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107
CHAPTER-IV
NOVEL AND EFFICIENT SUPRAMOLECULAR
SYNTHESIS OF PYRROLES IN THE PRESENCE OF β–
CYCLODEXTRIN IN WATER
108
INTRODUCTION
Heterocyclic molecules represent the most utilized scaffolds for the discovery of novel
synthetic drugs1like anti-hypertensive and anti-coagulation drugs
2,3 the pyrrole moiety can
be found both in natural and synthetic pharmaceutical products.4 In particular, pyrrole
derivatives play an important role as antibacterial, antiviral, anti-inflammatory,5antioxidant
agents,6and penicillin antibiotics.
7There are numerous drugs such as Tolmetin,
Zomepirac, and Bufotenin containing the pyrrole skeleton as shown in the (Figure
1). Moreover, the pyrrole ring system is an important structural attribute present in many
bioactive natural products,8 therapeutic compounds,
9 and new organic materials.
10 In
addition, the biological importance of pyrrole-containing natural products such as heme,
chlorophyll and vitamin B12 has stimulated extensive research on the synthesis and
reactivity of pyrrole derivatives.11
These compounds exhibit remarkable activities such as
antitumor, immunosuppressant, and anti HIV,12
and also find wide use in material science
and as structural elements in molecular recognition studies.13
The construction of the pyrrole ring system typically involves a multistep approach from
preformed intermediates, such as the classic Paal-Knorr cyclization reaction of 1, 4-
dicarbonyl compounds and amines.14
Figure 1. Some marketed drug with pyrrole skeleton.
Various literature methods reported for the preparation of pyrroles are described
hereunder
Azizi et al. approach15
Azizi and co-authors developed an operationally simple, practical, and economical
protocol for iron (III) chloride catalyzed Paal-Knorr pyrrole synthesis in water in good to
excellent yields. Several N-substituted pyrroles are readily prepared from the reaction of 2,
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5-dimethoxytetrahydrofuran and aryl/alkyl, sulfonyl and acyl amines under very mild
reaction conditions.
OOMeMeO
2 mol-%FeCl3.7H2O
H2O, 60 oC 1-4 h+R NH2
NR
Scheme 1
Banik et al. approach16
Banik and co-workers described an expeditious synthesis of N-substituted pyrroles by the
reaction of 2,5-dimethoxytetrahydrofuran with amines using a microwave-induced
molecular iodine-catalyzed reaction, under solvent free conditions.
OOMe OMe + R-NH2
I2/MWIN
R
Scheme 2
Das et al. approach17
Das and co-authors developed a three-component reaction between phenacyl bromide or its
derivative, amine, and dialkylacetylenedicarboxylate in the presence of iron (III) chloride
as a catalyst at room temperature affording polysubstituted pyrroles in high yields.
ArBr
O+ RNH2 + N
E
EAr
R
FeCl3 (15 mol%)
CH2Cl2, rt, 14-16 h
E
E Scheme 3
Knorr et al. approach18
Knorr approach involves the condensation of α-aminoketone or α-amino-β-ketoester with a
ketone or ketoester. The major drawback of this reaction is the self-condensation of
starting material α-aminoketone and as a consequence, this reaction is not regioselective,
when unsymmetrical β-diketones are used.
Scheme 4. Reagents and conditions: (a) NaNO2/AcOH; (b) Zn/AcOH; (c) CH3COCH2R3
110
Paal-Knorr et al. approach19
Paal-Knorr reported the synthesis of polysubstituted pyrroles from amines with 1, 4-
dicarbonyl compounds in the presence of acid medium.
Scheme 5
Hantzsch approach20
Hantzsch described the synthesis of pyrroles from α-halo ketones or aldehydes with β-
ketoesters or β-diketones in the presence of amine.
R1
Br
O
H2N R2
R3
N
R3
R2
Br
R1 N
R3
R2R1- HBr N
H
R1 R2
R3
Scheme 6
Mantellini et al. approach21
Mantellini and co-workers developed the synthesis of polysubstituted pyrroles using
Zinc(II)-Triflate as a catalyst. This divergent synthesis involves the initial formation of α-
aminohydrazones by Michael addition of primary amines to 1, 2-diaza-1, 3-dienes, which
upon treatment with dialkylacetylenedicarboxylate afford α-(N-enamino)-hydrazones,
which are subsequently converted into corresponding pyrroles.
