Current Microwave Chemistry - Volume 4, Issue 2, 2017

Background: The introduction of a cyano group has been widely investigated because a cyano group may easily be transformed into both a methylamino moiety and a carboxylic acid moiety. Therefore Michael addition between phenol and acrylonitrile for the introduction of a cyanoethoxy moiety has been reported by several groups, however, the long reaction time (20-40 h) of this reaction was problematic. In order to solve this difficulty, we investigated the Michael addition with the assistance of microwave irradiation. Methods: 4-Dimethylaminopyridine was added to a mixture of phenol and acrylonitrile, and the suspension was irradiated (107-115 W) for 4 h. Reaction conversion was determined by 1H NMR analysis of the mixture. Results: The addition reaction between phenols and acrylonitrile in the presence of 4-dimethylaminopyridine under microwave irradiation proceeded smoothly to afford the corresponding Michael adducts in good to moderate yield. Microwave-accelerated Michael addition in the presence of 4-dimethylaminopyridine proceeded more effectively without the use of additives such as solvents. This method was applicable to Michael addition between phenol and methyl acrylate, between aniline and acrylonitrile, and also between anilines and methyl acrylate. Conclusion: We have described a highly efficient and rapid method for Michael addition between phenols and acrylonitrile, between aniline and acrylonitrile, between phenol and methyl acrylate, and between anilines and methyl acrylate. Considering the present results, it is possible that the combination of microwave irradiation and the use of DMAP as a base constitute one of the most suitable procedures for the Michael addition of phenols and anilines.

Background: Recent developments in extraction techniques of natural materials for the value added compounds viz., pigments, volatile oil, bioactive compounds include application of ultra sonication, high pressure extraction, pulsed electric field application, microwave-assisted extraction and enzyme assisted extraction. Essential oil & bioactive compounds from spices are gaining lot of importance recently in view of the health benefits they posses. Enhanced extraction of cinnamon volatile oil by one of the emerging technologies viz., microwave application and its impact on flavour compounds and polyphenols is aimed at in this paper. Methods: Microwave treatment of cinnamon powder in water at varying powers viz., 100, 200, 300W and time 1-7 min. was carried out followed by hydro distillation for volatile oil extraction and solvent extraction fro polyphenol extraction. The physico-chemical quality of the oil obtained by microwave treatment was studied by measuring optical rotation, refractive index, specific gravity and GC profile. Conclusion: Microwave treatment for 5 minutes yielded highest yield of oil (3.09%) as against (2.34%) by conventional hydro distillation. Microwave treatment for 7 min yielded 3.08 % oil. The percentage recovery of oil was 72.7 % in the first hour of hydro distillation for 7 min microwave treatment, as against 54.5 % in the first hour for 5 min treatment. Microwave treatment of cinnamon resulted in enhanced extraction of volatile oil (32%), cinnamaldehyde (38%) the bio-active compound of cinnamon oil and polyphenols (11-31%). The rate of extraction of volatile oil with 5 min microwave pre-treatment followed first order kinetics with a rate constant value (k) 0.0131×10-3/min. of cinnamon volatile oil.

Background: Potassium phthalimide (PPI), a mild, green and commercially available organocatalyst used in the synthesis of a wide range of important bioactive compounds. 6-amino-1,4- dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives were synthesized via a four component reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehydes and malononitrile by utilizing various homogenous as well as heterogeneous catalysts, which usually involve relatively lower product yields and prolonged reaction times. We describe a simple and straightforward protocol to prepare pyrano[2,3-c]-pyrazole derivatives that address these drawbacks. Methods: Utilizing microwave irradiation (MWI) and with the use of water as a universal and green solvent, a series of 6-amino-1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives (5a-5o) have been efficiently prepared from the four component reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehydes and malononitrile. Results: The reactions proceeded in short periods of time (3-4 min) without side products, affording the products in 91-97 % yields. Reactions under microwave conditions were faster than those achieved with conventional heating. Water showed better result compared to other organic solvents in terms of product yield and reaction time. Conclusion: Short reaction times, mild reaction conditions, excellent product yields, use of inexpensive catalyst and easy work-up procedure and no use of toxic organic solvents are remarkable advantages of this approach. The discussed methodology can be applied to generate a variety of 6-amino- 1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives, which serve as precursors to compounds of pharmaceutical interest.

