AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

A monolith immobilised iridium Cp* catalyst for hydrogen transfer reactions under flow conditions

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Jan 082015
 

Graphical Abstract

http://pubs.rsc.org/en/Content/ArticleLanding/2015/OB/C4OB02376E#!divAbstract

A monolith immobilised iridium Cp* catalyst for hydrogen transfer reactions under flow conditions

*Corresponding authors
aDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK
bDepartment of Chemistry, University of Durham, South Road, Durham, UK
Org. Biomol. Chem., 2015, Advance Article

DOI: 10.1039/C4OB02376E

An immobilised iridium hydrogen transfer catalyst has been developed for use in flow based processing by incorporation of a ligand into a porous polymeric monolithic flow reactor. The monolithic construct has been used for several redox reductions demonstrating excellent recyclability, good turnover numbers and high chemical stability giving negligible metal leaching over extended periods of use.
info…………….
Insights into the iridium-catalyzed water oxidation mechanism from a DFT study

Dr. David Balcells, Prof. Odile Eisenstein, Prof. Robert H Crabtree, Agusti Lledos Departament de Quimica, Universitat Autonoma de Barcelona, Bellaterra, Spain; Institut Charles Gerhardt, Universite Montpellier 2, Montpellier, France; Department of Chemistry, Yale University, New Haven, United States

The development of a new energy model is a major challenge in modern chemistry. The climate change and the raise of oil prices prompt the development of clean and cheap energy resources. In this field, artificial photosynthesis is one of the most promising solutions.1 The catalytic oxidation of water to dioxygen is a fundamental part of this process. The mononuclear iridium complex Cp*Ir(ppy)(Cl) (ppy = phenylpyridine) is one of the most efficient catalysts reported for this reaction (Figure).2 DFT calculations support the oxo complex Cp*IrO(ppy) as the active species. The electronic structure of this complex is characterized by having the antibonding p*(Ir=O) orbitals half-occupied. The calculations suggest that the reaction mechanism consists of an intermolecular attack of water to the oxo ligand. This reaction involves the formation of the O-O bond and a proton transfer, which is assisted by the molecules of water solvating the catalyst.

Figure. Iridium-catalyzed water oxidation.

References
(1) Hammarström, L.; Hammes-Schiffer, S. Acc. Chem. Res. 200942, 1859-1860.
(2) Hull, J. F.; Balcells, D.; Blakemore, J. D.; Incarvito, C. D.; Eisenstein, O.; Brudvig, G. W.; Crabtree, R. H. J. Am. Chem. Soc.2009, 131, 8730-8731.

more info………….
The water-soluble iridium complex {Cp*Ir[6,6′-(OH)2bpy](H2O)}[OTf]2(Cp*=η5-pentamethylcyclopentadienyl, bpy=2,2′-bipyridine) was found to be a general and highly efficient catalyst for the N-alkylation of the poor nucleophilic sulfonamides with alcohols as alkylating agents in water. The presence of OH units in the bpy ligand is crucially important for the catalytic activity of the iridium complex. Mechanistic investigations revealed that the catalytically active species is a ligand-metal bifunctional iridium complex bearing an N,N′-chelated 2,2′-bipyridinated ligand and an aqua ligand. Notably, the present catalytic system and the proposed mechanism provide a new horizon and scope for the development of “hydrogen autotransfer (or hydrogen-borrowing) processes”.

The N-Alkylation of Sulfonamides with Alcohols in Water Catalyzed by the Water-Soluble Iridium Complex {Cp*Ir[6,6′-(OH)2bpy](H2O)}[OTf]2

  1. Panpan Qu,
  2. Chunlou Sun,
  3. Juan Ma and
  4. Feng Li*

Article first published online: 13 JAN 2014

DOI: 10.1002/adsc.201300711

http://onlinelibrary.wiley.com/doi/10.1002/adsc.201300711/abstract

 

 

 

 

http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-9-110

 

 

Functionalized carbenes

http://www.itqb.unl.pt/news/generating-new-catalysts

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Diastereoselective [2+2] Photocycloaddition of a Chiral Cyclohexenone with Ethylene in a Continuous Flow Microcapillary Reactor

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Jan 082015
 

The diastereoselective [2+2] photocycloaddition of ethylene to a chiral cyclohexenone was studied in a continuous flow microcapillary reactor. In all cases examined, the microcapillary reactor gave higher conversions and selectivity than the batch system, even after shorter irradiation times. These findings were explained by the superior temperature control, favorable light penetration, and generation of a gas–liquid slug flow with improved mass transfer in the microreactor.

