Journal of Inclusion Phenomena and Macrocyclic Chemistry 41: 99–105, 2001. © 2001 Kluwer Academic Publishers. Printed in the Netherlands. 99 Can Thiacalixarene Surpass Calixarene? NOBUHIKO IKI ∗ and SOTARO MIYANO Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07, Aoba-ku, Sendai 980-8579, Japan (Received: 15 July 2001; in final form: 31 August 2001) Key words: calixarene, chirality, coordination, inclusion, thiacalixarene, sulfinylcalixarene, sulfonylcalixarene Abstract Heteroatom-bridged calixarenes have been confined into the unexplored frontier of the vast realm of the calixarene chemistry because of their synthetic difficulty. Since we found facile one-step synthesis of thiacalix[4]arene, in which four methylene bridges of calix[4]arene are replaced by four sulfides, we have been engaged in the study on this new molecular platform regarding the improvements for the synthetic procedures, structural analyses, chemical modifications, and functional de- velopments. In this review are described the results of our own study to demonstrate the potentials over the limits of the conventional calixarenes, putting emphasis on the indispensable role of the bridging sulfur. Highlighted examples are (1) enlargement of the calix skeleton to provide larger cavity, (2) ready oxidizability to sulfoxide and sulfone for providing new members of S bridged calixarenes, and (3) coordination to specific metal ions controlled by the oxidation state of S. These indicate a hopeful future for the thiacalixarene platform in the forthcoming applications to functional molecular devices. Introduction Calixarenes (1) are often described as “macrocyles with (almost) unlimited possibility” [1] because of their versat- ility and utility as host molecules, which mostly comes from the ease in the synthesis of the basic platform and ready functionalization at the lower and upper rims to con- struct variously modified three-dimensional structures [2]. Although replacement of the CH 2 linkage by heteroatoms such as NH, O, and S had been a challenge in the calix- arene history [3], synthetic difficulty retarded the emergence of heteroatom-bridged calixarenes to explore the interesting properties expected. Rare examples of such heterocalix- arenes are thiacalix[4]arene (2) by Sone et al. [4] and silacalix[4]arene (3) by König et al. [5], both of which were prepared in low yields by stepwise joining of phenol units followed by cyclization. By contrast, in 1997, we reported the facile one-step synthesis of 2 by simply heating a mixture of a p-alkylphenol and S 8 in the presence of a base [6]. Soon after the ready obtainment of 2 in substantial quantities, we were aware of the potential importance of 2 as a new member of the calixarene family by possessing structural as well as electronic characteristics due to sulfide functionality, which led us [7], and also other research groups [8], to engage in the studies on the modifications, stereochemical aspects, and applications to functional materials. In this paper, we review our own results of such endeavors to demonstrate the inherent properties and functions not attainable by the conventional calixarenes. ∗ Author for correspondence. Synthesis and structure of thiacalix[n]arenes Although it has been documented that heating a mixture of a phenol and elemental sulfur gives linear oligomers of the phenol linked by sulfides [9], formation of the corresponding cyclic oligomers had not been mentioned. In this context, a paper by Hori et al. [10] attracted our attention, in which they disclosed a mass spectrum of a reaction mixture ob- tained by the treatment of calcium salt of p-nonylphenol with sulfur. Close inspection of the spectrum showed the presence of a peak of mass number of 1,000, coinciding with that of a cyclic tetramer of the phenol joined by sulfide, i.e., p-nonylthiacalix[4]arene. After extensive collaboration with Hori’s group, it was eventually successful to obtain p-tert-butylthiacalix[4]arene (2) by heating a mixture of p- tert-butylphenol and elemental sulfur in the presence of a base catalyst, NaOH, at 230 ◦ C in 54% yield (Scheme 1) [6]. The procedure is equally applicable to p-tert-octylphenol (tert-octyl = Oct t = 1,1,3,3-tetramethylbutyl) to give p-tert- octylthiacalix[4]arene (4) [11]. This allowed us to obtain several tens of grams of thiacalix[4]arenes at one time for studying their behaviors or further modifications for preparing functional materials as described below. Also