Syntheses and conformations of tetrahomodioxacalix[4]arene tetraamides and tetrathioamides

Article abstract of DOI:10.1021/jo011138i

A series of tetrahomodioxacalix[4]arene tetraamides and tetrathioamides with four p-phenyl groups on their upper rim were synthesized. From the ¹H and ¹³C NMR and crystal structure, N-butylamido homooxacalix[4]arene (4) was found to be in the 1,3-alternate conformation and has intramolecular hydrogen bonding between N-H and facing oxygen atoms of the carbonyl O=C group. This hydrogen bonding decreased the metal ion complex ability. Transformation of the 1,3-alternate N-butylamido (4) into N-butylthioamido homooxacalix[4]arene (5) using Lawesson's reagent gave a conformational change to the C-1,2-alternate.

Full text of DOI:10.1021/jo011138i

J . Org. Chem. 2002, 67, 3165-3168
3165
calix[4]arenes.7-10 Masci and co-worker11 reported that
the main conformation of tetrahomodioxa-p-tert-butylcalix-
[4]arene tetramethyl ether is C-1,2-alternate on the basis
of temperature-dependent NMR spectral analysis. Re-
cently, we reported that C-1,2-alternate tetrahomodioxa-
calix[4]arene tetraamide (2) selectively encapsulates Pb2+
over alkali, alkaline earth, ammonium, and transition
metal ions with formation of a 1:1 complex. In the solid-
state structure, the Pb2+ is bound to the carbonyl oxygens
of two adjacent amide substituents and an aryl-alkyl
ether oxygen of one of them.12 In this paper, we report
the synthesis of a series of tetrahomodioxa-p-phenylcalix-
[4]arene tetraamides and tetrathioamides and their two-
phase picrate extraction for metal cations.
Syn th eses a n d Con for m a tion s of
Tetr a h om od ioxa ca lix[4]a r en e Tetr a a m id es
a n d Tetr a th ioa m id es
Kwanghyun No,† J eong Hyeon Lee,† Seung Hwan Yang,‡
Sang Hyeok Yu,§ Moon Hwan Cho,§ Moon J ib Kim,| and
J ong Seung Kim*,‡
Department of Chemistry, Sookmyung Women’s University,
Seoul 140-742, Korea, Department of Chemistry,
Konyang University, Nonsan 320-711, Korea,
Department of Chemistry, Kangwon National University,
Chuncheon 200-711, Korea, and Department of Physics,
Soonchunhyang University, Asan 336-745, Korea
The synthetic routes for homooxacalix[4]amides (2 and
4) and homooxacalix[4]thioamides 3 and 5 are described
in Scheme 1. Reaction of 1 having a flexible conformation
with N,N-diethyl chloroacetamide gave 2, which is in the
C-1,2-alternate conformation.12 In an earlier paper, we
chose to designate one of the conformers of a tetrahomo-
dioxacalix[4]arene as a 1,4-alternate.12 On further reflec-
tion, however, we have decided that it would be prefer-
able to retain the 1,2-alternate designation for this
conformer and to differentiate between the two possible
1,2-alternate conformers in the following manner: the
1,2-alternate conformer in which the adjacent syn aryl
moieties are joined by a CH2 group is designated as the
C-1,2-alternate, while the 1,2-alternate conformer in
which the adjacent syn aryl moieties are joined by a CH2-
OCH2 moiety is designated as the COC-1,2-alternate.
Each conformation can be identified by 1H and 13C NMR
spectroscopy. Using Lawesson’s reagent, we obtained 3,
which retained the C-1,2-alternate conformation as proved
jongskim@konyang.ac.kr
Received December 11, 2001
Abstr a ct: A series of tetrahomodioxacalix[4]arene tetra-
amides and tetrathioamides with four p-phenyl groups on
their upper rim were synthesized. From the 1H and 13C NMR
and crystal structure, N-butylamido homooxacalix[4]arene
(4) was found to be in the 1,3-alternate conformation and
has intramolecular hydrogen bonding between N-H and
facing oxygen atoms of the carbonyl OdC group. This
hydrogen bonding decreased the metal ion complex ability.
