Catalyst-free four-component protocol for the synthesis of substituted pyrroles under reusable reaction media

Article abstract of DOI:10.1016/j.tetlet.2013.01.098

An efficient four-component protocol is described for the synthesis of diversely functionalized pyrroles under catalyst-free condition by using ionic liquid as a reaction media. The developed method is mild, high yielding, and amenable for a variety of am

Full text of DOI:10.1016/j.tetlet.2013.01.098

Tetrahedron Letters 54 (2013) 2296–2302
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Catalyst-free four-component protocol for the synthesis of substituted
pyrroles under reusable reaction media
⇑
H. M. Meshram , B. Madhu Babu, G. Santosh Kumar, Pramod B. Thakur, Vikas M. Bangade
Organic Chemistry Division-I, Natural Product Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient four-component protocol is described for the synthesis of diversely functionalized pyrroles
under catalyst-free condition by using ionic liquid as a reaction media. The developed method is mild,
high yielding, and amenable for a variety of amines as well as aldehydes. Moreover the procedure is of
environmentally benign nature in which ionic liquid 1-n-butylimidazolium tetrafluoroborate [Hbim]BF4
is used as a reusable and efficient reaction medium without using any additional catalyst or promoter.
Ó 2013 Published by Elsevier Ltd.
Received 16 October 2012
Revised 22 January 2013
Accepted 24 January 2013
Available online 30 January 2013
Keywords:
Ionic liquid [Hbim]BF4
Four-component reaction
Pyrrole
Catalyst-free reaction
Reusable media
Pyrrole is an important core unit found in many natural prod-
ucts,1 pharmaceutically active compounds, (Fig. 1) and electrical
conducting materials.2 In addition to this, pyrrole derivatives are
known to possess a wide range of biological activities such as anti-
tumor, anti-inflammatory, antibacterial, antioxidant, and anti-
fungal.3 Due to such prominence of pyrroles, numerous
methods4–10 have been reported for the synthesis of these
molecules where the most commonly used approaches include
Hantzsch4, Knorr5 and Paal–Knorr6 syntheses. In an alternate
method, the synthesis of pyrrole has been accomplished by the
reaction of bromonitrostyrenes with enamines.11 Recently a four-
component reaction of amines, aldehyde, diketone, and nitroalkane
is reported to give functionalized pyrroles12a,b by using FeCl3,12a
and NiCl2Á6H2O.12b However this method possesses certain draw-
backs such as the use of toxic metal catalysts and harsh reaction
conditions. Moreover these methods use non-ecofriendly organic
solvents and give a moderate yield of product even after a longer
reaction time. In this regard, the development of an efficient meth-
od for the synthesis of pyrrole derivatives under mild reaction con-
dition is highly desirable.
Nowadays, sustainable processes are highly in demand in the
chemical industry.13 The ‘process efficiency’ concept is not only
related to a high chemical yield, but also to minimize the use of
large amounts of harmful organic reagents, solvents, catalyst, and
undesired chemical waste.14 In this context, ionic liquids have been
emerging as a mild and environmentally benign reaction medium
in modern chemical synthesis.15 Also ionic liquid promotes the dif-
ferent organic transformations without the use of any additional
catalyst or solvent.16
In a recent article, Jana et al. found that, b-enaminone and b-
nitrostyrene are key intermediates in the pyrrole synthesis12b
and our literature survey revealed that the synthesis of these key
intermediates can be achieved in ionic liquid.17a,b Keeping this in
mind, we envisioned the catalyst-free four-component reaction
of amines, aldehyde, diketone, and nitroalkane to give functional-
ized pyrroles by using ionic liquid as a reaction medium (Scheme
1). To the best of our knowledge there is no report concerning
the catalyst-free four-component synthesis of pyrroles. Hence, as
a part of our16 ongoing interest in the application of ionic liquids
for the synthesis of biologically active molecules, herein we wish
HO
NEt2
HO
N
O
CO2H
NH
O
N
H
F
F
NH
O
N
H
sunitinib
atorvastatin
receptor tyrosine kinase
inhibitor (RTK)
competitive HMG-CoA-reductase
inhibitor
Figure 1. Representative examples of biologically active pyrrole derivatives.
⇑
Corresponding author. Tel.: +91 40 27191643; fax: +91 40 27193275.
E-mail address: hmmeshram@yahoo.com (H.M. Meshram).
