Nitrogen Heterocycles Research Articles

Electrochemical Generation of Nitrogen‐centered Radicals and its Application for the Green Synthesis of Heterocycles

AbstractElectrochemistry became a unique and powerful tool for the preparation of a plethora of valuable chemical species including functional materials, drug candidates and clinically approved pharmaceuticals. Organic electrosynthesis well satisfies main goals of green chemistry development and is considered as one of the useful approaches toward the creation of sustainable future. Since nitrogen heterocyclic scaffolds still retain their importance for the construction of novel materials and medications, one of the emerging trends in organic electrochemistry is the discovery of novel green and sustainable synthetic methods toward the assembly of heterocyclic subunits. In this regard, organic electrochemistry provides an efficient platform for environmentally benign generation of various nitrogen‐centered radicals which are prominent intermediates in the synthesis of nitrogen heterocycles. In this Review, recent developments in the creation of green synthetic methods for the construction of nitrogen heterocycles via electrochemical generation of nitrogen‐centered radicals are summarized. The special emphasis is devoted to the influence of solvent, electrodes and electrolytes on the electrochemical step, since these crucial parameters regulate the process efficiency.

Pyrolysis of polystyrene using low-cost natural catalysts: Production and characterisation of styrene-rich pyro-oils

This work aims to study the catalytic pyrolysis of polystyrene (PS) in order to obtain a styrene-rich liquid appealing for re-polymerisation processes. The process was performed in a fixed-bed reactor using low-cost materials such as ilmenite, olivine, calcium oxide (CaO) and dolomite as catalysts at 600 ºC. A non-catalytic test with sand was also conducted for comparison purposes. The resulting pyro-oil yield was between 89 and 96 wt%, and consisted mainly of styrene monomer, styrene dimer and styrene trimer, as well as other light aromatic compounds depending on the catalyst used. Olivine and CaO were capable to increase the styrene monomer concentration in the pyro-oil by about 10–12 % compared to non-catalytic pyrolysis, reaching up to 74.5 and 71.4 wt%, respectively. Furthermore, these catalysts reduced the concentration of styrene dimer and styrene trimer in the pyro-oil, which could be useful for further re-polymerisation processes. However, the presence of polyaromatics (PAHs) in the pyro-oils obtained from ilmenite, olivine and CaO was also identified, and other families such as mono-aromatics, di-aromatics, BTX, and nitrogen heterocyclic compounds were also increased in all pyro-oils obtained with catalysts compared to those obtained by non-catalytic pyrolysis. In addition, several inorganic species in the pyro-oil were reduced by the addition of the catalysts. This effect was observed after the addition of olivine and CaO, especially in the reduction of S, Mg, Ca and Fe. These results clearly demonstrate the potential of pyrolysis to convert PS waste into valuable building blocks for the production of new plastics.

The characteristic structural and functional dynamics of P. falciparum DHFR binding with pyrimidine chemotypes implicate malaria therapy design

Dihydrofolate reductase (DHFR) enzyme regulates de-novo folate synthesis in Plasmodium falciparum, hence a critical malaria drug target. Pyrimethamine inhibits DHFR, but resistance and lack of cross-species activity are key challenges. Therefore, this study is set to investigate more potent nitrogenous heterocyclic compounds against DHFR. Docking and MD simulations were employed to gain insight into the compounds’ binding free energies and conformational stabilities, while cross-species activity was determined using sequence alignment. Among the 500 screened compounds, PMD_01 (−12.2 kcal/mol), PMD_02 (−11.1 kcal/mol), PMD_03 (−10.7 kcal/mol), and PMD_04 (−10.7 kcal/mol) have the highest binding affinities against pfDHFR compared to pyrimethamine (−7.9 kcal/mol). Critical amino acids for binding interactions in the active site of pfDHFR include Leu45, Thr107, Ile164, and Thr170. PMD-bound systems showed higher binding free energy than pyrimethamine, except PMD_03. Hydrogen bonding interactions with Gly159, Ser101, Ser104, Ser160, Ile157, and Lys48 played significant roles in the binding interaction of these compounds as opposed to Asp53 in pyrimethamine. The four systems converged around 1.90 Å RMSD and showed more stability than pyrimethamine-bound and unbound pfDHFR. The pocket's residues across the four plasmodia were highly conserved, but Phe116 and Ile164 replaced Met in P. knowlesi and Tyr in the other species. PMD_01, PMD_02, PMD_03, and PMD_04 showed promising inhibition against pfDHFR and are, thus, potential antimalarial agents against plasmodia DHFR homologues.

