Synthesis of Meso-Substituted Chlorin Building Blocks
J . Org. Chem., Vol. 65, No. 10, 2000 3169
solidified upon standing in the freezer. Recrystallization from
hexanes/ethyl acetate gave pale yellow crystals (0.97 g, 85%):
mp 62 °C; H NMR (CDCl3) δ 2.44 (s, 3 H), 7.26-7.35 (m, 3
140.6, 172.1; FAB-MS obsd 506.0469, calcd 506.0477; νmax
-
-
(Nujol)/cm-1 991, 1501, 1621, 3272. Anal. Calcd for C22H8F10
1
N2O: C, 52.2; H, 1.6; N, 5.5. Found: C, 52.2; H, 1.7; N, 5.4.
H), 7.73-7.79 (m, 2 H), 7.91 (d, J ) 8.1 Hz, 2 H), 8.67 (m, 1
H); 13C NMR (CDCl3) δ 21.6, 123.5, 127.5, 129.4, 130.8, 133.9,
137.0, 144.8, 150.4, 151.4, 188.8; EI-MS obsd 229.0558, calcd
1-(4-Me t h ylb e n zoyl)-5-(4-iod op h e n yl)d ip yr r om e t h -
a n e (14). Samples of 8 (3.0 g, 8.6 mmol) and 10 (1.97 g, 8.6
mmol) were reacted as described above for the synthesis of
13, affording an orange glassy film (3.2 g, 79%). Recrystalli-
zation from methanol/H2O gave a light yellow powder: mp 80-
229.0561; νmax(Nujol)/cm-1 1602, 1165. Anal. Calcd for C13H11
-
NOS: C, 68.1; H, 4.8; N, 6.1. Found: C, 68.2; H, 4.8; N, 6.1.
1
82 °C; H NMR (CDCl3) δ 2.43 (s, 3 H), 5.49 (s, 1 H), 5.97 (s,
S-2-P yr id yl p en ta flu or oben zoth ioa te (11). Following a
general procedure,35 2-mercaptopyridine (1.0 g, 9.0 mmol) was
dissolved in 50 mL of CH2Cl2 to which pentafluorobenzoyl
chloride (1.29 mL, 9.0 mmol) was added. The reaction mixture
was allowed to stir at room temperature for 1 h, and then CH2-
Cl2 (100 mL) was added. The mixture was washed with 2 N
NaOH (100 mL) and water (100 mL) and dried over MgSO4.
The solvent was removed under vacuum to give a pale yellow
solid that turned brown at temperatures above 0 °C. Recrys-
tallization from hexanes gave brown crystals (2.07 g, 75%):
1 H), 6.05 (t, J ) 3.0 Hz, 1 H), 6.15 (m, 1 H), 6.71 (m, 1 H),
6.80 (t, J ) 3.0 Hz, 1 H), 6.92 (d, J ) 8.1 Hz, 2 H), 7.25 (d,
J ) 8.1 Hz, 2 H), 7.56 (d, J ) 8.1 Hz, 2 H), 7.71 (d, J ) 8.1 Hz,
2 H), 8.23 (br, 1 H), 9.78 (br, 1 H); 13C NMR (CDCl3) δ 21.6,
43.5, 92.5, 107.9, 108.2, 110.7, 118.2, 121.1, 128.9, 129.1, 130.2,
130.4, 130.9, 135.4, 137.5, 140.8, 141.3, 142.5, 184.8; FAB-MS
obsd 466.0560, calcd 466.0542. Anal. Calcd for C23H19IN2O: C,
59.2; H, 4.1; N, 6.0. Found: C, 59.2; H, 4.1; N, 5.9. νmax(Nujol)/
cm-1 1587, 1724, 3251.
1-(4-Met h ylb en zoyl)-5-{4-[2-(t r im et h ylsilyl)et h yn yl]-
p h en yl}d ip yr r om eth a n e (15). Samples of 9 (3.0 g, 9.4 mmol)
and 10 (2.15 g, 9.4 mmol) were reacted as described above for
the synthesis of 13. Recrystallization of the glassy film from
methanol/ethanol gave a brown solid (3.8 g, 92%): mp 152 °C;
