Sandwiches and other tasty things.

Sandwiches have a long and colourful tradition, said to have been invented by the Earl of Sandwich in the 18th century who apparently ordered his servant to bring him some meat tucked between two pieces of bread. So thus the delicacy was born. I can vouch for the town of Sandwich, in Kent, England, which is a beautiful place, full of old buildings and more importantly pubs selling good beer and guess what? Sandwiches.

Pfizer had a facility there, but in their infinite wisdom they recently closed it. Just up the road was a fireworks factory, lots of little huts dispersed about a rather large field, presumable to avoid explosion of rotten sandwiches. Even further up the road there used to be a hovercraft terminal, which, for a  large fee would transport you and your car over the English Channel to France. That was in the days before the channel tunnel.

To a chemist the word sandwich has another connotation, sandwich compounds in which a metal atom sits between two rings, usually cyclopentadienes. Recently a review appeared describing the discovery, structural elucidation and uses of these interesting compounds (1). I was amazed to read that R.B. Woodward also had his fingers in the pie, or rather sandwich, which I suppose is not too surprising.

Some 60 years ago reports appeared, in Nature and the Journal of the Chemical Society (2,3), describing attempts to prepare fulvalene by oxidising cyclopentadienylmagnesium bromide with FeCl3. They obtained yellow crystals, always nice to see, but they turned out not to be the correct compound, elemental analysis gave the formula FeC10H10 . This compound was soluble in conc. H2SO4 , without decomposition. You can’t say that about modern day sandwiches, except for the ones the railways serve on their roving buffet wagons.

As is the case, and there many examples of it, another group isolated the same compound from an unrelated series of experiments.So what was the structure of this new compound? The big names became involved in solving the puzzle, proposals came from Ernst Otto Fischer (right hand structure), R.B. Woodward, G, Wilkinson (left hand structure).

Their proposals were finally vindicated by X-ray crystallography.

Woodward published his thoughts (4, 5) and proposed the name “Ferrocene” which became generally accepted. Thus compounds of the type M(C5H5)2  became known as metallocenes. Wilkinson and others coined the name “Sandwich compounds”, which also became universally accepted. As an interesting aside; apparently the JACS editor who had the job of refereeing the Woodward communication wrote to him and Wilkinson suggesting that they may have been imbibing in some illegal substances!

The research into these compounds proceeded at a furious pace between 1952 and 1954 and it was observed that the “all’s fair in love and war” policy was strictly adhered to by both the Fisher and the Wilkinson groups. Nevertheless this work produced a plethora of remarkable compounds and I will leave it to the reader to investigate the original literature so well documented in this Angewandte Chemie essay (1).
In 1973 Fischer and Wilkinson were awarded the Nobel Prize for their sandwich work and it’s refinement. Not surprisingly there were those not quite so thrilled with this decision, even going as far as to suggest that a “grave injustice” had been committed. The Nobel Committee reacted appropriately to this correspondence.
Sandwiches have even made their way into the realms of medicinal chemistry. Very recently Salmon etal (6) described Metallocene-Based Inhibitors of Cancer-Associated Carbonic Anhydrase Enzymes IX and XII in the Journal of Medicinal Chemistry. They investigated 20 different sandwiches “comprising of extensive structural diversity” and evaluated their efficacy an inhibitors of carbonic anhydrase. The most potent compound, a sulfonamide, is reproduced here.                                                                                                                          

Derek Lowe at “In the Pipeline” commented on this paper and his contributors added more and the reader is recommended to peek in there (7)!

I myself dabbled in this chemistry, well I cheated and bought my ferrocene derivative. But all the chemistry planned worked and I even obtained an x-ray structure, which I think looks wonderful!

 

 

Well there it is, my first contribution of, I hope, many to Chemistry Blog. I hope you all enjoyed it. Any comments are welcome, except negative ones which will get a mouldy sandwich thrown at them. I recommend everyone to have a read at reference 1, if you can, it’s behind a paywall, as to be expected. We need open access journals.

References

  1. Helmut Werner, Angewandte Cheme International Edition English, 9th May, 2012, DOI: 10.1002/anie.201201598.
  2. T. J. Kealy, P. L. Pauson, Nature 1951, 168, 1039 – 1040.
  3. S. A. Miller, J. A. Tebboth, J. F. Tremaine, J. Chem. Soc. 1952, 632 – 635.
  4. G. Wilkinson, M. Rosenblum, M. C. Whiting, R. B. Woodward, J. Am. Chem. Soc. 1952, 74,2125 – 2126.
  5. R. B. Woodward, M. Rosenblum, M. C. Whiting, J. Am. Chem. Soc. 1952, 74, 3458 – 3459.
  6. Adam J. Salmon, Michael L. Williams, Quoc K. Wu, Julia Morizzi, Daniel Gregg, Susan A.Charman, Daniela Vullo, Claudiu T. Supuran, and Sally-Ann Poulsen; J. Med. Chem.,Publication Date (Web): April 27, 2012 (Article) DOI: 10.1021/jm300427m
  7. http://pipeline.corante.com/archives/2012/05/23/how_come.php
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3 Comments

  1. Great post, Quintus!

  2. Sandwiches, egos, and chemistry. Great first post!

  3. Pingback: Chemistry Blog » Blog Archive » Sandwiches, Gluttons and Picky Eaters

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