Heterocyclic Nitrogen Compounds as Potential PDE4B Inhibitors in Activated Macrophages

Cyclic-nucleotide phosphodiesterases (PDEs) represent a superfamily of enzymes playing a pivotal role in cell signaling by controlling cAMP and cGMP levels in response to receptor activation. PDE activity and expression are linked to many diseases including inflammatory diseases. In light of their specific biochemical properties, PDE inhibition has attracted the interest of several researrs In this context, PDE4 inhibition induces anti-inflammatory effects. Piclamilast and rolipram, well-known PDE4 inhibitors, are endowed with common side effects. The selective phosphodiesterase 4B (PDE4B) inhibitors could be a promising approach to overcome these side effects. In the present study, six potential PDE4B inhibitors have been investigated. Through this study, we identified three PDE4B inhibitors in human macrophages activated by lipopolysaccharide. Interestingly, two of them reduced reactive oxygen species production in pro-inflammatory macrophages.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study

BackgroundThe wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated.MethodsIn the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed.ResultsThe HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure.ConclusionsThis study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Recent Discovery of Nitrogen Heterocycles from Marine-Derived Aspergillus Species.

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.

Efficient synthetic strategies for fused pyrimidine and pyridine derivatives: A review

AbstractPyrimidine and its derivatives play a paramount role in drug discovery as privileged pharmacophores with considerable chemical and biological significance and its presence in genes. This review aims to assemble a systematic evaluation of synthetic tactics of various fused pyrimidine derivatives containing nitrogen heterocycles such as pyridopyridines, pyridopyrimidines, and pyrimidopyrimidine from a pharmacological point of view and deliver an overview of methodologies presenting the chemistry of fused pyrimidine derivatives. The review details the importance of various catalysts and ring substitution using various electrophilic and nucleophilic reagents. These synthetic strategies were elaborated based on the different synthetic routes that lead to the specific type of pyrimidine and pyridine fused derivatives. The literature accumulates various developments in one‐pot condensation, the Knoevenagel–Michael addition mechanism, microwave and ultrasound irradiation, intramolecular cyclization, nano‐catalytic reactions, and so forth. Short reaction times, catalyst reusability, solvent‐free conditions, excellent yields, and stereo‐selectivity are some of the benefits of certain synthetic approaches.

Exploration of Synthetic Potential of 2‐Chloro‐Quinoline‐3‐Carbaldehyde

Quinoline is one of the most important simple nitrogen heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. Specifically, quinoline is renowned antimalarial agents from several past decades and showed strong potential in this field. 3‐Formyl‐quinoline is a versatile precursor which transformed through the several easy methods into a wide range of biologically valuable scaffolds. The exploration of 3‐formyl‐quinoline gained much more attention to medicinal chemists in the field of drug discovery to design and synthesize new fused/tethered quinolines as potent therapeutical agents. The aim of this review, which covers the period from 2011 to 2023, is to update the role of formyl functionality of quinolines showing the extraordinary ability to play role in organic synthesis.

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013-2023).

This Perspective is a continuation of our analysis of U.S. FDA-approved small-molecule drugs (1938-2012) containing nitrogen heterocycles. In this study we report drug structure and property analyses of 321 unique new small-molecule drugs approved from January 2013 to December 2023 as well as information about frequency of important heteroatoms such as sulfur and fluorine and key small nitrogen substituents (CN and NO2). The most notable change is an incredible increase in drugs containing at least one nitrogen heterocycle─82%, compared to 59% from preceding decades─as well as a significant increase in the number of nitrogen heterocycles per drug. Pyridine has claimed the #1 high-frequency nitrogen heterocycle occurrence spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and morpholine (#9) being the big top 10 climbers. Also notable is high number of fused nitrogen heterocycles, apparently driven largely by newly approved cancer drugs.

