Application of supported Mn(iii), Fe(iii) and Co(ii) as heterogeneous, selective and highly reusable nano catalysts for synthesis of arylaminotetrazoles, and DFT studies of the products

Article abstract of DOI:10.1039/c4ra06463a

M@Si/Al (where M = Mn(iii), Co(ii) and Fe(iii) supported on nanosized SiO₂/Al₂O₃) is applied as an efficient, highly reusable and heterogeneous catalyst for the regiospecific synthesis of 1-aryl-5-amino-1H-tetrazole in dim

Full text of DOI:10.1039/c4ra06463a

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Application of supported Mn(III), Fe(III) and Co(II) as
heterogeneous, selective and highly reusable nano
catalysts for synthesis of arylaminotetrazoles, and
DFT studies of the products
Cite this: RSC Adv., 2014, 4, 47625
a
b
Davood Habibi, Ali Reza Faraji, Davood Sheikh,c Masoome Sheikhid
*
*
and Samaneh Abedie
M@Si/Al (where M ¼ Mn(III), Co(II) and Fe(III) supported on nanosized SiO2/Al2O3) is applied as an efficient,
highly reusable and heterogeneous catalyst for the regiospecific synthesis of 1-aryl-5-amino-1H-
tetrazole in dimethylformamide (DMF) as a solvent. The arylaminotetrazoles were efficiently synthesized
from the reaction of cyanamides and sodium azide in the presence of a catalytic amount of nano metal
catalyst under thermal conditions. 1-Aryl-5-amino-1H-tetrazoles (B isomer) can be obtained from the
arylcyanamides carrying electron releasing substituents on the aryl ring, while with electron withdrawing
groups, 5-arylamino-1H-tetrazole (A isomer) will be obtained. The advantages of this method include
high yields, relatively short reaction times, easy work-up, recovery and reusability of the catalyst and high
TON of catalyst. The nano catalyst can be easily recovered and reused several times without
considerable loss of activity. The quantum theoretical calculations for the synthesized components were
performed by density functional theory (DFT) methods using the 6-31G basis set, geometry and
thermodynamic parameters, frontier molecular orbitals (FMOs) as well as by using molecular
electrostatic potentials (MEPs).
Received 8th July 2014
Accepted 8th September 2014
DOI: 10.1039/c4ra06463a
www.rsc.org/advances
associated with these homogeneous catalysts.3 These disad-
vantages are minimized if homogeneous complexes are
Introduction
immobilized on organic polymers or inorganic solid supports
with excellent chemical and thermal stability and easy accessi-
bility such as clay, zeolites, SiO2, mixed oxides and mesoporous
materials. Covalent binding provides strong bonds between the
support and the active site and thus helps to reduce metal
contamination in the desired product. In the last decade, the
syntheses of metal nanoparticles (NPs) have been developed.
These nanoparticles are claimed to provide greater selectivity
and control in heterogeneous catalysis.2
In the synthesis of compounds, limitation of natural
resources, reduction of waste, maximizing renewability, and the
development of environmentally benign reagents are the next
challenges for the chemical sciences. Tetrazoles are widely used
as ligands, as stable surrogates for carboxylic acids in medicinal
chemistry, as explosive and information recording systems and
Technologies based on catalytic processes are of utmost
importance for producing chemicals that have medical, envi-
ronmental or economic importance. Many catalysts or catalytic
systems have been developed to achieve these goals.1 Homog-
enous catalysts due to their numerous available catalytic sites
have many advantages such as high reactivity and selectivity.2
Despite their advantages, some of the homogenous catalytic
processes have not been commercialized because of difficulties
encountered when attempting to separate and reuse the
expensive noble metals. Furthermore, some industrial prob-
lems such as corrosion and deposition on reactor walls are
aDepartment of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University,
Hamedan 6517838683, Iran. E-mail: davood.habibi@gmail.com; Fax: +98 81
38380709; Tel: +98 81 38380922
bYoung Researchers & Elite Club, Pharmaceutical Sciences Branch, Islamic Azad
University, Tehran, Iran. E-mail: alireza_ch57@yahoo.com; Fax: +98 21 2264 0051;
Tel: +98 21 2264 0051
also as precursors to
a variety of nitrogen-containing
compounds.4–7 Among tetrazoles, aminotetrazoles are very
interesting compounds and have received considerable atten-
tion as a result of their biological activity and interest to
medicinal chemistry.3,8 However, the lack of convenient
methods for the preparation of arylaminotetrazoles strongly
restricts their potential application in medical practice.
Although many 5-substituted tetrazoles are known, only a few
cYoung Researchers
& Elite Club, Hamedan Branch, Islamic Azad University,
Hamedan, Iran
dYoung Researchers & Elite Club, Gorgan Branch, Islamic Azad University, Gorgan,
Iran
eDepartment of Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University,
Tehran, Iran
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arylaminotetrazoles have been described. Generally, arylami-
notetrazoles are synthesized by the condensation reaction of
cyanamides with hydrazoic acid,10 HOAc9 and FeCl3–SiO2 (ref.
11) which results in a mixture of isomers, 5-arylamino-1H-tet-
razoles and 1-aryl-5-amino-1H-tetrazoles. Due to the wide range
of biological application of aminotetrazoles, the discovery and
introduction of milder, faster, eco-friendly conditions resulting
in high yields whilst using inexpensive reagents are in great
demand.
