Eighteen BODIPYs (1-18) were synthesized during the course of this study (Schemes 1-18). BODIPY core compounds (1-9) have been reported previously [11, 34-37, 121-123], while dyes (10-18) are novel. BODIPY core dyes have been used as precursors to prepare more complex 3,5-distyrl-substituted structures (10), (11), (12), (13), (14), (16), and (18) for use in the NLO studies described in Chapter 4. BODIPY cores (1), (4) and (6) were also used in the NLO studies, while (5) was conjugated to UCNPs in the work described in Chapter 5. BODIPYs (15) and (17) were only used as precursors to prepare final target compounds (16) and (18). Since the yields of the Knoevenagel condensation reactions involved were quite small, it was decided to only fully characterize BODIPYs (16) and (18).
2.4.1 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s- indacene (1)
The synthesis of the ester functionalized BODIPY was carried out in a single pot reaction. 2,4-Dimethylpyrrole (0.558 ml) and 4-methyl ester benzaldehyde (0.3 g) were added to dry DCM (30 ml). To this mixture, 3 drops of TFA were added, and the reaction was left to stir for 4 hours under Ar gas. Consumption of the 4-methyl ester benzaldehyde was monitored by thin layer chromatography (TLC) after which the temperature was lowered to 0°C, and p-
47
chloranil (0.539 g) was added. The solution was left to stir for 30 min. The temperature was lowered again to 0°C followed by the drop-wise addition of TEA (1.78 ml) and BF3·Et2O
(2.52 ml). After overnight stirring, the resulting solution was washed with deionized water and extracted with DCM.
Scheme 2.01 The acid catalyzed synthesis of 4,4′-difluoro-8-(4-methyl ester phenyl)- 1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (1) via the classic “1-pot 3- step” method, highlighting the structural changes that occur at each step.
Product (1) separated by flash column chromatography with ethyl acetate/hexane (1:4) as the eluent to obtain 72% yield. UV-Vis (DCM): 503 nm, IR (cm−1): 2957, 2945 (C-H), 1713 (C=O), 1278, 1186, 1066 (CN) 1H NMR (600 MHz, CDCl3) δ (ppm): 8.19 (d, 2H), 7.40 (d,
2H), 5.99 (s, 2H), 3.97 (s, 3H), 2.56 (s, 6H), 1.31 (s, 6H). Elemental Analysis for C21H21BF2N2O2: Expected: C, 65.99; H, 5.54; N, 7.33; found: C 65.42, H 5.01, N 6.97
2.4.2 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-2,6-diiodo-4-bora- 3a,4a-diaza-s-indacene (2)
200 mg of (1) and NIS (2.5 mole eq.) were dissolved in DCM (100 mL). The mixture was left to stir under Ar/N2 at room temperature for 2 h. The reaction was quenched with water and
48
Scheme 2.02 Synthesis of 4,4′-difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-2,6- diiodo-4-bora-3a,4a-diaza-s-indacene (2) via nucleophilic addition of iodine to BODIPY.
Product (2) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: deep red crystalline powder at 86% yield. UV-Vis (DCM): 539 nm, IR (cm−1): 2924, 2838 (C-H), 1715 (C=O), 1274, 1276, 1176,991 (CN), 520 (C-I). 1H NMR (600 MHz, CDCl3) δ (ppm): 8.22 (d, 2H), 7.37 (d, 2H), 3.99 (s, 6H), 2.64 (s, 3H), 1.34 (s,
6H). MALDI-TOF (M+H): Calc. for C21H19BF2I2N2O2: Expected: 633.96 amu; found:
634.40 amu.
2.4.3 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-2,6-dibromo-4-bora- 3a,4a-diaza-s-indacene (3)
260 mg of (1) and NBS (2.5 mole eq.) were dissolved in DCM (100 mL). The mixture was left to stir under Ar/N2 at room temperature for 2 h. The reaction was quenched with water
49
Scheme 2.03 Synthesis of 4,4′-difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-2,6- dibromo-4-bora-3a,4a-diaza-s-indacene (2) via nucleophilic addition of bromine to BODIPY (1).
