New applications of phosphoric acid supported on alumina (H 3PO4-Al2O3) as a reusable heterogeneous catalyst for preparation of 2,3-dihydroquinazoline-4(1H)-ones, 2H-indazolo[2,1-b]phthalazinetriones, and benzo[4,5]imidazo[1,2-a]pyrimidines

Article abstract of DOI:10.1007/s11164-013-1087-2

An eco-friendly procedure for synthesis of 2,3-dihydroquinazoline-4(1H)- one, 2H-indazolo[2,1-b]phthalazinetrione, and benzo[4,5]imidazo[1,2-a]pyrimidine derivatives by three-component reaction, with phosphoric acid supported on alumina as catalyst, is described. Noticeable features of the method are that it is solvent-free, work-up is easy, yields are excellent, and the catalyst is reusable.

Full text of DOI:10.1007/s11164-013-1087-2

Res Chem Intermed
DOI 10.1007/s11164-013-1087-2
New applications of phosphoric acid supported
on alumina (H3PO4–Al2O3) as a reusable heterogeneous
catalyst for preparation of 2,3-dihydroquinazoline-
4(1H)-ones, 2H-indazolo[2,1-b]phthalazinetriones,
and benzo[4,5]imidazo[1,2-a]pyrimidines
•
Hamid Reza Shaterian Nafiseh Fahimi Kobra Azizi
•
Received: 17 November 2012 / Accepted: 29 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract An eco-friendly procedure for synthesis of 2,3-dihydroquinazoline-4(1H)-
one, 2H-indazolo[2,1-b]phthalazinetrione, and benzo[4,5]imidazo[1,2-a]pyrimidine
derivatives by three-component reaction, with phosphoric acid supported on alumina as
catalyst, is described. Noticeable features of the method are that it is solvent-free, work-
up is easy, yields are excellent, and the catalyst is reusable.
Keywords 2,3-Dihydroquinazoline-4(1H)-ones ꢀ 2H-indazolo
[2,1-b]phthalazinetriones ꢀ Benzo[4,5]imidazo[1,2-a]pyrimidine ꢀ H3PO4–Al2O3
Introduction
Multi-component reactions (MCRs) are important in combinatorial chemistry
because of the ability to synthesize target compounds with greater efficiency and
atom economy by generating structural complexity in a single step from three or
more reactants [1]. In addition, MCRs have the advantage of simplicity and
synthetic efficiency over conventional chemical reactions [1]. MCRs have attracted
much attention for construction of heterocyclic ‘‘drug-like’’ libraries [1–4].
2,3-Dihydroquinazoline-4(1H)-ones are an important class of heterocyclic
compounds with a wide range of biological activity and pharmacological properties
[5]. They can also be easily oxidized to their quinazolin-4(3H)-one analogues,
which also have biological activity [5–7].
Phthalazine derivatives have been reported to have anticonvulsant [8], cardio-
tonic [9], and vasorelaxant [10] activity. Dihydropyrimidine derivatives have
significant therapeutic and medicinal properties [11–13]. Several marine alkaloids
H. R. Shaterian (&) ꢀ N. Fahimi ꢀ K. Azizi
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan,
PO Box 98135-674, Zahedan, Iran
e-mail: hrshaterian@chem.usb.ac.ir
123

H. R. Shaterian et al.
containing the dihydropyrimidine structure have interesting biological activity, for
example antiviral, antibacterial, and anti-inflammatory [14, 15]. Many functional-
ized derivatives of dihydropyrimidines have been used as calcium channel blockers,
antihypertensive agents and a1A antagonists [16, 17]. Therefore, preparation of this
heterocyclic structure has attracted much attention.
Phosphoric acid supported on alumina was prepared for the first time by Araujo
et al. [18], by mixing alumina with phosphoric acid. This heterogeneous catalyst
was characterized and catalytic evaluation of oleic acid conversion to biofuels and
biolubricant was studied [18]. The best catalytic performance was achieved by use
of the highest-surface-area alumina impregnated with H3PO4, a solid which
combined high total acidity with a large number of mesopores [18]. By use of 31P
NMR data [19], two aspects of the structure of the catalyst were confirmed
(Scheme 1):
1
2
different phosphorus and aluminium interactions in bridging structures [19]; and
linear phosphorus and aluminium bonding [19].
Development of efficient and environmentally benign chemical methods in which
heterogeneous recyclable catalysts are used under solvent-free conditions is a major
challenge for chemists in organic synthesis [20]. In continuation of our research on
solid heterogeneous acidic catalysts [21], we report herein a practical method for
synthesis of 2,3-dihydroquinazoline-4(1H)-one, 2H-indazolo[2,1-b]phthalazinetri-
one, and benzo[4,5]imidazo[1,2-a]pyrimidine derivatives under thermal solvent-
free conditions in the presence of H3PO4–Al2O3(50 % w/w) (Schemes 2, 3, 4).
Results and discussion
Synthesis of 2,3-dihydroquinazoline-4(1H)-ones
To optimize the reaction conditions for preparation of 2,3-dihydroquinazoline-
4(1H)-ones, we heated isatoic anhydride (1 mmol), aniline (1.1 mmol), and
benzaldehyde (1 mmol) at 100 °C in the presence of different amounts of H3PO4–
Al2O3 as catalyst under solvent-free conditions. It was found that 120 mg catalyst
resulted in maximum yield (89 %) in minimum time (33 min). Further increasing the
amount of catalyst (150 mg) led to shorter reaction times (1 or 2 min) but with
decreasing the yield of the product. Thus, 120 mg catalyst was found to be the
optimum quantity and sufficient to promote the reaction. To optimize the reaction
temperature we performed this model reaction with H3PO4–Al2O3 (120 mg) at
Scheme 1 Structures of
phosphoric acid supported on
alumina
OH
OH
O
Al
Al
Al O P(OH)2
O
P
O
Structure a
Structure b
123

