CC BY 4.0 · Synlett 2017; 28(20): 2855-2858
DOI: 10.1055/s-0036-1589096
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Rapid Continuous Ruthenium-Catalysed Transfer Hydrogenation of Aromatic Nitriles to Primary Amines

Ricardo Labes
a   Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK   eMail: svl1000@cam.ac.uk
,
Davir González-Calderón
a   Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK   eMail: svl1000@cam.ac.uk
,
Claudio Battilocchio
a   Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK   eMail: svl1000@cam.ac.uk
,
Carlos Mateos*
b   Centro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain   eMail: c.mateos@lilly.com
,
Graham R. Cumming
b   Centro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain   eMail: c.mateos@lilly.com
,
Oscar de Frutos
b   Centro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain   eMail: c.mateos@lilly.com
,
Juan A. Rincón
b   Centro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain   eMail: c.mateos@lilly.com
,
Steven V. Ley*
a   Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK   eMail: svl1000@cam.ac.uk
› Institutsangaben
This work was supported by Eli Lilly & Co. through the Lilly Research Award Program (LRAP). This work has also been funded by the EPSRC (SVL, grants EP/K009494/1, EP/M004120/1 and EP/K039520/1).
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Publikationsverlauf

Received: 23. Juni 2017

Accepted after revision: 18. Juli 2017

Publikationsdatum:
21. August 2017 (online)


Dedicated to our friend Vic Snieckus on the occasion of his 80th birthday

Abstract

A continuous flow method for the selective reduction of aromatic nitriles to the corresponding amine is reported. The method is based on a ruthenium-catalysed transfer-hydrogenation process, requires no additives, and uses isopropanol as both solvent and reducing agent. The process utilizes 1 mol% of the commercially available [Ru(p-cymene)Cl2]2, with a residence time of ca. 9 min, and a throughput of 50 mmol/h. The method was successfully applied to a range of aromatic nitriles providing the corresponding primary amines in good yields.

Supporting Information

 
  • References and Notes

  • 1 Hayes KS. Appl. Catal., A 2001; 221: 187
  • 2 Ruiz-Castillo P. Buchwald SL. Chem. Rev. 2016; 116: 12564
  • 3 Müller TE. Hultzsch KC. Yus M. Foubelo F. Tada M. Chem. Rev. 2008; 108: 3795
  • 4 Leonard J. Blacker AJ. Marsden SP. Jones MF. Mulholland KR. Newton R. Org. Process Res. Dev. 2015; 19: 1400
  • 5 Bähn S. Imm S. Neubert L. Zhang M. Neumann H. Beller M. ChemCatChem 2011; 3: 1853
  • 6 Gunanathan C. Milstein D. Angew. Chem. Int. Ed. 2008; 47: 8661
  • 7 Imm S. Bähn S. Zhang M. Neubert L. Neumann H. Klasovsky F. Pfeffer J. Haas T. Beller M. Angew. Chem. Int. Ed. 2011; 50: 7599
  • 8 Bagal DB. Bhanage BM. Adv. Synth. Catal. 2015; 357: 883
  • 9 Brieger G. Nestrick TJ. Chem. Rev. 1974; 74: 567
  • 10 Wang D. Astruc D. Chem. Rev. 2015; 115: 6621
  • 11 Werkmeister S. Bornschein C. Junge K. Beller M. Chem. A Eur. J. 2013; 19: 4437
  • 12 Vilches-Herrera M. Werkmeister S. Junge K. Borner A. Beller M. Catal. Sci. Technol. 2014; 4: 629
  • 13 Shao Z. Fu S. Wei M. Zhou S. Liu Q. Angew. Chem. Int. Ed. 2016; 55: 14653
  • 14 Mai VH. Nikonov GI. Organometallics 2016; 35: 943
  • 15 Irfan M. Glasnov TN. Kappe CO. ChemSusChem 2011; 4: 300
  • 16 Cossar PJ. Hizartzidis L. Simone MI. McCluskey A. Gordon CP. Org. Biomol. Chem. 2015; 13: 7119
  • 17 Ouchi T. Mutton RJ. Rojas V. Fitzpatrick DE. Cork DG. Battilocchio C. Ley SV. ACS Sustain. Chem. Eng. 2016; 4: 1912
  • 18 Ouchi T. Battilocchio C. Hawkins JM. Ley SV. Org. Process Res. Dev. 2014; 18: 1560
  • 19 Mennecke K. Cecilia R. Glasnov TN. Gruhl S. Vogt C. Feldhoff A. Vargas MA. L. Kappe CO. Kunz U. Kirschning A. Adv. Synth. Catal. 2008; 350: 717
  • 20 Solodenko W. Wen H. Leue S. Stuhlmann F. Sourkouni-Argirusi G. Jas G. Schönfeld H. Kunz U. Kirschning A. Eur. J. Org. Chem. 2004; 3601
  • 21 Saito Y. Ishitani H. Ueno M. Kobayashi S. ChemistryOpen 2017; 6: 211
  • 22 Sharma SK. Lynch J. Sobolewska AM. Plucinski P. Watson RJ. Williams JM. J. Catal. Sci. Technol. 2013; 3: 85
  • 23 Werkmeister S. Bornschein C. Junge K. Beller M. Eur. J. Org. Chem. 2013; 2013: 3671
  • 24 Paul B. Chakrabarti K. Kundu S. Dalton Trans. 2016; 45: 11162
  • 25 Lee S.-H. Nikonov GI. ChemCatChem 2015; 7: 107
  • 26 Garduño JA. García JJ. ACS Omega 2017; 2: 2337
  • 27 Labes R. Battilocchio C. Mateos C. Cumming G. R. de Frutos O. Rincón J. A. Binder K. Ley S.V. Org. Process Res. Dev. 2017; DOI: 10.1021/acs.oprd.7b00190.
  • 28 Uniqsis FlowSyn http://www.uniqsis.com/paFlowSystem.aspx (accessed Jun 7, 2017).
  • 29 ThalesNano. Phoenix Reactor http://thalesnano.com/phoenix-flow-reactor (accessed Jun 2, 2017).
  • 30 General Procedure A solution (50 mL) containing the nitrile (5 mmol), and dichloro(p-cymene)ruthenium(II) dimer (0.05 mmol) in IPA (solution was sonicated until the catalyst was solubilized 10–50 min) was pumped at 4 mL/min through the reactor coil heated at 200 °C. The Phoenix backpressure regulator was set to manual at 30%, which correlated to approximately 100 bar. A 10 mL fraction of the solution obtained from the system in steady state was used to prepare the hydrochloric salt. Yields are reported as isolated hydrochloride salts, unless otherwise stated. NMR Data for Entry 4 1H NMR (600 MHz, MeOD): δ = 7.02–6.94 (m, 2 H), 6.90 (m, 1 H), 6.02 (s, 2 H), 4.13 (s, 2 H). 13C NMR (151 MHz, MeOD): δ = 148.81, 148.35, 124.43, 123.86, 109.54, 108.27, 101.63, 50.34.
  • 31 Under the conditions in Table 1, entry 5 cyclohexanecarbonitrile was not successfully converted into considerable amounts of the desired product.