Facile synthesis of thiacalix[n]arenes (n ¼ 4, 6, and 8) consisting of p-tert-butylphenol and methylene/sulfide alternating linkage and metal-binding property of the n ¼ 4 homologue Noriyoshi Kon, *,   Nobuhiko Iki, * Yusuke Yamane, Shin Shirasaki and Sotaro Miyano Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07, Aoba-ku, Sendai 980-8579, Japan Received 18 July 2003; revised 19 September 2003; accepted 17 October 2003 Abstract—2,14-Dithiacalix[4]arene 3 4 was conveniently prepared in 16% yield by acid-catalyzed cyclocondensation of 2,2 0 -thiobis[4- tert-butylphenol] with formaldehyde. The present method also afforded the first isolation of the analogues with six and eight phenol units, 3 6 (10%) and 3 8 (5%), respectively. Solvent extraction showed that 3 4 had high selectivity toward Cu 2þ ion at pH 5.5 by coordination of the bridging sulfur with cooperative donation of the adjacent phenolate oxygens. Ó 2003 Elsevier Ltd. All rights reserved. 2,8,14,20-Tetrathiacalix[4]arene (e.g., 1 4 ), in which all four methylene bridges of the conventional calix- [4]arenes (e.g., 2 4 ) are replaced with sulfides, has been described as a new member of the calixarene family. 1 The convenient one-step synthesis of 1 4 from phenol and elemental sulfur (Scheme 1) 2 enabled a functional survey to reveal the role of sulfide linkages providing 1 4 various intrinsic characteristic features, which are not attainable by conventional calixarene 2 4 . Among them, especially noteworthy is the binding ability of 1 4 class compounds toward soft to intermediate metal ions according to the classification by the Ôhard and soft acids and bases (HSAB) ruleÕ. 3 X-ray structural analysis of several metal complexes of 1 4 has clearly elucidated that the bridging sulfide (S) in addition to the phenolate oxygen atoms (O  ) is able to serve as a coordination site to metal ions (Scheme 2). 4 Having the same O  ,S,O  -coordination manner, hexathiacalix[6]arene 1 6 was recently shown to have extractability 5 and to form a nano-sized decacop- per (II) complex by coordination of the bridging sul- fide. 6 On the other hand, synthesis of calixarenes, in which part, instead of all, of the methylene bridges of 2 n is replaced by heteroatoms, is, not to say difficult, but more laborious, because the synthetic protocol should be stepwise. 7 In such a trial, Sone et al. reported the synthesis of p-tert-butylthiacalix[4]arenes, 3 4 , 4, 5, and 6, in which one to three methylene bridges of 2 4 are X 1 X 2 OH OH Bu t Bu t n/2 1 n :X 1 =X 2 = S; n = 4, 6, 8 2 n :X 1 =X 2 = CH 2 ; n = 4, 6, 8 3 n :X 1 = S; X 2 = CH 2 ; n = 4, 6, 8 Bu t OH X 4 Bu t OH X 1 Bu t OH X 3 X 2 Bu t HO 4:X 1 = S; X 2 =X 3 =X 4 = CH 2 5:X 1 =X 2 = S; X 3 =X 4 = CH 2 6:X 1 =X 2 =X 3 = S; X 4 = CH 2 Keywords: thiacalixarenes; complexation; sulfide; extraction. * Corresponding authors. Tel.: +81-22-217-7222; fax: +81-22-217- 7293; e-mail: kon@toyota-ct.ac.jp; iki@orgsynth.che.tohoku.ac.jp   Present address: Toyota National College of Technology, Toyota 471-8525, Japan. Tel./fax: +81-565-36-5803. 0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2003.10.121 Tetrahedron Letters 45 (2004) 207–211 Tetrahedron Letters