1H NMR (CDCl3) δ 0.24 (s, 9 H), 2.42 (s, 3 H), 5.53 (s, 1 H),
5.96 (s, 1 H), 6.02 (m, 1 H), 6.15 (m, 1 H), 6.68 (m, 1 H), 6.80
(m, 1 H), 7.12 (d, J ) 8.1 Hz, 2 H), 7.25 (d, J ) 8.1 Hz, 2 H),
7.38 (d, J ) 8.1 Hz, 2 H), 7.72 (d, J ) 8.1 Hz, 2 H), 8.15 (br, 1
H), 9.66 (br, 1 H); 13C NMR (CDCl3) δ 0.1, 21.6, 43.9, 94.4,
104.8, 107.9, 108.3, 110.6, 117.9, 120.8, 121.9, 128.2, 129.1,
130.5, 130.9, 132.2, 135.2, 141.1, 141.3, 142.4, 184.6; FAB-MS
obsd 436.1976, calcd 436.1971; νmax(Nujol)/cm-1 1593, 1670,
2154, 3265. Anal. Calcd for C28H28N2OSi: C, 77.0; H, 6.5; N,
6.4. Found: C, 76.8; H, 6.5; N, 6.3.
1
mp 48-51 °C; H NMR (CDCl3) δ 7.36-7.40 (m, 1 H), 7.74-
7.85 (m, 2 H), 8.67-8.69 (m, 1 H); 13C NMR (CDCl3) δ 124.5,
137.7, 149.4, 150.8, 181.0; FAB-MS obsd 306.0023, calcd
306.0012; νmax(Nujol)/cm-1 1648, 1685. Anal. Calcd for C12H4F5-
NO3S: C, 47.2; H, 1.3; N, 4.6. Found: C, 47.2; H, 1.3; N, 4.5.
1-(4-Meth ylben zoyl)-5-m esityldipyr r om eth an e (12). Fol-
lowing an older acylation procedure,34 to a solution of EtMgBr
(1.0 M solution in THF, 27.2 mL, 27.2 mmol) was added
dropwise a solution of 6 (3.0 g, 11.34 mmol) in 20 mL of dry
THF over a 5 min period. The solution was stirred at room
temperature for 30 min, and then a solution of p-toluoyl
chloride (3.0 mL, 11.35 mmol) in 20 mL of THF was added
dropwise. The mixture was stirred for 3 h, and then 100 mL
of saturated aqueous NH4Cl was added to quench the reaction.
The mixture was combined with 100 mL of CH2Cl2, washed
with 100 mL of water, and dried. The solvent was removed
under vacuum, and the resulting solid was purified by gravity
column chromatography (twice) on silica packed with hexanes.
The eluting solvent was gradually increased in polarity from
hexanes to CH2Cl2 to remove a fast running yellow band,
followed by starting material and then the desired product,
which afforded an orange glassy film (1.6 g, 37%). Recrystal-
lization from methanol/H2O gave a yellow powder: mp 75-
1-Br om o-9-(4-m et h ylb en zoyl)-5-m esit yld ip yr r om et h -
a n e (16). Following a general procedure for R-bromination of
pyrroles,36 12 (1.0 g, 2.6 mmol) was dissolved in 25 mL of dry
THF and cooled to -78 °C under argon. NBS (455 mg, 2.6
mmol) was added in two portions, and the reaction mixture
was stirred for an additional 1 h at -78 °C. Hexanes and water
were added, and the mixture was allowed to warm to room
temperature. The organic layer was extracted and dried
(MgSO4), and the solvent was removed under vacuum without
heat. The resulting residue was purified by gravity column
chromatography (silica, hexanes/ethyl acetate (9:1) increasing
to (4:1)) to give a brown glassy film (0.96 g, 80%). Recrystal-
lization from methanol/H2O gave a light brown powder: mp
1
77 °C; H NMR (CDCl3) δ 2.10 (s, 6 H), 2.30 (s, 3 H), 2.43 (s,
3 H), 5.96 (s, 1 H), 6.12 (m, 2 H), 6.22 (m, 1 H), 6.68 (s, 1 H),
6.83 (m, 1 H), 6.90 (s, 2 H), 7.26 (d, J ) 7.5 Hz, 2 H), 7.77 (d,
J ) 7.5 Hz, 2 H), 7.85 (br, 1 H), 9.23 (br, 1 H); 13C NMR (CDCl3)
δ 20.6, 20.7, 21.5, 38.6, 107.1, 108.9, 109.9, 116.8, 120.1, 128.9,
129.1, 129.9, 130.5, 133.1, 135.7, 137.2, 137.4, 140.4, 142.1,
183.9; EI-MS obsd 382.2028, calcd 382.2045; νmax(Nujol)/cm-1
1598, 1724, 3275. Anal. Calcd for C26H26N2O: C, 81.6; H, 6.85;
N, 7.3. Found: C, 81.3; H, 6.9; N, 7.1.
