ENANTIOPURE PYRIDINO-18-CROWN-6 ETHER-BASED FLUORESCENT SENSOR MOLECULES
563
UV–vis spectra were taken on a Unicam (Cambridge, UK) UV4–100
spectrophotometer. Quartz cuvettes with path length of 1 cm were used.
Fluorescence emission spectra were recorded on a Perkin–Elmer LS 50B
luminescent spectrometer and were corrected by the spectrometer soft-
ware. Quartz cuvettes with path length of 1 cm were used. Fluorescence
quantum yields were determined relative to quinine sulfate (Φf = 0.53 in
0.1 M H2SO4).1 Enantiomers of PhEt, NapEt, PhgOMe, and PheOMe
were prepared in our laboratory.35 The concentrations of sensor
molecules (S,S)-1 and (S,S)-2 were 20 μM during the titrations. In order
to determine the stability constants of complexes by global nonlinear
regression analysis, the SPECFIT/32 software was used.
suspension. The reaction mixture was stirred at 0 °C for 10 min, at RT for
30 min, and refluxed for 3 h. The mixture was cooled to ꢁ60 °C and a solu-
tion of ditosylate 341 (1.81 g, 3.26 mmol) in THF (11 mL) was added, and
the reaction mixture was stirred at ꢁ60 °C for 30 min then at RT for 4 days.
The solvent was evaporated and the residue was triturated with ice-water
(20 mL). The mixture was washed into a separating funnel with ether
(60 mL). The phases were mixed well and separated. The aqueous phase
was extracted with ether (3 × 30 mL). The combined organic phase was
dried over MgSO4, filtered, and the solvent was removed. The residue
was purified by column chromatography on alumina using EtOH–toluene
1:160 mixture as an eluent to give (S,S)-7 (350 mg, 21%) as a colorless oil.
30
Rf: 0.44 (alumina TLC, EtOH–toluene 1:90); ½αꢀD = ꢁ8.2 (c = 1.0 in
EtOH); IR (neat): νmax 3082, 3065, 3033, 2952, 2922, 2867, 1596, 1576,
Preparation of Crown Ethers (S,S)-1, (S,S)-2, (S,S)-7, (S,S)-
9, (S,S)-11, and (S,S)-13
1453, 1384, 1349, 1321, 1245, 1149, 1112, 1044, 991, 952, 921, 866, 846,
736, 696 cmꢁ1; H NMR (500 MHz, CDCl3): δ 0.89 (d, J = 7 Hz, 6H, iBu-
1
General procedure for the synthesis of sensor molecules (S,S)-1
CH3), 0.93 (d, J = 7 Hz, 6H, iBu-CH3), 1.16–1.24 (m, 2H, iBu-CH2), 1.47–1.55
(m, 2H, iBu-CH2), 1.72–1.84 (m, 2H, iBu-CH), 3.43–3.63 (m, 12H, OCH2),
3.66–3.74 (m, 2H, OCH), δA 4.76 and δB 4.80 (AB q, JAB = 13 Hz, 4H, ben-
zylic type CH2), 5.10–5.16 (m, 2H, benzylic type CH2), 6.91 (s, 2H, Py-H),
7.31–7.44 (m, 5H, Ar-H); 13C NMR (125 MHz, CDCl3): δ 22.51, 23.56,
24.81, 41.22, 69.93, 70.76, 71.02, 72.34, 75.29, 76.20, 107.20, 127.72, 128.45,
128.87, 136.14, 160.45, 166.16; MS: calcd. For C30H45NO6, 515.3; found
[M + H]+, 516.3. Anal. calcd. For C30H45NO6: C 69.87, H 8.80, N 2.72;
found: C 69.85, H 8.95, N 2.71.
(4S,14S)-4,14-Diisobutyl-3,6,9,12,15-pentaoxa-21-azabicyclo[15.3.1]heneicosa-
17,20-diene-19(21H)-one [(S,S)-9]. (Benzyloxy)pyridino-crown ether
(S,S)-7 (700 mg, 1.36 mmol) was hydrogenated in EtOH (35 mL) in
the presence of Pd/C catalyst (105 mg, 10% palladium on charcoal, ac-
tivated). After the reaction was completed, the catalyst was filtered off
and the solvent was evaporated to give (S,S)-9 (550 mg, 95%) as a pale
yellow oil which was used without purification. Macrocycle (S,S)-9
prepared this way was identical in every aspect to that reported in
the literature.37
and (S,S)-2.
A
mixture of iodopyridino-crown ether (S,S)-1239
(114 mg, 0.252 mmol) or (S,S)-13 (135 mg, 0.252 mmol), anthracen-9-
ylboronic acid (62 mg, 0.277 mmol), Pd(PPh3)4 (7.3 mg, 0.0063 mmol),
powdered K3PO4 (80 mg, 0.378 mmol), and KBr (33 mg, 0.277 mmol)
in dioxane–water 6:1 (4 mL) was stirred at 85 °C under Ar for a day.
