Paal-Knorr Reaction Research Articles

Plant Juice Catalysed Synthesis of Substituted Pyrrole through Paal Knorr Reaction

The current research work proposed the novel methodology for the synthesis of N-substituted pyrrole catalysed by juice of Kalanchoe Pinnata plant leaves. The reaction was carried out between hexan 2,5 dione and aniline. This protocol is environmentally benign cost effective and fruitful which has produced the desired product in short reaction time and easy work up. The synthesised compounds has been confirmed by 1HNMR , IR and C13 spectroscopy. The natural abundance, cost effective, non toxic and good to excellent yields are some specific features of this catalyst.

Direct Multicomponent Synthesis of C3-Arylated Pyrroles under Catalyst-Free Conditions

AbstractAn operationally simple catalyst-free protocol for the direct regiospecific synthesis of C3-arylated/alkenylated pyrroles has been developed. The enamine-intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal–Knorr reaction in a direct multicomponent ‘just-mix’ protocol to furnish pyrroles in good yields. Several C3-substituted N-alkylpyrroles have been prepared under open-flask conditions, avoiding protection-deprotection chemistry.

Magnesium(II) porphyrazine with peripherally overloaded pyrrolyl substituents – Synthesis, optical and electrochemical characterization

Cross-coupling Suzuki-Miyaura reaction using Microwave Assisted Organic Synthesis (MAOS) approach of phenylboronic acid and magnesium(II) porphyrazines with peripheral dimethylamino and 3,4-dibromo-2,5-diphenylpyrrol-1-yl or 3-bromo-2,4,5-triphenylpyrrol-1-yl groups led to magnesium(II) porphyrazines with dimethylamino and 2,3,4,5-tetraphenylpyrrol-1-yl groups. MAOS approach was also used in the Paal-Knorr reaction to synthesise the modified diaminomaleonitrile intermediates. All intermediates and macrocycles were characterized using UV-Vis, 1H and 13C NMR spectroscopy, as well as ES or MALDI MS spectrometry. The optical and electrochemical properties of obtained porphyrazine macrocycles were assessed. It was found that the susceptibility of new macrocycles to oxidation/reduction processes analyzed by cyclic and differential pulse voltammetry depended on the presence of bromide and the number of phenyl substituents in the macrocyclic periphery.

Enhanced Antibacterial Activity of Vancomycin Loaded on Functionalized Polyketones.

Today, polymeric drug delivery systems (DDS) appear as an interesting solution against bacterial resistance, having great advantages such as low toxicity, biocompatibility, and biodegradability. In this work, two polyketones (PK) have been post-functionalized with sodium taurinate (PKT) or potassium sulfanilate (PKSK) and employed as carriers for Vancomycin against bacterial infections. Modified PKs were easily prepared by the Paal-Knorr reaction and loaded with Vancomycin at a variable pH. All polymers were characterized by FT-IR, DSC, TGA, SEM, and elemental analysis. Antimicrobial activity was tested against Gram-positive Staphylococcus aureus ATCC 25923 and correlated to the different pHs used for its loading (between 2.3 and 8.8). In particular, the minimum inhibitory concentrations achieved with PKT and PKSK loaded with Vancomycin were similar, at 0.23 μg/mL and 0.24 μg/mL, respectively, i.e., six times lower than that with Vancomycin alone. The use of post-functionalized aliphatic polyketones has thus been demonstrated to be a promising way to obtain very efficient polymeric DDS.

Effect of pyridine group in dithienyl pyrrole chain on electrochemical and spectrochemical properties: An excellent electrochromic polymer

In the present research, a novel high-performance polymeric electrochromic materials consisting of pyridine with the ditihenyl pyrrole derivative (SNS) was achieved by the Paal-Knorr reaction, and its conjugated homopolymer, pTPN, and copolymer with EDOT were obtained in the medium of 0.1 M LiClO4/AN via electroanalytical methods. Although high electrochemical and spectrochemical properties were expected for the polymer chain in the copolymerization process involving the EDOT comonomer, for this study, the homopolymer was determined to have exhibited excellent electrochemical properties even without the need for this process. The pTPN exhibited favorable kinetic properties, especially high optical contrast (87 %) and desired color efficiency (837.7 cm2 C−1). Compared to other SNS derivatives in the literature, the obtained polymer pTPN had the highest optical contrast and color efficiency. In conclusion, this study has supplied a new structural design for the electrochromic polymers that might be beneficial for understanding the dithienyl pyrrole conjugated polymers behaviors composed of the pyridine units.

