OH HO R R R R HO HO HO OH OH OH OOC COO H3C CH3 CH3 H3C COO COO COO OOC OOC OOC O O O O O O O O CO CO CO CO CO CO CO CO O O O O O O O O CO CO CO CO CO CO CO CO a R = Me b R = Ph c R = C6H4OH- p e 1 2 c b d 2 O CO f 5 O CO 6 4 O CO 1 3 O CO 4 3 H H H H a J. Chem. Research (S), 1997, 72–73 J. Chem. Research (M), 1997, 0509–0517 Synthesis and Solvent Inclusion Complexation Studies of Benzoyl Derivatives of Resorcinol-aldehyde Tetramers by 1H NMR and Thermogravimetric Analysis Harmit Singh* and Serjinder Singh Department of Food Science and Technology, Guru Nanak Dev University, Amritsar 143005, India Benzoyl derivatives of resorcinol-aldehyde cyclophanes have been synthesized in order to observe their binding behaviour towards inclusion complex formation with solvent molecules using thermogravimeteric and 1H NMR techniques.Tetrameric cyclophanes 1a–c, obtained from the cyclization of resorcinol and acetaldehyde, benzaldehyde and p-hydroxybenzaldehyde respectively, have been used to synthesize 2–4 by the Schotten–Baumann reaction.The increased number of phenyl moieties is supposed to increase the size of the hydrophobic cavity of 1a–c. The inclusion properties of 2 and 3 have been studied by 1H NMR and thermogravimeteric analysis in order to understand the hydrophobic effect of the additional phenyl group. The results confirm that the size of the cavity is smaller in 3 than in 2. Compound 3 does not form any inclusion complex with molecules containing bigger atoms, e.g.CHCl3, and is therefore more selective, whereas 2 is more versatile. 1H NMR spectroscopy showed maximum binding for smaller molecules like CH3CN and CHCl3 with host 2. Complexation appears to involve the benzoyl groups, as indicated by the complexation-induced shift in the 1H NMR signals of the host protons (Table 4). The substituted cyclophanes 2–4 were characterized by elemental analysis and NMR spectroscopy. The resorcinol protons of the tetramer 1a were overlapped by the benzoyl protons in 2–3 and 4 and integration favoured the formation of octabenzoates.There were no D2O-exchangeable protons, indicating the absence of any free resorcinol OH. The 13C NMR spectrum of 2 contained a quartet for C-1 at d 19.8 which was replaced by a singlet in 3 and 4. The carbonyl C-7 was at d 164.39 while C-3, C-4 and C-5 gave signals at d 130.2 (s), 151.67 (s) (due to attached O) and 116.89 (d) respectively. The C-2 doublet was present at d 44.94 (s) in 2 and 30.3 (s) in 3.C-3, C-6, C-8, C-9, C-10 and C-11 were very close to each other as overlapping signals at d 130.2 (s), 129.44 (d), 136.2 (s), 128.2 (d), 128.35 (d) and 131.6. As investigated by 1H NMR1,2 and X-ray crystallographic 72 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence.studies,3 the host 1a forms inclusion complexes with small guests like the methyl group of quaternary amines, CHCl3 and CH3CN, as these fitted best in the cavity.It was thought that the cavity size should increase with the presence of benzoyl phenyls around the central bowl of the cyclophane 1. As is clear from the present study the effective size of the cavity remains almost the same, although the benzoyl groups help in binding the guest, as supported by 1H NMR studies. Experiments were designed to check directly the loss of guest thermogravimetrically. The sample was weighed on a microbalance after recrystallization and drying at 25 °C by vacuum suction from the solvent guest.The same sample was also weighed after drying at 100 °C by vacuum suction. The difference in the weight gave the ratio of host to guest (Tables 1–3). Host 2 was found to accommodate small apolar molecules such as CH2Cl2, CHCl3, C6H6 and ethyl acetate, forming 1:1 host–guest complexes, while with acetone and methanol 2 formed 1: 2 complexes (Table 1). Host 3 forms a high complex ratio with methanol, i.e., 1: 4 (Table 2), and it was interesting that 3 did not form any inclusion complex with CHCl3 because of the three large chlorine atoms, con- firming the previously established fact4 that 1b is smaller than 1a (from which 3 and 2 were synthesized).To explore the effect of size in more detail, the more selective 3 was investigated further with regard to its binding with various alcohols (Table 3). It was clear from these studies that linear molecules were preferred over branched ones.tert-Butyl alcohol did not form any complex with 3 whereas n-butanol formed a 1:1 complex. 