Scheme 7
Shi et al. approach22
Shi et al. reported regioselective synthesis of polyfunctionalized pyrroles employing multi-
component condensation reaction from 1, 3- diketones, aldehydes and amines using low-
valent titanium reagent in combination with samarium powder.
111
Scheme 8
Liang et al. approach23
Liang and co-authors described the synthesis of poly substituted pyrroles from β-enamino
ketones or esters with dialkylacetylenedicarboxylates in the presence of copper iodide,
oxygen.
Scheme 9
Bi et al. approach24
Bi and co-workers reported the synthesis of poly functionalized pyrroles from 4-acetylenic
ketones with primary amines by using Iron (III) chloride as catalyst.
O
R1
R2
R3
R4NH2
FeCl3(10 mol%)
TolueneN R4
R1R2
R3
Scheme 10
Fernando et al. approach25
Fernando and co-workers developed a diversity oriented strategy for the synthesis of poly
functionalized pyrroles via consecutive coupled domino processes in one-pot operation by
microwave (µw)-irradiation assistance. The synthesis mainly involves the rearrangement of
1, 3-oxazolidines derived from trialkylamine catalyzed synthesis of enol-protected
propargylic alcohols in a domino sequence to the corresponding pyrroles.
Scheme 11
112
Hashemi et al. approach26
In this approach 2-alkyl-5-aryl-(1H)-pyrrole-4-ol derivatives were synthesized through the
multi-component approach of β-dicarbonyl compounds with arylglyoxal in the presence of
ammonium acetate in water.
Scheme 12
Jana et al. approach27
Jana et al. demonstrated the synthesis of poly substituted pyrroles from 1, 3-dicarbonyl
compounds, amines, aromatic aldehydes, and nitroalkanes by using iron(III) chloride under
reflux.
Scheme 13
Camp and Ngwerume approach28
An efficient and regio controlled synthesis of poly substituted pyrroles was obtained by
Gold-catalyzed rearrangement of O-vinyl oximes, which in turn can be prepared by the
reaction of oximes with electron deficient alkynes using DABCO as a nucleophilic
catalyst.
Scheme 14
Rao et al. approach29
Rao and co-authors developed several substituted pyrrole derivatives with multiple aryl
substituents were prepared conveniently in a one-pot protocol from but-2-ene-1, 4-diones
and but-2-yne-1, 4-diones via hydrogenation of carbon–carbon double bond/triple bond
113
followed by amination–cyclization process in polyethylene glycol-200 (PEG-200) under
microwave irradiation (MW) conditions.
Scheme 15
1 Scheidt and Bharadwaj approach
30
In this method, poly functionalized pyrroles was synthesized through one-pot
multicomponent reaction catalyzed by thiazolium salt utilizing Sila-Stetter/Paal-Knorr
reaction sequence between acylsilanes, unsaturated carbonyl compounds and amines.
Scheme 16
Narasaka et al. approach31
In their approach, highly substituted pyrrole synthesis was achieved by both thermal and
Cu catalyzed methods. Here, both the methods use vinyl azide as common intermediate to
afford polysubstituted N-H pyrroles. In thermal method the desired pyrrole motif can be
obtained by the 1, 2-addition of 1, 3-dicarbonyl compounds to the in situ generated 2H-
azirine intermediate from vinyl azide whereas in copper catalyzed method, 1, 4-addition
reaction of ethyl acetoacetate to vinyl azide gives polysubstituted pyrrole.
Scheme 17
Ma et al. approach32
In this approach, poly substituted pyrroles was achieved from alkylidenecyclopropyl
ketones and amines by using MgSO4 in acetonitrile.
114
Scheme 18
Zhan et al. approach33
Zhan and co-workers developed a novel an efficient one-pot synthesis of substituted
pyrroles using Zinc chloride, which involves the propargylation of propargylic acetates
with enoxysilanes, amination and 5-exo-dig cycloisomerization as intrinsic sequence of
reactions to afford substituted pyrroles.