0040-4039/$ - see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2013.01.098

H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
2297
Table 1
O
Screening of reaction mediaa
R
H
O
O
O
NH2
R
Ionic liquid
Entry
H3C NO2
Reaction media
Yieldb(%)
Time (min)
+
+
+
R
N
R
H
1
2
3
52
90
85
86
[Hbim]BF4
[Hbim]BF4
[bmim]BF4
Scheme 1. Envisioned reactions of amines, aldehyde, diketone, and nitroalkane for
the synthesis of substituted pyrroles under catalyst-free condition by using ionic
liquid.
90
78
71
4
5
6
[bmim]PF6
[emim]BF4
-
90
90
58
tracec
H
N
N
24 h
BF4
aReaction condition: cyclopropylamine 1a (1.2 mmol), benzaldehyde 2a (1 mmol),
acetylacetone 4 (1 mmol), and nitromethane 3 (1 mmol) in 5 mL ionic liquid.
bIsolated yield.
Figure 2. Chemical structure of 1-n-butylimidazolium tetrafluoroborate [Hbim]BF4
ionic liquid.
cUnder neat reaction condition.
O
R2
R1 NH2
O
+
H
+
O
O
[Hbim]BF4
of 5 mL [Hbim]BF4 as an optimized reaction condition for the syn-
thesis of substituted pyrrole 5aa by catalyst-free four-component
reaction of cyclopropylamine 1a, benzaldehyde 2a, acetylacetone
4, and nitromethane 3 at rt under reusable reaction media (Table
1, entry 1).
H3C NO2
+
R2
N
R1
5(aa-ff)
H
rt, 38-60 min
2(a-g)
1(a-f)
3
4
R1 = cyclic/acyclic aliphatic, R2 = aromatic, heteroaromatic
Further, for the general validity of the reaction, the optimized
condition18,19 was tested on several structurally varied amines as
well as aldehydes and the results are summarized in Table 2. The
reaction of benzylamine (entries 12–14) and 2-phenylethylamine
(entries 17–23) underwent smoothly in the standard reaction con-
dition to furnish the desired product in a high yield. It is worthy to
mention that the procedure is also applicable for cyclicamines like
cyclopropylamine and cyclohexylamine (entries 1–7 and 8–11,
respectively) and alkynylamines like propargylamine (entries 24–
29) which were totally unexplored in the pyrrole synthesis. The
efficiency of the reaction was further strengthened by the partici-
pation of heterocyclic aldehyde in this four-component reaction
(entries 5, 10, 21, 28). For example the reaction of cyclopropyl-
amine 1a with furfural 2e also proceeded same way and afforded
corresponding product 5ae in good yield (entry 5). Other diversely
functionalized aldehydes also participated effectively in the reac-
tion under optimized condition (Table 2). In our protocol, other dif-
ferent functional groups such as halides, hydroxyl, methoxy, acetyl,
nitro, and alkynyl remained unaffected and the exclusive forma-
tion of pyrrole derivative was observed. It is worthy to mention
that, in the present study the scope of the developed method
was tested on new substrates and hence all obtained substituted
pyrrole derivatives are new compounds.
Our next approach was to study the scope of reusability of
[Hbim]BF4 for this four-component reaction. Hence, after comple-
tion of the reaction, the reaction mixture was isolated from
[Hbim]BF4 by simply extracting with ether (3 Â 15 mL). Then the
[Hbim]BF4 was dried under vacuum and used for subsequent reac-
tions. We reused [Hbim]BF4 up to three cycles for this four compo-
nent reaction and did not find any substantial loss in the catalytic
activity of [Hbim]BF4 (first cycle: Table 2, entry 7, second cycle: Ta-
ble 2, entry 19, third cycle: Table 2, entry 24).
The tentative mechanistic pathway based on one of the litera-
ture reports12a is proposed for the catalyst-free synthesis of func-
tionalized pyrroles by using ionic liquid as a reaction medium as
shown in Scheme 3. We reasoned that the reaction proceeded to
form b-enaminone by the condensation of acetylacetone with ami-
ne.17a This reactive b-enaminone attacked on in situ generated b-
nitro styrene17b and forms five membered cyclic intermediate A.
Finally the cyclic intermediate undergoes aromatization by the
elimination of water molecule with the aid of ionic liquid and gives
substituted pyrrole derivative.
