[Bmim]5[PNiW11O39]·3H2O an organic–inorganic hybrid as catalyst for one-pot pseudo-five-component synthesis of tetrazolyldiazepines

Article abstract of DOI:10.1007/s13738-017-1116-y

In this research, two heterogeneous organic–inorganic hybrid catalysts, [bmim]₃[PW₁₂O₄₀]·3H₂O and [bmim]₅[PNiW₁₁O₃₉]·3H₂O, have been prepared. The catalysts were fully

Full text of DOI:10.1007/s13738-017-1116-y

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1116-y
ORIGINAL PAPER
[Bmim]5[PNiW11O39]·3H2O an organic–inorganic hybrid
as catalyst for one‑pot pseudo‑fve‑component synthesis
of tetrazolyldiazepines
Sajad Mousavifaraz1 · Zahra Nadealian1 · Valiollah Mirkhani1 · Abbas Rahmati1
Received: 20 October 2016 / Accepted: 12 April 2017
© Iranian Chemical Society 2017
Abstract In this research, two heterogeneous organic–
inorganic hybrid catalysts, [bmim]3[PW12O40]·3H2O and
[bmim]5[PNiW11O39]·3H2O, have been prepared. The cata-
lysts were fully characterized by several techniques such
as elemental analyses, Fourier transform infrared spec-
troscopy, thermo-gravimetric analysis, scanning electron
microscope and energy-dispersive X-ray analysis. Next, the
hybrid catalysts have been used for the synthesis of func-
tionalized diazepines containing tetrazole ring. Tetrazolyl-
1H-spiro[benzo[b]cyclopenta[e][1,4] diazepines products
were obtained in excellent yields and mild experimental
conditions using [bmim]5[PNiW11O39]·3H2O as cata-
lyst. This process was carried out via a one-pot, pseudo-
fve-component condensation reaction by means of a
1,2-diamine, isocyanide, TMSN3 and two molecules of a
linear or cyclic ketone in methanol, at ambient temperature.
In MCRs, three or more different starting materials react
together and produce products without a need for isola-
tion and purifcation of intermediates [2, 3]. Because of the
good reactivity, vast variety and commercially availability
of isocyanides, they have been broadly used in MCRs [4,
5]. The use of heterogeneous catalysts in IMCRs has been
well documented in the literature [6]. One type of heteroge-
neous catalysts is organic–inorganic hybrid polyoxometa-
lates [7–11]. They have been extensively used in various
organic reactions owing to their unique features such as
high thermal stability, low cost and toxicity, simple separa-
tion, facility of preparation and recyclability [9].
Heterocyclic compounds, especially heterocyclic com-
pounds containing nitrogen atom, are the main scaffold in
the structure of natural compounds and pharmaceutically
active compounds [12]. Two types of these compounds are
diazepines and tetrazoles [13–15]. Many of benzodiazepines
have received great attention because of their broad range
of biological properties such as anti-HIV [16], antipsychot-
ics [17] and antitumor agents [18]. Similarly, tetrazoles
rings have also been used as anti-TMV [19, 20], antifungal
[21], antiulcer [22] and anti-HCV compounds [23]. Diaz-
epines and tetrazoles have been synthesized using MCRs
and IMCRs [24–26]. It was reported that heterocyclic com-
pounds containing two or more heterocyclic rings have
synergic effect and increase pharmaceutical properties [27,
28]. A few syntheses of tetrazolodiazepines and tetrazolyl-
diazepines were already reported [29–35]. Shaabani et al.
recently have synthesized tetrazolylbenzodiazepine using
two different methods. In their frst method, the problems
were a two-step process, the use of expensive and very toxic
compounds, harsh reaction condition and tedious workup,
the use of large amount of organic solvents and low atom
economy of process. Although in their second report, a part
of problems was moderated with using of the one-pot MCR
Keywords Diazepine · Multi-component reaction ·
Organic–inorganic hybrid catalyst · Isocyanide
Introduction
Nowadays chemists are trying to design low-cost and
environment-friendly reactions. Multi-component reac-
tions (MCRs) in the presence of heterogeneous catalysts
can meet the above criteria [1]. Because MCRs are more
facile, fast, atom-effcient, practical, economical, green
approaches and environmentally benign process [2, 3].
