An investigation in continuous catalytic hydrogenation Francisca - PowerPoint PPT Presentation

An investigation in continuous catalytic hydrogenation Francisca Navarro Fuentes ( fn8@hw.ac.uk ) Supervisor : Prof. XiongWei Ni Co-supervisor : Prof. Mark Keane

Continuous Manufacturing and Advanced Crystallisation Structure 1. Objectives and challenges of this project 2. Results 2.1. STR 2.2. OBR 2.3. Comparison STR-OBR 3. Future plans

1. 1. Obje jectives and chall llenges 1.1. Objectives • Study the kinetics and parameters affecting kinetics of a chosen process • Understand operational challenges involving high pressures • Explore the possibility of establishing continuous hydrogenation in OBR as a platform synthesis in pharmaceutical industry Confidential - for internal use only

• Reaction model : Hydrogenation of alkynol in liquid phase 1.2. Challenges: - Sequential reaction. Target: intermediate Reaction control to maximize ‘ B ’ production - Confidential - for internal use only

Solid Gas Liquid H 2 inlet C L C G C S G-L interface L-S interface • Hydrogenation mechanism: 1. Transport of reactants to the catalyst 2. Adsorption of reactant on the catalyst 3. Reaction on the catalyst 4. Desorption of products from the catalyst 5. Transport of products away from the catalyst 1 or 5: Mass transfer control Rate determining step 2, 3 or 4: Kinetic control

• Hydrogen transfer: Affected by Improved by - Solubility of H 2 in solvent ↑ Pressure (Henry’s Law) - Mixing reactor - Bubble size STR OBR Flow motion and vortices Turbulent mixing Bubbles – small size Bubbles – big size Bubbles breakup and holdup favoured Coalescence phenomena Impeller flooding Longer bubble residence time Larger gas surface area COBR Plug flow at laminar flow  long RT at reduced lengths Linear scale up Confidential - for internal use only

2. . Results • Equipment involved A glass STR & a Parr OBR STR for elevated Gas Chromatography pressure trials Confidential - for internal use only

• STR TR – determine the best base condition Stirring speed Catalyst particle size Figure 1 . Effect of the stirring speed (RPM) on initial reaction rate (r o ). Figure 2 . Effect of catalyst particle size (d p ) on initial reaction rate (r o ). Reaction conditions: molar ratio A/Pd=8150, d p between 75-100 μm , Reaction conditions: molar ratio A/Pd=8150, 305 K, atmospheric 305 K and 50 mL min -1 H 2 . Y-Error bars correspond to experimental pressure, 700 rpm and 50 mL min -1 H 2 . error (5%). 200 160 180 140 160 -1 Pd) 120 140 Pd ) 100 120 -1 gr -1 gr 100 80 -1 -1 h h -1 80 r o (mol L r o ( mol L 60 60 40 40 20 20 0 0 0 45 75 100 150 200 38 125 0 200 400 600 800 1000 1200 d p (  m ) RPM Con Conclu lusions: : the reaction rate is maximized when stirring speed > 600 RPM (Fig. 1) and catalyst particle size < 45 μ m (Fig. 2) Confidential - for internal use only

• STR TR – determine the best base condition Catalyst weight H 2 flow rate Figure 3 . Effect of molar ratio organic/catalyst on initial reaction rate Figure 4 . Effect of H 2 flow rate on initial reaction rate (r o ). Reaction (r o ). Reaction conditions: catalyst used Pd/Al 2 O 3 (d p < 45 μm ), 305 K, conditions: molar ratio A/Pd=6100, d p < 45 μm , 305 K, atmospheric atmospheric pressure, 700 rpm and 50 mL min -1 H 2 . Error bars pressure and 700 rpm. Error bars correspond to experimental error correspond to experimental error (5%). (5%). 0.06 300 0.05 250 -1 Pd) 0.04 200 -1 ) -1 h -1 gr 0.03 150 r o (mol L -1 h r o (mol L 0.02 100 0.01 50 0.00 0 0 10000 20000 30000 40000 50000 0 50 100 150 200 250 300 350 Molar ratio organic/catalyst -1 ) H 2 flow rate (mL min Conclu Con lusions: : the reaction rate is maximized when the molar ratio A/Pd = 6100 (Fig. 3) and H 2 flow rate > 50 mL/min (Fig. 4) Confidential - for internal use only

• STR TR – Effect of temperature and pressure Figure 5 . Effect of pressure on initial reaction rate (r o ) at different temperatures ( black -25 C, red -32 C blue -50 C, pink -60 C). Experimental conditions: 700 RPM, dp < 45 μ m, molar ratio A/Pd = 6100 and molar ratio H 2 /Pd=961. Error bars correspond to experimental error (5%). 2000 25 C 32 C 50 C 1500 60 C ro (mol L-1h-1gr-1Pd) 1000 500 0 0 1 2 3 4 5 6 P (bar) Conclusions: Initial reaction rate increases with temperature and pressure. At constant pressure, optimum initial reaction rate is obtained at the highest temperature. STR Conclusions : Reaction rate is maximized when working at 700 RPM, dp < 45 μ m, molar ratio A/Pd = 6100 and molar ratio H 2 /Pd=961. The reaction rate is also maximized at 60 C, regardless the pressure in the system  This is is the be benchmark for or OB OBR Selectivity (>97%) was independent of mass transfer/kinetic control or temperature/pressure Confidential - for internal use only

• OBR BR – experiments Oscillatory mixing H 2 flow rate 0.30 0.40 0.35 0.25 0.30 0.20 0.25 -1 ) -1 ) -1 h -1 h 0.15 0.20 r o (mol L r o (mol L 0.15 0.10 0.10 0.05 0.05 0.00 0.00 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0 100 200 300 400 500 -1 ) uosc (m/s) H 2 flow rate (mL min Figure 6 . Effect of oscillatory velocity (u osc ) on initial reaction rate (r o ). Figure 7 . Effect of H 2 flow rate on initial reaction rate (r o ). Reaction Reaction conditions: molar ratio A/Pd=6100, molar ratio H 2 /Pd=961. conditions: molar ratio A/Pd=6100, P/V=5500 W/m 3 . 0.30 0.25 Conclusions: the reaction is under mass 0.20 ro (mol L-1h-1) transfer control at the best benchmarking 0.15 conditions identified, increases with H 2 0.10 Catalyst weight flow and mixing, while maximized with 0.05 catalyst weight. 0.00 0 20 40 60 80 100 catalyst weight (mg) Figure 8 . Effect of catalyst weight on initial reaction rate (r o ). Reaction conditions: P/V=5500 W/m 3 . Confidential - for internal use only

Comparison OBR BR vs STR TR • H 2 utilization Table 1. H 2 utilization and H 2 efficiency per gr Pd at different reaction conditions, both reactors (STR-OBR) working at P/V=5500 W/m 3 . Molar Molar Catalyst H 2 H 2 flow rate Eff. H 2 per RATIO RATIO REACTOR weight efficiency (mL/min) gr Pd (mg cat) % A/Pd H 2 /Pd STR 50 20 6108 961 6 343 170 68 6108 961 17.5 339 170 20 20361 3268 13 760 OBR 50 68 6108 283 48 1349 50 20 20361 961 37.5 3008 Con Conclu lusions: adjusting reaction conditions, reactor performance is maximized – 10 times better use of H 2 per gr Pd in OBR. Confidential - for internal use only

Comparison OBR BR vs STR TR • Table 2. H 2 utilization and H 2 efficiency per gr Pd at different reaction conditions, both reactors (STR-OBR) working at P/V=5500 W/m 3 . REACTOR H 2 flow Eff RATIO RATIO 60 C rate r o RT H 2 eff per gr 1 bar mL/min mgr cat nA/nPd nH2/nPd mol/L h min % Pd STR 50 20 6108 961 0.097 82.7 6 343 170 68 6108 961 0.216 36.2 17.5 339 170 20 20361 3268 0.174 49.5 13 760 OBR 50 68 6108 283 0.173 46.3 48 1349 50 20 20361 961 0.144 58.2 37.5 3008 Table 3. Initial reaction rate at different temperatures and pressures in STR working at P/V=5500 W/m 3 . Molar ratios A/Pd =6108 and H2/Pd=961. r o P, bar mol/L h 25 C 32 C 50 C 60 C 1 0.041 0.046 0.078 0.097 2 0.042 0.056 0.086 0.130 5 0.071 0.094 0.167 0.293 10 0.131 0.162 0.373 0.576

3. . F Future pla lans Short term • Carry out similar hydrogenation tests in pressurized OBR Long term • Transform batch OBR into a continuous OBR • Undertake experiments in the COBR Confidential - for internal use only

THANKS FOR YOUR ATTENTION ANY QUESTION? This work was supported by:

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