Org Prep Daily

May 22, 2014

A kilo-scale hydrogenation reactor?

Filed under: procedures — milkshake @ 8:22 pm

I have been running some hydrogenations of our polymers on kilo scale, at atmospheric pressure under balloons, and it is a bit of a chore. It would be nice to have something akin to a beer keg-sized Parr shaker and run the hydrogenation under few bars of H2, to reduce the catalyst loading and shorten the reaction time.

I wanted to ask the readers from process groups if they worked with a low-pressure batch stirred hydrogenation reactor that they liked and could recommend – for us to buy. Specifically,  we would need a hydrogenator that can accommodate 8-10 liters of a reaction mixture that has tendency to initially foam under reduced pressure (this means that the total available volume should be about 15-20 liters). Maximum operating pressure 3 bar would be enough, no heating or cooling is required and the typical solvent is water. I am not really interested in flow hydrogenation systems because they would be unsuitable to our particular case. A glass vessel or at least a glass window on the top would be nice to have, because of the foaming problem during evacuation.  Thank you for your suggestions!

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29 Comments »

  1. Wrote up my thoughts at the blog.

    Comment by Chemjobber — May 23, 2014 @ 1:20 pm

  2. nice setting on the picture though. Out of curiosity, why did you put paper towels under your flasks?

    Comment by fabrice pierre — May 23, 2014 @ 4:45 pm

    • the 5L round flasks are quite heavy, even when half full, and I did not want them to crack at the bottom because of pushing against the stirplate without support… Placing a cork ring in between would raise the distance of the stirbar from the stirplate too much so the stirring would be less effective. Instead of cutting the corks or looking for a foam pad, I did the lazy thing – putting few folded paper towels beneath.

      Comment by milkshake — May 23, 2014 @ 4:52 pm

      • Thanks for the explanation. Always nice to learn some tricks on your blog.

        Comment by fabrice pierre — May 23, 2014 @ 5:10 pm

  3. How about doing it in flow with a H-Cube? Personally, I’ve never used one, but I have heard very good things about them.

    Comment by Stu — May 24, 2014 @ 3:37 am

    • Milkshake specified that flow hydrogenation is unsuitable to his case (my guess is that as he is working with polymers, they are likely to be poorly soluble). My personal experience with H-cubes is that they are rather unreliable. One day it will work very nicely, and once you try to repeat the experiment with a bigger bath, everything goes down to the crapper.

      Comment by GT — May 24, 2014 @ 8:56 am

    • we will not use flow system, due to several limitations specific to our material and our project.
      In desperation I could rig a 5 gallon Cornelius soda keg to a paint shaker like they have in Home Depot.

      Comment by milkshake — May 25, 2014 @ 12:11 am

  4. I can recommend the pressure reactors from http://www.buchiglas.com/products/overview.html

    Comment by anomer — May 25, 2014 @ 5:15 pm

    • This looks very good, I going to write them request for a quote.Thank you! Please which of their autoclaves have you worked with?

      Comment by milkshake — May 26, 2014 @ 4:08 pm

  5. hate to hijack the comment string but i need to reach out directly to milkshake or anyone else in the community: can anyone advise how to hydrogenate a vinyl benzene while keeping an OBn ether in tact? thank you so much

    Comment by nitrosonium — May 28, 2014 @ 12:54 pm

    • 5% platinum on carbon, hydrogen balloon, ethyl acetate as a solvent, few hours. Styrene reduction should go very fast, monitor it so that you don’t get benzene ring saturation.

      You can also consider hydroboration, depending on what is in your molecule.

      Comment by milkshake — May 28, 2014 @ 2:16 pm

    • How about a diimide reduction assuming compatible functionalities?

      Comment by justsomedude — June 24, 2014 @ 9:53 pm

      • we are doing mainly a benzyl protecting group removal, so it is not applicable to our case, but diimide is a nice and under-used reagent for selective C=C reductions.

        Comment by milkshake — June 25, 2014 @ 1:22 pm

        • Sorry should’ve said my reply was for nitrosonium.

          Comment by justsomedude — June 27, 2014 @ 9:36 pm

  6. Hi milkshake, good to see a new post! Quick question. I am working with 4-azidobenzoic acid (for click chemistry purposes). I am aware aryl azides are photosensitive. But how much, exactly? Should I be working in the dark at all times or will my material survive being handled under normal bench conditions (i.e overhead lighting and outside light)

    Comment by NU Chemist — June 1, 2014 @ 4:22 pm

    • I don’t have experience with aryl azides (I only made a bunch of alkyl azides, for click chemistry) but I remember Sharpless saying the aryl azide decomposition temperature is a bit lower than with alkyl azides, often starting below 100C, and UV light might be a concern. I think it is not that bad. It is probably a good idea to protect your compounds from direct sunlight, by storing them in the fridge, but if azide photolysis was really that facile I think the biologist would not go into trouble of developing other obscure hard-to-make photoaffinity labels… Also, I remember preparing and isolating amide of o-azidobenzoic acid once, by accident (because of decomposition of used TDBTU coupling reagent) and there was nothing unusual about it

      Comment by milkshake — June 1, 2014 @ 11:59 pm

  7. How about a 20L flask with mechanical stirring? For balloon pressure hydrog thats the norm here…

    Comment by Anon — June 2, 2014 @ 2:36 am

    • 20L flasks/reactors are rather expensive, and too heavy to handle without walk-in fume hod, and too big and clumsy to clean in a regular-sized sink. The only advantage would be that I would need to analyze only one rather than three reaction mixtures for completion of the reaction.

