N-substituted Pyrrole Derivatives Research Articles

Nickel ferrite nanoparticles doped on hollow carbon microspheres as a novel reusable catalyst for synthesis of N-substituted pyrrole derivatives

Pyrroles are widely spread worldwide because of their critical applications, especially pharmacology. An expedition method for one-pot synthesis of N-substituted pyrrole derivatives has been presented by a reaction between 2,5-dimethoxytetrahydrofuran and various primary aromatic amines in the presence of NiFe2O4 anchored to modified carbon hollow microspheres (NiFe2O4@MCHMs) as a recoverable reactive catalyst. The Classon-Kass method has been used to synthesize the pyrroles in excellent yields and short reaction times in the same direction with green chemistry rules. This reaction was carried out by employing NiFe2O4@MCHMs as a catalyst to make a simple procedure with short activation energy in water as an accessible, non-toxic, and biodegradable solvent. This catalyst provides a promising pathway to synthesize N-substituted pyrroles several times in a row through the recyclability without remarkable loss of its catalytic activity. The NiFe2O4@MCHMs nanocatalyst was characterized by applying FT-IR, XRD, FE-SEM, TEM, EDS, BET, TGA, VSM, and elemental mapping techniques. Also, the synthesized N-substituted pyrrole derivatives were identified using melting point, FT-IR, and 1H NMR analyses.

Clauson-Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach.

Pyrrole is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson-Kaas reaction is a very old and well-known method for synthesizing a large number of N-substituted pyrroles. In recent years, due to global warming and environmental concern, research laboratories and pharmaceutical industries around the world are searching for more environmentally friendly reaction conditions for synthesizing compounds. As a result, this review describes the use of various eco-friendly greener protocols to synthesize N-substituted pyrroles. This synthesis involves the reaction of various aliphatic/aromatic primary amines, and sulfonyl primary amines with 2,5-dimethoxytetrahydrofuran in the presence of numerous acid catalysts and transition metal catalysts. The goal of this review is to summarize the synthesis of various N-substituted pyrrole derivatives using a modified Clauson-Kaas reaction under diverse conventional and greener reaction conditions.

Sustainable Synthesis of N-Alkyl-Pyrrolecarboxylic and Pyrrolepyrazinones Derivatives from Biosourced 3-Hydroxy-2-pyrones and Amines

Pyrroles are important compounds present in biological systems, used for drug synthesis and in material chemistry. A typical strategy for the pyrrolic ring formation is centered on the Paal–Knorr reaction, where 1,4-dicarbonyl compounds react with amines giving N-substituted pyrrole derivatives. Often, the main problem of this approach is the availability of the appropriate carbonyl compounds. Here, we report a sustainable synthesis of N-substituted pyrrole carboxylic acid derivatives by the reaction of primary amines and 3-hydroxy-2-pyrones. These last compounds can easily be prepared using renewable sources and show the property to be masked 1,4-dicarbonyl compounds that are able to react efficiently with amines to form substituted pyrrolic rings. The reactions can be performed under sustainable conditions without solvents at 50–75 °C or in basic water–methanol solutions at room temperature, obtaining symmetric and asymmetric pyrroles from good to high yields. Moreover, dihydropyrrolepyrazinone derivatives can easily be prepared in high yields by the reaction of 3-hydroxy-2-pyrones and ethylenediamine.

Microwave-assisted solvent-free tandem cross-metathesis/intramolecular isomerization-cyclization reaction for the synthesis of N-substituted pyrroles: It’s computational analysis

The microwave-assisted solvent-free reaction has been developed for the rapid synthesis of different pyrrole derivatives using cross-metathesis (CM) between N-allylamines and α, β-unsaturated carbonyl compounds with moderate to good yields. This method is solvent free, facile, rapid, and high yielding reaction for the synthesis N-substituted pyrrole derivatives. The effect of microwave irradiation versus classical thermal conditions is demonstrated through a series of comparative cross-metathesis reactions. In the present eco-friendly approach, the combination of solvent-free conditions and microwave irradiations leads to a substantial reduction in reaction times with improved yields. The computational analysis revealed that the microwave irradiation conditions favored the interconversion of ruthenacyclobutane (RuG to RuH) approximately 10-fold more than the conventional heating. Exclusive formation of pyrrole ring system (cyclization- aromatization cascade reaction) over piperazinone (aza-michael product) has been explained through DFT calculations.

