Page 203 - Mechanism and Theory in Organic Chemistry

strate is changed since the magnitude of a relative to /3 may change. A disadvan-
tage is the larger number of parameters. The effect of solvent on nucleophilic
reactivity is implicitly taken into consideration in the Edwards equation if H and
En are determined in the same solvent system used for the S,2 reactions.

The Leaving Group
Since the leaving group begins to pull a pair of electrons toward itself in the
transition state of an S,2 reaction, it is to be expected that the best leavin%g_~o_ups
will -_--- be those thatcan best stabilize ----- extra pair~felect.mm, t_hati~\_weak.ik.ewis
an
.
baze~ This is usually the case. For example, Tables 4.7 and 4.8 indicate that the
reactivity of the halogens seems always to be I > Br > C1 > F. Furthermore,
groups that have a positive charge in the original molecule but become small
+ + +
neutral molecules after they have departed, such as -SR,, -OH,, and -N,,
often make good leaving groups. This can be very useful because displacements
with leaving groups such as -OH, -OR, and -SH do not occur readily be-
cause OH-, OR-, and SH- are strong bases. If such groups are simply pro-
tonated, they can often be displaced.
However, one cannot predict the relative reactivities of two leaving groups
simply by a comparison of the pKa's of their conjugate acids. And indeed it
would be surprising if one could, since we are here again dealing with the
strengths of C-X, not H-X bonds. But this is not the only problem, as an
examination of Tables 4.7 and 4.8 reveals. The relative reactivities of the leaving
groups are dependent on the nucleophile and on the solvent. For example, in
Table 4.7 we see that in ethanol with p-toluenethiolate as the nucleophile, the
reactivity ofp-toluenesulfonate ("tosylate," OTs) as a leaving group lies between
that of bromide and that of chloride (cf. reactions 1, 3, and 5)-approximately
what would be expected from the pKa values-but in the same solvent with
ethoxide ion as the nucleophile, tosylate becomes more reactive than iodide
(Reactions 2,4, 6 in Table 4.7). The explanation suggested by Hoffmann is that
the reactivity of tosylate relative to the halides is a function of the amount of
substrate-leaving-group bond breaking in the transition state.53 When the
attacking reagent is the excellent nucleophile, p-toluenethiolate (nCH3, of C,H,S-
= 9.92), according to Hammond's postulate, the transition state occurs very early
in the course of the reaction, before there has been much bond breaking. Then
tosylate behaves normally in comparison to the halides. When the much poorer

53 H. M. R. Hoffmann, J. Chem. Soc., 6753 (1965) and references therein. In Section 5.2 we conclude
that although t,.,,/k,, is a good measure of the extent of bond breaking in SN2 reactions, this criterion
cannot be extended to SN1 reactions.