Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an efficient heteropolyacid-catalyzed procedure

Article abstract of DOI:10.3390/molecules16010092

An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs) was developed. High yields and short

Full text of DOI:10.3390/molecules16010092

Molecules 2011, 16, 92-99; doi:10.3390/molecules16010092
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis of Substituted 1,4-Diazepines and 1,5-Benzodiazepines
Using an Efficient Heteropolyacid-Catalyzed Procedure
Rachedine Kaoua 1, Norah Bennamane 1, Saliha Bakhta 1,2, Sihame Benadji 2,3, Cherifa Rabia 3
and Bellara Nedjar-Kolli 1,*
1
Laboratory of Applied Organic Chemistry, Houari Boumediene University of Sciences and
Technology, BP 31, El-Alia, Bab-Ezzouar, 16111, Algiers, Algeria
2
Center of Research in Physical and Chemical Analysis CRAPC, BP 248, Algiers RP 16004, Algiers,
Algeria
3
Laboratory of Natural Gas, Houari Boumediene University of Sciences and Technology, BP 31,
El-Alia, Bab-Ezzouar 16111, Algiers, Algeria
* Author to whom correspondence should be addressed; E-Mail: bnkollidz@gmail.com.
Received: 19 November 2010 / Accepted: 11 December 2010 / Published: 28 December 2010
Abstract: An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-
benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the
presence of Keggin-type heteropolyacids (HPAs) was developed. High yields and short
reaction times were obtained for both electron-releasing and electron-withdrawing
substituted 1,4-diazepine and 1,5-benzodiazepines derivatives.
Keywords: 1,4-diazepine; 1,5-benzodiazepine; dehydroacetic acid; 1,3-aminomethyl
propane; orthophenylene diamine; heteropolyacids
1. Introduction
Diazepines and benzodiazepines have various therapeutic applications. Many members of the
diazepine family are widely used as anticonvulsants, antianxiolitics, analgesics, sedatives,
antidepressives and hypnotic agents [1-4]. Benzodiazepine derivatives are used as dyes for acrylic
fibers [5]. In addition, benzodiazepines are valuable intermediates for the synthesis of fused ring
compounds such as triazolo-, oxadiazolo-, oxazino-, and furanobenzodiazepines [6-11].

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Due to their wide range of pharmacological activity and industrial applications, the development of
mild and efficient protocols for their preparation continues to be a challenging endeavor in the
synthetic organic chemistry [12-28]. The common procedure for the synthesis of these compounds is a
one pot condensation between o-phenylenediamines and carbonyl compounds [29]. However, a large
number of the modified methods reported in the literature, suffer from several drawbacks such as the
use of a large amount of catalysts, unsatisfactory product yields and critical product isolation
procedures. These disadvantages require a development of an efficient and practically useful process
of preparation [30].
In recent years, the use of polyoxometalates as catalysts in homogeneous and heterogeneous
systems has attracted great interest in organic synthesis because their acidic and redox properties can
be controlled at the molecular or atomic level and they also offer economical and environmental
benefits [31-35].
Among the different classes of polyoxometalates, the Keggin-type heteropolyacids (HPAs) offer a
strong option for efficient and cleaner processing compared to polluting and corrosive liquid acid
catalysts [36]. They have the particularity of possessing multi-functional properties as strong Brønsted
acidity and strong redox power. Their use allows eductions of costs and waste generation through
reuse and recycling [37,38].
We report here for the first time the synthesis of 1,4-diazepines 4 from enaminones 2 in the
presence of both CF3COOH and Keggin type HPA catalysts. 1,5-Benzodiazepines 5 have also been
prepared, again in the presence of the HPA catalysts [29].
Scheme 1. Synthesis of 1,4-benzodiazepines 4 and 1,5- benzodiazepines 5.
OH
O
H3C
O
CH3
O
1
EtOH
CH
3
CH
3
H N
2
NH
2
NH
H
N
2
2
HO
OH
H3C
CH3
N
N
CH3
CH3
O
O
H2N
NH
CH3
2 H3C
O
O
3
2
+
+
O=CHR EtOH /
H
EtOH /
H3C
H
O=CHR
HO
OH
N
CH3
N
CH3
CH3
O
O
NH
NH
O
O
5
4
R
R
R = C6H5, p-CH3C6H4, p-ClC6H4, p-BrC6H4.