Diastereoselective [2+2] Photocycloaddition of a Chiral Cyclohexenone with Ethylene in a Continuous Flow Microcapillary Reactor

http://www.akademiai.com/content/03163u0p80225v14/?p=bb18d4ec7c044f5c80013806493e8850&pi=2

Journal of Flow Chemistry
Publisher Akadémiai Kiadó
ISSN 2062-249X (Print)
2063-0212 (Online)
Subject Flow Chemistry
Issue Volume 2, Number 3/September 2012
Pages 73-76
DOI 10.1556/JFC-D-12-00005
Authors

 

Kimitada Terao1, Yasuhiro Nishiyama1, Hiroki Tanimoto1, Tsumoru Morimoto1, Michael Oelgemöller2, Kiyomi Kakiuchi1 Email for kakiuchi@ms.naist.jp

kakiuchi@ms.naist.jp, http://mswebs.naist.jp/LABs/kakiuchi/member/staff/CV_kakiuchi.pdf

1Nara Institute of Science and Technology (NAIST) Graduate School of Materials Science 8916-5 Takayama-cho, Ikoma Nara 630-0192 Japan
2James Cook University School of Pharmacy and Molecular Sciences Townsville QLD 4811 Australia

 

more………..

http://mswebs.naist.jp/LABs/kakiuchi/achevement/paper.htm

“Novel Enhancement of Diastereoselectivity of [2+2] Photocycloaddition of
Chiral Cyclohexenones to Ethylene by Adding Naphthalenes”

Ken Tsutsumi, Hiroaki Nakano, Akinori Furutani, Katsunori Endou, Abdurshit Merpuge
Takuya Shintani, Tsumoru Morimoto, Kiyomi Kakiuchi
J. Org. Chem. 200469, 3, 785-789.

 

“Diastereoselective [2+2] Photocycloaddition of Polymer-Supported
Cyclic Chiral Enone with Ethylene”

Takuya Shintani, Kazunori Kusabiraki, Atsuko Hattori, Akinori Furutani, Ken Tsutsumi,
Tsumoru Morimoto, Kiyomi Kakiuchi
Tetrahedron Lett. 200445, 9, 1849-1851.

 

“Diastereoselective [2+2] Photocycloaddition of Cyclohexenone Derivative with Olefines in Supercritical Carbon Dioxide
Yasuhiro Nishiyama, Kazuya Nakatani, Hiroki Tanimoto, Tsumoru Morimoto, Kiyomi Kakiuchi
J. Org. Chem. 201378, 7186-7193.

Highlighted in 
ChemInform 
201344(44)

 

 

“Diastereoselective [2+2] Photocycloaddition of Chiral Cyclic Enones with Olefins in Aqueous Media Using Surfactants”
Yasuhiro Nishiyama, Mikiko Shibata, Takuya Ishii, Tsumoru Morimoto, Hiroki Tanimoto,
Ken Tsutsumi, Kiyomi Kakiuchi
Molecules, 2013, 18, 1626-1637.

 

 

“Highly diastereodifferentiating and regioselective [2+2]-photoreactions using methoxyaromatic menthyl cyclohexenone carboxylates”
Inga Inhulsen, Naoya Akiyama, Ken Tsutsumi, Yasuhiro Nishiyama, Kiyomi Kakiuchi

Tetrahedron 2013, 69, 782-790.

 

“Diastereodifferentiating [2+2] Photocycloaddition of Chiral Cyclohexenone Carboxylates with Cyclopentene by a Microreactor”
Kimitada Terao, Yasuhiro Nishiyama, Shin Aida, Hiroki Tanimoto, Tsumoru Morimoto,
Kiyomi Kakiuchi
J. Photochem. Photobiol. A: Chem. 2012242, 13-19.

