Page 185 - Mechanism and Theory in Organic Chemistry

dence has been found that suggests that this is indeed a good description of the
pathway of a class of displacement reactions. We shall examine the evidence
below, but first, since this is the first chapter on reaction mechanisms, let us
emphasize that a mechanism is "good" only insofar as it explains the experimental data,
and that, therefore, although the experimental results that follow can be thought of as the
"characteristics" of the SN2 mechanism, they are in fact the observable data on whose basis
it has been conjectured. The data are facts; the mechanism is a theory deduced from those facts.

4.2 STEREOCHEMISTRY OF THE SN2 REACTION
In the 1890s, many years before the mechanism of direct substitution was pro-
posed by Hughes and Ingold, Walden had observed that some reactions of
optically active compounds give products of opposite absolute configuration
from the starting material^.^ Walden, however, was not able to discover what
conditions brought about this inversion of configuration. His task was compli-
cated by the fact that two compounds of the same absolute configuration may
nevertheless have opposite signs of optical rotation. In the following 40 years a
great deal ofwork and thought was given to the problem of the relation of Walden
inversion, as it is still called, to me~hanism.~ Then, in 1935, Hughes and co-
workers in ingenious experiments clearly showed that Walden inversion occurs in
direct nucleophilic substitution.1°
These workers studied the exchange reaction of optically active s-octyl
iodide with radioactive iodide ion in acetone (Equation 4.8) and found that: (1)
the kinetics are second-order, first-order each in octyl iodide and in iodide ion,
I-
*I- + CH3(CH2),CHCH3 + + CH3(CH2),CHCH3
I I (4.8)
I *I
and thus the mechanism is bimolecular; and (2) the rate of racemization is
twice the rate of incorporation of labeled iodide ion into the organic molecule.
The rate of racemization must be twice the rate of inversion. (If an optically
active compound begins to racemize, each molecule that undergoes inversion is
one of a racemic pair of molecules; for example, pure levorotatory starting
material is 100 percent racemized when only 50 percent of it has been converted
to the dextrorotatory isomer.) So, if the rate of racemization is twice the rate of
incorporation of radioactive iodide, then each attacking iodide ion inverts the molecule
it enters.
This one-to-one correlation of inversion with displacement must mean that
the incoming iodide enters the molecule from the side of the substitution site
opposite to the departing iodide every single time. It initially attacks the back
lobe of the sp3 orbital used for bonding with the iodide. The transition state pro-
posed by Hughes and co-workers is shown in 1. Carbon has rehybridized and is

a P. Walden, Chem. Ber., 26,2 10 (1893) ; 29, 133 (1896) ; 32, 1855 (1899).
For a comprehensive summary of this work see Ingold, Structure and Mechanism in Organic Chemisty,
pp. 509ff.
lo (a) E. D. Hughes, F. Juliusburger, S. Masterman, B. Topley, and J. Weiss, J. Chem. Soc., 1525
(1935); (b) E. D. Hughes, F. Juliusburger, A. D. Scott, B. Topley, and J. Weiss, J. Chem. Soc., 1173
(1936) ; (c) W. A. Cowdrey, E. D. Hughes, T. P. Nevell, and C. L. Wilson, J. Chem. Soc., 209 ( 1938).