Imperial College London

Henry Rzepa

The ionization of a C-X bond (X=halogen) to form what we call a
carbocation and which is known as the SN-1 reaction goes way back in the
history of chemistry. Julius Steglitz was probably the first person to
suggest such an ionization, back in 1899 (Steglitz, J.; *Am. Chem. J.*,
**1899**, 21, 101). The reaction became very famous during the 1920s
onwards, and could be regarded as one of the cornerstones of organic
chemistry. A question I like to ask whenever talking about a reaction is
"what is the transition state like?". Although answering such a question
can get tricky, one might imagine that it should be relatively simple
for such a fundamental reaction as the SN-1.

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SN-1 Reaction. Click on image to see 3D model
:::

Well, it turns out it is not!  Looking at the energy of the system as a
function of extending the  C-Cl distance usually produces a curve that
rises sharply, way past the actual free energy barrier for e.g. the
solvolysis of tert-butyl chloride (which is around  21 kcal/mol), and
which produces no actual transition state.  Such a gas-phase model is
simply not realistic, and to make it so, we have to include solvent.
 Such a model does yield a transition state, about which the following
aspects can be noted:

1.  At least 13 water molecules are needed to model this reaction; more
    would be better, but it gets increasingly difficult to fully
    optimise their positions as you add more
2.  The reason so many are needed is that they cross-polarise each
    other. One water molecule initiates an S~N~2 like attack from the
    back side of the t-butyl chloride. As the O...C bond develops, that
    water molecule becomes positively charged. This positive charged
    water forms an unusually strong hydrogen bond to a second molecule,
    which transfers part of this positive charge to the second water.
    This forms a H-bond to a third water, again stronger than usual
    because of the charge of the second. At the other end of the
    molecule, the C...Cl bond is gradually leaving and becomes a
    chloride anion. This too stabilises by forming a hydrogen bond to an
    adjacent water. Again this is stronger than normal due to the
    partial transfer of charge. Gradually, a chain of waters bridging
    the first water and the chloride forms.
3.  In fact, its better to form at least two such bridges rather than
    just one. Perhaps even three chains might form (but I have not yet
    succeeded in locating the transition state for such!).
4.  The bridging waters also form little water trimers as they go, a
    particularly stable arrangement for water. These too gain from the
    cross-polarisation.
5.  This arrangement allows a proper *close ion-pair* to form, and a
    properly locatable transition state on the way to this species to be
    characterized.
6.  Once the ion pair is formed, one of two things can now happen
    1.  The original water is still fully protonated, with the
        associated positive charge. It is easily the best leaving group
        in the system. So a neutral water can come in from the side of
        the chloride, and undergo a second S~N~2 like displacement of
        that charged water. Net effect? Production of t-butanol with
        **retention of configuration at the carbon**.
    2.  The polarisation induced by the first charge water, and the last
        charged chloride amounts to partial proton transfer via a chain
        like mechanism. In fact, it takes very little further energy to
        fully transfer one proton from the water end of things to the
        chloride. This produces t-butanol with **inversion of
        configuration at the carbon**.
7.  If each of the above two steps were to be equally likely. the
    outcome would be that the production of t-butanol occurs with
    apparent racemisation! In reality, the dynamics of the system will
    probably also play an important role in determining the outcome.
8.  Take a look at the transition state shown above. You will notice a
    remarkable degree of **rotation** of two of the methyl groups. This
    makes the transition state highly dependent on the **mass** of the
    hydrogens on these methyls. Now, it is known that replacing the Hs
    with deuterium induces a very large isotope effect on the reaction.
    Now we know why! It is more difficult to move a heavy atom in the TS
    than a light one. In fact, the isotope effect can be calculated from
    the transition state, and it agrees almost exactly with experiment.

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[https://orcid.org/0000-0002-8635-8390](https://orcid.org/0000-0002-8635-8390){target="_blank"
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:::


The ionization of a C-X bond (X=halogen) to form what we call a carbocation and which is known as the SN-1 reaction goes way back in the history of chemistry. Julius Steglitz was probably the first person to suggest such an ionization, back in 1899 (Steglitz, J.;
<em>
 Am. Chem. J.
</em>
,
<strong>
 1899
</strong>
, 21, 101). The reaction became very famous during the 1920s onwards, and could be regarded as one of the cornerstones of organic chemistry.

Messaggi di Rogue Scholar

The SN-1 Reaction live!