Synthesis of p-tert-Butylthiacalix[4]arene and its Inclusion Property 1 Nobuhiko Iki, a, * Chizuko Kabuto, b Takanori Fukushima, b Hitoshi Kumagai, c Haruhiko Takeya, c Setsuko Miyanari, c Tsutomu Miyashi b and Sotaro Miyano a a Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07, Aoba-ku, Sendai 980-8579, Japan b Department of Chemistry, Graduate School of Science, Tohoku University, Aoba, Aoba-ku, Sendai 980-8578, Japan c Chemical Technology Laboratory, Cosmo Research Institute, Satte, Saitama 340-1093, Japan Received 12 November 1999; accepted 6 January 2000 Abstract —A practical method for the synthesis of p-tert-butylthiacalix[4]arene (TC4A), in which the methylene bridges of p-tert-butyl- calix[4]arene (C4A) are replaced by epithio groups, is presented by heating a mixture of p-tert-butylphenol, elemental sulfur S 8 , and NaOH as a base catalyst in tetraethylene glycol dimethyl ether. The inclusion behavior of TC4A for a wide range of solvent molecules is examined by recrystallization, showing preference for the guests depending upon the size and/or the substituent of the guests. The X-ray structure of a 1:2 host–guest complex of TC4A with 1,2-dichloroethane reveals that one guest molecule is included in the cavity of TC4A, while the other is included in the crystal lattice to form a clathrate-type complex. It is shown that the inclusion in the cavity is attained by a cooperative deformation of both the host and the guest.  2000 Elsevier Science Ltd. All rights reserved. Introduction Calixarenes are often called ‘the third host molecules’ 2 or ‘macrocycles with (almost) unlimited possibilities,’ 3 because of their attractive features such as ready availability by base-catalyzed condensation of p-alkylphenols and ease in the functionalization via modification of their lower rims (phenolic OH groups) and/or upper rims (the p-position), 4–6 which are not attainable by the conventional hosts such as crown ethers and cyclodextrins. By use of these synthetic advantages, quite a number of calixarene-based receptors have been synthesized and their functions have been utilized in various manners such as sensory, chromatography, separation chemistry and so on. 6 On the other hand, there has been very little initiative to develop functions of calixarenes via direct replacement of the bridging methyl- ene groups by heteroatoms such as O, N, and S. As one of such endeavors, Sone et al. first synthesized p-tert-butyl- thiacalix[4]arene (TC4A, Scheme 1), in which bridging CH 2 groups of p-tert-butylcalix[4]arene (C4A) are replaced by S, by acid catalyzed cyclization of an acyclic tetramer (4% yield), 7 and they reported the results of 1 H NMR study. 8 Ko ¨nig et al. synthesized p-tert-butylsilacalix[4]arenetetra- methyl ether, in which the linking units (X) are Si(CH 3 ) 2 , by stepwise reaction of p-tert-butylmethoxybenzene and dichlorodimethylsilane followed by cyclization (13% yield). 9 However, these works were seemingly only limited to the synthesis and study of the physicochemical properties of hetero-calixarenes themselves, as the synthetic difficulty prevented investigation and development of the functions of such hetero-calixarenes as high-performance materials. Tetrahedron 56 (2000) 1437–1443 Pergamon TETRAHEDRON 0040–4020/00/$ - see front matter  2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00030-2 Keywords: thiacalixarenes; calixarenes; sulfurization; inclusion complex. * Corresponding author. Tel.: +81-22-217-7264; fax: +81-22-217-7293; e-mail: iki@orgsynth.che.tohoku.ac.jp Scheme 1. The structure and abbreviations of p-tert-butylcalix[n]arene (CnA) and p-tert-butylthiacalix[n]arene (TCnA).