Org Prep Daily

January 20, 2008

Wrestling with a robot

Filed under: industry life — milkshake @ 1:35 am

resslin.jpg credit: Adolf Born

The Varian NMR autosamplers that I worked with in my previous jobs had an oversized robotic arm grabbing on samples from a rack and then swinging around wildly, loading them into the magnet hole. The system punished users for making errors. A part of the problem was that the acquisition queue allowed the users to run the samples out of sequence and to occupy any arbitrary position in the large and rather poorly numbered rack. Absent-minded people would always enter an incorrect position or leave their sample in a wrong place.

When the robot would try to pick a sample that was missing and could not find any, it would freeze and sound angry alarm – this held up the queue until our NMR man came and re-set the damned bot. Things got worse when a sample was left in the rack position reserved for the preceding sample that was in the magnet – upon return the robotic arm would shatter both samples by smashing them one into another; this created awful mess that had to be cleaned up before the instrument could be re-set. (Also the mishap could damage the arm or ruin the spinners that cost few hundreds apiece). Sometimes I would see the dreadful thing just happening and I would run to deflect the steely arm – but you know, robots are strong and a man is no match…


  1. We have the same system you describe at my school. We’ve learned to work through most of the bugs, and it does the job for us, but I can’t tell you how poorly engineered the Varian system is. For example, if a sample breaks in the magnet and doesn’t pop back up, the robot may just continue to dump sample after sample in there! The gripper also seems to be pretty rough on the tubes– don’t use a chipped one. Not to mention that I think the software boots off a floppy disk! I guess because it’s a small volume product without competition the Varian folks can get away with doing doing such a crappy job. Our NMR people have spent weeks identifying software bugs which can shut it down.

    Comment by Canuck Chemist — January 20, 2008 @ 2:38 am

  2. We had one of those at my undergrad. It was wonderful when it worked- saved a lot of TA time and manpower, as all 700+ undergrads taking organic lab every semester had at least two NMRs to take. Using the robot was the only way it would have worked. However, it only worked on our extremely old Varian, easily from the early to mid-80’s, back when Varians still had dials. That thing was killer. EVERY chemistry major got to be very intimate with that machine.

    Even better was a Bruker that was so old it couldn’t interface with a modern computer or printer, so if you wanted to save or print your data, you first had to connect the NMR to an intermediate computer with DOS, THEN interface it with a Linux computer which could load the data. The NMR worked fine but man it was a hassle. Now my school has all-Varian, all modern equipment and I don’t take that for granted.

    Comment by excimer — January 20, 2008 @ 2:51 am

  3. I used to curse the the software engineers who wrote the Varian software – until I got to work with Bruker. At least the Solaris workstations that came from Varian were nice and stable (about twice, trice a month some persistant bug caused unfinished processes to multiply and tie up the machine untill someone killed all processes by hand – but that was the Varian software fault).

    The current Brukers use a ho-hum software runing in Red Hat Linux on a ho-hum PC. Every new updated software version means “old bugs out – new bugs in”. We are used to logging off or re-booting the PC quite frequently as the software likes to freeze-up unexpectedly.

    Taking care of our Bruker magnets has been annoying because the Helium level meters on our instruments got erratic after 2 years in Florida (icing?) Bruker has good engineers but our first brand-new auto-tune probe was a lemon: it is fortunate that one of their engineers lives within one-hour driving distance because he was trying to fix the probe problem at least dozen times – three times we would also pack the probe carefully and send it to Bruker for a factory repair – on the third time when it came back “repaired” and failed again I found myself threatening the Bruker company that we will return their instrument under our warranty unless they build us a new probe. (It was a strange situation because our NMR specialist was out for over 8 months and meanwhile I was supposed to take care of the two newly-installed instruments that I had no real knowledge about – with the buggy software plus one probe that refused to co-operate while the Bruker service center insisted “we can still repair this thing”).

    I should add that the Bruker revolver-like autosampler we have on one of our instruments is lovely – it lets you run only sequentionally-ordered queue, and it has one moving part (the carousel) and no steely arm flailing about

    Comment by milkshake — January 20, 2008 @ 2:56 am

  4. We have two types. One type is as you describe. An evil arm that drops samples into the magnet. The other is quite intelligent. It’s sort of a conveyor belt that you load the samples into and it drops it off. Unless you’re retarded and skip a hole, it’s impossible to fuck it up. Naturally, the shitty robot is for research and the awesome robot is for TAs and undergrads. But that’s life.

    Comment by Kyle Finchsigmate — January 20, 2008 @ 12:25 pm

  5. Excimer- Did you go to Arizona? What you described sounds just like the NMR facilities there, an ancient Varian and an even more ancient Bruker.

    Comment by Dan — January 20, 2008 @ 1:14 pm

  6. Dan- I sure did.

    Comment by excimer — January 20, 2008 @ 2:39 pm

  7. No kidding. I did an REU there last summer with Robin Polt. Who did you work with when you were there?

    Comment by Dan — January 20, 2008 @ 3:39 pm

  8. We have that same Varian system here at Virginia Tech. As finicky as it is, it’s essential. When the NMR staff takes off for two weeks in the summer we are left with no robot. All of the sudden the daylight queues on the other NMRs are filled to the brim two days in advance. All hell breaks loose with damn near fistfights over NMR time.

