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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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November 10, 2009

Lab Equipment: Any H-Cube Troubleshooters Out There?

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Posted by Derek

I mentioned the H-Cube hydrogenation machine here a couple of years ago as an early example of a commercial flow chemistry machine. As some readers may have guessed, my recent post on hydrogenations was partly inspired by a recent run of activity on this instrument, which came in quite handy.

Until the last couple of days, that is. Now there's a problem, and I'd be glad to hear from any H-Cube users who might know how to solve it. (If you haven't used one, you can probably bail out right now!) What's going on is: when I try to run a hydrogenation in "Full H2" mode, everything works fine until the H2 valve closes. The pump's fine, the flow through the instrument is fine. . .until the status switches to "Running". At that point the flow stops momentarily, then a gout of solvent runs from the outlet all at once, and then. . .nothing. Well, nothing except hydrogen gas - if I dip the outlet tube below the surface of some solvent, I can see that it's still producing that. But there's no flow. Lifting the solvent inlet from the reservoir, I can see that nothing's being taken up - an air bubble forms at the inlet, and just moves up and down.

So there's something going on when the system starts letting hydrogen into the flow, but I'm not sure what that might be. I can always call in the $250/hr folks, but I thought that throwing my problems out onto the blog was at least worth a try. Just to take care of some obvious fixes, so far I've cleaned the metal frit, replaced the Teflon membrane, sonicated the check valve, and tried changing catalyst cartridges. Anyone got any clues after that?

Comments (25) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. Mrs H on November 10, 2009 10:52 AM writes...

Have you replaced the H-Cube check valve? Sounds like it is sticking!

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2. George Costanza on November 10, 2009 12:34 PM writes...

Could be the Johnson Rod...

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3. Slimmy on November 10, 2009 2:03 PM writes...

I think Vanderlay Industries make replacement Johnson rods for the H-Cube

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4. Anonymous on November 10, 2009 3:06 PM writes...

You have a air bubble in your pump. You have to prime the pump. Detach the fingertight going from the pump to the H-Cube inlet valve, start the pump and attach a syringe to the fingertight and draw solvent through the pump. Once solvent is drawn through reattach the fingertight and all should be fine.

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5. Derek Lowe on November 10, 2009 4:05 PM writes...

I don't think it's an air bubble, because everything pumps fine until the H2 valve closes. I've pulled solvent through the pump itself (several times, and it seems OK. In fact, if I shut down the run after it stops on me as described, I can then pump solvent through the system normally if I choose the "No H2 mode".

As for the check valve, I've taken it out and tried cleaning it, but finally ordered a couple of new ones. That seems like a reasonable suspect, but we shall see. . .

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6. You're Pfizered on November 10, 2009 5:03 PM writes...

Sounds like your whatsamajigger is broken.

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7. Cosmo Kramer - Vanderlay Industries on November 10, 2009 5:32 PM writes...

The Vanderlay Johnson Rod assembly is a plug and play replacement for the whatsamagigger.

The assembly is made in Germany. Note the operational warning to prevent further mishaps:

Das machine is nicht fur der fingerpoken und mittengrabben. Is easy schnappen der springenwerk, blowenfusen und popencorken mit spitzen sparken. Das machine is diggen by experten only. Ist nicht fur gerwerken by das dummkopfen. Das rubbernecken sightseeren keepen das cottenpiken hands in die pockets. Relaxen und watchen das blinkenlights.

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8. Polymer Bound on November 10, 2009 6:30 PM writes...

I've heard bad things about the service and reliability of the H-Cube. Hopefully someone will come along with a more robust version of it some day...

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9. Jose on November 10, 2009 6:40 PM writes...

Ours works great when it works, which is 50% of the time. Pressure shutdowns, clogged frits, low flow rates, random errors... I think it is just still in beta testing mode.

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10. RichardA on November 10, 2009 7:58 PM writes...

grad school never ends.

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11. Anonymous on November 10, 2009 10:37 PM writes...

Try running at a higher solvent flow rate? Sometimes that has helped on my Cube.

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12. schinderhannes on November 11, 2009 3:32 AM writes...

