10.1002/chem.201902536
Chemistry - A European Journal
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room temperature, thereby showing a color change to purple. HRMS (EI):
Fluorescent probe 5: Yield 20% (42 mg); 1H-NMR (CDCl3, 300 MHz): δ
= 8.71 (s, 1H), 8.37 (s, 1H), 7.46 (s, 1H), 7.34 (dd, J = 8.2, 1.4 Hz, 1H),
7.11 (s, 2H), 6.44 (s, 1H), 4.72 (dt, J = 11.8, 5.8 Hz, 1H), 3.75 – 3.59 (m,
16H), 3.51 (s, 4H), 3.44 – 3.38 (m, 2H), 3.01 (s, 3H), 2.79 (t, J = 6.1 Hz,
2H), 2.04 – 1.93 (m, 2H), 1.38 ppm (d, J = 6.0 Hz, 6H); 13C-NMR (CDCl3,
75 MHz): δ = 157.1, 154.8, 150.5, 147.8, 134.4, 128.9, 127.7, 121.4, 119.8,
118.6, 117.0, 112.7, 107.3, 96.1, 71.1, 71.0, 70.7, 70.6, 70.5, 53.5, 51.1,
39.2, 27.4, 22.4, 21.6 ppm; HRMS (ESI): m/z calcd for C34H43N5O7+H+:
634.3241 [M+H+]; found: 634.3225.
m/z calcd for C19H32N2O6: 384.2260 [M+]; found: 384.2262.
General synthetic procedures for 17a, 17b and 17c: To a solution of the
corresponding amino compound 16a, 16b or 16c (cf. Scheme 3) (2.9
mmol) in 4M HCl (20 mL) was cooled to 0°C. Then, a solution of NaNO2
(200 mg, 2.9 mmol) in water (10 mL) was slowly added and the mixture
was stirred at 0°C for 10 min. Further, a solution of NaN3 (283 mg, 4.4
mmol) in water (10 mL) was added at 0°C and the mixture was stirred for
14 h at RT, neutralized with K2CO3, and extracted with CHCl3 (350 mL).
The organic layers were combined, dried over MgSO4, concentrated in
vacuo, and the residue was purified by column chromatography on silica
gel (CHCl3/MeOH, 95/5 v/v) to gave compounds 17a, 17b and 17c as
brown oils.
Fluorescent probe 6: Yield 58% (126 mg); M.p.: 165°C (decomp.); 1H-
NMR (CDCl3, 600 MHz): δ = 8.69 (s, 1H), 8.34 (s, 1H), 7.46 (s, 1H), 7.34
(d, J = 8.1 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 7.00 (s, 1H), 4.76 – 4.68 (m,
1H), 3.70 – 3.65 (m, 16H), 3.51 (s, 4H), 3.33 – 3.31 (m, 4H), 2.93 (t, J =
6.4 Hz, 2H), 2.79 (t, J = 6.1 Hz, 2H), 1.99 (dt, J = 18.7, 6.2 Hz, 4H), 1.37
ppm (d, J = 6.0 Hz, 6H); 13C-NMR (CDCl3, 125 MHz): δ = 157.3, 150.9,
150.7, 147.9, 147.0, 141.3, 134.9, 126.0, 123.8, 120.7, 119.9, 119.6, 118.5,
116.2, 112.6, 107.2, 106.3, 71.0, 70.7, 70.6, 70.4, 70.3, 53.4, 50.2, 49.8,
27.6, 22.3, 21.7, 20.3 ppm; HRMS (ESI): m/z calcd for C36H45N5O7+H+:
660.3397 [M+H+]; found: 660.3380.
N-(4-azido-2-methoxyphenyl)aza[15]crown-5 ether (17a): Yield: 78%
(829 mg); Analytical data of 17a can be found in reference[5d]
.
