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7/28/2019 Syn of -Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for Hg Ions
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Supporting Information
Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2012
Synthesis ofp-Extended Coumarins and Evaluation of Their Precursors asReactive Fluorescent Probes for Mercury Ions
Inae Kim, Dokyoung Kim, Sunderraman Sambasivan, and Kyo Han Ahn*[a]
ajoc_201200034_sm_miscellaneous_information.pdf
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Experimental section
General methods
The chemical reagents were purchased from Aldrich or TCI. Commercially available
reagents were used without further purification. Anhydrous solvents for organic synthesis
were prepared by passing through a solvent purification tower. Thin-layer
chromatography (TLC) was performed on precoated silica gel 60F-254 glass plates. 1H
and 13C NMR spectra were measured with a Bruker DPX-300 and DPX-500. Coupling
constants (J value) are reported in Hertz. Mass spectral analysis was recorded with Jeol
JMS 700 and was reported in units of mass to charge (m/z). HRMS was performed at the
Korea Basic Science Center, Kyungpook National University.
Spectroscopic analysis
UV/Vis absorption spectra were obtained using a HP 8453 UV/Vis
spectrophotometer. Fluorescence spectra were recorded on a Photon Technical
International Fluorescence System with a 1 cm standard quartz cell. The concentration of
dyes were 10 M. The fluorescence quantum yield was determined by using rhodamine
6G as the references.
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Synthesis
7-(Dimethylamino)naphthalen-2-ol (10). A solution of dimethylamine (40% in H 2O,
10.5 mL, 93.5 mmol) was added to a mixture of 2,7-dihydroxynaphthalene (9) (3 g, 18.7
mmol), sodium metabisulfite (7.11 g, 37.4 mmol), and H2O (8 mL) in a seal-tube. The
reaction mixture was stirred at 150 C for 8 h. After being cooled to room temperature,
dichloromethane (100 mL) was added, and then the organic layer was washed with brine,
dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel
column chromatography (eluent: 20% EtOAc in hexane) to afford compound 10 as a
white solid (2.10 g, 60%). 1H NMR (CDCl3, 300 MHz, 293K): 7.667.59 (m, 2H),
7.057.02 (m, 1H), 6.966.95 (d, 1H), 6.856.82 (m, 1H), 6.786.77 (d, 1H), 5.10 (s, 1H),
3.05 (s, 6H). 13C NMR (CDCl3, 75 MHz, 293K): 153.88, 149.17, 136.24, 129.39,
128.61, 122.44, 114.22, 113.80, 108.02, 105.32, 40.91. HRMS (m/z): calcd [M+H]+ for
C12H13NO 187.0997; found, 187.0999.
[7-(Methoxymethoxy)naphthalen-2-yl]dimethylamine (11). To a solution of compound
10 (1 g, 5.34 mmol) in DMF (10 mL), was added NaH (235 mg, 5.875 mmol) at 15 C.
The resulting mixture was stirred at room temp until evolution of hydrogen gas subsided.
To the mixture was then added chloromethyl methyl ether (0.4 mL, 5.34 mmol) dropwise
at the same temperature. The mixture was stirred at room temp for 6 h, and then treated
with water (50 mL). The two layers were separated, and the aqueous layer was extracted
with EtOAc (3 50 mL). The combined organic extracts were washed with brine, dried
over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column
chromatography (eluent: 10% EtOAc in hexane) to afford compound 11 as a white solid
(988 mg, 80%). 1H NMR (CDCl3, 300 MHz, 293K): 7.75 (d, 1H), 7.72 (d, 1H), 7.40
7.39 (d, 1H), 7.157.08 (m, 2H), 6.986.97 (d, 1H), 5.39 (s, 2H), 3.69 (s, 3H), 3.11 (s,
6H). 13C NMR (CDCl3, 75 MHz, 293K): 155.75, 149.16, 136.23, 129.11, 128.55,
123.00, 114.99, 114.58, 108.69, 105.96, 94.62, 56.07, 40.83. HRMS (m/z): calcd [M+H]+
for C14H17NO2 231.1259; found, 231.1262.
