Zirconocene dichloride catalysed one-pot synthesis of pyrroles through nitroalkene-enamine assembly

Article abstract of DOI:10.1039/c4ra09873k

Zirconocene dichloride in an environment-friendly ethanol medium was found to be an efficient catalyst for the synthesis of multi-substituted pyrroles by involving multi-component reactions of amines, β-dicarbonyl compounds and nitroalkenes. The reactions

Full text of DOI:10.1039/c4ra09873k

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Zirconocene dichloride catalysed one-pot
synthesis of pyrroles through nitroalkene-enamine
Cite this: RSC Adv., 2015, 5, 3187
assembly†
*
Sandeep Goyal, Jatinkumar K. Patel, Mukesh Gangar, Kapil Kumar and Vipin A. Nair
Received 5th September 2014
Accepted 12th November 2014
Zirconocene dichloride in an environment-friendly ethanol medium was found to be an efficient catalyst for
the synthesis of multi-substituted pyrroles by involving multi-component reactions of amines, b-dicarbonyl
compounds and nitroalkenes. The reactions undergo completion easily with high yields and no side-
products, allowing the purification of pyrroles in hassle-free and economical manner.
DOI: 10.1039/c4ra09873k
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nitroalkanes using iron(III) salts as catalysts.11a High-speed
vibration milling of ketones with N-iodosuccinimide, amines,
Introduction
b-dicarbonyl compounds, cerium(IV) ammonium nitrate and
silver nitrate affords polysubstituted pyrroles.13d
four-
Pyrroles constitute numerous natural products and pharma-
ceuticals1,2 (Fig. 1). The scaffold has also found use in material
science and supramolecular chemistry.3 Recent years witnessed
a shi from conventional methods to multi-component reac-
tions.4 This has helped to overcome several drawbacks such as
non-availability of suitable starting materials for desired
substitutions, functional group tolerance, multi-step synthesis,
and regioselectivity issues. Based on our interests in bioactive
heterocycles and metal-mediated reactions,5 we sought a highly
efficient, low-cost, non-toxic catalyst for a multi-component
reaction toward the synthesis of pyrroles. Several researchers
have investigated metal-mediated formation of C–C/C–N bonds
in pyrrole synthesis,6 and various metal salts have demon-
strated high efficiencies.7–19
Examination of the previous studies illustrates general
reaction patterns involving either a cycloisomerization or a
cycloaddition in the synthesis of pyrroles. The vast numbers of
methods available provide chemists with an arsenal of strate-
gies to choose, depending on the starting materials available or
the products desired. One of the interesting strategies available
for the synthesis of pyrroles involves the reaction between
enamines and nitroalkenes.11a–c,12,20 Among the several methods
that encompass this strategy, a few deserve mention on the
basis of the reagents/conditions employed. A three-component
reaction has been reported for the synthesis of pyrroles from
amines and nitrostyrenes using (diacetoxyiodo)benzene at
reux temperature in ethanol.20d The synthesis of highly func-
tionalized pyrroles have been achieved by coupling reactions of
1,3-dicarbonyl compounds, amines, aromatic aldehydes and
A
component protocol using ionic liquid media involves
primary amines, aldehydes, nitromethane and b-diketones for
the synthesis of functionalized pyrroles.20e One-pot, four-
component condensation reactions of aromatic aldehydes,
benzyl amines, b-ketoesters and nitroalkanes in the presence of
NiCl2$6H2O yields tetrasubstituted pyrroles.12
A
multi-
component synthesis of substituted pyrroles promoted by
CeCl3$7H2O under microwave irradiation of b-nitrostyrene, b-
diketones and aryl amines is also known to afford good yields of
pyrroles.13c Yb(OTf)3 effectively promotes the coupling reaction
of amines, 1,3-diketones and phenacyl bromide in a one-pot
reaction.19 Although this strategy has been well explored
during the past few years, the reactions in many cases are
undermined by long duration, low-to-moderate yields, poor
atom economy, high cost, environmentally non-benign
solvents, regio-/chemo-selectivity issues, toxicity, functional
group incompatibility, and tedious work-up and isolation
procedures. Contemplating on this, we decided to investigate
the reaction for an efficient, commercially available, high
yielding and inexpensive catalyst in an eco-friendly condition.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education
and Research, Sector 67, Mohali, Punjab 160062, India. E-mail: vn74nr@yahoo.
com; vnair@niper.ac.in; Fax: +91-172-2214692
† Electronic supplementary information (ESI) available: 1H NMR, 13C NMR and
Fig. 1 A few pyrrole-based biologically active molecules.
HRMS and IR spectra of all compounds. See DOI: 10.1039/c4ra09873k
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Table 1 Standardization of reaction conditionsa
Our investigations revealed the potential of zirconocene
dichloride (Cp2ZrCl2) in an ethanol medium as one of the most
effective catalysts for the in situ formation of enamines and their
subsequent reaction with nitroalkenes to afford pyrroles with
multiple substituents.
No.
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
NiCl2$6H2O
FeCl3
CuCl
TiCl4
ZrCl4
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
8
13
24
7
7
4
1.5
15
1.5
1.5
10
7
24
10
13
8
48
43
37
53
61
69
78
50
55
79
Trace
52
37
35
40
48
57
40
Results and discussion
CpZrCl3
Cp2ZrCl2
Cp2TiCl2
Cp2ZrCl2
Cp2ZrCl2
A one-pot, three-component reaction between aniline, 3-oxo-N-
phenylbutanamide and b-nitrostyrene was envisaged to provide
access to a multi-substituted pyrrole13c,20 (Scheme 1). With these
substrates, the reactions would proceed through the two key
steps of enamine formation from the amine and b-ketoamide
and a subsequent Michael addition of the resulting enamine to
the b-nitrostyrene. We anticipated that a suitable catalyst would
promote both of these reactions in succession to afford pyrrole
derivatives without any impediment. Although the commer-
cially available starting materials have been carefully chosen to
address the substitution, the difficulty was to identify a catalyst
that would promote both of these reactions effectively in
sequence. To provide an environmentally benign reaction
condition, EtOH was employed as the solvent, considering the
polar nature of the transition state that would be encountered.
The search for a cost-effective, mild and efficient metal catalyst
was initiated. The screening of the relatively inexpensive tran-
sition metal salts, such as chlorides of nickel, iron, copper,
titanium and zirconium, at a catalytic concentration of 5 mol%
gave modest yields, up to a maximum of 61% with ZrCl4 in 7 h,
providing impetus for further evaluation (Table 1). A variation
of the ligand was then tried by replacing ZrCl4 with CpZrCl3.
