Friday, November 28, 2008

Tetrabromo Anthracene from the Ground Up
Anthracene looks a lot like a big version of benzene, and to a large degree it is. If you wanted to make benzene with additional groups attached to it, such as bromine atoms, the chemistry is pretty well-established. If you want to add more than one group, and the exact positions of the groups are important, then it gets a little more complicated but it is still quite doable.

Anthracene on the other hand is rather less cooperative than benzene. The 9 and 10 positions on anthracene are very easy to modify, but the positions on the outer edges are a lot harder to get at with the same chemistry you would use on benzene. So how would you go about making anthracene with four bromines on the outer edges and not modify the 9 and 10 positions?

A recent article in the online Beilstein Journal of Organic Chemistry, the authors describe a synthesis of 2,3,6,7-tetrabromoanthracene in just four steps starting with benzene.

First they attach four iodines to benzene by reacting it overnight with I2, periodic acid and concentrated sulfuric acid. These seem like pretty forcing conditions, but they are necessary since iodine is the least reactive of the halogens. The periodic acid is necessary to oxidize the iodine to an "I+" species which then reacts with the benzene ring.

Next they use a coupling reaction to replace the iodines with tetramethylsilyl acetylene groups. The tetramethyl silyl (TMS)groups are protecting groups to prevent the acetylene from reacting at both ends. The coupling reaction itself is quite interesting and involves a palladium complex in which the palladium is effectively in the zero oxidation state - that is, chemically it is a palladium atom rather than being an ion. In the Sonogashira coupling reaction that they use, the Palladium complex and a Cu(I) ion interact with the pi-bonds to stitch together the acetylenes and the benzene ring in place of the iodines.

To remove the TMS groups they react the compound with a catalytic amount of Ag(I), which initially forms a silver acetylide compound. The acetylide ion does a nucleophilic attack on the bromine atom in N-bromo succinimide. In this case the bromine is effectively acting like Br+, with the succinimide acting as a leaving group.

At this point we have all the carbons and bromines needed for the tetrabromoanthracene, all that needs to be done is to make the rings on the ends. To do this they simply heat the compound in a high-pressure bomb. This is an example of a double Bergman cyclization, which can occur when you have an alkene with two alkyne groups attached to it - an "enediyne." This is a radical mechanism in which each of the alkynes donates one electron to make a new carbon carbon bond and close the ring. This produces a diradical. The cyclohexadiene is added as a hydrogen donor: when it donates two hydrogen atoms to the anthracene molecule the cyclohexadiene is converted to benzene.

Anthracene can undergo many of the same Electrophilic Aromatic Substitution reactions that are routine for benzene, but selectiviely modifying only the "end" positions is very difficult - the other positions on the rings are much more reactive - especially the middle 9 and 10 positions. So usually, any new additions end up in the 9 and 10 positions preferentially.  To get around this the somewhat counterintuitive solution is: don't start with anthracene.

Christian Schäfer, Friederike Herrmann, Jochen Mattay (2008). Synthesis of 2,3,6,7-tetrabromoanthracene Beilstein Journal of Organic Chemistry, 4 DOI: 10.3762/bjoc.4.41


Belle said...

Knowing you, you have great fun making such diagrams, but I do better with Greek than with this! Gah.

Steve W said...

Using a computer program (ChemSketch in my case) to make the structures can be rather tedious, but it looks a lot better than if I had drawn them by hand. I had a professor in grad school who drew structures on the board with such care and precision that they looked typeset. I've always envied him for that, but don't quite have the patience for it myself.