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

Abstract

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···N and Ophenol···O distances of ca. 2.7 Å, and two dihedral angles that fall within the range of typical peptide γ‐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.

1H-NMR as a Structural and Analytical Tool of Intra- and Intermolecular Hydrogen Bonds of Phenol-Containing Natural Products and Model Compounds

“…Castellano et al [40] investigated in detail, through Cambridge Structural Database (CSD) and literature mining, the occurrence of 7- membered intramolecular hydrogen bonding involving phenol hydroxyl group donors. The CSD revealed numerous accepting functional groups including alcohols, ethers, amides, amines, ketones, N- containing heterocycles, N- oxides, phosphates, and phosphane oxides, with O (phenol)•••N and O (phenol)•••O distances of c.a.…”

Hydration of the Carboxylate Group in Anti-Inflammatory Drugs: ATR-IR and Computational Studies of Aqueous Solution of Sodium Diclofenac

“…The formation of intramolecular N–H···O bonds of ring size 7 is quite a rare event. 98 , 99 Usually, intramolecular N–H···O bonds of ring size 6 100 with the strongly nonlinear N–H···O moiety 101 are presented.…”

Synthesis of Tripodal and Hexapodal Pyrazole- and Benzimidazole-Bearing Compounds

“…2a,b This procedure is a modified version of the procedure previously described for the synthesis of 5 and 9-11. 2a,b,8 The deprotonation of the heterocyclic unit with sodium hydride was undertaken in anhydrous acetonitrile before the corresponding bromomethyl-substituted benzene derivative was added, and the mixture was stirred at room temperature under nitrogen (in the synthesis reported previously, THF 2a,b or DMF 8 was used as the solvent). Then, the reaction was quenched by the addition of water, the mixture was extracted with chloroform and the product was purified by flash chromatography on silica gel using a chloroform-methanol mixture as the eluent.…”

“…In summary, we have reported three possible practical synthetic procedures for the preparation of new tripodal trimethoxybenzene-based (1-4) and triethylbenzenebased (6,8) compounds, as well as new hexapodal compounds (12, 13), bearing either bromo-substituted benzimidazole/pyrazole units or their analogues lacking the bromo substituents. In addition, the preparation of the new trisbenzimidazolium cage 14 [as the tribromide and the tris(hexafluorophosphate) salts 14a,b] was included in this work.…”

“…The pyrazole-containing compounds 9-11 are reported to be selective receptors for ammonium ions 2a,b and have been used as building blocks in the self-assembly of a three-dimensional cage, 7 whereas compound 5 was described as an intermediate in the synthesis of a phloroglucinol model compound. 8 The benzimidazole-bearing compound 7 has been described as an anion receptor with perchlorate binding preference. 2c These previously reported, interesting applications show the potential of these structurally rather simple molecules and clarifies the need for facile syntheses of related compounds.…”