Seven-Membered Intramolecular Hydrogen Bonding of Phenols: Database Analysis and Phloroglucinol Model Compounds

Seven-membered intramolecular hydrogen bonding (7MHB) arrangements involving phenolic hydroxyl group donors have been investigated through Cambridge Structural Database (CSD) and literature mining, and by the characterization of model compounds. The CSD reveals the numerous H-bond accepting functional groups that can participate in 7MHB when they are proximal to a phenolic OH, including alcohols, amides, amines, ethers, N-containing heterocycles, ketones, N-oxides, phosphates, and phosphane oxides. The HB contacts are defined by Ophenol center dot center dot center dot N and Ophenol center dot center dot center dot O distances of ca. 2.7 angstrom, and two dihedral angles that fall within the range of typical peptide ?-turns. Two of the identified 7MHB motifs have been readily mapped onto the phloroglucinol (1,3,5-trihydroxybenzene) scaffold to provide eight model compounds; intramolecular hydrogen bonding involving all three hydroxyl groups is shown to persist in solution and the solid state for the compounds. Intramolecular 7MHB enforces nonplanar conformations that should be useful when designing molecular hosts and catalysts.