A R T I C L E S
Maeda et al.
extracts were dried over anhydrous MgSO
4
and evaporated to give a
1,3-Bis(5-(2,6-dimethylphenyl)pyrrol-2-yl)-1,3-propanedione, 2c.
white solid. The residue was then chromatographed over flash silica
gel column (eluent: CH Cl /hexane ) 1/1) to give 2-(2,6-dimethylphe-
nyl)pyrrole as a white powder (50.2 mg, 15% from the starting
2 2
A CH Cl solution (10 mL) of 2-(2,6-dimethylphenyl)pyrrole (47.0 mg,
2
2
0.27 mmol) was treated with malonyl chloride (23.1 mg, 0.16 mmol)
at room temperature and stirred for 3 h at the same temperature. After
the consumption of the starting pyrrole was confirmed by TLC analysis,
1
arylbromide). R
CDCl , 20 °C): δ (ppm) 7.92 (br, 1H, NH), 7.17 (t, J ) 7.2 Hz, 1H,
Ar-H), 7.10 (d, J ) 7.8 Hz, 2H, Ar-H), 6.86 (m, 1H, pyrrole-H), 6.32
m, 1H, pyrrole-H), 6.08 (m, 1H, pyrrole-H). FABMS: m/z (%
f
) 0.26 (CH
2 2
Cl /hexane ) 1/3). H NMR (600 MHz,
3
the mixture was washed with saturated, aq Na
over anhydrous MgSO , filtered, and evaporated to dryness. The residue
was then chromatographed over flash silica gel column (eluent: 2%
MeOH/CH Cl ) and recrystallized from CH Cl /hexane to afford 2c
(38.7 mg, 69%) as a pale-yellow solid. R ) 0.43 (2% MeOH/CH
, 20 °C; diketone 2c is obtained as a
2 3
CO and water, dried
4
(
+
+
intensity): 171.1 (100, M ), 172.1 (100, M + 1). Calcd for C12
71.10.
,3-Di-(5-phenylpyrrol-2-yl)-1,3-propanedione, 2a. Analogous to
a literature procedure, a CH Cl
solution (30 mL) of 2-phenylpyrrole17
274.0 mg, 1.92 mmol) was treated with malonyl chloride (161.8 mg,
H13N:
2
2
2
2
1
f
2
-
1
1
2 3
Cl ). H NMR (600 MHz, CDCl
2
2
mixture of keto and enol tautomers in the ratio of 1:0.18): δ (ppm)
keto form 9.11 (br, 2H, NH), 7.21 (m, 2H, Ar-H), 7.19 (m, 2H, pyrrole-
H), 7.12-7.09 (m, 4H, Ar-H), 6.20 (m, 2H, pyrrole-H), 4.26 (s, 2H,
(
1
.15 mmol) at room temperature and stirred for 3 h at the same
temperature. After the consumption of the starting pyrrole was
confirmed by TLC analysis, the mixture was washed with saturated,
3
CH), 2.14 (s, 12H, CH ); enol form 16.58 (br, 1H, OH), 9.01 (br, 2H,
NH), 7.21 (m, 2H, Ar-H), 7.12-7.09 (s, 4H, Ar-H), 6.99 (m, 2H,
aq Na
evaporated to dryness. The residue was then chromatographed over
flash silica gel column (eluent: 2% MeOH/CH Cl ) and recrystallized
from CH Cl /hexane to afford 2a (153.9 mg, 45%) as a pale-yellow
solid. R ) 0.35 (2% MeOH/CH
0 °C; diketone 2a is obtained as a mixture of keto and enol tautomers
in the ratio of 1:0.28): δ (ppm) keto form 9.56 (br, 2H, NH), 7.58 (m,
H, Ar-H), 7.43 (m, 4H, Ar-H), 7.33 (m, 2H, Ar-H), 7.16 (m, 2H,
pyrrole-H), 6.60 (m, 2H, pyrrole-H), 4.26 (s, 2H, CH); enol form 16.69
br, 1H, OH), 9.44 (br, 2H, NH), 7.58 (m, 4H, Ar-H), 7.43 (m, 4H,
2
CO
3
and water, dried over anhydrous MgSO
4
, filtered, and
pyrrole-H), 6.36 (s, 1H, CH), 6.20 (m, 2H, pyrrole H), 2.18 (s, 12H,
+
+
CH ). FABMS: m/z (% intensity): 410.3 (76, M ), 411.3 (100, M +
3
2
2
1). Calcd for C H N O : 410.20.
