I2-catalyzed synthesis of substituted pyrroles from α-amino carbonyl compounds and aldehydes

Article abstract of DOI:10.1021/jo402620z

A direct method for the synthesis of 1,3,4-triarylpyrroles was achieved easily from cyclization of α-amino carbonyl compounds and aldehydes catalyzed by I₂. Various substituted groups can be employed, and this reaction can proceed smoothly in moderate to good yields.

Full text of DOI:10.1021/jo402620z

Note
pubs.acs.org/joc
I2‑Catalyzed Synthesis of Substituted Pyrroles from α‑Amino
Carbonyl Compounds and Aldehydes
Rulong Yan,* Xing Kang, Xiaoqiang Zhou, Xiaoni Li, Xingxing Liu, Likui Xiang, Yamin Li,
and Guosheng Huang*
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of
Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: A direct method for the synthesis of 1,3,4-triarylpyrroles was achieved easily from cyclization of α-amino carbonyl
compounds and aldehydes catalyzed by I2. Various substituted groups can be employed, and this reaction can proceed smoothly
in moderate to good yields.
We began our study by investigating the reaction of 1-
phenyl-2-(phenylamino)ethan-1-one (1a) and 2-phenylacetal-
dehyde (2a) with I2 catalysis in toluene at 100 °C. Gratifyingly,
the desired 1,3,4-triphenyl-1H-pyrrole (3aa) was isolated in
18% yield after 4 h (Table 1, entry 1). Obviously, I2 promotes
the reaction by coordinating with the oxygens of the organic
carbonyl compounds,9 and the high chemoselectivity of the
pyrrole formation suggests that 2a reacts with the NH group of
1a to generate intermediate 6, which directly produces
intermediate 7 via intramolecular nucleophilic cyclization
(Scheme 2). Then H2O is eliminated from 7 to afford pyrrole
3aa. There are very few examples of the synthesis of substituted
pyrroles with phenylacetaldehyde directly. This interesting
result encouraged us to optimize the reaction conditions to
provide a general protocol for the synthesis of substituted
pyrroles.
In order to improve the yield, 4 Å molecular sieves (M.S.)
were added to the reaction mixture, and the yield increased to
61% (Table 1, entry 2). Moreover, various metal salts were
screened, and we were pleased to find that ZnCl2 as a typical
activator for organic carbonyl compounds showed the highest
activity, affording pyrrole 3aa in 82% yield (entry 7).10 Other
metal salts such as Pd(OAc)2, AgOAc, FeCl2, and FeCl3
showed no overall improvement (entries 3−6). Acids such as
PivOH and HOAc were also examined, and no better results
were obtained (entries 8 and 9). After screening on different
parameters, including solvent and temperature (entries 10−13),
ubstituted pyrroles represent one of the most important
Sclasses of heterocyclic molecules found in numerous
natural and biologically active compounds.1 Furthermore,
substituted pyrroles are widely used as synthetic building
blocks, pharmacophores, and various kinds of functional
materials.2 Since the pyrroles were found from coal tar and
bone oil, chemists have been fascinated with their synthesis.
Traditional methods for the synthesis of substituted pyrroles
include the classical Knorr reaction, the Hantzsch reaction, and
the Paal−Knorr condensation reaction.3 Recently, new
procedures based on multicomponent coupling,4 tandem
reactions, transition-metal-catalyzed cyclization,5 and catalytic
C−H bond functionalization strategies have been developed
and drawn extensive and enduring attention.6 However, it is
still a great challenge to design a highly efficient chemical
reaction that can be used to construct the skeleton of pyrroles
with readily accessible substrates and few steps.
The use of commercially available amines and aldehydes to
synthesize heterocyclic compounds in few steps has drawn
more attention. Inspired by Jia’s synthesis of substituted
pyrroles using AgOAc-mediated cyclization of aldehydes and
anilines,7 we conceived a synthetic route for heterocyclic
compounds via cyclization of α-amino carbonyl compounds
and aldehydes (Scheme 1). As expected, substituted pyrroles
were successfully obtained through this reaction. On the basis
of our previous studies,8 herein we report a facile and
straightforward method to synthesize substituted pyrroles
from α-amino carbonyl compounds and aldehydes via I2
catalysis.
