Microporous zeolite catalyst system: An eco-approach for regioselective synthesis of pyrimidobenzimidazoles

Article abstract of DOI:10.1007/s11164-013-1441-4

Microporous zeolite, having well-defined pore sizes, was found to be most efficient catalyst for regioselective synthesis of pyrimidobenzimidazoles. Different kinds of zeolites were studied as supported microporous material and showed quite different cata

Full text of DOI:10.1007/s11164-013-1441-4

Res Chem Intermed
DOI 10.1007/s11164-013-1441-4
Microporous zeolite catalyst system: an eco-approach
for regioselective synthesis of pyrimidobenzimidazoles
•
Kapil Arya Ravi Tomar
Received: 12 March 2013 / Accepted: 10 October 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Microporous zeolite, having well-defined pore sizes, was found to be most
efficient catalyst for regioselective synthesis of pyrimidobenzimidazoles. Different kinds
of zeolites were studied as supported microporous material and showed quite different
catalytic activities due to high acidity, excellent textural parametersm and cage-type 3D
porous structure under microwaves, and hold great promise due to excellent reusability
properties. The structure of the products was confirmed by spectral and X-ray studies.
Furthermore, the reaction was performed over a considerably shorter reaction time and
generated significantly higher yields under microwaves than by traditional methods.
Keywords Microporous materials ꢀ Zeolite ꢀ Pyrimido[1, 2-a]benzimidazole ꢀ
Regioselectivity
Introduction
Catalysts which would be useful to make organic transformations eco-friendly and
economically viable are in great demand by academic laboratories and industries
[1]. In this respect, microporous materials provide new possibilities in catalytic
organic reactions because of their several advantages, such as acidic properties,
shape-selectivity, environment friendly, easy work-up, high purity of the products,
recycling of catalysts, and decrease in waste production [2]. The last decade has
witnessed a growing interest in microporous material as catalysts in many
biologically significant organic transformations [3]. These materials are reported
to be Brønsted acid sites in the micropores and on the external surface, and Lewis
acid sites predominantly at the internal surface due to the local defects [4].
K. Arya (&) ꢀ R. Tomar
Department of Chemistry, University of Delhi, Delhi 110007, India
e-mail: aryakapil2001@yahoo.com
123

K. Arya, R. Tomar
Pyrimido[1,2-a]benzimidazoles represent core structures that are useful tem-
plates for the design of a variety of biologically active compounds [5]. The
usefulness of alkenenitrile as starting material in heterocyclic syntheses has been
amply demonstrated [6]. An extensive literature survey of the reactions of
2-aminobenzimidazole with alkenenitrile leading to the formation of pyrimido[1,2-
a]benzimidazoles indicated that there is definite need to study the detailed
mechanistic pathway and regiochemistry of the synthetic processes, and for the
development of new methods for the regioselective synthesis of these compounds
[7, 8]. Up to now, numerous data have been reported on regioselective cyclizations
of benzimidazol- 2-amine with diethyl malonate and ethyl cyanoacetate [9], 1,3-
diketones [10], 3-oxo esters, and their derivatives [11, 12], a, b-unsaturated ketones
(chalcones) [13–16], and cinnamic acid esters [17]. Initial compounds may also be
1,3-bielectrophiles having an additional electrophilic center. Such substrates could
give rise to alternative reaction pathways with the formation of various
pyrimido[1,2-a]benzimidazoles. As benzimidazol-2-amine molecule has two non-
equivalent nucleophilic centers, therefore reactions of these compounds could take
different pathways leading to different products.
Reactions under microwave irradiation [18] provide a non-conventional energy
source that has the advantages of short reaction times with high yields and
regioselectivity. Extension of our previous study on synthesis of pyrimidobenzim-
idazoles using HY zeolites [19], and our expertise in field of biodynamic
heterocycles synthesis via greener approaches [20–22], prompted us to discover
the detailed mechanistic pathways of regioselective synthesis of biologically
important scaffold pyrimido[1,2-a] benzimidazoles by reacting 2-aminobenzimid-
azole with alkenenitrile and the catalytic effect of microporous material on reaction
mechanisms (Scheme 1). The choice of microporous material plays a critical factor
in the performance of the resulting titled compounds.
Experimental
IR spectra (KBr) were recorded on a Shimadzu FT IR-8400S spectrophotometer,
and 1H NMR and 13C NMR spectra were recorded on a Bruker DRX-300, at
300.15 and 200 MHz, respectively, using CDCl3 as solvent. High-resolution mass
spectra (HRMS) were obtained on a Finnigan MAT 8200 system using sector
double focus and an electron-impact source with an ionizing voltage of 70 eV.
DIPMS (direct insertion probe mass spectrum) values are reported in m/z. The
microwave-assisted reactions were carried out in a monomode system, purchased
from CEM DISCOVER (m = 2,450 MHz, 300 W) and coupled with a micro-
computer. All anilines were purchased used as received. NaY, HUSY, HZSM-5,
HM, and Hb zeolites were obtained from Zeolyst International, Netherland. The
SiO2/Al2O3 ratio was 5.12 in NaY, 8.10 in HUSY, 50 in HZSM-5, 20 in HM,
and 30 in Hb.
123

