Synthesis of new N-alkyl(aryl)-2,4-diaryl-1H-pyrrol-3-ols via aldol Paal–Knorr reactions (original) (raw)
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Paal–Knorr synthesis of pyrroles: from conventional to green synthesis
Catalysis Reviews, 2018
The pyrrole molecular framework is found in a large number of natural and synthetic compounds of great importance. Since functionalized pyrroles are essential for the progress of many branches of science, its synthesis by simple, efficient and ecofriendly routes are particularly attractive in modern organic and bio-organic chemistry. To this end, a number of synthetic methods have been developed, in which the Paal-Knorr pyrrole synthesis stands out to be the easiest route to synthesize pyrroles. In spite of the efficiency, Paal-Knorr synthesis of pyrroles is considered limited by harsh reaction conditions, such as prolonged heating in acid, which may degrade sensitive functionalities in many potential precursors. Through this route almost all dicarbonyls can be converted to their corresponding heterocycles and therefore it is a synthetically valued process. To address the adverse issues this reaction route has undergone numerous modifications recently and today it can be said that this reaction route is a prominent green route for the synthesis of pyrroles. This review is a tour from the evolution and application of this harsh synthetic route to the ecofriendly greener route developed for the synthesis of pyrroles.
Polystyrenesulfonate-catalyzed synthesis of novel pyrroles through Paal-Knorr reaction
Organic and Medicinal Chemistry Letters, 2012
Background: The classical Paal-Knorr reaction is one of the simplest and most economical methods for the synthesis of biologically important and pharmacologically useful pyrrole derivatives. Results: Polystyrenesulfonate-catalyzed simple synthesis of substituted pyrroles following Paal-Knorr reaction has been accomplished with an excellent yield in aqueous solution. This method also produces pyrroles with multicyclic polyaromatic amines. Conclusions: The present procedure for the synthesis of N-polyaromatic substituted pyrroles will find application in the synthesis of potent biologically active molecules.
Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones
Tetrahedron Letters, 2010
The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d were obtained from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 1, 2a-d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one ring.
A Novel Strategy for the Synthesis of 3-(N-Heteryl)pyrrole Derivatives
Organic Letters, 2012
A flexible approach to unknown 1-(1H-pyrrol-3-yl)pyridinium salts with selective control of the substitution patterns, by the reaction of pyridinium ylides with 2H-azirines, is disclosed. 3-(Pyridinium-1-yl)pyrrolides, a new type of stable ylide, were prepared from these salts in high yields by treatment with base. Atmospheric-pressure hydrogenation of the ylides with Adams' catalyst lead to 1-(pyrrol-3-yl)piperidines in good yields. Pyrrole is one of the most important simple heterocycles, whose structural unit is present in a large number of natural compounds, medical and material molecules. 1 By limiting ourselves to a short introduction it is impossible to reflect adequately the variety of chemistry and the value of pyrrole derivatives, so we will mention only recently published works in which the bioactivity of compounds containing 3-(pyridine-1-yl)pyrrole fragments were investigated, since compounds of this type are a subject of our research. The mentioned structural units are present in compounds which are antibacterial agents targeting DNA gyrase, 2 inhibitors of human DPP-4 for the treatment of type 2 diabetes, 3 NMDA receptor antagonists, 4 selective NK 1 antagonists, 5 and potent antagonists of VLA-4. 6 Although excellent preparative methods for the synthesis of substituted pyrroles have been developed, 1 it is still a great challenge to synthesize functionalized pyrroles from readily available and easily varied starting materials using a simple procedure. One such approach to the synthesis of pyrrole derivatives is based on the reactions of nucleophiles with 2H-azirines. The first example of reactions of 3-phenyl-2H-azirine with enolates leading to pyrrole derivatives was published by Sato. 7 2H-Pyrroles were prepared in good yields from 2H-azirines and enolates from activated
A Convenient Method for the Preparation of 1,5-Diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones
Chinese Journal of Chemistry, 2011
A simple and eco-friendly method for the preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones via the cyclo-condensation reaction of aldehydes, amines and ethyl pyruvate in the presence of silica supported ferric chloride (SiO 2-FeCl 3) as reusable heterogeneous catalyst is described. The present methodology offers several advantages such as excellent yields, simple procedure and short reaction times.
Skeletal Diversity in Catalytic Synthesis of (1,3-Oxazacycloalk-3-ylmethyl)-Substituted Pyrroles
Russian Journal of General Chemistry, 2019
A series of bi-and trinuclear pyrrole derivatives was prepared by the 5 mol % ZrOCl 2 •8Н 2 О-catalyzed CH-sp 2-aminomethylation reaction of pyrrole with bis(1,3-oxazacycloalk-3-yl)methanes. The reaction proceeds at the positions 2, 5 or 2 of pyrrole depending on the amount of aminomethylating reagents obtained from formaldehyde and α,ω-amino alcohols (2-aminoethan-1-ol, 3-aminopropan-1-ol, 4-aminobutan-1-ol). The aminomethylation reaction of indole with bis(1,3-oxazolidin-3-yl)methane proceeds at the position 3. In the case of carbazole, N-aminomethylation proceeds under these conditions.
A novel one-pot, four component synthesis of some densely functionalized pyrroles
Molecular Diversity, 2003
A new one-pot four component procedure for synthesis of densely functionalized pyrroles using commercially available ninhydrin with phosphorane intermediates produced in the reaction between triphenylphosphine, ammonium thiocyanate (or ammonium acetate) and various dialkyl acetylenedicarboxylates was developed.
Tetrahedron, 2018
Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also βhalovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4tetrasubstituted pyrroles. Since the vinylogous amides and β-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology. Our previous studies have established that vinamidinium salts 1 and related compounds are useful building blocks for the construction of five and six membered heterocyclic compounds and in particular highly functionalized, unsymmetrical pyrroles. The presence of the pyrrole core in a large number of natural (Fig. 1) and synthetic products has attracted the attention of many others and as a result, various synthetic approaches are currently available 2. The attention given to such pyrrole containing natural products arises from their very important biological properties 3. Such properties include potent anti-proliferative activity of lamellarin D 4 (2, Fig. 1) and lukianol A 5 (3, Fig. 1) on various cancer cell lines including those, which exhibit multidrugresistance. Lynamicin D 6 (1, Fig. 1) and related compounds have demonstrated good antibiotic activity against Staphylococcus aureus ATCC 43300-MRSA and Haemophilus influenzae ATCC 49247. Consequently, short and efficient methods for the regiocontrolled synthesis of symmetrical and unsymmetrical, polyfunctionalized pyrroles are of some importance.
Organic letters, 2014
A catalytic diastereoselective aldol reaction has been developed for N1-arylated/C2-O-silylated/C3-methylated and brominated/C4-O-methylated pyrroles in its reactions with various aldehydes. Syn adducts emerge with regard to the vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium-mediated coupling reactions, both without disturbing the newly created stereocenters.