Scheme 19
Jia et al. approach34a
Jia and co-authors reported the synthesis of pyrroles from aldehydes and anilines. Here the
reaction believed to proceed via oxidative homodimerization of aldehyde enamine
intermediate in the presence of AgOAc.
Scheme 20
Lingaiah et al. Approach34b
Lingaiah et al. demonstrated the synthesis of substituted pyrroles under PEG-400 medium
from phenacyl bromide, DEAD/DMAD and amines.
R
O
X
OR2
R2O
O
O
NR
R1
O
OR2
OR2
O
PEG-400
60 oC,10 hR1-NH2
Scheme 21
115
PRESENT WORK
Although there have been numerous synthetic methods reported for the polyfunctionalized
pyrroles, many of the aforementioned protocols suffer from drawbacks such as use of
anhydrous hazardous organic solvents, expensive catalytic systems, which are moisture
sensitive and tedious isolation procedures, which limit their practical applications. In view
of these short comings, exploration and development of a mild, efficient and
environmentally benign neutral synthetic procedure is highly desirable.
Due to increasing economic and environmental concerns, synthetic organic chemists are
looking for novel procedures and green protocols to optimize the efficacy leading to ideal
synthetic routes where complex molecules can be obtained by a single and multi-step
tandem reaction without isolating the intermediates. Multi-component reactions are tandem
reactions,35
in which the target molecule is prepared in a single one-pot operation
incorporating more or less all the atoms of starting materials. Multi-component reactions
(MCRs) are excellent reaction strategies, being employed in the synthesis of large
combinatorial libraries of heterocyclic compounds, which possess interesting
pharmaceutical applications.36
Multi-component reactions (MCRs) are convergent,
classically defined as reactions, where more than two starting materials react to form a
product in a single synthetic operation incorporating all the atoms of the starting materials.
Therefore, we envisioned a generally applicable, environmentally benign and mild
methodology for the synthesis of substituted pyrroles via multi-component condensation
protocol using β-cyclodextrin. Herein, the remarkable catalytic activity of β-cyclodextrin is
demonstrated in the reaction of amines, DEAD/DMAD and phenacyl bromide, to afford
substituted pyrroles under neutral conditions in water. (Scheme 22)
Scheme 22
In general, all the reactions were carried out by dissolving β-cyclodextrin in water and then
adding the amine followed by the addition of DEAD/DMAD and phenacyl bromide at 50-
60 oC to get the corresponding substituted pyrroles in high yields (80–89%) Table 2. This
method was compatible with various types of diversely substituted primary and secondary
116
aromatic amines. β-CD can be recovered and reused. All the products were isolated and
characterized by 1H,
13C NMR, mass and IR spectroscopy. The reaction was also
successful when NH4OAc is used as amine source and produced dimethyl 5-phenyl-1H-
pyrrole-2,3-dicarboxylate pyrrole in quantitative yield. The electronic factors of
substituents in the amines have played key role in governing the product yield.
m
p
o
NH2
1
2
3
Figure 2. 1H NMR spectra (400 MHz, DMSO-d6) of 1) Aniline 2) β-CD 3) Aniline:β-CD
inclusion complex
The catalytic activity of the β-CD was established by the fact that no pyrrole formation
was observed in the absence of β-cyclodextrin, even after longer reaction times. The
evidence for the formation of highly substituted pyrroles in presence of β-CD was
supported by 1H NMR studies of the inclusion complex between aniline and β-CD. The
hydrophobic environment of β-CD facilitates the formation of pyrrole via inclusion
complex of aniline/diethyl acetylenedicarboxylate carbanion stabilized by the primary and
secondary–OH groups of β-CD, which further reacts with aldehyde as indicated in
Figure 2.
117
Table 1. 400 MHz 1H-Chemical shifts of aniline and β-CD protons in free and
complexed statea
A comparative study of 1H NMR spectra of aniline, β-CD and β-CD/aniline complex was
undertaken (Table 1). In the 1H NMR spectrum (in DMSO-d6) of aniline, the aromatic
protons from ortho position appear as a doublet at 6.61 ppm (J = 8.2 Hz), while meta and
para protons appear as triplets at 7.06 (J = 7.4 Hz) and 6.55 (J = 6.7 Hz), respectively.