Encouraging enough was the result when a 5 mol% concen-
tration of CpZrCl3 under the reux condition afforded the
desired product in 69% yield while the time of the reaction was
reduced to 4 h. This prompted us to carry out the reaction under
similar conditions with the dicyclopentadienyl derivative Cp2-
ZrCl2, and gratifyingly, the yield increased to 78%. More
signicantly, the reaction underwent completion in 1.5 h. On
the contrary, a similar reaction with Cp2TiCl2 gave poor yield,
even aer 15 h.
c
9
d
10
11
12
13
14
15
16
17
18
—
Cp2ZrCl2
Cp2ZrCl2
Cp2ZrCl2
Cp2ZrCl2
Cp2ZrCl2
Cp2ZrCl2
Cp2ZrCl2
THF
Acetone
CH2Cl2
CCl4
DMSO
DMF
4
12
a
Amine (1.3 equiv.), 1,3-dicarbonyl compound (1.0 equiv.), nitroalkene
b
c
(1.0 equiv.), catalyst (0.05 equiv.), reux. Isolated yield. Catalyst
(0.025 equiv.). d Catalyst (0.10 equiv.).
suitable medium for the reaction. The scope of the reaction was
examined by varying the substituents on the reacting partners
(Table 2). Electron-donating and electron-withdrawing groups
on the aryl amines did not signicantly deter the yields.
Aliphatic amines were found to be slightly lower yielding and
less reactive than the aromatic counterparts (Scheme 2).
The b-dicarbonyl compounds dictated the substitution at the
2nd and 3rd positions of the pyrrole, whereas the amines could
decipher the N1 substituent. The reaction tolerated b-ketoesters
and b-diketones very well in place of b-ketoamides. The
substitutions at the b and a-positions of nitroalkenes were
reproduced at the 4th and 5th positions, respectively. The
reactions of penta-substituted pyrroles took a longer time to
complete, suggestive of the steric encumbrance faced during
the cyclocondensation. No signicant side-product was
observed during the course of the reactions. This allowed for the
easy purication of the desired products by elution through a
column of silica gel using hexane–ethyl acetate mixture as the
eluent to remove the trace amounts of impurities/starting
materials observed in some instances. A plausible mecha-
nism11e for the reactions is outlined in Fig. 2. Cp2ZrCl2 coordi-
nates to the electrophilic carbonyl oxygen of the dicarbonyl
compound B ensuring a nucleophilic attack by the amine A to
afford the imine C, which tautomerizes to the enamine D. The
enamine renders a nucleophilic attack on the electrophilic ni-
troalkene E, coordinated to zirconocene dichloride. The
resulting intermediate F tautomerizes to the corresponding
enamine and facilitates an intramolecular attack through the
nitrogen atom on the iminium ion stabilized by zirconocene
chloride. This affords the dihydro-1H-pyrrole intermediate G,
which undergoes an elimination reaction to gain aromaticity
with the consequent formation of substituted pyrrole H.
Cp2ZrCl2 displays the role of a mild and efficient catalyst
A study to optimize the concentration of Cp2ZrCl2 indicated
5 mol% to be the best, whereas the yields did not improve at
increased concentrations. At concentrations below optimum,
the reaction did not undergo completion, yet a trace amount of
the product was observed even in the absence of the catalyst. An
independent study carried out to examine the effect of solvents
revealed that the polar protic solvent EtOH itself was the most
Scheme 1 Cp2ZrCl2 catalysed one-pot synthesis of pyrrole.
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Table 2 Synthesis of pyrroles using Cp2ZrCl2 catalysta
Entry
R1
R2
R3
R4
R5
Product
Yieldb (%)
Timec (h)
1
2
3
4
5
6
7
8
–C6H5
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH(CH3)2
–CH(CH3)2
–CH(CH3)2
–CH3
–CH3
–CH3
–C6H5
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–OC2H5
–OC2H5
–OC2H5
–OC2H5
–OC2H5
–OC2H5
–CH3
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
–H
4a(i)
78
73
74
76
78
67
69
77
74
75
67
69
70
76
74
75
70
74
76
72
77
74
72
71
67
68
70
75
73
74
73
72
69
67
74
71
70
69
69
68
67
68
67
1.5
3
1.5
1.5
1.5
6
–C6H4–OMe-p
–C6H4–Me-p
–C6H4–Cl-p
–C6H4–Br-p
–C3H7
–CH2C6H5
–C6H5
–C6H4–Me-p
–C6H4–Br-p
–C3H7
–CH2C6H5
–CH2C6H4–OMe-p
–C6H5
–C6H4–Me-p
–C6H4–Br-p
–C3H7
–CH2C6H5
–C6H5
–C6H5
–C6H4–Me-p
–C6H4–Me-p
–C6H4–Br-p
–C6H4–Br-p
–C6H4–OMe-p–
–C6H4–Cl-p
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
4a(ii)
4a(iii)
4a(iv)
4a(v)
4a(vi)
4a(vii)
4b(i)
4b(ii)
4b(iii)
4b(iv)
4b(v)
4b(vi)
4c(i)
4c(ii)
4c(iii)
4c(iv)
4c(v)
6
1.5
1.5
1.5
6
6
6
1.5
1.5
1.5
6
6
3
1.5
3
1.5
3
1.5
3
3
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
34
35
36
37
38
39
40
41
42
43
–CH3
–CH3
–CH3
–CH3
–C6H5
–C6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–OC2H5
–OC2H5
–OC2H5
–OC2H5
–CH3
–C6H4–OMe-p
–C6H4–Cl-p
–C6H4–OMe-p
–C6H4–Cl-p
–C6H4–OMe-p
–C6H4–Cl-p
–C6H4–OMe-p
–C6H4–OMe-p
–C6H3–OH-p,–OMe-m
–C6H5
–C6H4–Me-p
–C6H4–F-p
–C6H4–OMe-p
–C6H4–Cl-p
–C6H3–OH-p,–OMe-m
–C6H5
–C6H4–OMe-p
–C6H4–Cl-p
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
4d(i)
4d(ii)
4d(iii)
4d(iv)
4d(v)
4d(vi)
4d(vii)
4d(viii)
4d(ix)
4d(x)
4d(xi)
4d(xii)
4e(i)
4e(ii)
4e(iii)
4e(iv)
4e(v)
4e(vi)
4f(i)
3
1.5
1.5
1.5
3
1.5
3
6
3
1.5
6
6
10
10
10
10
10
–C6H5
–C6H5
–C6H4–Me-p
–C6H5
–C6H5
–C6H5
–C6H4–OMe-p
–C6H5
–CH2C6H5
–C6H5
–C6H4–OMe-p
–C6H4–Me-p
–H
–H
–H
–H
–CH3
–CH3
–C6H5
–C6H5
–C6H4–F-p
–C6H4–F-p
–C6H4–F-p
–CH3
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
–NHC6H5
4f(ii)
4f(iii)
4f(iv)
4f(v)
4f(vi)
4f(vii)
a
Amine (1.3 equiv.), 1,3-dicarbonyl compound (1.0 equiv.), nitroalkene (1.0 equiv.). b Isolated yield. c Reaction time.
Scheme 2 Synthesis of multi-substituted pyrroles.
during the course of the reactions, which involve the forma-
tion of enamine, the reaction of enamine with nitroalkene
and, nally, cyclocondensation, favoring the reaction kinetics
to afford the product efficiently under mild conditions.
Fig. 2 Plausible reaction mechanism.
