An efficient and green synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines using highly active and stable poly acrylic acid-supported layered double hydroxides

Article abstract of DOI:10.1016/j.tet.2017.01.037

A facile and efficient method for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines has been achieved via highly active and reusable heterogeneous poly acrylic acid-supported layered double hydroxides (PAA-g-LDHs) catalyst promoted one-pot reaction of 1H-benzo[d]imidazol-2-amine, with α,β-unsaturated carbonyl compounds under solvent-free conditions. PAA-g-LDHs catalyst was successfully synthesized via reversible addition-fragmentation chain-transfer polymerization using grafting reaction and was characterized by different analytical techniques. The significant features of this reaction include expedient one-pot process, short reaction time, excellent yields, wide substrate scope and operational simplicity. Also, the catalyst could be reused for several consecutive runs without any apparent loss in its catalytic activity.

Full text of DOI:10.1016/j.tet.2017.01.037

Accepted Manuscript
An efficient and green synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines using highly
active and stable poly acrylic acid-supported layered double hydroxides
Mudumala Veeranarayana Reddy, Gangireddy Chandra Sekhar Reddy, Dong Wook
Kim, Nguyen Thi Kim Lien, Yeon Tae Jeong
PII:
S0040-4020(17)30060-1
10.1016/j.tet.2017.01.037
TET 28407
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 December 2016
Revised Date: 11 January 2017
Accepted Date: 17 January 2017
Please cite this article as: Veeranarayana Reddy M, Chandra Sekhar Reddy G, Kim DW, Thi Kim Lien
N, Jeong YT, An efficient and green synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines using highly active
and stable poly acrylic acid-supported layered double hydroxides, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.01.037.
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An efficient and green synthesis of benzo[4,5]imidazo
[1,2-a]pyrimidines using highly active and stable poly
acrylic acid-supported layered double hydroxides
Leave this area blank for abstract info.
MudumalaVeeranarayana Reddya,b, Gangireddy Chandra Sekhar Reddyc, Dong Wook Kimb* Nguyen Thi Kim
Liena, Yeon Tae Jeonga*
aDepartment of Image Science and Engineering, Pukyong National University, Busan 608-737, Korea
bDepartment of Chemistry, Inha University 100 Inha-ro, Nam-gu, Incheon 402-751 (Korea) Fax: (+82) 32-867-5604
cFire Chemistry Section, State Key Laboratory of Fire Science, University of Science and Technology of China, Jinzhai
Road 96, Hefei-230026, Anhui, P.R. China
HO
OH
R
O
N
N
R
NH2
+
OH
HO
R1
N
N
H
R1
N
PAA-g-LDHs
Neat, 80 o
(1)
(3)
C
(2)

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
An efficient and green synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines using highly
active and stable poly acrylic acid-supported layered double hydroxides
MudumalaVeeranarayana Reddyab, Gangireddy Chandra Sekhar Reddyc, Dong Wook Kimb*, Nguyen Thi
Kim Liena, Yeon Tae Jeonga*
aDepartment of Image Science and Engineering, Pukyong National University, Busan 608-737, Korea,
bDepartment of Chemistry, Inha University 100 Inha-ro, Nam-gu, Incheon 402-751 (Korea) Fax: (+82) 32-867-5604
cFire Chemistry Section, State Key Laboratory of Fire Science, University of Science and Technology of China, Jinzhai Road 96, Hefei-230026, Anhui, P.R.
China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A facile and efficient method for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines has been
achieved via highly active and reusable heterogeneous poly acrylic acid-supported layered
double hydroxides (PAA-g-LDHs) catalyst promoted one-pot reaction of 1H-benzo[d]imidazol-
2-amine, with α,β-unsaturated carbonyl compounds under solvent-free conditions. PAA-g-LDHs
catalyst was successfully synthesized via reversible addition-fragmentation chain-transfer
polymerization using grafting reaction and was characterized by different analytical techniques.
The significant features of this reaction include expedient one-pot process, short reaction time,
excellent yields, wide substrate scope and operational simplicity. Also, the catalyst could be
reused for several consecutive runs without any apparent loss in its catalytic activity.
Available online
Keywords:
poly acrylic acid-supported layered double
hydroxides
Benzo[4,5]imidazo[1,2-a]pyrimidines
Solvent-free conditions
2009 Elsevier Ltd. All rights reserved
.
1H-benzo[d]imidazol-2-amine
1. Introduction
of various solid-supported reagents4 and used as heterogeneous
supported catalysts in organic synthesis.
Since decades, heterogeneous supported catalysts have
attracted much attention due to their inherent advantages, such as
ease of handling, greater selectivity, stability, inexpensive,
environmental compatibility, and catalysts can be recovered
without measurable changes in their catalytic activity and
selectivity.1 Therefore, catalytic system have been obtained
enormous significance in pollution preventing processes in the
synthetic organic chemistry. Among them, polymer supported
catalytic systems have received attracted great attention in
synthetic organic chemistry and chemical industries because of
they have high catalytic activity with enhanced reaction rates by
high surface area, non-flammability with high thermal stability,
cleaner product yields with improved product selectivity by
decrease waste production, and easy to separation from reaction
products for further reusability with regard to the effortlessness
of the process and environmental reaction condition.2In addition
to these merits, small crystal size, hydrophobic cavity, and as
good candidates for polymer supporting applications layered
double hydroxides (LDHs)3 are applied for the preparation of
Either in pharmaceutical agents or numerous organic
materials,5 which are showing a wide variety of biological
activities, such as anti-cancer, antibacterial, anti-inflammatory
activities, anti-alzheimer’s activity, anti-hypertensive agents, V1b
receptor antagonists, anti-TMV, anti-tumor, anti-metabolic and
antimalarial agents6 omnipresent backbone of either naturally or
synthetically obtained either one or more nitrogen(s) containing
heterocycles. Furthermore, they can be used as dyes, biosensors,
for visualization of biomolecules as pH-sensitive fluorescent
material, and also in laser technologies.7 Amongst them,
benzo[4,5]imidazo[1,2-a]pyrimidines structure bearing two main
cores of nitrogen containing heterocycles (a imidazol and a
pyrimidine ring) is originated broadly in biologically interesting
compounds and natural products. As mentioned above, this core
unit have a broad range of biological and pharmacological
activities include anti-TMV, anti-vascular hypertension, anti-
cancer/anti-tumor,
anti-inflammatory,
anti-metabolic,
antimalarial agents and antimicrobial activities.8 In addition,
these derivatives are also played a role of antagonists of the
paralyzing action of anti-diabetic activity and are significant core
motifs in a wide range of biologically active compounds that are
frequently used in pharmaceuticals, agrochemicals and medicinal
——
Corresponding author:Tel.: +82-51-629-6411; fax: +82-51-629- 6408;
e-mail: ytjeong@pknu.ac.kr
Corresponding author. +(82) 32-867-5604; e-mail: kimdw@inha.ac.kr

2
Tetrahedron
ACCEPTED MANUSCRIPT
chemistry.8,9 Consequently, these structures are significant
synthetic targets for bio-organic chemists.