Several regiospecic syntheses of arylaminotetrazoles have
been reported through the [3 + 2] cycloaddition of cyanamides
using NaN3 in the presence of catalysts such as ZnCl2 (ref. 12),
AlCl3 (ref. 13) and Iranian natrolite zeolite.14 ZnCl2 and AlCl3 are
homogeneous catalysts which cannot be separated from the
reaction mixture. Reusability of the natrolite zeolite is an
advantage, but its lack of availability is a disadvantage. Thus,
the development of a catalytic synthetic method for tetrazoles
still remains an active research area.
Table 1 Synthesis of arylaminotetrazoles catalyzed by various nano
catalystsa
t
Entry Catalyst (mg)
T (ꢀC) (min) Yield (%) TONb TOFc
1
2
3
4
5
6
7
8
Blank
100
100
100
120
180
100
100
100
100
100
100
100
100
80
—
82
64
83
79
83
54
82
78
82
51
82
62
—
—
Co(II)@Si/Al (200)
Fe(III)@Si/Al (200)
Fe(III)@Si/Al (200)
42.15 0.4215
4.671 0.0467
6.058 0.0605
22.57 0.2257
57.34 0.5734
5.255 0.0525
7.980 0.0798
31.23 0.3123
84.97 1.062
7.445 0.1240
11.97 0.1088
35.42 0.3220
Mn(III)@Si/Al (200) 100
Co(II)@Si/Al (150)
Fe(III)@Si/Al (150)
Fe(III)@Si/Al (150)
100
100
120
9
Mn(III)@Si/Al (150) 100
10
11
12
13
Co(II)@Si/Al (100)
Fe(III)@Si/Al (100)
Fe(III)@Si/Al (100)
100
100
120
60
110
110
Mn(III)@Si/Al (100) 100
a
Reaction conditions: cyanamide (2 mmol), NaN3 (3 mmol), solvent (6
mL). b TON, turn over number, moles of substrate converted per mole of
metal. c TOF, turn over frequencies.
Industry favors catalytic processes induced by heterogeneous
catalysts over homogeneous processes in view of the ease of
handling, simple work-up, and regenerability.15 Among cata-
lysts, the application of nano catalysts has received consider-
able attention in recent decades as effective heterogeneous
catalysts for organic synthesis due to their unique physical,
surface chemical and catalytic properties.16,17
Synthesis of arylaminotetrazoles catalyzed by various
nanosized M@Si/Al
Due to safety considerations, we must avoid methods which
use expensive and homogeneous catalysts. Because of the
interesting applications of aminotetrazoles and in continuation
of our interest in the synthesis of nitrogen-containing
compounds and our ongoing research in heterogeneous catal-
ysis,12,17 herein we report our results for the synthesis of aryla-
minotetrazoles using nano catalysts as efficient heterogeneous
catalysts at the desired temperature (Scheme 1).
The engaged catalysts in this reaction were simple structural
Schiff base ligands that have the same support but different
metals, including Mn(III)@Si/Al, Fe(III)@Si/Al, and Co(II)@Si/Al
mixed oxide. The results are summarized in Table 1. Selected
transmission electron microscope images of the catalysts are
shown in Fig. 1. It can be seen that the appearance and size of
the nanoparticles of the different catalysts were similar,
demonstrating that the particles of SiO2–Al2O3 have good
mechanical stability and that they have not been destroyed
during the whole modication. However, the average particle
size in reverse micro emulsion solution of the catalysts was
around 30, 29 and 28 nm for Mn(III)@Si/Al, Fe(III)@Si/Al, and
Co(II)@Si/Al, respectively. Because of the small nanoparticle size
and ligand capping as an obstacle in agglomeration, the
M@Si/Al could be used as suitable catalysts for preparation of
arylaminotetrazoles.
Results and discussion
The catalytic activity and selectivity of different nano catalysts
for the synthesis of various arylaminotetrazoles were investi-
gated by using 2-chlorophenylcyanamide as a model substrate.
Initial studies were performed in order to optimize the reaction
conditions for the synthesis of 5-(2-chlorophenyl)amino-1H-
tetrazole (isomer A) with sodium azide in the presence of these
nano catalysts. To optimize the reaction conditions for
syntheses of 5-(2-chlorophenyl)amino-1H-tetrazole in the pres-
ence of nano catalysts, various parameters such as the amount
of the nano catalyst, the temperature, and the nature of the
solvent, were investigated for their effect on the performance of
the heterogeneous catalyst.
Fig. 1 TEM images corresponding to Mn@Si/Al sample (left) and
Scheme 1 Synthesis of arylaminotetrazoles using nano catalyst.
47626 | RSC Adv., 2014, 4, 47625–47636
Co@Si/Al (right).
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The comparison of the capability and efficiency of
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Mn(III)@Si/Al, Fe(III)@Si/Al, and Co(II)@Si/Al together with the
results of the application of these catalysts for the preparation
of arylaminotetrazoles are presented in Table 1. As listed in
Table 1, almost no reaction was observed in a blank experiment
Table
2
Effect of temperature on the synthesis of
arylaminotetrazolesa
Entry
Catalyst
T (ꢀC)
t (min)
Yield (%)
ꢀ
even though the reaction time was prolonged to 4 h at 120 C.
1
2
3
4
5
6
7
8
9
Co(II)@Si/Al
Co(II)@Si/Al
Co(II)@Si/Al
Co(II)@Si/Al
Co(II)@Si/Al
Fe(III)@Si/Al
Fe(III)@Si/Al
Fe(III)@Si/Al
Fe(III)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
Mn(III)@Si/Al
Mn(III)@Si/Al
Mn(III)@Si/Al
Mn(III)@Si/Al
R.T
60
80
100
120
R.T
60
300
100
100
100
100
100
100
100
100
100
100
100
100
100
100
9
However, addition of the nano catalyst to the reaction mixture
rapidly increased the synthesis of arylaminotetrazoles in high
yields. The catalytic activity of these nano catalysts appeared to
be dependent on the nature of the central ions. Co(II)@Si/Al
presented the best activity among the three nano catalysts, and
showed excellent catalytic performance under mild conditions.
