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

Structure

1. Objectives and challenges of this project 2. Results 2.1. STR 2.2. OBR 2.3. Comparison STR-OBR

• 3. Future plans

Continuous Manufacturing and Advanced Crystallisation

1.

• 1. Obje

jectives and chall llenges

Confidential - for internal use only

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

H2 inlet

G-L interface L-S interface

CG CL CS

• 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

Gas Liquid Solid

1 or 5: Mass transfer control 2, 3 or 4: Kinetic control Rate determining step

Confidential - for internal use only

• Hydrogen transfer:

Affected by

• Solubility of H2 in solvent
• Mixing
• Bubble size

STR OBR

Turbulent mixing Bubbles – big size Coalescence phenomena Impeller flooding Flow motion and vortices Bubbles – small size Bubbles breakup and holdup favoured

reactor Improved by ↑ Pressure (Henry’s Law)

COBR

Plug flow at laminar flow  long RT at reduced lengths Linear scale up

Longer bubble residence time Larger gas surface area

2. . Results

Confidential - for internal use only A glass STR & a Parr STR for elevated pressure trials

Gas Chromatography

OBR

• Equipment involved

Confidential - for internal use only

Con Conclu lusions: : the reaction rate is maximized when stirring speed > 600 RPM (Fig. 1) and catalyst particle size < 45 μm (Fig. 2)

Figure 1. Effect of the stirring speed (RPM) on initial reaction rate (ro). Reaction conditions: molar ratio A/Pd=8150, dp between 75-100 μm, 305 K and 50 mL min-1 H2. Y-Error bars correspond to experimental error (5%). Figure 2. Effect of catalyst particle size (dp) on initial reaction rate (ro). Reaction conditions: molar ratio A/Pd=8150, 305 K, atmospheric pressure, 700 rpm and 50 mL min-1 H2.

• STR

TR – determine the best base condition

20 40 60 80 100 120 140 160 180 200 200 150 125 100 75 38 45

dp (m)

ro (mol L

• 1

h

• 1

gr

• 1

Pd)

200 400 600 800 1000 1200 20 40 60 80 100 120 140 160

ro (mol L

• 1 h
• 1 gr
• 1 Pd)

RPM

Catalyst particle size Stirring speed

Confidential - for internal use only

Figure 3. Effect of molar ratio organic/catalyst on initial reaction rate (ro). Reaction conditions: catalyst used Pd/Al2O3 (dp < 45 μm), 305 K, atmospheric pressure, 700 rpm and 50 mL min-1 H2. Error bars correspond to experimental error (5%). Figure 4. Effect of H2 flow rate on initial reaction rate (ro). Reaction conditions: molar ratio A/Pd=6100, dp < 45 μm, 305 K, atmospheric pressure and 700 rpm. Error bars correspond to experimental error (5%).

Con Conclu lusions: : the reaction rate is maximized when the molar ratio A/Pd = 6100 (Fig. 3) and H2 flow rate > 50 mL/min (Fig. 4)

10000 20000 30000 40000 50000 0.00 0.01 0.02 0.03 0.04 0.05 0.06

ro (mol L

• 1 h
• 1)

Molar ratio organic/catalyst

50 100 150 200 250 300 350 50 100 150 200 250 300

ro (mol L

• 1h
• 1gr
• 1Pd)

H2 flow rate (mL min

• 1)

Catalyst weight H2 flow rate

• STR

TR – determine the best base condition

Confidential - for internal use only

Conclusions: Initial reaction rate increases with temperature and pressure. At constant

pressure, optimum initial reaction rate is obtained at the highest temperature.

Figure 5. Effect of pressure on initial reaction rate (ro) at different temperatures (black-25 C, red-32 C blue-50 C, pink-60 C). Experimental conditions: 700 RPM, dp < 45 μm, molar ratio A/Pd = 6100 and molar ratio H2/Pd=961. Error bars correspond to experimental error (5%).

STR Conclusions: Reaction rate is maximized when working at 700 RPM, dp < 45 μm,

molar ratio A/Pd = 6100 and molar ratio H2/Pd=961. The reaction rate is also maximized at 60 C, regardless the pressure in the system  This is is the be benchmark for

• r OB

OBR Selectivity (>97%) was independent of mass transfer/kinetic control or temperature/pressure

• STR

TR – Effect of temperature and pressure

1 2 3 4 5 6 500 1000 1500 2000 25 C 32 C 50 C 60 C

ro (mol L-1h-1gr-1Pd) P (bar)

Confidential - for internal use only

Conclusions: the reaction is under mass

transfer control at the best benchmarking conditions identified, increases with H2 flow and mixing, while maximized with catalyst weight.

Figure 6. Effect of oscillatory velocity (uosc) on initial reaction rate (ro). Reaction conditions: molar ratio A/Pd=6100, molar ratio H2/Pd=961.

0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.00 0.05 0.10 0.15 0.20 0.25 0.30

ro (mol L

• 1h
• 1)

uosc (m/s)

100 200 300 400 500 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40

ro (mol L

• 1h
• 1)

H2 flow rate (mL min

• 1)

20 40 60 80 100 0.00 0.05 0.10 0.15 0.20 0.25 0.30

ro (mol L-1h-1) catalyst weight (mg)

Figure 7. Effect of H2 flow rate on initial reaction rate (ro). Reaction conditions: molar ratio A/Pd=6100, P/V=5500 W/m3. Figure 8. Effect of catalyst weight on initial reaction rate (ro). Reaction conditions: P/V=5500 W/m3.

Oscillatory mixing H2 flow rate Catalyst weight

• OBR

BR – experiments

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Con Conclu lusions: adjusting reaction conditions, reactor performance is maximized – 10 times better use of H2 per gr Pd in OBR.

REACTOR H2 flow rate (mL/min) Catalyst weight (mg cat) Molar RATIO A/Pd Molar RATIO H2/Pd H2 efficiency %

• Eff. H2 per

gr Pd STR 50 20 6108 961 6 343 OBR 170 68 6108 961 17.5 339 170 20 20361 3268 13 760 50 68 6108 283 48 1349 50 20 20361 961 37.5 3008

Table 1. H2 utilization and H2 efficiency per gr Pd at different reaction conditions, both reactors (STR-OBR) working at P/V=5500 W/m3.

• Comparison OBR

BR vs STR TR

H2 utilization

REACTOR 60 C 1 bar H2 flow rate mL/min mgr cat RATIO nA/nPd RATIO nH2/nPd ro mol/L h RT min H2 eff % Eff per gr Pd

STR 50 20 6108 961 0.097 82.7 6 343 OBR 170 68 6108 961 0.216 36.2 17.5 339 170 20 20361 3268 0.174 49.5 13 760 50 68 6108 283 0.173 46.3 48 1349 50 20 20361 961 0.144 58.2 37.5 3008

P, bar ro 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 Table 2. H2 utilization and H2 efficiency per gr Pd at different reaction conditions, both reactors (STR-OBR) working at P/V=5500 W/m3. Table 3. Initial reaction rate at different temperatures and pressures in STR working at P/V=5500 W/m3. Molar ratios A/Pd =6108 and H2/Pd=961.

• Comparison OBR

BR vs STR TR

Confidential - for internal use only

• Carry out similar hydrogenation tests in pressurized OBR

3. . F Future pla lans

• Transform batch OBR into a continuous OBR
• Undertake experiments in the COBR

Short term Long term

This work was supported by:

THANKS FOR YOUR ATTENTION ANY QUESTION?

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