The application of palladium catalysts for the hydrogenation of aromatic nitriles in the liquid phase
Liam McMillan1, Justin Baker1, David T. Lundie2, Colin Brennan3, Alan Hall3 and David Lennon1 1. Department of Chemistry, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, U.K. 2. Hiden Analytical Ltd., 420 Europa Boulevard, Warrington, WA5 7UN, U.K. 3. Process Studies Group, Syngenta, PO Box A38, Leeds Road, Huddersfield, HD2 1FF, U.K.
4.0 Continued 1.0 Introduction • The hydrogenation of aromatic nitrile compounds is a reaction of considerable significance 0.025 0.06 Calculated within the agrichemical and pharmaceutical industries [1]. Raney-type nickel catalysts are often Benzonitrile Observed Benzylamine 0.020 used but in fine chemical applications they may compromise selectivity to the desired amine by 0.05
additionally facilitating the reduction of other functional groups [2]. Toluene -1 0.04 • Against this background, and following previous research [3], the effectiveness of a supported 0.015 palladium catalyst for this role was investigated.
0.03 The present work highlights some of the issues relevant to the hydrogenation of benzonitrile – • 0.010 a conventional liquid phase hydrogenation reaction – to develop an understanding of the 0.02
chemistry involved. Totalnumber of moles
Concentrationmol / L 0.01 0.005 N
C 0.00 0.000 NH2 2H2 0 50 100 150 200 250 300 0 50 100 150 200 250 300 Time / minutes Figure 4. PtOTime2 / Reactionminutes Profile Figure 5. PtO2 Mass Balance
Benzonitrile Benzylamine Scheme 1 Catalyst Selectivity to Benzylamine Initial Reaction Rate (%) at 50% Conversion (μ mol/L/s)
2.0 Experimental and Catalyst characterisation 5% Pd/C 38 27.16 PtO 71 9.97 Table 1 • A 5% Pd/C catalyst was used in the hydrogenation of benzonitrile in a Buchi autoclave at 4.0 2 bar and 338 K with a stirring speed of 800 rpm. • When the selectivity to benzylamine at 50% conversion is considered, PtO2 offers • The CO adsorption isotherm for the Pd/C catalyst was determined by mass spectrometry considerable improvement in selectivity (Table 1) over 5% Pd/C, despite its lower activity. (Hiden CATLAB), Figure 1. The maximum CO capacity corresponds to a Pd dispersion of 54% • However, a complete mass balance was unobtainable with this system (Figure 5). This is and a mean particle size of 2.0 nm. TEM analysis reveals a narrow particle size distribution. thought to arise from carbon laydown in the initial stages of the reduction process. This • The CO temperature programmed desorption (TPD) profile is presented in Figure 2 and shows could quite reasonably occur via oligomerisation of the amine product. 3 features centred around 500, 640 and 850K. The corresponding CO2 signal rises abruptly at ca. 550K and exhibits a maximum at peak ca. 710K. The CO band at 500K is assigned to CO chemisorption on Pd crystallites. The higher temperature CO bands are attributed to (partial) 4.1 Minimising conversion to toluene – Acid Additive decomposition of carboxy species present on the carbon support material [4].
