Preyssler catalyst-promoted rapid, clean, and efficient condensation reactions for 3H-1,5-benzodiazepine synthesis in solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2013.09.101

A simple, convenient, and environmentally benign synthesis of 1,5-benzodiazepines is developed by condensing different o-phenylenediamines and 1,3-aryl-1,3-propanodiones. The reaction is catalyzed by a Preyssler (NaH ₁₄P₅W₃₀

Full text of DOI:10.1016/j.tetlet.2013.09.101

Tetrahedron Letters 54 (2013) 6574–6579
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Preyssler catalyst-promoted rapid, clean, and efficient condensation
reactions for 3H-1,5-benzodiazepine synthesis in solvent-free
conditions
Gustavo A. Pasquale a,b, Diego M. Ruiz a, Jorge L. Jios c, Juan C. Autino a, Gustavo P. Romanelli a,b,
a Centro de Investigación y Desarrollo en Ciencias Aplicadas ‘Dr. Jorge J. Ronco’ (CINDECA-CCT-CONICET), Universidad Nacional de La Plata, Calle 47 N° 257,
⇑
B1900AJK La Plata, Argentina
b Cátedra de Química Orgánica, Facultad de Ciencias Agrarias y Forestales, Universidad Nacional de La Plata/CISaV, Calles 60 y 119 s/n, B1904AAN La Plata, Argentina
c Unidad Laseisic-Plapimu (UNLP-CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 esq. 115, (1900) La Plata, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple, convenient, and environmentally benign synthesis of 1,5-benzodiazepines is developed by
condensing different o-phenylenediamines and 1,3-aryl-1,3-propanodiones. The reaction is catalyzed
by a Preyssler (NaH14P5W30O110, HPA) heteropolyacid as a safe, clean, and recyclable catalyst. The method
is operationally simple and provides access to a variety of 1,5-benzodiazepines in good to excellent
yields.
Received 9 August 2013
Revised 14 September 2013
Accepted 21 September 2013
Available online 28 September 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
3H-1,5-Benzodiazepines
o-Phenylenediamine
1,3-Diaryl-1,3-propanediones
Preyssler catalyst
Solvent-free
Benzodiazepines are privileged heterocyclic ring systems due to
their broad and important biological properties.1 Some functional-
ized benzodiazepines have pharmacological properties such as
anti-inflammatory, analgesic, antiallergenic antiulcerative, antihis-
taminic, antipyretic, sedative, antidepressant, hypnotic, bactericide,
and fungicide2 properties, among others. Other benzodiazepines
have also been used in crop control such as pesticides, antifeedants
for insect control, herbicides, and fungicides.3 Their synthesis has
received special attention in the field of medicinal chemistry
because the use of 1H-1,5-benzodiazepines has been extended to
treat various diseases such as cancer, viral infection, and cardiovas-
cular disorders.2a
heteropolyacid catalysts using THF or acetonitrile as reaction
solvent20 has also been reported.
On the other hand, chemistry properly applied to chemical
processes can also be viewed as a series of reductions in waste,
energy, and auxiliary substances, leading always to the simplifica-
tion of the processes in terms of the number of chemicals and steps
involved.21 Due to the growing concern for the adverse influence of
organic solvents on the environment, solvent-free organic
reactions have attracted the attention of organic chemists.22
A
solvent-free reaction obviously reduces pollution and brings down
handling costs due to simplification of the experimental and
workup procedure and saving in labor.23
3H-1,5-Benzodiazepines are principally synthesized by conden-
sation of o-phenylenediamines with 1,3-dicarbonyl compounds
and b-halo-ketones, in general in the presence of an acid catalyst.4
Different reagents have been reported in the literature for the syn-
thesis of 1,5-benzodiazepines including: concd-HCl, SiO2, or poly-
Heteropolyacids are molecular arrangements with remarkable
and diverse electronic and molecular structures that give them
various applications in different areas such as medicine, material
sciences, and catalysis. Among the various possible HPA structures,
the Keggin-type primary structure deserves to be mentioned, due
to its widely reported applications.24 As part of a research project to
develop environmentally friendly organic reactions, we used bulk
or silica-supported heteropolyacids with Preyssler structure as
recyclable catalyst in the solvent-free synthesis of flavones,25 N-
sulfonyl-1,2,3,4-tetrahydroisoquinolines,26 phenyl cinnamates,27
and 1,1-diacetates28 to name some examples.
