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The ionic liquid, tributylmethylammonium methylcarbonate, has been employed as a catalytic base for clean N-methylation of indole with dimethylcarbonate. The reaction conditions were optimised under microwave heating to give 100% conversion and 100% selectivity to N-methylindole, and subsequently transferred to a high temperature/high pressure (285 °C/150 bar) continuous flow process using a short (3 min) residence time and 2 mol% of the catalyst to efficiently methylate a variety of different amines, phenols, thiophenols and carboxylic acid substrates. The extremely short residence times, versatility, and high selectivity have significant implications for the synthesis of a wide range of pharmaceutical intermediates, as high product throughputs can be obtained via this scalable continuous flow protocol. It has also been shown that the ionic liquid can be generated in situ from tributylamine, which has the net effect of transforming an ineffective stoichiometric base into a highly efficient catalyst for this broad class of reactions.

Microwave-assisted syntheses of colloidal nanocrystals (NCs), in particular CdSe quantum dots (QDs), have gained considerable attention due to unique opportunities provided by microwave dielectric heating. The extensive use of microwave heating and the frequently suggested specific microwave effects, however, pose questions about the role of the electromagnetic field in both the formation and quality of the produced QDs. In this work a one-pot protocol for the tunable synthesis of monodisperse colloidal CdSe NCs using microwave dielectric heating under carefully controlled conditions is introduced. CdSe QDs are fabricated using selenium dioxide as a selenium precursor, 1-octadecene as a solvent and reducing agent, cadmium alkyl carboxylates or alkyl phosphonates as cadmium sources, 1,2-hexadecanediol to stabilize the cadmium complex and oleic acid to stabilize the resulting CdSe QDs. Utilizing the possibilities of microwave heating technology in combination with accurate online temperature control the influence of different reaction parameters such as reaction temperature, ramp and hold times, and the timing and duration of oleic acid addition have been carefully investigated. Optimum results were obtained by performing the reaction at 240 °C applying a 5 min ramp time, 2 min hold time before oleic acid addition, 90 s for oleic acid addition, and a 5 min hold time after oleic acid addition (8.5 min overall holding at 240 °C). By using different cadmium complexes in the microwave protocol CdSe QDs with a narrow size distribution can be obtained in different sizes ranging from 0.5-4 nm by simply changing the cadmium source. The QDs were characterized by TEM, HRTEM, UV-Vis, and photoluminescence methods and the size distribution was monitored by SAXS. Control experiments involving conventional conductive heating under otherwise identical conditions ensuring the same heating and cooling profiles, stirring rates, and reactor geometries demonstrate that the electromagnetic field has no influence on the generated CdSe QDs. The resulting CdSe NCs prepared using either conductive or microwave dielectric heating exhibited the same primary crystallite size, shape, quantum yield and size distribution regardless of the heating mode.

The mechanism of the Dakin-West reaction has been thoroughly investigated by monitoring the reaction using ESI-MS/MS techniques in combination with M06-2X/6-311++G(d,p) calculations. Several of the key intermediates in the previously proposed "azlactone" mechanism have been experimentally detected and characterized. In particular, interception of the mixed anhydrides involved in the early and late stages of the mechanistic scheme, as well as of the cyclic acyl-oxazolone intermediate, supports the original pathway suggested by Dakin and West. All intermediates and transition structures involved in several competing mechanisms have been calculated. The theoretical calculations support the experimental results and corroborate the proposed "azlactone" mechanism. The pathway involving the cyclic oxazolone ("azlactone") intermediate represents an energy barrier more than 3 kcal mol(-1) lower than for the competing aldol-type mechanism, thus ruling out this alternative mechanism. The DFT calculations explain the observed ESI-MS data and assess those intermediates which the experiments cannot fully elucidate.

Background Calcium governs a wide range of cellular processes. Specifically, control of gene transcription involves Ca entry channels that are activated by either voltage, second messengers or depletion of intracellular stores. The family of classical transient receptor potential channels (TRPC) has been implicated in both the receptor/second messenger as well as in store-operated Ca entry pathway, and represents an attractive target for therapeutic intervention.

