Treatment of 1-bromooctane with NaCN in water for 6 h at
00 °C afforded 1-cyanooctane in 6% yield with 86% recovery
of the starting material (entry 1). However, when we carried out
the same reaction in the presence of the calixarene 1 (0.5
mol%), the yield of 1-cyanooctane increased to 83% (entry 5).
To evaluate the ability of 1 , we examined the reactions with a
conventional inverse phase-transfer catalyst, b-CD, and found
that the calixarene 1 is more efficient than b-CD by a factor of
.5 for cyanide substitution on 1-bromooctane, and 2.3 and 6.9
† The water-soluble calix[n]arenes 1
following literature methods (ref. 9) and identified by IR and NMR
spectroscopy as well as elemental analysis.
n
·nH
2
O (n = 4, 6 and 8) were prepared
1
‡
General procedure for the nucleophilic substitution reactions is as follows.
A mixture of substrate (4.6 mmol), nucleophilic reagent (10 mmol), a
catalytic amount (0.5 mol%) of 1 O and water (5 ml) was heated to 60
or 100 °C and stirred with a magnetic stirring bar. The resulting mixture was
extracted with CHCl . After the usual work-up, the crude product was
6
n n 2
· H
6
3
6
purified by preparative GPC and its isolated yield was determined. For the
reactions of 1-bromooctane and benzyl bromide with NaCN, the yield of
product was determined by GC analysis of a mixture of Et
5
for benzyl bromide and 2-(bromomethyl)naphthalene, re-
spectively (entries 13 and 21). Noteworthily, the use of as little
as 0.05 mol% of 1 is sufficient, showing its remarkable
6
2
O extracts and
an internal standard.
§
A mixture of 1
extracted with Et
over anhydrous Na
6
·6H
O (5 3 50 ml). The combined organic layer was dried
SO , and concentrated under reduced pressure. No
2
O (0.157 g, 0.106 mmol) and water (25 ml) was
2
catalytic activity (entry 14).
2
4
CDs function as inverse phase-transfer catalysts in aqueous–
organic two-phase reactions of alkyl halides with nucleophiles
owing to their ability to form host–guest complexes.5 The
water-soluble calixarenes may behave similarly to CDs, since
they also have the ability to include organic guest molecules in
their cavity. No acceleration effect is observed when
extract was detected by measurement of weight.
–7
1 For the first report of IPTC, see L. J. Mathias and R. A. Vaidya, J. Am.
Chem. Soc., 1986, 108, 1093.
(
p-methoxybenzyl)trimethylammonium chloride 2 is added to
the reaction mixture as a monomeric counterpart of 1 (entry 2).
The distribution of 1 into the organic phase was negligible,§
2 For reviews, see A. Harada, J. Synth. Org. Chem. Jpn., 1990, 48, 517;
Y. Goldberg, Phase Transfer Catalysis: Selected Problems and Applica-
tions, Gordon, Berkshire, 1992, pp. 359–366; C. M. Starks, C. L. Liotta
and M. Halpern, Phase-Transfer Catalysis: Fundamentals, Applications,
and Industrial Perspectives, Chapman, London, 1994, pp. 179–183.
6
6
indicating that the reaction catalysed by 1
predominantly in the aqueous phase.
The efficiency of the calixarenes 1
size and/or shape of the substrate molecules. For example, no
difference in the catalytic activities of 1 is detected in the
reaction of benzyl bromide (1 ≈ 1 ≈ 1 ). On the other hand,
their activities increase in the order of 1
6
takes place
3
For representative reviews, see C. D. Gutsche, Calixarenes, Monographs
in Supramolecular Chemistry, ed. J. F. Stoddart, The Royal Society of
Chemistry, Cambridge, 1989; Calixarenes: A Versatile Class of Macro-
cyclic Compounds, ed. J. Vicens and J. B o¨ hmer, Kluwer, Dordrecht,
1991; R. M. Izatt, H. S. Bradshaw, K. Pawlak, R. L. Bruening and B.
Tarbet, Chem. Rev., 1992, 92, 1261; S. Shinkai, Tetrahedron, 1993, 49,
n
varied depending on the
n
4
6
8
4
< 1
@ 1
-(bromomethyl)naphthalene. The size of the cavity of 1
is required for bulkier
-(bromomethyl)naphthalene. This result is consistently sup-
6
≈ 1
8
for
for
8
933; V. B o¨ hmer, Angew. Chem., 1995, 107, 785; Angew. Chem., Int. Ed.
1
-bromooctane and in the order of 1
4
6
< 1
8
Engl., 1995, 34, 713.
2
4
is
4
For the use of calixarenes as normal phase transfer-catalysts, see
E. Nomura, H. Taniguchi, K. Kawaguchi and Y. Otsuji, J. Org. Chem.,
large enough for benzyl bromide, but 1
8
2
1993, 58, 4709; K. Araki, A. Yanagi and S. Shinkai, Tetrahedron, 1993,
49, 6763; E. Nomura, H. Taniguchi and Y. Otsuji, Bull. Chem. Soc. Jpn.,
1994, 67, 309, 792; S. J. Harris, A. M. Kinahan, M. J. Meegan and
ported by the fact that p-sulfonatocalixarenes are capable of
molecular recognition on the basis of the hole-size selectivity in
an aqueous system.8
R. C. Prendergast, J. Chem. Res. (S), 1994, 342; Y. Okada, Y. Sugitani,
Y. Kasai and J. Nishimura, Bull. Chem. Soc. Jpn., 1994, 67, 586;
H. Taniguchi, Y. Otsuji and E. Nomura, Bull. Chem. Soc. Jpn., 1995, 68,
In conclusion, we have shown here that IPTC by water-
n
soluble calixarenes 1 provides a simple and effective means for
3
563.
conducting nucleophilic substitution reactions of activated and
unactivated organic halides, in which they exhibit much higher
activity than CDs. This is the first example of the use of water-
soluble calixarenes in organic reactions as inverse phase-
transfer catalysts.
We thank Takashi Suzuki and Naoyuki Shinoda for their
experimental assistance. The present work was partially
supported by a General Individual Research Grant for 1995
from Nihon University.
5
6
A. Z. Trifonov and T. T. Nikiforov, J. Mol. Catal., 1984, 24, 15.
N. Tanaka, A. Yamaguchi, Y. Araki and M. Araki, Chem. Lett., 1987,
7
15.
A. Deratani, G. Leli e´ vre, T. Maraldo and B. S e´ bille, Carbohydr. Res.,
989, 192, 215.
7
8
1
S. Shinkai, K. Araki and O. Manabe, J. Chem. Soc., Chem. Commun.,
1988, 187.
9 T. Arimura, T. Nagasaki, S. Shinkai and T. Matsuda, J. Org. Chem.,
1989, 54, 3766; T. Nagasaki, K. Sisido, T. Arima and S. Shinkai,
Tetrahedron, 1992, 48, 797.
Footnotes and References
*
E-mail: s5simizu@ccu.cit.nihon-u.ac.jp
Received in Cambridge, UK, 20th June 1997; 7/04347C
1630
Chem. Commun., 1997
Shimizu, Shoichi
