2198
B. H. Kim et al.
FEATURE ARTICLE
N,N-Dihydroxypyridine-2,6-dicarboximidoyl Dichloride (18)
Mp 147–148 °C.
10.3 Hz, CH=CH2), 5.54 (dd, 2 H, J = 11.2, 1.3 Hz, CH=CH2), 4.42
(d, 4 H, J = 13.3 Hz, ArCH2Ar), 3.95 (t, 4 H, J = 7.9 Hz, OCH2),
3.66 (t, 4 H, J = 6.8 Hz, OCH2), 3.10 (d, 4 H, J = 13.4 Hz,
ArCH2Ar), 2.00–1.79 (m, 8 H, CH2CH3), 1.05 (t, 6 H, J = 14.8 Hz,
CH3), 0.90 (t, 6 H, J = 14.9 Hz, CH3).
13C NMR (75 MHz, CDCl3): d = 163.9, 157.8, 153.5, 136.5, 134.7,
132.1, 131.7, 129.2, 127.1, 122.5, 121.1, 77.3, 77.0, 31.4, 23.8,
23.4, 11.1, 10.4.
IR (KBr): 3209, 3035, 2879, 1647, 1567, 1458, 1391, 1292, 1046,
1008, 939, 813, 733 cm–1.
1H NMR (300 MHz, CD3OD): d = 6.47–6.35 (m, 3 H, ArH).
13C NMR (75 MHz, CD3OD): d = 151.9, 138.7, 123.7.
EIMS m/z: [M+] 233.
MS (FAB) m/z: [M++H] 731.0, [M+] 730.0.
Diethylene Glycol Diacrylate (20)
To a vigorously stirred solution of diethylene glycol 19 (52.7 mmol)
in CH2Cl2 (100 mL) was added Et3N (158.0 mmol), followed by
acryloyl chloride (121.2 mmol). After stirring the mixture at r.t. for
1 h, it was poured into H2O (70 mL) and the mixture was extracted
with CH2Cl2. The combined organic extracts were dried with
MgSO4 and evaporated in vacuo. The resulting product on purifica-
tion by column chromatography (SiO2, hexane–EtOAc, 5:1) yielded
20 (99%) as a colorless oil.
5,17-Bis(ethynylamido)-25,26,27,28-tetrapropoxycalix[4]arene
(25)
To a solution of 5,17-diaminocalix[4]arene 23 (3.03 mmol) in tolu-
ene (15 mL) at 0 °C was added Me3Al (15.2 mmol, 2.0 M in tolu-
ene) dropwise. After complete addition the mixture was allowed to
warm to 25 °C and stirred for 1 h. To this aluminum complex was
added methyl propiolate (15.7 mmol), the reaction mixture was
heated to 45 °C and stirred for an hour. After completion of the re-
action, the solution was cooled to r.t., a 20% aq solution of Roch-
elle’s salt was added and the product was extracted with CH2Cl2.
The collective organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo to give the crude product. This on purifica-
tion by column chromatography (SiO2, hexane–EtOAc, 4:1) gave
25 (79%).
IR (CHCl3): 3023, 2956, 2889, 1723, 1638, 1619, 1409, 1285, 1193,
1136, 1070, 978, 810 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.26 (dd, 2 H, J = 17.5, 1.6 Hz,
CH=CH2), 5.99 (dd, 2 H, J = 17.5, 10.4 Hz, CH=CH2), 5.68 (dd,
1H, J = 10.4, 1.6 Hz, CH=CH2), 4.17–4.14 (m, 4 H, OCH2), 3.61–
3.58 (m, 4 H, OCH2).
13C NMR (75 MHz, CDCl3): d = 165.6, 130.6, 128.0, 68.7, 63.2.
EIMS m/z: [M++H] 215.
Mp 177–179 °C.
IR (CHCl3): 3219, 3261 (NH), 3062, 2962, 2933, 2876, 2108
(C∫C), 1660 (C=O), 1646, 1604, 1542, 1464, 1418, 1384, 1287,
1217, 1160, 1131, 1160, 1131, 1079, 1067, 1038, 1006, 966 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.64 (s, 2 H, NH), 6.97 (d, 4 H,
J = 7.3 Hz, ArH), 6.83 (t, 2 H, J = 7.3 Hz, ArH), 6.36 (s, 4 H, ArH),
4.42 (d, 4 H, J = 13.2 Hz, ArCH2Ar), 3.96 (t, 4 H, J = 7.8 Hz,
OCH2), 3.66 (t, 4 H, J = 6.8 Hz, OCH2), 3.21 (d, 4 H, J = 13.3 Hz,
ArCH2Ar), 2.42(s, 2 H, CCH), 1.98–1.83 (m, 8 H, CH2CH3), 1.05
(t, 6 H, J = 7.3 Hz, CH3), 0.90 (t, 6 H, J = 7.3 Hz, CH3).