6-Dimethylamino-3-(methoxymethoxy)naphthalene-2-carbaldehyde (12). To a
solution of compound 11 (2.26 g, 9.8 mmol) in Et2O (50 mL) cooled to 20 C was added
t-BuLi (1.7 M in pentane, 8.6 mL, 14.7 mmol) dropwise over a period of 30 min. The
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resulting mixture was stirred at 20 C for 2 h, which was treated with DMF (25 mL, 320
mmol) dropwise to give a pale brown suspension. The mixture was stirred at 20 C for
60 min, and then treated with 4 N HCl (10 mL) slowly under vigorous stirring. The
resulting two-phase system was stirred for 30 min. The organic layer was separated,
washed with 0.5 N HCl (200 mL), a saturated NaHCO 3 solution (200 mL), and brine (200
mL); it was dried (Na2SO4), and concentrated under reduced pressure to give a yellow
solid. The residue was purified by silica gel column chromatography (eluent: 10% EtOAc
in hexane) to afford compound 12 as a yellow solid (1.27 g, 50%).1H NMR (CDCl3, 300
MHz, 293K): 10.49 (s, 1H), 8.25 (s, 1H), 7.757.73 (d, 1H), 7.297.24 (d, 1H), 7.05
7.03 dd, 1H), 6.776.76 (d, 1H), 5.40 (s, 2H), 3.59 (s, 3H), 3.12 (s, 6H). 13C NMR
(CDCl3, 75 MHz, 293K): 189.61, 155.99, 150.71, 139.74, 131.16, 130.89, 122.26,
121.29, 114.76, 107.66, 104.30, 94.75, 56.39, 40.32. HRMS (m/z): calcd [M+H]+ for
C15H17NO3 259.1208; found, 259.1211.
6-Dimethylamino-3-(hydroxy)naphthalene-2-carbaldehyde (13). To a solution of
compound 12 (195 mg, 0.75 mmol) in isopropyl alcohol (10 mL) was added 5M HCl (5
mL). The reaction mixture was stirred at 60 C for 3 h. After being cooled to room
temperature, isopropyl alcohol was removed under reduced pressure, and then EtOAc
(100 mL) was added to the residue. The organic layer was washed with brine, dried over
anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column
chromatography (eluent: 20% EtOAc in hexane) to afford compound 13 as a yellow solid
(113 mg, 70%). 1H NMR (CDCl3, 300 MHz, 293K): 10.54 (s, 1H), 9.89 (s, 1H), 7.90 (s,
1H), 7.707.67 (d, 1H), 7.026.98 (m, 2H), 6.666.65 (d, 1H), 3.13 (s, 6H). 13C NMR
(CDCl3, 75 MHz, 293K): 195.26, 156.83, 151.39, 140.62, 137.75, 130.87, 120.63,
119.03, 114.18, 108.73, 103.22, 40.26. HRMS (m
/z
): calcd [M+H]
+
for C13H13NO2 215.0946; found, 215.0946.
6-Dimethylamino-3-(2-bromoethoxy)naphthalene-2-carbaldehyde (14). 1, 2dibromo
ethane (2.11 mL, 24.69 mmol) was added to a compound 13 (150 mg, 0.697 mmol) and
potassium hydroxide (144 mg, 2.56 mmol), tbutylammonium hydroxide (0.3 mL, 0.47
mmol). The reaction mixture was stirred at 50 C for 6 h. After being cooled to room
temperature, 1, 2dibromoethane was removed under reduced pressure, and then EtOAc
(20 mL) was added to the residue. The organic layer was washed with brine, dried over
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anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column
chromatography (eluent: 10% EtOAc in hexane) to afford compound 14 as a yellow solid
(166 mg, 74%). 1H NMR (CDCl3, 300 MHz, 293K): 10.53 (s, 1H), 8.26 (s, 1H), 7.65
7.72 (d, 1H), 7.056.94 (m, 2H), 6.746.73 (d, 1H), 4.514.47 (t, 2H), 3.793.75 (t, 2H),
3.13(s, 6H). 13C NMR (CDCl3, 75 MHz, 293K): 189.43, 156.96, 150.77, 139.67, 131.30,
130.84, 121.95, 120.93, 114.56, 104.99, 103.94, 67.94, 40.31, 28.82. HRMS (m/z): calcd
[M+H]+ for C15H16BrNO2 321.0364; found, 321.0366.