27
26
2
2
2
2
BF
2 2
Complex of 2a, 3a. To a CH Cl
solution (230 mL) of diketone
‚OEt (600.4 mg, 4.23 mmol)
2
1
f
2 2 3
Cl ). H NMR (600 MHz, CDCl ,
2
a (50.0 mg, 0.14 mmol) was added BF
3
2
2
and was stirred for 10 min at room temperature. After removal of the
solvent, flash silica gel column chromatography (eluent: 2% MeOH/
4
CH
2
Cl
2
) and crystallization from CH
2 2
Cl /hexane afforded 3a (54.4 mg,
1
9
2
7
6%) as a red solid. R
0 °C): δ (ppm) 9.67 (br, 2H, NH), 7.65 (d, J ) 7.2 Hz, 4H, Ar-H),
.48 (t, J ) 7.8 Hz, 4H, Ar-H), 7.39 (t, J ) 7.2 Hz, 2H, Ar-H), 7.22
f
) 0.35 (CH Cl ). H NMR (600 MHz, CDCl ,
2
2
3
(
Ar-H), 7.33 (m, 2H, Ar-H), 6.97 (m, 2H, pyrrole-H), 6.64 (m, 2H,
pyrrole-H), 6.37 (s, 1H, CH). FABMS: m/z (% intensity): 354.2 (58,
(
dd, J ) 2.4, 1.8 Hz, pyrrole-H), 6.74 (dd, J ) 2.4, 1.8 Hz, 2H, pyrrole-
+
+
M ), 355.21 (100, M + 1) Calcd for C23
H
18
N
2
O
2
: 354.14.
5
-1
-1
H), 6.55 (s, 1H, CH). UV/vis (CH
5
M
2
Cl
2
, λmax [nm] (ꢀ, 10 M cm )):
1
,3-Di-(5-(2-tolyl)pyrrol-2-yl)-1,3-propanedione, 2b. A CH
2
Cl
2
+
00.0 (1.24). FABMS: m/z (% intensity): 402.3 (100, M ), 403.3 (52,
solution (10 mL) of 2-(2-tolyl)pyrrole (41.8 mg, 0.27 mmol) was treated
with malonyl chloride (22.5 mg, 0.16 mmol) at room temperature and
stirred for 3 h at the same temperature. After the consumption of the
starting pyrrole was confirmed by TLC analysis, the mixture was
+
2 2 2
+ 1). Calcd for C23H17BF N O : 402.14. This compound was
further characterized by X-ray diffraction analysis.
BF Complex of 2b, 3b. To a CH Cl solution (60 mL) of diketone
b (23.0 mg, 0.06 mmol), was added BF ‚OEt (255.5 mg, 1.8 mmol)
and was stirred for 10 min at room temperature. After removal of the
solvent, flash silica gel column chromatography (eluent: CH Cl ) and
crystallization from CH Cl /hexane afforded 3b (21.7 mg, 84%) as a
vermillion red solid. R ) 0.40 (CH
0 °C): δ (ppm) 9.47 (br, 2H, NH), 7.44 (m, 2H, Ar-H), 7.31-7.30
m, 6H, Ar-H), 7.26-7.24 (m, 2H, pyrrole-H), 6.56 (m, 2H, pyrrole-
H), 6.56 (s, 1H, CH), 2.49 (s, 6H, CH ). UV/vis (CH Cl , λmax [nm] (ꢀ,
0 M cm )): 480.0 (0.93). FABMS: m/z (% intensity): 430.3 (100,
2
2
2
2
3
2
washed with saturated, aq Na
Na SO , filtered, and evaporated to dryness. The residue was then
chromatographed over flash silica gel column (eluent: 3% MeOH/
CH Cl ) and recrystallized from CH Cl /hexane to afford 2b (23.8 mg,
6%) as a pale-yellow solid. R ) 0.35 (3% MeOH/CH
600 MHz, CDCl , 20 °C; diketone 2b is obtained as a mixture of keto
and enol tautomers in the ratio of 1:0.19): δ (ppm) keto form 9.35
br, 2H, NH), 7.39 (m, 2H, Ar-H), 7.28-7.27 (m, 6H, Ar-H), 7.18 (m,
2 3
CO and water, dried over anhydrous
2
4
2
2
2
2
2
2
2
2
1
f
2 2 3
Cl ). H NMR (600 MHz, CDCl ,
1
4
f
2 2
Cl ). H NMR
2
(
(
3
3
2
2
(
5
-1
-1
1
2
6
2
H, pyrrole-H), 6.43 (m, 2H, pyrrole-H), 4.26 (s, 2H, CH), 2.46 (s,
H, CH ); enol form 16.65 (br, 1H, OH), 9.26 (br, 2H, NH), 7.43(m,
H, Ar-H), 7.28-7.27 (m, 6H, Ar-H), 6.98 (m, 2H, pyrrole-H), 6.46
). FABMS:
m/z (% intensity): 382.1 (73, M ), 383.2 (100, M + 1). Calcd for
: 382.17.
,3-Di-(5-(3-tolyl)pyrrol-2-yl)-1,3-propanedione, 2b′. A CH
+
+
M ), 431.3 (42, M + 1). Calcd for C25
compound was further characterized by X-ray diffraction analysis.
