Current Microwave Chemistry - Volume 1, Issue 2, 2014

In this paper, we report on a new procedure for nanocrystalline titania synthesis using microwave-assisted homogeneous hydrolysis under hydrothermal conditions. We show that this synthetic procedure promotes formation of low-aggregated TiO2 powders with very high specific surface area (up to 240 m2–/g) and small particle size (5-7 nm), and that it hinders SO2 2– ions’ sorption on the surface of nanoparticles.

In this study aza-Michael addition reactions were used as a Green chemistry protocol to synthesize propanenitrile derivatives. The reactions were performed in both presence and absence of lipases, under orbital shaking and microwave irradiation, using water as a protic solvent and hexane as an aprotic solvent. aza-Michael adducts were synthesized with acceptable yields, under microwave irradiation and water as solvent in the presence of lipase from Candida antarctica in a very short period of time (30 s). The study shows that lipases can be used as a microwave reactor to significantly reduce the reaction time so that yields similar to those of orbital shaking can be obtained.

Bismuth nitrate-catalyzed microwave-assisted one-pot three components Aza-Diels-Alder reaction has been investigated. This method has been used for an efficient synthesis of 2-azabicyclo[2,2,2] cyclooctanones.

A microwave-assisted reaction is developed to facilitate the construction of 1,2-dihydro[1,6]naphthyridines from methyl ketones, amines and malononitrile. This one-pot, catalyst-free, solvent-free, pseudo-five-component synthesis of [1,6]naphthyridines involves a sequential Knoevenagel reaction, Michael addition, ring closure and cyclizationaromatization cascades. The advantages of this method lie in its simplicity, cost effectiveness and environmental friendliness. High bond-forming efficiency, good yields and the use of readily available amines make this process convenient for parallel synthesis. Moreover, the versatility of nitrile as functional group is proved since it can be readily transformed into various other functional groups. It is believed that the time saved by implementing microwave strategy is potentially important in traditional organic syntheses and the combination of catalyst-free, solvent-free and microwave heating will be of importance in the search for green laboratory-scale synthesis.

An efficient, one-pot, solvent-free synthesis of ethyl 3,5-disubstituted-1H-pyrrole-2-carboxylate is achieved by a reaction of 1,3-disubstituted propen-2-one and ethylnitroacetate, in presence of diethylamine (Et2NH) and triethylphosphite (P(OEt)3) under microwave (MW) irradiation via cascade Michael-reductive cyclization. The mechanistic outcome of the reaction has also been described. This protocol establishes an easy access to disubstituted-1H-pyrrole-2- carboxylates in one pot.

A small library of twenty-two 3,4-dihydropyrimidin-2(1H)-ones and twenty-one thiones was synthesized under microwave irradiation using acetic acid as both solvent and catalyst. The oxidation of 3,4-dihydropyrimidin-2(1H)-ones to the corresponding pyrimidin-2(1H)-ones was systematically studied with heterogeneous and homogeneous oxidants. Microwave- assisted oxidation using potassium peroxydisulfate in an acetonitrile/water mixture at 100°C for 10 minutes produced the desired compounds in high yields for the majority of the 3,4-dihydropyrimidin-2(1H)-ones used. The decrease in the reaction yield observed in the case of 3,4-dihydropyrimidin-2(1H)-ones with bulky substituents at the C4 position was rationalized resorting to theoretical calculations. The oxidation of 3,4-dihydropyrimidine-2(1H)-thiones was also extensively studied. Using potassium peroxydisulfate or other powerful oxidants, such as oxone or hydrogen peroxide, pyrimidine-2(1H)-thione was not observed. However, evidence for the formation of this compound was obtained using 2,3-dichloro-5,6-dicyanobenzoquinone as oxidant under microwave irradiation. Electronic structure calculations indicate the stability of the 1,4-dihydropyrimidinethiol tautomer, which is deemed responsible for the different reactivity of these compounds.

The regio- and diastereoselective base catalyzed one-pot, multicomponent reaction of 4-hydroxycoumarin, aldehyde, and 2-bromo-1-phenylethanone giving trans 2,3-dihydrofuro[3,2-c]coumarins is greatly accelerated by a combination of 4-(N,N-dimethylamino)pyridine (DMAP) and microwave heating. The classical thermal reaction takes a long reaction time and uses environment unfriendly bases, pyridine, NaOH. The microwave reaction is carried out in Biotage Synthesizer at different temperatures under built-in pressure. Among the organic and inorganic bases used, DMAP is the best base. Further, replacement of pyridine/NaOH by DMAP makes the reaction greener. Microwave irradiation (140°C, 4 bar) accelerates the reaction greatly as compared to its thermal counterpart. The effect of microwaves could be correlated with the dielectric loss of the polar solvents. 1-propanol and ethanol that have high dielectric loss are the best solvents under microwave irradiation. In the reaction DMAP functions as a nucleophile, a base, and a good leaving group. The method is highly regioselective, diastereoselective and gives good yield of the product.

Novel solid-supported catalysts derived from palladium supported on silicon carbide were prepared. The resulting catalysts produced high methyl cinnamate yields (>80%) for more than 20 cycles of the Heck reaction of iodobenzene and methyl acrylate. The use of microwave heating during catalyst preparation was found to significantly improve the catalytic activity compared with conventional heating. This result is interpreted as being due to an accelerated decomposition of the palladium species resulting in improved palladium-nanoparticle dispersion under microwave heating.

A series of new imines of 7-Aminocephalosporinic acid (7-ACA) were synthesized by fragment-based design using smaller and functionally simpler adducts like alpha-halo ketones, N-heterocycles and 7-ACA with good success to generate chemical compounds with drug-like properties effective against Staphylococcus aureus and Pseudomonas aeruginosa which are resistant to several antibiotics and are responsible for a large number of community acquired infections. In the first step, N-aryl substituted ketones were synthesized in excellent yields (90-96%) in a single step reaction (Scheme 1) with various heterocyclic rings in the presence of solvents like ethanol/DMF using microwave irradiation method in shorter reaction times (10-12 mins) with higher yields (90-95%). Further, the microwave assisted synthesis of imines of 7-ACA from corresponding ketones (Scheme 2) with ethanol as the solvent in the presence of molecular sieves resulted in target compounds with improved yield (90-94%) in short reaction times (12-14 min). The use of microwave assisted synthetic route and greener and environmentally benign solvents resulted in improvement of rates (energy savings), yields and selectivity (reduced wastes) of the target compounds.

Microwave radiation, an electromagnetic radiation, is widely used as a source of heating in organic synthesis. Since the discovery of the microwave heating approach, microwave-assisted reaction has emerged as a new green-method in organic synthesis as it provides fast, higher yields, and higher product purities, and it reduces pollution of the environment. The purine ring system possesses undisputed biological importance and it is considered to be one of the most important heterocyclic rings in nature. Therefore, organic chemists have been engaged in extensive efforts to produce these compounds following various greener techniques, primarily to circumvent growing environmental concerns. This topic has received increasing interest owing to the wide variety of purine analogs as biologically significant drugs, and products for industrial application. In this review, we discuss only the microwave-assisted synthesis of purine and guanine analogs, and includes the syntheses of (i) imidazopyrimidines, (ii) pyrazolopyrimidines, (iii) imidazopyridines, and pyrazolopyridines (iv) via microwave.