Transformation of the 1,3-alternate N-butylamido (4) into
N-butylthioamido homooxacalix[4]arene (5) using Lawes-
son’s reagent gave a conformational change to the C-1,2-
alternate.
Calixarenes have been of interest both as complexation
hosts for ions and molecules and as frameworks for
elaborating more complex structures.1-3 Homooxacalix-
[4]arenes, which contain extra oxygen atoms in the
macrocyclic ring, however, have received relatively little
attention, mainly because they can be synthesized only
in rather low overall yields.4-6 There have only been
limited studies of the solution conformations, solid-state
structures, and complexation properties of homooxa-
1
by NMR spectroscopy. In the 600 MHz H NMR spec-
trum, the methylene protons of the ArCH2Ar bridge for
3 showed two AB doublets at δ 4.56 and 3.57 (∆ν )
596.28 Hz) with a geminal coupling constant of 13.5 Hz.
An AB pattern for the dimethylenoxy protons of ArCH2-
OCH2Ar appeared at δ 4.74 and 4.31 (∆ν ) 262.38 Hz)
with a geminal coupling constant of 12.09 Hz. Another
AB pattern for the methylene protons of ArOCH2CSNEt2
appeared at δ 4.97 and 4.45 (∆ν ) 312.18 Hz) with a
geminal coupling constant of 12.3 Hz. The 13C NMR
spectrum showed a single peak from a carbonyl carbon,
one peak at 67.38 ppm for the ArCH2O bridge methyl-
eneoxy carbons, and one peak at 30.89 ppm for the
ArCH2Ar bridge carbons implying that two adjacent
benzene rings are in a syn orientation. So, 3 is in the
stable C-1,2-alternate conformation.
* Corresponding author. Fax: +82-41-733-5240.
† Sookmyung Women’s University.
‡ Konyang University.
§ Kangwon National University.
| Soonchunhyang University.
(1) (a) Gutsche, C. D. Calixarenes; Royal Society of Chemistry:
Cambridge, 1989. (b) Gutsche, C. D. In Synthesis of Macrocycles:
Design of Selective Complexing Agents; Izatt, R. M., Christensen, J .
J ., Eds.; Wiley: New York, 1987; p 93. (c) Gutsche, C. D. Calixarenes
Revisited; Royal Society of Chemistry: Cambridge, 1998. (d) Bo¨hmer,
V.; McKervey, M. A. Chemie in unserer Zeit 1991, 195. (e) Gutsche, C.
D. Calixarenes, Monographs in Supramolecular Chemistry; Stoddart,
J . F., Ed.; Royal Society of Chemistry: Cambridge, UK, 1989; Vol. 1.
(f) Gutsche, C. D. In Inclusion Compounds; Atwood, J . L., Davies, J .
E. D., MacNicol, D. D., Eds.; Oxford University Press: New York, 1991;
Vol. 4, pp 27-63. (g) Van Loon, J .-D.; Verboom, W.; Reinhoudt, D. N.
Org. Prep. Proc. Int. 1992, 24, 437-462. (h) Ungaro, R.; Pochini, A. In
Frontiers in Supramolecular Organic Chemistry and Photochemistry;
Schneider, H.-J ., Eds.; VCH: Weinheim, Germany, 1991; pp 57-81.
(2) Calixarenes: A Versatile Class of Macrocyclic Compounds;
Vicens, J ., Bo¨hmer, V., Eds.; Kluwer: Dordrecht, 1991.
(3) (a) Kim, J . S.; Lee, W. K.; Kim, J . G.; Suh, I. H.; Yoon, J . Y.;
Lee, J . H. J . Org. Chem. 2000, 65, 7215. (b) Bo¨hmer, V. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 713.
Interestingly, reaction of 1 with N-butyl chloroacet-
amide instead of N,N-diethyl chloroacetamide provided
4, but corresponding NMR patterns were quite different
(7) (a) Thue`ry, P.; Nierlich, M.; Vicens, J .; Masci, B. Acta Crystallogr.
2001, C57, 70. (b) Asfari, Z.; Harrowfield, J . M.; Ogden, M. I.; Vicens,
J .; White, A. H. Angew. Chem., Int. Ed. Engl. 1991, 30, 854.