Microporous zeolite catalyst system
R1
N
N
R1
N
NaY Zeolite
NH
NH2
MW, 5-8 min., 92-82%
R2
X
N
H
R2
1
+
+
H2N
CN
5a-d
CN
R1
X
O
N
H-Beta Zeolite
H2C
CN
MW, 4-8 min., 90-79%
NH
2
3a-c
N
R2
NH2
R1=R2= H/Me X = Carbonyl compounds
-tetralone
3a = Cyclohexanone; 3b = Cyclopentanone; 3c =
CN
X
6a-e
Scheme 1 Synthesis of pyrimidobenzimidazole derivatives
Catalyst preparation and its applications
Ce- and La-exchanged catalysts involved the treatment of zeolite NaY [31] with
aqueous cerium chloride/lanthanum chloride solution (prepared using deionized
water with pH adjusted to 5.0) at 95 °C for 8 h. After cooling to room temperature,
the exchanged catalyst was filtered and washed with water. The % of Na? exchange
was determined by the ICAP method; this procedure was repeated twice, resulting
in a maximum exchange of 72 %. The Ce (72 %) Y and La (75 %) Y zeolite was
dried at 120 °C for 4 h and crystalline structural integrity was discerned by X-ray
analysis [32].
Synthesis of 40-amino-10H-spiro [cyclopentane-1,20-(pyrimido[1,2-
a]benzimidazole)]-30-carbonitrile (5b)
Pyrex glass vial containing an equimolar (0.01 mol) mixture of 1, 2, and 3b was
mixed with NaY zeolite (2 g) and placed in a screw-capped Teflon vessel.
Microwaves were applied for 5 min at 140 °C. After the completion of the reaction
(TLC analysis), recyclable zeolite was separated by filtration after eluting the
product with ethanol under reduced pressure, and the residue was washed with
methanol to give the pure product in high yield (Table 2). Compounds 5c and 5d
were similarly prepared by the above method.
40-Amino-10H-spiro [cyclopentane-1,20-(pyrimido[1,2-a]benzimidazole)]-30-carbo-
nitrile (5b) IR (KBr): v = 3,470–3,240 (br, NH & NH2), 2,920–2,880 (br, ali.
1
CH), 2,180 (sh, C:N), 1620 (sh, C=N); H NMR (300 MHz, CDCl3): d = 1.89
(2H, m, CH2), 2.04 (2H, m,CH2), 2.33 (2H, m, CH2), 2.57 (2H,m, CH2), 5.60 (2H, s,
NH2), 7.01–7.57 (4H, m, Ar–H), 7.62 (1H, s, NH) ppm; 13C NMR (200 MHz,
123