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Synthesis of Methoxyisopropyl (MIP)-Protected (R)-Mandelonitrile and Derivatives in a Flow Reactor

 SYNTHESIS  Comments Off on Synthesis of Methoxyisopropyl (MIP)-Protected (R)-Mandelonitrile and Derivatives in a Flow Reactor
Jan 042015
 

 

 

 

Cyanohydrins are synthetically versatile chiral building blocks in organic synthesis. They can be conveniently synthesized in enantiomerically pure form via chemoenzymatic hydrogen cyanide addition onto the corresponding aldehyde using hydroxynitrile lyase.

Recently, we reported that such transformations can be efficiently carried out in a continuous flow manner using microreactors. Since racemization of enantiopure cyanohydrins occurs readily under slightly basic conditions, they should be protected before the follow-up reactions, preferably under acidic conditions.

In this contribution, we demonstrate that the methoxyisopropyl protection of mandelonitrile can be conveniently optimized in an automated microscale continuous flow system and subsequently scaled up under the same conditions by applying a larger flow reactor.

 

Synthesis of Methoxyisopropyl (MIP)-Protected (R)-Mandelonitrile and Derivatives in a Flow Reactor

http://www.akademiai.com/content/9488206462627n38/?p=6ed413d7b9fb47fe9fe7e1262c37694f&pi=2

Journal of Flow Chemistry
Publisher Akadémiai Kiadó
ISSN 2062-249X (Print)
2063-0212 (Online)
Subject Flow Chemistry
Issue Volume 2, Number 4/December 2012
Pages 124-128
DOI 10.1556/JFC-D-12-00008

Radboud University

Authors
Mariëlle M.E. Delville, Jasper J.F. Gool, Ivo M. Wijk, Jan C.M. Hest, Floris P.J.T. Rutjes1 Email for f.rutjes@science.ru.nl  f.rutjes@science.ru.nl

1Institute for Molecules and Materials Radboud University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen the Netherlands

Floris P.J.T. Rutjes

Groepsfoto IMM 2014 klein-1

 

The IMM-office is located on the 3rd floor of the Huygens building, which is at walking distance (about 5 min.) from the railway station Nijmegen Heyendaal.

 

 

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Jan 012015
 

IMAGE……….http://www.laboratorytalk.com/life-sciences-and-clinical-laboratory-equipment/synthesis-systems/flow-chemistry-system-aids-synthesis-of-cns-drugs/404882.article

 

 

1…………………

 

Gleevec, developed by Novartis, is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours. The drug molecule represents a particularly challenging target for flow chemistry because of the low solubility of many of the reaction components required for its synthesis. The team devised a new synthesis route that prevents the equipment blockages from product precipitation and avoids many of the labour and time intensive practices of traditional batch-based preparation.

 

flow synthesisThe flow-based route required minimal manual intervention and was achieved despite poor solubility of many reaction componentsLINK………...http://www.rsc.org/chemistryworld/2013/01/flow-synthesis-anticancer-drug

2…………………..

Malaria is a serious global health issue. Artemisinin combination treatments are the first-line drugs, but supplies are limited because artemisinin is obtained solely by extraction from Artemisia annua. A continuous-flow process that converts dihydroartemisinic acid into artemisinin (see scheme) was shown to be an inexpensive and scalable process that can ensure a steady, affordable supply of artemisinin.

Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin

  1. Dr. François Lévesque1 and
  2. Prof. Dr. Peter H. Seeberger1,2,*

Article first published online: 16 JAN 2012

DOI: 10.1002/anie.201107446………….http://onlinelibrary.wiley.com/doi/10.1002/anie.201107446/abstract

 

 

IMAGE………..http://phys.org/news/2013-08-chemists-fresh-approach-alloy-nanomaterials.html

 

 

 

3……………….

 

http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-9-265

 

 

IMAGE……..http://www.chemistryviews.org/details/ezine/1058453/Women_in_ChemistryA_European_Journal.html

 

 

4…………………….