In an ongoing study of design and synthesis of
biologically active molecules under heterogeneous
catalysis10 and with the above two significant areas of
findings, herein, we prepared a novel poly acrylic acid
grafted layered double hydroxides (PAA-g-LDHs) as a
recyclable heterogeneous catalyst and it was successfully
applied for the construction of benzo[4,5]imidazo[1,2-
a]pyrimidines (
3
) in one-pot synthesis by coupling of 1
H-
benzo[d]imidazol-2-amine
(
1), with α,β-unsaturated
carbonyl compounds (
2
) at 80 °C under solvent-free
conditions (Scheme 1).
N
HO
OH
NH2
N
H
R
(
1
)
N
+
OH
HO
N
R1
O
N
PAA-g-LDHs
Neat, 80 o
C
Fig. 1. X-ray diffraction patterns of (a) the referrence of LDHs
(35-0964), (b) synthesized LDHs, (c) LDHs-BTPT, (d) PAA-g-
LDHs.
R
R1
(3a-t)
(2)
Scheme-1: Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines.
TGA analysis of PAA-g-LDHs
2. Results and Discussion
Synthesis of LDHs-g-POEGMA
The synthesis of PAA-g-LDHs has been successfully
described by an efficient and convenient approach of reversible
addition-fragmentation chain-transfer (RAFT) polymerization
reaction through the modified reported procedure.11 Initially
surface modification of LDHs (LDHs → LDHs-BTPT) with S′-
In order to know the thermal degradation properties of LDHs,
LDHs-BTPT, and PAA-g-LDHs performed a TGA of them and
interpreted in Fig. 2. At first, Herein, a closer relationship was
observed for LDHs and LDHs-BTPT. But on the other hand,
PAA-g-LDHs was shown clear deviation from them and it could
be explained as below. At first stage, due to release of absorbed
water the LDHs (Fig. 2a) and LDHs-BTPT (Fig. 2b) ware
showed a closer decomposition starting at 123.5 ºC and lost
12.7% of weight. At 211.76 & 223.3 °C they were showed a
second degradation curve due to losing of 21.0% of weight
corresponding to the interlayer anions. Finally, the weight loss of
41.2 and 42.8% respectively were shown between 330 - 800 °C
since encapsulated organic molecules decamped at high
temperature. But on the other hand, the newly prepared PAA-g-
LDHs was significantly start degradation at 147 °C and shown a
slower degradation up to 800 ºC with weight loss of 81.6% (Fig.
2c). Compare to LDHs and LDHs-BTPT the higher starting
degradation temperature of PAA-g-LDHs is due to the coverage
of polymer layers (38.8%) which were prevented the escape of
absorbed water and interlayer anions. Therefore, the TGA results
demonstrated that the brush polymers were successfully
(3-trimethoxysilyl)
propyltrithiocarbonate
(BTPT)
was
performed in first step as prescribed in reported procedure and
later followed by 2, 2′-azobis (2-methylpropionitrile) (AIBN)
initiated RAFT process using poly acrylic acid (PAA) in the next
step was obtained white powder, PAA-g-LDHs.
Scheme -2: Synthesis of PAA-g-LDHs.
XRD spectra of PAA-g-LDHs
The crystalline nature of the synthesized LDHs, LDHs-
BTPT and PAA-g-LDHs were confirmed with the reference
LDHs (35-0964) by XRD spectrum (Fig. 1). The newly
synthesized LDHs (Fig. 1b), LDHs-BTPT (Fig. 1c) and PAA-g-
LDHs (Fig. 2d) peaks are perfectly indexed to tetragonal phase
of referenced LDHs (Fig. 1a) with 2θ values of 11.68, 23.47, and
35 respectively with corresponding crystal planes of (003), (006),
and (012). These results are revealed that the grafting of polymer
did not alter the crystallinity of the LDHs.
decorated onto the LDHs.

3
Fig. 2. TGA spectra of (a) LDHs, (b) LDHs-BTPT, and (c) PAA-
g LDHs.
methylene group supporting the successful synthesis of the new
catalyst.
ACCEPTED MANUSCRIPT
Surface morphologies of PAA-g-LDHs
When observed the surface morphology of pristine LDHs
displays separate distinctly (Fig. 3a) but after grafting by RAFT
polymerization with PPA resulted PAA-g-LDHs could be
visualized relatively irregular shape which is due to covering of
polymer layer of PAA chains (Fig. 3b).
Fig. 5. FTIR results: (a) LDHs, (b) LDHs-BTPT, (c) PAA-g-
LDHs
Application of PAA-g-LDHs for the synthesis of
benzo[4,5]imidazo[1,2-a]pyrimidines
To adopt an efficient and environmentally benign procedure to
the newly synthesized catalyst, a one-pot condensed cyclo-
addition reaction of 1H-benzo[d]imidazol-2-amine (1) and (E)-3-
(4-isopropylphenyl)-1-phenylprop-2-en-1-one (2) was performed
and achieved the benzo[4,5]imidazo[1,2-a]pyrimidines (3a-t)
good to excellent yields (Table 2).
