Calix[4]arenes comprised of aniline units [24]

Full text of DOI:10.1021/ja005573q

J. Am. Chem. Soc. 2001, 123, 779-780
Scheme 1. Chelation-assisted SNAr Reaction
779
Calix[4]arenes Comprised of Aniline Units
Hiroshi Katagiri,† Nobuhiko Iki,*,† Tetsutaro Hattori,†
Chizuko Kabuto,‡ and Sotaro Miyano*,†
Department of Biomolecular Engineering
Graduate School of Engineering
Tohoku UniVersity, Aramaki-Aoba 07
Aoba-ku, Sendai 980-8579, Japan
Instrumental Analysis Center for Chemistry
Graduate School of Science, Tohoku UniVersity
Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan
ReceiVed September 4, 2000
because strong chelation of the substrate to the metal center of
the nucleophile facilitates a Michael-type conjugate addition of
the anionic moiety across the aromatic ring followed by displace-
ment of the alkoxy group to eventually afford the net-substitution
product.
Calix[n]arenes (e.g., 1) have provided versatile platforms for
supramolecular host compounds via various chemical modifica-
tions.1 For example, the hydroxy function has been advantageously
utilized for introducing quite a number of functional groups to
provide numerous derivatives of novel functions.2 On the other
hand, it has been well-known that introduction of any substituents
to the aromatic nucleus through cleavage of an aryl-oxygen bond
is quite difficult.3 Therefore, it is not surprising that there have
been only few examples of calixarenes bearing substituents other
than those of -OR types at the lower rim.4 In this context,
development of a method for introducing amino substituent to
the lower rim is highly desirable because such substituent is not
only a potential metal-ligating moiety but also the most reliable
starting functional group in synthetic aromatic chemistry for
transformation to various entities via diazonium methodology.
Although partially aminated calix[4]arenes such as 9 were reported
by Shinkai et al.,5 those comprised of only aniline units (i.e., 5)
are not precedented to the best of our knowledge.
Then, is it possible to extend the chelation-assisted SNAr
methodology to the calix[n]arene family to displace the lower-
rim hydroxy group only if we could provide cyclic oligophenols
bridged by the chelation-type activating groups? Our recent
success in the efficient synthesis of thiacalix[4]arene (2)8 and its
conversion to the sulfinyl (3) and sulfonyl counterparts (4)9
enabled us to partly answer the question, and herein we report
the transformation of the tetramethyl ethers of sulfinyl- and
sulfonylcalix[4]arene (14 and 11) to the tetraamino derivatives
of the thia-, sulfinyl-, and sulfonylcalix[4]arene (6, 7, and 8).
As we realized that a sulfonyl group has higher activating
power than a sulfinyl group,6 we first attempted the reaction of
11 rather than 14 with N-centered nucleophile (Scheme 2). The
prerequisite substrate 11 was prepared by tetra-O-methylation of
2 to 10 followed by oxidation. Treatment of 11 with lithium
benzylamide in THF at room temp. for 2 h displaced all the
methoxy groups with benzylamino substituents to give 12 in
high yield.10 This indicates that the sulfonyl group even in a
cyclic oligomer of alkoxybenzene is able to serve as an activating
group for the SNAr. Interestingly, the benzylamine 12 adopted
1,3-alternate conformation as evidenced by X-ray crystallography
(Figure 1a), suggesting that the substitution reaction proceeded
to avoid steric congestion imposed by four benzyl groups.
Although attempted hydrogenolytic removal of the benzyl moiety
of 12 was unsuccessful, treatment with NBS-BPO caused
dehydrogenation to give imine 13, which was then hydrolyzed
to tetraaminosulfonylcalix[4]arene 8 with four free amino sub-
stituents at the lower rim. Attempts to reduce the bridging
SO2 of both 8 and 12 to S by use of LiAlH4-TiCl4 in THF at
-78-0 °C were unsuccessful and cleaved the calix[4]arene ring.
