Continuous flow generation and reactions of anhydrous diazomethane using a Teflon AF-2400 tube-in-tube reactor.

A continuous process for generation, separation, and reactions of anhydrous diazomethane in a tube-in-tube reactor was developed. The inner tube of the reactor is made of hydrophobic, gas-permeable Teflon AF-2400. The diazomethane is formed in the inner tube and then diffuses through the permeable membrane into the outer chamber and subsequently reacts in the solution carried within. This technique allows safe and scalable reactions with dry diazomethane to be performed on a laboratory scale.

[1]  Steven V. Ley,et al.  Asymmetric Homogeneous Hydrogenation in Flow using a Tube-in-Tube Reactor , 2012 .

[2]  A. de Meijere,et al.  Natural occurrence, syntheses, and applications of cyclopropyl-group-containing alpha-amino acids. 1. 1-aminocyclopropanecarboxylic acid and other 2,3-methanoamino acids. , 2007, Chemical reviews.

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

[4]  R. Schoental.  Carcinogenic Action of Diazomethane and of Nitroso-N-methyl Urethane , 1960, Nature.

[5]  Steven V Ley,et al.  The continuous-flow synthesis of carboxylic acids using CO2 in a tube-in-tube gas permeable membrane reactor. , 2011, Angewandte Chemie.

[6]  Klavs F. Jensen,et al.  Mass Transport and Reactions in the Tube-in-Tube Reactor , 2013 .

[7]  M. Maggini,et al.  Scalable in Situ Diazomethane Generation in Continuous-Flow Reactors , 2012 .

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

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

[10]  K. Vávrová,et al.  Synthesis and Functionalization of 5-Substituted Tetrazoles† , 2012 .

[11]  T. Ye,et al.  Organic Synthesis with .alpha.-Diazo Carbonyl Compounds , 1994 .

[12]  M. Kerr,et al.  Heterocycles from cyclopropanes: applications in natural product synthesis. , 2009, Chemical Society reviews.

[13]  R. Zimmer,et al.  Donor-acceptor-substituted cyclopropane derivatives and their application in organic synthesis. , 2003, Chemical reviews.

[14]  Steven V. Ley,et al.  Hydrogenation in flow: Homogeneous and heterogeneous catalysis using Teflon AF-2400 to effect gas-liquid contact at elevated pressure†‡ , 2011 .

[15]  T. Hudlický,et al.  Use of cyclopropanes and their derivatives in organic synthesis , 1989 .

[16]  A. Padwa,et al.  Synthetic applications of 1,3-dipolar cycloaddition chemistry toward heterocycles and natural products , 2002 .

[17]  H. Löwe,et al.  Fluorenylmethoxycarbonyl‐N‐methylamino Acids Synthesized in a Flow Tube‐in‐Tube Reactor with a Liquid–Liquid Semipermeable Membrane , 2013 .

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

[19]  E. Lewinn.  DIAZOMETHANE POISONING: REPORT OF A FATAL CASE WITH AUTOPSY , 1949, The American journal of the medical sciences.

[20]  S. Ley,et al.  Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO concentration. , 2011, Organic & biomolecular chemistry.

[21]  Steven V Ley,et al.  Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal-Knorr pyrrole formation and gas concentration measurement by inline flow titration. , 2012, Organic & biomolecular chemistry.

[22]  T. Fukuyama,et al.  Modernized low pressure carbonylation methods in batch and flow employing common acids as a CO source. , 2013, Organic letters.

[23]  V. Branchadell,et al.  Mechanism of olefin cyclopropanation by diazomethane catalyzed by palladium dicarboxylates: a density functional study. , 2001, Journal of the American Chemical Society.

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

[25]  L. Proctor,et al.  Development of a Continuous Process for the Industrial Generation of Diazomethane1 , 2002 .