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In the past few years, the use of microwave energy to heat chemical reactions has become an increasingly popular theme in the scientific community. This nonclassical heating technique has slowly progressed from a laboratory curiosity to an established method commonly used both in academia and in industry. Because of its efficiency, microwave heating dramatically reduces reaction times (from days and hours to minutes and seconds) and improves product purities or material properties among other advantages. Since the early days of microwave chemistry, researchers have observed rate-accelerations and, in some cases, altered product distributions as compared with reactions carried out using classical oil-bath heating. As a result, researchers have speculated that so-called specific or nonthermal microwave effects could be responsible for these differences. Much of the debate has centered on the question of whether the electromagnetic field can exert a direct influence on a chemical transformation outside of the simple macroscopic change in bulk reaction temperature. In 2009, our group developed a relatively simple "trick" that allows us to rapidly evaluate whether an observed effect seen in a microwave-assisted reaction results from a purely thermal phenomenon, or involves specific or nonthermal microwave effects. We use a microwave reaction vessel made from silicon carbide (SiC) ceramic. Because of its high microwave absorptivity, the vessel shields its contents from the electromagnetic field. As a result, we can easily mimic a conventionally heated autoclave experiment inside a microwave reactor under carefully controlled reaction conditions. The switch from an almost microwave transparent glass (Pyrex) to a strongly microwave absorbing SiC reaction vial under otherwise identical reaction conditions (temperature profiles, pressure, stirring speed) then allows us to carefully evaluate the influence of the electromagnetic field on the particular chemical transformation. Over the past five years we have subjected a wide variety of chemical transformations, including organic reactions, preparations of inorganic nanoparticles, and the hydrolysis of proteins, to the "SiC test." In nearly all of the studied examples, we obtained identical results from reactions carried out in Pyrex vials and those carried out in SiC vials. The data obtained from these investigations confirm that in the overwhelming majority of cases a bulk temperature phenomenon drives the enhancements in microwave chemistry and that the electromagnetic field has no direct influence on the reaction pathway.

A continuous flow microwave system based on a transmission line short-circuited waveguide reactor concept is described. The continuous flow reactor is capable of operating in a genuine high-temperature/high-pressure process window (310°C/60 bar), applying a microwave transparent and chemical resistant cylindrical γ-Al2O3 tube as reaction zone. The system can be operated in an extremely energy efficient manner, utilizing 0.6–6 kW microwave power (2.45 GHz). The application of the reactor for processing four chemical transformations in a high-temperature/high-pressure regime with a throughout of 3.5–6.0 l/h is demonstrated.

A series of five known symmetric organocatalytic reactions at elevated temperatures are re-evaluated to detect the existence of specific or nonthermal microwave effects. The results obtained either with microwave irradiation or with microwave irradiation with simultaneous cooling might be reproduced by conventional heating at the same reaction temperature and time in an oil bath, though no evidence was found for specific or nonthermal effects.

Microwave-assisted organic synthesis in nonpolar solvents is investigated utilizing cylinders of sintered silicon carbide SiC, a chemically inert and strongly microwave absorbing material, as passive heating elements PHEs. Microwave energy is absorbed due to this heating, which subsequently transfer the generated thermal energy through conduction phenomena to the reaction mixture.

Research has been conducted on 2(1H)-pyrazinones. The study of the inter- and intramolecular hetero-Diels-Alder reactions carried out under controlled microwave irradiation in a series of functionalized 2(1H)-pyrazinones is presented.

Research has been conducted on the 4-alkyl- and 4-aryl-dihydropyrimidones. The structural features, electronic absorption and circular dichroism spectra of these dihydropyrimidones have been investigated and the use of the semispherical, ab initio and density functional theory methods is described.

Research has been conducted on the aryliminopropadienethiones. The generation of these compounds via the flash vacuum thermolysis of isoxazolones and their characterization via mass spectrometry and matrix isolation IR spectroscopy, chemical trapping and DFT calculations is described.

Research has been conducted on the nitrile ylides and their 1,5-electrocyclizations. The results of ab initio and density function calculations are presented.

Research was conducted to examine the pericyclic versus pseudopericyclic 1,5-electrocyclization of iminodiazomethanes using ab initio calculations and the density functional theory method. The ring closure reactions of (e)- and Z-iminodiazomethane (E)-, (Z), vinyldiazomethane and formyldiazomethane to 1H-1,2,3-triazole, 3H-pyrazole and 1,2,3-oxadiazole, respectively, were analyzed. Results provide evidence for a pseudopericyclic molecular orbital topology involving an in-plane attack of the imine lone pair on the terminal nitrogen of the diazo functionality.

Research was conducted to study the construction of the erythrinane skeleton using a triple cascade sequence approach. Mass spectra were determined at an ionizing voltage of 70 eV while the starting sulfoxide was consumed immediately upon the addition of the Pummerer promoter. Results indicated the inherent instability of the 2-aminofuran ring system. They also showed that the resulting cycloadduct was transformed to several types of arylnaphthalene lignans.