1
105-107 °C dec; H NMR (CDCl3) δ 2.04 (s, 6 H), 2.29 (s, 3
H), 2.40 (s, 3 H), 5.87 (s, 1 H), 6.00 (d, J ) 2.8 Hz, 1 H), 6.10
(m, 2 H), 6.81 (s, 1 H), 6.90 (s, 2 H), 7.25 (d, J ) 5.6 Hz, 2 H),
7.75 (d, J ) 8.0 Hz, 2 H and 1 NH), 9.15 (br, 1 H); 13C NMR
(CDCl3) δ 20.7, 20.8, 21.5, 38.6, 96.6, 109.2, 110.0, 110.8, 120.1,
128.9, 130.2, 130.6, 130.8, 132.4, 135.6, 137.4, 139.7, 142.3,
183.9; EI-MS obsd 460.1134, calcd 460.1150; νmax(Nujol)/cm-1
1594, 1704, 3260. Anal. Calcd for C26H25N2BrO: C, 67.7; H,
5.5; N, 6.1. Found: C, 67.4; H, 5.3; N, 6.0.
1-(P en t a flu or ob en zoyl)-5-(p en t a flu or op h en yl)d ip yr -
r om eth a n e (13). Following a general procedure,35 to a solu-
tion of EtMgBr (1.0 M solution in THF, 16.9 mL, 16.9 mmol)
was added dropwise a solution of 7 (2.60 g, 8.48 mmol) in 20
mL of dry toluene over a 5 min period. The solution was stirred
at room temperature for 10 min before cooling to -78 °C. A
solution of 11 (2.58 g, 8.43 mmol) in 40 mL of toluene was
added, and the mixture was stirred at -78 °C for a further 15
min before saturated aqueous NH4Cl (100 mL) was added. The
reaction mixture was allowed to warm to room temperature,
and the aqueous layer was removed and washed with toluene
(100 mL). The combined organic layer was washed with 2 N
HCl (50 mL), 2 N NaOH (50 mL), and water (50 mL) and then
dried over MgSO4. The solvent was removed under vacuum,
and the resulting oil was purified by flash column chroma-
tography on silica packed with hexanes. The eluting solvent
was gradually increased in polarity from hexanes to CH2Cl2
to remove a fast running yellow band, followed by starting
material and then the desired product to give an orange glassy
film (2.34 g, 55%). Recrystallization of the glassy film from
methanol/ethanol/water gave a yellow solid: mp 75-77 °C; 1H
NMR (CDCl3) δ 5.92 (s, 1 H), 6.07 (m, 1 H), 6.21 (m, 2 H), 6.64
(m, 1 H), 6.82 (m, 1 H), 8.28 (br, 1 H), 9.44 (br, 1 H); 13C NMR
(CDCl3) δ 33.2, 109.0, 111.2, 119.1, 122.4, 125.6, 131.3, 139.3,
1-Br om o-9-(pen taflu or oben zoyl)-5-(pen taflu or oph en yl)-
d ip yr r om et h a n e (17). Following the general procedure
outlined for the synthesis of 16, 13 (2.0 g, 3.95 mmol) was
reacted with NBS (0.7 g, 3.95 mmol) to give a glassy film (1.5
1
g, 65%): mp 60-62 °C; H NMR (CDCl3) δ 5.86 (s, 1 H), 6.10
(m, 3 H), 6.66 (s, 1 H), 8.19 (br, 1 H), 9.53 (br, 1 H); 13C NMR
(CDCl3) δ 33.4, 110.7, 111.1, 111.7, 122.7, 127.2, 131.5, 140.2,
172.5; FAB-MS obsd 583.9582, calcd 583.9582; νmax(Nujol)/cm-1
992, 1503, 1621, 3272. Anal. Calcd for C22H7BrF10N2O: C, 45.2;
H, 1.2; N, 4.8. Found: C, 45.4; H, 1.2; N, 5.0.
1-Br om o-9-(4-m et h ylb en zoyl)-5-(4-iod op h en yl)d ip yr -
r om eth a n e (18). Following the general procedure outlined
for the synthesis of 16, 14 (2.5 g, 5.4 mmol) was reacted with
NBS (0.95 g, 5.4 mmol) to give a glassy film. Recrystallization
from methanol/water gave a light brown solid (2.0 g, 70%): mp
88-90 °C; 1H NMR (CDCl3) δ 2.44 (s, 3 H), 5.44 (s, 1 H), 5.89
(m, 1 H), 6.05 (m, 1 H), 6.10 (m, 1 H), 6.81 (m, 1 H), 6.87 (d,
J ) 8.1 Hz, 2 H), 7.25 (d, J ) 8.1 Hz, 2 H), 7.53 (d, J ) 8.1 Hz,
2 H), 7.67 (d, J ) 8.1 Hz, 2 H), 8.65 (br, 1 H), 10.24 (br, 1 H);