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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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January 13, 2009

Lack of Experience, You Know

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Posted by Derek

OK, solid chemistry around here today. It looks as if I'll be running a ring-closing metathesis reaction soon. Nobel Prize in 2005, all over the chemistry journals for years. . .and I've never had occasion to use one until now. And when I think about it, there are quite a few other reactions in that category for me.

For example, I'm not at all sure that I've ever done a directed ortho-metalation. I've come close a few times, and I couldn't absolutely swear that I've never done the reaction, but none come to mind. No Fischer indole synthesis for me, because I've always been able to buy the indoles I need, and the same thing applies (fortunately) to the widely disliked Skraup cyclization for quinolines. I've never done an Eschweiler-Clarke reaction, although there have been several times I've needed to form methyl amines, and it probably would have been a good idea.

I've never done any of those multicomponent condensation reactions (Ugi, Passerini, etc.), partly because I've never done much combinatorial chemistry. And I've never done a Rosenmund reduction, but jeez, in this day and age, who has? No Julia olefination, no Fries rearranagements, no Kolbe-Schmitts (or Kolbe anything, come to think of it). And no Paterno-Buchi reactions, because I haven't really done any photochemistry for about twenty years.

I suppose the biggest gaps in my record are the RCM (soon to be filled) and the directed metalation (unless I can think of one that I've blocked from my memory somehow). Most of the other big ones I've done at one point or another, albeit perhaps only once or twice: the last time I ran a Wurtz coupling, on purpose, anyway, was twice in the summer of 1983. I have run a lot of the obscurities as well, of course (Shapiro elimination, anyone?) And I have a lot of fondness for some lesser-known reactions, such as the Prins cyclization, which got me out of a tight spot in my first year of grad school (I've been grateful ever since).

So here's my chem-geek question for the laboratory-bound part of my readership: what famous reactions have you never done? Have you been avoiding it for some reason, or have you just never needed the thing (and wondered why it's so darn famous)? Confess below!

Comments (44) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. ZAL on January 13, 2009 9:29 AM writes...

I've never done an RCM, too, but I've done some Eschweiler-Clarke reactions during my Ph.D. (always worked very well, BTW). My list of gaps is pretty extensive too, though: first that come to mind are Heck, Sonogashira, SAD, HWE...

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2. kmd on January 13, 2009 9:44 AM writes...

Pummerer rearrangement...I've never needed it, but I always thought it looked cool

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3. kh06 on January 13, 2009 10:06 AM writes...

I've never done a standard Grignard where you have to actually make the reagent yourself...I've done cuprate additions, used grignards out of bottles, but I've just never had the opportunity (or need) to get out the Mg turnings myself!

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4. Tot. Syn. on January 13, 2009 10:22 AM writes...

Err... kinda embarrassing, but I've never done a Diels Alder, Heck (or Keck), Henry or Reformatsky reaction. And those are only the well-known ones... Draw from a full list (like http://www.organic-chemistry.org/namedreactions/), and it's not looking good!

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5. rhodium on January 13, 2009 10:45 AM writes...

Never done any flavor of a Robinson annulation. And the Skraup cyclization richly deserves its reputation.

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6. Steve on January 13, 2009 10:49 AM writes...

The ring-closing metathesis is the only one out of those you mentioned that I've actually done, but I'm only a sophomore in undergrad... and we did it in my Orgo lab, but that's only because we've had some great research going on in our department on RCM. It was pretty awesome.

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7. milkshake on January 13, 2009 11:08 AM writes...

I have never done Sharpless asym epoxidation nor metathesis, nor Reformatsky, Cope reaaragement, Braun's N-dealkylation, Wittig rearrangement, Arbuzov reaction, photochemistry, any electrocyclic reaction, Pummerer reaction or Chichibabin amination, Corey-Fuchs, Barton, or even the classic Stille coupling. I can probably go through the whole book on named reaction and find at least three quarters of them alien to me.

Rhodium: I wanted to ask you for some time - please are you that bee, famous in a galaxy far, far away? Thnx

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8. carbazole on January 13, 2009 11:23 AM writes...