N-(4-azido-2-isopropoxyphenyl)aza[15]crown-5 ether (17b): Yield 80%
(920 mg); 1H-NMR (CDCl3, 500 MHz): δ = 7.05 (d, J = 8.5 Hz, 1H), 6.55
(dd, J = 8.5, 2.5 Hz, 1H), 6.45 (d, J = 2.5 Hz, 1H), 4.55 – 4.49 (m, 1H), 3.69
– 3.61 (m, 16H), 3.39 (t, J = 6.0 Hz, 4H), 1.32 ppm (d, J = 6.0 Hz, 6H); 13C-
NMR (CDCl3, 125 MHz): δ = 152.2, 138.7, 133.7, 122.8, 110.9, 106.4, 71.1,
70.7, 70.5, 70.4, 53.5, 22.2 ppm; HRMS (EI): m/z calcd for C19H30N4O5:
394.2216 [M+]; found: 394.2222.
CuACC procedure for 10: A mixture of the azido substituted crown
compound 17c (0.329 mmol) and 3-ethynyl-7-diethylcoumarin[12b] (cf.
Scheme 4) (0.329 mmol), CuSO4·5H2O (4.1 mg) and sodium ascorbate
(6.5 mg) in 9 ml THF/H2O (v/v, 2/1) was stirred at 60 °C for 48 hours. After
that 5 mL H2O were added to the mixture and then extracted with CHCl3
(30 mL). The organic layer was dried with MgSO4 and concentrated in
vacuo. The residue was purified by column chromatography on silica using
CHCl3/CH3OH (v/v, 99/5) as an eluent mixture to afford 10 as a yellow
solid.
N-(4-azido-2-ethoxymethoxyphenyl)aza[15]crown-5 ether (17c): Yield
12% (143 mg); Caution! 23 quickly decomposed if exposed to air at room
temperature, thereby showing a color change to dark brown. HRMS (EI):
m/z calcd for C19H30N4O6: 410.2165 [M+]; found: 410.2170.
Fluorescent probe 10: Yield 33% (71 mg); M.p.: 88°C (decomp.); 1H-
NMR (CDCl3, 600 MHz): δ = 8.72-8.67 (m, 2H), 7.46-7.42 (m, 2H), 7.23
(m, 2H), 6.65 (dd, J = 8.9, 2.2 Hz, 1H), 6.56 (d, J = 2.2 Hz, 1H), 4.30 – 3.30
(m, 31H), 1.24 ppm (t, J = 7.1 Hz, 6H); HRMS (ESI): m/z calcd for
C34H45N5O8+H+: 652.3346 [M+H+]; found: 652.3375.
General CuACC procedure for 2, 4, 5 and 6: A mixture of the
corresponding alkynyl substituted crown compound 13a or 13b (0.329
mmol) and the corresponding azidocoumarin derivative[12a] (cf. Scheme 4)
(0.329 mmol), CuSO4·5H2O (4.1 mg) and sodium ascorbate (6.5 mg) in 9
ml THF/H2O (v/v, 2/1) was stirred at 60 °C for 48 hours. After that 5 mL
H2O were added to the mixture and then extracted with CHCl3 (30 mL).
The organic layer was dried with MgSO4 and concentrated in vacuo. The
residue was purified by column chromatography on silica using
CHCl3/CH3OH (v/v, 99/5) as an eluent mixture to afford 2, 4 and 6 as yellow
solids and 5 as a yellow oil.
General CuACC procedure for 7,
8 and 9: A mixture of the
corresponding azido substituted crown compound 17a or 17b (0.415
mmol) and the corresponding alkynyl substituted fluorophore derivative[10]
(cf. Scheme 4) (0.415 mmol), CuSO4·5H2O (5.3 mg) and sodium
ascorbate (8.2 mg) in 9 ml DMF/H2O (v/v, 2/1) was stirred at 60 °C for 48
hours. After that 5 mL H2O were added to the mixture and then extracted
with CHCl3 (30 mL). The organic layer was dried with MgSO4 and
concentrated in vacuo. The residue was purified by column
chromatography on silica using CHCl3/CH3OH (v/v, 99/5) as an eluent
mixture to afford 7, 8 and 9 as a yellow oils.