The different behavior and catalytic activities of the Co(II), Fe(III)
and Mn(III) ions were probably inuenced by the stability of the 10
different valencies of the metal atoms and their electronic
potentials.18–21 As shown in Table 1, we calculated turn over
51
64
82
82
8
47
60
73
82
Trace
32
51
79
79
80
100
120
R.T
60
80
100
120
11
12
13
14
numbers (TON) and turn over frequencies (TOF) as measures of
the effectiveness of these catalysts in this reaction. The
comparison TON (Co: 42.15, Fe: 4.671 and Mn: 22.57) and TOF
(Co: 0.4215, Fe: 0.0467 and Mn: 0.2257) values of the nano
catalysts indicated that the cobalt nano catalyst is more effective
than the other nano catalysts. The catalytic activation of these
catalysts was in the sequence Co(II)@Si/Al > Mn(III)@Si/Al >
Fe(III)@Si/Al. The best result was obtained with the cyanamide–
sodium azide ratio of 2 : 2.5 with 0.1 g of the nano Co catalyst at
15
a
Reaction conditions: cyanamide (2 mmol), NaN3 (3 mmol), solvent (6
mL).
necessary for cycloaddition reactions and for this reason DMF is
most commonly used for this purpose.11,13–15
ꢀ
100 C (Table 1).
Synthesis of various arylaminotetrazoles catalyzed by nano
catalysts
Effect of temperature on the synthesis of 5-(2-chlorophenyl)
amino-1H-tetrazole
A series of phenylcyanamides were converted into the corre-
sponding arylaminotetrazoles with sodium azide by the nano
catalysts in high yields under the thermal conditions (Table 4).
Phenylcyanamides containing both electron-donating and
electron-withdrawing groups underwent the conversion in good
yields.
As shown in Table 4, we evaluated the electronic effect of the
substituents attached to the benzene ring in the cyanamides.
The substrates having electron donating groups (EDGs) on the
benzene rings (entries 7–9, 12 and 13) complete the reaction at
100 ꢀC aer 55 min, while species with electron-withdrawing
groups (EWGs) (entries 1–4 and 6) require longer reaction times.
The effect of the reaction temperature on the synthesis of 5-(2-
chlorophenyl) amino-1H-tetrazole catalyzed by the nano cata-
lysts was investigated, and the results are summarized in
Table 2. Increasing the temperature to accelerate the rate of
reaction was apparently effective. Consequently, the effects of
different temperatures (60 ꢀC, 80 ꢀC and 120 ꢀC) were monitored
for the synthesis of 5-(2-chlorophenyl)amino-1H-tetrazole aer
100 min in the presence of the nano catalysts. Generally, by
increasing the reaction temperature and time, the yields
increased (>80%). Thus increasing the temperature was effec-
tive for the synthesis of 5-(2-chlorophenyl)amino-1H-tetrazole
since at low temperature, the energy was not sufficient for the
activation of the catalytic circulation.
Table 3 Effect of solvent on the synthesis of arylaminotetrazolesa
Effect of solvent on the synthesis of 5-(2-chlorophenyl)amino-
1H-tetrazole
Entry
Catalystb
Solvent
t (min)
Yieldb (%)
In order to study the effects of solvents on the synthesis of 5-(2-
chlorophenyl)amino-1H-tetrazole, acetonitrile, ethanol, water,
benzene and dichloromethane were examined at 100 ꢀC
(Table 3). The reaction had low yields in the presence of coor-
dinating solvents, while using water as a solvent caused no
reaction to occur. It seems that the electron donor characteris-
tics of these solvents caused them to occupy the vacant space
around the metal in the catalysts, which prevented coordination
from substrate molecules.2,3 Therefore, water was not a suitable
solvent for the synthesis of arylaminotetrazoles. Furthermore,
not many organic solvents are stable at the high temperatures
1
2
3
4
5
6
7
8
9
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
DMF
DMF
DMF
DMSO
DMSO
DMSO
H2O
100
110
110
300
300
300
300
300
300
83
83
79
72
70
65
5
H2O
H2O
5
Trace
a
Reaction conditions: cyanamide (2 mmol), NaN3 (3 mmol), solvent
(6 mL). b Isolated yield.
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Table 4 Synthesis of arylaminotetrazoles using nano catalystsa
Entry Substrate (1)
Product (3) (isomer A or B)
Catalystb
Time (min) Yield (%) TONc
TOFd
Ref.
115
125
80
82.90
0.7201
Co(II)@Si/Al
Fe(III)@Si/Al
11 and 12
78
82
11.83
31.24
0.0910
0.2402
1
Mn(III)@Si/Al 130
100
110
82
82
83
84.97
11.97
31.62
0.8498
0.1088
0.2530
Co(II)@Si/Al
Fe(III)@Si/Al
2
11
Mn(III)@Si/Al 125
100
120
79
78
80
81.86
11.38
30.48
0.8187
0.0948
0.2344
Co(II)@Si/Al
Fe(III)@Si/Al
12
3
4
Mn(III)@Si/Al 130
Co(II)@Si/Al
Fe(III)@Si/Al
95
115
81
79
83
98.44
10.65
31.62
1.036
0.0927
0.2874
11–13
Mn(III)@Si/Al 110
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al 100
75
85
78
75
80
80.82
10.95
30.48
0.8508
0.1288
0.3048
5e
6
—
110
110
80
78
80
82.90
11.37
30.48
0.7536
0.1035
0.2540
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al 120
12
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
55
90
75
83
83
82
86.01
12.12
31.24
1.433
0.1346
0.4165
7
8
11–13
11–13
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
55
85
70
79
76
75
81.86
11.090 0.1305
28.57
1.488
0.4082
55
65
70
80
80
81
82.90
11.68
30.86
1.275
0.1800
0.4408
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
13
9
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
55
85
65
81
82
79
83.94
11.97
30.10
1.526
0.1408
0.4630
10
11
11 and 13
30
130
110
83
74
80
86.01
10.80
30.48
1.075
0.0831
0.2770
Co(II)@Si/Al
Fe(III)@Si/Al
Cat.3
12
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Table 4 (Contd.)
