Continuous flow synthesis of toxic ethyl diazoacetate for utilization in an integrated microfluidic system

An integrated microfluidic system for multiple reactions and separations of hazardous ethyl diazoacetate is presented. The integrated techniques include: a droplet technique for liquid–liquid and/or gas–liquid separation and in situ generation of the toxic reagent, a dual channel membrane technique based on a cheap polymeric microseparator for liquid–liquid separation, and a capillary microreactor for carrying out cascade reactions in a sequential and continuous manner.

[1]  J. Wang,et al.  DBU-promoted condensation of acyldiazomethanes to aldehydes and imines under catalytic conditions , 2002 .

[2]  C. Hayes,et al.  Rapid access to α-alkoxy and α-amino acid derivatives through safe continuous-flow generation of diazoesters. , 2011, Chemistry.

[3]  Ryan L. Hartman,et al.  Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. , 2011, Angewandte Chemie.

[4]  Andreas Kirschning,et al.  Ten key issues in modern flow chemistry. , 2011, Chemical communications.

[5]  B. Trost,et al.  Magnesium-catalyzed asymmetric direct aldol addition of ethyl diazoacetate to aromatic, aliphatic, and alpha,beta-unsaturated aldehydes. , 2009, Journal of the American Chemical Society.

[6]  Ryan L Hartman,et al.  Multistep microchemical synthesis enabled by microfluidic distillation. , 2010, Angewandte Chemie.

[7]  Fang,et al.  BtCH(2)TMS-assisted homologation of carboxylic acids: A safe alternative to the arndt-eistert reaction , 2000, Organic letters.

[8]  J. Wang,et al.  Direct catalytic asymmetric aldol-type reaction of aldehydes with ethyl diazoacetate. , 2003, Organic letters.

[9]  P. Seeberger,et al.  Safe, facile radical-based reduction and hydrosilylation reactions in a microreactor using tris(trimethylsilyl)silane. , 2008, Chemical communications.

[10]  G. Maas.  New syntheses of diazo compounds. , 2009, Angewandte Chemie.

[11]  G. Whitesides,et al.  Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. , 2003, Analytical chemistry.

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

[13]  C. Hayes,et al.  Synthesis of β-keto esters in-flow and rapid access to substituted pyrimidines. , 2010, The Journal of organic chemistry.

[14]  David C. Forbes,et al.  Recent Advances in Asymmetric Catalytic Metal Carbene Transformations. , 1998, Chemical reviews.

[15]  Guangwen Chen,et al.  Safe, efficient and selective synthesis of dinitro herbicides via a multifunctional continuous-flow microreactor: one-step dinitration with nitric acid as agent , 2013 .

[16]  Annegret Stark,et al.  Making diazomethane accessible for R&D and industry : generation and direct conversion in a continuous micro-reactor set-up , 2008 .

[17]  A. Pandit,et al.  Ultrasound and deep eutectic solvent (DES): a novel blend of techniques for rapid and energy efficient synthesis of oxazoles. , 2013, Ultrasonics sonochemistry.

[18]  C. Kappe,et al.  Continuous flow ozonolysis in a laboratory scale reactor. , 2011, Organic letters.

[19]  Siddhartha Sharma,et al.  Odorless isocyanide chemistry: an integrated microfluidic system for a multistep reaction sequence. , 2013, Angewandte Chemie.

[20]  B. Ondruschka,et al.  Microwave assisted phosgenation – alcoholysis using triphosgene , 2003 .

[21]  D. M. Hodgson,et al.  Catalytic enantioselective rearrangements and cycloadditions involving ylides from diazo compounds , 2001 .

[22]  Timothy Noël,et al.  Suzuki-Miyaura cross-coupling reactions in flow: multistep synthesis enabled by a microfluidic extraction. , 2011, Angewandte Chemie.

[23]  Dong‐Pyo Kim,et al.  Efficient photosensitized oxygenations in phase contact enhanced microreactors. , 2011, Lab on a chip.

[24]  Dong-Pyo Kim,et al.  Ultrafast and continuous synthesis of unaccommodating inorganic nanomaterials in droplet- and ionic liquid-assisted microfluidic system. , 2011, Journal of the American Chemical Society.

