5772
J. H. Gibbs et al. / Bioorg. Med. Chem. 21 (2013) 5770–5781
2.1.1.7. BODIPY 7 (4,4-difluoro-8-(thiophen-2-yl)-1,3,5,7-tetra-
methyl-4-bora-3a,4a-diaza-s-indacene). Obtained a red so-
2.1.2.1. BODIPY 1a (4,4-difluoro-8-phenyl-2,6-di-iodo-1,3,5,7-
tetramethyl-4-bora-3a,4a-diaza-s-indacene). Obtained as a
lid (0.3298 g) in 20% yield, mp = 190–191 °C; 1H NMR (400 MHz,
CDCl3) d 7.50 (d, J = 5.0 Hz, 1H, 5-thienyl H), 7.14 (t, J = 4.4 Hz,
1H, 4-thienyl H), 6.99 (d, J = 3.2 Hz, 1H, 3-thienyl H), 6.00 (s, 2H,
b-pyrrole H), 2.55 (s, 6H, 3,5-CH3), 1.58 (s, 6H, 1,7-CH3); 13C NMR
(100 MHz, CDCl3) d 156. 07, 143.50, 134.63, 134.00, 132.40,
127.81, 127.61, 127.41, 121.50, 14.65, 13.55; HRMS (ESI-TOF) m/z
331.1306 [M+H]+, calculated for C17H18BF2N2S: 331.1252. The
NMR data is in agreement with that previously reported.33
red solid (0.1618 g) in 91% yield from 1 (0.100 g, 0.3085 mmol), io-
dic acid (0.1085 g, 0.6169 mmol), iodine (0.0979 g, 0.7713 mmol),
mp = 204–206 °C; 1H NMR (400 MHz, CDCl3)
d 7.54 (dd,
J = 5.2 Hz, 1.4, 3H, o,p-phenyl H), 7.26 (dd, J = 7.2 and 2.2 Hz, 2H,
m-phenyl H), 2.65 (s, 6H, 3,5-CH3), 1.39 (s, 6H, 1,7-CH3); 13C
NMR (100 MHz, CDCl3) d 156.78, 145.37, 141.38, 134.74, 131.30,
129.54, 129.47, 127.79, 85.65, 16.95, 16.04; HRMS (ESI-TOF) m/z
575.9461 [M]+, calculated for C19H17BF2I2N2: 575.9543. The NMR
data is in agreement with that previously reported.35
2.1.1.8. BODIPY
1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
cene).
8 (4,4-difluoro-8-([2, 2’-bithiophen]-2-yl)-
2.1.2.2. BODIPY 2a (4,4-difluoro-2,6-di-iodo-8-(3,5-dimethoxy-
phenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
Obtained a dark red solid (0.4180 g) in 20% yield,
mp = 157 °C (decomposes); 1H NMR (400 MHz, CDCl3) d 7.28 (d,
J = 3.5 Hz, 1H, 50-bithienyl H), 7.23 (d, J = 3.5 Hz, 1H, 4-bithienyl
H), 7.20 (d, J = 3.5 Hz, 1H, 3-bithienyl H), 7.06 (dd, J = 4.9 and
3.7 Hz, 1H, 30-bithienyl H), 6.89 (d, J = 3.5 Hz, 1H, 40-bithienyl),
6.02 (s, 2H, b-pyrrole H), 2.56 (s, 6H, 3,5-CH3), 1.75 (s, 6H, 1,7-
cene).
Obtained as a red solid (0.0952 g) in 57% yield from 2
(0.100 g, 0.2603 mmol), iodic acid (0.1145 g, 0.6508 mmol), iodine
(0.0826 g, 0.6508 mmol), mp = 192–193 °C; 1H NMR (400 MHz, CDCl3)
d6.59 (t, J = 2.0 Hz, 2H,m-phenyl H), 6.41 (d, J = 2.0 Hz, 1H, p-phenyl H),
3.81 (s, 6H, OCH3), 2.65 (s, 6H, 3,5-CH3), 1.57 (s, 6H, 1,7-CH3); 13C NMR
(100 MHz, CDCl3) d 161.94, 156.84, 149.46, 145.42, 136.31, 131.12,
105.77, 101.45, 85.58, 55.65, 16.88, 16.06; HRMS (ESI-TOF) m/z
636.9810 [M+H]+, calculated for C21H21BF2I2N2O2: 636.9832.
