Aza-aromatic Compounds Research Articles

Shaping cycles with light: a regiodivergent approach to tetracyclic aza-aromatic compounds

We present a novel visible light-promoted regiodivergent cyclization, enabling the selective synthesis of distinct azapolyaromatic regioisomers from 2-alkynlazobenzenes.

The bacterial yjdF riboswitch regulates translation through its tRNA-like fold

Unlike most riboswitches, which have one cognate effector, the bacterial yjdF riboswitch binds to diverse azaaromatic compounds, only a subset of which cause it to activate translation. We examined the yjdF aptamer domain by small-angle X-ray scattering and found that in the presence of activating ligands, the RNA adopts an overall shape similar to that of tRNA. Sequence analyses suggested that the yjdF aptamer is a homolog of tRNALys, and that two of the conserved loops of the riboswitch are equivalent to the D-loop and T-loop of tRNA, associating to form an elbow-like tertiary interaction. Chemical probing indicated that this association is promoted by activating ligands such as chelerythrine and harmine. In its native mRNA context, activator ligands stabilize the tRNA-like fold of the yjdF aptamer, outcompeting the attenuated state in which its T-loop base pairs to the Shine–Dalgarno element of the mRNA. Moreover, we demonstrate that the liganded aptamer itself activates translation, as authentic tRNAs, when grafted into mRNA, can potently activate translation. Taken together, our data demonstrate the ability of tRNA to function as a small-molecule responsive cis regulatory element.

Computational, Mechanistic, and Experimental Insights into Regioselective Catalytic C-C Bond Activation in Linear 1-Aza-[3]triphenylene.

C–C bond activation by transition metal complexes in ring-strained compounds followed by annulation with unsaturated compounds is an efficient approach to generate structurally more complex compounds. However, the site of catalytic C–C bond activation is difficult to predict in unsymmetrically substituted polycyclic systems. Here, we report a study on the (regio)selective catalytic cleavage of selected C–C bonds in 1-aza-[3]triphenylene, followed by annulation with alkynes, forming products with extended π-conjugated frameworks. Based on density functional theory (DFT) calculations, we established the stability of possible transition metal intermediates formed by oxidative addition to the C–C bond and thus identified the likely site of C–C bond activation. The computationally predicted selectivity was confirmed by the following experimental tests for the corresponding Ir-catalyzed C–C cleavage reaction followed by an alkyne insertion that yielded mixtures of two mono-insertion products isolated with yields of 34–36%, due to the close reactivity of two bonds during the first C–C bond activation. Similar results were obtained for twofold Ir- or Rh-catalyzed insertion reactions, with higher yields of 72–77%. In a broader context, by combining DFT calculations, which provided insights into the relative reactivity of individual C–C bonds, with experimental results, our approach allows us to synthesize previously unknown pentacyclic azaaromatic compounds.

Synthesis and properties of azines functionalized graphene with extremely high adsorptive ability to Eu3+ ions

In this work, a versatile synthetic protocol for obtaining of new promising carbon materials based on the C–C coupling of graphenide lithium species with azaaromatic compounds (1,10-phenanthroline, phenyl-1,2,5-oxadiazolo[3,4-b]pyrazine) has been suggested. It was shown that more electrophilic oxadiazolopyrazine gave the product with high degree of graphene functionalization and demonstrated non-isomorphic properties. At the same time, phenanthrolinyl graphene has less functionalization degree due to a lower electrophilicity of azine. However, the large size of pores between organic residues in phenanthrolinyl graphene allows adsorbing almost 10% of Eu3+. The mesurment of adsorption isotherm showed an extremely high affinity of phenanthrolinylgraphene to Eu (III) ions in netural or alkaline conditions, and the obtained hybrid material could work at least 5 sorption/desorption cycles. The structures of azine-graphene dyads were verified by complex of modern physicochemical analyses methods (the Raman spectroscopy, FTIR, XPS, SEM, EDS and TGA analyses).

A molecular electron density theory study of the enhanced reactivity of aza aromatic compounds participating in Diels-Alder reactions.

