Synthesis of benzodiazepines catalyzed by CoFe2O4@SiO2-PrNH2 nanoparticles as a reusable catalyst

Article abstract of DOI:10.1515/znb-2017-0023

CoFe₂O₄@SiO₂-PrNH₂ nanoparticles have been used as an efficient catalyst for the preparation of benzodiazepines by multi-component reactions of 1,2-phenylenediamine, dimedone, different aldehydes or Meldrum's acid and isocyanides. This method provides several advantages including mild reaction conditions, the applicability to a wide range of substrates, the reusability of the catalyst and low catalyst loading.

Full text of DOI:10.1515/znb-2017-0023

Z. Naturforsch. 2017; 72(7)b: 497–503
Naiereh Sadat Miri and Javad Safaei-Ghomi*
Synthesis of benzodiazepines catalyzed by
CoFe O @SiO -PrNH nanoparticles as a reusable
2
4
2
2
catalyst
DOI 10.1515/znb-2017-0023
with a heterogeneous catalyst [15, 16]. The surface of mag-
netic nanoparticles (MNPs) can be functionalized simply
through suitable surface modifications to provide the
attachment of a variety of favorable functionalities. The
expansion of surface modification of MNPs as significant
candidates in the search for supporting catalysts is pres-
ently a subject of increasing interest [17, 18].
Received February 17, 2017; accepted March 31, 2017
Abstract: CoFe O @SiO -PrNH nanoparticles have been
2
4
2
2
used as an efficient catalyst for the preparation of benzo-
diazepines by multi-component reactions of 1,2-phenylen-
ediamine, dimedone, different aldehydes or Meldrum’s
acid and isocyanides. This method provides several
advantages including mild reaction conditions, the appli-
cability to a wide range of substrates, the reusability of the
catalyst and low catalyst loading.
Herein, we report the use of CoFe O @SiO -PrNH NPs
2
4
2
2
as an efficient catalyst for the preparation of benzodiaz-
epines by multi-component reactions of 1,2-phenylenedi-
amine, dimedone, different aldehydes or Meldrum’s acid
Keywords: benzodiazepines; CoFe O nanoparticles; het- and isocyanides (Scheme 1).
erogeneous catalyst; one-pot reaction.
2
4
2
Results and discussion
1
Introduction
The particle size and morphology of CoFe O @SiO -PrNH
2
4
2
2
Benzodiazepines have emerged as a group of important NPs was determined by scanning electronic microscopy
heterocycles in organic and medicinal chemistry due to (SEM). The statistic of results from SEM images clearly
their potency and wide spectrum of biological activities demonstrates that the average size of CoFe O @SiO -
2
4
2
including antimicrobial [1], anticancer [2], anti-anxiety PrNH is about 15–20 nm (Fig. S1, see Supplementary
2
[
3], inhibitors of HIV protease [4] and antipsychotics [5]. Information).
These activities make benzodiazepines attractive targets Figure S2 (see Supplementary Information) shows the
in organic synthesis. The synthesis of benzodiazepines powder X-ray diffraction (XRD) pattern. The pattern agrees
has been reported in the presence of diverse catalysts well with the reported pattern for CoFe O (JCPDS No.
2
4
such as Hg(OTf) [6], organic acid [7], Yb(OTf) [8], ceric 22-1086). The crystallite size of CoFe O @SiO -PrNH NPs
2
3
2
4
2
2
ammonium nitrate [9], Sc(OTf) [10], nano-Fe O /SiO [11], calculated by the Debye–Scherer equation is about 20 nm,
3
3
4
2
Fe O @cellulose composite [12], nano-Fe O @chitosan which is in good agreement with the result obtained by SEM.