K. Arya, R. Tomar
CDCl3): d = 20.4, 22.6, 30.8, 35.7, 58.6,, 75.8, 118.4, 122.2, 123.1, 126.1,132.2,
134.9, 139.4, 152.9, 171.5 ppm; DIPMS: m/z = 265 (M)?, 225(100); HRMS (EI):
calcd. 265.1327, found 265.1345.
70,80-Dimethyl-40-amino-10H-spiro[cyclohexane-1,20-(pyrimido[1,2-a]benzimidazole)]-
30-carbonitrile (5c) IR (KBr): v = 3,465–3,260 (br, NH & NH2), 2,940–2,870 (br,
ali. CH), 2,160 (sh, C:N), 1,615 (sh, C=N); 1H NMR (300 MHz, CDCl3):
d = 1.44 (2H, m, CH2), 1.59 (2H, m,CH2), 1.78 (4H, m, CH2), 2.32 (2H,m, CH2),
2.48 (6H, s, CH3), 5.45 (2H, s, NH2), 7.22–7.72 (4H, m, Ar–H), 7.85 (1H, s, NH)
ppm; 13C NMR (200 MHz, CDCl3): d = 19.2, 21.5, 22.8, 24.75, 32.7, 36.9, 60.2,
74.9, 115.8, 123.7, 126.9, 128.5,134.9, 138.7, 141.7, 155.6, 169.3 ppm; DIPMS: m/
z = 307 (M)?, 222(100); HRMS (EI): calcd. 307.180, found 307.260.
70,8040-Amino-10H-spiro
[cyclopentane-1,20-(pyrimido[1,2-a]benzimidazole)]-30-
carbonitrile (5d) IR (KBr): v = 3,480–3,260 (br, NH & NH2), 2,930–2,840 (br,
ali. CH), 2,170 (sh, C:N), 1,610 (sh, C=N); 1H NMR (300 MHz, CDCl3):
d = 1.82 (2H, m, CH2), 2.07 (2H, m,CH2), 2.21 (6H, s, CH3), 2.38 (2H, m, CH2),
2.64 (2H,m, CH2), 5.65 (2H, s, NH2), 7.15–7.72 (4H, m, Ar–H), 7.84 (1H, s, NH)
ppm; 13C NMR (200 MHz, CDCl3): d = 19.8, 23.2, 29.7, 34.6, 60.2, 74.6, 117.3,
121.6, 124.2, 127.5,131.3, 135.7, 142.1, 150.9, 172.7 ppm; DIPMS: m/z = 293
(M)?, 215(100); HRMS (EI): calcd. 293.366, found 293.356.
70-Amino-80H-spiro[cyclohexane-1,50-pyrimido[1,2-a]benzimidazole]-
60-carbonitrile(6a)
A Pyrex glass vial containing an equimolar (0.01 mol) mixture of 1, 2, and 3a was
mixed with Hb zeolite (2 g) and placed in a screw-capped Teflon vessel. Microwave
irradiation was applied for 4 min at 140 °C. After the completion of reaction (TLC
analysis), recyclable zeolite was separated by filtration after eluting the product with
ethanol under reduced pressure, and the residue was washed with methanol to give
pure product in high yield (Table 2). Compounds 6d and 6e were similarly prepared
by the above method and confirmed by spectroscopic methods.
70-Amino-80H-spiro[cyclohexane-1,50-pyrimido[1,2-a]benzimidazole]-60-carbonitrile
(6a) IR (KBr): v = 3,360–3,140 (br, NH & NH2), 2,910–2,870 (br, ali. CH), 2,170
(sh, C:N), 1,640 (sh, C=N) cm-1; 1H NMR (300 MHz, CDCl3): d = 1.75 (2H, m,
CH2), 1.87 (2H, m, CH2), 2.09 (2H, m, CH2), 2.33 (2H, m, CH2), 2.45 (2H, m, CH2),
5.70(2H, s, NH2), 7.30–7.85 (4H, m, Ar–H), 7.88 (1H, s, NH) ppm; 13C NMR
(200 MHz, CDCl3): d = 20.3, 22.5, 29.5, 32.6, 35.6, 51.5, 70.7, 117.5, 118.9, 125.7,
130.9, 134.7, 138.4, 141.6, 147.8, 169.4 ppm; DIPMS: m/z = 279 (M)?, 236(100);
HRMS (EI): calcd. 279.1484, found 279.1495.
70-Amino-80H-spiro[cyclopentane-1,50-pyrimido[1,2-a]benzimidazole]-60-carbonitrile
(6b) IR (KBr): v = 3,370–3,160 (br, NH & NH2), 2,940–2,860 (br, ali. CH), 2,160
(sh, C:N), 1,650 (sh, C=N) cm-1; 1H NMR (300 MHz, CDCl3): d = 1.72 (2H, m,
123