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2-Methyl-N,4-diphenyl-1-(p-tolyl)-1H-pyrrole-3-carboxamide,
4a(iii)
Conclusions
In summary, the inexpensive Cp2ZrCl2 was found to be an effi-
cient catalyst for the synthesis of multi-substituted pyrroles by
involving multi-component reactions of amines, b-dicarbonyl
compounds and nitroalkenes. The reactions were carried out
under environmentally benign conditions in an ethanol
medium. Various functional groups were tolerated, and choice
of the substituents allowed the formation of desired multi-
substituted pyrroles. The operationally simple procedure
affords the products easily with good yields. No signicant side
products were observed from the reactions, simplifying the
purication. Regioselectivity was in coherence with the sug-
gested reaction mechanism. We believe that this simple, cost-
effective, highly efficient, catalytic, one-pot procedure could be
a valuable addition and/or a viable alternative to the existing
methods for the synthesis of multi-substituted pyrroles.
Brownish solid; m.p. ¼ 98–100 C; IR (cmꢁ1): ꢀy ¼ 3335, 1648,
1516, 1432, 1311; 1H NMR (400 MHz, CDCl3) d 7.52 (d, J ¼
7.2 Hz, 2H), 7.45 (t, J ¼ 7.6 Hz, 2H), 7.39 (d, J ¼ 7.2 Hz, 1H), 7.20–
7.30 (m, 8H), 7.15 (brs, 1H), 7.02 (t, J ¼ 6.4 Hz, 1H), 6.75 (s, 1H),
2.53 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.99,
138.46, 138.08, 136.35, 135.76, 134.56, 129.91, 129.61, 128.88,
128.79, 127.43, 126.08, 123.42, 123.37, 120.26, 119.30, 114.95,
21.13, 12.44; ESI-HRMS (m/z): [M + Na]+ calcd for C25H22N2NaO,
389.1630, found, 389.1637.
ꢀ
1-(4-Chlorophenyl)-2-methyl-N,4-diphenyl-1H-pyrrole-3-
carboxamide, 4a(iv)
White solid; m.p. ¼ 191–193 ꢀC; IR (cmꢁ1): ꢀy ¼ 3330, 1646, 1520,
1438, 1311; 1H NMR (400 MHz, CDCl3) d 7.39–7.52 (m, 7H), 7.32
(d, J ¼ 8.6 Hz, 2H), 7.19–7.26 (m, 4H), 7.13 (brs, 1H), 7.03 (t,
J ¼ 6.9 Hz, 1H), 6.74 (s, 1H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 163.77, 138.33, 137.38, 135.54, 134.22, 134.01, 129.61,
129.58, 128.96, 128.84, 127.65, 127.51, 123.88, 123.58, 120.01,
Experimental section
Representative procedure for the synthesis of pyrrole 4a(i)
119.34, 115.55, 12.47; ESI-HRMS (m/z): [M + Na]+ calcd for C24
H19ClN2NaO, 409.1084, found 409.1084.
-
A mixture of aniline (68 mg, 0.73 mmol, 1.3 equiv.), 3-oxo-N-
phenylbutanamide (100 mg, 0.56 mmol, 1.0 equiv.), b-nitro-
styrene (84 mg, 0.56 mmol, 1.0 equiv.) and Cp2ZrCl2 (8.0 mg,
0.028 mmol, 0.05 equiv.) in ethanol (5 mL) was reuxed at 80 ꢀC.
Aer completion of the reaction (1.5 h), as monitored by TLC,
the solvent was evaporated. The residue was dissolved in ethyl
acetate and washed with water. The organic layer was dried,
concentrated and puried by eluting through a column of silica
gel using hexane–ethyl acetate mixture (95 : 5) as the eluent to
give 155 mg (78%) yield of 4a(i).
1-(4-Bromophenyl)-2-methyl-N,4-diphenyl-1H-pyrrole-3-
carboxamide, 4a(v)
White solid; m.p. ¼ 140–142 ꢀC; IR (cmꢁ1): ꢀy ¼ 3315, 1641, 1594,
1436, 1315; 1H NMR (400 MHz, CDCl3) d 7.64 (d, J ¼ 8.5 Hz, 2H),
7.39–7.52 (m, 5H), 7.20–7.25 (m, 6H), 7.13 (brs, 1H), 7.03 (t,
J ¼ 6.9 Hz, 1H), 6.74 (s, 1H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 163.75, 138.31, 137.89, 135.48, 134.20, 132.60, 129.58,
128.96, 128.83, 127.81, 127.65, 123.92, 123.58, 121.94, 119.94,
119.34, 115.60, 12.47; ESI-HRMS (m/z): [M + Na]+ calcd for
C
24H19BrN2NaO, 453.0578, found 453.0576.
2-Methyl-N-1,4-triphenyl-1H-pyrrole-3-carboxamide, 4a(i)
2-Methyl-N,4-diphenyl-1-propyl-1H-pyrrole-3-carboxamide,
4a(vi)
White solid m.p. ¼ 132–134 ꢀC; IR (cmꢁ1): ꢀy ¼ 3348, 1651, 1594,
1
1433, 1316; H NMR (400 MHz, CDCl3) d 7.38–7.55 (m, 10H),
Sticky solid; IR (cmꢁ1): ꢀy ¼ 3407, 1660, 1528, 1436, 1313; 1H
NMR (400 MHz, CDCl3) d 7.35–7.48 (m, 5H), 7.18–7.25 (m, 4H),
7.09 (brs, 1H), 6.99–7.03 (m, 1H), 6.59 (s, 1H), 3.85 (t, J ¼ 7.7 Hz,
7.24 (d, J ¼ 6.2 Hz, 4H), 7.17 (brs, 1H), 7.02–7.06 (m, 1H), 6.79 (s,
1H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.95, 138.94,
138.46, 135.67, 134.52, 129.61, 129.36, 128.90, 128.86, 128.08,
127.49, 126.30, 123.58, 123.46, 120.20, 119.34, 115.22, 12.47;
ESI-HRMS (m/z): [M + Na]+ calcd for C24H20N2NaO, 375.1473,
found 375.1479.
2H), 2.63 (s, 3H), 1.79–1.87 (m, 2H), 1.00 (t, J ¼ 7.4 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) d 164.16, 138.58, 134.98, 130.50, 129.61,
128.79, 128.75, 127.20, 123.27, 122.60, 119.25, 119.12, 113.98,
48.34, 24.17, 11.29, 11.12; ESI-HRMS (m/z): [M + Na]+ calcd for
C
21H22N2NaO, 341.1630, found 341.1650.
