A new synthesis of symmetric boraindacene (BODIPY) dyes

Article abstract of DOI:10.1039/b810503k

BODIPY dyes were synthesized from pyrrole-2-carbaldehyde derivatives in high yields; this constitutes a new approach to this dye framework. The Royal Society of Chemistry.

Full text of DOI:10.1039/b810503k

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SUPPORTING INFORMATION
A New Synthesis of Symmetric Boraindacene
(BODIPY) Dyes
Liangxing Wu and Kevin Burgess*
Texas A & M University, Chemistry Department, Box 30012, College Station, Texas 77842, USA
Email: burgess@tamu.edu
TABLE OF CONTENTS
General Experimental Methods
Preparation of Compounds 1a-h
Preparation of Compounds 2a-h
NMR and MS Study of the Self-condensation Reaction
References
S2
S3-S6
S7-S10
S11-S13
S14
Copies of 1H, 13C and 19F NMR Spectra
S15-S33
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General Experimental Methods
All reactions were carried out under an atmosphere of dry nitrogen. Glassware was oven-
dried prior to use. Unless otherwise indicated, common reagents or materials were
obtained from commercial source and used without further purification. All the solvents
were used after appropriate distillation or purification.
Flash column chromatography was performed using silica gel 60 (230-400 mesh).
Analytical thin layer chromatography (TLC) was carried out on Merck silica gel plates
with QF-254 indicator and visualized by UV. Fluorescence spectra were obtained on a
Varian Cary Eclipse fluorescence spectrophotometer at room temperature. Absorbance
spectra were obtained on a Varian 100 Bio UV-Vis spectrophotometer at room
temperature.
1H and 13C spectra were recorded on a Varian 300 (300 MHz 1H; 75 MHz 13C) or Varian
1
500 (500 MHz H; 125 MHz 13C) spectrometer at room temperature. Chemical shifts
1
13
were reported in ppm relative to the residual CDCl3 (ꢀ 7.24 ppm H; ꢀ 77.0 ppm C).
1
19F NMR were acquired on a Varian 300 (300 MHz H; 282 MHz 19F) spectrometer.
CFCl3 was used as an external reference for the 19F NMR spectra. H3PO4 was used as an
external reference for the 31P NMR spectra. Coupling constants (J) were reported in
Hertz.
Photophysical Properties and Determination of Quantum Yields
Steady-state fluorescence spectroscopic studies were performed on a Cary Eclipse
fluorometer. The slit width was 5 nm for both excitation and emission. The relative
quantum yields of the samples were obtained by comparing the area under the corrected
emission spectrum of the test sample with that of a standard. The quantum efficiencies of
fluorescence were obtained from multiple measurements (N=3) with the following
equation:
2
2
ꢁx = ꢁst (Ix/Ist) (Ast/Ax) (ꢂx /ꢂst )
Where ꢁst is the reported quantum yield of the standard, I is the area under the emission
spectra, A is the absorbance at the excitation wavelength and ꢂ is the refractive index of
the solvent used, measured on a pocket refractometer from ATAGO. X subscript denotes
test sample, and st denotes standard.
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(i) POCl3, DMF
ClCH2CH2Cl
CHO
N
N
H
(ii) NaOAc, H2O
H
1a
Typical Procedure for the Synthesis of Pyrrole-2-carboxaldehyde1
POCl3 (5.9 mL, 63.0 mmol) was added dropwise to DMF (4.9 mL, 63.0 mmol) at 0 oC.