Fig. 3. SEM pictures of (a) LDHs, and (b) PAA-g-LDHs.
XPS spectra of PAA-g-LDHs
The bonding nature of LDHs after PPA grafting was
measured by surface modification analysis by XPS spectra and
which showed the dominated elemental peaks of O, Mg and Al
corresponding of LDHs (Fig. 4). In addition, a strong C signal
along with more intensive O signal (associated with the grafted
PAA) was also observed. The characteristic peaks for C 1s
included 2 peaks at 284.9 eV (C-C bonding), 288.7 eV (O-C=O
bonding of carboxylic acid groups) suggesting that the polymer
was successfully introduced onto the LDH surface by covalent
linkages and resulting the formation of PAA-g-LDHs (See in full
details at supporting information Fig. S1-S3).
At first we are performed a model reaction using an equimolar
ratio of 1H-benzo[d]imidazol-2-amine (1) and (E)-3-(4-
isopropylphenyl)-1-phenylprop-2-en-1-one (2a) to find the
suitable conditions, and the results are presented at Table 1.
When run the reaction at 80 °C for 8 h under solvent and
catalyst-free conditions desired product 3a was obtained in low
yield (Table 1, entry 1). Gratifyingly, the desired 3a was offered
excellent yield (92%) even within 20 min, when carried out the
reaction in presence of 10 mg of PAA-g-LDHs under solvent-free
condition at 80 °C. (Table 1, entry 2).The catalyst ratio also
should played a vital role in this reaction. Therefore, we
examined the model reaction using 15 mg of PAA-g-LDHs and
could not further improve the yield of the product (Table 1, entry
2). When the model reaction was studded using 5 mg of catalyst
(Table 1, entry 3) under neat, we observed the product yield was
decreased and reaction time also increased. However, no more
increments were found for product 3a when the reaction
temperature was increasing from 80 to 100 °C (Table1, entry 4).
Subsequently, the effects of solvents were investigated. All
solvent mediums found that the rate of reactions were slower and
resulted moderate yields and prolonged reaction times (Table 1,
entries 9–12). But the model reaction already showed better
result under solvent-free condition (Table 1, entry 2).
.
Fig.4. XPS spectra of PAA-g-LDHs.
Table 1: Optimization of reaction conditions for the synthesis of
3aa
FT-IR spectra of PAA-g-LDHs
In addition to above all experimental data, FT-IR
spectrum (Fig.5c) of the synthesized PAA-g-LDHs was also
clearly evidenced about the successful drafting of PPA on LDHs-
BTPT which is resulted two new absorption bands at 1715 cm-1
corresponding to stretching vibration of C=O and a broad band
from 3700 to 3000 cm-1 due to the -OH groups of carboxylic acid
of PAA moieties. At the same time, in addition to the regular
absorption bands of LDHs (Fig. 5a) at 3450 cm−1 (Al–OH), 1355
cm-1 (interlayer Cl-) and a broad peak from 790 to 440 cm-1 (M–
O and O–M–O), the BTPT (Fig. 5b) and PAA-g-LDHs were
showed a distinguishable absorption band at 2918 cm-1 owing to
O
N
NH2
+
N
H
N
N
N
(1)
(3)
(2)
Entry
Solvent
Catalyst
Tem
(°C)
Time
(min)
Yieldb
(%)
1
Neat
Neat
80
480
25

4
Tetrahedron
ACCEPTED MANUSCRIPT
c2
3
Neat
Neat
PAA-g-LDHs
(10 mg)
80
80
20
92, 91,
the precipitated catalyst with acetone and dried in an oven. Then
90, 89
the dried catalyst was used for further four consecutive cycles
and obtained the product, 3a in excellent yields in order of 92%,
91%, 90% and 89% (Table 1, entry 2). These data demonstrate
that the high stability and reusability of the catalyst under those
optimized reaction conditions.
PAA-g-LDHs
(15 mg)
20
65
92
70
92
75
79
65
45
65
80
74
70
80
77
80
65
74
75
70
c4
5
Neat
PAA-g-LDHs
80
(5 mg)
Neat
PAA-g-LDHs
(10 mg)
100
80
20
Next we studied the catalytic activity of PAA-g-LDHs, and
were
successfully
engaged
for
the
synthesis
of
6
Acetonitrile
DMF
THF
PAA-g-LDHs
(10 mg)
55
benzo[4,5]imidazo[1,2-a]pyrimidines (3b-t) via different α,β-
unsaturated carbonyl compounds were reacted with 1H-
benzo[d]imidazol-2-amine. The reaction occurred well in all of
these cases, afforded good yields of product (Table 2). A variety
of functional groups substituted on the aromatic ring of α,β-
unsaturated carbonyl compounds, such as methoxy, ethoxy,
isopropyl and methyl have preceded the reaction smoothly and
resulted in the corresponding products in good to excellent
yields. The halogen-containing aldehydes such as –Cl, –Br, and –
F were also subjected to the reaction conditions, and obtained in
good to excellent yields of the desired products.