* Abbas Rahmati
a.rahmati@sci.ui.ac.ir
1
Department of Chemistry, University of Isfahan, P. O.
Box 81746-73441, Isfahan, Iran
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J IRAN CHEM SOC
method, the main problem (the use of p-TSA and HCl homo-
geneous acidic catalyst) is not resolved, yet. These catalysts
are not reusable and environmentally benign and are also
high corrosive. Therefore, proposing a convenient procedure
to use a safer catalyst is of great importance.
In continuation of our studies on IMCRs [36, 37],
here a new method is introduced for synthesis of 5-(1H-
tetrazol-5-yl)-4,5,6,7-tetrahydro-1H-1,4-diazepine-
2,3-dicarbonitrile derivatives 5a–e and 2-(1H-tetrazol-5-yl)-
2,3,4,5-tetrahydro-1H-benzo[b] [1, 4] diazepine derivatives
5f–o. These products are obtained in excellent yields
using a catalytic amount of [bmim]5[PNiW11O39]·3H2O
in methanol solvent at ambient temperature via one-pot
pseudo-fve-component reaction (Scheme 1).
Thermo-gravimetric analysis (TGA) of the catalyst was
carried out on a Mettler TA4000 instrument. Inductively
coupled plasma optical emission spectrometer (ICP-OES)
was carried out on a Varian Vista PRO Radial. Scanning
electron microscopy (SEM) and energy-dispersive X-ray
spectroscopy (EDX) studies were carried out with SEM-
HITCHI S4160.
Procedure for the preparation
of [bmim]3[PW12O40]·3H2O catalyst (catalyst A)
A mixture of sodium tungestate·2H2O (8.250 g, 25 mmol)
and sodium monohydrogen phosphate (0.320 g, 2.3 mmol)
was dissolved in a 50 mL of water in a round-bottomed
fask (250 mL) and stirred at room temperature for 1 h.
Next, pH of the solution was tuned to 4.8 by means of
HNO3. Then, [bmim]NO3 (2.412 g, 12 mmol) ionic liquid
was poured slowly to solution into 2 h. The precipitated
catalyst was fltered off, washed with cooled water and
dried. Finally, the product was obtained (5.725 g).
Experimental
General
All chemicals and reagents were purchased from Across,
Alfa Aesar, Daejung or Merck chemical companies
and were used without purifcation. The known organic
products were identifed by comparison of their melting
Procedure for the preparation
of [bmim]5[PW11NiO39]·3H2O catalyst (catalyst B)
1
points and H NMR spectral data with those reported in
the literature. New organic compounds fully charac-
A mixture of sodium tungestate·2H2O (8.250 g, 25 mmol)
and sodium monohydrogen phosphate (0.320 g, 2.3 mmol)
was dissolved in a 50 mL of water in a round-bottomed
fask (250 mL) and stirred at room temperature. After 1 h,
nickel nitrate (0.546, 3 mmol) was added to the solution
and stirred for 1 h. Next, the pH of the solution was tuned
to 4.8 using HNO3. Then, [bmim]NO3 (2.412 g, 12 mmol)
was added slowly to solution in 2 h. The precipitated cata-
lyst was fltered off, washed with cooled water and dried.
Finally, the product was obtained (4.938, g).
1
terized by FT-IR, H NMR and 13C NMR spectra and
elemental analysis. Melting points were recorded on a
Büchi B-545 apparatus in open capillary tubes. Progress
of the reactions was monitored by TLC using silica gel
SIL G/UV 254 plates. FT-IR spectra were recorded as
KBr pellets using a Shimadzu Corporation spectrometer
1
at 400–4000 cm−1. The H NMR and 13C NMR spectra
were recorded on a Bruker Avance DPX FT-NMR spec-
trometer at 400 and 100 MHz, respectively (δ in ppm).