The solvent was evaporated, and the residue was dissolved in a mixture
of CH2Cl2 (8 mL) and water (4 mL). The phases were mixed well and sep-
arated. The aqueous phase was extracted with CH2Cl2 (3 × 4 mL). The
combined organic phase was dried over MgSO4, filtered, and the solvent
was removed. The crude products were purified as described below for
each compound.
(4S,14S)-19-(Anthracen-9-yl)-4,14-dimethyl-3,6,9,12,15-pentaoxa-21-azabicyclo
[15.3.1]heneicosa-1(21),17,19-triene [(S,S)-1]. The crude product was purified
by column chromatography on alumina using first DME–hexane 1:4 then
DME–toluene 1:10 mixtures as eluents to give (S,S)-1 (48 mg, 38%) as a yel-
20
low oil. Rf: 0.27 (alumina TLC, DME–toluene 1:10); ½αꢀD = +25.2 (c = 1.0 in ac-
etone); IR (neat): νmax 3546 (br, complexed H2O), 3079, 3049, 3028, 2969,
2866, 1601, 1554, 1444, 1378, 1363, 1347, 1334, 1271, 1106, 1016, 977, 931,
887, 863, 842, 793, 738, 681, 669, 653, 633, 615, 555, 450, 437 cmꢁ1; 1H NMR
(500 MHz, CDCl3): δ 1.14 (d, J = 7 Hz, 6H, Me), 2.18 (br s, 1H, complexed
H2O), 3.35–3.77 (m, 12H, OCH2), 3.85–3.96 (m, 2H, OCH), δA 4.97 and δB
4.99 (AB q, JAB = 14 Hz, 4H, benzylic type CH2), 7.36–7.42 (m, 2H, Ar-H),
7.39 (s, 2H, Py-H), 7.46–7.51 (m, 2H, Ar-H), 7.61 (d, J = 9 Hz, 2H, Ar-H),
8.07 (d, J = 9 Hz, 2H, Ar-H), 8.54 (s, 1H, Ar-H); 13C NMR (75.5 MHz, CDCl3):
δ 17.23, 71.00, 71.19, 72.21, 74.28, 76.46, 123.09, 125.47, 126.08, 126.45, 127.52,
128.66, 129.66, 131.43, 134.51, 148.29, 159.12; MS: calcd. For C31H35NO5,
501.3; found [M + H]+, 502.3. Anal. calcd. For C31H35NO5·0.5 H2O: C 72.92,
H 7.11, N 2.74; found: C 72.69, H 7.20, N 2.58.
(4S,14S)-4,14-Diisobutyl-3,6,9,12,15-pentaoxa-21-azabicyclo[15.3.1]heneicosa-
1(21),17,19-triene-19-yl trifluoromethanesulfonate [(S,S)-11]. To a mixture of
pyridino-crown ether (S,S)-9 (550 mg, 1.29 mmol) and Et3N (262 mg,
0.36 mL, 2.58 mmol) in CH2Cl2 (7 mL) a solution of Tf2O (728 mg, 0.43 mL,
2.58 mmol) in CH2Cl2 (2 mL) was added dropwise under Ar at 0 °C. The reac-
tion mixture was allowed to warm to RT and stirred for 1 h. The reaction mix-
ture was poured into ice-water (20 mL) and the pH of the mixture was adjusted
to 10 with 25% aqueous NMe4OH. The mixture was washed into a separating
funnel with CH2Cl2 (40 mL). The phases were mixed well and separated.
The aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The combined or-
ganic phase was dried over MgSO4, filtered, and the solvent was removed. The
dark purple colored residue was purified by column chromatography on alu-
mina using EtOH–toluene 1:100 mixture as an eluent to give (S,S)-11
(460 mg, 64%) as a pale brown oil.
