Central Ring System Research Articles

X-ray crystal structures of solvated bisimidazole derivatives including a half-way analogous lophine-type compound

The tetrachloro and tetrabromo substituted bisimidazoles 1,4-bis(4,5-bis(4-chlorophenyl)-1H-imidazol-2-yl)benzene (1) and 1,4-bis(4,5-bis(4-bromophenyl)-1H-imidazol-2-yl)benzene (2), respectively, as well as a corresponding aldehydic intermediate imidazole 4-(4,5-bis(4-bromophenyl)-1H-imidazol-2-yl)benzaldehyde (3) have been synthesized. Respective solvated complexes [1 DMSO (1:2)] (1a), [2 (1,4-dioxane) (1:5)](2a) and [3 DMSO · H2O (1:1:1)] (3a) were isolated and structurally studied by single crystal X-ray diffraction. Although the central three-membered ring systems in 1 and 2 are almost coplanar, there is no relevant stacking between the molecules. However, 1 and 2 show a distinct difference in conformation with respect to the orientation of the imidazole rings which is cisoid in 1a and transoid in 2a, being attributed to the specific solvent interactions. Hydrogen bonds of N—H···O, C—H···O and C—H···π type are found in all structures while Cl···Cl contacts are characteristic of 1a, Br···O and C—H···Br of 2a, and O—H···O and Br···Br contacts of the crystal structure of 3a. Owing to the formation of solvated crystals, especially the compounds 1 and 2 are represented as potential new inclusion hosts.

Chlorido[1-phenyl-3-(2,3,5,6-tetramethylbenzyl)benzimidazol-2-ylidene]silver(I)

In the title compound, [AgCl(C24H24N2)], the terminal phenyl and tetra­methyl­benzene rings [which form a dihedral angle of 87.92 (14)°] make dihedral angles of 59.59 (11) and 83.19 (12)° with respect to the central benzimidazole ring system. The Ag—C and Ag—Cl single-bond lengths are 2.087 (3) and 2.3267 (9) Å. The C—Ag—Cl bond angle is 172.84 (7)°. C—H⋯π inter­actions contribute to the stabilization of the crystal structure. A very weak π–π stacking inter­action between adjacent tetra­methyl­benzene rings [centroid–centroid distance = 4.0610 (18) Å] is also observed.

Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.

COX inhibitors which selectively inhibits the inducible COX-2 is an oenzyme that causes inflammation. They are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicity. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular trombotic events such as myocardial infarction. Therefore, there is still a need to develop better therapeutic effect and tolerability COX-2 inhibitor. The majority of COX-2 inhibitors are diaryl heterocycles. For optimum COX-2 selectivity and inhibitory potency a -SO(3)CH(3) or a- SO(2)NH(2) substituent at the para-position of phenyl ring was essential. A wide variety of heterocycles can serve as central ring system of the diaryl heterocycles structures. We report the screening of various 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety, directly or indirectly bound to the ring system, using the Protein-Ligand ANT System (PLANTS) docking software against the COX-2 enzyme. Various molecular structures of ligands were docked and scored to identify structurally similar ligands to SC-558 (reference ligand) in binding interaction to COX-2 binding site. The results show that 2,3-disubstituted-4(3H)-quinazolinones possess pbenzenesulfonamide moiety at C-2, and phenyl moiety at N-3 binds directly or indirectly to the ring system with high binding affinity. The docked ligand has orientations similar to that observed with SC-558 satisfying Lipinski's rule of five.

A rearrangement–cycloaddition approach to spiro-fused indanones

Spiro-fused indanones were constructed using a [4+2]-cycloaddition approach from α-methylene indanone dienophiles, which were elaborated from 4-chromanone in a number of steps including a key rearrangement process. This type of spiro-fused structure forms the central core ring system found in natural products such as coleophomone A. The cycloaddition reactions using an α-methylene indanone dienophile led to the exo diastereoisomer as the major cycloadduct, whereas the 1,4-dione based dienophile predominantly led to the endo diastereoisomer.

Direct Synthesis of Pyrazolo[5,1‐a]isoindoles via Intramolecular Palladium‐Catalyzed CH Bond Activation

AbstractAn efficient, direct synthesis of pyrazolo[5,1‐a]isoindoles employing a palladium‐catalyzed intramolecular CH bond activation of 1‐(2‐halobenzyl)pyrazoles has been developed. The use of lithium chloride (LiCl) was found to be essential in these reactions, to suppress further CH bond activation at the C‐3 position of pyrazolo[5,1‐a]isoindole, when C‐3 is unsubstituted. This protocol can be applied to the synthesis of a pyrazolo[5,1‐a]isoquinoline possessing a six‐membered central ring system and a fully substituted pyrazolo[5,1‐a]isoindole using sequential intra‐ and intermolecular CH bond activation.