Scheme 1 Synthesis of tetrazolyldiazepines 5a–o in the presence of [bmim]5[PW11NiO39]·3H2O
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J IRAN CHEM SOC
Scheme 2 Synthesis of [bmim]3[PW12O40]·3H2O and [bmim]5[PW11NiO39]·3H2O catalysts
Table 1 EA, ICP and AA for determination of type and element wt% in catalysts by various methods
Entry
Method of determination
wt% of element
Catalyst A
Catalyst B
Experimental
Theoretical
Experimental
Theoretical
Elemental analyses
1
2
3
CHNS
C
8.72
1.52
2.53
0.92
–
8.61
1.54
2.51
0.92
–
13.78
2.30
13.78
2.34
H
N
4.10
4.02
ICP
P
0.87
0.89
Ni
W
Ni
W
1.62
1.68
65.75
–
65.88
–
58.27
1.50
58.01
1.68
Atomic absorption
65.60
65.88
58.49
58.01
Fig. 1 TGA of a [bmim]3[PW12O40]·3H2O and b [bmim]5[PW11NiO39]·3H2O
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J IRAN CHEM SOC
General procedure for the synthesis
tetrazolyldiazepines (5a–o) using
[bmim]5[PW11NiO39]·3H2O
and [bmim]5[PW11NiO39]·3H2O (5 mol%) in MeOH
(5 mL) was stirred for 2–4 h at room temperature. After
completion of the reaction, as indicated by TLC, the pre-
cipitate and catalyst was fltered off. The residue of prod-
ucts and catalyst was separated by washing with acetone.
Then the product was crystallized from acetone:ethanol to
give pure products 5a–o.
A solution of 1,2-diamine (1 mmol), ketone (2.2 mmol),
isocyanide (1 mmol) and trimethylsilylazide (1.2 mmol)
Characterization data for new compounds
3a-(1-cyclohexyl-1H-tetrazol-5-yl)-2,3,3a,4,9,10a-hexa-
hydro-1H-spiro[benzo[b]cyclopenta [e] [1, 4] diazepine-
10,1′-cyclopentane] (5 g): Yield 94%. White powder; mp
251–253 °C. IR (KBr) ʋ: 3382, 3018, 2937, 2872, 1598,
1
1505, 1472, 1444, 1400, 1310, 1261, 740 cm−1. H NMR
(400 MHz, DMSO-d6) δ: 1.12–2.22 (24H, m, 5CH2 of
Cyclohexyl and 7CH2 of Cyclopentyl), 3.63 (1H, m, CH
of Cyclopentyl), 4.43 (1H, s, NH), 4.82 (1H, m, CH of
Cyclohexyl), 5.62 (1H, s, NH), 6.39–6.71 (4H, m, H-Ar)
ppm. 13C NMR (100 MHz, DMSO-d6) δ: 21.84, 23.76,
24.10, 24.57, 27.44, 32.27, 32.73, 33.99, 40.54, 42.06,
53.42, 56.74, 64.47, 65.78, 117.89, 117.97, 118.33, 119.49,
134.21, 135.71, 160.14 ppm. Anal. Calcd for C23H32N6:
C, 70.37; H, 8.22; N, 21.41; found C, 69.60; H, 7.69; N,
21.55.
3a-(1-cyclohexyl-1H-tetrazol-5-yl)-6-methyl-
2,3,3a,4,9,10a-hexahydro-1H-spiro[benzo [b]cyclopenta[e]
[1, 4] diazepine-10,1′-cyclopentane] (5 k): Yield 96%.