6-Dimethylamino-3-(vinyloxy)naphthalene-2-carbaldehyde (15). DMSO (5.6 mL) was
added to a compound 14 (113 mg, 0.35 mmol) and potassium tert-butoxide (39 mg, 0.347
mmol). The reaction mixture was stirred at room temperature for 3 h. After 3 h, EtOAc
(20 mL) was added to the residue. The organic layer was washed with brine, dried over
anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column
chromatography (eluent: 10% EtOAc in hexane) to afford compound 15 as a yellow solid
(50 mg, 59%). 1H NMR (CDCl3, 300 MHz, 293K): 10.43 (s, 1H), 8.28 (s, 1H), 7.78
7.75 (d, 1H), 7.107.05 (m, 2H), 6.846.75 (m, 2H), 4.944.88 (d, 1H), 4.624.60 (d, 1H),
3.13(s, 6H). 13C NMR (CDCl3, 75 MHz, 293K): 189.02, 155.51, 150.75, 147.99, 139.45,
131.28, 130.96, 122.06, 121.98, 115.21, 109.94, 104.05, 96.63, 40.29. HRMS (m/z): calcd
[M+H]+ for C15H15NO2 241.1103; found, 241.1105.
((6-(dimethylamino)-3-(vinyloxy)naphthalen-2-yl)methylene)dimethylmalonate (5).
To a stirred solution of compound 15 (50 mg, 0.21 mmol) and dimethylmalonate (0.026
mL, 0.24 mmol) in THF (2 mL) at room temp under argon was added piperidine (6.96 L,
0.074 mmol). The reaction mixture was allowed to reflux for 6 h. After being cooled to
room temperature, the solvent was evaporated under reduced pressure, and the resultingresidue was purified by silica gel column chromatography (eluent: 20% EtOAc in hexane)
to afford compound 5 as a red solid (28 mg, 38%).1H NMR (CDCl3, 500 MHz, 293K):
8.17 (s, 1H), 7.76 (s, 1H), 7.647.61 (d, 1H), 7.107.03 (m, 2H), 6.766.68 (m, 2H),
4.914.86 (dd, 1H), 4.594.56 (dd, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.07 (s, 6H). 13C NMR
(CDCl3, 75 MHz, 293K): 167.59, 164.93, 153.41, 149.99, 147.76, 138.92, 137.26,
129.97, 129.72, 124.20, 122.48, 119.44, 115.01, 109.82, 104.44, 96.70, 52.48, 40.42.
HRMS (m/z): calcd [M+H]+ for C20H21NO5 355.1420; found, 355.1421.
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((6-(dimethylamino)-3-(vinyloxy)naphthalen-2-yl)methylene)malononitrile (7). To a
stirred solution of compound 15 (16 mg, 0.066 mmol) and malononitrile (9 mg, 0.14
mmol) in ethanol (1 mL) at room temp under argon was added piperidine (60 L, 0.61
mmol). The reaction mixture was allowed to stir at room temp for 1 h. The solvent was
evaporated under reduced pressure, and the resulting residue was purified by silica gel
column chromatography (eluent: 30% EtOAc in hexane) to afford compound 7 as a red
solid (12 mg, 63%). 1H NMR (CDCl3, 500 MHz, 293K): 8.75 (s, 1H), 8.28 (s, 1H),
7.777.73 (d, 1H), 7.097.04 (m, 2H), 6.746.67 (m, 2H), 4.994.94 (dd, 1H), 4.684.66
(dd, 1H), 3.17 (s, 6H). 13C NMR (CDCl3, 75 MHz, 293K): 153.40, 153.30, 151.70,
147.32, 139.88, 131.73, 131.45, 122.19, 117.18, 115.55, 115.46, 114.40, 109.34, 104.18,
98.19, 40.49. HRMS (m/z): calcd [M+H]+ for C18H15N3O 289.1215; found, 289.1213.
