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M. P. Trova et al. / Bioorg. Med. Chem. 11 (2003) 2695–2707
the preparation of 4, and using commercially available
ethyl glyoxylate (1b, 50% in toluene; 310 mg, 1.5 mol)
and dipyrromethane 3b, the porphyrins 9 (22 mg, 7%),
10 (10 mg, 2%), and 7 (3 mg, 0.5%) were isolated after
purification by column chromatography on silica gel
(gradient elution with 50–75% CH2Cl2/hexanes). For
(2.07 g, 20.5 mmol) and dipyrromethane 3b (3.00 g,
20.5 mmol), the porphyrins 17 (40 mg, 0.9%), 18 (11 mg,
0.2%), and 8 (trace) were isolated after purification by
column chromatography on silica gel (gradient elution
with 0–5% CH3OH/CH2Cl2). For porphyrin 17: 1H
NMR (300 MHz, CDCl3) d 10.26 (s, 1H), 10.23 (s, 1H),
9.33–9.42 (m, 8H), 3.81 (s, 6H), 2.80 (s, 3H), 2.73 (s,
3H), ꢁ3.48 (s, 1H), ꢁ3.58 (s, 1H). For porphyrin 18: 1H
NMR (300 MHz, CDCl3) d 10.25 (s, 2H), 10.22 (s, 1H),
9.43 (d, J=7.3 Hz, 2H), 9.42 (s, 4H), 9.34 (d, J=4.2 Hz,
2H), 3.78 (s, 3H), 2.72 (s, 3H), ꢁ3.85 (s, 2H).
1
porphyrin 9: H NMR (300 MHz, CDCl3) d 10.39 (s,
2H), 9.71 (d, 4H), 9.48 (d, 4H), 5.15 (q, 4H), 1.90 (t,
6H), ꢁ3.23 (s, 2H). For porphyrin 10: 1H NMR
(300 MHz, CDCl3) d 10.31 (s, 2H), 10.26 (s, 1H), 9.69
(d, J=4.7 Hz, 2H), 9.47 (d, J=4.7 Hz, 2H), 9.40–9.45
(m, 4H), 5.14 (q, J=6.9 Hz, 2H), 1.87 (t, J=6.9 Hz),
ꢁ3.74 (s, 2H); FAB MS m/z 382 [C23H18N4O2]+.
5,15-Bis(ethoxycarbonyl)-10,20-bis(4-fluoro-3-methoxy-
phenylcarbonyl)porphyrin (19) and 5,10,15-tris(ethoxy-
carbonyl)-20-(4-fluoro-3-methoxyphenylcarbonyl)porphyrin
(20). Following the procedure for the preparation of 4,
methyl 6-fluoro-3-formylbenzoate22 (650mg, 3.56mmol),
and dipyrromethane 3c (778 mg, 3.56 mmol), the por-
phyrins 19 (44 mg, 3.3%) and 20 (42 mg, 5.2%) were
isolated after purification by column chromatography
on silica gel (elution with CH2Cl2). For porphyrin 19:
1H NMR (300 MHz, CDCl3) d 9.47 (d, J=4.8 Hz, 4H),
8.89 (d, J=4.8 Hz, 4H), 8.78 (dd, J=6.2, 1.9 Hz, 2H),
8.32–8.36 (m, 2H), 7.6 (dd, J=9.4, 9.2 Hz, 2H), 5.09 (q,
J=7.2 Hz, 4H), 4.10 (s, 6H), 1.79 (t, J=7.2 Hz, 6H),
5,15-Bis(2,2,2-trifluoroethoxycarbonyl)porphyrin
(11)
and 5-(2,2,2-trifluoroethoxycarbonyl)porphyrin (12). Fol-
lowing the procedure for the preparation of 4, and using
freshly prepared 2,2,2-trifluoroethyl glyoxylate (1c,
1.6 g, 9.6 mmol) and dipyrromethane 3b (1.41 g,
9.6 mmol), the porphyrins 11 (54 mg, 1.2%), 12 (38 mg,
0.7%), and 8 (trace) were isolated after purification by
column chromatography on silica gel (gradient elution
1
with 50–80% CH2Cl2/hexanes). For porphyrin 11: H
NMR (300 MHz, CDCl3) d 10.42 (s, 2H), 9.70 (d, 4H),
9.50 (d, J=4.8 Hz, 4H), 5.44 (q, J=8.4 Hz, 4H), ꢁ3.11
(s, 2H). For porphyrin 12: 1H NMR (300 MHz, CDCl3)
d 10.35 (s, 2H), 10.30 (s, 1H), 9.70 (d, 2H), 9.51 (d, 2H),
9.43–9.49 (m, 4H), 5.43 (q, 2H), ꢁ3.58 (s, 2H).
1
ꢁ3.08 (s, 2H). For porphyrin 20: H NMR (300 MHz,
CDCl3) d 9.54 (s, 4H), 9.43 (d, J=4.8 Hz, 2H), 8.89 (d,
J=4.8 Hz, 2H), 8.75 (dd, J=6.0, 2.1 Hz, 1H), 8.29–8.32
(m, 1H), 7.6 (dd, J=9.2, 9.1 Hz, 1H), 5.13 (q, J=7.2 Hz,
6H), 4.01 (s, 3H), 1.83 (t, J=7.2 Hz, 9H), ꢁ3.13 (s, 2H).
