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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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June 10, 2011

Chem-Geekery: Name Reactions You've Never Run

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Posted by Derek

A colleague of mine is running a Diels-Alder reaction this morning, and turned out to have never run one before, despite many years of experience in chemistry. (I'd bet, though, that a fair number of chemists who have run the reaction did it in an undergraduate lab and never have since). I've run them - although it's been a while - and I've done the Claisen rearrangement (ditto), the Knoevenagel condensation, the Barbier reaction, and the Henry reaction. I've done plenty of Horner-Emmons-Wadsworth reactions (although not in the last few years), Jones oxidation, Birch reduction, the Arbuzov reaction, and a Chichibabin pyridine synthesis, many years ago. And I've done a Cannizzaro, the Gabriel synthesis, Ferrier rearrangements, the Shapiro reaction, Peterson olefination, and Lindlar reduction. I've run Sandmeyer reactions, the Prins, Staudinger reduction, Ullmann coupling, and Weinreb ketone synthesis. I've done the Wolff–Kishner reduction (once) and Wurtz coupling (once), a Dakin-West (once), a Darzens (once), and a Delepine reaction (once).

But I've never done a straight aldol condensation, at least, not on purpose. And I've never, as far as I can recall, actually done a Fischer indole synthesis, or the lovely Skraup reaction. I've never run a Bayliss-Hillman, a Ritter reaction, a Cope rearrangement, a Julia olefination, a Pictet-Spengler, a Nazarov cyclization, nor a pinacol, and I don't think I've ever set up an ene reaction.

So what's on your list? What's the most famous reaction you've never run? Is there some reaction you've always sort of wanted to do, but never had the reason?

Comments (52) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. opsomath on June 10, 2011 8:41 AM writes...

The first or second reaction I ran in grad school was a Hantzch pyridine synthesis. It had three distinct and lovely color changes, and smelled exactly like Doritos. I haven't been able to eat the things since.

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2. Steve on June 10, 2011 8:55 AM writes...

I've never done a traditional Wolff-Kishner (with isolation of the hydrazone. Always opted for the wonderfully named Huang-Minlon modification.

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3. InfMP on June 10, 2011 9:01 AM writes...

I ran a Huang Minlon yesterday. The guy doesn't give a first name or initial.

Delicate functionality is not an option.

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4. susurrus on June 10, 2011 9:01 AM writes...

I've always wanted to run an olefin metathesis reaction (does it have a proper "name"?) but never have. One of the obscure reactions that I have run is the Achmatowicz reaction. That one is cool because it's fun to say Achmatowicz out loud :)

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5. Yo're Pfizered on June 10, 2011 9:11 AM writes...

My graduate adviser had a fascination/obsession with the Pummerer Rearrangement, but finally conceded that maybe it just wasn't all that useful. Thankfully I never had to try it.

The Ugi, despite all the stuff floating around in the reaction, is a nice bit of chemistry. Then again all chemistry is nice if it works....

Always wanted to do a Sharpless Asymmetric Epoxidation, but never had a reason. I did do quite a few of his AD reactions in graduate school, though.

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6. Hap on June 10, 2011 9:15 AM writes...

1) Friedel-Crafts, though it's a tough choice - I have run almost no named reactions.

2) One's definition of delicate functionality when running reactions in refluxing ethylene glycol with KOH probably has to be pretty broad, I guess.

3) I always thought that if Beavis and Butt-head were chemists, they'd talk about succinimide a lot.

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7. BFS on June 10, 2011 9:20 AM writes...

Hantzsch thiazole synthesis: a-haloketone + thioamide.

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8. A Nonny Mouse on June 10, 2011 9:21 AM writes...

Grob fragmentation....it sounds so "nice".

Also, Lindlars best done in neat pyridine when they stop dead at the olefin.

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9. susurrus on June 10, 2011 9:26 AM writes...

I'm going to apologize in advance here...

#6 Hap: I think if Beavis and Butthead were chemists, they'd be obsessed with the But-Toy variation of the Mitsunobu reaction (JACS (2006), 128(30), 9636-9637.)

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10. AlchemistOrganique on June 10, 2011 9:43 AM writes...

Best...names..ever...wish I had run them:

Chichibabin Reaction (mmm...evolution of dihydrogen)

Kharasch Reaction (mmm...trihalomethane radicals)

Nenitzescu Indole Synthesis (it looks sooo easy)

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11. Matthew Salter on June 10, 2011 9:44 AM writes...

To my enormous shame I have never run a Swern Oxidation. Never done a Pauson-Khand either.

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12. Pete on June 10, 2011 9:54 AM writes...

Anybody ever run a Hooz reaction?

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13. OldLabRat on June 10, 2011 10:06 AM writes...