Product (3) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: deep red crystalline powder at 70% yield. UV-Vis (DCM): 539 nm, IR (cm−1): 2920, 2834 (C-H), 1716 (C=O), 1274, 1173, 1020 (CN), 550 (C-Br). 1H NMR (600 MHz, CDCl3) δ (ppm): 8.21 (s, 2H), 7.44 (s, 2H), 3.99 (s, 3H), 2.58 (s, 3H), 1.38 (s,
9H). MALDI-TOF (M+H): Calc. for C21H19BF2Br2N2O2: Expected: 539.99 amu; found:
539.31 amu.
2.4.4 4,4′-Difluoro-8-(4-dimethylamino phenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-
s-indacene (4)
The synthesis of the dimethylamino-functionalized BODIPY was carried out in a single pot reaction. 2,4-Dimethylpyrrole (0.613 ml) and 4-dimethylaminobenzaldehyde (0.3 g) were added to dry DCM (30 ml). To this mixture, 3 drops of TFA were added, and the reaction was left to stir for 4 hours under Ar gas. Consumption of the 4-methyl ester benzaldehyde was monitored by TLC after which the temperature was lowered to 0°C, and p-chloranil (0.678 g) was added. The solution was left to stir for 30 min. The temperature was lowered again to 0°C followed by the drop-wise addition of TEA (1.96 ml) and BF3·Et2O (2.278 ml).
50
After overnight stirring, the resulting solution was washed with deionized water and extracted with DCM.
Scheme 2.04 The acid catalyzed synthesis of 4,4′-difluoro-8-(4-dimethylaminophenyl)-
1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (4) via the classic “1-pot 3- step” method.
Product (4) was separated with flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: deep red crystalline powder at 48% yield. IR (cm−1): 2920, 2849, 2808 (C-H), 1303, 1184, 1050 (C-N). 1H NMR (600 MHz, CDCl3) δ (ppm): 7.09 (d,
2H), 6.86 (d, 2H), 5.97 (s, 2H), 3.05 (s, 6H), 2.60 (s, 6H), 1.47 (s, 6H). Elemental Analysis for C21H24BF2N3: Expected: C, 68.68; H, 6.59; B; N, 11.44. Found C, 68.23, H, 6.37, N,
11.38.
2.4.5 4,4′-Difluoro-8-(4-carboxyphenyl)-1,3,5,7-tetramethyl-2,6-diiodo-4-bora-3a,4a- diaza-s-indacene (5)
To a solution of the BODIPY (2) (0.060 g, 0.068 mmol), in EtOH (2mL) and H2O (1mL),
was added NaOH (0.027 g, 0.68 mmol). The mixture was stirred at room temperature for 10 hours until complete consumption of the starting material was observed by TLC using (H2O/EtOH, 1:4). The solution was then added HCl (10%) until neutral, then evaporated.
51
Scheme 2.05 Synthesis of 4,4′-difluoro-8-(4-carboxyphenyl)-1,3,5,7-tetramethyl-2,6-diiodo- 4-bora-3a,4a-diaza-s-indacene (5) via hydrolysis of BODIPY (1).
Product (5) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark red crystalline powder at 90% yield. IR (cm−1): 3171 (OH), 2928, 2849, 2808 (C-H stretch), 1682 (C=O), 1300, 1170, (C-O), 1535 (O-H). 1H NMR (600 MHz, DMSO) δ (ppm): 11.09 (s, 1H), 8.11 (d, 2H), 7.57 (d, 2H), 3.35 (s, 6H), 2.56 (s, 6H). MALDI-TOF (M+H): Calc. for C20H17BF2I2N2O2: Expected: 619.94 amu; found: 620.36
amu.
2.4.6 4,4′-Difluoro-8-(4-phenoxyphthalonitrile)-1,3,5,7-tetramethyl-2,6-4-bora-3a,4a- diaza-s-indacene (6)
4-(4-Formylphenoxy)phthalonitrile and 4-(4-meso-BODIPY-phenoxy)phthalonitrile was synthesized as reported in [123] with minor modifications.
4-(4-Formylphenoxy)phthalonitrile
4-Nitrophthalonitrile (1.00 g, 5.78 mmol) and 4-hydroxybenzaldehyde (0.71 g, 5.78 mmol) were dissolved in DMF (15 mL) and degassed with argon in a dual-bank vacuum-gas manifold system. After stirring for 15 min, finely ground anhydrous potassium carbonate (2 g, 14.45 mmol) was added portion-wise within 2 h period with the efficient stirring. The progress of the reaction was monitored by TLC using DCM / hexane (3/1) solvent system.
