20 results on '"Benjamin A. Chalmers"'
Search Results
2. The cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement
- Author
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James J. De Voss, G. Paul Savage, Maree T. Smith, Glen M. Boyle, Benjamin A. Chalmers, John Tsanaktsidis, Jeanette E. Stok, Vicky M. Avery, Paul V. Bernhardt, Hui Xing, Melissa Sykes, Craig M. Williams, Sevan D. Houston, Clementina Farfan Soto, Jed M. Burns, and Tyler Fahrenhorst-Jones
- Subjects
Tetrahydronaphthalenes ,Antiparasitic ,medicine.drug_class ,Antineoplastic Agents ,010402 general chemistry ,Benzoates ,01 natural sciences ,Biochemistry ,Cyclooctanes ,chemistry.chemical_compound ,Smooth muscle ,medicine ,Molecule ,Physical and Theoretical Chemistry ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,Benzene ,Combinatorial chemistry ,0104 chemical sciences ,3. Good health ,Cyclooctatetraene ,chemistry ,Nitroimidazoles ,Cubane ,Benznidazole ,Tamibarotene ,Bioisostere ,medicine.drug - Abstract
The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.
- Published
- 2019
3. CO2-responsive polyacrylamide copolymer vesicles with acid-sensitive morpholine moieties and large hydrophobic RAFT end-group
- Author
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David L. Cheung, Per B. Zetterlund, Benjamin A. Chalmers, Fawaz Aldabbagh, Christopher Magee, and ~|6201984|~
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Polymers and Plastics ,Co2 responsive ,Block copolymer ,Chemistry ,Vesicle ,Organic Chemistry ,Polyacrylamide ,General Physics and Astronomy ,Self-assembly ,02 engineering and technology ,Raft ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,End-group ,Acid sensitive ,Radical polymerization ,Morpholine ,Polymer chemistry ,Materials Chemistry ,Copolymer ,0210 nano-technology ,Micelle - Abstract
Sequential Reversible Addition Fragmentation Chain Transfer (RAFT) polymerizations using 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (VA-044) and 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) were used to give amphiphilic polyacrylamide block copolymers containing N-(2-morpholin-4-ylethyl)acrylamide (MEA), where the morpholine moieties are CO2-responsive. The order in which monomers were polymerized determined the placement of the large hydrophobic RAFT end group with more complex ABA′ type self-assembly (e.g. patterned and large worm-like vesicles, large compound micelles) obtained when the dodecyl trithiocarbonate end-group was attached to the hydrophilic poly(MEA) block. Cleaving the hydrophobic end group reverts self-assembly to simpler spherical vesicles observed in the triblock of the same chemical composition, but with the RAFT end group attached to the hydrophobic poly(tert-butyl acrylamide) block. Ionization of the hydrophilic poly(MEA) block through flushing with CO2 irreversibly shifts self-assembly towards lower order morphologies with spherical micelles being more favoured than vesicles. We thank the Irish Research Council (IRC) for a Government of Ireland Postdoctoral Fellowship for B.A. Chalmers and the IRC for a postgraduate scholarship award for C. Magee as part of the First IUPAC Transnational Call in Polymer Chemistry co-ordinated by F. Aldabbagh. We thank Eadaoin Timmins at the Centre of Microscopy and Imaging (NUI Galway) for TEM. peer-reviewed 2019-10-07
- Published
- 2017
4. Enantioselective synthesis of (R)-2-cubylglycine including unprecedented rhodium mediated C-H insertion of cubane
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Craig M. Williams, Sevan D. Houston, Benjamin A. Chalmers, and G. Paul Savage
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Chiral auxiliary ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Strecker amino acid synthesis ,Enantioselective synthesis ,chemistry.chemical_element ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Rhodium ,chemistry.chemical_compound ,chemistry ,Cubane ,Physical and Theoretical Chemistry - Abstract
The first enantioselective synthesis of (R)-2-cubylglycine, an analogue of (R)-2-phenylglycine in which the phenyl ring has been replaced by cubane, is disclosed. The key step was a telescoped Strecker reaction using (S)-2-amino-2-phenylethanol as a chiral auxiliary. Exploration of an alternative synthetic approach resulted in unprecedented cubane C–H insertion.
