Ultrasound-assisted synthesis of 2,5-dimethyl-N-substituted pyrroles catalyzed by uranyl nitrate hexahydrate

Article abstract of DOI:10.1016/j.ultsonch.2011.02.007

An efficient synthesis of different novel 2,5-dimethyl-N-substituted pyrrole derivatives by the Paal-Knorr condensation has been accomplished using uranyl nitrate hexahydrate as catalyst under soft conditions and ultrasonic irradiation. The synthesized compounds were confirmed through spectral characterization using IR, ¹H NMR, ¹³C NMR and mass spectra.

Full text of DOI:10.1016/j.ultsonch.2011.02.007

Ultrasonics Sonochemistry 18 (2011) 917–922
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
Ultrasound-assisted synthesis of 2,5-dimethyl-N-substituted pyrroles catalyzed
by uranyl nitrate hexahydrate
⇑
V.S.V. Satyanarayana, A. Sivakumar
Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632 014, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthesis of different novel 2,5-dimethyl-N-substituted pyrrole derivatives by the Paal–Knorr
condensation has been accomplished using uranyl nitrate hexahydrate as catalyst under soft conditions
and ultrasonic irradiation. The synthesized compounds were confirmed through spectral characterization
using IR, 1H NMR, 13C NMR and mass spectra.
Received 15 December 2010
Received in revised form 4 February 2011
Accepted 6 February 2011
Available online 27 February 2011
Ó 2011 Elsevier B.V. All rights reserved.
Keywords:
2,5-Dimethyl-N-substituted pyrroles
UO2(NO3)2.6H2O
Ultrasonic irradiation
Soft conditions
1. Introduction
tuted pyrroles reported above suffer from one or more disadvan-
tages, such as harsh reaction conditions, poor yields, prolonged
The pyrrole scaffold is an useful structural pattern for exhibiting
chemical functionality in biologically active molecules [1]. It has
established broad application in drug development for the treat-
ment as antibacterial, anti-inflammatory, antiviral, antitumoral,
and antioxidant agent [2]. The pyrrole ring system is one of the
most important substructures for biologically active compounds
such as indolizidine alkaloids, unsaturated g-lactams and bicyclic
lactams [3]. These structural units are found in a wide array of nat-
ural products, synthetic materials and bioactive molecules such as
vitamin B12, heme and cytochromes [1,4]. Therefore, preparation
of pyrroles has attracted considerable attention of chemists in re-
cent years. There are several methods for the synthesis of pyrrole
in the literature [5] from classical Hantzsch procedure [6], 1,3-dipo-
lar cycloaddition reaction [7], aza-Wittig reaction [8], reductive
coupling [9], titanium catalyzed hydroamination of diynes [10]
and other multistep operations [11]. The most widely used method
is the Paal–Knorr synthesis, which involves the cyclocondensation
reaction of 1,4-dicarbonyl compounds with primary amines to pro-
duce substituted pyrroles. Several catalysts have been used in this
reaction including HCl [12], p-TSA [13], HOAc [14], H2SO4 [15], I2
[16], different metal complexes [17–30], and montmorillonite
[16,31–32]. In addition, the above cyclocondensation process could
proceed in ionic liquid [33], microwave irradiation [34] or ultra-
sound irradiation using ZrCl4 as catalyst [35]. However, some of
the synthetic protocols for the synthesis of 2,5-dimethyl-N-substi-
reaction time period as well as use of corrosive, expensive reagents,
limiting these methods. Thus, simple, efficient and flexible proto-
cols for the synthesis of 2,5-dimethyl-N-substituted pyrroles are
still the need as there is scope for further improvement towards
milder reaction conditions, development of simple and inexpensive
reagents convenient procedures and higher product yields.
Ultrasonic-assisted organic synthesis as a green synthetic ap-
proach is a powerful technique that is being used more and more
to accelerate organic reactions [36,37]. A large number of organic
reactions can be carried out in higher yields, shorter reaction time
or milder conditions under ultrasound irradiation and considered a
processing aid in terms of energy conservation and waste minimi-
zation which compared with traditional methods.
Uranyl nitrate is usually used as an electron dense stain for
transmission electron microscopy. However, it has also found
application as 0.01% aqueous solution as a local catalyst in the
polymerization of methacrylates [38].
We report herein, a simple, mild and expeditious synthesis of
2,5-dimethyl-N-substituted pyrroles in high yields by reacting
1,4-dicarbonyl compound with substituted primary amines using
uranyl nitrate hexahydrate [UO2(NO3)2.6H2O] (Scheme 1) as cata-
lyst under soft conditions and ultrasonic irradiation.
2. Results and discussion
2,5-Dimethyl-N-substituted pyrroles (3a–k) were synthesized
by the cyclocondensation of commercially available 2,5-hexanedi-
one with different substituted primary amines using uranyl nitrate
⇑
Corresponding author.
E-mail address: profaskumar09@gmail.com (A. Sivakumar).