Photo-control of cancer cell growth by benzodiazo N-substituted pyrrole derivatives

In order to expand the class of diazocompounds able to act as photo-activable microtubule inhibitors the potential of azo-heteroarenes has been explored. In this paper we focus on the synthesis, physical properties and biological effects of methyl rac-2-(2-((E)-(4-((R)-2,3-dihydroxypropoxy)phenyl) diazenyl)-1H-pyrrol-1-yl)-3-hydroxypropanoate (1a) and methyl rac-2-(2-((E)-(4-((S)-2,3-dihydroxypropoxy)phenyl) diazenyl)-1H-pyrrol-1-yl)-3-hydroxypropanoate (1b). Preliminary biological studies on the HCT-116 p53-/- cancer cell line have shown that the weak antiproliferative action of the trans isomers of these molecules, especially of 1a, is enhanced upon LED light irradiation at 435 nm. On A375 cells the molecules have not shown any effect on cell viability either in the dark or under irradiation. Moreover, the two diastereomeric components of 1a as pure stereomers have been synthesized and characterized for their chemical-physical properties. Interestingly, upon irradiation, 1a has shown an antiproliferative activity on the HCT-116 p53-/- cells greater than that of the pure stereomers, 1RR and 1RS. Tubulin polymerization assay has also demonstrated that 1a, 1RR and 1RS inhibit tubulin aggregation mostly after exposure of the samples to LED light irradiation.

A facile synthesis of 1-aryl pyrroles by Clauson-Kaas reaction using oxone as a Catalyst under microwave irradiation

A new and efficient methodology to synthesize N-substituted pyrrole derivatives by Clauson Kaas reaction employing Oxone as catalyst was developed. The transformation was performed in acetonitrile under microwave irradiation. This procedure has several advantages such as high yield, clean product formation, and short reaction time. KEY WORDS : Synthesis, Pyrrole, Oxone, Microwave irradiation Bull. Chem. Soc. Ethiop. 2019 , 33(1), 143-148 DOI: https://dx.doi.org/10.4314/bcse.v33i1.14

Synthesis of N-Substituted Pyrrole Derivatives via Indium-Assisted One-Pot Reduction/N-Annulation Sequence Reaction

Synthesis of N-Substituted Pyrrole Derivatives via Indium-Assisted One-Pot Reduction/N-Annulation Sequence Reaction

Solvent Free Synthesis of N-Substituted Pyrrole Derivatives Catalyzed by Silica Sulfuric Acid

Sulfuric acid immobilized on silica gel is used as an efficient catalyst in the synthesis of N-substituted pyrrole derivatives by the Clauson–Kaas pyrrole synthesis. The solvent free reaction mixture is stirred by grinding. Within very short reaction time the process leads to the corresponding products without any decomposition recorded.

Bio-based Material as Medium, Mild and Reusable Catalyst for Paal– Knorr Pyrrole Synthesis with and Without Ultrasonic Irradiation

Background: Pyrrole moiety is found in naturally occurring compounds such as chlorophyll, haem, and vitamin B12 and present in a number of drugs for example atorvastatin, ketorolac, elopiprazole, tolmetin and sunitinib. Various methods have been used for the synthesis of pyrrole derivatives; however, still there is a need for environmentally benign and economic protocol. Method: We have reported a simple, mild and speedy synthesis of N-substituted 2,5-dimethyl pyrrole derivatives in ‘’GAAS’’ as medium and catalyst at room temperature and under ultrasound irradiation. Results: This protocol was employed for the synthesis of various 2,5-dimethyl-N-substituted pyrrolederivatives using both aliphatic as well as aromatic amines in short time (2 to 10 minutes)with excellent yield (84-95%) at room temperature and under ultrasonic irradiation. The catalytic system “GAAS’’ was regenerated and reused five times effectively without major loss of activity. Conclusion: In conclusion, we have developed an eco-friendly, simple, faster, reusable, mild, and efficient protocol for the synthesis of N-substituted pyrrole derivatives. This bio-based protocol is cost-effective and greener methodology for the synthesis of biologically active N-substituted pyrrole derivatives. Keywords: GAAS, ultrasound, N-substituted pyrrole derivatives, catalyst, organic synthesis, irradiation.

Microwave Promoted Green Synthesis of Pyrroles Using N-Methyl-2-Pyrrolidonium Hydrogen Sulfate as an Efficient Catalyst Under Solvent-Free Condition

A rapid and convenient synthesis of N-substituted pyrrole derivatives is described using ionic liquid as a homogeneous catalyst under microwave irradiation. The [HNMP][HSO4] catalyst possess a lot of unique properties such as very low vapor pressure, high thermal and chemical stability, noncorrosive, nonflammability properties and easy reaction work-up. This reaction was carried out using 2,5-dimethoxy tetrahydrofuran and primary amines under solvent-free and green chemistry conditions.

