High Catalytic Activity of Peptide Nanofibres Decorated with Ni and Cu Nanoparticles for the Synthesis of 5-Substituted 1H-Tetrazoles and N-Arylation of Amines

Article abstract of DOI:10.1071/CH17176

A rapid development of a new methodology for decarboxylative N-arylation of carboxylic acids and the preparation of 5-substituted 1H-tetrazoles catalysed by peptide nanofibres decorated with Cu and Ni nanoparticles is presented. Compared with conventional aryl halides, benzoic acids are extremely interesting and environmentally friendly options for the synthesis of secondary aryl amines.

Full text of DOI:10.1071/CH17176

CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH17176
High Catalytic Activity of Peptide Nanofibres Decorated
with Ni and Cu Nanoparticles for the Synthesis of
5-Substituted 1H-Tetrazoles and N-Arylation of Amines
A B
,
A
Arash Ghorbani-Choghamarani
and Zahra Taherinia
A
Department of Chemistry, Ilam University, PO Box 69315516, Ilam, Iran.
Corresponding author. Email: a.ghorbani@ilam.ac.ir
B
A rapid development of a new methodology for decarboxylative N-arylation of carboxylic acids and the preparation of
5-substituted 1H-tetrazoles catalysed by peptide nanofibres decorated with Cu and Ni nanoparticles is presented.
Compared with conventional aryl halides, benzoic acids are extremely interesting and environmentally friendly options
for the synthesis of secondary aryl amines.
Manuscript received: 30 March 2017.
Manuscript accepted: 29 May 2017.
Published online: 11 July 2017.
Introduction
costly effective palladium catalysts (including toxic phosphate-
containing ligands) for C–N bond formation. In addition, when
the term ‘N-arylation chemistry’ is stated, the fundamental
concern is the use of aryl halides or arylboronic acids as elec-
trophiles, which catalytically react with amines in the presence
of transition metals. However, aryl halides present several
problems, such as needing stoichiometric amounts of catalyst,
The development of mild and general procedures for C–N bond
formation via N-arylation coupling reactions catalysed by
transition metals has attracted significant attention in recent
years.[1–4] On the other hand, nickel-catalysed N-arylation
reactions have received less attention. There is still a growing
interest to use inexpensive copper and nickel catalysts instead of
HO
O
C
H
O
H
H
N
O
ꢂ
CH2
O
N
H
C
H
C
O
C
NH
C
O
C
C
H2
C
NH2
C
H2
C
O
C
H
H2
C
H2
C
H2C
CH2
H
H
C
CH
N
NH
H
C
N
H
O
CH
CH
N
H2N
HN
C
N
C
H2
NH
C
CH2 2 C
H2N
N
C
N
H
O
H2
H
O
H
H2
H2
H
OH
H2C
NH2
HN
OH
NH
H
O
N
H2C
C
C
O
C
C
O
NH
H2
N
C
C
H2
C
C
CH2
1) phosphate buffer solutions (pH 8)
and succinic anhydride
H
NH
C
CH2
O
N
H
C
H2
H2N
CH
N
ꢂ
C
H2
NH2
C
NH2
N
N
H
ꢀ
M
H2
O
H2
HN
ꢂ
p
N
NHꢀ
O2
2) Ni(NO3)23H2O
or CuCl
OH
H
O
HO
p
OH
M ꢁ Ni,Cu
HO
Scheme 1. Schematic synthesis of Ni and Cu nanoparticles supported on the peptide nanofibre.
Journal compilation ꢀ CSIRO 2017
www.publish.csiro.au/journals/ajc