1350-4177/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2011.02.007

918
V.S.V. Satyanarayana, A. Sivakumar / Ultrasonics Sonochemistry 18 (2011) 917–922
O
UO2(NO3)2.6H2O
R-NH2
+
N
R
MeOH, r.t. / ))))
2a
1
3
O
Scheme 1. Synthesis of 2,5-dimethyl-N-substituted pyrroles catalyzed by uranyl nitrate hexahydrate.
hexahydrate [UO2(NO3)2.6H2O] (Scheme 1) as catalyst under soft
conditions and ultrasonic irradiation. To optimize the reaction con-
ditions, the reaction between 2,5-hexanedione and aniline was
used as a model reaction. The results shown in Table 1 clearly indi-
cate the scope and generality of the reaction with respect to vari-
ous catalytic systems. In comparison with other catalysts such as
Bi(NO3)2.5H2O, [BMIm]I and RuCl3 which have been recently re-
ported in the synthesis of 2,5-dimethyl-N-substituted pyrroles,
UO2(NO3)2.6H2O employed here shows a more effective catalytic
activity than the others in terms of amount of catalyst, yield and
reaction time (Table 1, entry 8–10).The influence of other catalysts
such as Sr(NO3)2, Mg(NO3)2.6H2O were also examined. It is notable
that strontium nitrate was found to give quite high yields for this
transformation compared with magnesium nitrate hexahydrate
(Table 1, entry 6 & 7). However, in the absence of catalyst, the reac-
tion yielded only 22% of product after 24 h of reaction.
Before taking up the reaction using ultrasonic irradiation, it was
tried out using different solvents such as methanol, ethanol, aceto-
nitrile, dichloromethane and chloroform as well as solvent free
system under normal reaction conditions with 10 mol% of UO2-
(NO3)2.6H2O as the catalyst (Table 2). However, it was noticed that
the highest yield and shorter reaction duration was achievable
with methanol while the others took longer duration to yield lesser
product. Hence the ultrasonic irradiation which required only
5 min duration to complete reaction of aniline with 2,5-hexanedi-
one and the product yield was 96% is compared to the normal reac-
tion conditions, stirring at room temperature which have taken
30 min for reaction to completion and yield was slightly less
(94%) with methanol as solvent (Table 2, entry 5). It was clear that
the ultrasound could accelerate the reaction of amine and 2,5-
hexancedione.
Table 2
Synthesis of 2,5-dimethyl-N-phenyl pyrrolea (3a) using 10 mol% of UO2(NO3)2.6H2O
in different solvent systems.
Entry
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
Acetonitrile
CH2Cl2
CHCl3
Ethanol
Methanol
Solvent free
120
300
300
60
79
57
61
88
30/5c
60
94/96c
83
a
b
c
Aniline: 2,5-Hexanedione (1 mmol: 1.1 mmol).
Isolated yield.
At room temperature/Ultrasonic irradiation.
Apart from this, the shock wave produced by the bubble collapse
can disrupt the solvent structure which can influence the reactivity
by altering solvation of the reactive species present in the reaction
mixture. Sonochemical rate enhancement is a known phenomenon
in organic reactions [39]. It can be attributed that by the same
mechanism, the yield of 2,5-dimethyl-N-substituted pyrroles is
higher in ultrasound than in normal chemical reaction.
In order to evaluate the generality of the process, several diver-
sified examples illustrating the present method for the synthesis of
2,5-dimethyl-N-substituted pyrroles (3a–k) was studied (Table 3).
The reaction of 2,5-hexanedione (2a) with various aromatic/ali-
phatic substituted primary amines bearing electron donating
groups, electron withdrawing groups and several heterocyclic moi-
eties was carried out in the presence of UO2(NO3)2.6H2O as catalyst
under soft conditions and ultrasonic irradiation. The yields ob-
tained were good to excellent without formation of any side prod-
ucts and these results are illustrated in Table 3. From these
experiments, it is clearly demonstrated that the uranyl nitrate
hexahydrate [UO2(NO3)2.6H2O] is indeed an effective catalyst and
is undoubtedly superior to other catalysts, procedures with respect
to reaction time, availability of catalyst, work-up procedure and
yields. The compounds IVa–e were synthesized by refluxing differ-
ent substituted acetohydrazides (IIIa–e) and 2,5-hexanedione in
the presence of UO2(NO3)2.6H2O. The reaction time and yields of
the compounds IVa–e are depicted in Table 4. The compounds
IIIa–e were synthesized by refluxing the mixture of ethyl(substi-
tuted)mono/diacetate (IIa–e) and hydrazine hydrate in ethanol.
The compounds IIa–e were synthesized by the reaction of ethyl
chloroacetate with different mono and dihydroxy substituted aro-
matic compounds in the presence of K2CO3 as catalyst (Scheme 2)
[40]. Structure of new derivatives of 2,5-dimethyl-N-substituted
pyrroles (3b–c, 3k and IVa–e) properly characterized by their IR,
1H NMR, 13C NMR and mass spectra, while the known compounds
were identified by comparison of their spectroscopic data and
melting points with the reported values in literature.
The following is expected to be plausible reason for the higher
yield and lesser reaction time during ultrasonic irradiation:
Cavitation is a process of formation of bubbles having dynamic
life during ultrasonic irradiation. These bubbles can be filled with
gas or vapour and occur in organic solvents used in the ultrasonic
irradiation. When these bubbles burst, it results in high tempera-
ture and high pressure which facilitate the intermolecular reaction.