Unveiling the potential of a functionalized pyrrole-based polymer for efficient cadmium ion removal from wastewater: synthesis, characterization, and performance evaluation

Cadmium ion Cd2+ contamination is a major environmental issue caused by industry. Polyarylidene N-hexane pyrrole (PAPh) and crosslinked polyarylidene N-phenyl pyrrole (PAPD) were prepared from the previously synthesized polymer (polyarylidene ketone (PAK)) by using the advantage of repeating carbonyl groups at the 1,4 position and reacting it with hexylamine and P-phenylenediamine via the Paal–Knorr reaction. Various methods were used to characterize polymers, such as FT-IR spectroscopy, X-ray diffraction (XRD), thermogravimetry analysis (TGA), UV–visible spectroscopy, scanning electron microscope (SEM), zeta potential, and surface area measurements (BET), revealing successful fabrication, good thermostability, and well-defined microporous structures useful for Cd2+ adsorption. Optimal adsorption capacities of 55.8 mg g−1 for PAPh and 86.95 mg g−1 for PAPD indicate a significant enhancement in Cd2+ adsorption via their microporous structures, Cd2+ adsorption was also investigated in terms of contact time, initial concentration, and pH. A total input concentration of 30 ppm Cd ions, may yield an 84.3% removal rate for PAPh and an 89.2% removal rate for PAPD. The experimental results were well-fit by many models, including pseudo-second-order kinetics (PSO), Freundlich isotherms, intraparticle diffusion, and Langmuir. The varying adsorption performances of the two polymers studied, (PAPh) and (PAPD), were found to be derived from their respective chemical structures, which include various functional groups, according to studies conducted on Cd2+ in an aqueous solution. Cd2+ adsorption on polymers was considered physisorption; π–cation interactions and surface complexation played significant roles in adsorption. The PAP polymers may be considered promising substitutes and innovative adsorbents to remove Cd2+ ions from a water solution.

Onion (Allium cepa L.) Extract: A Green and Eco-friendly Catalyst for MW-Assisted Solvent-Free Synthesis of Pyrroles via Paal–Knorr Reaction

Onion (Allium cepa L.) Extract: A Green and Eco-friendly Catalyst for MW-Assisted Solvent-Free Synthesis of Pyrroles via Paal–Knorr Reaction

Pyrrole Compounds from the Two-Step One-Pot Conversion of 2,5-Dimethylfuran for Elastomer Composites with Low Dissipation of Energy.

A one-pot, two-step process was developed for the preparation of pyrrole compounds from 2,5-dimethylfuran. The first step was the acid-catalyzed ring-opening reaction of 2,5-dimethylfuran (DF), leading to the formation of 2,5-hexanedione (HD). A stoichiometric amount of water and a sub-stoichiometric amount of sulfuric acid were used by heating at 50 °C for 24 h. Chemically pure HD was isolated, with a quantitative yield (up to 95%), as revealed by 1H-NMR, 13C-NMR, and GC-MS analyses. In the second step, HD was used as the starting material for the synthesis of pyrrole compounds via the Paal-Knorr reaction. Various primary amines were used in stoichiometric amounts. 1H-NMR, 13C-NMR, ESI-Mass, and GC-Mass analyses confirmed that pyrrole compounds were prepared with very good/excellent yields (80-95%), with water as the only co-product. A further purification step was not necessary. The process was characterized by a very high carbon efficiency, up to 80%, and an E-factor down to 0.128, whereas the typical E-factor for fine chemicals is between 5 and 50. Water, a co-product of the second step, can trigger the first step and therefore make the whole process circular. Thus, this synthetic pathway appears to be in line with the requirements of a sustainable chemical process. A pyrrole compound bearing an SH group (SHP) was used for the functionalization of a furnace carbon black (CB). The functionalized CB (CB/SHP) was utilized in place of silica, resulting in a 15% mass reduction of reinforcing filler, in an elastomeric composite based on poly(styrene-co-butadiene) from solution anionic polymerization and poly(1,4-cis-isoprene) from Hevea Brasiliensis. Compared to the silica-based composite, a reduction in the Payne effect of about 25% and an increase in the dynamic rigidity (E' at 70 °C) of about 25% were obtained with CB/SHP.

