Grinding solvent-free paal-knorr pyrrole synthesis on smectites as recyclable and green catalysts

Article abstract of DOI:10.4314/bcse.v32i1.13

An environmentally benign method for the synthesis of N-substituted pyrroles from one-pot solvent-free condensation reaction of 2,5-hexanedione with various primary amines (Paal-Knorr pyrrole synthesis) on smectite clays as green and reusable heterogeneous Lewis acid catalysts is presented. The use of nontoxic, inexpensive, easily available and reusable catalysts under solvent-free conditions make this protocol practical, environmentally friendly and economically attractive.

Full text of DOI:10.4314/bcse.v32i1.13

Bull. Chem. Soc. Ethiop. 2018, 32(1), 139-147.
 2018 Chemical Society of Ethiopia and The Authors
DOI: https://dx.doi.org/10.4314/bcse.v32i1.13
ISSN 1011-3924
Printed in Ethiopia
GRINDING SOLVENT-FREE PAAL-KNORR PYRROLE SYNTHESIS ON
SMECTITES AS RECYCLABLE AND GREEN CATALYSTS
Omid Marvi* and Hossein Taherpour Nahzomi
Department of Chemistry, Payam Noor University, PO Box 19395-3697 Tehran, Iran
(Received September 3, 2017; Revised January 23, 2018; Accepted January 31, 2018)
ABSTRACT. An environmentally benign method for the synthesis of N-substituted pyrroles from one-pot
solvent-free condensation reaction of 2,5-hexanedione with various primary amines (Paal-Knorr pyrrole synthesis)
on smectite clays as green and reusable heterogeneous Lewis acid catalysts is presented. The use of nontoxic,
inexpensive, easily available and reusable catalysts under solvent-free conditions make this protocol practical,
environmentally friendly and economically attractive.
KEY WORDS: Paal-Knorr, Smectites, Pyrrole, Solvent-free, Grinding
INTRODUCTION
Paal–Knorr condensation has experienced a rekindled interest in the synthetic chemistry for
preparation of pyrrole, pyrazoles, and their derivatives, as important heterocyclic compounds
displaying remarkable pharmacological properties such as antibacterial, antiviral, anti-
inflammatory, antitumoral, and antioxidant activities [1]. The pyrrole moiety is found in many
naturally occurring compounds such as heme, chlorophyll, and vitamin B12 [2]. Pyrroles are also
present in various bioactive drug molecules such as atorvastatin, antiinflammatoryand antitumor
agents, and immunosuppressants [3, 4].
This reaction remains one of the most significant and simple methods which consists the
cyclocondensation of primary amines with 1,4-dicarbonyl compounds to produce N-substituted
pyrroles. Several catalysts have been used to promote this reaction including HCl [5a], p-TSA
[5b], H2SO4 [5c], Sc(OTf)3 [5d], Bi(NO3)35H2O [5e], SnCl2 2H2O [5f], Ti(OiPr)4 [5g], RuCl3
[5h], InCl3, InBr3, In(OTf)3 [5i], zeolite [5j], Al2O3 [5k], MgI2 etherate [5l], ZrOCl2.8H2O [5m],
ZrCl4 [5n], montmorillonite K10 [6a], silica sulfuric acid [6b], layered zirconium phosphate and
phosphonate [6c], Fe3+-montmorillonite [6d], montmorillonite KSF-clay and I2 [6e].
Additionally, the above cyclocondensation process could proceed in ionic liquid [6f] or
ultrasonic and microwave irradiation [6g].
Many of these procedures involve the use of expensive reagents, metal triflates, and
extended reaction times and produce a huge amount of corrosive, toxic waste products and
tedious workup and the use of extra energy source, such as high-power microwave irradiation or
ultrasound. So, a milder, nonhazardous, recyclable, and ecofriendly organic catalyst is still in
demand [7].
