Practical one-pot sequential procedure for the preparation of N-arylated 3,4-disubstituted pyrroles from alkenes

Article abstract of DOI:10.1016/j.jorganchem.2008.09.051

By using ^tBuONa and Cs₂CO₃ as a mixed base, van Leusen pyrrole synthesis and copper-catalyzed N-arylation of pyrrole proceeded sequentially in a single flask to give N-arylated 3,4-disubstituted pyrroles smoothly. Thus, a series of desired N-arylated pyrroles were prepared directly from the electron-deficient alkenes.

Full text of DOI:10.1016/j.jorganchem.2008.09.051

Journal of Organometallic Chemistry 693 (2008) 3897–3901
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Practical one-pot sequential procedure for the preparation of N-arylated
3,4-disubstituted pyrroles from alkenes
*
*
Rui Zhu, Lixin Xing, Yantao Liu, Fangkun Deng, Xinyan Wang , Yuefei Hu
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China
a r t i c l e i n f o
a b s t r a c t
By using tBuONa and Cs2CO3 as a mixed base, van Leusen pyrrole synthesis and copper-catalyzed N-ary-
lation of pyrrole proceeded sequentially in a single flask to give N-arylated 3,4-disubstituted pyrroles
smoothly. Thus, a series of desired N-arylated pyrroles were prepared directly from the electron-deficient
alkenes.
Article history:
Received 2 September 2008
Received in revised form 18 September
2008
Accepted 25 September 2008
Available online 4 October 2008
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Alkenes
Arylations
Copper
Coupling
Pyrroles
1. Introduction
the most suitable for the preparation of substituted pyrroles. Thus,
a highly practical one-pot sequential procedure for the preparation
N-Arylated substituted pyrroles have been found very impor-
tant applications in pharmaceutical researches [1–13]. Paal-Knorr
pyrrole synthesis offered a classic route for their preparation, but
with limitation by using pre-formed 1,4-diketones [8–13]. Re-
cently, many alternative synthetic methods have been developed
for this purpose. Prominent among them are those one-pot
sequential procedures [14–19], by which the N-arylated substi-
tuted pyrroles were prepared directly from simple, readily avail-
able and easily varied substrates. They also can be considered to
fall under the banner of ‘‘green chemistry” because only a single
reaction solvent, work-up procedure, and purification step was
required.
In our recent project on chemical biology, a variety of N-arylat-
ed 3,4-disubstituted pyrroles (1) were designed as synthetic inter-
mediates. For a rapid access to structural diversity, a two-step
route was designed including a van Leusen pyrrole synthesis [20]
starting from alkenes (2) followed by an N-arylation (Scheme 1).
In comparison with the other methods, Ullmann-type coupling of
pyrroles (3) and arylhalides (4) was chosen for the N-arylation step
because it represents a most straightforward and inexpensive
approach [21]. Although many highly efficient ligand-mediated
Ullmann-type couplings have been developed recently under mild
conditions [22–31], we found that Buchwald’s procedure [31] was
of N-arylated 3,4-disubstituted pyrroles (1) starting from alkenes
(2) was established as shown in Scheme 1.
2. Results and discussion
It is well-known that van Leusen pyrrole synthesis is one of the
most convenient methods for the preparation of 3,4-disubstituted
pyrroles (3) by reaction of an electron-deficient alkene (2) and Tos-
MIC (toluenesulphonylmethyl isocyanide) in the presence of a
base. Although the desired pyrrole products usually were obtained
in moderate yields, the method featured with readily available
starting materials. For example, the mixture of ethyl 3-phenylacry-
late (2a) and TosMIC in THF was treated with tBuONa at À30 °C for
10 min to give ethyl 4-phenylpyrrole-3-carboxylate (3a) in 56%
yield [32]. Subsequently, 3a underwent a copper-catalyzed N-ary-
lation of iodobenzene (4a) to give ethyl 1,4-diphenylpyrrole-3-car-
boxylate (1a) under the conditions in Scheme 2. We interestingly
found that the electron-withdrawing substituents on C3 and C4
of pyrroles facilitated the reaction time very much. For example,
the N-arylation of pyrrole was finished around 23 h [31], while
1a was produced in 80% yield within 8 h.
