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Z. Abada et al. / European Journal of Medicinal Chemistry 67 (2013) 158e165
J ¼ 190 Hz, CeF), 138.6 (m, Cq), 136.2 (m, Cq), 126.9 (2CH), 123.9
(Cq), 118.9 (2CH). 19F (CDCl3, 188 MHz)
14.8 Hz, 2F), ꢄ152.83 (tt, J ¼ 20.9, 1.7 Hz, 2F), ꢄ138.76 (m, 1H).
[M þ H]þ. HRMS-ESI: m/z calculated for [M þ H]þ 311.0608,
obtained 311.0608. Rf 0.63 (CH2Cl2).
general protocol afforded bis-(5-pentafluoro-phenyl)dipyrrinato)
iron (II) complex 3c (302.1 mg, 72%). 19F (CDCl3, 188 MHz)
d
ꢄ161.41 (dd, J ¼ 20.9,
d
ꢄ135.77
(brd, J ¼ 11.3 Hz, 4F), ꢄ151.91 (t, J ¼ 20.7 Hz, 2F), ꢄ160.23 (brt,
J ¼ 18.8 Hz, 4F). LRMS-APCI: m/z 674.2 [M]þ. HRMS-APCI: m/z
calculated for [M
674.0267. Rf 0.87 (Cyclohexane/AcOEt:7/3).
þ
H]þ. C30H13F10FeN4 674.0267, obtained
6.2.4. 5-(3,4,5-Trimethoxyphenyl)dipyrromethene (2d)
Reaction from 5-(3,4,5-methoxyphenyl)dipyrromethane 1d (1 g,
3.20 mmol) and DDQ (799 mg, 3.52 mmol) following the general
protocol afforded dipyrromethene 2d (690.8 mg, 69%). 1H (CDCl3,
6.3.4. Bis-(5-pentafluorophenyl)dipyrrinato)manganese (II)
complex (3d)
Reaction from 5-(3,4,5-methoxyphenyl)dipyrromethane 2c
(200 mg, 0.65 mmol) and Mn(OAc)2 (10 equiv.) bis-(5-penta-
fluorophenyl)dipyrrinato)manganese (II) complex 3d (84 mg, 39%).
300 MHz)
J ¼ 4.1 Hz, 2H), 6.71 (d, J ¼ 4.1 Hz, 2H), 6.75 (s, 2H), 7.65 (s, 2H), 12.6
(brs, 1H, NH). 13C (CDCl3, 75 MHz)
152.3 (Cq), 143.6 (CH), 141.7
d 3.86 (s, 6H, 2OCH3), 3.94 (s, 3H, OCH3), 6.41 (d,
d
19F (CDCl3, 188 MHz)
d
ꢄ142.32 (brs, 4F), ꢄ153.45 (t, J ¼ 20.7 Hz,
(Cq), 140.7 (Cq), 138.5 (Cq), 132.6 (Cq), 128.6 (CH), 117.5 (CH), 108.4
(CH), 60.9 (4OCH3), 56.2 (3OCH3). LRMS-APCI: m/z 310 [M þ H]þ.
HRMS-ESI: m/z calculated for [M þ H]þ C18H18N2O3 311.1396, ob-
tained 311.1396. Rf 0.62 (CH2Cl2).
2F), ꢄ161.60 (brs, 4F). LRMS-APCI: m/z 673.0 [M þ H]þ. HRMS-APCI:
m/z calculated for [M]þ. (55Mn) C30H12F10MnN4 673.0283, obtained
673.0277. Rf 0.7 (CH2Cl2).
6.4. Synthesis of porphyrins (4i) and (4j)
6.2.5. 5-(2,6-Dichlorophenyl)dipyrromethene (2e)
Reaction from 5-(2,6-dichlorophenyl)dipyrromethane 1e
(500 mg, 1.71 mmol) and DDQ (428 mg, 1.89 mmol, 1.1 equiv.)