[25]  Siddhartha Sharma,et al.  Safe use of a toxic compound: heterogeneous OsO4 catalysis in a nanobrush polymer microreactor. , 2013, Angewandte Chemie.

[26]  Dong-Pyo Kim,et al.  Continuous in situ generation, separation, and reaction of diazomethane in a dual-channel microreactor. , 2011, Angewandte Chemie.

[27]  Dong‐Pyo Kim,et al.  Droplet synthesis of well-defined block copolymers using solvent-resistant microfluidic device. , 2011, Lab on a chip.

[28]  Theodore C Marentis,et al.  Ultrasonic mixing in microfluidic channels using integrated transducers. , 2004, Analytical chemistry.

[29]  Dong‐Pyo Kim,et al.  Efficient and continuous monoacylation with superior selectivity of symmetrical diamines in microreactors. , 2012, Lab on a chip.

[30]  J. Wang,et al.  Recent Developments in Pd‐Catalyzed Reactions of Diazo Compounds , 2011 .

[31]  H. Girault,et al.  Monolithic and flexible polyimide film microreactors for organic microchemical applications fabricated by laser ablation. , 2010, Angewandte Chemie.

[32]  S. Buchwald,et al.  Highlights from the Flow Chemistry Literature 2013 (Part 1) , 2013, Journal of Flow Chemistry.

[33]  Steven V Ley,et al.  Continuous multiple liquid-liquid separation: diazotization of amino acids in flow. , 2012, Organic letters.

[34]  Christian V. Stevens,et al.  A HCN-based reaction under microreactor conditions: industrially feasible and continuous synthesis of 3,4-diamino-1H-isochromen-1-ones , 2007 .

[35]  Steven V. Ley,et al.  Flow ozonolysis using a semipermeable Teflon AF-2400 membrane to effect gas-liquid contact. , 2010, Organic letters.

[36]  W. Su,et al.  Continuous flow reactor for Balz–Schiemann reaction: a new procedure for the preparation of aromatic fluorides , 2013 .

[37]  K. Jensen,et al.  Integrated continuous microfluidic liquid-liquid extraction. , 2007, Lab on a chip.

[38]  Pedro Cintas,et al.  Merging microfluidics and sonochemistry: towards greener and more efficient micro-sono-reactors. , 2012, Chemical communications.

[39]  K. Jensen,et al.  Multistep continuous-flow microchemical synthesis involving multiple reactions and separations. , 2007, Angewandte Chemie.

[40]  Robin H. Liu,et al.  Hybridization enhancement using cavitation microstreaming. , 2003, Analytical chemistry.

[41]  M. M. Díaz‐Requejo,et al.  Highly active gold-based catalyst for the reaction of benzaldehyde with ethyl diazoacetate. , 2009, Chemical communications.

[42]  Steven V Ley,et al.  Safe and reliable synthesis of diazoketones and quinoxalines in a continuous flow reactor. , 2011, Organic letters.

[43]  Dominique Roberge,et al.  Synthesis of 5-substituted 1H-tetrazoles from nitriles and hydrazoic acid by using a safe and scalable high-temperature microreactor approach. , 2010, Angewandte Chemie.

[44]  M. Iwamoto,et al.  Selective synthesis of α-substituted β-keto esters from aldehydes and diazoesters on mesoporous silica catalysts , 2008 .

[45]  C. Kappe,et al.  Direct aerobic oxidation of 2-benzylpyridines in a gas–liquid continuous-flow regime using propylene carbonate as a solvent , 2013 .

[46]  Timothy F Jamison,et al.  Safe and efficient tetrazole synthesis in a continuous-flow microreactor. , 2011, Angewandte Chemie.

[47]  Klavs F. Jensen,et al.  Overcoming the Challenges of Solid Bridging and Constriction during Pd-Catalyzed C−N Bond Formation in Microreactors , 2010 .

[48]  Lili Lin,et al.  Catalytic asymmetric Roskamp reaction of alpha-alkyl-alpha-diazoesters with aromatic aldehydes: highly enantioselective synthesis of alpha-alkyl-beta-keto esters. , 2010, Journal of the American Chemical Society.