B
A. Ghorbani-Choghamarani and Z. Taherinia
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
(b)
(a)
Ni(NO3)2.6H2O
NiNP-PNF
Peptide nanofibre
250
350
450
550
650
750
ꢀ0.5
Wavelength [nm]
Fig. 3. UV-Visible absorption spectra for Ni(NO3)2ꢀ6H2O, peptide nano-
fibre, and NiNP-PNF.
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
CuCI
CuNP-PNF
Peptide nanofibre
Fig. 1. (a) Phosphate buffer solution containing peptide nanofibre and
CuCl (pH 8 by adding succinic anhydride which the final pH of the solution
was found to be 7). (b) Phosphate buffer solution containing CuCl (pH 7
without adding succinic anhydride).
250
350
450
550
650
750
ꢀ0.2
98
Wavelength [nm]
(a)
94
90
Fig. 4. UV-Visible absorption spectra for CuCl, peptide nanofibre, and
CuNP-PNF.
800
700
600
500
400
300
200
100
0
98
(b)
94
90
86
95
85
(c)
800
700
600
500
400
300
200
100
0
Wavelength [nm]
CuNP-PNF
Peptide nanofibre
NiNP-PNF
95
85
75
65
(d)
Fig. 5. Fluorescence spectra of peptide nanofibre and NiNP-PNF and
CuNP-PNF.
still the main substrates to the intended N-arylation products,
boronic acids likewise have attracted broad attention for this
aim. Unfortunately use of these compounds are also accompa-
nied with some drawbacks such as: the tricoordinate nature of
these compounds makes them highly moisture sensitive, to
minimise atmospheric oxidation and autoxidation, they should
be stored under an inert atmosphere, and their reaction needs
isolation and purification because of the formation of boroxines
that are easily produced by the simple dehydration of boronic
acids.[6] Therefore, in order to overcome the above mentioned
drawbacks there is still a great interest to find a new electrophilic
3500 3000 2500 2000
1500
1000
500
Wavenumber [cmꢀ1
]
Fig. 2. FT-IR spectra of (a) peptide powder, (b) peptide nanofibre,
(c) peptide nanofibres decorated with Cu nanoparticles, and (d) peptide
nanofibres decorated with Ni noparticles.
high temperature reaction media, being environmental pollu-
tants, producing by-products that need isolation and purification
processes of the desired products.[5] Although aryl halides are

Cu and NiNP-PNF for the Synthesis of Tetrazoles and Anilines
C
(b)
(a)
SEM HV: 30.0 kV
WD: 9.09 mm
Det SE
MIRA3 TESCAN
WD: 7.30 mm
Det: SE
SEM HV: 30.0 kV
MIRA3 TESCAN
View field: 2.50 μm
500 nm
200 nm
200 nm
View field: 1.23 μm
200 nm
SEM MAG: 111kx Date(m/d/y): 09/03/15
Kurdistan University
Kurdistan University
SEM MAG: 225 kx Date(m/d/y): 01/27/16
(d)
(c)
SEM HV: 30.0 kV
View field: 1.15 μm
WD: 7.30 mm
Det: SE
MIRA3 TESCAN
SEM HV: 30.0 kV
View field: 1.23 μm
SEM MAG: 225 kx
WD: 7.30 mm
Det: SE
Date(m/d/y): 01/27/16
MIRA3 TESCAN
200 nm
Kurdistan University
SEM MAG: 240 kx Date(m/d/y): 01/27/16
Kurdistan University
(e)
SEM HV: 30.0 kV
View field: 1.21 μm
WD: 7.30 mm
Det: SE
MIRA3 TESCAN
SEM MAG: 228 kx Date(m/d/y): 01/27/16
Kurdistan University
Fig. 6. SEM images of (a) peptide nanofibre, (b, c) immobilised Ni nanoparticles and (d, e) immobilised Cu nanoparticles on
the surface of the woven nanofibers.
reagent. Among nitrogen-containing heterocyclic compounds,
1H-tetrazoles are a class of synthetic organic compounds that
have been widely studied due to their wide range of applications
in photography and information recording systems,[7] pharma-
ceutical syntheses,[8] etc. So far, several procedures have been
introduced for the synthesis of 5-substituted 1H-tetrazoles. The
most important approaches are: (i) condensation of hydrazoic
acid with isocyanides,[9] (ii) the addition of sodium nitrite to
amino guanidines,[10] (iii) the three-component reaction of pri-
mary amines with sodium azide and triethyl orthoformate,[11] and
(iv) reaction of sodium azide to carbodiimides.[12] In general, the
most versatile method used for the synthesis of 5-substituted 1H-
tetrazoles is based on [3 þ 2] cycloaddition of the azide ion and
organic nitriles in the presence of a catalyst such as AgNO3,[13]
SiO2–H3BO3,[14] BF3–OEt2,[15] Zn(OTf)2,[16] Pd-2A3HP-MCM-
41 (Pd-(0)-2-amino-3-hydroxypyridine grafted onto mesoporous

