Chemistry Reference
In-Depth Information
water solution without the cyclodextrin the product was 60% p- and 40% o-chloroa-
nisole. The simplest idea could be that the cyclodextrin simply blocks the ortho posi-
tions in complex
63
, but this is not correct. The cyclodextrin actually accelerates the
reaction of the para position, so it is a catalyst, not just a blocker.
Also, in water solution the chlorination of anisole by HOCl shows second-order ki-
netics in HOCl; the chlorinating agent is the more powerful Cl
2
O, which is in equili-
brium with two HOCl molecules [143]. However, when the cyclodextrin is present the
chlorination shows only first-order dependence on [HOCl], indicating that a different
chlorinating species is involved in the catalytic reaction. We also examined the reaction
using
-cyclodextrin. Again, there was no ortho chlorination
of anisole in the complex, but now there was no acceleration of the para chlorination.
Thus, the catalyzed para chlorination process is faster with the well-fitting
b
-cyclodextrin instead of
a
a
-cyclodex-
trin than with the more loosely fitting
-cyclodextrin.
From all this we concluded that the catalysis by cyclodextrin involves the reversible
formation of a cyclodextrin hypochlorite (
64
), which can transfer chlorine to the ani-
sole para position but cannot reach the ortho position. The reaction is faster when the
RO-Cl group is held closer and more rigidly in the smaller
b
-cyclodextrin.
It is interesting that this artificial enzyme induces such selectivity whereas the en-
zyme chlorinase does not. The real enzyme produces a 60:40 mixture of para and ortho
chloroanisoles, presumably because it generates HOCl that reacts with free anisole in
solution. The artificial enzyme is more like a typical enzyme - which would be highly
selective in its products - than is this particular natural chlorinating enzyme!
Further insight came from our study of other aromatic substitution reactions. When
we blocked the para position of anisole in compound
65
, we saw that ortho chlorina-
tion was blocked by binding with
a
-cyclodextrin, so the only reaction was from the
substrate that was in free solution, not that which was bound. However, with p-cresol
(
66)
a
-
cyclodextrin. When p-cresol binds to the cyclodextrin, the polar phenol or phenoxide
group will be out of the cavity, bringing the ortho positions within reach of the cyclo-
there was still, of course, ortho chlorination but now it was catalyzed by the
a