White powder; mp 262-264 °C. IR (KBr) ʋ: 3371,
3306, 2935, 2859, 1594, 1502, 1448, 1395, 1315, 1251,
1
799 cm−1. H NMR (400 MHz, DMSO-d6) δ: 1.06–2.20
(27H, m, 5CH2 of Cyclohexyl, 7CH2 of Cyclopentyl and
1CH3), 3.60 (1H, m, CH of Cyclopentyl), 4.39 (1H, s, NH),
4.83 (1H, m, CH of Cyclohexyl), 5.45 (1H, s, NH), 6.21–
6.59 (3H, m, H-Ar) ppm. 13C NMR (100 MHz, DMSO-d6)
δ: 20.23, 22.00, 23.78, 24.14, 24.60, 27.59, 32.53, 32.83,
33.99, 40.49, 41.94, 53.39, 56.70, 64.50, 65.81, 118.41,
118.76, 119.91, 128.11, 131.55, 135.85, 160.12 ppm. Anal.
Fig. 2 FT-IR spectra of
[bmim]3[PW12O40]·3H2O and [bmim]5[PW11NiO39]·3H2O
a H3[PW12O40], b [bmim]NO3, c
Fig. 3 SEM images of a
[bmim]3[PW12O40]·3H2O and b
[bmim]5[PW11NiO39]·3H2O
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J IRAN CHEM SOC
Fig. 4 EDX images of a [bmim]3[PW12O40]·3H2O and b [bmim]5[PW11NiO39]·3H2O
Calcd for C24H34N6: C, 70.90; H, 8.43; N, 20.67; found C,
69.89; H, 8.70; N, 20.55.
White powder; mp >300 °C. IR (KBr) ʋ: 3375, 2941, 2872,
1
1590, 1490, 1463, 1400, 1298, 1224, 1132, 860 cm−1. H
(3a-(1-cyclohexyl-1H-tetrazol-5-yl)-2,3,3a,4,9,10a-hex-
ahydro-1H-spiro[benzo[b]cyclopean ta[e] [1, 4] diazepine-
10,1′-cyclopentane]-6-yl)(phenyl)methanone (5n): Yield
94%. White powder; mp >300 °C. IR (KBr) ʋ: 3369, 3345,
2938, 2861, 1628, 1584, 1566, 1496, 1444, 1395, 1336,
1290, 1132 cm−1. 1H NMR (400 MHz, DMSO-d6) δ: 1.02–
2.24 (24H, m, 5CH2 of Cyclohexyl and 7CH2 of Cyclopen-
tyl), 3.80 (1H, m, CH of Cyclopentyl), 4.71 (1H, m, CH of
Cyclohexyl), 5.71 (1H, s, NH), 5.94 (1H, s, NH), 6.43–7.56
(8H, m, H-Ar) ppm. 13C NMR (100 MHz, DMSO-d6) δ:
22.14, 24.04, 24.35, 24.49, 24.74, 27.82, 32.90, 33.02, 34.07,
40.86, 42.14, 52.17, 56.65, 64.28, 66.16, 116.45, 120.40,
124.14, 125.81, 128.12, 128.64, 130.97, 133.09, 139.00,
142.09, 159.63, 193.65 ppm. Anal. Calcd for C30H36N6O: C,
72.55; H, 7.31; N, 16.92; found C, 72.10; H, 7.26; N, 15.98.
6,7-dichloro-3a-(1-cyclohexyl-1H-tetrazol-5-yl)-
2,3,3a,4,9,10a-hexahydro-1Hspiro[benzo[b] cyclopenta[e]
[1, 4] diazepine-10,1′-cyclopentane] (5o): Yield 92%.
NMR (400 MHz, DMSO-d6) δ: 1.15–2.17 (24H, m, 5CH2
of Cyclohexyl and 7CH2 of Cyclopentyl), 3.69 (1H, m,
CH of Cyclopentyl), 4.74 (1H, m, CH of Cyclohexyl),
5.01 (1H, s, NH),6.01 (1H, s, NH), 6.59 (1H, s, H–Ar),
6.90 (1H, s, H–Ar) ppm. 13C NMR (100 MHz, DMSO-d6)
δ: 21.80, 23.85, 24.39, 24.54, 24.66, 27.42, 32.36, 33.24,
34.00, 40.65, 42.15, 55.91, 56.84, 64.30, 65.87, 118.20,
118.39, 120.09, 134.83, 136.66, 159.61 ppm. Anal. Calcd
for C23H30Cl2N6: C, 59.87; H, 6.55; N, 18.21; found C,
60.18; H, 6.81; N, 18.14.