Since both steps were base-promoted reactions and van Leusen
pyrrole synthesis proceeded very fast at À30 °C, we were encour-
aged to combine those two-steps into a one-pot sequential proce-
dure without separation of the intermediate 3a. Thus, the mixture
of 2a, TosMIC, PhI (4a), CuI, 1,10-phenanthroline in toluene was
* Corresponding authors. Tel.: +86 10 62795380; fax: +86 10 62771149.
E-mail address: yfh@mail.tsinghua.edu.cn (Y. Hu).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.051

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R. Zhu et al. / Journal of Organometallic Chemistry 693 (2008) 3897–3901
Table 1
One-Pot Sequencial Procedure
A brief screen on Cu resources and ligandsa,b,c
.
R
R1
R
R1
Copper and Ligand
van Leusen Pyrrole
Synthesis
Ullmann-Type
Coupling
R1
2a
1a
Entry Cu
source
Time Yieldd
Entry Ligand
Time
(h)
Yieldd
(%)
(h)
(%)
N
H
N
Ar
1
R
1
Cul
8
54
6
1,10-
8
54
Phenanthroline
MeNH(CH2)2NHMe
Me2N(CH2)2NH2
Proline
3
2
2
3
4
5
CuBr
Cu(OAc)2 10
CuO
Cu
8
50
30
24
20
7
8
9
10
8
58
24
24
24
Trace
20
24
Scheme 1.
10
8
2,2-Bipyridine
powder
a
The reaction proceeded with 2a (3.0 mmol), TosMIC (3.6 mmol), 4a (4.5 mmol),
tBuONa (3 mmol), Cs2CO3 (6.0 mmol), copper (0.15 mmol), ligand (0.3 mmol) in
toluene.
Ph
CO2Et
CO2Et
TosMIC (1.2 eq), t-BuONa
CO2Et
(1.0 eq), THF, -30 oC, 10 min
56%
b
1,10-Phenanthroline was used as a ligand in entries 1–5.
CuI was used in entries 6–10.
Isolated yields were obtained.
c
N
Ph
d
H
2a
3a
Ph
TosMIC (1.2 eq), PhI (4a, 1.5 eq), CuI (0.05 eq)
MeNH(CH2)2NHMe (0.1 eq), t-BuONa (1.0 eq)
Cs2CO3 (2.0 eq), PhMe, -30 oC to 110 oC, 8 h
PhI (4a, 1.5 eq), CuI (0.05 eq), Cs2CO3 (2.0 eq)
1,10-phenanthroline (0.1 eq), PhMe, 110 oC, 8 h
80%
N
2a
1a
Ph
1a
58%
Scheme 4.
Scheme 2.
Table 2
treated with 3.0 equiv. of tBuONa at À30 °C for 10 min and then the
resultant mixture was refluxed until the intermediate 3a was com-
pletely exhausted (monitored by TLC). Unfortunately, instead of
the expected product 1a, 1,4-diphenylpyrrole-3-carboxylic acid
(5) was obtained in 40% yield, that must result from the fact that
Preparation of 1a–j from 2a–j and 4aa,b,c
.
R1
I
R
R1
TosMIC
+
+
45-70%
N
R
t
the ester group of 3a was unstable to BuONa in the N-arylation
Ph
1a-j
step (110 °C) (Scheme 3). To overcome this problem, we tried to
use Cs2CO3 as a base, but 1a was not obtained at all because Cs2CO3
is not strong enough to generate a carbanion of TosMIC. Finally,
2a-j
4a
Entry 2 and 1
Time Yield Entry 2 and 1
Time Yield
(h)
(h)
of 1
(%)
of 1
(%)
t
when 1:2 mixture of BuONa and Cs2CO3 was used, 1a was ob-
R
R1
R
R1
tained as a single product and its total yield gained 10% more than
1(a)
2(b)
3(c)
Ph
CO2Et
8
8
6
58
56
52
6(f)
7(g)
8(h)
Ph
Ph
2-
BrPh
4-
MePh
4-
NO2Ph
COMe 10
50
70
66
t
that in two-step route. In this procedure, BuONa served as a base
PhCH2 CO2Et
CN
COPh
8
8
for van Leusen pyrrole synthesis and Cs2CO3 for the N-arylation,
respectively.