1-(4-Methoxyphenyl)-2-methyl-N,4-diphenyl-1H-pyrrole-3-
1-Benzyl-2-methyl-N,4-diphenyl-1H-pyrrole-3-carboxamide,
carboxamide, 4a(ii)
4a(vii)
Reddish brown solid; m.p. ¼ 160–162 C; IR (cmꢁ1): ꢀy ¼ 3324, Sticky solid; IR (cmꢁ1): ꢀy ¼ 3390, 1660, 1529, 1432, 1220; 1H
1648, 1595, 1437, 1316; 1H NMR (400 MHz, CDCl3) d 7.39– NMR (400 MHz, CDCl3) d 7.32–7.50 (m, 8H), 7.19–7.26 (m, 4H),
7.53 (m, 6H), 7.20–7.30 (m, 5H), 7.15 (brs, 1H), 7.00–7.04 (m, 7.13 (d, J ¼ 6.8 Hz, 2H), 7.00–7.04 (m, 1H), 6.65 (s, 1H), 5.12 (s,
3H), 6.72 (s, 1H), 3.89 (s, 3H), 2.51 (s, 3H); 13C NMR (100 MHz, 2H), 2.59 (s, 3H); 13C NMR (100 MHz, CDCl3) d 164.03, 138.51,
CDCl3) d 164.02, 159.25, 138.47, 136.00, 134.57, 131.77, 129.61, 136.75, 135.52, 134.76, 129.64, 128.96, 128.82, 128.78, 127.84,
128.89, 128.81, 127.52, 127.44, 123.43, 123.24, 120.45, 119.29, 127.32, 126.67, 123.37, 123.04, 119.74, 119.29, 114.56, 50.44,
114.74, 114.44, 55.60, 12.39; ESI-HRMS (m/z): [M + Na]+ calcd for 11.23; ESI-HRMS (m/z): [M + Na]+ calcd for C25H22N2NaO,
ꢀ
C
25H22N2NaO2, 405.1579, found 405.1578.
389.1630, found 389.1641.
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Ethyl 2-methyl-1,4-diphenyl-1H-pyrrole-3-carboxylate, 4b(i)
Reddish liquid; IR (cmꢁ1): ꢀy ¼ 2980, 1694, 1597, 1408, 1222; 1H
Ethyl 1-(4-methoxybenzyl)-2-methyl-4-phenyl-1H-pyrrole-3-
carboxylate, 4b(vi)
NMR (400 MHz, CDCl3) d 7.44–7.53 (m, 5H), 7.34–7.38 (m, 4H), Yellowish liquid; IR (cmꢁ1): ꢀy ¼ 3445, 1639, 1514, 1250, 1179; 1H
7.26–7.30 (m, 1H), 6.74 (s, 1H), 4.20 (q, J ¼ 7.2 Hz, 2H), 2.48 (s, NMR (400 MHz, CDCl3) d 7.25–7.40 (m, 5H), 7.04 (d, J ¼ 8.7 Hz,
3H), 1.16 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 2H), 6.87–6.89 (m, 2H), 6.57 (s, 1H), 5.01 (s, 2H), 4.16 (q, J ¼
165.85, 139.00, 136.58, 135.60, 129.33, 129.27, 128.07, 127.56, 7.2 Hz, 2H), 3.81 (s, 3H), 2.50 (s, 3H), 1.13 (t, J ¼ 7.1 Hz, 3H); 13
C
126.63, 126.34, 126.27, 120.84, 111.76, 59.48, 14.08, 12.66; ESI- NMR (100 MHz, CDCl3) d 165.91, 159.20, 136.32, 135.89, 129.26,
HRMS (m/z): [M + Na]+ calcd for C20H19NNaO2, 328.1313, 128.65, 128.05, 127.48, 126.07, 120.23, 114.28, 110.95, 59.36,
found 328.1324.
55.32, 50.04, 14.05, 11.51; ESI-HRMS (m/z): [M + Na]+ calcd for
C
22H23NNaO3, 372.1576, found 372.1576.
Ethyl 2-methyl-4-phenyl-1-(p-tolyl)-1H-pyrrole-3-carboxylate,
1-(2-Methyl-1,4-diphenyl-1H-pyrrol-3-yl)ethanone, 4c(i)
4b(ii)
Reddish solid; m.p. ¼ 107–109 C; IR (cmꢁ1): ꢀy ¼ 2923, 1638,
ꢀ
Off-white solid; m.p. ¼ 62–65 ꢀC; IR (cmꢁ1): ꢀy ¼ 2926, 1695,
1518, 1407, 1221; 1H NMR (400 MHz, CDCl3) d 7.41–7.43
(m, 2H), 7.19–7.35 (m, 7H), 6.68 (s, 1H), 4.17 (q, J ¼ 7.1 Hz, 2H),
2.44 (s, 3H), 2.42 (s, 3H), 1.13 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 165.89, 138.07, 136.69, 136.46, 135.68, 129.89,
129.27, 127.55, 126.44, 126.22, 126.14, 120.92, 111.50, 59.45,
21.11, 14.09, 12.63; ESI-HRMS (m/z): [M + Na]+ calcd for
1495, 1406, 1231; 1H NMR (400 MHz, CDCl3) d 7.43–7.54
(m, 3H), 7.41 (d, J ¼ 4.4 Hz, 4H), 7.33–7.40 (m, 3H), 6.70 (s, 1H),
2.44 (s, 3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) d 197.69,
138.78, 136.03, 135.31, 129.36, 129.34, 128.30, 128.12, 126.83,
126.32, 126.26, 122.59, 120.62, 31.12, 12.91; ESI-HRMS (m/z):
[M + Na]+ calcd for C19H17NNaO, 298.1208, found 298.1228.
C
21H21NNaO2, 342.1470, found 342.1498.
1-(2-Methyl-4-phenyl-1-(p-tolyl)-1H-pyrrol-3-yl)ethanone, 4c(ii)
White solid; m.p. ¼ 87–89 C; IR (cmꢁ1): ꢀy ¼ 2923, 1654, 1517,
ꢀ
Ethyl 1-(4-bromophenyl)-2-methyl-4-phenyl-1H-pyrrole-3-
carboxylate, 4b(iii)
1405, 1221; 1H NMR (400 MHz, CDCl3) d 7.37 (d, J ¼ 4.3 Hz, 4H),
7.27–7.32 (m, 3H), 7.19–7.22 (m, 2H), 6.64 (s, 1H), 2.42 (s, 3H),
2.40 (s, 3H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3) d 197.65,
138.13, 136.23, 136.13, 135.44, 129.92, 129.35, 128.27, 126.78,
126.17, 126.05, 122.41, 120.70, 31.10, 21.11, 12.88; ESI-HRMS
(m/z): [M + Na]+ calcd for C20H19NNaO, 312.1364, found
312.1382.
Reddish solid; m.p. ¼ 102–104 C; IR (cmꢁ1): ꢀy ¼ 2974, 1693,
ꢀ
1
1525, 1396, 1275; H NMR (400 MHz, CDCl3) d 7.63 (d, J ¼ 8.5
Hz, 2H), 7.43 (d, J ¼ 7.3 Hz, 2H), 7.36 (t, J ¼ 7.6 Hz, 2H), 7.29 (t,
J ¼ 7.0 Hz, 1H), 7.22 (d, J ¼ 8.5 Hz, 2H), 6.70 (s, 1H), 4.21 (q,
J ¼ 7.1 Hz, 2H), 2.48 (s, 3H), 1.16 (t, J ¼ 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 165.71, 137.96, 136.40, 135.33, 132.58,
129.24, 127.88, 127.63, 126.98, 126.44, 121.95, 120.58, 112.18,
59.61, 14.09, 12.68; ESI-HRMS (m/z): [M + Na]+ calcd for C20-
H18BrNNaO2, 406.0419, found 406.0419.
1-(1-(4-Bromophenyl)-2-methyl-4-phenyl-1H-pyrrol-3-yl)
ethanone, 4c(iii)
White solid; m.p. ¼ 122–124 ꢀC; IR (cmꢁ1): ꢀy ¼ 2924, 1654, 1494,
1409, 1221; 1H NMR (400 MHz, CDCl3) d 7.64 (d, J ¼ 8.6 Hz, 2H),
7.39–7.41 (m, 5H), 7.24 (d, J ¼ 8.7 Hz, 2H), 6.66 (s, 1H), 2.42 (s,
3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) d 197.64, 137.78,
135.76, 135.09, 132.60, 129.30, 128.35, 127.79, 126.98, 126.66,
122.93, 122.00, 120.34, 31.12, 12.85; ESI-HRMS (m/z): [M + Na]+
calcd for C19H16BrNNaO, 376.0313, found 376.0321.
Ethyl 2-methyl-4-phenyl-1-propyl-1H-pyrrole-3-carboxylate,
4b(iv)
Yellowish liquid; IR (cmꢁ1): ꢀy ¼ 2968, 1693, 1525, 1418, 1280; 1H
NMR (400 MHz, CDCl3) d 7.23–7.39 (m, 5H), 6.54 (s, 1H), 4.15 (q,
J ¼ 7.1 Hz, 2H), 3.81 (t, J ¼ 7.4 Hz, 2H), 2.54 (s, 3H), 1.73–1.83
(m, 2H), 1.13 (t, J ¼ 7.1 Hz, 3H), 0.97 (t, J ¼ 7.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 165.97, 136.06, 135.91, 129.25, 127.46,
125.99, 125.77, 119.72, 110.37, 59.27, 48.40, 24.12, 14.05, 11.35,
11.25; ESI-HRMS (m/z): [M + Na]+ calcd for C17H21NNaO2,
294.1470, found 294.1492.
1-(2-Methyl-4-phenyl-1-propyl-1H-pyrrol-3-yl)ethanone, 4c(iv)
Color-less liquid; IR (cmꢁ1): ꢀy ¼ 2926, 1649, 1509, 1414, 1276; 1H
NMR (400 MHz, CDCl3) d 7.31–7.38 (m, 5H), 6.52 (s, 1H), 3.82 (t,
J ¼ 7.4 Hz, 2H), 2.51 (s, 3H), 2.04 (s, 3H), 1.77–1.83 (m, 2H), 0.99
(t, J ¼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 197.57, 136.53,
134.76, 129.37, 128.19, 126.58, 125.60, 121.60, 119.53, 48.19,
31.01, 24.05, 11.50, 11.28; ESI-HRMS (m/z): [M + Na]+ calcd for
Ethyl 1-benzyl-2-methyl-4-phenyl-1H-pyrrole-3-carboxylate,
4b(v)
Sticky solid; IR (cmꢁ1): ꢀy ¼ 2928, 1693, 1526, 1417, 1282; 1H
NMR (400 MHz, CDCl3) d 7.12–7.43 (m, 8H), 7.11 (d, J ¼ 6.8 Hz,
2H), 6.62 (s, 1H), 5.10 (s, 2H), 4.19 (q, J ¼ 7.1 Hz, 2H), 2.51 (s,
3H), 1.16 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
C
16H19NNaO, 264.1364, found 264.1378.
1-(1-Benzyl-2-methyl-4-phenyl-1H-pyrrol-3-yl)ethanone, 4c(v)
1
165.90, 136.77, 136.43, 135.88, 129.30, 128.94, 127.80, 127.51, Color-less oil; IR (cmꢁ1): ꢀy ¼ 2925, 1651, 1510, 1413, 1354; H
126.58, 126.23, 126.13, 120.42, 111.08, 59.39, 50.54, 14.07, NMR (400 MHz, CDCl3) d 7.32–7.39 (m, 8H), 7.12 (d, J ¼ 7.1 Hz,
11.49; ESI-HRMS (m/z): [M + Na]+ calcd for C21H21NNaO2, 2H), 6.57 (s, 1H), 5.09 (s, 2H), 2.47 (s, 3H), 2.07 (s, 3H); 13C NMR
342.1470, found 342.1470.
(100 MHz, CDCl3) d 197.63, 136.58, 136.32, 135.16, 129.37,
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128.95, 128.22, 127.87, 126.71, 126.68, 125.93, 122.09, 120.12, (100 MHz, CDCl3) d 163.82, 159.26, 138.41, 137.97, 135.67,
50.32, 31.08, 11.58; ESI-HRMS (m/z): [M + Na]+ calcd for 135.41, 132.57, 130.80, 128.83, 127.82, 126.36, 123.52, 121.87,
C
20H19NNaO, 312.1364, found 312.1372.
119.83, 119.39, 115.54, 114.40, 55.43, 12.50; ESI-HRMS (m/z):
[M + Na]+ calcd for C25H21BrN2NaO2, 483.0684, found 483.0684.
4-(4-Methoxyphenyl)-2-methyl-N,1-diphenyl-1H-pyrrole-3-
carboxamide, 4d(i)
1-(4-Bromophenyl)-4-(4-chlorophenyl)-2-methyl-N-phenyl-1H-
pyrrole-3-carboxamide, 4d(vi)
Brown solid; m.p. ¼ 107–109 ꢀC; IR (cmꢁ1): ꢀy ¼ 3390, 2918,
1596, 1497, 1247; 1H NMR (400 MHz, CDCl3) d 7.51 (t, J ¼ 7.8 Hz, White solid; m.p. ¼ 205–207 ꢀC; IR (cmꢁ1): ꢀy ¼ 3291, 2918, 1638,
2H), 7.44 (d, J ¼ 8.4 Hz, 3H), 7.36 (d, J ¼ 7.2 Hz, 2H), 7.25–7.27 1495, 1314; 1H NMR (400 MHz, CDCl3) d 7.62–7.65 (m, 2H),
(m, 4H), 6.99–7.05 (m, 3H), 6.72 (s, 1H), 3.87 (s, 3H), 2.55 (s, 3H); 7.38–7.44 (m, 4H), 7.22–7.27 (m, 6H), 7.06 (q, J ¼ 4.7 Hz, 9.1 Hz,
13C NMR (100 MHz, CDCl3) d 164.05, 159.15, 138.95, 138.49, 1H), 7.03 (brs, 1H), 6.72 (s, 1H), 2.49 (s, 3H); 13C NMR (100 MHz,
135.57, 130.81, 129.34, 128.81, 128.01, 126.63, 126.28, 123.44, CDCl3) d 163.66, 138.13, 137.77, 133.43, 132.66, 132.62, 130.41,
123.12, 120.08, 119.38, 115.08, 114.35, 55.41, 12.54; ESI-HRMS 129.07, 128.96, 127.77, 125.98, 123.87, 122.72, 122.11, 120.06,
(m/z): [M + Na]+ calcd for C25H22N2NaO2, 405.1579, found 119.46, 115.78, 12.31; ESI-HRMS (m/z): [M + Na]+ calcd for
405.1580.
C24H18BrClN2NaO, 487.0189, found 487.0184.
