Water promoted C-C bond cleavage: Facile synthesis of 3,3-bipyrrole derivatives from dienones and tosylmethyl isocyanide (TosMIC)

Article abstract of DOI:10.1039/c3ob42570c

A simple and highly efficient synthetic strategy to access 3,3-bipyrrole derivatives by the reaction of dienone derivatives with TosMIC is reported. The reaction involves a van Leusen's pyrrole synthesis followed by an unusual C-C bond cleavage in the presence of water under mild conditions.

Full text of DOI:10.1039/c3ob42570c

Organic &
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Water promoted C–C bond cleavage: facile
synthesis of 3,3-bipyrrole derivatives from
dienones and tosylmethyl isocyanide (TosMIC)†
Cite this: Org. Biomol. Chem., 2014,
12, 1735
Rong Wang, Shun-Yi Wang* and Shun-Jun Ji*
Received 2nd December 2013,
Accepted 15th January 2014
A simple and highly efficient synthetic strategy to access 3,3-bipyrrole derivatives by the reaction of
dienone derivatives with TosMIC is reported. The reaction involves a van Leusen’s pyrrole synthesis fol-
lowed by an unusual C–C bond cleavage in the presence of water under mild conditions.
DOI: 10.1039/c3ob42570c
www.rsc.org/obc
Pyrroles1 represent an important class of five-membered ring demonstrate an efficient approach for the synthesis of 3,3-
heterocycles and useful synthons for alkaloids in natural bipyrrole derivatives 3 by the non-classical van Leusen’s reac-
product synthesis and medicinal chemistry, and this structural tion of dienone derivatives 1 with TosMIC 2 through a water-
motif can be found in many natural products and bioactive promoted C–C bond cleavage (Scheme 1).
molecules.2 Pyrroles also play crucial roles not only in hetero-
Initially, model reaction of (2E,5E)-2,5-dibenzylidenecyclo-
cyclic chemistry,3 but also in materials chemistry.4 Specifically, pentanone 1a with TosMIC 2 was studied in the presence of
bipyrrolic structures are also widespread in nature2d,5 and have t-BuOK in DMF. However, the expected 1,2-bis(4-phenyl-1H-
been the focus of material science6 and medicinal chemistry.7 pyrrol-3-yl)ethane 3a was only obtained in 32% isolated yield
Particularly, 3,3-bipyrroles were building blocks for the syn- (Table 1, entry 1). In our efforts to improve the yield of 3a,
thesis of the antitumor agent CC-1065.8 However, the efficient different bases were screened subsequently (Table 1, entries
synthesis of 3,3-bipyrroles is quite limited, and it also suffers 2–5). It was found that only a trace amount of product 3a was
from a number of drawbacks such as lengthy steps, harsh reac- observed when Cs2CO3 or DBU was used as the additive
tion conditions and poor yields. Although much effort has (Table 1, entries 4 and 5). Gratifyingly, the yield could be
been directed toward the synthesis and functionalization of improved (34%) when KOH was employed as a base (Table 1,
3,3-bipyrroles, relatively few reports in the literature are known entry 3). We further explored the reaction in various solvents,
for the preparation of 3,3-bipyrrole derivatives.8,9 Therefore, and DMF was demonstrated to be a suitable solvent (see ESI†).
using a simple and convenient synthetic approach toward 3,3- A lower yield was obtained when the reaction was performed at
bipyrrole derivatives is compatible with the efficient process.
Tosylmethyl isocyanide (TosMIC) is a versatile and widely
exploited reagent in organic synthesis.10 van Leusen’s pyrrole
synthesis is a well known method to prepare the pyrrole
moiety through the reaction of TosMIC with Michael accep-
tors. However, the synthesis of 3,3-bipyrroles through van
Leusen’s methodology has never been reported so far. More
recently, we have reported an efficient route for the synthesis
of pyrrole derivatives through a base-promoted reaction of
3-phenacylideneoxindole and TosMIC via C–C bond cleavage.11
As a continuation of our studies related to isonitriles,12
we reasoned that dienones could be applied in the reaction
with TosMIC to form the pyrrole moiety as well. Herein, we
0 °C (10% yield, see ESI†). The yield of 3a could be increased
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123,
China. E-mail: shunjun@suda.edu.cn; Fax: +86-512-65880305;
Tel: +86-512-65880305
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ob42570c
Scheme 1 Classical van Leusen’s pyrrole synthesis, our previous work
and this work.