To optimize conditions, a brief screen for Cu resources and li-
gands was made by using 2a as a substrate. As shown in Table 1,
CuI (entry 1) and N,N’-dimethyl-ethyldiamine (entry 7) proved to
be the best catalyst and ligand, respectively.
According to those experimental results, the optimized condi-
tions for the one-pot sequential preparation of 1a from 2a were
established as shown in Scheme 4 [33].
CO2Et
Me
CO2Et
CO2Me
COPh
4(d)
5(e)
8
8
45
68
9(i)
COPh
COPh
8
7
68
62
Ph
10(j)
a
The conditions in Scheme 4 were used.
b
c
Toluene was the solvent for entries 1–4 and DMF for entries 5–10.
Isolated yields were obtained.
To generalize this novel procedure, the reactions of iodoben-
zene (4a) with different electron-deficient alkenes (2a–j) were
tested under the optimized conditions. As shown in Table 2, all
acrylate derivatives (2a–d) gave the corresponding N-arylpyrroles
1a–d in satisfactory yields (entries 1–4). However, when chalcone
(2e) was used as a substrate, the intermediate 4-phenyl-3-benzoyl-
pyrrole (3e) [34] was isolated instead of the expected N-arylated
product 1,4-diphenyl-3-benzoylpyrrole (1e). The control experi-
ments proved that this problem was caused by the fact that 3e
had a very bad solubility in toluene. The solution is to simply re-
place toluene with DMF, by which 1e was obtained in 68% yield
(entry 5). Under the similar conditions, the all other chalcone
derivatives 2f–j were converted into the corresponding 1f–j
smoothly (entries 6–10).
TosMIC (1.2 eq), PhI (4a, 1.5 eq), CuI
Ph
CO2H
(0.05 eq), 1,10-phenanthroline (0.1 eq)
PhMe, -30 to 110 oC, 8 h, base (3 eq)
2a
1a
+
N
Then, the reactions of ethyl 3-phenylacrylate (2a) with different
phenylhalides (4b–i) were tested under similar conditions (Table
3). Since bromobenzene (4c) gave a very close result with that of
iodobenzene (4a) when prolonged reaction time was used (entry
2), the inexpensive phenylbromides (4c–j) were well employed
for our purpose. It was clearly observed that a pyridine ring had
Ph
Base (3 eq) Yield of 1a Yield of 5
tBuONa : Cs2CO3 = 3 : 0
0
0
54
40
0
0
5
0 : 3
1: 2
Scheme 3.

R. Zhu et al. / Journal of Organometallic Chemistry 693 (2008) 3897–3901
3899
Table 3
Preparation of 1k–p from 2a and 4b–ha,b
.
CO2Et
Ph
CO2Et
+
TosMIC
ArX
+
52-62%
N
Ph
Ar
1k-p
2a
4b-h
Entry
1
Ar-X (4)
Time (h)
5
Yield of 1 (%)
61 (k)
Entry
5
Ar-X (4)
Time (h)
24
Yield of 1 (%)
56 (n)
I
Br
Br
Br
Br
(b)
(f)
(g)
(h)
(i)
O2N
OMe
Cl
2
24
55 (a)
6
24
58 (o)
Br
(c)
3
4
24
24
52 (I)
7
8
5
62 (p)
0 (q)
Br
(d)
N
MeO
F
56 (m)
24
Br
Me
(e)
a
The conditions in Scheme 4 were used.
Isolated yields was obtained.
b
much more reactivity than benzene rings. 2-Bromopyridine (4h)
gave the product 1p in the best yield in the shortest reaction time
(entry 7). Like most reported results that 2-substitutents had hin-
dered effects [22–31], the N-arylation of 1-bromo-2-methyben-
zene (4i) failed under our conditions (entry 8).
corded on a VG-ZAB-MS spectrometer with 70 eV. Elementary
analysis data were obtained on a Perkin–Elmer-241C apparatus.
