Heterogeneous catalytic hydrogenation reactions in continuous-flow reactors.

Microreactor technology and continuous flow processing in general are key features in making organic synthesis both more economical and environmentally friendly. Heterogeneous catalytic hydrogenation reactions under continuous flow conditions offer significant benefits compared to batch processes which are related to the unique gas-liquid-solid triphasic reaction conditions present in these transformations. In this review article recent developments in continuous flow heterogeneous catalytic hydrogenation reactions using molecular hydrogen are summarized. Available flow hydrogenation techniques, reactors, commonly used catalysts and examples of synthetic applications with an emphasis on laboratory-scale flow hydrogenation reactions are presented.

[1]  D. Hönicke,et al.  Microfabricated components for heterogeneously catalysed reactions , 1996 .

[2]  Steven V Ley,et al.  Synthesis of acetal protected building blocks using flow chemistry with flow I.R. analysis: preparation of butane-2,3-diacetal tartrates. , 2009, Organic & biomolecular chemistry.

[3]  A. Baiker,et al.  In Situ Infrared Spectroscopy of Catalytic Solid−Liquid Interfaces Using Phase-Sensitive Detection: Enantioselective Hydrogenation of a Pyrone over Pd/TiO2 , 2002 .

[4]  P. Dyson,et al.  Structured fiber supports for ionic liquid-phase catalysis used in gas-phase continuous hydrogenation , 2007 .

[5]  Freek Kapteijn,et al.  Mass transfer characteristics of three-phase monolith reactors , 2001 .

[6]  A. Baiker,et al.  Enantioselective Hydrogenation on Palladium: Limitations of Continuous Fixed-Bed Reactor Operation , 2002 .

[7]  A. Lapkin,et al.  Liquid phase hydrogenation in a structured multichannel reactor , 2009 .

[8]  D. Murzin,et al.  Origin of ligand acceleration in heterogeneous ethyl pyruvate hydrogenation , 2006 .

[9]  G. Ertl,et al.  Handbook of Heterogeneous Catalysis , 1997 .

[10]  Jc Jaap Schouten,et al.  Selective Hydrogenation of 2-Methyl-3-butyne-2-ol in a Wall-Coated Capillary Microreactor with a Pd25Zn75/TiO2 Catalyst , 2009 .

[11]  A. Baiker,et al.  Continuous Enantioselective Hydrogenation of Ethyl Pyruvate in “Supercritical” Ethane: Relation between Phase Behavior and Catalytic Performance , 2001 .

[12]  D. Murzin,et al.  Modelling of transient kinetics in catalytic three-phase reactors: Enantioselective hydrogenation , 2010 .

[13]  R. S. Besser,et al.  Hydrocarbon hydrogenation and dehydrogenation reactions in microfabricated catalytic reactors , 2003 .

[14]  D. Ferri,et al.  Molecular insight into the dynamics of chiral modification of Pt/alumina , 2007 .

[15]  Didier Rognan,et al.  Increasing selectivity of CC chemokine receptor 8 antagonists by engineering nondesolvation related interactions with the intended and off-target binding sites. , 2009, Journal of medicinal chemistry.

[16]  Hydrogenation reactions using scCO2 as a solvent in microchannel reactors. , 2005, Chemical communications.

[17]  P. Wells,et al.  Enantioselective hydrogenation: II. variation of activity and optical yield with experimental variables in methyl pyruvate hydrogenation catalyzed by cinchona-modified platinum/silica (EUROPT-1) , 1991 .

[18]  Leonid B. Datsevich,et al.  Multiphase fixed-bed technologies: Comparative analysis of industrial processes (experience of development and industrial implementation) , 2004 .

[19]  Philipp Rudolf von Rohr,et al.  Transparent silicon/glass microreactor for high-pressure and high-temperature reactions , 2008 .

[20]  Volker Hessel,et al.  High Throughput Kinetic Investigations of Asymmetric Hydrogenations with Microdevices , 2003 .