(8) Harrowfield, J . M.; Ogden, M. I.; White, A. H. J . Chem. Soc.,
Dalton Trans. 1991, 979.
(9) Marcos, P. M.; Ascenso, J . R.; Lamartine, R.; Pereira, J . L. C.
Tetrahedron 1997, 53, 11791.
(4) Gutsche, C. D.; Dhawan, B.; No, K. H.; Muthukrishnan, R. J .
Am. Chem. Soc. 1981, 103, 3782.
(5) Bavoux, C.; Vocanson, F.; Perrin, M.; Lamartine, R. J . Incl.
Phenom. Mol. Recogn. Chem. 1995, 22, 119.
(10) Felix, S.; Ascenso, J . R.; Lamartine, R.; Pereira, J . L. C. Synth.
Commun. 1998, 28, 1793.
(11) Masci, B.; Saccheo, S. Tetrahedron Lett. 1993, 49, 10739.
(12) No, K. H.; Kim, J . S.; Shon, O. J .; Yang, S. H.; Suh, I. H.;. Kim,
J . G.; Bartsch, R. A.; Kim, J . Y. J . Org. Chem. 2001, 66, 5976.
(6) Dhawan, B.; Gutsche, C. D. J . Org. Chem. 1983, 48, 1536.
10.1021/jo011138i CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/11/2002

3166 J . Org. Chem., Vol. 67, No. 9, 2002
Sch em e 1. Syn th etic Rou tes for 2-5
Notes
N(1)-H-O(5) and N(4)-H-O(7) are 169.8 and 176.8°,
respectively, indicating that there are intramolecular
hydrogen bondings between amide N-H and the facing
oxygen atom of CdO. Using TLC to monitor the synthesis
of 4, we found that after 6 h the product was a mixture
of the 1,3- and C-1,2-alternate conformers. After 12 h,
however, the product was entirely the 1,3-alternate
conformer, suggesting that the C-1,2-alternate conformer
is the initially formed product that then changes to the
1,3-alternate conformer, which is more stable as a result
of intramolecular H-bonding. More interestingly, during
the preparation of thioamide 5 using Lawesson’s reagent,
the conformation changed to C-1,2-alternate again. In the
1H NMR spectrum, the methylene protons of the ArCH2-
Ar bridge for 5 showed two AB doublets at δ 4.81 and
3.59 (∆ν ) 730.38 Hz) with a geminal coupling constant
of 15.8 Hz. An AB pattern for the dimethylenoxy protons
of ArCH2OCH2Ar appeared at δ 4.78 and 4.08 (∆ν )
417.12 Hz) with a geminal coupling constant of 15.36 Hz.
Another AB pattern for the methylene protons of ArOCH2-
CSNHC4H9 appeared at δ 4.76 and 4.60 (∆ν ) 93.54 Hz)
with a geminal coupling constant of 10.62 Hz. The 13C
NMR spectrum showed one peak at 31.88 ppm for the
ArCH2Ar bridge carbons. On the basis of the NMR
spectra, one can assign the C-1,2-alternate conformation
to 5. In contrast to 4, the thioamide 5 is less strongly
intramolecularly H-bonded, with the result that the
C-1,2-alternate conformer does not convert to the 1,3-
alternate conformer.
F igu r e 1. ORTEP drawing of 4.
from those of 2. A singlet at δ 4.01 in the 1H NMR
spectrum and a singlet at 38.9 ppm in the 13C NMR
spectrum indicated that 4 is in the 1,3-alternate confor-
mation. No other conformations were observed. The X-ray
crystal structure of 4 is also a positive proof for the 1,3-
alternate conformation as shown in Figure 1. In the
crystalstructure,distances for N(1)H‚‚‚O(5)and N(4)H‚‚‚O(7)
were found to be 2.08 and 2.01 Å, respectively. Angles of
To prove the conformational change of 4 when it forms
from 1, we carried out an amination of the C-1,2-alternate
homooxacalix-tetraethyl ester 6 as shown in Scheme 2.