Received: November 26, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo402620z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 1. Synthesis of Substituted Pyrroles Using Amines and Aldehydes
chloro, and fluoro groups on the substrates all survived and
gave the target molecule. As shown in Table 2, electron-
donating groups for R1 played a positive role in the reaction
and resulted in higher yields than electron-withdrawing groups.
Further studies showed that electron-rich and electron-deficient
groups for R2 and R3 displayed similar efficiencies and did not
significantly affect the yield of the products. Notably, ortho-
substitution on the aryl rings had an obvious impact on the
results, suggesting that the transformation is sensitive to steric
hindrance of the α-amino carbonyl compounds and aldehydes.
For example, the desired pyrrole (3ba) was generated only in
72% yield when 1b was employed as a substrate. 1-
(Naphthalen-1-yl)-3,4-diphenyl-1H-pyrrole (3la) was obtained
in 52% yield when 2-(naphthalen-1-ylamino)-1-phenylethan-1-
one (1l) was used as a substrate. However, the substituted
pyrrole 3rd was not obtained when 1r and 2d were used as
substrates. Unfortunately, when butyraldehyde and 1a were
subjected to the standard conditions, no desired product was
detected (Scheme 3).
It is worth mentioning that when 1-phenyl-2-(phenylamino)-
ethan-1-one (1a) and 3-phenylpropanal (4a) were employed as
substrates under the optimized conditions, the desired product
3-benzyl-1,4-diphenyl-1H-pyrrole (4aa) was isolated in 52%
yield (Scheme 4).
In summary, we have developed a direct I2-catalyzed method
for synthesis of 1,3,4-triarylpyrroles from α-amino carbonyl
compounds and aldehydes in a one-pot manner under air. A
variety of substituents such as alkyl, methoxyl, bromo, chloro,
and fluoro groups were tolerated by the cyclization reaction,
which proceeded smoothly in moderate to good yields.
Scheme 2. Construction of Substituted Pyrrole 3aa from 1a
and 2a
a
Table 1. Optimization of the Reaction Conditions
T
(°C)
yield
b
entry catalyst
additive (equiv)
solvent
(%)
1
2
I2
none
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
100
100
100
100
100
100
100
100
100
100
100
100
80
18
61
27
16
72
63
82
29
48
46
57
34
71
−
I2
4 Å M.S.
3
I2
Pd(OAc)2 (0.1) + 4 Å M.S.
AgOAc (0.1) + 4 Å M.S.
FeCl2 (1.0) + 4 Å M.S.
FeCl3 (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
PivOH (1.0) + 4 Å M.S.
HOAc (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
ZnCl2 (1.0) + 4 Å M.S.
4
I2
5
I2
6
I2
7
I2
I2
8
9
I2
10
11
12
13
14
I2
I2
PhCl
I2
DMF
I2
toluene
toluene
none
100
a
EXPERIMENTAL SECTION
Reaction conditions: 1a (0.3 mmol), 2a (0.36 mmol), catalyst (0.03
■
General Remarks. 1H and 13C NMR spectra were recorded at 400
and 100 MHz, respectively, in CDCl3. All chemical shifts (δ) are given
in parts per million with reference to tetramethylsilane (TMS) as an
internal standard. HRMS was performed on an FT-ICR mass
mmol), and additive (4 Å M.S., 100 mg) in 2 mL of solvent for 4 h.
b
Isolated yields.
1
the highest yield of 3aa was achieved when the reaction was
carried out with I2 (0.1 equiv), ZnCl2 (1.0 equiv), and 4 Å M.S.
in toluene at 100 °C.
spectrometer using electrospray ionization (ESI). Copies of the H
and 13C NMR spectra of the products are provided in the Supporting
Information. Products were purified by flash chromatography on 200−
300 mesh silica gels. All melting points were determined without
correction. Commercially available reagents and solvents were used
without further purification except as noted.
With the optimized reaction conditions established (Table 1,
entry 7), we then extended the scope of this reaction, and the
results are illustrated in Table 2. Fortunately, a variety of α-
amino carbonyl compounds and aldehydes successfully
produced the desired products 3 in moderate to high yields.