Studies made by Biginelli in 1893 showed how dihydropyrimidines of type 4 were synthesized through a simple one-pot condensation reaction of ethyl acetoacetate, benzaldehyde and urea. In this study, the mechanism of the three-component Biginelli dihydropyrimidine synthesis was reinvestigated using H and C nuclear magnetic resonance spectroscopy. NMR spectroscopy results show that there is no evidence that the first step in the Biginelli reaction is an acid-catalyzed aldol reaction of ethyl acetoacetate and benzaldehyde which leads to a carbenium ion intermediate.

A novel method for the synthesis of conformationally restricted polycyclic dihydropyrimidines (DHPs) was developed based on the utilization of omicron-alkenylaryl-tethered DHP-fused mesomeric betaines. The synthetic process was characterized by the intramolecular 1,3-dipolar cycloaddition reaction of the mesomeric betaine which led to the formation of the target compounds. The cycloaddition reaction was characterized by a reqioselective two-step annulation sequence which induced the formation of a rigid, polycyclic DHPs.

The Diels-Alder reaction of 2-amino-5(alkylthio)-substituted isobenzofurans was analyzed to characterize the influence of the amine on intramolecular cycloaddition. Analysis of the Pummerer-induced cyclization-cycloaddition reaction sequence involving 2-amino-substituted isobenzofurans indicated the efficiency of the tandem-amido-Pummerer-Diels-Alder reaction sequence in the generating vinylogous C-acyliminium ions. Furthermore, the activation barrier of the reaction sequence was reduced by amide incorporation which lowered the transition state energies.

Several thieno[2,3-c]furans and furo[3,4-b]indoles with polyheterocyclic ring systems were synthesized by utilizing tandem Pummerer-Diels-Alder reaction sequence. The sequence utilizes alpha-thioisobenzofurans as key intermediates in the cascade process which forms 4+2-cycloadducts when combined with a specific dienophile. The tandem-cascade process exhibited intramolecular variation on the thiophene series during the subsequent reactions.

A new synthetic route to the phenylnaphthyl skeleton of 1-arylnaphthalene lignans is introduced. The procedure involves the Pummerer cyclization of o-benzoyl-substituted sulfoxide precursors followed by the Diels-Alder cycloaddition of the alpha-thio isobenzofuran intermediate with added dienophiles. It has been applied to the preparation of taiwanin C and E as well as justicidin E.

Matrix photolysis and flash vacuum pyrolysis (FVP) from four different precursors yields acetylketene. The infrared spectra of the conformers produced are identified by matrix isolation of the infrared spectroscopy. The acetylketene conformers are found to have equal energy and a rotational barrier of ca. 39 kilojoules per mole.

Neutralization-reionization mass spectrometric studies reveal that (methylimino)ethenethione and iminoethane-thione radical cations are stable on the microsecond time scale. The imino-radical cation tautomerizes to H-CS-CN on generation from isoxazolones. Ab initio G2(MP2) level-based calculations yield the structures and stabilities of the two radical cations. Predicted IR and UV spectra and ionization energies of both radical cations agree well with experimental data.

A study was made on the preparative and mechanistic aspects of the formation of simple mono- and bifunctionalized trioxabicyclononadienes. The methods entailed the addition of nucleophiles to alpha-oxoketene 5 following a multistep reaction sequence. The results indicated the viability of the methods which permit the synthesis of several varieties of mono- and bifunctionalized derivatives as opposed to previous approaches which showed limited synthetic value.

Dipivaloylketene dimerization in several polar and nonpolar media leads to the formation of the (2 + 4) dimer while in dimethyl sulfoxide pyridine or tributylphosphine, dimerization takes place at the C=O bond leading to the formation of a dioxinone. The latter dimerization reaction is a new type of alpha-oxo ketene dimerization. Cycloaddition reactions of dipivaloylketene with a number of compounds reveal that dipivaloylketene undergoes both (2 + 4) and (2 + 2) addition the general aspects of which are discussed.

Oscillatory flow reactors (OFRs) superimpose an oscillatory flow to the net movement through a flow reactor. OFRs have been engineered to enable improved mixing, excellent heat- and mass transfer and good plug flow character under a broad range of operating conditions. Such features render these reactors appealing, since they are suitable for reactions that require long residence times, improved mass transfer (such as in biphasic liquid-liquid systems) or to homogeneously suspend solid particles. Various OFR configurations, offering specific features, have been developed over the past two decades, with significant progress still being made. This review outlines the principles and recent advances in OFR technology and overviews the synthetic applications of OFRs for liquid-liquid and solid-liquid biphasic systems. [ABSTRACT FROM AUTHOR]

Experimental and computational techniques are applied to examine the thermodynamic properties and reaction mechanism of the Morita-Baylis-Hillman (MBH) reaction. The results obtained from the theoretical approach which are in agreement with all the experimental/kinetic evidence such as reaction order, acceleration by protic species (methanol, phenol) and autocatalysis helped to resolve the existing controversy about the character of the key proton transfer in the MBH reaction (Aggarwal versus McQuade pathways).