3
4
3
4
[
13] and nano-Fe O [14]. Despite the use of these ways,
Figure S3 (see Supplementary Information) shows
3
4
there remains adequate purpose to offer a new way for Fourier transform infrared (FT-IR) spectra of CoFe O @
2
4
−1
an efficient, high yielding and mild approach to achieve SiO -PrNH NPs. The bands at 464, 1079, 1628 and 3418 cm
such systems. The eco-compatibility and utilization of are the characteristic absorptions of SiO , which shows evi-
2
2
2
multicomponent reactions (MCRs) are enhanced when dence for the formation of a silica shell. The presence of
the multicomponent strategy is applied in conjugation Co–O and Fe–O bonds in magnetic particles is confirmed
−1
by the characteristic peak appeared at 592 cm . The intense
−1
and broad peaks near 1079 and 3400 cm are characteris-
tic absorption bands of the vibration of OH moieties, which
*
Corresponding author: Javad Safaei-Ghomi, Department of
Chemistry, Qom Branch, Islamic Azad University, Qom, I.R. Iran; and
Department of Organic Chemistry, Faculty of Chemistry, University of
Kashan, PO Box 87317-51167, Kashan, I.R. Iran,
overlap with the NH vibrations. The enhancement of the
2
−1
bands at 1628 cm provides direct evidence to verify the
existence of the N–H deformation vibration [19].
e-mail: safaei@kashanu.ac.ir
Naiereh Sadat Miri: Department of Chemistry, Qom Branch, Islamic
Azad University, Qom, I.R. Iran
Initially, we had explored and optimized different
reaction parameters for the synthesis of benzodiazepines
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

4
98ꢀꢀꢀꢀꢁꢀN.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH
2
4
2
2
CoFe O @SiO -PrNH
2
4
2
2
O
O
O
O
H
N
O
O
R2 N C
H
N
O
Ar
3
O
NH2
NH2
O
O
O
3'
2'
2
NH-R2
N
H
N
H
CH Cl , r.t.
2
2
EtOH, r.t.
Ar
4'a−e
1
4a−e
Scheme 1:ꢀSynthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH nanoparticles.
2
4
2
2
by the MCR of 1,2-phenylenediamine, dimedone and as substrates (Table 2). The above results obviously show
4
-chlorobenzaldehyde as a model reaction. Meanwhile, that the present catalytic procedure is extendable to a
we carried out the MCR among 1,2-phenylenediamine, wide variety of substrates to construct a diversity-oriented
Meldrum’s acid and tert-buthyl isocyanide at room tem- library of benzodiazepines.
perature as a model reaction in the presence of different
Reusability of the catalysts is one of the significant
catalysts (Table 1). These reactions were carried out in properties of every catalyst used in large-scale produc-
the presence of various catalysts, such as SiO , CH COOH, tion. Therefore, the reusability of the heterogeneous cata-
2
3
CH SO H, CF COOH, triethylamine, MgO NPs, CuO NPs, lyst was explored using the model reaction system under
3
3
3
p-toluene sulfonic acid (p-TSA), nano-CoFe O , CoFe O @ the optimized conditions. After completion of the reac-
2
4
2
4
SiO and nano-CoFe O @SiO -PrNH . The best results were tion, the magnetic nanocatalyst is easily and efficiently
2
2
4
2
2
obtained in the presence of nano-CoFe O @SiO -PrNH . In separated from the product by an external magnetic field.
2
4
2
2
order to optimize the reaction conditions, we performed The nano-CoFe O @SiO -PrNH was washed three to four
2
4
2
2
the reaction using varied quantities of the catalyst. There times with ethanol and dried at room temperature for 5 h.
was no difference in yield and reaction time when catalyst The reusability of the nano-catalyst was examined for
loading was enhanced to 30 mg.
the synthesis of 4a, and it was found that product yields
To investigate the scope and limitation of this catalytic decreased to a small extent on each reuse (run 1: 95%; run
process, different aldehydes and isocyanides were chosen 2: 95%; run 3: 94%; run 4: 94%; run 5: 93%, run 6: 91%).