    The robot works fine so long as everyone plays by the rules… NO cracked or ‘shortened’ NMR tubes

    The loading is handled each day by the NMR staff so all of those sequencing issues are avoided.


    Comment by Javaslinger — January 20, 2008 @ 4:28 pm

  9. McGrath. I worked for him for about 2 1/2 years

    Comment by excimer — January 20, 2008 @ 5:00 pm

  10. You guys ever used lindlar catalyst before? I don’t have any fancy hydrogenation things… so I am pretty much just gonna stir my reaction under 1atm of H2 gas and check progress using TLC. Think this should be fine?

    Comment by Tom — January 21, 2008 @ 7:14 pm

  11. I used Lindlar catalyst recently, to hydrogenate acetylene in the presence of furoic acid amide, under H2 baloon, sampling react mixture for HPLC and LC/MS – and it worked great. (I got the ethyl group from my unhindered terminal acetylene but this did not bother me too much because the ethyl product was useful also. Normal Pd-C promptly turned my furoyl into tetrahydrofuroyl). Please use Fluka Lindlar, I heard Aldrich Lindlar tends to over-hydrogenate acetylenes easily

    Comment by milkshake — January 21, 2008 @ 7:20 pm

  12. I got the acros lindlar.. my school has some sort of deal with acros… so thats what I have to get each time…

    Also I got some pd tetrakis from them as well.. which was orange upon arrival but seems to work pretty well.

    Comment by Tom — January 21, 2008 @ 11:19 pm

  13. Tom, another option is to skip tetrakis altogether. I never use it anymore; Pd(OAc)2 and 3.0 Eq PPh3 works just as well, and often better (free coordination site). No waiting for things to warm to rt or worrying about funky colors; everything is bench stable!

    Comment by Jose — January 22, 2008 @ 12:07 pm

  14. Ah.. that does sound like a good idea… I actually just got in some pd(OAc)2 which I was using for some copper free couplings….Now I can actually use it. Do you have any references/procedures?

    Comment by Tom — January 22, 2008 @ 2:37 pm

  15. I think it also depends on the react temperature: if I was doing room-temp allylation with allyl acetate like I am doing right now I would use Pd tetrakis because it is Pd(0) already. Thetrakis is easy to keep healthy – you store it in freezer and flush the bottle with Ar after each use.

    Comment by milkshake — January 22, 2008 @ 4:22 pm

  16. I just received a shipment of pd tetrakis from Strem…about to do my first Sonogashira coupling. Is it a pretty robust reaction or do I need to be extra careful with my Schlenk techniques?

    Comment by William Wallace — January 23, 2008 @ 1:16 am

  17. nah, some Sonogashiras are done even without deoxygenation – in a capped vial filled to the top. Only important thing: don’t overload your reaction with copper – just 1 mol % CuI is more than plenty because acetylide formation/coordination to Pd is not rate limiting and too much CuI causes your acetylene to dimerise. I would add CuI last together with tetrakis – mix everything in a common recovery 14/20 flask, then dump in tetrakis solid mixed with CuI, then promptly put on septa with a needle as a outlet – then stick in a long needle under the level of reaction mix, with a Ar (or N2) baloon attached and bubble for few minutes and you are ready to go.
    If you have a sonicator bath (the common cleaning type) available, do the bubbling with sonication, the deoxygenation will be lot faster/more thorough.

    Comment by milkshake — January 23, 2008 @ 2:00 am

  18. First Sonogashira reaction for William Wallace?

    Ah, I remember the days… *sigh*

    We used PdCl2(PPh3)/CuI and all was well. The only downside was making very long, repetitious phenyl acetylenes, and having to column out the homo-coupled junk. The sweet smell of trimethylsilylacetylene is anchored deep in my past, and the sheer quantities we used must have paid the year end bonus of many a Sigma-Aldrich sales rep.

    As an aside, using H2 as an atmosphere (as opposed to N2 or Ar) apparently enhances the yield of the Sonogashira rather nicely.

    Comment by Rhenium — January 23, 2008 @ 11:45 am

  19. TMS acetylene is one expensive volatile bitch – we used to have a half-liter bottle of it from some obscure company. When we started running low I looked into Aldrich catalog to re-order the stuff and was in for a nasty surprise to find out how much it would cost.

    But it did Sonogshira most beautifully.

    Some branched terminal acetylene have an awesome smell – I made terpenic-looking beast once (with a terminal acetylene on a quat carbon and with cyclohexane ring with exocyclic =CH2 sticking out of it. It had the most enjoyable smell of mango peel and fresh pine needles.

    Comment by milkshake — January 23, 2008 @ 6:39 pm

  20. The only downside was making very long, repetitious phenyl acetylenes, and having to column out the homo-coupled junk.