Table 1
Comparison of effect of catalysts in the formation of 2,5-dimethyl-N-phenyl pyrrolea
(3a) at room temperature.
Entry
Catalyst
Mole %
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
No Catalyst
–
1
2.5
5
10
20
20
100
1.5 g
5
24
2
2
22
57
69
88
UO2(NO3)2.6H2O
UO2(NO3)2.6H2O
UO2(NO3)2.6H2O
UO2(NO3)2.6H2O
Sr(NO3)2
Mg(NO3)2.6H2O
Bi(NO3)2.5H2O
[BMIm]I
1
0.5/5c
4
94/96c
73
4
10
3
55
3. Experimental
96[19]
96[33]
94[30]
RuCl3
0.5
3.1. General
a
b
c
Aniline: 2,5-Hexanedione (1 mmol: 1.1 mmol).
Isolated yield.
At room temperature (h)/ultrasonic irradiation (min).
All reagents purchased from Aldrich, Hi Media and Qualigens
were used without further purification. UO2(NO3)2.6H2O

V.S.V. Satyanarayana, A. Sivakumar / Ultrasonics Sonochemistry 18 (2011) 917–922
919
Table 3
purchased from LOBA Chemie and used as received. Infrared (IR)
spectra were recorded at room temperature from 4000 cmꢀ1 to
400 cmꢀ1 with KBr pellets at a resolution of 4 cmꢀ1, using Avatar
330 equipped with DTGS detector. Most of the obtained vibrational
bands of the IR spectrum were identified and compared with those
values available in literature. The 1H NMR was recorded on a
Bruker AMX-400 (400, 500 MHz) instrument at room temperature
using the X-WIN NMR version X-WIN NMR 1.3 cn drx software.
Approximately 0.03 M solutions in CDCl3 or DMSO-d6 using TMS
as internal reference were used for recording 1H NMR spectra.
The accuracy of the 1H shifts considered as 0.02 ppm. The coupling
constants J are in Hz. 13C NMR spectra were recorded on Bruker
Avance III (125.75 MHz) spectrometer. Mass spectra were obtained
using JEOL GC MATE II HRMS (EI) mass spectrometry. Sonication
was performed in a SONICS, Vibra Cell, VC 130, ultrasonic proces-
sor equipped with a 3 mm wide and 140 mm long probe, which
was immersed directly into the reaction mixture. The operating
frequency was 20 kHz and the output power was 0–130 Watt
through manual adjustment. Melting points were determined in
open capillaries and are uncorrected.
Synthesis of 2,5-dimethyl-N-substituted pyrroles (3a-k) catalyzed by uranyl nitrate
hexahydrate.
Entry Amine
Product
Time
Yield
M.P.
(°C)
(min)a (%)b
1
2
Ph-NH2
30/5
60/6
94/96 48–50
Ph
Br
N
3a
89/90 56–58
Br
NH2
N
3b
3
4
5
6
60/6
45/6
60/5
86/88 62–64
86/84 60–62
87/90 144–146
I
NH2
I
N
3c
H3CO
NH2
H3CO
O2N
N
3d
O2N
NH2
N
3e
3.2. Procedure for the synthesis of 2,5-dimethyl-N-substituted pyrroles
(3a–k)
120/8 76/72 140–142
120/10 83/81 120–122
N
N
NH2
N
N
N
N
N
3f
3.2.1. Method A
To a solution of the amine 1 (1 mmol) and 2,5-hexanedione 2a
(1.1 mmol) in methanol (2 mL) at room temperature, uranyl nitrate
hexahydrate (10 mol%) was added. The mixture was stirred at
room temperature for a period specified in Table 3. The progress
of reaction was monitored by TLC. After completion of reaction
the resulting mixture was filtered, washed with a 5% HCl solution
to remove the excess amine and washed with a small amount of
cold water. The crude product was weighed and recrystallized
from 10% aqueous methanol. The reaction mixture was cooled in
ice and the product was collected and dried.
NH2
7
N
3g
H2C-CH2
8
9
NH2(CH2)2NH2
180/15 87/85 134–136
180/15 90/87 248–250
N
N
3h
H2N
NH2
N
N
3i
10
11
PhCH2NH2
90/6
88/86 40–42
3.2.2. Method B
PhH2C
N
3j
To a solution of the amine 1 (1 mmol) and 2,5-hexanedione 2a
(1.1 mmol) in methanol (2 mL) at room temperature, uranyl nitrate
hexahydrate (10 mol%) was added and the resulting reaction mix-
ture was subjected to ultrasonic irradiation using ultrasonic pro-
cessor equipped with a 3 mm wide and 140 mm long probe,
which was immersed directly into the reaction mixture for a period
as shown in Table 3. The operating frequency was 16 kHz and the
output power was 104 Watt through manual adjustment. The
progress of reaction was monitored by TLC. After completion of
300/16 81/83 156–158
CONHNH2
CONHN
3k
a
Under reflux conditions/Ultrasonic irradiation.