- Published
- 2019
5. Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
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Susan K. Nilsson, Andy Kuo, Hui Xing, Andrea Reitsma, James J. De Voss, Maree T. Smith, David A. Winkler, Paul V. Bernhardt, Cody‐Ellen P. Murray, Carly J. Pierce, Sevan D. Houston, Benjamin A. Chalmers, Helen M. Cooper, Gimme H. Walter, John Tsanaktsidis, Jeanette E. Stok, James S. McCarthy, Sussan Ghassabian, Glen M. Boyle, Benjamin Cao, Charlotte Clark, Peter G. Parsons, Craig M. Williams, Cielo Pasay, Stuart W. Littler, and G. Paul Savage
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010405 organic chemistry ,Stereochemistry ,Bioactive molecules ,Benzene ,General Medicine ,Mice, SCID ,General Chemistry ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Mice ,chemistry.chemical_compound ,chemistry ,Mice, Inbred NOD ,Cubane ,Struktur aktivitats beziehungen ,Animals ,Humans ,Molecule ,Market place ,Bioisostere ,Aged - Abstract
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
- Published
- 2016
6. Corrigendum: Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
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Cielo Pasay, John Tsanaktsidis, Jeanette E. Stok, Craig M. Williams, Carly J. Pierce, Hui Xing, James S. McCarthy, Benjamin Cao, Sevan D. Houston, Andy Kuo, James J. De Voss, Peter G. Parsons, Charlotte Clark, Glen M. Boyle, Sussan Ghassabian, Paul V. Bernhardt, Susan K. Nilsson, Maree T. Smith, David A. Winkler, Benjamin A. Chalmers, Cody Ellen P. Murray, Helen M. Cooper, Stuart W. Littler, Gimme H. Walter, Andrea Reitsma, and G. Paul Savage
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chemistry.chemical_compound ,chemistry ,010405 organic chemistry ,Cubane ,Library science ,General Chemistry ,Bioisostere ,010402 general chemistry ,01 natural sciences ,Molecular science ,Catalysis ,0104 chemical sciences - Abstract
In this Communication, a La Trobe University affiliation is missing for the author David A. Winkler. The penultimate author address entry must read: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052 (Australia) and La Trobe Institute for Molecular Science, La Trobe University, Bundoora, 3084 (Australia).
- Published
- 2018
7. Synthesis of n-[(dialkylamino)methyl)]acrylamides and n-[(dialkylamino)methyl]methacrylamides from schiff base salts: useful building blocks for smart polymers
- Author
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Fawaz Aldabbagh, Benjamin A. Chalmers, Abdullah Alzahrani, Styliana I. Mirallai, and Patrick McArdle
- Subjects
aqueous-solution ,Schiff base ,dimethyl(methylene)ammonium iodide ,010405 organic chemistry ,Hydrochloride ,Organic Chemistry ,aminals ,Iminium ,010402 general chemistry ,sensitivity ,01 natural sciences ,Biochemistry ,Smart polymer ,0104 chemical sciences ,mannich ,chemistry.chemical_compound ,Monomer ,chemistry ,Polymer chemistry ,derivatives ,Hydroxymethyl ,acid ,Physical and Theoretical Chemistry ,Methylene ,Mannich reaction - Abstract
The traditional thermal Mannich reaction is unsuitable for preparing polymerizable N-methylene amino substituted acrylamides and methacrylamides. Herein we provide a facile multi-gram high yield synthesis of these monomeric precursors to stimuli-responsive polymers by the addition of acrylamides and methacrylamides onto in situ generated or freshly isolated methylene Schiff base (iminium) salts. The X-ray crystal structure of the hydrated iminium salt, 1-(hydroxymethyl)azocan-1-ium chloride and monomer center dot HCl salt (N-[(azocan-1-yl)methyl]prop-2-enamide hydrochloride) is described.