New applications of phosphoric acid
O
O
R
H3PO4 / Al2O3 (Catalyst)
R'CHO
N
O
RNH2
or
N
H
R'
N
O
NH4OAc
H
Scheme 2 Synthesis of 2,3-dihydroquinazoline-4(1H)-ones
O
O
H3PO4 / Al2O3 (Catalyst)
O
NH
NH
N
+
ArCHO
+
N
O
O
Ar
O
O
R1
N
Scheme 3 Synthesis of 2H-indazolo[2,1-b]phthalazinetriones
O
O
R3
CHO
H3PO4 / Al2O3 (Catalyst)
N
X
R2
R3
NH2
O
X
R1
N
R2
X=NH, S
Scheme 4 Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine
different temperatures under solvent-free conditions. The best results were obtained
by use of 120 mg catalyst at 120 °C (Tables 1, 2).
Next, we applied this optimum procedure to a diversity of primary amines or
ammonium acetate (as the source of ammonia), aldehydes, and isatoic anhydride.
We studied the scope of this reaction for preparation of a variety of 2,3-
dihydroquinazolin-4(1H)-one derivatives (Table 3). As shown in Table 3, the direct
three-component reactions worked well with a variety of aromatic aldehydes
Table 1 Optimization of the amount of H3PO4–Al2O3 as catalyst in the reaction of isatoic anhydride
(1 mmol), aniline (1.1 mmol), and benzaldehyde (1 mmol) under solvent-free conditions at 100 °C
Entry
Catalyst (mg)
Time (min)
Yield (%)a
1
2
3
4
a
80
60
45
33
31
70
85
89
87
100
120
150
Yields refer to the isolated pure products
123

H. R. Shaterian et al.
Table 2 Optimization of the temperature for reaction of isatoic anhydride (1 mmol), aniline (1.1 mmol),
and benzaldehyde (1 mmol) in the presence of H3PO4–Al2O3 (120 mg) as catalyst under solvent-free
conditions
Entry
Temperature (°C)
Time (min)
Yield (%)a
1
2
3
4
5
a
60
52
43
33
30
28
55
75
89
91
88
80
100
120
150
Yields refer to the isolated pure products
including those bearing electron-withdrawing and electron-donating groups, for
example OMe, Cl, Br, and NO2, and the desired compounds were obtained in good
to high yields (Table 3, Entries 1–31).
We also applied this efficient and environmental friendly approach to the
synthesis of heterocyclic 3-(20-benzothiazolo)-2,3-dihydroquinazolin-4(1H)-ones by
three-component condensation of 2-aminobenzothiazole, isatoic anhydride, and
aromatic or aliphatic aldehydes under thermal solvent-free conditions. The products
were obtained in good yields (Scheme 5; Table 3, Entries 9–18).
Three 3-(20-benzimidazolo)-2,3-dihydroquinazolin-4(1H)-one derivatives were
synthesized for the first time by three-component condensation reaction of
2-aminobenzimidazole, isatoic anhydride, and aryl aldehydes under the same
conditions (Scheme 6; Table 3, Entries 19–21).
If ammonium acetate is used as the source of ammonia (Scheme 2, R = H) in
this reaction, 2-aryl-2,3-dihydroquinazolin-4(1H)-one derivatives are produced in
good to high yields (Table 3, Entries 22–31).
The mechanism suggested for the H3PO4–Al2O3-catalyzed preparation of 2,3-
dihydroquinazoline-4(1H)-ones is shown in Scheme 7. According to mechanisms
reported in the literature [22, 23, 30], H3PO4–Al2O3 can act as catalyst on isatoic
anhydride and produce the reactive intermediate I. N-Nucleophilic primary amine
attack on the carbonyl unit of I produces the reactive intermediate II, which affords
III by decarboxylation. Proton transfer by III affords the 2-amino-N-substituted
amide IV. Subsequent reaction of the activated aldehyde with IV furnishes the
imine intermediate V. The amide functional group in intermediate IV could be
formed by tautomerism in the presence of the catalyst. Thus, intermediate VI could
be prepared by intermolecular nucleophilic attack of the amide nitrogen on the
activated imine carbon, and subsequent 1,5-proton transfer yields the final 2,3-
dihydroquinazoline-4(1H)-ones as products (Scheme 7).
We also investigated recycling of the catalyst under solvent-free conditions,
using reaction of isatoic anhydride with aniline and benzaldehyde (Table 3, Entry 1)
as a model. After completion of the reaction, the reaction was cooled to room
temperature and the crude solid product was dissolved in ethyl acetate. The mixture
was filtered for separation of the catalyst. The catalyst was washed with ethyl
acetate (2 9 5 mL). The recovered solid catalyst was dried under vacuum and used
123

New applications of phosphoric acid
Table 3 Synthesis of 2,3-dihydroquinazoline-4(1H)-one derivatives (Scheme 2)
Entry
R (amine)
R0 (aldehyde)
Time
(min)
Yield
(%)a
Found m.p. (°C)/(Lit. m.p.
(°C)) Ref.
1
Ph
Ph
30
38
30
25
32
38
18
30
14
10
8
91
89
85
90
90
90
78
88
87
82
90
93
90
88
90
89
80
214–216/(214–215) [22]
193–195/(194–196) [23]
213–215/(214–217) [24]
205–207/(204–205) [23]
219–221/(222–225) [23]
215–218/(216–217) [25]
208–210/(209–211) [23]
198–205/(196–199) [23]
231–234/(233–236) [26]
192–195/(190–193) [26]
228–231/(231–234) [26]
180–185/(184–186) [26]
224–231/(225–230) [26]
199–202/(198–200) [26]
146–149/(148–151) [23]
221–223/(215–222) [23]
2
Ph
4-NO2C6H4
4-ClC6H4
4-MeOC6H4
4-BrC6H4
Ph
3
Ph
4
Ph
5
Ph
6
4-ClC6H4
4-MeOC6H4
4-MeC6H4
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
7
Ph
8
Ph
9
Ph
10
11
12
13
14
15
16
17
4-ClC6H4
4-BrC6H4
4-MeOC6H4
2-MeOC6H4
2-MeC6H4
CH3(CH2)5
CH3–
12
16
10
14
12
8
2,5(MeO)2C6H3
225–226/(Prepared for
the first time)
18
Benzothiazolyl
2,3-(Cl)2C6H3
7
82
246–248/(Prepared for
the first time)
19
20
21
22
23
24
25
26
27
28
29
30
31
a
Benzoimidazolyl
4-NO2C6H4
2-MeOC6H4
2,5-(MeO)2C6H3
4-MeOC6H4
2,4-(MeO)2C6H3
4-NO2C6H4
4-MeC6H4
10
9
90
93
90
80
83
87
93
89
92
91
90
95
90
[300/(Prepared for the first time)
275/(Prepared for the first time)
235/(Prepared for the first time)
193–195/(192–193) [27]
185–187/(186–187) [22]
212–215/(213–214) [22]
231–234/(233–234) [25]
202–204/(205–206) [25]
200–202/(199–200) [26, 28]
210–212/(210–213) [29]
219–222/(221–223) [23]
206–208/(205206) [22]
Benzoimidazolyl
Benzoimidazolyl
8
H
H
H
H
H
H
H
H
H
H
10
8
11
9
4-BrC6H4
17
15
14
9
4-FC6H4
3,4-(MeO)2C6H3
Ph
4-ClC6H4
12
9
3-NO2C6H4
214–215/(216–217) [28]
Yields refer to the isolated pure products. The desired pure products were characterized by comparison
1
of their physical data (melting points, FT-IR, H NMR and 13C NMR) with those of known compounds
[22–29]. The reaction was carried out under thermal solvent-free conditions in an oil bath at 100 °C
123

