Paal–Knorr Pyrrole Synthesis in Water

Akbaşlar, Dilek; Demirkol, Onur; Giray, Sultan

doi:10.1080/00397911.2013.857691

Cited by 29 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pyrrole and its derivatives are a class of important five-membered nitrogen heterocyclic compounds, which can be synthesized by condensation from 1,4-dicarbonyl compounds, known as Paal-Knorr reaction. Though a variety of methods have been developed for pyrrole synthesis, Paal-Knorr condensation still remains the most widely used approach 1,2 . As is well known, the intermediates of an organic reaction may vary significantly depending on reaction conditions 3 .…”

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of the reaction between aniline and acetonylacetone using extractive electorspray ionization tandem mass spectrometry

Zhang

Miao-rong

et al. 2019

Sci Rep

View full text Add to dashboard Cite

In this work an on-line monitoring method was developed to study the mechanism of acetic acid catalyzed reaction between aniline and acetonylacetone using extractive electorspray ionization-tandem mass spectrometry (EESI-MS). The signals of reactants, intermediates and various byproducts were continuously detected as a function of reaction time. The chemical assignment of each signal was done via multi-stage collision induced dissociation (CID) analysis, and the reaction mechanism between aniline and acetonylacetone was deduced based on the generated molecular ions and fragment ions. The results indicate that on-line EESI-MS is an effective technique for the real time analysis of chemical reactions. EESI avoids off-line sample pretreatment and provides “soft” ionization, which allows direct analysis of various analytes at molecular level.

show abstract

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of the reaction between aniline and acetonylacetone using extractive electorspray ionization tandem mass spectrometry

Zhang

Miao-rong

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…An alternative to the usual procedures consists of carrying out the Paal-Knorr reaction with alternative solvents such as ionic liq- uids [45], water [46], and under solvent and catalyst-free conditions (Scheme 12). In the subsequent cases, although the process may take a while longer for the reaction of some substrates, the procedure becomes simpler, more selective and environmentally friendlier due to the high atom economy, low energy consumption (it prevents conventional heating), and being a condensation reaction, the only by-product of the process is water, covering most of the principles of Green Chemistry [47].…”

Section: Paal-knorr Methodsmentioning

confidence: 99%

“…Pyrroles are obtained by three classical condensation methods: Hantzsch reaction [13], Knorr and Paal-Knorr reactions [14]. Other pyrrole synthesis methods include multicomponent, addition, anne-lation and Wittig reactions [15]. However, these processes have disadvantages such as the long reaction time, the use of toxic and volatile solvents, low yields, complex purification methods, and the need of high temperature for the occurrence of some reactions [16].…”

Section: Introductionmentioning

confidence: 99%

Green Synthesis of Pyrrole Derivatives

Zúñiga

Sathicq

Martínez

et al. 2017

COS

View full text Add to dashboard Cite

Background: Pyrroles are organic cyclic compounds with an extensive and fascinating chemistry. These compounds have a wide structural variety and they are an important basis in technological development as they can be used as drugs, dyes, catalysts, pesticides, etc. Therefore, the production of these heterocyclic compounds by efficient clean methodologies is a great achievement in contemporary chemistry. In this paper, we show recent green procedures in the synthesis of pyrrole derivatives such as Hantzsch, Knorr and Paal- Knorr syntheses, as well as new eco-friendly synthetic procedures with high efficiency and low environmental impact. Objective: This work focusses on the recent advances in the pyrrole synthesis using clean techniques like ultrasound (US), microwaves (MW), high speed vibration milling (HSVM), catalysts use, solvent replace and other methodologies applied to common reactions to obtain the pyrrole core which follow the green chemistry principles. Conclusion: The main challenge of Green Chemistry is to gradually eliminate the generation of hazardous or harmful materials or replace them with less toxic and safer ones. However, this process must be driven by scientific developments. Its application in the synthesis of heterocyclic compounds such as pyrrole derivatives involves multiple economic and social benefits due to the biological importance of these compounds and their direct impact on the pharmaceutical industry. Although many processes are still under investigation using novel methodologies of green activation such as microwaves, ultrasound and HSVM, as well as synthetic processes in continuous flow and processes at room temperature, promising results such as cost and waste reduction and greater efficiency are achieved.

show abstract

“…Such a possibility was recently suggested by Akbaşlar and coworkers, though they did not employ explicit acidic medium in the reaction. 37 Considering the basic nature of the imine and enamine intermediates, this pathway is a challenging process, which is supported by the difficulties encountered during the computational analysis. Please do not adjust margins Table 1 for energies).…”

Section: Monoenol Pathwaymentioning

confidence: 99%

“…[23][24][25][26][27][28][29][30] Use of nano catalysts [31][32][33] and organo-catalysts 34,35 is also being practised for the Paal-Knorr synthesis. Green chemistry methods employing nanomagnetically modified sulfuric acid 36 and water 37 catalysts for the Paal-Knorr pyrrole synthesis were also reported. Very recently, catalyst and solvent-free conditions have been employed to synthesize underivatized and N-substituted pyrroles by Cho et al 38 The importance of this synthetic reaction is highlighted in the synthesis of the drugs Atorvastatin (antitriglyceride), [39][40][41] Aloracetam (anti-Alzheimer's), 42 Prodiogiosin (antibacterial, anti-fungal and anti-malarial) 43, 44 and Roseophilin (antitumour) ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the Paal–Knorr reaction: the importance of water mediated hemialcohol pathway

et al. 2015

View full text Add to dashboard Cite

The Paal-Knorr synthesis of furan, pyrrole and thiophene rings is one of the most important methods of generating these very important heterocycles, but the mechanism of this reaction is not well understood. Though several mechanistic paths are suggested, the exact energy requirements of this reaction, the structural features of transition states associated with the cyclization step, have not been established, especially for furan and thiophene synthesis. In this work, we explore the mechanism of the Paal-Knorr method and establish the energy requirements, using quantum chemical methods. The Paal-Knorr reaction to give furans is endergonic by 3.7 kcal/mol whereas the same reaction is exergonic for pyrrole and thiophene generation by 16.4 and 15.9 kcal/mol, using G2MP2 method. The cyclization step is associated with high energy barrier, however, explicit water participation reduces the barrier significantly. For example, under the neutral condition two water mediated pathways -(i) monoenol and (ii) hemiketal, are possible on the reaction leading to furan. The cyclization step in these two pathways require 28.9 and 27.1 kcal/mol, respectively. The ring formation step becomes highly favorable in the presence of H3O + with a barrier of only 11.5 kcal/mol (solvent phase) from the monoenol to dihydrofuran derivative and 5.5 kcal/mol (solvent phase) from hemiketal to dihydroxy dihydrofuran derivative. Similarly, a water mediated pathway involving the intermediacy of hemialcohols has been found to be energetically preferred mechanism for pyrrole and thiophene also.

show abstract

Paal–Knorr Pyrrole Synthesis in Water

Cited by 29 publications

References 24 publications

Real-time monitoring of the reaction between aniline and acetonylacetone using extractive electorspray ionization tandem mass spectrometry

Real-time monitoring of the reaction between aniline and acetonylacetone using extractive electorspray ionization tandem mass spectrometry

Green Synthesis of Pyrrole Derivatives

Mechanism of the Paal–Knorr reaction: the importance of water mediated hemialcohol pathway

Contact Info

Product

Resources

About