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Table 1 Optimization of reaction conditionsa
Table 2 Substrate scope for the synthesis of 1,2-bis(4-phenyl-1H-
pyrrol-3-yl)ethanesa
Entry
Base
Solvent
Temp (°C)
Yieldb (%)
Entry
R1
Product
Yieldb (%)
1
2
3
4
5
6
7
8
t-BuOK
NaOH
KOH
Cs2CO3
DBU
KOH
KOH
KOH
KOH
KOH
KOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
25
25
25
25
25
32
29
34
Trace
Trace
67
72
71
58
80
86
82
1
2
3
4
5
6
7
8
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
86
91
85
88
91
85
88
87
85
86
84
88
2-CH3
3-CH3
4-CH3
2-OCH3
3-OCH3
4-F
3-Cl
4-Cl
4-Br
3-NO2
4-NO2
80
100
150
100
100
100
100
9
Dry DMF
10
11
12
Dry DMF + 40 µl H2O
Dry DMF + 80 µl H2O
Dry DMF + 100 µl H2O
9
10
11
12
3j
3k
3l
KOH
a The reactions were performed with 1a (0.5 mmol, 1.0 eq.) and
TosMIC 2 (1.2 mmol, 2.4 eq.) in the presence of a base. b Isolated yield.
a The reactions were performed with 1 (0.5 mmol, 1.0 eq.) and 2
(1.2 mmol, 2.4 eq.) in the presence of KOH in DMF at 100 °C.
b Isolated yield.
to 72% by elevating the reaction temperature to 100 °C
(Table 1, entry 7). However, increasing the temperature to
150 °C did not increase the yield of the desired product at all
(Table 1, entry 8). To our surprise, the product could be
afforded in 58% yield when dry DMF was used as the solvent
(Table 1, entry 9). Undoubtedly, water was involved in the reac-
tion and promoted the reaction. Thus, we explored the effects
of the amount of water on this reaction (Table 1, entries
10–12). Gratifyingly, the reaction worked more efficiently when
80 µl (about 8.9 equiv.) water was added, delivering the corres-
ponding product 3aa in 86% yield (Table 1, entry 11).
respectively. Similarly, the reaction of (2E,5E)-2,5-bis(furan-
2-ylmethylene)cyclopentanone 1o with TosMIC
2 worked
equally well, leading to the corresponding product 3o in 81%
yield (Table 3).
Subsequently, (2E,6E)-2,6-dibenzylidenecyclohexanone 1p
and (3Z,5Z)-3,5-dibenzylidenedihydro-2H-thiopyran-4(3H)-one
1q were subjected to the reactions under the optimal reaction
conditions. As anticipated, the desired products 3p and 3q
were obtained in 84% and 83% yields (Scheme 2, eqn (1) and
(2)), respectively. In addition, the reaction using (3E,5E)-3,5-
dibenzylidene-1-methylpiperidin-4-one 1r afforded not only
the expected product 3r in 71%, but also bis(4-phenyl-1H-
pyrrol-3-yl)methanone 3s in 10% yield through C–C bond clea-
vage in other positions (Scheme 2, eqn (3)).
To better understand the reaction mechanism, two control
experiments were carried out (Scheme 3). When the reaction
of 1a with 2 was performed in dry DMF in the presence of
KOH at 0 °C, an unstable dual [3 + 2] cycloaddition product 4
could be formed (determined by crude NMR and LC-MS). In
comparison, when 8.9 equiv. H2O was added to the reaction
system and the reaction temperature was increased to 100 °C,
We next explored the scope of this reaction involving
(2E,5E)-2,5-dibenzylidenecyclopentanone
1 and TosMIC 2
under the optimized conditions (3.0 equiv. of KOH, dry DMF
with 8.9 equiv. H2O, 100 °C). The results are summarized in
Table 2. In all cases, (2E,5E)-2,5-dibenzylidenecyclopentanone
1b–l reacted with TosMIC 2 leading to the corresponding sub-
stituted 1,2-bis(4-phenyl-1H-pyrrol-3-yl)ethane 3bl in good to
excellent yields. For instance, 1c and 1d with methyl substitu-
ents in different positions were examined in the reaction,
which afforded the corresponding products 3c and 3d in good
yields, respectively. The sterically more hindered substrate 1b
furnished the desired product 3b in 91% yield. We next exam-
ined the reaction of (2E,5E)-2,5-dibenzylidenecyclopentanone
1e–l with varying substituents on the aromatic ring. To our
delight, during the reaction process, the methoxy, fluoro,
bromo, and nitro groups on the phenyl ring did not affect
the final outcomes, affording the expected products in good
yields.
