Paal-Knorr Reaction Research Articles

Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal–Knorr pyrrole formation and gas concentration measurement by inline flow titration

Using a simple and accessible Teflon AF-2400 based tube-in-tube reactor, a series of pyrroles were synthesised in flow using the Paal-Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

ChemInform Abstract: Preparation of Chiral Pyrrole Derivatives by the Paal—Knorr Reaction.

A new approach has been developed for the synthesis of N-alkylpyrroles with a chiral substituent at the nitrogen atom by the Paal-Knorr reaction using esters of amino acids as the source of chirality.

ChemInform Abstract: Synthesis of New N‐Alkyl(aryl)‐2,4‐diaryl‐1H‐pyrrol‐3‐ols via Aldol Paal—Knorr Reactions.

AbstractFully substituted pyrrol‐3‐ol derivatives (V) are prepared via aldol reactions of propane‐2‐one with phenylglyoxal followed by Paal—Knorr reaction with amines.

Synthesis of Benzo[c]azocanones and Indeno[1,2‐b]pyrroles from Oxoindanecarboxylates

AbstractEthyl 1‐oxo‐indane‐2‐carboxylate with a 1,4‐diketone motif gave a benzo[c]azocane‐1‐one derivative ― an eight‐membered ring lactam ― in a bismuth‐mediated ring‐expansion reaction with methylamine (40 % yield). Yields with other primary amines were significantly lower. The ester function in the heterocyclic product could be saponified to give the free carboxylic acid, which was further amidated with para‐bromoaniline. The molecular structure of the latter was established by X‐ray single‐crystal analysis. Benzo[c]azocanones exist in two diastereoisomeric conformations, causing double signal sets in the NMR spectra. Slow interconversion between these conformers was proved by EXSY NMR spectroscopy. Moreover, a conformational analysis by DFT calculations revealed the two diastereoisomers to be boat conformers that interconvert through a twist conformer. The maximum barrier for this process was calculated to be approximately 70 kJ/mol. Reaction of the corresponding methyl 1‐oxoindane‐2‐carboxylate with methylamine gave the benzo[c]azocanone in lower yield. A spirolactam and an indeno[1,2‐b]pyrrole were formed as further products. When using an indanone‐derived 1,4‐diketone without an ester function, several primary amines could be used in a bismuth‐catalyzed Paal–Knorr reaction to give indeno[1,2‐b]pyrrole derivatives with up to quantitative yields in several cases. Attempts to synthesize a caprolactam derivative from a cyclobutanone derived β‐oxo ester with 1,4‐diketone motif were unsuccessful.

Catalytic applications of nano β-PbO in Paal–Knorr reaction

Abstract Several 2,5-dimethyl-N-substituted pyrroles were prepared by the condensation of different substituted anilines with 2,5-hexanedione using nano lead oxide as an efficient and recyclable catalyst. All the synthesized compounds are confirmed through IR, 1H NMR, 13C NMR and mass spectral data. Nano lead oxide β-PbO (P85) was prepared by dissolving lead acetate dihydrate in 1-propanol at a pH 9.0 under stirring at 85 °C. The structural study and surface morphology of the lead oxide (PbO) were characterized using X-ray diffraction (XRD), Scanning electron microscopy (SEM) and the functional groups of the PbO sample were investigated using infrared spectrophotometer.

Preparation of chiral pyrrole derivatives by the Paal-Knorr reaction

A new approach has been developed for the synthesis of N-alkylpyrroles with a chiral substituent at the nitrogen atom by the Paal-Knorr reaction using esters of amino acids as the source of chirality.

ChemInform Abstract: Facile Synthesis and Characterization of New Polymerizable Conjugated 2,5‐Di(selenophen‐2‐yl)pyrroles and 2,5‐Difuranylpyrroles.

AbstractThe target compounds are prepared via Paal—Knorr reaction and their photophysical and electrochemical properties are studied.