52
The stirring of the suspension was maintained at room temperature for a further 24 h. The resulting mixture was poured into an iced-water/acetone mixture (5/1: v/v). The precipitate was collected by filtration, washed several times with ethanol, and dried in vacuum.
The synthesis of the phthalonitrile functionalized BODIPY was synthesized in a similar manner to that described in the literature [123] with minor modifications. 2,4-dimethylpyrrole (0.613 ml) and 4-(4-formylphenoxy)phthalonitrile (0.3 g) were added to dry DCM (30 ml). To this mixture, 3 drops of TFA were added, and the reaction was left to stir for 4 hours under Ar gas. Consumption of the 4-methyl ester benzaldehyde was monitored by TLC after which the temperature was lowered to 0°C, and p-chloranil (0.678 g) was added. The solution was left to stir for 30 min. The temperature was lowered again to 0°C followed by the drop- wise addition of TEA (1.96 ml) and BF3·Et2O (2.278 ml). After overnight stirring, the
resulting solution was washed with deionized water and extracted with DCM.
Scheme 2.06 The acid catalyzed synthesis of 4,4′-difluoro-8-(4-phenoxyphthalonitrile)-
1,3,5,7-tetramethyl-2,6-4-bora-3a,4a-diaza-s-indacene (6) via the classic “1- pot 3-step” method, highlighting the structural changes that occur at each step.
53
The phthalonitrile product was separated by flash chromatography using ethyl acetate/petroleum ether (1:2) as an eluent. The desired pure compound was obtained as a yellowish powder in sufficient purity. Yield 90 %. IR (cm−1): 3105-3041(C-H), 2805–2764 (O-C-H), 2237 (C≡N), 1691 (C=O), 1587–1506 (C=C), 1489–1309 (C-C), 1255 (Ar-O-Ar), 1209, 1155, 1111, 1087, 950, 858, 839, 821. 1H-NMR (CDCl3) δ (ppm): 10.03 (s, 1H,
OCH)), 8.01 (d, 2H, ArH), 7.81 (d, 1H, ArH), 7.41–7.34(m, 2H, ArH), 7.23 (d, 2H, ArH).
Product (6) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: red crystalline powder at 74 % yield. IR (cm−1): 3115–3038 (C-H), 2232 (C≡N), 1685 (C=N), 1590–1537 (C=C),1250 (Ar-O-Ar ). 1 H-NMR (CDCl3) δ (ppm): 7.97 (s, 2H), 7.83 (d, 1H), 7.69 (d, 2H), 7.43–7.37 (m, 2H), 7.27–7.25 (m, 2H), 6.97 (d, 2H), 6.60 (d, 2H). 2.4.7 4,4′-Difluoro-8-(4-hydroxyphenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s- indacene (7)
The synthesis of the hydroxyl functionalized BODIPY was carried out in a single pot reaction as reported [121] with minor modifications. 2,4-Dimethylpyrrole (0.750 ml) and 4- hydroxybenzaldehyde (0.3 g) were added to dry DCM (30 ml). To this mixture, 3 drops of TFA were added, and the reaction was left to stir for 4 hours under Ar gas. Consumption of the 4-hydroxybenzaldehyde was monitored by TLC after which the temperature was lowered to 0°C, and p-chloranil (0.720 g) was added. The solution was left to stir for 30 min. The temperature was lowered again to 0°C followed by the drop-wise addition of TEA (2.40 ml) and BF3·Et2O (3.40 ml). After overnight stirring, the resulting solution was washed with
54
Scheme 2.07 The acid catalyzed synthesis of 4,4′-difluoro-8-(4-hydroxyphenyl)-1,3,5,7- tetramethyl-4-bora-3a,4a-diaza-s-indacene (7) via the classic “1-pot 3-step” method, highlighting the structural changes that occur at each step.
