Efficient Biginelli Synthesis of 2-Aminodihydropyrimidines under Microwave Irradiation

Synlett ◽  
2018 ◽  
Vol 29 (08) ◽  
pp. 1047-1054 ◽  
Author(s):  
Fulvia Felluga ◽  
Fabio Benedetti ◽  
Federico Berti ◽  
Sara Drioli ◽  
Giorgia Regini
Keyword(s):  
Microwave Irradiation ◽  
Guanidine Hydrochloride ◽  
Reaction Times ◽  
Conventional Heating ◽  
Dicarbonyl Compounds ◽  
Simple Protocol ◽  
Twofold Excess ◽  
General Method

A practical and general method for the Biginelli cyclocondensation of guanidine with aldehydes and β-dicarbonyl compounds is described and illustrated with the synthesis of a set of 26 functionalized 2-amino-3,4-dihydropyrimidines. The simple protocol involves the ­microwave-mediated reaction of a twofold excess of guanidine hydrochloride with the required reaction partners in an alcohol at 120 °C. Yields are generally good, with short reaction times and a simple workup. The scope is considerably wider than that of similar reactions ­carried out under conventional heating.

Regioselective Synthesis of Potent 4,5,6,7-Tetrahydroindazole Derivatives via Microwave-assisted Vilsmeier-Haack Reaction and their Antioxidant Activity Evaluation

2019 ◽  
Vol 16 (3) ◽  
pp. 194-201 ◽  
Author(s):  
Renu Bala ◽  
Vandana Devi ◽  
Pratibha Singh ◽  
Navjot Kaur ◽  
Pawandeep Kaur ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Microwave Irradiation ◽  
Biological Activities ◽  
Reaction Times ◽  
Conventional Heating ◽  
High Chemical ◽  
Microwave Assisted ◽  
Work Up ◽  
Active Methylene ◽  
By Products

Background: Tetrahydroindazole, a member of the fused-pyrazole system, is a least studied class of heterocyclic compounds owing to its scarcity in nature. However, a large number of synthetically prepared tetrahydroindazoles are known to show a variety of biological activities such as interleukin- 2 inducible T-Cell kinase inhibitors, AMPA receptor positive allosteric modulators, antitumor, antituberculosis, anti-inflammatory and antimicrobial activities. Vilsmeier-Haack reaction is one of the most important chemical reactions used for formylation of electron rich arenes. Even though Vilsmeier- Haack reaction was studied on a wide variety of hydrazones derived from active methylene compounds, literature lacks the examples of the use of 4-substituted cyclohexanones as a substrate for the synthesis of 4,5,6,7-tetrahydroindazoles. The study of the reaction of Vilsmeier-Haack reagent with hydrazones derived from cyclic keto compounds having active methylene has been considered the interested topic of investigation. In the present study, ethyl cyclohexanone-4-carboxylate was treated with one equivalent of various hydrazines for two hours and the resulted hydrazones were further treated with an OPC-VH reagent (Vilsmeier-Haack reagent isolated from phthaloyl dichloride and N,Ndimethylformamide) afforded 4,5,6,7-tetrahydroindazoles in excellent yields. The synthesized compounds 4a-f and 5a-f were screened for their antioxidant activities using the DPPH radical scavenging assay. The target compounds were synthesized regioselectively using 4+1 approach in excellent yields. A number of experiments using both conventional heating as well as microwave irradiation methods were tried and on comparison, microwave irradiation method was found excellent in terms of easy work up, high chemical yields, shortened reaction times, clean and, no by-products formation. Some of the synthesized compounds showed significant antioxidant activity. The microwave assisted synthesis of 4,5,6,7-tetrahydroindazoles from ethyl cyclohexanone-4-carboxylate has been reported under mild conditions in excellent yield. Easy work up, high chemical yield, shortened reaction times, clean and no by-products formation are the major advantages of this protocol. These advantages may make this method useful for chemists who are interested in developing novel 4,5,6,7-tetrahydroindazole based drugs.

scholarly journals Orthoamide, LXII [1]. – Mikrowellen-unterst ¨ utzte Formylierung schwach CH2-acider Verbindungen mit dem Bredereck-Simchen Reagenz – Umwandlung der Kondensationsprodukte in Heteroaromaten / Orthoamides, LXII [1]. – Microwave Assisted Formylation of Weak CH2-Acidic Compounds with the Bredereck-Simchen Reagent – Preparation of Heteroaromatic Compounds from the Condensation Products