I must say, other than the awful smell of the isocyanide, Ugi reactions are fantastic. I'm currently using one in a total synthesis, it's step 1, and I've done it on 200 g scale. I had never done a Rosenmund reduction till a few months ago, I always thought that was one of those reactions in the soph. textboook that never really work well, but wow, was it clean.

Never done any metathesis, never gotten a Stetter to actually work (was trying a difficult system), never done an Alder-ene reaction, never done anything with radicals on purpose, probably a lot else. The field is so vast it's probably tough to find someone with a complete repertoire, unless they made a point of going through the name reactions book and did one of each just for fun.

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9. Lab Chemist on January 13, 2009 11:25 AM writes...

Among many of the others already named, I've also never done a Swern

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10. vasili on January 13, 2009 11:27 AM writes...

I have a million named reactions undone but I specially remember a RCM from my PhD work when we prepared the 2nd gen grubbs catalyst (commercial but expensive) from the corresponding carbene.

We tested it with diethyl 2,2-diallylmalonate, I charge some diene and a spatula tip of catalyst. Wait a bit then concentrate and by NMR only product was there.

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11. pfiz alum on January 13, 2009 12:15 PM writes...

heard the news is hitting groton as i type this....anyone know more????

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12. anon on January 13, 2009 12:24 PM writes...

http://www.bizjournals.com/stlouis/stories/2009/01/12/daily23.html

800 researchers "by the end of 2009" between Groton, La Jolla, St. Louis & Sandwich

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13. T on January 13, 2009 12:25 PM writes...

Pfiz alum, take a look:

http://www.wtopnews.com/?nid=111&sid=1572417

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14. Toluene on January 13, 2009 12:32 PM writes...

I've been around a long time but I've never performed a Huang-Minlon modification of the Ponndorf-Verley reaction!

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15. rhodium on January 13, 2009 12:36 PM writes...

Steve-since I do not understand your reference, I guess I am not. I just like the element that got me tenure. And if you want a reason to think twice about investing in precious metals, look at the rhodium chart: http://www.kitco.com/charts/rhodium.html

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16. rhodium on January 13, 2009 12:38 PM writes...

Milkshake-sorry, I need new glasses!

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17. Kerry Fowler on January 13, 2009 12:52 PM writes...

The Chichibabin reaction. I just like saying "Chichibabin".

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18. Hap on January 13, 2009 12:59 PM writes...

It would be easier to name the ones I have done - Friedel-Crafts, Mitsunobu (well, tried, anyway - eight-membered ring gives lots of elimination), Horner (again, failed miserably because I was an undergrad and didn't understand the point of separating the diastereomeric hydroxy phosphonates - ?) and ... er... I hadn't done a Grignard until I was a TA in grad school (the prepn. of Ph3COH).

This is not a good list for me.

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19. Hap on January 13, 2009 1:01 PM writes...

Sorry for the triple post - I think Corante's servers are choking.

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20. Chemdaddy on January 13, 2009 1:01 PM writes...

Ah the Nazarov....never had a chance to close thy ring

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21. Eraser on January 13, 2009 1:07 PM writes...

A McMurry no plans to do one either.

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22. American Journal of Medicine on January 13, 2009 1:26 PM writes...

Interesting blog. We have linked your blog to the AJM blog roll.

Pamela J. Powers, MPH
Managing Editor

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23. RTW on January 13, 2009 1:38 PM writes...

2. kmd on January 13, 2009 9:44 AM writes...

Pummerer rearrangement...I've never needed it, but I always thought it looked cool

That was the topic of my first published paper. Always had a special appeal to me. You probably have done one but it was called something else. Several named reaction oxidations that utilize sulfoxides in the reaction are actually Pummerer reactions mechanistically I believe. Swern Oxidation being the best example. I probably have every reference known concerning this reaction, up until about three years ago. Since then its not been easy for me to keep up with the area not having library search capability any more.

I suspect that the longer you work the more you will find you may end up trying new chemistry. I initially avoided Pt, Pd coupling chemistry for a long time because it was pretty hit and miss, particularly when used on heterocycles in the early days. But as the field matured, it became one of my favorite techniques.

I probably did a lot more "old" name chemistry than most people I guess. Quite a few of the reactions mentioned above I am pretty sure I had at least tried at one time another. Rhodium chemistry is probably an exception, though I would probably have gotten around to it at sometime had I not been driven out of Big Pharma chemistry and into Informatics.