The proposed mechanism for the reaction is shown
in Scheme 2. Initially, intermolecular imine formation
Table 1:ꢀOptimization of reactions conditions using different catalysts. from 1,2-phenylenediamine and dimedone promoted by
the CoFe O @SiO -PrNH nanocatalyst occurs. The amino
2
4
2
2
Entryꢁ Catalyst
ꢁ
Time (min)ꢁ Yield (%)
ꢂa/ꢂ′a ꢂa/ꢂ′a
groups distributed on the surface of CoFe O @SiO acti-
2
4
2
vate the C=O groups of dimedone through hydrogen
ꢂ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
–
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢄꢅꢅ/ꢆꢅꢅꢃ ꢂꢅ/trace bonding, and the amino group of 1,2-phenylenediamine
ꢇ
SiO NPs (ꢈ mol%)
ꢇꢅꢅ/ꢆꢅꢅꢃ
ꢇꢈꢅ/ꢆꢅꢅꢃ
ꢇꢈꢅ/ꢆꢅꢅꢃ
ꢇꢅꢅ/ꢇꢄꢅꢃ
ꢇꢅꢅ/ꢆꢅꢅꢃ
ꢊꢅ/ꢆꢅꢅꢃ
ꢊꢅ/ꢆꢅꢅꢃ
ꢉꢅ/ꢇꢅꢅꢃ
ꢉꢅ/ꢇꢅꢅꢃ
ꢈꢅ/ꢂꢅꢅꢃ
ꢈꢅ/ꢂꢅꢅꢃ
ꢈꢅ/ꢂꢅꢅꢃ
ꢄꢈ/ꢉꢅ
ꢆꢊ/ꢈꢇ
ꢇꢅ/ꢇꢊ
ꢈꢅ/ꢉ9
ꢈꢈ/ꢄꢈ
ꢇ
attack the carbonyl group of dimedone with elimination
ꢆ
MgO NPs (ꢆ mol%)
Triethylamine (ꢇꢅ mol%)
CuO NPs (ꢆ mol%)
p-TSA (ꢋ mol%)
of H O leading to imine intermediate I. A 1,3-hydrogen
2
ꢄ
shift then results in isomeric form (tautomerized) to give
ꢈ
enamine II. After this step, the other amino group of the
ꢉ
ꢋ
CH SO H (ꢈ mol%)
ꢉꢈ/ꢈꢇ 1,2-phenylenediamine part of enamine II attacks the car-
ꢆ
ꢆ
ꢊ
CF COOH (ꢆ mol%)
ꢉꢅ/ꢈꢈ
ꢆ
bonyl group of aldehyde, which is itself activated by the
9
CoFe O NPs (ꢆꢅ mg)
ꢋꢅ/ꢉꢈ
ꢇ
ꢄ
catalyst through hydrogen bonding to form intermediate
ꢂꢅ
ꢂꢂ
ꢂꢇ
ꢂꢆ
CoFe O @SiO (ꢆꢅ mg)
ꢋꢈ/ꢋꢂ
ꢇ
ꢄ
ꢇ
III. Finally, the seven-membered ring products 4a–e are
CoFe O @SiO -PrNH NPs (ꢂꢅ mg)ꢃ
ꢊꢋ/ꢊꢄ
ꢇ
ꢄ
ꢇ
ꢇ
afforded via intramolecular cyclization of III [13].
CoFe O @SiO -PrNH NPs (ꢇꢅ mg)ꢃ
9ꢈ/9ꢇ
ꢇ
ꢄ
ꢇ
ꢇ
a
b
CoFe O @SiO -PrNH NPs (ꢆꢅ mg)ꢃ
9ꢈ /9ꢇ
A possible mechanism for the formation of prod-
ucts 4′a–e is shown in Scheme 3. It is conceivable that
the initial event is the formation of intermediate II from
a condensation reaction between o-phenylenediamine
and Meldrum’s acid. The amino groups distributed on
ꢇ
ꢄ
ꢇ
ꢇ
aIsolated yield (reaction conditions: 1,2-phenylenediamine, dimedone
and 4-chlorobenzaldehyde at room temperature in EtOH).
b
Isolated yield (reaction conditions: 1,2-phenylenediamine, Meldrum’s
acid and tert-buthyl isocyanide at room temperature in CH Cl ).