5,15-Bis(n-propoxycarbonyl)porphyrin (13) and 5-(n-pro-
poxycarbonyl)porphyrin (14). Following the procedure
for the preparation of 4, and using freshly prepared
n-propyl glyoxylate (1d, 0.5 g, 4.3 mmol) and dipyrro-
methane 3b (0.63 g, 4.3 mmol), the porphyrins 13
(30 mg, 2.9%), 14 (10 mg, 1.2%), and 8 (trace) were
isolated after purification by column chromatography
on silica gel (gradient elution with 50–80% CH2Cl2/
hexanes). For porphyrin 13: 1H NMR (300 MHz,
CDCl3) d 10.38 (s, 2H), 9.69 (d, J=4.8 Hz, 4H), 9.47 (d,
J=4.8 Hz, 4H), 5.03 (t, J=7.1 Hz, 4H), 2.20–2.27 (m,
4H), 1.31 (t, J=1.3 Hz, 6H), ꢁ3.33 (s, 2H). For por-
phyrin 14: 1H NMR (300 MHz, CDCl3) d 10.36 (s, 2H),
10.33 (s, 1H), 9.70 (d, J=4.8 Hz, 2H), 9.51 (d,
J=4.8 Hz, 4H), 9.48 (d, J=4.8 Hz, 2H), 5.04 (t,
J=6.7 Hz, 2H), 2.22–2.28 (m, 2H), 1.31 (t, J=7.3 Hz,
3H), ꢁ3.62 (s, 2H).
5,15-Bis(ethoxycarbonyl)-10,20-bis(ethyl)porphyrin (21).
In a foil-covered round-bottomed flask equipped with
an air condenser, dipyrromethane 3c (150 mg,
0.687 mmol) was stirred in propionic acid (5 mL), H2O
(0.2 mL), and pyridine (17 mL) at 90 ꢃCfor 5 min. Pro-
pionaldehyde (25 mL, 0.34 mmol) was added and the
reaction mixture was stirred for 40 min. Another por-
tion of propionaldehyde (10 mL, 0.14 mmol) was added
to the reaction mixture, stirred for 2 h and diluted with
CH2Cl2 (15 mL). The organic phase was washed with
H2O (10 mL), 0.05 N NaOH (2 ꢄ 10 mL), and H2O
(10 mL), dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was dissolved in CH2Cl2 (250 mL)
and DDQ (108 mg, 0.48 mmol) was added. After stirring
overnight, the sample was adsorbed onto silica gel (4 g).
Purification by column chromatography on silica gel
(gradient elution with 50–100% CH2Cl2/hexanes) pro-
5,15-Bis(n-butoxycarbonyl)porphyrin (15). Following the
procedure for the preparation of 4, and using freshly
prepared n-butyl glyoxylate (1e, 1.0 g, 7.7 mmol) and
dipyrromethane 3b (1.12 g, 7.7 mmol), porphyrins 15
(137 mg, 7%) and 16 (15 mg, 1.3%) were isolated after
purification by column chromatography on silica gel
(gradient elution with 50–66% CH2Cl2/hexanes) as
1
vided porphyrin 21 (12 mg, 10%) as a purple solid: H
NMR (300 MHz, CDCl3) d 9.54 (d, J=4.5 Hz, 4H), 9.44
(d, J=4.5 Hz, 4H), 5.11–4.99 (m, 8H), 2.13 (t,
J=7.3 Hz, 6H), 1.81 (t, J=7.0 Hz, 6H); FAB MS m/z
511 [C30H30N4O4+H]+.
1
purple solids. For porphyrin 15: H NMR (300 MHz,
5,15-Bis(n-butoxycarbonyl)-10,20-bis(methoxycarbonyl)-
porphyrin (22) and 5-methoxycarbonyl-10,15,20-tris-
(n-butoxycarbonyl)porphyrin (23). Following the proce-
dure for the preparation of 4 and using freshly distilled
methyl glyoxylate (1a, 376 mg, 4.27 mmol) and dipyrro-
methane 3d (1.04 g, 4.23 mmol), the porphyrins 22
(75 mg, 2.8%) and 23 (20 mg, 0.7%) were isolated after
purification by column chromatography. For porphyrin
CDCl3) d 10.19 (s, 2H), 9.58 (d, 4H), 9.37 (d, 4H), 5.07
(t, 4H), 2.13–2.27 (m, 4H), 1.69–1.81 (m, 4H), 1.16 (t,
6H), ꢁ3.71 (s, 2H). Porphyrin 18 was not characterized
and was used directly in the preparation of 48.
5,15-Bis(dimethylamido)porphyrin (17) and 5-(dimethyl-
amido)porphyrin (18). Following the procedure for the
preparation of 4, and using freshly prepared amide 1g
1
22: H NMR (300 MHz, CDCl3) d 9.49 (s, 8H), 5.05 (t,