Isolated yield.
b
O
O
K2CO3, DMF
QX
H
+
QX
Cl
Stirr at 80 o
C
(I)
(II)
O
O
X = O, N
Q = aryl / heteroaryl
substituents
H2N-NH2.H2O
O
H
N
H
N
O
QX
N
QX
NH2
Catalyst,
Reflux / ))
)
)
(III)
O
(IV)
O
Scheme 2. Synthetic protocol of compounds IVa–e.

920
V.S.V. Satyanarayana, A. Sivakumar / Ultrasonics Sonochemistry 18 (2011) 917–922
Table 4
Synthesis of compounds (IVa–e) using uranyl nitrate hexahydrate as catalyst.
Entry
1
Reactant
Product
Time (h/min)a
2/16
Yield (%)a,b
87/84
M.P (°C)
O
204–206
O
O
NH2
N
H
O
N
N
H
(IIIa)
(IVa)
2
3
O
4/20
4/20
79/73
82/75
214–216
240–242
O
O
O
O
NH2
O
O
O
N
N
H
N
H
(IIIb)
(IVb)
Ph
N
Ph
N
H
N
H
N
N
N
N
NH2
O
Ph
O
Ph
(IVc)
(IIIc)
Ph
Ph
4
5
6/25
6/25
76/71
71/68
224–226
170–172
H
H
N
H
N
H
N
N
N
N
O
O
N
H2N
O
O
NH2
NH2
O
O
(IVd)
(IVe)
(IIId)
(IIIe)
O
O
H
H
H
N
H
N
N
N
O
O
N
H2N
O
O
O
O
O
O
a
Under reflux conditions/Ultrasonic irradiation.
Isolated yield.
b
reaction the resulting mixture was filtered, washed with a 5% HCl
solution to remove the excess amine and washed with a small
amount of cold water. The separated product was filtered, washed
with ice cold water, recrystallized from 10% aqueous methanol and
dried at room temperature.
3.6. N-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide (3k)
max, cmꢀ1): 3263, 3062, 2934, 1664,
mp 156–158 °C. IR (KBr,
m
1602, 1537, 1488, 1282, 748. 1H NMR (300 MHz, CDCl3) dH: 2.13
(s, 6H, CH3 on pyrrole), 5.77 (s, 2H, CH on pyrrole), 7.49 (m, 3H,
ArH), 7.86 (d, 2H, J = 7.2 Hz, ArH), 8.15 (s, 1H, CONH). 13C NMR
(125.75 MHz, CDCl3) dC: 11.47, 103.61, 127.39, 127.50, 127.96,
128.12, 128.71, 128.76, 129.20, 131.51, 131.75, 132.39, 132.78,
166.28. ESI-MS: m/z calcd for C13H14N2O: 214.11; found: 214.51
[M]+. HRMS (EI): m/z [M]+ calcd for C13H14N2O: 214.1106; found:
214.1200.
3.3. 1-(4-phenyl)-2,5-dimethyl-1H-pyrrole (3a)
mp 48–50 °C. IR (KBr,
m
max, cmꢀ1): 3053, 2922, 1596, 1491,
1400, 1316, 1218, 1037, 999, 747. 1H NMR (500 MHz, CDCl3) dH:
7.49 (m, 2H, m,m’-ArH), 7.43 (m, 1H, p-ArH), 7.25 (m, 2H, o,o’-
ArH) 5.94 (s, 2H, pyrrole), 2.07 (s, 6H, 2CH3). 13C NMR
(125.75 MHz, CDCl3) dC: 139.02, 129.05, 128.82, 128.27, 127.63,
105.63, 13.02. HRMS (EI): m/z [M]+ calcd for C12H13N: 171.10;
found: 171.1059.
3.7. Procedure for the synthesis of compounds (IVa–e)
3.7.1. Method A
To a suspensions of different substituted acetohydrazides IIIa–e
(0.001 mol) in methanol/chloroform (1:1) mixture (20 mL) were
added acetonyl acetone (0.002 mol) and uranyl nitrate hexahy-
drate (10 mol%) and the reaction mixture was refluxed for a period
specified in Table 4. The reaction mixture was concentrated to half
of the original volume and poured into crushed ice. The separated
solid was filtered, washed with water and dried.
3.4. 1-(4-Bromophenyl)-2,5-dimethyl-1H-pyrrole (3b)
mp 56–58 °C. IR (KBr,
m
max, cmꢀ1): 3078, 2917, 1519, 1484,
1435, 1402, 1320, 1065, 998, 840, 760. 1H NMR (300 MHz, CDCl3)
dH: 2.01 (s, 6H, 2CH3), 5.79 (s, 2H, pyrrole), 7.08 (d, 2H, J = 8.4 Hz,
o,o0-ArH), 7.57 (d, 2H, J = 8.4 Hz, m,m’-ArH). 13C NMR
(125.75 MHz, CDCl3) dC: 12.97, 106.13, 121.53, 128.67, 129.88,
132.32, 138.07. HRMS (EI): m/z [M + H]+ calcd for C12H12BrN:
249.0153; found: 250.1000.
3.7.2. Method B
To a suspensions of different substituted acetohydrazides IIIa–e
(0.001 mol) in methanol/chloroform (1:1) mixture (20 mL) were
added acetonyl acetone (0.002 mol) and uranyl nitrate hexahy-
drate (10 mol%) and the resulting reaction mixture was subjected
to ultrasonic irradiation using ultrasonic processor equipped with
a 3 mm wide and 140 mm long probe, which was immersed di-
rectly into the reaction mixture for a period as shown in Table 3.
