Multistep synthesis of amides from alcohols and amines in continuous flow microreactor systems using oxygen and urea hydrogen peroxide as oxidants

By integrating a heterogeneous oxidation step, gas–liquid separation, and an oxidative amidation reaction to form a continuous system, a multistep synthetic protocol has been demonstrated to produce amides under mild conditions using alcohols and amines as the starting materials. The use of inexpensive oxygen and urea hydrogen peroxide as the only oxidants affords an economical and adaptable synthetic route for amides.

[1]  J. Schwartz,et al.  Organometallics , 1987, Science.

[2]  A. Baiker,et al.  Oxidation of alcohols with molecular oxygen on solid catalysts. , 2004, Chemical reviews.

[3]  David Milstein,et al.  Direct Synthesis of Amides from Alcohols and Amines with Liberation of H2 , 2007, Science.

[4]  Jun-ichi Yoshida,et al.  Generation and reactions of o-bromophenyllithium without benzyne formation using a microreactor. , 2007, Journal of the American Chemical Society.

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

[6]  R. Madsen,et al.  Amide synthesis from alcohols and amines by the extrusion of dihydrogen. , 2008, Journal of the American Chemical Society.

[7]  A. Watson,et al.  Ruthenium-catalyzed oxidation of alcohols into amides. , 2009, Organic letters.

[8]  Steven J. Broadwater,et al.  The continuous-flow synthesis of Ibuprofen. , 2009, Angewandte Chemie.

[9]  Jean‐Valère Naubron,et al.  Catalyzed dehydrogenative coupling of primary alcohols with water, methanol, or amines. , 2009, Angewandte Chemie.

[10]  K. Shimizu,et al.  Direct dehydrogenative amide synthesis from alcohols and amines catalyzed by gamma-alumina supported silver cluster. , 2009, Chemistry.

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

[12]  R. Crabtree,et al.  Dehydrogenation as a substrate-activating strategy in homogeneous transition-metal catalysis. , 2010, Chemical reviews.

[13]  Yongxin Li,et al.  Well-Defined N-Heterocyclic Carbene Based Ruthenium Catalysts for Direct Amide Synthesis from Alcohols and Amines , 2010 .

[14]  K. K. Hii,et al.  Catalysis in flow: the practical and selective aerobic oxidation of alcohols to aldehydes and ketones , 2010 .

[15]  Soon Hyeok Hong,et al.  Oxidative amide synthesis directly from alcohols with amines. , 2011, Organic & biomolecular chemistry.

[16]  Zhiyong Wang,et al.  Highly efficient amide synthesis from alcohols and amines by virtue of a water-soluble gold/DNA catalyst. , 2011, Angewandte Chemie.

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

[18]  Shuj Kobayashi,et al.  Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or -cobalt nanoparticles. , 2011, Journal of the American Chemical Society.

[19]  Jonathan M. J. Williams,et al.  Metal-catalysed approaches to amide bond formation. , 2011, Chemical Society reviews.

[20]  Jean Martínez,et al.  Copper‐Catalyzed Direct Synthesis of Benzamides from Alcohols and Amines , 2012 .

[21]  Klavs F. Jensen,et al.  Direct oxidative amidation of aromatic aldehydes using aqueous hydrogen peroxide in continuous flow microreactor systems , 2012 .

[22]  Youquan Deng,et al.  Dehydrogenative amide synthesis from alcohol and amine catalyzed by hydrotalcite-supported gold nanoparticles , 2012 .