Heteropolyacids as green and reusable catalysts for the synthesis of 3,1,5-benzoxadiazepines

Article abstract of DOI:10.3390/12020255

Synthesis of 3,1,5-benzoxadiazepines from the condensation of o-phenylenediamine (o-PDA) and acyl chlorides in the presence of a catalytic amount of various heteropolyacids (HPAs) is reported.

Full text of DOI:10.3390/12020255

Molecules 2007, 12, 255-262
molecules
ISSN 1420-3049
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Full Paper
Heteropolyacids as Green and Reusable Catalysts for the
Synthesis of 3,1,5-Benzoxadiazepines
Majid M. Heravi 1,∗, Samaheh Sadjadi 1, Hossein A. Oskooie 1, Rahim Hekmat Shoar 1 and
Fatemeh F. Bamoharram 2,†
1
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
2
Department of Chemistry, School of Sciences, Azad University, Khorasan Branch, Mashhad, Iran
* Author to whom correspondence should be addressed; E-mail: mmh1331@yahoo.com
Received: 8 January 2007; in revised form: 10 February 2007 / Accepted: 12 February 2007 /
Published: 26 February 2007
Abstract: Synthesis of 3,1,5-benzoxadiazepines from the condensation of
o-phenylenediamine (o-PDA) and acyl chlorides in the presence of a catalytic amount of
various heteropolyacids (HPAs) is reported.
Keywords: 3,1,5-Benzoxadiazepines, recyclable catalysts, heteropolyacids, heterocycle.
Introduction
Heteropolyacids (HPAs) are well defined molecular clusters that are remarkable for their molecular
and electronic structural diversity and their quite diverse significance in many areas, e.g., catalysis,
medicine, and materials science [1-2].
The applications of heteropolyacids, HPAs, in the field of catalysis are growing continuously.
These compounds possess unique properties such as Brönsted acidity, possibility to modify their acid-
base and redox properties by changing their chemical composition (substituted HPAs), ability to
accept and release electrons, high proton mobility, easy work-up procedures, easy filtration, and
minimization of cost and waste generation due to reuse and recycling of these catalysts [3-7]. Because
of their stronger acidity, they generally exhibit higher catalytic activity than conventional catalysts
such as mineral acids, ion exchange resins, mixed oxides, zeolites, etc. [8]. In the context of Green
Chemistry, the substitution of harmful liquid acids by solid reusable HPAs as catalysts in organic
synthesis is the most promising application of these acids [9,10].

Molecules 2007, 12
256
Benzoxadiazepines have been found to possess marked biological effects as CNS stimulants. They
have also been reported as antibacterial and anti-inflammatory agents, pesticides and insecticides [11].
Few methods are reported in the literature for the synthesis of benzoxadiazepines [12-14]. During the
course of our studies towards the development of HPAs as efficient heterogeneous catalysts [15-18]
herein we wish to report the synthesis of 3,1,5-benzoxadiazepines derivatives by cyclization of o-PDA
and acyl chlorides in the presence of a catalytic amount of various type of HPAs, including
H14[NaP5W30O110], H5[PMo10V2O40] and H6[P2W18O62]. (Scheme1).
Scheme 1.
R4
R3
N
N
R3
R2
NH2
NH2
O
Heteropolyacid
solvent, reflux
Cl
O
+
R4
R2
R4
R1
R1
Results and Discussion
Due to the ever-mounting environmental concern in the field of chemistry, it is advisable to use
easily recovered and recycled catalysts, especially expensive or toxic metallic ones [19]. In this
respect, only few of the aforementioned catalysts meet this Green Chemistry criterion.
In connection with our program of using heteropolyacids in organic reactions [20] we wish to
report the results of a study on the use of three type of HPAs, including Preyssler, H14[NaP5W30O110],
Keggin, H4[PMo11VO40] and Wells-Dawson types H6[P2W18O62] in the synthesis of 3,1,5-benzoxa-
diazepines and the effects of reaction parameters such as the type of HPA, temperature and reaction
times on the reaction yields.
The results indicate that the nature of the catalyst plays an important role on their catalytic
activities. As shown in Table 1, H14[NaP5W30O110] showed the highest activity and gave better yields.
Table 1. Synthesis of 3,1,5-benzoxadiazepines derivatives using various heteropolyacids
under refluxing conditions.
Entry
R1
H
H
H
H
H
H
R2
H
R3
H
H
H
H
H
H
R4
Catalyst
Yield %a
80
1
2
3
4
5
6
CH3
CH3
CH3
CH3
CH3
CH3
H14[NaP5W30O110
H6[P2W18O62]
H5[PMo10V2O40]
H14[NaP5W30O110
H6[P2W18O62]
H5[PMo10V2O40]
]
]
H
74.8
60
H
CH3
CH3
CH3
85.7
78.25
61
a) Yields were analyzed by GC.
Preyssler’s anion, [NaP5W30O110]14-, has an approximate D5h symmetry and consists of a cyclic
assembly of five PW6O22 units. A sodium ion is located within the polyanion on the fivefold axis and
1.25 above the pseudo mirror plane that contains the five phosphorus atoms [21]. Preyssler polyanion

Molecules 2007, 12
257
as a large anion can provide many ‘‘sites’’ on the oval-shaped molecule that are likely to render the
catalyst effective.
The Keggin anions have an assembly of 12 corner-shared octahedral MoO6 from trimetallic groups
[Mo3O13] around a heteroatom tetrahedron PO4. The introduction of vanadium (V) into the Keggin
framework of [PMo12O40]3- is beneficial for catalysis reactions. Usually positional isomers are possible
and coexist when two or more vanadium atoms are incorporated into the Keggin structure. Studies on
these isomers in catalytic reactions indicate that different isomers cause to show different reactivities.
With respect to the catalytic performance of these catalysts and the overall effects of all isomers,
we cannot control the reaction conditions for the synthesis of positional vanadium-substituted isomers
separately, indicating that the relationship between the H3+xPMo12-xVxO40 (x = 1) structures and hence
study of their catalytic activity is difficult. However, because the metal substitution may modify the
energy and composition of the LUMO and redox properties, for mentioned heteropolyacids with
different charges, the energy and composition of the LUMOs have significant effects on the catalytic
activity. Substitution of vanadium ions into the molybdenum framework stabilize the LUMOs because
these orbitals derive, in part, from vanadium d-orbitals which have been assumed to be more stable
than those of molybdenum and tungsten [22]. The abundance of different isomers may also play an
important role in catalytic performance. In addition, different positional Mo atom(s) substituted by the
V atom(s) in [PMo12O40]3- may create different vanadium chemical environments, thus causing these
catalysts to exhibit varying catalytic performances. Considering the above explanations we suggest
that the rigidity, steric hindrance and lower number of protons in H4[PMo11VO40] are tentatively
assumed to be responsible for its observed lower activity. The larger number of protons may lower the
activation barrier to the reaction.
As noted from the data in Table 1, electron-donating groups on o-PDA increased the yield of the
reactions. The effect of temperature was studied by carrying out the reactions at different temperatures
[room temperature, 25°C, 50°C and under refluxing temperature (82°C)]. As shown in Table 2, the
reaction yields increased as the reaction temperature was raised. From these results, it was decided that
refluxing temperature would be the best temperature for all reactions.
For investigation of the best reaction time the reaction yields were studied at different times (0.5, 1,
2, 3, 4h). The results indicate that in each reaction, the yield is a function of the reaction time and the
best time for all reactions was optimized to be 4h.
When 4-nitrophenylenediamine, 3,5-dinitrophenylenediamine and benzoyl chloride were used as
substrates in this reaction the corresponding benzodimidazoles were obtained instead of 3,1,5-
benzoxadiazepines (Scheme 2).
Scheme 2.
R3
R2
R3
R2
NH2
NH2
N
O
Heteropolyacid
solvent, reflux
Cl
R4
+
R4
N
H
R1
R1

Molecules 2007, 12
Table 2. Effect of different reaction time and temperature on synthesis of 3,1,5-
258
benzoxadiazepines derivatives using various heteropolyacids.
Time
Yield%a
50°C
44
Entry R1 R2
R3 R4
Catalyst
(h)
0.5
1
25°C
41
50
56
67
73
38
47
54
59
65
23
29
33
46
53
44
52
61
60
66
39
48
55
64
70
22
29
35
49
57
82°C
50
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H6[P2W18O62]
]
]
]
]
]
2
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
55
59
3
H
2
60
65
4
H
3
69
74
5
H
4
77
80
6
H
0.5
1
43
48
7
H
H6[P2W18O62]
51
55
8
H
H6[P2W18O62]
2
59
63
9
H
H6[P2W18O62]
3
67
68
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
H
H6[P2W18O62]
4
70
74.8
29
H
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H14[NaP5W30O110
H6[P2W18O62]
0.5
1
27
H
33
37
H
2
38
42
H
3
49
53
H
4
57
60
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
]
]
]
]
]
0.5
1
52
58
59
63
2
67
71
3
69
76
4
72
85.7
48
0.5
1
42
H6[P2W18O62]
52
57
H6[P2W18O62]
2
59
64
H6[P2W18O62]
3
68
70
H6[P2W18O62]
4
72
78.25
36
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
H5[PMo10V2O40]
0.5
1
30
35
40
2
41
48
3
51
53
4
59
61
a) Yields were analyzed by GC.
1
The products were characterized using H-NMR and IR spectroscopy and GC–MS analysis.
Analytical data were in accord with those reported for authentic samples.