3.1. A typical procedure for one-pot sequential preparation of 1,4-
diphenylpyrrole-3-carboxylic acid ethyl ester (1a)
In conclusion, a highly practical one-pot sequential procedure
for the preparation of N-arylated 3,4-disubstituted pyrroles was
developed, which in fact proceeded through a van Leusen pyrrole
synthesis followed by a ligand-mediated copper-catalyzed N-aryla-
tion of pyrroles. Although both reactions are promoted by bases,
they could not share a common base because significantly different
strengths of bases were required for each of them. When the mix-
ture of t-BuONa and Cs2CO3 was used in the procedure, each step
proceeded sequentially with extremely high orderliness and effi-
ciency. By using the novel procedure, one work-up procedure
was saved and total yields of the products were increased signifi-
cantly. Thus, a series of N-arylated 3,4-disubstituted pyrroles were
prepared directly from the electron-deficient alkenes. It can be ex-
pected that any alkenes suitable for van Leusen pyrrole synthesis
can be converted into the corresponding N-arylated 3,4-disubsti-
tuted pyrroles conveniently by our procedure.
To a stirred mixture of ethyl 3-phenylacrylate (2a, 530 mg,
3 mmol), TosMIC (700 mg, 3.6 mmol), PhI (4a, 920 mg, 4.5 mmol),
CuI (29 mg, 0.15 mmol), (MeNHCH2)2 (26.5 mg, 0.3 mmol) and
Cs2CO3 (1.95 g, 6 mmol) in toluene (30 mL) was treated with
t-BuONa (300 mg, 3.15 mmol) at À25 °C under nitrogen. Ten min-
utes later, the system was heated to reflux for 8 h (monitored by
TLC). Then the resultant mixture was cooled to room temperature
and H2O was added respectively. After it filtered through a pad of
Celite (eluted by CH2Cl2), the organic layer was separated and
washed with H2O, brine and dried over Na2SO4. Removal of the sol-
vent yielded the crude product, which was purified by chromatog-
raphy (PE:EtOAc:DCM = 10:1:1) to give pure product 1a (510 mg,
58%) as colorless crystals.
The similar procedure was used in the preparation of 1b–p.
DMF was used as a reaction solvent in the 1e-j in Table 1.
3.1.1. 1,4-Diphenylpyrrole-3-carboxylic acid ethyl ester (1a)
m .
3141, 3049, 1672, 1601 cmÀ1
3. Experimental
M.p. 68–70 °C (EtOAc-PE). IR:
1H NMR: d 7.77 (d, J = 2.7 Hz, 1H), 7.58–7.28 (m, 10H), 7.07 (d,
J = 2.7 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H). 13C
NMR: d 164.1, 139.1, 134.1, 129.5, 129.0, 128.1, 127.5, 126.6,
126.5, 125.6, 120.3, 119.3, 115.1, 59.4, 14.1. MS m/z (%): 291 (M+,
100). Anal. Calc. for C19H17NO2 (291.34): C, 78.33; H, 5.88; N,
4.81. Found: C, 78.03; H, 5.78; N, 4.85%.
All melting points were determined on a Yanaco melting point
apparatus and are uncorrected. IR spectra were recorded on a Nico-
let FT-IR 5DX spectrometer. The 1H NMR and 13C NMR spectra were
recorded on a JEOL JNM-ECA 300 spectrometer in CDCl3 with TMS
as internal reference. The J values are given in Hz. MS were re-

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R. Zhu et al. / Journal of Organometallic Chemistry 693 (2008) 3897–3901
3.1.2. 1-Phenyl-4-benzylpyrrole-3-carboxylic acid ethyl ester (1b)
M.p. 60–61 °C (EtOAc-PE). IR: 3135, 3054, 2976, 1694,
1599 cmÀ1 1H NMR: d 7.69 (d, J = 2.0 Hz, 1H), 7.42–7.19 (m,
10H), 6.61 (d, J = 2.1 Hz, 1H), 4.26 (q, J = 7.2 Hz, 2H), 4.15 (s, 2H),
1.31 (t, J = 7.2 Hz, 3H). 13C NMR: d 164.8, 141.1, 139.6, 129.5,
128.8, 128.2, 127.0, 126.4, 125.7, 125.0, 120.5, 119.5, 116.0, 59.4,
32.4, 14.4. MS m/z (%): 305 (M+, 36.6), 259 (100). Anal. Calc. for
C20H19NO2 (305.37): C, 78.66; H, 6.27; N, 4.59. Found: C, 78.77;
H, 6.19; N, 4.58%.
3.1.10. 1-Phenyl-4-(4-nitrophenyl)-3-benzoylpyrrole (1j)
M.p. 162–164 °C (EtOAc-PE). IR: .