Background: The p-toluenesulfonyl (tosyl) group is one of the most versatile protecting groups for phenols and alcohols, but its removal requires drastic conditions due to their high stability. Methods: In the course of reaction, (Et4N)O2 was generated in situ by the phase transfer reaction of KO2 and Et4NBr in dry DMF was subsequently allowed to react with tosyl esters, under microwave irradiation. Results: Tosyl esters were readily deprotected to their corresponding phenols and alcohols. Conclusion: In conclusion, a mild and efficient method for the removal of tosyl protecting group, using in situ generated tetraethylammonium superoxide under microwave irradiation, has been described.

Background: The advantages of microwave (MW)-assisted chemistry reactions have led several research groups to apply this technique to the optimization of synthetic processes and the preparation of new compounds. This research focuses on Knoevenagel condensation with additives supported on natural fibers (Fibroin and Kapok) under MW. Methods: Under these experimental conditions, 2-benzylidenemalononitrile was synthesized at 60°C under MW radiation of 10 min using acid and base additives like soluble imidazole and CuSO4, solid silica, and inert fibers (e.g., Fibroin and Kapok). Results: The reactions afforded good yield for 2-benzylidenemalononitrile using the fibroin functionalized. Fibroin-CuSO4 can be reused at least three times and synthesizes several 2-arylidenemalononitrile derivatives (71-77 % at 60°C for 10 min) under MW used MeOH as solvent. Conclusion: This study investigated the use of fibroin functionalized with CuSO4 on Knoevenagel condensation under microwave radiation to synthesize 2-benzylidenemalononitriles in eco-friendly conditions.

Background: Although several methods are reported for the synthesis of thiazolidin-4-ones analogues, the microwave assisted method reported in this work is simple and proceeds with high yields in short time. Methods: In the synthetic method, the targeted thiazolidin-4-ones were synthesized with the help of the microwave by reacting aldehydes, benzyl amine and thioglycolic acid in the presence of zirconium oxychloride and ethanol. Results: All the thiazolidin-4-ones were obtained in good yield (95%-98%) with the help of a microwave technique (6-8 min), in less time as compared to the conventional method (2-4 h). Conclusion: Microwave assisted synthesis will be a useful alternative method for the synthesis of diverse range of thiazolidin-4-ones.

Background: A convenient synthesis of series of functionalized 5-(substituted phenyl)-3-phenylisoxazole (4a-f) has been carried out by using established procedures. First of all,α,β- unsaturated carbonyl compounds, Chalcones (3) were synthesized by reacting different substituted benzaldehydes (1) with acetophenone (2) based on the mechanism involved in Claisen-Schimidt condensation. Methods: Various Isoxazole derivatives (4a-f) were prepared by the reaction of Chalcones (3) with hydroxylamine hydrochloride in the presence of sodium acetate with the help of both microwave and conventional heating methods to compare their product yields and reaction time. The newly synthesized compounds were characterized by IR, 1H NMR spectral data and thin layer chromatography. Results: It is noteworthy that the synthetic reaction which requires 6-8 h in conventional method (yield 58-69%) was completed within 6-10 minutes by microwave irradiation synthesis with improved yield (67-82%). So, the use of microwave accelerated synthesis results in improvement of reaction rate, high yield in shorter reaction time and selectivity by reducing formation of waste products. Conclusion: The antimicrobial activities of titled compounds were evaluated in vitro against various strains of microorganisms. Some of these compounds exhibited pronounced antimicrobial activity in comparison with standard drugs.

Background: Stress testing as an important segment in the process of getting drug to the market and are intended to reveal stability issues. Methods: In stress testing, it is mentioned to perform the task (hydrolytic or thermolytic degradation) at elevated temperature as and when required. Elevation in temperature by means of microwave irradiation has picked up lot of consideration owing to the in-core heating of the medium. Results: In stress testing of pharmaceuticals, degradation of drug can be achieved with in very short duration of time using microwave assisted heating compare to conventional heating. But at the same time it is essential to monitor and optimize parameters of microwave irradiation otherwise there are chances of false interpretation of the results. Conclusion: This review article is focused on the principle of microwave heating, types of microwave apparatus and use of microwave radiation for hydrolytic forced degradation studies of pharmaceuticals. It is tried to compare degradation profile of drug obtained by conventional heating and microwave heating.

