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).