7
PAA-g-LDHs
(10 mg)
120
80
85
8
PAA-g-LDHs
(10 mg)
85
9
Water
Toluene
Dioxane
Benzene
Neat
PAA-g-LDHs
(10 mg)
100
100
80
110
75
10
11
12
13
14
15
16
17
18
19
20
PAA-g-LDHs
(10 mg)
PAA-g-LDHs
70
(10mg)
PAA-g-LDHs
(10 mg)
80
125
80
Table 2: Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidinesa
PAA
80
Entry
1
R1
H
R
Product
3a
Time
(min)
Yieldb
(%)
Neat
LDHs
80
60
4-CH-(CH3)2-
C6H4
20
92
Neat
LDHs-BTPT
PSPTSA
PTSA
80
60
2
3
H
H
3-OMe -C6H4
3b
3c
3d
3e
3f
22
22
28
24
29
20
25
29
28
24
89
90
91
90
91
92
85
89
91
91
4-Cl-C6H4
4-Me-C6H4
4-F-C6H4
Neat
80
60
4
H
5
H
Neat
80
120
86
6
H
3-4-5-OMe -C6H2
4-OEt-C6H4
3-NO2-C6H4
3-Br-C6H4
Neat
Proline
InCl3
80
7
H
3g
3h
3i
8
H
Neat
80
110
90
9
H
10
11
3-OMe
3-Me
3-Me-C6H4
2-Me-C6H4
3j
Neat
FeCl3
80
3k
aReaction 1H-benzo[d]imidazol-2-amine (1,
1
mmol) and ((E)-3-(4-
12
13
14
15
4-Me
4-Me
4-Br
3-F-C6H4
4-Me-C6H4
2-F-C6H4
3l
3m
3n
3o
28
23
29
22
89
90
91
92
isopropylphenyl)-1-phenylprop-2-en-1-one (2a, 1 mmol); bIsolated yield;
cCatalyst was reused four times.
4-Me
4-CH-(CH3)2-
C6H4
3-4-5-OMe -C6H2
To confirm the catalytic activity and merits of the PAA-g-
LDHs a comparison study was conducted with various catalysts,
including LHDs, and LDHs-BTPT and also PAA as a controlled
catalyst under neat conditions at 80 °C and observed moderate to
good catalytic properties (Table 1, entries 13–20). Herein,
compared to that of PAA-g-LDHs, the substrate, LDHs,
intermediate (LDHs-BTPT) and the used controlled PAA are
showed lower yields (Table 1, entries 13-15). Even in them, the
LDHs showed better yield rather than PAA, because of may be
the hydroxyl groups should facilitating better hosting than the
PAA. But, on the other hand, the intermediate, LDHs-BTPT was
showed lesser yield than the LDHs. It might be decreasing the
hosting effect of LDHs-BTPT surface due to grafting of BTPT.
On the other hand, the simple organic acids and metallic salts and
amino acid, Proline, are also showed the similar results with lower
yields (Table 1, entries 16-20). From these overall results
demonstrated that 10 mg PAA-g-LDHs under solvent-free
conditions at 80 °C are optimized reaction conditions for the
synthesis of 3a (Table 1, entry 2).
16
17
18
19
20
4-Me
4-Me
4-F
3p
3q
3r
3s
3t
25
29
26
25
27
89
88
87
89
87
4-Br-C6H4
2-Cl-C6H4
4-F-C6H4
4-F
4-Br
3-Me-C6H4
aReaction of 1H-benzo[d]imidazol-2-amine (1, 1 mmol) and α,β-unsaturated
carbonyl compounds (2, 1 mmol) catalyzed by 5 mg of PAA-g-LDHs under
neat conditions at 80 °C. bIsolated yield.
Based upon the results, herein, a reasonable reaction
mechanism has been proposed (Scheme 3). At first, the reactants,
α,β-unsaturated
carbonyl
compounds
(2)
and
1H-
benzo[d]imidazol-2-amine (1) are interacted by the catalyst PAA-
g-LDHs and they aligned on the surface of the catalyst with the
formation of either hydrogen bonding or n→π/π→π interaction.
After that close proximate of ketone group of chalcone would be
combine with 1°-amine and forms the imine intermediate (4)
which on rapid intramolecular cyclization gave another
intermediate, 4a. Finally by elimination of H2 molecule obtained
In the context of financial viability and sustainable
development of catalyst, the PAA-g-LDHs was isolated by the
simple filtration using 10 mL of ethyl acetate (EA) and washed
the
desired
benzo[4,5]imidazo[1,2-a]pyrimidines
(3)

5
conveniently. In this mechanism, the catalyst PAA-g-LDHs
washed with DCM for three times to remove all unreacted
ACCEPTED MANUSCRIPT
should plays a key role, help as acid at initial step to form the
imine intermediate and later it’s acting as strong base in the final
step for the removal of H2 molecule to get the desired product.
BTPT. The final
product was dried under vacuum overnight.
4.3. Preparation of PAA-g-LDHs by RAFT polymerization
2 g of AA, 0.080 g of LDHs-BTPT, 20 mg of AIBN, and
4 ml of dry DMF were placed in a round bottom flask. The
polymerization reaction was performed at 70 ºC for 10 h under N2.
The mixture was precipitated in diethyl ether and washed three
times with methanol. The product was dried under vacuum at
40 ºC overnight.
4.4.
Synthesis
of
4-(4-isopropylphenyl)-2-
phenylbenzo[4,5]imidazo[1,2-a]pyrimidine (4a).
A mixture of 1H-benzo[d]imidazol-2-amine (1, 1
mmol) and ((E)-3-(4-isopropylphenyl)-1-phenylprop-2-en-1-one
(2a, 1 mmol) and PAA-g-LDHs (10 mg) was stirred at 80 °C
under solvent-free condition for 20 min. The progress of the
reaction was monitored by thin layer chromatography (TLC).
After completion of the reaction, the mixture was washed with
ethyl acetate and filtered to recover the catalyst. The filtrate was
evaporated, and the crude product was recrystallized from
ethanol to afford pure 3a in excellent yield 92%.
4.4.1
4-(4-isopropylphenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4a). Yield 92%; yellow solid; Mp: 204-206 oC; 1H
NMR (400 MHz, CDCl3): δ 8.21 (d, J=8.4 Hz, 2H), 7.93 (d, J
=7.7, Hz, 1H), 7.61-7.71 (m, 5H), 7.40 (t, J=7.7 Hz, 1H), 7.35 (d,
J=8.1 Hz, 2H), 7.20 (s, 1H), 6.98 (t, J=7.7 Hz, 1H), 6.65 (d,
J=8.4 Hz, 1H), 2.93-3.0 (m, 1H), 1.28 (d, J=6.6 Hz, 6H); 13C
NMR (100 MHz, CDCl3): δ 161.06, 152.69, 149.18, 134.30,
132.69, 131.04, 129.42, 128.47, 127.95, 127.11, 125.80, 121.04,
120.13, 114.54, 105.23, 34.17, 23.85; HRMS (ESI, m/z): calcd
for C25H21N3 (M+H+) 363.1735, found: 363.1730.
