Two novel 1,3-calix[4]azacrowns

Article abstract of DOI:10.1016/S0040-4039(00)00382-8

Two 1,3-calix[4]azacrowns-5 in the 1,3-alternate conformation have been constructed from calix[4]arene. They formed 1:1 endo and 1:2 endo-endo complexes with NH₄⁺ in CDCl₃. Comparison with 1,3-calix[4]-bis-crown-5 lead us

Full text of DOI:10.1016/S0040-4039(00)00382-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3345–3348
Two novel 1,3-calix[4]azacrowns
Jong Seung Kim,a,∗ Won Ku Lee,a Kwanghyun No,b Zouhair Asfari c and Jacques Vicens c,∗
aDepartment of Chemistry, Konyang University, Nonsan 320-711, South Korea
bDepartment of Chemistry, Sookmyung Women’s University, Seoul 140-742, South Korea
cEcole Chimie Polymères Matériaux, Laboratoire de Chimie des Interactions Moléculaires Spécifiques, associé au C.N.R.S.,
25 rue Becquerel F-67087 Strasbourg, France
Received 20 December 1999; accepted 2 March 2000
Abstract
Two 1,3-calix[4]azacrowns-5 in the 1,3-alternate conformation have been constructed from calix[4]arene. They
+
formed 1:1 endo and 1:2 endo–endo complexes with NH4 in CDCl3. Comparison with 1,3-calix[4]-bis-crown-5
lead us to conclude a better binding by replacement of the central O atom by NH group in the crown. © 2000
Elsevier Science Ltd. All rights reserved.
Calix[4]arenes constrained to the 1,3-alternate conformation,1,2 and more particularly, 1,3-calix[4]-
bis-crowns3 and aza-crown systems4 have received much attention because of their structural peculiari-
ties. They present two binding sites departed on both sides of the calixarene and are linked to each other
by a π-basic benzene tunnel. This symmetrical arrangement is well adapted for the formation of 1:1
and 1:2 complexes. Interestingly, in the 1:1 complexes with 1,3-calix[4]-bis-crown-5, the cation switches
from one binding site to the other through the π-basic benzene tunnel.5 This property has recently been
used to design a ‘molecular syringe’.6
+
As part of our work on calix[4]azacrowns7 we report herein the synthesis and NH4 binding behavior
of ligands 5 and 8 corresponding to 1,3-calix[4]-bis-crown-5 in which the central donor O atoms have
been replaced once or twice by a NH group.
According to Scheme 1, calix[4]arene 1 was reacted with 2 equiv. of the tosylate of 2-(2-
chloroethoxy)ethanol and 1 equiv. of K2CO3 in refluxing CH3CN for 24 h. Dichlorocalix[4]arene
derivative 2 was obtained pure by crystallization from Et2O in 90% yield. Compound 2 was deduced to
be in cone conformation and selectively 1,3-dialkylated due to the presence of two doublets at 3.40 and
4.45 ppm with J=13.5 Hz for the methylene protons of the ArCH2Ar of the calix and of two triplets for
the para-protons on the phenolic units. Condensation of 2 with 1.8 equiv. of tetraethyleneglycolditosylate
with 3 equiv. of Cs2CO3 was achieved by refluxing CH3CN for 24 h. The crude residue was purified on
∗
Corresponding authors. Fax: [82]4617335240/[33](0)388136932; e-mail: jongskim@kytis.konyang.ac.kr (J. S. Kim),
vicens@chimie.u-strasbg.fr (J. Vicens)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00382-8
tetl 16662

3346
Scheme 1. Synthesis of ligands 5 and 8

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silica to afford calixcrown 3 as an oil in 73% yield. The 1,3-alternate conformation of 3 was deduced
from the presence of a singlet at 3.87 ppm for the ArCH2Ar in the calix unit. Ring-closure of dichloro
3 was performed with 1 equiv. of p-toluenesulfonamide by heating at 70°C in DMF for 24 h. The crude
residue was chromatographed on silica to afford 1,3-calix[4]-crown-5N-tosyl crown-5, 4 in 24% yield.