[21]  Holger Löwe,et al.  Chemie in Mikrostrukturreaktoren , 2004 .

[22]  A. Baiker,et al.  Continuous enantioselective hydrogenation in fixed-bed reactor: towards process intensification , 2003 .

[23]  F. Fülöp,et al.  Origin of the rate enhancement and enantiodifferentiation in the heterogeneous enantioselective hydrogenation of 2,2,2-trifluoroacetophenone over Pt/alumina studied in continuous-flow fixed-bed reactor system , 2010 .

[24]  Asterios Gavriilidis,et al.  Catalyst preparation and deactivation issues for nitrobenzene hydrogenation in a microstructured falling film reactor , 2003 .

[25]  M. N. Kashid,et al.  A novel compact reactor for three-phase hydrogenations , 2010 .

[26]  Simon J. F. Macdonald,et al.  Mesoscale Flow Chemistry: A Plug-Flow Approach to Reaction Optimisation , 2007 .

[27]  Peter R Bernstein,et al.  De novo design of a picomolar nonbasic 5-HT(1B) receptor antagonist. , 2010, Journal of medicinal chemistry.

[28]  Hans-Joachim Gabius,et al.  Synthesis of bivalent lactosides based on terephthalamide, N,N'-diglucosylterephthalamide, and glycophane scaffolds and assessment of their inhibitory capacity on medically relevant lectins. , 2009, The Journal of organic chemistry.

[29]  K. Nitta,et al.  Continuous hydrogenation reactions in a tube reactor packed with Pd/C. , 2005, Chemical communications.

[30]  M. Madou Fundamentals of microfabrication , 1997 .

[31]  James G. Stevens,et al.  Maximising opportunities in supercritical chemistry: the continuous conversion of levulinic acid to gamma-valerolactone in CO(2). , 2007, Chemical communications.

[32]  C. Bellefon,et al.  Micro-structured reactors as a tool for chiral modifier screening in gas-liquid-solid asymmetric hydrogenations , 2007 .

[33]  D. Murzin,et al.  Continuous Enantioselective Hydrogenation of Ethylbenzoylformate over Pt/Al2O3 Catalyst: Bed Dilution Effects and Cinchonidine Adsorption Study , 2004 .

[34]  Trond Ulven,et al.  A multistep continuous-flow system for rapid on-demand synthesis of receptor ligands. , 2009, Organic letters.

[35]  K. Jensen,et al.  Design and fabrication of microfluidic devices for multiphase mixing and reaction , 2002 .

[36]  Nathalie Tanchoux,et al.  Microreactors for Dynamic, High Throughput Screening of Fluid/Liquid Molecular Catalysis , 2000 .

[37]  Volker Hessel,et al.  Sustainability through green processing – novel process windows intensify micro and milli process technologies , 2008 .

[38]  Michael P. Harold,et al.  Micromachined reactors for catalytic partial oxidation reactions , 1997 .

[39]  I. Collins,et al.  Synthesis and reactivity of 3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones: development of a novel kinase-focussed library , 2010 .

[40]  Lauren J. Kang,et al.  Recycling the waste: the development of a catalytic wittig reaction. , 2009, Angewandte Chemie.

[41]  Fernando Benito-Lopez,et al.  High pressure in organic chemistry on the way to miniaturization , 2008 .

[42]  C. Kappe,et al.  Heterogeneous hydrogenation reactions using a continuous flow high pressure device. , 2005, Journal of combinatorial chemistry.

[43]  Roger A. Sheldon,et al.  The E Factor: fifteen years on , 2007 .

[44]  P. Licence,et al.  Continuous catalytic reactions in supercritical fluids , 2001 .

[45]  F. Kapteijn,et al.  Fast gas–liquid–solid reactions in monoliths: A case study of nitro-aromatic hydrogenation , 2005 .

[46]  西村 重夫 Handbook of heterogeneous catalytic hydrogenation for organic synthesis , 2001 .