Amine protons in aniline appear as singlet at 5.05 ppm. The 1H NMR spectrum of β-
CD/aniline inclusion complex shows upfield shift of aromatic protons as well as amine
protons of aniline. This upfield shift of aniline protons can be due to the inclusion of
aniline inside β-CD cavity. Apart from the upfield shift of aniline protons due to the
incorporation inside the β-CD cavity, the protons located in the β-CD cavity (C3–H and
C5–H) are also shifted upfield in 0.02 ppm due to the magnetic anisotropy caused by the
guest (aniline) molecule.37
In conclusion, an elegant and simple methodology was presented for the synthesis of
highly substituted pyrroles in the presence of β-cyclodextrin in water. This straightforward
methodology may find wide spread applications in organic and medicinal chemistry. (This
work was published in Chin. Chem. Lett., 2012, 23, 1331-1334)
119
aReaction conditions: Aniline (1.0 mmol), DMAD/DEAD (1.0 mmol), Phenacyl bromide (1.0 mmol), β-
Cyclodextrin (10 mol %), 50-60 oC.
bIsolated yield.
EXPERIMENTAL
General procedure for the synthesis of substituted pyrroles:
β-Cyclodextrin (10 mol %) was dissolved in water (15 ml), and to this clear solution,
aniline (1.0 mmol) was added, stirred for 15 min, followed by the addition of
dimethyl/diethyl acetylenedicarboxylate (DMAD/DEAD 1.0 mmol) and phenacyl bromide
(1.0 mmol). The reaction mixture was heated at 50-60 oC until completion of the reaction
as indicated by TLC. The reaction mixture was cooled to 5 oC and β-cyclodextrin was
filtered. The aqueous layer was extracted with ethyl acetate (3 x 10 ml). The combined
organic layers were washed with water, saturated brine solution, and dried over anhydrous
Na2SO4. The combined organic layers were evaporated under reduced pressure and the
resulting crude product was purified by column chromatography using ethyl acetate and
120
hexane (2:8) as eluent. The identity and purity of the product were confirmed by 1H,
13C
NMR, and mass spectra.
Preparation of β-CD-aniline inclusion complex:
β-CD (1.0 mmol) was dissolved in water (15 mL) by warming to 60 oC until a clear
solution was formed, and then aniline (1.0 mmol) was added drop wise, stirred for 3h and
allowed to come to room temperature. It was cooled to 5 oC and β-cd was filtered.
Spectroscopic data for all the compounds
Diethyl1,5-Diphenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 1)
Colorless oil
Yield : 319 mg (88%)
FT-IR (neat) : 3376, 2954, 1738, 1614, 1510, 1441, 1279, 1216,
1023, 836 cm-1
1H NMR (300MHz, CDCl3) : δ 8.22 (d, 2H, J = 8.8 Hz), 7.60 (d, 2H, J = 8.8 Hz), 7.48-
