General questions concerning flow chemistry

Questions about CatCarts®, catalysts

1. How much compound can be reduced on one catalyst column?

It depends on the type and the molecular weight of the compound. Also, the lifetime of the catalyst is affected by polarity, molecular weight, purity, solvent and types of functional groups, e.g. sulphur groups which may poison the catalyst. With the shortest column, on average, at least 500 mg is reduced, but we have reduced up to 10 g of certain compounds without any catalyst deactivation.

2. How do you dispose of a used CatCart®?

A deactivating vial containing a solution of sodium hydrogen sulfite comes with a CatCart® purchase. Once the CatCart® is finished with, it is placed in the deactivation vial and this renders the catalyst non-pyrophoric. You can dispose of the deactivated cartridge in the same way as you would heterogeneous catalyst from a batch reactor.

3. Is there any partially poisoned catalyst available?

A selection of poisoned catalysts for selective reduction are available, including Lindlar's catalyst and Pt sulfided catalysts.

4. Can the catalyst in the CatCart® be used longer than the catalyst in a batch reactor?

In certain reactions, the product formed, e.g. primary amine, will bind strongly to the catalyst leading to deactivation overtime. In the H-Cube®, the deactivation will take place over a longer period of time because the deactivating product is always flowed out of the catalyst, so the product has a very short residence time on the catalyst. In a batch reactor, the product, starting material, and catalyst mixture are always in contact with each other throughout the entire experiment. As the product concentration increases, the deactivation of the catalyst will also increase.

5. How do we know that the catalyst is still active after repeated use?

You can either try one of the validation reactions (e.g. 5-nitroindole reduction) on a 50 mg scale, or you can make your reactions in more fractions, test the result of each, and recycle back the non-reduced fraction on a new column.

6. After a reaction, is there any problems that a catalyst is stored in original tube?

If you wish to store the CatCart® in the original vial, the vial must be filled with deionized water because if you let the catalyst dry, it will catch fire.

7. After a reaction, is it better to remove the catalyst from the H-Cube®?

ThalesNano recommends that the catalyst be removed at the end of the reaction after the system is washed.

8. Do you have a technique to avoid contamination?

Wash the system with pure solvent after each reaction for at least 10 minutes and then test using an LC or GCMS to see if there is any contaminant. If there is, wash for a further 10 minutes.

9. What is preservative solution of Raney Ni?

If you wish to store Raney Ni or any other catalyst after use, ALWAYS use deionized water. Never use acid with Raney Ni because you will dissolve the nickel.

10. Is it possible to use CatCarts® for H-Cube® on an H-Cube Midi™?

The cartridges for H-Cube® and H-Cube Midi™ are different sizes and so H-Cube® cartridges cannot be used on the H-Cube Midi™ system.

Questions about Reactions

11. What kind of solvents cannot be used in the H-Cube®?

With the PEEK H-Cube®:
Marginally Suitable (these solvents do not attack the PEEK tubing but may cause swelling which may weaken the PEEK tubing)

• Dichloromethane (DCM)
• Tetrahydrofuran (THF)
• Dimethyl sulfoxide (DMSO)
• Triethylamine (TEA)

Not recommended (these chemicals will attack the PEEK tubing)

• Aqua regia
• Bromine/dibromoethane
• Bromine (dry)
• Bromine (wet)
• Chlorine (liquid)
• Hydrobromic acid (100%)
• Hydrobromic acid (20%)
• Hydrobromic acid (10%)
• Hydrofluoric Acid (100%)
• Nitric acid (100%)
• Phenol (conc.)
• Sulphuric acid (100%)
• Sulphuric acid (70%)

With the SS H-Cube®

Usual solvents to be used are: EtOH, MeOH. Click here to download H-Cube® CatCart® solvent compatibility table. However, if you are still unsure please contact askthechemist@thalesnano.com
 

12. How viscous can a liquid be and still be pumped through a KNAUER analytical pump? 

Maximum 1 Poise (CGS unit), i.e. 0.1 Pas (Pascal x sec, SI units), i.e. 100 mPa·s.

This would correspond to the viscosity of oils.

Liquids such as honey (100 Poise) can be pumped with a gear-type pump.
 

Dynamic Viscosities of Newtonian Liquids at 20°C 
 

100 Centipoise = 1 Poise

1 Centipoise = 1 mPa s (milliPascal second)

1 Poise = 0.1 Pa s (Pascal second)

13. How pure is the Hydrogen and how much is the water content of it?

99.99% H₂. A water separator is responsible for the removal of H₂O.