- Published
- 2018
8. Investigations into cubane based analogues of current pharmaceuticals
- Author
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Benjamin A. Chalmers
- Subjects
Antifungal ,chemistry.chemical_compound ,chemistry ,Cubane ,medicine.drug_class ,Functional group ,medicine ,A diamond ,Bioisostere ,Chemotherapeutic drugs ,Ring (chemistry) ,Combinatorial chemistry - Abstract
The cubane core has been shown to be physically similar to benzene across the body diagonal, yet remains electronically and physically different in all other ways. It is proposed that this similarity may allow cubane to act as a bioisostere for benzene in pharmaceutical applications. As such, a number of novel synthetic approaches have been used to develop new routes to previously unknown cubane derivatives. The synthesis of several novel cubane based compounds is described herein. The synthetic routes contained within provide further insight into the potential functional group modifications for the cubane framework. These derivatives form key intermediates in the synthesis of a number of target analogues based in a variety of drug classes. These classes include anticancer chemotherapeutic drugs, novel Alzheimer’s disease compounds, antibacterial compounds, topical scabies medications as well as a well known antifungal compound. The overall study is designed to act as a base level investigation into the potential of cubane to act as a bioisostere for benzene in pharmaceutical analogues. Compounds were selected based upon the presence of a benzene ring, drug class as well as potential synthetic approach. The described compounds are thus designed to be analogous to current pharmaceutical drugs which are undergoing Phase I clinical trials, later testing, or are already available for purchase. Biological tests of these novel compounds have been subjected to, at least, base level comparison to the known drug analogue. Results of these studies have demonstrated that cubane analogues have similar biological activity to a number of benzene analogues in a variety of classes and thus merit further investigation into the use of cubane as a bioisostere for benzene. Further to this a P450 oxidation study has also been performed to help understand the metabolic processes that may be imparted upon the cubane core in a biological system. The results herein also demonstrate that cubane derived compounds hold great potential for their application in pharmaceutical compounds, yet underline the fact that cubane remains a diamond in the rough, for which many syntheses remain undiscovered.
- Published
- 2017
9. Efficient synthesis and RAFT polymerization of the previously elusive N -[(cycloalkylamino)methyl]acrylamide monomer class
- Author
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Fawaz Aldabbagh, Benjamin A. Chalmers, Gerard Hawkins, and Abdullah Alzahrani
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Polymers and Plastics ,Chemistry ,Organic Chemistry ,Radical polymerization ,Cationic polymerization ,Chain transfer ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,chemistry ,01 natural sciences ,0104 chemical sciences ,Living free-radical polymerization ,Chain-growth polymerization ,Polymerization ,Polymer chemistry ,Materials Chemistry ,Living polymerization ,Reversible addition−fragmentation chain-transfer polymerization ,0210 nano-technology ,biological - Published
- 2017
10. Approaches to the Synthesis of a Water-Soluble Carboxy Nitroxide
- Author
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Benjamin A. Chalmers, Steven E. Bottle, Kathryn E. Fairfull-Smith, and Komba Thomas
- Subjects
chemistry.chemical_compound ,Phthalic anhydride ,Nitroxide mediated radical polymerization ,Potassium permanganate ,Water soluble ,chemistry ,Nitrile ,Radical ,Yield (chemistry) ,Organic Chemistry ,Organic chemistry ,Isoindoline ,Physical and Theoretical Chemistry - Abstract
The robust and diversely useful isoindoline nitroxide, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (1; CTMIO), has previously been synthesised in low-to-moderate yields from phthalic anhydride (3). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11, derive from 5-bromo-1,1,3,3-tetramethylisoindoline (6). The third approach starts from the readily accessible starting material, 4-methylphthalic anhydride (12), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16–18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9.