Different functionalities on the aryl rings of the α-amino
carbonyl compounds and aldehydes demonstrated that both
electron-withdrawing and electron-donating groups are com-
patible with this reaction. For example, alkyl, methoxy, bromo,
General Procedure for the Synthesis of the Desired Pyrroles
3. An oven-dried tube was charged with the α-amino carbonyl
compound [e.g., 1-phenyl-2-(phenylamino)ethanone (1a)] (0.3
mmol) and toluene (2 mL). The mixture was stirred at room
temperature until the solid was completely dissolved. Then the
aldehyde [e.g., 2-phenylacetaldehyde (2a)] (0.36 mmol), anhydrous
ZnCl2 (0.3 mmol), I2 (0.03 mmol), and 4 Å M.S. (100 mg) were
B
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The Journal of Organic Chemistry
Note
a
Table 2. Synthesis of Substituted Pyrroles from α-Amino Carbonyl Compounds and Aldehydes
b
entry
1
R1
R2
2
R3
product
yield (%)
1
2
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
H
H
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3aa
3ba
3ca
3da
3ea
3fa
82
72
85
83
76
80
70
76
74
62
66
52
60
64
75
72
61
72
74
61
78
42
70
55
50
65
55
76
61
42
trace
trace
trace
2-Me
3-Me
4-Me
2,3-Me2
3,5-Me2
4-iPr
4-tBu
4-Cl
3-Br
4-F
3
4
5
6
7
1g
1h
1i
3ga
3ha
3ia
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
1j
3ja
1k
1l
3ka
3la
1-naphthyl
H
1m
1n
1o
1p
1a
1a
1a
1a
1a
1a
1a
1d
1d
1d
1i
4-Me
4-MeO
4-Cl
4-Br
H
3ma
3na
3oa
3pa
3ab
3ac
3ad
3ae
3af
H
H
H
H
2-Me
3-Me
4-Me
4-Et
3-MeO
2-F
H
H
H
H
H
H
H
H
H
H
2g
2h
2i
3ag
3ah
3di
3dd
3dg
3id
3if
H
H
4-F
4-Me
4-Me
4-Me
4-Cl
4-Cl
4-Me
4-Cl
4-Cl
2-COOMe
4-NO2
H
3,4-Me2
4-Me
2-F
H
2d
2g
2d
2f
H
H
4-Me
3-MeO
H
1i
H
1q
1r
1r
1s
1t
4-MeO
4-Br
4-Br
H
2a
2a
2d
2a
2a
3qa
3ra
3rd
3sa
3ta
H
4-Me
H
H
H
a
b
Conditions: see Table 1, entry 7. Isolated yields.
the residue was purified by column chromatography, eluting with
petroleum ether/EtOAc (20:1) to afford the desired pyrrole (e.g.,
3aa).
Scheme 3. Attempted Reaction of 1a and Butyraldehyde
1,3,4-Triphenyl-1H-pyrrole (3aa). Yellow solid (72.8 mg, 82%
yield), mp 98.3−102.4 °C. 1H NMR (400 MHz, CDCl3): δ 7.48−7.42
(m, 4H), 7.34−7.20 (m, 13H). 13C NMR (100 MHz, CDCl3): δ 140.2,
135.3, 129.7, 128.5, 128.2, 126.0, 125.8, 125.6, 120.2, 118.5. HRMS
(ESI) m/z: calcd for C22H18N [M + H]+ 296.1434, found 296.1436.
3,4-Diphenyl-1-o-tolyl-1H-pyrrole (3ba). Yellow solid (66.7 mg,
Scheme 4. Reaction of 1a and 4a To Give 4aa
1
72% yield), mp 117.3−118.4 °C. H NMR (400 MHz, CDCl3): δ
7.34−7.24 (m, 12H), 7.22−7.18 (m, 2H), 6.90 (s, 2H), 2.34 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 140.1, 135.6, 133.5, 131.2, 128.5,
128.2, 127.6, 126.7, 126.4, 125.7, 124.0, 121.5, 18.1. HRMS (ESI) m/z:
calcd for C23H20N [M + H]+ 310.1589, found 310.1587.
