Continuous Liquid Vapor Reactions Part 2: Asymmetric Hydroformylation with Rhodium-Bisdiazaphos Catalysts in a Vertical Pipes-in-Series Reactor

Asymmetric hydroformylation (AHF) of 2-vinyl-6-methoxynaphthalene demonstrates important design characteristics of a vertical pipes-in-series plug flow reactor (PFR). The regio- and enantioselectivity of the AHF reaction provide a chemical probe of gas–liquid mixing in a flow reactor for comparison with well-stirred batch reactors. Results obtained with the flow reactor compare favorably to those obtained in batch. Thus, AHF provides an efficient, in-flow enantioselective synthesis of (S)-Naproxen.

[1]  and Peter J. Harrington,et al.  Twenty Years of Naproxen Technology , 1997 .

[2]  C. Landis,et al.  A reactor for high-throughput high-pressure nuclear magnetic resonance spectroscopy. , 2015, The Review of scientific instruments.

[3]  C. Landis,et al.  Asymmetric hydroformylation of Z-enamides and enol esters with rhodium-bisdiazaphos catalysts. , 2014, Journal of the American Chemical Society.

[4]  Martin D. Johnson,et al.  Continuous Liquid Vapor Reactions Part 1: Design and Characterization of a Reactor for Asymmetric Hydroformylation , 2016 .

[5]  W. Childers,et al.  Oxidation of α,β-un saturated aldehydes , 1981 .

[6]  C. Landis,et al.  Origin of pressure effects on regioselectivity and enantioselectivity in the rhodium-catalyzed hydroformylation of styrene with (S,S,S)-BisDiazaphos. , 2010, Journal of the American Chemical Society.

[7]  Martin D. Johnson,et al.  Development and Scale-Up of a Continuous, High-Pressure, Asymmetric Hydrogenation Reaction, Workup, and Isolation , 2012 .

[8]  G. R. Astbury,et al.  Spontaneous ignition of hydrogen leaks: A review of postulated mechanisms , 2007 .

[9]  B. Hashiguchi,et al.  Highly enantioselective hydroformylation of aryl alkenes with diazaphospholane ligands. , 2008, Organic letters.

[10]  C. Nájera,et al.  The First Fluoride-Free Hiyama Reaction of Vinylsiloxanes Promoted by Sodium Hydroxide in Water , 2006 .

[11]  B. Breit,et al.  Easily Accessible TADDOL-Derived Bisphosphonite Ligands: Synthesis and Application in the Asymmetric Hydroformylation of Vinylarenes , 2015 .

[12]  Ian A. Tonks,et al.  Very Low Pressure Rh-Catalyzed Hydroformylation of Styrene with (S,S,S-Bisdiazaphos): Regioselectivity Inversion and Mechanistic Insights , 2013 .

[13]  A. McFarland,et al.  Reaction characterization by flow NMR: quantitation and monitoring of dissolved H₂ via flow NMR at high pressure. , 2014, Chemical communications.

[14]  I. Blumenthal Carbon Monoxide Poisoning , 2001, Journal of the Royal Society of Medicine.

[15]  R. Lazzaroni,et al.  Regioselectivity in the rhodium-catalyzed hydroformylation of styrene as a function of reaction temperature and gas pressure , 1989 .