[47]  M. Bartók,et al.  Novel Evidence on the Role of the Nucleophilic Intermediate Complex in the Orito-Reaction: Unexpected Inversion in the Enantioselective Hydrogenation of 2,2,2-Trifluoroacetophenone on Pt-Cinchona Chiral Catalyst Using Continuous-Flow Fixed-Bed Reactor , 2010 .

[48]  F. Darvas,et al.  Nanoparticle synthesis completed with in situ catalyst preparation performed on a high-pressure high-temperature continuous flow reactor , 2008 .

[49]  H. Müller‐Bunz,et al.  Synthesis of sugar-lactams from azides of glucuronic acid. , 2007, Carbohydrate research.

[50]  Jun-ichi Yoshida,et al.  Flash chemistry: fast chemical synthesis by using microreactors. , 2008, Chemistry.

[51]  A. Schmidt,et al.  Partial hydrogenation of sunflower oil in a membrane reactor , 2007 .

[52]  Jeffrey Y. Pan,et al.  Construction and validation of an automated flow hydrogenation instrument for application in high-throughput organic chemistry. , 2008, Journal of combinatorial chemistry.

[53]  Steven V. Ley,et al.  ReactIR Flow Cell: A New Analytical Tool for Continuous Flow Chemical Processing , 2010 .

[54]  C. Kappe,et al.  Microwave-assisted solution phase synthesis of dihydropyrimidine C5 amides and esters , 2006 .

[55]  Andreas Kirschning,et al.  Combining enabling techniques in organic synthesis: continuous flow processes with heterogenized catalysts. , 2006, Chemistry.

[56]  R. DesJarlais,et al.  Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors. , 2009, Journal of medicinal chemistry.

[57]  A. Milewska,et al.  Biphasic hydrogenation of α-pinene in high-pressure carbon dioxide , 2005 .

[58]  S. Schaus,et al.  Asymmetric Mannich reaction of dicarbonyl compounds with alpha-amido sulfones catalyzed by cinchona alkaloids and synthesis of chiral dihydropyrimidones. , 2007, The Journal of organic chemistry.

[59]  J. Kobayashi,et al.  Multiphase organic synthesis in microchannel reactors. , 2006, Chemistry, an Asian journal.

[60]  F. Joó,et al.  Selective catalytic hydrogenations in a microfluidics-based high throughput flow reactor on ion-exchange supported transition metal complexes: A modular approach to the heterogenization of soluble complex catalysts , 2007 .

[61]  Wolfgang Ehrfeld,et al.  State-of-the-art in microreaction technology : concepts, manufacturing and applications , 1999 .

[62]  W. Leitner,et al.  Continuous Enantioselective Hydrogenation with a Molecular Catalyst in Supported Ionic Liquid Phase under Supercritical CO2 Flow , 2010 .

[63]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[64]  Dieter Hönicke,et al.  Heterogeneously Catalyzed Gas-Phase Hydrogenation of cis,trans,trans-1,5,9-Cyclododecatriene on Palladium Catalysts Having Regular Pore Systems , 1996 .

[65]  P. Canu,et al.  Kinetic experiments and modeling of a three-phase catalytic hydrogenation reaction in supercritical CO2 , 1999 .

[66]  P. Robinson,et al.  Supported transition metal complexes: V. Liquid phase catalytic hydrogenation of hexene-1, cyclohexene and isoprene under continuous flow conditions , 1976 .

[67]  E. L. Moreno,et al.  Tetralin hydrogenation on dealuminated Y zeolite-supported bimetallic Pd-Ir catalysts , 2008 .

[68]  Continuous catalytic hydrogenation of polyaromatic hydrocarbon compounds in hydrogen-supercritical carbon dioxide. , 2007, Environmental science & technology.

[69]  Claude de Bellefon,et al.  High-Throughput Screening of Molecular Catalysts Using Automated Liquid Handling, Injection, and Microdevices , 2002 .

