Hydrophobic Concave Surfaces and Cavities by Combination of Calix[4]arenes and Resorcin[4]arenes

Coupling reactions of calix[4]arenes and modified resorcin[4]arenes have been investigated. Reaction of mono(chloroacetamido)calix[4]arene 4 with tetrahydroxycavitand 9 gave the 1:1 coupled product 13 in 61% yield. Combination of upper‐rim 1,3‐difunctionalized calix[4]arene 5 with 9 afforded predominantly the 2:1 calix‐resorcinarene 18 in 47% yield. Reaction of 1,2‐difunctionalized calix[4]arene 6 with 9 gave five products, namely, endo 1:1 (19), exo 1:1 (20), endo‐endo 2:1 (21), endo‐exo 2:1 (22), and exo‐exo 2:1 (23) in ratios that depend on the reaction conditions. The stereochemistry of the different products was determined with NOESY experiments. The structures of 21 a and 23 b were calculated by using molecular mechanics, which revealed that intramolecular hydrogen bonds are only present in the former. Reaction of 1,2‐bis(chloroacetamido)calix[4]arene 26, which has two additional nitro groups at the remaining aromatic rings, with 9 yielded three different products, namely, endo 1:1 (28), endo‐endo 2:1 (30), and endo‐exo 2:1 (32) in ratios that depend on the reaction conditions. There is a preference for the endo orientation in the formation of the 1:1 coupled product, probably owing to an interaction of the nitro groups with the cavitand in the transition state. After conversion of the nitro groups in 28 into chloroacetamido moieties, reaction with Cs₂CO₃ in DMF under high‐dilution conditions afforded holand 33 in 26% yield together with calix[4]arene‐based carceplex 34 with an encapsulated DMF molecule (27% yield). Holand 33 was obtained in 33% yield by reaction of the tetrakis(chloroacetamide) endo‐endo 2:1 isomer 31 with tetrahydroxycavitand 9. Holand 33 contains a cavity of nanosize dimensions. Molecular mechanics simulations indicate that holand 33 adopts a conformation with eight hydrogen bonds and a large, preorganized cavity with two entrances of smaller dimensions. Molecular dynamics simulations of holand 33 in both CHCl₃ and THF showed that four solvent molecules can be accommodated in the cavity at well‐defined positions.