 

http://www.rsc.org/chemistryworld/2014/09/antimalarial-flow-synthesis-commercialisation-artemisinin

 

 

 

 

5…………………………….

http://pipeline.corante.com/archives/2014/04/

 

http://www.chemistryviews.org/details/ezine/5753931/Liliana_Mammino_Research_and_Education_in_Sub-Saharan_Africa.html

 

 

 

6…………………………

http://pubs.rsc.org/en/content/articlelanding/2013/ob/c2ob27003j#!divAbstract

 http://www.amnh.org/learn-teach/young-naturalist-awards/winning-essays2/2013-winning-essays/optimizing-algae-biofuels-applied-natural-selection-to-improve-lipid-synthesis

 

 

 

7…………………..

 

http://onlinelibrary.wiley.com/doi/10.1002/anie.201305429/abstract

http://www.rsc.org/chemistryworld/2012/04/iron-lady

 

 

8………………………..

http://www-medchem.ch.cam.ac.uk/hot_topics.php

http://www.ollusa.edu/s/1190/ollu.aspx?pgid=2674

 

 

 

9…………………………

http://www.mdpi.com/1420-3049/19/7/9736

http://www.ed.ac.uk/alumni/services/news/news/femalechemists

 

 

 

10…………………

 

http://newdrugapprovals.org/2014/12/31/continuous-flow-synthesis-of-alpha-halo-ketones-building-blocks-for-anti-retroviral-agents/

main image

 

http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_26-9-2013-11-6-53

 

 

 

 

11……………………

 

http://pubs.rsc.org/en/content/articlehtml/2013/ob/c3ob41464g

 

http://emmittnlxe.soup.io/

 

 

 

 

12………………………..

http://pubs.rsc.org/en/content/articlelanding/2012/sc/c2sc21850j#!divAbstract

 

IMAGE……..http://evnewsreport.com/tag/battery/

 

 

 

 

13……………….

 

 

http://www.leygroup.ch.cam.ac.uk/research/continuous-flow-methodology/heterocycles-flow

IMAGE……….http://www.chemistryviews.org/details/ezine/1059875/Women_in_Chemistry__Interview_with_Zeinab_Shaaban_Abd_El-Ati_Abou_El-Naga.html

 

 

 

14………………..

 

http://www.sfu.ca/chemistry/groups/britton/publications.html

 

 

 

IMAGE……….http://www.greentechnolog.com/green_chemistry/

 

 

 

 

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RUFINAMIDE….FLOW SYNTHESIS

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Jan 012015
 

A report (Org Process Res Dev 2014, ASAP article) out of Jamison’s group at MIT, provides a 3-step synthesis of Rufinamide in 92% overall yield. The process illustrates a continuous and convergent method, moving away from the isolation of a key organic azide intermediates and a Cu coiled-tube reactor for the cycloaddition reaction to the corresponding desired triazole.

http://pubs.acs.org/doi/abs/10.1021/op500166n

Small molecules bearing 1,2,3-triazole functionalities are important intermediates and pharmaceuticals. Common methods to access the triazole moiety generally require the generation and isolation of organic azide intermediates. Continuous flow synthesis provides the opportunity to synthesize and consume the energetic organoazides, without accumulation thereof. In this report, we described a continuous synthesis of the antiseizure medication rufinamide. This route is convergent and features copper tubing reactor-catalyzed cycloaddition reaction. Each of the three chemical steps enjoys significant benefits and has several advantages by being conducted in flow. The total average residence time of the synthesis is approximately 11 min, and rufinamide is obtained in 92% overall yield.

 

 

 

 

 

Thumbnail image of graphical abstract

Give it a flow: A continuous-flow process for the synthesis of a 1,2,3-triazole precursor of Rufinamide has been developed. The protocol involves a solvent- and catalyst-free operation and utilizes reaction temperatures above the melting point of the target product to prevent microreactor clogging, resulting in a decrease of the operating time from hours to minutes.

