Heterocyclic Units Research Articles

Synthesis of 2 carbon-14 analogue of thioflavanones.

Thioflavanones are prevalent heterocyclic structural units in pharmaceutical and biologically active compound (Scheme ). In this paper, the synthesis of 2-phenylthiochroman-4-ones and 2-phenyl-4H-1-benzothiopyran-4-one labeled with carboxyl-14 is demonstrated.

Regioselective Transition‐Metal‐Free Synthesis of Diverse Benzothiazoles by Thermally Induced Cyclization of ortho‐Halobenzanilides

AbstractThe highly regioselective and efficient synthesis of diverse substituted‐benzothiazoles, including heterocyclic units and amino groups, was achieved in moderate to high yields from ortho‐bromothiobenzanilides, ortho‐bromoarylthioureas, ortho‐bromobenzanilides, and ortho‐dibromobenzanilides, regardless of the electron density and substituted positions, via the prevalent carbon‐sulfur bond formation by thermally induced intramolecular cyclization reaction without using any metal sources or other additives. Polysubstituted‐benzothiazoles, particularly 2,4‐, 2,6‐disubstituted, and 2,4,6‐trisubstituted benzothiazoles, could be efficiently synthesized by a facile cascade reaction from appropriate ortho‐bromobenzanilides under general thiolation conditions. This benign reaction represents a straightforward and practical approach toward diverse substituted‐benzothiazoles. In addition, the remaining bromine substituent of the resulting products was further utilized as a functional handle for the additional diversification and exploited as a complementary solution for the adjustment of harsh reaction condition. This methodology not only allows for the elaboration of benzothiazole molecules, but also provides a new valuable synthetic tool for a range of pharmaceutical applications.

Rationally designed tri-armed imidazole–indole hybrids as naked eye receptors for fluoride ion sensing

ABSTRACTThe present communication describes the design, synthesis, and characterization of unique tri-armed imidazole–indole hybrids RA-RE for naked eye detection of fluoride ion in 9:1 DMSO–water at concentration level of 1.5 ppm, which is recommended permissible limit of fluoride ion. Molecular structures of the receptors are so fabricated that both heterocyclic units, namely, indole and imidazole have been rationally used as chromophore and binding unit, respectively. Strategical introduction of nitro group(s) at the fifth position of indole ring remarkably enhances the binding ability of receptor RD making it highly selective toward fluoride ion (tetrabutylammonium salt) over other typical anionic species. The sensing event can be visualized by naked eyes swiftly with color change. This observation is well corroborated by a redshift of 80 nm in UV–visible spectroscopic studies. A peak at 16.1 ppm due to in 1H NMR titration validates the deprotonation of imidazolium N‒H by fluoride ion.

Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC 15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics.

Nucleoside antibiotics are a large class of pharmaceutically relevant chemical entities, which exhibit a broad spectrum of biological activities. Most nucleosides belong to the canonical N-nucleoside family, where the heterocyclic unit is connected to the carbohydrate through a carbon-nitrogen bond. However, atypical C-nucleosides were isolated from Streptomyces bacteria over 50 years ago, but the molecular basis for formation of these metabolites has been unknown. Here, we have sequenced the genome of S. showdoensis ATCC 15227 and identified the gene cluster responsible for showdomycin production. Key to the detection was the presence of sdmA, encoding an enzyme of the pseudouridine monophosphate glycosidase family, which could catalyze formation of the C-glycosidic bond. Sequence analysis revealed an unusual combination of biosynthetic genes, while inactivation and subsequent complementation of sdmA confirmed the involvement of the locus in showdomycin formation. The study provides the first steps toward generation of novel C-nucleosides by pathway engineering.

1,2,3]-triazole derivatives: Mesomorphic property dependence on the molecular shape

ABSTRACTNowadays, heterocyclic units have been extensively studied for the preparation of thermotropic liquid crystals due to their ability to impart lateral and/or longitudinal dipoles and induce changes in molecular shape. Key parameters to accede to stable mesophases are the position of the heterocycle and the nature of terminal and linking functions. We present in this paper, an overview of several series of 1,2,3-triazole liquid crystalline derivatives that we designed and characterized. We highlight the effect of different connecting functions and the geometry of mesogenic core on the mesomorphic behavior of these derivatives.

