Org Prep Daily

May 29, 2010

Back in the lab

Filed under: Uncategorized — milkshake @ 12:42 am

Today was my first day at the new job.

48 Comments »

  1. Excellent!!!!!!!!

    Comment by chemgeek — May 29, 2010 @ 1:17 am

  2. excelente!

    Comment by james — May 29, 2010 @ 3:58 am

  3. All the very best..

    Marto

    Comment by marto — May 29, 2010 @ 6:26 am

  4. Welcome back Milkshake! Good luck!

    XXOX

    Comment by Taitauwai — May 31, 2010 @ 5:05 am

  5. saweet!

    Comment by T — May 31, 2010 @ 7:01 am

  6. I assume ethyl acetate and ethyl ether now smell slightly different to you than they used to – at least they should for the next 2-3 days!

    Comment by HPCC — May 31, 2010 @ 5:04 pm

  7. Congrats!!! Best of luck with this one mate. Should be good to see some more exciting procedures being posted now!

    Comment by OrganicOverdose — May 31, 2010 @ 7:19 pm

  8. My sincerest congratulations! I hope that all is well.

    Comment by partial agonist — June 1, 2010 @ 4:41 pm

  9. still in the good ole southeast? fill us in with what you can…

    Comment by fng — June 1, 2010 @ 7:46 pm

    • its with an academic medchem group but I cannot go much into the details

      Comment by milkshake — June 1, 2010 @ 10:27 pm

  10. Congratulations!!!

    Comment by JG — June 1, 2010 @ 8:20 pm

  11. Congrats! Be sure to tell us all about it!

    Comment by joshuca — June 1, 2010 @ 9:16 pm

  12. CONGRATULATIONS!!!
    Cheers

    Comment by madforit — June 8, 2010 @ 3:33 am

  13. Good luck. On a side note, does anyone here know how to remove a suzuki catalyst (triphenylphosphino-whatever) from a crude reaction mixture?

    I have like 800 mg’s of the stuff, can I remove it with an aqueous wash, and then run the organic layer over celite?

    Will this remove >95% of it>

    Comment by Cathy — June 8, 2010 @ 12:35 pm

    • If your product is not too sensitive to oxidation I would add few drops of hydrogen peroxide to the reaction mix, that should promptly oxidize all phosphines to phosphine oxides and Pd to Pd(II). Pd(II) should wash away during aqueous workup (you can add some EDTA or cyanide during the extraction if you need really low levels of Pd) and phosphinoxides should stay on the start of the column, they are quite polar.

      Comment by milkshake — June 8, 2010 @ 1:44 pm

      • Thanks Milshake! But I think my product is very sensitive to oxidation, it’s too risky adding hydrogen peroxide.

        Do you think a simple wash with aq.acid + filter over celite would do if I’m only looking to remove about 90% of the catalyst!?

        Thanks!

        Cathy

        Comment by Cathy — June 8, 2010 @ 2:42 pm

      • In that case I would use a aqueous sodium cyanide or sodium sulfide to complex out Pd – once I had a problem like this before (my diaminopyrimidine compounds were strong chelators and acrried metals with them, I added TMSCN during the workup to get Pd and Cu out)

        Comment by milkshake — June 8, 2010 @ 3:40 pm

  14. Speaking of the Suzuki reaction, does anyone know where I could find information about the toxicology of the catalyst?

    I got a few drops of the catalyst dissolved in DCM on my gloves last week. I’m always paranoid when it comes to metals!

    Comment by Kirsty — June 9, 2010 @ 8:16 pm

    • Kristy EMEA guidelines contains some general info on Metals including Pd but may not be as specific as desired.

      http://www.ema.europa.eu/pdfs/human/swp/444600.pdf

      I would also search MSDS data bases. If you have a CAS# would help, however unless happen to get one that has details is either going to be useless or just more general info.

      Good luck

      Comment by CMCguy — June 9, 2010 @ 10:32 pm

      • Pd has only negligible toxicity (even nickel is lot more toxic than Pd) but unfortunately Pd can be detected in extremely low traces in the product and since it is classified as a “heavy metal”, a carry-over of Pd-related cotaminants into the final product is a serious complication in manufacturing active drug substances. As far as you dying of Pd poisoning I think you are safe unless you drink gram quantities of the stuff.