2
2
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

N.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH ꢌꢁꢀꢀꢀꢌ499
2
4
2
2
Table 2:ꢀSynthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH nanoparticles.
2
4
2
2
Entry
Product
Time (min)
Yield (%)a
M.p. (°C)
M.p. (°C) [ref.]
O
ꢂ
ꢈꢅ
9ꢈ
ꢇꢆꢄ–ꢇꢆꢉ
ꢇꢆꢋ–ꢇꢆꢊ [ꢂꢆ]
H
N
N
H
4a
Cl
O
ꢇ
ꢉꢅ
ꢊꢋ
ꢇꢇꢈ–ꢇꢇꢋ
ꢇꢇ9–ꢇꢆꢂ [ꢇꢅ]
H
N
N
H
OCH
3
4b
O
ꢆ
ꢄ
ꢈꢈ
ꢈꢅ
9ꢅ
9ꢈ
ꢇꢄꢅ–ꢇꢄꢇ
ꢇꢆꢈ–ꢇꢆꢋ
ꢇꢄꢉ–ꢇꢄꢊ [ꢇꢅ]
ꢇꢄꢂ–ꢇꢄꢇ [ꢇꢅ]
H
N
N
H
4
c
O
H
N
N
H
Br
4d
O
ꢈ
ꢈꢆ
9ꢇ
ꢇꢆꢅ–ꢇꢆꢇ
ꢇꢆꢇ–ꢇꢆꢆ [ꢂꢆ]
H
N
Cl
N
H
4e
H
N
O
ꢉ
ꢋ
ꢂꢅꢅ
ꢂꢇꢅ
9ꢇ
ꢊꢉ
>ꢆꢅꢅ
>ꢆꢅꢅ [ꢇꢂ]
O
NH
N
H
O
4
ꢀa
H
N
O
ꢇꢊꢉ–ꢇꢊꢊ
ꢇꢊꢉ–ꢇꢊꢊ [ꢂꢄ]
O
NH
N
H
O
4ꢀb
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

5
00ꢀꢀꢀꢀꢁꢀN.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH
2
4
2
2
Table 2ꢀ(continued)
Entry
Product
Time (min)
Yield (%)a
M.p. (°C)
M.p. (°C) [ref.]
H
N
O
ꢊ
ꢂꢂꢅ
ꢊꢊ
ꢆꢅꢄ–ꢆꢅꢉ
ꢆꢅꢉ–ꢆꢅꢊ [ꢂꢄ]
O
NH
OCH
N
H
3
O
4ꢀc
H
N
O
9
ꢂꢂꢅ
ꢂꢂꢅ
9ꢇ
9ꢅ
>ꢆꢅꢅ
>ꢆꢅꢅ [ꢇꢂ]
O
NH
N
H
O
4
ꢀd
H
N
O
ꢂꢅ
ꢇꢊꢅ–ꢇꢊꢇ
–
O
NH
OCH
N
H
3
O
4ꢀe
aIsolated yield.
H
OH
NH2
NH2
O
N
O
H
O
N
O
N
O
NH2
2
− H O
NH2
NH2
I
II
O
H
Ar
H
N
Ar
N
N
Ar
HN
O
NH2
HN
N
N
H
Ar
O
O
O
II
III
=
CoFe2O4@SiO2-PrNH2
Scheme 2:ꢀProposed reaction pathway for the synthesis of 4a–e.
the surface of CoFe O @SiO activate the C=O groups of reaction with nucleophiles through hydrogen bonding
2
4
2
Meldrum’s acid and intermediate I through hydrogen [22, 23].