Scheme 2. Synthesis of substituted pyrroles under catalyst-free condition by using
[Hbim]BF4 as a reaction medium.
to report the catalyst-free, mild, and high yielding four component
protocol for the synthesis of diversely functionalized pyrroles by
using ionic liquid 1-n-butylimidazolium tetrafluoroborate
[Hbim]BF4 (Fig. 2) as a reusable reaction medium.
As a model reaction we first attempted the reaction of cyclopro-
pylamine 1a (1.2 mmol), benzaldehyde 2a (1 mmol), acetylacetone
4 (1 mmol), and nitromethane 3 (1 mmol) in 5 mL ionic liquid 1-n-
butylimidazolium tetrafluoroborate [Hbim]BF4 (Scheme 2) and
progress of the reaction was monitored continuously by TLC. The
reaction proceeded smoothly within 52 min at room temperature
to give substituted pyrrole 5aa which was confirmed by analyzing
spectral data (Table 2, entry 1). The formation of the desired prod-
uct was also confirmed by comparison with the spectral data ob-
tained for a sample prepared by one of the available literature
procedures.12a The above observations reveal that the substituted
pyrrole can be obtained by four-component reaction of amines,
aldehyde, diketone, and nitroalkane in ionic liquid under cata-
lyst-free condition.
These encouraging observations promoted us to screen the dif-
ferent imidazole based ionic liquids to study the model reaction in
detail. We have studied model reaction in different ionic liquids
such as, 1-n-butylimidazolium tetrafluoroborate [Hbim]BF4, 1-bu-
tyl-3-methylimidazolium tetrafluoroborate [bmim]BF4, 1-butyl-3-
methylimidazolium hexafluoro phosphate [bmim]PF6, and 1-
ethyl-3-methylimidazolium tetrafluoroborate [emim]BF4. After
this extensive screening, we found ionic liquid [Hbim]BF4 as a most
suitable reaction medium for model reaction in terms of reaction
time and isolated yield (Table 1, entry 1). We found that the reac-
tion worked very well in ionic liquid [Hbim]BF4 without using
additional catalyst and gave very high yields of product within a
shorter reaction time at rt as compared to the previous meth-
ods.12a,b The exact reason for this is not well understood, but we as-
sume that, due to the distinctive acidity and polarity associated
with [Hbim]BF4, it plays a dual role as catalyst as well as solvent
and hence resulted in a higher yield of product. As a part of study,
we have also performed control reaction under a neat reaction con-
dition; however the desired product was formed in very trace
amount even after strengthening the reaction time up to 24 h (Ta-
ble 1, entry 6). On the basis of above study we have chosen the use

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H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
Table 2
Synthesis of substituted pyrrolesa in [Hbim]BF4
Entry
Amine (R1)
Aldehyde (R2)
Time (min)
52
Yieldb (%)
Product
O
NH2
O
1a
1
85
N
5aa
2a
O
NH2
O
N
1a
2
3
50
52
87
87
N
5ab
2b
O
O
O
NH2
O
1a
O
5ac
2c
O
O
OH
NH2
O
O
1a
4
50
85
OH
2d
N
N
5ad
NH2
O
O
O
1a
5
6
54
60
88
70
2e
5ae
O
Br
NH2
O
1a
N
2f
5af
Br
O
O2N
NH2
O
1a
7
8
60
54
75
82
N
2g
5ag
NO2
O
O
NH2
1b
1b
N
5ba
2a
O
O
NH2
O
O
9
55
83
N
O
5bc
2c O
O
NH2
NH2
O
O
2e
O
10
11
56
60
89
70
N
1b
5be
O
Br
O
1b
N
5bf
Br
2f

H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
2299
Table 2 (continued)
Entry
Amine (R1)
Aldehyde (R2)
Time (min)
Yieldb (%)
Product
O
O
12
13
NH2
40
90
1c
N
5cb
2b
O
O
O
O
1c
NH2
40
38
86
89
5cc
N
2c
O
O
O
O
O
HO
1c
14
NH2
N
5cd
OH
2d
2a
O
O
5da
N
1d
1d
15
45
93
NH2
O
O
O
O
HO
5dd
N
16
38
90
OH
2d
NH2
O
O
O
O
1e
1e
1e
17
18
45
40
93
90
NH2
NH2
5ea
N
2a
2b
O
5eb
N
O
O
O
O
O
NH2
19
20
40
38
88
92
O
2c
O
N
N
5ec
5ed
O
HO
1e
NH2
OH
2d
(continued on next page)

2300
H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
Table 2 (continued)
Entry
Amine (R1)
Aldehyde (R2)
Time (min)
Yieldb (%)
Product
O
O
O
O
21
22
40
87
2e
1e
NH2
NH2
N
5ee
O
Br
O
1e
1e
55
75
2f
5ef
Br
N
O
O2N
O
NH2
23
55
78
2g
5eg
NO2
N
O
NH2
O
1f
1f
1f
24
25
50
48
88
90
5fa
2a
N
O
O
NH2
2b
5fb
N
O
O
NH2
NH2
O
O
26
40
89
O
2c
5fc
5fd
N
N
O
O
O
HO
1f
27
28
48
40
94
89
N
OH
2d
2e
O
NH2
NH2
1f
1f
O
O
O
5fe
O
Br
O
29
55
77
2f
5ff
N
Br
a
All products exhibited physical and spectral (NMR, Mass, and IR) properties in accordance with the assigned structure.