Scheme: 3 plausible mechanisms.
3. Conclusion
In summary, we have developed first time an efficient
and highly active PAA-g-LDHs catalyst for the synthesis of
benzo[4,5]imidazo[1,2-a]pyrimidines under neat conditions. The
notable features of this procedure are its high catalytic activity,
inexpensiveness, analytical simplicity, non-volatile, lack of
diffusion phenomena, reusability, high thermal stability, good
structural stability short reaction time, excellent yields, and
operational simplicity and mild reaction conditions.
4.4.2.
4-(3-methoxyphenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4b). Yield 89%; yellow solid; Mp: 180-182 oC; 1H
NMR (400 MHz, CDCl3): δ 8.27 (d, J=8.1, 1H), 7.95 (d, J =8.4
Hz, 1H), 7.62-7.70 (m, 5H), 7.50 (s, 1H), 7.40-7.45 (m, 2H), 7.12
(t, J=7.7 Hz, 1H), 6.98 (d, J=8.4 Hz, 2H), 6.68 (d, J=8.4 Hz, 1H),
3.87 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.26, 158.07,
152.28, 147.64, 145.37, 132.88, 132.20, 131.98, 130.85, 129.32,
128.53, 127.41, 126.62, 125.68, 121.33, 120.87, 120.12, 114.59,
111.54, 110.10, 55.71; HRMS (ESI, m/z): calcd for C23H17N3O
(M+H+) 351.1372, found: 351.1365.
4. Experimental
4.1 General
Chemicals were purchased from Aldrich and Alfa Aesar
Chemical Companies. NMR spectra were recorded in ppm in
CDCl3 on a Jeol JNM ECP 400 NMR instrument using TMS as
an internal standard. Mass spectra were recorded on a Jeol JMS-
700 mass spectrometer. An Elmasonic S 100 H (with a frequency
of 35 kHz and a nominal power 550 W) ultrasonic bath was used
for ultrasonic irradiation. All melting points were determined
using open capillaries on an Electrothermal-9100 (Japan)
instrument. Fourier transform infrared (FTIR) spectra were
4.4.3.
4-(4-chlorophenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4c). Yield 90%; yellow solid; Mp: 228-230 C; 1H
NMR (400 MHz, CDCl3): δ 8.16 (d, J=8.8 Hz, 2H), 7.90 (d, J
=8.1 Hz, 1H), 7.63-7.73 (m, 5H), 7.42 (d, J=8.8 Hz, 3H), 7.14 (s,
1H), 6.98 (t, J=8.1 Hz, 1H), 6.64 (d, J=8.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ 159.66, 151.93, 149.62, 145.57, 137.61,
135.07, 132.49, 131.20, 129.48, 129.18, 129.06, 128.44, 127.44,
126.05, 121.35, 120.25, 114.63, 104.92; HRMS (ESI, m/z): calcd
for C22H14ClN3 (M+H+) 355.0876, found: 355.0870.
o
measured on
a
Agilent Cary 600 FTIR spectrometer.
Thermogravimetric analysis (TGA) was conducted with Perkin-
Elmer Pyris 1 analyzer (USA). The morphology analyzes of the
hybrids were carried out by using scanning electron microscopy
(SEM) images equipped (Hitachi JEOL-JSM-6700F system,
Japan). Surface composition of samples was investigated by an
X-ray Photoelectron Spectroscopy (XPS) (Thermo VG Multilab
2000) in an ultra-high vacuum with Al Ka radiation. The 1H-
NMR spectrum of BTPT was recorded using a JNM-ECP 400
(JEOL) spectrophotometer in CDCl3. LDHs was prepared
according to reported procedure.11
4.4.4. 2-phenyl-4-(p-tolyl)benzo[4,5]imidazo[1,2-a]pyrimidine
o
1
(4d). Yield 91%; yellow solid; Mp: 209-211 C; H NMR (400
MHz, CDCl3): δ 8.17 (d, J=8.4 Hz, 2H), 7.93 (d, J =8.4 Hz, 1H),
7.61-7.66 (m, 3H), 7.38-7.41 (m, 1H), 7.33 (d, J=8.1 Hz, 1H),
7.27 (d, J=8.1 Hz, 2H), 7.19 (s, 1H), 7.16 (d, J=8.1 Hz, 1H), 6.98
(t, J=7.7 Hz, 1H), 6.64 (d, J=8.4 Hz, 1H), 2.39 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 161.09, 152.29, 149.19, 145.52, 141.88,
133.92, 132.69, 131.06, 129.71, 128.42, 128.99, 128.47, 127.80,
127.53, 126.67, 125.84, 121.06, 120.14, 114.53, 105.23, 21.55;
4.2. Anchoring of BTPT onto LDHs surface (LDHs-BTPT)
The mixture of 0.7g of LDHs and 20 ml of dry toluene was
stirred at 100 °C. Then, 0.724 g (2 mmol) of BTPT in 10 ml dry
toluene was injected into the flask under N2. The reaction was
conducted for 24 h. The crude product was filtered off and

6
Tetrahedron
HRMS (ESI, m/z): calcd for C23H17N3 (M+H+) 335.1422,
132.14, 131.99, 129.95, 128.41, 126.68, 125.64, 121.32, 120.76,
ACCEPTED MANUSCRIPT
found: 335.1427.
120.05, 114.75, 111.53, 110.16, 55.70, 21.68; HRMS (ESI, m/z):
calcd for C24H19N3O (M+H+) 365.1528, found: 365.1524.
4.4.5.