H. R. Shaterian et al.
S
O
O
N
S
N
N
H3PO4/Al2O3 (120 mg)
O
H2N
R'CHO
Solvent-Free
T=120 oC
N
H
R'
N
H
O
Scheme 5 Synthesis of heterocyclic 3-(20-benzothiazolo)-2,3-dihydroquinazolin-4(1H)-ones
HN
O
O
N
N
H3PO4/Al2O3 (120 mg)
N
O
H2N
R'CHO
Solvent-Free
T=120 oC
N
H
N
H
R'
N
H
O
Scheme 6 Preparation of 3-(20-benzimidazolo)-2,3-dihydroquinazolin-4(1H)-one derivatives
for subsequent catalytic runs. The recovered catalyst was reused five times without
any loss of its activity (Fig. 1).
In Table 4 our results from preparation of 2,3-dihydroquinazoline-4(1H)-ones are
compared with those reported in the literature [22, 24, 25, 30–33]. The table shows
that H3PO4–Al2O3 is the most efficient catalyst with regard to reaction times and
product yield..
Synthesis of 2H-indazolo[2,1-b]phthalazinetriones
To optimize the conditions for preparation of 2H-indazolo[2,1-b]phthalazinetrione
derivatives, reaction of benzaldehyde, dimedone, and phthalhydrazide was selected
as model system. The reaction was performed at different temperatures (60, 80, 100,
120, and 150 °C) and with different amounts of catalyst (0.08, 0.1, 0.12, and 0.13 g)
under solvent-free conditions. The best results were obtained by use of a 1.0:1.0:1.2
molar ratio of dimedone, phthalhydrazide, and aldehyde in the presence of 0.12 g
H3PO4–Al2O3 as catalyst at 100 °C under solvent-free conditions (Scheme 3,
Tables 5, 6).
Using these optimized reaction conditions, the scope and efficiency of these
procedures were investigated for synthesis of a wide variety of substituted 2H-
indazolo[2,1-b]phthalazinetriones. Interestingly, a variety of aryl aldehydes, includ-
ing ortho, meta, and para-substituted and with electron-donating or electron-
withdrawing substituents, participated well in this reaction and gave the 2H-indaz-
olo[2,1-b]phthalazinetrione derivatives in good to excellent yield (Table 7).
A
possible mechanism for formation of 2H-indazolo[2,1-b]phthalazine-
1,6,11(13H)-triones is proposed in Scheme 8. Knoevenagel condensation of
dimedone I and arylaldehyde II forms a heterodiene III. Subsequent Michael-
type addition of the phthalhydrazide IV to the heterodiene III followed by
cyclization and dehydration affords the corresponding product VI.
123

New applications of phosphoric acid
H3PO4/Al2O3
R
O
RNH2
N
H
H
H3PO4/Al2O3
O
CO2
NH
H3PO4/Al2O3
O
O
(II)
O
O
NH
R
N
H
H
H PO /Al O
3
O
---
O
3
4
2
O
(I)
N
N
H
O
H
isatoic anhydride
(III)
O
(Catalyst)
H3PO4/Al2O3
R
N
H
NH2
(IV)
H3PO4/Al2O3
OH
OH
R
N
R
N
H
R'
N
R'
N
O
H3PO4/Al2O3
R'
(VI)
H3PO4/Al2O3
(V)
1,5-H transfer
O
R
N
N
H
R'
Product
Scheme 7 Mechanism suggested for H3PO4–Al2O3 catalyzed preparation of 2,3-dihydroquinazoline-
4(1H)-ones
Fig. 1 Results from investigation of the recycling of H3PO4–Al2O3 in the synthesis of 2,3-dihydroquinazoline-
4(1H)-ones
123

H. R. Shaterian et al.
Table 4 Comparison of results obtained by use of H3PO4–Al2O3, Ga(OTf)3 [22], KAl(SO4)2ꢀ12H2O
(alum) [24], silica sulfuric acid [25], Al(H2PO4)3 [30], p-TSA [31], Fe3O4 nanoparticles [32], copolymer-
P-TSA [33] as catalysts for synthesis of 2,3-dihydroquinazoline-4(1H)-ones
Entry
Catalyst
Conditions
Time (h)
Yield (%)a
1
p-TSA (50 mol %)
H2O
2.5
79
2
KAl(SO4)2ꢀ12H2O (alum) (200 mg)
KAl(SO4)2ꢀ12H2O (alum) (200 mg)
Ga(OTf)3 (1 mol %)
EtOH, reflux
H2O, reflux
4
78
3
1
65
4
EtOH, reflux
H2O, 80 °C
EtOH, reflux
Solvent-free, 80 °C
Solvent-free, 100 °C
Solvent-free, 120 °C
H2O, reflux
60 min
4.5
79
5
Silica sulfuric acid (15 mol.%)
Silica sulfuric acid (30 mol.%)
Silica sulfuric acid (20 mol.%
Al(H2PO4)3 (16 mol.%)
85
6
6.5
80
7
5
80
8
35 min
30 min
2
80
9
H3PO4–Al2O3 (120 mg, 50 % w/w)
Nano Fe3O4 (50 mol.%)
91 (this work)
10
11
a
80
82
Copolymer-p-TSA (300 mg)
EtOH, reflux
6.5
Based on the reaction of isatoic anhydride, aniline, and benzaldehyde
Table 5 Optimization of the temperature for reaction of benzaldehyde, dimedone, and phthalhydrazide
in the presence of H3PO4–Al2O3 (0.12 g) as catalyst under solvent-free conditions
Entry
Temperature (°C)
Time(min)
Yield (%)a
1
2
3
4
5
a
60
3
70
88
93
90
91
80
18
10
9
100
120
150
9
Yields refer to isolated pure product
Table 6 Optimization of the amount of H3PO4–Al2O3 as catalyst for reaction of benzaldehyde, dime-
done, and phthalhydrazide under solvent-free conditions at 100 °C
Entry
Catalyst (g)
Time (min)
Yield (%)a
1
2
3
4
a
0.08
0.1
25
18
10
9
70
88
93
90
0.12
0.13
Yields refer to isolated pure product
Reusability of catalysts is an important benefit, because of their suitability for
commercial application. Thus, recovery and reusability of H3PO4–Al2O3 was
investigated, with reaction of benzaldehyde, dimedone, and phthalhydrazide as
model. In this procedure, after completion of the reaction, the reaction mixture was
cooled to room temperature, and the crude solid product was dissolved in ethyl
acetate. The mixture was filtered for separation of the catalyst. The catalyst was
123

New applications of phosphoric acid
Table 7 Preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives using H3PO4–
Al2O3 as reusable catalyst
Entry Aromatic aldehyde
Time
(min)
Yield
(%)a
M.p. (°C) (Lit. m.p. (°C)) [Ref.]
1
2
3
4
5
6
Benzaldehyde
10
93
91
91
88
85
85
205–207
(207–209) [34]
(204–206) [35]
(204–206) [36]
260–261
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-Fluorobenzaldehyde
4-Nitrobenzaldehyde
2-Chlorobenzaldehyde
8
(259–261) [34]
(258–260) [35]
(262–264) [36]
261–263
10
15
10
14
(258–260) [34]
(258–260) [35]
(265–267) [36]
220–221
(224–226) [34]
(221–223) [35]
(217–219) [36]
220–221
(217–219) [34]
(216–218) [35]
(223–225) [36]
265–267
(264–266) [34]
(266–269) [35]
(264–266) [36]
270–272
7
8
3-Nitrobenzaldehyde
4-Methylbenzaldehyde
16
14
86
80
(270–272) [34, 36]
(269–271) [35]
228–230
(226–228) [34]
(226–231) [35]
(227–229) [36]
233–235
9
3,4,5-Trimethoxybenzaldehyde
2-Methylbenzaldehyde
8
89
78
86
(232–234) [34]
(232–234) [35]
240–241
10
11
23
11
(241–243) [34]
(243–245) [35]
217–220
2,4-Dichlorobenzaldehyde
(219–221) [34]
(218–220) [35]
123

H. R. Shaterian et al.
Table 7 continued
Entry Aromatic aldehyde
Time
(min)
Yield
(%)a
M.p. (°C) (Lit. m.p. (°C)) [Ref.]
12
13
3-Chlorobenzaldehyde
20
76
208–210
(204–206) [34]
(207–209) [35]
245–247
4-Hydroxy-3-
methoxybenzaldehyde
15
80
(250–252) [34]
(248–250) [35]
216–217
14
15
a
4-Methoxybenzaldehyde
10
9
88
87
(218–220) [37]
206–208
3,4-Dimethoxybenzaldehyde
(205–206) [37]
Yields refer to isolated pure product. The structures all known products were confirmed by comparison
of their melting points and spectral data (FT-IR, 1H NMR, 13C NMR) with those reported in the literature
[34–37]
washed with ethyl acetate (2 9 5 ml). The recovered catalyst was dried at 100 °C
and used for subsequent catalytic runs. The recovered catalyst was reused five times
without any loss of its activity (Fig. 2).
O
O
O
(II)
Ar
H
(I)
H3PO4/Al2O3
(Catalyst)
O
CHAr
O
N
O
O
N
Ar
(VI)
(III)
O
H2O
O
O
H
O
O
N
O
NH
NH
(IV)
Ar
(V)
N
O
Scheme 8 The suggested mechanism for preparation of 2H-indazolo[2, 1-b]phthalazine-1, 6, 11(13H)-
triones
123

New applications of phosphoric acid
To show the merits of this work we compared results obtained by use of H3PO4–
Al2O3 with those reported in the literature [35–38] for synthesis of 3,3-dimethyl-13-
phenyl-3,4-dihydro-2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione by reaction
of benzaldehyde, dimedone, and phthalhydrazide. As shown in Table 8, H3PO4–
Al2O3 is an effective catalyst with regard to reaction time, amount of the catalyst,
and product yield. Thus, this procedure with H3PO4–Al2O3 catalyst is convincingly
superior to some catalytic methods reported in the literature (Table 8).
Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines
To prepare benzo[4,5]imidazo[1,2-a]pyrimidines more efficiently in minimum time,
at low temperature, and with the minimum amount of catalyst, reaction of
benzaldehyde (1 mmol), methyl acetoacetate (1 mmol), and 2-aminobenzothiazole
(1 mmol) was selected as model system to study the effect of different reaction
temperatures (60, 80, 100, 120 and 150 °C) and different amounts of catalyst (0.08,
0.1, 0.12, 0.13, 0.14 g). The best result was obtained by use of a 1.0:1.0:1.0 molar
ratio of benzaldehyde, methyl acetoacetate, and 2-aminobenzothiazole in the
presence of 120 mg H3PO4–Al2O3 as catalyst at 100 °C under solvent-free
conditions (Tables 9, 10).
Using these optimized reaction conditions, the scope and efficiency of the
procedure were investigated for synthesis of a wide variety of substituted
benzo[4,5]imidazo[1,2-a]pyrimidines. Interestingly, a variety of ortho, meta, and
para-substituted aryl aldehydes participated well in this reaction and gave the
benzo[4,5]imidazo[1,2-a]pyrimidine derivatives in good to excellent yield
(Table 11). Table 11 shows that aromatic aldehydes carrying electron-donating or
electron-withdrawing substituents react well under these conditions.
According to the literature [39], the reaction presumably proceeds in two steps.
Condensation of aldehyde 1 and the b-dicarbonyl compound 2 by standard
Knoevenagel reaction produces 3-benzylidene-2,4-pentanedione 3. 2-Aminobenz-
imidazole or 2-aminobenzothiazole 4 then reacts with intermediate 3 by Michael
addition and produces intermediate 5. Cyclization and subsequent dehydration then
afford benzo[4,5]imidazo[1,2-a]pyrimidine derivatives 6 (Scheme 9).
Fig. 2 Results from investigation of the reusability of H3PO4–Al2O3 for preparation of 2H-indazolo[2,1-
b]phthalazine-1,6,11(13H)-triones
123

H. R. Shaterian et al.
Table 8 Comparison of results obtained by use of H3PO4–Al2O3, phosphomolybdic acid (PMA)–SiO2
[38], H2SO4 in water–ethanol or ionic liquid [37], p-TSA [37], and Mg(HSO4)2 [35] for preparation of
3,3-dimethyl-13-phenyl-3,4-dihydro-2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione
Entry Catalyst
Amount of Catalyst
(g)
Time
(min)
Yield(%)a
1
2
Phosphomolybdic acid [(PMA)–
SiO2]
1
30
30
85
86
H2SO4 in water–ethanol or ionic
liquid
0.015
3
4
5
p-TSA
0.05
0.025
0.12
10
10
10
86
85
Mg(HSO4)2
H3PO4–Al2O3
93 (Present
Work)
Table 9 Optimization of temperature in the reaction of benzaldehyde, methyl acetoacetate, and
2-aminobenzothiazole in the presence of H3PO4–Al2O3 (0.1 g) as catalyst under solvent-free conditions
Entry
Temperature (°C)
Time (min)
Yield (%)a
1
2
3
4
5
a
60
105
98
90
70
85
88
86
85
80
100
120
150
89
88
Yields refer to isolated pure product
Table 10 Optimization the amount of H3PO4–Al2O3 as catalyst in the reaction of benzaldehyde, methyl
acetoacetate, and 2-aminobenzthiazole under solvent-free conditions at 100 °C
Entry
Catalyst (g)
Time (min)
Yield (%)a
1
2
3
4
a
0.08
0.1
95
90
80
78
78
88
94
90
0.12
0.15
Yields refer to isolated pure product
In Table 12 the results obtained in this work are compared with those reported in
the literature for use of TMGT [39], and sulfamic acid [40]. The table shows that
H3PO4–Al2O3 (50 % w/w) is the most efficient catalyst for preparation of 4H-
pyrimido[2,1-b]benzazoles with regard to reaction time, temperature, and yield. The
catalyst is also widely applicable (Table 12).
We also investigated recycling of the catalyst under solvent-free conditions for
reaction of benzaldehyde, ethyl acetoacetate, and 2-aminobenzimidazole as model.
After completion of the reaction, the mixture was cooled to room temperature and
123

New applications of phosphoric acid
Table 11 One-pot synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine derivatives by condensation of
aldehydes, b-dicarbonyl compounds, and 2-aminobenzimidazole or 2-aminobenzothiazole in the presence
of H3PO4–Al2O3 as catalyst at 100 °C
Entry R1
R2
R3
X
Time
(min)
Yield
(%)a
Found m.p. (°C) (Lit. m.p. (°C)) [Ref.]
1
2
3
4
5
6
7
8
9
10
C6H5
OMe Me
OMe Me
OMe Me
S
S
S
S
S
S
S
S
S
S
80
80
80
95
80
90
95
90
95
72
94
90
89
92
90
91
88
87
89
79
140–142 (143–145) [39]
153–155 (150–153) [39]
86–88 (78–81) [39]
4-MeOC6H4
4-NO2C6H4
C6H5
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
Me
Ph
173-175 (173–175) [39]
145–147 (140–143) [39]
114–116 (110–114) [39]
150–152 (150–152) [39]
77–80 (84–86) [39]
4-MeOC6H4
4-BrC6H4
4-O2NC6H4
C6H5
4-O2NC6H4
3-O2NC6H4
Ph
160 dec (158 dec) [39]
OMe Me
[300 (The product was synthesized for
the first time)
11
12
C6H5
OEt
OEt
Me
Me
N
N
85
62
90
89
275 ([260) [39]
3-ClC6H4
[300 (The product was synthesized for
the first time)
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
4-MeOC6H4
4-O2NC6H4
4-MeOC6H4
4-O2NC6H4
4-FC6H4
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
Ph
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
84
90
95
85
90
95
75
85
90
85
95
100
80
95
90
80
85
80
85
80
90
85
80
44
80
85
82
87
82
88
80
82
89
85
81
90
95
88
88
90
90
89
94
93
94
90
89
87
94
85
93
88
250–253 (256–258) [39]
228 dec (225 dec) [39]
200–202 (117–120) [39]
250 dec (248 dec) [39]
[300 ([300) [39]
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4-ClC6H4
[300 ([300) [40]
4-BrC6H4
4-MeOC6H4
4-O2NC6H4
3-O2NC6H4
C6H5
[300 ([300) [40]
280–282 (272–273) [40]
[300 ([300) [40]
297–299 (294–296) [40]
295–297 (294–296) [40]
[300 ([300) [40]
2,4-Cl2 C6H3
2-ClC6H4
[300 ([300) [40]
C6H5
[300 ([300) [41]
4-FC6H4
Me
[300 ([300) [41]
4-ClC6H4
Me
[300 ([300) [41]
4-BrC6H4
4-O2NC6H4
4-MeC6H4
3-O2NC6H4
2,4-Cl2 C6H3
2-ClC6H4
Me
[300 ([300) [41]
Me
[300 ([300) [41]
Me
277–278 (279–281) [41]
[300 (290–292) [41]
[300 ([300) [41]
Me
Me
Me
[300 ([300) [41]
4-O2NC6H4
3-O2NC6H4
2,4-Cl2 C6H3
4-BrC6H4
OMe Me
OMe Me
OMe Me
OMe Me
278–279 (281–283.6) [41]
255–257 (267.5–269.5) [40]
280–281 (279.2) [40]
263–264 (263–265) [40]
123

H. R. Shaterian et al.
Table 11 continued
Entry R1
R2
R3
X
Time
(min)
Yield
(%)a
Found m.p. (°C) (Lit. m.p. (°C)) [Ref.]
39
3,4-
(MeO)2C6H3
3-FC6H4
OMe Me
OMe Me
N
N
12
80
76
92
257–259 (258–261) [40]
242–244 (247.1–249) [40]
40
a
Yields refer to the isolated pure products. The desired pure products were characterized by comparison
of their physical data (melting points, FT-IR, 1H and 13C NMR) with those of known compounds [39–41]
O
O
R2
R3
CHO
(1)
(2)
R1
O
O
H
R2
R3
(3)
H3PO4 / Al2O3
(Catalyst)
R1
R1
N
NH2
R3
X
(4)
X=NH, S
N
O
O
O
X
N
R2
(6)
X=NH, S
R2
X
R3
N
NH2
R1
X=NH, S
(5)
Scheme 9 Mechanism suggested for preparation of benzo[4,5]imidazo[1,2-a]pyrimidine derivatives
Table 12 Comparison of results obtained by use of H3PO4–Al2O3, TMGT, and sulfamic acid in the
synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine derivatives
Entry Catalyst
Amount of catalyst
(g)
Conditions
Time
Yield (%)
1
2
TMGT
0.08
0.01
100 °C
85 °C, Solvent-
free
5 h
8 h
73
88
Sulfamic acid
3
H3PO4–Al2O3 (50 % w/ 0.12
w)
100 °C, Solvent-
free
85 min 95 (this
work)
a
Based on the reaction of benzaldehyde, ethyl acetoacetate, and 2-aminobenzimidazole
123

New applications of phosphoric acid
the crude solid product was dissolved in ethyl acetate. The mixture was filtered for
separation of the catalyst. The catalyst was washed with ethyl acetate (4 9 5 mL)
and the recovered catalyst was then dried in an oven at 100 °C for 3 h. The
recovered catalyst was then used for subsequent catalytic runs. It was reused five
times without any loss of its activity (Fig. 3).
Conclusion
We have developed a green and straightforward procedure for synthesis of 2,3-
dihydroquinazoline-4(1H)-one, 2H-indazolo[2,1-b]phthalazinetrione, and benzo[4,5]im-
idazo[1,2-a]pyrimidine derivatives using H3PO4–Al2O3 as reusable catalyst under
solvent-free conditions. These procedures have several advantages, including cleaner
reactions, easier work-up, reduced reaction times, and eco-friendly strategy.
Experimental
General
All reagents were purchased from Merck and Aldrich and used without further
purification. H3PO4–Al2O3 (50 % w/w) was prepared in accordance with a
procedure reported elsewhere [41]. All yields refer to isolated products after
purification. Products were characterized by comparison of spectroscopic data (FT-
IR, 1H NMR, 13C NMR spectra) and melting points with those of authentic samples.
NMR spectra were recorded on a Bruker Avance DEX 500 MHz instrument. The
spectra were measured in CDCl3 relative to TMS (0.00 ppm). IR spectra were
recorded on a Jasco FT-IR 460 plus spectrophotometer. Melting points were
determined in open capillaries with a Buchi 510 melting point apparatus. TLC was
performed on Polygram SIL G/UV 254 silica gel plates.
General procedure for preparation of 2,3-dihydroquinazoline-4(1H)-one
derivatives
A stirred mixture of isatoic anhydride (1 mmol), primary amine (1.1 mmol) or
ammonium acetate (1.2 mmol), aldehyde (1 mmol) and H3PO4–Al2O3 (120 mg, 50
w/w %) was reacted in an oil bath at 120 °C for the appropriate time. After
completion of the reaction (monitored by TLC) the mixture was cooled to room
temperature and the crude solid product was dissolved in ethyl acetate and filtered
for separation of the catalyst. The organic filtrate solution was concentrated. The
solid crude product was purified by recrystallization from aqueous EtOH (70 %).
All the products were characterized by comparison of their spectroscopic and
physical data with those of authentic samples [22–29]. Spectral data of unknown
products are given below.
123

H. R. Shaterian et al.
3-(Benzo[d]thiazol-2-yl)-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
one (Table 3, Entry 17)
m.p.: 225–226 °C, IR (KBr) m/cm-1: 3383, 1671, 1612, 1503, 1439, 1303, 1284, 1237,
753; 1H NMR (500 MHz, DMSO-d6): d (ppm): 8.00 (1H, d, J = 7.8 Hz), 7.85 (1H, d,
J = 8.1 Hz), 7.72 (2H, d, J = 8.1 Hz), 7.59 (1H, d, J = 3.3 Hz), 7.40 (1H, t,
J = 7.4 Hz), 7.33 (2H, q, J = 7.5 Hz), 6.99 (1H, d, J = 8.8 Hz), 6.86 (1H, d,
J = 8.2 Hz), 6.79–6.76 (2H, m), 6.32 (1H, s), 3.87 (3H, s), 3.49 (3H, s); 13C NMR
(125 MHz, DMSO-d6): d (ppm): 162.0, 156.9, 152.4, 150.5, 147.5, 146.5, 135.3, 132.5,
128.0, 127.9, 126.1, 124.0, 121.5, 120.9, 118.0, 115.4, 112.7, 112.6, 112.5, 112.4, 65.1,
56.2, 55.0; MS (EI, 70 eV) m/z (%):43(23), 57(24), 69(32), 77(19), 105 (18), 132 (32),
149 (21), 210 (25), 238 (17), 268 (80), 283 (100), 417 (79); Anal. Calcd. for:
C23H19N3O3S: C, 66.17; H, 4.59; N, 10.07 %. Found: C, 66.16; H, 4.60; N, 10.05 %.
3-(Benzo[d]thiazol-2-yl)-2-(2,3-dichlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(Table 3, Entry 18)
m.p.: 246–248 °C, IR (KBr) m/cm-1: 3378, 3065, 1639, 1619, 1513, 1432, 1389,
1243, 753, 738; 1H NMR (500 MHz, DMSO-d6): d (ppm): 8.14 (1H, s), 7.99 (1H, d,
J = 6.9 Hz), 7.92 (1H, d, J = 7.0 Hz), 7.73–7.68 (2H, m), 7.53 (1H, d,
J = 7.2 Hz), 7.38 (2H, s), 7.31 (1H, s), 7.18 (1H, d, J = 7.2 Hz), 7.04 (1H, d,
J = 6.9 Hz), 6.88–6.84 (2H, m); 13C NMR(125 MHz, DMSO-d6) d (ppm): 161.5,
156.7, 147.3, 145.2, 139.1, 135.6, 132.9, 132.5, 130.6, 129.6, 128.3, 128.2, 126.2,
124.1, 124.0, 121.6, 121.0, 118.7, 115.9, 112.7, 66.8; MS (EI, 70 eV) m/z (%): 43
(16), 57 (21), 77 (36), 105 (25), 130 (19), 186 (24), 211 (20), 254 (17), 276 (89), 291
(100), 390 (17), 425 (20); Anal. Calcd. for: C21H13Cl2N3OS: C, 59.16; H, 3.07; N,
9.86 %. Found: C, 59.20; H, 3.10; N, 9.92 %.
3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydro-2-(4-nitrophenyl) quinazolin-4(1H)-one
(Table 3, Entry 19)
m.p.: [ 300 °C, IR (KBr) m/cm-1: 3360, 3209, 3078, 1685, 1613, 1518, 1343, 1243,
1160, 1107, 998; 1H NMR (500 MHz, DMSO-d6) d (ppm): 12.6 (1H, s), 8.34 (1H, d,
J = 5.4 Hz), 8.17 (2H, d, J = 8.5 Hz), 7.79 (1H, d, J = 7.7 Hz), 7.59–7.55 (3H, m),
7.45–7.36 (3H, m), 7.16–7.10 (2H, m), 6.94 (1H, d, J = 7.9 Hz), 6.81 (1H, t, J = 7.9);
13C NMR(125 MHz, DMSO-d6) d (ppm): 161.0, 150.4, 148.6, 147.2, 145.7, 138.9(2C),
133.0, 128.3, 127.8(2C), 123.7(2C), 123.3(2C), 117.5, 115.2(2C), 115.0, 113.8, 72.9;
MS (EI, 70 eV) m/z (%): 43 (27), 57 (31), 77 (37), 105 (37), 119 (39), 152 (21), 178 (28),
194 (26), 207 (88), 220 (95), 236 (47), 253 (100), 268 (32), 385 (94); Anal. Calcd. for:
C21H15 N5O3: C, 65.45; H, 3.92; N, 18.17 %. Found: C, 65.59; H, 3.76; N, 18.21 %.
3-(1H-benzo[d]imidazol-2-yl) -2-(2-methoxyphenyl) -2,3-dihydroquinazolin-4(1H)-
one (Table 3, Entry 20)
m.p.: 275 °C, IR (KBr) m/cm-1: 3383,3205, 3208, 2923, 2836, 1669, 1614, 1538,
1
1494, 1450, 1385, 1278, 1240, 1109, 1020, 747; H NMR (500 MHz, DMSO-d6) d
123

New applications of phosphoric acid
Fig. 3 Results from investigation of recycling of the catalyst in the preparation of
benzo[4,5]imidazo[1,2-a]pyrimidine derivatives
(ppm): 12.54 (1H, s), 7.86 (1H, d, J = 7.8 Hz), 7.53 (2H, d, J = 8.1 Hz), 7.44 (1H,
d, J = 3.4 Hz), 7.39 (1H, d, J = 7.5 Hz), 7.29 (1H, t, J = 7.6 Hz), 7.22 (1H, t,
J = 7.7 Hz), 7.11–7.05 (3H, m), 6.89 (1H, d, J = 7.4 Hz), 6.83 (1H, d,
J = 8.1 Hz), 6.74 (2H, q, J = 7.2 Hz), 3.93 (3H, s); 13C NMR (125 MHz,
DMSO-d6) d (ppm): 162.6, 156.4, 146.5(2C), 139.7, 134.8, 133.0, 129.5, 127.9,
127.2, 125.0, 121.3(2C), 119.6, 117.7, 117.2, 115.3, 113.5, 111.7, 111.4, 64.6, 55.7;
MS (EI, 70 eV) m/z (%): 77 (27), 105 (24), 132 (41), 167 (23), 194 (25), 209 (20),
220 (88), 236 (93), 253 (76), 339 (42), 370 (100); Anal. Calcd. for: C22H18N4O2: C,
71.34; H, 4.90; N, 15.13 %. Found: C, 71.30; H, 4.61; N, 15.10 %.
3-(1H-benzo[d]imidazol-2-yl) -2-(2,5-dimethoxyphenyl) -2,3-dihydroquinazolin-
4(1H)-one (Table 3, Entry 21)
m.p.: 235 °C, IR (KBr) m/cm-1: 3353, 3150, 2928, 1657, 1612, 1533, 1499, 1447,
1388, 1292, 1226, 1048, 1024; 1H NMR (500 MHz, DMSO-d6) d (ppm): 12.55 (1H,
s), 7.86 (1H, d, J = 7.6 Hz), 7.53 (2H, d, J = 7.5 Hz), 7.39 (2H, s), 7.30 (1H, t,
J = 7.5 Hz), 7.12–7.06 (2H, m), 6.97 (1H, d, J = 8.8 Hz), 6.84 (1H, d,
J = 8.1 Hz), 6.77 (2H, q, J = 6.8 Hz), 6.43 (1H, s), 3.87 (3H, s), 3.50 (3H, s);
13C NMR (125 MHz, DMSO-d6) d (ppm): 162.5, 152.3, 150.4, 146.5, 139.7, 134.8,
133.0, 128.4, 127.8, 121.3(2C), 117.8, 117.2(2C), 115.3, 113.5, 112.9, 112.2, 112.1,
111.7, 64.5, 56.1, 55.1; MS (EI, 70 eV) m/z (%): 77 (27), 105 (34), 132 (42), 194
(25), 210 (30), 220 (79), 236 (31), 250 (42), 268 (39), 283 (48), 341 (16), 369 (100),
400 (38); Anal. Calcd. for: C23H20N4O3: C, 68.99; H, 5.03; N, 13.99 %. Found: C,
69.01; H, 5.02; N, 13.89 %.
General procedure for preparation of 2H-indazolo[2,1-b]phthalazinetrione
derivatives
A mixture of phthalhydrazide (10 mmol), dimedone (10 mmol), aldehyde
(12 mmol), and H3PO4–Al2O3 (0.1 g, 50 % w/w) was heated at 100 °C in an oil
bath for the appropriate time (Table 3). After completion (monitored by TLC) the
reaction mass was cooled to 25 °C then the solid residue was dissolved in ethyl
123

H. R. Shaterian et al.
acetate. The catalyst was washed with (2 9 5 ml) ethyl acetate. The recovered
catalyst was dried at 100 °C. The filtrate solution was evaporated and the solid
crude product was purified by recrystallization from aqueous EtOH (25 %) to obtain
the pure products. The compounds were characterized by comparison of their
physical and spectral data with those reported in the literature [34–37]. Selected
spectral data for one product are given below.
3,3-Dimethyl-13-(4-chlorophenyl)-3,4-dihydro-2H-indazolo[1,2-b]phthalazine-
1,6,11(13H)-trione (Table 7, Entry 2)
m.p.: 259–261 °C 1H NMR (500 MHz, CDCl3): d = 1.23 (s, 3H), 1.24(s, 3H), 2.35
(s, 2H), 3.26 (dd, J = 1.8, 19.0 Hz, 1H), 3.45 (d, J = 19.0 Hz, 1H), 6.45 (s, 1H),
7.31–8.38 (m, 8H) ppm; 13C NMR (125 MHz, CDCl3): d = 28.6, 28.8, 34.6, 38.1,
50.8, 64.4, 118.2, 127.7, 128.2, 128.6, 128.8, 128.9, 129.1, 133.8, 134.4, 134.7,
134.9, 151.2, 154.4, 156.1, 192.1 ppm; IR (KBr, cm-1): 3037, 2958, 1687, 1654,
1623, 1467, 1390, 1362, 1311, 1268, 1147, 1013, 840, 794, 697.
General procedure for preparation of benzo[4,5]imidazo[1,2-a]pyrimidine
derivatives
A stirred mixture of aldehyde (1 mmol), b-dicarbonyl compound (1 mmol),
2-aminobenzimidazole or 2-aminobenzothiazole (1 mmol), and H3PO4–Al2O3 as
catalyst (0.12 g, 50 % w/w) was reacted in an oil bath at 120 °C for the appropriate
time. On completion of the reaction (indicated by TLC) the mixture was cooled to
room temperature. The crude solid product was dissolved in ethyl acetate, and
filtered for separation of the catalyst. The organic filtrate solution was concentrated.
The solid product was purified by recrystallization from aqueous EtOH (96 %). The
authenticity of the products was established by comparing their melting points and
1
FT-IR, 13C NMR, and H NMR spectra with those of known compounds [39–41].
The spectral data for the unknown compounds (Table 11, Entries 10 and 12) are
given below.
Methyl-2-methyl-4-(4-methoxyphenyl)-4H-primido[2,1-b][1,3]benzothiazole-3-
carboxylate (Table 11, Entry 10)
IR (KBr) (m): 3415, 3064, 2921, 1702, 1596, 1510, 1432, 1384, 1242, 1081,
1
738 cm-1; H NMR (500 MHz, CDCl3): d = 2.49 (s, 3H), 3.76 (s, 3H), 6.57 (s,
1H), 7.08 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.31–7.28 (m, 1H),
7.53–7.47(m, 2H), 7.77 (d, J = 7.7 Hz, 1H), 8.11 (ddd, J = 10.0 Hz, J = 2.0 Hz,
J = 0.9 Hz) 8.31 (t, J = 1.93 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3):
d = 23.7, 51.3, 57.2, 102.0, 111.4, 121.9, 122.5, 123.4, 123.9, 124.5, 126.9,
130.0, 132.9, 137.4, 143.2, 148.3, 155.8, 163.6, 166.6 ppm; MS (EI, 70 eV) m/
z (%): 381(27), 322(7.4), 259(100), 199(16), 175(6), 134(5); Anal. Calcd for
C19H15N3O4S: C, 59.83; H, 3.96; N, 11.02 %; Found: C, 59.66; H, 3.79; N,
10.98 %.
123

New applications of phosphoric acid
Ethyl-2-methyl-4-(3-chlorophenyl)-4,10-dihydropyrimido
[1,2-a][1,3]benzimidazole-3-carboxylate: (Table 11, Entry 12)
IR (KBr) (m): 3235, 3102, 3025, 2980, 2927, 2853, 1655, 1572, 1515, 1284, 1111,
1013, 835, 730 cm-1; 1H NMR (500 MHz, CDCl3): d = 1.31 (t, J = 7.10 Hz, 3H),
2.79 (s, 3H), 4.20 (m, 2H), 6.46 (s, 1H), 7.15 (m, 2H), 7.22 (t, J = 7.0 Hz, 1H), 7.27
(d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 7.95 Hz, 1H), 10.4 (s,
1H); 13C NMR (125 MHz, CDCl 3): d = 14.2, 19.5, 56.3, 60.0, 98.9, 109.6, 116.4,
120.8, 121.1, 122.7, 123.5, 128.7 (2C), 131.3, 133.8, 139.9, 141.0, 146.2, 146.5,
165.7 ppm; MS (EI, 70 eV) m/z (%): 367(50), 338(29), 294(21), 256(100), 228(38),
182(14), 90(7); Anal. Calcd for C20H18ClN3O2: C, 65.31; H, 4.93; N, 11.42 %;
Found: C, 65.28; H, 4.72; N, 11.41 %.
Acknowledgments We are grateful to the University of Sistan and Baluchestan Research Council for
partial support of this research.
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