688
J. Kertész et al. / Tetrahedron: Asymmetry 22 (2011) 684–689
sodium (80.4 mg, 3.50 mmol) and propanol (2 mL). Chromatogra-
phy on alumina using EtOH–acetone mixture (1:10) as an eluent
gave crown ether (S,S)-3 (10.5 mg, 31%) as a yellow oil. Rf: 0.37
86%) as a pale yellow oil. Ditosylate (S,S)-6 had the same physical
properties and spectroscopic data as the one prepared above using
Et3N as a base.
(alumina TLC, EtOH–acetone 1:10); ½a D25
¼ þ7:7 (c 0.36, CH2Cl2);
ꢂ
IR (KBr) mmax 3419, 2963, 2926, 2855, 1720, 1639, 1468, 1461,
4.5. (8S,16S)-8,16-Dimethyl-6,9,12,15,18-pentaoxa-25-
azatetracyclo[21.3.1.05,26.019,24]heptacosa-1(26),2,4,19,21,23-
hexaene-27-one [(S,S)-8]
1397, 1262, 1099, 1022, 865, 801, 725, 531 cmꢀ1
;
1H NMR
(500 MHz, CD3CN) d 1.31 (d, J = 6 Hz, 6H), 3.55–3.76 (m, 8H),
4.25–4.29 (m, 4H), 4.33–4.36 (m, 2H), 7.16 (d, J = 8 Hz, 2H), 7.51
(t, J = 8 Hz, 2H), 7.67 (d, J = 8 Hz, 2H), 8.89 (s, 1H); 13C NMR
(75.5 MHz, CD3CN) d 16.53, 67.08, 71.20, 72.83, 73.65, 109.75,
121.75, 127.72, 129.33, 137.69, 141.81, 154.87. Anal. Calcd for
A mixture of 4,5-dihydroxyacridone monohydrate 735 (0.38 g,
1.55 mmol), ditosylate (S,S)-6 (0.91 g, 1.71 mmol), and finely pow-
dered anhydrous K2CO3 (2.15 g, 15.5 mmol) was stirred in either
dry and pure DMF (70 mL) or in dry and pure MeCN (70 mL) vigor-
ously under Ar at rt for 10 min and then at 50 °C for six days. The
solvent was removed, after which the residue was taken up in a
mixture of water (120 mL) and CH2Cl2 (120 mL). The phases were
shaken well and separated. The aqueous phase was extracted with
CH2Cl2 (3 ꢁ 40 mL). The combined organic phase was shaken with
water (60 mL), dried over MgSO4, filtered, and the solvent was re-
moved. The crude product was purified by chromatography on sil-
ica gel using EtOAc–hexane mixture (4:1) as an eluent and then
was recrystallized from EtOH to give macrocycle (S,S)-8 (109 mg,
17% using DMF as a solvent or 51 mg, 8% using MeCN as a solvent)
as pale yellow crystals. Crown ether (S,S)-8 obtained using either
DMF or MeCN as a solvent had the same physical properties and
spectroscopic data. Mp: 149–149.5 °C (EtOH); Rf: 0.23 (silica gel
C
25H33NO5ꢃH2O: C, 66.49; H, 7.04; N, 3.37. Found: C, 66.27; H,
6.97; N, 3.15. MS Calcd for C23H27NO5: 397.19. Found (M+1)+:
398.17.
4.3.2. Starting from acridine-4,5-diol 9
A mixture of acridine-4,5-diol 99 (0.203 g, 0.874 mmol), ditosy-
late (S,S)-6 (0.512 g, 0.961 mmol) and finely powdered anhydrous
K2CO3 (1.33 g, 8.74 mmol) was stirred in dry and pure DMF
(15 mL) vigorously under Ar at rt for 10 min then at 50 °C for five
days. The solvent was removed, and the residue was taken up in
a mixture of water (30 mL) and EtOAc (60 mL). The phases were
shaken well and separated. The aqueous phase was extracted with
EtOAc (4 ꢁ 40 mL). The combined organic phase was dried over
MgSO4, filtered and the solvent was removed. The crude product
was purified by chromatography on alumina using EtOH–acetone
mixture (1:10) as an eluent to give macrocycle (S,S)-3 (48 mg,
12%) as a pale yellow oil. Crown ether (S,S)-3 had the same physical
properties and spectroscopic data as the one prepared above start-
ing from acridono-crown ether (S,S)-8.
