Size-Dependency of Hückel’s Rule in Neutral Molecules: Alternating Behavior in Global Ring Current of Furan-Acetylene Macrocycles

Global aromaticity is commonly observed in charged macrocycles, but rarely in their neutral state. Therefore, the significance of global effects in neutral macrocycles, as well as their size dependency, remains an open question. Here we present a series of furan-acetylene macrocycles, ranging from pentamer to octamer, which display alternating contributions of the global aromatic and antiaromatic ring currents at their neutral state. Calculations and X-ray structures reveal relatively planar geometries regardless of the macrocycle size. We find that the odd-membered macrocycles display global aromatic characteristics, while the even-membered macrocycles display contributions from globally antiaromatic ring current. These factors are expressed electronically (oxidation potentials), optically (emission spectra), and magnetically (chemical shifts). DFT calculations support the experimental findings, showing HOMO and LUMO degeneracy for the odd-membered macrocycles and HOMO-1 and LUMO+1 degeneracy for antiaromatic macrocycles. The global characteristics are more pronounced for small macrocycles and are attenuated for larger members, establishes furan-acetylene macrocycles as shape-persistent models for the study of global aromaticity

Bis(benzyltrimethylammonium) bis[(4SR,12SR,18RS,26RS)-4,18,26-trihydroxy-12-oxido-13,17-dioxaheptacyclo[14.10.0.03,14.04,12.06,11.018,26.019,24]hexacosa-1,3(14),6,8,10,15,19,21,23-nonaene-5,25-dione] sesquihydrate: dimeric structure formation via [O—H—O]−negative charge-assisted hydrogen bonds (–CAHB) with benzyltrimethylammonium counter-ions

The reaction between bis-ninhydrin resorcinol and benzyltrimethylammonium fluoride in ethanol has produced the title compound, 2C10H16N+·2C24H13O8−·1.5H2O, which contains a unique centrosymmetric supramolecular dimeric entity, where two deprotonated ligands are held together via two strong and short [O...O = 2.4395 (13) Å] [O—H—O]− bonds of the type negative charge-assisted hydrogen bonds (–CAHB). The central aromatic rings of the ligands create parallel-displaced π–π stacking at an interplanar distance of 3.381 (1) Å, which helps stabilize the dimer. In the crystal, two symmetry-related solvent water molecules with a site occupancy of 0.75 are attached to the carbonyl groups of the dimer by weaker O—H...O hydrogen bonds, forming chains along [101]

Alternating behavior in furan-acetylene macrocycles reveals the size-dependency of Hückel’s rule in neutral molecules

Abstract Aromaticity can be assigned by Hückel’s rule, which predicts that planar rings with delocalized (4n + 2) π-electrons are aromatic, whereas those with 4n π-electrons are antiaromatic. However, for neutral rings, the maximal value of “n” to which Hückel’s rule applies remains unknown. Large macrocycles exhibiting global ring current can serve as models for addressing this question, but the global ring current are often overshadowed in these molecules by the local ring current of the constituent units. Here, we present a series of furan-acetylene macrocycles, ranging from the pentamer to octamer, whose neutral states display alternating contributions from global aromatic and antiaromatic ring currents. We find that the odd-membered macrocycles display global aromatic characteristics, whereas the even-membered macrocycles display contributions from globally antiaromatic ring current. These factors are expressed electronically (oxidation potentials), optically (emission spectra), and magnetically (chemical shifts), and DFT calculations predict global ring current alternations up to 54 π-electrons

5-[2,4-Dihydroxy-5-(5-hydroxy-2,4,6-trioxo-3,5-dihydro-1H-pyrimidin-5-yl)-3-methoxyphenyl]-5-hydroxy-3,5-dihydro-1H-pyrimidine-2,4,6-trione pentahydrate

The title compound, C15H12N4O11·5H2O, has a `propeller-like' structure. The two alloxan units have screw-boat conformations. Their mean planes are normal to the central aromatic ring with dihedral angles of 87.91 (7) and 88.27 (7)°, and they are inclined to one another by 40.86 (7)°. In the crystal, molecules are linked via O—H...O and N—H...O hydrogen bonds, forming a three-dimensional framework. There are also C—H...O hydrogen bonds present within the framework

Fenchone Derivatives as a Novel Class of CB2 Selective Ligands: Design, Synthesis, X-ray Structure and Therapeutic Potential

A series of novel cannabinoid-type derivatives were synthesized by the coupling of (1S,4R)-(+) and (1R,4S)-(−)-fenchones with various resorcinols/phenols. The fenchone-resorcinol derivatives were fluorinated using Selectfluor and demethylated using sodium ethanethiolate in dimethylformamide (DMF). The absolute configurations of four compounds were determined by X-ray single crystal diffraction. The fenchone-resorcinol analogs possessed high affinity and selectivity for the CB2 cannabinoid receptor. One of the analogues synthesized, 2-(2′,6′-dimethoxy-4′-(2″-methyloctan-2″-yl)phenyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (1d), had a high affinity (Ki = 3.51 nM) and selectivity for the human CB2 receptor (hCB2). In the [35S]GTPγS binding assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 2.59 nM, E(max) = 89.6%). Two of the fenchone derivatives were found to possess anti-inflammatory and analgesic properties. Molecular-modeling studies elucidated the binding interactions of 1d within the CB2 binding site