Fast hydrothermal co-liquefaction of high-ash sludge and Chlorella for biocrude production

Fast hydrothermal liquefaction (HTL) shows great potential for producing biocrude. This research examined the influences of mixing ratios of sludge and Chlorella during both isothermal (300 °C, 1800 s) and fast (500 °C, 20 s) co-HTL. Adding Chlorella could efficiently retard repolymerization reaction and increase the biocrude production. The highest co-liquefaction effect was achieved from a sludge to Chlorella ratio of 2:6 by fast HTL, producing a biocrude yield of 29.65 wt%, closely approaching the calculated yield of 29.39 wt% and demonstrating an additive effect. However, for the high ash content of sludge, all isothermal and other fast HTL conditions presented an antagonistic effect on biocrude production. Meanwhile, co-liquefaction also exhibited a slight antagonistic effect on the heating value and energy recovery of biocrude, with experimental values reaching 32.73 MJ·kg−1 and 52.74 %, respectively. FT-IR and maturity analyses indicated that compared to isothermal co-HTL, fast co-HTL biocrude was more favorable for the conversion into gasoline/diesel due to its lower paleo-temperature. GC–MS analysis identified amides (isothermal co-HTL) and nitrogen heterocycles (fast co-HTL) as the dominant components, suggesting that the holding time significantly influenced the competition of Maillard and amidation reactions. Besides biocrude, the major composition of aqueous phase products (APs) was also nitrogen heterocycles. Notably, fast co-HTL induced a substantial decrease in COD, NH3-N, and TN contents of APs, reducing the discharge challenge of the by-products.

Ammonia recovery via stripping from hydrothermal liquefaction aqueous from sludge for anaerobic co-digestion pretreatment

Hydrothermal liquefaction (HTL) is a thermo-chemical method of processing wastewater solids that could be preferential over anaerobic digestion (AD) because it produces a greatly reduced volume of solids. Instead, the effluent can be separated into biocrude refined into fuel, hydrochar a carbon-rich solid and HTL aqueous waste. Unfortunately, HTL aqueous is high in ammonia, phenolics, and nitrogen heterocyclic compounds that can inhibit AD if used for treatment. Ammonia stripping was tested for pretreatment of HTL aqueous from dewatered mixed sludge at 350 °C, 15 min and recovering ammonia. Seven stripping reactor conditions were run, and the best results were seen at 85 °C, a pH of 9.3 and 500 mL/min air flow rate. This case achieved ammonia and total phenolic compounds removal of 79.5 ± 0.1 and 32 ± 1 %, respectively, in 4 h. The ammonia stripping was coupled with acid adsorption to produce an ammonium sulphate salt with fertilizer value. The ideal ammonia stripping conditions produced a salt with a purity of 98.0 ± 0.05 % and represented an ammonia recovery of 73.9 ± 0.04 %. Semi-continuous flow bench-scale thermophilic anaerobic co-digestion of HTL aqueous with municipal sludge found that 12 % of influent chemical oxygen demand (COD) can come from HTL aqueous without inhibition if pretreated with ammonia stripping, while the digester fed with a similar COD from non-pretreated HTL aqueous showed inhibition. Under mesophilic conditions, semi-continuous flow anaerobic co-digestion was successful for non-pretreated and pretreated HTL aqueous even with 24 % and 22 % of influent COD provided by HTL aqueous, respectively.

Anti-inflammatory and cytotoxicity nitrogenous merosesquiterpenoids from the sponge Pseudoceratina purpurea

Fourteen undescribed nitrogenous merosesquiterpenoids, purpurols A−D (1–4) and puraminones A−J (5–14), along with three known related compounds (15–17) were isolated from the sponge Pseudoceratina purpurea collected in the South China Sea. Their structures and absolute configurations were unambiguously elucidated by a combination of spectroscopic data, X-ray diffraction analysis, electronic circular dichroism calculations, and chemical derivatization. Purpurols A−D (1–4) incorporated nitrogenous heterocycles, compounds 1 and 2 feature an unusual benzothiazole ring, while 3 and 4 feature benzoxazole ring. Puraminones A−J (5–14) represent sesquiterpenoid aminoquinones with different amine and amino acid side chains at C-20. Additionally, twenty unreported sesquiterpenoid aminoquinone analogues were obtained through chemical derivatization. It is worth noting that all compounds are featured with unusual rearranged 4,9-friedodrimane subunit. In the bioassays, purpurols A and B showed weak anti-inflammation in zebrafish, as well as some compounds showed activities against tumor cells, therefore, preliminary structure–cytotoxicity relationships are also discussed.