The mixture was warmed to room temperature and stirred for 15 min. The ice bath was
replaced to cool the mixture back to 0 °C, then 30 mL of 1,2-dichloroethane was added to
the mixture. A solution of 2,4-dimethyl pyrrole (5.0 g, 52.5 mmol) in 50 mL of 1,2-
dichloroethane was added dropwise over 20 min at 0oC. After the addition was complete,
the reaction mixture was refluxed for 30 min and then cooled to room temperature. A
solution of NaOAc (23.7 g, 289 mmol) in 100 mL of water was added. The reaction
mixture was again refluxed for 30 min. The cooled mixture was washed with water (1 x
100 mL), saturated Na2CO3 solution (2 x 50 mL) and brine (1 x 50 mL). The organic
layer was dried over Na2SO4 and the solvents were removed under reduced pressure. The
residue was purified by flash chromatography (SiO2, 20 % EtOAc/Hexanes) to afford the
1
pure product as a light yellow solid (5.8 g, 89 %). H NMR (300 MHz, CDCl3) ꢀ 9.96 (br,
1H), 9.44 (s, 1H), 5.84 (d, 1H, J = 2.6 Hz), 2.30 (s, 3H), 2.28 (s, 3H); 13C NMR (75 MHz,
CDCl3) ꢀ 175.9, 138.4, 134.7, 128.7, 112.0, 13.2, 10.6.
1b-1h were prepared using similar method as described for 1a.
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CHO
N
H
1b
4,5-Dihydro-1H-benzo[g]indole-2-carbaldehyde (1b)
1
Yellow solid (910 mg, 85 %). H NMR (300 MHz, CDCl3) ꢀ 10.74 (br, 1H), 9.48 (s, 1H),
7.71 (d, 1H, J = 7.4 Hz), 7.32-7.19 (m, 3H), 6.84 (d, 1H, J = 2.0 Hz), 2.96 (t, 2H, J = 7.5
13
Hz), 2.78 (t, 2H, J = 7.5 Hz); C NMR (75 MHz, CDCl3) ꢀ 178.4, 137.2, 136.7, 132.5,
128.5, 128.0, 127.4, 127.0, 122.7, 121.7, 120.6, 29.6, 21.3. MS (ESI) m/z calcd for
(M+H)+ C13H12NO 198.09; found 198.09.
CHO
N
H
MeO
1c
7-Methoxy-4,5-dihydro-1H-benzo[g]indole-2-carbaldehyde (1c)
1
Light green solid (345 mg, 100 %). H NMR (300 MHz, CDCl3) ꢀ 10.59 (br, 1H), 9.39
(s, 1H), 7.61 (d, 1H, J = 8.2 Hz), 6.82-6.78 (m, 3H), 3.81 (s, 3H), 2.91 (t, 2H, J = 7.5 Hz),
2.74 (t, 2H, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3) ꢀ 177.8, 159.6, 139.3, 137.1, 132.0,
123.1, 121.4, 120.9, 120.5, 114.5, 112.0, 55.3, 30.0, 21.3. MS (ESI) m/z calcd for
(M+H)+ C14H14NO2 228.10; found 228.10.
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Ph
CHO
N
Ph
H
1d
3,5-Diphenyl-1H-pyrrole-2-carbaldehyde (1d)
1
White solid (290 mg, 86 %). H NMR (300 MHz, CDCl3) ꢀ 10.04 (br, 1H), 9.63 (s, 1H),
13
7.70-7.67 (m, 2H), 7.55-7.52 (m, 2H), 7.48-7.33 (m, 6H), 6.72 (d, 1H, J = 2.8 Hz); C
NMR (75 MHz, CDCl3) ꢀ 179.4, 139.1, 138.5, 133.5, 130.4, 129.2, 129.1, 129.0, 128.8,
128.7, 127.9, 125.3, 109.0. MS (ESI) m/z calcd for (M+H)+ C17H14NO 248.11; found
248.11.
Et
CHO
N
H
1e
4-Ethyl-3,5-dimethyl-1H-pyrrole-2-carbaldehyde (1e)
1
Brown solid (1.1 g, 85 %). H NMR (300 MHz, CDCl3) ꢀ 10.08 (br, 1H), 9.42 (s, 1H),
2.36 (q, 2H, J = 7.5 Hz), 2.25 (s, 3H), 2.24 (s, 3H), 1.03 (t, 3H, J = 7.5 Hz); 13C NMR (75
MHz, CDCl3) ꢀ 175.5, 135.9, 132.2, 127.8, 124.8, 16.9, 15.0, 11.4, 8.7. MS (ESI) m/z
calcd for (M+H)+ C9H14NO 152.11; found 152.10.