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2. Results and Discussion
Previously, we have synthesized 1,5-benzodiazepine 5 products [29] from the reaction between
product 3 and aromatic aldehydes in the presence of catalytic amounts of trifluroacetic acid in ethanol
under reflux conditions. In continuation of this work on the synthesis of diazepine rings, we have now
prepared a series of novel 1,4-diazepines 4 from derivatives 2 following to the same procedure
(Scheme 1). The results (Table 1) show that the reaction is slow with unsatisfactory yields.
Table 1. Synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives using CF3COOH
as catalyst under reflux conditions.
CF3COOH
Compounds
R
Ratio of aldehyde
Times (min) / Yields (%)
420/60
4a
4b
4c
4d
5a
5b
5c
5d
C6H5
1.5
1.5
2.5
2.5
1.5
1.5
3
p-CH3C6H5
p-ClC6H5
p-BrC6H5
C6H5
420/55
360/64
360/69
360/79
p-CH3C6H5
p-ClC6H5
p-BrC6H5
420/83
720/64
3
720/74
Due to strong Brønsted acidity and high oxidative power of Keggin type HPAs, that give them a
bifunctional character, we decided to test the following series of HPAs in the preparation of derivatives
4 and 5: H3PW12O40 and H3+xPMo12-xVxO40, with x = 0-3, as catalysts. The obtained results are shown
in Table 2.
Table 2. Synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives using equimolar
reactants in presence of various heteropolyacids under refluxing conditions.
R
Times (min) / Yields (%)
4a
C6H5
600/72
300/69
180/70
30/85
60/83
4b
4c
4d
5a
5b
5c
5d
p-CH3C6H5
p-ClC6H5
p-BrC6H5
C6H5
p-CH3C6H5
p-ClC6H5
p-BrC6H5
660/75
640/69
600/75
420/87
390/82
360/70
360/76
300/79
300/73
300/71
220/79
220/83
220/77
220/73
180/77
180/73
180/72
120/85
120/82
120/75
120/74
30/80
30/78
30/75
15/90
15/88
15/93
15/91
60/83
60/74
60/77
40/78
40/89
40/87
40/94

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The catalysts were used with equimolar amounts of reactants in refluxing ethanol; the reaction
proceeded smoothly, affording the products in good to excellent yields. The results indicate that the
catalytic activity depends on the composition of the catalyst. The substitution of one to three
molybdenum atoms by vanadium atoms decreases the reaction time and increases the product yields.
This is can be attributed to the character more oxidative and less acidic compared to those of
H4PMo11VO40 , H3PMo12O40 and H3PW12O40 [31,35,38]. As shown in Table 2, the order of efficiency
follows the sequence: H5PMo10V2O40> H6PMo9V3O40> H4PMo11VO40 > H3PMo12O40 > H3PW12O40.
Since the best results in term of yield and reaction time have been achieved with H5PMo10V2O40, this
was selected for its better catalytic performance for the synthesis of diazepine rings.
To optimize the reaction, temperature and molar ratio of H5PMo10V2O40 catalyst and reactants were
checked. No reaction was detected at room temperature. Intramolecular cyclization of 2 or 3 via
respectively intermediate A or B (Scheme 2) under reflux conditions in the presence of only 0.1 % of
H5PMo10V2O40 catalyst is enough to drive the reaction forward; higher amounts of catalysts did not
improve the results.
Scheme 2. Synthetic route to compounds 4 and 5.
.
.
.
.
.
.
H
.
.
N+
N
N
NH2
N
N
N
H
N
R
R
HO
R
HO
HO
CH2
HO
CH3
CH3
-HPAs
EtOH
HPAs
EtOH
HCOR
EtOH
O
O
O
O
O
O
O
O
H3C
H3C
H3C
H3C
a)
b)
A
B
4
5
2
3
H
C
CH
3
3
.
.
a)
.
b)
.
.
It is difficult to clarify how HPAs acts as a catalyst in this reaction. On the basis of a previously
reported mechanism [29], it was suggested that the formation time of derivatives 5 depends on the
nature of the substituent R on the aldehyde ring. Formation of 5 is particularly rapid when R is a
strong donor group, whereas a withdrawing substituent inhibits the formation of compounds 5. Yields
are also affected by electronic effects and they significantly increased by using an excess of aldehyde
(Table 1). Similarly, intermediate A undergoes intramolecular cyclization under acidic conditions,
according to the described conditions [29] leading to products 4. Yields and reaction times are very
comparable to those obtained with intermediate B. These results can be explained by the nature of
substituent R as shown in Table 1. When the optimized conditions (in presence of HPAs) are applied
to substrates, high yields of 4 and 5 are obtained. These results show that the electronic nature of the
substituent seems not to have a great effect on the reaction yields and that both acidic and redox
properties of the heteropolyacids are involved during the synthesis.
The nature and the composition of the polyanion have an important effect on the catalytic properties
of the HPAs. However, it is very difficult to clarify the difference between catalytic behaviour of these
systems in this reaction. We believe that there is a complex relationship between the activity, the
chemical composition and the position of the vanadium atoms in the Keggin polyanions.