UV Light-Driven Nitric Oxide Release from Porous Nitrogen Heterocyclic Polymers.

In this study, porous polymers with nitrogen heterocyclic core structures are synthesized through the condensation of enaminonitrile and terephthalaldehyde monomers. These polymers are used as a platform to store bioactive nitric oxide (NO) and control its release. NO loading is achieved by nitrosating the polymers with acidified nitrite, a process that also imparts photoresponsivity to the polymers. Polymer composition and porosity affect NO storage and release. It is observed that under UV light at 365nm in a PBS solution, the polymers (NO@DHP-POP) can release NO in a manner fully controlled by UV lighting. Under experimental conditions, these porous polymers release NO at a rate of ≈10.0-50.0µmol g-1 over 60 min. These findings demonstrate the potential of these polymers for integrating NO delivery into phototherapy applications.

Well-defined nanomagnetic nitrilotriacetic acid complex of Cu(ii) supported on silica-coated nanosized magnetite: a new highly efficient and magnetically separable catalyst for C-N bond formation.

A nitrilotriacetic acid (NTA) complex of Cu(ii) supported on silica-coated nanosized magnetite Fe3O4@SiO2-Pr-DEA-[NTA-Cu(ii)]2 was prepared as a new well-defined magnetically separable nanomaterial and fully characterized via IR, XRD, FESEM, TEM, TGA, DLS, BET, VSM, solid-state UV-vis spectroscopy, EDX, ICP-OES, and FESEM-EDX map analyses. Thereafter, it was successfully applied as a new easily magnetically separable and reusable heterogeneous nanocatalyst for the Buchwald-Hartwig C-N bond formation reaction in DMF at 110 °C. Using this method, various kinds of nitrogen heterocycles, such as imidazoles, 2-methyl-1H-imidazole, benzimidazole, indole, and 10H-phenothiazine as well as aliphatic secondary amines such as piperidine, piperazine, morpholine, dimethylamine, and diethylamine, were reacted with aryl halide compounds, and the desired products were obtained with good to excellent yields. In all cases, the applied catalyst could be recovered easily and rapidly using an external magnet and reused 7 times without significant loss of catalytic activity.

Ferrocenyl Azoles: Versatile N-Containing Heterocycles and their Anticancer Activities.

The medicinal chemistry of ferrocene has gained its momentum after the discovery of biological activities of ferrocifen and ferroquine. These ferrocenyl drugs have been designed by replacing the aromatic moiety of the organic drugs, tamoxifen and chloroquine respectively, with a ferrocenyl unit. The promising biological activities of these ferrocenyl drugs have paved a path to explore the medicinal applications of several ferrocenyl conjugates. In these conjugates, the ferrocenyl moiety has played a vital role in enhancing or imparting the anticancer activity to the molecule. The ferrocenyl conjugates induce the cytotoxicity by generating reactive oxygen species and thereby damaging the DNA. In medicinal chemistry, the five membered nitrogen heterocycles (azoles) play a significant role due to their rigid ring structure and hydrogen bonding ability with the biomolecules. Several potent drug candidates with azole groups have been in use as chemotherapeutics. Considering the importance of ferrocenyl moiety and azole groups, several ferrocenyl azole conjugates have been synthesized and screened for their biological activities. Hence, in the view of a wide scope in the development of potent drugs based on ferrocenyl azole conjugates, herein we present the details of synthesis and the anticancer activities of ferrocenyl compounds bearing azole groups such as imidazole, triazoles, thiazole and isoxazoles.

Exploring the Scaling Factors for Infrared Modes of PANHs - A Case Study on Cationic 3-Azafluoranthene⋅+ and Protonated 3-Azafluoranthene.