Isolated Yield.
b

H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
2301
O
R2
O
O
N
R1
4
+
R1 NH2
5
1
[Hbim]BF4
O
-HNO2
H
-H2O
..
NH
R1
O
O
Aromitization
2
R2
+
[Hbim]BF4
H3C
NO2
O
R2
O
H
OH
OH
N
N
3
R2
H
N
R1
A
Attck of enaminone on
nitrostyrene
Cyclization
O
R2
O
R2
N
OH
N
OH
N
R1
NH
R1
O
O
Scheme 3. Plausible mechanistic pathway for the formation of substituted pyrrole in the presence of [Hbim]BF4.
3. (a) Teixeira, C.; Barbault, F.; Rebehmed, J.; Liu, K.; Xie, L.; Lu, H.; Jiang, S.; Fan,
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In conclusion, we have demonstrated an operationally simple,
efficient, and catalyst-free method for the synthesis of diversely
functionalized pyrrole derivatives using ionic liquid [Hbim]BF4 as
a reusable reaction medium. Moreover the method is applicable
to variety of amines as well as aldehydes and the yields are high.
This method ought to be of great value as a mild, rapid, and general
procedure for the synthesis of highly substituted pyrroles. Further
studies for the scope and limitations of this methodology are cur-
rently ongoing in our laboratory and results will be published else-
where in due course.
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Acknowledgments
The authors B.M.B., G.S.K., P.B.T., and V.M.B. thank the CSIR-UGC
for the award of a fellowship and Dr. A. Kamal, Director IICT, for his
support and encouragement.
Supplementary data
Supplementary data (spectral data for synthesized compounds)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2013.01.098.
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2302
H. M. Meshram et al. / Tetrahedron Letters 54 (2013) 2296–2302
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3H), 7.09–7.03 (m, 3H), 6.74–6.67 (m, 3H), 6.47 (s, 1H), 4.98 (s, 2H), 2.36 (s,
3H), 2.02 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 199.1, 156.2, 137.2, 136.2,
135.6, 129.4, 128.8, 127.8, 126.6, 125.9, 121.7, 120.7, 120.2, 116.3, 114.0, 50.2,
17. (a) Gholap, A. R.; Chakor, N. S.; Daniel, T.; Lahoti, R. J.; Kumar, V. S. J. Mol. Catal.
A: Chem. 2006, 245, 37; (b) Alizadeh, A.; Khodaei, M. M.; Eshghi, A. J. Org. Chem.
2010, 75, 8295; (c) Luzzio, F. A. Tetrahedron 2001, 57, 915; (d) Menzel, A.;
Ohrlein, R.; Griesser, H.; Wehner, V.; Jager, V. Synthesis 1999, 9, 1691.
18. General procedure: A mixture of amine (1.2 mmol), acetylacetone (1 mmol) in
5 mL ionic liquid [Hbim]BF4 was stirred for 10 min at room temperature then
the aldehyde (1 mmol) and nitromethane (1 mL) were added and the mixture
was stirred at rt for a stipulated time (see Table 1). The progress of the reaction
was monitored by TLC. After the completion of the reaction, the reaction
mixture was extracted with ether (3 Â 15 mL). The combined organic layers
were washed with brine solution, and dried over Na2SO4. Na2SO4 was filtered
off and the solvent was removed under vacuum. The residue obtained was then
purified by silica gel column chromatography (100–200 mesh) using ethyl
acetate/hexane (5:95 to 20:80) as eluent to get corresponding products. All the
obtained products were characterized by 1H NMR, 13C NMR, Mass, and IR
spectral data.