bonding. Then, intermediate II under a Knoevenagel
condensation reaction with in situ liberated acetone pro-
duces intermediate III. Then, isocyanides reacts with
α,β-unsaturated carbonyl compound (intermediate III) 3 Conclusions
to form intermediate IV (Michael-type addition reaction),
followed by nucleophilic attack of a H O molecule on the In conclusion, we have developed a straightforward and
2
nitrilium moiety to form the product [21]. In this mecha- efficient method for the synthesis of benzodiazepines
nism, CoFe O @SiO -PrNH acts as a highly efficient and by multi-component reactions of 1,2-phenylenediamine,
2
4
2
2
+
green catalyst activating the C=O, C≡N groups for better dimedone, different aldehydes or Meldrum’s acid and
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

N.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH ꢌꢁꢀꢀꢀꢌ501
2
4
2
2
co-precipitation method using FeCl ꢀ·ꢀ6H O and CoCl ꢀ·ꢀ6H O
3
2
2
2
NH2
NH2
Product
O
as precursors. FeCl ꢀ·ꢀ6H O (5.4 g) and CoCl ꢀ·ꢀ6H O (2.38 g)
O
3 2 2 2
were dissolved in 100 mL distilled water. Then, the mixture
solution was transferred into a three-necked flask equipped
with a mechanical stirrer. Fifty milliliters of 3 mol/L NaOH
solution was added into the flask under vigorous stirring.
The mixture was heated to reflux for 1 h to yield a black dis-
persion. When the reaction had finished, the black product
was washed with doubly distilled water for several times
until the pH value of the solution became neutral. The
black precipitate was separated by a permanent magnet,
followed by washing three times with ethanol and drying
at 100°C in a vacuum for 24 h.
O
O
O
H O
2
O
H
N
R N
H
O
N
H
N
O
O
IV
NH2 OH
I
O
H
N
R-N
C
H O
2
N
H
H
N
O
O
O
III
Coating of a layer of silica on the surface of the CoFe O
2
4
N
H
O
NPs was achieved by pre-mixing (ultrasonic) a dispersion
of the purified CoFe O NPs (1 g) obtained previously with
II
2
4
distilled water (80 mL) for 1 h at 40°C. A concentrated
ammonia solution (1.5 mL) was added and the resulting
CoFe2O4@SiO2-PrNH2 mixture stirred at 40°C for 30 min. Subsequently, tetraethyl
orthosilicate (1.0 mL) was charged to the reaction vessel
and the mixture continuously stirred at 40°C for 24 h.
The silica-coated NPs were collected using a permanent
H
O
O
N
product =
=
NH-R
O
N
H
Scheme 3:ꢀProposed reaction pathway for the synthesis of 4′a–e.
magnet, followed by washing three times with ethanol,
diethyl ether and drying at 100°C in a vacuum for 24 h.
CoFe O @SiO (1 g) was added to the solution of 3-ami-
isocyanides. The method offers several advantages includ-
2
4
2
ing cleaner reaction profiles, easy availability, high yields, nopropyltriethoxysilane (2 mmol, 0.44 g) in dry toluene
shorter reaction times, reusability of the catalyst and low (20 mL) and refluxed for 24 h. After the reaction had fin-
catalyst loading.
ished, the aminated CoFe O @SiO were separated by a
2 4 2
permanent magnet, washed with doubly distilled water
and anhydrous ethanol, and dried at 80°C for 8 h to give
the surface-bound amino group CoFe O @SiO -PrNH .
4
Experimental section
2
4
2
2
All organic materials were purchased commercially from
the Sigma-Aldrich and Merck and were used without 4.2 General procedure for the preparation
further purification. All melting points are uncorrected
and were determined in a capillary tube on a Boetius
of benzodiazepines (4a–e)
melting point microscope. FT-IR spectra were recorded A mixture of 1,2-phenylenediamine (1 mmol), dimedone
with KBr pellets using a Magna-IR spectrometer 550 (1 mmol), aldehyde (1 mmol) and CoFe O @SiO -PrNH
2
4
2
2
(
Nicolet). NMR spectra were recorded on a Bruker 400 MHz nanocatalyst (20 mg) was stirred in EtOH (10 mL) at room
spectrometer with dimethyl sulfoxide (DMSO) as solvent temperature. After completion, as indicated by thin-layer
and tetramethylsilane (TMS) as an internal standard. chromatography (TLC) (EtOAc:n-hexane, 3:1), the catalyst
Powder XRD was carried out on a Philips diffractometer of was separated from the mixture using an external magnet,
X’pert Company. Microscopic morphology of products was and the residue was washed with EtOH to give pure ben-
visualized by SEM (MIRA3 TESCAN).
zodiazepines 4a–e.