The enhanced reactivity of a series of four aza aromatic compounds (AACs) participating in the Diels-Alder (DA) reactions with ethylene has been studied using Molecular Electron Density Theory (MEDT). The analysis of the electronic structure of these AACs allows establishing that the substitution of the C-H unity by the isoelectronic N: unity linearly decreases the ring electron density (RED) of these compounds and concomitantly decreases their aromatic character and increases their electrophilic character. These behaviours not only decrease drastically the activation energies of these DA reactions, but also increase the reaction energies when they are compared with the very unfavourable DA reaction between benzene and ethylene. Very good correlations between the NICS(0) values and the electrophilicity ω indices of these AACs with the RED values are found. The present MEDT study makes it possible to establish two empirical electron density unity (EDU) indices accounting for the contribution of the C and N unities, 2.77 and 2.19 e, respectively, for the RED, which is mainly responsible for the reactivity of these AACs. Comprehensive chemical concepts such as electron density, aromaticity and electrophilicity make it possible to explain the chemical reactivity of these AACs participating in DA reactions towards ethylene.

An nπ* gated decay mediates excited-state lifetimes of isolated azaindoles.

Aiming to serve as a guide to understand the relaxation mechanisms of more complex aza-aromatic compounds, such as purine bases, we have studied the non-radiative channels of a set of azaindole structural isomers: 4-, 5-, 6- and 7-azaindole (AI). The relaxation of the isolated molecules, after excitation at the low energy portion of their spectra, has been tracked by femtosecond time-resolved ionization, and the decay paths have been obtained with MS-CASPT2//TD-DFT calculations. Although the ultrashort measured lifetimes for 5- and 6-AI are in contrast to the long-living excited state found in 7-AI, the calculations describe a common relaxation pathway. Along it, the initially excited ππ* states decay to the ground state through a conical intersection accessed through an nπ* state that functions as a gate state. The work reveals that the position of the nitrogen atoms in the purine ring determines the barrier to access the gate state and therefore, the rate of the non-radiative relaxation.

Recent progress of pyrimidine derivatives for high-performance organic light-emitting devices

Pyrimidine is an electron-deficient azaaromatic compound containing two nitrogen atoms at 1, 3-positions that plays a key role as an organic semiconductor or semiconducting material. Because of the high electron-accepting property induced by C═N double bonds and due to its coordination ability, pyrimidine has been incorporated as a building block in phosphorescent emitters, fluorescent emitters, bipolar host materials, and electron transporting materials in organic light-emitting devices (OLEDs). Recently, pyrimidine-based thermally activated delayed fluorescent emitters combined with various electron donors have been developed, and their device performances were far better than those based on conventional fluorescent emitters. In this review, recent progress of pyrimidine-based OLED materials is presented and accompanied by a historical overview, current status, key issues, and outlook for the next generation of high-performance OLED materials.

Structure–metabolism relationships in human-AOX: Chemical insights from a large database of aza-aromatic and amide compounds

Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported and only "very local" structure-metabolism relationships based on a small number of similar compounds have been developed. This study reports a more comprehensive coverage of the chemical space of structures with a high risk of AOX phase I metabolism in humans. More than 270 compounds were studied to identify the site of metabolism and the metabolite(s). Both electronic [supported by density functional theory (DFT) calculations] and exposure effects were considered when rationalizing the structure-metabolism relationship.

The yjdF riboswitch candidate regulates gene expression by binding diverse azaaromatic compounds.

The yjdF motif RNA is an orphan riboswitch candidate that almost exclusively associates with the yjdF protein-coding gene in many bacteria. The function of the YjdF protein is unknown, which has made speculation regarding the natural ligand for this putative riboswitch unusually challenging. By using a structure-probing assay for ligand binding, we found that a surprisingly broad diversity of nitrogen-containing aromatic heterocycles, or “azaaromatics,” trigger near-identical changes in the structures adopted by representative yjdF motif RNAs. Regions of the RNA that undergo ligand-induced structural modulation reside primarily in portions of the putative aptamer region that are highly conserved in nucleotide sequence, as is typical for riboswitches. Some azaaromatic molecules are bound by the RNA with nanomolar dissociation constants, and a subset of these ligands activate riboswitch-mediated gene expression in cells. Furthermore, genetic elements most commonly adjacent to the yjdF motif RNA or to the yjdF protein-coding region are homologous to protein regulators implicated in mitigating the toxic effects of diverse phenolic acids or polycyclic compounds. Although the precise type of natural ligand sensed by yjdF motif RNAs remains unknown, our findings suggest that this riboswitch class might serve as part of a genetic response system to toxic or signaling compounds with chemical structures similar to azaaromatics.

ChemInform Abstract: Facile Synthesis of Acridine Derivatives by ZnCl2‐Promoted Intramolecular Cyclization of o‐Arylaminophenyl Schiff Bases.

A concise and efficient method for the synthesis of a wide range of acridine derivatives and polycyclic aza-aromatic compounds from a ZnCl2-promoted cyclization reaction of readily available o-arylaminophenyl Schiff base compounds under convenient conditions was developed. Reaction conditions and scope of the new method were examined in detail.

Facile Synthesis of Acridine Derivatives by ZnCl2-Promoted Intramolecular Cyclization of o-Arylaminophenyl Schiff Bases

A concise and efficient method for the synthesis of a wide range of acridine derivatives and polycyclic aza-aromatic compounds from a ZnCl2-promoted cyclization reaction of readily available o-arylaminophenyl Schiff base compounds under convenient conditions was developed. Reaction conditions and scope of the new method were examined in detail.

Simple and one-pot C-arilation from reaction between azines (isoquinoline or phenanthridine) and acetylenic esters in the presence of phenol derivatives

Three-component condensation reactions between azines (isoquinoline or phenanthridine) and acetylenic esters were undertaken in the presence of phenol derivatives (2,6-di-tert-butyl-phenol, 2,4-di-tert-butyl-phenol, 2,6-dimethyl phenol and 2,4-dimethyl phenol) for generation of C-arilation in good yields. The reactions proceeded smoothly at room temperature without using any catalyst. This method is very useful to functionalize aza-aromatic compounds in a one-pot operation. .

ChemInform Abstract: Simple, One‐Pot, and Three‐Component Coupling Reactions of Azaarenes (Phenanthridine, Isoquinoline, and Quinoline), with Acetylenic Esters Involving Methyl Propiolate or Ethyl Propiolate in the Presence of NH‐Heterocyclic or 1,3‐Dicarbonyl Compounds.

Abstract Three-component reactions involving azaarenes (quinoline, isoquinoline, and phenanthridine) with acetylenic esters such as methyl propiolate or ethyl propiolate in the presence of NH-heterocyclic compounds (carbazole, maleimide, 5-nitroindazole, 2-benzoxazolinone, indole, and 2-methylindole) or 1,3-dicarbonyl compounds involving acetylacetone and N,N′-dimethylbar bituric acid are described. The reactions proceeded smoothly at room temperature without a catalyst and with excellent yields. This method is very useful for functionalizing aza-aromatic compounds in a one-pot operation.

Simple, One-Pot, and Three-Component Coupling Reactions of Azaarenes (Phenanthridine, Isoquinoline, and Quinoline), with Acetylenic Esters Involving Methyl Propiolate or Ethyl Propiolate in the Presence of NH-Heterocyclic or 1,3-Dicarbonyl Compounds

Three-component reactions involving azaarenes (quinoline, isoquinoline, and phenanthridine) with acetylenic esters such as methyl propiolate or ethyl propiolate in the presence of NH-heterocyclic compounds (carbazole, maleimide, 5-nitroindazole, 2-benzoxazolinone, indole, and 2-methylindole) or 1,3-dicarbonyl compounds involving acetylacetone and N,N′-dimethylbar bituric acid are described. The reactions proceeded smoothly at room temperature without a catalyst and with excellent yields. This method is very useful for functionalizing aza-aromatic compounds in a one-pot operation.

Reissert-like Alkenylation of Azaaromatic Compounds with Alkenylzirconocene Chloride Complexes

Reissert-like Alkenylation of Azaaromatic Compounds with Alkenylzirconocene Chloride Complexes

Indium-Catalyzed Construction of Polycyclic Aromatic Hydrocarbon Skeletons via Dehydration

Polycyclic aromatic compounds can be synthesized from 2-benzylic- or 2-allylbenzaldehydes using a catalytic amount of In(III) or Re(I) complexes. By using this method, polycyclic aza-aromatic compounds can also be prepared efficiently. In these reactions, only water is formed as a side product.

ChemInform Abstract: Heteroaromatic Sulfoxides and Sulfones: Ligand Exchange and Coupling in Sulfuranes and Ipso-Substitutions

Publisher Summary This chapter explores the chemistry of both organic sulfur compounds and azaaromatic compounds, and discusses the chemical behaviors of organosulfur compounds of azaheteroaromatics, particularly pyridine and its related six-membered derivatives. The contents are divided into the following items: (1) a new concept of ligand-coupling reactions and ligand exchange within σ-sulfuranes formed in the reactions of the sulfoxides, bearing azaheteroaromatics, with grignard and organolithium reagents; (2) ipso substitution and desulfurization reactions of the sulfoxides and sulfones in which both the sulfinyl and the sulfonyl groups become good leaving groups; (3) thione-thiol tautomerism and its applications to the organic synthesis; and (4) miscellaneous reactions on the organosulfur compounds bearing azaheterocycles. Physicochemical behavior of these heteroaromatic systems is also compared to the corresponding aromatic systems. One remarkable feature is that the heteroaromatics bearing a sulfur atom are more reactive than the corresponding aromatic derivatives mainly because of the strong electron-releasing or withdrawing property of the heteroaromatics.

Structure and Hydrogen-Bond Vibrations of Water Complexes of Azaaromatic Compounds: 7-(3′-Pyridyl)indole

Complexes with water have been studied in the regime of supersonic jet isolation for 7-(3'-pyridyl)indole, a bifunctional molecule possessing hydrogen bond donor and acceptor groups. Two rotameric forms, syn and anti, are possible, of which only the former is able to form cyclic hydrogen bonds with protic solvents. Infrared-induced ion depletion spectroscopy was used to obtain vibrational patterns for 1:1 and 1:2 complexes in the hydrogen bond stretching region. The analysis of the spectra, supported by DFT calculations, revealed that for both stoichiometries the dominant forms correspond to cyclic, doubly or triply hydrogen-bonded species. The frequencies of NH...O, OH...N, and OH...O stretching vibrations were compared with the literature data to assess the strength of single vs multiple hydrogen bonds. Several new assignments and reassignments were proposed.

Operating lifetime recovery in organic light-emitting diodes having an azaaromatic hole-blocking/electron-transporting layer

Azaaromatic compounds (AACs) are widely used in organic light-emitting diodes (OLEDs), especially as efficient electron transporters. Yet, the operating lifetime of OLEDs is always compromised when AACs are involved in anything more than electron transport (e.g., hole blocking). We show (i) the operating lifetime of OLEDs incorporating AACs as a hole-blocking/electron-transporting layer (HBETL) depends strongly on the charge-conducting ability and excited state energy of the light-emitting layer (LEL) materials and (ii) shifting the charge recombination zone away from the LEL∣HBETL interface deeper into the LEL can recover the lost lifetime. Thus, a pure red fluorescent OLED is demonstrated having 5.3 V drive voltage, 6.5% external quantum efficiency, 6.6 cd/A electroluminescent yield, and ∼125 000 h half-life, all at 20 mA/cm2. This device utilizes an AAC as HBETL followed by an aluminum triquinolate (Alq) ETL doped with Li metal. Alternatively, the lifetime recovery might be assigned to the presence of the n-dopant (Li) at the LEL∣HBETL interface (e.g., effected by diffusion of Li) because such presence stabilizes a wide range of OLEDs, e.g., those based on Alq mixed with polycyclic aromatic hydrocarbons and those based on 9,10-diarylanthracenes. Yet, this rationale is discarded in view of a strong deleterious interaction between the triazine-based AAC used in this work and n-dopants.

Three-component coupling reactions of isoquinolines, dimethyl acetylenedicarboxylate and indoles: a facile synthesis of 3-indolyl-1,2-dihydro-2-isoquinolinyl-2-butenedioate

A three-component coupling of isoquinolines, dimethyl acetylenedicarboxylate (DMAD) and indoles is achieved for the first time to produce dimethyl (E)-2-[1-(1H-3-indolyl)-1,2-dihydro-2-isoquinolinyl]-2-butenedioates in excellent yields and with high selectivity. The reaction proceeds smoothly at room temperature without a catalyst. Quinoline, DMAD and indole also undergo smooth coupling to furnish dimethyl (E)-2-[2-(1H-3-indolyl)-1,2-dihydro-1-quinolinyl]-2-butenedioate under similar conditions. This method is very useful to functionalize both indoles and aza-aromatic compounds in a one-pot operation.