[70]  Q. Xin,et al.  Heterogeneous asymmetric hydrogenation of ethyl pyruvate on chirally modified Pt/Al2O3 catalyst with fixed-bed reactor , 2000 .

[71]  J. Grunwaldt,et al.  Continuous catalytic "one-pot" multi-step synthesis of 2-ethylhexanal from crotonaldehyde. , 2007, Chemical communications.

[72]  Zheng Wang,et al.  Development of a continuous-flow system for asymmetric hydrogenation using self-supported chiral catalysts. , 2009, Chemistry.

[73]  Xiaohong Li,et al.  Enantioselective Hydrogenation of Ethyl-2-oxo-4-phenylbutyrate on Cinchonidine-Modified Pt/γ-Al2O3 Catalyst Using a Fixed-Bed Reactor , 2001 .

[74]  F. Dautzenberg,et al.  New Catalyst Synthesis and Multifunctional Reactor Concepts for Emerging Technologies in the Process Industry , 2004 .

[75]  Ryan L Hartman,et al.  Microchemical systems for continuous-flow synthesis. , 2009, Lab on a chip.

[76]  A. Baiker,et al.  Hydrogenation of citral over Pd/alumina: comparison of supercritical CO2 and conventional solvents in continuous and batch reactors , 2004 .

[77]  R. Bogel-Łukasik,et al.  Effect of Flow Rate of a Biphasic Reaction Mixture on Limonene Hydrogenation in High Pressure CO2 , 2009 .

[78]  Sven K. Weber,et al.  High-throughput screening of catalysts by combining reaction and analysis. , 2007, Angewandte Chemie.

[79]  Roger A. Sheldon,et al.  Introduction: Green Chemistry and Catalysis , 2007 .

[80]  D. Covell,et al.  Enantioselective synthesis of (+)-chamaecypanone C: a novel microtubule inhibitor. , 2009, Angewandte Chemie.

[81]  P. Licence,et al.  Continuous Asymmetric Hydrogenation in Supercritical Carbon Dioxide using an Immobilised Homogeneous Catalyst , 2006 .

[82]  T. Wirth,et al.  Advanced organic synthesis using microreactor technology. , 2007, Organic & biomolecular chemistry.

[83]  Yongdan Li,et al.  The effect of sulfur compound on the hydrogenation of tetralin over a Pd–Pt/HDAY catalyst , 2008 .

[84]  Eric J. Beckman,et al.  Supercritical and near-critical CO2 in green chemical synthesis and processing , 2004 .

[85]  M. Poliakoff,et al.  Selective catalytic hydrogenation of organic compounds in supercritical fluids as a continuous process , 1998 .

[86]  I. Toth,et al.  Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein PL1 epitope. , 2009, Bioorganic & medicinal chemistry letters.

[87]  Steven V Ley,et al.  A flow reactor process for the synthesis of peptides utilizing immobilized reagents, scavengers and catch and release protocols. , 2006, Chemical communications.

[88]  J. Clayden,et al.  Electrophile-induced dearomatizing spirocyclization of N-arylisonicotinamides: a route to spirocyclic piperidines. , 2008, Organic letters.

[89]  L. Blomberg,et al.  Synthesis of fatty alcohol mixtures from oleochemicals in supercritical fluids , 2000 .

[90]  G. Brunner,et al.  Phase equilibrium-driven selective hydrogenation of limonene in high-pressure carbon dioxide , 2007 .

[91]  J. Hartley,et al.  Synthesis of a novel C2/C2'-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate. , 2009, Bioorganic & medicinal chemistry letters.

[92]  Ferenc Fülöp,et al.  Reversal of the ee in enantioselective hydrogenation of activated ketones in continuous-flow fixed-bed reactor system , 2010 .

[93]  E. Chornet,et al.  High Yield Conversion of Residual Pentoses into Furfural via Zeolite Catalysis and Catalytic Hydrogenation of Furfural to 2-Methylfuran , 2010 .