Table 3 Investigation of the scope of the reaction involving dienones
1m–q and TosMIC 2
Furthermore, a number of conformationally restricted die-
nones 1m–q, some of them bearing pyridyl or furyl groups
instead of the phenyl group, were also examined. As expected,
both (2E,5E)-2,5-bis(pyridin-2-ylmethylene)cyclopentanone 1m
and (2E,5E)-2,5-bis(pyridin-3-ylmethylene)cyclopentanone 1n
can provide the products 3m and 3n in 80% and 81% yields,
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Scheme 4 A possible mechanism for the formation of 3,3-bipyrroles 3.
Scheme 2 Investigation of the scope of the reaction of dienones 1p–r
and TosMIC 2.
reaction intermediates as proposed in Scheme 4 to construct
new stable spiro compounds as well as other useful hetero-
cycles, which is currently ongoing in our laboratory.
Experimental
General
All reactions were carried out at ambient temperature in oven-
dried glassware. All solvents were dried and distilled according
to standard procedures. Column chromatography was gener-
ally performed on silica gel (300–400 mesh) and reactions were
monitored by thin layer chromatography (TLC) using UV light
to visualize the course of the reactions. Melting points were
recorded on an electrothermal digital melting point apparatus
and are uncorrected. IR spectra were recorded on an FT-IR
spectrometer using KBr optics. NMR spectra were recorded at
room temperature in d6-DMSO at 300/400 Hz and 75/100 Hz
with TMS as an internal reference. High resolution mass
spectra (HRMS) were obtained on a TOF MS instrument with
ESI source. X-ray diffraction data were recorded with graphite
monochromatic Mo-Kα radiation.
Scheme 3 Control experiments.
3a could also be obtained in good yield (Table 1, entry 11).
Then, we tried the reaction of 1t with 2 under similar
conditions. Interestingly, 2-((4-phenyl-1H-pyrrol-3-yl)methyl)-
benzoic acid 3t was obtained in 58% yield (Scheme 3, eqn (5)).
These results indicated that water is important for the C–C
bond cleavage.
Based on van Leusen’s pyrrole synthesis mechanism and
the above results, we proposed a plausible mechanism for this
reaction (Scheme 4). The 1,4-addition of 2 to 1a in the pres-
ence of KOH gives the enolate intermediate A. A subsequent
intramolecular cyclization occurs to produce a spirocyclic
intermediate B. Then, the spirocyclic intermediate C could be
formed after further detosylation of B. After an iterative
process, the bispirocyclic 4 is generated. In the presence of
water and KOH, one of the spiro rings is opened to give inter-
mediate D, followed by decarboxylation and protonation to
give the desired product 3.
General procedures for products 3a–3s
Dienones 1 (0.5 mmol), TosMIC 2 (1.2 mmol, 2.4 equiv.) and
KOH (1.5 mmol, 3.0 equiv.) were suspended in 2 mL of dry
DMF in an oven-dried flask. 80 µl H2O was added to the
mixture, which was stirred at 100 °C for 2 h. After cooling the
mixture to ambient temperature, the reaction mixture was
quenched with H2O (10 mL) and extracted with EtOAc (3 ×
15 mL). The combined organic phase was washed with brine
(15 mL) and dried over anhydrous Na2SO4. After filtration and
evaporation of the solvents under vacuum, the residue was
purified by preparative silica gel column chromatography to
give the corresponding products 3 as a white solid.
In conclusion, we have demonstrated a simple and highly
efficient synthetic strategy to access 3,3-bipyrrole derivatives.
