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ChemWiki: The Dynamic Chemistry E-textbook > Reference > Lab Techniques > Recrystallization

Recrystallization

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This technique is no longer as widely used as it was before the advent of flash chromatography, but it's still quite useful! A particular advantage is that compounds can be recrystallized in amounts that are somewhere between streaky and impossible to column. Do you have over 50 mg of a compound that should be a solid?[1]  Can you find something in the lab that will dissolve it?  If the answer to both questions is yes, hie thee to the oil bath and get to work![2]

  1. Find a solvent.  If your compound has been previously published, you may get lucky here. If you have Beilstein access, check under the melting point section--appropriate recrystallization solvents are sometimes listed.  Otherwise, group lore and common sense prevail. If a particular solvent works for a similar compound, give it a shot.  What you want is for your material of interest to be minimally soluble in cold solvent but reasonably soluble in hot solvent.  The ideal solvent should boil higher than, say, DCM or ether, but you can use solubility in the low-boiling stuff to point you in the direction of something more appropriate. If DCM seems like it may work, try recrystallizing in 1,2-dichloroethane.  If pentane (or hexane or pet ether) looks good, use heptane.
  2. Set up.  Common sense should dictate the size of glassware you use. Plan on the total volume of your solution taking up at least, like, a fifth of the total volume, but no more than about half or two thirds--head space is your friend.  You're going to want an appropriately sized stir bar, too, and an oil bath. While heat gun recrystallizations may seem quick and easy, I don't recommend them--it's easy to scorch small amounts of very precious materials with a heat gun. Use an oil bath. Add your compound to the flask, and add a smallish amount of solvent.  Heat to about 10-20 degrees above the boiling point of the solvent.[3]
  3. Just enough solvent--not too much.  If you screw up anything, it'll probably be this step, so be patient and go slowly.  Wait until your initial amount of solvent has been refluxing for at least 5 minutes.  Check to see if your stuff has dissolved. If not, add a little more solvent, wait, and check again.  Repeat as needed.  If you happen to notice that a stubborn bit of material just won't dissolve no matter how much solvent you add, you're probably going to have to start over--you have an insoluble impurity.  Take a hot coarse frit (use a heat gun or oven to get it nice and toasty) and vacuum filter your hot solution.  This will remove the insoluble crud you don't want.[4]  Once all your material is in solution, you're ready to go on. 
  4. Cool down.  As a side note, some people recommend a hot filtration every time.  If you see anything solid, or suspect that there is any dust or other crud that could serve as a nucleation hotspot, you need to take your stuff through a hot frit.  If your material absorbs like mad, and the solution is so dark it's opaque, swirl the flask and see if any little chunks are visible--some usually stick to the glassware.  If you see them, you need to hot filter.  If no solids are visible, you can just turn off the stirring, pull out of the oil bath a little, and let the solution settle for a minute.  Then decant very carefully.  Whatever you decant or filter into should ideally be as pristine and unscratched as possible.  Once the solution is in the nice unscratched glassware, cover it (do not use parafilm! it will melt) and place it in an out-of-the-way hiding spot.  You are hiding it from yourself.  Leave it alone for at least an hour or two.  Do not pick it up.  Do not disturb the solution.  You may gently feel the side of the flask after it has been sitting neglected for an hour.  Wait until it's room temperature--not remotely warm!--before you do anything else. 
  5. Wait for shiny things.  Once your solution is room temperature, you may relocate it to a refrigerator.  Be careful that your solvent won't FREEZE in said refrigerator--this can be a problem when water is the solvent, but seldom otherwise.  If freezing is a possibility, or you have no refrigerator, use an ice bath.  Either way, let it sit in the cold for a good long while.  Overnight in an ice bath won't work so well because the ice will melt, but I like to do at least overnight if in the refrigerator.  Be very patient and leave your growing crystals alone.  Slow growth is best!  If you're recrystallizing something colorful, you can watch as the solution becomes more and more pale--and then you know it's ready.  Watch for shiny solids.
  6. Harvest Filter, and rinse with a little bit of very cold recrystallization solvent.  Let dry and TLC or NMR to ensure that they are sufficiently pure--sometimes more than one recrystallization is necessary.

References

  1. Superior synthetic ninjas may be able to work with less material--I can't.  Conveniently, the upper limit of the amount of material that can be made shiny in a single batch is determined by the size of your glassware.
  2. A very important caveat: If your material is too dirty, this just won't work.  If the TLC shows any spots of comparable intensity to your goodies, take the stuff through a silica plug before you even try to get it shiny.  If other spots are there but much fainter, you have a good chance.
  3. UNLESS you have a good reason to keep the temperature lower.  If you strongly suspect that your material isn't thermally stable at, say, 140 ºC, and you're using toluene, don't heat that high.  You'll be fine only going to, say, 70 ºC--I've done this before on many occasions.
  4. Check to make sure  it is not your compound of interest.  Sometimes it is.  It is quite confusing when this occurs, and you could be very sad if you happen to toss anything without making sure it's junk.

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  • psi*psi

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Last Modified
02:26, 26 Dec 2013

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