(4S,14S)-19-(Anthracen-9-yl)-4,14-diisobutyl-3,6,9,12,15-pentaoxa-
21-azabicyclo[15.3.1]heneicosa-1(21),17,19-triene [(S,S)-2]. The crude
product was purified by column chromatography on alumina using first
DME–hexane 1:20 then DME–toluene 1:30 mixtures as eluents to give
(S,S)-2 (77 mg, 52%) as a yellow oil. Rf: 0.29 (alumina TLC, DME–toluene
25
Rf: 0.78 (alumina TLC, EtOH–toluene 1:30); ½αꢀD = ꢁ16.4 (c = 1.0 in
CH2Cl2); IR (neat): νmax 3086, 3069, 3037, 2956, 2925, 2870, 1956, 1581,
1:30); ½αꢀ2D5 = ꢁ13.1 (c = 1.0 in acetone); IR (neat): νmax 3326 (br, complexed
H2O), 3083, 3060, 3032, 2953, 2918, 2867, 1601, 1566, 1457, 1420, 1385, 1366,
1350, 1316, 1263, 1110, 1042, 930, 884, 871, 844, 818, 791, 777, 758, 736, 722,
685, 630, 615, 556 cmꢁ1; 1H NMR (500 MHz, CDCl3): δ 0.81 (d, J = 7 Hz, 6H,
iBu-CH3), 0.82 (d, J = 7 Hz, 6H, iBu-CH3), 1.17–1.24 (m, 2H, iBu-CH2),
1.37–1.45 (m, 2H, iBu-CH2), 1.68–1.78 (m, 2H, iBu-CH), 2.83 (br s, 1H, com-
plexed H2O), 3.35–3.65 (m, 12H, OCH2), 3.79–3.85 (m, 2H, OCH), δA 4.90
and δB 5.01 (AB q, JAB = 13 Hz, 4H, benzylic type CH2), 7.41–7.45 (m, 2H,
Ar-H), 7.43 (s, 2H, Py-H), 7.51–7.55 (m, 2H, Ar-H), 7.63 (dd, J = 9 Hz,
J = 1 Hz, 2H, Ar-H), 8.15 (d, J = 9 Hz, 2H, Ar-H), 8.68 (s, 1H, Ar-H); 13C
NMR (125 MHz, CDCl3): δ 22.67, 23.85, 25.36, 42.26, 71.41, 71.62, 73.17,
75.80, 76.44, 123.67, 126.35, 126.91, 126.98, 128.35, 129.54, 130.36, 132.39,
135.38, 148.84, 160.18; MS: calcd. For C37H47NO5, 585.3; found [M + H]+,
586.3. Anal. calcd. For C37H47NO5·0.5 H2O: C 74.72, H 8.13, N 2.35; found:
C 74.54, H 8.03, N 2.22.
1468, 1426, 1387, 1368, 1350, 1296, 1243, 1211, 1139, 1118, 1044, 965, 874,
819, 765, 605, 572, 516 cmꢁ1 1H NMR (300 MHz, CDCl3): δ 0.90 (d,
;
J = 6 Hz, 6H, iBu-CH3), 0.92 (d, J = 6 Hz, 6H, iBu-CH3), 1.10–1.30 (m, 2H,
iBu-CH2), 1.44–1.58 (m, 2H, iBu-CH2), 1.66–1.86 (m, 2H, iBu-CH),
3.38–3.63 (m, 12H, OCH2), 3.66–3.78 (m, 2H, OCH), δA 4.85 and δB 4.89
(AB q, JAB = 14 Hz, 4H, benzylic type CH2), 7.20 (s, 2H, Py-H); 13C NMR
(75.5 MHz, CDCl3): δ 22.46, 23.41, 24.85, 40.96, 70.77, 71.20, 71.83, 75.68,
76.91, 112.10, 118.79 (q, J = 321 Hz, CF3), 157.43, 163.12; MS: calcd. For
C24H38F3NO8S, 557.2; found [M + H]+, 558.2. Anal. calcd. For C24H38F3NO8S:
C 51.69, H 6.87, N 2.51, S 5.75; found: C 51.50, H 7.01, N 2.39, S 5.61.
(4S,14S)-19-Iodo-4,14-diisobutyl-3,6,9,12,15-pentaoxa-21-azabicyclo[15.3.1]
heneicosa-1(21),17,19-triene [(S,S)-13]. To a solution of triflate (S,S)-11
(460 mg, 0.825 mmol) in toluene (9 mL) was first added NaI (619 mg,
4.13 mmol) followed by concentrated H2SO4 (105 mg, 58 μL, 1.07 mmol),
and the resulting mixture was stirred under Ar at RT for 5 h. The solvent
was evaporated, the residue was triturated with water (12 mL), and the pH
of the mixture was adjusted to 10 with 1 M NaOH. The mixture was washed
into a separating funnel with CH2Cl2 (24 mL). The phases were mixed well
and separated. The aqueous phase was extracted with CH2Cl2 (3 × 12 mL).
The combined organic phase was washed with 5% aqueous Na2S2O3
(4S,14S)-19-Benzyloxy-4,14-diisobutyl-3,6,9,12,15-pentaoxa-21-azabicyclo
[15.3.1]heneicosa-1(21),17,19-triene [(S,S)-7].
A suspension of NaH
(417 mg, 10.4 mmol, 60% dispersion in mineral oil) in pure and dry THF
(6 mL) was stirred under Ar at 0 °C. A solution of tetraethylene glycol
(S,S)-528 (1.00 g, 3.26 mmol) in THF (14 mL) was added dropwise to the
Chirality DOI 10.1002/chir