3137, 3073, 1638, 1595 cmÀ1
m
m
.
1H NMR: d 8.12 (d, J = 7.5 Hz, 2H), 7.88 (d, J = 7.8 Hz, 2H), 7.60–7.30
(m, 12H). 13C NMR: d 190.7, 146.1, 141.2, 139.2, 138.9, 132.2,
129.9, 129.3, 129.0, 128.3, 128.2, 127.5, 126.4, 123.3, 121.3,
120.9. MS m/z (%): 368 (M+, 87.4), 292 (50.6), 77 (100). Anal. Calc.
for C23H16N2O3 (368.38): C, 74.99; H, 4.38; N, 7.60. Found: C, 74.89;
H, 4.34; N, 7.55%.
3.1.11. 1-(4-Nitrophenyl)-4-phenylpyrrole-3-carboxylic acid ethyl
3.1.3. 1-Phenylpyrrole-3,4-dicarboxylic acid diethyl ester (1c)
M.p. 46–48 °C (EtOAc-PE) (lit. [34] 48 °C). 1H NMR: d 7.60 (s, 2 H),
7.48–7.42 (m, 5H), 4.33 (q, J = 7.2 Hz, 4H), 1.37 (t, J = 7.2 Hz, 6H). 13C
NMR: d 163.1, 138.7, 129.7, 127.4, 125.7, 120.8, 117.6, 60.1, 14.1.
ester (1k)
M.p. 176–178 °C (EtOAc-PE). IR:
m .
3132, 3082, 2988, 1675 cmÀ1
1H NMR: d 8.36–8.33 (m, 2H), 7.86 (d, J = 2.8 Hz, 1H), 7.61–7.38 (m,
7H), 7.15 (d, J = 2.4 Hz, 1H), 4.24 (q, J = 6.9 Hz, 2H), 1.27 (t, J = 6.9
Hz, 3H). 13C NMR: d 163.8, 145.6, 143.9, 133.4, 129.7, 129.1,
127.8, 127.1, 125.6, 125.4, 120.0, 119.0, 117.3, 60.0, 14.2. MS m/z
(%): 336 (M+, 100), 291 (51.9). Anal. Calc. for C19H16N2O4
(336.34): C, 67.85; H, 4.79; N, 8.33. Found: C, 67.88; H, 4.72; N,
8.36%.
3.1.4. 1-Phenyl-4-methylpyrrole-3-carboxylic acid methyl ester (1d)
[35]
Colorless oil. 1H NMR: d 7.64 (d, J = 2.4 Hz, 1H), 7.42–7.27 (m,
5H), 6.82 (d, J = 2.4 Hz, 1H), 3.82 (s, 3H), 2.33 (s, 3H). 13C NMR: d
165.0, 139.2, 129.2, 126.0, 124.3, 122.6, 119.8, 118.5, 115.9, 50.2,
11.3.
3.1.12. 1-(4-Methoxyphenyl)-4-phenylpyrrole-3-carboxylic acid ethyl
ester (1l)
3.1.5. 1,4-Diphenyl-3-benzoylpyrrole (1e)
M.p. 100–101 °C (EtOAc-PE). IR: m .
3139, 3055, 1707 cmÀ1 1H
M.p. 118–120 °C (EtOAc-PE). IR:
m
3270, 3116, 1644, 1630,
NMR: d 7.68 (m, 1H), 7.52 (m, 2H), 7.37–7.32 (m, 5H), 6.99–6.96
(m, 3H), 4.23 (q, J = 7.2 Hz, 2H), 3.86 (s, 3H), 1.25 (t, J = 7.2 Hz,
3H). 13C NMR: d 164.4, 158.4, 134.3, 132.9, 129, 2 127.9, 127.6,
126.5, 126.1, 122.2, 120.0, 114.8, 114.7, 59.5, 55.4, 14.2. MS m/z
(%): 321 (M+, 100), 276 (49.4). Anal. Calc. for C20H19NO3 (321.37):
C, 74.75; H, 5.96; N, 4.36. Found: C, 74.84; H, 6.00; N, 4.32%.
1596 cmÀ1 1H NMR: d 7.85 (d, J = 7.3 Hz, 2H), 7.47–7.17 (m,
.