7.46 (m, 3H), 7.37-7.34 (m, 2H), 7.26 (s, 1H), 7.07 (s,
1H), 4.33 (q, J = 7.0 Hz, 2H), 4.16 (q, J =7.0 Hz,
2H), 1.30 (t, J = 7.0 Hz, 3H), 1.15 (t, J = 7.0 Hz, 3H)
13C NMR (50MHz, CDCl3) : δ 165.3, 159.7, 146.5, 140.1, 139.0, 128.9, 128.7,
128.2, 125.9, 123.7, 122.6, 122.3, 61.5, 61.1, 13.9,
13.7
Mass (ESI-MS) : m/z 364 [M+ H]
Dimethyl1,5-Diphenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 2)
Colorless oil
Yield : 298 mg (89%)
FT-IR (neat) : 3334, 2955, 2924, 1740, 1615, 1510, 1440, 1281,
1217, 1098, 1022 cm-1
1H NMR (300MHz, CDCl3) : δ 8.21 (d, 2H, J = 8.8 Hz), 7.57 (d, 2H, J = 8.6 Hz) 7.49–
7.45 (m, 3H), 7.36-7.33 (m, 2H), 7.25 (s, 1H), 7.03 (s,
1H), 3.82 (s, 3H), 3.72 (s, 3H)
121
13C NMR (50MHz, CDCl3) : δ 165.8, 160.2, 140.0, 138.8, 129.0, 128.8, 128.2,
126.0, 125.8, 122.8, 52.4, 52.1
Mass (ESI-MS) : m/z 336 [M+ H]
Dimethyl5-Phenyl-1-(4-tolyl)-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 3)1
Colorless oil
Yield : 296 mg (85%)
FT-IR (neat) : 3277, 2982, 1735, 1617, 1276, 1141, 1037, 822 cm-1
1H NMR (300MHz, CDCl3) : δ 7.43–7.31 (m, 3H), 7.30–7.20 (m, 4H), 7.19–7.02
(m, 2H), 6.95 (s, 1H), 3.81 (s, 3H), 3.70 (s, 3H), 2.41
(s, 3H)
13C NMR (50MHz, CDCl3) : δ 129.4, 128.5, 127.7, 127.0, 125.9, 52.1, 29.7
Mass (ESI-MS) : m/z 350 [M+ H]
Diethyl5-Phenyl-1-(4-tolyl)-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 4)1
Colorless oil
Yield : 316 mg (84%)
FT-IR (neat) : 3372, 2952, 1736, 1612, 1519, 1279, 1214, 1021,
838 cm-1
1H NMR (300MHz, CDCl3) : δ 7.42 (d, J = 8.0 Hz, 2H), 7.33 (t, J = 8.0 Hz, 2H),
7.30–7.21 (m, 5H), 6.94 (s, 1H), 4.30 (q, J = 7.0 Hz,
2H), 4.15 (q, J = 7.0 Hz, 2H), 2.41 (s, 3H), 1.31 (t, J
= 7.0 Hz, 3H), 1.18 (t, J = 8.0 Hz, 3H)
13C NMR (50MHz, CDCl3) : δ 166.2, 159.9, 138.3, 137.0, 133.2, 130.8, 129.3,
128.4, 127.7, 126.9, 125.9, 125.7, 61.2, 60.7, 29.6,
21.1, 14.0, 13.8
Mass (ESI-MS) : m/z 378 [M+ H]
Diethyl5-(4-Nitrophenyl)-1-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 5)1
Colorless oil
Yield : 326 mg (80%)
122
FT-IR (neat) : 3286, 2952, 2854, 1738, 1615, 1496, 1280, 1143 cm-1
1H NMR (300MHz, CDCl3) : δ 8.20 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H),
7.52–7.44 (m, 3H), 7.39–7.33 (m, 2H), 7.08 (s, 1H),
4.31 (q, J = 7.0 Hz, 2H), 4.16 (q, J = 7.0 Hz, 2H),
1.30 (t, J = 7.0 Hz, 3H), 1.10 (t, J = 7.0 Hz, 3H)
13C NMR (50MHz, CDCl3) : δ 163.4, 160.1, 158.1, 141.2, 138.7, 129.2, 128.9,
128.1, 125.4, 124.5, 122.8, 122.6, 121.9, 61.2, 61.1,
13.1, 13.0
Mass (ESI-MS) : m/z 409 [M+ H]
Dimethyl5-(4-Nitrophenyl)-1-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 6)1
Colorless oil
Yield : 307 mg (81%)