The question “why should microwave chemistry be green?” is evaluated in the context of the twelve principles of green chemistry, with a focus on the 6th principle: design for energy efficiency. A significant number of publications on microwave-assisted organic transformations during the past 25 years describe this non-classical heating technology as being “green”, assuming that microwave dielectric heating is more energy efficient than classical conductive heat transfer methods. In this Perspective article, we critically assess the energy efficiency of microwave-assisted transformations in the context of scaling-up this technology to production quantities.

This paper describes a simple/low volume enzymatic extraction method for selenomethionine (SeMet) determination in selenized yeast samples. In contrast to traditional methods which generally utilize large sample volumes consuming significant amounts of costly enzymes, the modified protocol employs a microtiter plate format allowing a reduction of the required sample volumes to 1 mL per extract. The extraction is performed in a parallel (5 × 4 = 20 position microtiter plate) reaction platform made out of sintered silicon carbide, fitted with standard disposable glass HPLC/GC vials. Due to the high thermal conductivity of silicon carbide, this set-up can be placed on a standard hotplate to accurately maintain the desired extraction conditions (37 °C, 20 h) for all positions of the microtiter plate. Hydrolysis of selenium-enriched yeast with a combination of protease XIV and lipase VII (ratio 2 : 1, w/w) using these low-volume conditions provided identical results to the more traditional high-volume method. The amount of SeMet was determined by HPLC/ICPMS and confirmed a high recovery rate for SeMet (93 ± 2%, n = 3) for the certified reference material SELM-1.

This paper explains the phenomena which occur in commercially available laboratory microwave equipment, and highlights several situations where experimental observations are often misinterpreted as a 'microwave effect'. Electromagnetic simulations and heating experiments were used to show the quantitative effects of solvent type, solvent volume, vessel material, vessel internals and stirring rate on the distribution of the electric field, the power density and the rate of heating. The simulations and experiments show how significant temperature gradients can exist within the heated materials, and that very different results can be obtained depending on the method used to measure temperature. The overall energy balance is shown for a number of different solvents, and the interpretation and implications of using the results from commercially available microwave equipment are discussed.

The Pd(0)-catalyzed intramolecular olefination of vinyl and aryl triflates has been studied with a view to gaining insight into the question of kinetically preferred reductive elimination when at least two options are available. In either series, a non-activated alkene participant was found to be converted most readily into the non-conjugated cyclization product. This trend is seen despite the more forcing conditions necessary to engage the less reactive aryl triflates in ring closure. On the other hand, when the pendant chain is terminated by an alpha-methyl acrylate unit, the conjugated diene is kinetically preferred. The two reactions appear to be closely balanced energetically since product distributions are not greatly disparate. Nevertheless, their complementarity could be utilized to advantage in the synthesis of polycyclic molecules possessing multiple sterogenic centers.

The use of sealed-vessel microwave-assisted organic synthesis in combination with 4 Å molecular sieves as water scavengers is investigated. Two classical model transformations, namely acetal formation and imine formation, are evaluated under both conventional heating and microwave dielectric heating. The results obtained in these studies indicate that molecular sieves cannot be used effectively as water scavengers in microwave-assisted transformations owing to the fact that these zeolites are generally most effective in adsorbing water at room temperature. For both acetal and imine formation, performing these reversible reactions at a higher temperature in the presence of molecular sieves leads to significantly reduced conversions compared with experiments at room temperature.

First described more than two decades ago, microwave-assisted organic synthesis has matured from a laboratory curiosity to an established technique that today is heavily used in both academia and industry. One of the most valuable advantages of using controlled microwave dielectric heating for chemical synthesis is the dramatic reduction in reaction times: from days and hours to minutes and seconds. As will be explained in this tutorial review, there are many more good reasons why organic chemists are nowadays incorporating dedicated microwave reactors into their daily work routine.

The multicomponent reaction of methylsulfonylacetone (or α-methylsulfonylacetophenone) with aromatic aldehydes and aminoazoles (or urea) under microwave irradiation to yield 5,8-dihydroimidazolo[1,2-a]pyrimidines and 4,7-dihydro[l,2,4]triazolo[l,5-a]pyrimidines was studied. The influence of the type of aminoazole building block on the reactivity was established. In addition, an unusual reaction pathway for the Biginelli-type condensation of methylsulfonylacetone with aldehydes and urea leading to non-classical Hantzsch-type dihydropyridines was found.