Bithiazole: An Intriguing Electron‐Deficient Building for Plastic Electronic Applications

The heterocyclic thiazole unit has been extensively used as electron-deficient building block in π-conjugated materials over the last decade. Its incorporation into organic semiconducting materials is particularly interesting due to its structural resemblance to the more commonly used thiophene building block, thus allowing the optoelectronic properties of a material to be tuned without significantly perturbing its molecular structure. Here, we discuss the structural differences between thiazole- and thiophene-based organic semiconductors, and the effects on the physical properties of the materials. An overview of thiazole-based polymers is provided, which have emerged over the past decade for organic electronic applications and it is discussed how the incorporation of thiazole has affected the device performance of organic solar cells and organic field-effect transistors. Finally, in conclusion, an outlook is presented on how thiazole-based polymers can be incorporated into all-electron deficient polymers in order to obtain high-performance acceptor polymers for use in bulk-heterojunction solar cells and as organic field-effect transistors. Computational methods are used to discuss some newly designed acceptor building blocks that have the potential to be polymerized with a fused bithiazole moiety, hence propelling the advancement of air-stable n-type organic semiconductors.

Effect of Heterocyclic Anchoring Sequence on the Properties of Dithienogermole-Based Solar Cells.

The synthesis and characterization of two new small molecular donor materials, DTGe(ThFBTTh2)2 and DTGe(FBTTh3)2, are presented for application in organic solar cells. These two materials represent structural evolutions of the high-efficiency, dithienogermole (DTGe)-cored small molecule DTGe(FBTTh2)2, in which the conjugation length in the backbone was extended by incorporating additional thiophene units. Using the same molecular framework, we have evaluated how the anchoring sequence of heterocyclic units influences material properties and function in solar cell devices. It was found that incorporating additional thiophene units into the backbone, regardless of the position in the molecular platform, caused a small reduction in band gaps; however, both highest occupied molecular orbitals and lowest unoccupied molecular orbital energy bands were at lower energies when the thiophenes were incorporated near the terminus of the molecule. The film morphologies of both materials could be controlled by either thermal or solvent vapor annealing to yield phase separation on the order of tens of nanometers and improved crystallinity. Peak power-conversion efficiencies of 3.6% and 3.1% were obtained using DTGe(ThFBTTh2)2 and DTGe(FBTTh3)2, after solvent vapor treatment and thermal annealing, respectively. Our study provides a detailed analysis of how the ordering sequence of heterocyclic building blocks influences the properties and function of organic solar cells.

Enantioselective Synthesis of Chiral Oxygen-Containing Heterocycles Using Copper-Catalyzed Aryl C-O Coupling Reactions via Asymmetric Desymmetrization.

An enantioselective desymmetric aryl C-O coupling reaction was demonstrated under the catalysis of CuI and a chiral cyclic diamine ligand. A series of chiral oxygen-containing heterocyclic units such as 2,3-dihydrobenzofurans, chromans, and 1,4-benzodioxanes with tertiary or quaternary stereocarbon centers were synthesized with this method. DFT calculations were also carried out for a better understanding of the model for enantiocontrol.

Significant light absorption enhancement by a single heterocyclic unit change in the π-bridge moiety from thieno[3,2-b]benzothiophene to thieno[3,2-b]indole for high performance dye-sensitized and tandem solar cells

Thieno[3,2-b]indole-based organic sensitizers were synthesized to enhance the light absorption ability and exhibited superior performance for dye-sensitized solar cells.

ChemInform Abstract: Visible‐Light Photoredox‐Catalyzed Coupling Reaction of Azoles with α‐Carbamoyl Sulfides.

A simple, straightforward strategy for the synthesis of N-substituted azoles is reported that involves a visible-light photoredox-catalyzed coupling reaction of azoles with α-carbamoyl sulfides. A variety of heterocyclic units, including pyrazoles, benzopyrazoles, benzoimidazoles, and purines, can be efficiently incorporated under mild reaction conditions in respectable yields.