FT-IR (neat) : 3378, 2956, 1740, 1614, 1512, 1279, 1025, 838 cm-1
1H NMR (300MHz, CDCl3) : δ 8.23 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H),
7.50–7.40 (m, 3H), 7.37–7.32 (m, 2H), 7.01 (s, 1H),
3.84 (s, 3H), 3.72 (s, 3H)
13C NMR (50MHz, CDCl3) : δ 165.2, 159.1, 145.5, 138.9, 138.2, 128.9, 128.8,
128.2, 126.1, 125.9, 125.2, 123.9, 122.7, 120.1, 52.3,
52.2
Mass (ESI-MS) : m/z 381 [M+ H]
Diethyl5-(4-Bromophenyl)-1-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 7)1
Colorless oil
Yield : 374 mg (85%)
FT-IR (neat) : 3386, 2924, 1738, 1613, 1515, 1436, 1279, 1218,
1028, 970 cm-1
1H NMR (300MHz, CDCl3) : δ 7.53–7.39 (m, 6H), 7.39–7.24 (m, 3H), 6.92 (s, 1H),
4.24 (q, J = 7.0 Hz, 2H), 4.14 (q, J = 7.0 Hz, 2H),
1.24 (t, J = 7.0 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H)
123
13C NMR (50MHz, CDCl3) : δ 165.1, 159.3, 138.2, 132.1, 130.8, 129.2, 129.1,
128.2, 126.1, 124.6, 122.1, 62.2, 61.1, 13.8, 13.1
Mass (ESI-MS) : m/z 442 [M+ H]
Dimethyl5-(4-Bromophenyl)-1-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2,
entry 8)1
Colorless oil
Yield : 346 mg (84%)
FT-IR (neat) : 3287, 2954, 1738, 1674, 1511, 1439, 1282, 1217,
1099, 833 cm-1
1H NMR (300MHz, CDCl3) : δ 7.54–7.44 (m, 5H), 7.39–7.20 (m, 4H), 6.94 (s,
1H), 3.83 (s, 3H), 3.68 (s, 3 H)
13C NMR (50MHz, CDCl3) : δ 165.6, 160.4, 140.2, 138.9, 133.3, 132.4, 130.1,
128.5, 128.2, 128.1, 128.0, 126.2, 124.2, 123.5,
120.9, 52.2, 52.1
Mass (ESI-MS) : m/z 414 [M+ H]
Diethyl5-(4-Nitrophenyl)-1-(4-tolyl)-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 9)2
Colorless oil
Yield : 350 mg (83%)
FT-IR (neat) : 3270, 2952, 1738, 1612, 1503,1273, 1039, 860 cm-1
1H NMR (300MHz, CDCl3) : δ 8.22 (d,1H, J = 8.0 Hz), 8.02 (d, J = 8.0 Hz, 1H),
7.57 (d, J = 8.0 Hz, 2H), 7.29–7.06 (m, 4H), 6.98 (s,
1H), 4.27 (q, J = 7.0 Hz, 2H), 4.15 (q, J = 7.0 Hz,
2H), 2.43 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H), 0.91 (t, J
= 7.0 Hz, 3H)
13C NMR (50MHz, CDCl3) : δ 129.8, 129.6, 128.6, 128.2, 125.7, 123.8, 61.4, 61.1,
29.6, 13.9
Mass (ESI-MS) : m/z 423 [M+ H]
Dimethyl1-(4-Fluorophenyl)-5-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2,
entry 10)2
124
Colorless oil
Yield : 296 mg (84%)
FT-IR (neat) : 3264, 2930, 1610, 1277, 1142, 1092, 771 cm-1
1H NMR (300MHz, CDCl3) : δ 7.50–7.29 (m, 7H), 7.12 (t, J = 7.0 Hz, 2H), 6.98
(s, 1H), 3.83 (s, 3H), 3.71 (s, 3H)
13C NMR (50MHz, CDCl3) : δ 167.0, 160.5, 136.9, 133.2, 128.7, 128.5, 127.8,
127.3, 126.8, 125.5, 124.0, 52.3, 51.6
Mass (ESI-MS) : m/z 354 [M+ H]
Dimethyl5-(4-Nitrophenyl)-1-(4-tolyl)-1H-pyrrole-2,3-dicarboxylate (Table 2,
