonero, [a] and Pere M. Deyà* [a] Keywords: Molecular recognition / Noncovalent interactions / Ab initio calculations / pi interactions We report the synthesis and X-ray characterization of an N,N'-tetramethylenebis(2-aminopyrimidinium) tetrafluoro- borate salt that exhibits anion–π interactions that are respon- sible for the crystal packing. The anion forms a sandwich complex with two pyrimidine rings. When the anion is ni- trate, the crystal packing is governed by anion–π interactions Introduction Noncovalent interactions are very important in modern chemistry, especially in the fields of supramolecular chemis- try and molecular recognition. [1] In particular, interactions involving aromatic rings [2] are key processes in both chemi- cal and biological recognition, since aromatic rings are om- nipresent in these systems. Interaction of cations with aro- matic systems, namely cation–π interactions, [3] are impor- tant for the binding of acetylcholine to the active site of the enzyme acetylcholine esterase [4] and for the ion selectivity of potassium channels. [5] In addition, they also play an im- portant role in transport of nitrogen through the membrane by the ammonia transport protein. [6] Anion–π interac- tions [7] are also important noncovalent forces that have at- tracted considerable attention. They have been observed ex- perimentally, supporting the theoretical predictions and the promising proposal for the use of anion receptors based on anion–π interactions in molecular recognition. [8] In ad- dition, π-acidic oligonaphthalenediimide rods have recently been proposed as transmembrane anion–π slides. [9] A recent review by P. Gamez et al. deals with anion-binding involv- ing π-acidic heteroaromatic rings. [10] Anion–π interactions are energetically less favorable than their cation–π counter- parts, because anions have larger van der Waals radii than [a] Department of Chemistry, Universitat de les Illes Balears, Crta. de Valldemossa km 7.5, 07122 Palma de Mallorca, Spain Fax: +971-173426 E-mail: toni.frontera@uib.es [b] Institut de Ciència de Materials de Barcelona (CSIC), Campus de la UAB, 08193 Cerdanyola, Barcelona, Spain Supporting information for this article is available on the WWW under http://www.eurjoc.org or from the author. Eur. J. Org. Chem. 2007, 5821–5825 © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5821 and hydrogen bonds, and the sandwich complex is not formed. Finally, a theoretical study of the anion–π interac- tions in charged pyrimidine rings is in good agreement with the experimental findings. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) cations and the binding energies strongly depend upon dis- tance. To solve this issue, the use of charged aromatic rings is a good strategy [11] to improve the interaction. In this paper we report the synthesis and X-ray charac- terization of N,N'-tetramethylenebis(2-aminopyrimidinium) tetrafluoroborate (1; Figure 1). We also analyze the effect of the anion on the crystal packing by comparing the solid- state structure of 1 with that of the previously reported N,N'-tetramethylenebis(2-aminopyrimidinium) nitrate (2). Relevant anion–π interactions are present in both structures and are responsible for the differences in the crystal pack- ing. Figure 1. N,N'-Tetramethylenebis(2-aminopyrimidinium) tetrafluo- roborate (1) and nitrate (2), and the 2-(methylamino)pyrimidinium cation.