The reaction involves a van Leusen’s pyrrole synthesis followed
by an unusual C–C bond cleavage in the presence of water
under mild conditions. It is very interesting to trap the
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General procedures for product 3t
13C NMR (d6-DMSO, 75 MHz): δ 134.6, 134.1, 129.3, 127.4,
122.9, 121.0, 116.6, 116.2, 27.9, 21.1; MS: Anal. calcd for
C24H24N2: 340.1939. Found: 339.1867 (M − H+); IR (KBr,
cm−1): ν 3353, 1530, 1497, 1112, 1075, 887, 794.
1,2-Bis(4-(2-methoxyphenyl)-1H-pyrrol-3-yl)ethane (3e). Yield:
91%; white solid; melting point: 77.9–80.1 °C; 1H NMR
(400 MHz, d6-DMSO): δ 10.99 (s, 2H), 7.68 (t, J = 7.6 Hz, 2H),
7.59 (d, J = 7.1 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 7.37 (t, J =
7.3 Hz, 2H), 7.16 (s, 2H), 6.99 (s, 2H), 4.14 (s, 6H), 2.99 (s, 4H);
13C NMR (d6-DMSO, 75 MHz): δ 157.0, 131.1, 127.2, 126.2,
122.9, 120.4, 119.3, 117.3, 115.1, 111.4, 55.3, 27.6; MS: Anal.
calcd for C24H24N2O2: 372.1838. Found: 371.1769 (M − H+); IR
(KBr, cm−1): ν 3380, 1726, 1580, 1458, 1178, 984.
(E)-2-Benzylidene-2,3-dihydro-1H-inden-1-one 1t (0.5 mmol),
TosMIC 2 (0.6 mmol, 1.2 equiv.) and KOH (1.0 mmol,
2.0 equiv.) were suspended in 2 mL of dry DMF in an oven-
dried flask. 40 µl H2O was added to the mixture, which was
stirred at 100 °C for 2 h. After cooling the mixture to ambient
temperature, the reaction mixture was neutralized with 6 M
HCl and extracted with EtOAc (3 × 15 mL). The combined
organic phase was washed with brine (15 mL) and dried over
anhydrous Na2SO4. After filtration and evaporation of the sol-
vents under vacuum, the residue was purified by preparative
silica gel column chromatography to give the corresponding
products 3t as a white solid.
1,2-Bis(4-(3-methoxyphenyl)-1H-pyrrol-3-yl)ethane (3f). Yield:
85%; white solid; melting point: 125.1–126.3 °C; 1H NMR
(400 MHz, d6-DMSO): δ 10.68 (s, 2H), 7.19 (t, J = 7.9 Hz, 2H),
General procedures for intermediate D
(2E,5E)-2,5-Dibenzylidenecyclopentanone 1a (0.5 mmol), 6.90 (dd, J = 13.0, 6.7 Hz, 6H), 6.71 (d, J = 6.8 Hz, 2H), 6.63 (s,
TosMIC 2 (1.2 mmol, 2.4 equiv.) and KOH (1.5 mmol, 2H), 3.71 (s, 6H), 2.78 (s, 4H); 13C NMR (d6-DMSO, 75 MHz):
3.0 equiv.) were suspended in 2 mL of dry DMF in an oven- δ 159.7, 138.9, 129.7, 122.76, 121.1, 119.9, 116.8, 112.9, 110.7,
dried flask. The reaction mixture was stirred at 0 °C for 3 h. 107.9, 55.2, 27.8; MS: Anal. calcd for C24H24N2O2: 372.1838.
The reaction mixture was quenched with H2O (10 mL) and Found: 371.1765 (M − H+); IR (KBr, cm−1): ν 3370, 1596, 1460,
extracted with EtOAc (3 × 15 mL). The combined organic phase 1247, 1016, 860.
was washed with brine (15 mL) and dried over anhydrous
1,2-Bis(4-(4-fluorophenyl)-1H-pyrrol-3-yl)ethane (3g). Yield:
Na2SO4. After filtration and evaporation of the solvents under 88%; white solid; melting point: 161.4–162.8 °C; 1H NMR
vacuum, the residue was purified by preparative silica gel (400 MHz, d6-DMSO): δ 10.68 (s, 2H), 7.32 (t, J = 8.7 Hz, 4H),
column chromatography to give the corresponding products D 7.10 (t, J = 8.7 Hz, 4H), 6.84 (s, 2H), 6.63 (s, 2H), 2.72 (s, 4H);
as a white solid.