Product (7) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent to obtain orange crystals at 65% yield. IR (cm−1): 3106 (O-H stretch) 2918, 2849 (C-H stretch), 1521, 917 (O-H bend), 2863,3120,1135,1085 (C-O stretch). 1H NMR (600 MHz, CDCl3) δ (ppm): 7.15 (d, 2H), 6.98 (d, 2H), 6.00 (s, 2H), 5.37 (s, 1H), 2.57 (s, 6H),
1.46 (s, 6H).
2.4.8 4,4′-Difluoro-8-(4-hydroxyphenyl)-1,3,5,7-tetramethyl-2,6-dibromo-4-bora-3a,4a- diaza-s-indacene (8)
100 mg of (7) and NBS (2.5 mole eq.) were dissolved in DCM (100 mL). The mixture was left to stir under Ar/N2 at room temperature for 2 h. The reaction was quenched with water,
and the organic phase was dried and separated via column chromatography [122].
Scheme 2.08 Synthesis of 4,4′-difluoro-8-(4-hodroxy phenyl)-1,3,5,7-tetramethyl-2,6- dibromo-4-bora-3a,4a-diaza-s-indacene (8) via nucleophilic addition of bromine to BODIPY (7).
55
Product (8) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as eluent, red crystals obtained at 83% yield. IR (cm−1): 3106 (O-H) 2918, 2849 (C-H), 1521, 917 (O-H), 2863, 3120, 1135, 1085 (C-O), 520 (C-Br). 1H NMR (600 MHz, CDCl3) δ (ppm):
7.43 (d, 2H), 6.98 (d, 2H), 2.62 (s, 6H), 1.41 (s, 6H).
2.4.9 4’-difluoro-8-(4-methyl ester phenyl)-1,3,5,7-tetramethyl-2,6-diethyl-4-bora- 3a,4a-diaza-s-indacene (9)
The synthesis of the ester-functionalized BODIPY was carried out in a single pot reaction. 2,3-Ethyl-2,4-dimethylpyrrole (0.750 ml) and 4-methyl ester benzaldehyde (0.3 g) were added to dry DCM (30 ml). To this mixture, 3 drops of TFA were added, and the reaction was left to stir for 4 hours under Ar gas. Consumption of the 4-methyl ester benzaldehyde was monitored by TLC after which the temperature was lowered to 0°C, and p-chloranil (0.720 g) was added. The solution was left to stir for 30 min. The temperature was lowered again to 0°C followed by the drop-wise addition of TEA (2.40 ml) and BF3·Et2O (3.40 ml).
After overnight stirring, the resulting solution was washed with deionized water and extracted with DCM.
Scheme 2.09 The acid catalyzed synthesis of 4,4′-difluoro-8-(4-dimethylamino phenyl)- 1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (9) via the classic “1-pot 3- step” method.
56
Since compound (9) was used as a precursor for the preparation of target compounds (10) and (18) in this study, the final target compounds were the only ones to be fully characterized.
2.4.10 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-2,6-diethyl-3,5,-di-styryl-(4' benzyloxy)-4-bora-3a,4a-diaza-s-indacene (10)
(100 mg) of (9), 4-(benzyloxy)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.10. Knoevenagel condensation of 4-(benzyloxy) benzaldehyde and (9) resulting in the synthesis of di-(4-benzyloxy)styryl BODIPY (10).
(10) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder at 30% yield. 1H NMR (600 MHz, CDCl3) δ
57
3H), 6.94 (s, 4H), 5.06 (s, 4H), 3.92 (s, 3H), 2.53 (s, 4H), 1.24 (s, 6H), 1.08 (s, 6H). MALDI- TOF (M+H): Calc. for Chemical Formula: C53H49BF2N2O4: 826.38 amu, found: 826.99 amu.
2.4.11 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-3,5,-di-styryl-(4'-benzyloxy)- 4-bora-3a,4a-diaza-s-indacene (11)
100 mg of (1), 4-(benzyloxy)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.11 Knoevenagel condensation of 4-(benzyloxy)benzaldehyde and (1) resulting in the synthesis of di-(4-benzyloxy)styryl BODIPY (11).
