Posts Tagged ‘first professor’

The mechanism of diazo coupling: more hidden mechanistic intermediates.

Saturday, March 8th, 2014

The diazo-coupling reaction dates back to the 1850s (and a close association with Imperial College via the first professor of chemistry there, August von Hofmann) and its mechanism was much studied in the heyday of physical organic chemistry.[1] Nick Greeves, purveyor of the excellent ChemTube3D site, contacted me about the transition state (I have commented previously on this aspect of aromatic electrophilic substitution). ChemTube3D recruits undergraduates to add new entries; Blue Jenkins is one such adding a section on dyes.

diazonium

The mechanism can be rate limiting either in the initial electrophilic attack (black arrows) or in the subsequent proton removal (red arrows using an intermolecular base such as chloride anion).[2].‡ The product is normally assumed to be the trans-diazo compound rather than cis. This distribution is certainly true in the crystal structure database (below, although some examples of cis are known, including azobenzene itself). Would this distribution be reflected in the transition states? Initial attempts by the ChemTube3D team had resulted only in a cis-transition state being located, and they asked me to check this out.

diazo

ωB97XD/6-311G(d,p)/SCRF=water calculations using phenyl diazonium chloride (I do like my counter-ions) coupling to benzene resulted in location of both cis[3] and trans[4] transition states, the former being the lower by 1.0 kcal/mol in free energy (this might well be due to the dispersion stabilisation from π-π stacking).† The IRC for the cis is shown below.[5]

cis-diazocis-diazoEcis-diazoG

You can see that the entire process is concerted. The Wheland intermediate normally invoked as part of the mechanism of aromatic electrophilic substitution is not a proper intermediate but a hidden one for the reaction with X=Y=H. The reaction coordinate has a flat top, and that passage along this part represents the hidden Wheland. The reaction barrier is high however, and it is certainly observed that only activated arenes (phenols, anilines, X,Y=OH, NH2) actually couple with diazonium cations. For these, the hidden intermediate is stabilized by the substituent, and no doubt emerges as a real intermediate.

For my thesis work, I studied[2] diazo-coupling of indoles. I might have a go at returning to that work, to see if calculations can replicate my finding, that for unhindered indoles proton removal from the Wheland intermediate is fast, but add a few t-butyl hindering groups and it becomes slow.

PS. Here is the IRC for the formation of trans-diazobenzene.[6]

trans

‡Such diazo compounds make up a significant proportion of the 50 or so real molecules I have personally added to the collection of 84 million or so thus far identified.

†Working with ions has one statistical problem that covalent systems do not have; where to geometrically place the counter-ion. One should really stochastically explore reasonable locations before concluding the likely location of the globally lowest energy pose.

References

  1. S.B. Hanna, C. Jermini, H. Loewenschuss, and H. Zollinger, "Indices of transition state symmetry in proton-transfer reactions. Kinetic isotope effects and Bronested's .beta. in base-catalyzed diazo-coupling reactions", Journal of the American Chemical Society, vol. 96, pp. 7222-7228, 1974. https://doi.org/10.1021/ja00830a009
  2. B.C. Challis, and H.S. Rzepa, "The mechanism of diazo-coupling to indoles and the effect of steric hindrance on the rate-limiting step", Journal of the Chemical Society, Perkin Transactions 2, pp. 1209, 1975. https://doi.org/10.1039/p29750001209
  3. H.S. Rzepa, "Gaussian Job Archive for C12H11ClN2", 2014. https://doi.org/10.6084/m9.figshare.956138
  4. H.S. Rzepa, "Gaussian Job Archive for C12H11ClN2", 2014. https://doi.org/10.6084/m9.figshare.956139
  5. H.S. Rzepa, "Gaussian Job Archive for C12H11ClN2", 2014. https://doi.org/10.6084/m9.figshare.956209
  6. H.S. Rzepa, "Gaussian Job Archive for C12H11ClN2", 2014. https://doi.org/10.6084/m9.figshare.956213

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Historical detective stories: colourful crystals.

Friday, October 21st, 2011

Organic chemists have been making (more or less pure) molecules for the best part of 180 years. Occasionally, these ancient samples are unearthed in cupboards, and then the hunt for their origin starts. I have previously described tracking down the structure of a 120 year-old sample of a naphthalene derivative. But I visited a colleague’s office today, and recollected having seen a well-made wooden display cabinet there on a previous visit. Today I took a photo of one of the samples:

One of the "Hofmann" collection.

No date, no name, but a structure! As I noted before, when it comes to structures, you have to research the conventions (and numbering) used at the time. Thus note the apparent cyclohexane rings, the N(Me)2 group and the lack of stereochemistry around the alkenes. The former dates the sample to before 1950, whilst the use of Me to mean methyl puts it in the 20th century. Which is shame, since it had been known as the “Hofmann” collection, meaning some sort association with August von Hofmann, the first professor of organic chemistry in the UK, who occupied that position from 1845-1864. Samples that old are very rare. The one above by the way is very deep green (the photo does not do it justice), and very crystalline! Tracing the history of where the display cabinet might have been did indeed reveal that it probably started its life at the same institute as Hofmann was working in (and where I now work), but little more than this was known about it.

A search of the Beilstein database (nowadays known as Reaxys) revealed a collection of samples corresponding to the above structure (with benzenes of course, not cyclohexanes), but co-crystallised with different molecules, and dating from 1921. These were known as the Heilbron collection, and this was encouraging, since Heilbron was indeed a successor to Hofmann, being active in the 1920s. During his career, he and his students probably made 100s, if not 1000s of compounds, so why did they go to the considerable expense of having beautiful wooden cases built to house these particular samples? Probably because the basic colour varied from yellow to black (perhaps 400nm difference in λmax) and for which they had no explanation! So, much like some people are cryofrozen in the hope an advanced civilisation might bring them back to life in the future, these samples were mounted in a display cabinet in the hope that someone would find out the origins of their variable colour.

Well, in 1984 (some 63 years after the event) researchers in the Technion-lsrael Institute of Technology, Haifa, came upon the 1921 article (but not the samples; if they read this they might be amazed that these still exist!), repeated (most of the) syntheses, and determined the crystal structure of three of the molecules (but conspicuously not the one above). One 3D structure is shown below. The colours were ascribed to charge-transfer interactions between the components of the molecules.

DADZIR. Click for 3D

As I noted previously, it is well worth preserving chemical samples for future generations (and sometimes that generation is 120 years in the future!). Sadly, health and safety aspects (real or imagined) mean that such collections are being lost to posterity at an every increasing rate. Soon, there may be no collections of old chemicals left. That would be indeed a loss to science. So if you know of a lovingly preserved case of old chemicals, go take a look at it. And if it’s in danger of being put in the skip, then rescue it. There is no telling what may be scientifically interesting about it.

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