Synthesis, X-ray characterization and computational Studies of N-imidazolyl and N-pyrazolyl pyrimidine derivatives Marta Torres a , Pablo Ca ~ nellas a , Carolina Estarellas a , Angel García-Raso a, * , Juan J. Fiol a , Francisca M. Albertí a , Antonio Frontera a, * , Elies Molins b , Ignasi Mata b , Pere M. Dey  a a a Departament de Química, Universitat de les Illes Balears, Crta. Valldemossa km 7.5, E-07122 Palma de Mallorca, Baleares, Spain b Institut de Ci encia dels Materials (CSIC), Campus de la Universitat Aut onoma, E-0183 Cerdanyola del Vall es, Barcelona, Spain article info Article history: Received 22 November 2011 Received in revised form 3 January 2012 Accepted 11 January 2012 Available online 24 January 2012 Keywords: Pyrimidines Imidazole and benzimidazole Ab initio calculations X-ray crystal structures Anionep interactions abstract In this manuscript we report the synthesis and X-ray characterization of neutral 2-(1H-imidazol-1-yl)- pyrimidine (1), 2-(1H-pyrazol-1-yl)-pyrimidine (2) and 1-(2-pyrimidinyl)-1H-benzimidazole (3). We have also obtained crystals of the corresponding hydrochlorides of compounds 1 and 3. Finally, the outer sphere complex of protonated 2-(1H-imidazol-1-yl)-pyrimidine with [CoCl 4 ] 2 as counterion is de- scribed. In several charged structures interesting anionep interactions determine the crystal packing. Moreover, in neutral systems some stacking interactions are governed by double lone pairep in- teractions. High level ab initio calculations (RI-MP2/def2-TZVP) have been used to evaluate the non- covalent interactions observed in the solid state and the interplay between them. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction For many years there has been great interest in the chemistry of pyrazoles, imidazoles, pyrimidines and related N-containing het- erocyclic derivatives. 1,2 Such systems play a significant role in many biological processes, due to their coordinating ability to metal ions. 3 The chemistry of transition metals associated with polydentate li- gands with sp 2 hybridised nitrogen atoms has been developed and very interesting inorganic architectures have been generated using this approach. 4 In particular, ligands designed for this purpose consist of triazine or pyrimidine moieties attached to one or more pyrazol-1-yl substituents. 5 These architectures are usually gov- erned by a variety of noncovalent interactions. 6 These forces in- clude hydrogen-bonding, 7 pep stacking, 8 cationep 9 and CeH/ p 8b,10 contacts, which are very common and well accepted among the supramolecular chemists. For around ten years, a new type of supramolecular interaction, namely anionep interaction, 11 has been increasingly reported in the literature, notwithstanding the preliminary improbability of considering repulsive interactions among the aromatic clouds and electron rich molecules. 12 The de- sign of highly selective anion receptors and channels represent important advances in this nascent field of supramolecular chemistry. Matile et al. 13 have also published remarkable synthetic ion channels based on anionep interactions. In addition, its im- portant role in enzymatic processes has been recently described. 14 The closely related lone pair (lp)ep interactions have been recently reviewed by Gamez et al., 15 designating the lone pairep contacts as a new supramolecular bond and rigorous analysis of the Cambridge Structure Database revealed that such contacts are not unusual in organic compounds, but have been overlooked in the past. Egli et al. have studied the importance of lone pairep interactions in bio- macromolecules (Z-DNA and RNA). 16 Indeed, lone pairep in- teractions have been found to be of great importance for the stabilization of biological macromolecules, as well as for the bind- ing of inhibitors in the binding pocket of biochemical receptors. 17 We have recently reported that protonated adenines and py- rimidines are well suited for establishing strong anionep in- teractions with a variety of anions, including BF 4  , NO 3  , Cl  , ZnCl 4 2 , etc. 18 In this manuscript we report the synthesis of 2-(1H-imidazol- 1-yl)-pyrimidine (imipyr, 1), 2-(1H-pyrazol-1-yl)-pyrimidine (pyr- apyr, 2) and 1-(2-pyrimidinyl)-1H-benzimidazole (bimipyr, 3). Their molecular structures in the solid state have been elucidated by X-ray diffraction analysis. Furthermore, we also report the synthesis and X-ray characterization of the corresponding hydro- chlorides of 1 and 3 (compounds 4 and 5, respectively). Moreover, a multicomponent assembly has been characterized by X-ray crystallography (compound 6), which consist in a co-crystal of 2 and the nitrate salt of protonated pyrimidin-2-one (see Fig. 1). * Corresponding authors. Fax: þ34 971 173426; e-mail addresses: angel.gar- cia-raso@uib.es (A. García-Raso), toni.frontera@uib.es (A. Frontera). Contents lists available at SciVerse ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2012.01.023 Tetrahedron 68 (2012) 2374e2382