8-Dimethylamino-2-oxo-2H-benzo[g]chromene-3-methylcarboxylate (6). To a solution
of compound 13 (128 mg, 0.595 mmol) and dimethylmalonate (73.65 L, 0.643 mmol) at
room temp under argon was added piperidine (18.56 L, 0.188 mmol), and the resulting
solution was stirred 70C for 3 h. Then, the solvent was evaporated under reduced
pressure, and the residue was purified by silica gel column chromatography (eluent: 20%
EtOAc in hexane) to afford compound 6 as a red solid (63 mg, 36%). 1H NMR (CDCl3,,
300 MHz, 293K): 8.65 (s, 1H), 7.95 (s, 1H), 7.807.77 (d, 1H), 7.42 (s, 1H), 7.187.14
(dd, 1H), 6.826.81 (d, 1H), 3.98 (s, 3H), 3.18 (s, 6H). 13C NMR (CDCl3,, 75 MHz,
293K): 164.36, 157.68, 151.80, 150.74, 149.95, 138.73, 130.95, 130.41, 123.51, 116.09,
114.38, 114.19, 109.53, 103.89, 52.67, 40.29. HRMS (m/z): calcd [M+H]+ for C16H13N3O
297.1001; found, 297.0997.
8-Dimethylamino-2-imino-2H-benzo[g]chromene-3-carbonitrile (8). To a solution ofcompound 13 (27 mg, 0.125 mmol) and malononitrile (66 mg, 0.125 mmol) in ethanol (2
mL) at room temp under argon was added piperidine (124 L, 1.25 mmol), and the
resulting solution was stirred at room temp for 1 h. Then, the solvent was evaporated
under reduced pressure, and the residue was purified by silica gel column
chromatography (eluent: 40% EtOAc in hexane) to afford compound 8 as a red solid
(29.7 mg, 90%). 1H NMR (DMSO, 300 MHz, 293K): 8.75 (s, 1H), 8.30 (s, 1H), 7.90 (s,
1H), 7.797.76 (d, 1H), 7.247.15 (m, 2H), 6.86 (s, 1H), 3.08 (s, 6H). 13C NMR (DMSO,
75 MHz, 293K): 152.11, 150.45, 150.21, 146.82, 137.81, 130.38, 130.20, 122.28,
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115.91, 115.68, 113.37, 108.20, 103.83, 100.56. HRMS (m/z): calcd [M+H]+ for
C16H13N3O 263.1059; found, 263.1058.
Spectroscopic data for the S/N 3
550 600 650 700 7500
1
2
3
4
5Vinyl ether 5 +HgCl
2(18 ppb)
IF
nm
(a)
Vinyl ether 5
550 600 650 700 7503
4
5
6
Vinyl ether 7
Vinyl ether 7 +HgCl2(50 ppb)
(b)
IF
nm
Figure S1. Fluorescence spectra of vinyl ether5 and 7 (3 M) upon addition of HgCl2
showing a signaltonoise ration is more than three: (a) vinyl ether 5 with HgCl2 (18
ppb) obtained after 30 min with excitation wavelength at 460 nm; (b) vinyl ether7 with
HgCl2 (50 ppb) obtained after 120 min, with excitation wavelength at 446 nm.
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NMR spectra for the compounds synthesized
Compound 10
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Compound 11
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Compound 12
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Compound 13
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Compound 14
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Compound 15
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Compound 5
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Compound 7
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Compound 6
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Compound 8
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