It is often said if you can’t explain something to a six-year-old, you don’t understand.
I am not convinced, but maybe I don’t understand. Anyway, I thought I would follow from my previous post with an account of my PhD thesis. It started dramatically. My young supervisor gave me a choice of projects but only one looked sensible. I started that, then found the answer just published. Fortunately, only month wasted, but I had no project and supervisor was off on vacation. Head of Department suggested I find myself a project, so I did. There was a great debate going on whether the electrons in cyclopropane could delocalize into other parts of a molecule. To explain, carbon forms bonds at an angle of 109.5 degrees, but the three carbons of cyclopropane have to be formally at 60 degrees. In bending them around, the electrons come closer together and the resultant electric repulsions mean the overall energy is higher. The higher energy difference is called strain energy. One theory was the strain energy could be relieved if the electrons could get out and spread themselves over more space. Against that, there was no evidence of single bonds being able to do this.
My proposal was to put a substituted benzene ring on one corner, and an amine on the other. The idea was, amines are bases and react with acid, and when they do that the electrons on the amine are trapped. If the cyclopropane ring could delocalize electrons there was one substituent I could put on the benzene ring that would have different effects on that basicity depending on whether the cyclopropane ring did delocalize electrons or not. There was a test through something called the Hammett equation. My supervisor had published on this, but this would be the first time the equation might be used to do something of significance. Someone had tried that scheme with carboxylic acids, but with an extra carbon atom they were not very responsive and there were two reports with conflicting answers. My supervisor, when he came back, was not very thrilled with this proposal, but his best alternative was to measure the rates of a sequence of reactions for which I had found a report that said the reaction did not go. So he agreed. Maybe I should have been warned. Anyway, I had some long-winded syntheses to do.
When it came to reaching the end-position, my supervisor went to North America on sabbatical, and then sequentially looking for a new position in North America, so I was on my own. The amine results did not yield the desired result because the key substituent, a nitro group, reacted with the amine very quickly. That was a complete surprise. I could make the salt, but the solution with some amine quickly discoloured. However, in a fleeting visit my supervisor made a useful suggestion: react the acids in toluene with a diazo compound. While the acids previously had been too similar in properties in water, it turned out that toluene greatly amplified the differences. The results were clear: the cyclopropane ring did not delocalize electrons.
However, all did not go well. The quantum mechanical people who had shown the extreme stability of polywater through electron delocalization turned their techniques to this problem and asserted it did. In support, they showed that the cyclopropane ring stabilized adjacent positive charge. However, if the strain energy arose through increased electron repulsion, a positive charge would reduce that. There would be extra stability with a positive charge adjacent, BUT negative charge would destabilize it. So there were two possible explanations, and a clear means of telling the difference.
Anions on a carbon atom are common in organic chemistry. All attempts at making such an anion adjacent to a cyclopropane ring failed. A single carbon atom with two hydrogen atoms, and a benzene ring attached forms a very stable anion (called a benzyl anion). A big name replaced one of the hydrogen atoms of a benzyl anion with a cyclopropane ring, and finally made something that existed, although only barely. He published a paper and stated it was stabilized by delocalization. Yes, it was, and the stabilization would have come from the benzene ring. Compared with any other benzyl anion it was remarkably unstable. But the big names had spoken.
Interestingly, there is another test from certain spectra. In what is called an n->π* transition (don’t worry if that means nothing to you) there is a change of dipole moment with the negative end becoming stronger close to a substituent. I calculated the change based on the polarization theory, and came up with almost the correct answer. The standard theory using delocalization has the spectral shift due to the substituent in the opposite direction.
My supervisor, who never spoke to me again and was not present during the thesis write-up, wrote up a paper on the amines, which was safe because it never showed anything that would annoy the masses, but he never published the data that came from his only contribution!
So, what happened? Delocalization won. A review came out that ignored every paper that disagreed with its interpretation, including my papers. Another review dismissed the unexpected spectral shift I mentioned by saying “it is unimportant”. I ended up writing an analysis to show that there were approximately 60 different sorts of observation that were not in accord with the delocalization proposition. It was rejected by review journals as “This is settled” (that it was settled wrongly was irrelevant) and “We do not publish logic analyses.” Well, no, it seems they do not, and do not care that much.
The point I am trying to make here is that while this could be regarded as not exceptionally important, if this sort of wrong behaviour happens to one person, how much happens across the board? I believe I now know why science has stopped making big advances. None of those who are established want to hear anyone question their own work. The sad part is, that is not the only example I have.