4-(4-Chlorophenyl)-2-methyl-N,1-diphenyl-1H-pyrrole-3-
1,4-Bis(4-methoxyphenyl)-2-methyl-N-phenyl-1H-pyrrole-3-
carboxamide, 4d(ii)
carboxamide 4d(vii)
Reddish sticky liquid; IR (cmꢁ1): ꢀy ¼ 3312, 1642, 1594, 1494, Brown solid; m.p. ¼ 132–135 ꢀC; IR (cmꢁ1): ꢀy ¼ 3319, 2836,
1
1439; 1H NMR (400 MHz, CDCl3) d 7.52 (t, J ¼ 7.7 Hz, 2H), 7.44– 1642, 1593, 1438, 1315; H NMR (400 MHz, CDCl3) d 7.43–7.47
7.47 (m, 3H), 7.40 (d, J ¼ 8.5 Hz, 2H), 7.36 (d, J ¼ 7.6 Hz, 2H), (m, 2H), 7.23–7.30 (m, 7H), 6.99–7.06 (m, 5H), 6.68 (s, 1H), 3.89
7.25–7.29 (m, 3H), 7.07–7.09 (m, 2H), 6.78 (s, 1H), 2.51 (s, 3H); (d, J ¼ 4.5 Hz, 6H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) d
13C NMR (100 MHz, CDCl3) d163.94, 138.75, 138.21, 135.48, 164.10, 159.20, 159.09, 138.53, 135.91, 131.83, 130.82, 128.81,
133.21, 132.87, 130.40, 129.43, 129.02, 128.94, 128.22, 126.23, 127.52, 126.71, 123.39, 122.79, 120.32, 119.34, 114.62, 114.42,
123.81, 122.34, 120.33, 119.47, 115.35, 12.34; ESI-HRMS (m/z): 114.33, 55.59, 55.41, 12.43; ESI-HRMS (m/z): [M + H]+ calcd. for
[M + Na]+ calcd for C24H19ClN2NaO, 409.1084, found 409.1083.
C26H25N2O3, 413.1865, found: 413.1855.
4-(4-Methoxyphenyl)-2-methyl-N-phenyl-1-(p-tolyl)-1H-pyrrole-
3-carboxamide, 4d(iii)
1-(4-Chlorophenyl)-4-(4-methoxyphenyl)-2-methyl-N-phenyl-
1H-pyrrole-3-carboxamide, 4d(viii)
Deep yellow solid; m.p. ¼ 133–135 ꢀC; IR (cmꢁ1): ꢀy ¼ 3390, 2918, White solid m.p. ¼ 101–103 ꢀC; IR (cmꢁ1): ꢀy ¼ 3306, 2837, 1639,
1
1662; 1516, 1438, 1313; H NMR (400 MHz, CDCl3) d 7.40–7.44 1594, 1435, 1316; 1H NMR (CDCl3, 400 MHz) d 7.42–7.50
(m, 2H), 7.21–7.29 (m, 9H), 6.96–7.03 (m, 3H), 6.67 (s, 1H), 3.85 (m, 4H), 7.24–7.32 (m, 7H), 6.99–7.04 (m, 3H), 6.68 (s, 1H), 3.87
(s, 3H), 2.51 (s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) d (s, 3H), 2.54 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.82, 159.25,
164.09, 159.13, 138.55, 138.02, 136.43, 135.68, 130.83, 129.90, 138.40, 137.45, 135.46, 133.94, 130.79, 129.56, 128.81, 127.50,
128.81, 126.74, 126.09, 123.95, 123.39, 120.16, 119.37, 114.87, 126.37, 123.50, 123.45, 119.88, 119.38, 115.47, 114.39, 55.41,
114.35, 55.42, 21.12, 12.50; ESI-HRMS (m/z): [M + Na]+ calcd for 12.47; ESI-HRMS (m/z): [M + Na]+ calcd for C25H21ClN2NaO2,
C
26H24N2NaO2, 419.1735, found 419.1737.
439.1189, found 439.1188.
4-(4-Chlorophenyl)-2-methyl-N-phenyl-1-(p-tolyl)-1H-pyrrole-3-
4-(4-Hydroxy-3-methoxyphenyl)-2-methyl-N,1-diphenyl-1H-
carboxamide, 4d(iv)
pyrrole-3-carboxamide, 4d(ix)
White solid; m.p. ¼ 182–184 ꢀC; IR (cmꢁ1): ꢀy ¼ 3302, 2918, 1638, Reddish brown solid, m.p. ¼ 160–162 C; IR (cmꢁ1): ꢀy ¼ 3392,
ꢀ
1
1517, 1432; H NMR (400 MHz, CDCl3) d 7.43 (dd, J ¼ 8.4 Hz, 2959, 1647, 1532, 1439, 1316; 1H NMR (400 MHz, CDCl3) d 7.35–
11.9 Hz, 4H), 7.24–7.33 (m, 8H), 7.08 (brs, 2H), 6.76 (s, 1H), 2.51 7.54 (m, 7H), 7.26–7.28 (m, 3H), 6.99–7.06 (m, 4H), 6.75 (s, 1H),
(s, 3H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.92, 138.29, 5.80 (brs, 1H), 3.80 (s, 3H), 2.55 (s, 3H); 13C NMR (100 MHz,
138.24, 136.25, 135.61, 133.19, 133.00, 130.43, 129.96, 128.99, CDCl3) d 164.09, 146.72, 145.29, 138.90, 138.45, 135.62, 129.36,
128.92, 126.04, 123.73, 122.17, 120.40, 119.44, 115.15, 21.11, 129.03, 128.88, 128.07, 126.28, 123.52, 123.48, 122.40, 120.10,
12.27; ESI-HRMS (m/z): [M + Na]+ calcd for C25H21ClN2NaO, 119.29, 115.02, 114.80, 112.32, 55.94, 12.53; ESI-HRMS (m/z):
423.1240, found 423.1255.
[M + Na]+ calcd for C25H22N2NaO3, 421.1528, found 421.1529.
1-(4-Bromophenyl)-4-(4-methoxyphenyl)-2-methyl-N-phenyl-
1H-pyrrole-3-carboxamide, 4d(v)
White sticky solid; IR (cmꢁ1): ꢀy ¼ 3397, 2836, 1661, 1595, 1492, 1594, 1432, 1315; 1H NMR (400 MHz, CDCl3) d 7.47–7.55 (m,
1314; 1H NMR (400 MHz, CDCl3) d 7.65 (d, J ¼ 8.6 Hz, 2H), 7.44 5H), 7.37–7.41 (m, 4H), 7.26–7.33 (m, 5H), 7.10 (brs, 1H), 7.04–
(d, J ¼ 8.7 Hz, 2H), 7.25–7.28 (m, 7H), 7.03–7.06 (m, 1H), 7.01 (d, 7.08 (m, 1H), 6.71 (s, 1H), 3.19–3.26 (m, 1H), 1.39 (d, J ¼ 7.1 Hz,
J ¼ 8.7 Hz, 2H), 6.70 (s, 1H), 3.89 (s, 3H), 2.56 (s, 3H); 13C NMR 6H); 13C NMR (100 MHz, CDCl3) d 164.79, 143.12, 139.74,
2-Isopropyl-N,1,4-triphenyl-1H-pyrrole-3-carboxamide, 4d(x)
White solid; m.p. ¼ 177–180 ꢀC; IR (cmꢁ1): ꢀy ¼ 3404, 2964, 1663,
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138.38, 134.41, 129.19, 128.82, 128.74, 128.47, 127.32, 126.88, 6.70 (s, 1H), 5.67 (brs, 1H), 4.22 (q, J ¼ 7.1 Hz, 2H), 3.91 (s, 3H),
123.74, 123.57, 119.99, 119.69, 115.31, 26.60, 21.89; ESI-HRMS 2.46 (s, 3H), 1.19 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
(m/z): [M + Na]+ calcd for C26H24N2NaO, 403.1786, found, 165.91, 145.70, 144.37, 138.98, 136.44, 129.34, 128.07, 127.71,
403.1787.