CH3); 13C NMR (100 MHz, CDCl3)
d 156.28, 143.44, 133.14,
128.65, 127.98, 125.02, 124.33, 123.73, 121.58, 14.66, 13.95; HRMS
(ESI-TOF) m/z 413.1116 [M+H]+, calculated for C21H20BF2N2S:
413.1129.
2.1.2.3. BODIPY 3a (4,4-difluoro-8-(3,5-di-t-butylphenyl)-2,6-di-
iodo-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
2.1.1.9. BODIPY
9
(4,4-difluoro-8-(5-bromothiophen-2-yl)-
1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
cene).
Obtained as a red solid (0.3658 g) in 93% yield from 3
cene).
Obtained a dark red solid (0.3740 g) in 18% yield,
(0.250 g, 0.5729 mmol), iodic acid (0.2016 g, 1.1458 mmol) and io-
dine (0.1818 g, 1.4323 mmol); 1H NMR (400 MHz, CDCl3) d 7.54 (t,
J = 1.8 Hz, 1H, p-phenyl H), 7.08 (d, J = 1.3 Hz, 2H, o-phenyl H), 2.66
(s, 6H, 3,5-CH3), 1.37 (s, 6H, 1,7-CH3), 1.33 (s, 18H, t-butyl H); 13C
NMR (100 MHz, CDCl3) d 156.40, 152.48, 145.35, 142.94, 133.76,
131.39, 122.46, 121.87, 85.45, 35.15, 31.40, 16.69, 15.99; HRMS
(ESI-TOF) m/z688.0730[M]+, calculatedforC27H33BF2I2N2: 688.0794.
mp = 167–168 °C; 1H NMR (400 MHz, CDCl3) d 7.10 (d, J = 3.5 Hz,
1H, 4-thienyl-H), 6.77 (d, J = 3.9 Hz, 1H, 3-thienyl-H), 6.01 (s, 2H,
b-pyrrole H), 2.54 (s, 6H, 3,5-CH3), 1.69 (s, 6H, 1,7-CH3); 13C NMR
(100 MHz, CDCl3)
d 156.57, 143.34, 136.32, 132.11, 130.36,
128.43, 121.75, 113.83, 14.65, 13.87; HRMS (ESI-TOF) m/z
409.0315 [M+H]+, Calculated for C17H17BBrF2N2S: 409.0357.
2.1.1.10. BODIPY 10 (4,4-difluoro-8-(5’-bromo-[2,2’-bithio-
2.1.2.4. BODIPY 4a (4,4-difluoro-8-(3,4-dimethoxyphenyl)-2,6-
phen]-2-yl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
cene).
di-iodo-1,3,5,7-tetramethyl-4-bora-3a,
cene). Obtained as a red solid (0.3907 g) in 94% yield from 4
4a-diaza-s-inda-
Obtained as a dark red solid (0.7439 g) from 50-
bromo-[2,20-bithiophen]-5-carbaldehyde19 (1.3658 g) in 30%
yield, mp = 205 °C (decomposes); 1H NMR (400 MHz, CDCl3) d
7.14 (d, J = 3.5 Hz, 1H, 4,40-bithienyl-H), 7.01 (d, J = 3.5 Hz, 1H,
4,40-bithienyl H), 6.97 (d, J = 3.9 Hz, 1H, 3,30-bithienyl-H), 6.89
(d, J = 3.9 Hz, 1H, 3,30-bithienyl-H), 6.03 (s, 2H, b-pyrrole H),
2.56 (s, 6H, 3,5-CH3), 1.73 (s, 6H, 1,7-CH3); 13C NMR (100 MHz,
CDCl3) d 156.42, 143.36, 135.64, 133.70, 132.29, 130.75, 128.76,
124.41, 123.96, 121.64, 111.80, 14.67, 13.93; HRMS (ESI-TOF, neg-
ative ion) m/z 489.0089 [M+H]+, calculated for C21H17BBrF2N2S2:
489.0078.