[94]  D. Murzin,et al.  Continuous hydrogenation of 1-phenyl-1,2-propanedione under transient and steady-state conditions: regioselectivity, enantioselectivity and catalyst deactivation , 2002 .

[95]  M. Yaqoob,et al.  Oxazolomycins: natural product lead structures for novel antibacterials by click fragment conjugation. , 2010, Bioorganic & medicinal chemistry letters.

[96]  Peter Claus,et al.  Application of a capillary microreactor for selective hydrogenation of α,β-unsaturated aldehydes in aqueous multiphase catalysis , 2005 .

[97]  G. Hutchings,et al.  Observation of high enantioselectivity for the gas phase hydrogenation of methyl pyruvate using supported Pt catalysts pre-modified with cinchonidine. , 2003, Chemical communications.

[98]  Lanny D. Schmidt,et al.  The engineering of chemical reactions , 1997 .

[99]  S. Ley,et al.  A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly. , 2006, Chemical communications.

[100]  C. Pai,et al.  Investigation of multiphase hydrogenation in a catalyst-trap microreactor , 2009 .

[101]  Charles N. Satterfield,et al.  Heterogeneous catalysis in practice , 1980 .

[102]  W. Shen,et al.  Characterization and Activity of MnO/γ‐Al2O3 for Hydrogenation of Methyl Benzoate to Benzaldehyde , 2010 .

[103]  C. Oliver Kappe,et al.  Continuous Flow Hydrogenation of Functionalized Pyridines , 2009 .

[104]  J. Snyder,et al.  Synthesis of unique scaffolds via Diels-Alder cycloadditions of tetrasubstituted cyclohexadienes. , 2010, Organic letters.

[105]  John E A Shaw,et al.  A mesh microcontactor for 2-phase reactions. , 2003, Lab on a chip.

[106]  M. Härröd,et al.  Hydrogenation of fatty acid methyl esters to fatty alcohols at supercritical conditions , 1999 .

[107]  A. Baiker,et al.  Continuous Semihydrogenation of a Propargylic Alcohol over Amorphous Pd81Si19 in Dense Carbon Dioxide: Effect of Modifiers , 2001 .

[108]  J. Högberg,et al.  Partial hydrogenation of fatty acid methyl esters at supercritical conditions , 1999 .

[109]  Etzer Darout,et al.  The synthesis of azabicyclic heterocycles , 2010 .

[110]  Yonghua Zhou,et al.  Selective Hydrogenation of 1,5-Cyclo-octadiene over Porous Pd/α-Al2O3 Active Membrane , 2007 .

[111]  P. Rohr,et al.  Solid catalyzed hydrogenation in a Si/glass microreactor using supercritical CO2 as the reaction solvent , 2009 .

[112]  Roger A. Sheldon,et al.  Continuous kinetic resolution catalysed by cross-linked enzyme aggregates, ‘CLEAs’, in supercritical CO2 , 2006 .

[113]  A. Santana,et al.  Sunflower oil hydrogenation on Pd in supercritical solvents: Kinetics and selectivities , 2007 .

[114]  M. F. Williams,et al.  Hydrogenation of tetralin on silica–alumina-supported Pt catalysts II. Influence of the support on catalytic activity , 2007 .

[115]  J. Grunwaldt,et al.  Palladium Supported on an Acidic Resin : A Unique Bifunctional Catalyst for the Continuous Catalytic Hydrogenation of Organic Compounds in Supercritical Carbon Dioxide , 2008 .

[116]  Andrew B. Mahon,et al.  Synthesis of Symmetric Diester-Functionalised Tröger's Base Analogues , 2009 .

[117]  C. Oliver Kappe,et al.  Continuous flow organic synthesis under high-temperature/pressure conditions. , 2010, Chemistry, an Asian journal.

[118]  M. Härröd,et al.  Hydrogenation of oleochemicals at supercritical single-phase conditions: influence of hydrogen and substrate concentrations on the process , 2001 .

