Page 187 - Mechanism and Theory in Organic Chemistry

groups, both of which carry a partial negative charge, to be as far away from
each other as possible, thus minimizing electrostatic repulsion.ll That this
explanation is not correct is shown by the fact that even reactions of charge type 3,
in which the entering and leaving groups bear opposite charges, go by inversion.12
Hughes and co-workers carried out the reactions shown in Scheme 1.
A sample of optically active 1-phenylethyl chloride was converted to the
corresponding azide with sodium azide while another was converted to the thiol
with sodium hydrogen sulfide. Both of these second-order reactions are of charge
type 1, processes already shown to proceed with inversion. Thus both the thiol
and the azide have the configuration opposite to that of the starting chloride.
The azide was then reduced with hydrogen over platinum to the corresponding
amine, and the thiol was converted to the dimethylsulfonium salt. Neither of these
processes disturbs the chiral center, and therefore both of these compounds have
the opposite configuration to that of the starting material. Then, in another
second-order substitution reaction, the sulfonium salt was converted to the azide
and the azide reduced to the amine. This amine had the opposite configuration
of the amine produced by the first route, and therefore the substitution (of charge
type 3) of azide ion on the sulfonium salt must occur with inversion of configura-
tion.
There is now a great deal of evidence that all SN2 reactions of all charge
types proceed with inversion.13

Substitution in Bridged Ring Compounds
Proof that a site incapable of undergoing inversion is also incapable of under-
going a second-order substitution reaction has been obtained from bicyclic
compounds. The bridgehead carbon of rigid bicyclic systems cannot invert with-
out fragmenting the molecule, and indeed, compounds such as l-bromotripty-
cene (2) and 7,7-dimethyl-[2.2.1 .I-bicycloheptyl- 1--ate (3) are
completely inert when treated with a nucleophile under SN2 conditions.14

l1 N. Meer and M. Polanyi, Z. Phys. Chem., B19, 164 (1932).
l2 S. H. Harvey, P. A. T. Hoye, E. D. Hughes, and C. K. Ingold, J. Chem. SOC., 800 (1960).
l3 See (a) note 10, p. 174; (b) note 12; (c) H. M. R. Hoffmann and E. D. Hughes, J. Chem. SOC.,
1252, 1259 (1964).
l4 (a) P. D. Bartlett and L. H. Knox, J. Amer. Chem. Soc., 61, 3184 (1939); (b) P. D. Bartlett and
E. S. Lewis, J. Amer. Chem. SOC., 72, 1005 (1950).