Microporous zeolite catalyst system
CH2), 1.84 (2H, m, CH2), 2.25 (2H, m, CH2), 2.48 (2H, m, CH2), 5.55(2H, s, NH2),
7.20–7.67 (4H, m, Ar–H), 7.95 (1H, s, NH) ppm; 13C NMR (200 MHz, CDCl3):
d = 21.2, 23.7, 28.5, 31.8, 38.9, 55.2, 74.7, 114.9, 119.7, 128.4, 131.9, 133.1, 140.4,
145.3, 150.4, 172.0 ppm; DIPMS: m/z = 265 (M)?, 210(100); HRMS (EI): calcd.
265.133, found 265.154.
20,30-Dimethyl-70-amino-80H-spiro[cyclohexane-1,50-pyrimido[1,2-a]benzimidazole]-
60-carbonitrile (6c) IR (KBr): v = 3,380–3,140 (br, NH & NH2), 2,920–2,850 (br,
1
ali. CH), 2,190 (sh, C:N), 1,630 (sh, C=N) cm-1; H NMR (300 MHz, CDCl3):
d = 1.80 (2H, m, CH2), 1.84 (2H, m, CH2), 2.05 (2H, m, CH2), 2.15 (6H, s, CH3),
2.38 (2H, m, CH2), 2.50 (2H, m, CH2), 5.67 (2H, s, NH2), 7.28-7.92 (4H, m, Ar–H),
8.02 (1H, s, NH) ppm; 13C NMR (200 MHz, CDCl3): d = 19.6, 21.8, 23.7, 25.5,
30.8, 33.7, 38.9, 54.2, 72.3, 115.8, 119.7, 124.9, 131.7, 136.2, 139.1, 143.2, 150.3,
170.2 ppm; DIPMS: m/z = 307 (M)?, 225(100); HRMS (EI): calcd. 307.180, found
307.224.
20,30-Dimethyl-70-amino-80H-spiro[cyclopentane-1,50-pyrimido[1,2-a]benzimidazole]-
60-carbonitrile (6d) IR (KBr): v = 3,365–3,155 (br, NH & NH2), 2,950–2,870 (br,
1
ali. CH), 2,165 (sh, C:N), 1,630 (sh, C=N) cm-1; H NMR (300 MHz, CDCl3):
d = 1.70 (2H, m, CH2), 1.89 (2H, m, CH2), 2.12 (6H, s, CH3), 2.28 (2H, m, CH2),
2.41 (2H, m, CH2), 5.62(2H, s, NH2), 7.07–7.65 (4H, m, Ar–H), 7.90 (1H, s, NH)
ppm; 13C NMR (200 MHz, CDCl3): d = 19.1, 21.8, 22.9, 30.2, 34.7, 40.5, 58.3,
72.3, 115.9, 120.4, 127.3, 131.2, 135.7, 138.5, 144.1, 152.9, 169.2 ppm; DIPMS: m/
z = 293 (M)?, 195(100); HRMS (EI): calcd. 293.366, found 293.375.
Results and discussion
In our study, we assumed two different possible pathways for the reaction of
aminobenzimidazoles 1 with alkenenitrile depending on the reaction medium
(Scheme 1). In the conventional manner, malononitrile 2 was treated with
aminobenzimidazoles 1 and carbonyl compounds 3 under reflux in N,N-
dimethylformamide/ethanol or triethyamine and gave different products [23].
However, in microwave irradiation, 2-aminobenzimidazole reacts with alkenenitrile
in the presence of microporous zeolite and gave 70-amino-80H-spiro[cyclohexane-
1,50-pyrimido[1,2-a]benzimidazole]-60-carbonitrile (6), and 40-amino-10H-spiro
[cyclohexane-1,20-(pyrimido[1,2-a]benzimidazole)]-30-carbonitrile (5) in quantita-
tive yield (Scheme 1).
The reaction of 1 with alkenenitrile may proceed by two possible mechanistic
pathways (Schemes 2 or 3) depending on whether the initial attack of the
alkenenitrile is by ring nitrogen (Scheme 2) or by the nitrogen of the side chain
(Scheme 3), to give the isomeric pyrimidobenzimidazoles 5 or 6.
In order to distinguish between the isomeric pyrimidobenzimidazoles 5 and 6, 1H
nuclear Overhauser effect (NOE) experiments [24, 25] were used. Enhancement of
the H-6 signal (26 %) was observed when the C-11 methylene proton was irradiated
123