The tosyl group was removed by refluxing 4 with 6% Na(Hg) amalgam in the presence of Na2HPO4 in
a mixture of 5:1 dioxane:methanol for 2 days. Compounds 4 and 5 were deduced to be the 1,3-alternate
conformation with a singlet at 3.87 ppm for ArCH2Ar in the calix. Calix[4]-bis-azacrown-5, 8, was
prepared in a similar way via tetrachloroethyleneglycol calix[4]-arene 6 (70% yield), double closure into
1,3-calix[4]-bis-N,N0-ditosyl crown-5, 7 (65% yield) and reaction with 6% Na(Hg) amalgam (52%).
Compound 8 was shown to be in the 1,3-alternate conformation with a singlet at 3.88 ppm for the
methylene protons ArCH2Ar of the calix. All products were fully characterized.8
+
Complexation of NH4 Pic− was run to compare to results previously obtained with 1,3-calix[4]-bis-
+
crown-5.5,6 Ligands 5 and 8 (5–10 mg) were mixed with an excess of NH4 Pic− in CDCl3 at rt for various
1
times. The unreacted solid was filtrated before recording H NMR spectra. The stoichiometries of the
complexes were estimated by integration of the ArH-picrate resonance vs those for the ArH aromatic
+
signals of the calix. The 1:1 complex 5:NH4 was obtained after 1 h. The singlet signal of the picrate
appeared at 8.79 ppm. The largest δ shifts were observed for the singlets of NH and OCH2CH2NHCH2
while the triplets corresponding to ArOCH2CH2O belonging to the crown-5 remained unchanged. We
+
concluded that NH4 preferred to be in the azacrown-5. A spectrum indicating a C2v symmetry, similar
to the one of 5, was obtained after 24 h. Upfield shifts of ArOCH2CH2O showed that ligand 5 formed an
endo–endo complex 5:2NH4 . Complexes 8:NH4+ and endo–endo 8:2NH4+ were observed after 6 h and
+
24 h, respectively. These results differ from previous observations that 1,3-calix[4]-bis-crown-5 forms
with NH4 a 1:1 complex with cation–ligand exchanges and an endo–exo 1:2 complex5,6 allowing us
+
to ascertain that the modified NH–crown-5 displays a better binding behavior than the crown-5 does for
ammonium cation. Future work will be devoted to thermodynamical studies (UV and potentiometry) to
determine possible acido-basic interactions between the ligand and other different cations.
Acknowledgements
This research was fully supported by the Korea Research Foundation (BSRI Grant No. 1999-015-
DP0203).
References
1. Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713–1734 and references cited therein.
2. Asfari, Z.; Wenger, S.; Vicens, J. Pure Appl. Chem. 1995, 67, 1037–1043.
3. Asfari, Z.; Nierlich, M.; Thuéry, P.; Lamare, V.; Dozol, J.-F.; Leroy, M.; Vicens, J. J. Anal. Quim. Int. Ed. 1996, 92, 260–266.
4. Koh, K. N.; Araki, K.; Shinkai, S.; Asfari, Z.; Vicens, J. Tetrahedron Lett. 1995, 36, 6095–6098.
5. Wenger, S., PhD Dissertation, Strasbourg, June 1996.
6. Ikeda, A.; Tsudera, T.; Shinkai, S. J. Org. Chem. 1997, 62, 3568–3571.
7. Kim, J. S.; Ko, J. W.; Cho, M. H.; Yu, I. Y.; Shon, O. J.; Vicens, J. J. Org. Chem. 2000, in press.
1
8. General: Mps, capillaries under nitrogen, Büchi 500, SiO2 Merck (Art. 11567). H NMR (δ in ppm, J in Hz) in CDCl3,
Bruker SY200 at Strasbourg and Bruker ARX-400 at Taejon. Elemental analysis, Vario EL of Elemental Analyzer and FAB+
mass spectra, JEOL-JMS-HX 110A High Resolution Tendem Mass Spectrometry in Korea Basic Science Institute in Taejon.