Results and discussion
Synthesis and characterization of catalysts
Both the organic–inorganic hybrid catalysts were synthe-
sized via two-step one-pot method (Scheme 2).
Table 2 Comparison of
Entry
Catalyst
Time (h)b (Yield (%)d)
Time (h)c (Yield (%)d)
catalysts with other catalysts in
model reactiona
1
2
–
24(–)
6(60)
6(62)
6(71)
6(94)
6(30)
6(22)
6(9)
–
H3[PW12O40]
H4[SiW12O40]
[Bmim]3[PW12O40]·3H2O
[Bmim]5[PW11NiO39]·3H2O
HCl
8(76)
8(72)
7(86)
4(94)
11(51)
14(35)
10(12)
10(48)
–
3
4
5
6
7
H2SO4
8
MgCl2
9
NiCl2
6(35)
24(–)
10
[Bmim]NO3
a
Benzene-1,2-diamine (1 mmol), cyclopentanone (2.2 mmol), cyclohexylisocyanide (1 mmol) and tri-
b
methylsilylazide (1.2 mmol) in methanol (5 mL), in the presence of catalyst (20 mol %), constant time
(6 h), c completion of reaction time by TLC, d isolated yield
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J IRAN CHEM SOC
Time (h) (Yield (%)b)
Table 3 Effect of solvent, time
and temperature on the model
reactiona
Entry
Solvent
Amount of catalyst (mol%)
Temperature (°C)
1
EtOAc
Toluene
EtOH
20
20
20
20
20
20
20
20
20
20
20
20
20
10
5
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
45
60
r.t.
r.t.
r.t.
6(–)
2
6(–)
3
6(15)
6(–)
4
CH2Cl2
H2O
5
6(–)
6
MeCN
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
6(–)
7
6(94)
4(94)
3(90)
2(74)
1(53)
3(94)
3(94)
4(94)
4(94)
4(81)
8
9
10
11
12
13
14
15
16
2
a
Benzene-1,2-diamine (1 mmol), cyclopentanone (2.2 mmol), cyclohexylisocyanide (1 mmol) and tri-
methylsilylazide (1.2 mmol) in the presence of [bmim]5[PW11NiO39]·3H2O (20 mol%), b isolated yield
EA, AA, ICP-OES, TG-DTG, FT-IR, SEM and EDX
have been used to confrm the formation of the catalysts.
The structure of the catalysts was determined using EA,
AA, ICP-OES (Table 1) and TG-DTG analysis (Fig. 1).
Elemental analysis by CHNS analyzer showed that cationic
part of [bmim]NO3 ionic liquid connected to the polyox-
ometalate in both of the catalysts. Also, EA revealed that
total wt% of the H, C and N atoms was 12.77 and 20.18%
in structures of A and B catalysts. Atomic absorption and
ICP results showed that polyoxometalate moiety of het-
eropolyacid exist in the fnal structure of catalysts. Corre-
spondingly, these analyses revealed that total wt% of the P
and W atoms is 66.59% in structure of A catalyst and that
of P, Ni and W was 52.81% in structure of B catalyst. On
the other hand, the weight loss of the catalysts was deter-
mined in the range of 25–650 °C using TGA (Fig. 1). TGA
analysis showed thermal decomposition for both catalysts.
The frst step was removal of water that takes placed in the
range of 170–200 °C. The second step was for organic parts
decomposition that occurred in the range of 250–380 °C.
In A catalyst, decomposition of organic part take placed in
two stages. In the frst step of decomposition, the amount of
the weight loss was 1.60 and 1.53% for A and B catalysts,
respectively. Calculations, exactly confrmed the presence
of three water molecules in structure of both catalysts. In
the second part of decomposition, 12.45 and 19.96% the
amount of the weight loss were observed for A and B cata-
lysts, respectively. Therefore, total weight loss for A and B
catalysts was 14.05 and 21.49%, respectively. This 14.05%
was equal with three water molecules and three cationic
[bmim] unit that connected to an anionic [PW12O40] unit.