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CHO
N
H
Et
1f
5-Ethyl-1H-pyrrole-2-carbaldehyde (1f)
1
Red solid (1.0 g, 78 %). H NMR (300 MHz, CDCl3) ꢀ 10.58 (br, 1H), 9.34 (s, 1H),
6.92-6.90 (m, 1H), 6.09-6.07 (m, 1H), 2.72 (q, 2H, J = 7.5 Hz), 1.26 (t, 3H, J =7.5 Hz);
13C NMR (75 MHz, CDCl3) ꢀ 178.2, 145.4, 131.8, 123.4, 108.8, 21.0, 13.1. MS (ESI)
m/z calcd for (M+H)+ C7H10NO 124.08; found 124.07.
CHO
N
H
1g
4,5,6,7-Tetrahydro-1H-indole-2-carbaldehyde (1g)
1
Yellow solid (960 mg, 78 %). H NMR (300 MHz, CDCl3) ꢀ 10.21 (br, 1H), 9.29 (s, 1H),
6.69 (d, 1H, J = 2.4 Hz), 2.67 (t, 2H, J = 6.1 Hz), 2.51 (t, 2H, J = 6.0 Hz), 1.84-1.69 (m,
13
4H); C NMR (75 MHz, CDCl3) ꢀ 177.9, 138.9, 131.2, 121.2, 121.1, 23.3, 23.0, 22.6
(2C: 22.61, 22.59). MS (ESI) m/z calcd for (M+H)+ C9H12NO 150.09; found 150.09.
O
CHO
N
H
1h
4-Acetyl-3,5-dimethyl-1H-pyrrole-2-carbaldehyde (1h)
1
Light yellow solid (481 mg, 40 %). H NMR (300 MHz, CDCl3) ꢀ 10.20 (br, 1H), 9.62
13
(s, 1H), 2.58 (s, 3H), 2.56 (s, 3H), 2.45 (s, 3H); C NMR (75 MHz, CDCl3) ꢀ 194.9,
177.6, 143.1, 134.6, 128.2, 123.7, 31.3, 15.2, 11.4. MS (ESI) m/z calcd for (M+H)+
C9H12NO2 166.09; found 166.09.
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(i) POCl3, CH2Cl2
0 - 25 oC, 12 h
CHO
N
N
N
H
B
(ii) Et3N, BF3OEt2
25 oC, 12 h
F2
1a
2a
Typical Procedure for the Synthesis of Symmetric BODIPYs
3,5-Dimethyl-1H-pyrrole-2-carbaldehyde 1a (246 mg, 2 mmol) was dissolved in 10 mL
o
CH2Cl2 and POCl3 (0.22 mL, 2.4 mmol) was added dropwise over 1 min at 0 C. The
solution was warmed to room temperature slowly and stirred for 12 h. The mixture was
o
cooled to 0 C and Et3N (1.4 mL, 10 mmol) was added dropwise over 5 min. After
stirring for 15 min, BF3OEt2 (2.0 mL, 16 mmol) was added dropwise to the solution over
5 min. The reaction mixture was warmed to room temperature and stirred for 12 h. The
mixture was passed through a short pad of silica gel eluting with CH2Cl2 to remove the
polar impurities. The solvents were removed under reduced pressure. The residue was
dissolved in CH2Cl2 and water was added, and the mixture was stirred at room
temperature overnight. (to decompose excess BF3OEt2 and other impurities).
The
organic layer was washed with water, brine and dried over Na2SO4. The solvent was
removed under reduced pressure and the residue was purified by flash chromatography (5
1
% EtOAc/hexanes) to give the pure product 2a (229 mg, 92 %) as a red solid. H NMR
13
(CDCl3, 500 MHz) ꢀ 7.01 (s, 1H), 6.02 (s, 2H), 2.51 (s, 6H), 2.22 (s, 6H); C NMR
(CDCl3, 125 MHz) ꢀ 156.7, 141.2, 133.4, 120.0, 119.0, 14.6, 11.2; 19F NMR (CDCl3, 282
MHz) ꢀ 30.68 (q, J = 33.5 Hz). HRMS (ESI) m/z calcd for (M+H)+ C13H16BF2N2
249.1375; found 249.1373.
