Doris Dallinger

Controlled microwave heating in modern organic synthesis: highlights from the 2004-2008 literature.

Direct and rapid heating by microwave irradiation in combination with sealed vessel processing in many cases enables reactions to be carried out in a fraction of the time generally required using conventional conditions. This makes microwave chemistry an ideal tool for rapid reaction scouting and optimization of conditions, allowing very rapid progress through hypotheses–experiment–results iterations. The speed at which multiple variations of reaction conditions can be performed allows a morning discussion of “What should we try?” to become an after-lunch discussion of “What were the results” Not surprisingly, therefore, many scientists both in academia and industry have turned to microwave synthesis as a front-line methodology for their projects. In this review, more than 220 published examples of microwave-assisted synthetic organic transformations from the 2004 to 2008 literature are discussed. An additional ca. 500 reaction schemes are presented in the Electronic Supplementary Material, providing the reader with an overall number of ca. 930 references in this fast-moving and exciting field.

Microwave Effects in Organic Synthesis: Myth or Reality?

on the use ofmicrowaveirradiationto“accelerate”organicchemicaltrans-formations, there has been considerable speculation anddiscussion of this effect. Much of the debate has centeredaround the question whether the observed effects can in allinstances be rationalized by purely thermal/kinetic phenom-ena (thermal microwave effects) arising from the rapidheating and high bulk reaction temperatures attained withmicrowave dielectric heating, or whether some effects areconnected to so-called specific or nonthermal microwaveeffects.

Practical microwave synthesis for organic chemists

Practical microwave synthesis for organic chemists , Practical microwave synthesis for organic chemists , کتابخانه دیجیتال جندی شاپور اهواز

Solid- and solution-phase synthesis of bioactive dihydropyrimidines

With the emergence of high-throughput screening in the pharmaceutical industry over a decade ago, synthetic chemists were faced with the challenge of preparing large collections of molecules to satisfy the demand for new screening compounds. The unique exploratory power of multicomponent reactions such as the Biginelli three-component reaction was soon recognized to be extremely valuable to produce compound libraries in a time- and cost-effective manner. The present review summarizes synthetic advances from our laboratories for the construction of Biginelli libraries via solution-and solid-phase strategies that are amenable to a high-throughput or combinatorial format.

An Investigation of Wall Effects in Microwave-Assisted Ring-Closing Metathesis and Cyclotrimerization Reactions

Challenging Ru-catalyzed ring-closing metathesis transformations leading to eight-membered-ring systems and Ni- or Co-catalyzed [2+2+2] cyclotrimerizations were evaluated at elevated temperatures applying microwave dielectric heating or conventional thermal heating in order to investigate the role of wall effects. All reactions were conducted in a dedicated reactor setup that allowed accurate internal reaction temperature measurements using fiber-optic probes for both types of heating modes. For ring-closing metathesis best results were achieved using an open vessel-gas sparging protocol in 1,2-dichloroethane at reflux temperature (83 degrees C), while cyclotrimerizations were performed under sealed vessel conditions in toluene between 80 and 160 degrees C. For all studied transformations the results achieved in a single-mode microwave reactor could be reproduced by conventional heating in an oil bath by carefully matching the temperature profiles as close as possible during the entire heating and cooling cycle. In contrast to previous literature reports, no evidence that direct in-core microwave heating can increase catalyst lifetime by minimization or elimination of wall effects was obtained. At the same time, no indication for the involvement of nonthermal microwave effects in these homogeneous transition metal-catalyzed transformations was seen.

Creating chemical diversity space by scaffold decoration of dihydropyrimidines

The demand for diverse compound libraries for screening in drug discovery and materials science is the driving force behind the development of new technologies for rapid parallel and combinatorial synthesis. The focus of this article will be on the scaffold decoration of biologically active dihydropyrimidines (DHPMs) of the Biginelli type, exploring the diversity on all six positions around the scaffold. This opens up the generation of a very large number of analogs given the commercial availability of the building blocks that are used in the functionalization process.

Rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol using controlled microwave-assisted synthesis

We present here a protocol for the synthesis of the dihydropyrimidine (DHPM) derivative monastrol, which is known to be a specific mitotic kinesin Eg5 inhibitor. By applying controlled microwave heating under sealed-vessel conditions, the synthesis via the one-pot three-component Biginelli condensation can be performed in a shorter reaction time (30 min) compared with conventional heating methods that normally require several hours of reflux heating. For the purification of the crude target compound, two different methods are presented. The first protocol includes a simple precipitation/filtration step to provide monastrol in 76% isolated yield and high purity so that no recrystallization step is necessary. This can be ascribed to the microwave heating technology in which less side-product formation is typically one of the advantages. In an alternative purification step, column chromatography is performed, which provides the product in a slightly higher yield (86%). Monastrol synthesis can be conducted in ∼2 h by employing the precipitation/filtration purification method.

Insights into the microwave-assisted preparation of supported iron oxide nanoparticles on silica-type mesoporous materials

A detailed investigation on the microwave-assisted preparation of iron oxide nanoparticles on mesoporous Si-SBA-15 support is described, employing a dedicated single-mode microwave reactor with internal reaction temperature control. Using iron(II) chloride as iron precursor and ethanol as solvent, extensive optimization studies demonstrate that after 3–5 min at 150–200 °C well-defined 3–5 nm iron oxide nanoparticles (Fe2O3, hematite phase) are obtained. In contrast to the chosen reaction temperature, reaction time and stirring efficiency are of critical importance in the preparation of these supported nanoparticles. Extended reaction times (>10 min) lead to a significant proportion of larger aggregates while inefficient stirring also produces low quality nanoparticles as a result of poor dispersion and delivery of the iron precursor to the mesoporous support. Carefully executed control studies between microwave and conventionally heated experiments applying otherwise identical reaction conditions demonstrate that the quality of the obtained supported iron oxide nanoparticles is largely independent on the heating mode, as long as a the exact same temperature profile can be maintained.

Structure–Activity Relationships and Molecular Docking of Novel Dihydropyrimidine-Based Mitotic Eg5 Inhibitors

Dihydropyrimidine‐based compounds belong to the first discovered inhibitors of the human mitotic kinesin Eg5. Although they are used by many research groups as model compounds for chemical genetics, considerably less emphasis has been placed on the improvement of this type of inhibitor, with the exception of two recent studies. Dihydropyrimidines can be divided into class I (analogues that bind in the S configuration) and class II type inhibitors, which bind in the R configuration. Herein we report the synthesis and optimization of novel class II type dihydropyrimidines using a combination of in vitro and docking techniques.

Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane

A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of α-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask.