Microwave-assisted efficient synthesis of benzo[4,5]imidazo[1,2-a] pyrimidine derivatives in water under catalyst-free conditions

Article abstract of DOI:10.1002/jhet.5570440625

(Chemical Equation Presented) Benzo[4,5]imidazo[1,2-a]pyrimidine derivatives were synthesized via the three-component reaction of aldehyde, β-dicarbonyl compound and 2-aminobenzimidazole in water under microwave irradiation and without catalyst conditions. The new protocol has the advantages of higher yield, lower cost, reduced environment impact, wider scope and convenient procedure.

Full text of DOI:10.1002/jhet.5570440625

Nov-Dec 2007
1401
Microwave-assisted Efficient Synthesis of benzo[4,5]imidazo[1,2-a]-
pyrimidine Derivatives in Water under Catalyst-free Conditions
Shujiang Tuꢀ* Qingqing Shao, Dianxiang Zhou, Longji Cao, Feng Shi, Chunmei Li
Department of Chemistry, Xuzhou Normal University, Key Laboratory of Biotechnology on Medical Plant,
Xuzhou, Jiangsu 221116, PR China
Received January 10, 2007
R1
O
H
N
O
O
H2O
R1CHO
+
N
R2
CH3
+
NH2
H3C
R2 MWI
N
N
N
H
1
2
3
4
Benzo[4,5]imidazo[1,2-a]pyrimidine derivatives were synthesized via the three-component reaction of
aldehyde, ꢀ-dicarbonyl compound and 2-aminobenzimidazole in water under microwave irradiation and
without catalyst conditions. The new protocol has the advantages of higher yield, lower cost, reduced
environment impact, wider scope and convenient procedure.
J. Heterocyclic Chem., 44, 1401 (2007).
of carbon-heteroatoms, especially carbon-nitrogen bonds,
has been reported [24-27].
INTRODUCTION
The rapid assembly of molecular diversity is an
important goal of synthetic organic chemistry and one of
the key paradigms of modern drug discovery [1,2]. One
approach to address this challenge involves the
development of multicomponent reactions (MCRs), in
which three or more reactants are combined together in a
single reaction flask to generate a product incorporating
most of the atoms contained in the starting materials [3,4].
Diversity can be achieved by simply varying each
component or just changing the reaction conditions [5,6].
In addition to the intrinsic atom economy and selectivity
underlying such reactions, simpler procedures and
equipment, time, and energy savings, as well as
environmental friendliness have all led to a sizable effort
to design and implement MCRs in both academia and
industry [7].
The classic version of the Biginelli three-component
condensation reaction [28], which combines an aldehyde,
urea or thiourea and an open-chain ꢀ-dicarbonyl compound
under acidic conditions in ethanol to give a monocyclic 3,4-
dihydropyrimidin-2(1H)-one (DHPs), has extended into
widespread use of generating large collections of molecules
in combinatorial synthesis [29,30].
Recently much attention has been devoted towards
dihydropyrimidine derivatives due to their significant
therapeutic and medicinal properties [31-33]. Several
marine alkaloids having the dihydropyrimidine core unit
were found to show interesting biological activities such
as antiviral, antibacteriala and anti-inflammatory activities
[34,35]. Many functionalized derivatives are used as
calcium channel blockers, antihypertensive agents and ꢁ-
la antagonists [36,37]. Therefore, the preparation of this
heterocyclic core unit has gained much importance.
Julio Alvarez-Builla and co-workers reported the
synthesis of benzo[4,5]imidazo[1,2-a]-pyrimidine
derivatives with an requisite arylmethyleneacetoacetate,
which could be synthesized via standard Knoevenagel
reaction of aldehyde and ꢀ-ketoester. NaOAc was used as
catalyst and DMF as organic solvent in the protocol [38]
(Scheme 1).
As early as in the 1980's Breslow demonstrated
hydrophobic effects could strongly enhance the rate of
some organic reactions and rediscovered the use of water
as solvent in organic chemistry [8,9]. Since then, the use
of water as a solvent has attracted considerable research
interest [10-12]. Water, compared with organic solvents,
is abundant, nontoxic and environment-friendly.
Therefore, it has become an attractive medium for many
organic reactions [13-15], not only for the advantages
concerning the avoidance of expensive drying agents,
catalysts and solvents, but also for some unique reactivity
and selectivity [16-19].
Scheme 1
R1
R1
H
N
The microwave (MW) assisted organic synthesis has
been a topic of continued studies as it could lead to higher
yields of pure products, easier operation and shorter
reaction time as compared to the traditional heating
methods [20-23]. Use of MW irradiation for the formation
NH2
N
CO2R2
CH3
CO2R2
CH3
N
NaOAc, DMF, MWI
N
N
O
H

1402
S. Tu, Q.Q. Shao, D. X. Zhou, L.J. Cao, F. Shi, C. M. Li
Vol 44
Ahmad Shaabani and co-workers also reported the
Based on these optimized reaction conditions, a series
of benzo[4,5]imidazo[1,2-a]pyrimidine derivatives were
synthesized by equimolecular amounts of aldehyde, ꢀ-
dicarbonyl compound and 2-aminobenzimidazole in water
under microwave irradiation. After irradiation for 3-6
min, the benzo[4,5]imidazo[1,2-a]pyrimidine derivatives
were obtained in excellent yields (84-95%) (Scheme 3).
The results were summerized in Table 2.
three-component condensation reaction of an aldehyde, ꢀ-
ketoester and 2-aminobenzimidazole in 1,1,3,3-N,N,N',
N'-tetramethylguanidinium trifluoroacetate (TMGT) as an
ionic liquid affording 4H-pyrimido[2,1-b]benzazolea
derivatives, with the shortage of long reaction time and
the limitation that the benzaldehydes must be substituted
in the para-position (Scheme 2) [39].
Scheme 2
Scheme 3
R1
R1CHO
R1
R1
O
1
H
N
O
O
H2O
N
R2
CH3
NH2
H3C
R2
+
O
N
H
N
CHO
O
O
MWI
N
N
H
TMGT
100oC/5h
N
R3
NH2
R2
R3
+
2
3
4
N
N
N
R2
H
As shown in Table 2, this protocol could be applied not
only to the aromatic aldehydes with either electron-
withdrawing groups or electron-donating groups, but also
to aliphatic aldehydes, which highlighted the wide scope
of this three-component condensation. Furthermore, the
procedure is easy to operate and the workup procedure is
just simple filtration.
Interested in biological activity of a significant number
of compounds containing condensed pyrimidine ring
system, MCRs and Biginelli-like reactions, we wish to
report a facile, rapid and green protocol for the three
component condensation reactions of an aldehyde, a ꢀ-
dicarbonyl compound and 2-aminobenzimidazole.
Moreover, we performed the synthesis of 4b under
both MWI and classical heating conditions. The
reaction was efficiently promoted by MWI and the
reaction time was strikingly shortened to 6 min from 5 h
required under traditional heating condition and the
yield was increased to 92% from 51%. Therefore,
microwave irradiation exhibited several advantages
over the conventional heating by significantly reducing
the reaction time and dramatically improving the
RESULTS AND DISCUSSION
Choosing an appropriate solvent is of crucial
importance for successful MW promoted synthesis in
view of a rapid rise of temperature in the reaction mixture.
In order to search for the optimum solvent, the MW
assisted reaction of 4-chlorobenzaldehyde (1b), ethyl 3-
oxobutanoate and 2-aminobenzimidazole was examined
using water, ethyleneglycol, ethanol, glacial acetic acid
and DMF as solvent, respectively, at 90 °C. All the
reactions were carried out at the power of 200 W. The
results are summarized in Table 1.
reaction yield owing to
microwave effect [40].
a
specific nonthermal
Although the detailed mechanism of the above reaction
remains to be fully clarified, the formation of benzo[4,5]-
Table 1
imidazo[1,2-a]pyrimidine derivatives
4
could be
Solvent Optimization for the Synthesis of 4b under MWI at 90 °C
explained by the reaction sequence presented in Scheme
4. During the course of reaction, the colour of bright
yellow appeared first, while the reaction system was
rather pale when the reaction ended. The bright yellow
substance was Schiff base 5, condensed of aldehyde and
2-aminobenzimidazole, which was characterized by IR
and 1H NMR spectral data.
Time (
min)
Entry
Solvent
Water
Power ( W)
Yield (ꢀ)
1
200
200
6
8
92
90
2
3
4
5
ethyleneglycol
EtOH
200
200
200
10
20
14
76
50
45
HOAc
DMF
We therefore proposed that the reaction proceeded via a
sequence of condensation, addition, elimination, addition,
cyclization and dehydration. First, the condensation of
aldehyde and 2-aminobenzimidazole gave Schiff base 5.
The addition of Schiff base to 1,3- dicarbonyl compound,
then after elimination furnished the intermediate product
8. Then the addition of 2-aminobenzimidazole to 8 gave
the intermediate product 10, which upon intermolecular
cyclization and dehydration gave rise to 4ꢁ
It is shown in Table 1 the reaction with water as solvent
resulted in the most excellent yield and shortest reaction
time. Water was used as the solvent for all further micro-
wave-assisted reactions as it is also environmentally friendly
and the use of expensive organic reagents can be avoided.
Microwave irradiation power was also optimized for
the synthesis of 4b. The most suitable irradiation power
was 200 W.

Nov-Dec 2007
Microwave-assisted Efficient Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine Derivatives
1403
Table 2
Physical Data of Compounds 4
Compound No.
R1
3
R2
Time(min)
Yield(%)
91
Mp(°C)
>300
4a
4b
4c
4d
4e
4f
4-FC6H4
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
CH3
5
6
6
5
4
4
5
3
5
4
5
5
6
4
5
6
4
5
5
4-ClC6H4
4-BrC6H4
4-MeOC6H4
4-NO2C6H4
3-NO2C6H4
C6H5
92
>300
90
>300
88
272-273
>300
91
90
294-297
294-297
>300
4g
4h
4i
90
2,4-Cl2C6H3
2-ClC6H4
4-FC6H4
94
90
>300
4j
87
>300
4k
4l
4-ClC6H4
4-BrC6H4
4-MeOC6H4
4-NO2C6H4
3-NO2C6H4
C6H5
CH3
89
>300
CH3
88
>300
4m
4n
4o
4p
4q
4r
4s
CH3
85
279-282
>300
CH3
90
CH3
91
290-292
>300
CH3
86
2,4-Cl2C6H3
2-ClC6H4
n-C4H9
CH3
95
>300
CH3
89
>300
CH3
84
236.3-237
Scheme 4
OH
O
O
O
H
N
H
N
H3C
CHR1
R2
H
N
-H2O
R2
NH CHR1
CH3
R1CHO
+
NH2
N
N
3
N
N
1
2
5
6
O
O
N
N
R1
H
O
OH
NH2
R2
CH3
N
R2
CH3
CH3
R2
N
H
NH CHR1
R1
HN
O
O
N
H
N
8
7
H
9
O
O
O
H3C OH
HN
CH3
N
O
H3C
R2
R2
HN
R2
H2N
-H2O
N
R1
N
R1
N
N
N
10
11
4
To test the proposed mechanism, we carried out the
synthesis of 4b in two steps, first of which was to get the
pure Schiffe base 5b, and then reacted with 3a under
similar conditions. The target compound of 4b was
obtained with yield similar to the one-pot reaction. The
fact supported the proposed mechanism (Scheme 4).
In this study, all the products were characterized by
1
melting point, IR and H NMR spectral data, as well as
elemental analyses. Furthermore, the structure of 4d
was established by X-ray crystallographic analysis
(Figure 1).

1404
S. Tu, Q.Q. Shao, D. X. Zhou, L.J. Cao, F. Shi, C. M. Li
Vol 44
4-(4-Chloro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]imi-
dazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4b). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3234, 3101, 3025, 2981, 2863, 1696,
1
1617, 1572, 1516, 1385, 1284, 1168, 893, 753cm-1; H nmr
(DMSO-d6): ꢁ 10.87 (s, 1H, NH), 7.40-7.26 (m, 6H, ArH), 7.05
(t, 1H, J = 7.6 Hzꢁ ArH), 6.96 (t, 1H, J = 7.2 Hzꢁ ArH), 6.46 (s,
1H, CH), 4.02 (q, 2H, J = 8.0 Hz, CH2), 2.46 (s, 3H, CH3), 1.15
(t, 3H, J = 7.2 Hzꢁ CH3). Anal. Calcd. for C20H18ClN3O2: C,
65.31; H, 4.93; N, 11.42. Found: C, 65.41; H, 4.89; N, 11.44.
4-(4-Bromo-phenyl)-2-methyl-1,4-dihydrobenzo[4,5]imi-
dazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4c). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3233, 3101, 3023, 2978, 2849, 1698,
1618, 1571, 1487, 1385, 1234, 1010, 893, 801, 730 cm-1; 1H nmr
(DMSO-d6): ꢁ 10.87 (s, 1H, NH), 7.47 (d, 2H, J = 8.4 Hz, ArH),
7.36-7.32 (m, 3H, ArH), 7.26 (d, 1H, J = 8.0 Hz, ArH), 7.06 (t,
1H, J = 7.6 Hz, ArH), 6.96 (t, 1H, J = 8.0 Hz, ArH), 6.45 (s, 1H,
CH), 4.02 (q, 2H, J = 8.0 Hz, CH2), 2.46 (s, 3H, CH3), 1.16 (t,
3H, J = 7.2 Hz, CH3). Anal. Calcd. for C20H18BrN3O2: C, 58.26;
H, 4.40; N, 10.19. Found: C, 58.16; H, 4.52; N, 10.20.
4-(4-Methoxy-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4d).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3231, 3011, 2907, 2839,
1703, 1511, 1297, 1179, 1022, 911, 876, 734, 632 cm-1; 1H nmr
(DMSO-d6): ꢁ 10.77 (s, 1H, NH), 7.34 (d, 1H, J = 8.0 Hz, ArH),
7.29-7.25 (m, 3H, ArH), 7.04 (t, 1H, J = 7.2 Hz, ArH), 6.95 (t,
1H, J = 7.6 Hz, ArH), 6.81 (d, 2H, J = 4.8 Hz, ArH), 4.02 (q,
2H, J = 8.0 Hz, CH2), 3.67 (s, 3H, OCH3), 2.45 (s, 3H, CH3),
1.16 (t, 3H, J = 7.2 Hz, CH3). Anal. Calcd. for C21H21N3O3: C,
69.41; H, 5.82; N, 11.56. Found: C, 69.52; H, 5.78; N, 11.61.
4-(4-Nitro-phenyl)-1,4-dihydro-benzo[4,5]imidazo[1,2-a]-
pyrimidine-3-carboxylic acid ethyl ester (4e). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3234, 3105, 2978, 2861, 1697, 1619,
Figure 1
In conclusion, we have developed a three-component reaction
of an aldehyde, ꢀ-dicarbonyl compound and 2-aminobenzimida-
zole in water under microwave irradiation conditions for the
synthesis of benzo[4,5]imidazo[1,2-a]-pyrimidine derivatives.
Particularly valuable features of this method include excellent
yields of the products, shorter reaction time, reduced environ-
mental impact, and straightforward procedure.
EXPERIMENTAL
Microwave irradiation was carried out in a monomodal
EmrysTM Creator from Personal Chemistry, Uppsala, Sweden.
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a TENSOR 27
spectrometer in KBr. 1H NMR spectra were measured on a DPX
400 spectrometer operating at 400 MHz, using DMSO-d6 as
solvent and TMS as internal standard. Elemental analyses were
determined by using a Perkin-Elmer 240c elemental analysis
instrument.
General Procedure for the synthesis of benzo[4,5]imidazo-
[1,2-a]pyrimidine derivatives (4a-4s). In a 10 mL EmrysTM
reaction vial, aldehyde (1 mmol),ꢀ ꢀ-dicarbonyl compound (1
mmol), 2-aminobenzimidazole (1 mmol) and water (2 mL) were
mixed and then capped. After irradiation for 3-6 min, the
reaction mixture was cooled to room temperature. Then the
mixture was filtered to give the crude product, which was further
purified by crystallized from 95% EtOH.
4-(4-Fluoro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]imi-
dazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4a). This
compound was obtained according to above general procedure;
ir (potassium bromide): cm-1 3235, 3039, 2929, 1697, 1617,
1458, 1303, 1096, 792, 637; 1H nmr (DMSO-d6): ꢁ 10.84 (s, 1H,
NH), 7.43-7.40 (m, 2H, ArH), 7.35 (d, 1H, J = 8.0 Hz, ArH),
7.28 (d, 1H, J = 7.6 Hz,ArH), 7.12-7.03 (m, 3H, ArH), 6.96 (t,
1H, J = 7.6 Hz, ArH), 6.46(s, 1H, CH), 4.02 (q, 2H, J = 7.2 Hz,
CH2), 2.46 (s, 3H, CH3), 1.15 (t, 3H, J = 7.2 Hzꢁ CH3). Anal
calcd. for C20H18FN3O2: C, 68.36; H, 5.16; N, 11.96. Found: C,
68.46; H, 5.11; N, 11.89.
1
1572, 1518, 1458, 1235, 870, 755, 715, 608 cm-1; H nmr
(DMSO-d6): ꢁ 10.99 (s, 1H, NH), 8.15 (d, 2H, J = 8.4 Hz, ArH),
7.66 (d, 2H, J = 8.8 Hz, ArH), 7.37 (d, 1H, J = 7.6 Hz, ArH),
7.28 (d, 1H, J = 7.6 Hzꢁ ArH), 7.06 (t, 1H, J = 7.2 Hz, ArH),
6.96 (t, 1H, J = 7.2 Hz, ArH), 6.62 (s, 1H, CH), 4.03 (q, 2H, J =
7.6 Hz CH2), 2.48 (s, 3H, CH3), 1.16 (t, 3H, J = 7.2 Hz, CH3).
Anal. Calcd. for C20H18N4O4: C, 63.48; H, 4.79; N, 14.81.
Found: C, 63.35; H, 4.81; N, 14.79.
4-(3-Nitro-phenyl)-1,4-dihydro-benzo[4,5]imidazo[1,2-a]-
pyrimidine-3-carboxylic acid ethyl ester (4f). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3232, 3092, 3023, 2980, 2903, 2844,
1707, 1618, 1573, 1457, 1350, 1170, 891, 820, 743 cm-1; 1H nmr
(DMSO-d6): ꢁ 10.99 (s, 1H, NH), 8.08–8.06 (m, 1H, ArH), 7.76
(d, 2H, J = 8.0 Hz, ArH), 7.58 (t, 1H, J = 8.0 Hz, ArH), 7.37 (d,
1H, J = 8.0 Hz, ArH), 7.32 (d, 1H, J = 8.0 Hz, ArH), 7.07 (t, 1H,
J = 7.6 Hz, ArH), 6.96 (t, 1H, J = 7.2 Hz, ArH), 6.67 (s, 1H,
CH), 4.02 (q, 2H, J = 7.2 Hz, CH2), 2.48 (s, 3H, CH3), 1.17 (t,
3H, J = 6.8 Hz, CH3). Anal. Calcd. for C20H18N4O4: C, 63.48; H,
4.79; N, 14.81. Found: C, 63.35; H, 4.81; N, 14.79.
2-methyl-4-phenyl-1,4-dihydro-benzo[4,5]imidazo[1,2-a]-
pyrimidine-3-carboxylic acid ethyl ester (4g). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3234, 3103, 3026, 2928, 2865, 1698,
1
1615, 1572, 1365, 1255, 1092, 893, 794, 730 cm-1; H nmr
(DMSO-d6): ꢁ 10.82 (s, 1H, NH), 7.35 (t, 3H, J = 6.8 Hz, ArH)ꢁ

Nov-Dec 2007
Microwave-assisted Efficient Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine Derivatives
1405
7.27 (t, 3H, J = 8.0 Hz, ArH), 7.20-7.16 (m, 1H, ArH)ꢀ 7.04(t,
1H, J = 8.0 Hz, ArH), 6.95 (t, 1H, J = 7.6 Hz, ArH), 6.43 (s, 1H,
CH), 4.02 (q, 2H, J = 7.2 Hz, CH2), 2.46 (s, 3H, CH3), 1.14 (t,
3H, J = 7.2 Hz, CH3). Anal. Calcd. for C20H19N3O2: C, 72.05; H,
5.74; N, 12.60. Found: C, 72.18; H, 5.82; N, 12.54.
659 cm-1; 1H nmr (DMSO-d6): ꢀ 10.75 (s, 1H, NH), 7.43 (d, 1H,
J = 8.0 Hz, ArH), 7.05-6.97 (m, 2H, ArH), 6.83 (d, 2H, J = 8.0
Hz, ArH), 6.57 (s, 1H, CH), 3.67 (s, 3H, OCH3), 2.47 (s, 3H,
CH3), 2.22 (s, 3H, CH3). Anal. Calcd. for C20H19N3O2: C, 72.05;
H, 5.74; N, 12.60. Found: C, 72.13; H, 5.66; N,12.50.
4-(2,4-Dichloro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4h).
This compound was obtained according to above general
procedure; ir (potassium bromide): 3233, 3101, 2973, 2929,
2863, 1698, 1618, 1515, 1458, 1385, 1046, 909, 866, 694 cm-1;
1H nmr (DMSO-d6): ꢀ 10.98 (s, 1H, NH), 7.58-7.49 (m, 2H,
ArH)ꢀ 7.40-7.36 (m, 2H, ArH), 7.16 (d, 1H, J = 8.0 Hz, ArH)ꢀ
7.07 (t, 1H, J = 7.2 Hz, ArH), 6.98 (t, 1H, J = 7.2 Hz, ArH),
6.75 (s, 1H, CH), 4.01 (q, 2H, J = 8.0 Hz, CH2), 2.47 (s, 3H,
1-[4-(4-Nitro-phenyl)-1,4-dihydro-benzo[4,5]imidazo[1,2-a]-
pyrimidin-3-yl]-ethanone (4n). This compound was obtained
according to above general procedure; ir (potassium bromide):
3229, 3022, 2840, 1655, 1592, 1455, 1347, 1230, 824, 742 cm-1;
1H nmr (DMSO-d6): ꢀ 11.00(s, 1H, NH), 8.13 (d, 2H, J = 8.0 Hz,
ArH), 7.67 (d, 2H, J = 8.0 Hz, ArH), 7.41-7.36 (m, 2H, ArH),
7.06 (t, 1H, J = 7.2 Hz, ArH), 6.99 (t, 1H, J = 7.6 Hz, ArH), 6.73
(s, 1H, CH), 2.52 (s, 3H, CH3), 2.29 (s, 3H, CH3). Anal. Calcd.
for C19H16N4O3: C, 65.51; H, 4.63; N, 16.08. Found: C, 65.60; H,
4.58; N, 16.02.
CH3), 1.11(t, 3H,
J = 7.2 Hz, CH3).Anal. Calcd. for
C20H17Cl2N3O2: C, 59.71; H, 4.26; N, 10.45. Found: C, 59.82;
H, 4.32; N, 10.42.
1-[4-(3-Nitro-phenyl)-1,4-dihydro-benzo[4,5]imidazo[1,2-a]-
pyrimidin-3-yl]-ethanone (4o). This compound was obtained
according to above general procedure; ir (potassium bromide):
3215, 3087, 2881, 1649, 1560, 1458, 1267, 1059, 959, 888, 737,
690 cm-1; 1H nmr (DMSO-d6): ꢀ 11.01 (s, 1H, NH), 8.28 (s, 1H,
ArH), 8.05 (d, 1H, J = 8.0 Hz, ArH), 7.81 (d, 1H, J = 8.0 Hz,
ArH), 7.58 (t, 1H, J = 7.6 Hz, ArH), 7.45 (d, 1H, J = 8.0 Hz,
ArH), 7.37 (d, 1H, J = 8.0 Hz, ArH), 7.06 (t, 1H, J = 7.2 Hz,
ArH), 6.99 (t, 1H, J = 7.6 Hz, ArH), 6.77 (s, 1H, CH), 2.53 (s,
3H, CH3), 2.30 (s, 3H, CH3). Anal. Calcd. for C19H16N4O3:
C,65.51; H, 4.63; N,16.08. Found: C, 65.60; H, 4.58; N, 16.02.
1-(2-Methyl-phenyl-4-methyl-1,4-dihydro-benzo[4,5]imi-
dazo[1,2-a]pyrimidin-3-yl)-ethanone (4p). This compound was
obtained according to above general procedure; ir (potassium
bromide): cm-1; 1H nmr (DMSO-d6): ꢀ 10.83 (s, 1H, NH), 7.42
(d,3H, J = 8.0 Hz, ArH), 7.35-7.26 (m, 3H, ArH), 7.20-7.16 (m,
1H, ArH), 7.06-6.95 (m, 2H, ArH), 6.60 (s, 1H, CH), 2.49 (s,
3H, CH3), 2.23(s, 3H, CH3). Anal. Calcd. for C19H17N3O: C,
75.23; H, 5.65; N, 13.85. Found: C, 75.26; H, 5.76; N, 13.91.
1-[4-(2,4-Dichloro-phenyl)-1,4-dihydro-benzo[4,5]imidazo-
[1,2-a]pyrimidin-3-yl]-ethanone (4q). This compound was
obtained according to above general procedure; ir (potassium
bromide) 3230, 3104, 3022, 2840, 1659, 1612, 1523, 1457,
4-(2-Chloro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]imi-
dazo[1,2-a]pyrimidine-3-carboxylic acid ethyl ester (4i). This
compound was obtained according to above general procedure;
ir (potassium bromide): 3238, 3157, 3106, 2978, 2927, 2849,
1700, 1662, 1576, 1520, 1473, 1366, 1019, 892, 833, 796, 718
cm-1; 1H nmr (DMSO-d6): ꢀ 10.93 (s, 1H, NH), 7.46 (d, 1H, J =
8.0 Hz, ArH), 7.40-7.35 (m, 2H, ArH), 7.30-7.19 (m, 3H, ArH),
7.05 (t, 1H, J = 7.2 Hz, ArH), 6.96 (t, 1H, J = 7.6 Hz, ArH), 6.76
(s, 1H, CH), 3.97 (q, 2H, J = 8.0 Hz CH2), 2.47 (s, 3H, CH3),
1.09 (t, 3H, J = 7.2 Hz, CH3). Anal. Calcd. for C20H18ClN3O2: C,
65.31; H,4.93; N, 11.42. Found: C, 65.48; H, 4.88; N, 11.36.
1-[4-(4-Fluoro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidin-3-yl]-ethanone (4j). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3227, 3100, 3022, 2914, 2840, 1653,
1627, 1565, 1459, 1330, 1229, 1006, 954, 854, 747 cm-1; 1H nmr
(DMSO-d6): ꢀ 10.85 (s, 1H, NH), 7.48-7.42 (m, 3H, ArH), 7.35
(d, 1H, J = 8.0 Hz, ArH)ꢀ 7.12-6.98 (m, 4H, ArH)ꢀ 6.62 (s, 1H,
CH), 2.49 (s, 3H, CH3)ꢀ 2.24 (s, 3H, CH3). Anal. Calcd. for
C19H16FN3O: C, 71.01; H, 5.02; N, 13.08. Found: C, 71.00; H,
5.04; N, 13.05.
1
1270, 866, 806, 739: cm-1; H nmr (DMSO-d6): ꢀ 10.98 (s, 1H,
1-[4-(4-Chloro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidin-3-yl]-ethanone (4k). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3227, 3100, 3022, 2838, 1654, 1610,
NH), 7.54-7.49 (m, 2H, ArH), 7.37 (d, 2H, J = 8.0 Hz, ArH),
7.24 (d, 1H, J = 8.0 Hz, ArH), 7.07 (t, 1H, J = 7.6 Hz, ArH),
6.99 (t, 1H, J = 7.6 Hz, ArH), 6.79 (s, 1H, CH), 2.50 (s, 3H,
CH3), 2.27 (s, 3H, CH3). Anal. Calcd. for C19H15ClN3O: C,
61.30; H, 4.06; N, 11.29. Found: C, 61.48; H, 4.08; N, 11.32.
1-[4-(2-Chloro-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidin-3-yl]-ethanone (4r). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3225, 3097, 3019, 2835, 1654, 1611,
1564, 1472, 1436, 1327, 1266, 984, 889, 742, 699 cm-1; 1H nmr
(DMSO-d6): ꢀ 10.92 (s, 1H, NH), 7.48 (d, 1H, J = 6.8 Hz, ArH),
7.31-7.20 (m, 3H, ArH), 7.06 (t, 1H, J = 7.2 Hz, ArH), 6.98 (t,
3H, J = 8.0 Hz, ArH), 6.82 (s, 1H, CH), 2.49 (s, 3H, CH3), 2.25
(s, 3H, CH3). Anal. Calcd. for C19H16ClN3O: C, 67.56; H, 4.77;
N, 12.44. Found: C, 67.64; H, 4.85; N, 12.39.
1
1566, 1522, 1436, 1380, 1228, 830, 747, 694 cm-1; H nmr
(DMSO-d6): ꢀ 10.88 (s, 1H, NH), 7.44-7.33 (m, 6H, ArH)ꢀ
7.08-6.98 (m, 2H, ArH), 6.61 (s, 1H, CH), 2.49 (s, 3H, CH3)ꢀ
2.25 (s, 3H, CH3)ꢁꢂAnal. Calcd. for C19H16ClN3O: C, 67.56; H,
4.77; N, 12.44. Found: C, 67.67; H, 4.67; N, 12.48.
1-[4-(4-Bromo-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidin-3-yl]-ethanone (4l). This compound
was obtained according to above general procedure; ir
(potassium bromide): 3297, 3227, 3099, 2918, 2839, 1650,
1607, 1560, 1456, 1308, 887, 742, 655 cm-1; 1H nmr (DMSO-d6):
ꢀ 10.86 (s, 1H, NH), 7.47 (d, 2H, J = 8.0 Hz, ArH), 7.41-7.34
(m, 4H, ArH), 7.08-7.04 (m, 1H, ArH), 7.01-6.97 (m, 1H, ArH),
6.59 (s, 1H, CH), 2.49 (s, 3H, CH3), 2.25 (s, 3H, CH3). Anal.
Calcd. for C19H16BrN3O: C, 59.70; H, 4.22; N, 10.99. Found: C,
59.81; H, 4.38; N, 11.10.
1-[4-(4-Hydroxy-phenyl)-2-methyl-1,4-dihydro-benzo[4,5]-
imidazo[1,2-a]pyrimidin-3-yl]-ethanoe; compound with
ethane (4m). This compound was obtained according to above
general procedure; ir (potassium bromide): 3227, 3099, 3002,
2832, 1654, 1628, 1590, 1514, 1459, 1335, 1228, 958, 807, 744,
1-(4-Butyl-1,4-dihydro-benzo[4,5]imidazo[1,2-a]pyrimidin-
3-yl]-ethanone (4s). This compound was obtained according to
above general procedure; ir (potassium bromide): 3225, 3097,
3019, 2834, 1654, 1610, 1564, 1472, 1436, 1327, 1266, 984,
889, 742, 699 cm-1; 1H nmr (DMSO-d6): ꢀ 10.50 (s, 1H, NH),
7.50-7.48 (m, 1H, ArH), 7.40-7.38 (m, 1H, ArH), 7.13-7.06 (m,
2H, ArH), 5.70 (s, 1H, CH), 2.40 (s, 3H, CH3), 2.36 (s, 3H,
CH3), 1.91-1.57 (m, 2H, CH2), 1.11-0.73 (m, 4H, 2CH2), 0.70 (t,

1406
S. Tu, Q.Q. Shao, D. X. Zhou, L.J. Cao, F. Shi, C. M. Li
Vol 44
1983, 24, 1901.
3H, J = 8.0 Hz, CH3).Anal. Calcd. for C17H21N3O: C, 72.06; H,
7.47; N, 14.83. Found: C, 72.14; H, 7.45; N, 14.78.
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5008.
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[22] Bose, A. K.; Manhas, M. S.; Ganguly, S. N.; Sharma, A. H.;
Banik, B. K. Synthesis, 2002, 1578.
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(E)-N-(4-chlorobenzylidene)-1H-benzo(d)imidazol-2-amine
(5b). In a 10-mL EmrysTM reaction vial, 4-chlorobenzaldehyde
(1 mmol),ꢀ 2-aminobenzimidazole (1 mmol) and water (2 mL)
were mixed and then capped. After irradiation for 1 min, the
reaction mixture was cooled to room temperature. Then the
mixture was filtered to give the crude product, which was further
purified by recrystallization from 95% EtOH. Ir (potassium
bromide): 3245, 3078, 2973, 2764, 1684, 1585, 1389, 1090, 852,
1
cm-1; H nmr (DMSO-d6): ꢀ 12.74 (s, 1H, NH), 9.47 (s, 1H,
CH), 8.11-8.10 (d, 2H, J = 8.0 Hz, ArH), 7.67 (d, 2H, J = 8.0 Hz,
ArH), 7.61-7.59 (m, 1H, ArH), 7.46-7.45(m, 1H, ArH), 7.21-
7.19(m, 2H, ArH). Anal. Calcd. for C14H10N3Cl: C, 65.76; H,
3.94; N, 16.43. Found: C, 65.71; H, 3.96; N, 16.39.
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Lett. 2004, 6, 1001.
Acknowledgement. We thank for the National Natural
Science Foundation of China (No. 20672090), the Nature
Science Foundation of the Jiangsu Province (No. BK 2006033)
for financial support.
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[41] The single-crystal growth was carried out in ethanol at room
temperature. X-ray crystallographic analysis was performed with a
Siemens SMART CCD and a Siemens P4 diffractometer. Crystal data
for 4d: C21H21N3O3, colorless, crystal dimension 0.20 x 0.15 x 0.09 mm,
Triclinic, space group P-1, a= 6.3173 (13), b = 10.970(2), c = 13.956(3)
Å, ꢀ = 73.277 (3)ꢂ, ꢁ = 80.566 (3)ꢂ, ꢂ = 89.565(3)ꢂ, V = 912.9(3) Å3,
Mr = 363.41, Z = 2, Dc = 1.322 g/cm3, ꢀ = 0.71073 Å, μ (Mokꢁ) =
0.090mm-1, F(000) = 384, S =1.008, R1= 0.0469, wR2 = 0.1144.
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