13C NMR (d6-DMSO, 75 MHz): δ 160.6 (C–F, J = 240.0 Hz),
1,2-Bis(4-phenyl-1H-pyrrol-3-yl)ethane (3a). Yield: 86%; 133.9 (C–C, J = 3.0 Hz), 129.2 (C–H, J = 7.5 Hz), 122.0, 120.9,
white solid; melting point: 217.2–218.1 °C; 1H NMR (400 MHz, 116.7 (C–H, J = 24.0 Hz), 115.5, 115.3, 27.7; MS: Anal. calcd for
d6-DMSO): δ 10.66 (s, 2H), 7.33 (d, J = 7.5 Hz, 4H), 7.28 (t, J = C22H18N2F2: 348.1438. Found: 347.1370 (M − H+); IR (KBr,
7.5 Hz, 4H), 7.13 (t, J = 6.8 Hz, 2H), 6.86 (s, 2H), 6.63 (s, 2H), cm−1): ν 3358, 1529, 1492, 1212, 1155, 1071, 878.
2.77 (s, 4H); 13C NMR (d6-DMSO, 100 MHz): δ 137.7, 130.0,
1,2-Bis(4-(3-chlorophenyl)-1H-pyrrol-3-yl)ethane (3h). Yield:
129.0, 127.7, 125.4, 121.3, 117.1, 116.8, 28.1; MS: Anal. calcd 87%; white solid; melting point: 98.0–99.4 °C; 1H NMR
for C22H20N2: 312.1626. Found: 311.1547 (M − H+); IR (KBr, (400 MHz, d6-DMSO): δ 10.64 (d, J = 135.6 Hz, 2H), 7.36 (s,
cm−1): ν 3363, 1603, 1532, 1432, 1076, 976, 845.
1,2-Bis(4-o-tolyl-1H-pyrrol-3-yl)ethane
2H), 7.29 (s, 4H), 7.18 (s, 2H), 6.98 (s, 2H), 6.65 (s, 2H), 2.76 (s,
(3b). Yield:
91%; 4H); 13C NMR (d6-DMSO, 75 MHz): δ 139.7, 133.5, 130.5, 126.8,
white solid; melting point: 101.1–102.4 °C; 1H NMR (400 MHz, 125.8, 125.0, 121.4, 120.9, 117.3, 117.2, 27.7; MS: Anal. calcd
d6-DMSO): δ 10.51 (s, 2H), 7.17 (d, J = 6.9 Hz, 2H), 7.10 (dt, J = for C22H18N2Cl2: 380.0847. Found: 379.0770 (M − H+); IR (KBr,
14.3, 7.0 Hz, 4H), 6.98 (d, J = 6.9 Hz, 2H), 6.55 (s, 2H), 6.49 (s, cm−1): ν 3368, 1595, 1466, 1150, 1074, 976, 888.
2H), 2.35 (s, 4H), 2.07 (s, 6H); 13C NMR (d6-DMSO, 75 MHz):
1,2-Bis(4-(4-chlorophenyl)-1H-pyrrol-3-yl)ethane (3a). Yield:
δ 136.9, 136.6, 130.9, 130.0, 126.3, 125.5, 122.3, 122.0, 116.4, 85%; white solid; melting point: 118.2–119.3 °C; 1H NMR
115.3, 27.4, 20.6; MS: Anal. calcd for C24H24N2: 340.1939. (400 MHz, d6-DMSO): δ 10.75 (s, 2H), 7.34 (d, J = 8.8 Hz, 8H),
Found: 339.1879 (M − H+); IR (KBr, cm−1): ν 3372, 1604, 1525, 6.91 (s, 2H), 6.65 (s, 2H), 2.74 (s, 4H); 13C NMR (d6-DMSO,
1479, 1597, 1061, 1302, 991, 893.
75 MHz): δ 136.4, 129.8, 129.0, 128.7, 121.6, 120.9, 117.2,
1,2-Bis(4-m-tolyl-1H-pyrrol-3-yl)ethane (3c). Yield: 85%; 116.9, 27.7; MS: Anal. calcd for C22H18N2Cl2: 380.0847. Found:
white solid; melting point: 76.8–77.4 °C; 1H NMR (400 MHz, 379.0768 (M − H+); IR (KBr, cm−1): ν 3351, 1522, 1461, 1067,
d6-DMSO): δ 10.64 (s, 2H), 7.14 (d, J = 9.3 Hz, 6H), 6.95 (d, J = 1007, 966, 824.