3,4-Diphenyl-1-m-tolyl-1H-pyrrole (3ca). Yellow solid (78.8
mg, 85% yield), mp 101.7−103.5 °C. 1H NMR (400 MHz, CDCl3): δ
7.34−7.19 (m, 15H), 7.09−7.07 (d, 1H), 2.42 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 140.2, 139.7, 135.4, 129.5, 128.5, 128.2, 126.6, 126.0,
125.5, 120.9, 118.6, 117.3, 21.5. HRMS (ESI) m/z: calcd for C23H20N
[M + H]+ 310.1589, found 310.1586.
added, and the reaction mixture was stirred at 100 °C for 4 h. After
cooling to room temperature, the mixture was filtered to remove
suspended particles and washed with EtOAc. The solvent was diluted
with 20 mL of ethyl acetate, washed with 10 mL of brine, and dried
over anhydrous Na2SO4. After the solvent was evaporated in vacuo,
C
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The Journal of Organic Chemistry
Note
3,4-Diphenyl-1-p-tolyl-1H-pyrrole (3da). Yellow solid (76.9 mg,
118.3, 118.0, 113.7, 55.2. HRMS (ESI) m/z: calcd for C23H20NO [M
+ H]+ 326.1539, found 326.1534.
1
83% yield), mp 107.3−110.4 °C. H NMR (400 MHz, CDCl3): δ
7.37−7.21 (m, 14H), 7.17 (s, 2H), 2.38 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 137.9, 135.7, 135.4, 130.2, 128.5, 128.2, 125.9, 125.3, 120.1,
118.6, 20.9. HRMS (ESI) m/z: calcd for C23H20N [M + H]+ 310.1589,
found 310.1587.
3-(4-Chlorophenyl)-1,4-diphenyl-1H-pyrrole (3oa). Yellow
solid (74.0 mg, 75% yield), mp 108.3−111.5 °C. 1H NMR (400
MHz, CDCl3): δ 7.46−7.45 (d, 4H), 7.30−7.28 (t, 5H), 7.23 (s, 5H),
7.18 (t, 2H). 13C NMR (100 MHz, CDCl3): δ 140.1, 135.0, 133.8,
131.8, 129.7, 129.6, 128.5, 128.4, 128.3, 126.2, 126.0, 125.5, 124.4,
120.2, 118.7, 118.5. HRMS (ESI) m/z: calcd for C22H17ClN [M + H]+
330.1043, found 330.1041.
3-(4-Bromophenyl)-1,4-diphenyl-1H-pyrrole (3pa). Yellow
solid (80.6 mg, 72% yield), mp 108.8−112.5 °C. 1H NMR (400
MHz, CDCl3): δ 7.46−7.45 (d, 4H), 7.40−7.38 (d, 2H), 7.30−7.22
(m, 6H), 7.18−7.16 (d, 4H). 13C NMR (100 MHz, CDCl3): δ 140.1,
135.0, 134.3, 131.4, 130.0, 129.7, 128.5, 128.4, 126.2, 126.0, 125.5,
124.4, 120.2, 119.9, 118.8, 118.5. HRMS (ESI) m/z: calcd for
C22H17BrN [M + H]+ 374.0538, found 374.0532.
1-(2,3-Dimethylphenyl)-3,4-diphenyl-1H-pyrrole (3ea). Yel-
1
low solid (73.6 mg, 76% yield), mp 138.8−142.3 °C. H NMR (400
MHz, CDCl3): δ 7.34−7.17 (m, 13H), 6.87 (s, 2H), 2.36 (s, 3H), 2.18
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 140.3, 138.4, 135.7, 132.7,
129.2, 128.5, 128.2, 125.9, 125.7, 124.4, 123.8, 121.8, 20.5, 14.5.
HRMS (ESI) m/z: calcd for C24H22N [M + H]+ 324.1746, found
324.1743.
1-(3,5-Dimethylphenyl)-3,4-diphenyl-1H-pyrrole (3fa). Yel-
1
low solid (77.5 mg, 80% yield), mp 125.7−128.3 °C. H NMR (400
MHz, CDCl3): δ 7.33−7.18 (m, 12H), 7.09 (s, 2H), 6.91 (s, 1H), 2.37
(s, 6H). 13C NMR (100 MHz, CDCl3): δ 140.2, 139.4, 135.4, 128.5,
128.2, 127.6, 125.9, 125.3, 118.7, 118.1, 21.4. HRMS (ESI) m/z: calcd
for C24H22N [M + H]+ 324.1746, found 324.1742.