Entry Substrate (1)
Product (3) (isomer A or B)
Catalystb
Time (min) Yield (%) TONc
TOFd
Ref.
55
80
80
78
72
80
80.82
10.51
30.48
1.616
0.1314
0.3810
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
12
11–13
55
80
65
78
74
76
80.82
10.80
28.95
1.469
0.1350
0.4454
Co(II)@Si/Al
Fe(III)@Si/Al
Mn(III)@Si/Al
13e
—
a
Reaction conditions: cyanamide (2 mmol), NaN3 (3 mmol), solvent (6 mL). b Co(II)@Si/Al (100 mg); Fe(III)@Si/Al (100 mg); Mn(III)@Si/Al (150 mg).
TON, turn over number, moles of substrate converted per mole of metal. d TOF, turn over frequencies. e Analytical data (m.p., 1H NMR, 13C NMR
c
and elemental analysis) for selected compound.
Also, the arylaminotetrazoles were completely regiospecic. In catalyst is crucial for this reaction. According to the proposed
most cases, in the synthesis of arylaminotetrazoles from cyan- mechanism, the nano catalyst may show complexation towards
amides, only the 1-aryl-5-amino-1H-tetrazole (B) or a mixture of the nitrile group of cyanamides and thus may enhance the
isomers (A + B) was obtained10 and the nature of the substituent electrophilic character. It involves activation of the nitrile group
did not have any effect.22–26 Previously, Garbrecht and coworkers over the surface of the nano catalyst and subsequent nucleo-
showed that different substituents (such as the p-methyl and philic attack of the sodium azide.12–15 The results indicated that
the p-nitrophenyl group) permit the formation of the same type the process was completely regiospecic. There is an excellent
of compound (isomer B).9 However, in our methods, arylami- correlation between the type of different substitution on the aryl
notetrazole derivatives (3) are strongly affected by the type of ring and the major product. Indeed, when the substitution on
substituents in the phenylcyanamides (1) which determine the the benzene ring is electron-donating in arylcyanamides (Table
obtained isomers 1-aryl-5-amino-1H-tetrazoles (B) or 5-aryla- 4, entries 7–13), the formation of 1-aryl-5-amino-1H-tetrazoles
mino-1H-tetrazoles (A) (Table 4). Generally, when the substit- (B) is favored via a guanidine azide intermediate (II) and as the
uent on the aryl ring of 1 is an EDG, formation of 1-aryl-5- electronegativity of the substituent is increased (Table 4, entries
amino-1H-tetrazoles (B) is favored (entries 7–9, 12 and 13, Table 1–6), the type of product is changed to 5-arylamino-1H-tetrazole
4), and as the electronegativity of the substituent is increased, (A). In other words, if cyclization [3 + 2] were to involve the
the product is shied toward 5-arylamino-1H-tetrazoles (A) nitrogen carrying the aryl substituent in the guanidine azide
(entries 1–4 and 6, Table 4). This observation correlates with intermediate (II), 1-aryl-5-amino-1H-tetrazoles would result.
results obtained from the synthesis of arylaminotetrazoles
using ZnCl2, AlCl3 or natrolite zeolite.12,13
4-Nitrophenylcyanamide (Table 4, entry 1) interestingly gave reaction when the reaction is carried out for 24 h at 120 C. In
5-(4-nitrophenyl) amino-1H-tetrazole (A isomer), while with
In addition, our results indicated that the nature of the
substituent plays a minor role in directing the course of the
ꢀ
HN3, AcOH and FeCl3–SiO2, 1-(4-nitrophenyl)-5-amino-1H-tet-
razole (B isomer) or the mixture of isomers (A + B) were
obtained.8–10 Interestingly 1k afforded the double-addition
product in 83% isolated yield (Table 4, entry 11).
Proposed mechanism
The nano catalyst probably has an important role in the
promotion of the synthesis of arylaminotetrazoles as a Lewis
acid and the plausible mechanism is shown in Scheme 2. To
further elucidate the reaction mechanism, a series of experi-
ments was conducted. When the synthesis of arylaminote-
trazoles was conducted in the absence of nano catalyst, the yield
of reaction could only reach 5%. However, the yields were
remarkably increased by adding nano catalyst to the mixture
Scheme
2 Mechanism of nano metal catalyzed synthesis of
(Table 4, 82%, entry 2). The results indicate that the nano arylaminotetrazoles.
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such as energy of the highest occupied molecular orbital
(EHOMO), energy of the lowest unoccupied molecular orbital
(ELUMO), energy gap (DE) between LUMO and HOMO, atomic
charges, dipole moment (m) and point group were determined.
The optimized molecular structures and HOMO and LUMO
surfaces were visualized using the GaussView 03 program.28 We
also studied the thermodynamic parameters of molecules 3a–
3m using the B3LYP/6-31G level, and obtained the energy (DE),
enthalpies (DH), Gibbs free energy (DG), entropies (S) and
constant volume molar heat capacity (Cv) of the derivatives.29
The optimized geometrical parameters, such as dipole
moment (m; Debye), energy of structure formation (DE; Hartree
Fock) and point group, using the B3LYP/6-31G level are listed in
Table 5. According to Table 5, the geometry of the structures
under investigation is C1 point group symmetry.
