O. Middel, W. Verboom, D. N. Reinhoudt
FULL PAPER
OCH2), 4.15Ϫ4.22 (m, 6 H, ArOCH2), 4.42 (s, 2 H, ArCH2O), 6.53 H, OCH2), 4.06 (t, J ϭ 6.0 Hz, 18 H, OCH2), 4.95 (br. s, 6 H,
(s, 2 H, ArH) ppm. 13C NMR (CDCl3): δ ϭ 38.7, 57.1, 68.8, 69.1,
ArCH2O), 6.54 (s, 2 H, ArH), 6.56 (s, 2 H, ArH), 6.59 (s, 2 H,
69.3, 70.0, 70.2, 70.2, 71.3, 71.5, 109.1, 132.9, 138.4, 152.0 ppm. ArH), 7.29 (s, 2 H, ArH) ppm. 13C NMR (CD3OD): δ ϭ 58.3,
FAB MS: m/z ϭ 726.3 [M ϩ H]ϩ, calcd. for C33H60O16: 726.4.
67.8, 68.0, 68.0, 68.2, 68.9, 69.1, 69.8, 69.9, 70.1, 71.3, 71.6, 71.7,
71.7, 105.6, 105.7, 106.1, 106.8, 109.4, 123.4, 131.1, 132.2, 132.9,
136.4, 136.8, 137.2, 137.4, 142.5, 151.6, 151.8, 151.9, 152.1, 170.2
ppm. Maldi-TOF MS: m/z ϭ 2296.4 [M], 2319.4 [M ϩ Na]ϩ,
2335.5 [M ϩ K]ϩ, calcd. for C109H186O50: 2296.6.
3,4,5-Tris(methyltetraethyleneoxy)benzyl Chloride (13): A solution
of thionyl chloride (1.34 g, 11.22 mmol) in CH2Cl2 (20 mL) was
added dropwise to a solution of 12 (1.00 g, 1.38 mmol) in CH2Cl2
(50 mL). After the reaction mixture had been stirred for 1 h, it was
concentrated to dryness to give 13 (1.01 g, 100%) as a yellowish oil.
1H NMR (CDCl3): δ ϭ 3.23 (br. s, 9 H, OCH3), 3.53Ϫ3.88 (m, 42
H, OCH2), 4.12Ϫ4.21 (m, 6 H, OCH2), 4.38 (s, 2 H, ArCH2Cl),
6.46 (s, 2 H, ArH) ppm. 13C NMR (CDCl3): δ ϭ 46.0, 58.4, 68.4,
69.1, 69.9, 70.0, 70.1, 70.2, 71.4, 71.5, 107.8, 132.2, 138.0, 152.1
ppm. EI MS m/z ϭ 744.3651 [M]Ϫ, calcd. for C34H61ClO15:
744.3700.
Tetraethylene Glycol Substituted Cavitand 18: A mixture of cavitand
17 (120 mg, 0.15 mmol), NaH (60% in mineral oil, 300 mg, large
excess), and tosyl tetraethylene glycol monomethyl ether (620 mg,
large excess) in DMF (10 mL) was stirred overnight. Addition of
H2O (5 mL) and concentration to dryness was followed by column
chromatography of the residue (Et2O, Rf ϭ 0.2), giving 18 (166 mg,
1
72%) as a colourless oil. H NMR (CD3OD): δ ϭ 1.61Ϫ1.68 (m,
8 H, CH2), 1.97 (s, 12 H, ArCH3), 2.27Ϫ2.41 (br. s, 8 H, OCH2),
3.38 (s, 12 H, OCH3), 3.53Ϫ3.65 (m, 56 H, OCH2), 3.65Ϫ3.76 (br.
s, 8 H, OCH2), 4.26 (d, JAB ϭ 6.9 Hz, 4 H, OCHO), 4.70Ϫ4.82 (m,
4 H, ArCHAr), 5.89 (d, JAB ϭ 6.9 Hz, 4 H, OCHO), 6.75 (s, 4 H,
ArH) ppm. 13C NMR (CDCl3): δ ϭ 13.6, 19.2, 26.5, 29.2, 36.6,
52.2, 58.5, 63.1, 69.4, 70.0, 71.4, 101.2, 115.3, 127.8, 136.9, 138.3,
153.1 ppm. FAB MS: m/z ϭ 1608.7 [M ϩ Na]ϩ, calcd. for
C84H128NaO28: 1608.8.