        Comment by milkshake — June 10, 2010 @ 7:33 am

  15. Okey Dokey Milkshake! Let’s hope those triphenylphospine ligands aren’t too toxic! ;)

    I read about a chemist in the states some years ago who got a few drops of dimethyl mercury on her gloves and died some months later :O

    Fortunately, I only got a few drops of this stuff on my gloves, and I was wearing two paris (nitrile 2x 0.11 mm) and took them off after contamination I’d say in <30 seconds. But dam, DCM eats nitrile!

    Comment by Kirsty — June 10, 2010 @ 11:21 am

  16. hi guys,
    does here anybody know how to make acrylamide of poor nuclophile nitrogen atom, such as pyrrole, indole etc!acyl chloride and mixed carbonate (acrylic acid and isobutylchloroformate with NMM in THF)did not work well..
    thanks!!

    Comment by madforit — June 11, 2010 @ 5:41 am

    • yah, this is a serious problem with acryloyl chloride and other activated forms of acrylic acid – they crap up very easily, for example by conjugate addition.

      I would try an experiment with a weak base like pyridine (or 2,6-lutidine) and acryloyl chloride. If this does not work I would suggest the N-silylation trick with acryloyl chloride and CuCl2 as a catalyst, as described in: Catriona Thom and Philip Kocienski: Synthesis (1991 or 1992, I am not sure) page 582-586

      Comment by milkshake — June 11, 2010 @ 3:42 pm

  17. Thank you so much…
    cheers

    Comment by madForIt — June 12, 2010 @ 8:52 am

  18. Hi Milkshake,

    Is it possible to use a rotevap to seperate DCM and toluene, I mean, if the pressure is redued enough, somtimes the DCM misses the first trap, and goes straight into the second trap at the back…and the toluene goes into the first trap.

    ?

    Thanks,

    Tim.G

    Comment by Timmy — June 12, 2010 @ 2:41 pm

    • sorry i don’t understand what you mean, most lab-scale rotovaps that I saw had only one condenser (unless you use oil pump as a vacuum source – a pump which should be protected with additional cold trap – but highvac would be totally inappropriate for evaporating DCM).

      Any distillation setup should be able to reasonably separate DCM and toluene because their boiling points are far apart and they probably do not form an azeotrope – but the purity of the recovered solvents would not be sufficient to put them back in the bottle (unless you are using these solvents only for a non-demanding application like solvent extraction). I would be very reluctant about using recycled solvents as a reaction media. Besides, these solvents are cheap enough to buy. The only concern is that DCM is somewhat expensive to dispose as a halogenated waste on large scale, and there are OSHA-mandated exposure limits, so thats why process chemists do not like to use it.

      If you are concerned with a process-related question “how to recycle your solvent mix” I may not be the best person to ask because I never worked on process reactor scale.

      Comment by milkshake — June 12, 2010 @ 3:03 pm

  19. Congrats!

    I don’t have any lab questions.

    Comment by Sili — June 12, 2010 @ 4:22 pm

  20. Does anyone know how I could destroy trimethylsiloxy-derivatives? Can I pull them into teh aq.phase somehow?

    Comment by James — June 13, 2010 @ 3:17 am

    • you can treat them with a small amount of aqueous HF diluted in acetonitrile, TMS-F is a gas. Definitely wear gloves

      Comment by milkshake — June 13, 2010 @ 1:53 pm

  21. Won’t that convert the trimethysiloxy derivates to a trimethylhydroxy silane product

    i.e replace Si-O-R with Si-O-H which is water soluble?

    Comment by James — June 13, 2010 @ 5:17 pm

    • Sorry James but you need to look up the basics for your silicone chemistry: 1) silanols are not water soluble at all: they are quite greasy in fact 2) Me3SiOH is unstable in free form and quickly dehydrates to Me3SiOSiMe3 on its own. (Hexamethyldisiloxan is a reasonably volatile liquid, with boiling 101C). 3) fluoride quickly transforms silyl ethers and silanols to silyl fluorides (compounds which are volatile and very greasy). Why don’t you find some organic textbook with a chapter on organosilicone chemistry and read it before posting even more comments?

      Comment by milkshake — June 14, 2010 @ 7:30 am

  22. Wow, Kirsty you’re a safe one! I am only double glove for nasties like liquid bromine or HMPA!

    You should be a-OK, the DCM is FAR more toxic than the phosphines or Pd. (coming from someone who bathed in the contents of a 4-L jug of DCM, (boy is it COLD!)

    Comment by Jose — June 16, 2010 @ 10:18 pm

  23. Great to see you back, Milkshake. I hope the new digs are working out for you.

    Comment by chemoptoplex — June 18, 2010 @ 9:27 am

    • I should see soon – Right now I am still setting up my lab space, learning the way around the institute and getting known the people, and bringing up some building blocks (I am still quite far from making anything that would be worth testing.)