1,3-Diphenyl-4-o-tolyl-1H-pyrrole (3ab). Yellow solid (56.5 mg,
1
61% yield), mp 101.3−104.1 °C. H NMR (400 MHz, CDCl3): δ
7.48−7.43 (m, 4H), 7.32−7.22 (m, 10H), 7.21−7.12 (m, 1H), 7.06−
7.05 (d, 1H), 2.07 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 140.3,
137.2, 135.8, 135.4, 131.0, 130.0, 129.6, 128.3, 127.0, 126.8, 126.4,
125.7, 125.6, 125.5, 125.1, 120.0, 119.0, 116.9, 20.4. HRMS (ESI) m/z:
calcd for C23H20N [M + H]+ 310.1589, found 310.1585.
1-(4-Isopropylphenyl)-3,4-diphenyl-1H-pyrrole (3ga). Yellow
1
oil (77.8 mg, 70% yield). H NMR (400 MHz, CDCl3): δ 7.40−7.37
(d, 2H), 7.33−7.17 (m, 14H), 2.99−2.92 (m, J = 7.2 Hz, 1H), 1.29−
1.28 (d, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 146.7,
138.2, 135.4, 128.5, 128.2, 127.6, 125.9, 125.3, 120.3, 118.7, 33.6, 24.0.
HRMS (ESI) m/z: calcd for C25H24N [M + H]+ 338.1902, found
338.1900.
1,3-Diphenyl-4-m-tolyl-1H-pyrrole (3ac). Yellow oil (66.7 mg,
1
72% yield). H NMR (400 MHz, CDCl3): δ 7.48−7.43 (m, 4H),
7.34−7.14 (m, 10H), 7.10−7.03 (m, 2H), 2.30 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 140.3, 137.8, 135.3, 135.2, 129.7, 129.1, 128.4,
128.2, 128.1, 126.8, 126.0, 125.8, 125.7, 125.6, 120.1, 118.5, 118.4,
21.4. HRMS (ESI) m/z: calcd for C23H20N [M + H]+ 310.1589, found
310.1586.
1-(4-tert-Butylphenyl)-3,4-diphenyl-1H-pyrrole (3ha). Yellow
1
oil (80.0 mg, 76% yield). H NMR (400 MHz, CDCl3): δ 7.47−7.45
(d, 2H), 7.40−7.38 (d, 2H), 7.33−7.17 (m, 12H), 1.36 (s, 9H). 13C
NMR (100 MHz, CDCl3): δ 149.0, 137.8, 135.4, 128.5, 128.2, 126.5,
125.9, 125.3, 119.9, 118.6, 34.5, 31.4. HRMS (ESI) m/z: calcd for
C26H26N [M + H]+ 352.2059, found 352.2055.
1,3-Diphenyl-4-p-tolyl-1H-pyrrole (3ad). Yellow oil (68.6 mg,
74% yield). 1H NMR (400 MHz, CDCl3): δ 7.46−7.44 (t, 3H), 7.34−
7.17 (m, 11H), 7.10−7.08 (t, 2H), 2.34 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 140.3, 135.6, 135.4, 132.3, 129.6, 129.0, 128.5, 128.4, 128.2,
126.0, 125.8, 125.6, 120.1, 118.4, 118.3, 21.1. HRMS (ESI) m/z: calcd
for C23H20N [M + H]+ 310.1589, found 310.1587.
3-(4-Ethylphenyl)-1,4-diphenyl-1H-pyrrole (3ae). Yellow oil
(59.1 mg, 61% yield). 1H NMR (400 MHz, CDCl3): δ 7.48−7.08 (m,
16H), 2.68−2.62 (q, J = 7.6 Hz, 2H), 1.27−1.23 (t, J = 7.6 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 141.9, 140.3, 135.4, 132.5, 129.6,
128.5, 128.4, 128.2, 127.7, 125.9, 125.7, 125.6, 120.1, 118.4, 118.3,
28.5, 15.4. HRMS (ESI) m/z: calcd for C24H22N [M + H]+ 324.1746,
found 324.1743.