6.8 Hz, 2H), 6.84 (s, 2H), 6.61 (s, 2H), 2.76 (s, 4H), 2.27 (s, 6H);
1,2-Bis(4-(4-bromophenyl)-1H-pyrrol-3-yl)ethane (3a). Yield:
13C NMR (d6-DMSO, 75 MHz): δ 137.6, 137.4, 128.6, 128.2, 86%; white solid; melting point: 158.4–159.8 °C;
125.9, 124.6, 123.0, 121.1, 116.7, 116.4, 27.8, 21.6; MS: Anal. 1H NMR (400 MHz, d6-DMSO): δ 10.76 (s, 2H), 7.45 (d, J =
calcd for C24H24N2: 340.1939. Found: 339.1880 (M − H+); IR 8.2 Hz, 4H), 7.28 (d, J = 8.3 Hz, 4H), 6.91 (s, 2H), 6.65 (s, 2H),
(KBr, cm−1): ν 3371, 1602, 1523, 1480, 1068, 900, 838.
1,2-Bis(4-p-tolyl-1H-pyrrol-3-yl)ethane (3d). Yield:
2.74 (s, 4H); 13C NMR (d6-DMSO, 75 MHz):
δ
136.8,
88%; 131.6, 129.4, 121.6, 120.9, 118.1, 117.2, 116.9, 27.7; MS:
white solid; melting point: 149.1–151.3 °C; 1H NMR (400 MHz, Anal. calcd for C22H18N2Br2: 467.9837. Found: 466.9745 (M −
d6-DMSO): δ 10.61 (s, 2H), 7.22 (d, J = 7.5 Hz, 4H), 7.09 (d, J = H+); IR (KBr, cm−1): ν 3360, 1523, 1475, 1399, 1123, 1074,
7.5 Hz, 4H), 6.81 (s, 2H), 6.61 (s, 2H), 2.74 (s, 4H), 2.27 (s, 6H); 1003, 899.
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1,2-Bis(4-(3-nitrophenyl)-1H-pyrrol-3-yl)ethane (3a). Yield: (s, 2H), 3.69 (s, 4H); 13C NMR (d6-DMSO, 100 MHz): δ 136.7,
84%; yellow solid; melting point: 222.5–223.3 °C; 1H NMR 128.8, 127.6, 125.5, 123.0, 119.2, 117.0, 116.5, 27.9; MS: Anal.
(400 MHz, d6-DMSO): δ 10.93 (s, 2H), 8.09 (s, 2H), 7.94 (d, J = calcd for C22H20N2S: 344.1347. Found: 343.1260 (M − H+); IR
7.8 Hz, 2H), 7.78 (d, J = 7.5 Hz, 2H), 7.53 (t, J = 7.9 Hz, 2H), (KBr, cm−1): ν 3352, 1737, 1630, 1556, 1321, 1032, 981.
7.10 (s, 2H), 6.72 (s, 2H), 2.82 (s, 4H); 13C NMR (d6-DMSO,
N-Methyl-1-(4-phenyl-1H-pyrrol-3-yl)-N-((4-phenyl-1H-pyrrol-
75 MHz): δ 148.4, 139.1, 133.6, 130.1, 121.0, 120.8, 120.7, 3-yl)methyl)methanamine (3a). Yield: 71%; white solid;
119.8, 117.9, 117.7, 27.8; MS: Anal. calcd for C22H18N4O4: melting point: 86.3–86.8 °C; 1H NMR (400 MHz, d6-DMSO):
402.1328. Found: 401.1244 (M − H+); IR (KBr, cm−1): ν 3390, δ 10.77 (s, 2H), 7.60 (d, J = 7.2 Hz, 4H), 7.13 (t, J = 7.6 Hz, 4H),
1531, 1341, 1143, 1084, 993, 875.