Preparation of 2. Calix[4]arene 1 (10.02 g, 23.6 mmol), tosylate of 2-(2-chloroethoxy)ethanol (13.87 g, 49.5 mmol), K2CO3
(3.31 g, 23.6 mmol) and CH3CN (200 ml) were refluxed for 24 h under N2. The crude residue was solubilized in CH2Cl2
and acidified (10% aqueous HCl). The organic layer was dried (MgSO4). Recrystallization from Et2O gave 2 as a solid,

3348
1
mp 174–175°C. H NMR (400 MHz, CDCl3): δ 7.34 (s, 2 H, -OH), 7.08 (d, J=7.5 Hz, 4 H, ArHm-calix), 6.90 (d, J=7.5
Hz, 4 H, ArHm-calix), 6.77 (t, J=7.5 Hz, 2 H, ArHp-calix), 6.70 (t, 2 H, J=7.5 Hz, ArHp-calix), 4.45 (d, J=13.5 Hz, 4 H,
ArCH2Ar), 4.21–4.19 (m, 4 H, ArOCH2CH2), 4.06–4.04 (m, 4 H, OCH2CH2Cl), 3.99 (t, J=6.5 Hz, 4 H, ArOCH2CH2), 3.75
(t, J=6.5 Hz, 4 H, OCH2CH2Cl), 3.40 (d, J=13.5 Hz, 4 H, ArCH2Ar). FAB-MS m/z (M+) calcd 634.9, found 635.2. Anal.
calcd for C36H38Cl2O6: C, 68.03; H, 5.98. Found: C, 68.00; H, 5.95. Yield 90%. Preparation of 3. Compound 2 (10.08 g,
16.5 mmol), tetraethyleneglycol ditosylate (9.12 g, 18.1 mmol), Cs2CO3 (16.15 g, 49.5 mmol) and CH3CN (200 ml) were
refluxed for 24 h under N2. The crude mixture was solubilized in CH2Cl2 and acidified (10% aqueous HCl). The organic
layer was dried (MgSO4). Chromatography on silica with 1:2 EtOAc:hexane as eluent gave 3 as an oil. 1H NMR (400 MHz,
CDCl3): δ 7.12–7.08 (m, 8 H, ArHm-calix), 6.93–6.86 (m, 4H, ArHp-calix), 3.87 (s, 8H, ArCH2Ar), 3.61–3.41 (m, 24H,
-CH2-), 3.20–3.13 (m, 8H, -CH2-). FAB-MS m/z (M+) calcd 793.2, found 793.8. Anal. calcd for C44H52Cl2O9: C, 55.48; H,
6.55. Found: C, 55.45; H, 6.57. Yield 73%. Preparation of 4. p-Toluenesulfonamide (0.90 g, 5.26 mmol), Cs2CO3 (6.54 g,
20.1 mmol) and DMF (100 ml) were heated to 70°C for 30 min. Then, compound 3 (4.04 g, 5.04 mmol) dissolved in DMF
(20 ml) was added dropwise for 3 h. After refluxing for 24 h, the crude mixture was solubilized in CH2Cl2 and treated with
10% aqueous NaHCO3. The organic layer was dried (MgSO4). Chromatography on silica with 1:2 EtOAc:hexane as eluent
gave 4 as a solid. mp 125–127°C. 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=8.1 Hz, 2 H, ArH-tosyl), 7.34 (d, J=8.1 Hz, 2H,
ArH-tosyl), 7.12 (d, J=7.5 Hz, 4H, ArHm-calix), 7.05 (d, J=7.5 Hz, 4H, ArHm-calix), 6.91 (t, J=8.7 Hz, 2H, ArHp-calix), 6.82
(t, J=8.7 Hz, 2H, ArHp-calix), 3.87 (s, 8H, Ar-CH2-Ar), 3.63 (s, 4H, OCH2CH2O), 3.57 (s, 4H, OCH2CH2NH), 3.49-3.46
(m, 8H, ArOCH2CH2O), 3.34–3.28 (m, 8H, ArOCH2CH2O), 3.16–3.07 (m, 8 H, OCH2CH2O), 2.46 (s, 3 H, ArCH3-tosyl).