30.6, 11.5 ppm; IR(KBr):
m = 3152, 1621, 1592, 1450, 1415, 1231, 874, 774, 725,
704 cmÀ1; MS-ESI: m/z = 306 [M+1]+. 1-(4-(3,4-Dimethoxyphenyl)-2-methyl-1-
phenethyl-1H-pyrrol-3-yl) ethanone (5ec, Table 2, entry 19): White solid, mp
107–109 °C; 1H NMR (300 MHz, CDCl3): d 7.32–7.24 (m, 3H), 7.14–7.09 (m,
2H), 6.88–6.78 (m, 3H), 6.38 (s, 1H), 4.06 (t, J = 7.55 Hz, 2H), 3.91 (s, 3H), 3.87
(s, 3H), 3.01 (t, J = 7.55 Hz, 2H), 2.40 (s, 3H), 2.03 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d 197.2, 148.3, 147.8, 137.5, 134.4, 128.9, 128.5, 128.5, 128.2,
126.7, 125.3, 121.3, 119.1, 112.6, 110.8, 55.6, 55.6, 47.8, 37.3, 30.7, 11.2 ppm;
IR(KBr):
m
;
= 3422, 2937, 1641, 1508, 1413, 1224, 1174, 1131, 1025, 756,
703 cmÀ1
MS-ESI: m/z = 364 [M+1]+. 1-(4-(3-Hydroxyphenyl)-2-methyl-1-
phenethyl-1H-pyrrol-3-yl) ethanone (5ed, Table 2, entry 20): White solid, mp
153–155 °C; 1H NMR (300 MHz, CDCl3): d 7.31–7.20 (m, 3H), 7.15–7.08 (m,
3H), 6.76–6.69 (m, 3H), 6.43 (s, 1H), 4.06 (t, J = 6.65 Hz, 2H), 3.00 (t, J = 6.65 Hz,
2H), 2.31 (s, 3H), 2.01 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 199.4, 156.4,
138.4, 137.6, 135.9, 132.4, 128.8, 127.9, 126.8, 123.9, 120.6, 117.1, 116.4, 109.4,
19. Spectral data for synthesized compounds:
1-(1-cyclopropyl-4-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrol-3-yl)
ethanone
109.1, 50.2, 37.6, 28.9, 11.4 ppm; IR(KBr): m = 3186, 1622, 1598, 1508, 1450,
(5ac, Table 2, entry 3): White solid, mp 100–102 °C; 1H NMR (300 MHz,
CDCl3): d 6.90–6.79 (m, 3H), 6.49 (s, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.20–3.11
(m, 1H), 2.58 (s, 3H), 2.02 (s, 3H), 1.09–1.01 (m, 2H), 1.00–0.92 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3): d 197.1, 148.3, 147.8, 137.0, 128.9, 124.5, 121.7,
121.3, 119.1, 112.6, 110.8, 55.7, 55.6, 30.6, 27.9, 11.9, 6.5 ppm; IR(KBr):
1419, 1363, 1237, 1165, 876, 778, 749,707 cm-1; MS-ESI: m/z = 320 [M+1]+.
