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October 11, 2005
The Old Stuff
Posted by Derek
I was telling a story the other day about using a reagent called PCC, pyridinium chlorochromate and yes, I'm a real laugh riot with these things, when it hit me: nobody much uses that stuff any more. Twenty, twenty-five years ago it was all over the place, and now it's slipping into history. I haven't used it myself in what - eight years or so. There are too many other reagents that do similar things and are easier to clean up (and that don't involve so much chromium waste).
Organic chemistry is littered with reactions that have been superseded. You don't see many Oppenauer oxidations these days ,for one. (I know that if you follow that link it gives you a 2002 reference. But it's for a reaction that about a dozen things would do just as easily, at least on a bench scale.) How about the Rosenmund reduction? Such things show up once in a while in carefully optimized process chemistry routes, but they're no longer part of anyone's normal tool kit. Does anyone use manganese dioxide much these days, or potassium permanganate? (That last one is a real loss, one of the most beautiful purples in all of chemistry - it and copper sulfate were my first loves when I got a chemistry set as an eight-year-old.)
But simultaneously, there are hundred-year-old reactions that are still getting up in the morning and going to work. Grignard reagents go back that far, and there's not an organic synthesis lab on Earth that doesn't use one once in a while. The Dieckmann condensation is still going strong, as is Fischer esterification. It would be worth knowing which category is better-remembered today: novels from the 1890s, or chemical reactions. . .
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1. Tom McEntee on October 12, 2005 8:37 AM writes...
My transition from post-doc to industrial process development chymist occured in 1973. The changes I had to deal with were (a) going from the 500-cc 3-neck RBs to the 2000-4000 gallon Pfaudlers and (c) getting accustomed to thinking in terms of $ per unit of product. Oxidations and reductions are fundamentally simple processes when compared to C-C bond formation. The cost of Raney nickel and hydrogen was low compared to LiAlH4 (LAH), and safer when you think of what would be involved in the portionwise addition of 400 pounds of LAH to a 2000-gal reactor. I developed a process for a nitric acid oxidation using 5 percent of theory HNO3 and using oxygen to regenerate the acid...this is really cheap on a per-pound basis. Derek is correct about Grignard reagents...we developed processes for manufacture of all kinds of Grignard reagents in 2000 to 4000-gal vessels and sold these reagents on the open market. They're cheap and are efficient reagents for C-C bond formation. With respect to books from the 1890s, as industrial chemists we did make far more use of the old German literature than I ever did in grad school. They had a limited number of feedstocks to work with and I'm sure that many of the "name reactions" represent the inventor's ingenuity in manipulating these to a specific end.
Permalink to Comment2. RKN on October 12, 2005 8:42 AM writes...
or potassium permanganate?
Permalink to CommentAs far as I know it's still used in modern protein-DNA footprinting assays. It preferentially oxidizes (unbound) thymidine bases.
3. Tom Bartlett on October 12, 2005 9:02 AM writes...
I'll take a Swern over Chromium most of the time. Swern's smell bad, but chromium is just plain nasty. But, I really think people are just doing fewer oxidations in Med Chem. Who's doing steroids these days? Now, it's all palladium coupling and the like.
Permalink to Comment4. Niels Hartog on October 12, 2005 10:07 AM writes...
or potassium permanganate?
Permalink to CommentPermanganate is used for the remediation of groundwater and soils polluted with organic contaminants. Especially used to clean up chlorinated solvents such as perchloroethylene due to its specifity for the double bond.
5. milo on October 12, 2005 12:01 PM writes...
What I think is funny is how some named reactions have become "standard" knowledge. For instance, the Schotten-Bauman reaction...and the Finkelstein reaction.
Permalink to Comment6. J Suggs on October 12, 2005 12:49 PM writes...
Its nice to see science moving on. It is hard to see any simple functional group interchange reagent lasting more than a generation, although things that form new frameworks such as aldols and Diels Alders should endure.
Permalink to CommentReaders of this blog may appreciate the backstory of PCC. It was a pure accident. Jan Rocek had given a talk about chromium oxidations focusing on Cr(V) and EJ came up with the idea of trying out a Cr(V) species as an oxidant, since it is a two electron oxidant, matching the alcohol to aldehyde change. I found an old literature prep that involved bubbling HCl through a cold acetic acid solution of chromium trioxide (all you bench chemists can appreciate the fun that was). I isolated the pyridine salt and found the powder was a great oxidant (on small scales). When I had used almost all of it it, I tried a second prep, and being more careful, got the real Cr(V) oxidant this time, which was pretty useless (why I still dont know). Some very tense days followed until I looked at the UV of the first batch and decided it looked like Cr(VI), which led me to PCC. And the rest is a footnote to history (although another story I recall is how Alfred Bader complained he ruined some large scale equipment the first time his plant made a big batch of PCC, I guess the reactor he was using did not like the HCl-CrO3 combination). Bottom line is if you carry out three reactions a day, sooner or later something will work, as long as you keep your eyes open.
7. Derek Lowe on October 12, 2005 1:43 PM writes...
Well! I'm very glad to hear from Prof. Suggs himself. And I'm also glad to add to my list of discoveries that came about at least partly by accident, too.
Permalink to CommentBack when I used a lot of PCC (mid-1980s), we used to make it fresh. Aldrich was selling it, but by the time we got it the reagent was often rather brownish, as opposed to the vivid yellow-orange of the fresh stuff.
8. Drew on October 12, 2005 2:16 PM writes...
I recently had the pleasure of a running a Wilgerodt-Kindler reaction (Chem Berichte, 1887, 20, 2467). Superb 19th century chemistry!
Permalink to Comment9. Mark on October 15, 2005 4:51 AM writes...
"Does anyone use manganese dioxide much these days, or potassium permanganate?"
Both are used extensively in clandestine hobbyist chemistry. As are many other superseded methods (usually because of limited accesibility to reagents).
Permalink to Comment10. Peter North on October 15, 2005 3:26 PM writes...
"better-remembered today: novels from the 1890s, or chemical reactions. . ." just heard a 1960's version of Sherlock Holmes on the BBC
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