2005 ◽  
Vol 60 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Willi Kantlehner ◽  
Gerhard Simchen ◽  
Jochen Mezger ◽  
Edmont V. Stoyanov ◽  
Ralf Kreß ◽  
...  
Keyword(s):  
Microwave Irradiation ◽  
Reaction Times ◽  
Conventional Heating ◽  
Methyl Anthranilate ◽  
Prolonged Heating ◽  
Heteroaromatic Compounds ◽  
Microwave Assisted ◽  
Condensation Products ◽  
Acidic Compounds ◽  
Isoxazole Derivatives

The diformylation of the dinitriles 4 and diesters 7 with the Bredereck-Simchen reagent HC[N(CH3)2]2[OC(CH3)3] (1) under microwave irradiation give the bis-enamines 6 and 8 with dramatically reduced reaction times and improved yields compared to conventional heating. The condensation products formed can be easily converted to bis-pyrazole and bis-isoxazole derivatives 13 and 20, respectively. Methyl anthranilate reacts on prolonged heating with the orthoamide 21 to give ketene aminal 23 in low yield (8 %). Under microwave irradiation the same reagents lead to a mixture of 23 (14 %) and dihydropyrane 24 (28 %).

scholarly journals Conventional vs. Microwave- or Mechanically-Assisted Synthesis of Dihomooxacalix[4]arene Phthalimides: NMR, X-ray and Photophysical Analysis

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1503
Author(s):  
Alexandre Miranda ◽  
Paula Marcos ◽  
José Ascenso ◽  
M. Robalo ◽  
Vasco Bonifácio ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Microwave Irradiation ◽  
Ball Milling ◽  
Column Chromatography ◽  
Photophysical Properties ◽  
Reaction Times ◽  
Good Method ◽  
Conventional Heating ◽  
Cone Conformation ◽  
X Ray

Direct O-alkylation of p-tert-butyldihomooxacalix[4]arene (1) with N-(bromopropyl)- or N-(bromoethyl)phthalimides and K2CO3 in acetonitrile was conducted under conventional heating (reflux) and using microwave irradiation and ball milling methodologies. The reactions afforded mono- and mainly distal di-substituted derivatives in the cone conformation, in a total of eight compounds. They were isolated by column chromatography, and their conformations and the substitution patterns were established by NMR spectroscopy (1H, 13C, COSY and NOESY experiments). The X-ray structures of four dihomooxacalix[4]arene phthalimide derivatives (2a, 3a, 3b and 5a) are reported, as well as their photophysical properties. The microwave (MW)-assisted alkylations drastically reduced the reaction times (from days to less than 45 min) and produced higher yields of both 1,3-di-substituted phthalimides (3a and 6a) with higher selectivity. Ball milling did not reveal to be a good method for this kind of reaction.

scholarly journals Efficient Eco-Friendly Solvent-Free Obtaining Bis-Selenium-Alkenes with High Biological Potential

2020 ◽  
Vol 2 (1) ◽  
pp. 20
Author(s):  
Pâmella Cordeiro ◽  
Matheus Silva Prado ◽  
José Neto ◽  
Vanessa Nascimento
Keyword(s):  
Green Chemistry ◽  
Microwave Irradiation ◽  
Reaction Times ◽  
13C Nmr Spectroscopy ◽  
Conventional Heating ◽  
Diphenyl Diselenide ◽  
Organoselenium Compounds ◽  
1H And 13C Nmr ◽  
Reaction Optimization ◽  
Biological Potential

Organocalcogenides, in particular, organoselenium compounds, have been widely studied due to their large number of synthetic and biological applications. Among organoselenium compounds, a class of bis-selenide-alkene derivatives has attracted attention. Recently, some studies have been developed for the synthesis of vinyl chalcogen derivatives, since these are also highly valuable intermediates in several synthetic applications. However, the methodologies developed so far have extensive reaction times, and use toxic solvents as well as heavy metals. Therefore, there is an emerging need to develop protocols for the synthesis of these molecules that are in accordance with the principles of green chemistry. In this work, we developed an alternative synthesis of bis-selenium-alkene derivatives, through an environmentally appropriate methodology. Reaction optimization was evaluated from the diphenylacetylene and diphenyl diselenide, using I2/DMSO as a catalytic system under microwave irradiation or conventional heating. The variations of these conditions were carried out through different equivalences between the reagents, the amount of catalyst (I2), temperature, DMSO and the reaction process (Microwave or conventional). Even now, it was found that the best established condition was using diphenylacetylene, diphenyl diselenide, 30 mol% I2 in DMSO, under microwave irradiation at 100 °C for 10 min. In this condition, the product was obtained in 82% yield and its characterization was performed using 1H and 13C NMR spectroscopy. Therefore, the methodology that is being developed, in addition to perfectly attending to the principles of green chemistry, will allow to evaluate the reaction scope using different alkenes and diselenides or even disulfides and ditellurides.