3,4,5-Tris(methyltetraethyleneoxy)benzylamine (14): A mixture of
KH (35% in mineral oil, 100 mg, 0.74 mmol) and 1,1,3,3-tetra-
methyldisilazane in THF (10 mL) was stirred at 0 °C for 1 h, after
which a solution of benzyl chloride 13 (500 mg, 0.67 mmol) in THF
(5 mL) was added. After stirring for an additional 2 h at 0 °C, the
reaction mixture was quenched with NH4Cl (aq) and acidified with
0.5 HCl (9.5 mL). The pH of the reaction mixture was adjusted
to 8.0Ϫ9.0 with dilute NH4OH, after which the reaction mixture
was extracted with Et2O (2 ϫ 100 mL). Drying of the combined
organic layers with Na2SO4, followed by precipitation by addition
of n-hexane (400 mL), gave 14 (208 mg, 68%) as a white solid. M.p.
30Ϫ35 °C. 1H NMR (D2O): δ ϭ 3.23 (br. s, 9 H, OCH3), 3.40Ϫ4.10
(m, 48 H, OCH2), 4.48 (s, 2 H, ArCH2), 6.56 (s, 2 H, ArH) ppm.
13C NMR (CD3OD): δ ϭ 50.2, 58.1, 68.4, 69.3, 69.7, 70.0, 70.0,
70.2, 71.3, 71.5, 106.9, 132.5, 137.9, 152.1 ppm. FAB MS: m/z ϭ
726.3 [M]ϩ, calcd. for C34H63NO15: 726.4. C34H63NO15·2.0H2O
(761.9): C 53.60, H 8.86, N 1.84; found C 53.77, H 8.82, N 2.10.
G-1-Substituted Cavitand 19: A mixture of tetraamine 5 (27 mg,
30.5 µmol), G-1Ϫcarboxylic acid 11 (100 mg, 134 µmol), EDC
(26 mg, 152 µmol), and tBuOH (18.0 mg, 152 µmol) in CH2Cl2
(30 mL) was stirred for 7 d, after which the solvents were evapor-
ated to dryness. The residue was redissolved in H2O (10 mL) and
purified by the standard dialysis procedure to afford 19 (103 mg,
1
89%) as a bright yellow oil. H NMR (CDCl3): δ ϭ 1.42Ϫ1.56 (m,
8 H, CH2), 2.24Ϫ2.42 (m, 8 H, CH2), 3.35Ϫ3.80 (m, 200 H,
ArCH2, OCH2CH2O, CH2O, OCH3), 3.98Ϫ4.23 (m, 24 H, Ar-
OCH2), 4.30 (br. s, 8 H, ArCH2N), 4.33 (d, JAB ϭ 7.2 Hz, 4 H,
OCHO), 4.48 [s, 8 H, ArCH2(O)], 4.67 (s, 8 H, ArCH2N), 4.71 (t,
J ϭ 7.5 Hz, 4 H, ArCHAr), 5.89 (d, JAB ϭ 7.2 Hz, 4 H, OCHO),
6.94 (br. s, 2 H, NH), 6.88 (s, 8 H, ArH), 7.24 (br. s, 2 H, NH),
7.30 (s, 4 H, ArH) ppm. 13C NMR (CDCl3): δ ϭ 25.6, 30.2, 33.7,
36.4, 57.2, 60.8, 67.7, 68.1, 68.9, 69.4, 69.6, 69.7, 69.8, 71.0, 71.7,
99.5, 105.8, 107.5, 120.0, 123.6, 128.8, 137.4, 140.1, 151.2, 151.8,
153.5, 166.8 ppm. Maldi-TOF MS: m/z ϭ 3799.4 [M ϩ Na]ϩ,
calcd. for C184H292N4NaO76: 3799.3.