Synthesis and Photophysical Properties of Expanded Dehydrobenzoannulenoannulene Trefoils

A sequential Sonogashira cross-coupling/Pd-mediated oxidative homocoupling strategy affords two-dimensional dehydrobenzoannulene trefoils containing different sizes of the central annulenic ring system. Use of these conditions instead of Cu-mediated homocoupling conditions yields a structural isomer possessing a triphenylene ([6]annulene) core. Noticeable differences in the absorption and emission spectra are observed depending upon the core unit.

5,10,15,20-Tetrakis(4-tolyl)porphyrin]zinc(II) dichloromethane solvate

In the title complex, [Zn(C48H36N4)]·CH2Cl2, the ZnII atom lies on an inversion center and the dichloro­methane solvent mol­ecule is disordered around an inversion center. The tolyl substituents are twisted compared to the central aromatic ring system of the porphyrin, similar to what is seen in previously published structures of this molecule [Dastidar & Goldberg (1996 ▶). Acta Cryst. C52, 1976–1980]. The dihedral angles between the mean planes of the tolyl rings and the central ring are 66.98 (6) and 60.40 (6)°.

3,3′-Diethyl-1,1′-[anthracene-9,10-diylbis(oxyethylene)]diimidazolium diiodide

In the title centrosymmetric compound, C28H32N4O2 2+ 2I−, the two midazole rings are approximately perpendicular to the central anthracene ring system [dihedral angle = 86.6 (2)°]. The ionic units are linked into a two-dimensional network parallel to (01) by C—H⋯I hydrogen bonds and π–π inter­actions involving the anthracene ring system and imidazole rings [centroid–centroid distance = 3.717 (3) Å].

1-Benzyl-3-phenyl-imidazolium hexa-fluoro-phosphate.

in the title compound, C16H15N2 +·PF6 −, a precursor of N-heterocyclic carbene, the phenyl and benzyl rings are twisted away from the central imidazolium ring system, making dihedral angles of 70.30 (8) and 32.03 (10)°, respectively. The crystal structure is stabilized by C—H⋯F hydrogen bonds. Furthermore, P—F⋯π inter­actions involving imidazolium rings are observed [F⋯π = 2.9857 (16), P⋯π = 4.1630 (16) Å, P—F⋯π = 127.92 (6)°].

Ethyl 2-(2,6-difluorobenzyloxy)-4-(4,6-dimethoxypyrimidin-2-yl)quinoline-3-carboxylate

In the title compound, C25H21F2N3O5, the pyrimidine and difluoro­benz­yloxy rings are twisted away from the central quinoline ring system, making dihedral angles of 54.6 (1) and 74.1 (1)°, respectively. A weak C—H⋯O inter­action links symmetry-related mol­ecules, forming a pseudo-dimer. π–π inter­actions between the quinoline rings of symmetry-related mol­ecules [centroid–centroid distance = 3.5479 (10) Å] link these dimers into chains parallel to [101]. Weak C—H⋯π inter­actions join adjacent chains, forming a two-dimensional layer parallel to (101).

Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system

Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and improved solubility are delineated.

6-(4-Methylphenyl)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

In the mol­ecule of the title compound, C19H18N4O3S, the central heterocylic ring system is oriented with respect to the trimethoxy­phenyl and 4-methyl­phenyl rings at dihedral angles of 1.1 (5) and 15.1 (5)°, respectively. The dihedral angle between the two benzene rings is 16.1 (4)°. In the crystal structure, mol­ecules are linked by inter­molecular C—H⋯O hydrogen bonds, and an intra­molecular C—H⋯N inter­action also occurs.

2,4-Bis(4-fluorophenyl)-3-azabicyclo[3.3.1]nonan-9-one

In the title compound, C20H19F2NO, a crystallographic mirror plane bis­ects the mol­ecule, passing through the N, O and two C atoms of the central ring system. The mol­ecule exists in a twin-chair conformation with equatorial dispositions of the 4-fluoro­phenyl groups on both sides of the secondary amino groups; the dihedral angle between the aromatic ring planes is 28.67 (3)°.