      Comment by milkshake — June 18, 2010 @ 12:40 pm

  24. Is there any way to selectively hydrogenate only a tetrasubstituted olefin in the presence of a disubstituted alkene?

    Comment by Mad Hatter — June 20, 2010 @ 2:16 pm

    • You can use excess of triethylsilane in DCM at 0C to room temperature with your substrate and add TFA slowly, to saturate tetrasubst C=C in the presence of disubst C=C (but disubst C=C will be left alone only if the disubst C=C is not conjugated with anything). Ketones will be likely reduced to alcohols by the system. It proceeds by C=C protonation and the formed stabilized carbocation abstracts hydride from the silane. In rigid polycyclic systems like terpenoids the tetrasubst C=C between rings that gets saturated often ends as a trans ring junction – the thermodynamically more stable product is the main one.

      Comment by milkshake — June 22, 2010 @ 1:10 pm

  25. Thank you very much, milkshake. I am impressed by how much you know! I am planning on reducing a tetrasubstituted olefin which sits a the ring junction in a 6,5-fused ring system, and I want the cis-fused stereochemistry in the product. This should (by far) be the most thermodynamically stable product, and I will thus try this methodology that you kindly mentioned.

    Comment by Mad Hatter — June 23, 2010 @ 11:33 am

    • I remember vaguely that delta G energy difference between the cis and trans isomer in hydrindane systems is not as great (but the cis should be still favored by something like 1 kcal/mol). I think you may end up with a mixture of both. Maybe you could try at first to run it at 0C – and if you get a poor cis/trans ratio you could try again at -78C and use triethylsilane with some stronger acid like TfOH in DCM for protonation (or better yet, TFA with added BF3.Et2O for extra kick)

      Comment by milkshake — June 23, 2010 @ 12:37 pm

  26. Is there any electron-withdrawing group attached to that tetra-substituted olefin? In which case then you might be able to use dissolving metal single-electron reductions, such as Li or Na in NH3(l) with a proton source, such as tBuOH. Sometimes, there are run in a proton source, such as EtOH… In these cases, I seem to remember that protonation of the forming carbanion is thermodynamically driven… Something to consider, provided, of course, that your olefin is electron-poorer than your disusbstituted one that you want to avoid harming.

    Comment by HPCC — June 23, 2010 @ 5:35 pm

  27. No, there is not. What I am planning to do is a Birch reduction of 2-indanol, then selectively saturate only the tetrasubstituted olefin and finally oxidizing the secondary alcohol to the corresponding ketone. As mentioned, I want the cis-fused stereochemistry in the product and this is now my only worry.

    Comment by Mad Hatter — June 24, 2010 @ 1:49 pm

    • This will be an interesting transformation – please let us know how this went. (And in case that you have a nice procedure to share I would be totally delighted to put it up here for you.)

      Comment by milkshake — June 24, 2010 @ 4:23 pm

  28. Yes, I will be happy to. I have now ordered the needed chemicals and will hopefully be able to test the chemistry in the next week.

    Comment by Mad Hatter — June 25, 2010 @ 11:20 am

  29. Congratulations and good luck!

    Comment by wolfgang — June 28, 2010 @ 11:54 am

  30. Congratulations and good luck!

    Comment by BFW — July 24, 2010 @ 4:08 pm

  31. Congratulations and best of luck with the new job.

    Comment by Reaction Runner — July 26, 2010 @ 4:31 pm

  32. Query for you.

    Can we use Et3B as a radical initiator instead of conventional AIBN/benzoyl peroxide for radical mediated side cahin bromination of alkyl benzenes. I end up in monobrominated, dibrominated and unreacted starting materials with either NBS OR dimethyldibromohydantoin using AIBN/benzoyl peroxide. Are there any ways to control the dibromnation. Because Et3B is known to initiate reactions even at -78 deg cel, will it be worth running bromination at lower temp using Et3B as initiator. Your expert comments are appreciated.

    All the best with the new job .

    regards
    pasupathy

    Comment by pash — September 24, 2010 @ 4:12 am

  33. Hi. Does anyone know how to remove the smell of the acryloyl chloride from the glassware and syringes after the use?
    Thanks.

    Comment by sk4350 — June 26, 2012 @ 8:05 am

    • I think ammonia diluted with some alcohol should do it

      Comment by milkshake — June 26, 2012 @ 9:11 am


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