Optical, electrochemical, and sensing properties of polyfluorenes bearing thiazole or oxazole and triphenylamine in the main chain

ABSTRACTPolyfluorenes bearing thiazole (PFTH) or oxazole (PFOX) heterocyclic units as well as triphenylamine (TPA) in the main chain were synthesized. The ratio of thiazole or oxazole/TPA in the polymer chain varies from 100/0 to 25/75. The optical properties of polymers depend on thiazole or oxazole contents. Cyclic voltammetry reveals that thiazole or oxazole hinder the oxidation of polymers and only polymers with TPA show reversible oxidation. The Electron Affinities do not practically depend on composition of the polymer chain. The sensing properties of polymers PFTH100 and PFOX100 are investigated toward several cations and anions. Polymers detect two analytes, Fe2+ and Hg2+. PL quenching shows linear response to Fe2+ in wide concentration region 1–800 μΜ. I− anions quench the emission of polymers. Hg2+ turns on the emission of the polymer/I− complex at concentrations as low as 1 μM. Enhancement of polymer/I− emission exhibits linear response to Hg2+ concentration. PFTH100 is able to detect Fe2+ and Hg2+ that coexist in a solution. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 243–254

Visible-Light Photoredox-Catalyzed Coupling Reaction of Azoles with α-Carbamoyl Sulfides.

A simple, straightforward strategy for the synthesis of N-substituted azoles is reported that involves a visible-light photoredox-catalyzed coupling reaction of azoles with α-carbamoyl sulfides. A variety of heterocyclic units, including pyrazoles, benzopyrazoles, benzoimidazoles, and purines, can be efficiently incorporated under mild reaction conditions in respectable yields.

The Effect of Asymmetric Heterocyclic Units on the Microstructure and the Improvement of Mechanical Properties of Three Rigid‐Rod co‐PI Fibers

Three kinds of rigid‐rod copolyimide (co‐PI) fibers are prepared by wet‐spinning of their precursor poly(amic acid)s, which are copolymerized from 3,3′,4,4′‐biphenyltetracarboxylic dianhydride (BPDA), p‐phenylenediamine (PDA), and the third asymmetric heterocyclic diamines, including 2‐(4‐aminophenyl)‐5‐aminobenzoxazole (BOA), 2‐(4‐aminophenyl)‐5‐aminobenzimidazole (PABZ), and 2,5‐bis(4‐aminophenyl)‐pyrimidine (PRM), respectively. The asymmetry is increasing in the order PRM < BOA ≈ PABZ. The introduction of asymmetric heterocyclic units results in mesomorphic order structure and decreases the size of microvoid of PI fiber, which apparently improves the toughness of PI fiber and shows positive effects on mechanical properties. The tensile strength and initial modulus of co‐PI fibers are in the ranges of 2.6–3.2 GPa and 91.8–133.5 GPa, respectively. The lowest asymmetry leads to the highest lateral order, crystal orientation, and initial modulus of BPDA/PDA/PRM co‐PI. Moreover, the introduction of asymmetric heterocyclic units can effectively improve compressive properties. BPDA/PDA/PABZ co‐PI fiber shows the highest loop strength and recoil compressive strength due to hydrogen bonding interactions. The highest orientation leads to the lowest transverse strength of BPDA/PDA/PRM co‐PI fibers, reducing the recoil compressive strength. image

Tunable crystal packing for enhanced electroluminescent properties based on novel thiazole derivatives with different connecting positions of carbazole

Two novel deep-blue fluorescent compounds, namely, 2-(4-(9-phenyl-9H- carbazol-3-yl)phenyl)benzo [d]thiazole (BCzBTZ) and 2-(4'-(9H-carbazol-9-yl)-[1.1'- biphenyl]-4-yl)benzo [d]thiazole (CzBBTZ) were designed, synthesized and characterized. It is particularly intriguing to compare their crystal packing of BCzBTZ and CzBBTZ, both of them construct with the same heterocyclic units and linker. Their crystal packing can be effectively regulated by changing the connecting position of carbazole. Their thermal stabilities, optical and electrochemical properties were studied systematically and exhibited ideal performance for electroluminescent emitters. The device based on BCzBTZ as emitter shows deep-blue emission with the CIE (x, y) of (0.15, 0.08), which is close to the blue standard (0.14, 0.08) of National Television System Committee (NTSC). The maximal external quantum efficiency is 1.4% and current efficiency is 1.39 cd/A with low efficiency roll-off.