Intramolecular macrolactonization, photophysical and biological studies of new class of polycyclic pyrrole derivatives.

Herein, we report an efficient synthesis of N-substituted pyrrole derivatives and their application to construct macrocyclic oxazocinone via a two-component coupling reaction followed by base mediated intramolecular cyclization. This methodology provides an easy two-step approach to constitute a library of fused pyrrolo-oxazocinone derivatives in good yields under mild reaction conditions. The present methodology offers an easy access to the synthesis of a library of fluorescent pyrole derivatives. Among them, tert-butyl 2-(2-(3-hydroxypropyl)-7-methoxy-4,5-dihydro-2H-benzo[e]isoindol-1-yl)acetate has been employed in bio-analytical imaging which shows efficient cellular internalization along with no obvious cellular toxicity.

Silica tungstic acid and sulphated silica tungstic acid as highly efficient solid acid catalysts for the synthesis of pyrrole derivatives

In the present study silica supported tungstic acid (STA) and sulphated silica tungstic acid (SSTA) were applied as efficient and cost-effective solid acid catalysts in the synthesis of N-substituted pyrrole derivatives via the Paal–Knorr reaction of 2,5-hexadione with aromatic and aliphatic amines at room temperature. The reaction completed in short time under mild conditions with high yield. The catalysts could be easily recovered upon reaction completion. Structures of all products were confirmed by elemental analysis, FT-IR, 1H and 13C NMR spectra.

Flexibility and electrical and humidity-sensing properties of N-substituted pyrrole derivatives and composite films of Au nanoparticles/N-substituted pyrrole derivatives

Novel impedance-type humidity sensors were fabricated by coating 2,5-dimethyl-1-phenyl-1H-pyrrole (1), 1-(4-aminophenyl)-2,5-dimethyl-1H-pyrrole (2), 1-(4-nitrophenyl)-2,5-dimethyl-1H-pyrrole (3) and gold nanoparticles/compound 3 (AuNPs/compound 3) composite films on alumina and plastic substrates. Compound 1, compound 2, compound 3 and AuNPs/compound 3 composite films were analyzed using atomic force microscopy (AFM) and UV–vis spectroscopy. The effects of the substituents on the benzene ring of compound 1 on the electrical and humidity-sensing properties of the compound 1 film were studied. The humidity sensor that was fabricated with the compound 3 exhibited high sensitivity but a higher resistance at low humidity than that which was made of the compound 1. The effects of the AuNPs on the electrical and humidity sensing properties of the AuNPs/compound 3 composite film on a PET substrate were investigated. The sensor that was made of the AuNPs/compound 3 composite film exhibited high sensitivity, good linearity, small hysteresis, high flexibility, a short response/recovery time, a weak dependence on temperature and high long-term stability. The linearity of the humidity sensor depended on the applied frequency. The sensing mechanism of the AuNPs/compound 3 composite film was elucidated with reference to impedance plots.

Effect of N-α Substitution on the Electropolymerization of N-Substituted Pyrroles: Structure–Reactivity Relationship Studies

Structure–reactivity relationship (SRR) studies to understand the effect of N-α substitution toward electroactive poly(pyrrole) film formation have carefully been performed. To conduct these SRR studies, a selected chemical library of 21 different N-substituted pyrrole derivatives has been developed using the key well-known Clauson–Kass synthetic reaction from corresponding amine precursors. While investigating electropolymerization features of these novel N-substituted pyrroles, we observed that the steric factor due to α-substitution, one among other factors, plays the most significant role in preventing electropolymerization of these oxidizable chemical species. Interestingly, even a sterically small chemical group like a CH3 one present at α-position is large enough to prevent monomer electropolymerization. Density functional theory calculations were carried out to analyze the polymerization of substituted pyrrole molecules and to understand the effect of N-substituents on electropolymerization toward...