Fluorescent probe 2: Yield 38% (76 mg); M.p.: 76°C (decomp.); 1H-NMR
(CDCl3, 300 MHz): δ = 8.74 (s, 1H), 8.37 (d, J = 5.7 Hz, 1H), 7.47 (s, 1H),
7.38 (d, J = 7.7 Hz, 1H), 7.13 (d, J = 5.9 Hz, 2H), 6.44 (s, 1H), 3.93 (s, 3H),
3.68 (m, 20H), 3.44 – 3.39 (m, 2H), 3.02 (s, 3H), 2.82 – 2.76 (m, 2H), 2.02
– 1.94 ppm (m, 2H); 13C-NMR (CDCl3, 75 MHz): δ = 157.2, 154.8, 152.8,
150.6, 134.5, 129.1, 127.7, 121.4, 119.9, 118.5, 116.9, 109.4, 107.3, 98.6,
96.1, 71.1, 71.0, 70.6, 70.3, 70.2, 55.9, 53.1, 51.1, 39.2, 27.4, 21.6 ppm;
HRMS (ESI): m/z calcd for C32H39N5O7+H+: 606.2922 [M+H+]; found:
606.2928.
Fluorescent probe 7: Yield 30% (99 mg); 1H-NMR (CDCl3, 300 MHz): δ
= 7.94 (s, 1H), 7.09 (s, 2H), 6.81 – 6.71 (m, 1H), 6.63 (t, J = 4.8 Hz, 1H),
6.08 (dd, J = 6.2, 0.9 Hz, 2H), 4.67-4.55 (m, 3H), 4.33 (q, J = 7.1 Hz, 4H),
3.77 – 3.46 (m, 20H), 2.97 (d, J = 4.9 Hz, 2H), 1.41 – 1.28 ppm (m, 12H);
13C-NMR (CDCl3, 75 MHz): δ = 166.6, 161.6, 150.9, 144.8, 141.9, 141.0,
130.8, 120.7, 112.5, 110.5, 107.8, 103.1, 102.9, 71.0, 70.5, 70.4, 70.3,
61.6, 53.2, 42.0, 35.3, 30.0, 22.0, 14.2 ppm; HRMS (ESI): m/z calcd for
C38H49N5O14+H+: 800.3354 [M+H+]; found: 800.3328.
Fluorescent probe 4: Yield 55% (115 mg); M.p.: 123°C (decomp.); 1H-
NMR (CDCl3, 300 MHz): δ = 8.70 (s, 1H), 8.43 (s, 1H), 7.49 – 7.38 (m, 2H),
7.37 – 7.31 (m, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.68 (dd, J = 8.9, 2.2 Hz, 1H),
6.56 (d, J = 2.0 Hz, 1H), 4.72 (dt, J = 11.9, 5.9 Hz, 1H), 3.80 – 3.60 (m,
16H), 3.52 – 3.42 (m, 8H), 1.37 (d, J = 6.0 Hz, 6H), 1.24 ppm (t, J = 7.0
Hz, 6H); 13C-NMR (CDCl3, 75 MHz): δ = 157.0, 156.0, 151.9, 148.1, 134.3,
130.1, 121.6, 121.2, 119.8, 118.9, 117.7, 113.4, 110.3, 107.6, 97.5, 71.3,
70.9, 70.7, 70.6, 70.5, 53.7, 45.2, 22.5, 12.6 ppm; HRMS (ESI): m/z calcd
for C34H45N5O7+H+: 636.3397 [M+H+]; found: 636.3382.
Fluorescent probe 8: Yield 23% (74 mg); 1H-NMR (CDCl3, 300 MHz): δ
= 7.98 (s, 1H), 7.14 (s, 2H), 6.97 – 6.81 (m, 1H), 6.67 – 6.58 (m, 1H), 6.07
(d, J = 6.7, Hz, 2H), 4.62 (s, 2H), 4.34 (q, J = 6.6 Hz, 4H), 4.00 – 3.34 (m,
23H), 2.98 (s, 2H), 1.40 – 1.19 ppm (m, 6H); 13C-NMR (CDCl3, 75 MHz): δ
= 166.6, 161.6, 153.1, 144.9, 141.9, 141.0, 128.8, 120.8, 112.6, 110.6,
105.1, 103.2, 102.9, 70.9, 70.6, 70.4, 69.9, 61.6, 53.4, 42.0, 35.3, 29.6,
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