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
› Author Affiliations

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).
Further Information

Publication History

Received: 23 June 2017

Accepted after revision: 18 July 2017

Publication Date:
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