4
.1 Preparation of CoFe O @SiO -PrNH NPs 4.3 General procedure for the preparation
2
4
2
2
of benzodiazepines (4′a–e)
CoFe O @SiO -PrNH NPs were prepared according to
2
4
2
2
the method reported in the literature with some modifi- CoFe O @SiO -PrNH NPs(20mg)wereaddedtoamixtureof
2
4
2
2
cations [19]. CoFe O NPs were prepared by a chemical 1,2-phenylenediamines (1 mmol), Meldrum’s acid (1 mmol)
2
4
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

5
02ꢀꢀꢀꢀꢁꢀN.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH
2
4
2
2
and isocyanide (1 mmol) in 5 mL dichloromethane. The (400 MHz, [D ]DMSO): δ (ppm)ꢀ=ꢀ1.21 (9H, s, C(CH ) ), 1.37
6
3 3
progress of the reaction was continuously monitored by (6H, s, 2CH ), 3.18 (1H, s, CH), 6.15–7.15 (5H, bs, 4H-Ar
3
1
3
TLC. After completion of the reaction the residue was dis- and –NH), 10.38 (2H, bs, 2NH). – C NMR (100 MHz, [D ]
solved in methanol and the nanocatalyst was separated by DMSO): δ (ppm)ꢀ=ꢀ23.12 (2CH ), 28.92 (C(CH ) ), 43.63 (CH),
6
3
3 3
the use of an external magnet. The solvent was evaporated 50.42 (C), 55.10 (C), 122.42, 125.41, 130.32, 167.12, 177.30 (2
under vacuum and the solid obtained was washed several CO). – Analysis for C H N O : C 64.33, H 7.30, N 13.24;
17
23
3
3
times with acetone to afford pure benzodiazepine.
found: C 63.90, H 7.26, N, 13.09.
4
.4 Physical and spectroscopic data
4.4.4 2-(2,3,4,5-Tetrahydro-2,4-dioxo-1H-benzo[b][1,4]
diazepin-3-yl)-N-(4-methoxy-3-methyl phenyl)-2-
methylpropanamide (4′e)
4.4.1 3,3-Dimethyl-2,3,4,5,10,11-hexahydro-11-[(4-chloro)-
phenyl]-1H-dibenzo[b,e][1,4]diazepin-1-one (4a)
White powder, yield: 90%; m.p. 280–282°C. – IR (KBr):
−1
1
Pale green solid, yield: 95%; m.p. 234–236°C. – IR (KBr): νꢀ=ꢀ3448, 1705, 1662, 1518, 1246 cm . – H NMR (400 MHz,
νꢀ=ꢀ3302, 3237, 3055, 2957, 1587, 1382, 1534, 1328, 1425, [D ]DMSO): δ (ppm)ꢀ=ꢀ1.51 (s, 6H, 2CH ), 2.29 (s, 3H, CH ),
6
3
3
−1
1
1
276 cm . – H NMR (400 MHz, [D ]DMSO): δ (ppm)ꢀ=ꢀ1.02 (s, 3.44 (s, 1H, CH), 3.89 (s, 3H, OCH ), 6.99–7.55 (m, 7H, ArH),
6
3
1
3
3
H, CH ), 1.07 (s, 3H, CH ), 2.12 (A.Bq, 2H, Jꢀ=ꢀ16.0 Hz, CH ), 8.18 (bs, 1H, NH), 10.37 (bs, 2H, 2NH). – C NMR (100 MHz,
3
3
2
2
.54 (s, 2H, CH CO), 4.96 (s, 1H, NH), 6.07 (s, 1H, CH), 6.46 (d, [D ]DMSO): δ (ppm)ꢀ=ꢀ19.92, 42.70, 43.62, 55.22, 56.84,
2
6
1
H, Jꢀ=ꢀ8.2 Hz, Ar), 6.54 (m, 3H, Ar), 6.85 (d, 1H, Jꢀ=ꢀ8.2 Hz, Ar), 122.73, 123.75, 125.56, 128.58, 130.84, 131.52, 135.32, 136.63,
6
.97 (d, 2H, Jꢀ=ꢀ8.4 Hz, Ar), 7.01 (d, 1H, Jꢀ=ꢀ8.4 Hz, Ar), 8.61 (s, 138.45, 142.25, 167.77, 169.84.