2b-2h were prepared using similar methods as described for 2a.
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N
N
B
F2
2b
BODIPY 2b
1
Green solid (360 mg, 91 %). H NMR (300 MHz, CDCl3) ꢀ 8.73 (d, 2H, J = 8.0 Hz),
7.45-7.39 (m, 2H), 7.33-7.23 (m, 4H), 6.98 (s, 1H), 6.76 (s, 2H), 2.90 (t, 4H, J = 7.0 Hz),
2.72 (t, 4H, J = 7.0 Hz); 13C NMR (75 MHz, CDCl3) ꢀ 152.6, 140.5, 136.3, 133.1, 129.7,
128.3, 128.2, 128.1, 127.5, 124.8, 124.1, 30.5, 22.3; 19F NMR (CDCl3, 282 MHz) ꢀ 39.67
(q, J = 33.6 Hz). MS (MALDI) m/z calcd for M+ C25H19BF2N2 396.16; found 395.88.
N
N
B
F2
MeO
OMe
2c
BODIPY 2c
1
Blue solid (194 mg, 85 %). H NMR (300 MHz, CDCl3) ꢀ 8.69 (d, 2H, J = 9.0 Hz), 6.95
(dd, 2H, J = 9.0, 2.8 Hz), 6.86 (s, 1H), 6.78 (d, 2H, J = 2.8 Hz), 6.69 (s, 2H), 3.85 (s, 6H),
13
2.87 (t, 4H, J = 6.9 Hz), 2.70 (t, 4H, J = 6.9 Hz); C NMR (75 MHz, CDCl3) ꢀ 160.6,
151.9, 142.8, 135.9, 131.9, 129.9 (t, J = 11.1 Hz), 124.2, 122.2, 121.4, 114.3, 112.4, 55.3,
19
30.8, 22.3; F NMR (CDCl3, 282 MHz) ꢀ 39.15 (q, J = 33.6 Hz). MS (MALDI) m/z
calcd for M+ C27H23BF2N2O2 456.18; found 455.88.
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Ph
Ph
Ph
Ph
N
N
B
F2
2d
BODIPY 2d
1
Green solid (52 mg, 21 %). H NMR (300 MHz, CDCl3) ꢀ 7.98-7.95 (m, 4H), 7.54-7.42
(m, 17H), 6.73 (s, 2H); 13C NMR (75 MHz, CDCl3) ꢀ 157.8, 145.7, 134.4, 133.3, 132.3,
19
129.7, 129.4 (t, J = 3.5 Hz), 129.1, 128.7 (2C), 128.2, 127.7, 119.0; F NMR (CDCl3,
282 MHz) ꢀ 45.58 (q, J = 33.5 Hz). MS (MALDI) m/z calcd for M+ C33H23BF2N2 496.19;
found 495.93.
Et
Et
N
N
B
F2
2e
BODIPY 2e
1
Organge solid (227 mg, 75 %). H NMR (300 MHz, CDCl3) ꢀ 6.92 (s, 1H), 2.47 (s, 6H),
13
2.36 (q, 4H, J = 7.5 Hz), 2.14 (s, 6H), 1.04 (t, 6H, J = 7.5 Hz); C NMR (75 MHz,
CDCl3) ꢀ 154.6, 136.6, 132.4, 131.6, 118.5, 17.3, 14.6, 12.5, 9.4; 19F NMR (CDCl3, 282
MHz) ꢀ 30.93 (q, J = 33.6 Hz). MS (MALDI) m/z calcd for M+ C17H23BF2N2 304.19;
found 303.96.