7
phosphoric acid (PPA),5 BF3-OEt,6 Yb(OTf)3, Ga(OTf)3,8 NaBH4,9
MgO/POCl3,10 AgNO3,11 molecular iodine,12 CH3COOH using micro-
wave,13 and ionic liquid.14 Recently, the synthesis of benzodiaze-
pines using different solid acid catalysts such as sulfated
zirconia,15 Al2O3/P2O5,16 PVP-FeCl3,17 zeolite,18 bentonite,19 and
According to our interest in the green protocols in organic syn-
thesis, here we describe the use of a Preyssler heteropolyacid as a
⇑
Corresponding author. Tel.: +54 221 423 6758x438; fax: +54 221 425 2346.
E-mail address: gpr@quimica.unlp.edu.ar (G.P. Romanelli).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.101

G. A. Pasquale et al. / Tetrahedron Letters 54 (2013) 6574–6579
6575
Table 1
NaH14P5W30O110-catalyzed reactions of o-phenylenediamine and 1-(2-hydroxyphenyl)-3-phenyl-1,3-propanedione
HO
N
OH
O
O
NH2
NH2
Preyssler catalyst
Solvent-free
+
N
1
2
3 g
Entry
HPA (mol %)
Molar ratio 1:2
Temperature (°C)
Time (min)
3g Yielda (%)
1
2
3
4
5
6
7
8
9
—
1
0.5
1
1
1
1
1
1
2:1
2:1
2.1
1:1
2:1
2.1
2.1
2.1
2.1
130
130
130
130
110
80
140
130
110
30
15
15
15
15
15
15
30
30
5
93
53
76
49
—
88
92
—
a
Isolated yield after flash chromatography.
Table 2
1,5-Benzodiazepines from o-phenylenediamines and 1,3-diaryl-1,3-propanediones
Compounds
Product
Yielda (%)
Mp (°C)
N
137–138
3a
53
Lit. 138–14029
N
CH3
N
N
98–100
New compound
3b
3c
3d
3e
3f
95
84
76
—
N
N
Cl
Br
160–162
Lit. no data30
N
N
170–172
Lit. no data
N
N
—
O2N
N
N
—
—
N
(continued on next page)

6576
G. A. Pasquale et al. / Tetrahedron Letters 54 (2013) 6574–6579
Table 2 (continued)
Compounds
Product
HO
Yielda (%)
Mp (°C)
N
N
180–181
3g
3h
3i
93
70
75
Lit. 183–18431
HO
N
CH3
187–188
Lit. 187–18831
N
HO
N
Cl
183–184
186–18731
N
187–188 °C
New compound
N
N
HO
3f
59
80
N
HO
N
191–193 °C
New compound
3g
Cl
HO
N
HO
N
CH3
3h1
58
141–143
3h2
152–153
New compounds
+
3h
Regioisomermixture
1:2
N
N
CH3
3h1
3h2
HO
N
HO
N
O2N
3i
—
—
+
O2N
N
N
a
Isolated yield after flash chromatography.
solid and reusable catalyst, in the solvent-free synthesis of 1H-1,
5-benzodiazepines, by condensation reaction of o-phenylenediam-
ines with several 1,3-diaryl-1,3-propanediones (Scheme 1).
First, we prepare the HPA catalyst, and then we study its cata-
lytic activity in the mentioned reaction. The Preyssler heteropoly-
anion was prepared from Na2WO4.2H2O and H3PO4 according to
R2
R1
R1
O
O
NH2
NH2
Preyssler catalyst
N
Ar
R
+
R
Solvent-free
X
R2
X
N
Ar
R = H, 2-CH3 ,3-Cl, 3-Br, 3-NO2
R1 = H, OH
R2 = H, 4-Cl, 5-Cl, 4-CH3
Ar = aryl, 1-naphtyl, 2-naphtyl
X = CH, N
Scheme 1. General scheme of reaction.

G. A. Pasquale et al. / Tetrahedron Letters 54 (2013) 6574–6579
6577
Table 3
the previously reported method, and converted to the correspond-
ing acid H14[NaP5W30O110] by passing it through a Dowex-50-X8
ion-exchange column.27 The HPA catalyst was characterized by
31P MAS-NMR and FT-IR spectroscopy.32 The 31P NMR-MAS spectra
show five peaks at À10.2, À10.6, À12.8, À13.5, and À13.8 ppm.
Meanwhile, the FTIR spectrum also shows characteristic bands of
Recyclability of the HPA in the synthesis of 3f over 5 runs
Entry
Cycle
Yield 3f (%)
1
2
3
4
5
Use
93
90
89
89
88
1st reuse
2nd reuse
3rd reuse
4th reuse
the Preyssler anion at 1641, 1164, 1087, 958, 916, and 798 cmÀ1
respectively.27 In a previous work, we reported a study about the
,
Scheme 2. Suggested mechanism for the formation of 1,5-benzodiazepines catalyzed by a Preyssler catalyst.

6578
G. A. Pasquale et al. / Tetrahedron Letters 54 (2013) 6574–6579
acidic characteristic of this catalyst using potentiometric tritra-
tion.27 The maximum acid strength of the acid sites (E) for the cat-
alyst is 862 mV. This E value indicates very Brönsted strong acid
sites for the catalyst, and it was similar to the obtained for bulk
commercial Keggin HPA.
regeneration of the HPA and the production of the imino
compound 5; (E) the activation of the other carbonyl group present
in 5 with the heteropolyacid (HPA) to generate—in a way analo-
gous to the step (B)—a new intermediate 6; (F) the intramolecular
nucleophilic attack of the amino group to the activated carbonyl
group giving the formation of the heterocyclic intermediate that
undergoes the same proton transference as in step (C) with a
loss of a second molecule of water to give intermediate 7; and
(G) the loss of a proton to give the HPA regeneration and benzodi-
azepine 8.
In conclusion, a very simple and convenient catalytic method
was developed for the synthesis of 1,5-benzodiazepine derivatives
from a multicomponent condensation reaction, under solvent-free
conditions. The procedure has the advantages of low environmen-
tal impact, high yields, high selectivity, short reaction time, and the
recovery of the catalyst by simple filtration. The use of an insoluble
catalyst instead of soluble inorganic acids contributes to waste
reduction. Further investigations about the use of this catalyst in
the more sophisticated heterocyclic synthesis and in the biomass
valorization are in progress in our laboratory.
The optimal reaction conditions were examined employing 1-
(2-hydroxyphenyl)-3-phenyl-1,3-propanodione (1 mmol), and
1,2-phenylenediamine as substrates.33 Several reaction conditions
were checked: temperature, reaction time, amount of catalyst, and
molar ratio of substrates (Table 1). When a mixture of both
substrates and the catalyst (1 mmol % of active phase) was stirred
at 130 °C under solvent-free conditions, the corresponding 3H-1,
5-benzodiazepine (Table 1, entry 2) was formed as the only
reaction product with a 93% yield and in a short reaction time
(15 min). Under the same reaction conditions and in the absence
of the catalyst, the corresponding 1H-1,5-benzodiazepine was
obtained only with 5% yield (Table 1, entry 2). In this test several
unidentified side products were detected by TLC. In these
equilibrium reactions, the excess of one of the reactants improves
yields. Although yields are good when reactants react in an
equimolar ratio (76%, Table 1, entry 4), rising to 93% when using
a 100% excess of the diamine substrate (Table 1, entry 2).
Acknowledgements
Encouraged by the remarkable results obtained with the above
reaction and in order to show the generality and scope of this
catalytic method, the 1H-1,5-benzodiazepine synthesis from a
series of 1,2-phenylenediamines and 1,3-diaryl-1,3-propanediones
was studied under similar reaction conditions. The results are
summarized in Table 2. In most of the studied cases, the reaction
proceeded smoothly. 1,2-Phenylenediamines having either weak
electron-withdrawing or electron-releasing substituents, including
2-methyl, 3-chloro, and 3-bromo, reacted efficiently to give good to
excellent yields of the desired 1,5 benzodiazepines (Table 2).
However, strongly electron-withdrawing groups or electron-
deficient aromatic rings decrease dramatically the nucleophilicity
of amines and the reaction does not take place. As shown in Table 2
when 4-nitro-1,2-phenylenediamine and 2,3-diaminopyridine
were used as substrate, the benzodiazepines 3e, 3f, 3i1, and 3i2
were not obtained. It is noteworthy, that when we studied the
We thank Universidad Nacional de La Plata, CONICET and
ANPCyT for financial support. G.R. is member of CONICET. We also
thank Michael Pope for his permission to use his figure of the
Preyssler structure.
References and notes
1. (a) Schultz, H. Benzodiazepines; Springer, Heidelberg: Germany, 1982; (b)
Randall, L. O.; Kappel, B. In Benzodiazepines; Garattini, S., Mussini, E., Randall, L.
O., Eds.; Raven Press: New York, 1973; (c) Landquist, J. K. In Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, UK,
1984; (d) Pan, X.; Zou, Z.; Zhang, W. Tetrahedron Lett. 2008, 49, 5302–5308.
2. (a) Radatz, C.; Silva, R.; Perin, G.; Lenardao, E.; Jacob, R.; Alves, D. Tetrahedron
Lett. 2011, 52, 4132–4136; (b) Abdollahi-Alibeik, M.; Mohammadpoor-Baltork,
I.; Zaghaghi, Z.; Yousefi, B. Catal. Commun. 2008, 9, 2496–2502; (c) Atwal, K. S.;
Bergey, J. L.; Hedberg, A.; Moreland, S. J. Med. Chem. 1987, 30, 635–640; (d)
Braccio, M. D.; Grossi, G.; Roma, G.; Vargiu, L.; Mura, M.; Marongiu, M. E. Eur. J.
Med. Chem. 2001, 36, 935–949.
reaction
between
3-methyl-1,2-phenylenediamine
and
1-(2-hydroxyphenyl)-3-phenyl-1,3-propanodione as substrate,
two regioisomers were obtained as expected (58%). The regioisom-
ers were purified by repeated flash chromatography and recrystal-
lization to give the compounds 3h1 and 3h2 with 9% and 12%
yields, respectively, after recrystallization. All products listed in
Table 2 were characterized by 1H NMR and 13C NMR, and the
corresponding melting points and elemental analysis were
determined.
We also investigated the reuse of the catalyst. For this purpose
after completion of the reaction, toluene (2 Â 2 mL) was added to
the semisolid reaction mixture.34 The catalyst was dried under vac-
uum (25 °C) and reused in these conditions for a new reaction cy-
cle. The yields of benzodiazepine 3g for the first, second, third, and
fourth reuse were 90%, 89%, 89%, and 88%, respectively (see
Table 3).
A rational mechanism for the formation of compound 8 is pos-
tulated in Scheme 2 for the reaction of 1,2-phenylenediamine and
1,3-diphenyl-1,3-propanodione. The reaction is thought to take
place in seven steps: (A) the activation of one of the carbonyl
groups of 1,3-diphenyl-1,3-propanedione 1 with the Preyssler het-
eropolyacid (HPA) to give the intermediate 2; (B) the nucleophilic
attack of an amino group of the 1,2-phenylenediamine 3 to the
activated carbon to give the intermediate 4; (C) the transfer of
the proton from the amino group (4) to the hydroxyl group (4a)
to give the intermediate 4b through the HPA and the consecutive
loss of a molecule of water with the formation of the intermediate
4c; (D) the loss of the imino proton of the intermediate 4c and the
3. (a) Reddy, R. J.; Ashok, D.; Sharma, P. N. Indian J. Chem. 1993, B32, 404–410; (b)
Clifford, D. P.; Jackson, D.; Edwards, R. V.; Jeffrey, P. Pestic. Sci. 1976, 7, 453–458.
4. Majid, S.; Khanday, W.; Tomar, R. J. Biomed. Biotechnol. 2012, 6.
5. Jung, D.; Song, J.; Kin, Y.; Lee, D.; Lee, Y.; Park, Y.; Choi, S.; Hahn, J. Bull. Korean
Chem. Soc. 2007, 28, 1877–1880.
6. Herbert, J. A. L.; Suschitzky, H. J. Chem. Soc., Perkin Trans. 1 1974, 2657–2661.
7. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O. Tetrahedron Lett. 2001, 42,
3193–3195.
8. Pan, X. Q.; Zou, J. P.; Huang, Z. H.; Zhang, W. Tetrahedron Lett. 2008, 49, 5302–
5308.
9. Morales, H. R.; Bulbarela, A.; Contreras, R. Heterocycles 1986, 24, 135–139.
10. Balakrishna, M. S.; Kaboudin, B. Tetrahedron Lett. 2001, 42, 1127–1129.
11. Kumar, R.; Chaudhary, P.; Nimesh, S.; Verma, A. K.; Chandra, R. Green Chem.
2006, 8, 519–521.
12. Chen, W. Y.; Lu, J. Synlett 2005, 1337–1339.
13. Minothora, P.; Julia, S. S.; Constantinos, A. T. Tetrahedron Lett. 2002, 43, 1755–
1758.
14. Jarikote, D. V.; Siddiqui, S. A.; Rajagopal, R.; Thomas, D.; Lahoti, R. J.; Srinivasan,
K. V. Tetrahedron Lett. 2003, 44, 1835–1838.
15. Reddy, B. M.; Sreekamth, P. M.; Reddy, V. R. J. Mol. Catal. A 2005, 225, 71–78.
16. Kaboudin, B.; Navaee, K. Heterocycles 2001, 55, 1443–1446.
17. Chari, M. A.; Syamasundar, K. Catal. Commun. 2005, 6, 67–70.
18. Hegedüs, A.; Hell, Z.; Potor, A. Catal. Lett. 2005, 105, 229–232.
19. Muñoz, M.; Sathicq, G.; Romanelli, G.; Hernández, S.; Cabello, C.; Botto, I.;
Capron, M. J. Porous Mater. 2013, 20, 65–73.
20. (a) Heravi, M.; Sadjadi, S.; Oskooie, H.; Hekmatshoar, R.; Bamoharram, F. J. Chin.
Chem. Soc. 2008, 55, 842–845; (b) Yadav, J. S.; Reddy, B. V. S.; Praveenkumar, S.;
Nagaiah, K.; Lingaiah, N.; Saiprasad, P. S. Synthesis 2004, 901–904.
21. (a) Watson, W. Green Chem. 2012, 14, 251–256; (b) Kalidindi, S.; Jagirdar, B.
ChemSusChem 2012, 5, 65–75; (c) Mulvihill, M.; Beach, M.; Zimmerman, E.;
Anastas, P. Annu. Rev. Environ. Resour. 2011, 36, 271–293.
22. (a) Singh, M.; Chowdhury, S. RSC Advances 2012, 2, 4547–4592; (b) Shearouse,
W.; Waddell, D.; Mack, J. Curr. Opin. Drug Disc. Dev. 2009, 12, 772–783; (c)
Kalita, P.; Kumar, R. Microporous Mesoporous Mater. 2012, 149, 1–9.
23. Nagendrappa, G. Resonance 2002, 59–68.

G. A. Pasquale et al. / Tetrahedron Letters 54 (2013) 6574–6579
6579
24. (a) Timofeeva, M. N. Appl. Catal. A: General 2003, 256, 19–35; (b) Romanelli, G.;
Autino, J. Mini-Rev. Org. Chem. 2009, 6, 359–366.