Molecules 2011, 16
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3. Experimental
3.1. General
Melting points were measured on a Buchi 512 apparatus and were uncorrected. FTIR spectra were
1
13
taken in Nujol on a Perkin –Elmer spectrometer. The H-NMR spectra (250 and 300 MHz) and C-
NMR (63 MHz) were run on a Bruker spectrometer in CDCl3 using tetramethylsilane as internal
standard. The impact ionisation (IE) mass spectra were recorded on a Nermag R-10-10C at 70 ev.
Chemicals were purchased from Aldrich and Fluka. Compounds 2 and 3 were prepared according to
the literature [39]. All the products were identified by comparison of analytical data (mp, NMR) with
those reported (in the case of derivatives 5) or with authentic samples prepared by the conventional
method using CF3COOH as catalyst (in the case of compounds 4).
3.2. Catalyst preparation
Phosphomolybdic and phosphotungstic acid samples, H3PMo12O40 and H3PW12O40 were obtained
according to the method of Tsigdinos [40] by heating MoO3 (WO3) with a solution of diluted H3PO4.
Synthesis of mono-, di- and tri-vanadium substituted phosphomolybdic acids, H3+x[PMo12−xVxO40]
(x = 1–3) was carried out according to the procedure of Tsigdinos and Hallada [41] by acidifying with
concentrated H2SO4 an appropriate mixture solutions of Na2HPO4, Na2MoO4 and NaVO3 in
appropriate molar ratio. The HPAs formed were extracted with diethyl ether.
3.3. General procedure for the heteropolyacid-Keggin acid catalyzed synthesis of derivatives 4 and 5
A mixture of 2 or 3 (10 mmol) and aldehyde (10 mmol) in presence of Keggin acid catalyst
(1% mmol) dissolved in ethanol (15 mL) was refluxed with stirring for the indicated time (see Table
2). The reaction was followed by TLC. When the reaction time was over, the organic solution was
concentrated in vacuum. Then the compounds were filtered and washed twice with ethanol
(2 × 10 mL). The catalyst was recovered after evaporating of ethanol.
3-(2,2-Dimethyl-7-phenyl-2,3,6,7-tetrahydro-1H-1,4-diazepin-5-yl)-4-hydroxy-6-methyl-2H-pyran-2-
1
one (4a).Yellow solid, m.p. 186 ºC; H-NMR (CDCl3, 250 MHz): δ 1.45 (s, 3H, CH3), 1.48 (s, 3H,
CH3), 2.13 (s, 3H, CH3), 3.58 (s, 2H, CH2-N=), 4.32 (t, 1H, J = 9 Hz, CH-Ar), 4.75 (dd, 2H, J = 9,
2 Hz, CH2-CH), 5.85 (s, 1H, =CH), 7.16-7.37 (m, 5H, H-Ar), 7.52 (s, 1H, NH), 13.80 (s, 1H, OH);
13C-NMR (CDCl3): δ 20, 22, 30, 52, 53, 55, 62, 96, 108, 128, 129, 132, 143, 163, 164, 179, 184; MS
m/z (%): 326 ([M·]+, 6), 235 (19) , 181 (60), 151 (27), 136 (14), 43 (37).
3-[2,2-Dimethyl-7-(4-methylphenyl)-3,6-dihydro-2H-1,4-diazepin-5-yl]-4-hydroxy-6-methyl-2H-
pyran-2-one (4b).Yellow solid, m.p. 220 ºC; 1H-NMR (CDCl3, 250 MHz): δ 1.37 (s, 3H, CH3), 1.38 (s,
3H, CH3), 2.14 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.54 (s, 2H, CH2-N=), 4.17 (t, 1H, J = 9 Hz, CH-Ar),
4.70 (dd, 2H, J = 9, 2 Hz, CH2-CH), 5.75 (s, 1H, =CH), 7.00-7.10 (d, 2H, J = 8.3 Hz, H-Ar), 7.10-7.20
13
(d, 2H, J = 8.1 Hz, H-Ar), 7.80 (s, 1H, NH), 14.03 (s, 1H, OH); C-NMR (CDCl3): δ 20, 21, 32, 51,
53, 55, 61, 95, 108, 128 - 129, 134, 146, 163, 164, 178, 18; MS m/z (%): 340 ([M·]+, 2), 235 (16), 181
(40), 151 (4), 136 (1), 43 (70).