7.02 (t, J = 7.6 Hz, 4H), 6.73 (s, 2H), 3.38 (s, 4H), 2.18 (s, 3H);
1,2-Bis(4-(4-nitrophenyl)-1H-pyrrol-3-yl)ethane (3a). Yield: 13C NMR (d6-DMSO, 100 MHz): δ 136.9, 128.5, 127.6, 125.0,
88%; yellow solid; melting point: 270.7–271.1 °C; 1H NMR 123.8, 120.4, 117.5, 116.7, 53.2, 42.2; MS: Anal. calcd for
(400 MHz, d6-DMSO): δ 11.05 (s, 2H), 8.11 (d, J = 8.5 Hz, 4H), C23H23N3: 341.1892. Found: 340.1808 (M − H+); IR (KBr,
7.61 (d, J = 8.5 Hz, 4H), 7.20 (s, 2H), 6.77 (s, 2H), 2.86 (s, 4H); cm−1): ν 3341, 1756, 1595, 1460, 1295, 1128, 981.
13C NMR (d6-DMSO, 75 MHz): δ 144.9, 144.5, 127.2, 124.2,
Bis(4-phenyl-1H-pyrrol-3-yl)methanone (3a). Yield: 10%;
121.3, 120.9, 119.2, 118.4, 27.8; MS: Anal. calcd for white solid; melting point: 293.7–294.1 °C; 1H NMR (400 MHz,
C22H18N4O4: 402.1328. Found: 401.1260 (M − H+); IR (KBr, d6-DMSO): δ 11.37 (s, 2H), 7.35 (d, J = 6.4 Hz, 4H), 7.24 (d, J =
cm−1): ν 3390, 1590, 1495, 1324, 1107, 923, 852.
1,2-Bis(4-(pyridin-2-yl)-1H-pyrrol-3-yl)ethane
19.5 Hz, 6H), 7.12 (d, J = 6.2 Hz, 2H), 6.99 (s, 2H); 13C NMR
(3a). Yield: (d6-DMSO, 75 MHz): δ 196.4, 136.1, 128.5, 128.0, 127.0, 125.7,
80%; white solid; melting point: 143.6–1449.5 °C; 1H NMR 125.4, 123.5, 119.4; MS: Anal. calcd for C21H16N2O: 312.1263.
(400 MHz, d6-DMSO): δ 10.81 (s, 2H), 8.44 (d, J = 3.6 Hz, 2H), Found: 311.1181 (M − H+); IR (KBr, cm−1): ν 3260, 1723, 1580,
7.63 (t, J = 7.4 Hz, 2H), 7.51 (d, J = 7.9 Hz, 2H), 7.28 (s, 2H), 1546, 1512, 1445, 1084, 848.
7.02 (t, J = 7.4 Hz, 2H), 6.67 (s, 2H), 3.02 (s, 4H); 13C NMR (d6-
2-((4-Phenyl-1H-pyrrol-3-yl)methyl)benzoic acid (3a). Yield:
DMSO, 75 MHz): δ 156.5, 149.2, 136.5, 122.8, 122.5, 120.4, 58%; white solid; melting point: 146.8–147.2 °C; 1H NMR
119.8, 119.1, 117.4, 28.5; MS: Anal. calcd for C20H18N4: (400 MHz, d6-DMSO): δ 12.77 (s, 1H), 10.73 (s, 1H), 7.78 (d, J =
314.1531. Found: 313.1456 (M − H+); IR (KBr, cm−1): ν 3160, 7.7 Hz, 1H), 7.39 (t, J = 7.4 Hz, 1H), 7.33 (d, J = 7.5 Hz, 2H),
1727, 1590, 1521, 1474, 1155, 1081, 982.
1,2-Bis(4-(pyridin-3-yl)-1H-pyrrol-3-yl)ethane
7.27 (t, J = 7.3 Hz, 3H), 7.17 (d, J = 7.6 Hz, 1H), 7.12 (t, J =
(3a). Yield: 7.1 Hz, 1H), 6.96 (s, 1H), 6.27 (s, 1H), 4.27 (s, 2H); 13C NMR
81%; white solid; melting point: 149.1–150.2 °C; 1H NMR (d6-DMSO, 100 MHz): δ 169.5, 143.1, 137.2, 131.8, 131.1, 130.8,
(400 MHz, d6-DMSO): δ 10.84 (s, 2H), 8.58 (s, 2H), 8.34 (d, J = 130.3, 128.8, 127.3, 126.2, 125.4, 123.2, 119.41, 118.31, 117.0,
4.1 Hz, 2H), 7.69 (d, J = 7.7 Hz, 2H), 7.29 (t, J = 7.4 Hz, 2H), 30.29; MS: Anal. calcd for C18H15NO2: 277.1103. Found:
7.00 (s, 2H), 6.69 (s, 2H), 2.77 (s, 4H); 13C NMR (d6-DMSO, 276.1022 (M − H+); IR (KBr, cm−1): ν 3060, 2959, 1720, 1532,
