Upper rim tetrathiafulvalene-bridged calix[4]arenes Matthias H. Düker a , Rafael Gómez b , Christophe M. L. Vande Velde c , Vladimir A. Azov a,⇑ a University of Bremen, Department of Chemistry, Leobener Str. NW 2C, D-28359 Bremen, Germany b Universidad Complutense, Departamento de Química Orgánica, Avda. Complutense s/n, E-28040 Madrid, Spain c Karel de Grote University College, Department of Applied Engineering, Salesianenlaan 30, 2660 Antwerp, Belgium article info Article history: Received 17 February 2011 Revised 22 March 2011 Accepted 28 March 2011 Available online 5 April 2011 Keywords: Calixarenes Tetrathiafulvalenes Cyclic voltammetry Molecular recognition Weak hydrogen bonds abstract The synthesis of novel upper rim calix[4]arene–tetrathiafulvalene conjugates 1a–d has been performed by bridging the tetrachloromethylated calix[4]arene derivative 4 with the corresponding tetrathiafulva- lene-dithiolates. The cyclic voltammetry of 1a–d shows a two-step oxidation behavior, whereas NMR binding titrations showed their binding affinity to pyridinium salts. X-ray structure of 4 features calixa- rene fixed in the pinched cone conformation; its crystal packing is defined by the network of C–HÁÁÁCl weak hydrogen bonds. Ó 2011 Elsevier Ltd. All rights reserved. Tetrathiafulvalenes 1 have an established history of application in various areas of chemistry and materials science. Initially, these electron-rich heterocyclic compounds found extensive use in molecular electronics. 2 In later years, due to their unique electronic properties, they have been widely employed as building blocks in diverse supramolecular systems, where they have played the role of redox switching units 3 in a variety of architectures, 4 among which interlocked supramolecular devices 5 are one of the most fascinating. Calixarenes, 6 a family of macrocyclic compounds, have been shown to be superb molecular scaffolds for the construction of mac- romolecular and supramolecular architectures. 7 Being interested in host–guest chemistry and in the design of redox-responsive assem- blies based on the tetrathiafulvalenes, 8 we have turned our atten- tion to the excellent scaffolding features of the calix[4]arene moiety. Calix[4]arenes, the smallest members of the family, have a bowl shape in the cone conformation with a cavity suitable for encapsulation of guest molecules. Until now, only relatively few tet- rathiafulvalene–calix[4]arene derivatives have been reported, 9,10 and almost all of them were lower rim conjugates. 10 Some of these compounds displayed sensing properties toward cationic and anionic species. 10b–e,g Additionally, 1,3-alternate thiacalix[4]arene– TTFs, 11 as well as calix[4]pyrrolo-TTFs 12 and TTF-bridged resor- cin[4]arene cavitands, 13 which possess structurally-related architectures, are worth mentioning. Thus, we decided to extend the bowl of calix[4]arenes by the attachment of the two tetrathiafulvalene bridges 14 to its upper rim (compound 1, Scheme 1). Molecular modeling 15 using semi- empirical methods has shown that such structures should have a rather broad conformational space. Several low-lying conforma- tions with comparable energies within a rather narrow energy range could be determined. In a set of ‘closed’ conformations, two tetrathiafulvalene units are extending above the calix[4]arene bowl and are being tilted into the cavity; the degree of tilt can vary, together with the deformation of the calixarene bowl (cone— pinched cone conformations). In ‘open’ conformations, the two TTF moieties are far away from each other pointing outside the cavity. Closed conformations possess an empty cavity suitable for guest encapsulation. We expected that the presence of electron- rich TTF moieties may contribute to the binding of electron- deficient guests. In addition, redox-active TTF moieties offer the potential of sensing through electrochemical methods and switch- ing of the receptor’s binding ability by oxidation/reduction. Herein, we present the synthesis, electrochemical, and binding properties of four novel upper rim calix[4]arene–tetrathiafulvalene electroac- tive conjugates. The calixarene backbone was prepared from commercially avail- able 4-tert-butylcalix[4]arene 2. First, the tert-butyl groups in com- pound 2 were removed in a ‘retro-Friedel–Crafts’ reaction and the four hydroxyl groups were propylated in a Williamson etherification reaction, using NaH as the base, to afford calix[4]arene 3 fixed in the cone conformation (Scheme 1). Then, 3 was chloromethylated using paraformaldehyde/HCl in dioxane/H 3 PO 4 /AcOH to afford the key functionalized intermediate 4. 14b Calix[4]arene–tetrathiafulvalene 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.03.140 ⇑ Corresponding author. Tel.: +49 421 218 63126; fax: +49 421 218 63120. E-mail address: vazov@uni-bremen.de (V.A. Azov). Tetrahedron Letters 52 (2011) 2881–2884 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet