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The serendipitous rearrangement of an oxazole nucleus to a thiazoline ring under mild conditions is described. This transformation was achieved by a multicomponent reaction (MCR) featuring 2‐(bromomethyl)oxazoles, thiosemicarbazide, and a carbonyl compound to provide oxazole‐derived isothiosemicarbazones, which undergo oxazole ring‐opening and recyclization to 2‐hydrazono‐3‐thiazolines in a one‐pot procedure. This straightforward route produced highly functionalized thiazolines (34–98 % yield) in a chemo‐ and stereoselective manner. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A visible‐light‐induced decarboxylative radical cascade cyclization reaction between N‐(2‐cyanoaryl)‐acrylamides and alkyl N‐(acyloxy)phthalimide (NHPI esters) for the construction of phenanthridine derivatives has been developed. This approach utilizes lithium iodide (LiI) and triphenylphosphine (PPh3) as the redox catalysts and the alkyl radical is produced through the photoactivation of the electron donor‐acceptor (EDA) complex. A series of primary, secondary, and tertiary alkyl‐substituted phenanthridines are prepared in up to 82% yield without transition‐metal catalysts, chemical oxidants, or metal‐/organic dye‐based photocatalysts. [ABSTRACT FROM AUTHOR]

In our previous work we could show, that Imidazo[1,5‐a]quinolines are compounds with interesting optical properties. In this work, we optimized the photoluminescent properties of imidazo[1,5‐a]quinolines by following outlined trends in our previous work. By introducing electron‐rich and electron‐poor residual groups on the imidazole ring, the quantum yield (QY) could be significantly increased. This indicated a clear advantageous substitution pattern for this system. In addition, cyclic voltammetric and UV/vis measurements in solid state lay the foundation for applications, such as organic light‐emitting diodes (OLEDs). [ABSTRACT FROM AUTHOR]

Reactions of 5,6‐dihydro‐4H‐1,2‐oxazine N‐oxides with enol diazoacetates were studied. A particular reaction path depends on the amount of catalyst and the order of the addition of the substrates. Use of Rh2(Oct)4 (2 mol.%) leads to chemoselective [3+3]‐annulation producing 1,2‐oxazine‐fused 1,2‐oxazine derivatives. With lower catalyst loadings (0.03 mol.%) enol diazoacetates are converted to cyclopropene derivatives, which in situ react with 1,2‐oxazine N‐oxides via tandem [3+2]‐cycloaddition‐rearrangement producing oxazine‐fused aziridines. Both transformations showed a wide substrate scope and produced target products with good yields and diastereoselectivity, thus allowing selective preparation of these rare heterocyclic systems. A mechanistic rationale for observed chemo‐ and stereo‐ selectivities was proposed. [ABSTRACT FROM AUTHOR]

Highly efficient one‐pot synthesis of a series of indeno[2,1‐b]quinolin‐6‐ones 10 and indolo[1,2‐b]isoquinoline‐6,12‐diones 12 is portrayed from easily accessible starting materials such as indan‐1‐ones 7 and 2‐nitrobenzaldehydes 9. The reaction mechanism studies by control experiments and computational analysis reveal that the reactions are initiated by attack of a conjugate base of indanones 7 to the aldehyde group or the adjacent nitro group of 2‐nitrobenzaldehydes 9 followed by intramolecular cyclization involving a second anion to furnish the appropriate products. The heterocyclic compounds were obtained in moderate to good yields. [ABSTRACT FROM AUTHOR]

The emergence of drug‐resistant strains of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is on the rise and increasing antimicrobial resistance is a global threat. This phenomenon necessitates new drug design methods such as a prodrug strategy to develop novel antitubercular agents. The prodrug strategy is a viable and useful means to improve the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of pharmacologically active agents. Granulomas are a pathological hallmark of M.tb infection and bear a remarkable resemblance to the tumour microenvironment, including regions of hypoxia. The hypoxic environment observed in the two structures offer an exceptional opportunity to deliver antitubercular agents selectively in a similar manner to hypoxia activated prodrugs in cancer therapy. Nitroimidazoles have been studied extensively as bioactivated prodrugs of cancer, and their suitability as substrates for mammalian reductases highlight their huge potential. This review will discuss the mechanism of action and resistance mechanisms of the current prodrugs used for the treatment of tuberculosis. It will also highlight the potential advantages and challenges of using hypoxia activated prodrugs as a viable strategy to target latent M.tb in hypoxic regions of granulomas. [ABSTRACT FROM AUTHOR]

We report herein a reexamination of the reactions between sulfoxonium ylides and acetylenic esters. Continuing our previous study of conjugate additions using α‐carbonyl sulfoxonium ylides, we came across an interesting transformation when dimethyl acetylenedicarboxylate (DMAD) was employed as a Michael acceptor. Trisubstituted electron‐deficient 1,3‐dienes and α‐carbonyl vinyl sulfoxides were obtained for the first time from these sulfur ylides, in a stereoselective manner (exclusively forming the E‐isomer), achieving yields of up to 70 % and 83 %, respectively. Selected dienes were subsequently utilized in the synthesis of novel nitrogen heterocycles. Interestingly, when di‐tert‐butyl acetylenedicarboxylate (DtBAD) or alkyl propiolates were evaluated, the isolated product arose from the classical Michael addition, yielding α‐carbonyl vinyl sulfoxonium ylides in yields of up to 89 %. [ABSTRACT FROM AUTHOR]

Metal‐nitrenes are valuable reactive intermediates for synthesis and are widely used to construct biologically relevant scaffolds, complexes and functionalized molecules. The ring expansion of cyclic molecules via single‐nitrogen‐atom insertion via nitrene or metal‐nitrenoid intermediates has emerged as a promising modern strategy for driving advantageous nitrogen‐rich compound synthesis. In recent years, the catalytic insertion of a single nitrogen atom into carbocycles, leading to N‐heterocycles, has become an important focus of modern synthetic approaches with applications in medicinal chemistry, materials science, and industry. Catalytic single‐nitrogen‐atom insertions have been increasing in prominence in modern organic synthesis due to their capability to construct high‐value added nitrogen‐containing heterocycles from simple feedstocks. In this review, we will discuss the rapidly growing field of skeletal editing via single‐nitrogen‐atom insertion using transition metal catalysis to access nitrogen‐containing heterocycles, with a focus on nitrogen insertion across a wide spectrum of carbocycles. [ABSTRACT FROM AUTHOR]

Nitrogen heterocycles are valuable structural elements in the molecules of antibacterial drugs approved and used to treat bacterial infections. Pyrrole is a five-atom heterocycle found in many natural compounds with biological activity, including antibacterial activity. Numerous compounds are being develop based on the pyrrole heterocycle as new potential antibacterial drugs. Due to the phenomenon of antibacterial resistance, there is a continuous need to create new effective antibacterials. In the scientific literature, we have identified the most relevant studies that aim to develop new compounds, such as pyrrole derivatives, that are proven to have antibacterial activity. Nature is an endless reservoir of inspiration for designing new compounds based on the structure of pyrrole heterocycles such as calcimycin, lynamycins, marinopyrroles, nargenicines, phallusialides, and others. However, many other synthetic compounds based on the pyrrole heterocycle have been developed and can be optimized in the future. The identified compounds were classified according to the type of chemical structure. The chemical structure–activity relationships, mechanisms of action, and antibacterial effectiveness of the most valuable compounds were highlighted. This review highlights scientific progress in designing new pyrrole-containing compounds and provides examples of lead compounds that can be successfully optimized further. [ABSTRACT FROM AUTHOR]

An efficient access to novel families of 7‐membered dibenzodiazepines and 6‐membered benzo[c]cinnoline derivatives has been elaborated. The synthetic strategy is based on a copper‐catalyzed double N‐arylation of cyclic diaryliodoniums with imidamides and 4‐substituted 1, 2, 4‐triazoline‐3, 5‐diones (TADs) respectively under ambient reaction conditions. A mechanistic rationale for the double N‐arylation is discussed. [ABSTRACT FROM AUTHOR]

The synthesis of ethyl (hetero)arylidene cyanoacetates, valuable intermediates in organic chemistry, has been investigated using several commercially available and synthetic nitrogen-based organocatalysts. 4,4′-Trimethylenedipiperidine (TMDP) was chosen as an efficient organocatalyst regarding short reaction times, excellent yield with a conversion of 100%, and high selectivity. The pure products could be isolated and devoid of a costly workup. The residue could be directly reused for the next catalytic run. Encouragingly, TMDP exhibited chemical stability and high recyclability in five subsequent runs without a significant loss in catalytic activity. Scale-up experiments also demonstrate the current strategy's promising industrial application. Mechanistic studies were conducted to provide insights into the reaction pathways and possible interaction/reaction between organocatalyst and each reactant through performing control experiments and studying FTIR in neat state and NMR spectra in aprotic and protic deuterated solvents. The developed metal-free and halogen-free catalytic strategy offers cost-effectiveness, low toxicity, and enhanced sustainability. [ABSTRACT FROM AUTHOR]

The corresponding amide derivatives of 11-oxoindeno[1,2-b]quinoxaline-6-carboxylic acid were synthesized in good yields by interaction with amines (N,N-dimethylpropane-1,3-diamine, novocaine, 2,6-dimethylpyrimidin-4-amine). The technique is simple and well reproducible. It provides preliminary activation of the carboxyl group by ethyl ester of monochlorocarbonic acid with its conversion to anhydride in chloroform in the presence of triethylamine. Anhydride gently reacts with amines under the same conditions without preliminary isolation to form the corresponding derivatives. Physicochemical and pharmacokinetic properties of the synthesized compounds were predicted using the ADMETlab 3.0 program. All tested compounds corresponded to Lipinsky's rule and can be classified as «drug-like». Pharmacokinetic parameters (clearance, half-life, ability to penetrate the blood-brain barrier and be absorbed in the intestine) indicated the possibility of their oral use. Computer screening using the PharmMapper database confirmed the ability of the synthesized compounds to bind to a number of biological targets involved in cell replication and division. This indicates their potential for intercalation into DNA for the treatment of viral infections and tumors and the prospects for their further studies using in vitro methods. [ABSTRACT FROM AUTHOR]

A dearomative addition of readily available carboranyllithium reagents to isoquinolinium salts gave a series of carborane cage C‐substituted 1,2‐dihydroisoquinolines in 43–85 % yields. Subsequent hydrogenation enabled the facile synthesis of corresponding carboranyl 1,2,3,4‐tetrahydroisoquinolines in 65–95 % yields. The addition‐reduction pathway is applicable to a wide range of substituted isoquinolinium salts and o‐carborane or m‐carborane. [ABSTRACT FROM AUTHOR]

Azoloazine derivatives are known as promising small molecules that are potentially able to counteract a broad spectrum of RNA viruses including SARS‐CoV‐2. However, a pool of synthetic pathways to provide convenient structural modification of such compounds without de novo construction of the heterocyclic scaffold is rather limited so far. This work proposes an approach to the direct C(sp2)−H functionalization of azolopyrimidine substrates with aromatic thiol residues, mediated by the iodine/persulfate reagent system. The reported herein sulfenylation protocol has afforded a series of previously undescribed azolopyrimidine‐based thioethers obtained in yields of up to 87 %. Applicability of the approach to the selenium‐centered synthons has been demonstrated as well. Besides, the in silico study with regard to the achieved cross‐coupling products has suggested the possible affinity to the SARS‐CoV‐2 main protease (Mpro), as follows from the conducted pharmacophore search and the molecular docking experiments. As a result, the developed synthetic transformation is expected to be of utility in the design of novel antiviral agents based on small azaheterocyclic molecules. [ABSTRACT FROM AUTHOR]

A direct alkoxylation of the electron‐deficient olefinic C(sp2)−H bond in pyrido[1,2‐a]pyrimidin‐4‐ones using aliphatic alcohols has been developed under transition metal and external chemical oxidant‐free electrochemical conditions. Azidotrimethylsilane (TMSN3) is utilized as a hydrogen atom transfer (HAT) reagent to enable the homolytic cleavage of the unfunctionalized O−H bond in alcohols, thereby generating the electrophilic alkoxy radicals. Moreover, the effectiveness of this method is demonstrated with d4‐methanol (CD3OD), leading to the synthesis of d3‐methoxylated N‐heterocycles in good yields under sustainable conditions. The proposed mechanism, based on alkoxy or trideuteromethoxy radicals, is substantiated by control experiments and cyclic voltammetry (CV) studies. [ABSTRACT FROM AUTHOR]

A widely used method to obtain tetrazoles is through the azide and nitrile [3+2] cycloaddition. However, this process often involves using non‐recyclable transition metals or Lewis acid catalysts and stoichiometric amounts of oxidants and additives, which reduces atom efficiency. We have discovered a convergent paired electrochemical reaction to perform this cycloaddition reaction, without the need for metal catalysts or oxidants. This tetrazolation strategy uses azidotrimethylsilane (TMSN3) and N‐heterocycles in an undivided cell at a constant current. We use a mixture of CH3CN and equivalent amounts of H2O as co‐solvent at room temperature. It is crucial to produce a stoichiometric amount of active hydroxyl ions through the cathodic reduction of water. Cyclic voltammetry (CV) studies and control experiments confirm that the cycloaddition reaction is specific to the electrode electron transfer process, eliminating the need for a mediator to shuttle electrons. This metal‐ and oxidant‐free strategy is highly compatible with different functional groups and produces products with moderate to good yields. We have successfully tetrazolated bioactive compounds at a late stage, scaled up batches efficiently, and synthesized free amino‐containing N‐heterocycles via denitrogenation of tetrazoles. [ABSTRACT FROM AUTHOR]

We have successfully improved the fluorescence quantum yield of isoindolo[2,1‐a]quinoline derivatives by suppressing the rotation of the phenyl groups at positions 5 and 11 (or 13). Additionally, we found that the planarity of these phenyl groups at positions 5 and 11 (or 13) of isoindolo[2,1‐a]quinoline derivatives is crucial for two‐photon absorption properties. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: We herein describe a Cp*RhIII‐catalyzed C(sp3)–H mono‐arylation of 8‐methylquinolines with benign arylsilanes. The use of 1‐adamantane carboxylic acid can benefit the efficiency in this transformation, and AgF was both activator and reoxidant. Control experiments indicated inability of C—H cleavage in determining the rate of the reaction. [ABSTRACT FROM AUTHOR]

A straightforward protocol for the synthesis of a previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic system was developed. The described approach is based on tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamide derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-d][1,2,3]triazin-7(6H)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or thermostable components of functional organic materials.

π-Stacking is common in materials, but different π–π stacking modes remarkably affect the properties and performances of materials. In particular, weak interactions, π-stacking and hydrogen bonding often have a significant impact on the stability and sensitivity of high-energetic compounds. A fused [5,7,5]-tricyclic energetic compound with a conjugated structure has been designed and synthesized. 4 H -[1,2,5]Oxadiazolo[3,4- e ][1,2,4]triazolo[3,4- g ][1,2,4]triazepin-8-amine is obtained in 48% yield from 3-amino-4-carboxy-1,2,5-oxadiazole through an efficient two-step reaction. Owing to its layered planar structure and weak π interactions between layers, 4 H -[1,2,5]oxadiazolo[3,4- e ][1,2,4]triazolo[3,4- g ][1,2,4]triazepin-8-amine exhibits high thermal stability (Td = 318 °C), low sensitivity (IS = 40 J, FS = 360 N), and relatively excellent detonation performance (D = 7059 ms–1 , P = 20.2 GPa). This detonation performance is superior to that of the conventional explosive TNT. The developed procedure provides a new method for the synthesis of fused ring compounds. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: An efficiently catalytic method toward the synthesis of indolin‐2‐ones featuring an allylic derived C3‐quaternary stereocenter via an intramolecular Heck cyclization/Suzuki coupling of N‐substituted‐N‐(2‐bromophenyl)acrylamides and organoboron reagents was successfully developed by using a 1,3‐bis(2,6‐diisopropylphenyl)acenaphthoimidazol‐2‐ylidene (AnIPr)‐ligated oxazoline palladacycle. It enabled a very broad substrate scope tolerating different functional groups, electronic properties and steric bulkiness. Notably, it revealed a great potential to build diverse heterocycle‐fused indoline alkaloids via the same intermediate 3‐allyl‐1,3‐dimethylindolin‐2‐ one. [ABSTRACT FROM AUTHOR]

Introduction of non‐hexagons and/or heteroatoms allows for finely tuning the physicochemical properties of nanographenes. Heteroatoms doping have dominated the modulation of nanographenes with tunable band gap, rich electrochemical activities and so on. The pair of non‐hexagons, for instance, pentagon‐heptagon pairs, have furnished nanographenes with aromatic and/or antiaromatic characteristics, open‐shell properties and so on. In order to meet the growing demand for versatile nanographenes in materials science, research on novel nanographenes with heteroatom doped non‐hexagonal pairs has been aroused in recent years. In this review, we focus on nanographenes with nitrogen‐doped non‐hexagonal paris including the synthesis, structure analysis, photophysical properties, and potential applications in organic devices. [ABSTRACT FROM AUTHOR]

Hypervalent iodine reagents are versatile and readily accessible reagents that have been extensively applied in contemporary synthesis in modern organic chemistry. Among them, iodonitrene (ArI=NR), is a powerful reactive species, widely used for a single‐nitrogen‐atom insertion reaction, and skeletal editing to construct N‐heterocycles. Skeletal editing with reactive iodonitrene components has recently emerged as an exciting approach in modern chemical transformation. These reagents have been extensively used to produce biologically relevant heterocycles and functionalized molecular architectures. Recently, the insertion of a nitrogen‐atom into hydrocarbons to generate N‐heterocyclic compounds using hypervalent iodine reagents has been a significant focus in the field of molecular editing reactions. In this review, we discuss the rapidly emerging field of nitrene insertion, including skeletal editing and nitrogen insertion, using hypervalent iodine reagents to access nitrogen‐containing heterocycles, and the current mechanistic understanding of these processes. [ABSTRACT FROM AUTHOR]

A detailed mechanistic probe of the organolanthanide‐mediated tandem insertion/annulation of alkynylbenzonitriles with secondary amines by an archetypical homoleptic lanthanum silylamide starting material is presented. An in‐depth computational scrutiny of alternatively plausible pathways for relevant productive steps and also performance‐degrading pathways identified the pathway likely traversed in productive catalysis. It entails the transformation of the starting material into various of silylamide/amide compounds, of which the lanthanum bis‐silylamide/amide is thermodynamically prevalent, capable of promoting the process. Benzonitrile insertion is irreversible to readily afford the lanthanum amidinate, which can adopt various easily interconvertible ligation pattern. The rather rapid protonolysis of the La─N imine linkage would lead to undesirable aminoamidines, but its net endergonicity renders this performance‐degrading avenue nonviable. Instead, the lanthanum amidinate is converted back into catalytically competent lanthanum bis‐silylamide/amide with the release of the observed aminoisoindole product. This transformation favors a stepwise insertative cyclisation/La─C alkenyl protonolysis sequence over an otherwise kinetically noncompetitive proton‐triggered stepwise N─C/C─H bond forming process. The operative insertative pathway comprises turnover‐limiting and irreversible insertion of the alkyne C≡C tether into the La─N amidinate linkage followed by La─C alkenyl aminolysis at the intervening lanthanum alkenylisoindinyl intermediate. The DFT‐assessed barrier for turnover‐limiting insertative N─C ring closure favorably compares with reported performance data. [ABSTRACT FROM AUTHOR]

A KOtBu‐promoted robust strategy has been described for the regioselective synthesis of pyrrolo[3,4‐b]quinolin‐1‐one and naphthyridin‐1(2H)‐one derivatives from o‐alkynylquinolinecarbonitriles in good to excellent yields. The reaction proceeds through in situ transformation of the nitrile moiety into an amide group followed by the selective C−N bond formation through a 5‐exo‐dig or 6‐endo‐dig annulation reaction. Among the synthesized derivatives, 6‐endo‐dig naphthyridin‐1(2H)‐ones displayed good photophysical properties. The present approach is superior to other established methodologies as it avoids use of transition metals and column chromatographic purification and affords the products in high yields. Additionally, the current methodology provides several additional advantages, such as one‐pot operation, high atom economy, broad substrate scope and a step‐economical process. [ABSTRACT FROM AUTHOR]

