Iodine-promoted formal [5+1] annulation of 2-vinylanilines and thiuram: a facile approach for the synthesis of 2-aminoquinolines

Quinolines especially 2-aminoquinolines are highly important heterocycles in medicinal chemistry. 2-Aminoquinolines can be synthesized via stepwise construction of quinoline ring followed by additional amination, however the protocol is cumbersome. Herein, we describe a [5+1] cyclization of 2-vinylanilines with tetraalkylthiuram disulfide in the presence of iodine and copper(II) triflate. This reaction directly employs readily available and low-cost thiuram as both C1 synthon and nitrogen source, providing a facile approach for one-step synthesis of a variety of 2-aminoquinolines in good to excellent yields.

Role of pK a in establishing the crystal structures of six hydrogen-bonded compounds of 4-methylquinoline with different isomers of chloro- and nitro-substituted benzoic acids

The structures of the six hydrogen-bonded 1:1 compounds of 4-methylquinoline (C10H9N) with chloro- and nitro-substituted benzoic acids (C7H4ClNO4), namely, 4-methylquinolinium 2-chloro-4-nitrobenzoate, C10H10N+·C7H3ClNO4 −, (I), 4-methylquinoline–2-chloro-5-nitrobenzoic acid (1/1), C10H9N·C7H4ClNO4, (II), 4-methylquinolinium 2-chloro-6-nitrobenzoate, C10H9.63N0.63+·C7H3.37ClNO4 0.63−, (III), 4-methylquinolinium 3-chloro-2-nitrobenzoate, C10H9.54N0.54+·C7H3.46ClNO4 0.54−, (IV), 4-methylquinolinium 4-chloro-2-nitrobenzoate, C10H10N+·C7H3ClNO4 −, (V), and 4-methylquinolinium 5-chloro-2-nitrobenzoate, C10H10N+·C7H3ClNO4 −, have been determined at 185–190 K. In each compound, the acid and base molecules are linked by a short hydrogen bond between a carboxy (or carboxylate) O atom and an N atom of the base. The O...N distances are 2.5652 (14), 2.556 (3), 2.5485 (13), 2.5364 (13), 2.5568 (13) and 2.5252 (11) Å, respectively, for compounds (I)–(VI). In the hydrogen-bonded acid–base units of (III) and (IV), the H atoms are each disordered over two positions with O site:N site occupancies of 0.37 (3):0.63 (3) and 0.46 (3):0.54 (4), respectively, for (III) and (IV). The H atoms in the hydrogen-bonded units of (I), (V) and (VI) are located at the N-atom site, while the H atom in (II) is located at the O-atom site. In all the crystals of (I)–(VI), π–π stacking interactions between the quinoline ring systems and C—H...O hydrogen bonds are observed. Similar layer structures are constructed in (IV)–(VI) through these interactions together with π–π interactions between the benzene rings of the adjacent acid molecules. A short Cl...Cl contact and an N—O...π interaction are present in (I), while a C—H...Cl hydrogen bond and a π–π interaction between the benzene ring of the acid molecule and the quinoline ring system in (II), and a C—H...π interaction in (III) are observed. Hirshfeld surfaces for the title compounds mapped over d norm and shape index were generated to visualize the weak intermolecular interactions.

Oxalylacetylenes as Dielectrophiles for Annulation of Quinoline Ring: Synthesis of Highly Functionalized 1,3-Oxazinoquinolines

Oxalylacetylenes act as dielectrophiles in the annulation of quinolines with highly functionalized 1,3-oxazine cycle decorated by the ethynyl, oxalyl, ester and aryl substituents. The annulation proceeds under mild condition (room temperature, without catalysts) in 2:1 mode with respect to acetylene and quinoline to deliver 1,3-oxazinoquinolines in 45-88% yields. A beneficial feature of the reaction is that, in contrast to results on the reaction of quinolines with trifluoroacetylacetylenes in the presence of water, where H2O acted as a third electrophile, this reaction well tolerates the aqueous medium. This reaction tolerates also isoquinoline and phenanthridine.

Plausible Pnicogen Bonding of epi-Cinchonidine as a Chiral Scaffold in Catalysis

As a non-covalent interaction of a chiral scaffold in catalysis, pnicogen bonding of epi-cinchonidine (epi-CD), a cinchona alkaloid, was simulated to consider whether the interaction can have the potential controlling enantiotopic face like hydrogen bonding. Among five reactive functional groups in epi-CD, two stable complexes of the hydroxyl group (X-epi-CD1) at C17 and of the quinoline ring (X-epi-CD2) at N16 with pnictide family analytes [X = substituted phosphine (PX), i.e., F, Br, Cl, CF3, CN, HO, NO2, and CH3, and pnictide family analytes, i.e., PBr3, BiI3, SbI3, and AsI3] were predicted with intermolecular interaction energies, charge transfer (QMulliken and QNBO), and band gap energies of HOMO–LUMO (Eg) at the B3LYP/6-31G(d,p) level of density functional theory. It was found that the dominant site of pnicogen bonding in epi-CD is the quinoline ring (N16 atom) rather than the hydroxyl group (O36 atom). In addition, the UV-Vis spectra of the complex were calculated by time-dependent density functional theory (TD-DFT) at the B3LYP/6-31+G(d,p) level and compared with experimental measurements. Through these calculations, two intermolecular interactions (H-bond vs. pnicogen bond) of epi-CD were compared.

New (Iso)Quinolinyl-Pyridine-2,6-dicarboxamide G-Quadruplex Ligands. A Structure-Activity Relationship Study

Quadruplex-interactive small molecules have a wide potential application, not only as drugs but also as sensors of quadruplexes structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4. Insertion of a positive charge upon methylation of quinoline/isoquinoline nitrogen increases compounds capacity to selectively stabilize G4s compared to duplex DNA, with a preference for parallel structures. Among these, compounds having a relative 1,3-position between the charged methylquinolinium/isoquinolinium nitrogen and the amide linker are the best G4 stabilizers. More interestingly, these ligands showed different capacities to selectively block DNA polymer-ization in a PCR-stop assay and to induce G4 conformation switches of hybrid h-Telo G4. Mo-lecular dynamic simulations with the parallel k-RAS G4 structure showed that the relative spatial orientation of the two methylated quinoline/isoquinoline rings determines the ligands mode and strength of binding to G4s.

Recent developments of quinoline derivatives and their potential biological activities

: Heterocyclic compounds containing the quinoline ring play a significant role in organic synthesis and therapeutic chemistry. Polyfunctionalized quinolines have attracted the attention of many research groups, especially those who work on the drug discovery and development. These derivatives have been widely explored by the research biochemists and are reported to possess wide biological activities. This review focuses on the recent progress in the synthesis of heterocyclic compounds based-quinoline and their potential biological activities.

Recent Advances in Transition Metal Mediated Synthetic Approaches to Quinoline Derivatives

Abstract:: Synthesis of heterocyclic compounds containing quinoline scaffold attracted a significant attention of organic chemists due to their importance as therapeutic agent in pharmaceutical industry. Quinolone molecule exhibit extensive biological activities a few of which are antiviral, anti-inflammatory antibacterial, antifungal, antiproliferative, anthelmintic and anticonvulsant. A variety of synthetic routes has been developed for construction compounds bearing quinoline nucleus due to its broad spectrum of pharmacological activities. This review describes recent development in transition metal mediated synthetic protocols of these important heterocycles by formation of quinoline ring or by substitution of quinoline rings including both modified conventional name reactions and novel routes with highly functionalized quinoline products.

Tailored Quinolines Demonstrates Flexibility to Exert Antitumor Effects through Varied Mechanisms - A Medicinal Perspective

Background: Quinoline is considered to be a privileged heterocyclic ring owing to its presence in diverse scaffolds endowed with promising activity profiles. In particular, quinoline containing compounds have exhibited substantial antiproliferative effects through diverse mechanism of actions which indicates that the heteroaryl unit is flexible as well as accessible to subtle structural changes that enables its inclusion in chemically distinct antitumor constructs. Methods: Herein, we describe a medicinal chemistry perspective on quinolines as anticancer agents by digging into the peer reviewed literature as well as patents published in the past few years. Results: This review will serve as a guiding tool for medicinal chemists and chemical biologist to gain insights about the benefits of quinoline ring installation to tune the chemical architectures for inducing potent anticancer effects. Conclusion: Quinoline ring containing anticancer agents presents enough optimism and promise in the field of drug discovery to motivate the researchers towards the continued explorations on such scaffolds. It is highly likely that adequate efforts in this direction might yield some potential cancer therapeutics in future.

Crystal structure of 7,7′-[(pyridin-2-yl)methylene]bis(5-chloroquinolin-8-ol)

In the title compound, C24H15Cl2N3O2, one quinoline ring system is essentially planar and the other is slightly bent. An intramolecular O—H...N hydrogen bond involving the hydroxy group and a pyridine N atom forms an S(5) ring motif. In the crystal, two molecules are associated into an inversion dimer with two R 2 2(7) ring motifs through intermolecular O—H...N and O—H...O hydrogen bonds. The dimers are further linked by an intermolecular C—H...O hydrogen bond and four C—H...π interactions, forming a two-dimensional network parallel to (001).