[119]  G. Hutchings,et al.  Continuous stable enantioselective hydrogenation of alkyl pyruvate esters using pre-modified cinchonidine platinum catalysts , 2005 .

[120]  F. Fülöp,et al.  New data in the enantioselective hydrogenation of ethyl pyruvate on Pt-cinchona chiral catalyst using continuous-flow fixed-bed reactor system: The origin of rate enhancement , 2009 .

[121]  Asterios Gavriilidis,et al.  Experimental studies of nitrobenzene hydrogenation in a microstructured falling film reactor , 2004 .

[122]  F. Fülöp,et al.  New data to the origin of rate enhancement on the Pt-cinchona catalyzed enantioselective hydrogenation of activated ketones using continuous-flow fixed-bed reactor system , 2008 .

[123]  G. Hutchings,et al.  Inversion of enantioselectivity for the hydrogenation of ethyl pyruvate in the gas-phase over Pt/SiO2 modified with derivatives of hydroquinidine , 2006 .

[124]  Helmut Pennemann,et al.  Asymmetric catalytic hydrogenations at micro-litre scale in a helicoidal single channel falling film micro-reactor , 2005 .

[125]  Atsushi Urakawa,et al.  On-chip Raman analysis of heterogeneous catalytic reaction in supercritical CO2: phase behaviour monitoring and activity profiling. , 2008, The Analyst.

[126]  Steven V Ley,et al.  The use of a continuous flow-reactor employing a mixed hydrogen-liquid flow stream for the efficient reduction of imines to amines. , 2005, Chemical communications.

[127]  A. Baiker,et al.  Enantio selective hydrogenation of isopropyl-4,4,4-trifluoroacetoacetate in a continuous flow reactor , 2003 .

[128]  Klavs F. Jensen,et al.  Microfabricated multiphase packed-bed reactors : Characterization of mass transfer and reactions , 2001 .

[129]  D. Murzin,et al.  Effect of Cinchonidine and Dissolved Oxygen in Continuous Enantioselective Hydrogenation of Ethyl Pyruvate , 2004 .

[130]  D. Murzin,et al.  Application of transient methods in three-phase catalysis: hydrogenation of a dione in a catalytic plate column , 2003 .

[131]  M. Freifelder Hydrogenation of Pyridines and Quinolines , 1963 .

[132]  T. Salmi,et al.  Supported Ionic Liquid Catalysts (SILCA) for Preparation of Organic Chemicals , 2010 .

[133]  J. Kobayashi,et al.  Triphase Hydrogenation Reactions Utilizing Palladium‐Immobilized Capillary Column Reactors and a Demonstration of Suitability for Large Scale Synthesis , 2005 .

[134]  M. Ueno,et al.  Development of microchannel reactors using polysilane-supported palladium catalytic systems in capillaries. , 2008, Chemical communications.

[135]  M. Poliakoff,et al.  Continuous Flow Hydrogenation of a Pharmaceutical Intermediate, [4-(3,4-Dichlorophenyl)-3,4-dihydro-2H-naphthalenyidene]-methylamine, in Supercritical Carbon Dioxide , 2007 .

[136]  Ferenc Darvas,et al.  Continuous-flow high pressure hydrogenation reactor for optimization and high-throughput synthesis. , 2006, Journal of combinatorial chemistry.

[137]  A. Baiker,et al.  Continuous Semihydrogenation of Phenylacetylene over Amorphous Pd81Si19 Alloy in “Supercritical” Carbon Dioxide: Relation between Catalytic Performance and Phase Behavior , 2001 .

[138]  P. Mäki-Arvela,et al.  Liquid-phase hydrogenation of citral over an immobile silica fibre catalyst , 2000 .

[139]  K. Wilson,et al.  Coupling of Heck and hydrogenation reactions in a continuous compact reactor , 2009 .

[140]  O. Trapp,et al.  Hochdurchsatz‐Screening von Katalysatoren durch Integration von Reaktion und Analyse , 2007 .

[141]  B. Trost,et al.  On inventing reactions for atom economy. , 2002, Accounts of chemical research.

