J . Org. Chem. 1999, 64, 2577-2578
2577
Im p r oved Syn th esis of Ca vita n d s
Sch em e 1. Th e P r ep a r a tion of Ca vita n d s fr om
Octols
Esteban Rom a´ n, Carlos Peinador, Sandra Mendoza, and
Angel E. Kaifer*
Center for Supramolecular Science and Chemistry
Department, University of Miami,
Coral Gables, Florida 33124-0431
Received November 5, 1998 (Revised Manuscript Received
J anuary 25, 1999)
In tr od u ction
Methylene-bridged resorcin[4]arene cavitands have
been used for a variety of purposes because of their rigid
structures, bowl-shaped cavities, and synthetic acces-
sibility. Cavitands have served as precursors to car-
Ta ble 1. Yield s for th e P r ep a r a tion of Ca vita n d s fr om
th e Cor r esp on d in g Octols
1
reported
yield, %
yield
(this work), %
cerands and hemicarcerands, which are usually pre-
cavitand
reference
pared in rather low yields with high dilution techniques.
Therefore, the efficient synthesis of cavitands is an
important goal in the development of the chemistry of
these hosts and their complexes, which are often kineti-
cally stable and, thus, provide a unique chemical envi-
ronment for the incarcerated guest.
2
4
6
8
55
56
92
52
4
6
7
8
95
88
92
a
94
a
The reaction was carried out in DMF.
Our group is particularly interested in the electro-
chemical behavior of redox active guests encapsulated
inside hemicarcerand hosts.2 This work requires the
solubilization of hemicarcerands and their inclusion
complexes in polar solvents, suitable for electrochemical
experiments. Recently, Cram and co-workers have re-
ported the preparation of a water-soluble hemicarcerand,3
which would be ideal for electrochemical experimenta-
tion. A key step in the preparation of this hemicarcerand
is the synthesis of cavitand 2. Here, we report a consider-
ably improved procedure for the synthesis of 2 and
related cavitands.
more, the almost quantitative yield greatly simplifies the
workup, eliminating the need for any chromatographic
separations. We have also investigated similar reaction
conditions for the preparation of another three commonly
utilized cavitands (4, 6, and 8) and found that the
procedure reported here leads to vastly improved yields
after shorter reaction times for two of them (4 and 8, see
Table 1). The yield of the fourth cavitand (6) is already
quite high using the previously reported method. There-
fore, our reaction conditions only lead to shortened
reaction times in this particular case.
In summary, we have found a simple procedure for the
preparation of cavitands 2, 4, 6, and 8 in higher yield,
shorter reaction times, and significantly easier workup
as compared to the previously reported methods.
Resu lts a n d Discu ssion
The reported procedure4 for the preparation of 2
involves the reaction of octol 1 with CH
2
BrCl at 60-70
°C for 24 h (see Scheme 1). After column chromatography,
Exp er im en ta l Section
5
necessary to separate 2 from partially bridged cavitands
and other byproducts, the pure cavitand was isolated in
5% yield. The key difficulty with this procedure is the
low normal boiling point of CH BrCl (68 °C), which limits
All solvents and reagents were commercially available and
used without further purification. The four octols used in his
work were prepared according to literature procedures.
spectra were recorded in a 400 MHz spectrometer. MS spectra
were recorded in FAB mode. Combustion analyses were per-
formed by Atlantic Microlab (Atlanta, GA).
Gen er a l P r oced u r e for th e Syn th esis of Ca vita n d s. A
mixture of the corresponding octol (1.00 g), Cs
mmol), and CH BrCl (3.0 mL, 46 mmol) in dry DMSO (20 mL)
(15 mL of DMF and 0.80 g of octol for the synthesis of 8) was
stirred in a sealed tube (Ace pressure tube, Aldrich) at 88 °C
for 3 h. (Caution: Changes in the reaction conditions may result
in much larger internal pressures.) After cooling, the mixture
was poured into 2% HCl (200 mL), and the solid formed was
filtered and dried at 100 °C under high vacuum to yield the
corresponding cavitand. All cavitands were suitable for use in
subsequent reactions. A small sample of every cavitand was
recrystallized from chloroform and dried to give samples with
4
,6-8
5
NMR
2
the reaction temperature. We solved this problem by
heating the reaction mixture at 88 °C in a sealed tube.
(CAUTION: The reaction vessel must be able to with-
2 3
CO (3.00 g, 9.21
stand an internal pressure of several atmospheres.) The
higher temperature leads to a much shorter reaction time
2
(3 h) and substantially increased yield (95%). Further-
*
Corresponding author. Tel: (305) 284-3468. Fax: (305) 444-1777.
E-mail: akaifer@umiami.ir.miami.edu.
1) (a) Cram, D. J .; Cram, J . M. Container Molecules and their
Guests; Stoddart, J . F., Ed.; Royal Society of Chemistry: Cambridge,
(
1
994. (b) Sherman, J . C. Tetrahedron 1995, 51, 3395.
2) Mendoza, S.; Davidov, P. D.; Kaifer, A. E. Chem. Eur. J . 1998,
, 864.
(
4
(
(
3) Yoon, J .; Cram, D. J . Chem. Commun. 1997, 497.
4) Cram, D. J .; Karbach, S.; Kim, H.-E.; Knobler, C. B.; Maverick,
(6) Bryant, J . A.; Blanda, M. T.; Vincenti, M.; Cram, D. J . J . Am.
Chem. Soc. 1991, 113, 2167.
(7) Boerrigter, H.; Verboom, W.; Reinhoudt, D. N. J . Org. Chem.
1997, 62, 7148.
E. F.; Ericson, J . L.; Helgeson, R. C. J . Am. Chem. Soc. 1988, 110,
229.
5) Timmerman, P.; Boerrigter, H.; Verboom, W.; Van Hummel, G.
J .; Harkema, S.; Reinhoudt, D. N. J . Incl. Phenom. 1994, 19, 167.
2
(
(8) Sherman, J . C.; Cram, D. J . J . Am. Chem. Soc. 1989, 111, 4527.
1
0.1021/jo982218y CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/18/1999