K. Arya, R. Tomar
H
R1
R2
R2
R1
O
N
H
N
N H
N
N H
+
H
3a
C N
C N
N
+
C
C H
C N
C N
N C
C N
H2C
4a
1
2
7a
R1
R2
10
N
9
R1
N
8
1
N H2
N H
H
N
C
N
2
R2
5
7
5a
N
N H2
H
6
4
C
H
3
H
C N
11
15
12
C N
NOE
14
13
8a
6a
Scheme 2 Plausible mechanism of pyrimidobenzimidazole synthesis using Hb zeolite
H
R1
N
H
NH
R2
O
N
N
Δ, (C2H5)3N
50 hrs
R2
H
N
H
C
Δ, (C2H5)3N
3a
NC
N
H
+
C
18 hrs
R1
NC
CN
CN
CN
NC
H2C
9a
4a
2
MW
NaY zeolite
5-8 min.
72hrs
Δ, (C2H5)3N
R1
N
R1
N
NH
NH
N
R2
N
R2
H
HN
H
NC
H2N
CN
8a
5a
Scheme 3 Plausible mechanism of pyrimidobenzimidazole synthesis using NaY zeolite
in compound 6a, whereas irradiation of H-6 induced enhancement of H-7 (23 %)
and H-11 (20 %) signals, thus indicating that H-6 and H-12 protons are in close
spatial proximity, further confirming the formation of 6a. The NOE experiment also
permitted the unambiguous assignment of all the proton signals in structure 6a.
X-ray study of the reaction products from the reaction of 2-aminobenzimidazoles
123

