Page 240 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN011A-543 February 12, 2002 12:40

Organic Macrocycles 527

Synthetic supramolecular chemistry is currently receiv-
ing considerable attention. The creation of multicom-
ponent macrocyclic architectures utilizing noncovalent
bonding interactions and the synthesis of discrete molec-
ular entities interlocked or intertwined by covalent bonds
and mechanical associations assisted by intermolecu-
lar, noncovalent interactions is driven by the desire to
understand and engineer well-defined, self-assembled
structures with desirable properties. In the beginning,
(4)
these supramolecular compounds were prepared in low
yield via “statistical” methods. Advances in synthetic
Compound 12 has shown chiral recognition for the
methodologies that take advantage of complexation and
enantiomers of various organic ammonium salts in that
noncovalent association properties make the synthesis
enantiomerically pure 12 forms a stronger complex with
of these molecules more available. Self-assembly as a
one enantiomer of a chiral organic ammonium salt than
synthetic tool shows promise for supramacrocyclic com-
with the other enantiomer. Chiral crown 15 (Fig. 1) syn-
pounds. A single representation of supramolecular syn-
thesized in a similar manner has been used to effect an
thesis is given in Eq. (7). The first step is the association
NADH type of asymmetric reduction of certain aromatic
of the organic ammonium cation with the crown ether in
ketones.
a process called threading. Then large bulky groups are
There are a great number of ways to prepare the aza-
linked to each end which prevents dethreading of the or-
crown ethers which include the cyclic polyamines such
ganic ammonium ion.
as cyclam (compound 7, Fig. 1). Some of these syntheses
include the cycloaddition reaction of a diacid dichloride
andadiaminefollowedbyreductionofthemacrocyclicdi-
amide and treatment of a dihalide with a bistosylamide fol-
lowed by removal of the N-tosyl groups. A more recent in-
novation to prepare a cyclam is the treatment of a diamine
with a bis(α-chloroamide) as shown in Eq. (5) for the
preparation of trimethylcyclam. The bis(α-chloroamide)
is readily prepared from a diamine and chloroacetyl
choride or chloroacetic anhydride. The two amide nitro-
gen atoms can contain hydrogens since the amide nitrogen
cannot act as the nucleophile. Cryptand 2.2.2 (compound
4, Fig. 1) was initially prepared by Lehn and co-workers
in a multistep process. A recent advance in the synthe-
sis of macrobicyclic compounds is the one-step reaction
of the appropriate bisprimary amine with two moles of a
ditosylate as shown in Eq. (6). The ditosylate is the key to
this one-step synthesis which results in the preparation of
the cryptands in relatively high yields.

(5)
(7)

Thirty years after Pedersen’s discovery of crown ethers,
the host–guest concept has firmly established itself in
the realm of synthetic chemistry, as evidenced by the
expansion of the macrocyclic into the self-assembled
(6) supramolecular synthesis.