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3-[7-(4-Chlorophenyl)-2,2-dimethyl-2,3,6,7-tetrahydro-1H-1,4-diazepin-5-yl]-4-hydroxy-6-methyl-2H-
pyran-2-one (4c).Yellow solid, m.p. 223 ºC; 1H-NMR (CDCl3, 250 MHz): δ 1.38 (s, 3H, CH3), 1.39 (s,
3H, CH3), 2.15 (s, 3H, CH3), 3.65 (s, 2H, CH2-N=), 4.39 (t, 1H, J = 9 Hz, CH-Ar), 4.70 (dd, 2H, CH2,
J = 9, 2 Hz, CH2-CH), 5.90 (s, 1H, =CH), 7.20-7.25 (m, 2H, H-Ar), 7.25-7.30 (m, 2H, H-Ar), 7.96 (s,
13
1H, NH), 13.82 (s, 1H, OH); C-NMR (CDCl3): δ 19, 20, 30, 50, 54, 55, 63, 96, 105, 129, 130, 133,
136, 165, 166, 177, 182; MS m/z (%): 360 ([M·]+, 24), 235 (14), 181 (100), 151 (8), 136 (8), 43 (28).
3-[7-(4-bromophenyl)-2,2-dimethyl-2,3,6,7-tetrahydro-1H-1,4-diazepin-5-yl]-4-hydroxy-6-methyl-2H-
1
pyran-2-one (4d). Yellow solid, m.p. 245 ºC; H-NMR (CDCl3, 250 MHz): δ 1.44 (s, 3H, CH3), 1.47
(s, 3H, CH3), 2.15 (s, 3H, CH3), 3.62 (s, 2H, CH2-N=), 4.36 (t, 1H, J = 9 Hz, CH-Ar), 4.70 (dd, 2H,
J = 9, 2 Hz, CH2-CH), 5.90 (s, 1H, =CH), 7.10-7.20 (m, 2H, H-Ar), 7.35-7.45 (m, 2H, H-Ar), 7.99 (s,
13
1H, NH), 13.79 (s, 1H, OH); C-NMR (CDCl3): δ 19, 20, 34, 53, 54, 56, 60, 95, 107, 130, 131, 135,
145, 163, 165, 178, 181; MS m/z (%): 371 ([M·]+, 0.5), 235 (18), 181 (20), 151 (3), 136 (5), 43 (66).
4. Conclusions
We present here the synthesis of a new series of 1,4-benzodiazepine derivatives 4 using two
different catalyst classes, a conventional catalyst, CF3COOH, and HPAs. The results have shown the
superior catalytic efficiency of the heteropolyacids. The principal features of the methodology using
HPAs as catalyst are high-yields and shorter reaction times for both electron-releasing and electron-
withdrawing substituted derivatives 4 and 5, substances with potentially interesting biological and
medicinal properties.
References and Notes
1. Schutz, H. Benzodiazepines; Springer: Heidelberg, Germany, 1982.
2. Landquist, J.K. Comprehensive Heterocyclic Chemistry; Katritzky, A.R., Rees, C.W., Eds.;
Pergamon: Oxford, UK, 1984; Volume 1, pp. 166-170.
3. Fryer, R.I. Bicyclic Diazepines. In Comprehensive Heterocyclic Chemistry; Taylor, E.C., Ed.;
Wiley: New York, NY, USA, 1991; Volume 50, Chapter ІІ.
4. Randall, L.O.; Kappel, B. Benzodiazepines; Garattini, S., Musini, E., Randall, L.O., Eds.; Raven
Press: New York, NY, USA, 1973; p. 27.
5. Harris, R.C.; Straley, J.M. Cationic polymethine dyes for acrylic fibers. U.S. Patent 1,537,757,
1968; [Chem. Abstr. 1970, 73, 100054w].
6. Bennamane, N.; Kaoua, R.; Hammal, L.; Nedjar-Kolli, B. Synthesis of new amino-1,5-
benzodiazepine and benzotriazole derivatives from dimedone. Org. Commun. 2008, 1, 62-68.
7. Hammal, L.; Bouzroura, S.; André, C.; Nedjar-Kolli, B.; Hoffmann, P. Versatile Cyclization of
Aminoanilino Lactones: Access to Benzotriazoles and Condensed Benzodiazepin-2-thiones. Synt.
Commun. 2007, 37, 501-511.
8. Aversa, M.C.; Ferlazzo, A.; Gionnetto, P.; Kohnke, F.H. A convenient synthesis of novel
[1,2,4]triazolo[4,3-a][1,5]benzodiazepine derivatives. Synthesis 1986, 3, 230-231.

