But But ClH2C CH2Cl R HSH2C CH2 SH But But R S S + 6 3 8 But But 1 1 But R R = H R = Me R = OMe 2a 2b 2c 18 i ii 5 But But 11 9 6 2 But But Me Me 16 15 5 13 3a 3b 3c R = H R = Me R = OMe 4a 4b 4c R = H R = Me R = OMe 168 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 168–169† Synthesis and Structure of Novel 1,8-Bridged Fluorenophanes† Akihiko Tsuge,*a Yasuhiro Ueda,a Tadashi Arakia Tetsuji Moriguchi,a Kazunori Sakata,a Keizo Koya,b Shuntaro Matakab and Masashi Tashirob aDepartment of Chemistry, Kyushu Institute of Technology, Tobata-ku, Kitakyushu 804, Japan bInstitute of Advance Material Study, Kyushu University, Kasuga, Fukuoka 816, Japan A novel 1,8-bridged fluorenophane (4a) is found to assume an ‘inward-folded’ conformation with the bulky tert-butyl group located in the cavity, a situation which is different from the conformation of the corresponding dithiafluorenophane (3a).Cyclophanes are cyclic compounds consisting of aromatic units.Many aromatic components have been used in the cyclophane skeleton.1 Considerable attention has been paid to particular properties of the components, because of the strained structure of the ring system and its ability to form p-electronic interactions. It is of interest to examine the properties of a fluorene unit in cyclophane compounds, because of its aromatic nature and acidic proton. To the best of our knowledge, however, [2.2](2,7)fluorenophane is the only example2 to have been investigated so far.This is due to difficulties in introducing a functional group into sites other than the 2- and 7-positions by electrophilic reactions. In previous work3 we found that a chloromethyl group can be introduced into the 1,8-positions of the fluorene molecule by treatment with chloromethyl methyl ether in the presence of an appropriate Lewis acid. This chloromethylated fluorene should be a precursor for the synthesis of fluorenophane compounds. Thus, we describe here the synthesis of novel 1,8-bridged fluorenophanes and their conformational properties. Treatment of 3,6-di-tert-butylated fluorenophane with chloromethyl methyl ether in the presence of TiCl4 gave the 1,8-bis(chloromethyl)fluorene 1 in 58% yield.Bromination of 4-tert-butyl-m-xylene with N-bromosuccinimide (NBS), followed by treatment with thiourea afforded the bis(thiol) 2a. Compounds 2b and 2c were obtained according to reported methods.4 Cyclization of 1 and 2a–c using CsOH as a base under highly dilute conditions afforded the corresponding dithiafluorenophanes (3a–c) in 72–84% yields (Scheme 1).The 1H NMR spectra of 3a–c are summarized in Table 1. Signals for the CH2 bridge reflect the dynamic behaviour of the dithiafluorenophane. The C-9 hydrogens of 3a show a broad singlet, indicating that inversion of the ring at room temperature is slow on the NMR time-scale. In contrast, a pair of doublets with a separation of 22 Hz was observed in the spectra of 3b and 3c.These results strongly suggest that the barrier to inversion in dithiafluorenophanes depends on the bulkiness of the inner substituent (R). In order to determine for 3a the coalescence temperature and the free energy of activation for inversion, the temperature- dependent 1H NMR technique was employed. The measured barrier for the observed dynamic process is 11.54 kcal molµ1 at µ15 °C in CDCl3.