Stirring the reaction mixture of 6 and butylamine for 6
h gave 4 as a mixture of 1,3- and C-1,2-alternate con-
formers with 55 and 45% yields, respectively. In a 24 h

Notes
J . Org. Chem., Vol. 67, No. 9, 2002 3167
Sch em e 2. Syn th etic Rou tes for 4 fr om Hom ooxa ca lix[4]a r en e Tetr a eth yl Ester 6
Ta ble 1. Extr a cta bility (%) of 2-5 for Ca tion s in P icr a te
is shown to be in the 1,3-alternate conformation and
there is intramolecular hydrogen bonding between N-H
and the facing oxygen atoms of the carbonyl OdC group.
This hydrogen bonding decreases the metal ion complex
ability. Transformation of N-butylamido homooxacalix-
[4]arene (4) into N-butylthioamido homooxacalix[4]arene
(5) caused a conformational change from 1,3-alternate
to C-1,2-alternate. One can conclude that N,N-dialkyl-
amido and the corresponding thioamido homooxacalix-
[4]arene exist as an C-1,2-alternate conformation, while
N-monoalkylamido homooxacalix[4]arene favors the 1,3-
alternate conformation due to intramolecular H-bonding.
Extr a ction
extractability (%)a for cations
+
ligand Na+ K+ Rb+ Cs+ NH4
Ag+
14.49 86.55 9.50
4.03 6.51 5.04 5.65 3.58 158.64 4.89 6.22
3.47 4.36
7.70 2.69 3.82 2.40 7.78 179.04
Pb2+ Sr2+
2
3
4
5
0
0.16 2.16 1.01 3.97
0
0
0
0
0
0
7.90 9.55
a
Extractability ) (metal ion concentration extracted into
organic layer)/(ligand concentration used) × 100.
reaction, the conformation completely changed to 1,3-
alternate as observed in Scheme 1 as well. This is also
ascribed to the intramolecualr H-bonding between the
N-H and the facing oxygen atom of CdO in the 1,3-
alternate conformation. To investigate the conformational
change of 6 itself at high temperatures, ethanol solution
of 6 was refluxed for 7 days, but no conformational
changes were observed at all.
Exp er im en ta l Section
Unless otherwise noted, reagents were obtained from com-
mercial suppliers and used without further purification. Melting
points were taken in evacuated and sealed capillary tubes. IR
spectra were determined as KBr pellets and are available in
Supporting Information. Chemical shifts are recorded in parts
per million relative to TMS as an internal standard.
It has been noted that for calix[4]arene ester and amide
derivatives, the latter are stronger metal ion complexing
agents.13,14 To obtain insight into the metal ion affinity
of homooxacalixarene-based ligands, extractabilities to-
ward metal ions by 2-5 were determined by the metal
picrate extraction method. The results are listed in Table
1. The C-1,2-alternate tetrahomodioxacalix[4]arene tet-
raamide (2) selectively binds Pb2+ over other cations with
formation of a 1:1 complex.12 However, the binding ability
of 4 for all the cations remarkably decreased. This is
obviously because the 1,3-alternate conformation driven
by stable intramolecular H-bonding gives an unsuitable
binding site for the cations. C-1,2-Alternate thioamide
derivatives 3 and 5 showed Ag+ ion selectivity due to the
sulfur atoms of the carbonyl group. In the case of Ag+
ion, the complex ratio of 3‚Ag+ to 5‚Ag+ was found to be
1:2 by mass spectral analysis. This is the reason 100%
extractability was obtained in the case of 3 and 5. The
N-butylamide group seems to be less hindered for silver
ion than the N,N-diethylamide group, resulting in higher
extractability with 5.
Compounds 1,7 2,12 and 613-15 were prepared from adaptation
of the reported procedures.
Syn th eses: 7,13,21,27-Tetr a p h en yl-29,30,31,32-tetr a k is-
(d ieth ylth ioca r ba m oyl)m eth oxy-2,3-16,17-tetr a h om o-3,17-
d ioxa ca lix[4]a r en e (3). To a solution of 2 (504 mg, 0.41 mmol)
in dry toluene (20 mL) was added 0.37 g (0.91 mmol) of
Lawesson’s reagent. The mixture was heated for 20 h at 90 °C.