D
A. Ghorbani-Choghamarani and Z. Taherinia
Table 1. Optimisation of the reaction conditions for the C–N coupling
reaction in the presence of CuNP-PNF
and Ni ions as an effective catalyst for the decarboxylative
N-arylation of substituted benzoic acids as well as for the
synthesis of 5-substituted 1H-tetrazoles. The PNFs were used
as templates for the synthesis of NPs and Fig. 1 shows their effect
on NP formation.
H
NH2
CO2H
N
CuNP-PNF (cat.)
ꢂ
solvent, base, ΔCO2↑
Cl
Cl
Cl
Cl
5.5 h
Results and Discussion
EntryA Solvent Temp. [8C] Base
Base [mmol] Yield [%]
Characterisation of Supported Cu and Ni NPs on the PNFs
The interactions between the PNF and Ni and Cu NPs were
investigated by IR spectroscopy, fluorescence spectroscopy,
ultraviolet-visible (UV-vis) spectroscopy, and scanning elec-
tron microscopy (SEM) techniques.
1
DMSO
DMF
130
130
130
130
130
130
130
130
100
80
KOH
KOH
KOH
KOH
–
7
7
7
7
–
7
7
7
7
7
5
2
7
90
2
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
23
3
PEG
4
H2O
Fig. 2 shows a typical FTIR spectrum of the PNF (CuNP-
PNF and NiNP-PNF). In the spectra (Fig. 2a) the peak at
1644 cmꢁ1 corresponds to the bending vibration of NH groups
for the PNF while this peak for CuNP-PNF and NiNP-PNF
shifted to 1635 and 1640 cmꢁ1, respectively. The lowering in
this frequency in the PNF indicates coordination of the nitrogen
with metal. UV-Vis absorption spectroscopy is the most widely
used method for characterising the optical properties of NPs.
Figs 3 and 4 show the UV-vis absorption spectra of a PNF, CuCl,
Ni(NO3)2ꢀ6H2O, CuNP-PNF, and NiNP-PNF. The adsorption of
metal on the PNF could be invoked to explain the increase of the
UV absorption and the peak shape changes. The visible spectra
of the NiNP-PNF and CuNP-PNF show a maximum absorption
compared with the free PNF and metallic salts. This may be due
to a d–d electron transition or charge-transfer transition.[33]
Also, enhancement of fluorescence through complexation could
be observed (Fig. 5). In the absence of metal ions the fluores-
cence of the ligand is probably quenched by the occurrence of a
photoinduced electron transfer (PET) process due to the pres-
ence of lone pairs of electrons of the donor atoms in the ligand,
thus the fluorescence intensity may be greatly enhanced by the
coordination with metals (Ni or Cu). The chelation of the ligand
to metals increases the rigidity of the ligand and thus reduces the
loss of energy by thermal vibrational decay.[34] The SEM
images show that the Cu and Ni NPs were regularly immobilised
on the surface of woven PNFs (Fig. 6).
5
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
6
K2CO3
Na2CO3
Et3N
KOH
KOH
KOH
KOH
KOH
7
8
9
10
11
12
13
N.R.
51
130
130
130
23
11B
AReaction conditions: benzoic acid (1.3 mmol), amine (3 mmol), CuNP-
PNF (200 mL), and solvent (3 mL). N.R. ¼ no reaction.
BReaction catalysed with CuCl in the absence of peptide nanofibre.
MCM-41),[17] Fe3O4@SiO2@L-arginine,[18] AlCl3,[19] CdCl2,[20]
and montmorillonite.[21]
Recently, considerable attention has been given to the design
and immobilisation of different catalysts on various supports,
such as polymeric and inorganic materials, including zeo-
lites,[22] metal oxides,[23] mesoporous silica,[24] activated car-
bon,[25] carbon nanotubes,[26] and peptide nanofibres (PNFs).[27]
