Posts Tagged ‘Metal ions in aqueous solution’

I’ve started so I’ll finish. The ionisation mechanism and kinetic isotope effects for 1,3-dimethylindolin-2 one

Thursday, January 7th, 2016

This is the third and final study deriving from my Ph.D.[1]. The first two topics dealt with the mechanism of heteroaromatic electrophilic attack using either a diazonium cation or a proton as electrophile, followed by either proton abstraction or carbon dioxide loss from the resulting Wheland intermediate. This final study inverts this sequence by starting with the proton abstraction from an indolinone by a base to create/aromatize to a indole-2-enolate intermediate, which only then is followed by electrophilic attack (by iodine).  Here I explore what light quantum chemical modelling might cast on the mechanism.

Indole diazocoupling

The concentration of I3– is used to follow the reaction, given by the expression:  [I3–] = k1[B][indolinone]t – k-1/k2*ln[I3–] + const, where  k2* = k2/715[I–] + k2' , the latter being the rate coefficient for the reaction between the enolate intermediate and I3–. With appropriate least squares analysis of this rate equation,‡ a value for k1 using either 1H or 2H (≡ D) isotopes can be extracted and this gives an isotope effect k1H/k1D of 6.3 ± 0.6. Note that this value does NOT depend on [B]. Here, I am going to try to see if I can construct a quantum mechanical model which reproduces this value.

Indole diazocoupling

  1. Model 1 uses just three water molecules as a proton relay (B3LYP+D3/Def2-TZVP/SCRF=water).
  2. Model 2 uses 2H2O.NaOH solvated by two extra passive water molecules. Since under these conditions, the NaOH is largely ionic, [B] ≡ [OH–]
Model ΔG‡298 (ΔH‡298) kH/kD (298K) DataDOIs
1 28.0 (22.9) 10.3 [2],[3],[4]
2 2.5 (2.8) 4.4 [5],[6],[7]

The plot of rate vs [B] shows[1] that the uncatalysed (water) rate is very slow (intercept passes more or less through zero) and the calculated free energy barrier (28.0 kcal/mol) confirms a slow rate at ambient temperatures. Note in the final (aromatized) product, there is a noticeable hydrogen bond between the 3-carbon and a water molecule (2.14Å). The calculated kinetic isotope effect[8] is substantially larger than observed experimentally for the base catalysed contribution.

Indolineone ionization using 3 water molecules

In the presence of NaOH (standard state = 1 atm = 0.044M), the enthalpy barrier drops very substantially to 2.8 kcal/mol and the free energy to 2.5 kcal/mol. Similar behaviour was noted previously on this blog for the hydrolysis of thalidomide. Although the magnitude of the reduction in barrier in fact implies an extremely fast reaction, recollect that [B]=[OH–] appears in the rate equation  and since its value is very much less than 0.044M, the observed rate is relatively slow.

Indolineone ionization using 3 water molecules + NaOH

The calculated KIE for the hydroxide catalysed mechanism is much smaller that for the water route, but also smaller than is observed. This is a value uncorrected for tunnelling, which given the small barrier might be significant. 

These calculations show how a model for ionization of indolinone can be constructed, and used to e.g. probe the sensitivity of KIE to perturbations induced by ring substituents, which may form the basis of a future post.

‡This is a non-linear equation with kinetics that straddle zero and first order behaviour. In 1972, it was not easily possible to graph such functions in a manner where the slope of a linear plot would yield the rate constant. It was only computers and languages such as Fortran which allowed such non-linear least squares analysis of the rate. In the event, it turned out that the presence of 50% methanol in the mixed aqueous solutions was the cause; in other solvents the kinetics approximated zero order behavour very well.

References

  1. B.C. Challis, and H.S. Rzepa, "Heteroaromatic hydrogen exchange reactions. Part VIII. The ionisation of 1,3-dimethylindolin-2-one", Journal of the Chemical Society, Perkin Transactions 2, pp. 1822, 1975. https://doi.org/10.1039/p29750001822
  2. H.S. Rzepa, "C 10 H 17 N 1 O 4", 2016. https://doi.org/10.14469/ch/191786
  3. H.S. Rzepa, "C 10 H 17 N 1 O 4", 2016. https://doi.org/10.14469/ch/191765
  4. H.S. Rzepa, "C10H17NO4", 2016. https://doi.org/10.14469/ch/191784
  5. H.S. Rzepa, "C 10 H 20 N 1 Na 1 O 6", 2016. https://doi.org/10.14469/ch/191787
  6. H.S. Rzepa, "C 10 H 20 N 1 Na 1 O 6", 2016. https://doi.org/10.14469/ch/191782
  7. H.S. Rzepa, "C10H20NNaO6", 2016. https://doi.org/10.14469/ch/191785
  8. H. Rzepa, "Mechanisms and kinetic isotope effects for the base catalysed ionisation of 1,3-dimethyl indolinone.", 2016. https://doi.org/10.14469/hpc/202

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Discovering chemical concepts from crystal structure statistics: The Jahn-Teller effect

Saturday, May 30th, 2015

I am on a mission to persuade my colleagues that the statistical analysis of crystal structures is a useful teaching tool.  One colleague asked for a demonstration and suggested exploring the classical Jahn-Teller effect (thanks Milo!). This is a geometrical distortion associated with certain molecular electronic configurations, of which the best example is illustrated by octahedral copper complexes which have a d9 electronic configuration. The eg level shown below is occupied by three electrons and which can therefore distort in one of two ways to eliminate the eg degeneracy by placing the odd electron into either a x2-y2 or a z2 orbital. Here I explore how this effect can be teased out of crystal structures.