In the past few years, the use of microwave energy to heat and drive chemical reactions has become increasingly popular in the medicinal chemistry community. First described 20 years ago, this non-classical heating method has matured from a laboratory curiosity to an established technique that is heavily used in academia and industry. One of the many advantages of using rapid 'microwave flash heating' for chemical synthesis is the dramatic reduction in reaction times: from days and hours to minutes and seconds. As will be discussed here, there are good reasons why many organic chemists are incorporating microwave chemistry into their daily work routine.

The formation of thioacylthioketenes has been observed in Flash Vacuum Pyrolysis of various 1, 2-dithiole derivatives. In some cases C3S2, l, 2-propadiene-l, 3-dithione is formed too.

Methyleneketenes 2 and imidoylketenes 4, generated from Meldrum's acid derivatives 1 and 2,3-dihydropyrrole-2,3-diones 3, respectively, both rearrange thermally to oxoketenimines 5; the imidoylketene–oxoketenimine rearrangement is reversible and much accelerated by electropositive migrating groups (SMe).

Trioxabicyclononadienes 2 and 4, easily obtained by addition of nucleophiles to the stable α-oxoketene 1, are transformed into the corresponding 2,4,6,8-tetraoxaadamantanes 3 and 5 in high yields by acid-catalysed hydrolysis.

The synthesis of some 5-cyano-4-hydroxy-2-pyridone derivatives (3 a–c) by condensation of 3-aminocrotononitrile (1) with substituted diethylmalonates (2 a–c) is described. Reaction of3 a with phosphorus oxychloride yields 4,6-dichloro-3-pyridinecarbonitrile (7 a), which reacts with various nucleophiles to give substituted 3-pyridinecarbonitriles (8–10).

The existence of selective microwave absorption phenomena in the synthesis of CdSe quantum dots has been investigated. These types of microwave effects involving selective microwave absorption by specific reagents have recently been proposed in the microwave-assisted synthesis of various nanoparticles. In the present study, the microwave synthesis of CdSe quantum dots was investigated according to a protocol published by Washington and Strouse to clarify the presence of selective microwave heating. Importantly, control experiments involving conventional conductive heating were executed under otherwise (except for the heating mode) identical conditions, ensuring the same heating and cooling profiles, stirring rates, and reactor geometries. Comparison of powder X-ray diffraction, UV-vis, photoluminescence, and transmission electron microscopy data of the obtained CdSe quantum dots reveals that identical types of nanoparticles are obtained independently of the heating mode. Therefore, no evidence for a selective microwave absorption phenomenon could be obtained.

The synthesis of 4-aryl-2-(thioxo)oxo-3,4-dihydropyri- midine-5-carboxylic acids is reported using two orthogonal solid- phase variations of the Biginelli condensation. In the first method, polymer-bound -ketoesters are treated with aromatic aldehydes and urea under acidic conditions. The transient N-acyliminium ion that is initially formed from the aldehyde and urea precursors, is then intercepted by the resin-bound -ketoesters. In an alternative approach, resin-bound -ketoesters are condensed with aldehydes and O-methylisourea under basic conditions. Both orthogonal con- densation procedures provide fair to excellent overall yields of the desired target structures.

The attempted synthesis of the unknown 8,10,12-triazatricyclo(7.3.1.02,7)tridecatriene scaffold 6a by cyclization (intramolecular Michael-addition) of 4-(2-aminophenyl)-2-oxo-1,2,3,4- tetrahydro-pyrimidine-5-carboxylates of type 5a is described. The synthesis of the amino precursor 10 is achieved by microwave-promoted catalytic transfer hydrogenation of the corresponding nitro analog 9. Subsequent acid-catalyzed intramolecular Michael addition leads to the desired polycyclic scaffold 11 as a transient intermediate which spontaneously disintegrates in a retro-Michael fashion to the quinoline 13.