100 MHz): δ 148.2, 146.3, 134.3, 133.1, 123.9, 121.1, 119.3, 1362, 1243, 990.
117.3, 117.2, 27.6; MS: Anal. calcd for C20H18N4: 314.1531.
Found: 313.1459 (M − H+); IR (KBr, cm−1): ν 3221, 1719, 1576, 202.5–203.6 °C; H NMR (400 MHz, d6-DMSO): δ11.88 (s, 2H),
1471, 1258, 1137, 1076, 986. 7.41–7.34 (m, 8H), 7.26 (t, J = 6.4 Hz, 2H), 7.18 (s, 2H), 2.92 (s,
Intermediate
(D). White
solid;
melting
point:
1
1,2-Bis(4-(furan-2-yl)-1H-pyrrol-3-yl)ethane (3a). Yield: 81%; 4H); 13C NMR (d6-DMSO, 75 MHz): δ 171.8, 135.5, 130.4, 128.9,
white solid; melting point: 101.6–103.5 °C; 1H NMR (400 MHz, 128.8, 127.3, 126.3, 125.2, 122.8, 24.7; MS: Anal. calcd for
d6-DMSO): δ 10.77 (s, 2H), 7.50 (s, 2H), 7.00 (s, 2H), 6.66 (s, C14H14N2O3: 322.0106. Found: 321.0035 (M − H+); IR (KBr,
2H), 6.43 (s, 2H), 6.19 (s, 2H), 2.79 (s, 4H); 13C NMR (d6-DMSO, cm−1): ν 3061, 2860, 1732, 1586, 1461, 1398, 1265, 1160, 1082.
75 MHz): δ 152.0, 140.1, 120.4, 116.8, 116.0, 113.8, 111.6,
102.6, 27.3; MS: Anal. calcd for C18H16N2O2: 292.1212. Found:
291.1137 (M − H+); IR (KBr, cm−1): ν 3378, 1617, 1444, 1156,
1078, 992, 879.
Acknowledgements
1,3-Bis(4-phenyl-1H-pyrrol-3-yl)propane (3a). Yield: 84%; We gratefully acknowledge the Natural Science Foundation of
white solid; melting point: 101.7–103.3 °C; 1H NMR (400 MHz, China (no. 21172162, 21372174), the Young National Natural
d6-DMSO): δ 10.65 (s, 2H), 7.31–7.28 (m, 8H), 7.14 (d, J = 5.9 Science Foundation of China (no. 21202111), the Young
Hz, 2H), 6.86 (s, 2H), 6.57 (s, 2H), 2.58 (t, J = 7.0 Hz, 4H), 1.71 Natural Science Foundation of Jiangsu Province (BK2012174),
(t, J = 7.0 Hz, 2H); 13C NMR (d6-DMSO, 75 MHz): δ 137.5, Key Laboratory of Organic Synthesis of Jiangsu Province
128.7, 127.4, 125.2, 122.86, 120.8, 116.9, 116.6, 31.9, 26.3; MS: (KJS1211), PAPD, and Soochow University for financial
Anal. calcd for C23H22N2: 326.1783. Found: 325.1731 (M − H+); support.
IR (KBr, cm−1): ν 3451, 3357, 1600, 1526, 1432, 1112, 1074,
981.
Bis((4-phenyl-1H-pyrrol-3-yl)methyl)sulfane
(3qa). Yield:
Notes and references
83%; white solid; melting point: 99.2–99.8 °C; 1H NMR
(400 MHz, d6-DMSO): δ 10.82 (s, 1H), 7.46 (d, J = 7.8 Hz, 4H),
7.29 (t, J = 7.2 Hz, 4H), 7.15 (t, J = 7.1 Hz, 2H), 6.94 (s, 2H), 6.75
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