Current Microwave Chemistry - Volume 5, Issue 1, 2018

Background: This paper describes the synthesis of novel fused heterocycles from the reaction 2-Bromo-N-(phenyl sulfonyl) acetamide derivatives with nitrogen nucleophilic reagents were carried out under microwave radiation and conventional heating. The synthesized compounds are excellent utilizing microwave irradiation rather than conventional heating. Methods: Synthesis of sulfonamide derivatives was carried out under microwave radiation and conventional heating. Results: Schotten-Baumann reaction for the synthesis of Bromo-N-(phenyl sulfonyl) acetamide derivatives by treatment of sulfonyl chloride derivatives with 2-bromoacetamide in pyridine. Reactivity of Bromo-N-(phenyl sulfonyl)acetamide derivatives towards urea derivatives to afford the corresponding aminothiazole and aminooxazole derivatives, benzofused heterocyclic derivatives. Conclusion: In this investigation, we have synthesized novel aminothiazole, amino oxazole, benzo[e] [1,3]oxazin, benzo[e][1,3]thiazin, quinazoline-2-yl, (pyridine-4-ylamino)acetamide, 2-(benzo[d]thiazole- 2-ylthio) and 2-((1H-benzo[d]imidazol-2-yl)thio) derivatives incorporating sulphonamide moiety utilizing Microwave irradiation and Conventional heating. The products were obtained under microwave reaction in excellent yields in a short reaction time.

Background: Microwave (MW) assisted synthesis of chemicals and catalysts are considered as an environmentally friendly, faster and energy efficient approach than conventional heating methods. The aim of this paper is to demonstrate MW heating power for the synthesis of heterogeneous layered double hydroxide catalysts (LDHs) and evaluation of catalysts under MW reaction condition for glycerol carbonate synthesis in terms of time, temperature and solvent free approach. The work reported in the manuscript lies in understanding the effect of reaction environment along with optimized process condition and catalyst amount on the product profile during carbonylation of glycerol with urea using microwave. Methods: Microwave assisted synthesis of hydrotalcite catalysts with zinc, magnesium and aluminum metal ions was done by in situ co-precipitation method. The catalytic activities were tested for the synthesis of glycerol carbonate under microwave reflux condition using glycerol and urea and optimized. The products were separated from catalyst and characterized by 13C inverse gated NMR and quantified. Result: Layered double hydroxide catalysts incorporated with zinc show good conversion and selectivity towards glycerol carbonate formation. The reaction conditions are optimized with temperature, time, concentration and catalyst amount under microwave heating condition. Conclusion: Microwave assisted method has reduced synthesis time with good conversion and selectivity towards glycerol carbonate formation. The catalytic activity of Zn-Mg-Al layered double hydroxide with higher zinc content shows better activity and selectivity towards glycerol carbonate formation and comparable to literature reports with benefits of faster reaction time and low temperature and easy separation.

Background: A large number of compounds with important biological properties contain the pyrrole heterocyclic system as main structural feature. Methods: The synthesis of substituted pyrrole derivatives was carried out via a one-pot multicomponent reaction of sodium diethyl oxalacetate (3) with an equimolar amount of various aromatic aldehydes 1 and primary amines 2, in ethanol, using microwave irradiation. The newly synthesized compounds were evaluated for their potential cytostatic and antiviral activities in various cell culture lines. Results: A range of novel pyrrole derivatives (4-13) were synthesized in a convenient one-step procedure. 3-Hydroxy-1-methyl-2-oxo-5-(3-chlorophenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid ethyl ester (9b) showed a noteworthy activity against leukemia, while all new pyrrole adducts were potent against the Yellow Fever Virus in Vero cells. Conclusion: A new protocol, employing a three-component reaction under microwave irradiation, enabled the rapid synthesis of 3-hydroxy-2-oxopyrroles has been developed, providing access to compounds with significant antiviral activities.

Background: Isoquinolones are widely used compounds as bioactive substances and antibiotics. Therefore, it is important to establish their synthetic process. One possibility for this purpose is the use of Curtius rearrangement. Such reactions are applied to produce heterocycles containing nitrogen atom. In this study, shortening of the synthetic process is discussed using the Friedel-Crafts type cyclization reaction. Furthermore, high yields and highly selective reactions are required during the microwave irradiation. Methods: The reactions were carried out under microwave irradiation conditions as well as conventional heating conditions. The microwave irradiation effect was investigated by comparing their yields. Results: The reactions occurred in several nonpolar solvents. Especially, in decalin, the yields under the microwave irradiation conditions were higher than under the conventional heating conditions. This would be due to selective absorption of microwaves by the substrates. For the improvement of the yields, the Friedel-Crafts type cyclization reactions were carried out in the presence of FeCl3. The addition of FeCl3 at a higher temperature would not be effective for this Friedel-Crafts type cyclization reaction. The use of FeCl3 enable to proceed the reaction at lower temperature. Conclusion: The microwave accelerating effect was observed in a nonpolar solvent. In this solvent, microwaves would be selectively absorbed not by the solvent, but by the substrate. Furthermore, by the use of FeCl3 as a catalyst, the reaction was able to proceed at a lower temperature. This would result in the adduct formation between the substrate and FeCl3. These results show that the microwave irradiation can be a potential tool to proceed the Friedel-Crafts type cyclization reaction, but further optimization of the reaction conditions would be required.