Natural alumosilicates, such as zeolites and clays, are solid acids that could act as an
efficient alternative to liquid acids. Natural and modified clays have attracted attention due to
their extremely versatile properties and high potential in green chemistry [8]. Many clay based
catalysts such as K-10 and KSF montmorillonites, hectorite, bentonite, kaolin, envirocat, etc. are
commercially available and two most common clays applied in organic synthesis are K-10 and
KSF clays. Though the physicochemical properties of the clays are similar their BET surface
areas differ.
__________
*Corresponding author. E-mail: marviomid@yahoo.com
This work is licensed under the Creative Commons Attribution 4.0 International License

140
Omid Marvi1 and Hossein Taherpour Nahzomi
In continuation of ongoing investigations exploring the use of solid supports in organic
synthesis [9], this paper reports a simple, efficient, inexpensive and solvent free procedure for
the Paal-Knorr synthesis of N-substituted pyrroles on smectite clays as efficient heterogeneous,
green and recyclable catalysts employing grindstone technique (Scheme 1). The solid clays can
be recovered later and reused in the subsequent reactions. Details of recyclability of the
recovered solid clays have been shown in the Table 1.
(1-16) a
Scheme 1. Solvent-free grinding synthesis of N-substituted pyrroles on smectites.
Table 1. The yields and reaction times for smectite supported solvent-free grinding Paal–Knorr synthesis of
N-substituted pyrroles.
Yield*, %
Time, min
Entry Amine
Product
KSF/ Bentonite
Hectorite/ K10
KSF/ Bentonite
Hectorite/ K10
96(93)/98(96)
95(92)/94(92)
3/2
4/4
1
1a
95(91)/98(95)
96(92)/96(94)
4/2
3/3
2
3
4
5
6
2a
3a
4a
5a
6a
97(94)/98(95)
93(90)/93(92)
3/2
3/4
97(93)/98(94)
94(92)/97(92)
4/3
3/4
98(96)/98(95)
95(92)/96(93)
4/3
5/4
95(91)/98(95)
93(90)/94(91)
4/3
4/4
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Paal-Knorr pyrrole synthesis on smectites as recyclable and green catalysts
141
96(93)/98(95)
94(92)/95(92)
4/2
3/4
7
8
7a
8a
96(92)/97(95)
93(85)/94(92)
4/3
4/5
93(89)/94(91)
91(87)/92(88)
5/5
5/6
9
9a
92(88)/95(92)
90(85)/90(86)
5/4
5/5
10
11
12
13
14
10a
11a
12a
13a
14a
5/3
4/5
91(89)/93(89)
89(86)/90(87)
94(88)/95(90)
88(84)/91(86)
5/3
5/5
90(86)/93(87)
89(85)/89(83)
4/2
3/4
95(91)/98(95)
90(88)/90(84)
5/4
5/5
95(91)/97(95)
90(88)/94(93)
5/3
5/4
15
16
15a
16a
92(87)/95(90)
91(90)/94(89)
4/2
3/3
*Isolated yields after recrystallization. The yields indicated in the parenthesis correspond to those reactions
which the recovered clays were used (1st run).
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Omid Marvi1 and Hossein Taherpour Nahzomi
RESULTS AND DISCUSSION
The clay supported grinding synthesis of N-substituted pyrroles were through the reaction of
hexane-2,5-dione with primary amines (Scheme 1) under solvent-free conditions. Results
summarized in the Table 1 indicate the scope and generality of the reaction with respect to the
various primary amines. The nature of the substituents on the aromatic ring of primary amines
has different influences. The presence of the electron donating groups such as methyl and ethyl
give high yields of products compared to aniline (entries 4a, 5a and 6a).
The catalysts studied were smectite-type laminar silicates. The structure of an elementary
sheet of these materials consists of an octahedral layer of Al[O4(OH)2] (for montmorillonites
KSF, K-10, and bentonite) or Mg[O4(OH)2] (for hectorite) sandwiched between two tetrahedral
layers of SiO4 tetrahedral. The total concentration of acid sites on the catalyst surface was
determined by NH3 adsorption [10a] and the surface area by the BET method [10b]. The key
factor for the reaction is the acidity of the clay, while the surface area seems to play a less
important role. Indeed, all clays display activity in the reaction, but of all the catalysts
examined, the bentonite, which shows the greatest overall acidity, is the most efficient catalyst
[11]. Chemical composition, surface area and surface acidity of the applied clays are shown in
Table 2. In this method, the reaction time has been shortened and the synthesis of these
compounds has the feature of rapid reaction, convenient operation, high yield, and clean. The
use of the solid clay catalyst in this method offers high yields of products compared to
conventional procedures. From the other advantages of our method is the recyclability of solid
clay. The used clay catalysts in the first cycle were recovered by filtration, washed with
methanol and reused.