1H NMR Complexation-induced Shifts of Solvent Guest Protons with Host 2.·It was interesting to study the less selective host 2 for its size discrimination by 1H NMR investigations. Compound 2, with a large hydrophobic cavity encircled by twelve phenyl groups, was recrystallized from various solvents. The host–guest inclusion complexation was studied by the shifts in the host as well as the guest signals. The shift in signals indicates clearly the interaction of various guests with different sites of 2.The Ha protons of host 2 were shifted upfield by d 0.274–0.165 for various solvents, but the effect on Hb was negligible (except for benzene), signifying that the effect on Ha is due to strain in the cyclophane ring while binding the guest. The protons of the resorcinol units, i.e. Hc and Hd, are deeply buried under the benzoyl groups and did not interact with the guest, as indicated by negligible shifts in the signals for these protons (Table 4).The maximum shift of the benzoyl signals was from d µ0.463 to µ0.297 for the He and d 0.456 for the Hf protons. The He protons showed a downfield shift implying a decrease in electron density at the ortho position of the benzoyl groups in the inclusion complexes. That the Hf protons showed the maximum upfield shift of all the host 2 protons indicated quite clearly that the benzoyl groups are enclosing the guest.The trend of the complexation-induced shifts also shows that the basic cavity, lined by four resorcinol units in 1a, is supplemented for its binding behaviour in 2 by the addition of eight benzoyl units which act as a source of lipophilic interactions. The signal shifts for the guest also indicate clearly the role of the benzoyl groups in 2 in binding the guest. The CH3OH groups show only a negligible shift (Table 4), indicating that in solution the cavity may be too hydrophobic after addition of the eight phenyls to attract hydrophilic molecules such as methanol.Shifts are maximal for apolar guests such as CHCl3, CH3CN and C6H6 (d 0.19, 0.29 and 0.17 respectively) (Table 4). Financial aid from CSIR and DST (New Delhi) is greatly acknowledged. Techniques used: 1H NMR, 13C NMR, microanalysis, thermogravimetry References: 15 Tables: 4 Received, 27th March 1996; Accepted, 13th November 1996 Paper E/6/02153K References cited in this synopsis 1 H.Schnieder, D. Guttes and U. Schnieder, Angew. Chem., Int. Ed. Engl., 1986, 25, 647. 2 J. R. Moran, S. Kharbach and D. J. Cram, J. Am. Chem. Soc., 1982, 104, 5828. 3 T. M. Linda, J. A. Tucker, E. D. Jurgen, W. I. A. Breyent, J. C. Shermon, R. C. Helgeson, C. B. Knobler and D. J. Cram, J. Org. Chem., 1989, 54, 1305. 4 S. Singh and H. Singh, Indian J. Chem., 1990, 29B, 601. J. CHEM. RESEARCH (S), 1997 73 Table 1 Inclusion complexes of 2 with various solvent guests Loss calculated Loss Host:guest Solvent for 1:1 observed ratio in guest complex (mg) (mg) complex CH2Cl2 CHCl2 C6H6 AcoEt Me2CO MeOH 1,4-Dioxane THF 0.28 0.18 0.22 0.16 0.29 0.05 0.30 0.32 0.30 0.18 0.23 0.14 0.58 0.09 0.97 0.53 1:1 1:1 1:1 1:1 1:2 1:2 1:2 2:3 Table 2 Inclusion complexes of 3 with various solvent guests Loss calculated Loss Host:guest Solvent for 1:1 observed ratio in guest complex (mg) (mg) complex CH2Cl2 CHCl3 C6H6 AcOEt Me2CO MeOH THF 0.08 0.20 0.05 0.25 0.14 0.04 0.20 0.04 0.06 0.14 0.23 0.08 0.17 0.19 2:1 1:0 1:3 1:1 2:1 1:4 1:1 Table 3 Inclusion complexes of 3 with various alcohols Loss calculated Loss Host:guest for 1:1 observed ratio in Alcohol complex (mg) (mg) complex MeOH PriOH BuiOH BunOH EtOH 0.04 0.17 0.15 0.15 0.1 0.17 0.24 0.17 0 0.09 1:4 2:3 1:0 1:1 1:1 Table 4 1H NMR complexation-induced shifts of host 2 and guest solventsa Dd (shift for host protons) MeOH CHCl3 MeCN C6H6 EtOH Et2O Ha Hb Hc Hd He Hf Shift of guest signal 0.27 0.02 0.09 0.06 µ0.29 0.54 0.02 0.20 0.03 0.09 0.05 µ0.36 0.48 0.19 0.26 0.03 0.06 0.00 µ0.29 0.51 0.29 0.24 0.17 0.06 0.06 µ0.29 0.61 0.17 0.16 µ0.02 0.03 0.03 µ0.39 0.45 0.09b 0.20 0.03 0.03 0.05 µ0.46 0.048 0.07b aNegative indicates a downfield shift.bShift for CH3.