Background: An efficient, microwave assisted, copper catalyzed synthetic protocol for α- ketoamides has been developed by using secondary amines. Methods: In the synthetic method, the targeted α-ketoamides were synthesized with the help of microwave by reacting secondary amines and aryl methyl ketones in the presence of copper chloride and hydrogen peroxide. Results: α-ketoamides were prepared in good yields (within 10mins) with the help of a microwave irradiation. The reported protocol is ligand free and the yields of the derivatives were modest to excellent. Conclusion: Microwave assisted technique will be a useful alternative method for the preparation of α-ketoamides.

Background: Grafting of polyacrylamide and locust bean gum was performed by microwave assisted copolymerization using of cerric ammonium nitrate as the reaction initiator. Methods: The grafting process was optimized in terms of concentration of acrylamide, amount of CAN and microwave irradiation time fixed quantity of locust bean gum (LBG). The characterization of grafted gum was performed by XRD, FTIR, SEM, DSC swelling studies, elemental analysis. Results: Small quantity of nitrogen was found in elemental analysis of pure gum (0.942%) however grafted gum depicted a significant amount (15.66%) confirming the acrylamide grafting of LBG. Acute oral toxicity study showed the grafted gum to be non-toxic. Conclusion: Grafted LBG was utilized to prepare colon targeted delayed release tablets of budesonide. The drug release via in vitro procedure revealed that modified gum has probable application in colonic drug delivery system.

Background: Trans-epoxide of (+)-3-carene is one of the most easily prepared products of primary functionalization and can be synthesized by oxidation of (+)-3-carene. The trans-epoxide undergoes ring opening reactions when treated with different nucleophilic reagents giving rise to the corresponding vicinal bis-heteroatomic derivatives which are considered as promising chiral reagents. The ring opening with heterocyclic amines is of special interest because the resulting amino alcohols are perspective chiral ligands for asymmetric organic synthesis and are used as chiral auxiliary in the preparation of promising drugs. The ring opening of the trans-epoxide of (+)-3-carene by aromatic amines does not take place when using traditional approaches. Methods: Microwave irradiation was studied as a factor providing the required transformations. The experiments were carried out using a monomodal microwave reactor with the temperature control by built-in IR sensor. The reaction products were studied by modern spectroscopic techniques. The results of synthetic experiments were rationalized within the model build up by quantum chemical calculations (DFT). Results: Reaction of trans-epoxide of (+)-3-carene with sodium salts of heterocyclic amines under microwave irradiation in methanol at 120°C for 1 h resulted in epoxide ring cleavage to produce the corresponding 4-substituted 1S,4S,3S,6R-caran-3-ols in good isolated yields (60-83%). The reaction takes place only in the case of sterically unhindered heterocyclic amines (imidazole, pyrazole, 1H-1,2,3- triazole, 4-(4-bromophenyl)-1H-imidazole, benzotriazole, benzimidazole). Bulky heterocyclic amines do not cause substitution reaction but induce decomposition of the starting epoxide. Alkylation of benzotriazole with trans-epoxide of (+)-3-carene proceeds regioselectively, whereas alkylation of benzotriazole with 1,2-epoxycyclohexane affords both regioisomers. Conclusion: Microwave irradiation of mixtures containing trans-epoxide of (+)-3-carene and sodium salts of sterically unhindered heterocyclic amines induces regio- and stereoselective SN2 epoxide ring cleavage to produce the corresponding chiral 4-substituted 1S,4S,3S,6R-caran-3-ols which belong to novel group of prospective chiral reagents.

Background: Microwave-assisted synthesis is an important field of research in relation to the drug discovery and development process. Particularly, microwave-assisted organic synthesis (MAOS) is a significant strategy by which the synthetic chemists achieve their goals in a fraction of time as compared to conventional methods. Methods: Over the past decades, the development of novel and efficient methodologies has been reported on C-N bond formation. Here, an efficient, solvent-free, environmentally benign, microwaveassisted synthesis of substituted piperazine benzazole derivatives is reported. The reaction time for the synthesis of benzazole derivatives was drastically reduced from a reported 2-4 h to only 30-180 sec. Results: The protocol achieves wider substrate scope and good to excellent yields with ease of purification, in which compounds will get separated without using chromatographic technique. Conclusion: We have developed a simple and highly efficient eco-friendly approach under microwave assisted conditions without adding any external solvent, for the preparation of various aryl piperazine and aryl sulfonylpiperazine benzazoles derivatives. The salient features of this methodology are efficacy, environmentally benign nature, wider scope of substrate choice, ease of product purification, and non-involvement of catalyst, base or solvent.

Background: Microwave irradiation usage has reduced the time of reactions in organic synthesis. Nano-Fe2O3 proved to be a highly efficient and recyclable catalyst for the synthesis of organic molecules. Objective: One pot synthesis of substituted oxadiazoles using ultrasonic irradiation and nano- Fe2O3 as catalyst at ambient conditions. Method: Probe sonicator was used for ultrasonication synthesis along with nano- Fe2O3 as catalyst. Results: The synthesised substituted oxadiazoles were obtained in high yields and shorter reaction time. Conclusion: Eco-friendly protocols, easy recovery of catalyst, efficient recyclability, high stability of catalyst, high yields and lesser reaction time render the protocol sustainable and economic.