13
1
H, NH). – C NMR (100 MHz, [D ]DMSO): δ (ppm)ꢀ=ꢀ28.16,
6
2
8.69, 32.25, 44.85, 49.90, 56.43, 109.38, 120.62, 120.73, 121.05,
1
23.11, 123.29, 128.36, 131.45, 138.07, 146.08, 150.02, 152.06,
1
92.82. – Analysis for C H ClN O: Calcd. C 71.48, H 6.00, N 5 Supplementary information
2
1
21
2
7.94; found C 71.54, H 6.09, N 7.95.
Some characteristics of the CoFe O @SiO -PrNH nanopar-
2
4
2
2
ticles and copies of the H NMR spectra of the products are
given in the Supplementary Information available online
4
.4.2 3,3-Dimethyl-2,3,4,5,10,11-hexahydro-11-[(2-chloro)-
phenyl]-1H-dibenzo[b,e][1,4]diazepin-1-one (4e)
(
DOI: 10.1515/znb-2017-0023).
White solid; yield: 92%; m.p. 230–232°C. – IR (KBr):
νꢀ=ꢀ3293, 3236, 3064, 2958, 1586, 1383, 1517, 1317, 1424,
Acknowledgments: The authors are grateful to the Univer-
sity of Qom for supporting this work. The authors are also
grateful to Dr. Hossein Shahbazi-Alavi for his help.
−1
1
1
279 cm . – H NMR (400 MHz, [D ]DMSO): δ (ppm)ꢀ=ꢀ1.02
6
(
s, 3H, CH ), 1.06 (s, 3H, CH ), 2.08 (A.Bq, 2H, Jꢀ=ꢀ16.0 Hz,
3 3
CH ), 2.52 (s, 2H, CH CO), 5.72 (s, 1H, NH), 5.75 (s, 1H, CH),
2
2
6
.35 (d, 1H, Jꢀ=ꢀ7.2 Hz, Ar), 6.45–6.65 (m, 2H, Ar), 6.72 (d, 1H,
References
Jꢀ=ꢀ7.6 Hz, Ar), 6.83 (d, 1H, Jꢀ=ꢀ7.6 Hz, Ar), 6.86–7.02 (m, 2H,
1
3
Ar), 7.20 (d, Jꢀ=ꢀ7.6 Hz, 1H, Ar), 8.53 (s, 1H, NH). – C NMR
100 MHz, [D ]DMSO): δ (ppm)ꢀ=ꢀ28.15, 28.73, 32.25, 44.85,
[
1] L. Z. Wang, X. Q. Li, Y. S. An, Org. Biomol. Chem. 2015, 13,
(
4
6
5
4ꢍ7.
9.87, 56.43, 109.33, 120.61, 120.65, 121.14, 123.14, 123.43,
26.11, 128.53, 128.62, 131.42, 138.05, 146.07, 149.59, 151.08,
[
2] Y. Chen, V. Le, X. Xu, X. Shao, J. Liu, Z. Li, Bioorg. Med. Chem.
Lett. 2014, 24, 3ꢍ48.
1
1
92.83. – Analysis for C H ClN O: Calcd. C 71.48, H 6.00, N [3] B. E. Leonard, Hum. Psychopharmacol. Clin. Exp. 1999, 14, 125.