I generally preferred the old chemistry most of the time because when it worked it often worked VERY well. After all it had usually needed to be general and work well to become a named reaction....

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24. Mark M on January 13, 2009 1:49 PM writes...

to RTW:

If you like the Pummerer, may I interest you in the Ramberg-Backlund (useful for preparation of cis alkenes and dna-cleaving enediynes)?

http://en.wikipedia.org/wiki/Ramberg-B%C3%A4cklund_reaction

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25. MTK on January 13, 2009 2:10 PM writes...

Lot of the reactions named, I've attempted once or twice, failed to get anything, and have never tried again. I'm not sure if that counts. What's amazing is that just about every reaction that has been named, I recall having tried at one point. The Skraup, Paterno-Buchi, and Eschweiler-Clarke are about the only ones I haven't tried. OK, the Huang-Minlon modification of PV reduction is one I don't even know, much less tried.

Ones that I've never tried, always wanted to, but could never find a good reason to: Grob fragmentation, Peterson olefination, Fleming-Tamao oxidation.

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26. Sili on January 13, 2009 4:18 PM writes...

I couldn't even get the Cannizzaro to work in my first synthetic lab course. And I tried Pd couplings in one of the later courses. No guesses as to the results.

No wonder I ended up doing coördination chemistry (with other people's ligands) and crystallography (not all that well).

I'm not a good cook either.

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27. suzuki on January 13, 2009 4:57 PM writes...

I have never done a Suzuki coupling...just kidding!!!!!!!!!!!

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28. Suzuki-2 on January 13, 2009 5:11 PM writes...

> I have never done a Suzuki coupling...
> just kidding!!!!!!!!!!!

Because my students & postdocs do all the chemistry, while I write (some of) the papers & teach!

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29. Anonymous on January 13, 2009 5:14 PM writes...

So many different reactions out there that even if one thinks have done many probably only a small percentage of total available. Some labs Mitsunobu and Weinreb amide reactions seemed to be standard fare for every synthesis route but never managed to do either myself.

Don't pooh pah the Rosenmund reduction as a couple times found worked well for sensitive and/or functionalized aldehydes where more "modern" aldehyde routes Crashed and Burned.

RTW correct that "Named" reactions typically implies well established chemistry however a few times I felt cursed as ran into odd substrates that did not perform as expected.

#17 KF most chemists seem to have similar name affinity. I knew a someone in Grad School who liked saying Chichibabin also so they intentionally devised a use for the reaction so was in their Thesis.

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30. RTW on January 13, 2009 7:16 PM writes...

24. Mark M

Thanks for the Ramberg-Backlund reference. Looking at that I wonder if instead of using a sulfone, one attempted the conditions with a sulfoxide if you would be left with an interesting sulfide containing product that could be further elaborated? Too bad I don't have access to a lab anymore. I like stinky organo sulfide chemistry!

On another note a friend of mine has written a couple of great books about the Named Reactions. Jie Jack Li, has written the following two books:

Name reactions in Heterocyclic Chemistry - Wiley 2004
Name Reactions for Functional Group Transformations Wiley 2007.

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31. RTW on January 13, 2009 7:19 PM writes...

One more.

Name Reactions. A Collection of Detailed Reaction Mechanisms, Third and Expanded Edition by Jie Jack Li Springer 2006.

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32. Hap on January 13, 2009 7:27 PM writes...

One of the people has the latter Li book at work, and it seemed pretty decent when I looked at it. I thought it was expensive, but Amazon has it for $60, so I guess not. Kurti/Czako is also not bad for similar things (though I don't think it has as many reactions).

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33. Nadia on January 13, 2009 8:27 PM writes...

I've never done a Curtius or any of those type of rearrangements, they almost seem like a fairytale to me - the mechanisms work so beautifully on paper.

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34. eugene on January 14, 2009 1:40 AM writes...

I've never done an RCM, I know that for sure, but I'm not too sure about many of the other ones.

You see, I'm really bad with names and I've always been more of a visual person when it comes to chemistry. I can't seem to remember people's names and reactions is just asking way too much. That thingy where a diene comes together with a double bond I've done, and also the one where you put the amine onto the pyridine with sodium amide. Yeah, I did that. It took me a while to figure out it was the Chichibabin reaction though. It was a little easier to remember because of the unusual name than all the others that I forgot the name of.

