Henry Rzepa

Chemistry with a twist

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Hidden intermediates in the benzidine rearrangement. The monoprotonated mechanism. »

The mechanism of the Benzidine rearrangement.

0000-0002-8635-8390

The benzidine rearrangement is claimed to be an example of the quite rare [5,5] sigmatropic
migration[1], which is a ten-electron homologation of the very common [3,3] sigmatropic reaction
(e.g. the Cope or Claisen). Some benzidine rearrangements are indeed thought to go through the
[3,3] route[2]. The topic has been reviewed here[3].

In this post, I offer a calculated transition state and IRC for this reaction, to see what insights might
accrue. How was this obtained?

1. At the ωB97XD/6-311G(d,p)/SCRF=water level. This procedure would allow for

any dispersion-like effects to be allowed for in the π-π-stacking.

2. The rearrangement is normally promoted by acid, and the active species is

thought to be diprotonated[4]‡ (although monoprotonated catalysis is also
 observed[1]. Here I report just the diprotonated route, together with chloride
anions to balance the charges, and have added a continuum water field to allow
this double ion-pair to be at least partially stabilised.

3. The rate determining step is the N-N cleavage/C-C bond formation. This is
followed by presumed rapid proton transfers, which are not modelled here.

The [5,5] transition state for the benzidine rearrangement. Click for 3D.

This [5,5] transition state is 2.9 kcal/mol lower in ΔG‡298 than the transition state for the isomeric
[3,3] rearrangement. The NCI (non-covalent-interactions) shows the forming C-C bond to be on the
border of covalent, and non-covalent (blue), but that the π-π-stacking region is all weakly attractive
(green). You can also observe the strong hydrogen bonds between the chloride anion and an N-H
group (blue), and the weak attractive zones between the two nitrogen centres, between the chloride
and the ortho-C-H hydrogens, and even between the two chloride anions (blue-green or green). I
should point out that the initial position for these anions was over the aryl ring, but they migrated to
the NH region during optimisation of the transition state.
 NCI surface. Click for 3D.

The molecular electrostatic potential (isosurface = 0.11 au) shows both aryl rings as a single unit
attracted by a positive potential (blue)

Calculated electrostatic potential. Click for 3D.

The highest-occupied molecular orbital shows the two bonds involved in the [5,5] shift (N-N and C-C)
are both bonding, but more significantly, the central region of the two stacked aryl rings is also
bonding. This is a clear manifestation of a π-complex, which the benzidine rearrangement has often
(and it has to be said controversially) described as, and which elevates this particular reaction from
that of a simple bond forming/bond cleaving sigmatropic. Another way of looking at it is that
secondary orbital interactions (such as often invoked in Diels-Alder cycloadditions) are exceptionally
important here.

HOMO for 5,5 benzidine rearrangement. Click for 3D.

The LUMO is strongly antibonding in that region; indeed adding two electrons to form a 12-electron
process would be strongly destabilising. In this regard, this unusual sigmatropic reaction follows the
same 4n+2 electron rule as more conventional ones.

LUMO. Click for 3D.

The next two diagrams illustrate the competing (higher energy) [3,3] shift, which also has some π-
complex character.

A [3,3] alternative to the benzidine rearrangement. Click for 3D.

NCI surface for 3,3 rearrangement. Click for 3D.

I will end with three autobiographical notes.

 1. The benzidine rearrangement was one of the earliest reactions I did in my home
laboratory, at the age of about 13. As I recollect, I prepared about 1.5 grams
(blissfully ignorant of how carcinogenic it is), and used it via diazotization to
couple to phenol. My fascination with chemistry most certainly started with colour
(and how to express the bonding in nitric oxide).

2. About eight years later, I was about to commence my Ph.D. studies. The
objective was to use kinetic isotope effects to infer the structure of transition
states. In my case (proton transfers to indoles) I never did achieve this objective.
But it is noteworthy that the mechanism of the benzidine rearrangement was
largely unravelled using such isotopic studies.

3. By 1974 as a post-doctoral researcher, I had moved on to studying mechanisms

using quantum theory and had decided that it was easier to invert the use of
isotope effects by predicting a transition structure using this method, and then
seeing if the computed isotope effects matched the experiment. We did this for
the Diels-Alder reaction[5] and more generally[6], and then for some gas-phase
eliminations[7], this latter being my first entirely independent publication.

4. So, putting all this together, one might infer that armed with a computed
transition state structure for the benzidine rearrangement, it is trivial to compute
the kinetic isotope effects and hence to see if they correspond to those
measured. You might expect a report on this in a future post here.

