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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: Twitter: Dereklowe

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January 25, 2008

Extractions: A Way of Life

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Posted by Derek

Over at Org Prep Daily, Milkshake did an excellent post earlier this month on extraction techniques. It’s well worth looking over, even for experienced lab crew. Solvent extractions are a way of life for organic chemists, a fact that has not changed since the beginning days of the science, because (for one) we still do the bulk of our reactions in one sort of solvent or another, and (two) because the bulk of our reactions need to have garbage removed from them, and this is the first line of cleanup. (Here it is in real life - scroll down).

For those readers who aren’t chemists, three paragraphs of explanation: extraction works on the “like dissolves like” principle. A look at a bottle of oil-and-vinegar based salad dressing that’s been sitting for a while will show the familiar layers, with the oil on top and the aqueous layer below. If you were to take samples out of each and analyze them, you’d find that they contain rather different parts of the dressing mixture. The oil layer will have the compounds that can’t dissolve in water very well – organic pigments like carotenes or lycopenes, for example. They’re better off in with the oil molecules; they don’t have any polar molecular features strong enough to horn in on the hydrogen bonds that water uses to stick to itself.

Down in the water layer, on the other hand, is all the stuff that has such polarity. All the amino acids and most proteins will be there, as will the sugars and other soluble carbohydrates. These compounds have a lot of groups (hydroxyls, amines, carboxylic acids) that can interact strongly with the small, polar water molecules. Since there’s a lot of vinegar in there, too, acid-base chemistry will be a factor. The compounds with strongly basic groups (fishy amines and the like) will be protonated by that acetic acid, and the resulting salt is a natural for the water layer. A few base-containing things that might otherwise be just as happy in the oil layer will be pulled in by this effect.

So if you have a messy mixture of stuff, you can separate the greasy components from the polar ones by shaking up the lot in a mixture of water and some solvent that’ll form a separate layer. Sometimes you’ll want one layer, sometimes the other, depending on what your product is like, but most of the time organic chemists are throwing out the water layer and keeping the other one. There are other tricks – for example, if your compound’s acidic or basic, you can adjust the aqueous layer the other way to hold it as a salt, wash out all the other goo with solvent, and then change the acidity so that your compound will now go into a fresh solvent wash. In all these cases, you drain off the appropriate layers with one of these.

I would not like to hazard a guess at how many extractions I’ve done. Shaking a sep funnel is such a basic act of organic chemistry – every time you mix something up and wait for the layers to separate, you’re participating in a rite that goes back to the days when labs were only illuminated by sunlight or fire. It’s one of the few things that a scientist from the 1850s would immediately recognize if teleported in front of my fume hood, that’s for sure (the fume hood itself would be a revelation, for starters).

I have to say, though, that Milkshake’s nom de blog is an unfortunate one for the topic, since one of the worst things that can happen to you during an extraction is a thick emulsion. That’s when the layers don’t want to separate – millions of tiny droplets of each component decide, for various irritating reasons, that they’re happy where they are, thanks, and don’t pair off with their former comrades. The result is a thick, opaque mess, so the name for the most intractable emulsions is, naturally, “milkshake”.

One of the things he mentions as seldom seen these days is actually one of my favorite pieces of lab apparatus: the liquid-liquid continuous extractor. Sad to say, I don’t have one these days, but I could find or buy one if the need arose. There’s something appealing about setting up a continuous, automatic purification. Being able to see the results over time (the solvent pot in these things gets uglier) makes you feel as if you’re getting something done even if all you’re doing is standing there watching the extractor. A fine apparatus it is, and worth a post of its own some day. . .

Comments (4) + TrackBacks (0) | Category: Life in the Drug Labs


1. walt on January 25, 2008 11:16 AM writes...

Another continous extractor used extensively prior to HPLC was counter current distribution. The apparatus is an absolute piece of glass-blowing art and quite effective also. We had one in the attic in the early '80s at Lederle Labs.

Extraction is even more of a mainstay for lipid chemists who all have had a healthy (or unhealthy) exposure over the years to chloroform.

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2. Chrispy on January 25, 2008 5:55 PM writes...

One of my favorite bit of extraction apparatus is the soxhlet extractor.

There is just something so entertaining about watching it fill and dump, fill and dump all day long...

One trick I have seen the old-timer chemists employ with nasty emulsions is to walk over to the biologists' area and pop it in a centrifuge. That will separate your layers right quick!

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3. milkshake on January 25, 2008 8:36 PM writes...

ah that's where all this traffic is comming from -Thank you for the plug Derek!

I did a thesis work on alkyl phospholipids and they are wonderful emulgators. One quickly learns not to do liquid-liquid extractions on these compounds.

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4. Georg Felis on March 4, 2008 2:03 PM writes...

Heck, continuous flow separators have been around for a lot of years, up to the point where in at least one industry they have become obsolete. My parents used to use one in their industry for many years, first hand cranked, then later electrical. We kids called it a Cream Separator, and many a cows output was put thru it during our time as a Grade A Dairy :) That was way back when the cream was the good part of the milk, now it is just used as a mailbox post.

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