Cosmo Kramer!
Thanks a lot for the lough!
Your German is so spot on.
I should now, I´m one of them.
ROTFLH

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13. Anonymous on November 11, 2009 4:56 AM writes...

#9: Jose, have you ever worked with a regular Parr reactor? For example, on the third time replacing the same valve I reached the conclusion that the valve design isn't up to the manufacturer's specs. (That is, rated for 300 C / 200 bar but the seals fail after a day in

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14. Anonymous on November 11, 2009 4:58 AM writes...

120 C / 100 bar.) I also considered the H-Cube, but since it doesn't do high pressure, it was of no interest. A high pressure is surprisingly good for improving selectivity and reaction rate.

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15. Jpot on November 11, 2009 5:03 AM writes...

Hey Kramer.

I think your German would be easily understood in Holland and Belgium, but not in Germany

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16. LizC on November 11, 2009 10:56 AM writes...

Our H-Cube works reasonably well, though our particular whatsamajigger has yet to break.

@Jose: you can easily avoid clogged frits if you make sure your sample is soluble. I have even had success with the instrument when using DMF as a solvent.

Let us know what the end result is please, Derek, as we will suffer H-Cube breakdown at somepoint.

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17. Jal-frezi on November 11, 2009 12:17 PM writes...

From our resident H-cuber....
"By the sounds of it, I would say it was the check valve on the H-Cube that has blown and the one on the pump probably isn't too clever. The pump is able to deliver enough oomph to counter the back pressure generated by the system but as soon as the H2 valve is opened then there is an additional 7 or so bar, which goes off in all directions including past the check valve. If he ran it in no H2 mode with, say, 40 bar back pressure, he'd see the same prob."

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18. Derek Lowe on November 11, 2009 12:22 PM writes...

J-F, that makes a lot of sense. I've ordered new check valves just because that seemed to be the most likely problem, but the combo of the H-Cube's valve and the pump certainly does seem to fit the facts. . .

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19. Dr. Van Nostrand on November 11, 2009 12:34 PM writes...

That's correct...

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20. SPRITY on November 11, 2009 12:49 PM writes...

We had the same problem a couple years ago after running a larger scale reaction with the H-Cube in which the compound solution was pumped through the LC pump. The compound simply gummed up the check valve and nothing could go into the H-Cube. We replaced the LC pump check valve and the problem was solved. Since then we would not put any compound in the solvent reservoir. Just repeat injection into the 5 mL sample loop.

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21. Cosmo Kramer - Vanderlay Industries on November 11, 2009 12:51 PM writes...

By the way, have you checked out our Latex catalog?

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22. Dr. J on November 12, 2009 10:55 AM writes...

You may have an issue with the pump check valves rather than the H-Cube Check Valve. If the pump check valves get worn out after a time the pump isn't able to handle the extra back pressure generated from the influx of hydrogen into the line when the valve opens. To check this, run a reaction at 100 bar in No H2 mode using solvent. If the system can't generate the pressure, then it is more than likely the pump check valves. This is a simple fix, but you will need to order a set of new check valves from your local rep to fix it. Feel free to e-mail me for any help with changing them over.

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23. Ben on November 17, 2009 7:41 AM writes...

One other thing to try - disconnect HPLC pump from the Hcube and run a load of solvent through it at high flow rate. this sometimes gets it working for a short time (cleans crud out of the pump which stops check valves from working properly) but you're probably going to need to replace the checkvalve soon as others have said.

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24. Infohunter on September 26, 2011 3:53 AM writes...

Some updates?

We also recently have some troubles due to the hydrogen check valve and we observed that the force of the screw which maintains it has a strong influence of hydrogen flow. (I believe It could help people in same cases)

For example when hydrogen flow (bubles) stops during a run (service table indicates an open hydrogen vanne at 0020, and a correct pressure for hydrogen tank). The screw must be slack a very little.

Our main problem remains that we didn't get the full "User Manual" with our H-Cube (for HC-2.SS) and if someone could send us page 50 to 60 (general maintenance pages), that would be really help full

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25. LC on October 26, 2011 2:35 AM writes...

I have a problem with our H-cube. It´s written on the screen "security alert. call for service". Is there a method to solve this problem. Thank you.

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