The operating frequency was 16 kHz and the output power was
104 Watt through manual adjustment. The progress of reaction
was monitored by TLC. After completion of reaction the resulting
mixture was poured into crushed ice. The separated product was
filtered, washed with ice cold water and dried at room
temperature.
3.5. 1-(4-Iodophenyl)-2,5-dimethyl-1H-pyrrole (3c)
mp 62–64 °C. IR (KBr,
m
max, cmꢀ1): 3073, 2916, 1583, 1484,
1434, 1403, 1321, 1053, 997, 838, 760. 1H NMR (500 MHz, CDCl3)
dH: 2.06 (s, 6H, 2CH3), 5.94 (s, 2H, pyrrole), 7.01 (d, 2H, J = 8.5 Hz,
o,o’-ArH), 7.83 (d, 2H, J = 8.5 Hz, m,m’-ArH). 13C NMR
(125.75 MHz, CDCl3) dC: 13.06, 92.98, 106.18, 128.66, 130.17,
138.34, 138.74. HRMS (EI): m/z [M]+ calcd for C12H12IN:
297.0014; found: 297.1000.

V.S.V. Satyanarayana, A. Sivakumar / Ultrasonics Sonochemistry 18 (2011) 917–922
921
3.8. N-(2,5-dimethyl-1H-pyrrol-1-yl)-2-(naphthalen-2-
yloxy)acetamide (IVa)
CDCl3) dH: 1.57–1.65 (m, 6H, CH3 on bisphenol), 2.05 (s, 12H, CH3
on pyrrole), 4.75 (s, 4H, OCH2), 5.80 (s, 2H, CONH), 6.89 (d, 4H,
J = 8.4 Hz, ArH), 7.19 (d, 4H, J = 8.4 Hz, ArH), 8.57 (s, 2H, CONH).
13C NMR (125.75 MHz, CDCl3) dC: 11.36, 31.19, 41.80, 66.61,
103.55, 114.74, 127.34, 127.89, 144.00, 155.79, 168.03. ESI-MS:
m/z calcd for C31H36N4O4: 528.27; found: 529.52 [M + H]+. HRMS
(EI): m/z [M]+ calcd for C31H36N4O4: 528.2737; found: 528.1000.
mp 204–206 °C. IR (KBr, m
max, cmꢀ1): 3216, 3060, 2923, 1688,
1629, 1511, 1465, 1432, 1391, 1256, 1219, 1184, 1122, 1068, 963,
844, 754. 1H NMR (400 MHz, CDCl3) dH: 1.61 (s, 3H, CH3 on pyrrole),
2.02–2.41 (m, 3H, CH3 on pyrrole), 4.60 (s, 1H, OCH), 4.83–4.91 (m,
1H, OCH), 6.85 (s, 2H, CH on pyrrole), 7.00–7.14 (m, 4H, ArH), 7.57–
7.82 (m, 3H, ArH), 8.26 (s, 1H, CONH). 13C NMR (125.75 MHz, CDCl3)
dC: 11.41, 66.59, 103.60, 107.73, 119.20, 124.46, 127.06, 127.14,
127.36, 128.04, 129.32, 129.88, 134.41, 155.90, 167.85. ESI-MS: m/z
calcd for C18H18N2O2: 294.14; found: 295.34 [M + H]+. HRMS (EI):
m/z [M]+ calcd for C18H18N2O2: 294.1368; found: 294.3500.
4. Conclusion
It may be reasonably concluded that the present procedure for
the synthesis of 2,5-dimethyl-N-substituted pyrroles through a
one pot condensation of 1,4-dicarbonyl compounds and substi-
tuted primary amines establishes the potential of uranyl nitrate
hexahydrate [UO2(NO3)2.6H2O] as a good catalyst under soft condi-
tions/ultrasonic irradiation for such condensation reactions and
gives hope for further useful applications in organic synthesis.
Moreover, this methodology offers substantial advantages with re-
spect to simplicity of operation, yield of products, reaction times,
availability of catalyst, choice of substituents on the pyrrole ring,
easy work-up procedure under mild reaction conditions. Pyrroles
with different N-substituted heterocyclic moieties (IVa–e) were
prepared by using uranyl nitrate hexahydrate as catalyst under re-
flux conditions and ultrasonic irradiation.
3.9. N-(2,5-dimethyl-1H-pyrrol-1-yl)-2-(4-methyl-2-oxo-2H-
chromen-7-yloxy)acetamide (IVb)
mp 214–216 °C. IR (KBr, m
max, cmꢀ1): 3258, 3087, 2921, 1716,
1687, 1616, 1504, 1427, 1390, 1295, 1202, 1156, 1079, 846, 776.
1H NMR (400 MHz, CDCl3) dH: 1.52 (s, 3H, CH3 on coumarin),
2.07 (s, 6H, 2CH3 on pyrrole), 4.89 (s, 2H, OCH2), 5.90 (s, 2H, CH
on pyrrole), 7.23 (s, 1H, CH on coumarin), 7.42 & 7.49 (2d, 1H,
J = 6.8 & 7.6 Hz, ArH), 7.75–7.84 (m, 2H, ArH), 8.62 (s, 1H, CONH).
13C NMR (125.75 MHz, CDCl3) dC: 11.39, 18.60, 66.75, 102.27,
103.65, 112.06, 112.99, 114.29, 127.03, 127.31, 153.82, 154.95,
160.48, 160.92, 167.32. ESI-MS: m/z calcd for
326.13; found: 327.36 [M + H]+. HRMS (EI): m/z [M]+ calcd for
18H18N2O4: 326.1267; found: 326.5646.
C18H18N2O4:
Acknowledgment
C
Authors, express thanks to the Administration of VIT University,
Vellore for providing required facilities to support this work.
3.10. N-(2,5-dimethyl-1H-pyrrol-1-yl)-2-(2,4,5-triphenyl-1H-
imidazol-1-yl)acetamide (IVc)
Appendix A. Supplementary data
mp 240–242 °C. IR (KBr,
1213 cmꢀ1 1H NMR (500 MHz, DMSO-d6) dH: 1.80 (s, 6H, C2,5–CH3
m
max, cmꢀ1): 3251, 3056, 2923, 1685,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ultsonch.2011.02.007.
.
onpyrrolering), 4.65 (s, 2H, N-CH2-CO), 5.63 (s, 2H, C3,4–Hon pyrrole
ring), 7.15 & 7.22 (2t, 3H, J = 7.75 Hz, p-ArH of 2,4,5-phenyl rings),
7.39–7.44 (m, 4H, o,o0-ArH of 4,5-phenyl rings), 7.52–7.54 (m, 6H,
m,m’-ArHof2,4,5-phenylrings), 7.66–7.68(m, 2H, o,o’-ArHof 2-phe-
nyl ring), 10.88 (s, 1H, CONH). 13C NMR (125.75 MHz, CDCl3) dC:
10.39, 10.75, 45.90, 104.00, 105.24, 126.49, 126.70, 126.83, 127.11,
127.33, 127.92, 128.07, 128.12, 128.57, 128.74, 128.96, 129.07,
129.15, 129.18, 129.25, 129.42, 129.89, 130.13, 130.21, 130.30,
130.66, 130.87, 131.19, 134.04, 137.66, 148.37, 148.48, 171.07. LC-
MS: m/z calcd for C29H26N4O: 446.21; found: 447.2 [M + H]+. HRMS
(EI): m/z [M]+ calcd for C29H26N4O: 446.2107; found: 446.5400.
References
[1] R.A. Jones, G.P. Bean, The Chemistry of Pyrroles, Academic, London, 1977.
[2] A. Furstner, A catalytic approach to (R)-(+)-Muscopyridine with integrated
‘‘Self-Clearance’’, Angew. Chem, Int. Ed. 42 (2003) 3528–3532.
[3] (a) R. Ragno, G.R. Marshall, R.D. Santo, R. Costi, S. Massa, R. Rompei, M. Artico,
Antimycobacterial pyrroles: synthesis, Anti- Mycobacterium tuberculosis
activity and QSAR studies, Bioorg. Med. Chem. 8 (2000) 1423–1432;
(b) C. Franc, F. Denone, C. Cuisiner, L. Ghosez, A general synthesis of 2-formyl-
3-arylpyrroles, Tetrahedron Lett. 40 (1999) 4555–4558;
(c) J.-H. Liu, Q.-C. Yang, T.C.W. Mak, H.N.C. Wong, Highly regioselective
synthesis of 2 3 4-trisubstituted 1 H -pyrroles: A formal total synthesis of
Lukianol A, J. Org. Chem. 65 (2000) 3587–3595;
(d) R.K. Dieter, H. Yu, A facile synthesis of polysubstituted pyrroles, Org. Lett. 2
(2000) 2283–2286;
(e) C.W. Jefford, K. Sienkiewicz, S.R. Thuruton, Short, Enantiospecific Syntheses
3.11. 2,2’-(Naphthalene-2,7-diylbis(oxy))bis(N-(2,5-dimethyl-1H-
pyrrol-1-yl)acetamide) (IVd)
of Indolizidines 209B and 209D, and Piclavine A from diethyl-
Helv. Chim. Acta 78 (1995) 1511–1524;
(f) R.I.J. Amos, B.S. Gourlay, P.P. Molesworth, J.A. Smith, O.R. Sprod, Annulation
of pyrrole: application to the synthesis of indolizidine alkaloids, Tetrahedron
61 (2005) 8226–8230.
L-glutamate,
mp 224–226 °C. IR (KBr, m
max, cmꢀ1): 3324, 2920, 1707, 1631,
1514, 1435, 1389, 1252, 1209, 1162, 1062, 835, 754. 1H NMR
(400 MHz, CDCl3) dH: 2.05 (s, 12H, CH3 on pyrrole), 4.84 (s, 4H,
OCH2), 5.82 (s, 4H, CH on pyrrole), 7.12 (s, 2H, ArH on C1 & C8 of
naphthalene ring), 7.13 (d, 2H, J = 8.2 Hz, ArH on C3 & C6 of naphtha-
lenering), 7.78(d, 2H, J = 8.6 Hz, ArHonC4&C5of naphthalenering),
8.74 (s, 2H, CONH). 13C NMR (100.6 MHz, CDCl3) dC: 10.81, 11.15,
66.99, 103.95, 104.46, 107.20, 116.23, 125.72, 127.74, 130.04,
135.32, 155.68, 167.01. ESI-MS: m/z calcd for C26H28N4O4: 460.21;
found: 460.50 [M]+. HRMS (EI): m/z [M]+ calcd for C26H28N4O4:
460.2111; found: 460.5200.