130.4, 130.5, 136.3, 137.4, 137.5, 139.1, 140,4, 151.8, 153.9. Anal. Calcd for
C22H18N2: C, 85.13; H, 5.85; N, 9.03. Found: C, 85.10; H, 5.81; N, 9.00.
Compound 3d 1H NMR (DMSO-d6, 400 MHz): d 3.70 (2H, br s), 7.42–7.50 (8H,
m), 7.79 (1H, dd J = 2 Hz; 0.6 Hz), 7.97–8.00 (4H, m); 13C NMR (DMSO-d6,
100 MHz): 35.2, 118.3, 128.2, 128.2, 128.5, 128.8, 128.8, 130.3, 130.9, 131.0,
131.1, 136.9, 137.0, 139.7, 141.7, 154.5, 154.0. Anal. Calcd for C21H15BrN2: C,
67.21; H, 4.03; N, 7.47. Found: C, 67.18; H, 4.06; N, 7.50. Compound 3i 1H NMR
(DMSO-d6, 400 MHz): d 3.80 (2H, br s), 6.96 (1H, d J = 8), 7.29 (1H, dd J = 2;
J = 9), 7.37–7.46 (2H, m), 7.51–7.58 (4H, m), 7.66 (1H, dd J = 2; J = 8), 7.76 (1H, d
J = 2.5), 8.04–8.08 (2H, m), 14.45 (1H, s); 13C NMR (DMSO-d6, 100 MHz): d 33.4,
118.7, 119.9, 123.2, 126.0, 126.7, 127.8, 127.9, 128.4, 128.9, 129.1, 131.3, 133.3,
136.4, 136.9, 141.7, 154.7, 157.0, 161,0. Anal. Calcd for C21H15ClN2O: C, 72.73;
H, 4.36; N, 8.08. Found: C, 72.71; H, 4.32; N, 8.07. Compound 3g 1H NMR
(DMSO-d6, 400 MHz): d 3.75 (2H, br s), 6.56 (1H, dd, J = 3; J = 8 Hz), 7.00 (1H, d,
J = 2 Hz), 7.06 (1H, d, J = 8 Hz), 7.43–7.70 (8H, m), 7.93–8.00 (3H, m), 14.45 (1H,
s); 13C NMR (DMSO-d6, 100 MHz): d 38.7, 116.5, 118.3, 119.1, 125.0, 125.0,
126.3, 126.5, 126.6, 127.0, 127.4, 127.8, 128.8, 128.9, 129.3, 130.5, 130.9, 134.0,
135.9, 136.8, 139.0, 141.3, 156.9, 157.2, 163.1. Anal. Calcd for C25H17ClN2O: C,
75.66; H, 4.32; N, 7.06. Found: C, 75.63; H, 4.32; N, 7.07. Compound 3h1 1H
NMR (DMSO-d6, 400 MHz): d 2.60(3H, s), 3.70 (2H, br s), 6.86–6.90 (1H, m),
7.01 (1H, dd J = 1.5; J = 8 Hz), 7.27–7.38 (3H, m), 7.48–7.53 (4H, m), 7.80 (1H,
dd J = 1.5; J =8 Hz), 8.02–8.07 (2H, m), 14.80 (1H, s); 13C NMR (DMSO-d6,
100 MHz): d 19.2, 33.7, 118.0, 118.4, 118.6, 126.0, 126.8, 127.1, 128.3, 128.4,
128.8, 131.0, 133.5, 134.9, 136.1, 136.8, 141.6, 155.0, 157.2, 162.6. Anal. Calcd
for C22H18N2O: C, 80.96; H, 5.56; N, 8.58. Found: C, 80.93; H, 5.55; N, 8.54.
Compound 3h2 1H NMR (DMSO-d6, 400 MHz): d 2.58 (3H, s), 3.70 (2H, br s),
6.91–6.95 (1H, m), 7.01 (1H, dd, J = 1.5; J = 8 Hz), 7.27–7.31 (2H, m), 7.35–7.43
(2H, m), 7.47–7.50 (3H, m), 7.91 (1H, dd J = 1.5; J = 8 Hz), 8.10–8.14 (2H, m),
14.60 (1H, s), 13C NMR (DMSO-d6, 100 MHz): d 18.6, 33.2, 117.9, 118.5, 118.5,
125.5, 125.6, 127.4, 128.3, 128.4, 128.7, 130.8, 133.5, 136.8, 136.8, 136.9, 140.1,
152.8, 158.3, 162.6. Anal. Calcd for C22H18N2O: C, 80.96; H, 5.56; N, 8.58.