Product (11) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder. 1H NMR (600 MHz, CDCl3) δ 8.22 (s,
2H), 7.63 (d, J = 16.6 Hz, 6H), 7.45 (d, J = 25.2 Hz, 10H), 7.38 (s, 2H), 7.24 (d, J = 16.2 Hz, 2H), 7.02 (s, 4H), 6.64 (s, 2H), 5.14 (s, 4H), 4.00 (s, 3H), 1.60 (s, 6H) ppm. 13C NMR (151 MHz, CDCl3) δ 166.62, 159.65, 153.10, 141.43, 140.23, 136.66, 136.44, 136.07, 132.68,
58
130.67, 130.28, 129.74, 129.14, 129.02, 128.68, 128.15, 127.55, 117.77, 117.21,115.08, 70.09, 31.23, 14.21 ppm. MALDI-TOF (M+H): Calc. for C49H41BF2N2O4: 770.7 amu, found:
771.3 amu.
2.4.12 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-2,6-dibromo-3,5,-di-styryl- (4'-benzyloxy)-4-bora-3a,4a-diaza-s-indacene (12)
100 mg of (3), 4-(benzyloxy)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.12 Knoevenagel condensation of 4-(benzyloxy)benzaldehyde and (3) resulting in the synthesis of di-(4-phenoxy)styryl BODIPY (12).
Product (12) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder. 1H NMR (600 MHz, CDCl3) δ
59
(d, J = 16.2 Hz, 2H), 7.02 (s, 4H), 6.64 (s, 2H), 5.14 (s, 4H), 4.00 (s, 3H), 1.60 (s, 6H). MALDI-TOF (M+H): Calc. for C49H39B1Br2F2N2O3: 928.1 amu, found: 929.1 amu.
2.4.13 4,4′-Difluoro-8-(4-hydroxyphenyl)-1,7-dimethyl-3,5,-di-styryl-(4'-benzyloxy)-4- bora-3a,4a-diaza-s-indacene (13)
100 mg of (7), 4-(benzyloxy)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.13 Knoevenagel condensation of 4-(benzyloxy)benzaldehyde and (7) resulting in the synthesis of di-(4-phenoxy)styryl BODIPY (13).
Product (13) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder. 1H NMR (600 MHz, CDCl3) δ 7.58 (d, J
= 7.7 Hz, 5H), 7.46 (s, 4H), 7.42 (s, 5H), 7.36 (s, 3H), 7.22 (s, 1H), 7.19 (s, 1H), 7.14 (s, 2H), 7.01 (s, 4H), 6.96 (s, 2H), 6.61 (s, 2H), 5.12 (s, 4H), 1.49 (s, 6H) ppm. 13C NMR (151 MHz, CDCl3) δ 159.51, 152.56, 141.88, 136.66, 135.65, 133.57, 129.90, 129.76, 129.07, 128.70,
60
128.14, 127.59, 117.37, 116.04, 115.15, 70.07, 29.65, 14.91 ppm. MALDI-TOF (M+H): Calc. for C47H39BF2N2O3: 728.6 amu, found: 729.3 amu.
2.4.14 4,4′-Difluoro-8-(4-hydroxyphenyl)-1,7-dimethyl-2,6-dibromo-3,5,-di-styryl-(4' benzyloxy)-4-bora-3a,4a-diaza-s-indacene (14)
100 mg of (8), 4-(benzyloxy)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.14 Knoevenagel condensation of 4-(benzyloxy)benzaldehyde and (8) resulting in the synthesis of di-(4-benzyloxy)styryl BODIPY (14).
Product (14) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder. 1H NMR (600 MHz, CDCl3) δ 8.15 (d, J
= 16.6 Hz, 2H), 7.63 (t, J = 13.7 Hz, 6H), 7.48 (d, J = 7.2 Hz, 4H), 7.46 (s, 2H), 7.44 (t, J = 7.5 Hz, 5H), 7.38 (t, J = 7.1 Hz, 3H), 7.05 (d, J = 8.5 Hz, 4H), 5.15 (s, 4H), 1.54 (s, 6H) ppm.
13
61
132.14, 132.05, 129.89, 129.44, 128.70, 128.18, 127.51, 116.15, 115.17 (m), 111.08, 70.22, 53.79, 33.52, 32.29, 29.74, 29.12, 24.65, 22.76, 14.48 ppm. MALDI-TOF (M+H): Calc. for C47H38B1Br2F2N2O3: 887.4 amu, found: 888.1 amu.