      As for mechanical stirring, this is not advantageous unless you want to continuously sparge with H2 gas – because of the shaft seal leak. Viscosity of hydrogen is extremely low, this means it leaks through any gap, order-of-magnitude faster than nitrogen or air. Thats is why I never attempted to hydrogenate in our 20L jacketed stirred reactor because it cannot be sealed well enough for hydrogen work.

      The main issue at hand is the relatively slow hydrogenation rate under atmospheric pressure, which in turn requires too much of the (expensive) catalyst, to complete the hydrogenation in a reasonable time, i.e. two days at room temp. (Heating deactivates the catalyst so you can’t accelerate it that way). But if we could go to 3 bars of overpressure, it would increase the hydrogen solubility four times, with the expected boost in the reaction rate or saving on the catalyst loading.

      I think we have found a feasible improvised alternative: a keg from a solvent purification station, a 17L stainless steel keg rated to 3 bars, with Swagelock connectors, and it even stirs through on a IKA magnetic stirrer and its lid has a sparge inlet tube. I will run blank pressure tests on it, with nitrogen first, and then try to hydrogenate some not-so-valuable test material. Maybe I will write up here on the success/failure of this setup if I have enough fingers, eyes left

      Comment by milkshake — June 2, 2014 @ 3:21 am

      • Its standard practoce where I work and we use mechanical stirring with no problems – a tru-bore type stirrer shaft with a little silicone oil to lubricate works fine and maintains the hydrogen.

        The other problem you may be having is poor interfacial mixing for the dissolution of hydrogen… With mech stirring you can set the paddle at the appropriate height to give a bit of splashing.

        I appreciate the advantage of having a walk in hood for large scale work though, and I’m interested to hear of your successes with the improvised vessel.

        Comment by Anon — June 3, 2014 @ 2:44 am

  8. Hi Milkshake. I’m quite certain I’ve read you talking about a relatively simple functional group that is metabolized to a potent CNS toxin. There are probably quite a few that fit the bill, but I seem to recall it was something like an aminopyridine, or some sort of piperidine that is converted to a pyridine? Does this ring a bell to you?

    Comment by PotStirrer — June 2, 2014 @ 8:40 am

    • maybe it was MPTP and its analogs, used for inducing Parkinson disease – N-methylated 3,4-dehydropiperidine with a greasy substituent in the 4 position, i.e. aryl or cyclohexyl. It gets taken by dopamine transport system into neurons, and metabolized by monoamine oxidases to N-methyl-4-subst pyridinium salt, which acts like mitochondria decoupler causing lots of reactive oxygen-derived radicals, leading to degeneration of dopaminergic neurons and neuronal death.

      Comment by milkshake — June 2, 2014 @ 1:41 pm

  9. That’s it! Thanks.

    Comment by PotStirrer — June 3, 2014 @ 2:40 am

  10. Hello! I would recommend you a company http://www.ChemLabTrends.com. The company provide the Snap-Reactor. It is a hydrogenation apparatus for all organic chemists. Snap-Reactor consists of two general parts that are connected together: the Snap-Manifold and the Snap-Vessel. The vessels could be of different sizes (100 mL – 4L, even larger) to which the Snap-Manifolds matches. It could be custom-made.
    It is easy to purge, since you can regulated vacuum line. Hydrogenation could be under the steady flow of a gas with monitored applied pressure. Good Luck !!

    Visit the company website- http://www.ChemLabTrends.com
    Tel. 1-508-925-5674

    Comment by Helena — June 3, 2014 @ 11:35 am

  11. Can’t you put the catalyst in a column and pump the reactant through it with a counter-current of hydrogen?

    Comment by Patrick Sweetman — June 30, 2014 @ 12:14 am

    • no. There are specifics of our process and properties of our material that I cannot get into, but we will never use a flow system for this application – I think I wrote it clearly enough, and three times already.

      Comment by milkshake — June 30, 2014 @ 12:20 am

  12. Ace Glass has nice 5 l pressure reactors rated for 40 psi at 100°C adaptable for both magnetic or mechanical stirring. If mixing is not a problem for you, the magnetically stirred setup can be fine . These reactor are the lowest price solution. For 10-20 l, Buchi is standard choice: but the prices are a couple of orders of magnitude the price of an Ace system. The only time we was involved in an hydrogenation on the 20 l scale, we evaluate hydrogen transfer (the most classical one, with ammonium formate).

    Comment by processchemist — July 7, 2014 @ 4:28 am

    • I know, transfer hydrogenation can be nice, that is what we used before, but there were difficulties related to the weird properties of our polymers. Also, it turns out that heating a good grade high activity Pearlman’s catalyst really deactivates it and ammonium formate does not work well at room temp. (We could have tried other H sources for transfer hydrogenation, i.e. 1,4-cyclohexadiene, but just putting the mix under hydrogen balloon resulted in such an improvement in product purity and offered a simplicity of reaction analysis an workup that we did not look further)

      I will try the stainless steel solvent keg first. If there are problems I would go with the Ace 5L flask on a stirplate, just as you suggested, we could feed it from our old Par shaker (using it just as a manifold for evacuation/filling)

      Comment by milkshake — July 7, 2014 @ 12:22 pm

  13. Get with the times! Stop living in the ancient era of organic chemistry. Buy a H-Cube and hook that crap up to flow!

    Comment by Frank — July 15, 2014 @ 12:15 am


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