Vinylazulenes chromophores: Synthesis and characterization

Several vinylazulenes containing heterocyclic units were prepared using Knoevenagel condensation. The condensation took place between electron rich 1-azulenecarbaldehyde derivatives and their vinylogues with heterocycles. The catalysts were chosen in order to catalyze the reaction without giving side reactions, such as heterocycle decomposition or formylazulene decarbonylation. Several NMR signals were briefly discussed. The optical properties of the colored substances were evidenced as a function of their structure. The pH-dependence of the chromophores was evidenced for two compounds; as well as their active solvatochromism. Their electrochemical properties were evaluated from the redox potentials and correlated to their structure.

Nitrone Cycloadditions of 1,2-Cyclohexadiene.

We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis.

Reversal of enantioselectivity induced by the achiral part of an organocatalyst in a Diels–Alder reaction

A new series of chiral organocatalysts was developed by attaching achiral heterocyclic units via a methylene group to (S)-2-hydroxyethylbenzimidazole for the asymmetric Diels–Alder reaction between anthrone enolate and maleimides. While organocatalysts with pyridine, quinoline, and 1,3,4-oxadiazole achiral heterocyclic subunits gave Diels–Alder adducts with an (S,S)-configuration, the organocatalyst with a benzotriazole subunit caused formation of the (R,R)-configuration for the Diels–Alder adducts

Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents

Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency in vitro than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.

"Hummingbird" behaviour of N-heterocyclic carbenes stabilises out-of-plane bonding of AuCl and CuCl units.

An N-heterocyclic carbene substituted by two expanded 9-ethyl-9-fluorenyl groups was shown to bind an AuCl unit in an unusual manner, namely with the AuX rod sitting out of the plane defined by the heterocyclic carbene unit. As shown by X-ray studies and DFT calculations, the observed large pitch angle (21°) arises from an easy displacement of the gold(I) atom away from the carbene lone-pair axis, combined with the stabilisation provided by weak CH⋅⋅⋅Au interactions involving aliphatic and aromatic H atoms of the NHC wingtips. Weak, intermolecular Cl⋅⋅⋅H bonds are likely to cooperate with the H⋅⋅⋅Au interactions to stabilise the out-of-plane conformation. A general belief until now was that tilt angles in NHC complexes arise mainly from steric effects within the first coordination sphere.

Photochemical Conversion of Phenanthro[9,10-d]imidazoles into π-Expanded Heterocycles.

We discovered that phenanthro[9,10-d]imidazoles bearing a 2-halogenoaryl substituent at position 2 undergo swift photochemically driven direct arylation, leading to barely known phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines. The reaction is high-yielding, and it does not require any sensitizer or base. The discovered process is tolerant of a variety of substituents present both at positions 1 and 2; i.e., strongly electron-donating and electron-withdrawing substituents are tolerated as well as various heterocyclic units. Steric hindrance does not affect this process. The evidence gathered here indicates that SRN1 mechanism is operating in this case with the formation of radical anion as a critical step, followed by heterolytic cleavage of a carbon-halogen bond. Also TfO groups were shown to undergo cyclization, which allows the use of salicylaldehydes in the construction of heterocyclic systems. Efficiency of this photochemically driven direct arylation has been demonstrated by the synthesis of two systems possessing 13 and 17 conjugated rings, respectively. Phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines are blue-emitters, and they exhibit strong fluorescence in solution and in the solid state in direct contrast to their precursors.