FAB-MS m/z (M+) calcd 893.1, found 894.0. Anal. calcd for C51H59NO11S: C, 68.53; H, 6.60. Found: C, 68.50; H, 6.63. Yield
50%. Preparation of 5. To a solution of dioxane (100 ml) and CH3OH (20 ml) were added 4 (6.09 g, 6.7 mmol), Na2HPO4
(2.23 g, 14.76 mmol) and 6% Na(Hg) amalgam (5.00 g). The mixture refluxed for 2 days at 80°C. The crude mixture was
solubilized in CH2Cl2 and treated with 10% aqueous Na2HPO4. The organic layer was dried (MgSO4). Recrystallization
1
from Et2O gave 5 as a solid, mp 158–160°C. H NMR (400 MHz, CDCl3): δ 9.45 (bs, 1 H, NH), 7.18 (d, J=7.5 Hz, 4
H, ArHm-calix), 7.08 (s, 4 H, ArHm-calix), 6.94 (t, J=7.5 Hz, 4H, ArHp-calix), 3.90–3.84 (m, 8H, OCH2CH2O), 3.79 (s,
8H, Ar-CH2-Ar), 3.65–3.63 (m, 12H, OCH2CH2NH, OCH2CH2O), 3.56 (t, J=6.5 Hz, 4H, ArOCH2CH2O-crown-5), 3.28
(t, J=6.5 Hz, 4H, ArOCH2CH2O-crown-5), 2.98 (s, 4H, OCH2CH2NH). FAB-MS m/z (M+) calcd 739.1, found 739.5. Anal.
calcd for C44H53NO9: C, 71.44; H, 7.17. Found: C, 71.49; H, 7.15. Yield 50%. Preparation of 6. Same procedure as for 2
with calix[4]arene 1 (5.04 g, 11.7 mmol), tosylate of 2-(2-chloroethoxy)ethanol (13.13 g, 47.1 mmol), K2CO3 (8.13 g, 58.8
mmol) and CH3CN (100 ml), reflux 24 h, N2. Recrystallization from (4:1) Et2O:hexane gave 6 a solid, mp 149–151°C. 1H
NMR (400 MHz, CDCl3): δ 7.07–6.99 (m, 8H, ArHm-calix), 6.79–6.67 (m, 4H, ArHp-calix), 3.77–3.62 (m, 40H, ArCH2Ar,
OCH2CH2O, OCH2CH2Cl). FAB-MS m/z (M+) calcd 721.77, found 722.60. Anal. calcd for C42H50Cl2O6: C, 69.83; H, 6.93.