6-(4-Pyridyl)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

In the mol­ecule of the title compound, C17H15N5O3S, the planar central heterocylic ring system is oriented at dihedral angles of 5.32 (4) and 9.41 (4)°, respectively with respect to trimethoxy­phenyl and pyridine rings. Intra­molecular C—H⋯N, C—H⋯O and C—H⋯S hydrogen bonds result in the formation of a nearly planar six-membered ring, which is oriented at a dihedral angle of 3.07 (5)° with respect to the central heterocylic ring system, and non-planar six- and five-membered rings having twist and envelope conformations, respectively. In the crystal structure, inter­molecular C—H⋯N and C—H⋯O hydrogen bonds link the mol­ecules. There is a C—H⋯π contact between the pyridine ring and a methyl group and a π–π contact between the central heterocylic ring system and the trimethoxy­phenyl ring [centroid–centroid distance = 3.758 (1) Å].

Antalarmin

In the mol­ecule of the title compund [systematic name: N-butyl-N-ethyl-2,5,6-trimethyl-7-(2,4,6-trimethyl­phen­yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine], C24H34N4, the pyrrolopy­rimidine ring system is nearly planar, its five- and six-membered rings forming a dihedral angle of 5.3 (2)°. The benzene ring is nearly orthogonal to the central ring system. The N atom carrying the ethyl and n-butyl groups is flattened pyramidal.

3,6-Bis(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

In the mol­ecule of the title compound, C21H22N4O6S, the planar central heterocyclic ring system is oriented with respect to the trimethoxy­phenyl rings at dihedral angles of 2.60 (5) and 3.60 (6)°. Intra­molecular C—H⋯N and C—H⋯S hydrogen bonds result in the formation of planar five- and six-membered rings. In the crystal structure, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules. There is a C—H⋯π contact between a methyl group and a trimethoxy­phenyl ring, and a π–π contact between the central heterocyclic ring system and a trimethoxy­phenyl ring [centroid–centroid distance = 3.640 (1) Å].

6-(2-Methylphenyl)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

In the mol­ecule of the title compound, C19H18N4O3S, the planar central heterocylic ring system is oriented with respect to the trimethoxy­phenyl and 2-methyl­phenyl rings at dihedral angles of 4.43 (3) and 4.32 (3)°, respectively. The dihedral angle between the two benzene rings is 7.65 (4)°. In the crystal structure, inter­molecular C—H⋯N hydrogen bonds link the mol­ecules into centrosymmetric R 2 2(18) dimers. These dimers are connected via a C—H⋯π contact between the 2-methyl­phenyl and trimethoxy­phenyl rings, and a π–π contact between the thia­diazole and trimethoxy­phenyl rings [interplanar distance 3.51 Å, dihedral angles 4.17(4)°]. An intramolecular C—H⋯N hydrogen bond is also present.

6-(3-Pyridyl)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

In the mol­ecule of the title compound, C17H15N5O3S, the planar central heterocylic ring system is oriented with respect to the benzene and pyridine rings at dihedral angles of 6.61 (3) and 19.22 (3)°, respectively. An intra­molecular C—H⋯N hydrogen bond results in the formation of a six-membered ring, adopting a flattened boat conformation. In the crystal structure, inter­molecular C—H⋯N hydrogen bonds link the mol­ecules.

Enantioselective Synthesis of the Central Ring System of Lomaiviticin A in the Form of an Unusually Stable Cyclic Hydrate

A model system representing a protected form of the four central rings of the antitumor compound lomaiviticin A has been synthesized (outlined in red in the picture). The approach features an intramolecular furan Diels–Alder reaction, a stereoselective oxidative enolate coupling to dimerize the “halves,” and a base-initiated cascade reaction. The 1,4-diketone of the central ring system exists as a stable cyclic hydrate. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z704830_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Enantioselective Synthesis of the Central Ring System of Lomaiviticin A in the Form of an Unusually Stable Cyclic Hydrate

Ein Modellsystem, das eine geschützte Form der vier zentralen Ringe der antitumoralen Verbindung Lomaiviticin A darstellt, wurde synthetisiert (rot in der gezeigten Struktur). Die Synthese umfasst eine intramolekulare Diels-Alder-Reaktion eines Furans, eine stereoselektive oxidative Enolatkupplung zur Dimerisierung der Molekülhälften und eine durch Basen ausgelöste Reaktionskaskade. Das 1,4-Diketon des zentralen Ringsystems liegt als stabiles cyclisches Hydrat vor.