Microporous zeolite catalyst system
and dimethyl allene-1,3-dicarboxylate [26] have proved that the product obtained
results from the attack of the alkene by the ring nitrogen in the case of Hb zeolite.
In NaY zeolite, the base protected ring nitrogen was not available to attack the
alkenenitrile, so the side chain nitrogen attacked, yielding 5, and no enhancement of
the signal was observed in NOE. This involves the condensation of the carbonyl
compound with active methylene reagent to afford the corresponding alkenenitrile
(4) followed by the addition of exocyclic amino function of 2-aminobenzimidazole
to the activated double bond system in 9 to form Michael adduct (10) which
undergoes intramolecular cyclization to give 5.
In continuation, we can also assume that acidic zeolites (having smaller pores
compared to Y-zeolites) do not absorb 2-aminobenzimidazole in their cavities but
rather it stays adsorbed on the surface where condensation takes place. The overall
reaction facilitation instead arises from fast acid-catalyzed condensation of the
ketones with malononitrile to form the Michael acceptor. On the other hand, with
basic zeolites (NaY zeolite), it seems that 2-aminobenzimidazole enters the pores
through a cation–pi interaction-driven orientation, and thus the primary amine more
likely stays out of the cavity and reacts, giving products such as 5. X-ray analysis of
the product of multi-component reaction of 1, 2, and 3 has proved the structure 5
[19]. The assignment of structures 5 and 6 obtained in this work is thus conclusively
confirmed.
Five kinds of zeolites were studied, and the results are listed in Table 1. It can be
observed that both low conversion and selectivity was obtained when the catalyst
was not employed in the reaction mixture. However, they can be improved by using
these zeolites. Finally, in order to check the possible catalytic effects of the zeolites,
in the case of compound 5a, an experiment was also tried under neat conditions with
or without microwaves, giving lower conversion to the product under microwave
irradiation, while in neat condition only traces of the product showed the catalytic
effect of the zeolite (Table 1, Entries 23, 24).
In order to check the possible intervention of ‘a specific (non-thermal)
microwave effect’, the best result obtained under microwave irradiation was
extrapolated to conventional heating. In the case of compounds 6a and 5a (Table 1),
the reaction was carried out using a preheated oil bath under the same reaction
conditions (time, temperature, pressure, and vessel). It was found that no reaction
occurred and that the reactants remain unchanged. After an extended reaction time
(up to 5 h), the product was obtained in low yield demonstrating that the effect of
microwaves is not simply thermal.
As shown in Table 1, Hb exhibited a high conversion while HM showed a low
conversion under microwave irradiation. The percentages of conversion and
selectivity for the target product 6 could be arranged in the order Hb [ HZSM-
5 [ HUSY [ HY [ HM. Basic zeolites selectivity of the targeted product was
NaY [ CeY [ LaY, since the number and strength of acid sites in zeolite increase
with metal cation exchanged in the order of H? \ Na? \ Ce2 \ La3? [27]. Such
results could be explained by the differences of the zeolite channel structures and
acidic properties, while in case of neat conditions (Entry 24), the product gave
higher yield compared to LaY (Entry 22) zeolite under MW irradiation which can
123

K. Arya, R. Tomar
Table 1 Effect of various zeolite and reaction method on synthesis of pyrimidobenzimidazole
Entry
Compound
no.
Reaction
conditions
Method
Time
(min.)
Temp.
(°C)
Yield (%)a
1b
6a
Hb
D
600
4
R.T.
140
140
140
R.T.
140
R.T.
140
R.T.
140
R.T.
140
R.T.
140
140
140
R.T.
140
140
140
R.T.
140
R.T.
140
70
2
3c
4d
5b
MW
D
86
4
No reaction
D
280
720
15
42
6a
6a
6a
6a
5a
HUSY
HY
D
45
6
7b
MW
D
68
1200
18
38
8
9b
MW
D
64
HM
1080
20
47
10
11b
12
13b
14
15c
16d
17b
18
19c
20d
21b
22
23b
24
a
MW
D
55
HZSM-5
NaY
720
7
58
MW
D
72
900
6
64
MW
D
88
6
Trace
D
240
1080
10
48
5a
CeY
D
45
MW
D
68
10
Trace
D
220
1320
15
42
5a
5a
LaY
Neat
D
Mixture of products
MW
D
40
1440
8
Trace of products
45
MW
Isolated yield
b
Compound 6a prepared using DMF/ethanol as reaction medium, while 5a was synthesized using
triethylamine as reaction medium
c
Thermal reaction using a preheated oil bath under the same reaction conditions (time, temperature,
pressure, and vessel) as microwaves
d
Yield of desired product after extended reaction time at same reaction temperature and vessel as
microwaves using preheated oil bath
be explained by possible destruction of the LaY zeolite structure under microwaves
due to low hydrothermal stability [28].
The NH3-TPD profiles (Figs. 1, 2) showed that the acidic properties of zeolites
were quite different, and the conversion and selectivity by the six kinds of zeolites
were not well related to either their total acidities or their distributions of acid
strength. An assumption would therefore be proposed that not only the acidic
properties but also the pore structures of zeolites would play roles in the reaction.
The total acidities of HZSM-5 and Hb, both having a higher SiO2/Al2O3 ratio, were
123

