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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,

109

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)

118

Table 2. Synthesis of substituted pyrroles.a

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


127

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