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N
N
B
F2
Et
Et
2f
BODIPY 2f
1
Orange solid (70 mg, 28 %). H NMR (300 MHz, CDCl3) ꢀ 7.05 (s, 1H), 6.94 (d, 2H, J =
4.2 Hz), 6.32 (d, 2H, J = 4.2 Hz), 3.02 (q, 4H, J = 7.5 Hz), 1.31 (t, 6H, J = 7.5 Hz); 13C
NMR (75 MHz, CDCl3) ꢀ 164.1, 134.4, 130.1, 127.1, 117.4, 22.0, 12.6; 19F NMR (CDCl3,
282 MHz) ꢀ 31.94 (q, J = 33.4 Hz). MS (MALDI) m/z calcd for M+ C13H15BF2N2 248.13;
found 247.85.
N
N
B
F2
2g
BODIPY 2g
1
Red solid (65 mg, 22 %). H NMR (300 MHz, CDCl3) ꢀ 6.89 (s, 1H), 6.59 (s, 2H), 3.01
13
(t, 4H, J = 6.2 Hz), 2.52 (t, 4H, J = 6.2 Hz), 1.86-1.78 (m, 4H), 1.76-1.68 (m, 4H); C
19
NMR (75 MHz, CDCl3) ꢀ 158.0, 134.0, 129.3, 125.9, 125.3, 24.7, 23.1, 22.8, 22.3; F
NMR (CDCl3, 282 MHz) ꢀ 27.29 (q, J = 33.5 Hz). MS (MALDI) m/z calcd for M+
C17H19BF2N2 300.16; found 299.91.
O
O
N
N
B
F2
2h
BODIPY 2h
Messy reaction, obtained complex mixtures.
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+
O-
CHO
POCl3, CH2Cl2
P Cl
Cl
NH NH
O
NH
25 oC, 12 h
1a
3
NMR and MS Study of the Self-condensation Reaction:
Compound 1a (25 mg, 0.2 mmol) was dissolved in 1 mL of CDCl3 and then POCl3 (50
13
μL) was added. The reaction was monitored by 1H, C and 31P over 10 min intervals at
room temperature.
d
1H NMR
b
c
d
+
e
e
c
NH NH
a
a
b
3
31P NMR
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1H NMR
12h
13C NMR
12h
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+
MS
NH NH
3
O-
MS
P Cl
Cl
O
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References:
1.
R. Silverstein, E. Ryskiewicz and C. Willard, Org. Synth., 1963, 4, 831-833.
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1H NMR (CDCl3)
CHO
N
H
1a
13C NMR (CDCl3)
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CHO
1H NMR (CDCl3)
N
H
1b
13C NMR (CDCl3)
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1H NMR (CDCl3)
CHO
N
H
MeO
1c
13C NMR (CDCl3)
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Ph
1H NMR (CDCl3)
CHO
N
H
Ph
1d
13C NMR (CDCl3)
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1H NMR (CDCl3)
Et
CHO
N
H
1e
13C NMR (CDCl3)
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1H NMR (CDCl3)
CHO
N
Et
H
1f
13C NMR (CDCl3)
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CHO
1H NMR (CDCl3)
N
H
1g
13C NMR (CDCl3)
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Ac
1H NMR (CDCl3)
CHO
N
H
1h
13C NMR (CDCl3)
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1H NMR (CDCl3)
N
N
B
F2
2a
13C NMR (CDCl3)
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19F NMR (CDCl3)
N
N
B
F2
2a
N
N
B
19F NMR (CDCl3)
F2
2b
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1H NMR (CDCl3)
N
N
B
F2
2b
13C NMR (CDCl3)
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N
N
B
1H NMR (CDCl3)
F2
MeO
OMe
2c
13C NMR (CDCl3)
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N
N
B
19F NMR (CDCl3)
F2
MeO
OMe
2c
Ph
Ph
19F NMR (CDCl3)
N
N
B
F2
Ph
Ph
2d
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Ph
Ph
Ph
Ph
N
N
B
1H NMR (CDCl3)
F2
2d
13C NMR (CDCl3)
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1H NMR (CDCl3)
N
N
B
F2
2e
13C NMR (CDCl3)
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19F NMR (CDCl3)
N
N
B
F2
2e
19F NMR (CDCl3)
N
N
B
F2
2f
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