[4] [a] J.A. Joule, K. Mills, Heterocyclic Chemistry, fourth ed., Blackwell, Science,
Oxford, 2000;
[b] F. Bellina, R. Rossi, Synthesis and biological activity of pyrrole, pyrroline
and pyrrolidine derivatives with two aryl groups on adjacent positions,
Tetrahedron 62 (2006) 7213–7256;
[c] M.S. Butler, The role of natural product chemistry in drug discovery, J. Nat.
Prod. 67 (2004) 2141–2153;
[d] H. Hoffmann, T. Lindel, Synthesis of the pyrrole-imidazole alkaloids,
Synthesis (2003) 1753–1783.
[5] (a) C.W. Jefford, Q. Tang, A. Zaslona, Short, enantiogenic syntheses of (ꢀ)-
indolizidine 167B and (+)-monomorine, J. Am. Chem. Soc. 113 (1991) 3513–
3518;
3.12. 2,2’-(4,4’-(propane-2,2-diyl)bis(4,1-phenylene)) bis(oxy)bis(N-
(2,5-dimethyl-1H-pyrrol-1-yl)acetamide) (IVe)
(b) C.W. Jefford, F.V. Naide, K. Sienkiewicz, The synthesis of chiral 1-(1H-
pyrrole) derivatives, Tetrahedron: Asymmetry 7 (1996) 1069–1076;
[c] C. Bird, G.W.H. Cheeseman, Comprehensive Heterocyclic Chemistry, vol. 4,
Pergamon, Oxford, 1994.
mp 170–172 °C. IR (KBr,
1435, 1246, 1210, 1182, 1068, 831, 753, 580. 1H NMR (300 MHz,
m
max, cmꢀ1): 3237, 2971, 1689, 1506,
[6] F. Palacios, D. Aparico, J.M.D.L. Santos, J. Vicario, Regioselective alkylation
reactions of hydrazones derived from phosphine oxides and phosphonates.

922
V.S.V. Satyanarayana, A. Sivakumar / Ultrasonics Sonochemistry 18 (2011) 917–922
Synthesis of phosphorus substituted 1-amino-pyrrolones, Pyridinones and
pyrroles, Tetrahedron 57 (2001) 1961–1972.
[7] F. Berree, E. Marchand, G. Morel, Base mediated reactions in solid-liquid media.
A 1, 3-dipolar cycloaddition route to pyrrolines and pyrroles from imino
chlorosulfides, Tetrahedron Lett. 33 (1992) 6155–6158.
[8] A. Katritzky, J. Jiang, P.J. Steel, L-Aza-1, 3-bis(triphenylphosphorany-
1idene)propane: A Novel =CHCHzN= Synthon, J. Org. Chem. 59 (1994) 4551–
4556.
[9] A. Furstner, H. Weintritt, A. Hupperts, A new, titanium-mediated approach to
pyrroles: first synthesis of Lukianol A and Lamellarin O dimethyl ether, J. Org.
Chem. 60 (1995) 6637–6641.
[24] R. Sreekumar, R. Padmakumar, Simple, efficient and convenient synthesis of
pyrroles and pyrazoles using zeolites, Synth. Commun. 28 (1998) 1661–1665.
[25] F. Texier-Boullet, B. Klein, J. Hamelin, Pyrrole and pyrazole ring closure in
heterogeneous media, Synthesis (1986) 409–411.
[26] M. Kidwai, K. Singhal, S. Rastogi, Paal knorr reaction for novel pyrrolo [2, 3-d]
pyrimidines, J. Heterocyclic Chem. 43 (2006) 1231–1236.
[27] G. Song, B. Wang, G. Wang, Y. Kang, T. Yang, L. Yang, Fe3-Montmorillonite as
effective, recyclable catalyst for Paal–Knorr pyrrole synthesis under mild
conditions, Synth. Commun. 35 (2005) 1051–1057.
[28] K.D. Surya, Ruthenium (III) chloride as a novel and efficient catalyst for the
synthesis of substituted pyrroles under solvent-free conditions, Catal. Lett. 124
(2008) 174–177.
[29] C.R. Brindaban, G. Sudip, D. Arijit, Zinc tetrafluoroborate-catalysed synthesis of
highly substituted pyrroles by a solvent-free reaction, Mendeleev Commun. 16
(2006) 220–221.
[10] B. Ramanathan, A.J. Keith, D. Armstrong, A.L. Odom, Pyrrole syntheses based on
Titanium-catalyzed hydroamination of diynes, Org. Lett. 6 (2004) 2957–2960.
[11] G. Balme, Pyrrole syntheses by multicomponent coupling reactions, Angew.
Chem, Int. Ed. 43 (2004) 6238–6241.
