[Nescafe]

Hello,

I just saw a paper where the authors treated Styrene oxide  with sodium azide and got a mixture of regioisomers with the azide attacking the benzylic carbon being favoured (77%) v.s. he 2 position (23%). Is this because the benzylic carbon is more stable and thus why the preferred position for a nucelophile to attack? As initially, I thought due to sterics the azide would attack the 2-position.

THanks in advance,

Nescafe.

[Nescafe]

Any idea guys?

Looking into it I think what I suggested is correct but can one of you geniuses confirm please?

[Dan]

This is sometimes called the S_N2 benzylic effect - it should be mentioned in most organic textbooks. The rationale is often presented as similar to the increased rate of S_N2 alpha to a carbonyl (π* orbital stabilises the lone pair of the incoming nucleophile in the transition state). While logical, whether or not this is the primary reason for the rate increase is debatable.

For a fairly recent paper with a more sophisticated explanation and discussion, see: http://pubs.acs.org/doi/abs/10.1021/ja802246y

[Babcock_Hall]

In the case of forming a bromohydrin from styrene, the water attacks the benzylic position to form 2-bromo-1-phenylethanol.  The bromonium intermediate is similar to an epoxide.  See McMurry, 8th edition, p. 268.

[Dan]

In the case of forming a bromohydrin from styrene, the water attacks the benzylic position to form 2-bromo-1-phenylethanol.  The bromonium intermediate is similar to an epoxide.  See McMurry, 8th edition, p. 268.

I think this is perhaps a risky comparison - under acidic conditions, I would agree that a protonated epoxide is similar to a bromonium. This example is an opening of the epoxide under basic conditions though, so I don't think the comparison is a good one.

The regioselectivity of epoxide opening under acidic and basic conditions is usually different ("loose S_N2" vs S_N2).

[Babcock_Hall]

Dan,

As always you raise some good points.  I was struck by the fact that in the addition of HCl to epoxides, that chloride attacks a 2° carbon in preference to a 1° carbon.  Yet chloride attacks a 1° in preference to a 3°.  On the other hand, bromide ion behaves differently (McMurry, pp. 687-688).  I have not yet found styrene epoxides treated in this textbook, but I will keep looking as time permits.