‡
Crystal structures of diprotonated dimethyl hydrazines[4] show a N-N bond length of ~1.45Å (typical
counter-anions being nitrate, perchlorate or sulfate). That calculated for the diprotonated diphenyl
hydrazine is ~2.5Å, which suggests that with the phenyl group, electrons from the N-N region may be
borrowed to contribute to the π-π-complex.

References
1. H.J. Shine, K.H. Park, M.L. Brownawell, and J. San Filippo, "Benzidine
rearrangements. 19. The concerted nature of the one-proton rearrangement of
2,2'-dimethoxyhydrazobenzene", Journal of the American Chemical Society, vol.
106, pp. 7077-7082, 1984. http://dx.doi.org/10.1021/ja00335a035

2. H.J. Shine, L. Kupczyk-Subotkowska, and W. Subotkowski, "Heavy-atom kinetic

isotope effects in the acid-catalyzed rearrangement of N-2-naphthyl-N'-
phenylhydrazine. Rearrangement is shown to be a concerted process", Journal of
the American Chemical Society, vol. 107, pp. 6674-6678,
1985. http://dx.doi.org/10.1021/ja00309a041

3. H.J. Shine, "Reflections on the ?-complex theory of benzidine

rearrangements", Journal of Physical Organic Chemistry, vol. 2, pp. 491-506,
1989. http://dx.doi.org/10.1002/poc.610020702
 4. C.M. Sabaté, and H. Delalu, "Energetic Salts of Symmetrical Dimethylhydrazine
(SDMH)", European Journal of Inorganic Chemistry, vol. 2012, pp. 866-877,
2011. http://dx.doi.org/10.1002/ejic.201101115

5. M.J.S. Dewar, S. Olivella, and H.S. Rzepa, "Ground states of molecules. 49.
MINDO/3 study of the retro-Diels-Alder reaction of cyclohexene", Journal of the
American Chemical Society, vol. 100, pp. 5650-5659,
1978. http://dx.doi.org/10.1021/ja00486a013

6. S.B. Brown, M.J.S. Dewar, G.P. Ford, D.J. Nelson, and H.S. Rzepa, "Ground states
of molecules. 51. MNDO (modified neglect of diatomic overlap) calculations of
kinetic isotope effects", Journal of the American Chemical Society, vol. 100, pp.
7832-7836, 1978. http://dx.doi.org/10.1021/ja00493a008

7. H.S. Rzepa, "MNDO SCF-MO calculations of kinetic isotope effects for

dehydrochlorination reactions of chloroalkanes", Journal of the Chemical Society,
Chemical Communications, pp. 939,
1981. http://dx.doi.org/10.1039/C39810000939
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Hidden intermediates in the benzidine rearrangement. The monoprotonated mechanism.

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Tags: higher energy, Historical, π-complex, pericyclic, Reaction Mechanism

This entry was posted on Sunday, January 6th, 2013 at 5:35 pm and is filed under Interesting chemistry. You can follow any
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4 Responses to “The mechanism of the Benzidine rearrangement.”

1. Hidden intermediates in the benzidine rearrangement. The

monoprotonated mechanism. « Henry Rzepa says:

January 8, 2013 at 12:58 pm

[…] Chemistry with a twist « The mechanism of the Benzidine rearrangement. […]

Reply

2. The Benzidine rearrangement. Computed kinetic isotope

effects. « Henry Rzepa says:

January 11, 2013 at 8:22 pm

[…] The match between experiment and theory for TS(CC) is reasonable (given the

approximations in both the theory and the difficulty of the experiments and ensuring

isotopic purities) but not so for TS(NN). But TS(CC) is a “stepwise-concerted”

reaction as a closed shell singlet; as shown in the IRC computed from TS(CC. […]

Reply

3. Why is N,O-diphenyl hydroxylamine (PhNHOPh) unknown? «

Henry Rzepa says:

January 16, 2013 at 10:31 am

 […] noticed my noting in previous posts that the benzidine rearrangement proper is

normally promoted by double protonation, and that reaction via monoprotonation

has a significantly higher barrier. So what are the […]

Reply

4. Why diphenyl peroxide does not exist. « Henry Rzepa says:

April 29, 2013 at 11:44 am

[…] few posts back, I explored the “benzidine rearrangement” of diphenyl hydrazine.

This reaction requires diprotonation to proceed readily, but we then […]

Reply

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