2.4.15 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-3,5,-di-styryl-(4'- dimethylamino)-4-bora-3a,4a-diaza-s-indacene (15)
100 mg of (1), 4-(dimethylamino)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.15 Knoevenagel condensation of 4-(dimethylamino)benzaldehyde and (1) resulting in the synthesis of di-(4-dimethylamino)styryl BODIPY (15).
Product (15) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder at 22 % yield. 1H NMR (600 MHz, CDCl3) δ (ppm): 8.17 (s, 2H), 7.54 (s, 6H), 7.21 (s, 4H), 6.72 (s, 4H), 6.60 (s, 2H), 3.03 (s,
62
2.4.16 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-3,5,-di-styryl-(4'- dimethylamino)-4-bora-3a,4a-diaza-s-indacene (16)
To a solution of the BODIPY (15) (0.060 g, 0.068 mmol), in EtOH (2mL) and H2O (1mL),
was added NaOH (0.027 g, 0.68 mmol). The mixture was stirred at room temperature for 10 hours until complete consumption of the staring material was observed by TLC (H2O/EtOH,
1: 4). The solution was then added HCl (10%) until neutral, then evaporated.
Scheme 2.16 Synthesis of 4,4′-difluoro-8-(4-carboxyphenyl)-1,3,5,7-tetramethyl-2,6-diiodo- 4-bora-3a,4a-diaza-s-indacene (16) via hydrolysis of BODIPY (15).
Product (16) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder at 90% yield. 1H NMR (600 MHz, CDCl3) δ (ppm): 8.17 (s, 2H), 7.54 (s, 6H), 7.21 (s, 4H), 6.72 (s, 4H), 6.60 (s, 2H), 3.03 (s,
12H), 2.17 (s, 6H). MALDI-TOF (M+H): Calc. for C37H35BF2N4O2 Expected: 630.30 amu;
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2.4.17 4,4′-Difluoro-8-(4-methyl ester phenyl)-1,7-dimethyl-2,6-diethyl-3,5, -di-styryl-(4'- dimethylamino)-4-bora-3a,4a-diaza-s-indacene (17)
100 mg of (16), 4-(dimethylamino)benzaldehyde (0.535 mmol, 3 mole eq.) and glacial acetic acid (0.4 mL) were dissolved in dry benzene (20 mL) under Ar with stirring. Piperidine (0.4 mL) was added slowly, and the solution was heated to reflux for 2 h under Ar. A Dean-Stark trap was employed for the azeotropic removal of water formed during the condensation reaction. The reaction was quenched with water, and the organic phase was dried and separated using column chromatography with silica gel.
Scheme 2.17 Knoevenagel condensation of 4-(dimethylamino)benzaldehyde and (9) resulting in the synthesis of di-(4-dimethylamino)styryl BODIPY (17).
2.4.18 4,4′-Difluoro-8-(4-carboxyphenyl)-1,7-dimethyl-2,6-diethyl-3,5,-di-styryl-(4'- dimethylamino)-4-bora-3a,4a-diaza-s-indacene (18)
To a solution of the BODIPY (17) (0.060 g, 0.068 mmol), in EtOH (2mL) and H2O(1mL),
was added NaOH (0.027 g, 0.68 mmol). The mixture was stirred at room temperature for 10 hours until complete consumption of the starting material was observed by TLC (H2O/EtOH,
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Scheme 2.18 Knoevenagel condensation of 4-(dimethylamino) benzaldehyde and (9) resulting in the synthesis of di-(4-dimethylamino)styryl BODIPY (17). Hydrolysis of BODIPY (17) to obtain BODIPY (18).
Product (17) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder at 30% yield.
Product (18) was separated by flash chromatography using ethyl acetate/petroleum ether (1:4) as an eluent. Obtained: dark blue crystalline powder at 50% yield. 1H NMR (600 MHz, DMF) δ (ppm): 8.27 (s, 2H), 7.68 (s, 4H), 7.60 (s, 4H), 7.39 (s, 2H), 6.93 (d, J = 50.5 Hz, 4H), 3.08 (s, 12H), 1.80 (s, 4H), 1.39 (s, 6H), 1.17 (s, 6H). MALDI-TOF (M+H): Calc. for Chemical Formula: C42H45BF2N4O2: 686.36 amu, found: 687.04 amu.
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