I just hope no one in real life figures out that I have no clue what they are talking about when they mention a 'name-reaction' half the time... I knew I should have gotten that screen saver that pops up a mechanism and a name every five seconds like the guy in the next lab had.

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35. carbazole on January 14, 2009 2:29 AM writes...

I find as a older chem grad student that the Kurti/Czako book is great, mostly for how many references it has. For a lot of older reactions, sometimes it can be a chore to try and dig up a decent (or recent) paper, and it's nice that they have 30-50 references for each reaction. I also think it has a greater number of reactions than the Jie Jack Li book. I'm a big fan, well worth the investment if you're an advanced undergrad or new grad student. Make sure if you don't have one, someone in your lab does.

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36. processchemist on January 14, 2009 5:04 AM writes...

Fischer Indole synthesis: some are a lot of fun on the 1-3l scale: charge all, heat the whole, appreciate the fast change in color, quickly replace the heating mantle with an ice-water while noting it before the eruption of the reaction mixture from the top of the condenser...

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37. John Spevacek on January 14, 2009 10:50 AM writes...

Congratulations, you've just (re)invented the "I've never..." game for chemists.

Variations abound, but a family version is to give/sell everyone 10 chips, and then go from person to person: each person has to say "I've never (insert something that you've never done)". All the people who have done that have to toss a chip into the pot. Last person with a chip wins the pot.

The idea is to come up with things that make you a freak because you've never done them. I have a brother who is a real champ: he's never paid more than $500 for a car, he's never been married...

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38. NS29 on January 14, 2009 3:36 PM writes...

There are many named reactions and mechanisms I have learned/memorized for exams and I have never ever performed in the lab. Most of them standard things to cover questions such as "how do you form three-membered rings?" - "Name a methodology for ring contraction", "In which reaction nitrous oxide is formed as a byproduct". Having done a PhD and PostDoc in methodology groups hasn't really helped broadening my repertoire of reactions actually performed by myself...but the likes of Simmons-Smith, Favorskii and Nef will probably keep hanging around in the back of my head for the rest of my life.

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39. Martin on January 14, 2009 7:06 PM writes...

we used to play a game back in my Ph.D. days where we'd tick off elements on the periodic table and see how many you could get though before your time was up...

The metals were obviously the most fun.

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40. Eva on January 15, 2009 1:57 AM writes...

Just as we were told the US economy is strong and real estate always goes up, we see many paid propaganda articles touting the absence of scientists in the US.

Yet another article in the San Francisco chronicle (paid for like by a Stanford or some other local college). The colleges are attempting to create a new generation of addicts. They are EVIL.

http://tinyurl.com/7pydo2

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41. A Nonny Mouse on January 15, 2009 7:16 AM writes...

As for the McMurray (post 21), the "in situ" version can be very good for the formation of heterocyles. Uses zinc and TiCl4.

I developed a process to loratadine using this system which is operated on an industrial scale.

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42. Hap on January 15, 2009 1:38 PM writes...

One of my professors wrote a book article discussing the Corey synthesis of gibberellin A(?). One of the steps was a McMurry coupling with TiCl4 and K to form a bicyclic diol intermediate, and the author made special note of the excitement of quenching multiple equivalents of titanium and potassium metal on multigram scale.

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43. Norepi on January 16, 2009 9:59 PM writes...

I remember in my second year of grad school taking an advanced synthesis class, and having to memorize a whacking load of name reactions, of which I believe I had actually done, like, three of.

Most of my chemistry is assembling various heterocycles, so I do a lot of Friedlander-type chemistry (the latter of which not many people have heard of). Most of my reactions are old-timey, medieval things (Swern, Friedel-Crafts, Vilsmeier), things that have no name, or neat literature tricks.

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44. RTW on January 17, 2009 1:15 PM writes...

For those interested in new and improved methods. I just read where some very interesting cross coupling reactions are being done with in-situ generated Grignard reagents in the presence of iron. Less hazardous and perhaps a little green friendly. See Angew. Chem. Int. Ed. 2009, 48, p607.

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