15H). 13C NMR: d 191.1, 139.5, 139.3, 134.1, 131.7, 129.7, 129.4,
128.7, 128.6, 127.9, 127.1, 126.9, 126.5, 123.5, 120.7, 119.9. MS
m/z (%): 323 (M+, 100), 246 (65.8), 77 (80). Anal. Calc. for
C23H17NO (323.39): C, 85.42; H, 5.30; N, 4.33. Found: C, 85.31; H,
5.28; N, 4.37%.
3.1.13. 1-(4-Fluorophenyl)-4-phenylpyrrole-3-carboxylic acid ethyl
3.1.6. 1,4-Diphenyl-3-acetylpyrrole (1f)
ester (1m)
Light yellow oil. IR:
m
3128, 2923, 1716, 1655, 1598 cmÀ1
.
1H
M.p. 104–106 °C (EtOAc-PE). IR: m .
3078, 2980, 1710 cmÀ1 1H
NMR: d 7.69 (d, J = 1.5 Hz, 1H), 7.50–7.34 (m, 10H), 7.05 (d,
J = 1.5 Hz, 1H), 2.34 (s, 3H). 13C NMR: d 193.6, 139.2, 134.4,
129.6, 129.1, 127.7, 127.6, 126.8, 126.7, 125.6, 124.9, 120.6,
120.3, 28.5. MS m/z (%): 261 (M+, 67.8), 247 (18.9), 246 (100), 77
(45.5). Anal. Calc. for C18H15NO (261.32): C, 82.73; H, 5.79; N,
5.36. Found: C, 82.70; H, 5.89; N, 5.33%.
NMR: d 7.69 (d, J = 2.4 Hz, 1H), 7.53–7.51 (m, 2H), 7.42–7.29 (m,
5H), 7.15–7.14 (m, 2H), 6.99 (d, J = 2.7 Hz, 1H), 4.25 (q, J = 3.6 Hz,
2H), 1.25 (t, J = 3.6 Hz, 3H). 13C NMR: d 164.3, 162.8, 159.6, 134.1,
129.2, 128.4, 127.7, 126.7, 126.1, 122.6, 122.5, 119.8, 116.7,
116.4, 115.5, 59.7, 14.2. MS m/z (%): 309 (M+, 100), 264 (76.5). Anal.
Calc. for C19H16FNO2 (309.33): C, 73.77; H, 5.21; N, 4.53. Found: C,
73.66; H, 5.18; N, 4.50%.
3.1.7. 1,4-Diphenyl-3-cyanopyrrole (1g)
M.p. 87–88 °C (EtOAc-PE). IR:
m
3142, 3127, 3051, 2221,
3.1.14. 1-(3-Methoxyphenyl)-4-phenylpyrrole-3-carboxylic acid ethyl
1598 cmÀ1
.
1H NMR: d 7.68 (d, J = 3.8 Hz, 2H), 7.58–7.24 (m,
ester (1n)
10H). 13C NMR: d 138.6, 132.1, 129.7, 128.6, 128.1, 127.5, 127.4,
127.2, 126.2, 120.7, 117.7, 116.2, 93.3. MS m/z (%): 244 (M+, 100).
Anal. Calc. for C17H12N2 (244.29): C, 83.58; H, 4.95; N, 11.47.
Found: C, 83.65; H, 4.89; N, 11.40%.
M.p. 77–78 °C (EtOAc-PE). IR: m .
3153, 2975, 1679 cmÀ1 1H
NMR: d 7.73 (d, J = 2.4 Hz, 1H), 7.53 (s, 1H), 7.51 (s, 1H), 7.38-
7.23 (m, 4H), 7.01–6.79 (m, 4H), 4.20 (q, J = 7.2 Hz, 2H), 3.76 (s,
3H), 1.24 (t, J = 7.2 Hz, 3H). 13C NMR: d 164.2, 160.5, 140.4,
134.1, 130.4, 129.1, 128.1, 127.5, 126.5, 125.7, 119.5, 115.2,
112.7, 112.0, 106.7, 59.5, 55.2, 14.1;MS m/z (%): 321 (M+, 100),
276 (46.7). Anal. Calc. for C20H19NO3 (321.37): C, 74.75; H, 5.96;
N, 4.36. Found: C, 74.79; H, 5.91; N, 4.33%.