126.46, 126.33, 122.17, 120.65, 113.67, 112.25, 111.70, 59.49,
55.88, 14.25, 12.73; ESI-HRMS (m/z): [M + Na]+ calcd for
C
21H21NNaO4, 374.1368, Found 374.1390.
2-Isopropyl-N,1-diphenyl-4-p-tolyl-1H-pyrrole-3-carboxamide,
4d(xi)
Yellow solid; m.p. ¼ 162–165 ꢀC; IR (cmꢁ1): ꢀy ¼ 3398, 2974,
Ethyl 2,4-diphenyl-1-p-tolyl-1H-pyrrole-3-carboxylate, 4e(iv)
1655, 1592, 1432, 1307; H NMR (400 MHz, CDCl3) d 7.43–7.52 Sticky solid; IR (cmꢁ1): ꢀy ¼ 2957, 1708, 1517, 1459, 1378; 1H
(m, 3H), 7.36–7.38 (m, 4H), 7.22–7.26 (m, 4H), 7.17 (d, J ¼ 7.8 NMR (400 MHz, CDCl3) d 7.53–7.56 (m, 2H), 7.39–7.43 (m, 2H),
Hz, 2H), 7.12 (brs, 1H), 7.02–7.06 (m, 1H), 6.65 (s, 1H), 3.17–3.24 7.29–7.34 (m, 6H), 7.09 (d, J ¼ 8.1 Hz, 2H), 7.00–7.03 (m, 2H),
(m, 1H), 2.36 (s, 3H), 1.36 (d, J ¼ 7.1 Hz, 6H); 13C NMR (100 6.96 (s, 1H), 4.07 (q, J ¼ 7.1 Hz, 2H), 2.34 (s, 3H), 0.97 (t, J ¼
MHz, CDCl3) d 164.85, 143.06, 139.81, 138.45, 136.58, 131.39, 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 165.44, 137.79, 137.15,
129.44, 129.16, 128.80, 128.64, 128.41, 127.33, 123.68, 123.50, 136.77, 135.05, 131.61, 131.07, 129.53, 128.97, 127.86, 127.76,
119.89, 119.74, 115.22, 26.60, 21.87, 21.16; ESI-HRMS (m/z): 127.55, 126.64, 126.47, 125.79, 122.03, 113.57, 59.79, 21.01,
1
[M + H]+ calcd for C27H27N2O, 395.2123, found, 395.2123.
13.67; ESI-HRMS (m/z): [M + H]+ calcd for C26H24NO2, 382.1807,
found, 382.1805.
4-(4-Fluorophenyl)-2-isopropyl-N,1-diphenyl-1H-pyrrole-3-
carboxamide, 4d(xii)
1-(4-(4-Methoxyphenyl)-2-methyl-1-phenyl-1H-pyrrol-3-yl)
ethanone, 4e(v)
White solid; m.p. ¼ 182–185 ꢀC; IR (cmꢁ1): ꢀy ¼ 3391, 2958, 1654,
1594, 1434, 1313; 1H NMR (400 MHz, CDCl3) d 7.44–7.55 (m, Reddish solid; m.p. ¼ 107–109 C; IR (cmꢁ1): ꢀy ¼ 2930, 1650,
5H), 7.37–7.40 (m, 2H), 7.28–7.30 (m, 4H), 7.05–7.11 (m, 4H), 1598, 1498, 1246; 1H NMR (400 MHz, CDCl3) d 7.43–7.52 (m,
6.68 (s, 1H), 3.15–3.22 (m, 1H), 1.38 (d, J ¼ 7.1 Hz, 6H); 13C NMR 3H), 7.30–7.36 (m, 4H), 6.94 (d, J ¼ 8.7 Hz, 2H), 6.65 (s, 1H), 3.86
(100 MHz, CDCl3) d 164.81, 142.90, 139.61, 138.25, 130.45, (s, 3H), 2.42 (s, 3H), 2.09 (s, 3H); 13C NMR (100 MHz, CDCl3) d
130.10, 130.03, 129.23, 128.92, 128.53, 127.29, 123.92, 122.50, 197.72, 158.70, 138.79, 135.22, 130.41, 129.34, 128.33, 128.06,
119.88, 119.64, 115.75, 115.54, 115.40, 26.57, 21.94; ESI-HRMS 126.24, 125.91, 122.59, 120.43, 113.73, 55.29, 31.08, 12.99; ESI-
(m/z): [M + H]+ calcd for C26H24FN2O, 399.1873, found, HRMS (m/z): [M + Na]+ calcd for C20H19NNaO2, 328.1313,
ꢀ
399.1873.
found 328.1326.
Ethyl 4-(4-methoxyphenyl)-2-methyl-1-phenyl-1H-pyrrole-3-
1-(4-(4-Chlorophenyl)-2-methyl-1-phenyl-1H-pyrrol-3-yl)
carboxylate, 4e(i)
ethanone, 4e(vi)
White solid; m.p. ¼ 118–120 ꢀC; IR (cmꢁ1): ꢀy ¼ 2930, 1693, 1524, Sticky solid; IR (cmꢁ1): ꢀy ¼ 2923, 1655, 1500, 1412, 1222; 1H
1402, 1280; 1H NMR (400 MHz, CDCl3) d 7.43–7.52 (m, 3H), NMR (400 MHz, CDCl3) d 7.46–7.52 (m, 3H), 7.32–7.39 (m, 6H),
7.33–7.38 (m, 4H), 6.91 (d, J ¼ 8.7 Hz, 2H), 6.69 (s, 1H), 4.21 (q, 6.69 (s, 1H), 2.42 (s, 3H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
J ¼ 7.1 Hz, 2H), 3.85 (s, 3H), 2.46 (s, 3H), 1.19 (t, J ¼ 7.1 Hz, 3H); d 197.24, 138.62, 135.56, 134.53, 132.80, 130.51, 129.41, 129.10,
13C NMR (100 MHz, CDCl3) d 165.89, 158.31, 139.02, 136.43, 128.48, 126.26, 125.58, 122.49, 120.76, 31.17, 12.93; ESI-HRMS
130.32, 129.32, 128.01, 126.34, 126.22, 120.57, 115.73, 113.06, (m/z): [M + Na]+ calcd for C19H16ClNNaO, 332.0818, found
111.66, 59.47, 55.28, 14.21, 12.77; ESI-HRMS (m/z): [M + Na]+ 332.0823.
calcd for C21H21NNaO3, 358.1419, found 358.1440.