Infrared (IR) emission bands by interstellar polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic nitrogen heterocycles (PANHs) are observed towards a large variety of interstellar objects and offer detailed insights into the chemistry and physics of the interstellar medium. The analysis of the emission bands, and thus the interpretation of the molecular characteristics of the carriers, heavily relies on the use of density functional theory (DFT) calculated IR spectra. However, there are significant challenges in accurately predicting the experimental IR band positions, particularly for PANH emission vibrational modes around 6 μm. In this work, we present gas-phase mid-infrared (mid-IR) spectra of cationic 3-azafluoranthene (3AF⋅+) and protonated 3-azafluoranthene (3AFH+) to investigate their experimental IR band positions in relation to DFT calculated bands. The experimental spectra are compared to DFT simulated spectra, where different approaches were followed to correct for anharmonicities. The best agreement is achieved by scaling frequencies of modes with large nitrogen displacements with a different factor. Even though our findings might be limited to a small number of PANH structures, they indicate, that nitrogen atom incorporation needs to be accounted for by carefully adjusting the corresponding scaling factors while computing IR spectra of PANHs on DFT level.

Chemoenzymatic Synthesis of 2‐Aryl Thiazolines from 4‐Hydroxybenzaldehydes Using Vanillyl Alcohol Oxidases

AbstractNitrogen heterocycles are commonly found in bioactive natural products and drugs. However, the biocatalytic tools for nitrogen heterocycle synthesis are limited. Herein, we report the discovery of vanillyl alcohol oxidases (VAOs) as efficient biocatalysts for the one‐pot synthesis of 2‐aryl thiazolines from various 4‐hydroxybenzaldehydes and aminothiols. The wild‐type biocatalyst features a broad scope of 4‐hydroxybenzaldehydes. Though the scope of aminothiols is limited, it could be improved via semi‐rational protein engineering, generating a variant to produce previously inaccessible cysteine‐derived bioactive 2‐aryl thiazolines using the wild‐type VAO. Benefiting from the derivatizable functional groups in the enzymatic products, we further chemically modified these products to expand the chemical space, offering a new chemoenzymatic strategy for the green and efficient synthesis of structurally diverse 2‐aryl‐thiazoline derivatives to prompt their use in drug discovery and catalysis.

Chemoenzymatic Synthesis of 2-Aryl Thiazolines from 4-Hydroxybenzaldehydes Using Vanillyl Alcohol Oxidases.

Nitrogen heterocycles are commonly found in bioactive natural products and drugs. However, the biocatalytic tools for nitrogen heterocycle synthesis are limited. Herein, we report the discovery of vanillyl alcohol oxidases (VAOs) as efficient biocatalysts for the one-pot synthesis of 2-aryl thiazolines from various 4-hydroxybenzaldehydes and aminothiols. The wild-type biocatalyst features a broad scope of 4-hydroxybenzaldehydes. Though the scope of aminothiols is limited, it could be improved via semi-rational protein engineering, generating a variant to produce previously inaccessible cysteine-derived bioactive 2-aryl thiazolines using the wild-type VAO. Benefiting from the derivatizable functional groups in the enzymatic products, we further chemically modified these products to expand the chemical space, offering a new chemoenzymatic strategy for the green and efficient synthesis of structurally diverse 2-aryl-thiazoline derivatives to prompt their use in drug discovery and catalysis.

Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a ceteris paribus approach

ABSTRACT Background Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors. Research design and methods A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed. Results The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors. Conclusions The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

Microwave‐Assisted Synthesis of Fluorinated 5‐Membered Nitrogen Heterocycles

AbstractThe fluorinated 5‐membered N‐containing heterocyclic compounds have wide utility in varied fields. The importance of these compounds has encouraged researchers to explore environment‐friendly synthetic techniques for their synthesis. In this context, microwave‐assisted synthesis has proved beneficial for the synthesis of fluorinated 5‐membered N‐heterocycles in an environmentally benign and energy‐efficient manner. Compared to conventional heating, it offers several advantages, including quick heating, short reaction times, higher yields, and fewer side reactions. This article highlights the microwave‐assisted fluorination of 5‐membered N‐heterocyclic compounds along with the synthesis of fluorinated 5‐membered N‐heterocyclic compounds using fluorinated starting materials.