Background: Microwave couples directly with the molecules that are present in the reaction mixture, leading to a rapid, efficient, and instantaneous heating process. For a specific reaction system, the level of this internal heating is depended on the microwave power. Methods: The acid-catalyzed esterification of benzoic acid with butanol was selected as a model reaction to study the influence of the microwave power on the reaction rate. The kinetic behavior of the reaction was studied in a preheated temperature-controlled oil bath. The formation of butyl benzoate was measured as a function of time at six different temperatures between 60°C to 120°C. The concentrations of butyl benzoate present in solution were determined by means of HPLC with naphthalene as an internal standard. The plots of the natural logarithms of the concentrations versus time at each temperature and reaction rates were obtained, generating Arrhenius equation of the reaction. The reaction rates of microwave-assisted reactions under different power modes were determined similarly. The actual reaction temperature under microwave conditions were derived from Arrhenius equation. Results: The results indicate that the microwave power can affect the heating rate of the reaction mixture and cause the superheating phenomena at the initial reaction stage. When performing the esterification at a setup microwave power of 40 W or higher, the more microwave power, the more obvious superheating phenomena. An approximate linear relationship between the initial microwave power and the actual temperature of reactions was observed. When using the appropriate power mode, such as switching the Powermax mode off, with the appropriate heating rate, the superheating at the initial reaction stage disappears. Conclusion: The application of simultaneous cooling would lengthen the heating time but increase the actual temperature of the reaction. When using a significantly lower initial microwave power of 10 W, the actual temperature of the reaction abnormally increased.

Background: An efficient, microwave assisted, copper catalyzed synthetic protocol for substituted benzamides has been developed by using salts of carboxylic acids. Methods: In the synthetic method, the targeted substituted benzamides were synthesized with the help of microwave by reacting salts of carboxylic acid and benzamides in the presence of copper and dimethyl formamide. Results: All substituted benzamides were obtained in good yield (93-99%) with the help of a microwave technique (12-15 min) in the less time as compared to the conventional method. Conclusion: Microwave assisted technique will be a useful alternative protocol for the preparation of diverse range of substituted benzamides.

Background: Aminolysis of lactones is an important reaction for the synthesis of hydroxy amides. This reaction generally requires rather harsh conditions, such as high pressure and temperature or strong alkali metal catalysts. Microwave-assisted reactions have provided a great impetus to organic synthesis, especially for accelerating the reactions. The combination of microwave heating and solventfree conditions is a particularly attractive methodology in modern organic synthesis because it leads to enhanced conversion rates, easier work-up, higher yields and in general cleaner reactions. Methods: A simple, efficient and eco-friendly procedure was developed for the preparation of hydroxy amides from a variety of amines and lactones using microwave irradiation under solvent- and catalystfree conditions. Results: In the synthesis of hydroxy amides described herein, the reactions were conducted using microwave irradiation at temperatures of 130 °C and reaction times of 30-60 min. We investigated reactions of lactones with amines of different nucleophilic character and steric hindrance. Primary, secondary, aliphatic, aromatic and cyclic amines (2 equiv.) were used in the reactions with γ-butyrolactone or γ-valerolactone (1 equiv.). The yields of the purified products were generally very good and varied according to the amine used in most cases. An important feature is that despite no additive/catalyst is used the reaction times were shorter compared to all the works described so far. Neither an inert atmosphere nor solvent and additives/catalysts are required in this microwave irradiation procedure. Conclusion: In summary, we have demonstrated a simple and efficient method for the preparation of hydroxy amides, employing a green methodology. Simple work-up procedure and high yields obtained using MW irradiation, under solvent-, support and catalyst-free conditions show the superiority of this work over the existing methods.

Background: We describe herein a convenient one-pot, microwave-assisted methodology for the synthesis of dihydrospiro[indeno[1,2-b]quinoline-10,3'-indole]-2',4',11(1'H,5H,5'H)-trione derivatives from enaminones, isatins and indane-1,3-dione under catalyst-free condition. Method: The advantages of this microwave-assisted protocol are simplicity, rapidity, high yielding and environmentally benign procedure. Result: In addition, one of the most important aspects is that all the compounds were isolated in good to excellent yields without the need for any chromatographic separations. Conclusion: Microwave-assisted synthesis has become a mainstream method in both academia and industry, because of the commercially availability of instruments which reduces dramatically the reaction times: from days and hours to minutes and seconds. Here, we have successfully developed an effective, rapid, clean and most importantly, environmentally benign three component one pot methodology using catalyst-free micro-wave irradiation.