Found: C, 80.92; H, 5.57; N, 8.58. (s: singlet, m: multiplet, d: doublet, t:triplet,
dd: double doublet, br s: broad singlet).
25. Romanelli, G.; Virla, E.; Duchowicz, P.; Gaddi, A.; Ruiz, D.; Bennardi, D.; Del
Velle Ortíz, E.; Autino, J. J. Agric. Food Chem. 2010, 58, 6290–6295.
26. Romanelli, G.; Ruiz, D.; Autino, J.; Giaccio, H. Mol. Diversity 2010, 14, 803–807.
27. Ruiz, R.; Romanelli, G.; Vázquez, P.; Autino Appl, J. Appl. Catal. A: General 2010,
374, 110–119.
28. Romanelli, G.; Ruiz, D.; Vázquez, P.; Thomas, H.; Autino, J. Chem. Eng. J. 2010,
161, 355–362.
29. Tsoleridis, C.; Pozarentzi, M.; Mitkidou, S.; Stephanatou, J. ARKIVOC 2008, XV,
193–209.
30. Takahashi, M.; Takada, T.; Sakagami, T. J. Heterocycl. Chem. 1987, 24, 797–799.
31. Ahmad, R.; Zia-Ul-Haq, M.; Hameed, S.; Nadeem, H.; Duddeck, H. J. Chem. Soc.
Pak. 2000, 22, 302–308.
32. Catalyst preparation and characterization. The catalyst was prepared by
a
procedure described in the literature and it was characterized by 31P MAS
NMR, and FT-IR XRD. The 31P MAS NMR spectra were recorded in Bruker MSL-
400 equipment operating at frequencies of 121.496 MHz. A sample holder of
5 mm diameter and 17 mm in height was used. The spin rate was 2.1 kHz, and
several hundreds of pulse responses were collected. Chemical shifts were
expressed in parts per million with respect to 85% H3PO4 as external standard
for 31P NMR. The Fourier transform infrared (FT-IR) spectra of the solids were
obtained using a Bruker IFS 66 FT-IR spectrometer and pellets in KBr in the
400–4000 cmÀ1 wavenumber range. Potentiometric titration was performed
using a Metrohm Titrino Basic 794, with LL Solvotrode LiCl electrode.
33. General procedure for the synthesis of 1,5-benzodiazepines 3. A mixture of 1.3-
diaryl-1,3-propanodione, 1,2-phenylenediamine and 1 mmol % of HPA (ca.
57 mg) was stirred and heated at 120 °C in a preheated oil bath for approx.
15 min. After completion of the reaction as indicated by TLC (ethyl acetate–
hexane, 1:4), hot toluene was added (5 mL). The solvent was dried over
Na2SO4, filtered and concentrated under reduced pressure to leave the crude
product that was cleaned by short column chromatography over silica gel
(mixtures of ethyl acetate–hexane). After chromatographic separation the
products were purified by recrystallization from EtOH. Characterization of
selected compounds: 3b 1H NMR (DMSO-d6, 400 MHz): d 2.60 (3H, s), 3.70 (2H,
br s), 7.24–7.30 (2H, m), 7.41–7.51 (7H, m), 7.98–8.06 (4H, m); 13C NMR
(DMSO-d6, 100 MHz): d 18.7, 35.0, 125.1, 126.5, 128.1, 128.2, 128.6, 128.7,
34. Catalyst reuse. Stability tests of the catalysts were carried out by running five
consecutive experiments under the same reaction conditions. After each test,
the catalyst was separated from the reaction mixture by filtration, washed
with toluene (2 Â 2 mL), dried under vacuum, and then reused.