Scheme
conditions.
3 Transformation of isomer B to isomer A in harsh
Table 5 Dipole moment (m), DE and point group of molecules 3a–3m
obtained using B3LYP/6-31G level
Substrate
m (Debye)
DE (Hartree Fock)
Point group
Dipole moment (m) is a good measure for the asymmetry of a
molecule. The values listed in Table 5 show that among mole-
cules 3a–3m, the largest value of dipole moment is obtained for
molecule 3g and the smallest value is obtained for molecule 3d.
According to Table 5, energy of structure formation (DE) for
molecule 3d is more negative, therefore product 3d has the
most stable structure. Product 3e has the most unstable
structure.
3a
3b
3c
3d
3e
3f
3g
3h
3i
5.2294
3.7543
2.0515
1.2847
1.6960
2.1027
7.9860
7.8898
7.3901
7.5465
6.2357
7.7578
7.3499
ꢁ748.9052
ꢁ1004.0463
ꢁ1463.6192
ꢁ3115.4547
ꢁ544.4830
ꢁ697.0849
ꢁ583.7897
ꢁ623.0982
ꢁ583.7893
ꢁ698.0883
ꢁ856.7596
ꢁ658.9646
ꢁ623.0978
C1
C1
C1
C1
C1
C1
C1
C1
C1
C1
C1
C1
C1
3j
3k
3l
Frequency calculations
3m
The relative energy (DE), standard enthalpies (DH), entropies
(DS), Gibbs free energy (DG) and constant volume molar heat
capacity (Cv) values of derivatives 3a–3m were obtained by
theoretical methods using the B3LYP/6-31G level to obtain
minima of the potential energy. The calculated results in Table
6 show that relative energy, Gibbs free energy and standard
enthalpy values of all molecules are negative, therefore we
found that all molecules are stable. As indicated in Table 6, and
according to the previous section, we found that the product 3d
has maximum stability because it has the greatest amount of
these conditions, substituents which differ in their electrical
effects (such as methyl or p-methoxy group) permit the forma-
tion of compound (A) as a stable product in high yield (>95%),
presumably through the intermediate formation of a guanyl
azide (Scheme 3).
Theoretical calculations
We have carried out quantum theoretical calculations of tetra- relative energy (DE), Gibbs free energy (DG) and standard
zole derivatives using the B3LYP/6-31G level (DFT) by the enthalpy (DH) whereas the product 3e has the most instability
Gaussian 03 soware package.27 Some electronic properties because it has the smallest values of DE, DG and DH. The
Table 6 The calculated thermodynamic parameters of molecules 3a–3m using the B3LYP/6-31G level
Substrate
DE (kcal molꢁ1
)
DG (kcal molꢁ1
)
DH (kcal molꢁ1
)
S (cal/molK)
CV (cal/molK)
3a
3b
3c
3d
3e
3f
3g
3h
3i
ꢁ469 851.856
ꢁ629 963.214
ꢁ918 355.754
ꢁ469 876.359
ꢁ629 986.918
ꢁ918 380.791
ꢁ469 844.142
ꢁ629 956.142
ꢁ918 347.883
ꢁ1 954 884.588
ꢁ341 570.073
ꢁ437 303.344
ꢁ366 217.668
ꢁ390 865.585
ꢁ366 217.407
ꢁ437 928.325
ꢁ537 497.290
ꢁ413 387.157
ꢁ390 865.297
108.056
103.221
110.375
104.378
94.595
112.321
106.050
115.083
103.942
108.208
122.005
108.511
112.794
43.132
38.881
42.845
38.671
34.566
46.772
42.177
48.219
42.165
47.669
55.727
45.595
48.110
ꢁ1 954 891.651
ꢁ341 576.225
ꢁ437 311.693
ꢁ366 225.235
ꢁ390 874.303
ꢁ366 224.904
ꢁ437 936.322
ꢁ537 506.888
ꢁ413 395.218
ꢁ390 873.897
ꢁ1 954 915.709
ꢁ341 598.276
ꢁ437 336.832
ꢁ366 249.287
ꢁ390 899.897
ꢁ366 248.398
ꢁ437 960.587
ꢁ537 533.666
ꢁ413 419.509
ꢁ390 898.926
3j
3k
3l
3m
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Fig. 2 Frontier molecular orbitals of compounds 3a–3m. (DE: energy gap between LUMO and HOMO).
entropies (DS) and constant volume molar heat capacity (Cv) energy of the lowest unoccupied molecular orbital (LUMO) and
values do not seem to follow a similar trend.
the highest occupied molecular orbital (HOMO) and their
energy gaps reect the chemical activity of the molecules.31
According to HOMO and LUMO orbital pictures (Fig. 2), it is
found that the lled p-orbital (HOMO) is mostly located on the
tetrazole ring of the compounds, while the unlled anti p-
orbital (LUMO) is on the benzene ring. When electron transi-
tions take place, electrons are mainly transferred from the tet-
razole ring to the phenyl ring. The HOMO can act as an electron
Frontier molecular orbital analysis
The EHOMO, ELUMO and HOMO–LUMO energy gap of molecules
3a–3m were calculated using the B3LYP/6-31G level. Molecular
orbitals and their properties, such as energy and frontier elec-
tron density, are important and are used to determine the
reactive position in p-electron systems.30 Therewith, values of
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Fig. 3 The molecular electrostatic potential surface of molecules 3a–3m.