entry 11)2
Colorless oil
Yield : 327 mg (83%)
FT-IR (neat) : 3380, 2931, 1735, 1607, 1515, 1219, 1172, 1044,
778 cm-1
1H NMR (300MHz, CDCl3) : δ 8.23 (d, J = 8.0 Hz, 2H), 8.05 (d, J = 8.0 Hz, 2H),
7.59–7.48 (m, 4H), 6.99 (s, 1H), 3.83 (s, 3H), 3.72 (s,
3H), 2.43 (s, 3H)
13C NMR (50MHz, CDCl3) : δ 129.9, 129.6, 128.7, 128.2, 126.1, 125.5, 123.8,
52.4, 52.0, 31.8, 29.6, 22.6, 14.0
Mass (ESI-MS) : m/z 395 [M+ H]
Diethyl1-(4-Fluorophenyl)-5-(4-nitrophenyl)-1H-pyrrole-2,3-dicarboxylate (Table 2,
entry 12)1
Colorless oil
Yield : 349 mg (82%)
FT-IR (neat) : 3282, 2927, 1734, 1612, 1514, 1273, 1175, 1037, 826
cm-1
1H NMR (300MHz, CDCl3) : δ 8.26 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H),
7.42–7.29 (m, 2H), 7.16 (t, J = 8.0 Hz, 2H), 7.09 (s,
1H), 4.32 (q, J = 7.0 Hz, 2H), 4.18 (q, J = 7.0 Hz,
125
2H), 1.24 (t, J = 7.0 Hz, 3H), 0.96 (t, J = 7.0 Hz, 3H)
13C NMR (50MHz, CDCl3) : δ 166.1, 163.9, 146.0, 141.1, 136.8, 130.9, 128.1,
129.0, 128.9, 124.9, 122.5, 122.2, 120.1, 116.6,
115.0, 62.2, 61.8, 13.6, 12.8
Mass (ESI-MS) : m/z 460 [M+ H]
Dimethyl 5-(4-bromophenyl)-1-(p-tolyl)-1H-pyrrole-2,3-dicarboxylate (Table 2, entry
13)2
Colorless oil
Yield : 367 mg (86%)
FT-IR (neat) : 3284, 2982, 1736, 1667, 1610, 1517, 1452, 1371,
1274, 1207, 1141, 1099, 1038 cm-1
1H NMR (300MHz, CDCl3) : δ 7.45-7.23 (m, 8H), 6.95 (s, 1H), 4.33-4.13 (m, 6H),
2.41(s, 3H)
13C NMR (50MHz, CDCl3) : δ 129.1, 128.2, 124.9, 110.8, 52.1, 51.6, 29.8
Mass (ESI-MS) : m/z 428 [M+H]
Diethyl 5-(4-bromophenyl)-1-(4-fluorophenyl)-1H-pyrrole-2,3-dicarboxylate (Table 2,
entry 14)2
Colorless oil
Yield : 386 mg (84%)
FT-IR (neat) : 3282, 2980, 1737, 1656, 1513, 1272, 1207, 1141,
1099, 1038 cm-1
1H NMR (300MHz, CDCl3) : δ 7.43-7.22 (m, 8H), 6.94 (s, 1H), 4.26 (q, 2H, J1 = 6.7
Hz) 4.13 (q, 2H, J = 6.7 Hz) 1.27 (t, 3H, J = 7.0 Hz),
1.16 (t, 3H, J = 8.0 Hz)
13C NMR (50MHz, CDCl3) : δ 166.1, 159.8, 139.5, 133.1, 128.7, 128.4, 127.6,
127.0, 126.1, 125.6, 124.6, 61.2, 60.7, 61.2, 29.6,
13.9, 13.8
Mass (ESI-MS) : m/z 460 [M+ H]
126
Dimethyl5-Phenyl-1H-pyrrole-2,3-dicarboxylate (Table 2, entry 15)1
Colorless oil
Yield : 212 mg (82%)
FT-IR (neat) : 3332, 2953, 1740, 1608, 1512, 1454, 1215, 1023, 836
cm-1
1H NMR (300MHz, CDCl3) : δ 9.35 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.43 (t, J =
8.0 Hz, 2H), 7.32 (t, J = 8.0 Hz, 1H), 6.84 (d, J = 2.0
Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H)
13C NMR (50MHz, CDCl3) : δ 164.5, 159.9, 136.1, 129.5, 128.8, 128.4, 125.5,
124.6, 122.4, 110.8, 51.7, 50.5
Mass (ESI-MS) : m/z 260 [M+ H]
127
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