Solvent- and Catalyst-Free Huisgen Cycloaddition to Rufinamide in Flow with a Greener, Less Expensive Dipolarophile

  1. Svetlana Borukhova1,
  2. Dr. Timothy Noël1,*,
  3. Bert Metten2,
  4. Eric de Vos2 and
  5. Prof. Dr. Volker Hessel1,*

Article first published online: 23 SEP 2013

DOI: 10.1002/cssc.201300684

http://onlinelibrary.wiley.com/doi/10.1002/cssc.201300684/abstract

 

 

 

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An Integrated Synthesis–Purification System to Accelerate the Generation of Compounds in Pharmaceutical Discovery

 SYNTHESIS  Comments Off on An Integrated Synthesis–Purification System to Accelerate the Generation of Compounds in Pharmaceutical Discovery
Dec 302014
 

An Integrated Synthesis–Purification System to Accelerate the Generation of Compounds in Pharmaceutical Discovery

http://www.akademiai.com/content/r1t41145nn051252/?p=27bf59e482ec4093985c1e9ec3df3aba&pi=1

Flow Chemistry
Issue Volume 1, Number 2/December 2011
Pages 56-61
DOI 10.1556/jfchem.2011.00013
Authors
Jill E. Hochlowski1, Philip A. Searle2, Noah P. Tu1, Jeffrey Y. Pan3, Stephen G. Spanton1, Stevan W. Djuric2 Email for stevan.w.djuric@abbott.com

1Structural Chemistry, Advanced Technology, Global Research and Development, Abbott Laboratories 100 Abbott Park Road 60064 Abbott Park, IL USA
2Medicinal Chemistry Technologies, Advanced Technology, Global Research and Development, Abbott Laboratories 100 Abbott Park Road 60064 Abbott Park, IL USA
3Automation Engineering, Advanced Technology, Global Research and Development, Abbott Laboratories 100 Abbott Park Road 60064 Abbott Park, IL USA

Abstract

We report herein a high-throughput integrated ynthesis–purification platform termed SWIFT (synthesis with integrated-flow technology) and processes that accelerate the rate at which validated small-molecule organic compounds are generated. A segmented-flow synthesizer was integrated to a preparative HPLC-MS, where each reaction product was purified immediately upon reaction completion. Further, automated structure-validation processes accelerate the rate at which drug discovery candidates are available for biological screening.

Keywords
flow synthesis, high-throughput organic synthesis, high-throughput purification, segmented flow, meso-flow

 

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Ensuring Process Stability with Reactor Temperature Control Systems

 PROCESS, spectroscopy, SYNTHESIS  Comments Off on Ensuring Process Stability with Reactor Temperature Control Systems
Dec 272014
 

Temperature control plays an important role in industrial processes, pilot plants, and chemical and pharmaceutical laboratories. When controlling reactors, both exothermic and endothermic reactions must be offset with high speed and reliability. Therefore, different conditions and effects must be taken into account when specifying an optimum and highly dynamic temperature control system.

Temperature Control of Reactors

Most temperature control systems are used with chemical reactors made of either steel or glass. The former is more rugged and long-lasting, while the latter enables chemists to observe processes inside the reactor.

However, in the case of glass reactors, extensive precautions have to be followed for safe usage. Reactors usually include an inner vessel to hold the samples, which need temperature control. This inner vessel is enclosed by a jacket containing heat-transfer liquid. This reactor jacket is linked to the temperature control system.

In order to control the reactor’s temperature, the temperature control system pumps the heat-transfer liquid through the reactor’s jacket. Rapid temperature change inside the reactor is balanced by instant cool-down or heat-up, and the liquid is either cooled or heated inside the temperature control system. Figure 1 shows a schematic of a simple temperature control system.

Figure 1. Functional view of reactor temperature control

Process Stability

Both materials and reactor design can affect the temperature control of highly dynamic reactor systems. However, the heat transferred by a glass-walled vessel will be different than that transferred by a steel-walled vessel. In addition, both wall thickness and surface area can also affect accuracy. Therefore, proper mixing of the initial materials inside the reactor is important to obtain good uniformity, which in turn will guarantee optimal heat exchange.

