Forming a stabilized m-benzyne.

The story so far. Inspired by the report of the most polar neutral compound yet made, I suggested some candidates based on the azulene ring system that if made might be even more polar. This then led to considering a smaller π-analogue of azulene, m-benzyne. Here I ponder how a derivative of this molecule might be made, using computational profiling as one reality check.

One reaction as envisaged is to prepare the penta-substituted benzene as shown below.

Abstraction of the proton using strong base might result in 1,3-elimination of the leaving group X to form the m-benzyne. For the substituent X=Cl, a ωB97XD/Def2-TZVPP/SCRF=thf calculation (DOI: 10.14469/hpc/2057) of the reaction profile shows a relatively large barrier to elimination, with an endothermic product.

A better leaving group might be X=OTf. Unlike, X=Cl, this reaction is nicely exoenergic (ΔΔG -10.6 kcal/mol) with an accessible activation free energy of 22.5 kcal/mol (DOI: 10.14469/hpc/2066, 10.14469/hpc/2123, 10.14469/hpc/2096)

Perhaps then this, the smaller homologue of azulene, might indeed be capable of synthesis?

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2 Responses to “Forming a stabilized m-benzyne.”

  1. Martin Walker says:

    I like this idea! It would be wonderful to see such a molecule. Azulene is on my mind now as my organic class just completed their literature search for their spring “research project” – trying to make 1-methylazulene. I thought it would be fun for them to make a blue liquid while learning about aromaticity!

    Would it be possible to make the chlorine analogue of your molecule, from tetra or pentachloroaniline or its N,N-dimethyl equivalent? These are commercially available or easily made. I can imagine that ortho lithiation of one of those might lead to your proposed structure, provided that chlorine can provide enough stabilisation.

    Thanks for your many interesting posts!

  2. Martin Walker says:

    I apologize for missing (in my excitement!) your mention that the reaction requires something like OTf as a leaving group, and Cl will probably fail. I did find one paper that you may find relevant, though: D. J. Berry, I. Collins, S. M. Roberts, H. Suschitzky and B. J. Wakefield J. Chem. Soc. C, 1969, 1285-1294. (DOI: 10.1039/J39690001285) The paper mentions lithiation as I proposed gives mixtures; it also describes some more conventional benzyne chemistry.

    I’ll certainly ponder this to see if there is a viable route. Thanks again!
    Martin A. Walker

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