Posts Tagged ‘hydrazine’

What is the approach trajectory of enhanced (super?) nucleophiles towards a carbonyl group?

Wednesday, May 11th, 2016

I have previously commented on the Bürgi–Dunitz angle, this being the preferred approach trajectory of a nucleophile towards the electrophilic carbon of a carbonyl group. Some special types of nucleophile such as hydrazines (R2N-NR2) are supposed to have enhanced reactivity[1] due to what might be described as buttressing of adjacent lone pairs. Here I focus in on how this might manifest by performing searches of the Cambridge structural database for intermolecular (non-bonded) interactions between X-Y nucleophiles (X,Y= N,O,S) and carbonyl compounds OC(NM)2.

The search query[2] is shown above and involves plotting the distance from the nucleophilic atom (N above) to the carbon of the carbonyl group. The carbon is defined as having 3-coordination, one of which is O=C and two non-metal attachments. The torsion is constrained to values of |70-110|° to ensure that the approach of the nucleophile is approximately perpendicular to the plane of the carbonyl in order to overlap with the π*-orbital as electrophile. The pairwise sums of van der Waals radii are NC, 3.25; OC, 3.22 and SC, 3.5Å and the plots show all contacts shorter than these. The results of the searches are shown below.

The general observation is that the red hotspots do tend to come at trajectory angles of <100° and many are <90° such as the X=Y=N or X=Y=S examples. Given that the original Bürgi–Dunitz hypothesis (actually based on a small number of molecules synthesized for the purpose) proposed rather larger angles (105±5°) corresponding to optimum alignment of the nucleophile with the carbonyl π*-orbital, we might speculate whether the use of enhanced nucleophiles is the reason for the apparent decrease in the angle. And if so, what the underlying reasons would be.

I also cannot help but observe that the term supernucleophile is quite rare in the literature; SciFinder gives only 45 hits, but most are about neither hydrazines nor peroxides. There are also some unusual nucleophile varieties such as Cob(I)alamin[3], of which there are probably insufficient examples to reflect in the crystal structure statistics shown above. Given the interest in superbases, the relative lack of examples of unusual supernucleophiles seems surprising.

References

  1. G. Klopman, K. Tsuda, J. Louis, and R. Davis, "Supernucleophiles—I", Tetrahedron, vol. 26, pp. 4549-4554, 1970. https://doi.org/10.1016/s0040-4020(01)93101-1
  2. H. Rzepa, "Crystal structure search using enhanced nucleophiles", 2016. https://doi.org/10.14469/hpc/487
  3. K.P. Jensen, "Electronic Structure of Cob(I)alamin:  The Story of an Unusual Nucleophile", The Journal of Physical Chemistry B, vol. 109, pp. 10505-10512, 2005. https://doi.org/10.1021/jp050802m

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Posted in Chemical IT, crystal_structure_mining | 1 Comment »

Tunable bonds

Saturday, July 3rd, 2010

Car transmissions come in two types, ones with fixed ratio gears, and ones which are continuously variable. When it comes to chemical bonds, we tend to think of them as being very much of the first type. Bonds come in fixed ratios; single, aromatic, double, triple, etc. OK, they do vary, but the variations are assumed as small perturbations on the basic form. Take for example the molecule shown below. The bonds as shown are all clearly single (the wedge and hashed bond are merely stereochemical notations). No-one would really think of drawing this molecule in any other way, and this idea of the transferability of bonds between molecules (all double bonds react in specific ways which are different from single bonds, and they also have characteristic spectroscopic properties, etc) is what allows molecules to be classified.

A Highly tunable molecule

With this molecule however, there really is an elephant in the room; the three electron lone pairs associated with each nitrogen atom (not shown above, but most chemists are trained to recognize their implicit presence). Where are they? Well, each lone pair will tend to orient itself such that it is aligned with an adjacent σ-bond. It has two such bonds to choose from, an adjacent C-N bond or a C-Cl bond. One might now envisage the following permuations; all three N lone pairs gang-up on the C-Cl bond, or perhaps only two do, or only one, or none. What happens in each of these scenarios? The table below shows these permutations calculated using B3LYP/6-31G(d).

app lone pairs
to C-Cl		 Relative free
energy, kcal/mol		 C-Cl bond
length, Å		 ν C-Cl, cm-1
3 0.0 2.542 158
2 4.2 2.099 221
1 7.3 1.937 352
0 14.4 1.869 441

3 app lone pairs. Click for animation

2 app lone pairs. Click for animation

1 app lone pairs. Click for animation

0 app lone pairs. Click for animation

The C-Cl bond length changes from a normal single bond length (1.87Å) when none of the nitrogen lone pairs are antiperiplanar to the C-Cl bond, to a very abnormal 2.54Å when all three are, and the C-Cl stretching mode decreases in wavenumber from 441 to 158 cm-1. There is lots of other fun to be had inspecting the geometries and vibrations, but  I will leave that for you to explore rather than discuss it here. Click on the thumbnails above to start.

This effect does have a name, sugar chemists call it the anomeric effect. But this one is supercharged! It would be quite reasonable to say that at some stage, the C-Cl single bond turns from being covalent to being ionic (and indeed, repeating the calculation using an applied solvent field certainly accelerates this process). Whilst this might be a contrived example and hence an extreme example, it does serve to remind us that on occasion, molecules may come with continuously variable transmissions rather than with fixed ratio gears!

And a postscript. I mentioned the nitrogen lone pairs ganging up on the C-Cl bond. How might one go even one step further? A standard trick to enhance the donating power of a nitrogen lone pair is to replace the NH2 group with a hydrazine group, H2N-NH. The lone pair derived from the second nitrogen buttresses the first. This too has a name, it is called the α-effect.

An anomeric effect on steroids

For this example (see digital repository), the C-Cl bond length lengthens even further to 2.90Å, which interestingly, is the same value as for the SN1 transition state!

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Posted in Interesting chemistry | 3 Comments »