A Green Approach for Organic Transformations Using Microwave Reactor

2019 ◽  
Vol 16 (5) ◽  
pp. 730-764 ◽  
Author(s):  
Subrata Das ◽  
Rupak Banik ◽  
Brajesh Kumar ◽  
Subhadip Roy ◽  
Noorussabah ◽  
...  
Keyword(s):  
Microwave Irradiation ◽  
Microwave Heating ◽  
Organic Synthesis ◽  
Reaction Times ◽  
Green Technology ◽  
Conventional Heating ◽  
Organic Transformations ◽  
Green Approach ◽  
Site Selectivity ◽  
Recent Developments

Microwave-assisted organic transformation (MAOR) is presently gaining wide popularity in the field of organic synthesis. The conventional heating technique is gradually being removed from the laboratory and a novel microwave heating technique established to be used in both academia and industry. As compared to the classical organic methodology, the green technology tools have several advantages like dramatically reduced reaction times, improved yields, site selectivity, and the increased product purities with simplification of work-up procedures. In the current study, we have briefly described the overview of recent developments and applications of microwave irradiation in organic transformation with schematic compiling of the organic reactions, bioactive heterocyclic compounds, and so on. This review also presents a critical analysis of the various advantages of microwave irradiation in organic synthesis/transformation compared to the classical or conventional heating. So, we believe that our current study of the green microwave heating technique will be highly beneficial for the researchers from both academia and industry in their near future.

Eaton’s reagent in polybenzimidazole synthesis

2017 ◽  
Vol 30 (6) ◽  
pp. 699-709 ◽  
Author(s):  
Jessica Olvera-Mancilla ◽  
Joaquín Palacios-Alquisira ◽  
Larissa Alexandrova
Keyword(s):  
Mechanical Properties ◽  
High Temperature ◽  
Microwave Irradiation ◽  
Benzoic Acid ◽  
Reaction Times ◽  
Polymer Structure ◽  
Conventional Heating ◽  
Reaction Conditions ◽  
Molecular Weights ◽  
Microwave Effect

The polycondensations of 3,3′-diaminobenzidine with two acids, 4,4′-oxybis(benzoic acid) and hexafluoroisopropylidene bis(benzoic acid), were conducted in Eaton’s reagent at the unusually high temperature of 180°C and under microwave irradiation at 90°C. Both protocols resulted in soluble polybenzimidazoles, OPBI and CF3PBI, of high molecular weights in very short reaction times. The synthesized polybenzimidazoles exhibited high thermostability and excellent mechanical properties. The influence of the reaction conditions on the polymer structure and molecular weights was studied. The “microwave effect” was demonstrated by comparison of the polycondensations conducted under microwave irradiation and conventional heating.

Green Formation of Novel Pyridinyltriazole-Salicylidene Schiff Bases

2019 ◽  
Vol 16 (2) ◽  
pp. 309-313
Author(s):  
Mustafa Kemal Gümüş
Keyword(s):  
Microwave Irradiation ◽  
Schiff Bases ◽  
Guanidine Hydrochloride ◽  
Alternative Methods ◽  
Second Step ◽  
Green Method ◽  
Maximum Reaction ◽  
Pyridine Carboxylic ◽  
High Yields ◽  
Amine Hydrochlorides

Aim and Objective: In this work, water was used as solvent for the eco-friendly synthesis of imines under microwave irradiation. In the first step of the study, 5-pyridinyl-3-amino-1,2,4-triazole hydrochlorides were synthesized in the reaction of amino guanidine hydrochloride with different pyridine carboxylic acids under acid catalysis. A green method for 5-pyridinyl-3-amino-1,2,4-triazoles was developed with the assistance of microwave synthesis. In the second step, the eco-friendly synthesis of imines was achieved by reacting 5- pyridinyl-2H-1,2,4-triazol-3-amine hydrochlorides with salicylic aldehyde derivatives to produce 2-(5- pyridinyl-2H-1,2,4-triazol-3-ylimino)methyl)phenol imines. Materials and Methods: Microwave experiments were done using a monomode Anton Paar Monowave 300 microwave reactor (2.45 GHz). Reaction temperatures were monitored by an IR sensor. Microwave experiments were carried out in sealed microwave process vials G10 with maximum reaction volume of 10 mL. Results: When alternative methods were used, it was impossible to obtain good yields from ethanol. Nevertheless, the use of water was successful for this reaction. After 1-h microwave irritation, a yellow solid was obtained in 82% yield. Conclusion: In this work an eco-friendly protocol for the synthesis of Schiff bases from 5-(pyridin-2-, 3- or 4- yl)-3-amino-1,2,4-triazoles and substituted salicylic aldehydes in water under microwave irradiation was developed. Under the found conditions the high yields for the products were achieved at short reaction time and with an easy isolation procedure.