The Chichibabin reaction is fun as is the Robinson ring annulation. I always wanted to run a Suzuki, but what the Heck, I never had reason to do so. I was also Curtius about the Grubb reaction, but left the lab before it was revealed.

What do you want, it's Friday.

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14. John Spevacek on June 10, 2011 10:19 AM writes...

#4 - You could call it a Grubbs reaction - assuming you were using a Grubbs catalyst.

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15. RB Wood on June 10, 2011 10:28 AM writes...

I always wanted to use the van Boom reagent and thumb my nose at Fate.

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16. RB Woodweird on June 10, 2011 10:59 AM writes...

Damn reagent exploded and blew half my name off.

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17. NHR_GUY on June 10, 2011 11:08 AM writes...

Bischler–Napieralski for dihydroisoquinolines.....done in neat P(O)Cl3. I loved this reaction. Very reliable but nasty work-up :)
Never did a D-A but always wanted to.
Friedel-Krafts though old school, is another good reliable C-C reaction I've done.
Newman-Kwart (Kahn) reaction converts phenols into thiophenols by refluxing thiocarbamtes in diphenyl ether at ~ 200oC. I like this one as well. Someone should adapt it for the microwave. There is an easy Tett. Lett. there for anyone who wants to do the work.

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18. Kugelrohr on June 10, 2011 11:14 AM writes...

I've always wanted to run a Willergodt-Kindler reaction on some long chain aryl ketone like 1-nonadecaphenone. Seems so amazing that such simple conditions would zip the ketone stepwise down the alkyl chain to give the terminal thioamide.

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19. Anonalso on June 10, 2011 11:19 AM writes...

Never ran an Ugi till recently, but have since fell in love with the Corey-Link amino acid synthesis. Easy, cheap and does not need to be hammered with acid at the end to get a hold of the final product.

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20. Phil on June 10, 2011 11:28 AM writes...

The Fischer indole synthesis was the first reaction sequence I ran as an undergrad.

We used a Ritter-type reaction in early development to install a tertiary amine. It was with hydrazoic acid instead of HCN. The engineers were not enthused about scaling that one up.

I'd like to run an ene, Claisen or Cope, only because it would mean I figured out a clever way to set a bunch of stereocenters by relaying stereochemistry in a pericyclic reaction. Hasn't happened yet.

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21. johnnyboy on June 10, 2011 11:51 AM writes...

Out of curiosity (i'm not a chemist): why all the proper names on these reactions ? We have a bit of the same in the medical fields of course, but they're mainly leftovers from olden times that no one has had the power to change yet; more recently described diseases or cells are given more 'functional' names. Is it the same with chemistry, ie. all these reactions you're talking about were developed long ago ?. It's certainly entertaining to read them, though.

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22. processchemist on June 10, 2011 11:58 AM writes...

A Fischer indole synthesis was the only reaction that scared me seriously on the 1 l scale. I was young an inexepert and when they passed me the protocol (all the reactants in, then heat to 100°C) I did not valuate the controlled addition at high temperature as an option. No accidents, ma to see a flask that stays at 110°C (acetic acid, reflux) when immersed in an ice/water bath makes you think...

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23. MTK on June 10, 2011 12:01 PM writes...

Too many name reactions. Not enough time.

Tons that I haven't run including many already mentioned. Don't ask me why but the Fleming-Tamao oxidation is one that I would love to do, but never really had the need.

The Nazarov reaction can be a mess. You usually end up with some ugly dark reaction mixture with a bunch of black floaties in it. Yuck.

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24. BS on June 10, 2011 12:21 PM writes...

@21

Part of it is a leftover from turn-of-the-century chemistry, part tradition, but mostly it makes things easier to remember. There's no convenient naming convention for the combination of substrate, reagent, solvent, temperature, and resulting product so it all gets lumped under a title named after a famous chemist that discovered/described it.

Kind of in the same way if someone says they're doing a Whipple as shorthand for a pancreaticoduodenectomy, except chemists don't even have the convenience of that.

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25. Anonymous on June 10, 2011 12:25 PM writes...

@21: If you want to describe a reaction, you could list the starting materials, the reagents used, the reaction conditions, and the products. Or you could use the well accepted name and everyone familiar with the reaction will know exactly what you are talking about. So maybe we use the names because we are lazy?

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26. organic on June 10, 2011 2:22 PM writes...

Ran a Skraup quinoline synthesis on 250g scale with a substituted aniline. The reaction itself was really pure anger. After heating at 100°C for roughly 1h massive boiling of product starts (internal temp > 250°C!!!). Had two reflux condensers on both sides of my 6L-three-neck. As recommended from the authors from OrgSynthesis (procedure from the 1940´s) I cooled my flask from outside with a giant towel. After 3 batches I really had a feeling for this reaction and got 75% isolated yield of pure 5-methyl-8-chloroquinoline.