Table 2. Chemical composition, surface area and surface acidity of applied smectites.
Surface
Surface acidity SiO2
Al2O3
(%)
Fe2O3
(%)
CaO
(%)
MgO Na2O K2O
Clay
area (m2/g) (meq. H+/g)
(%)
(%)
(%)
(%)
KSF Clay
K-10 Clay 200±10
Bentonite 205 ± 10
15±10
0.70
0.65
0.77
0.21
54.0
73.0
70.9
34.7
17.0
14.0
20.1
0.7
5.2
2.7
0.2
1.5
0.2
1.2
2.5
1.1
2.5
0.4
0.6
0.4
1.3
1.5
1.9
0.5
0.1
Hectorite
63 ± 10
0.3(FeO) 23.4
15.3
Scheme 2. Possible mechanism for smectite supported grinding solvent-free synthesis of N-
substituted pyrroles.
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Paal-Knorr pyrrole synthesis on smectites as recyclable and green catalysts
143
Reusability of the catalyst
The feasibility of repeated use of smectite clay was also examined. Recovery of the catalyyst was
very easy. After completion
o
f the reaction and extraction of the product, smectite clay was
filtered and washed with et
h
temperature. The catalyst is innsoluble in ethanol and was simply filtered. The recycled c
was washed with ethanol onc
more, filtered off and dried at 100 oC for 1 h. The reused c
n conditions, and its activity in terms of yields was s
umber of reaction cycles. Hence, the loss of catalytic activvity for
aatalyst
ee
aatalyst
was stable under the reacti
decreased with an increasing
o
n
o
llightly
reused catalyst one after five cycles was negligible. Recyclability of the bentonite smectite for
the synthesis of 1-phenyl-2,5-dimethyl-1H-pyrrole (1a) for five runs is shown in Figure 1.
998
96
94
92
91
100
80
60
40
20
0
Figure 1. Recyclability of the
bb
entonite for the synthesis of 1a.
EXPERIMENTAL
Chemicals were purchased f
r
r
om Aldrich and Merck chemical companies and used
wwithout
further purification. Commer
ccially available heterogeneous clays, montmorillonites KSSF and
K10 (Fluka), hectorite [SHCa-118 (Clay Source)] and bentonite [Bieliaca (Rudex)] were tested
in this method.
Melting points were meas
u
u
red on an Electro thermal 9100 apparatus. 1H NMR spectr
a
a
were
were
recorded by a FTNMR Brukerr DRX 500 Avence spectrometer (500 MHz). Chemical shiftss
measured in ppm from TMS.
CDCl3 was used as solvent as well as the internal standard. TThe IR
spectra were recorded on a Perrkin Elmer FT-IR GX instrument in KBr discs.
General procedure
2,5-hexanedione (10 mmol)
for 2 min. Amine (10 mmol) was added to this mixture and grinding was continued att room
temperature for the time pres nted in Table 1 to complete the reaction (monitored by T C, n-
hexane/ ethyl acetate, 1/3). Af er completing the reaction the product was extracted with CCH2Cl2
aand 1 g smectiteclaywas ground together in a mortar using pestle
ee
LL
t
t
(2×15 mL) and the clay filtereed off. The organic layer after washing with water, was driedd over
MgSO4, filtered and the solvvent was evaporated under vacuum to afford the product. The
products were isolated as low melting crystals or oils.The solid pyrroleswerewashed thor ughly
o
with water, dried, and then r crystallized from methanol. The oily products were purifiied by
e
e
column chromatography using hexane and ethyl acetate as the eluent. The solid clay portion was
washed with ethanol and drried at 100 °C under a reduced pressure to be reused in the
subsequent reactions which showed the gradual decrease in the activity (Table 1). Issolated
Bull. Chem. Soc. Ethiop. 2018, 32(1)

144
Omid Marvi1 and Hossein Taherpour Nahzomi
1
products were characterized by the melting points, IR, H NMR spectrometric data and were
compared with the literature or authentic samples.