following the general protocol afforded dipyrromethene 2e
To a round bottom flask, containing a magnetic bar, solid
reagents were weighed : 5-bromo-10,15-diphenylporphyrin 4d
(31 mg, 0.05 mmol, 1 equiv.), Pd2dba3 (1.6 mg, 0.0018 mmol, 10 mol
%), Xantphos (4.1 mg, 0.0071 mmol, 40 mol%) and Cs2CO3 (23.2 mg,
0.071 mmol, 2 eq.) and the flask was purged with nitrogen. A so-
(73.4 mg, 15%). 1H (CDCl3, 300 MHz)
d
6.37 (m, 4H, CH), 7.34 (dd,
J ¼ 9.0, 6.9 Hz, 1H), 7.40 (d, J ¼ 7.0 Hz, 1H), 7.45 (d, J ¼ 1.49 Hz, 1H),
7.64 (s, 2H), 11.8 (brs, 1H, NH). 13C (CDCl3, 75 MHz)
144.4 (CH),
d
lution of pyrrolidinone (30.8 ml, 0.40 mmol, 8 equiv.) in Dioxane was
139.9 (CH), 135.6 (C), 134.9 (CeCl), 134.8 (CeCl), 130.1 (C), 127.9
(CH), 126.7 (CH), 118.3 (CH). LRMS-ESI: m/z 290 [M þ H]þ. HRMS-
ESI: m/z calculated for [M þ H]þ 289.0299, obtained 289.0290. Rf
0.67 (CH2Cl2).
added and the flask was purged again with nitrogen. The reaction
mixture was stirred at 100 ꢁC for 24 h. The flask tube was cooled
down to room temperature and then concentrated. The crude re-
action mixture was then purified on a silica gel column (solid de-
posit) and purified affording the title porphyrin 4j (28 mg, 89%)
along mono coupled porphyrin 4i (4 mg, 11%).
6.3. General protocol for the synthesis of dipyrromethenes
complexes 3aee
6.4.1. 5,15-Di-(N-(20-Pyrrolidinone-yl)-10,20-diphenylporphyrin
To a solution of dipyrromethene 2aee in 1:1/CHCl3:MeOH was
added Et3N (1 equiv) followed by the metal salt, e.g. FeCl2$2H2O or
Mn(OAc)2 (10 equiv). The reaction mixture was then heated to
reflux and controlled by TLC until complete conversion. The reac-
tion mixture was then diluted with CH2Cl2, washed with brine and
deionized water, dried over sodium sulfate, filtered, and concen-
trated under vacuum. The residue was purified over neutral
alumina (CH2Cl2: Et3N, 99:1) to furnish complexes (39e98%)
(4j) [16]
1H (CDCl3, 300 MHz)
d
ꢄ2.87 (s, 2H), 2.83 (m, 4H), 3.24 (m, 4H),
4.73 (td, 4H, J ¼ 6.7 Hz, J ¼ 14.3 Hz), 7.79 (m, 6H, Ar), 8.17 (m, 4H,
Ar), 8.90 (d, 4H, J ¼ 4.9 Hz), 9.13 (d, 4H, J ¼ 4.7 Hz). 13C (CDCl3,
75 MHz)
d 178.3 (NeC]O), 141.2 (Cq), 134.6 (CH), 127.8 (CH), 41.9
(CH2), 32.0 (CH2), 20.2 (CH2). UVevisible (nm,
3 , c 0.06 mM,
CH2Cl2): 421 (36,860), 513 (7805), 547 (2623), 590 (2670), 646
(1696). LRMS-APCI: m/z 629 [M þ H]þ. HRMS-MALDI: m/z calcu-
lated for [M þ H]þ C40H33N6O2 629.2659, obtained 629.2629. IR
(cmꢄ1): 2037, 2023, 1397, 1277, 750. Rf 0.27 (AcOEt).