Microwave-assisted Synthesis of Benzoxazoles Derivatives

2020 ◽  
Vol 7 (3) ◽  
pp. 183-195
Author(s):  
Musa Özil ◽  
Emre Menteşe
Keyword(s):  
Microwave Irradiation ◽  
Reaction Medium ◽  
Pharmaceutical Chemistry ◽  
Conventional Heating ◽  
High Yield ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Optical Brighteners ◽  
Chemistry Research ◽  
Extensive Class

Background: Benzoxazole, containing a 1,3-oxazole system fused with a benzene ring, has a profound effect on medicinal chemistry research owing to its important pharmacological activities. On the other hand, the benzoxazole derivative has exhibited important properties in material science. Especially in recent years, microwave-assisted synthesis is a technique that can be used to increase diversity and quick research in modern chemistry. The utilization of microwave irradiation is beneficial for the synthesis of benzoxazole in recent years. In this focused review, we provide a metaanalysis of studies on benzoxazole in different reaction conditions, catalysts, and starting materials by microwave technique so far, which is different from conventional heating. Methods: Synthesis of different kind of benzoxazole derivatives have been carried out by microwave irradiation. The most used method to obtain benzoxazoles is the condensation of 2-aminophenol or its derivatives with aldehydes, carboxylic acids, nitriles, isocyanates, and aliphatic amines. Results: Benzoxazole system and its derivatives have exhibited a broad range of pharmacological properties. Thus, many scientists have remarked on the importance of the synthesis of different benzoxazole derivatives. Conventional heating is a relatively inefficient and slow method to convey energy in orientation to the reaction medium. However, the microwave-assisted heating technique is a more effective interior heating by straight coupling of microwave energy with the molecules. Conclusion: In this review, different studies were presented on the recent details accessible in the microwave- assisted techniques on the synthesis of the benzoxazole ring. It presents all examples of such compounds that have been reported from 1996 to the present. Benzoxazoles showed an extensive class of chemical substances not only in pharmaceutical chemistry but also in dyestuff, polymer industries, agrochemical, and optical brighteners. Thus the development of fast and efficient achievement of benzoxazoles with a diversity of substituents in high yield is getting more noteworthy. As shown in this review, microwave-assisted synthesis of benzoxazoles is a very effective and useful technique.

scholarly journals Microwave-Assisted Asinger Synthesis of Thiazolines

2020 ◽  
Vol 3 (1) ◽  
pp. 27
Author(s):  
Raúl Eduardo Gordillo-Cruz ◽  
Liliana Gonzalez-Reyes ◽  
Milton Coporo-Reyes ◽  
Nieves Zavala-Segovia ◽  
Bernardo A. Frontana-Uribe ◽  
...  
Keyword(s):  
Microwave Irradiation ◽  
Reaction Times ◽  
Reaction Conditions ◽  
Microwave Assisted

An array of 2,4-disubstituted thiazolines was obtained through Asinger reaction approach from the straightforward treatment of diverse aldehydes/ketones with 1-mercaptopropan-2-one, in the presence of NH3 assisted by microwave irradiation, displaying similar and sometimes higher yields, as well as shorter reaction times that traditional Asinger reaction conditions at room and lower temperatures.

Microwave Irradiated Acetylation of p-Anisidine: A Step towards Green Chemistry

2008 ◽  
Vol 6 (1) ◽  
Author(s):  
Mousumi Chakraborty ◽  
Vaishali Umrigar ◽  
Parimal A. Parikh
Keyword(s):  
Acetic Acid ◽  
Reaction Time ◽  
Green Chemistry ◽  
Acetic Anhydride ◽  
Microwave Irradiation ◽  
Organic Solvent ◽  
Reaction Times ◽  
Microwave Energy ◽  
Operating Parameters ◽  
Feed Composition

The present study aims at assessing the effect of microwave irradiation against thermal heat on the production of N-acetyl-p-anisidine by acetylation of p-anisidine. The acetylation of p-anisidine under microwave irradiation produces N-acetyl-p-anisidine in shorter reaction times, which offers a benefit to the laboratories as well as industries. It also eliminates the use of excess solvent. Effects of operating parameters such as reaction time, feed composition, and microwave energy and reaction temperature on selectivity to the desired product have been investigated. The results indicate as high as a 98% conversion of N-acetyl-p-anisidine can be achieved within 12-15 minutes using acetic acid. The use of acetic acid as an acetylating agent against conventionally used acetic anhydride eliminates the handling of explosive acetic anhydride and also the energy intensive distillation step for separation of acetic acid. Organic solvent like acetic anhydride are not only hazardous to the environment, they are also expensive and flammable.

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