‡ In contrast, there were no changes in the NMR signals for 3b or 3c, even at 150 °C in [2H6]Me2SO, indicating that 3b and 3c have rigid structures.We have already prepared various metacyclophanes consisting of three aromatic rings and confirmed their ‘inwardfolded’ conformation, which is characterized by one aromatic ring being folded into the cavity produced by the other two aromatic rings.5 Taking into account these results and the chemical shifts of the tert-butyl protons, it may be deduced that the dithia- fluorenophanes 3a–c assume a conformation in which the substituent R of the benzene ring is accommodated inside the cavity.After oxidation of 3a–c with m-chloroperbenzoic acid (MCPBA), pyrolysis was carried out in order to obtain the fluorenophanes 4a–c (Scheme 1). However, in spite of repeated trials, all attempts to prepare 4b and 4c resulted in failure, in most cases only the dimethyl compound 5 being isolated from very complex mixtures. In contrast, in the case of 3a the desired fluorenophane 4a was obtained in 29% yield.This is certainly due to steric hindrance of the substituent R during recombination of radical intermediates in pyrolysis: even when hydrogen was the substituent, the yield was not good. Data for the 1H NMR spectrum of 4a are also shown in Table 1. In 4a it is noted that the protons of the tert-butyl group attached to the benzene ring show an unexpectedly upfield shift, suggesting a conformation in which the tertbutyl group is located in the cavity formed by the p-cloud of the fluorene ring.This is in fairly good agreement with a considerable upfield shift of the aromatic protons adjacent to *To receive any correspondence (e-mail: tsuge@che.kyutech.ac.jp). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡1 cal=4.184 J. Scheme 1 Reagents and conditions: i, CsOH, EtOH;; ii, MCPBA, then 500 °C, 2 TorrBut But S H S But But H But But d 5.84 4a 3a J.CHEM. RESEARCH (S), 1997 169 the tert-butyl group. Inversion of one aromatic ring occurs during the transformation into a smaller cyclic system (Scheme 2). Further investigations of other types of 1,8-bridged fluorenophanes are in progress. Experimental All melting points are uncorrected. 1H NMR spectra were recorded at 500 MHz on a Nippon Denshi JEOL a-500 spectrometer in CDCl3 with Me4Si as an internal reference.Mass spectra were obtained on a Nippon Denshi JEOL DX-300 spectrometer at 75 eV using a direct-inlet system. Elemental analyses were carried out on a Yanaco MT-3 spectrometer. Column chromatography was performed on silica gel (Wako gel, C-300). (3-tert-Butyl-5-sulfanylmethylphenyl)methanethiol 2a.·A solution of 1,3-bis(bromomethyl)-5-tert-butylbenzene (30 g, 93 mmol) and thiourea (18.0 g, 0.24 mol) in DMSO (450 ml) was stirred at room tempearture for 15 h under an argon stream.After the reaction mixture had been poured into cold 10% aqueous NaOH (500 ml) and acidified with 10% hydrochloric acid, it was extracted with CH2Cl2. The extract was washed with water, dried over MgSO4, and evaporated in vacuo to leave a residue which was distilled to afford the bis(thiol) 2a (16.5 g, 79%) as a colourless liquid, bp 140–145 °C at 2 Torr (Found: C, 63.86; H, 8.13. C12H18S2 requires C, 63.65; H, 8.03%); m/z 226 (M+); dH 1.31 (9 H, s), 1.75 (2 H, t, J 8 Hz), 3.70 (4 H, d, J 8 Hz), 7.12 (1 H, s), 7.19 (2 H, s).Dithiafluorenophanes 3. General Procedure: Preparation of 6 , 1 5 , 1 8 - t r i - t e r t - b u t y l - 2 , 1 1 - d i t h i a [ 3 ] m e t a c y c l o [ 3 ] ( 1 , 8 ) f l u o r e n o p h a n e 3a.