donor and the LUMO can act as the electron acceptor. A higher with a low-energy empty molecular orbital. As shown in Fig. 2,
HOMO energy (EHOMO) for the molecule indicates a higher the HOMO energy of compound 3e has the highest value (ꢁ5.78
electron-donating ability to an appropriate acceptor molecule eV). In addition, a large energy gap implies high stability for the
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molecule. Fig. 2 shows that the energy gap of compound 3m has reaction did not proceed at all; the data indicated that the
the highest value (5.8 eV) therefore it is less reactive than other leaching of metal from the solid support was low. For practical
structures. Also the energy gap of structure 3a has the lowest applications of heterogeneous catalysts, the reusability is a very
value (3.89 eV), which indicates that it is more reactive. It
implies that the electronic transfer in molecule 3a is easier. The
existence of the electron withdrawing nitro group (–NO2) in
molecule 3a reduces the energy of the HOMO.
Molecular electrostatic potential
Molecular electrostatic potential (MEP) is related to the elec-
tronic density and is important in understanding sites for
electrophilic attack and nucleophilic reactions.32–34 MEP is a
graphic model and a real physical property.35 This methodology
is used to investigate the electronic distribution in molecules
and to evaluate the electronic distribution around molecular
surfaces for compounds.36,37
To indicate the sites on the molecules for interaction with
electrophilic and nucleophilic species, MEP was calculated at
the B3LYP/6-31G optimized geometry for structures 3a–3m. As
shown in both Fig. 3 and 4, electrophilic reactivities are red in
color which indicates the negative regions of the molecule,
while the nucleophilic reactivities are colored in blue and
indicate the positive regions of the molecule. The nitro and
carbonyl oxygen atoms are surrounded by a greater negative
charge surface, making these sites potentially more favorable
for electrophilic attack. According to Fig. 3 and 4, in the MEP of
molecules 3a–3m, negative centers include the tetrazole ring,
phenyl ring and oxygen atoms (red color). Among the MEPs of
molecules 3a–3f, the MEPs of molecules 3a and 3e indicate that
their phenyl ring and oxygen atom have higher electronic
density than other molecules (Fig. 3). Also, it can be seen from
Fig. 3, that the main negative center is focused on the tetrazole
ring. Among molecules 3g–3m, molecule 3l has the greatest
electronic density on the tetrazole ring (Fig. 3).
The electronic density of the atoms of derivatives 3a–3m is
shown in Fig. 4. The negative charges are mainly located on N
atoms, C phenyl ring atoms and O atoms. All H atoms are
positive. According to Fig. 4, the highest negative charge in
molecules 3a–3f focused on an N atom attached to the phenyl
ring (N–H) while the highest negative charge in molecules 3g–
3m is focused on N (N–H2) on the tetrazole ring (attached to the
phenyl ring).
Catalyst reuse and stability
In order to examine the leaching of metal (Mn and Co) from the
heterogeneous catalyst, a series of experiments was conducted
in which the nano catalyst was ltrated aer 20, 30 and 60 min
and the reactions were continued with the ltrate. For this
purpose, the reaction of 5-(2-chlorophenyl) amino-1H-tetrazole
with sodium azide in the presence of nano catalyst in DMF
solvent was studied. Aer 20 min (the reaction normally
completed within 100 min with 82% yield of product), the
reaction was stopped and catalyst was removed by ltration
from the reaction mixture. Then the mixture without the solid
catalyst which contains unreacted substrates was allowed to
continue under the same conditions. In these conditions the Fig. 4 Electronic density of the atoms of structures 3a–3m.
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signicant factor. The reusability of the catalysts was checked in values are given in Hz. IR (KBr) spectra were recorded on a
the reaction of 4-methylphenylcyanamide with sodium azide as Shimadzu 470 and Perkin-Elmer 781 spectrophotometer.
the substrates under the present reaction conditions (Table 1, Melting points were taken in open capillary tubes with a BUCHI
entry 2). Aer completion of the reaction in the rst run, the 510 melting point apparatus and were uncorrected. The
catalyst was separated from the reaction mixture by a simple elemental analysis was performed using a Heraeus CHN-O-
ltration and the resulting solid mass was reused for the next Rapid analyzer. Thin layer chromatography (TLC) was per-
run. In the case of the cobalt nano catalyst the recovered catalyst formed on silica gel polygram SIL G/UV 254 plates.
activities of ve consecutive runs were about 83%, 82%, 81%,
81% and 80% respectively. This demonstrates the practical
recyclability of this catalyst. Furthermore, in the case of Mn(III)
Preparation of nanosized organometallic-SiO2/Al2O3
@Si/Al and Fe(III)@Si/Al, the nano catalysts have been recovered Nanosized SiO2/Al2O3 was used as the support and prepared by
for 7 runs with some decrease in the catalytic activity of the the sol–gel method.18,19 At rst, 3.5 g nanosized SiO2/Al2O3 was
catalyst.
activated at 500 ꢀC for 5 h under air and then was reuxed with
4.3 mL of trimethoxysilylpropylamine (3-APTMS) in dry toluene
(50 mL) for 24 h. The solid achieved during this process was
ltered and washed off with dry methanol at 100 ꢀC under
Experimental
All reagents were purchased from the Merck and Aldrich vacuum for 5 h. Then bipyridylketone (BPK) was added to a
chemical companies and used without further purication. All suspended solution of the Si/Al–APTMS in dry methanol. To
compounds were characterized by different spectroscopic synthesize Si/Al–APTMS–BPK–Co(II) and Si/Al–APTMS–BPK–
methods (IR, FT-IR, 1H NMR and 13C NMR), elemental analysis Mn(III), 2.0 g Si/Al–APTMS–BPK was suspended in 50 mL of
(CHN) and melting points and identied by comparison of their ethanol in a round bottom ask followed by addition of 3.0
physical and spectroscopic data with those of authentic mmol Co(OAc)2$4H2O and Mn(OAc)2$4H2O, respectively. The
samples. The NMR spectra were recorded in acetone, DMSO mixture was reuxed during 24 h under magnetic stirring.
