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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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March 8, 2005

The Latest from the Fume Hood

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Posted by Derek

Now, today's reaction in my hood looked like some chemistry, and no mistake. Bright yellow-green, and fizzing! Some of my readers may read that description and say "Hmmm. . .ethyl diazoacetate insertion reaction." Right you are. The color is from the diazo group - a lot of small diazo compounds have it, or so I hear. They tend to go ka-boom if handled roughly, so it's not like I have a big data set. Diazomethane (and its trimethylsilyl variation) are the only other ones I've seen, and I won't be broken up if the list doesn't get longer.

The fizzing is the diazo group breaking down, with nitrogen gas being given off as the compound reacts. Having a reaction that gives off a gaseous by-product is a wonderful way to drive the process to completion, since there's no way for the reaction to run in reverse once the gas has departed. And its formation is almost always a big downhill step for the free energy of the reaction, which puts thermodynamics on your side. Of course, that big leap to a lower energy state is something you don't want these things to just make on their own - that's where that ka-boom business comes in.

It's nice to have an indicator of success like those nitrogen bubbles; you know that you're probably not wasting your time. With diazomethane itself, you can watch its color disappear and know that something's happening. Another famous indicator is the smell of a Swern oxidation, which turns DMSO into stinky dimethyl sulfide. I agree with a friend from grad school who said that he'd come to actually enjoy the aroma, since it was the smell of success.

Most reactions, though, don't let you know what they're up to. They just look a little darker (well, often a lot darker) at the end than they did when they started. You have to interrogate them yourself, taking out a drop for thin-layer chromatography or some spectral technique. No problem with doing that, unless your reaction is being run at below-zero temperatures, in which case the sample you're removing has surely warmed up by the time you've analyzed it. It's a common beginner's mistake to check a cold reaction that way and conclude (prematurely) that it's finished. Live and learn.

Comments (3) + TrackBacks (0) | Category: Life in the Drug Labs


1. The Novice Chemist on March 9, 2005 10:01 AM writes...

Aren't Swerns wonderful? I've come to really, really love them. Just like you said, I've come to check for the smell while I'm running a TLC to make sure that it's done. What metal are you using with the diazoacetate reaction? I've had little success with it...

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2. Derek Lowe on March 9, 2005 10:16 AM writes...

I'm using tin (II) chloride to react it with an aldehyde, as in JOC 54, 3258. Unfortunately, I can't go into details about what aldehyde I'm reacting it with and just why I'm doing that. But it looks like it worked, anyway.

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3. The Novice Chemist on March 9, 2005 1:21 PM writes...

Geez, Derek -- I've actually got that same paper. Looks like it worked better for your substrate than it did for mine... Just as well; I made the product with LDA and it did fine.

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