For each type of reactor, maximum pressure values have been provided as per the specifications established by reactor manufacturers and in the Pressure Equipment Directive 97/23/EG. Regardless of any temperature control application, these limit values may not be surpassed during operation under any situations. Prior to starting a temperature control application, the applicable limits must be programmed within the temperature control unit.

Another important criterion in reactors is the maximum permissible temperature difference, which is referred to as Delta-T limit. It defines the highest difference between the temperature of the contents of the reactor and the actual thermal fluid temperature.

When compared to steel reactors, glass reactors are more susceptible to thermal stress. For that matter, any temperature control system should enable users to program reactor-specific values for the Delta-T limit per time unit. Within the temperature control equipment itself, three components considerably affect the stability of the process and these include heat exchanger, pump, and control electronics.

 

Heat Exchanger

It is important to ensure that a temperature control system has sufficient heating and cooling capacity, as this can significantly affect the speed to reach the preferred temperatures. In order to determine the preferred heating and cooling capacities, users must consider the essential differences in temperature, the volume of the samples, the preferred heat-up and cool-down times, and the specific heat capacity of the temperature control medium.

Highly dynamic temperature control solutions are commercially available in the market with water or air cooling. Air-cooled systems do not utilize water and may be deployed where there is sufficient air flow.

The heat thus removed from the reactor is eventually transferred to ambient air. Water-cooled systems need to be joined to a cooling water supply, but they operate more quietly and do not add surplus heat in small labs. These units could be completely enclosed by the application, if required.

 

 

 

Pump

The integrated pump of the temperature control unit equipment must be sufficiently strong to obtain the preferred flow rates at stable pressure. To ensure that pressure limit values mentioned above are not exceeded, the pump should provide the preferred pressure quickly and with maximum control.

Operating conditions and pressure specifications of the reactor must always be taken into account, and regulation of pump capacity must be done by presetting a limit value. Sophisticated temperature control solutions include pumps that balance the variations of the viscosity of the heat transfer liquid to make sure that energy efficiency is maintained continuously.

This is because viscosity influences flow and hence the heat transfer. An additional advantage provided by magnetically coupled pumps is that they guarantee a hydraulically-sealed thermal circuit. Also, self-lubricated pumps are beneficial as they require only minimum maintenance.

The closed loop circuit prevents contact between the ambient air and the heat transfer liquid. This not only prevents permeation of oxidation and moisture, bit also prevents oil vapors from entering into the work environment.

 

Additionally, an internal expansion vessel must permanently absorb temperature-induced volume variations inside the heat exchanger. Individual cooling of the expansion vessel will help in ensuring that the temperature control unit does not overheat and ultimately ensures operator safety.

A temperature control equipment should operate consistently even at high ambient temperatures. In majority of cases, the real work environment will diverge from the ideal temperature of 20°C. During hot summer months, temperature control solutions are exposed to adverse conditions. In laboratories, ambient temperatures are usually higher because of energy saving measures. These instances demonstrate the benefits of temperature control solutions that work consistently at temperatures as high as 35°C.

 

 

Control Electronics

Temperature control equipment includes advanced control electronics that monitor and control the process inside the reactor and also the internal processes of the system. When a control variable changes, the system is capable of readjusting the variable to the setpoint sans overshooting.

Accurate control electronics are needed to maintain the stability of a temperature control application. One option to assess control electronics is to look at the effort needed to set parameters. In a temperature control unit, users can enter a setpoint. Control electronics must be self-optimizing throughout the temperature control process to ensure optimum results.

 

 

Conclusion

To sum up, the process safety and stability during reactor temperature control relies on the effectiveness of heat transfer, the type of reactor, and the efficiency of the components within the temperature control unit. Therefore, different conditions and effects must be considered when specifying a highly dynamic temperature control system.

 

 

 

 

 

 

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5-hydroxy-4-keto-pentenoic acid (HKPA).