1-(4-Chlorophenyl)-3,4-diphenyl-1H-pyrrole (3ia). Yellow oil
(73.3 mg, 74% yield). 1H NMR (400 MHz, CDCl3): δ 7.42−7.37 (m,
4H), 7.33−7.20 (m, 10H), 7.14 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 138.8, 135.0, 131.3, 129.8, 128.5, 128.3, 126.2, 126.1, 121.2,
118.4. HRMS (ESI) m/z: calcd for C22H17ClN [M + H]+ 330.1043,
found 330.1039.
1-(3-Bromophenyl)-3,4-diphenyl-1H-pyrrole (3ja). Yellow
1
solid (69.4 mg, 62% yield), mp 97.3−98.4 °C. H NMR (400 MHz,
CDCl3): δ 7.64−7.63 (t, 1H), 7.41−7.38 (m, 2H), 7.32−7.27 (m,
9H), 7.26−7.20 (m, 2H), 7.17 (s, 2H). 13C NMR (100 MHz, CDCl3):
δ 141.3, 134.9, 131.0, 128.7, 128.5, 128.3, 126.3, 126.2, 123.3, 123.2,
118.5, 118.3. HRMS (ESI) m/z: calcd for C22H17BrN [M + H]+
374.0538, found 374.0535.
3-(3-Methoxyphenyl)-1,4-diphenyl-1H-pyrrole (3af). Yellow
1
solid (76.0 mg, 78% yield), mp 97.3−99.7 °C. H NMR (400 MHz,
1-(4-Fluorophenyl)-3,4-diphenyl-1H-pyrrole (3ka). Yellow
CDCl3): δ 7.48−7.43 (m, 4H), 7.35−7.17 (m, 9H), 6.93−6.91 (d,
1H), 6.86−6.85 (d, 1H), 6.78−6.76 (m, 1H), 3.67 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 159.4, 140.2, 136.6, 135.3, 129.7, 129.2, 128.6,
128.2, 126.1, 125.9, 125.7, 125.5, 120.9, 120.2, 118.5, 113.7, 112.0,
55.0. HRMS (ESI) m/z: calcd for C23H20NO [M + H]+ 326.1539,
found 326.1531.
1
solid (62.0 mg, 66% yield), mp 93.4−96.8 °C. H NMR (400 MHz,
CDCl3): δ 7.44−7.40 (m, 2H), 7.32−7.20 (m, 10H), 7.16−7.12 (t,
4H). 13C NMR (100 MHz, CDCl3): δ 162.0−159.6 (d, J = 243 Hz),
136.7−136.6 (d, J = 3 Hz), 135.2, 128.5, 128.3, 126.1, 125.7, 122.0−
121.9 (d, J = 8 Hz), 118.8, 116.6−116.4 (d, J = 23 Hz). HRMS (ESI)
m/z: calcd for C22H17FN [M + H]+ 314.1339, found 314.1335.
1-(Naphthalen-2-yl)-3,4-diphenyl-1H-pyrrole (3la). Yellow oil
3-(2-Fluorophenyl)-1,4-diphenyl-1H-pyrrole (3ag). White oil
(39.4 mg, 42% yield). 1H NMR (400 MHz, CDCl3): δ 7.49−7.43 (m,
4H), 7.30−7.19 (m, 9H), 7.10−7.01 (m, 3H). 13C NMR (100 MHz,
CDCl3): δ 161.2−158.8 (d, J = 244 Hz, 1C), 140.2, 135.4, 131.8−
131.7 (d, J = 3 Hz, 1C), 129.7, 128.3, 127.9−127.8 (d, J = 5 Hz, 1C),
127.7, 126.4, 126.0−126.0 (d, J = 8 Hz, 1C), 123.7−123.7 (d, J = 3 Hz,
1C), 123.1, 122.9, 120.3, 120.2−120.2 (d, J = 4 Hz, 1C), 118.2, 118.1,
115.8−115.6 (d, J = 22 Hz, 1C). HRMS (ESI) m/z: calcd for
C22H17FN [M + H]+ 314.1339, found 314.1335.