·A solution of 13 (1.09 g, 2.9 mmol) and 2a (0.70 g, 3.1 mmol) in EtOH–benzene (1:1; 300 ml) was added dropwise from a Hershberg funnel with stirring to a solution of CsOH (1.21 g, 8.07 mmol) and NaBH4 (0.12 g, 3.2 mmol) in EtOH (2 l) for 1 h.After solvents had been evaporated, the residue was extracted with CH2Cl2. The extract was washed with water, dried over MgSO4, and evaporated in vacuo to give 3a (1.22 g, 79%) as colourless prisms, mp 234–235 °C (from hexane) (Found: C, 79.32; H, 8.41. C35H44S2 requires C, 79.47; H, 8.40%); m/z 528 (M+); dH 1.34 (9 H, s), 1.38 (18 H, s), 2.70 (2 H, br s), 3.70 (4 H, s), 3.74 (4 H, s), 7.17 (2 H, d, J 1.5 Hz), 7.19 (2 H, s), 7.45 (1 H, s), 7.62 (2 H, d, J 1.5 Hz). 6 , 1 5 , 1 8 -T r i - t e r t - b u t y l- 2 , 1 1 -d i t h i a [ 3 ] m e t a c y c l o [ 3 ] ( 1 , 8 )f l u o r e n o - phane 3b.·3b was obtained according to the general procedure. Thus 13 (0.53 g, 1.41 mmol) and 2b4 (0.35 g, 1.46 mmol) gave 3b (0.64 g, 84%) as colourless prisms, mp 189–191 °C (from hexane) (Found: C, 79.83; H, 8.49. C36H46S2 requires C, 79.63; H, 8.56%); m/z 542 (M+); dH 1.32 (9 H, s), 1.36 (18 H, s), 1.90 (1 H, d, J 22 Hz), 2.39 (3 H, s), 2.90 (1 H, d, J 22 Hz), 3.48 (2 H, d, J 12 Hz), 3.74 (2 H, d, J 14 Hz), 3.95 (2 H, d, J 14 Hz), 3.99 (2 H, d, J 12 Hz), 7.14 (2 H, s), 7.15 (2 H, d, J 1.5 Hz), 7.61 (2 H, d, J 1.5 Hz). 6 , 1 5 , 1 8 - T r i - t e r t - b u t y l - 9 - m e t h o x y- 2 , 1 1 - d i t h i a [ 3 ] m e t a c y c l o [ 3 ] - (1,8)fluorenophane 3c.·3c was obtained according to the general procedure. Thus 13 (0.32 g, 0.85 mmol) and 2c4 (0.23 g, 0.90 mmol) gave 3c (0.34 g, 72%) as colourless prisms, mp 191–193 °C (from hexane) (Found: C, 77.58; H, 8.50.C36H46S2O requires C, 77.35; H, 8.31%); m/z 558 (M+); dH 1.32 (9 H, s), 1.35 (18 H, s), 2.03 (1 H, d, J 22 Hz), 3.21 (1 H, d, J 22 Hz), 3.51 (2 H, d, J 12 Hz), 3.60 (2 H, d, J 14 Hz), 3.86 (3 H, s), 3.93 (2 H, d, J 14 Hz), 3.99 (2 H, d, J 12 Hz), 7.13 (2 H, d, J 1.5 Hz), 7.18 (2 H, s), 7.58 (2 H, d, J 1.5 Hz). 5,13,16-Tri-tert-butyl[2]metacyclo[2](1,8)fluorenophane 4a.—The sulfone derivative of 3a (0.52 g, 0.88 mmol) was pyrolysed at 500 °C under reduced pressure (2 Torr) in a horizontal quartz tube.The resultant product was chromatographed with hexane as an eluent to afford 4a (0.12 g, 29%) from the first fraction as colourless needles, mp 296–298 °C (from hexane) (Found: C, 90.16; H, 9.66. C35H44 requires C, 90.44; H, 9.54%); m/z 464 (M+); dH 0.69 (9 H, s), 1.37 (18 H, s), 2.93–3.86 (8 H, m), 3.07 (1 H, d, J 19 Hz), 3.80 (1 H, d, J 19 Hz), 5.83 (2 H, s), 6.91 (2 H, d, J 1.5 Hz), 7.09 (1 H, s), 7.23 (2 H, d, J 1.5 Hz).Received, 5th August 1996; Accepted, 21st January 1997 Paper E/6/05440D References 1 F. V�ogtle, Supramolecular Chemistry, Wiley, Chichester, 1989; F. Diederich, Cyclophanes, The Royal Society of Chemistry, Cambridge, 1991; F. V�ogtle, Cyclophane Chemistry, Wiley, Chichester, 1989. 2 M. W. Haenel, Tetrahedron Lett., 1976, 3121; 1977, 1273. 3 A. Tsuge, T. Yamasaki, T. Moriguchi, T. Matsuda, Y. Nagano, H. Nago, S. Mataka, S. Kajigaeshi and M. Tashiro, Synthesis, 1993, 205. 4 M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 1543. 5 A. Tsuge, T. Sawada, S. Mataka, N. Nishiyama, H. Sakashita and M. Tashiro, J. Chem. Soc., Chem. Commun., 1990, 1066; A. Tsuge, T. Sawada, S. Mataka, N. Nishiyama, H. Sakashita and M. Tashiro, J. Chem. Soc., Perkin Trans 1, 1992, 1489; A. Tsuge, H. Takeo, H. Kabashima, T. Moriguchi, S. Mataka and M. Tashiro, Chem. Lett., 1996, 425. Scheme 2 Table 1 1H NMR spectra of fluorenophanes [d values (CDCl3)] Compound But R 9-H 1 1.41 (18 H) 3.95 (s) 3a 1.33 (9 H) 7.09 2.69 (br s) 1.37 (18 H) (Ar-H) 3b 1.32 (9 H) 2.39 1.89 (d, J 22 Hz) 1.36 (18 H) (CH3) 2.90 (d, J 22 Hz) 3c 1.32 (9 H) 3.86 2.03 (d, J 22 Hz) 1.36 (18 H) (OCH3) 3.20 (d, J 22 Hz) 4a 0.69 (9 H) 7.09 3.07 (d, J 19 Hz) 1.37 (18 H) (Ar-H) 3.80 (d, J 19