- Published
- 2013
11. Frontispiece: Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
- Author
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G. Paul Savage, Sussan Ghassabian, Peter G. Parsons, Hui Xing, Cielo Pasay, Gimme H. Walter, Paul V. Bernhardt, Craig M. Williams, Stuart W. Littler, Cody‐Ellen P. Murray, Carly J. Pierce, Benjamin A. Chalmers, Andy Kuo, James J. De Voss, Charlotte Clark, Glen M. Boyle, Maree T. Smith, David A. Winkler, Andrea Reitsma, Helen M. Cooper, John Tsanaktsidis, Jeanette E. Stok, James S. McCarthy, Sevan D. Houston, Susan K. Nilsson, and Benjamin Cao
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chemistry.chemical_compound ,Chemistry ,Cubane ,Stereochemistry ,Struktur aktivitats beziehungen ,General Chemistry ,Bioisostere ,Benzene ,Catalysis - Published
- 2016
12. Berichtigung: Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
- Author
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Craig M. Williams, Sussan Ghassabian, Carly J. Pierce, Gimme H. Walter, Hui Xing, Andrea Reitsma, Benjamin A. Chalmers, Paul V. Bernhardt, Sevan D. Houston, Benjamin Cao, John Tsanaktsidis, Jeanette E. Stok, James J. De Voss, James S. McCarthy, Cody‐Ellen P. Murray, G. Paul Savage, Maree T. Smith, Andy Kuo, Helen M. Cooper, David A. Winkler, Stuart W. Littler, Peter G. Parsons, Glen M. Boyle, Charlotte Clark, Susan K. Nilsson, and Cielo Pasay
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chemistry.chemical_compound ,chemistry ,010405 organic chemistry ,Cubane ,General Medicine ,Bioisostere ,010402 general chemistry ,Benzene ,01 natural sciences ,Medicinal chemistry ,0104 chemical sciences - Published
- 2018
13. TMIO-PyrImid hybrids are profluorescent, site-directed spin labels for nucleic acids
- Author
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Benjamin A. Chalmers, Kye-Simeon Masters, Tri Nguyen, Snorri Th. Sigurdsson, Steven E. Bottle, John C. McMurtrie, and Subham Saha
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Benzimidazole ,Stereochemistry ,Pyridines ,Isoindoles ,Biochemistry ,law.invention ,chemistry.chemical_compound ,symbols.namesake ,law ,Stokes shift ,Nucleic Acids ,Molecule ,Physical and Theoretical Chemistry ,Electron paramagnetic resonance ,Molecular Structure ,Organic Chemistry ,Electron Spin Resonance Spectroscopy ,RNA ,DNA ,Fluorescence ,chemistry ,Nucleic acid ,symbols ,Benzimidazoles ,Spin Labels - Abstract
We report the synthesis of a new class of molecules which are hybrids of long-lived tetramethylisoindolinoxyl (TMIO) radicals and the pyrido[1,2-a]benzimidazole (PyrImid) scaffold. These compounds represent a new lead for noncovalently binding nucleic acid probes, as they interact with nucleic acids with previously unreported C (DNA) and C/U (RNA) complementarity, which can be detected by electron paramagnetic resonance (EPR) techniques. They also have promising properties for fluorimetric analysis, as their fluorescent spin-quenched derivatives exhibit a significant Stokes shift.
- Published
- 2014
14. A novel protecting group methodology for syntheses using nitroxides
- Author
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Kathryn E. Fairfull-Smith, Steven E. Bottle, Richard S. Grainger, Benjamin A. Chalmers, and Jason C. Morris
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Nitroxide mediated radical polymerization ,Chemistry ,Metals and Alloys ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,Methoxyamine ,Yield (chemistry) ,Materials Chemistry ,Ceramics and Composites ,Organic chemistry ,Moiety ,Protecting group - Abstract
The methoxyamine group represents an ideal protecting group for the nitroxide moiety. It can be easily and selectively introduced in high yield (typically >90%) to a range of functionalised nitroxides using FeSO4·7H2O and H2O2 in DMSO. Its removal is readily achieved under mild conditions in high yield (70–90%) using mCPBA in a Cope-type elimination process.
- Published
- 2013
15. ChemInform Abstract: A Novel Protecting Group Methodology for Syntheses Using Nitroxides
- Author
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Jason C. Morris, Kathryn E. Fairfull-Smith, Steven E. Bottle, Benjamin A. Chalmers, and Richard S. Grainger
- Subjects
chemistry.chemical_compound ,Nitroxide mediated radical polymerization ,Chemistry ,Methoxyamine ,Yield (chemistry) ,Moiety ,General Medicine ,Protecting group ,Combinatorial chemistry - Abstract
The methoxyamine group represents an ideal protecting group for the nitroxide moiety. It can be easily and selectively introduced in high yield (typically >90%) to a range of functionalised nitroxides using FeSO4·7H2O and H2O2 in DMSO. Its removal is readily achieved under mild conditions in high yield (70–90%) using mCPBA in a Cope-type elimination process.