1
(53.8 mg, 52% yield). H NMR (400 MHz, CDCl3): δ 8.02−7.99 (t,
1H), 7.95−7.88 (m, 2H), 7.57−7.51 (m, 4H), 7.39−7.37 (d, 4H),
7.31−7.27 (t, 4H), 7.24−7.20 (m, 2H), 7.12 (s, 2H). 13C NMR (100
MHz, CDCl3): δ 137.7, 135.5, 134.3, 129.4, 128.5, 128.2, 128.2, 128.0,
127.1, 126.7, 125.8, 125.3, 124.3, 123.2, 123.1, 122.6. HRMS (ESI) m/
z: calcd for C26H20N [M + H]+ 346.1589, found 346.1587.
1,3-Diphenyl-4-p-tolyl-1H-pyrrole (3ma). Yellow oil (55.6 mg,
60% yield). 1H NMR (400 MHz, CDCl3): δ 7.46−7.45 (t, 3H), 7.34−
7.18 (m, 11H), 7.10−7.08 (d, 2H), 2.34 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 140.2, 135.6, 135.4, 132.3, 129.6, 129.0, 128.4, 128.3, 128.2,
125.9, 125.7, 125.5, 120.1, 118.4, 118.3, 21.1. HRMS (ESI) m/z: calcd
for C23H20N [M + H]+ 310.1589, found 310.1587.
3-(4-Fluorophenyl)-1,4-diphenyl-1H-pyrrole (3ah). Yellow oil
1
(65.7 mg, 70% yield). H NMR (400 MHz, CDCl3): δ 7.46−7.45 (t,
4H), 7.29−7.16 (m, 10H), 6.99−6.95 (t, 2H). 13C NMR (100 MHz,
CDCl3): δ 162.8−160.4 (d, J = 243 Hz, 1C), 140.2, 135.1, 131.3−
131.3 (d, J = 3 Hz, 1C), 130.0−129.9 (d, J = 8 Hz, 1C), 129.7, 128.4,
128.3, 126.1, 125.9, 125.6, 124.6, 120.2, 118.5, 118.4, 115.2−115.0 (d,
J = 21 Hz, 1C). HRMS (ESI) m/z: calcd for C22H17FN [M + H]+
314.1339, found 314.1334.
3-(4-Methoxyphenyl)-1,4-diphenyl-1H-pyrrole (3na). Yellow
1
oil (62.4 mg, 64% yield). H NMR (400 MHz, CDCl3): δ 7.47−7.41
(m, 4H), 7.33−7.19 (m, 9H), 7.15−7.14 (d, 1H), 6.84−6.82 (d, 2H),
3.80 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.1, 140.3, 135.4,
129.6, 129.6, 128.4, 128.2, 127.8, 125.9, 125.7, 125.5, 125.3, 120.1,
3-(3,4-Dimethylphenyl)-4-phenyl-1-(p-tolyl)-1H-pyrrole
(3di). Yellow oil (55.6 mg, 55% yield). 1H NMR (400 MHz, CDCl3):
D
dx.doi.org/10.1021/jo402620z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
δ 7.36−7.27 (m, 4H), 7.25−7.13 (m, 8H), 7.02 (s, 2H), 2.38 (s, 3H),
2.25 (s, 3H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 138.0,
136.3, 135.5, 135.5, 134.2, 132.8, 130.1, 129.6, 129.5, 128.4, 128.1,
126.0, 125.8, 125.3, 125.2, 120.1, 118.4, 20.9, 19.8, 19.4. HRMS (ESI)
m/z: calcd for C25H24N [M + H]+ 338.1902, found 338.1896.
3-Phenyl-1,4-di-p-tolyl-1H-pyrrole (3dd). Yellow oil (48.4 mg,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (21202067) and the Fundamental
Research Funds for the Central Universities (lzujbky-2012-74).
1
50% yield). H NMR (400 MHz, CDCl3): δ 7.36−7.20 (m, 11H),
7.16−7.14 (m, 2H), 7.10−7.08 (d, 2H), 2.38 (s, 3H), 2.34 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 138.0, 135.6, 135.5, 132.4, 130.1, 129.1,
129.0, 128.7, 128.4, 128.4, 128.2, 125.9, 125.2, 120.1, 118.5, 118.4,
21.1, 20.9. HRMS (ESI) m/z: calcd for C24H22N [M + H]+ 324.1746,
found 324.1742.