Molecules 2007, 12
259
The results are summarized in Table 3. It is presumed that the amine group meta to the NO2 group
participated in the reaction, while the amine groups para or ortho to the nitro could not participate
because the latter are considered to be powerful electron withdrawing groups and may reduce the
nucleophilicity of the amine. In the case of benzoyl chloride the steric effect of phenyl groups prevent
the formation of 3,1,5-benzoxadiazepines.
Table 3. Synthesis of benzimidazole derivatives using various heteropolyacids under
refluxing conditions.
Entry
R1
R2
R3
R4
Catalyst
Yield %a
1
H
H
NO2
NO2
NO2
NO2
NO2
NO2
H
H
H
CH3
CH3
CH3
H14[NaP5W30O110
H6[P2W18O62]
]
]
]
]
98.5
97
2
3
H
H
H5[PMo10V2O40]
95.7
98
4
H
H
C6H5 H14[NaP5W30O110
C6H5 H6[P2W18O62]
C6H5 H5[PMo10V2O40]
5
H
H
94
6
H
H
85
7
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
CH3
CH3
CH3
H14[NaP5W30O110
H6[P2W18O62]
97
8
H
95.7
90.4
85.7
78.2
77.3
9
H
H5[PMo10V2O40]
10
11
12
H
C6H5 H14[NaP5W30O110
C6H5 H6[P2W18O62]
C6H5 H5[PMo10V2O40]
H
H
a yields are analyzed by GC
As shown in Table 3, the reaction yields for the synthesis of benzimidazole derivaties are high.
Thus, heteropolyacids can be used as efficient catalysts for the synthesis of benzimidazoles, especially
for derivatives with electron withdrawing groups (such as nitro groups). The more electron
withdrawing groups present the lower the yields obtained were. On the other hand, the steric effect of
phenyl groups also reduced the yield of reactions. The same trend of catalyst efficiency was observed
for this reaction. Thus the same explanation could be applied here.
Experimental
General
All chemicals were obtained from Merck and used as received. H14[NaP5W30O110] was prepared
according to earlier reports [8,16,4]. H4[PMo11VO40] and H5[PMo10V2O40] were prepared according to
the literature [22]. The Wells-Dawson species H6[P2W18O62] was prepared as described elsewhere
[23], from an aqueous solution of α/β K6P2W18O62·10H2O salt, which was treated with ether and
concentrated (37%) HCl solution. GC–MS analyses were performed on a GC–MS system consisting of
an Agilent 5973 network mass selective detector and a model 6890 GC. IR spectra were obtained with
a Buck Scientific 500 spectrometer. 1H-NMR spectra were recorded on a Bruker 90 MHz FT-NMR.
General Procedure

Molecules 2007, 12
260
o-PDA (6 mmol) was dissolved in acetonitrile (10 mL) and acyl chloride (12 mmol) was added to
the solution, followed by the catalyst (0.1 mmol). The reaction mixture was heated at reflux
temperature for 4 h. The progress of the reaction was monitored by TLC using 1:2 EtOAc-hexane as
eluent. After completion of the reaction, the catalyst was filtered off and the solvent was evaporated.
The pure products were obtained by column chromatography. All products were identified by
comparison of their physical and spectroscopic data with those reported for authentic samples.
Spectral data for selected samples
2,4-Dimethyl-3,1,5-benzoxadiazepine (Table 1, Entry 1): IR (KBr/υ): 1673 (C=N), 1042 (C-O-C) cm-1;
1H-NMR (CDCl3): 7.2 (m, 4H, Ar-H), 2.2 (s, 6H, CH3); MS: m/z 174 [M+].
6-Nitro-2-methyl-1H-benzimidazole (Table 3, Entry 1): IR (KBr/υ): 1604 (C=N), 1355 (NO2), 3261
1
(NH) cm-1; H-NMR spectra (CDCl3): 7.7 -8.0 (m, 3H, Ar-H), 2.4 (s, 3H, N=C-CH3), 4 (br. s, 1H,
N-H); MS: m/z 177 [M+].
6-Nitro-2-phenyl-1H-benzimidazole (Table 3 Entry 4): IR (KBr/υ): 1604 (C=N), 1355 (NO2), 3261
1
(NH) cm-1; H-NMR (CDCl3): 7.6 -8.4 (m, 3H, Ar-H), 7.3-8.1 (m, 5H, N=C-C6H5), 4.5 (br. s, 1H,
N-H); MS: m/z 239 [M+].
5,7-Dinitro-2-methyl-1H-benzimidazole (Table 3, Entry 7): IR (KBr/υ): 1604 (C=N), 1355-1400
1
(NO2), 3261 (NH) cm-1; H-NMR (CDCl3): 8 (s, 1H, Ar-H), 8.7 (s, 1H, Ar-H), 2.58 (s, 3H, N=C-
CH3), 4 (br. s, 1H, N-H); MS: m/z 222 [M+].
5,7-Dinitro-2-phenyl-1H-benzimidazole (Table 3, Entry 10): IR (KBr/υ): 1604 (C=N), 1355-1400
1
(NO2), 3261 (NH) cm-1; H-NMR (CDCl3): 8 (s, 1H, Ar-H), 8.7 (s, 1H, Ar-H), 7.3-8 (m, 5H, N=C-
C6H5), 4.5 (br. s, 1H, N-H); MS: m/z 284 [M+].
Catalyst reusability
At the end of the reaction, the catalyst could be recovered by a simple filtration. The recycled
catalyst could be washed with dichloromethane and used in a second run of the reaction process. The
results of the first and subsequent experiments were almost consistent in yields.
Acknowledgments
The authors are thankful for the partial financial assistance from Alzahra University Research
Council.

Molecules 2007, 12
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Sample Availability: Samples of the compounds presented in this paper are available from authors.
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