Ru-Catalyzed ring-closing metathesis transformations leading to eight-membered-ring systems and Ni- or Co-catalyzed [2+2+2] cyclotrimerizations are analyzed at elevated temperatures applying microwave dielectric heating or conventional thermal heating in order to examine the role of wall effects. The results have shown no evidence that direct in-core microwave heating can increase catalyst lifetime by minimization or elimination of wall effects is obtained.

Standard linear Fmoc/t-Bu solid-phase synthesis of the 42-mer [beta]-amyloid (1-42) peptide is achieved under controlled microwave conditions by using inexpensive DIC/HOBt as coupling reagent on ChemMatrix resin. The racemization of the sensitive amino acids is avoided by performing the coupling of the three His residues in the difficult peptide sequence at room temperature.

The microwave dielectric heating and conventional thermal heating were used to study the lipase-catalyzed kinetic resolution of rac-1-phenylethanol with vinyl acetate as acyl donor and cyclohexane as solvent and probe the existence of nonthermal microwave effects. The observed reactivities and enantioselectivities in microwave and oil bath experiments for all five studied immobilized lipases were identical and hence not related to the presence of the microwave field.

The Pd-catalyzed cross-coupling of cyclic thioamides and thioureas with alkenylboronic acids, vinyl- and (het)arylstannanes, and arylsiloxanes in the presence of stoichiometric amounts of a Cu(I) cofactor is presented. The desulfitative C-C cross coupling protocol of the Liebeskind-Srogl type is performed under neutral conditions and is applied to a range of heterocyclic structures with embedded thioamide fragments.

An instructional laboratory experiment that teaches microwave-assisted synthesis is presented. The experiments use readily available starting materials and are relatively inexpensive to carry out.

N,N'-diisopropylcarbodiimide/1-hydroxybenzotriazole as coupling reagent on polystyrene, tentagel, and ChemMatrix resins were used to perform microwave-assisted Fmoc/t-Bu solid-phase peptide synthesis (SPPS). The results revealed that the main effect of microwave irradiation applied to solid-phase peptide synthesis is a purely thermal effect not related to the electromagnetic field.

The performance of SiC passive heating aids as power modulators for microwave-assisted chemical transformations is evaluated. The applied microwave power has no affect on the reaction rate and only the attained temperature has governed the outcome of a specific chemical process under microwave conditions.

A two-step bromination/phosphination protocol starting from the basic biheteroaryl core is used to synthesize the mono- and bisphosphine ligands derived from the 4,4'-bisquinolone framework. The method involved the direct microwave-assisted palladium-catalyzed carbon-phosphorus cross-coupling reaction by using the corresponding heteroaryl bromides and diphenylphosphine as substrates.

The concept of nonthermal microwave effects in four organic reactions is investigated using a reactor setup with multiple fiber-optic probes to measure internal reaction temperatures. No evidence is seen of any microwave effect, though the observed effects are purely thermal and not due to the microwave field.

A computerized algorithm is described for the determination of the amount of each labeled species differing in the number of incorporated isotope labels based on mass spectroscopic data. The [alpha]-labeled deuterium ketones are reduced by biocatalytic hydrogen transfer to the corresponding enantiopure chiral alcohols and the deconvolution algorithm is validated by regression analysis of a mixture of labeled and unlabeled ketones/alcohols.

Functionalized 4,4'-bisquinolones are synthesized by microwave-assisted palladium(0)-catalyzed one-port borylation/Suzuki cross-coupling reactions or via nickel(0)-mediated homocouplings of 4-chloroquinolin-2(1H)-one precursors. The procedures are very important for the preparation of novel types of symmetrical bisquinolones.

Biologically active 4-aryl-3-alkenyl-substituted quinolin-2(1H)-ones is synthesized in a short and concise manner employing readily available 4-hydroxyquinolin-2(1H)-ones as intermediates. Some of the key steps in the synthesis include the derivatization of the quinolin-2(1H)-one cores using palladium-catalyzed Suzuki and Heck reactions, installing the 4-aryl and 3-alkenyl substituents.

Tandem processes allow ready conversion of sulfoxide to erythrinane skeleton in a stereo- and regio-controlled manner. The 2-substituted furan derivatives of sulfoxides undergo intramolecular diels-alder reaction to form an adduct, which generates C-acyliminium ion via ring opening. This iminium ion cyclizes to give erythrinane skeleton where the ring and carbon-carbon bond formation occur in a single operation.

Either five membered ammonium or carbonyl ylides, dependant on the conditions of the reactions used, have been produced by the rhodium(II)-catalyzed transformation of alpha-Diazo esters containing an amido group in the gamma-position.

Important differences have been observed when performing microwave-enhanced organic transformations, using open and closed vessel conditions. For the hydrolysis of benzamide with sulfuric acid in sealed vessels, where no volatile products are formed, no appreciable difference in reaction performance as a function of the filling volume of the vials or the reaction scale were detected. However, in the cyclocondensation of tetrahydroquinoline with substituted malonic esters, where 2 equiv. of ethanol are formed, the outcome of the reaction under sealed vessel conditions is critically dependent on the scale of the reaction. [Copyright &y& Elsevier]