TLC, EtOAc–hexane 4:1); ½a D19
¼ þ54:2 (c 0.25, CH2Cl2); IR (KBr)
ꢂ
mmax 3424, 2928, 2896, 2872, 1628, 1616, 1600, 1532, 1448,
1424, 1376, 1336, 1272, 1228, 1136, 1120, 1088, 1040, 980, 848,
784, 744, 728, 704, 588 cmꢀ1 1H NMR (500 MHz, CDCl3) d 1.36
;
(d, J = 6 Hz, 6H), 1.96 (broad s, half mol of complexed H2O, 1H),
3.70–3.86 (m, 8H), 4.07–4.10 (m, 2H), 4.11–4.25 (m, 4H), 7.06 (d,
J = 8 Hz, 2H), 7.17 (t, J = 8 Hz, 2H), 8.06 (d, J = 8.5 Hz, 2H), 9.42 (s,
NH, 1H); 13C NMR (125 MHz, CDCl3) d 16.70, 69.58, 71.13, 73.32,
73.76, 118.74, 120.88, 122.34, 146.86, 178.18. MS Calcd for
4.4. (2S,20S)-2,20-Oxybis[(ethane-2,1-diyloxy)propane-2,1-diyl]
bis(4-methylbenzenesulfonate) [(S,S)-6]
C
C
23H27NO6: 413.18. Found (M+1)+: 414.38. Anal. Calcd for
23H27NO6ꢃ0.5H2O: C, 65.39; H, 6.68; N, 3.32. Found: C, 65.41; H,
4.4.1. Using Et3N as a base
To a solution of diol (S,S)-534 (0.99 g, 4.5 mmol) in Et3N (25 mL)
was added tosyl chloride (1.88 g, 9.9 mmol) at rt, and the reaction
mixture was stirred vigorously at rt for 5 h. The solvent was re-
moved, and the residue was taken up in a mixture of 5% aqueous
HCl solution (50 mL) and CH2Cl2 (50 mL). The phases were shaken
well and separated. The aqueous phase was extracted with CH2Cl2
(20 mL). The combined organic phase was shaken with water
(3 ꢁ 40 mL), dried over MgSO4, filtered and the solvent was re-
moved. The crude product was purified by chromatography on
silica gel using acetone–hexane mixture (1:3) as an eluent to give
ditosylate (S,S)-6 (1.79 g, 76%) as a pale yellow oil. Rf: 0.41 (silica
6.60; N, 3.27.
Acknowledgements
Financial supports of the Hungarian Scientific Research Fund
(OTKA No. K81127, T46403, NF72194) and the National Develop-
ment Agency (Project ID: KMOP-1.1.2-07/1-2008-0002) are grate-
fully acknowledged. This work is connected to the scientific
programme of the ‘Development of quality-oriented and harmo-
nized R+D+I strategy and functional model at BME’ project, sup-
ported by the New Hungary Development Plan (Project ID:
TÁMOP-4.2.1/B-09/1/KMR-2010-0002).
gel TLC, acetone–hexane 1:2); ½a D23
¼ ꢀ6:7 (c 1.2, CH2Cl2); IR (neat)
ꢂ
mmax 2998, 2943, 2872, 1600, 1496, 1452, 1364, 1296, 1188, 1152,
1096, 988, 816, 800, 668, 552 cmꢀ1 1H NMR (500 MHz, CDCl3) d
;
1.12 (d, J = 6 Hz, 6H), 2.44 (s, 6H), 3.51–3.60 (m, 8H), 3.67–3.70
(m, 2H), 3.91–3.98 (m, 4H), 7.34 (d, J = 8 Hz, 4H), 7.78 (d, J = 8 Hz,
4H); 13C NMR (75.5 MHz, CDCl3) d 16.91, 21.79, 69.05, 70.89,
72.80, 73.65, 128.11, 130.01, 133.15, 144.98.
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