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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: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

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April 18, 2005

A Smelly Riddle

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Posted by Derek

Here's a chemical puzzle for you: all of us who have worked in an organic chemistry lab can agree, I think, that pyridine reeks to the skies. My descriptive powers aren't up to conveying its smell, because it's really unique - foul, penetrating, and like nothing else but pyridine.

And we'll have no trouble agreeing that thiophenol is a stinker, too. It's one of the prototype stinkers, actually, since it's the main smell of burning rubber. (Imagine that aroma concentrated and ready for use in a bottle, and you've got thiophenol.) Now, what if we take those two structures and combine them?

You'd figure that, say, 2-mercaptopyridine would be impossible to take. But it has no smell whatsoever. (Some of you may be ready to e-mail me about how this compound isn't completely an SH, that it has some thioamide character. But before you do that, recall that thioamides are unbearable, too.) No, this seems to be a case of smells cancelling out at our nasal receptors. For whatever reason, a molecule with the combination of a pyridine nitrogen and an aromatic thiol doesn't set off our sensors.

And that's a good thing, considering what it would be like. Now, I guess you could make a one-molar solution of thiophenol in pyridine, and that would do the trick. I'll bet nothing would cancel out then! Fortunately, I've never come across that reagent combination, and if I ever do, I'll find something else that urgently needs my attention. . .

Comments (6) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. John Johnson on April 18, 2005 10:24 AM writes...

Are these compounds smellier than carbon diselenide?

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2. Peter Norman on April 18, 2005 10:31 AM writes...

Best effect I ever saw was when a colleague was using 2-marcaptoethanol and the hood vented onto a low roof from which the buildin's computer room took its air intake.

On a still day this led to an evacuation of the computer room.

Permalink to Comment

3. Derek Lowe on April 18, 2005 11:18 AM writes...

No, I wouldn't class either of them above carbon diselenide, at least based on (nose)witness testimony to its powers. But neither of them are things you'd willingly snort, that's for sure.

Permalink to Comment

4. The Novice Chemist on April 18, 2005 4:13 PM writes...


Do you think the 'canceling' has something to do with a weird hydrogen-bonding effect? I'm just trying to explain the difference...

Permalink to Comment

5. Daniel Newby on April 18, 2005 8:50 PM writes...

This paper talks some about the theory of odors. The current working hypothesis is that each type of odor receptor is sensitive to a band of vibrational energies. That helps explain why replacing hydrogen with deuterium can noticeably change a compound's odor, even though the shape and chemistry change very little.

The only spectra I could find for your three compounds were the Raman spectra from Aldrich, but they show that 2-mercaptopyridine is missing the thiol line near 2500 wavenumbers, which the Turin paper quotes as giving thiols (and boranes) their characteristic smell. The pyridine lines also change quite a bit but I have no idea of the significance.

Interaction with a zinc atom also seems to be important for olfaction. I have no idea whether or why 2-mercaptopyridine would differ in that regard. Perhaps a real chemist could enlighten me...

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6. Giagan on April 19, 2005 12:17 PM writes...

I'm trying to recall a funny smell-related description from memory. In the Encyclopedia of Reagents for Organic Synthesis (red volumes edited by Paquette), under "Form supplied in" Lawesson's reagent is described as "evil-smelling yellow crystals"!

The reagent is a conglomeration of sulfur and phosporus atoms so no real surprise that it reeks, but having used the reagent, I now know what evil smells like!

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