2,5-Dimethyl-N,1,4-triphenyl-1H-pyrrole-3-carboxamide, 4f(i)
Yellow solid; m.p. ¼ 182–184 ꢀC; IR (cmꢁ1): ꢀy ¼ 3393, 1657,
Ethyl 4-(4-chlorophenyl)-2-methyl-1-phenyl-1H-pyrrole-3-
carboxylate, 4e(ii)
1594, 1438, 1311; 1H NMR (400 MHz, CDCl3) d 7.41–7.57
White solid; m.p. ¼ 62–64 C; IR (cmꢁ1): ꢀy ¼ 2918, 1698, 1517, (m, 8H), 7.30 (d, J ¼ 7.0 Hz, 2H), 7.20 (t, J ¼ 7.4 Hz, 2H), 7.11 (d,
ꢀ
1413, 1221; 1H NMR (400 MHz, CDCl3) d 7.41–7.51 (m, 3H), J ¼ 7.5 Hz, 2H), 7.07 (brs, 1H), 6.98 (t, J ¼ 7.3 Hz, 1H), 2.44 (s,
7.28–7.37 (m, 6H), 6.69 (s, 1H), 4.19 (q, J ¼ 7.1, 2H), 2.45 (s, 3H), 3H), 1.93 (s, 3H); 13C NMR (100 MHz, CDCl3) d 164.03, 138.63,
1.17 (t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 165.60, 137.71, 135.38, 135.29, 131.04, 129.46, 128.95, 128.71, 128.61,
138.88, 136.88, 134.15, 132.17, 130.57, 129.38, 128.21, 127.69, 128.30, 127.48, 126.44, 123.14, 119.45, 119.11, 114.10, 12.62,
126.35, 125.50, 120.93, 111.63, 59.54, 14.16, 12.68; ESI-HRMS 11.20; ESI-HRMS (m/z): [M + Na]+ calcd for C25H22N2NaO,
(m/z): [M + Na]+ calcd for C20H18ClNNaO2, 362.0924, found 389.1630, found 389.1627.
362.0933.
1-(4-Methoxyphenyl)-2,5-dimethyl-N,4-diphenyl-1H-pyrrole-3-
Ethyl 4-(4-hydroxy-3-methoxyphenyl)-2-methyl-1-phenyl-1H-
carboxamide, 4f(ii)
pyrrole-3-carboxylate, 4e(iii)
White solid, m.p. ¼ 168–170 ꢀC; IR (cmꢁ1): ꢀy ¼ 3400, 2838, 1660,
Sticky solid; IR (cmꢁ1): ꢀy ¼ 3434, 1639, 1518, 1405, 1232; 1H 1594, 1436; 1H NMR (400 MHz, CDCl3) d 7.37–7.47 (m, 4H) 7.33
NMR (400 MHz, CDCl3) d 7.33–7.52 (m, 5H), 6.92–6.99 (m, 3H), (d, J ¼ 7.1 Hz, 1H) 7.16–7.25 (m, 6H) 7.11–7.14 (m, 2H) 7.00–7.04
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(m, 1H) 3.89 (s, 3H) 2.27 (s, 3H) 1.94 (s, 3H); 13C NMR (100 MHz, 6.99–7.22 (m, 10H), 6.85–6.89 (m, 2H), 6.72 (t, J ¼ 8.7 Hz, 2H),
CDCl3) d 164.05, 159.51, 138.66, 135.61, 135.48, 131.03, 130.37, 2.52 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.90,
129.27, 128.92, 128.69, 127.41, 126.74, 123.08, 119.18, 119.08, 149.36, 138.46, 138.20, 136.45, 134.92, 134.78, 132.54, 132.46,
114.57, 113.85, 55.55, 12.57, 11.14; ESI-HRMS (m/z): [M + Na]+ 131.34, 130.41, 129.68, 128.84, 128.74, 128.43, 127.54, 123.31,
calcd. for C26H24N2NaO2, 419.1735, found 419.1734.
121.07, 119.19, 114.82, 114.61, 21.16, 12.63; ESI-HRMS (m/z):
[M + Na]+ calcd for C31H25FN2NaO, 483.1849, found 483.1848.
2-Methyl-N,1,4,5-tetraphenyl-1H-pyrrole-3-carboxamide, 4f(iii)
White sticky solid; IR (cmꢁ1): ꢀy ¼ 3390, 2912, 1660, 1497, 1311;
1H NMR (400 MHz, CDCl3) d 7.32–7.37 (m, 7H), 7.15–7.21 (m,
4H), 7.07–7.10 (m, 3H), 6.98–7.01 (m, 4H), 6.87–6.89 (m, 2H),
2.54 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.97, 138.53,
137.81, 136.29, 134.94, 131.48, 131.41, 131.37, 130.88, 128.95,
128.80, 128.79, 128.74, 128.13, 127.58, 127.47, 126.71, 123.30,
121.10, 119.23, 115.02, 12.67; ESI-HRMS (m/z): [M + Na]+ calcd
for C30H24N2NaO, 451.1786, found 451.1795.
Acknowledgements
We are thankful to the Department of Science and Technology,
Government of India, for research funding and the University
Grants Commission for a fellowship (RGNF) to S. G.
Notes and references
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1-Benzyl-2-methyl-N,4,5-triphenyl-1H-pyrrole-3-carboxamide,
4f(iv)
White solid; m.p. ¼ 140–143 ꢀC; IR (cmꢁ1): ꢀy ¼ 3269, 3030, 1648,
1529, 1436, 1319; 1H NMR (400 MHz, CDCl3) d 7.27–7.34 (m,
8H), 7.14–7.22 (m, 5H), 7.05–7.09 (m, 5H), 6.94–6.99 (m, 3H),
5.08 (s, 2H), 2.59 (s, 3H); 13C NMR (100 MHz, CDCl3) d 163.99,
138.56, 137.67, 135.49, 134.93, 131.65, 131.43, 131.33, 131.12,
128.83, 128.71, 128.62, 128.13, 127.72, 127.31, 127.23, 125.72,
123.22, 120.98, 119.18, 114.84, 47.77, 11.80; ESI-HRMS (m/z):
[M + H]+ calcd for C31H27N2O, 443.2123, found, 443.2123.
´ ´
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1594, 1436, 1313; 1H NMR (400 MHz, CDCl3) d 7.38 (s, 8H), 7.07–
7.23 (m, 7H), 6.99 (t, J ¼ 7.4 Hz, 1H), 6.84–6.88 (m, 2H), 6.71 (t,
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132.48, 131.34, 130.42, 129.07, 128.87, 128.77, 128.75, 128.27,
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C
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5-(4-Fluorophenyl)-2-methyl-N,4-diphenyl-1-(p-tolyl)-1H-
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1
1662, 1595, 1315; H NMR (400 MHz, CDCl3) d 7.36 (brs, 5H),
3194 | RSC Adv., 2015, 5, 3187–3195
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