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1
White solid (63.8 mg, 65% yield), mp 131.1−135.2 °C. H NMR
(400 MHz, CDCl3): δ 7.37−7.35 (d, 2H), 7.28−7.18 (m, 11H), 7.09−
6.99 (m, 3H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 161.2−
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131.8−131.8 (d, J = 4 Hz, 1C), 130.2, 128.3, 127.9, 127.7−127.6 (d, J
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117.9, 115.8−115.6 (d, J = 22 Hz, 1C), 20.9. HRMS (ESI) m/z: calcd
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1-(4-Chlorophenyl)-3-phenyl-4-(p-tolyl)-1H-pyrrole (3id).
1
Yellow oil (56.6 mg, 55% yield). H NMR (400 MHz, CDCl3): δ
7.40−7.39 (d, 3H), 7.32−7.18 (m, 7H), 7.14−7.07 (m, 5H), 2.34 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 138.8, 135.8, 135.1, 132.0,
131.2, 129.7, 129.0, 128.4, 128.3, 128.2, 126.1, 126.0, 121.2, 118.3,
118.2, 21.1. HRMS (ESI) m/z: calcd for C23H19ClN [M + H]+
344.1200, found 344.1196.
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1
role (3if). Yellow oil (81.8 mg, 76% yield). H NMR (400 MHz,
CDCl3): δ 7.43−7.31 (m, 4H), 7.30−7.26 (m, 4H), 7.24−7.14 (m,
4H), 6.91−6.89 (d, 1H), 6.84−6.83 (t, 1H), 6.79−6.76 (m, 1H), 3.67
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131.3, 129.8, 129.2, 128.6, 128.2, 126.2, 126.1, 125.9, 121.2, 120.9,
118.4, 113.7, 112.1, 55.0. HRMS (ESI) m/z: calcd for C23H19ClNO
[M + H]+ 360.1149, found 360.1147.
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3-(4-Methoxyphenyl)-4-phenyl-1-p-tolyl-1H-pyrrole (3qa).
1
Yellow oil (62.0 mg, 61% yield). H NMR (400 MHz, CDCl3): δ
7.36−7.22 (m, 11H), 7.16−7.15 (d, 1H), 7.12−7.11 (d, 1H), 6.84−
6.82 (d, 2H), 3.80 (s, 3H), 2.38 (s, 3H). 13C NMR (100 MHz,
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125.8, 125.2, 124.9, 120.1, 118.4, 118.2, 113.7, 55.2, 20.8. HRMS (ESI)
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3-(4-Bromophenyl)-1-(4-chlorophenyl)-4-phenyl-1H-pyrrole
(3ra). Yellow oil (51.3 mg, 42% yield). 1H NMR (400 MHz, CDCl3):
δ 7.44−7.38 (m, 6H), 7.30−7.26 (m, 5H), 7.17−7.14 (t, 4H). 13C
NMR (100 MHz, CDCl3): δ 138.6, 134.7, 134.0, 131.5, 131.4, 130.0,
129.8, 128.5, 128.4, 126.4, 126.0, 124.8, 121.3, 120.1, 118.7, 118.4.
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408.0145.
3-Benzyl-1,4-diphenyl-1H-pyrrole (4aa). Yellow oil (48.2 mg,
52% yield). 1H NMR (400 MHz, CDCl3): δ 7.45−7.34 (m, 8H),
7.28−7.19 (m, 8H), 6.74−6.73 (d, 1H), 4.01 (s, 2H). 13C NMR (100
MHz, CDCl3): δ 141.5, 140.4, 135.7, 129.5, 128.8, 128.4, 128.3, 128.0,
126.8, 126.0, 125.8, 125.4, 123.5, 120.0, 118.9, 117.2, 32.3. HRMS
(ESI) m/z: calcd for C23H20N [M + H]+ 310.1589, found 310.1586.
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S
* Supporting Information
NMR spectra of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: yanrl@lzu.edu.cn.
*E-mail: hgs@lzu.edu.cn. Fax: +86 931 8912596. Tel: +86 931
8912586.
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̈
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