Microporous zeolite catalyst system
Fig. 1 NH3-TPD profile of
NaY zeolite
Fig. 2 NH3-TPD profile of
zeolites
very close. The reason would be that the pore mouth of HZSM-5 (0.51–0.56 nm)
would hinder the reactants (aminobenzimidazoles and alkenenitrile, size larger than
0.7 nm) from entering the interior of the zeolites. So catalysis would mainly take
place at exterior surface acid sites, and the acid sites at the mouth of the pores
resulted in the lowest conversion.
Since both the nature of the acid sites and the pore structures affect the catalytic
performance of the zeolites, it could be deduced that the suitable pore mouth size
(0.72 9 0.62 nm) and expedited tridirectional structure of H-beta zeolite may
account for the catalytic activity. However, the HY and HUSY zeolites possessing
tridirectional large pores (0.75 nm) with a large cavity of 1.3 nm did not exhibit any
catalytic activity under the above conditions, which could be due to the incongruous
nature of their acid sites. Figure 1 presents the NH3-TPD results of these five
zeolites and shows that H-beta and HZSM-5 zeolites, which possess less total acid
amounts considering their high SiO2/Al2O3 ratios, reveal similar desorption profiles.
Excessive strong acid sites on the HM, HY, and HUSY zeolites would chemisorb
123

K. Arya, R. Tomar
Table 2 Physical data of synthesized compounds
Cmpd
no.
R1
R2
Carbonyl
compound (X)
Reaction
medium
Time
(min.)
M.P.
(oC)
Yield
(%)
5a
5b
5c
5d
6a
6b
6c
6d
6e
H
H
3a: Cyclohexanone
3b: Cyclopentanone
3a: Cyclohexanone
3b: Cyclopentanone
3a: Cyclohexanone
3b: Cyclopentanone
3a: Cyclohexanone
3b: Cyclopentanone
3c: a-Tetralone
NaY Zeolite
6
5
5
8
4
4
8
6
7
240 [13]
170
88
92
85
82
86
90
82
84
79
H
H
NaY Zeolite
CH3
CH3
H
CH3
CH3
H
NaY Zeolite
205
NaY Zeolite
225
H-Beta Zeolite
H-Beta Zeolite
H-Beta Zeolite
H-Beta Zeolite
H-Beta Zeolite
285
H
H
296
CH3
CH3
H
CH3
CH3
H
272
340
325
100
90
80
70
60
50
40
30
20
10
0
Fig. 3 Recyclability of the Hb
catalyst (Entry 2, Table 1)
1
2
3
4
5
Number of cycles
reactants and corresponding complex compounds intensively, then deactivate
rapidly [29, 30].
In the case of basic zeolite, it was found that more basic NaY zeolite provided a
higher yield compared with CeY and LaY zeolites (Table 1, Entries 12, 14, 16).
Since the number and strength of acid sites increases with metal cation exchange in
the order Na? \ Ce2? \ La3?, the decreases in yield in this order suggests that
basic sites on zeolites work as active sites for this reaction. The physical data of all
synthesized compounds are summarized in Table 2.
The economic point of view, the stability, and the sustained activity of the
catalyst are of great importance. Thus, the recovery and reusability of catalyst was
investigated. The recyclability of the catalyst in the reaction of 2-aminobenzim-
idazole and alkenenitrile in the presence of Hb zeolite was checked (Table 1, Entry
2) and had no loss of its activity after washing five times with methanol and drying
at 200 °C (Fig. 3).
123

Microporous zeolite catalyst system
Conclusion
In conclusion, we have demonstrated that Hb and NaY zeolites are a new efficient and
green catalyst for regioselective synthesis of pyrimidobenzimidazole under greener
methodologies. The suggested procedure using microporous materials offers
remarkable advantages like: inexpensive catalyst, non-toxic, easy handling and
reusable, simple work-up procedure, short reaction time, high yields of regioselective
product, and with better purity and green aspect by avoiding toxic catalysts and
hazardous solvents under microwaves. The suggested synthetic technology using
microporous zeolite based on environmentally friendly zeolite catalysts coupled with
microwaves could, therefore, replace the conventional corrosive and polluting acid
catalysts in the one-pot synthesis of pyrimidobenzimidazoles.
Acknowledgments K.A. acknowledges the D.S.T. (SR/FT/CS-69/2013), New Delhi, India and the
University of Delhi, Delhi, India for financial support.
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