Solvent was removed in vacuo, and the residue was extracted
with CH2Cl2. The combined CH2Cl2 extracts were washed with
water, dried over MgSO4, and evaporated in vacuo. The residue
was triturated with MeOH to give 501 mg (94.5%) of the 5 as a
pale yellow, crystalline solid with mp 255 °C. Anal. Calcd for
C78H88O6N4S4: C, 71.74; H, 6.79. Found: C, 71.56; H, 6.70.
7,13,21,27-Te t r a p h e n yl-29,30,31,32-t e t r a k is(b u t ylca r -
b a m oyl)m et h oxy-2,3-16,17-t et r a h om o-3,17-d ioxa ca lix[4]-
a r en e (4). The procedure was the same as that for 2: yield
45%; crystalline solid with mp 240 °C. Anal. Calcd for C78H88
10N4: C, 75.46; H, 7.14. Found: C, 75.40; H, 7.05.
Am in a tion (4) fr om 6 (See Sch em e 2). To a solution of 6
-
O
(500 mg, 0.44 mmol) in absolute ethanol (25 mL) was added 8
mL of n-butylamine under an Ar atmosphere. The mixture was
refluxed for 7 days. Solvent was evaporated in vacuo, and the
residue was triturated with MeOH to give 470 mg (85.8%) of 4
as colorless crystals.
7,13,21,27-Tet r a p h en yl-29,30,31,32-t et r a k is(b u t ylt h io-
ca r ba m oyl)m eth oxy-2,3-16,17-tetr a h om o-3,17-d ioxa ca lix-
[4]a r en e (5). The procedure was the same as that for 3: yield
76.2%; colorless crystalline solid; mp 238 °C dec. Anal. Calcd
for C78H88O10N4: C, 75.46; H, 7.14. Found: C, 75.42; H, 7.05.
In conclusion, a series of tetrahomodioxacalix[4]arene
tetraamides and tetrathioamides with four p-phenyl
groups on their upper rim were synthesized. From the
1H and 13C NMR and crystal structure, N-butylamido (4)
(13) No, K. H. Bull. Korean Chem. Soc. 1999, 20, 33.
(14) No, K. H.; Park, Y. J .; Choi, E. J . Bull. Korean Chem. Soc. 1999,
20. 905.
(15) Masci, B.; Finelli, M.; Varrone, M. Chem. Eur. J . 1998, 4, 2018.

3168 J . Org. Chem., Vol. 67, No. 9, 2002
Notes
Meta l P icr a te Extr a ction . Metal picrates were prepared by
reaction of picric acid with the appropriate metal carbonate.16,17
To determine the extractability of the ligand for a metal picrate,
an aqueous solution (2.0 mL) containing 0.20 mM metal picrate
and a chloroform solution (2.0 mL) of the extractant (0.10 mM)
were shaken for 30 min at 25 °C. The concentration of picrate
anion extracted from the aqueous phase into the organic layer
was determined by UV spectrophotometry (λmax ) 373 nm).
Three independent experiments were carried out for each
combination of ligand and metal picrate. The extractability
values listed in Table 1 are averages.
MeOH. A crystal of 0.3 × 0.3 × 0.1 mm was mounted and aligned
on a diffractometer.18-20 The final X-ray data are given in Table
S1 (Supporting Information).
Ack n ow led gm en t. This research was supported by
a grant from the Korea Research Foundation (KRF-
2000-015-DP0246).
Su p p or tin g In for m a tion Ava ila ble: An additional Table
S1 and Data S1-3. This material is available free of charge
via the Internet at http://pubs.acs.org.
Solid -Sta te Str u ctu r e. Yellow crystals of 4 were obtained
by slow evaporation of the solvent of a solution of 4 in CH3CN-
J O011138I
(18) Structure Determination Package; Enraf-Nonius: Delft, The
Netherlands, 1994.
(19) Sheldrick, G. M. SHELXS86. Acta Crystallogr. 1990, A46, 467.
(20) Sheldrick, G. M. SHELX97 - Programs for Crystal Structure
Analysis; University of Goettingen: Goettingen, Germany, 1997.
(16) Bartsch, R. A.; Yang, I. W.; J eon, E. G.; Walkowiak, W.;
Charewicz, W. A. J . Coord. Chem. 1992, 27, 75.
(17) Pedersen, C. J . Fed. Proc. Fed. Am. Soc. Expl. Biol. 1968, 27,
1305.