Molecules 2011, 16
98
9. Essaber, M.; Hasnaoui, A.; Benharref, A.; Lavergne, J.P. Synthesis of new tri- and
tetraheterocyclic systems: 1,3-dipolar cycloaddition of nitrilimines on 2,7-dimethyl-4-phenyl-3H-
1,5-benzodiazepin. Synth. Commun. 1998, 28, 4097-4104.
10. El-Sayed, A.M.; Abdel-Ghany, H.; EI-Saghier, A.M.M. A novel synthesis of pyrano(2,3-c)-, 1,3-
oxazino(2,3 b)-,1,2,4-triazolo(3,4-b)-, oxazolo(2,3-b)-, furano(3,2-c)-, and 3-substituted-
(1,5)benzodiazepin-2-ones. Synth Commun. 1999, 29, 3561-3572.
11. Chimirri, A.; Grasso, S.; Ottana, R.; Romeo, G.; Zappala, M. Synthesis and stereochemistry of
novel [1,2,4]oxadiazolo[4,5-a][1,5]benzodiazepine derivatives. J. Heterocycl. Chem. 1990, 27,
371-374.
12. Herbert, J.A.L.; Suschitzky, H. Syntheses of heterocyclic compounds. Part XXIX. Substituted 2,3-
dihydro-1H-1,5-benzodiazepines. J. Chem. Soc., Perkin Trans. 1974, 1, 2657-2661.
13. Morales, H.R.; Ulbarela, B.A.; Contreras, R. New synthesis of dihydro- and tetrahydro-1,5-
benzodiazepines by reductive condensation of o-phenylenediamine and ketones in the presence of
sodium borohydride. Heterocycles 1986, 24, 135-139.
14. Jung, D.I.; Choi, T.W.; Kim, Y.Y.; Kim, I.S.; Park, Y.M.; Lee, Y.G.; Jung, D.H. Synthesis of 1,5-
benzodiazepine derivatives. Synth. Commun. 1999, 29, 1941-1951.
15. Balakrishna, M.S.; Kaboudin, B. A simple and new method for the synthesis of 1,5
benzodiazepine derivatives on a solid surface. Tetrahedron Lett. 2001, 42, 1127-1129.
16. Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. Corrigendum to Ytterbium triflate
promoted synthesis of 1,5-benzodiazepine derivatives. Tetrahedron Lett. 2001, 42, 3193-3195.
17. Kaboudin, B.; Navaee, K. Alumina/Phosphorus Pentoxide (App) as an Efficient Reagent for the
Synthesis of 1,5-Benzodiazepines under Microwave Irradiation. Heterocycles 2001, 55, 1443-
1446.
18. Pozarentzi, M.; Stephanatou, J.S.; Tsoleridis, C.A. An Efficient Method for the Synthesis of 1,5-
Benzodiazepine Derivatives under Microwave Irradiation without Solvent. Tetrahedron Lett.
2002, 43, 1755-1758.
19. Yadav, J.S.; Reddy, B.V.S.; Eshwaraiah, B.; Anuradha, K. Amberlyst-15: Anovel and recyclable
reagent for the synthesis of 1,5-benzodiazepines anionic liquids. Green Chem. 2002, 4, 592-594.
20. Sabitha, G.; Reddy, G.S.K.K.; Reddy, K.B.; Reddy, N.M.; Yadav, J.S. A new, efficient and
environmentally benign protocol for the synthesis of 1,5-benzodiazepines using cerium (III)
chloride/sodium iodide supported on silica gel. Adv. Synth. Catal. 2004, 346, 921-923.
21. Yadav, J.S.; Reddy, B.V.S.; Kumar, S.P.; Nagaiah, K. Indium(III) bromide: A novel and efficient
reagent for the rapid synthesis of 1,5-benzodiazepines under solvent-free conditions. Synthesis
2005, 480-484.
22. Jarikote, D.V.; Siddiqui, S.A.; Rajagopal, R.; Daniel, T.; Lahoti, R.J.; Srinivasan, K.V. Room
temperature ionic liquid promoted synthesis of 1,5- benzodiazepine derivatives under ambient
conditions. Tetrahedron Lett. 2003, 44, 1835-1838.
23. De, S.K.; Gibbs, R.A. Scandium(III) triflate as an efficient and reusable catalyst for synthesis of
1,5-benzodiazepine derivatives. Tetrahedron Lett. 2005, 46, 1811-1813.
24. Varala, R.; Ramu, E.; Sreelatha, N.; Adapa, S.R. Ceric ammonium nitrate (CAN) promoted
efficient synthesis of 1,5-benzodiazepine derivatives. Synlett 2006, 1009-1014.

Molecules 2011, 16
99
25. Pasha, M.A.; Jayashankara, V.P. Synthesis of 1,5-benzodiazepine derivatives catalyzed by zinc
chloride. Heterocycles 2006, 68, 1017-1023.
26. Kumar, R.; Chaudhary, P.; Nimesh, S.; Verma, A.K.; Chandra, R. An efficient synthesis of 1,5-
benzodiazepine derivatives catalyzed by silver nitrate. Green Chem. 2006, 8, 519-521.
27. Reddy, B.M.; Sreekanth, P.M.; Lakshmanan, P. Sulfated zirconia as an efficient catalyst for
organic synthesis and transformation. J. Mol. Catal. A: Chem. 2005, 237, 93-100.
28. Yadav, J.S.; Reddy, B.V.S.; Satheesh, G.; Srinivasulu, G.; Kunwar, A.C. InCI3-catalyzed
stereoselective synthesis of optically pure 1,5-benzodiazepines. Arkivoc 2005, iii, 221-227.
29. Fodili, M.; Amari, M.; Kolli, B.; Robert, A.; Baudy-Floch, M.; Le Grel, P. An efficient Synthesis
of New 2-pyronyl-1,5-benzodiazepine derivatives. Synthesis 1999, 5, 811-814.
30. Heravi, M.M.; Sadjadi, S.; Oskooie, H.A. An Efficient Synthesis of 3H-1,5-benzodiazepine
Derivatives Catalyzed by Heteropolyacids as a Heterogeneous Recyclable Catalyst. J. Chin.
Chem. Soc. 2008, 55, 842-845.
31. Khozhevnikov, I.V. Catalysis by heteropolyacids and multicomponent polyoxometalates in liquid-
phase reactions. Chem. Rev. 1998, 98, 171-198.
32. Ono, Y., Thomas, J.M., Zamaraev, K.I., Eds. Perspectives in Catalysis; Blackwell: London, UK,
1992; p. 341.
33. Khozhevnikov, I.V.; Matveev, K.I. Homogeneous Catalysts Based on Heteropolyacids. Appl.
Catal. 1983, 5, 135-150.
34. Izumi, Y.; Urabe, K.; Onaka, A. Zeolite, Clay and Heteropolyacids in Organic Chemistry;
Kodansha, Tokyo-VCH: Weinheim, Germany, 1992; p. 99.
35. Khozhevnikov, I.V. Heteropolyacids and related compounds as catalysts for fine chemical
synthesis. Catal. Rev.-Sci. Eng. 1995, 37, 311-352.
36. Heravi, M.M.; Derikvand, F.; Haeri, A.; Oskoie, H.A.; Bamoharram, F.F. Heteropolyacids as
Green and Reusable Catalysts for the Synthesis of Isoxazole Derivatives. Synth. Commun. 2008,
38, 135-140.
37. Schwegler, M.A.; Bekkum, H.; Van Munck, N. Heteropolyacids as catalysts for the production of
phthalate diesters. Appl. Catal. 1991, 74, 191-204.
38. Mizuno, N.; Misono, M. Studies of the activity of catalysts based on heteropolyacids. J. Mol.
Catal. 1994, 86, 319-342.
39. Maiti, B.C.; Maitra, S.K. Reaction of dehydroacetic acid with aliphatic, aromatic and heterocyclic
amines. Indian J. Chem. 1998, 37, 710-712.
40. Tsigdinos, G.A. Preparation and Characterization of 12-Molybdophosphoric and 12-
Molybdosilicic Acids and Their Metal Salts. Ind. Eng. Chem., Prod. Res. Dev. 1974, 13, 267-274.
41. Tsigdinos, G.A.; Hallada, C.J. Molybdovanadophosphoricacids and their salts (I) Investigation of
methodsof preparation and characterization. Inorg. Chem. 1968, 7, 437-441.
Sample Availability: Samples of the compounds are available from the authors.
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