Diaza[12]annulene: Would You have Known Better?

The recent retraction of two papers regarding diaza[12]annulenes by Yamaguchi et al. and Shi et al. from separate groups have strengthened the argument for stronger peer review and more thorough literature review by authors. http://dx.doi.org/10.1002/anie.200704704

But anyone can be an armchair synthetic chemist and point fingers at what should have been done after the fact. The easiest finger to point, is presumably between 7 coauthors, 4 reviewers, 2 editors no one ran the appropriate literature searches to find that these reactions are known and yield products with exactly 1/2 the mass as those reported in the papers. But, now we come to the bitter truth in modern chemical research, we simply do not perform the thorough literature searches of yester’year. Some will say this is a problem, but assuming those 13 scientists are typical of scientists of today then it simply isn’t a fair commentary to make. So, I thought it would be more beneficial to reread the papers and see if I would have come to the same conclusions given the same series of data, as I’m oblivious to heterocyclic chemistry in general and the Zincke reaction in particular, and have a typically topical background like most chemistry graduate students (I’m a Nuclear Chemist after all).

First up the Yamaguchi paper: http://dx.doi.org/10.1021/ol061585q
The title is the One-Pot Synthesis of N-Substituted Diaza[12]annulenes. Just looking at the title, we should be expecting 1H,13C-NMR, definitely MS data, and likely a crystal structure since the molecule would have two cationic-like centers. Picture shown below.

As can be seen in the structure this monstrosity should have some serious pi-pi stacking possibilities, and isolating crystals shouldn’t have been too problematic, but none are isolated. An image of their NMR data for the structure above is below.

It would be at this point that the little voice in my head would be like, “hmm…. why do I have aromatic proton peaks? I should probably count those pesky buggers again. Yup, 12 delocalized electrons.” If one is postulating that this is antiaromatic, then one hallmark of antiaromatic hydrogens, located on the outside ring, are that they shift upfield (lower ppm) and lie to the right of 8 ppm and likely 7ppm. So, it would have been at that point where the paper would of confused me.

Second up the Shi paper: http://dx.doi.org/10.1002/anie.200702140
The title is the [12]Annulene Gemini Surfactants: Structure and Self-Assembly. So, we should be expecting yucky yellow oils, and with the word structure, perhaps even a crystal structure. The molecules examined are shown below.

Independently, they confirm the odd aromatic protons of Yamaguchi and they obtained a yellow powder, not necessarily an oil, but well within reasonable expectations. They did some calculations with Gaussian and discovered the results below.

The expected distorted structure is seen in II but lied 1.7 kcal/mol higher in energy than I. This is just odd, for a cyclic antiaromatic system we should expect to see 2nd order Jahn-Teller distortions shift the molecule away from planarity and this was not seen by calculations. This is where the authors and reviewers can be faulted, at that point some one should have suggested an experiment to see whether the NMR peaks would move upfield as a function of temperature. As scientists, we love making graphs, and that would have been a neat confirmation of both the structural predictions from calculations, and an easily verifiable hypothesis.

In summary, I don’t feel it is fair to fault the authors, reviewers, editors for not knowing every obscure heterocyclic named reaction. However, it is prudent upon all of us to ask the right questions about our research, to put-off deadlines if necessary, and to apply our full intellect and diligence to our experiments.

Some Armchair commentary here:



  1. I agree with your comments: “I don’t think it is fair …”. I think that it is normal and even desirable for scientists to make mistakes- at least people who make mistakes are pushing some envelope, somewhere: even if the people involved are not operating at a global frontier of science (in this specific case), it is clearly a personal frontier. The only real “sin” is not handling mistakes properly by corrections or retractions, once the real story is understood.

    It is worth remembering that many of the greatest scientists made mistakes (though they usually weren’t careless).

    So, personal finger-pointing serves no useful purpose, as you indicate, but the wake-up call is valuable to all of us, as are the correct results. Thanks for the reminder! J

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