4-(4-fluorophenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4e). Yield 90%; yellow solid; Mp: 202-204 oC; 1H
NMR (400 MHz, CDCl3): δ 8.21-8.24 (m, 2H), 7.89 (d, J =8.1
Hz, 1H), 7.64-7.71 (m, 5H), 7.39 (t, J=7.5 Hz, 1H), 7.11 (t, J=8.4
Hz, 3H), 6.97 (t, J=7.7 Hz, 1H), 6.62 (d, J=8.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ 159.73, 151.96, 149.47, 145.47,
136.93, 132.47, 131.13, 129.93, 129.83, 129.41, 128.40, 127.38,
125.91, 121.20, 120.12, 116.05, 115.83, 114.56, 104.90; HRMS
(ESI, m/z): calcd for C22H14FN3 (M+H+) 339.1171, found:
339.1168.
4.4.11.
2-(m-tolyl)-4-(o-tolyl)benzo[4,5]imidazo[1,2-
a]pyrimidine (4k). Yield 91%; yellow solid; Mp: 182-184 oC; 1H
NMR (400 MHz, CDCl3): δ 7.96 (d, J=8.1 Hz, 1H), 7.62 (d,
J=7.7 Hz, 1H), 7.50 (d, J=8.1 Hz, 2H), 7.42 (d, J=7.7 Hz, 3H),
7.23-7.35 (m, 3H), 7.02 (t, J=7.7 Hz, 1H), 6.92 (s, 1H), 6.82 (d,
J=8.1 Hz, 1H), 2.63 (s, 3H), 2.52 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 164.57, 149.10, 145.35, 141.42, 137.87, 137.08,
131.48, 130.00, 129.78, 129.70, 129.48, 128.21, 126.02, 125.80,
121.01, 120.19, 114.78, 109.16, 21.65, 21.05; HRMS (ESI, m/z):
calcd for C24H19N3 (M+H+) 349.1579, found: 349.1573.
4.4.6.
2-phenyl-4-(3,4,5-
trimethoxyphenyl)benzo[4,5]imidazo[1,2-a]pyrimidine (4f).Yield
91%; yellow solid; Mp: 241-243 oC; 1H NMR (400 MHz,
CDCl3): δ 7.88 (d, J=8.4 Hz, 1H), 7.67-7.71 (m, 5H), 7.53 (s,
2H), 7.39 (t, J=7.3 Hz, 1H), 7.16 (s, 1H), 6.97 (t, J=7.7 Hz, 1H),
6.62 (d, J=8.4 Hz, 1H), 3.95 (s, 6H), 3.93 (s, 3H); 13C NMR (100
MHz, CDCl3): δ; 160.15, 153.40, 149.08, 145.33, 140.98, 132.45,
131.75, 129.34, 128.70, 128.40, 127.38, 125.80, 121.08, 119.89,
114.42, 104.92, 60.94, 56.33; HRMS (ESI, m/z): calcd for
C25H21N3O3 (M+H+) 411.1582, found: 411.1576.
4.4.12.
4-(3-fluorophenyl)-2-(p-tolyl)benzo[4,5]imidazo[1,2-
o
1
a]pyrimidine (4l). Yield 89%; yellow solid; Mp: 238-240 C; H
NMR (400 MHz, CDCl3): δ 8.21-8.24 (m, 2H), 7.90 (d, J=7.3
Hz, 1H), 7.51 (d, J=7.7 Hz, 2H), 7.44 (d, J=7.7 Hz, 2H), 7.39 (t,
J=7.7 Hz, 1H), 7.11 (t, J=7.3 Hz, 3H), 6.98 (t, J=7.3 Hz, 1H),
6.73 (d, J=8.4 Hz, 1H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 164.05 (d, J = 245.2Hz), 159.72, 149.77, 141.49,
132.84, 130.03, 129.90, 129.82, 129.57, 128.27, 125.87, 121.08,
120.06, 116.03, 115.82, 114.72, 104.96, 21.70; HRMS (ESI,
m/z): calcd for C23H16FN3 (M+H+) 353.1328, found: 353.1335.
4.4.7.
4-(4-ethoxyphenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4g). Yield 92%; yellow solid; Mp: 212-214 oC; 1H
NMR (400 MHz, CDCl3): δ 8.18 (d, J=7.7, 2H), 7.90 (s, 1H),
7.61-7.65 (m, 5H), 7.37 (s, 1H), 7.10 (s, 1H), 6.89-6.96 (m, 3H),
6.61 (d, J=7.7 Hz, 1H), 4.0 (q, J=7.0 Hz, 2H), 1.39 (t, J=7.0 Hz,
3H), 13C NMR (100 MHz, CDCl3): δ 161.71, 160.49, 148.90,
145.44, 132.63, 130.93, 129.42, 129.31, 128.78, 128.42, 125.59,
120.78, 119.87, 114.61, 114.41, 104.84, 63.61, 14.74; HRMS
(ESI, m/z): calcd for C24H19N3O (M+H+) 365.1528, found:
365.1522.
4.4.13. 2,4-di-p-tolylbenzo[4,5]imidazo[1,2-a]pyrimidine (4m).
o
1
Yield 90%; yellow solid; Mp: 218-220 C; H NMR (400 MHz,
CDCl3): δ 8.14 (d, J=8.1 Hz, 2H), 7.92 (d, J=8.1 Hz, 1H), 7.49
(d, J=8.1 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.38 (d, J=7.7 Hz,
1H), 7.24 (d, J=8.1 Hz, 2H), 7.14 (s, 1H), 6.98 (t, J=8.1 Hz, 1H),
6.73 (d, J=8.1 Hz, 1H), 2.53 (s, 3H), 2.36 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 160.95, 149.39, 141.73, 141.33, 133.90, 129.99,
129.74, 129.63, 128.30, 127.72, 125.71, 120.86, 120.03, 114.65,
105.20, 21.69, 21.52; HRMS (ESI, m/z): calcd for C24H19N3
(M+H+) 349.1579, found: 349.1581.