BF Complex of 2b′, 3b′. To a CH Cl solution (30 mL) of diketone
2b′ (15.0 mg, 0.039 mmol) was added BF ‚OEt (167.5 mg, 1.2 mmol)
2 2 2
H21BF N O : 430.17. This
3
2
2
2
(m, 2H, pyrrole-H), 6.38 (s, 1H, CH), 2.49 (s, 6H, CH
3
+
+
3
2
and was stirred for 10 min at room temperature. After removal of the
solvent, flash silica gel column chromatography (eluent: 1% MeOH/
25 22 2 2
C H N O
1
2 2
Cl
CH
2
Cl
2
) and crystallization from CH
) 0.36 (CH
2
Cl
2
/hexane afforded 3b′ (14.7 mg,
solution (20 mL) of 2-(3-tolyl)pyrrole (81.7 mg, 0.52 mmol) was treated
with malonyl chloride (43.6 mg, 0.31 mmol) at room temperature and
stirred for 3 h at the same temperature. After the consumption of the
starting pyrrole was confirmed by TLC analysis, the mixture was
1
8
2
7
7%) as a red solid. R
0 °C): δ (ppm) 9.63 (br, 2H, NH), 7.44 (m, 4H, Ar-H), 7.35 (t, J )
.8 Hz, 2H, Ar-H), 7.21 (m, 2H, Ar-H), 7.19 (m, 2H, pyrrole-H), 6.72
f
2
Cl
2
). H NMR (600 MHz, CDCl
3
,
(
Cl
m, 2H, pyrrole-H), 6.54 (s, 1H, CH), 2.44 (s, 6H, CH
3
). UV/vis (CH
2
-
washed with saturated, aq Na
Na SO , filtered, and evaporated to dryness. The residue was then
chromatographed over flash silica gel column (eluent: 3% MeOH/
CH Cl ) and recrystallized from CH Cl /hexane to afford 2b′ (35.5 mg,
6%) as a pale-yellow solid. R ) 0.35 (3% MeOH/CH
600 MHz, CDCl , 20 °C; diketone 2b′ is obtained as a mixture of
keto and enol tautomers in the ratio of 1:0.21): δ (ppm) keto form
2 3
CO and water, dried over anhydrous
5
-1
-1
2
, λmax [nm] (ꢀ, 10 M cm )): 502.0 (0.83). FABMS: m/z (%
2
4
+
+
intensity): 430.2 (100, M ), 431.2 (42, M + 1). Calcd for C25
BF : 430.17. This compound was further characterized by X-ray
diffraction analysis.
BF Complex of 2c, 3c. To a CH
2c (25.0 mg, 0.061 mmol) was added BF
21
H -
2 2 2
N O
2
2
2
2
1
3
f
2 2
Cl ). H NMR
(
3
2
2
Cl
2
solution (60 mL) of diketone
‚OEt (259.7 mg, 1.83 mmol)
3
2
9
2
2
2
.53 (br, 2H, NH), 7.38 (m, 4H, Ar-H), 7.31 (m, 2H, Ar-H), 7.16 (m,
H, pyrrole-H), 7.13 (m, 2H, Ar-H), 6.58 (m, 2H, pyrrole-H), 4.25 (s,
and was stirred for 10 min at room temperature. After removal of the
solvent, flash silica gel column chromatography and crystallization from
H, CH), 2.39 (s, 6H, CH
3
); enol form 16.71 (br, 1H, OH), 9.42 (br,
CH
0.40 (CH
2 2 f
Cl /hexane afforded 3c (20.8 mg, 78%) as a yellow solid. R )
1
H, NH), 7.38 (m, 4H, Ar-H), 7.31 (m, 2H, Ar-H), 7.13 (m, 2H, Ar-
2 2 3
Cl ). H NMR (600 MHz, CDCl , 20 °C): δ (ppm) 9.24 (br,
H), 6.96 (m, 2H, pyrrole-H), 6.62 (m, 2H, pyrrole-H), 6.36 (s, 1H,
2H, NH), 7.27 (m, 2H, pyrrole-H), 7.24 (t, J ) 7.8 Hz, 2H, Ar-H),
7.12 (d, J ) 7.8 Hz, 4H, Ar-H), 6.61 (s, 1H, CH), 6.34 (m, 2H, pyrrole-
H), 2.17 (s, 12H, CH ). UV/vis (CH Cl , λmax [nm] (ꢀ, 10 M cm )):
3 2 2
+
CH), 2.41 (s, 6H, CH
3
). FABMS: m/z (% intensity): 382.2 (72, M ),
+
5
-1
-1
3
83.2 (100, M + 1). Calcd for C25
H N
22 2
O
2
: 382.17.
13670 J. AM. CHEM. SOC.
9
VOL. 129, NO. 44, 2007