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27. Hap on June 10, 2011 4:55 PM writes...

"the reaction itself was pure anger"

That reminds me of this post from CBC (language not for less sensitive eyes). If "Vicks Vap-o-Cancer" or "fires of hell" appear prominently in your reaction description, then I hope that 1) it works and 2) that I don't ever have to do it.

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28. Sili on June 10, 2011 5:17 PM writes...

I can't remember names, I'm not much of a synthesist, and I fscked up the Cannizzaro in my undergrad lab.

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29. See Arr Oh on June 10, 2011 6:23 PM writes...

It's funny, since I came up in a more organometallic lab, I've done all the fun metals ones: Barbier, Sonogashira, Suzuki, McMurry, and a few room-temp Copes and Claisens.

I've had cause to do some of the more esoteric sigmatropics, such as the 2,3-Wittig and a Meisenheimer or two. Oxy-Cope is an old friend. So is Mannich. Swern's cousin Parikh-Doering was always good to me.

However, Derek, I trend with you in the old classics: never any aldols, Dieckmanns, and the only Diels Alder was in undergrad. Never a Birch. And I always wanted to do a Krapcho, just for the name, but didn't get around to it!

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30. rtw on June 10, 2011 6:34 PM writes...

@5. Yo're Pfizered, that wouldn't have been a certain Prof at MTU would it? Made me a disciple of the Pummerer and related reactions. Looked for ways to incorporate sulfur in every hetercycle I made for years, afterward. Still collect literature on the topic, have copies of all the major reviews.... And I was only an undergrad, also a former Pfizerite.

A friend of mine now at BMS has writen a couple books about Name reactions.. There are many I probably would have liked to try, but never got the chance while in industry. I am a fan of the many rearrangement and condensation Name reactions.

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31. entrepreneur on June 10, 2011 9:05 PM writes...

Like #4, I always wanted to run olefin metathesis reaction. Not only recently I got a chance to do so, but it gave us nice IP position. Really cool reaction to make macrocycles.

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32. MTK on June 11, 2011 8:37 AM writes...

The best (meaning most reliable and high yielding) name reaction I've ever done is a Pechmann condensation to form coumarins.

That thing is like falling off a log.

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33. newnickname on June 11, 2011 9:22 AM writes...

I guess I've done MANY name reactions but maybe I'm just into using the "names" more than others. I disagree with #25 Anonymous about describing conditions and reagents; it's often more about the overall synthetic transformation (bond breaking and bond making; FG interconversion) than reagents and conditions.

Look at the Mitsunobu: there are well over 100 variations but, to me, they are all Mitsunobus. (More correctly, they are all just variations of Mukaiyama's "Oxidation - Reduction Condensation Reaction" paradigm.)

Some people mistakenly use Jones Oxidation to describe a range of Cr(VI) oxidations that really aren't Jones's original Jones (CrO3 / H2SO4) but I still give them 8/10 or even 10/10 for getting the basic idea right.

Name reactions make it easy to describe variations, too. #4 susurrus mentioned the Achmatowicz. There's also the AZA-Achmatowicz (by Ciufolini). In addition to the oxy-Name, aza-Name, homo-Name, phospha-Name, epi-Name, bishomo-aquo-epi-seleno-Name, there are also just the "anomalous Name" reactions, too.

Years ago, I was running some Baeyer-Villigers and getting anomalous rearrangement products. It was disappointing not to get the needed compounds but exciting to have discovered something new and unexpected, maybe "The Newnickname Reaction"! (The results were never published because the PI said they weren't the desired products.) Except I eventually found a few other cases in the literature so it just remains "the anomalous B-V".

I am probably MORE curious about "UNNamed Reactions You Have Run or Discovered." I am positive that there are unprecedented UN-Named Reactions that remain unpublished and undisclosed -- scientific "nulltiples" and that Derek's readers probably have more than a few. I have several, myself. (I'm unable to post the link to the paper describing multiple versus nulltiple discoveries. See Note 7 in the Serendipity entry at Wikipedia for the free PDF. Or google "nulltiple" and pick a hit with the PDF link.)

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34. jackgg on June 11, 2011 4:51 PM writes...

I always want to run an Aldo, but never get a chance. For most cases, we purchase the chemical. I have done a lot of Fisher Indole synthesis for a MNAR project, and it seems to be very neat. You just through things together in acetic acid and cook.

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35. T on June 11, 2011 7:49 PM writes...

