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C Oliver Kappe

Publications and source records attributed to C Oliver Kappe.

At least 19 recordsLinked to original sources
PubMed2006

Silicon carbide passive heating elements in microwave-assisted organic synthesis.

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). These heating inserts absorb microwave energy and subsequently transfer the generated thermal energy via conduction phenomena to the reaction mixture. The use of passive heating elements allows otherwise microwave transparent or poorly absorbing solvents such as hexane, carbon tetrachloride, tetrahydrofuran, dioxane, or toluene to be effectively heated to temperatures far above their boiling points (200-250 degrees C) under sealed vessel microwave conditions. This opens up the possibility to perform microwave synthesis in unpolar solvent environments as demonstrated successfully for several organic transformations, such as Claisen rearrangements, Diels-Alder reactions, Michael additions, N-alkylations, and Dimroth rearrangements. This noninvasive technique is a particularly valuable tool in cases where other options to increase the microwave absorbance of the reaction medium, such as the addition of ionic liquids as heating aids, are not feasible due to an incompatibility of the ionic liquid with a particular substrate. The SiC heating elements are thermally and chemically resistant to 1500 degrees C and compatible with any solvent or reagent.

Journal Article↗
PubMed2006

Rapid solid-phase peptide synthesis using thermal and controlled microwave irradiation.

A rapid and efficient microwave-assisted solid-phase synthesis method is described for the preparation of the nonapeptide WDTVRISFK, using conventional Fmoc/Bu(t) orthogonal protection strategy. The synthesis protocol is based on the use of cycles of pulsed microwave irradiation with intermittent cooling of the reaction during the removal of the Fmoc protecting group and during the coupling. The desired nonapeptide was obtained in highest yield and purity by employing MicroKan technology. The chemical reactions were carried out in a single-mode microwave reactor, equipped with a fiber-optic probe to monitor the reaction temperature continuously.

Biochemistry↗
PubMed2006

The impact of microwave synthesis on drug discovery.

In the past few years, using 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 pharmaceutical companies are incorporating microwave chemistry into their drug discovery efforts.

Chemistry, Pharmaceutical↗
PubMed2005

Microwave-assisted multistep synthesis of functionalized 4-arylquinolin-2(1H)-ones using palladium-catalyzed cross-coupling chemistry.

[reaction: see text] Biologically active 4-aryl-3-alkenyl-substituted quinolin-2(1H)-ones have been synthesized in a short and concise manner employing readily available 4-hydroxyquinolin-2(1H)-ones as intermediates. 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. All synthetic transformations (six steps) required for the synthesis of the desired target quinolin-2(1H)-one were carried out using controlled microwave-assisted organic synthesis.

Catalysis↗
PubMed2004

Controlled microwave heating in modern organic synthesis.

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

Chemistry, Organic↗
PubMed2004

Synthesis of functionalized 1,3-thiazine libraries combining solid-phase synthesis and post-cleavage modification methods.

The solid-phase synthesis of diverse sets of 1,3-thiazine-5-carboxylates on Wang resin is described. Acetoacetylation, followed by Knoevenagel condensation and an acid-promoted ring-closure reaction with thioureas furnished polymer-bound 1,3-thiazines. As an alternative to transesterification, a de-novo synthesis of beta-keto esters, starting from polymer-bound malonic acid through reaction with acyl imidazoles, was applied to increase the diversity. To reduce contamination, an on-bead purification of resin-bound 1,3-thiazines that makes use of differences in the reactivity of ester bonds toward alkoxides is reported. A final four-step post-cleavage modification of thiazine-5-carboxylates, derived by TFA cleavage from the Wang linker, leads to esters or amides. Twenty 1,3-thiazines were obtained in yields of up to 61 % over either 9 or 13 steps.

Journal Article↗
PubMed2003

Microwave-assisted ring-closing metathesis revisited. On the question of the nonthermal microwave effect.

The ring-closing metathesis reactions (RCM) of six standard diene substrates leading to five-, six-, or seven-membered carbo- or heterocycles were investigated under controlled microwave irradiation. RCM protocols were performed with standard Grubbs type II and a cationic ruthenium allenylidene catalyst in neat and ionic liquid-doped methylene chloride under sealed vessel conditions. Very rapid conversions (15 s) were achieved utilizing 0.5 mol % Grubbs II catalyst under microwave conditions. Careful comparison studies indicate that the observed rate enhancements are not the result of a nonthermal microwave effect.

Journal Article↗
PubMed2003

High-throughput synthesis of N3-acylated dihydropyrimidines combining microwave-assisted synthesis and scavenging techniques.

[reaction: see text] The solution-phase synthesis of N3-acylated dihydropyrimidines was achieved utilizing microwave flash heating both in the synthesis (acylation) and purification (scavenging) steps. Quenching times for excess anhydrides using polystyrene or silica-supported diamine sequestration reagents were reduced from several hours to minutes utilizing microwave irradiation. The use of water as sequestration agent, coupled with an efficient solid-phase extraction workup technique allowed the rapid generation of a 20-member library of N3-acylated dihydropyrimidines.

Journal Article↗
PubMed2003

Enantioseparation of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidones on chiral stationary phases based on 3,5-dimethylanilides of N-(4-alkylamino-3,5-dinitro)benzoyl L-alpha-amino acids.

Three novel chiral packing materials for high-performance liquid chromatography were prepared by covalently binding of (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]propan-amide (7), (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]-4-methylpentanamide (8), and (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonyl-amino]-2-phenylacetamide (9) to aminopropyl silica. The resulting chiral stationary phases (CSPs 1-3) proved effective for the resolution of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidone derivatives (TR 1-14). The mechanism of their enantioselection, supported by the elution order of (S)-TR 13 and (R)-TR 13 and molecular modeling of the complex of the slower running (S)-TR 13 with CSP 1 is discussed.

Amino Acids↗
PubMed2003

Microwave-enhanced transition metal-catalyzed decoration of 2(1H)-pyrazinone scaffolds.

The 2(1H)-pyrazinones have been demonstrated to be versatile building blocks for the synthesis of biologically active compounds. Here, an efficient method is described for the decoration of these interesting scaffolds. Microwave-assisted palladium catalyzed reactions allow the easy introduction of different substituents at the C3- and even at the rather unreactive C5-position of the pyrazinones. Stille, Suzuki, Heck, Sonogashira reactions, in addition to reductive dechlorinations, and cyanation reactions are investigated.

Catalysis↗
PubMed2003

A one-pot microwave-assisted synthesis of pyrido[2,3-d]pyrimidines.

A high yield multicomponent reaction providing multifunctionalized pyrido[2,3-d]pyrimidines with up to four diversity centers in a one-pot microwave-assisted cyclocondensation of alpha,beta-unsaturated esters, amidine systems and malononitrile (or ethyl cyanoacetate) is described.

Algorithms↗