Atroposelective synthesis of N–N axially chiral pyrrolyl(aza)-quinolinone by de novo ring formation

A chiral phosphoric acid-catalyzed Paal–Knorr reaction was achieved for constructing axially chiral pyrrolyl(aza)quinolinones with ‘6–5’-membered rings as a new family member of N–N atropisomers.

Enantioselective Synthesis of N-N Amide-Pyrrole Atropisomers via Paal-Knorr Reaction.

The catalytic asymmetric construction of monoheteroaryl N-N axially chiral compounds and chiral five-membered aryl-based scaffolds remains challenging. Herein, we present a highly efficient enantioselective synthesis of monoheteroaryl N-N atropisomers via an asymmetric Paal-Knorr reaction, affording a diverse array of N-N amide-pyrrole atropisomers with excellent enantioselectivities. Gram-scale synthesis and post-transformations of the product demonstrated the synthesis utility of this method. Racemization experiments confirmed the configurational stability of these N-N axially chiral products. This study not only provides the first de novo cyclization example for accessing an asymmetric monoheteroaryl N-N scaffold but also offers a new member of the N-N atropisomer family with potential synthetic and medicinal applications.

Crystallographic, spectroscopic and thermal studies of 1-(4-bromophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methyl-1H-pyrazole.

The new title pyrrole-pyrazole derivative, C16H16BrN3, was synthesized through a citric acid-catalyzed Paal-Knorr reaction between acetonylacetone and 1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-amine under mild reaction conditions. This synthetic protocol is noteworthy for its utilization of stoichiometric amounts of the reactants, an ecofriendly solvent and a cost-effective, non-toxic and biodegradable organocatalyst. A comprehensive understanding of the molecular structure was gained through spectroscopic, thermal and X-ray crystallographic analyses. The crystal structure is characterized by weak interactions, where only C-H...π connections contribute to the hydrogen-bond contacts. The supramolecular assembly is controlled by dispersion forces. However, the energy frameworks demonstrate that these forces act in three dimensions, providing enough stability, as observed in TGA-DSC (thermogravimetric analysis-differential scanning calorimetry) studies.

Effect of intermolecular interactions on the glass transition temperature of chemically modified alternating polyketones

Thermal properties of polymers depend on the chemical structure of the polymer chain and intermolecular forces arising from hydrogen bonding and π-π stacking. Here we analyzed the effect of increasing the amount of supramolecular interactions on the glass transition temperature of polyketones by chemically modifying the same polymer backbone with five amine derivatives, namely (1-(3-aminopropyl)-imidazole, 4-(aminomethyl) benzoic acid, 6-aminohexanoic acid, benzylamine or hexylamine, at various molar concentrations. The grafting was performed via the Paal-Knorr reaction and the interactions between the pyrrole backbone and different grafted functional groups were elucidated by proton nuclear magnetic resonance, Fourier transform infrared and X-ray photoelectron spectroscopy as well as differential scanning calorimetry and computational modeling. The modification of polyketone with 4-(aminomethyl) benzoic acid and 6-aminohexanoic acid, allowed for new possibilities of hydrogen bonding and led to a significant increase in the glass transition temperature as compared to the neat polymer and pyrrole-containing polymers that did not bear reactive side groups. In contrast, modification with the imidazole derivative was found to introduce new and more robust CH⋯π interactions between imidazole groups and the π-system of the pyrrole backbone chain, based on electrostatic effects. Both types of supramolecular interactions affect the mobility of the backbone chains and this systematic study demonstrates how the combined effect of π-π stacking and hydrogen bonding to carboxylate moieties can be used to tune the molecular mobility and phase transition temperature of these chemically modified polyketones.

Mechanism study of the N-butoxycarbonyl-2,5-dimethylpyrrole synthesis reaction based on in-situ FTIR monitoring

The reaction pathway of many Paal-Knorr reactions for pyrrolic compounds hasn’t been thoroughly studied and remains controversial. In this work, the synthesis of an important anti-ultraviolet agent N-butoxycarbonyl-2,5-dimethylpyrrole based on the Paal-Knorr reaction was studied via in-situ Fourier transform infrared (FTIR) analysis combined with density functional theory (DFT) calculation. The online spectral data were analyzed using K-means clustering in order to find the characteristic wavenumbers of intermediates. It was found that the reaction with 2,5-hexadione and butyl carbamate are more favorable to form the imine and enamine intermediates by nucleophilic addition, which is different from another Paal-Knorr reaction with 2, 5-hexadione and ethanolamine. In addition, the reaction kinetic model was established through chemometric methods, with parameters of two rate-limiting reaction steps calculated. This approach of FTIR analysis is proven to be an effective tool for mechanism study of organic synthesis.

Polyketone-Based Anion-Exchange Membranes for Alkaline Water Electrolysis.

Anion-exchange membranes (AEMs) are involved in a wide range of applications, including fuel cells and water electrolysis. A straightforward method for the preparation of efficient AEMs consists of polymer functionalization with robust anion-exchange sites. In this work, an aliphatic polyketone was functionalized with 1-(3-aminopropyl)imidazole through the Paal-Knorr reaction, with a carbonyl (CCO %) conversion of 33%. The anion-exchange groups were generated by the imidazole quaternization by using two different types of alkyl halides, i.e., 1,4-iodobutane and 1-iodobutane, with the aim of modulating the degree of crosslinking of the derived membrane. All of the membranes were amorphous (Tg ∼ 30 °C), thermally resistant up to 130 °C, and had a minimum Young's modulus of 372 ± 30 MPa and a maximum of 86 ± 5 % for the elongation at break for the least-crosslinked system. The ionic conductivity of the AEMs was determined at 25 °C by electrochemical impedance spectroscopy (EIS), with a maximum of 9.69 mS/cm, i.e., comparable with that of 9.66 mS/cm measured using a commercially available AEM (Fumasep-PK-130). Future efforts will be directed toward increasing the robustness of these PK-based AEMs to meet all the requirements needed for their application in electrolytic cells.

Synthesis and pyrolysis of various novel pyrrole ester fragrance precursors

AbstractDue to the disadvantages of low fragrance threshold and high volatility of pyrrole monomer under high‐temperature process in tobacco or food, it cannot meet the market requirements. In order to develop pyrrole flavour precursors, 2,5‐dimethyl‐N‐pyrroleacetic acid was synthesized by the Paal–Knorr reaction using 2,5‐hexanedione and glycine as raw materials. Various pyrrole fragrance precursors such as 2‐ethyl‐4‐oxo‐4H‐pyran‐3‐yl 2‐(2,5‐dimethyl‐1H‐pyrrol‐1‐yl)acetate (5a), 4‐formyl‐2‐methoxyphenyl 2‐(2,5‐dimethyl‐1H‐pyrrol‐1‐yl)acetate (5b), pyridine‐2‐ylmethyl 2‐(2,5‐dimethyl‐1H‐pyrrol‐1‐yl)acetate (5c) and thiophen‐2‐ylmethyl 2‐(2,5‐dimethyl‐1H‐pyrrol‐1‐yl)acetate (5d) were synthesized by esterification from 2,5‐dimethyl‐N‐pyrroleacetic acid with ethyl maltol, vanillin, 2‐pyridinemethanol and 2‐thiophenemethanol, respectively. As part of the study, IR, NMR and HRMS were used to characterize the target compounds. Using gas chromatography–mass spectrometry‐olfactometer (GC–MS‐O), the pyrrole esters obtained were evaluated for the characteristics of their aromas. The thermal stability was analysed using thermogravimetric analysis and pyrolysis gas chromatography/mass spectrometry. In addition, the pyrolysis mechanism was speculated. With TG‐DTG results, the main mass loss phase of 5a occurred between 108°C and 450°C, with a dramatic mass loss reduction of 83.07%. At 118.60°C and 450°C, 5b showed a mass loss reduction of 60.80%. Furthermore, according to the Py‐GC/MS analysis results, compounds 5a and 5b formed 8 and 7 pyrolysis products. The main pyrolysis products of 5a and 5b were 1‐ethyl‐2,5‐dimethyl‐1H‐pyrrole, ethyl maltol, and vanillin, which are all aroma components used to blend cigarette smoke, can slow down the rate at which aromas are lost and mask unpleasant smoke. Study results provide a reference for the tobacco industry to further develop new high‐temperature release aroma ingredients.