1-Phenyl-2,5-dimethyl-1H-pyrrole (1a). M.p. 52-54 oC (reported m.p. 50–51 oC [12a]);
νmax/cm−1 3051, 2925, 1609, 1527, 1488, 1412, 1318; δH (500 MHz, CDCl3): 2.09 (s, 6H, CH3),
5.69 (s, 2H, pyrrole ring), 7.13–7.29 (2H, m, Ar H), 7.45–7.53 (3H, m, ArH).
1-Benzyl-2,5-dimethyl-1H-pyrrole (2a). Oily solid (reported m.p. 40–41 oC [6d]; νmax/cm−1 3059,
2928, 2849, 1568, 1522, 1493, 1401, 1323; δH (500 MHz, CDCl3): 2.11 (6H, s, CH3), 4.98 (2H,
s, CH2),5.93 (2H, s, pyrrole ring), 6.88–6.94 (2H, m, Ar H),7.25–7.39 (3H, m, Ar H).
1-(2-Phenylethyl)-2,5-dimethyl-1H-pyrrole (3a). Oil (reported as oil [12b]); δH (500 MHz,
CDCl3): 2.31 (6H, s, CH3), 3.12 (t, J = 7.5 Hz, 2H), 4.18 (t, J = 7.5 Hz, 2H), 5.95 (2H, s, pyrrole
ring), 6.81–6.88 (2H, m, Ar H), 7.42–7.50 (3H, m, Ar H).
1-(p-Tolyl)-2,5-dimethyl-1H-pyrrole (4a): Oil (reported as oil [12b]); δH (500 MHz, CDCl3):
2.23 (6H, s, CH3), 2.34 (3H, s, CH3), 5.87 (2H, s, pyrrole ring), 6.69 (d, J = 9 Hz, 2H), 7.31 (d, J
= 9.0 Hz, 2H).
1-(p-Ethylphenyl)-2,5-dimethyl-1H-pyrrole (5a). Oil (reported as oil [12b]); δH (500 MHz,
CDCl3): 2.10 (6H, s, CH3), 2.72 (q, J = 7.5 Hz, 2H), 5.90 (s, 2H, pyrrole ring), 1.35 (t, J = 7.5
Hz, 3H); 7.19 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.8 Hz, 2H).
1-(m-Tolyl)-2,5-dimethyl-1H-pyrrole (6a). Oil (reported as oil [12b]); δH (500 MHz, CDCl3):
2.09 (6H, s, CH3), 2.37 (3H, s, CH3), 5.85 (2H, s, pyrrole ring), 7.02-7.29 (m, 4H, Ar).
1-Butyl-2,5-dimethyl-1H-pyrrole (7a). Oil (reported as oil [12b]); δH (500 MHz, CDCl3): 0.91 (t,
J = 7.2 Hz, 3H), 1.32 (m, 2H), 1.65 (m, 2H), 2.21 (s, 6H, CH3), 3.71 (t, J = 7.2 Hz, 2H), 5.86 (s,
2H, pyrrole ring).
1-Propyl-2,5-dimethyl-1H-pyrrole (8a). Oil (reported as oil [12b]); νmax/cm−1 3100, 2965, 2932,
2875, 1519, 1348, δH (500 MHz, CDCl3): 1.02 (t, J = 7.4 Hz, 3H), 1.65 (m, 2H), 2.34 (s, 6H,
CH3), 3.78 (t, J = 7.5 Hz, 2H), 5.83 (s, 2H, pyrrole ring).
o
o
1-(4-Nitrophenyl)-2,5-dimethyl-1H-pyrrole (9a). M.p. 145-147 C (reported m.p. 143–144 C,
[12b]); δH (500 MHz, CDCl3): 2.12 (s, 6H), 5.96 (s, 2H, pyrrole ring), 6.92 (d, J = 8.7 Hz, 2H,
Ar), 7.74 (d, J = 8.7 Hz, 2H, Ar).