 PROCESS, SYNTHESIS  Comments Off on 5-hydroxy-4-keto-pentenoic acid (HKPA).
Dec 262014
 

 

C. Oliver Kappe, University of Graz, Austria, and colleagues prepared for the first time the potential new platform molecule H2MF in pure form and converted it to the polyester precursor 5-hydroxy-4-keto-pentenoic acid (HKPA).

read at

http://www.chemistryviews.org/details/ezine/7176481/.html

 

cokappe

C. Oliver Kappe

THE KAPPE LABORATORY
Institute of Chemistry, University of Graz, Austria

C. Oliver Kappe is Professor of Chemistry at the University of Graz, Austria. He received his diploma- (1989) and his doctoral (1992) degrees in organic chemistry from the University of Graz where he worked with Professor Gert Kollenz on cycloaddition and rearrangement reactions of acylketenes. After periods of postdoctoral research work on reactive intermediates and matrix isolation spectroscopy with Professor Curt Wentrup at the University of Queensland in Brisbane, Australia (1993-1994) and on synthetic methodology/alkaloid synthesis with Professor Albert Padwa at Emory University in Atlanta, USA (1994-1996), he moved back to the University of Graz in 1996 to start his independent academic career. He obtained his “Habilitation” in 1998 in organic chemistry and was appointed Associate Professor in 1999. Since 2011 he holds the position of Professor of “Technology of Organic Synthesis” (Organische Synthesetechnologie) at the Instittue of Chemistry at the University of Graz. He has spent time as visiting scientist/professor at e.g. the Scripps Research Institute (La Jolla, USA, Professor K. Barry Sharpless, 2003), the Toyko Institute of Technology (Toyko, Japan, Professor T. Takahashi, 2008), the University of Sassari (Sassari, Italy, 2008), the Sanford-Burnham Institute for Medical Research (Orlando, USA, 2010) and the Federal University of Rio de Janeiro (Ri de Janeiro, Brazil, 2013).

The co-author of ca. 350 publications, his main research interests have in the past focused on multicomponent reactions, combinatorial chemistry and the synthesis of biologically active heterocycles. More recently his research group has been involved with enabling and process intensification technologies, including microwave and continuous flow chemistry. For his innovative work in microwave chemistry he received the 2004 Prous Science Award from the European Federation for Medicinal Chemistry and the 2010 Houska Prize (100.000 €) in addition to a number of other awards.

C. Oliver Kappe is currently Editor-in-Chief of the Journal of Flow Chemistry (Akadémiai Kiadó) and a board member of the Flow Chemistry Society. In addition he has been an Editor of the Journal QSAR and Combinatorial Sciences (Wiley-VCH, 2003-2007) and has served/serves on the Editorial/Advisory Boards of the Journal of Combinatorial Chemistry (ACS), Molecular Diversity (Springer), ChemMedChem and ChemSusChem (Wiley-VCH), Journal of Heterocyclic Chemistry (Wiley-VCH) and a number of other journals.

SEE

http://oneorganichemistoneday.blogspot.in/2014/12/dr-c-oliver-kappe.html

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(S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on (S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE
Dec 192014
 

 

 

 

(S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone

bp 85–87°C at 3.7 mm, [α]21D + 23.0° (CHCl3, c 2.0)

The spectral properties of (S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone are as follows:

 

IR vmax (film) cm−1: 3470 (s), 1705 (s), 1120 (m), 1055 (s), 985 (s), 965 (m);

 

1H NMR (250 MHz, CDCl3) δ: 1.11 (s, 3 H), 1.15 (s, 3 H), 1.60–1.71 (m, 1 H), 1.76–1.86 (m, 1 H), 1.96–2.05 (m, 2 H), 2.16 (br s, 1 H), 2.35–2.45 (m, 2 H), 3.69 (dd, 1 H, J = 7.6, 2.9);

 

13C NMR (76 MHz, CDCl3) δ: 19.7, 20.7, 22.9, 29.0, 37.3, 51.3, 77.8, 215.3.