An oil spill is a catastrophic event that results in various toxic polycyclic aromatic hydrocarbons (PAHs) entering the environment. Polycyclic aromatic nitrogen heterocycles (PANHs) are more toxic to the environment than their parent PAHs. The high cost and paucity of available PANH standards, the lower abundance of PANHs relative to PAHs, and the difficult separation due to co-elution with PAHs have all contributed to the scarcity of related published literature on the determination of these compounds. To overcome these challenges, a new quantitative method has been successfully developed and validated for the inclusion of 113 polycyclic aromatic carbon (PAC) compounds in a single injection. The 113 compounds consist of PAHs, nitrogen heterocycles, sulfur heterocycles, and alkylated equivalents. Distinct separation of the PANHs and their alkylated counterparts (APANHs) from PAHs was achieved using a gas chromatography quadrupole time-of-flight (GC-QToF) mass spectrometer. The instrument resolved compounds by the high-resolution extraction of monoisotopic masses, allowing response correction factors (RCFs) to be determined from available PANH standards and to calculate concentrations from PAH calibration standards. The developed method was applicable to crude oil samples, generating concentrations of PANHs and relevant information on compound stability for use in oil spill forensics investigation. Development of this practical PAC method provides a powerful tool for screening toxic contaminants, assessing environmental impact, and monitoring recovery following an oil spill. [ABSTRACT FROM AUTHOR]

Aminals, characterized by a central carbon linking two nitrogen atoms, are versatile building blocks in modern chemistry. This review addresses a literature gap by exploring the synthesis and applications of aminals, with a focus on drug discovery and molecular diversity. Beyond medicinal chemistry, aminals find applications as key components in bioactive compounds and as versatile tools in materials chemistry. The review covers fundamental characteristics, synthetic methodologies, stability, and applications, emphasizing alternative synthetic methods to the well-established aldehyde–amine condensation. This inclusive exploration provides insights into diverse synthetic pathways that expand the versatility of the aminal scaffold. 1 Introduction 2 The Aminal Group 3 Aminal Synthesis 3.1 Metal-Free Approaches 3.2 Metal-Catalyzed Approaches 3.3 Photoredox Methodologies 3.4 Via Rearrangements 3.5 Via Decarboxylative Coupling 4 Aminals as Synthetic Tools 5 Synthesis of Aminal-Containing Natural Products 6 Aminal-Based Materials 7 Conclusions [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A novel visible‐light‐induced radical cascade 6‐endo cyclization of dienes (N‐(2‐vinylphenyl)acryl amides) is developed utilizing α‐carbonyl bromides as alkyl reagents. This approach affords an efficient way for synthesizing six‐membered benzo‐fused lactam derivatives with chemo‐ and regio‐selectivity and good functional group tolerance. Primary, secondary, and tertiary bromides are well‐compatible with this cascade cyclization reaction. [ABSTRACT FROM AUTHOR]

Conversion of quinoline C−H bonds into C−C bonds is essential for obtaining the enormous array of derivatives required for pharmaceutical and agrochemical development. Despite over a century of synthetic efforts, direct alkylation and alkenylation at C3−H positions in a wide array of quinoline precursors remain predominantly challenging and elusive. This report outlines the first successful quinoline C3−H alkylation and alkenylation reactions, exhibiting exceptional regio‐ and stereoselectivity, all achieved under redox‐neutral and transition‐metal‐free conditions. The method involves a three‐step, one‐pot or two‐pot sequence, including 1,4‐dearomative addition, functionalization at C3, and elimination or transalkylation to produce 3‐alkylated/alkenylated quinolines. The presence of a carbonyl group in these products allows for further synthetic manipulations, enabling the production of cyanides, amides, amines, and simple alkyl derivatives. [ABSTRACT FROM AUTHOR]

Diazoalkenes readily react with tert‐butylphosphaalkyne (tBuCP) and white phosphorus (P4) to afford novel phosphorus heterocycles, 3H‐1,2,4‐diazamonophospholes and 1,2,3,4‐diazadiphospholes. Both species represent rare examples of neutral heterophospholes. The mechanism of formation and the electronic structures of these formal (3+2) cycloaddition products were analyzed computationally. The new phospholes form structurally diverse coordination compounds with transition metal and main group elements. Given the growing number of stable diazoalkenes, this work offers a straightforward route to neutral aza(di‐)phospholes as a new ligand class. [ABSTRACT FROM AUTHOR]

Numerous appropriately substituted pyridyl or phenyl groups serve as a particularly advantageous activation motif for the electrochemical oxidation of amines. Such groups enable a general, mild method for the electrochemical α‐functionalization of tertiary amines across numerous activating groups and amine scaffolds. Notably, the method accommodates an unprecedented range of nucleophile classes, allowing for the introduction of diverse functional groups to the readily prepared amine substrates. The utility of this method is then demonstrated through applications to unsymmetrical bisfunctionalization, site‐selective functionalization of N‐pyridyl amines vs. other activated amines, a formal synthesis of ivosidenib and the diversification of FDA‐approved drugs or natural product substrates. [ABSTRACT FROM AUTHOR]

Sterically loaded, anionic pyridine has been synthesized and utilized successfully in the stabilization of a isoleptic series of coinage metal complexes. The treatment of [4‐(Ph3B)‐2,6‐Trip2Py]K (Trip=2,4,6‐iPr3C6H2) with CuBr(PPh3), AgCl(PPh3) or AuCl(PPh3) (Py=pyridine) afforded the corresponding [4‐(Ph3B)‐2,6‐Trip2Py]M(PPh3) (M=Au, Ag, Cu) complexes, via salt metathesis, as isolable, crystalline solids. Notably, these reactions avoid the facile single electron transfer chemistry reported with the less bulky ligand systems. The X‐ray structures revealed that they are two‐coordinate metal adducts. The M−N and M−P bond distances are longest in the silver and shortest in the copper adduct among the three group 11 family members. Computational analysis revealed an interesting stability dependence on steric bulk of the anionic pyridine (i. e., pyridyl borate) ligand. A comparison of structures and bonding of [4‐(Ph3B)‐2,6‐Trip2Py]Au(PPh3) to pyridine and m‐terphenyl complexes, {[2,6‐Trip2Py]Au(PPh3)}[SbF6] and [2,6‐Trip2Ph]Au(PPh3) are also provided. The Au(I) isocyanide complex, [4‐(Ph3B)‐2,6‐Trip2Py]Au(CNBut) has been stabilized using the same anionic pyridylborate illustrating that it can support other gold‐ligand moieties as well. [ABSTRACT FROM AUTHOR]

Phenyldiazenyl moiety has been utilized both as a protective and activating group to synthesize C-1-substituted tetrahydroisoquinolines via lithiation–substitution strategy. This reaction sequence involves generation of α-amino carbanions, derived from N -phenyldiazenyl tetrahydroisoquinolines, followed by coupling with various electrophiles, e.g., aldehyde, ketones, alkyl halide, oxiranes, isocyanates, and with in situ generated arynes. Deprotection of the protecting group was carried out under acidic conditions to afford the desired α-substituted products in moderate to good yields. So, triazene as a protecting/directing group and its compatibility with strong bases provide a good synthetic utility for the synthesis of a variety of α-substituted secondary amines via lithiation substitution reaction. [ABSTRACT FROM AUTHOR]

Piperazines and diazepines are examples of nitrogen heterocycles present in many marketed drugs highlighting their importance in the discovery of novel bioactive compounds. However, their synthesis often faces challenges, including complex functionalization and lengthy reaction sequences. Multicomponent reactions, notably the Ugi reaction, have emerged as powerful tools to address these hurdles. Here, we have demonstrated the possibility of using the combination of arylglyoxals and carboxylic acids tethered to nonprotected deactivated amines as a powerful strategy for the synthesis of complex fused heterocycles. The limited nucleophilic character of the amino group of the anthranilic acid, indole-2-carboxylic acid, pyrrole-2-carboxylic acid or N-phenylglycine has allowed the use of these compounds in the Ugi reaction without triggering competitive reactions. The additional functional group present in the resulting Ugi adduct can be leveraged in different post-condensation strategies to easily generate multiple fused nitrogen heterocycles including benzodiazepinone and piperazinone cores.

Abstract The anaerobic digestion of aqueous condensate from fast pyrolysis is a promising technology for enhancing carbon and energy recovery from waste. Syngas, another pyrolysis product, could be integrated as a co-substrate to improve process efficiency. However, limited knowledge exists on the co-fermentation of pyrolysis syngas and aqueous condensate by anaerobic cultures and the effects of substrate toxicity. This work investigates the ability of mesophilic and thermophilic anaerobic mixed cultures to co-ferment syngas and the aqueous condensate from either sewage sludge or polyethylene plastics pyrolysis in semi-batch bottle fermentations. It identifies inhibitory concentrations for carboxydotrophic and methanogenic reactions, examines specific component removal and assesses energy recovery potential. The results show successful co-fermentation of syngas and aqueous condensate components like phenols and N-heterocycles. However, the characteristics and load of the aqueous condensates affected process performance and product formation. The toxicity, likely resulting from the synergistic effect of multiple toxicants, depended on the PACs’ composition. At 37 °C, concentrations of 15.6 gCOD/gVSS and 7.8 gCOD/gVSS of sewage sludge-derived aqueous condensate inhibited by 50% carboxydotrophic and methanogenic activity, respectively. At 55 °C, loads between 3.9 and 6.8 gCOD/gVSS inhibited by 50% both reactions. Polyethylene plastics condensate showed higher toxicity, with 2.8 gCOD/gVSS and 0.3 gCOD/gVSS at 37 °C decreasing carboxydotrophic and methanogenic rates by 50%. At 55 °C, 0.3 gCOD/gVSS inhibited by 50% CO uptake rates and methanogenesis. Increasing PAC loads reduced methane production and promoted short-chain carboxylates formation. The recalcitrant components in sewage sludge condensate hindered e-mol recovery, while plastics condensate showed high e-mol recoveries despite the stronger toxicity. Even with challenges posed by substrate toxicity and composition variations, the successful conversion of syngas and aqueous condensates highlights the potential of this technology in advancing carbon and energy recovery from anthropogenic waste streams. Graphical Abstract

The anaerobic digestion of aqueous condensate from fast pyrolysis is a promising technology for enhancing carbon and energy recovery from waste. Syngas, another pyrolysis product, could be integrated as a co-substrate to improve process efficiency. However, limited knowledge exists on the co-fermentation of pyrolysis syngas and aqueous condensate by anaerobic cultures and the effects of substrate toxicity. This work investigates the ability of mesophilic and thermophilic anaerobic mixed cultures to co-ferment syngas and the aqueous condensate from either sewage sludge or polyethylene plastics pyrolysis in semi-batch bottle fermentations. It identifies inhibitory concentrations for carboxydotrophic and methanogenic reactions, examines specific component removal and assesses energy recovery potential. The results show successful co-fermentation of syngas and aqueous condensate components like phenols and N-heterocycles. However, the characteristics and load of the aqueous condensates affected process performance and product formation. The toxicity, likely resulting from the synergistic effect of multiple toxicants, depended on the PACs' composition. At 37 °C, concentrations of 15.6 gCOD/gVSS and 7.8 gCOD/gVSS of sewage sludge-derived aqueous condensate inhibited by 50% carboxydotrophic and methanogenic activity, respectively. At 55 °C, loads between 3.9 and 6.8 gCOD/gVSS inhibited by 50% both reactions. Polyethylene plastics condensate showed higher toxicity, with 2.8 gCOD/gVSS and 0.3 gCOD/gVSS at 37 °C decreasing carboxydotrophic and methanogenic rates by 50%. At 55 °C, 0.3 gCOD/gVSS inhibited by 50% CO uptake rates and methanogenesis. Increasing PAC loads reduced methane production and promoted short-chain carboxylates formation. The recalcitrant components in sewage sludge condensate hindered e-mol recovery, while plastics condensate showed high e-mol recoveries despite the stronger toxicity. Even with challenges posed by substrate toxicity and composition variations, the successful conversion of syngas and aqueous condensates highlights the potential of this technology in advancing carbon and energy recovery from anthropogenic waste streams. [ABSTRACT FROM AUTHOR]