6.3.1. Bis-(5-(3,4,5-methoxyphenyl)dipyrrinato)iron (II) complex
(3a)
Reaction from 5-(3,4,5-methoxyphenyl)dipyrromethene 2d
(345 mg, 1.11 mmol) and FeCl2$H2O (10 equiv.) following the gen-
eral protocol afforded bis-(5-(3,4,5-methoxy-phenyl)dipyrrinato)
6.4.2. 5-Bromo-15-(N-(20-pyrrolidinone-yl)-10,20-
diphenylporphyrin (4i)
1H (CDCl3, 400 MHz)
d
ꢄ2.78 (s, 2H, 2NH), 2.82 (quint, J ¼ 7.5 Hz,
2H), 3.23 (t, J ¼ 7.9 Hz, 2H), 4.71 (t, J ¼ 7.1 Hz, 2H), 7.78 (m, 6H, Ar),
8.17 (m, 4H, Ar), 8.86 (m, 4H, -H), 9.65
-H), 9.10 (d, J ¼ 4.5 Hz, 2H,
(d, J ¼ 4.5 Hz, 178.1 (NeC]O), 141.3
-H). 13C (CDCl3, 100 MHz)
iron (II) complex 3a (255.8 mg, 68%). 1H (CDCl3, 300 MHz)
d 10.46 (s,
4H), 4.90 (s, 12H), 4.66 (s, 6H). LRMS-APCI: m/z 674.4 [M]þ. HRMS-
APCI: m/z calculated for [M þ H]þ. C36H35FeN4O6 674.1828, ob-
tained 674.1815. Rf 0.26 (Cyclohexane/AcOEt: 7/3).
b
b
b
d
(Cq), 134.7 (CH), 134.6 (CH), 134.5 (CH), 128.1 (CH), 126.9 (CH), 126.8
(CH),121.1 (Cq),114.6 (Cq), 58.4 (CH2), 32.0 (CH2), 20.2 (CH2). LRMS-
APCI: m/z 624 [M þ H]þ. HRMS-MALDI: m/z calculated for [M þ H]þ
C36H27N5OBr 624.1393, obtained 624.1395. UVevisible (nm,
6.3.2. Bis-(5-(3,4,5-methoxyphenyl)dipyrrinato)manganese (II)
complex (3b)
Reaction from 5-(3,4,5-methoxyphenyl)dipyrromethene 2d
(345 mg,1.11 mmol) and Mn(OAc)2 (10 equiv.) following the general
protocol afforded bis-(5-(3,4,5-methoxy-phenyl)dipyrrinato)man-
3
0.1 mM, CHCl3): 421 (19,923), 517 (2070), 551 (1017), 593 (892),
652 (732). Rf 0.56 (AcOEt).
ganese (II) complex 3b (395.1 mg, 98%). 1H (CDCl3, 300 MHz)
d
7.46
6.5. 5,15-Di-(3,4,5-trimethoxyphenyl)-10-(5-oxopyrrolidine-2(S)-
carboxylate)) porphyrin (4f)
(brs, 4H), 3.91 (s, 6H), 3.81 (s, 12H). LRMS-APCI: m/z 674.2 [M þ H]þ.
HRMS-APCI: m/z calculated for [M þ H]þ. C36H35MnN4O6 674.1932,
obtained 674.1921. Rf 0.17 (Cyclohexane/AcOEt: 7/3).
Methyl ester 4g (133 mg, 0.17 mmol, 1 equiv.) was dissolved in a
CH2Cl2/MeOH (1:1) mixture and NaOH 3M (1 ml) was added. The
mixture was stirred at room temperature for 4 h then the reaction
was neutralized with a solution of 10% HCl until pH 4e5 was
reached. The solution was extracted with dichloromethane several
6.3.3. Bis-(5-pentafluorophenyl)dipyrrinato)iron (II) complex (3c)
Reaction from 5-(3,4,5-methoxyphenyl)dipyrromethane 2c
(388.9 mg, 1.25 mmol) and FeCl2$H2O (10 equiv.) following the