3.1.8. 1-Phenyl-4-(2-bromophenyl)-3-benzoylpyrrole (1h)
M.p. 142–143 °C (EtOAc-PE). IR:
m .
3127, 3066, 1640, 1594 cmÀ1
1H NMR: d 7.84 (d, J = 6.9 Hz, 2H), 7.53–7.47 (m, 7 H), 7.42–7.23
(m, 5H), 7.20–7.06 (m, 2H). 13C NMR: d 190.7, 139.3, 139.2,
135.7, 132.5, 131.7, 131.6, 129.7, 129.3, 128.3, 127.9, 126.9,
126.9, 125.8, 124.9, 120.8, 120.7. MS m/z (%): 402 (0.1), 400 (M+,
0.1), 323 (26.7), 322 (100), 77 (15.5). Anal. Calc. for C23H16BrNO
(402.28): C, 68.67; H, 4.01; N, 3.48. Found: C, 68.77; H, 4.06; N,
3.49%.
3.1.15. 1-(3-Chlorophenyl)-4-phenylpyrrole-3-carboxylic acid ethyl
ester (1o)
M.p. 99–101 °C (EtOAc-PE). IR:
m .
3144, 3074, 2978, 1686 cmÀ1
1H NMR: d 7.75 (d, J = 3.0 Hz, 1H), 7.51–7.32 (m, 9H), 7.05 (d,
J = 3.0 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H). 13C
NMR: d 146.1, 140.4, 135.4, 133.9, 130.7, 129.2, 128.8, 127.7,
126.8, 125.6, 120.8, 119.3, 118.6, 116.0, 59.7, 14.2. MS m/z (%):
325 (M+, 100), 280 (54.3). Anal Calcd for C19H16ClNO2 (325.79):
C, 70.05; H, 4.95; N, 4.30. Found: C, 70.09; H, 4.89; N, 4.34%.
3.1.9. 1-Phenyl-4-(4-methylphenyl)-3-benzoylpyrrole (1i)
M.p. 135–137 °C (EtOAc-PE). IR:
m 3118, 3063, 2917, 1627,
1597 cmÀ1 1H NMR: d 7.86 (d, J = 2.4 Hz, 2H), 7.47–7.33 (m,
.
11H), 7.13-7.10 (m, 3 H), 2.33 (s, 3H). 13C NMR: d 191.0, 139.6,
139.3, 136.0, 131.6, 131.1, 129.7, 129.4, 128.6, 128.4, 127.9,
127.1, 126.8, 123.4, 120.6, 119.6, 21.0. MS m/z (%): 337 (M+, 100),
260 (48.5), 77 (30.1). Anal. Calc. for C24H19NO (337.41): C, 85.43;
H, 5.68; N, 4.15. Found: C, 85.33; H, 5.71; N, 4.13%.
3.1.16. 1-(Pyridin-2-yl)-4-phenylpyrrole-3-carboxylic acid ethyl ester
(1p)
M.p. 38–39 °C (EtOAc-PE). IR:
m 3163, 3094, 2972, 1708,
1595 cmÀ1 1H NMR: d 8.47 (d, J = 0.7 Hz, 1H), 8.21 (d, J = 2.4 Hz,
.

R. Zhu et al. / Journal of Organometallic Chemistry 693 (2008) 3897–3901
3901
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1H), 7.83–7.78 (m, 1H), 7.57–7.51 (m, 3H), 7.41–7.26 (m, 5H), 4.24
(q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H). 13C NMR: d 164.1, 149.9,
148.6, 138.6, 134.0, 129.1, 128.4, 127.5, 126.6, 124.4, 121.2, 117.8,
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3.1.17. 1,4-Diphenylpyrrole-3-carboxylic acid (5)
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m
3144, 3057, 2627, 1680,
1654 cmÀ1 1H NMR (DMSO-d6):
.
d 11.99 (br. 1H), 7.89 (d,
J = 1.5 Hz, 1H), 7.61–7.15 (m, 11H). 13C NMR (DMSO-d6): d 165.7,
139.3, 134.8, 130.3, 129.5, 128.2, 127.9, 127.1, 126.8, 126.4,
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Acknowledgments
This work was supported by NNSF of China (20672066,
30600779).
Appendix A. Supplementary material
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