4.4.8.
4-(3-nitrophenyl)-2-phenylbenzo[4,5]imidazo[1,2-
a]pyrimidine (4h). Yield 85%; yellow solid; Mp: 228-230 oC; 1H
NMR (400 MHz, CDCl3): δ 7.95 (d, J=7.7, 2H), 7.19 (d, J =6.2
Hz, 1H), 7.61-7.68 (m, 4H), 7.55 (t, J=7.3 Hz, 1H), 7.45 (t, J=6.6
Hz, 2H), 7.05 (t, J=7.7 Hz, 2H), 6.79 (s, 1H), 6.75 (d, J=7.7 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ 160.59, 149.57, 148.42,
145.24, 133.62, 133.24, 131.89, 131.56, 131.37, 130.68, 129.48,
128.36, 126.32, 124.74, 121.83, 120.38, 114.93, 107.89; HRMS
(ESI, m/z): calcd for C22H14N4O2 (M+H+) 366.1116, found:
366.1110.
4.4.14. 4-(4-isopropylphenyl)-2-(p-tolyl)benzo[4,5]imidazo[1,2-
a]pyrimidine (4n). Yield 91%; yellow solid; Mp: 186-188 oC; 1H
NMR (400 MHz, CDCl3): δ 8.21 (d, J=8.4 Hz, 2H), 7.94 (s, 1H),
7.50 (d, J=8.1 Hz, 2H), 7.44 (d, J=7.7 Hz, 2H), 7.40 (d, J=7.3
Hz, 1H), 7.35 (d, J=8.1 Hz, 2H), 7.18 (s, 1H), 6.99 (t, J=7.3 Hz,
1H), 6.75 (d, J=8.1 Hz, 1H), 2.93-3.00 (m, 1H), 2.54 (s, 3H),
1.28 (d, J=7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 161.06,
152.63, 141.37, 134.38, 130.04, 128.34, 127.94, 127.10, 125.76,
120.93, 120.08, 114.69, 105.30, 34.18, 23.86, 21.72; HRMS
(ESI, m/z): calcd for C26H23N3 (M+H+) 377.1892, found:
377.1888.
4.4.9.
4-(3-bromophenyl)-2-phenylbenzo[4,5]imidazo[1,2-
o
1
a]pyrimidine (4i). Yield 89%; yellow solid; Mp: 195-197 C; H
NMR (400 MHz, CDCl3): δ 7.98 (s, 1H), 7.83 (d, J =7.3 Hz, 1H),
7.61-7.65 (m, 6H), 7.43 (t, J=7.0 Hz, 2H), 7.28 (t, J=7.7 Hz, 1H),
7.17 (s, 1H), 7.01 (t, J=7.3 Hz, 1H), 6.75 (d, J=7.7 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ 162.75, 148.32, 139.18, 133.58,
132.35, 131.95, 131.15, 129.39, 128.33, 127.84, 125.95, 121.42,
121.37, 114.85, 109.83; HRMS (ESI, m/z): calcd for C22H14BrN3
(M+H+) 400.2707, found: 400.2700.
4.4.15.
2-(p-tolyl)-4-(3,4,5-
(4o).
1
trimethoxyphenyl)benzo[4,5]imidazo[1,2-a]pyrimidine
o
Yield 92%; yellow solid; Mp: 262-264 C; H NMR (400 MHz,
CDCl3): δ 7.91 (d, J=8.1, 1H), 7.54-7.56 (m, 4H), 7.47 (d, J=8.1
Hz, 2H), 7.42 (t, J=7.7 Hz, 1H), 7.16 (s, 1H), 7.01 (t, J=7.6 Hz,
1H), 6.73 (d, J=8.1 Hz, 1H), 3.97 (s, 6H), 3.93 (s, 3H), 2.56 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 160.30, 153.53, 149.45,
145.50, 141.49, 131.97, 130.07, 128.35, 125.89, 121.08, 120.03,
114.63, 105.04, 61.04, 56.45, 21.72; HRMS (ESI, m/z): calcd for
C26H23N3O3 (M+H+) 425.1739, found: 425.1735.
4.4.10. 2-(3-methoxyphenyl)-4-(m-tolyl)benzo[4,5]imidazo[1,2-
o
a]pyrimidine (4j). Yield 91%; yellow solid; Mp: 186-188 C; 1H
NMR (400 MHz, CDCl3): δ 8.26 (d, J=8.1, 1H), 7.95 (d, J =8.1
Hz, 1H), 7.51 (d, J=8.1 Hz, 2H), 7.48 (s, 1H), 7.41-7.44 (m, 4H),
7.11 (t, J=7.3 Hz, 1H), 7.02 (d, J=7.7 Hz, 1H), 6.98 (d, J=8.1 Hz,
1H), 6.77 (d, J=8.1 Hz, 1H), 3.88 (s, 3H), 2.53 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 161.23, 158.06, 147.93, 145.36, 141.14,
4.4.16.
2-(p-tolyl)-4-(4-bromophenyl)benzo[4,5]imidazo[1,2-
a]pyrimidine (4p). Yield 89%; yellow solid; Mp: 240-242 oC; 1H
NMR (400 MHz, CDCl3): δ 7.99 (d, J=8.1 Hz, 1H), 7.85 (d,

7
Mahak, D.; Vivek, P.; Bhalchandra, M. B. Green
ACCEPTED MANUSCRIPT
J=7.7 Hz, 1H), 7.67 (d, J=8.1 Hz, 1H), 7.53 (d, J=8.1 Hz, 2H),
7.43-7.48 (m, 4H), 7.31 (t, J=7.5 Hz, 1H), 7.17 (s, 1H), 7.06 (t,
J=6.9 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 2.54 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 162.85, 148.58, 145.43, 141.55, 139.32,
133.63, 132.04, 131.15, 130.08, 129.47, 128.31, 127.88, 127.43,
126.02, 121.47, 121.32, 120.46, 114.95, 109.89, 21.74; HRMS
(ESI, m/z): calcd for C23H16BrN3 (M+H+) 414.2972, found:
414.2968.