[142]  Paul T Anastas,et al.  Origins, current status, and future challenges of green chemistry. , 2002, Accounts of chemical research.

[143]  P. Mäki-Arvela,et al.  Batchwise and continuous enantioselective hydrogenation of 1-phenyl-1,2-propanedione catalyzed by new Pt/SiO2 fibers , 2001 .

[144]  A. Lawal,et al.  Catalytic hydrogenation of o-nitroanisole in a microreactor : Reactor performance and kinetic studies , 2007 .

[145]  Tomoki Suzuki,et al.  Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide Y Y1 receptor antagonists. , 2009, Bioorganic & medicinal chemistry letters.

[146]  Jasbir Singh,et al.  Continuous hydrogenation reactions in supercritical CO2“without gases” , 2005 .

[147]  J. Porco,et al.  Enantioselective synthesis of bicyclo[2.2.2]octenones using a copper-mediated oxidative dearomatization/[4 + 2] dimerization cascade. , 2008, Journal of the American Chemical Society.

[148]  Steven V. Ley,et al.  Optimisation of Conditions for O‐Benzyl and N‐Benzyloxycarbonyl Protecting Group Removal using an Automated Flow Hydrogenator , 2007 .

[149]  Jeremy L. Steinbacher,et al.  Greener approaches to organic synthesis using microreactor technology. , 2007, Chemical reviews.

[150]  A. Baiker,et al.  Continuous platinum-catalyzed enantioselective hydrogenation in ‘supercritical’ solvents , 2001 .

[151]  Toshiro Yokoyama,et al.  Development of a Novel Catalytic Membrane Reactor for Heterogeneous Catalysis in Supercritical CO2 , 2010, International journal of molecular sciences.

[152]  M. Esashi,et al.  Thin palladium membrane microreactors with oxidized porous silicon support and their application , 2005 .

[153]  Peter Licence,et al.  Chemical reactions in supercritical carbon dioxide: from laboratory to commercial plantThis work was presented at the Green Solvents for Catalysis Meeting held in Bruchsal, Germany, 13–16th October 2002. , 2003 .

[154]  C. Pai,et al.  Multiphase flow regimes for hydrogenation in a catalyst-trap microreactor , 2008 .

[155]  Xiang-Qun Xie,et al.  Construction of a bicyclic beta-benzyloxy and beta-hydroxy amide library through a multicomponent cyclization reaction. , 2009, Journal of combinatorial chemistry.

[156]  G. Hutchings,et al.  Unexpected inversion of enantioselectivity during the hydrogenation of ethyl pyruvate using hydroquinine and hydroquinidine modified Pt/Al2O3 , 2006 .

[157]  M. Garland,et al.  Chiral fixed bed reactor for stereoselective heterogeneous catalysis: modification, regeneration, and multiple product syntheses , 2004 .

[158]  A. Baiker,et al.  Continuous enantioselective hydrogenation of activated ketones , 1999 .

[159]  Peter H Seeberger,et al.  Microreactors as tools for synthetic chemists-the chemists' round-bottomed flask of the 21st century? , 2006, Chemistry.

[160]  Á. Molnár,et al.  H–D exchange, configurational isomerization, and hydrogenolysis of 1,2-dimethylsilacycloalkanes on copper , 1982 .

[161]  Paul Watts,et al.  Recent advances in synthetic micro reaction technology. , 2007, Chemical communications.

[162]  Martyn Poliakoff,et al.  Supercritical hydrogenation and acid-catalysed reactions "without gases". , 2004, Chemical communications.

[163]  A. Lawal,et al.  Experimental studies on hydrogenation of anthraquinone derivative in a microreactor , 2007 .

[164]  P. Murphy,et al.  Synthesis of macrolide-saccharide hybrids by ring-closing metathesis of precursors derived from glycitols and benzoic acids. , 2007, The Journal of organic chemistry.

