Cyclotribenzoin

Dedicated to Peter Vollhardt, for fifteen years of chemistry- and lifestyle-related inspiration

Abstract

Using cyanide-assisted benzoin condensation of isophthaldehyde, we prepared cyclotribenzoin: a cone-shaped macrocycle whose three benzene rings define a cuplike cavity, while six of its C–H bonds convergently point in the opposite direction. This combination of convergently oriented cation- and anion-binding groups, coupled with an exceedingly simple synthesis, promises to make cyclotribenzoin an appealing platform for supramolecular chemistry studies.

Key words

condensation - macrocycles - host–guest systems - molecular recognition - supramolecular chemistry

• References and Notes

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See also:
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• 12 Synthesis of Macrocycle 2 Isophthaldehyde (1, 684 mg, 5.10 mmol), EtOH (5 mL), and deionized H₂O (5 mL) were added to a round-bottom flask equipped with a stirring bar, and the mixture was heated at reflux under nitrogen until all of 1 dissolved. At that time, NaCN (25 mg, 0.51 mmol) was added into the round-bottom flask and heating was continued for 48 h. The precipitate obtained was filtered and then washed with deionized H₂O (10 mL), EtOH (10 mL), and Et₂O (10 mL). After recrystallization from 2-methoxyethanol, pure 2 was obtained (280 mg, 41%) as a white solid; mp 245 °C (decomp.). UV/vis (THF): λ_max (log ε) = 248 (4.29), 288 (3.46) nm. IR (neat): 3456 (w, ν_O–H), 3070 (w, ν_C–H), 2925 (w, ν_C–H), 1682 (s, ν_C=O), 1583 (s), 1432 (s), 1395 (s), 1274 (m), 1182 (m), 1083 (m), 796 (s), 743 (s), 692 (s) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.78 (s, 3 H), 7.63 (d, ³ J _H–H = 7.8 Hz, 3 H), 7.45 (d, ³ J _H–H = 7.8 Hz, 3 H), 7.35 (dd, ³ J _H–H = 7.8, 7.3 Hz, 3 H), 6.42 (d, ³ J _H–H = 5.5 Hz, 3 H), 6.01 (d, ³ J _H–H = 5.5 Hz, 3 H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 198.4, 140.8, 134.9, 132.4, 130.2, 130.0, 128.2, 74.7 ppm. ESI-LRMS: m/z [M – H]⁻ calcd for C₂₄H₁₈O₆: 401.11; found: 401.13. Single crystals of 2 were obtained over 7 d by vapor diffusion of CHCl₃ into its solution in THF (0.5 mg mL^–1).
• 13 Crystallographic information file (CIF) for compound 2 has been deposited with Cambridge Structural Database under deposition code CCDC 1055400.
• 14 Hua Y, Flood AH. Chem. Soc. Rev. 2010; 39: 1262 ; and the references cited therein.
• 15 Synthesis of Macrocycle 3 Compound 2 (128 mg, 0.32 mmol), imidazole (1.30 g, 19.1 mmol), and dry CH₂Cl₂ (15 mL) were added to a thick-walled 20 mL microwave vial. The mixture was stirred under nitrogen for 10 min. The reagent TBDMSCl (2.90 g, 19.1 mmol) was then added to the mixture. The vial was sealed, and then placed into a Biotage microwave reactor, where it was heated for 10 h at 40 °C. The reaction mixture was diluted with CHCl₃ (50 mL), washed with H₂O (50 mL), and the organic layer was separated and dried over anhydrous MgSO₄. After removal of solvent, the crude product was isolated as a light yellow oil. Pure compound 3 was obtained after recrystallization from pentane at –78 °C (142 mg, 60%); mp 167 °C. UV/vis (THF): λ_max (log ε) = 286 (3.61), 326 (3.18) nm. IR (neat): 3070 (w, ν_C–H), 2929 (w, ν_C–H), 1713 (s, ν_C=O), 1674 (s), 1581 (s), 1471 (s), 1362 (s), 1257 (m), 1120 (m), 1028 (m), 862 (m), 781 (s), 735 (s), 698 (s) cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.88 (s, 3 H), 7.72 (d, ³ J _H–H = 8.0 Hz, 3 H), 7.73 (d, ³ J _H–H = 7.6 Hz, 3 H), 7.33 (dd, ³ J _H–H = 8.0, 7.4 Hz, 3 H), 5.82 (s, 3 H), 0.87 (s, 27 H), 0.09 (s, 9 H), 0.08 (s, 9 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 198.3, 139.2, 135.7, 131.6, 129.5, 128.9, 127.0, 79.4, 25.9, 18.5, –4.6, –4.7 ppm. ESI-LRMS: m/z [M + Na⁺] calcd for C₄₂H₆₀O₆Si₃: 767.36; found: 767.38; m/z [2M + Na⁺] calcd: 1511.73; found: 1511.09.