Found: C, 69.71; H, 6.96. Yield 70%. Preparation of 7. Same procedure as for 4 with p-toluenesulfonamide (2.11 g, 12.3
mmol), K2CO3 (0.96 g, 6.95 mmol), DMF (60 ml), 6 (5.00 g, 5.88 mmol), reflux 24 h, N2. Silica column (1:8 EtOAc:hexane)
provided 7 as a solid, mp 148–151°C. 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J=8.0 Hz, 4H, ArH-tosyl), 7.33 (d, J=8.0 Hz,
4H, ArH-tosyl), 7.05 (d, J=8.6 Hz, 8H, ArHm-calix), 6.82 (t, J=8.3 Hz, 4H, ArHp-calix), 3.80 (dd, J=15.8 Hz, J=9.5 Hz, 8H,
ArCH2Ar), 3.53–3.24 (m, 20H, OCH2CH2O), 3.06 (bs, 4H, OCH2CH2NCH2), 2.46 (s, 6H, ArCH3-tosyl). FAB-MS m/z (M+)
calcd 819.2, found 820.3. Anal. calcd for C49H57NO8S: C, 71.79; H, 6.96. Found: C, 71.52; H, 6.94. Yield 65%. Preparation
of 8. Same procedure as for 5 with 5:1 dioxane:CH3OH (150 ml), 7 (3.02 g, 2.86 mmol), 6% Na(Hg) (5.00 g) and Na2HPO4
(0.85 g, 6.0 mmol) reflux 2 days, 80°C. Recrystallization from Et2O gave 8 as a solid, mp 185–188°C. 1H NMR (400 MHz,
CDCl3): δ 7.17 (d, J=8.4 Hz, 8H, ArHm-calix), 6.82 (t, J=8.3 Hz, 4H, ArHp-calix), 3.88 (s, 8H, ArCH2Ar), 3.67–3.46 (m,
24H, OCH2CH2O), 2.81 (s, 8H, OCH2CH2NCH2), 1.76 (bs, 2H, NH). FAB-MS m/z (M+) calcd. 738.9, found 739.1. Anal.
+
calcd for C44H54N2O8: C, 71.5; H, 7.31. Found: C, 71.51; H, 7.33. Yield 52%. Spectral data of the 1:1 complex 5:NH4
:
1H NMR (200 MHz, CDCl3): δ 9.45 (bs, 1H, NH), 8.79 (s, 2H, ArH-picrate), 7.31 (d, J=7.5 Hz, 4H, ArHm-calix), 7.21 (s,
4H, ArHm-calix), 7.14–6.92 (m, 4H, ArHp-calix), 3.96–3.84 (m, 8H, OCH2CH2NH, OCH2CH2O), 3.77 (s, 8H, Ar-CH2-Ar),
3.54 (t, J=6.5 Hz, 4H, ArOCH2CH2O), 3.26 (t, J=6.5 Hz, 4H, ArOCH2CH2O), 3.06 (s, 4H, OCH2CH2NHCH2). Spectral
1
data of the 1:2 complex 5:2NH4+: H NMR (200 MHz, CDCl3): δ 10.39 (bs, 1H, NH), 8.78 (s, 4H, ArH-picrate), 7.32 (d,
J=7.5 Hz, 4H, ArHm-calix), 7.21 (s, J=7.5 Hz, 4H, ArHm-calix), 6.98 (t, J=7.5 Hz, 4H, ArHp-calix), 3.96–3.46 (m, 20H,
OCH2CH2NH, OCH2CH2O, ArOCH2CH2O), 3.79 (s, 8H, Ar-CH2-Ar), 3.06 (broad s, 4H, OCH2CH2NHCH2). Spectral data
of the 1:1 complex 8:NH4+: 1H NMR (200 MHz, CDCl3): δ 8.87 (s, 2H, ArH-picrate), 7.24 (d, J=7.5 Hz, 4H, ArHm-calix),
7.20 (d, J=7.5 Hz, 4H, ArHm-calix), 7.00 (t, J=7.5 Hz, 2H, ArHp-calix), 6.89 (d, J=7.5 Hz, 2H, ArHp-calix), 4.63–2.81 (m,
24H, -CH2-), 3.75 (s, 8H, ArCH2Ar), 3.15–2.70 (m, 8H, OCH2CH2NHCH2), 1.74 (bs, 2H, NH). Spectral data of the 1:2
complex 8:2NH4+: 1H NMR (200 MHz, CDCl3): δ 8.86 (s, 4H, ArH-picrate), 7.33 (bd, 8H, ArHm-calix), 7.09 (bt, 4H, ArHp-
calix), 4.84 (bs, 8H, OCH2CH2O), 3.93–3.50 (bm, 24H, ArCH2Ar, OCH2CH2O), 2.82 (bs, 8H, OCH2CH2NCH2), 1.67 (bs,
2H, NH).