JT

The search is set up with Cu specified as precisely 6-coordinate, and X=oxygen. The six X-Cu distances are defined as DIST1-DIST6. The R-factor is specified as < 0.05 (no disorder, no errors). The problem now is how to plot what is in effect a six-dimensional set of data, from which we are exploring whether four of the distances are different from the other two, and whether those four are the longer or the shorter. This requires analysis beyond the capability (as far as I know) of the Conquest program, and so here I will show sets of plots showing just the relationship between any two distances at a time. Of the 15 possible combinations of two distances, only four are shown below.

Some obvious patterns can already be spotted in the 400 or so compounds which satisfy the search criteria.

  • The largest clustering occurs at ~1.95Å, with two clusters each of fewer hits at ~2.5Å. The Wikipedia page notes that for Cu(OH2)6 the Jahn-Teller distortion favours four short bonds at ~1.95Å and two long ones at ~2.38Å, which agrees approximately with the positions and sizes of the centroids of these clusters.†
  • Plots 1 and 2 show very little along the diagonals, where the two plotted distances have the same value. This probably means that one of the distances relates to an equatorial ligand and the other to an axial ligand.
  • Plots 3 and 4 show a strong diagonal trend, and so these distances both relate to either axial or equatorial, but not one of each.
  • All four plots show a hot spot at ~1.95Å, which hints that the Jahn-Teller distortion is four short bonds/two long.
  • Plot 4 also shows a green spot at ~2.5Å which is a tantalising suggestion of examples of four long bonds/two short.‡
  1. CuO-12
  2. CuO-34
  3. CuO-56
  4. CuO-13

Clearly this analysis can be followed up by a visual inspection of individual molecules in each cluster (as well as the outliers which appear to follow no pattern!), together with a more bespoke analysis of the six distances. Unfortunately, the spin state of the complexes cannot be quickly checked (are they all doublets?) since the database does not record these.  But the basic search described above takes only a few minutes to do, and it is surprising at how quickly the Jahn-Teller effect can be statistically tested with real experimental data obtained for ~400 molecules. Of course, here I have only explored X=O but this can easily be extended to X=N or X=Cl, to other metals or to alternative coordination numbers such as e.g. 4 where the Jahn-Teller effect can also in principle operate.

‡ One genuine example of this type, also called compressed octahedral coordination, was reported for the species CuFAsF6 and CsCuAlF6[1]

† The measured geometry of Cu(H2O)6 may in fact manifest with six equal Cu-O bond lengths due to the dynamic Jahn-Teller effect, because the kinetic barrier separating one Jahn-Teller distorted form and another (equivalent) isomer is small and hence averaged atom positions are measured which mask the effect. Thus the Jahn-Teller effects shown in the plots above may be under-estimated because of this dynamic masking. Reducing the temperature of the sample at which data was collected would reduce this dynamic effect. Indeed, Cu(D2O)6 collected at 93K shows a very clear Jahn-Teller distortion[2] with four long bonds ranging from 1.97-1.99Å and two long bonds 2.37-2.39Å.[3] Another example measured at 89K with dimethyl formamide replacing water and coordinated via oxygen[4] shows four short (1.97-1.98Å) and two long (2.315Å) bonds. This latter example is also noteworthy because this analysis is as yet unpublished in a journal, but the data itself has a DOI via which it can be acquired. A nice example of modern research data management!

References

  1. Z. Mazej, I. Arčon, P. Benkič, A. Kodre, and A. Tressaud, "Compressed Octahedral Coordination in Chain Compounds Containing Divalent Copper: Structure and Magnetic Properties of CuFAsF<sub>6</sub> and CsCuAlF<sub>6</sub>", Chemistry – A European Journal, vol. 10, pp. 5052-5058, 2004. https://doi.org/10.1002/chem.200400397
  2. W. Zhang, L. Chen, R. Xiong, T. Nakamura, and S.D. Huang, "New Ferroelectrics Based on Divalent Metal Ion Alum", Journal of the American Chemical Society, vol. 131, pp. 12544-12545, 2009. https://doi.org/10.1021/ja905399x
  3. Zhang, Wen., Chen, Li-Zhuang., Xiong, Ren-Gen., Nakamura, T.., and Huang, S.D.., "CCDC 755150: Experimental Crystal Structure Determination", 2010. https://doi.org/10.5517/cctbspl
  4. M.M. Olmstead, D.S. Marlin, and P.K. Mascharak, "CCDC 1053817: Experimental Crystal Structure Determination", 2015. https://doi.org/10.5517/cc14cl36

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