Supporting Information

 Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2012

Synthesis of p-Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for Mercury Ions
Inae Kim, Dokyoung Kim, Sunderraman Sambasivan, and Kyo Han Ahn*[a]
ajoc_201200034_sm_miscellaneous_information.pdf

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 and
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prepared

by

passing

through

solvent

purification

tower.

Thin-layer

chromatography (TLC) was performed on precoated silica gel 60F-254 glass plates. 1H C 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 2 O, 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 H 2 O (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 Na 2 SO 4 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 (CDCl 3 , 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).
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C NMR (CDCl 3 , 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 C 12 H 13 NO 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 Na 2 SO 4 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 (CDCl 3 , 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).
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C NMR (CDCl 3 , 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 C 14 H 17 NO 2 231.1259; found, 231.1262. 6-Dimethylamino-3-(methoxymethoxy)naphthalene-2-carbaldehyde (12). To a

solution of compound 11 (2.26 g, 9.8 mmol) in Et 2 O (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 (Na 2 SO 4 ), 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 (CDCl 3 , 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).
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C NMR

(CDCl 3 , 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 C 15 H 17 NO 3 259.1208; 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 Na 2 SO 4 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 (CDCl 3 , 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).
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C NMR

(CDCl 3 , 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 C 13 H 13 NO 2 215.0946; 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 Na 2 SO 4 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 (CDCl 3 , 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 (CDCl 3 , 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 C 15 H 16 BrNO 2 321.0364; 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 Na 2 SO 4 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 (CDCl 3 , 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 (CDCl 3 , 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 C 15 H 15 NO 2 241.1103; 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 resulting residue 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 (CDCl 3 , 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 (CDCl 3 , 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 C 20 H 21 NO 5 355.1420; 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 (CDCl 3 , 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).
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C NMR (CDCl 3 , 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 C 18 H 15 N 3 O 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 (CDCl 3 ,, 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).
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C NMR (CDCl 3 ,, 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 C 16 H 13 N 3 O 297.1001; found, 297.0997. 8-Dimethylamino-2-imino-2H-benzo[g]chromene-3-carbonitrile (8). To a solution of compound 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).
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C 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 C 16 H 13 N 3 O 263.1059; found, 263.1058.

Spectroscopic data for the S/N 3

(a)
5
Vinyl ether 5 + HgCl2 (18 ppb)

(b)
6

4 3
5

Vinyl ether 7 + HgCl2 (50 ppb)

IF

2
Vinyl ether 5

IF
4
Vinyl ether 7

1 0
550 600 650 700 750

3
550 600 650 700 750

nm

nm

Figure S1. Fluorescence spectra of vinyl ether 5 and 7 (3 M) upon addition of HgCl 2 showing a signaltonoise ration is more than three: (a) vinyl ether 5 with HgCl 2 (18 ppb) obtained after 30 min with excitation wavelength at 460 nm; (b) vinyl ether 7 with HgCl 2 (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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