    Gee Rhenium, that sounds awfully familiar…

    Our group orders TMS-acetylene by the gallon from GFS chemicals. It’s expensive, but making it yourself is a complete pain in the ass. The nice thing about TMS acetylene is its low boiling point, so if your Sonogashira doesn’t go, you can add like five equivs and vap off the rest- the homocoupled TMSA elutes quickly in most solvents.

    If you’re just too cheap to use TMSA, though, you can always use the omega-cheap dimethylpropargyl alcohol, which deprotects with NaOH in refluxing benzene (which can be tricky). Also, it’s a polar protecting group, which is nice if your molecules are greasy.

    PdCl2(PPh3)2/CuI is fine for just about every Sonogashira I’ve done. Whenever I use 1 mol% CuI, my reactions don’t go to completion, so I’d recommend against that- 3-5% is typical for me. That Cu-mediated dimerization probably won’t happen unless you’re cooking the hell out of it.

    Comment by excimer — January 23, 2008 @ 7:08 pm

  21. I’m running a couple of Sonogoshira cross croupling reactions, and I’m starting from catechols and dihydroxybenzoates, does anyone know where I can get ethyl or methyl or anything ester for that matter but going with the example of ethyl, where I can ethyl 1,2-diiodobenz-4oate?

    Also, does anyone know of a better solvent to make my triflates other than CH2Cl2? Do you recommend a base in there, or can I do without it. Also, the work-up is killing me.

    Why is it necessary to wash with HCl after the cross coupling? Is it to neutralize the base used? (Stupid question, but I want to be sure).

    Last random question, for one of the catechol derivatives I bought from Sigma-aldrich, the NMR was done in a mixture of CDCl3 and DMSO-d6, does anyone know why that’s necessary? they don’t mention the ratio either, so i’m wondering, if I should run the triflate in a similar mixture?

    P.S.: I realize this is not a forum, but alas the google gods(aka googlebots) have brought me to your page.

    Comment by Chemistry Enthusiast??? — April 3, 2008 @ 6:27 pm

  22. CDCl3+DMSO is a bad idea because the shifts will vary a lot depending on the ratio. (It looks like someone tried to dissolve a highly crystalline material in CDCl3, failed, and was lazy to evaporate or prepare a new sample). Dont use mixtures if you can help it – with mixed deuterated solvents your shift values become irreproducible and your instrument can get confused when looking for a deuterium signal to lock on.

    Triflates: Use 2,6-collidine as a base, in DCM. I suppose you can use other chlorinated solvents as well but why bother. Some people used NEt3 or iPr2NEt but collidine is the bestestst.

    Sonogashira does not need strong acid wash during the workup – you can use whatever you want for your workup. In case that you worry about problem with Cu, Pd carrying over into your product you can as well wash it with either EDTA (bis Na salt, with some aqueous ammonia) solution or with cyanide.

    As for the starting material searching, I recommend ACD database of commercial chemicals – with the MDL-provided database search. You can also search commercial availability through Scifinder but ACD/MDL is far better. (There are other alternative search engines for ACD but I hated them.)

    Comment by milkshake — April 3, 2008 @ 8:34 pm

  23. Milkshake, you are the man (and I mean that in a strictly non sexist kinda way for the lady visitors).

    Here is one of the work-ups I found:
    -I ran the rxn in Et3N
    -filter through celite
    -washed with saturated NH4Cl
    -extract in DCM/water
    -washed with 1N HCl (2x) is that to neutralize the base?
    -wash with brine
    -dry over MgSO4
    -evaporate solvent
    -purify by column chromatography

    I don’t know why I wash with NH4Cl, nor do I get the acid. I checked the pH, and it wasn’t neutral after 3 washes.

    btw, are you in grad school or industry or else?

    Comment by Chemistry Enthusiast??? — April 4, 2008 @ 9:12 am

  24. Thanks Milkshake. I thought I posted a few questions earlier, but they don’t seem to show. Is it because you have to publish it before it shows or should I repost it?

    Comment by Chemistry Enthusiast??? — April 4, 2008 @ 9:58 pm

  25. You love me like a man, I know.

    I have an industry-kind of job in academia – the best of the two worlds, realy.

    The reason why the automated spam-eater here ate your comment was that it was formated like one annoyingly frequent list of adverts. By the way, the spam/genuine comment ratio averages 20:1, without the spam filter we would be lost.

    Comment by milkshake — April 5, 2008 @ 12:53 am

  26. Thanks for following up, I appreciate it. I’m going to try something else, but regardless of the results, I’ll be sure to give you an update.

    P.S.: Don’t you get tired of chemistry sometimes? The fact that we don’t see what we make? We see the bulk, but really we react on the molecular level…just wondering.

    It’s monday, but that’s not excuse,

    Chemistry Enthusiast???

    P.S.: Does this mean you actually saw my previous questions?

    Comment by Chemistry Enthusiast?:?? — April 14, 2008 @ 3:52 pm

  27. Oh never mind, i just saw it.

    Comment by Chemistry Enthusiast?:?? — April 14, 2008 @ 3:53 pm

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