To our pleasure, the SNAr process proceeded quite smoothly
even via the SO route for the synthesis of tetraaminosulfinyl-
calix[4]arene 7 and tetraaminothiacalix[4]arene 6 (Scheme 2): As
has been shown before, controlled oxidation of 2 afforded
sulfinylcalix[4]arene 3 with trans-trans-trans configuration with
regard to the disposition of four SO linkages.11 The substrate 14
was obtained by tetra-O-methylation of 3. By the same method
used for 11, all of the methoxy groups of 14 were substituted by
benzylamino groups to give 15 in a comparable yield. The
Previously, we have developed the chelation-assisted nucleo-
philic aromatic substitution (SNAr) reaction for replacement of
an ortho alkoxy group of aromatic substrates bearing substituents
such as ester, sulfinyl, and sulfonyl groups by a C-, O-, or
N-centered nucleophile (Scheme 1).6,7 This type of substitution
proceeds far more readily than the “classical” SNAr process,3
* Corresponding authors. E-mail: iki@orgsynth.che.tohoku.ac.jp, miyano@
orgsynth.che.tohoku.ac.jp.
† Department of Biomolecular Engineering.
‡ Instrumental Analysis Center for Chemistry.
(1) (a) Gutsche, C. D. Calixarenes, Monographs in Supramolecular
Chemistry; Stoddart, J. F., Ed.; The Royal Society of Chemistry: Cambridge
and London, 1989. (b) Gutsche, C. D. Calixarenes ReVisited, Monographs in
Supramolecular Chemistry; Stoddart, J. F., Ed.; The Royal Society of
Chemistry: Cambridge, 1998.
(2) See chapter 5 of refs 1a and 1b.
(3) (a) Miller, J. Aromatic Nucleophilic Substitution; Elsevier: Amsterdam,
1968. (b) March, J. AdVanced Organic Chemistry, 4th ed.; Wiley: New York,
1992; Chaper 13 and references therein.
(4) For replacement of the OR with H, S, and N, see § 5.1.4 of ref 1b.
(5) Ohseto, F.; Murakami, H.; Araki, K.; Shinkai, S. Tetrahedron Lett. 1992,
33, 1217.
(8) (a) Kumagai, H.; Hasegawa, M.; Miyanari, S.; Sugawa, Y.; Sato, Y.;
Hori, T.; Ueda, S.; Kamiyama, H.; Miyano, S. Tetrahedron Lett. 1997, 38,
3971. (b) Iki, N.; Kabuto, C.; Fukushima, T.; Kumagai, H.; Takeya, H.;
Miyanari, S.; Miyashi, T.; Miyano, S. Tetrahedron, 2000, 56, 1437.
(9) Iki, N.; Kumagai, H.; Morohashi, N.; Ejima, K.; Hasegawa, M.;
Miyanari, S.; Miyano, S. Tetrahedoron Lett. 1998, 39, 7559.
(6) Hattori, T.; Suzuki, M.; Tomita, N.; Takeda. A.; Miyano, S. J. Chem.
Soc., Perkin Trans. 1 1997, 1117, and literatures cited therein.
(7) Cf. the oxazoline-mediated Meyers reaction as the prototype of the
chelation-assisted SNAr reaction: (a) Reuman, M.; Meyers, A. I. Tetrahedron
1985, 41 837. (b) Gant, T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
(10) Among the several metal amides examined which included alkali metal
and magnesium amides and alkylamides, lithium benzylamide gave the best
results with respect to the yield of the desired product.
(11) Morohashi, N.; Iki, N.; Kabuto C.; Miyano, S. Tetrahedron Lett. 2000,
41, 2933 and references therein.
