Syn of π-Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for...

7/28/2019 Syn of -Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for Hg Ions

1/17

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


2/17

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.

- S1 -


3/17

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

- S2 -


4/17

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


- S3 -


5/17



(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




(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.

- S4 -


6/17

((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,

- S5 -


7/17

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.

- S6 -


8/17

NMR spectra for the compounds synthesized

Compound 10

- S7 -


9/17

Compound 11

- S8 -


10/17

Compound 12

- S9 -


11/17

Compound 13

- S10 -


12/17

Compound 14

- S11 -


13/17

Compound 15

- S12 -


14/17

Compound 5

- S13 -


15/17

Compound 7

- S14 -


16/17

Compound 6

- S15 -


17/17

Compound 8

- S16 -

Syn of π-Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for...

Documents

Transcript of Syn of π-Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for...