How to scale up hydrogenation reactions using the H-Cube® Midi

H-Cube® Midi Application Note

The difficulties involved with scaling up reactions from laboratory to process scale are well known.' The H-Cube® Midi designed so that the scale up of reactions from the milligram scale on the H-Cube® to 100s of grams is easy and non-problematic. Using several industrial examples, this application note will describe how reactions were scaled up.

WHERE TO START?

The H-Cube® Midi is capable of reacting compounds at 150°C, 100 bar, and 25 mL/min. Temperature, pressure, and flow rate may be changed during tne reaction for fast optimization. Concentrations of up to 0.4 M may also be used. With these wide range of potential conditions, it may be difficult for the user to know where to start. Tne recommended scale up procedure for the H-Cube® Midi are the following:

1) Take the optimum reaction temperature and pressure achieved using the H-Cube® and apply these to the H-Cube® Midi.
2) Start the reaction at a flow-rate of 10mL/min and a concentration of 0.15 M. Take a sample and note conversion.
3) Alter the flow rate until 100% conversion is achieved.
4) Increase the flow rate with temperature and/or pressure to see if production rate can be increased.
5) Repeat the procedure at higher concentrations if necessary.
6) Once the optimum conditions have been found, éeave the system to run to generate the required amount of compound.

SCALE UP EXAMPLES

The following 3 examples illustrate how the H-Cube® Midi was used to scale up reactions performed on the H-Cube®. The reactions were performed by one of ThalesNano’s industrial partners using their own compounds.

SCALE UP OF BENZONITRILE REDUCTION

ConditionsH-Cube®H-Cube® Midi
Catalyst20% Pd(OH)2/C20% Pd(OH)2/C
Temperature60°C60°C
Pressure50 bar50 bar
Flow Rate1 mL/min12 mL/min
Concentration0.05 M0.15 M
Conversion100%100%
Production Rate300 mg/hour10 g/hour

SCALE UP OF BENZALDEHYDE REDUCTION

ConditionsH-Cube®H-Cube® Midi
CatalystRaney NiRaney Ni
Temperature60°C60°C
Pressure50 bar50 bar
Flow Rate1 mL/min12 mL/min
Concentration0.05 M0.15 M
Conversion100%100%
Production Rate300 mg/hour10 g/hour

SCALE UP OF OXIME REDUCTION

ConditionsH-Cube®H-Cube® Midi
CatalystRaney NiRaney Ni
Temperature60°C60°C
Pressure50 bar50 bar
Flow Rate1 mL/min7 mL/min
Concentration0.05 M0.15 M
Conversion100%100%
Production Rate500 mg/hour10 g/hour

DISCUSSION

Each example took less than 1 hour to perform tne necessary optimization experiments. All examples resultes in 100% conversion to the product. Tne production rate increase in the nitrile and benzaldehyde examples was 33 times that of the original the H-Cube®.

CONCLUSION

The examples demonstrate that the production rate of the H-Cube® reactions can be increased by at least 20 times on the H-Cube® Midi reactor. The time taken to perform the optimization process is less than 1 hour making the process much faster than standard batch reactors where the process can take weeks to optimize reactions.

References

RSC environment, health and safety commitee note on Safety Issues in the Scale up of Chemical Reactions, Version /1/3/99.