Recyclization of furan in the synthesis of pyrrolo[1,2-d][1,4]diazepinone

Pyrrolodiazepines are an important class of heterocyclic compounds due to their broad spectrum of pharmacological activity [1-4]. Additionally, the pyrrolodiazepinone framework is the basic structural fragment of natural anthramycin alkaloids which show antitumor activity [5]. All of this is responsible for the high interest in developing synthetic methods for these compounds. However, the Paal-Knorr reaction has been virtually unused in the preparation of pyrrolodiazepinones. Only two examples of its use have been reported. The first involves successive closing of the pyrrole and diazepinone rings [6] and the second a simultaneous formation of both rings [7]. This is likely associated with the fact that the synthesis of suitable 1,4-dicarbonyl compounds as precursors of the pyrrolodiazepinones is a multistage and laborious process [7]. It is well known that furan derivatives in the presence of acids can serve as precursors of 1,4-diketones [8]. This property of furan compounds allowed us to develop a simple and efficient method for preparing pyrrolo[1,2-a][1,4]diazepinones based on the recyclization of N-(furfuryl)anthranilamides [9]. This process is a one-pot domino reaction in which opening of the furan ring and the formation of the diazepinone and pyrroles ring occur. We now report the use of this methodology for preparing pyrrolo[1,2-d][1,4]diazepinones. Acylation of the furylethylamine 1 by the 2-phthalimidoacetyl chloride 2 in benzene gave amide 3, treatment of which with hydrazine hydrate in ethanol led to the removal of the phthalimido protection and formation of the amine 4. Holding compound 4 in a mixture of acetic and hydrochloric acids for 1 day at room temperature and subsequent work up of the reaction mixture with an aqueous solution of NaHCO3 gave the target compound 6. Evidently the reaction takes place via intermediate formation of the diketone 5. The yield of the pyrrolodiazepinone 6 is 21% which compares with the results in the study [6]. However, bearing in mind the simplicity of these procedures in our proposed method, it can be used in the preparation of other pyrrolo[1,2-d][1,4]diazepinones and in further work we intend to carry out an optimization of the method. H and C NMR spectra were recorded on a Bruker DPX-300 spectrometer (300 and 75 MHz respectively) using CDCl3 as solvent. The standards used were the residual protons of the deuterated solvent CDCl3 (7.25 ppm for H and 77.0 ppm for C). Mass spectra were obtained on a Kratos MS-30 spectrometer by EI with ionizing energy 70 eV and ionization chamber temperature 200oC.

Synthesis of new N-alkyl(aryl)-2,4-diaryl-1H-pyrrol-3-ols via aldol Paal–Knorr reactions

New N-alkyl(aryl)-2,4-diaryl-1H-pyrrol-3-ol derivatives have been synthesized in moderate to good yields in a novel and efficient process by aldol reaction of 1-(4-methoxyphenyl)propan-2-ones with phenylglyoxal in the presence of DABCO in water, followed by Paal–Knorr reaction with amines in the presence of a catalytic amount of p-TSA in toluene at reflux.

Facile synthesis and characterization of new polymerizable conjugated 2,5-di(selenophen-2-yl)pyrroles and 2,5-difuranylpyrroles

A facile synthesis of novel π-conjugated 2,5-di(selenophen-2-yl)pyrroles (SeNSe) and 2,5-difuranylpyrroles (ONO) via Paal–Knorr reaction as the key step is presented. Photophysical and electrochemical studies of the various products have been explored. A bathochromic shift of the emission maximum is observed for all SeNSes over ONOs. Extended conjugation with a phenyl moiety further promotes the bathochromic shift. These SeNSe and ONO derivatives exhibit lower oxidation potentials than their terselenophene and terthiophene analogues.

ChemInform Abstract: Preparation and Properties in vitro and in vivo of Antitubercular Pyrroles.

AbstractThe title compounds (III) are conveniently prepared by Paal—Knorr reaction of hydrazides (II) with hexane‐2,5‐dione without an acid catalyst.

Synthesis of Pyrroles via [3,3]-Rearrangement and Paal-Knorr Reaction

Reported is the synthesis of 2,4- and 2,3,4-substituted pyrroles via [3,3]-sigmatropic rearrangement and subsequent Paal-Knorr reaction. The iridium-catalyzed isomerization products 1 were isolated with vinyl E/Z ratios of approximately 1:2. The Paal-Knorr intermediate A was identified by NMR spectroscopy. The target pyrroles may also be afforded in a one-pot reaction in yields comparable to those obtained in the two-step procedure. Interestingly, as long as R² = CN, the reaction proceeded directly from O-allyl oximes to pyrroles without the need for molecular sieves at lower temperature (25 ˚C).

Synthesis of new 2,5-dimethyl pyrrole derivatives from acetonylacetone

Acetonylacetone 1 was treated with thiourea, aniline, glycin and glutamic acid to give pyrrole derivatives 2, 3, 5, and 9 by Paal–Knorr reaction, respectively. Then 3 was successfully transformed into the related pyrrole derivative 4 by Mannich reaction. Compounds 6, 7 and 8 were obtained by reacting 5 with phenethyl alcohol, phenylallylic alcohol and leaf alcohol by esterification reactions, respectively. The structures of all new products were elucidated by IR, NMR and HRMS spectra.

ChemInform Abstract: Nano‐Organocatalyst: Magnetically Retrievable Ferrite‐Anchored Glutathione for Microwave‐Assisted Paal—Knorr Reaction, aza‐Michael Addition, and Pyrazole Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ionic Liquid as Catalyst and Reaction Medium: A Simple and Efficient Procedure for Paal–Knorr Furan Synthesis

The ionic liquid 1-butyl-3-methyl-imidazolium hydrogen sulfate, [bmim]HSO4, efficiently catalyzes Paal–Knorr furan synthesis without any organic solvent. A wide range of aliphatic and aromatic 1,4-diketones easily undergo condensations to form furan derivatives, providing a general and convenient procedure. The Paal–Knorr reaction of ester-substituted 1,4-diketones is first reported. The ionic liquid can be recovered and reused for subsequent runs without any appreciable loss of efficiency.

Nano-organocatalyst: magnetically retrievable ferrite-anchored glutathione for microwave-assisted Paal–Knorr reaction, aza-Michael addition, and pyrazole synthesis

Postsynthetic surface modification of magnetic nanoparticles by glutathione imparts desirable chemical functionality and enables the generation of catalytic sites on the surfaces of ensuing organocatalysts. In this article, we discuss the developments, unique activity, and high selectivity of nano-organocatalysts for microwave-assisted Paal–Knorr reaction, aza-Michael addition, and pyrazole synthesis. Their insoluble character coupled with paramagnetic nature enables easy separation of these nano-catalysts from the reaction mixture using external magnet, which eliminates the requirement of catalyst filtration.

Organic Catalytic Multicomponent One-Pot Synthesis of Highly Substituted Pyrroles

A multicomponent synthesis of highly substituted pyrroles catalyzed by thiazolium salts has been disclosed. The reaction employs an acyl anion conjugate addition reaction of aldegyde and unsaturated ketones to generate 1,4-dicarbonyl compounds in situ. The subsequent addition of various amines promotes a Paal–Knorr reaction, affording the desired pyrrole nucleus in an efficient one-pot process.

Synthesis and characterization of periphery-functionalized porphyrazines containing mixed pyrrolyl and pyridylmethylamino groups

The condensation reaction of 2-amino-3-[(3-pyridylmethyl)amino]-2(Z)-butene-1,4-dinitrile with a series of diketones led to novel dinitriles, of which 2-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[methyl(3-pyridylmethylene)amino]-2(Z)-butene-1,4-dinitrile, the product of the Paal-Knorr reaction, was successfully utilized in the Linstead macrocyclization towards symmetrical and unsymmetrical porphyrazines. NMR and X-ray study revealed an almost perpendicular orientation of the pyrrolyl groups in relation to the porphyrazine platform. The newly synthesized macrocycles with different peripheral groups show interesting spectroscopic and electrochemical properties. Due to selective sensor/coordination properties they are expected to find applications as chemical sensors and electronic materials.

Magnetic nanoparticle-supported glutathione: a conceptually sustainable organocatalyst

A conceptually novel nanoparticle-supported and magnetically recoverable organocatalyst has been developed, which is readily prepared from inexpensive starting materials in a truly sustainable manner; which catalyzes the Paal-Knorr reaction with high yield in pure aqueous medium that avoids the use of toxic organic solvents, even in the workup step.

Synthesis of novel 5‐chlorinated 2‐aminothiophenes using 2,5‐dimethylpyrrole as an amine protecting group

Abstractmagnified imageA new synthetic methodology towards substituted 2‐amino‐5‐chlorothiophenes is described. Compounds of this type are important as building blocks for oligomers used in polymer research. Easily available 2‐aminothiophenes underwent Paal‐Knorr reaction to protect the free amino group before electrophilic substitution. Although the chlorination was predicted to proceed at the thiophene ring, only free positions of 2,5‐dimethylpyrrole were substituted. To direct chlorination to the thiophene ring acetamido derivative was prepared first and then chlorinated. Transamination with hexane‐2,5‐dione created a 2,5‐dimethyl pyrrole ring from the acetamido group. In the final step, after treatment with hydroxylamine dihydrochloride, the pyrrole ring is removed and a free amino group is regenerated.