Triethylene Glycol Diacrylate (22)
To a vigorously stirred solution of triethylene glycol 21 (7.5 mmol)
in CH2Cl2 (20 mL) was added Et3N (22.5 mmol), followed by acry-
loyl chloride (17.3 mmol). After stirring the reaction mixture for 1
h at r.t., it was poured into H2O (15 mL) and extracted with CH2Cl2.
The combined organic extracts were dried with MgSO4 and evapo-
rated in vacuo. The resulting product on column chromatographic
(SiO2, hexane–EtOAc, 5:1) purification yielded 22 (99%) as a col-
orless oil.
13C NMR (75 MHz, CDCl3): d = 157.7, 153.8, 150.3, 136.4, 134.9,
130.8, 129.3, 122.9, 121.3, 78.2, 77.0, 74.9, 31.4, 23.8, 23.4, 11.1,
10.3.
IR (CHCl3): 3021, 2954, 2889, 2401, 1722, 1637, 1409, 1298, 1196,
1127, 810, 725 cm–1.
MS (FAB) m/z: [M++H] 727.4, [M+] 726.4.
1H NMR (300 MHz, CDCl3): d = 6.20 (dd, 2 H, J = 17.0, 1.2 Hz,
CH=CH2), 5.94 (dd, 2 H, J = 17.0, 10.2 Hz, CH=CH2), 5.63 (dd, 2
H, J = 10.2, 1.2 Hz, CH=CH2), 4.11–4.08 (m, 4 H, OCH2), 3.55–
3.51 (m, 4 H, OCH2), 3.45 (s, 4 H, OCH2).
13C NMR (75 MHz, CDCl3): d = 165.4, 130.3, 127.9, 70.1, 68.6,
63.1.
Anal. Calcd for C46H50N2O6: C, 76.01; H, 6.81; N, 3.68. Found: C,
75.75; H, 6.93; N, 3.85.
Macrocycles by Cycloadditive Macrocyclization; General
procedure
To a mixture of bis(hydroxamic acid chloride) (2.15 mmol) and bi-
functional dipolarophile (2.15 mmol) in EtOH (250 mL) was added
drop wise a solution of Et3N (4.95 mmol) in EtOH (10 mL) using a
syringe pump over a period of 10 h. The reaction mixture was
stirred for an additional period of 10 h at r.t. Evaporation of solvent
followed by column chromatography afforded cycloadducts 26–32,
34–35, and 37–44 as white crystalline solids in moderate to good
yields.
EIMS m/z: [M++H] 259.
5,17-Bis(acrylamido)-25,26,27,28-tetrapropoxycalix[4]arene
(24)
5,17-Diaminocalix[4]arene 23 (1.98mmol) was dissolved in THF
(20mL) at 0 °C containing NaH (5.00 mmol, 60% dispersion in
mineral oil) and it was further treated with acryloyl chloride (4.93
mmol). After stirring the mixture for 10 min, it was poured into ex-
cess H2O to destroy unreacted sodium hydride. The reaction mix-
ture was extracted with CH2Cl2. Column chromatographic (SiO2,
CH2Cl2–EtOAc, 9:1) purification of the crude product yielded 24
(79%) as a white powder.
Macrocycle (26)
(SiO2, CH2Cl2-MeOH, 25:1).
Mp 221 °C dec.
IR (KBr): 2964, 2884, 1761, 1734, 1454, 1374, 1335, 1204, 1127,
1052, 954, 927 cm–1.
Mp 195 °C dec.
1H NMR (300 MHz, CDCl3–DMSO-d6, 1:1): d = 8.09–8.03 (m, 2
H, ArH), 7.50–7.43 (m, 2 H, ArH), 5.28–5.23 (m, 1 H, OCHCH2),
4.91–4.87 (m, 1 H, OCHCH2), 4.85–4.54 (m, 3 H), 4.30–4.16 (m, 3
H), 3.87–3.38 (m, 6 H).
IR (CHCl3): 3062, 2962, 2934, 2875, 2740, 1914, 1665 (C=O),
1603 (C=C), 1544, 1465, 1419, 1385, 1332, 1303, 1287, 1217,
1162, 1131, 1106, 1081, 1067, 1038, 1006, 966 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.58 (s, 2 H, NH). 6.94 (d, 4 H,
J = 7.3 Hz, ArH), 6.80 (t, 2 H, J = 7.4 Hz, ArH), 6.39 (s, 4 H, ArH),
6.24 (dd, 2 H, J = 14.3, 1.3 Hz, CH=CH2), 6.00 (dd, 2 H, J = 16.8,
MS (FAB) m/z: [M++H] 375.
Synthesis 2001, No. 14, 2191–2202 ISSN 0039-7881 © Thieme Stuttgart · New York