Also, 21.49% was equal with three water molecules and
fve cationic [bmim] unit that connected to an anionic
[PW11NiO39] unit. The results of theoretical weight per-
cent for both catalysts are presented in Table 1. There is
good agreement between theoretical and experimental
wt% which confrmed the proposed structures. In addi-
tion, the weight percents of elements in catalysts exactly
confrmed that [bmim]3[PW12O40]·3H2O (catalyst A) and
[bmim]5[PW11NiO39]·3H2O (catalyst B) are the structures
of catalysts.
FT-IR spectra of the catalysts ([bmim]3[PW12O40]·3H2O
and [bmim]5[PW11NiO39]·3H2O) were compared with
those from the starting material ([bmim]NO3) and a
well-known catalyst H3[PW12O40] (Fig. 2). FT-IR spec-
tra confrm the formation of the catalysts. The broad peak
related to O–H stretching of the water appeared at 3400–
3600 cm−1. The vibrational frequency of CH2 and CH3
groups was observed at 2850–2950 cm−1, and the vibra-
tions at 1637 and 1450 cm−1 were attributed to stretching
frequencies of C=N and C=C functional groups in the
starting material and the catalysts. Based on the literature
[38, 39], the stretching frequencies observed at 891, 984
and 1079 cm−1 are attributed to P–O, W=O and W–O–W
bands of the terminal oxygen of polyoxometalate moiety,
respectively. These bands demonstrate the presence of
[bmim] and polyoxometalate moieties in the structure of
catalysts.
The scanning electron microscope (SEM) micro-
graphs of the catalysts showed that the particles did not
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J IRAN CHEM SOC
Scheme 3 Structure products, isolated yields and reaction times of synthesized tetrazolyldiazepines in the presence of
[bmim]5[PW11NiO39]·3H2O catalyst
Fig. 5 Recyclability of catalyst
B of 5a product
100
90
80
70
60
50
40
30
20
10
0
run 1
run 2
run 3
run 4
run 5
run 6
run 7
Number of run
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J IRAN CHEM SOC
performed using commercially polyoxometalates and dif-
ferent Brønsted and Lewis acid catalysts (20 mol%) in
methanol at room temperature (entries 2–9, Table 2). For
each catalyst two experiments were done: one at a constant
time (6 h) and another continued up to disappearance of the
starting material on TLC. The polyoxometalate catalysts
exhibited better results compared to the normal Brønsted
and Lewis acids (Table 2). Among polyoxometalate, the
best yield was obtained with [bmim]5[PW11NiO39]·3H2O.
On the other hand, no product was obtained in the absence
of catalyst after 24 h (entry 1, Table 2). Moreover, the reac-
tion was performed in the presence of [bmim]NO3, and any
product was not obtained in this condition after 24 h (entry
10, Table 2).
Next, using [bmim]5[PW11NiO39]·3H2O as the best cat-
alyst, we tried to optimized the reaction condition. Differ-
ent solvents, such as H2O, CH2Cl2, MeOH, EtOH, EtOAc,
CH3CN and toluene were used (entries 1–7, Table 3). The
reaction in MeOH had higher yield than the other reac-
tions. Therefore, MeOH was chosen as the reaction sol-
vent. Afterward, reaction time was optimized. The results
suggested that 4 h was the best reaction time (entries 7–11,
Table 3). We also observed that higher temperature did not
improve the yield and reaction time. Finally, the effect of
different amount of the catalyst (2, 5, 10 and 20 mol%) was
evaluated. The results indicated that 5 mol% of catalyst was
optimal amount. Higher amounts of catalyst did not lead to
a signifcant change in yield.