1
and CDCl3. H NMR spectra were recorded on Bruker Avance Furthermore, to synthesize Si/Al–APTMS ¼ ferrocene, the fer-
DRX 100, 300 and 500 MHz instruments. The chemical shis (d) rocenecarboxaldehyde (FCA) was added to a suspended solution
are reported in ppm relative to the TMS as internal standard. J of Si/Al supported aminopropyl (Si/Al–APTMS) in dry methanol.
Scheme 4 Schematic representation of the preparation process for nano catalysts.
47634 | RSC Adv., 2014, 4, 47625–47636
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The mixture was reuxed for 24 h to make a Fe nano catalyst on tiny decrease in activity. The proposed methodology could be
the surface of nano scale Si/Al (Scheme 4). The formation of used in organic synthesis for the syntheses of
nano catalyst on the SiO2/Al2O3 mixed oxides was veried using arylaminotetrazoles.
BET, elemental analysis, FT-IR, UV-vis, BET, ICP, SEM, EDS,
XPS, TGA and TEM.2,3,18,19
In the present work, we have performed theoretical analyses
of tetrazole derivatives by density functional theory calculations
using the B3LYP/6-31G level. The thermodynamic parameters,
frontier molecular orbitals (HOMO and LUMO), and electronic
density (MEP) were obtained. Based on the thermodynamic
parameters we found that all molecules are stable. The presence
of the nitro group (NO2) in molecule 3a reduces the energy of
the HOMO, therefore the HOMO–LUMO energy gap of molecule
3a is the smallest (3.89 eV). The other molecular properties such
as dipole moment (m), energy of structure formation (DE; Har-
tree Fock) and point group were calculated. As shown by the
MEPs, among molecules 3a–3f, molecules 3b and 3c have the
greatest electronic density on the tetrazole ring and among 3g–
3m, molecule 3l has the greatest electronic density on the tet-
razole ring.
General procedure for the synthesis of arylaminotetrazoles
using the nano catalyst
The nano catalyst was added to a mixture of cyanamides (1a–m)
(2 mmol), sodium azide (200 mg, 3 mmol) and distilled dime-
thylformamide (6 mL) and stirred at the desired temperature for
the appropriate time (Table 4). Aer completion of the reaction
(as monitored by TLC), the catalyst was centrifuged, washed
with ethyl acetate and the centrifugate was treated with EtOAc (3
ꢂ 10 mL) and 5 N HCl (20 mL) and stirred vigorously. The
resultant organic layer was separated and the aqueous layer was
again extracted with ethyl acetate (25 mL). The combined
organic layers were washed with water, the solvent removed and
the crude solid arylaminotetrazole recrystallized (aqueous
ethanol). The pure products were characterized by IR and NMR.
The physical data (mp, IR, 1H NMR, 13C NMR) of known
compounds were found to be identical with those reported in
the literature.11–14
Acknowledgements
We thank the research council of Bu-Ali Sina and the Islamic
Azad University for nancial support.
Notes and references
Analytical data for selected compounds
5-(4-Acethylphenyl)amino-1H-tetrazole (1e, Table 4, entry 6).
1 R. J. Herr, Bioorg. Med. Chem., 2002, 10, 3379.
2 D. Habibi, A. R. Faraji, M. Arshadi and J. L. G. Fierroc, J. Mol.
Catal. A: Chem., 2013, 372, 90; M. Uyanik, M. Akakura and
K. Ishihara, J. Am. Chem. Soc., 2009, 131, 251.
3 D. Habibi and A. R. Faraji, C. R. Chim., 2013, 16, 888;
M. Uyanik and K. Ishihara, Chem. Commun., 2009, 2086;
B. Zeynizadeh and P. Lot, Asian J. Chem., 2009, 21, 3617.
4 G. F. Holland and J. N. Pereira, J. Med. Chem., 1967, 10, 149.
5 L. A. Flippin, Tetrahedron Lett., 1991, 32, 6857.
6 P. Rhonnstad and D. Wensbo, Tetrahedron Lett., 2002, 43,
3137.
1
M.p.: 215–217ꢀC; H NMR (300 MHz, DMSO-d6): 10.38 (s, 1H),
7.92 (d, J ¼ 7.95 Hz, 2H), 7.14 (d, J ¼ 7.64 Hz, 1H), 1.10 (s, 1H)
ppm; 13C NMR (75 MHz, DMSO-d6): 196.7, 145.3, 130.4, 130.1,
116.2, 31.7, 26.8; IR (KBr): ꢀn ¼ 3403, 3282, 3177, 3024, 2978,
2839, 2780, 2440, 1651, 1627, 1605, 14 579, 1470, 1426, 1364,
1285, 1258, 1195, 1055, 1024, 962, 885, 865, 835, 733, 592 cmꢁ1
;
anal. calcd for C9H5N5O: C, 53.20; H, 4.46; N, 34.47. Found: C,
53.16; H, 4.39; N, 35.12%.