COMPUTATIONAL STUDY OF HIV-1 gp41 NHR TRIMER: INHIBITION MECHANISMS OF N-SUBSTITUTED PYRROLE DERIVATIVES AND FRAGMENT-BASED VIRTUAL SCREENING

Fusion of HIV-1 viral and host cellular membranes is an important step for HIV infection. The HIV-1 envelope glycoprotein mediating the membrane fusion consists of subunits gp120 and gp41 whereas gp120 recognizes the cell-surface receptors and gp41 promotes viral-cell membrane fusion. The trimeric helical complex composed of heterodimer of N-terminal and C-terminal extraviral segments has been used for the gp41 function study, and the trimeric N-terminal teptad repeat (NHR) is considered as an antiviral drug target for developing HIV-1 membrane fusion inhibitors. By using computational solvent probe mapping, we have explored druggable sites on the trimeric NHR peptides, and identified residues K574 and R579 as the hot spots for inhibitor designing. We further demonstrated that although NB-2 and NB-64 are all N-substituted Pyrrole derivatives and have very similar chemical structures, it is possible that diverse inhibitory mechanisms targeting different negative electrostatic residues (K574 and R579) exist. Results from fragment-based virtual screening identified series of potential lead compounds which could be used for further design of fusion inhibitors.

A novel enzyme-catalyzed synthesis of N-substituted pyrrole derivatives

A novel method for the synthesis of substituted pyrroles catalyzed by α-amylase from hog pancreas via Paal-Knorr reaction was developed. A series of pyrrole derivatives were synthesized under mild conditions and the products were obtained with good to excellent yields (60-99 %). The impact of factors, such as solvents, enzyme amount, and temperature, on the reaction were investigated. This study reports an efficient route for the synthesis of N-substituted pyrrole derivatives.

Clauson Kaas Pyrrole Synthesis Catalyzed by Acidic Ionic Liquid under Microwave Irradiation

A new procedure to synthesize the N-substituted pyrrole derivatives by Clauson Kaas reaction catalyzed by acidic ionic liquid under microwave irradiation was developed. This procedure provides several advantages such as high yield, clean product formation, and short reaction time.

Docking studies of pyrrole derivatives using Hex

N-substituted pyrrole derivatives block HIV fusion. Docking used for virtual screening of database and for the prediction of the strongest binders based on various scoring functions. Docking studies were carried out on different pyrrole derivatives for better anti-HIV-l activity which is important for the development of a new class of inhibitors. Protein-ligand interaction plays an important role in structural based drugs design. In our research we have selected different receptor which shows anti-HIV-1 activity. The receptors were docked with different pyrrole derivatives and the energy value obtained. Our study reveals that the highest energy values observed for all the three ligands are with 3MNW: for 2-Amino-l-(4-Iodophenyl)-oxo-4, 5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester energy value is -265.9, for 2-Amino-l-(4-Fluoro-phenyl)-oxo-4, 5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester energy value is -228.23 and for 2-Amino-l-(4-Methoxy-phenyl)-oxo-4, 5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester energy value is -227.13. From this we can say that Iodo pyrrole derivative shows high interaction energy compared to other Fluoro and methyl derivatives. By synthesizing few more analogous, we can further improve the interaction energy values and hence better analogous derivatives can be predicted.

Ultrasound-assisted bismuth nitrate-induced green synthesis of novel pyrrole derivatives and their biological evaluation as anticancer agents

A series of novel N-substituted pyrrole derivatives have been designed and synthesized following ultrasound-assisted and bismuth nitrate-catalyzed eco-friendly route. This reaction has also provided a general method to prepare diverse varieties of N-substituted pyrroles with less nucleophilic polyaromatic amines. Based on 1H NMR spectroscopy, a plausible mechanistic pathway has been advanced. Cytotoxicity of some selected N-substituted pyrrole derivatives has been evaluated in vitro in a panel of mammalian cancer cell lines which includes liver cancer cell lines (HepG2 and Hepa1-6), colon cancer cell lines (HT-29 and Caco-2), a cervical cancer cell line (HeLa) and NIH3T3 cells. Two compounds, 5-(1H-pyrrol-1-yl)-1,10-phenanthroline (9) and 1-(phenanthren-2-yl)-1H-pyrrole (10) have shown good cytotoxicity against some cancer cell lines. Furthermore, these compounds have exhibited cytotoxic specificity against liver cancer cell lines in vitro when compared with normal cultured primary hepatocytes.

Paal–Knorr Pyrrole Synthesis Using Recyclable Amberlite IR 120 Acidic Resin: A Green Approach

Amberlite IR 120 acidic resin, a polymer matrix, has been demonstrated as a catalyst for Paal-Knorr condensation of 2,5-hexadione with primary amines under solvent-free conditions. This is an efficient, mild, and green methodology for N-substituted pyrrole derivatives.