[12] D.J. Shaw, W.F. Wood, Preparation of 2, 5-dimethyl-1-phenylpyrrole, J. Chem.
Edu. 69 (1992) A313.
[13] S. Raghavan, K. Anuradha, Solid-phase synthesis of heterocycles from 1, 4-
diketone synthons, Synlett (2003) 711–713.
[14] H.S. Broadbent, W.S. Burnham, R.K. Olsen, R.M. Sheeley, Sterically-crowded
pyrroles, J. Heterocyclic Chem. 5 (1968) 757–767.
[15] S.E. Drewes, C.J. Hogan, Furan derivatives from cyclodehydratign of brackein-
like 1, 4-dicarbonyl compounds, Synth.Commun. 19 (1989) 2101–2107.
[16] B.K. Banik, S. Samajdar, I. Banik, Simple synthesis of substituted pyrroles, J.
Org. Chem. 69 (2004) 213–216.
[30] J.-X. Chen, M.-C. Liu, X.-L. Yang, J.-C. Ding, H.-Y. Wu, Indium(III)-catalyzed
synthesis of N-substituted pyrroles under solvent-free conditions, J. Braz.
Chem. Soc. 19 (2008) 877–883.
[31] S. Samajdar, F.F. Becker, B.K. Banik, Montmorillonite KSF-mediated facile
synthesis of pyrroles, Heterocycles 55 (2001) 1019–1022.
[32] M. Abid, Q. Spaeth, B. Torok, Solvent-free solid acid-catalyzed electrophilic
annelations: a new green approach for the synthesis of substituted five-
membered N-heterocycles, Adv. Synth. Catal. 348 (2006) 2191–2196.
[33] B. Wang, C. Gu, Y.L. Luo, T. Yang, L.M. Yang, J.S. Suo, Pyrrole synthesis in ionic
liquids by Paal–Knorr condensation under mild conditions, Tetrahedron Lett.
45 (2004) 3417–3419.
[17] J. Chen, H. Wu, Z. Zheng, C. Jin, X. Zhang, W. Su, An approach to the Paal–Knorr
pyrroles synthesis catalyzed by Sc(OTf)3 under solvent-free conditions,
Tetrahedron Lett. 47 (2006) 5383–5387.
[34] T.N. Danks, Microwave assisted synthesis of pyrroles, Tetrahedron Lett. 40
(1999) 3957–3960.
[18] B. Temelli, C. Unaleroglu, A novel method for the synthesis of dipyrromethanes
by metal triflate catalysis, Tetrahedron 62 (2006) 10130–10135.
[35] Z.-H. Zhan, J.-J. Li, T.-S. Li, Ultrasound-assisted synthesis of pyrroles catalyzed
by zirconium chloride under solvent-free conditions, Ultrason. Sonochem. 15
(2008) 673–676.
[19] B.K. Banik, I. Banik, M. Renteria, S.K. Dasgupta,
A straightforward highly
efficient Paal–Knorr synthesis of pyrroles, Tetrahedron Lett. 46 (2005) 2643–
2645.
[20] P. Armugam, P.T. Perumal, SnCl2 2H2O-An alternative to Lewis acidic ionic
liquids, Chem. Lett. 35 (2006) 632–633.
[21] J.S. Yadav, B.V.S. Reddy, B. Eeshwaraiah, M.K. Gupta, Bi(OTf)3/[bmim]BF4 as
novel and reusable catalytic system for the synthesis of furan, pyrrole and
thiophene derivatives, Tetrahedron Lett. 45 (2004) 5873–5876.
[22] M. Curini, F. Montanari, O. Rosati, E. Lioy, R. Margarita, Layered zirconium
phosphate and phosphonate as heterogeneous catalyst in the preparation of
pyrroles, Tetrahedron Lett. 44 (2003) 3923–3925.
[36] H. Xu, W.-M. Liao, H.-F. Li, A mild and efficient ultrasound-assisted synthesis of
diaryl ethers without any catalyst, Ultrason. Sonochem. 14 (2007) 779–782.
[37] K.P. Guzen, A.S. Guarezemini, A.T.G. Orfao, R. Cella, C.M.P. Pereiraa, H.A.
Stefani, Eco-friendly synthesis of imines by ultrasound irradiation,
Tetrahedron Lett. 48 (2007) 1845–1848.
[38] M.A. Hayat, Principles and Techniques of Electron Microscopy, Van Nostrand
Reinhold, New York, 1970.
[39] T.J. Mason, J.P. Lorimer, B.P. Mistry, The effect of ultrasound on the solvolysis of
2-chloro-2-methylpropane in aqueous ethanol, Tetrahedron 41 (1985) 5201–
5204.
[23] S.-X. Yu, P.W.L. Quesne, Quararibea metabolites. 3. Total synthesis of ( ) –
funebral, a rotationally restricted pyrrole alkaloid, using a novel Paal–Knorr
reaction, Tetrahedron Lett. 36 (1995) 6205–6208.
[40] V.S.V. Satyanarayana, P. Sreevani, A. Sivakumar, V. Vijayakumar, Synthesis and
antimicrobial activity of new Schiff bases containing coumarin moiety and
their spectral characterization, ARKIVOC xvii (2008) 221–233.