Synthesis of N-Substituted Pyrroles Catalyzed by Low-Cost and Commercially Available Aluminas

The Paal-Knorr reaction of acetonylacetone with primary amines catalyzed by CATAPAL 200 under conventional heating at 60 °C for 45 min afforded N-substituted pyrroles in 68–97% yields. The pyrrole 3g was studied by single-crystal and powder X-ray diffraction. The high percentage of Brønsted–Lewis acid sites (23%) and pore diameter (37.8 nm) of CATAPAL 200 favor the formation of the pyrrole ring because an increase in Brønsted acid sites efficiently catalyzes condensation and dehydration processes. This protocol is distinguished by its operational simplicity, high yields, reduced reaction time, no solvent required, stoichiometric amounts of reactants, low catalyst loading, and clean reaction profile. In addition, the CATAPAL 200 is cheap and commercially available leading to an efficient and lower-cost chemical transformation. The reusability of the catalyst for up to five cycles without appreciable loss of its catalytic activity makes the present protocol sustainable and advantageous compared to conventional methods.

Reaction Analysis and Process Optimization with Online Infrared Data Based on Kinetic Modeling and Partial Least Squares Quantitation.

In-situ Fourier transform infrared (FT-IR) spectroscopy has been recognized as an important technology for online monitoring of chemical reactions. However, analysis of the real-time IR data for identification and quantification of uncertain reactants or intermediates is often ambiguous and difficult. Here, we propose an analysis algorithm based on reaction kinetic modeling and the chemometric method of partial least squares (PLS) to comprehensively and quantitatively study reaction processes. Concentration profiles and apparent kinetic parameters can be simultaneously calculated from the spectral data, without the demand of complicated analysis on characteristic absorbance peaks or tedious sampling efforts for multivariate modeling. Paal-Knorr reactions and glyoxylic acid synthesis reactions were selected as typical reactions to validate the algorithm. A lack of fit of the Paal-Knorr reaction spectra was less than 2.5% at various conditions, and the absolute errors between the predicted values and HPLC measurement of glyoxylic acid synthesis were less than 6% during the reaction process. Moreover, the reaction kinetic models extracted from FT-IR data were used to simulate reaction processes and optimize the conditions in order to maximize product yields, which proved that this analysis method could be used for process optimization.

Enantioselective Direct Synthesis of C3-Hydroxyalkylated Pyrrole via an Amine-Catalyzed Aldol/Paal-Knorr Reaction Sequence.

Creating functionality with chirality at position C3 of pyrrole is challenging. An operationally simple organocatalytic method has been developed to generate functionality with a chiral tertiary/quaternary stereocenter at position C3 of pyrrole. The process proceeds through an amine-catalyzed direct aldol reaction of succinaldehyde with various acceptor carbonyls, followed by a Paal-Knorr reaction with a primary amine in the same pot. A series of chiral C3-hydroxyalkylated N-alkyl/Ar/H-pyrroles have been synthesized for the first time with good to high yields and excellent enantioselectivity.

Sequential One-Pot Carbene-Catalyzed Intramolecular Stetter Reaction and Acid-Mediated Condensation: Access to Heteroatom Analogues of π-Extended Polyaromatic Hydrocarbons.

In this Letter, we disclose a simple and effective method to access a variety of phenanthro[9,10-b]furan and 1H-dibenzo[e,g]indole derivatives based on the design of a carbene-catalyzed intramolecular Stetter reaction followed by a Paal-Knorr reaction in one-pot. These compounds are a class of π-extended polycyclic aromatic hydrocarbon (PAH) derivatives containing an oxygen/nitrogen atom. The practical utility of the developed transformation was demonstrated on the gram scales and postsynthetic transformations thereof.

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.