G-2؊Methyl Benzoate 15: A mixture of methyl 3,4,5-trihydroxy-
benzoate (89.0 mg, 0.48 mmol), 3,4,5-tris(methyltetraethyleneoxy)-
benzyl chloride (13) (1.15 g, 17.38 mmol), and K2CO3 (900 mg,
68.13 mmol) in DMF (75 mL) was stirred at 65 °C overnight. The
reaction solvents were evaporated to dryness, and the residue was
taken up in a mixture of CH2Cl2 (100 mL) and H2O (50 mL), after
which the organic layer was washed with H2O (2 ϫ 400 mL) and
the solvents were evaporated to dryness. Purification of the residue
by the standard dialysis procedure gave 15 (0.83 g, 78%) as a yel-
low-brown oil. 1H NMR (D2O): δ ϭ 3.36Ϫ3.42 (m, 30 H, OCH3),
3.52Ϫ3.60 (m, 18 H, OCH2), 3.60Ϫ3.78 (m, 72 H, OCH2),
3.78Ϫ3.90 (m, 18 H, OCH2), 3.92 (t, J ϭ 6.0 Hz, 2 H, OCH2),
4.07Ϫ4.22 (m, 34 H, OCH2), 5.05 (br. s, 6 H, ArCH2O), 6.59 (s, 2
H, ArH), 6.66 (s, 2 H, ArH), 6.67 (s, 2 H, ArH), 7.34 (s, 2 H, ArH)
ppm. 13C NMR (CDCl3): δ ϭ 51.6, 57.5, 58.4, 64.2, 68.1, 68.2,
68.7, 69.1, 69.1, 69.2, 69.9, 70.0, 70.2, 70.8, 71.3, 71.7, 74.0, 76.7,
105.8, 106.1, 106.5, 107.5, 109.0, 112.3, 121.5, 124.7, 131.5, 132.3,
133.1, 136.4, 137.0, 137.2, 137.4, 137.5, 139.8, 141.7, 151.8, 151.9,
152.0, 152.2, 152.3, 165.7 ppm. FAB MS: m/z ϭ 2333.7 [M ϩ Na]ϩ,
calcd. for C110H188NaO50: 2333.2.
G-2-Substituted Cavitand 20: A mixture of tetraamine 5 (27 mg,
30.5 µmol), G-2Ϫcarboxylic acid 16 (620 mg, 268 µmol), EDC
(26 mg, 152 µmol) and tBuOH (18.0 mg, 152 µmol) in CH2Cl2
(50 mL) was stirred for 7 d, after which the reaction solvents were
evaporated to dryness. The residue was redissolved in H2O (10 mL).
Extraction with toluene (5 ϫ 50 mL), concentration of the com-
bined layers to dryness, and dialysis of the residue by the standard
procedure gave 20 (165 mg, 44%) as a greenish oil. 1H NMR
(CD3OD): δ ϭ 1.36Ϫ1.58 (m, 8 H, CH2), 2.12Ϫ2.60 (m, 16 H,
CH2O, ArCCH2), 3.16Ϫ3.24 (br. s, 135 H, OCH3), 3.20Ϫ4.20 (m,
722 H, OCHO, ArCH2N, OCH2), 4.36Ϫ4.38 (br. s, 1 H, ArCHAr),
4.44Ϫ4.54 (br. s, 3 H, ArCHAr), 4.92 (s, 4 H, ArCH2O), 4.93 (s, 2
H, ArCH2O), 5.00 (s, 24 H, ArCH2O), 5.09Ϫ5.10 (br. s, 4 H, Ar-
G-2؊Carboxylic Acid 16: An aqueous solution (50 mL) of G-
2Ϫmethyl benzoate 15 (1.00 g, 4.44 mmol) at pH ϭ 10.24 was CH2O), 5.19Ϫ5.22 (br. s, 6 H, ArCH2O), 5.44 (m, 2 H, OCHO),
heated under reflux for 72 h, after which the pH was adjusted to 5.99 (d, JAB ϭ 6.9 Hz, 2 H, OCHO), 6.08Ϫ6.17 [m, 4 H, NHC(O)],
7.0 by addition of dilute HCl (aq). The reaction mixture was con-
6.62 (s, 8 H, ArH), 6.68 (s, 2 H, ArH), 6.69 (s, 16 H, ArH), 6.80
centrated to approximately 10 mL, and purification by the standard (s, 1 H, ArH-cav), 6.85 (s, 2 H, ArH-cav), 6.96 (s, 1 H, ArH-cav),
dialysis procedure gave 16 (941 mg, 94%) as a yellow-brown oil. 1H
NMR (D2O): δ ϭ 3.30Ϫ3.44 (m, 27 H, OCH3), 3.44Ϫ3.60 (m, 18
7.16 (s, 1 H, ArH), 7.17 (s, 1 H, ArH), 7.19 (s, 1 H, ArH), 7.21 (s,
1 H, ArH), 7.39 (s, 8 H, ArH), 7.54Ϫ7.63 (br. s, 2 H, ArH) ppm.
H, OCH2), 3.60Ϫ3.68 (m, 72 H, OCH2), 3.68Ϫ3.76 (m, 18 H, 13C NMR (CD3OD): δ ϭ 29.7, 30.0, 30.0, 34.5, 34.6, 40.4, 40.6,
OCH2), 3.87 (t, J ϭ 5.9 Hz, 2 H, OCH2), 4.00 (t, J ϭ 6.1 Hz, 16 40.8, 62.2, 64.7, 65.2, 65.3, 71.9, 72.1, 73.0, 73.7, 73.8, 74.0, 74.0,
2594
Eur. J. Org. Chem. 2002, 2587Ϫ2597