- Published
- 2014
16. A Radical Protection
- Author
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Steven E. Bottle, Kathryn E. Fairfull-Smith, Richard S. Grainger, Benjamin A. Chalmers, Yanchuan Zhao, Jason C. Morris, and Timothy M. Swager
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Chemistry ,Organic chemistry ,Photochemistry - Published
- 2014
17. Spin-coated carbon
- Author
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Kathryn E. Fairfull-Smith, Steven E. Bottle, Alison Chou, Benjamin A. Chalmers, and James P. Blinco
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Tetrafluoroborate ,Materials science ,Graphene ,Radical ,Aryl ,Inorganic chemistry ,Selective chemistry of single-walled nanotubes ,chemistry.chemical_element ,General Chemistry ,Carbon nanotube ,Glassy carbon ,law.invention ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,law ,Carbon - Abstract
We describe a novel and facile approach to covalently graft molecules containing stable free radicals onto carbon surfaces including graphene, carbon nanotubes, glassy carbon and carbon fibres. The new technique employs a stable aryl nitroxide radical diazonium tetrafluoroborate salt. The salt may be isolated and added to carbon surfaces in solution, suspension or electrochemically and represents a convenient, versatile and highly efficient means to adorn graphitic materials with large numbers of free radical spin systems.
- Published
- 2013
18. Cubane: A New NMR Internal Standard
- Author
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G. Paul Savage, Benjamin A. Chalmers, Annette P.-J. Chen, and Craig M. Williams
- Subjects
chemistry.chemical_compound ,Computational chemistry ,Carbon-13 NMR satellite ,Chemistry ,Cubane ,Chemical shift ,Ionic liquid ,Supramolecular chemistry ,Reactivity (chemistry) ,General Chemistry ,Carbon-13 NMR ,Quantum chemistry - Abstract
Cubane can be considered the ideal internal standard for reactions observed by NMR, due to an almost complete benign reactivity and uniquely reliable 1H and 13C NMR resonances, in wide variety of deuterated solvents.
- Published
- 2010
19. Microwave-Induced Molecular Rearrangements. Flash Thermolysis in the Gas-Phase and in Solution: Synthesis of Quinolones and Naphthyridones
- Author
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Rakesh N. Veedu, Curt Wentrup, Paul V. Bernhardt, Delphine Lecoq, Benjamin A. Chalmers, and David Kvaskoff
- Subjects
Green chemistry ,Reaction mechanism ,chemistry.chemical_compound ,chemistry ,Biocatalysis ,Ionic liquid ,Thermal decomposition ,Organic chemistry ,Infrared spectroscopy ,General Chemistry ,Photochemistry ,Dimethylamine ,Catalysis - Abstract
3- and 4-Pyridyliminopropadienones were prepared by flash vacuum thermolysis of Meldrum’s acid derivatives and characterized by low temperature IR spectroscopy. They react with dimethylamine to afford 1,5-, 1,6-, and 1,7-naphthyridones. The same naphthyridones are also obtained by microwave irradiation of the Meldrum’s acid derivatives. Quinolones were obtained by microwave irradiation of phenylaminomethylene-Meldrum’s acids and 1-phenylpyrrole-2,3-diones.
- Published
- 2009
20. Microwave-Induced Molecular Rearrangements. Flash Thermolysis in the Gas-Phase and in Solution: Synthesis of Quinolones and Naphthyridones.
- Author
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Delphine Lecoq, Benjamin A. Chalmers, Rakesh N. Veedu, David Kvaskoff, Paul V. Bernhardt, and Curt Wentrup
- Subjects
- *
REARRANGEMENTS (Chemistry) , *MICROWAVES , *SOLUTION (Chemistry) , *QUINOLINE , *NAPHTHYRIDINES , *ORGANIC synthesis , *ALLENE , *DIOXANE - Abstract
3- and 4-Pyridyliminopropadienones were prepared by flash vacuum thermolysis of Meldrum's acid derivatives and characterized by low temperature IR spectroscopy. They react with dimethylamine to afford 1,5-, 1,6-, and 1,7-naphthyridones. The same naphthyridones are also obtained by microwave irradiation of the Meldrum's acid derivatives. Quinolones were obtained by microwave irradiation of phenylaminomethylene-Meldrum's acids and 1-phenylpyrrole-2,3-diones. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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