14. Do you have any cross-contamination when using different compounds on the same cartridge?

If enough washing with fresh solvent and hydrogen is allowed between samples, e.g. 10 ml, to wash off any residual product from the column, there will be no cross-contamination. The amount of solvent used depends on how polar the compound is and the type of solvent used.

15. Do you have to de-gas the solvent before the reaction?

No, because the amount of O₂ is so small.

16. How can you perform selective hydrogenation reactions?

Vary the pressure of hydrogen (Henry's Law), temperature or use a more selective catalyst from the list.

Questions about the H-Cube® System

17. What happens with the oxygen?

It is separated from the hydrogen by an SPE (Solid Polymer Electrolyte) membrane, and then recycled back out of cell with the water and then vented out the back of the instrument.

18. How many times is it recommended to top up the water level?

When full, the water reservoir has enough water to generate hydrogen for a full working week. However, for the sake of procedure, we recommend you check the water level every day, e.g. every morning before you start working with H-Cube®. The stainless steel model has a water level monitor on the touch screen.

19. Is there a safety shut-off if the water tank is empty?

Ony on the the stainless steel version of the H-Cube. A message will appear warning the user that the water tank is empty and the user will not be allowed to operate the H-Cube® until the water tank has been refilled.

20. What happens if the cell runs dry?

The membrane inside the cell will dry out and it eventually causes the cell to malfunction.

21. What is the internal volume of hydrogen in the H-Cube®?

The internal volume of hydrogen at 1 bar is approximately 3 cm³, therefore at 100 bar it is 300 cm³.

22. What is the maximum H₂ flow in the H-Cube®?
30 cm³/min (in Full H2 mode).

23. What is the volume of the reaction line in the H-Cube®?

The H-Cube reaction line volume is approximately 2.5 cm³ ,including a 30 mm CatCart®. When connected to the HPLC pump the total volume is 4 mL, therefore the time taken for the compound to pass through the reactor at 1mL/min is 4 minutes.

24. What happens if there is a H₂ leak inside the machine?

There is a H₂ detector, which automatically shuts down the H-Cube® when hydrogen is detected. The power supply is located in a separate unit outside of the H-Cube® box to remove the risk of sparks.

25. Does the machine stop automatically if the pressure goes higher than 100 bar?

No, but if the pressure exceeds 200 bar, the HPLC pump will stop with a blinking “57”, which results in the quick drop of the pressure.

26. How can I perform deuteration reactions in the H-Cube®?

To perform a deuteration reaction it is very important that as much H₂O is removed from the system as possible.

Step 1: A stainless steel system is essential for this because it has the Purge water function on the service screen.
Step2: Drain the water from the reservoir using a syringe.
Step 3: Remove the back of the water reservoir with the allan key. Clean and dry the insides with a paper towel.
Step 4: Go to the service screen. Press Purge water function and press stop at 10 seconds.
Step 5: Replace water reservoir. Add 30 mL of deuterated water. Press Purge Water for 10 seconds.
Step 6: Undo water reservoir, dry insides, again and press Purge water for 10 seconds again.
Step 7: Replace water reservoir and fill with deuterated water. Press Purge water to refill cell with D₂O.
Step8: Take a blank cartridge(titanium) and pass an aprotic solvent (a solvent which doesn't have OH or COOH in the structure) and run the system at Full H2 mode for 10 minutes. Remove blank cartridge.

System is now ready for deuteration experiment.

Deuterated water absorbs water from the air rapidly, so the water reservoir hole must be sealed when not in use. It may be best to have the hole sealed and have a nitrogen stream going into the hole through a needle. Make sure there is another needle allowing the N₂ and O2 out again.
The water separator will handle D₂O as well as H₂O.
The solvent and catalyst used is very important. As mentioned above the solvent should have no OH's or COOH's or any group that can donate a hydrogen. Deuterium and Hydrogen undergo exchange readily. Solvents like toluene are readily used for reactions such as this.

The catalyst is also important. Avoid Raney catalysts because they come presaturated with hydrogen. A fresh Pd or Pt should do the trick.

27. What is the minimum size of the reaction when H-Cube Midi™ is used?

Due to the large amount of catalyst in the cartridge going below 500 mg in scalein not advised. Microgram quantities are not suitable for the H-Cube Mid™, the compound would stick to the catalyst and it would not come off.

Questions about Support

28. What can I do if ThalesNano doesn’t supply the catalyst that I want?

If you describe what you want, ThalesNano can prepare it for you. Ask info@thalesnano.com for details.

29. What can I do if I encounter a system problem (e.g. hydrogen leaking, no solvent is coming out from the reactor)?

Please read the user manual for directions. It tells you what do to with the different problems you may encounter. If you can not solve your problem or the user manual recommends, please contact us at techsupport@thalesnano.com.