2
1
21
2
[
4] J. Schimer, P. Cigler, J. Vesely, K. G. Saskova, M. Lepsik,
J. Brynda, P. Rezacova, M. Kozisek, I. Cisarova, H. Oberwinkler,
H. G. Kraeusslich, J. Konvalinka, J. Med. Chem. 2012, 55,
10130.
7.94; found C 71.51, H 6.10, N 7.90.
4
.4.3 N-tert-butyl-2-(2,3,4,5-tetrahydro-2,4-dioxo-1H-
benzo[b][1,4]diazepin-3-yl)-2-methyl
propanamide (4′a)
[
[
5] A. Leyva-Perez, J. R. Cabrero-Antonino, A. Corma, Tetrahedron
2
010, 66, 8203.
6] G. Maiti, U. Kayal, R. Karmakar, R. N. Bhattacharya, Tetrahedron
Lett. 2012, 53, 1460.
White powder, yield: 92%; m.p. >300°C. – IR (KBr): [7] H. Thakuria, A. Pramanik, B. M. Borah, G. Das, Tetrahedron Lett.
−1
1
νꢀ=ꢀ3387, 2967, 2902, 1691, 1646, 1601, 1528 cm . – H NMR
2006, 47, 3135.
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM

N.S. Miri and J. Safaei-Ghomi: Synthesis of benzodiazepines catalyzed by CoFe O @SiO -PrNH ꢌꢁꢀꢀꢀꢌ503
2
4
2
2
[
[
8] M. Curini, F. Epifano, M. C. Marcotullio, O. Rosati, Tetrahedron
Lett. 2001, 42, 31ꢍ3.
[18] A. Kumar, V. Kumar, Chem. Rev. 2014, 114, 7044.
[1ꢍ] P. H. Li, B. L. Li, Z. M. An, L. P. Mo, Z. S. Cui, Z. H. Zhang, Adv.
Synth. Catal. 2013, 355, 2ꢍ52.
ꢍ] R. Varala, R. Enugala, S. Nuvula, S. R. Adapa, Synlett, 2006, 7,
1
00ꢍ.
[20] N. N. Kolos, E. N. Yurchenko, V. D. Orlov, S. V. Shishkina, O. V.
Shishkin, Chem. Heterocycl. Compd. 2004, 40, 1550.
[21] A. Shaabani, A. H. Rezayan, S. Keshipour, A. Sarvary, S. W. Ng,
Org. Lett. 2009, 11, 3342.
[22] A. Maleki, R. Paydar, RSC Adv. 2015, 5, 33177.
[23] J. Safaei-Ghomi, H. Shahbazi-Alavi, P. Babaei, Z. Naturforsch.
2016, 71b, 84ꢍ.
[
[
[
[
[
10] S. K. De, R. A. Gibbs, Tetrahedron Lett. 2005, 46, 1811.
11] A. Maleki, Tetrahedron 2012, 68, 7827.
12] A. Maleki, M. Kamalzare, Catal. Commun. 2014, 53, 67.
13] A. Maleki, M. Kamalzare, Tetrahedron Lett. 2014, 55, 6ꢍ31.
14] M. A. Ghasemzadeh, N. Ghasemi-Seresht, Res. Chem.
Intermed. 2015, 41, 8625.
[
[
[
15] J. Safaei-Ghomi, H. Shahbazi-Alavi, P. Babaei, H. Basharnavaz, S.
G. Pyne, A. C. Willis, Chem. Heterocycl. Compd. 2016, 52, 288.
16] J. Safaei-Ghomi, H. Shahbazi-Alavi, R. Teymuri, Polycyclic
Aromat. Compd. 2016, 36, 834.
Supplemental Material: The online version of this article
(DOI: 10.1515/znb-2017-0023) offers supplementary material,
available to authorized users.
17] A. H. Lu, E. L. Salaba, F. Schüth, Angew. Chem. Int. Ed. 2007,
46, 1222.
Brought to you by | New York University
Authenticated
Download Date | 7/4/17 12:54 PM