1-(4-(Furan-2-yl)-2-methyl-1-phenethyl-1H-pyrrol-3-yl) ethanone (5ee, Table 2,
entry 21): White solid, mp 119–121 °C; 1H NMR (300 MHz, CDCl3): d 7.39 (d,
J = 2.00 Hz, 1H), 7.27–7.17 (m, 3H), 7.04 (d, J = 7.99 Hz, 2H), 6.56 (s, 1H), 6.39
(dd, J = 2.99, 2.00 Hz, 1H), 6.32 (d, J = 2.99 Hz, 1H), 3.97 (t, J = 6.99 Hz, 2H), 2.93
(t, J = 6.99 Hz, 2H), 2.30 (s, 3H), 2.12 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
196.1, 148.9, 141.2, 137.2, 135.0, 128.5, 128.4, 126.7, 120.7, 120.4, 114.4, 110.8,
m
= 3424, 1644, 1508, 1456, 1417, 1239, 1171, 1137, 1016, 852, 814, 760 cmÀ1
;
MS-ESI: m/z = 300 [M+1]+. 1-(1-cyclopropyl-4-(furan-2-yl)-2-methyl-1H-pyrrol-
3-yl) ethanone (5ae, Table 2, entry 5): White solid, mp 103–105 °C; 1H NMR
(300 MHz, CDCl3): d 7.44 (d, J = 1.13 Hz, 1H), 6.69 (s, 1H), 6.42 (dd, J = 2.83,
1.13 Hz, 1H), 6.34 (d, J = 2.83 Hz, 1H), 3.19–3.10 (m, 1H), 2.59 (s, 3H), 2.14 (s,
3H), 1.10–1.01 (m, 2H), 1.00–0.91 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): d
196.2, 149.0, 141.4, 137.7, 121.0, 120.7, 113.7, 110.9, 107.5, 29.6, 28.1, 12.1,
107.5, 47.8, 37.2, 29.6, 11.2 ppm; IR(KBr):
m = 3053, 1654, 1448, 1412, 1018,
996, 812, 793, 764 cmÀ1; MS-ESI: m/z = 294 [M+1]+. 1-(4-(4-Bromophenyl)-2-
methyl-1-phenethyl-1H-pyrrol-3-yl) ethanone (5ef, Table 2, entry 22): Red
viscous liquid; 1H NMR (300 MHz, CDCl3): d 7.46 (d, J = 8.30 Hz, 2H), 7.30–
7.24 (m, 3H), 7.15–7.11 (m, 2H), 7.08 (d, J = 8.30 Hz, 2H), 6.37 (s, 1H), 4.04 (t,
J = 7.55 Hz, 2H), 2.99 (t, J = 7.55 Hz, 2H), 2.35 (s, 3H), 2.00 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d 197.0, 137.3, 135.1, 134.9, 131.7, 131.0, 130.6, 128.5, 127.5,
6.6 ppm; IR(KBr):
m ;
= 3119, 1652, 1574, 1439, 1165, 985, 859, 783, 767 cmÀ1
MS-ESI: m/z = 230 [M+1]+. 1-(4-(4-Bromophenyl)-1-cyclopropyl-2-methyl-1H-
pyrrol-3-yl) ethanone (5af, Table 2, entry 6): Red viscous liquid; 1H NMR
(300 MHz, CDCl3): d 7.47 (d, J = 8.49 Hz, 2H), 7.17 (d, J = 8.49 Hz, 2H), 6.51 (s,
1H), 3.20–3.12 (m, 1H), 2.56 (s, 3H), 2.02 (s, 3H), 1.10–0.90 (m, 4H) ppm; 13C
NMR (75 MHz, CDCl3): d 197.0, 137.5, 135.1, 131.7, 131.0, 130.6, 127.5, 123.5,
126.8, 124.2, 120.4, 119.4, 47.9, 37.2, 30.8, 11.2 ppm; IR(KBr):
m = 3355, 2925,
1646, 1552, 1507, 1417, 1382, 1176, 1010, 831, 754, 701 cmÀ1; MS-ESI: m/
z = 382 [M]+, 384 [M+2]+. 1-(2-Methyl-4-phenyl-1-(prop-2-ynyl)-1H-pyrrol-3-yl)
ethanone (5fa, Table 2, entry 24): White solid, mp 69–71 °C; 1H NMR (300 MHz,
CDCl3): d 7.43–7.30 (m, 5H), 6.68 (s, 1H), 4.65 (d, J = 3.02 Hz, 2H), 2.58 (s, 3H),
2.48 (t, J = 3.02 Hz, 1H), 2.04 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 197.8,
136.4, 134.7, 130.0, 129.2, 128.9, 127.8, 119.1, 119.0, 78.3, 74.2, 36.1, 21.1,
119.5, 30.7, 28.0, 12.0, 6.6 ppm; IR(KBr):