8‐Aryl xanthines are selective enzyme inhibitors modified from naturally occurring methylxanthines. However, the low water solubility of substituted xanthines restricts their clinical applications. We developed a strategy to improve the water solubility of biologically privileged 8‐aryl xanthines. A series of glucosylated 5‐(arylidene)‐6‐aminouracil was synthesized as 8‐aryl‐1,3‐dimethyl xanthine precursors and fully characterized with spectroscopic methods. Koenigs‐Knorr reaction was used to synthesize β‐O‐glucosylated aromatic aldehydes which were then reacted with 5,6‐diamino‐1,3‐dimethyluracil to obtain the corresponding 5‐(arylidene)‐6‐aminouracils. The strategy was validated by the ring‐closing reaction of a β‐O‐glucosylated 5‐(arylidene)‐6‐aminouracil derivative with iodine (I2) in dimethoxyethane. The water solubility of the glucosylated 8‐aryl‐1,3‐dimethyl xanthine and its non‐glycosylated counterpart was compared. Glucosylation improved the water solubility of the compound. The effect of glucosylation on the bioactivity of the compounds was investigated by measuring their inhibition effect on some common enzymes. The glucosylated 8‐aryl xanthine demonstrated significantly better efficiency. Molecular docking was performed to elucidate the ligand‐protein interactions. Since the target enzymes are primarily related to brain disorders, the blood‐brain barrier (BBB) penetration ability of 8‐aryl xanthine partners was investigated. According to adsorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, glucosylated 8‐aryl xanthine was found to be BBB permeable. [ABSTRACT FROM AUTHOR]

A series of novel 2‐(2‐pyridyl)quinazoline luminophores containing a donor aryl fragment at position 4 and methyl or methoxy groups at benzene ring has been synthesized by efficient three‐step route. The linear optical properties have been studied by UV/Vis absorption and photoluminescence spectra in two solvents. We revealed that introduction of additional methyl group or the replacement of methyl substituents with methoxy ones lead to sequentially shift of absorption and emission maximum to blue region. 9H‐Carbazol‐9‐yl‐containing derivative is characterized by hypsochromically shifted absorption band compared to its NEt2 and NPh2 counterparts. Unlike 9H‐carbazol‐9‐yl‐derivative, Et2N‐ and Ph2N‐bearing quinazolines demonstrate considerable decrease in quantum yield values when going from toluene to MeCN. Solvatochromic properties have been explored, the pronounced bathochromic shift was observed in fluorescence spectra with the increase of solvents polarity. Moreover, the compounds show significant shift of emission band with the increase of water fraction in DMSO/H2O mixture. Two‐photon optical properties have been also studied, the two‐photon absorption cross‐sections in MeCN and toluene reached 120 GM and 210 GM, respectively. The presence of additional methyl group has little impact on δTPA value, while introduction of methoxy substituents dramatically decreases TPA cross sections. Additionally, a quantum‐chemical calculations of synthesized compounds were performed to support the experimental data. [ABSTRACT FROM AUTHOR]

Nitrogen heterocycles have drawn considerable attention because of their structurally novel and significant biological activities. Marine-derived fungi, especially the Aspergillus species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This review prioritizes the structural diversity and biological activities of nitrogen heterocycles that are produced by marine-derived Aspergillus species from January 2019 to January 2024, and their relevant biological activities. A total of 306 new nitrogen heterocycles, including seven major categories—indole alkaloids, diketopiperazine alkaloids, quinazoline alkaloids, isoquinoline alkaloids pyrrolidine alkaloids, cyclopeptide alkaloids, and other heterocyclic alkaloids—are presented in this review. Among these nitrogen heterocycles, 52 compounds had novel skeleton structures. Remarkably, 103 compounds showed various biological activities, such as cytotoxic, antimicrobial, anti-inflammatory, antifungal, anti-virus, and enzyme-inhibitory activities, and 21 compounds showed potent activities. This paper will guide further investigations into the structural diversity and biological activities of nitrogen heterocycles derived from the Aspergillus species and their potential contributions to the future development of new natural drug products in the medicinal and agricultural fields. [ABSTRACT FROM AUTHOR]