[165]  F. Fülöp,et al.  Enantioselective hydrogenation of α,β-unsaturated carboxylic acids in fixed-bed reactor , 2007 .

[166]  A. Baiker,et al.  Semihydrogenation of a propargylic alcohol over highly active amorphous Pd81Si19 in “supercritical” carbon dioxide , 2002 .

[167]  Martyn Poliakoff,et al.  Continuous hydrogenation of organic compounds in supercriticalfluids , 1997 .

[168]  Takehiko Kitamori,et al.  A Microfluidic Device for Conducting Gas-Liquid-Solid Hydrogenation Reactions , 2004, Science.

[169]  Gerard V. Smith,et al.  Heterogeneous Catalysis in Organic Chemistry , 1999 .

[170]  Ferenc Darvas,et al.  A Novel Method for High-Throughput Reduction of Compounds through Automated Sequential Injection into a Continuous-Flow Microfluidic Reactor , 2005 .

[171]  B. Subramaniam,et al.  Fixed-bed hydrogenation of organic compounds in supercritical carbon dioxide , 2001 .

[172]  Geoffrey I. Webb,et al.  The effect of hydrogen concentration on propyne hydrogenation over a carbon supported palladium catalyst studied under continuous flow conditions , 2000 .

[173]  R. Schlögl,et al.  Understanding palladium hydrogenation catalysts: when the nature of the reactive molecule controls the nature of the catalyst active phase. , 2008, Angewandte Chemie.

[174]  G. Hutchings,et al.  Enantioselective Hydrogenation Using Cinchona-Modified Pt/γ-Al2O3 Catalysts: Comparison of the Reaction of Ethyl Pyruvate and Buta-2,3-dione , 2004 .

[175]  F. Fülöp,et al.  Continuous enantioselective hydrogenation of activated ketones on a pt-cd chiral catalyst: use of h-cube reactor system , 2006 .

[176]  J. Cossy,et al.  Rearrangement of N-alkyl 1,2-amino alcohols. Synthesis of (S)-toliprolol and (S)-propanolol , 2009 .

[177]  Louis-S. Bouchard,et al.  NMR Imaging of Catalytic Hydrogenation in Microreactors with the Use of para-Hydrogen , 2008, Science.

[178]  J. Grunwaldt,et al.  Heterogeneous Catalytic Hydrogenation in Supercritical Fluids: Potential and Limitations , 2008 .

[179]  D. Hönicke Formation of an Al2O3-coated catalyst with a metallic core by anodic oxidation of aluminium , 1983 .

[180]  Andreas Jess,et al.  Kinetics of catalytic hydrogenation of β-ionone and application of a presaturated one-liquid flow reactor for the production of fine chemicals , 2005 .

[181]  A. Schmidt,et al.  Selectivity of partial hydrogenation reactions performed in a pore-through-flow catalytic membrane reactor , 2005 .

[182]  James G. Stevens,et al.  Real-time product switching using a twin catalyst system for the hydrogenation of furfural in supercritical CO2. , 2010, Angewandte Chemie.

[183]  Modeling of cyclohexene hydrogenation and dehydrogenation reactions in a continuous-flow microreactor , 2007 .

[184]  A. Lawal,et al.  Comparison of performance of microreactor and semi-batch reactor for catalytic hydrogenation of o-nitroanisole , 2007 .

[185]  N. López,et al.  Molecular understanding of alkyne hydrogenation for the design of selective catalysts. , 2010, Dalton transactions.

[186]  Paul Watts,et al.  Continuous Flow Reactors, a Tool for the Modern Synthetic Chemist , 2008 .

[187]  M. Härröd,et al.  Fixed-Bed Hydrogenation at Supercritical Conditions To Form Fatty Alcohols: The Dramatic Effects Caused by Phase Transitions in the Reactor , 2001 .

[188]  Shuaipeng Liu,et al.  A continuous process for the production of 2,2,6,6-tetramethylpiperidin-4-ol catalyzed by Cu–Cr/γ-Al2O3 , 2010 .