m = 3354, 3014, 1648, 1553, 1511,
1417, 1383, 1222, 1071, 1010, 831, 762 cmÀ1; MS-ESI: m/z = 318 [M]+, 320
[M+2]+. 1-(1-Cyclohexyl-4-(furan-2-yl)-2-methyl-1H-pyrrol-3-yl) ethanone (5be,
Table 2, entry 10): Orange Yellow viscous liquid; 1H NMR (300 MHz, CDCl3): d
7.44 (d, J = 1.97 Hz, 1H), 6.76 (s, 1H), 6.42 (dd, J = 2.96, 1.97 Hz, 1H), 6.32 (d,
J = 2.96 Hz, 1H), 3.91–3.84 (m, 1H), 2.51 (s, 3H), 2.13 (s, 3H), 2.02–1.16 (m,
10H) ppm; 13C NMR (75 MHz, CDCl3): d 196.7, 149.4, 141.4, 134.7, 120.6, 117.1,
11.3 ppm; IR(KBr):
m = 3291, 3116, 1644, 1507, 1413, 1118, 943, 768, 703, 670,
630 cmÀ1 MS-ESI: m/z = 238 [M+1]+. 1-(4-(Furan-2-yl)-2-methyl-1-(prop-2-
;
ynyl)-1H-pyrrol-3-yl) ethanone (5fe, Table 2, entry 28): Orange Yellow viscous
liquid; 1H NMR (300 MHz, CDCl3): d 7.43 (d, J = 2.00 Hz, 1H), 6.81 (s, 1H), 6.42
(dd, J = 2.99, 2.00 Hz, 1H), 6.36 (d, J = 2.99 Hz, 1H), 4.58 (d, J = 2.99 Hz, 2H), 2.51
(s, 3H), 2.46 (t, J = 2.99 Hz, 1H), 2.14 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
196.1, 148.4, 141.3, 139.9, 120.1, 114.4, 110.8, 110.4, 107.5, 76.5, 74.3, 35.9,
114.4, 110.9, 107.4, 55.0, 33.8, 29.7, 25.7, 25.2, 11.3 ppm; IR(KBr):
m = 3137,
1655, 1530, 1187, 1059, 978, 843, 762, 727 cmÀ1; MS-ESI: m/z = 272 [M+1]+. 1-
(4-(4-Bromophenyl)-1-cyclohexyl-2-methyl-1H-pyrrol-3-yl) ethanone (5bf, Table
2, entry 11): Red viscous liquid; 1H NMR (300 MHz, CDCl3):
d
7.44 (d,
29.5, 11.1 ppm; IR(KBr):
732 cm-1; MS-ESI: m/z = 228 [M+1]+. 1-(4-(4-Bromophenyl)-2-methyl-1-(prop-
2-ynyl)-1H-pyrrol-3-yl) ethanone (5ff, Table 2, entry 29): Red viscous liquid; 1
m = 3182, 1652, 1452, 1397, 1132, 1082, 987, 889, 812,
J = 8.49 Hz, 2H), 7.14 (d, J = 8.49 Hz, 2H), 6.53 (s, 1H), 3.92–3.76 (m, 1H), 2.42 (s,
3H), 1.96 (s, 3H), 1.88–1.12 (m, 10H) ppm; 13C NMR (75 MHz, CDCl3): d 196.4,
135.8, 132.9, 130.1, 125.2, 123.3, 122.1, 107.9, 107.4, 59.7, 33.7, 29.1, 25.9,
H
NMR (300 MHz, CDCl3): d 7.48 (d, J = 8.99 Hz, 2H), 7.18 (d, J = 8.99 Hz, 2H), 6.63
(s, 1H), 4.61 (d, J = 2.99 Hz, 2H), 2.52 (s, 3H), 2.45 (t, J = 2.99 Hz, 1H), 2.02 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3): d 196.4, 134.5, 131.2, 130.7, 130.3, 127.3,
25.3, 11.8 ppm; IR(KBr):
m = 3276, 2932, 2856, 1648, 1605, 1556, 1413, 1304,
1196, 1010, 830, 756 cmÀ1; MS-ESI: m/z = 360 [M]+, 362 [M+2]+. 1-(1-Benzyl-2-
methyl-4-p-tolyl-1H-pyrrol-3-yl) ethanone (5cb, Table 2, entry 12): White solid,
mp 70–72 °C; 1H NMR (300 MHz, CDCl3): d 7.27–7.02 (m, 9H), 6.58 (s, 1H), 4.97
(s, 2H), 2.35 (s, 3H), 2.26 (s, 3H), 1.97 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
123.9, 120.1, 119.0, 76.6, 74.2, 35.7, 30.4, 10.8 ppm; IR(KBr):
m = 3292, 2923,
1648, 1552, 1513, 1415, 1383, 1189, 1136, 1010, 831, 763 cmÀ1; MS-ESI: m/
z = 316 [M]+, 318 [M+2]+.