1-(4-Fluorophenyl)-2,5-dimethyl-1H-pyrrole (10a). Oil (reported as oil [12b]); δH (500 MHz,
CDCl3): 2.01 (s, 6H, CH3); 5.88 (s, 2H, pyrrole ring), 7.17 (d, J = 9.0 Hz, 2H, Ar), 7.31(d, J =
9.0 Hz, 2H, Ar).
o
1-(4-Chlorophenyl)-2,5-dimethyl-1H-pyrrole (11a). M.p. 77-79 C (reported m.p. 75 oC, [12b]);
δH (500 MHz, CDCl3): 2.07 (s, 6H, CH3); 5.64 (s, 2H, pyrrole ring), 7.19 (d, J = 8.8 Hz, 2H,
Ar), 7.68 (d, J = 8.8 Hz, 2H, Ar).
o
1-(4-Bromophenyl)-2,5-dimethyl-1H-pyrrole (12a). M.p. 75-77 C (reported m.p. 75 oC, [12b]);
δH (500 MHz, CDCl3): 2.05 (s, 6H, CH3); 5.73 (s, 2H, pyrrole ring), 7.15 (d, J = 8.8 Hz, 2H,
Ar), 7.71 (d, J = 8.8 Hz, 2H, Ar).
o
o
1-(4-Methoxyphenyl)-2,5-dimethyl-1H-pyrrole (13a). M.p. 60-63 C (reported m.p. 59–60 C,
[11]); δH (500 MHz, CDCl3): 1.98 (s, 6H, CH3); 3.82 (OCH3, s, 3H), 5.81 (s, 2H, pyrrole ring),
6.92 (d, J = 8.5 Hz, 2H, Ar), 7.24 (d, J = 8.5 Hz, 2H, Ar).
Bull. Chem. Soc. Ethiop. 2018, 32(1)

Paal-Knorr pyrrole synthesis on smectites as recyclable and green catalysts
145
2-(2,5-Dimethyl-1H-pyrrol-1-yl) pyridine (14a). Oil (reported as oil [12b]); δH (500 MHz,
CDCl3): 2.08 (s, 6H, CH3),5.91(s, 2H, pyrrole ring), 7.25-7.38 (Ar, m, 2H), 7.73-7.86(Ar, m,
1H), 8.68-8.75 (Ar, m, 1H).
o
1-(Naphthalene-1-yl)-2,5-Dimethy-1H-pyrrole (15a). M.p. 123-126 C (reported m.p. 120–121
oC, reported [12b]); δH (500 MHz, CDCl3): 1.95 (s, 6H, CH3), 6.12 (s, 2H, pyrrole ring), 7.18
(d, J = 8.6 Hz, 1H, Ar), 7.30–7.48 (m, 4H, Ar), 7.91 (d, J = 8.6 Hz, 2H, Ar).
o
1-(4-Methylbenzyl)-2,5-dimethyl-1H-pyrrole (16a). M.p. 48-50 C (reported m.p. 44–47 oC,
[12b]); δH (500 MHz, CDCl3): 2.08 (s, 6H, CH3), 2.41 (CH3, s, 3H), 4.98 (s, 2H, CH2, benzylic),
5.94 (s, 2H, pyrrole ring), 6.95 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H).
CONCLUSION
In conclusion, a simple and efficient procedure for the synthesis of N-substituted pyrroles was
established. This present method is superior since it is eco-friendly, advantageous over
previously described methods in yield, requires no special apparatus, there is simplicity of
operation, and is non-hazardous, simple and convenient. In addition, the simple experimental
and product isolation procedures combined with the easy recovery and reuse of these
worthwhile natural smectite clays play an important role in development of the clean and
environmentally friendly strategy in this new and benign method.
ACKNOWLEDGEMENT
The authors thank Roodsar Payam Noor University for financial support.
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