Chem. 2016, 18, 5890-5899; (e) Chetan, K. K.; Deelip,
S. R.; Ganesh, U. C. New J. Chem, 2016, DOI:
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Alex, M. M.; Haidi, D. F.; Faruk, N. J. Org. Chem.
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Zhang, W.; Wang, Q.; Wu, H.; Wu, P.; He, M. Green
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Gholinejad, M.; Hameda, F.; Bij, P. Dalton Trans.
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630-636; (c) Gu, Z.; Athertona, J. J.; Xu, Z. P. Chem.
Commun. 2015, 51, 3024-3036; (d) Zhu, H.; Huang, S.;
Yang, Z.; Liu, T. J. Mater. Chem. 2011, 21, 2950-2956;
(e) Ji-Kuan, Z.; Yan-Fang, X.; Jie, X.; Wan-Guo, H.
Acta Phys. Chim. Sin. 2015, 31, 1199-1206; (f) Buffet,
J. C.; Byles, C. F. H.; Felton, R.; Chen, C.; OHare, D.
Chem. Commun. 2016, 52, 4076-4079; (g) Fan, G.; Li,
F.; Evans, D. G.; Duan, X. Chem. Soc. Rev. 2014, 43,
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4. (a) Zhoua, H.; Zhuob, G. L.; Zhen Jiang, X. J. Mol.
Catal. A: Chem. 2006, 248, 26-31; (b) Choudary, B. M.;
Chowdari, N. S.; Jyothi, K. J. Mol. Catal. A: Chem.
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Chowdari, N. S. J. Am. Chem. Soc. 2002, 124, 14127-
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4.4.17.
4-(2-chlorophenyl)-2-(4-
fluorophenyl)benzo[4,5]imidazo[1,2-a]pyrimidine (4q). Yield
88%; yellow solid; Mp: 250-252 oC; 1H NMR (400 MHz,
CDCl3): δ 8.02 (d, J=7.3, 1H), 7.64-7.71 (m, 5H), 7.47 (t, J=7.3,
1H), 7.34-7.40 (m, 1H), 7.31 (d, J =8.1 Hz, 1H), 7.13 (t, J =8.1
Hz, 1H), 7.06 (t, J=8.4 Hz, 1H), 6.88 (s, 1H), 6.78 (d, J=8.4 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ 161.77, 159.26, 157.27,
151.50, 149.23, 145.43, 133.96, 132.08, 131.26, 131.17, 129.45,
128.40, 126.23, 125.90, 121.61, 120.67, 114.91, 114.83, 114.61,
110.11; HRMS (ESI, m/z): calcd for C22H13ClFN3 (M+H+)
373.0782, found: 373.0785.
4.4.18.
2,4-bis(4-fluorophenyl)benzo[4,5]imidazo[1,2-
a]pyrimidine (4r). Yield 87%; yellow solid; Mp: 256-258 C; 1H
NMR (400 MHz, CDCl3): δ 8.49-8.55 (m, 1H), 8.96 (d, J=8.1
Hz, 1H), 7.62-7.73 (m, 5H), 7.45 (t, J=8.1 Hz, 1H), 7.34 (s, 1H),
7.08 (t, J=8.4 Hz, 1H), 7.03 (t, J=8.5 Hz, 1H), 6.90-6.95 (m, 1H),
6.71 (d, J=8.4, 1H); 13C NMR (100 MHz, CDCl3): δ 160.46 (d,
J= 250.2Hz), 156.92, 151.67, 149.24, 145.41, 133.23, 133.13,
132.42, 131.16, 129.44, 128.43, 126.12, 121.35, 120.27, 114.73,
112.48, 108.52, 108.39, 104.66 ; HRMS (ESI, m/z): calcd for
C22H13F2N3 (M+H+) 357.1077, found: 357.1072.
o
4.4.19.
4-(3-bromophenyl)-2-(p-tolyl)benzo[4,5]imidazo[1,2-
o
a]pyrimidine (4s). Yield 89%; yellow solid; Mp: 244-246 C; 1H
NMR (400 MHz, CDCl3): δ 8.09 (d, J=8.4 Hz, 2H), 7.92 (s, 1H),
7.57 (d, J=8.1 Hz, 2H), 7.52 (d, J=8.1 Hz, 2H), 7.45 (d, J=7.7
Hz, 2H), 7.40 (t, J=6.4 Hz, 1H), 7.12 (s, 1H), 7.00 (t, J=7.3 Hz,
1H), 6.75 (d, J=8.4 Hz, 1H), 2.55 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 159.66, 149.94, 141.57, 135.55, 132.11, 130.09,
129.23, 128.30, 126.00, 121.25, 120.15, 114.80, 104.92, 21.75;
HRMS (ESI, m/z): calcd for C23H16BrN3 (M+H+) 414.2972,
found: 414.2978.
4.4.20.
2-(4-bromophenyl)-4-(2-
fluorophenyl)benzo[4,5]imidazo[1,2-a]pyrimidine (4t). Yield
87%; yellow solid; Mp: 205-207 oC; 1H NMR (400 MHz,
CDCl3): δ 8.64 (d, J=6.6, 1H), 7.97 (d, J=6.6, 1H), 7.64-7.72 (m,
5H), 7.54-7.57 (m, 1H), 7.46 (t, J=7.3, 1H), 7.36 (s, 1H), 7.02-
7.09 (m, 2H), 6.73 (d, J=7.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 161.71 (d, J = 240.5Hz), 156.25, 149.49, 145.56,
135.42, 134.25, 131.27, 129.52, 128.46, 126.30, 121.59, 118.52,
118.26, 114.86, 108.59, 108.45; HRMS (ESI, m/z): calcd for
C22H13BrFN3 (M+H+) 418.2611, found: 418.2615.
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Supporting Information
All Compounds NMR spectra were provided as Supplementary
material.
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