• Previous studies have shown H2SO4 to be a useful additive in controlling the selectivity to primary amine in nitrile hydrogenation reactions [7]. The acid functions by forming a salt o o 1.0x10-4 with primary amine product, thus preventing formation of 2 /3 amines or by-products – in 1.20E-008 this case, toluene. Hydrogenation reactions were carried out using 5% Pd/C with equimolar 9.0x10-5 CO CO 1.00E-008 2 amounts of benzonitrile and acid. 8.0x10-5 850K
7.0x10-5 8.00E-009 0.025 cat 0.06 6.0x10-5 Benzonitrile 6.00E-009
Benzylamine -5 640K 0.020 5.0x10 0.05 Toluene
-5 TorrPressure / 4.00E-009 500K
4.0x10 -1
Uptakemoles/g / 0.04 -5 0.015 3.0x10 2.00E-009
-5
2.0x10 0.03
0.00E+000 0.010 1.0x10-5 -7 -6 -6 -6 -6 -6 0.02 0.0 5.0x10 1.0x10 1.5x10 2.0x10 2.5x10 3.0x10
300 400 500 600 700 800 900 Numberof moles Exposure / moles of CO
Temperature / K molConcentration / L 0.01 0.005 Figure 1. CO Adsorption Isotherm Figure 2. CO TPD Profile
0.00 0.000 0 10 20 30 40 50 60 3.0 Hydrogenation of benzonitrile 0 50 100 150 200 250 300
Time / minutes Time / minutes Figure 6. Reaction Profile With Acid Additive Figure 7. H2 Consumption Plot • This reaction profile was unexpected. The 0.06
catalyst readily hydrogenated the NH2 NH3 NH2 0.05 H2SO4 D2O benzonitrile to the desired primary amine, HSO4
however, disappointingly, this was then -1 0.04 Benzonitrile further hydrogenated to produce low value Benzylamine Benzylamine Benzylamine Benzylamine Sulfonate Salt Scheme 3
toluene. 0.03 Toluene
• This latter step is an example of a • H2 consumption plot (Figure 7) confirms no 0.02 Benzylamine hydrogenolytic reaction that, although well further reaction after conversion of benzonitrile Hydrogenation Product
documented in conventional synthetic 0.01 and no toluene is observed in the reaction profile. organic chemistry literature [5], is rarely Concentrationmol / L The rate of hydrogenation was comparable to –CH2– reported in the heterogeneous catalysis 0.00 reactions when an acid additive is not used literature [3]. (26.12 μ mol/L/s). A white solid product was –C6H5 -0.01 – NH2 0 50 100 150 200 250 identified as the desired benzylamine-sulfonate Figure 3. 5%Time Pd/C / minutes Reaction Profile salt in a yield of 82% and, after dissolving in D2O, NMR analysis identified benzylamine as the sole • Clearly, there is no economic drive to N product (Figure 8). C CH3 produce toluene via such a valuable NH2 10 8 6 4 2 0 2H H2 intermediate as the desired primary amine 2 ppm -NH product. How does one control selectivity 3 Figure 8. 1H NMR Spectrum of Product to the amine and therefore limit its Benzonitrile Benzylamine Toluene £30.60/100mL £61.60/100mL £0.08/100mL conversion to toluene? Scheme 2 5.0 Conclusions
• Hydrogenation of an aromatic amine over a Pd/C catalyst results in an unfavourable hydrogenolytic step. 4.0 Minimising conversion to toluene – Choice of catalyst • This reaction can be avoided using Adam’s catalyst, however, that reaction system returns an incomplete mass balance. • Two possible ways of limiting conversion to toluene include: • The primary amine product is obtainable in high yield (82%) by running the Pd/C catalyst under acidic conditions, and then affecting an aqueous work-up. 1. The choice of catalyst and, 2. Employing favourable chemistry i.e. the use of additives.
6.0 References • Literature indicates that Adam’s catalyst (PtO2) has useful application in this type of hydrogenation reaction [6]. The reaction profile (Figure 4) shows a much slower reaction rate 1. C. Debellefon, P. Fouilloux. Catalysis Reviews: Science and Engineering, 36 (1994), 459. than with Pd/C, but interestingly the profile reveals a decrease in hydrogenolysis as is observed 2. I. Ortiz-Hernandez, C.T. Williams, Langmuir, 23 (2007), 3172. by the low levels of toluene. Indeed at high conversion, benzylamine selectivity improved from 3. L. Hegedus, T. Mathe, Applied Catalysis A: General, 296 (2005), 209. 4. D.Lennon, N.G.Hamilton, Catalysis Today, 126 (2007), 219. 0% over Pd/C to 86% over PtO2. 5. B.M. Trost, M.J. Krische, R.Radinov, G. Zanoni, J. Am. Chem. Soc., 118 (1996), 6297. 6. US Patent 4025459. 7. W. H. Carothers, and G. A. Jones, J. Chem. Soc. 47 (1925), 3051.