Fig. 6 FT-IR spectra comparing the fresh catalyst B (a) and after the
7th run (b)
Under the optimized conditions, the ability and limita-
tion of the best catalyst was checked by varying the struc-
ture of the diamine, ketone and isocyanide components
(Scheme 3). All the reactions showed high yields (89–96%)
and the products were purifed by crystallization in acetone.
Structure of known compounds was confrmed by melt-
agglomerated completely. The size of the particles is in
nanorange (10–100 nm) (Fig. 3).
The energy-dispersive X-ray spectroscopy (EDX) of
the nanocatalysts proved the presence of carbon, nitro-
gen, oxygen, tungsten and phosphorous elements in
[bmim]3[PW12O40]·3H2O and carbon, nitrogen, oxy-
gen, nickel, tungsten and phosphorous elements in
[bmim]5[PW11NiO39]·3H2O as expected (Fig. 4a, b).
1
ing point and H NMR while the structure of new com-
1
pounds was characterized by IR, H NMR, 13C NMR and
elemental analysis.
One of the advantages of heterogeneous catalysts is their
recyclability. The reusability of this catalyst was investi-
gated in the model reaction under the optimized conditions.
For each of the repeated reactions, the catalyst was recov-
ered easily by simple fltration technique and then washed
with ethanol (5 mL) twice and dried at 50 °C in an oven.
The separated catalyst was reused successively in seven
times in model reaction without a considerable loss of cata-
lytic activity (Fig. 5) Comparison of the FT-IR spectra of
the catalyst after the 7th run and the fresh catalyst showed
that no obvious changes in the structure of catalyst and the
characteristic bands (Fig. 6). Also, CHNS analysis after the
7th run from the catalyst illustrated that the results are the
similar to the fresh catalyst. Therefore, catalyst is stable
and the decreasing of reaction yield undoubtedly is due to
the method.
Application of the catalysts in synthesis
of tetrazolyldiazepines
The catalysts were applied in the synthesis of a tetrazolyl-
diazepines (5 g) in order to compare their effciency. Ben-
zene-1,2-diamine, cyclopentanone, cyclohexyl isocyanide
and trimethyl silylazide were mixed in methanol in the
presence of each catalyst at room temperature. The pro-
gress of the reactions was monitored by TLC. The reaction
was worked up, and the desired products were confrmed
by H-NMR and melting point. Good yields of product
encouraged us to optimize reaction conditions.
We compared the effciency of our catalysts with that
of the other catalysts. For this purpose, the reaction was
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J IRAN CHEM SOC
Scheme 4 Possible mechanism for the formation of product 5a in the presence of catalyst B
The possible mechanism for the formation of product 5a
is shown in Scheme 4. The acid sites in catalyst facilitate
the reaction by activating the carbonyl group of ketone 2. It
is feasible that the initial event is the formation of diamine 6
from condensation between diamine 1a and two molecules
of acetone 2. Then by aid of catalyst imine–enamine tau-
tomerism, compound 7 was created. Next, imine group of
7 was activated by the catalyst and fnally intramolecular
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J IRAN CHEM SOC
a
b
Scheme 5 Two reactions to prove the reaction mechanism in the presence of catalyst
cyclizatin produced a seven-membered ring 8. On the basis
of the well-established chemistry of the reaction of isocya-
nides with imines, intermediate 9 was produced by nucleo-
philic attack of isocyanide 3 to iminium 8. Subsequently,
by the reaction between intermediate 9 and azide ion (in
which was obtained from TMSN3) compound 10 is pro-
duced. Followed by the intramolecular electron transfer
between the C=N and azide group in 10, intermediate 11
was achieved. Finally, product 5a formed from compound
11 using cyclization. In order to prove the reaction mecha-
nism, two different reactions were performed (Scheme 5).
The frst reaction was the reaction of 1,2-phenylene
diamine and two equivalent acetone in the absence of iso-
cyanide and azide ion source that produced benzodiazepine
12 [40]. The other was reaction of 1,2-phenylene diamine,
isocyanide and two equivalent acetone without TMSN3
compound that produced benzodiazepine 13 [41].
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