RSC Advances
Paper
equilibrium shis back to reform the hydroxy-enamine and M508056/1) are thanked for the award of studentships (LM,
hydroxy-imine species. From here, routes A and B can be fol- LG and MMcA) and project support. Technical support within
lowed to furnish phenethylamine as previously described. the University of Glasgow's School of Chemistry was provided by
Against this reasoning, it is proposed that the reaction proceeds Mr James Gallagher (SEM), Mr James McIver (ICP-OES), Mr
via either pathway A and/or pathway B.
Michael Beglan (AAS) and Mr Andrew Monaghan (TGA). Dr
Unfortunately, pathways A and B cannot be differentiated Donald MacLaren and Mr Colin How of the University of Glas-
using the chromatographic methods presented here, as the gow School of Physics and Astronomy's Materials and
corresponding intermediates are undetectable in the liquid Condensed Matter Research Group are thanked for the provi-
phase. It is therefore proposed that in the hydrogenation of sion of TEM analysis.
mandelonitrile, phenethylamine formation has the potential to
proceed via either one or both of these routes. Further investi-
gation into the more conclusive identication of the active
References
pathway or pathways involved in this reaction constitutes ‘work
in progress’.
1 D. B. Bagal and B. M. Bhanage, Adv. Synth. Catal., 2015, 357,
883.
2
J. J. W. Bakker, A. G. van der Neut, M. T. Kreutzer,
J. A. Moulijn and F. Kapteijn, J. Catal., 2010, 274, 176.
L. Heg ´e dus and T. M ´a the, Appl. Catal., A, 2005, 296, 209.
5. Conclusions
3
The liquid phase hydrogenation of mandelonitrile over a 5%
Pd/C catalyst has been investigated. An acid additive proved to
be not only essential for sustained catalytic activity (Section 3.1),
but also played a vital role in catalysing the homogeneous
reaction responsible for formation of the ketone intermediate 2-
aminoacetophenone (Section 3.2). The resultant tautomeric
pathway is thought to open-up additional routes that could
subsequently aid phenethylamine formation. A tentative global
reaction scheme is proposed (Scheme 6) to account for the
pathways accessible within this chemical network; the scheme
includes contributions from species assumed to be solely
4 B. Miriyala, S. Bhattacharyya and J. S. Williamson,
Tetrahedron, 2004, 60, 1463.
5 J. Neumann, C. Bornschein, H. Jiao, K. Junge and M. Beller,
Eur. J. Org. Chem., 2015, 5944.
6 P. Sabatier and J. B. Senderens, C. R. Hebd. Seances Acad. Sci.,
1905, 140, 482.
7 J. Volf and J. Pa ˇs ek, Stud. Surf. Sci. Catal., 1986, 27, 105.
8 C. de Bellefon and P. Fouilloux, Catal. Rev.: Sci. Eng., 1994,
36, 459.
9 I. Ortiz-Hernandez and C. T. Williams, Langmuir, 2007, 23,
3172.
adsorbed as well as entities that are partitioned between 10 R. Juday and H. Adkins, J. Am. Chem. Soc., 1955, 77, 4559.
solvated and adsorbed states at the liquid/solid interface.
For a single batch run, successful production of the primary
11 P. Sch ¨a rringer, T. E. M u¨ ller, A. Jentys and J. A. Lercher, J.
Catal., 2009, 263, 34.
amine, phenethylamine, was achieved with full conversion 12 J. Braun, G. Blessing and F. Zobel, Chem. Ber., 1923, 36, 283.
mandelonitrile ¼ 100%; Sphenethylamine ¼ 87%, Fig. 1). Production 13 A. Chojecki, M. Veprek-Heijman, T. E. M u¨ ller, P. Sch ¨a ringer,
of 2-amino-1-phenylethanol accounts for the remaining 13% S. Veprek and J. A. Lercher, J. Catal., 2007, 245, 237.
selectivity and completes the mass balance (Fig. 2). When the 14 R. K. Marella, K. S. Koppadi, Y. Jyothi, K. S. R. Rao and
kinetics of the conversion of the proposed intermediate 2-
D. R. Burri, New J. Chem., 2013, 37, 3229.
amino-1-phenylethanol were considered, it was found that this 15 M. Chatterjee, H. Kawanami, M. Sato, T. Ishizaka,
process was signicantly slower than the overall production of T. Yokoyama and T. Suzuki, Green Chem., 2012, 12, 87.
phenethylamine. This nding excluded the possibility that 2- 16 A. J. Yap, B. Chan, A. K. L. Yuen, A. J. Ward, A. F. Masters and
amino-1-phenylethanol is an intermediate and is instead T. Machmeyer, ChemCatChem, 2011, 3, 1496.
designated as a by-product of the reaction. Moreover, it was 17 A. J. Yap, A. F. Masters and T. Maschmeyer, ChemCatChem,
indicated that an alternative route from reagent to product 2012, 4, 1179.
must be operational. Consequently it is proposed that the 18 D. J. Segobia, A. F. Trasarti and C. R. Apestegu ´ı a, Appl. Catal.,
hydrogenolytic cleavage of the C–OH bond occurs on either one,
A, 2012, 445–446, 69.
or both, of the highly reactive hydroxy-imine and hydroxy- 19 L. McMillan, L. F. Gilpin, J. Baker, C. Brennan, A. Hall,
(X
enamine species. Differentiation between these two proposed
pathways, however, was not possible by the chromatographic
procedures employed here.
D. T. Lundie and D. Lennon, J. Mol. Catal. A: Chem., 2016,
411, 239.
20 M. I. McAllister, C. Boulho, L. McMillan, L. F. Gilpin,
C. Brennan and D. Lennon, Org. Process Res. Dev., 2019, 23,
9
77.
Conflicts of interest
2
1 M. I. McAllister, C. Boulho, L. McMillan, L. F. Gilpin,
There are no conicts to declare.
S. Wiedbrauk, C. Brennan and D. Lennon, RSC Adv., 2018,
8
, 29392.
2
2 C. Dai, S. Zhu, X. Wang, C. Zhang, W. Zhang, Y. Li and
C. Ning, New J. Chem., 2017, 41, 3758.
Acknowledgements
Syngenta, the University of Glasgow and the EPSRC (grant 23 Y. Hao, M. Li, F. Cardenas-Lizana and M. A. Keane, Catal.
numbers: EP/P503582/1, EP/J500434/1, EP/L50497X/1 and EP/ Lett., 2016, 146, 109.
26124 | RSC Adv., 2019, 9, 26116–26125
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