(0.250 g, 0.6507 mmol), iodic acid (0.2289 g, 1.3013 mmol), iodine
(0.2065 g, 1.6268 mmol), mp = 215–217 °C; 1H NMR (400 MHz,
CDCl3) d 7.02 (d, J = 7.8 Hz, 1H, 5-phenyl H), 6.82 (dd, J = 8.7 Hz,
1.5, 2H, 6-phenyl H), 6.74 (d, J = 1.5 Hz, 2-phenyl H), 3.98 (s, 3H,
OCH3), 3.87 (s, 3H, OCH3), 2.65 (s, 6H, 3,5-CH3), 1.49 (s, 6H, 1,7-
CH3); 13C NMR (100 MHz, CDCl3)
d 156.70, 150.10, 149.97,
145.37, 141.28, 131.62, 126.78, 120.33, 111.76, 111.81, 85.58,
56.18, 56.01, 17.07, 16.01; HRMS (ESI-TOF) m/z 635.9840 [M]+, cal-
culated for C21H21BF2I2N2O2: 635.9754. The NMR data is in agree-
ment with that previously reported.36
2.1.1.11. BODIPY 11 (4,4-difluoro-8-pentafluorophenyl-1,3,5,7-
2.1.2.5. BODIPY 5a (4,4-difluoro-2,6-di-iodo-8-(4-(methoxycar-
tetramethyl-4-bora-3a,4a-diaza-s-indacene).
Obtained as a
bonyl)phenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
red solid (0.3820 g) in 52% yield, mp = 109 °C (decomposes); 1H
NMR (400 MHz, CDCl3) d 6.06 (s, 2H, b-pyrrole H), 2.57 (s, 6H,
3,5-CH3), 1.62 (s, 6H, 1,7-CH3); 13C NMR (100 MHz, CDCl3) d
157.78, 145.26, 142.77, 141.50, 139.44, 137.10, 130.99, 122.73,
122.26, 14.76, 13.57; HRMS (ESI-TOF) m/z 415.1337 [M+H]+, calcu-
lated for C19H15BF7N2: 415.1216. The NMR data is in agreement
with that previously reported.34
cene).
Obtained as a red solid (0.3570 g) in 86% yield from 5
(0.250 g, 0.6541 mmol), iodic acid (0.2301 g, 1.3082 mmol), iodine
(0.2075 g, 1.6353 mmol), mp = 215 °C (decomposes); 1H NMR
(400 MHz, CDCl3) d 8.23 (d, J = 7.9 Hz, 2H, m-phenyl H), 7.40 (d,
J = 7.9 Hz, 2H, o-phenyl H), 3.99 (s, 3H, COOCH3), 2.65 (s, 6H, 3,5-
CH3), 1.37 (1,7-CH3); 13C NMR (100 MHz, CDCl3)
d 166.24,
157.34, 145.07, 139.81, 139.46, 131.34, 130.81, 130.66, 128.24,
86.04, 52.53, 17.14, 16.12; HRMS (ESI-TOF) m/z 634.9663 [M+H]+,
calculated for C21H20BF2I2N2O2: 634.9676. The NMR data is in
agreement with that previously reported.37
2.1.2. General procedure for Iodination of BODIPYs 1–11
Iodic acid (2 equiv) was dissolved in a minimal amount of water
and added drop-wise to a solution of the BODIPY (1 equiv) and io-
dine (2.5 equiv) in a solution of 50:50 ethanol/DCM (ꢂ35
l
M solu-
2.1.2.6. BODIPY 6a (4,4-difluoro-8-(4-bromophenyl)-2,6-di-
iodo-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-inda-
tion). The resulting mixture was stirred at 60 °C for 2 h. After
cooling, the solvent was evaporated under vacuum and the result-
ing residue was purified by silica gel column chromatography
using 50:50 hexanes/DCM for elution.
cene).
Obtained as a red solid (0.4422 g) in 71% yield from 6
(0.250 g, 0.6202 mmol), iodic acid (0.2182 g, 1.2405 mmol), iodine
(0.1968 g, 1.5505 mmol), mp = 232 °C (decomposes); 1H NMR