10.1021/ja005573q CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/05/2001

780 J. Am. Chem. Soc., Vol. 123, No. 4, 2001
Communications to the Editor
Scheme 2. Reaction Conditions, Reagents, and Yieldsa
a (i) CH3I, K2CO3, acetone, reflux; (ii) H2O2, CHCl3-CF3CO2H, reflux; (iii) PhCH2NHLi, THF, rt; (iv) NBS, BPO, PhH, reflux; (v) conc. HCl,
CHCl3, reflux; (vi) LiAlH4-TiCl4, THF, rt; (vii) NaBO3, CHCl3-CH3CO2H, 50 °C.9
Figure 2. X-ray structure of 7 showing a portion of 2-dimensional
network via intermolecular hydrogen bondings.
Figure 1. X-ray structure of 12 (a) and 6 (b).
Table 1. 1H NMR Chemical Shift and IR Absorption Band of
Interest
conformation of 15 was assigned to be 1,3-alternate by its
oxidation to 1,3-alternate 12. Here again, the dehydrogenation
with NBS-BPO afforded imine 16, which was then hydrolyzed
to amine 7. Treatment of 7 with LiAlH4-TiCl4 in THF at room
temperature smoothly afforded tetraaminothiacalix[4]arene 6.
The calix[4]arene analogues (6-8) comprised of four aniline
units bridged by S, SO, and SO2 have some interesting structural
features. The X-ray crystallographic analysis revealed that 6
adopts 1,3-alternate conformation with crystallographic 4h sym-
metry (Figure 1b). The dihedral angle between the distal phenyl
rings is 10.57(8)° to form an almost rectangular cavity. The
intramolecular NH‚‚‚‚‚S bondings are observed between an amino
group and the ortho sulfides.12 This may cause the lone pair of
amino group to direct toward outside the cavity.
δ
NH2/ppm
ν
NH2/cm-1 a
ν
SdO/cm-1 a
6
7
8
4.88b
5.06c
5.64c
3464, 3362
3452, 3371
3468, 3389
-
1030
1313, 1151
a Measured in KBr matrix. b In CDCl3 at 27 °C. c In CDCl3 at
50 °C.
be said that the larger δNH2 value of 8 than that of 7 may be
caused by formation of hyrdogen bonding NH‚‚‚OdSO as well
as by the deshielding effect of SO2 to withdraw electrons more
strongly.
In conclusion, we have shown here that the chelation-assisted
SNAr methodology is applicable to the calix[4]arene analogues
bearing sulfinyl and sulfonyl bridges for the synthesis of
tetraaminocalix[4]arene derivatives (6-8), which should provide
a new series of molecular platforms for functional materials and
supramolecular assembly.
Sulfinyl derivative 7 also adopts 1,3-alternate conformation with
crystallographic 4h symmetry (Figure 2). The dihedral angle
between distal phenyl rings is 10.9(1)°, showing a cavity
quite similar to that of 6. Contrary to 6, there are found not
only intramolecular but also intermolecular hydrogen bondings,
NH‚‚‚OdS, between an amino group and sulfinyl oxygen atoms.13
This may let the lone pair of the amino group direct toward inside
the cavity. The significant outcome of the intermolecular hydrogen
bonding is that molecules of 7 form 2-dimensional molecular
network.
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research on Priority Areas (No. 10208202) from the Ministry
of Education, Science, Sports and Culture, Japan as well as by JSPS
Research for the Future Program.
Table 1 lists the selected spectroscopic data of 6-8. Although
crystallographic evidence for 8 is not yet available, it may
Supporting Information Available: Details of syntheses and proper-
ties of compounds shown in Scheme 2, tables of crystallographic data,
and ORTEP drawings (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
(12) N-S: 3.060(2), 3.072(2); N-H: 0.91(3), 0.84(2); H‚‚‚S: 2.58(3),
2.68(2) Å; N-H‚‚‚S: 113(2), 110(2)°.
(13) For intramolecular hydrogen bonding, O-N: 3.071(4), N-H: 0.84(4),
O‚‚‚H: 2.46(4) Å, N-H‚‚‚O: 130(3)°. For intermolecular one, O-N:
2.997(4), N-H: 0.82(3), O‚‚‚H: 2.27(4) Å, N-H‚‚‚O: 146(3)°.
JA005573Q