Tempted by the unique medicinal and biological potential of indole‐containing heterocycles, chemists, especially those specializing in heterocycle synthesis and drug discovery, are actively pursuing their efficient construction. This review spotlights the latest advancements in microwave‐assisted (M. W.) synthesis of diverse indole‐based heterocyclic compounds. We systematically categorize the reported methods based on the specific indole substitution patterns. This review concise the microwave assisted synthesis of indole based‐pyridine derivatives, indole based‐pyrimidine, indole based‐oxindole, spiro‐oxindole, Fischer indole Heck‐isomerization derivatives, functionalized indole, substituted indoles, indolyl quinoline, indole triazole and indolylnicotinonitriles derivatives. Ultimately, this review aims to provide organic and medicinal chemists with a concise yet informative guide to recent methodologies employing indole derivatives in the microwave‐powered synthesis of heterocycles. [ABSTRACT FROM AUTHOR]

We present a method for the synthesis of substituted indolo[1,2‐a]quinoline‐5(6H)‐ones starting from 1‐(2‐ethynylphenyl)‐1H‐indoles. The transformation involves gold‐catalyzed oxidation of the triple bond followed by acid‐promoted intramolecular cyclization at the indole C2 position. Demonstrating noteworthy versatility, the reaction tolerates a wide array of substituents on the indole core and proceeds in good to excellent yields (up to 93 %). [ABSTRACT FROM AUTHOR]

The development of site‐selective functionalization of N‐heteroarenes is highly desirable in streamlined synthesis. In this context, direct amination of pyridines stands as an important synthetic methodology, with particular emphasis on accessing 4‐aminopyridines, a versatile pharmacophore in medicinal chemistry. Herein, we report a reaction manifold for the C4‐selective amination of pyridines by employing nucleophilic substitution of hydrogen (SNH). Through 4‐pyridyl pyridinium salt intermediates, 4‐aminopyridine products are obtained in reaction with aqueous ammonia without intermediate isolation. The notable regioselectivity was achieved by the electronic tuning of the external pyridine reagents along with the maximization of polarizability in the proton elimination stage. Further mechanistic investigations provided a guiding principle for the selective C−H pyridination of additional N‐heteroarenes, presenting a strategic avenue for installation of diverse functional groups. [ABSTRACT FROM AUTHOR]

In the light of recent progress in the development of SARS-CoV-2 main protease inhibitors, the synthesis of their key fragment, heterocyclic amino acids, is of great interest. Here, we report a method for the preparation of two new quisqualic acid analogs containing hydantoin and imidazolidinone moieties. The hydantoin analog was obtained using an amide ester cyclization, while the imidazolidinone unit was constructed by reductive amination and subsequent cyclization of a substituted ethylenediamine with carbonyldiimidazole. The presented approach provides the convergent synthesis of target analogs in 8 and 5 steps respectively. [ABSTRACT FROM AUTHOR]

Minireview describes recent (2014–2024) advances in the synthesis of five- to seven-membered azaheterocycles using heteroannulation of monosubstituted ferrocenes. Most of the methods described here are based on asymmetric transition metal catalysis. [ABSTRACT FROM AUTHOR]

2‐(2‐methoxyphenyl)benzoxazole (MBO) displays similar photophysical properties to 2‐(2‐hydroxyphenyl)benzoxazole (HBO), but it lacks the large Stokes shifts necessary for fluorescence microscopy applications. In this paper, we report the 5‐substitution of MBO with aryl groups to produce 2‐(4‐methoxy‐[1,1'‐biphenyl]‐3‐yl)benzoxazoles (MBBOs) with large Stokes shifts. The synthesis of MBBOs 6–15 was accomplished in moderate to good yields by microwave‐assisted Sonogashira cross couplings. Crystal structures for compounds 6–9 and 15 are provided. MBBOs 6–10, 12, and 14 displayed considerably blue‐shifted absorption maxima and slight bathochromic shifts of their fluorescence maxima relative to the unsubstituted MBO. [ABSTRACT FROM AUTHOR]

Diboradiazene compounds, derived in one step from the boron‐mediated reduction of dinitrogen (N2), were treated separately with sulfur and acetic anhydride, providing heterocyclic compounds that are BN isosteres of thiophene and 1,3‐oxazole, respectively. These simple reactions represent the final steps in two‐step routes to complex heterocycles from N2 that both circumvent the need for transition metal reagents and completely bypass the traditional intermediate ammonia. [ABSTRACT FROM AUTHOR]

The synthesis of chiral succinimides bearing all‐carbon quaternary stereocenters at the C3 position is important, but remains challenging. The present work demonstrates conjugate additions with catalysis by a chiral 1,10‐phenanthroline‐Pd complex (L1‐PdCl2) that exhibit complete regioselectivity with a high degree of enantioselectivity. These reactions afford chiral 3,3‐disubstituted succinimides having all‐carbon quaternary stereocenters with 40–99% ee. Importantly, chiral 3,3‐diaryl succinimides could also be obtained in 35–98% yields and 40–99% ee. Moreover, the present L1‐PdCl2‐catalyzed asymmetric conjugate addition could be performed on the gram scale and was also used to introduce such stereocenters into bioactive molecules. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A new family of dibenzoullazine derivatives was synthesized through 1,3‐dipolar cycloaddition of polycyclic aromatic azomethine ylides with alkynylbenziodoxoles followed by oxidation. The benziodoxole moiety in the resulting products was used as a versatile linchpin for the synthesis of structurally diverse functional dibenzoullazines that are difficult to access by other synthetic methods. [ABSTRACT FROM AUTHOR]