There are tons of obsolete oxidations out there, but I've always wanted to run a Corey-Kim oxidation - since it *uses* dimethyl sulfide!

http://en.wikipedia.org/wiki/Corey-Kim_oxidation

It's pretty rare to see in use.

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36. Josh on June 11, 2011 9:48 PM writes...

Polonovski reaction. Simmons-Smith

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37. Anonymous on June 11, 2011 11:46 PM writes...

Zincke-Suhl reaction. Did it, recovered and then had to do it again on a much larger scale!!! Smells like a rat's behind lol!

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38. inorganicman on June 12, 2011 3:02 AM writes...

do people really remember all those names and what reaction they refer to?

i'm glad there are so few inorganic named reactions, we tend to describe reactions by class or category which is much more informative and much less... Well... I think the profligacy of named reactions in organic chemistry is an aspect of the field that relates strongly to the... erm... arrogance involved.

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39. Secondaire on June 12, 2011 1:44 PM writes...

Why has nobody mentioned the Friedlander/Friedlander-Borsche condensation? Excellent for hammering out substituted quinolines; high-yielding with a Dean-Stark trap.

Also: I have a fond memory of doing the Clemmensen reduction to whack an aryl ketone to corresponding benzylwhatsit. Nothing sticks quite with you like when you're 19 and amalgamating zing and mercury by shaking Zn(0) and HgCl2 together in a big Erlenmeyer with HCl.

#17 - there used to be a guy in my lab who used so much POCl3 for this very purpose that he'd regularly have drops of phosphoric acid condensing and running down the glass of his hood.

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40. gippgig on June 12, 2011 4:18 PM writes...

#33 - it's note 10b in the Serendipity Wikipedia entry.

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41. C on June 12, 2011 5:29 PM writes...

@17 - Newman-Kwart reactions have been done under microwave conditions, and there's a palladium-catalysed variant which allows for lower temperatures (ACIE 2009, 7612-7615).

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42. fred on June 12, 2011 6:30 PM writes...

Funny, I never thought of "aldol" and "ene" reactions as "name reactions" because they weren't "proper" names.

@41 The Newman-Kwart is great fun over a bare sand bath at 200 plus C.

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43. Secondaire on June 12, 2011 7:22 PM writes...

@ 42 - reminds me of my Pd-catalyzed dehydrogenation of dihydromethylenephenanthrenes, done in the sand at 320 ˚C. It's kind of sobering to see this eerie blue fluorescent-tinged solution of molten polycyclic stuff...

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44. NHR_GUY on June 12, 2011 10:53 PM writes...

@41 Sweeeet thanks for the tip...Been a while since I did a N-K...I'll look it up

@42 try using a Woods Metal Bath...nice boiling cauldron of toxic (I just looked it up on wiki and found out it contains Cd) molten metal...we used to use it to heat N-K's

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45. MTK on June 13, 2011 8:27 AM writes...

@38,

I certainly don't remember all of them, but I'd say the majority of the name reactions mentioned so far I remember, or at least have some idea of how they work.

I perhaps am at a disadvatange however, since I'm not primarily a heterocycle chemist. They seem to have a name for every reaction that forms a different heterocycle.

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46. Better late than never on June 13, 2011 5:07 PM writes...

I always try and fit a Delayed-reaction into my daily schedule

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47. Baltic on June 15, 2011 2:26 PM writes...

I've never tried the Runaway reaction (well, at least not a serious one), and don't plan on trying one anytime soon.

Seriously, though, there are very few name reactions I have run.

I've always wanted to try a mild oxidation of some sort. This far, when I've had to run an oxidation, it has always been the "methyl-fused-aromatic-brickdust to fused-aromatic-brickdust-carboxylic acid" kind. Those usually required as brutal as possible conditions. And more often than not they failed.
Oh, and I most certainly would like to run Birch reduction - just because I've heard they look pretty. I love nice-looking reactions, even when they don't work nearly as good as they look.

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48. Acantais on June 15, 2011 5:39 PM writes...

I've always wanted to do a Tollen's test, just for the Silver left overs. Maybe someday...

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49. BARNOWL on June 15, 2011 7:41 PM writes...

French work-up and Chinese work-up

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50. Hap on June 16, 2011 1:11 PM writes...

You probably want to be careful if you do a Tollens test - I think the silver salts are explosive.

http://pubs.acs.org/cen/safety/19960108.html

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51. GSDecay on June 16, 2011 2:39 PM writes...

I'm sure I once remember seeing a paper by a certain Dr Flippin. A modification of the Heck reaction no less. You've guessed it: Flippin-Heck reaction anyone?
Can't say I've run the rxn though - such a shame.

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52. Dap on June 22, 2011 4:17 AM writes...

Beautiful names? Hell-Volhardt-Zelinsky! Useful too!

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