The optical purity of (S)-(+)-3-hydroxy-2,2-dimethylcyclohexanone can be determined by HPLC analysis.
The (S)-α-methoxy-α-trifluoromethylphenylacetate (MTPA ester) is prepared according to the reported procedure:3 HPLC analysis (Column, Nucleosil® 50-5, 25 cm × 4.6 mm; eluant, hexane : THF = 30 : 1, 1.03 mL/min; detected at UV 256 nm) retention time 35.6 min (98.0–99.4%) and 29.6 min (0.6–(2.0%). Therefore, the optical purity is determined to be 96.0–98.8% ee.
Analysis of the MTPA ester of this product by 250 MHz 1H NMR and capillary GLC (12.5 m, 5% methyl silicone column) failed to detect any more of the minor diastereomer than would have been expected from the purity (98% ee) of the MTPA-Cl employed.

 

NOTE….Intermediate is

2,2-dimethylcyclohexane-1,3-dione bp 92–97°C (4 mm)

37–38°C.

The spectra are as follows: 1H NMR (250 MHz, CDCl3) δ: 1.29 (s, 6 H), 1.93 (5 lines, 2 H, J = 6.5), 2.67 (t, 4 H, J = 6.9); 13C NMR (76 MHz, CDCl3) δ: 18.1, 22.3, 37.4, 61.8, 210.6.

 

Natural products synthesized from (S)-3-hydroxy-2,2-dimethylcyclohexanone
Figure 1. Natural products synthesized from (S)-3-hydroxy-2,2-dimethylcyclohexanone

 


References and Notes
  1. Department of Agricultural Chemistry, The University of Tokyo, Yayoi 1-1-1, Bunkyo-Ku, Tokyo 113, Japan.
  2. Mekler, A. B.; Ramachandran, S.; Swaminathan, S.; Newman, M. S. Org. Synth., Coll. Vol. V 1973, 743, 3.
  3. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
  4. Kieslich, K. “Microbial Transformations of Non-Steroid Cyclic Compounds;” Georg Thieme; Stuttgart, 1976, pp. 28–31.
  5. Lu, Y.; Barth, G.; Kieslich, K.; Strong, P. D.; Duax, W. L.; Djerassi, C. J. Org. Chem. 1983, 48, 4549.
  6. Mori, K.; Mori, H. Tetrahedron 1985, 41, 5487.
  7. Yanai, M.; Sugai, T.; Mori, K. Agric. Biol. Chem. 1985, 49, 2373.
  8. Mori, K.; Watanabe, H. Tetrahedron 1986, 42, 273.
  9. Mori, K.; Nakazono, Y. Tetrahedron 1986, 42, 283.
  10. Mori, K.; Mori, H.; Yanai, M. Tetrahedron 1986, 42, 291.
  11. Mori, K.; Tamura, H. Tetrahedron 1986, 42, 2643.
  12. Sugai, T.; Tojo, H.; Mori, K. Agric. Biol. Chem. 1986, 50, 3127.
  13. Mori, K.; Mori, H. Tetrahedron 1986, 42, 5531.
  14. Mori, K.; Mori, H. Tetrahedron 1987, 43, 4097.
  15. Mori, K.; Komatsu, M. Liebigs Ann. Chem. 1988, 107.

 

 

 

 

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Dithiocarbamates: Reagents for the Removal of Transition Metals from Organic Reaction Media

 SYNTHESIS  Comments Off on Dithiocarbamates: Reagents for the Removal of Transition Metals from Organic Reaction Media
Dec 162014
 

Figure

Dithiocarbamates: Reagents for the Removal of Transition Metals from Organic Reaction Media

http://pubs.acs.org/doi/abs/10.1021/op500336h

Chemical Development, Bristol-Myers Squibb Co., 1 Squibb Drive, New Brunswick, New Jersey 08903,United States
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/op500336h
Dithiocarbamates (DTCs) are ligands known to chelate with Cu and other transition metals to form insoluble complexes. Wastewater treatment protocols have utilized DTCs to remove trace (ppb) metals from waste streams. We have extended the applicability of DTCs to a protocol that readily enables control of the residual Cu in isolated material in a quick and cost-effective manner. Formation of the chelate complex typically results in purging of Cu and a variety of other metals in an array of reaction media to ≤10 ppm. Furthermore, the simplicity of the method makes it very attractive for large-scale applications late in a synthetic sequence because of the low toxicity and efficient removal of the metal complex by filtration.
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