1-(2,6-Dimethylphenyl)-5-amino-1H-tetrazole (1m, Table 4,
1
entry 13). M.p. 148–149ꢀC; H NMR (500 MHz, DMSO-d6): 7.02
(s, 3H), 5.19 (s, 2H), 2.27 (s, 6H) ppm; 13C NMR (125 MHz,
DMSO-d6): 157.5, 137.6, 136.6, 128.3, 126.3, 18.5 ppm; IR (KBr):
ꢀn ¼ 3430, 3295, 3070, 2955, 2920, 2854, 1654, 1600, 1579, 1535,
1477, 1440, 1376, 1349, 1260, 1217, 1160, 1114, 917, 869, 760,
700, 662, 636, 546, 516, 496 cmꢁ1; anal. calcd for C9H11N5: C,
57.12; H, 5.86; N, 37.02. Found: C, 57.45; H, 5.67; N, 36.57%.
7 E. O. John, R. L. Kirchmeier and J. M. Shreeve, Inorg. Chem.,
1989, 28, 4629.
8 N. P. Peet, L. E. Baugh, S. Sundler, J. E. Lewis,
E. H. Matthews, E. L. Olberding and D. N. Shah, J. Med.
Chem., 1968, 29, 2403.
9 W. L. Garbrecht and R. M. Herbst, J. Org. Chem., 1953, 18,
1014.
10 A. R. Modarresi-Alam and M. Nasrollahzadeh, Turk. J. Chem.,
2009, 33, 267.
Conclusions
In conclusion, a simple and convenient method has been 11 D. Habibi and M. Nasrollahzadeh, Synth. Commun., 2010, 40,
developed for the synthesis of arylaminotetrazoles in the pres- 3159.
ence of the nano catalyst as a heterogeneous reusable catalyst 12 M. Nasrollahzadeh, D. Habibi, A. R. Faraji and Y. Bayat,
under thermal conditions. Well-dispersed Fe, Mn and Co Tetrahedron, 2010, 66, 3866.
nanoparticles have been prepared on a SiO2/Al2O3 nanosized 13 D. Habibi, M. Nasrollahzadeh and Y. Bayat, Synth. Commun.,
heterogeneous support and have been successfully employed 2011, 41, 2135.
and tested in the syntheses of arylaminotetrazoles. The signif- 14 M. Nasrollahzadeh, D. Habibi, Z. Shahkarami and Y. Bayat,
icant advantages of this methodology are high yields, mild Tetrahedron, 2009, 65, 10715.
reaction conditions, elimination of dangerous and harmful 15 D. Azarifar and D. Sheikh, Synth. Commun., 2013, 43, 2517;
hydrazoic acid and a simple work-up procedure. The nano
F. Himo, Z. P. Demko, L. Noodleman and K. B. Sharpless,
catalyst can be recovered and reused by simple ltration with a
J. Am. Chem. Soc., 2002, 124, 12210.
This journal is © The Royal Society of Chemistry 2014
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16 V. Ponec and G. C. Bond, Catalysis by Metals and Alloys, 27 M. J. Frisch, W. W. Turcks, H. B. Schegel, G. E. S. Scuseria,
Elsevier, Amsterdam, 1996.
M. A. Robb and J. R. Cheeseman, Gaussian 03 revision B03,
17 C. W. Lim and I. S. Lee, Nano Today, 2010, 5, 412.
Gaussian Inc., Pittsburgh, PA, 2003.
18 D. Habibi, A. R. Faraji, M. Arshadi, S. Heydari and A. Gil, 28 A. Frisch, A. B. Nielson and A. J. Holder, Gaussview User
Appl. Catal., A, 2013, 466, 282.
19 D. Habibi and A. R. Faraji, Appl. Surf. Sci., 2013, 276, 487.
20 W. Partenheimer, Adv. Synth. Catal., 2004, 346, 1495.
Manual, Gaussian Inc., Pittsburgh, PA, 2000.
29 L. Shiri, D. Sheikh, A. R. Faraji, M. Sheikhi and S. A. Seyed
Katouli, Lett. Org. Chem., 2014, 11, 18.
21 D. Habibi, A. R. Faraji, M. Arshadi, H. Veisi and A. Gil, J. Mol. 30 K. Fukui, T. Yonezawa and H. J. Shingu, J. Chem. Phys., 1952,
Catal. A: Chem., 2014, 382, 41. 20, 722.
22 W. G. Finnegan, R. A. Henry and E. Lieber, J. Org. Chem., 31 Y. Li, Y. Liu, H. Wang, X. Xiong, P. Wei and F. Li, Molecules,
1953, 18, 779. 2013, 18, 877.
23 R. A. Henry, W. G. Finnegan and E. Lieber, J. Am. Chem. Soc., 32 E. Scrocco and J. Tomasi, Adv. Quantum Chem., 1978, 11, 115.
1954, 76, 88.
33 F. J. Luque, J. M. Lopez and M. Orozco, Theor. Chem. Acc.,
2000, 103, 343.
34 N. Okulik and A. H. Jubert, J. Mol. Des., 2005, 4, 17.
24 R. A. Henry, W. G. Finnegan and E. Lieber, J. Am. Chem. Soc.,
1955, 77, 2264.
25 W. L. Garbrecht and R. M. Herbst, J. Org. Chem., 1953, 18, 35 P. Politzer and D. G. Truhlar, Chemical Applications of Atomic
1003.
and Molecular Electrostatic Potentials, Plenum Press, New
York, 1981.
26 W. L. Garbrecht and R. M. Herbst, J. Org. Chem., 1953, 18,
1022.
36 K. C. D. Politzer, The Force Concept in Chemistry, Van
Nostrand Reinhold Publisher, New York, 1981.
37 S. Ramachandran and G. Velraj, Rom. J. Phys., 2013, 58, 305.
47636 | RSC Adv., 2014, 4, 47625–47636
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