Among these supports, PNFs are the best choice due to their
unique properties such as a high surface area-to-volume
ratio.[28] Among the applications of PNFs, their catalytic appli-
cations in organic reactions have attracted broad attention;
hence, as a part of our research program towards the utility of
PNFs, herein we report the preparation of Cu nanoparticles
(NPs) and Ni NPs immobilised on PNFs, which were used as
catalysts for the decarboxylative N-arylation of substituted ben-
zoic acids as well as the synthesis of 5-substituted 1H-tetrazoles.
Decarboxylation of carboxylic acids by loss of carbon dioxide
(as a green and completely non-toxic by-product) has recently
emerged as a promising coupling agent in organic synthesis such
as for the formation of a bond between an aryl ring and an sp2
carbon,[29] and for the formation of carbon–sulfur bonds via a
palladium–copper-catalyzed decarboxylative cross-coupling
reaction between a 2-substituted arene carboxylic acid and a thiol
or a disulfide inthe presence ofan electron-withdrawing group on
the arene carboxylic acid.[30] Recently decarboxylative etherifi-
cation has been reported, for which the desired products have
been achieved only for substrates with s-electron-withdrawing
substituents.[31] It is particularly noteworthy that amide bonds are
typically formed from the reaction of amines and pre-activated
carboxylic acid derivatives such as acid chlorides. Zhang also
reported direct N-arylation of aryl carboxylic acids with ortho,
meta, or para-electron-withdrawing groups with amines.[32] In a
recent publication we reported the synthesis of PNFs using
arginine as a building block (Scheme 1) and we showed that a
self-assembled peptide was formed at pH 7.[27] The PNF’s
features led us to investigate the activity of nanofibres with Cu
Catalytic Studies
After the preparation and characterisation of Cu and Ni NPs
supported on the PNF, the catalytic activity of these compounds
was investigated for the synthesis of secondary amines from the
reaction of carboxylic acids and amines. In this study, a direct
synthesis of aliphatic and aromatic amines via combination of
carboxylic acids and amines in the presence of PNFs decorated
withCuand/orNi NPs without productionof amide as by-product
has been presented. Initially, the reaction of 4-chlorobenzoic
acid with 4-chloroaniline in the presence of Cu NPs supported
on the PNF as a catalyst was selected as a model reaction, and
different parameters including the type of base, solvent, and
temperature were optimised (the results are summarised in
Table 1). It was found that the influence of base type and solvent
significantly affect the performance of a reaction. The reaction
rate was also increased by increasing the reaction temperature. It
is noteworthy that the reaction was also conducted in the pres-
ence of CuCl without PNF, and the observed yield of product
was very low.
With optimal conditions in hand, a variety of secondary
amines was synthesised using a combination of benzoic acid and
amine at 1308C (Table 2).

Cu and NiNP-PNF for the Synthesis of Tetrazoles and Anilines
E
Table 2. Synthesis of secondary amines via reaction of substituted benzoic acids and amines catalysed by Cu or NiNP-
PNF in DMSO
CuNP-PNF (cat.)
or
H
N
NH2
CO2H
NiNP-PNF (cat.)
ꢂ
DMSO, KOH, 130°C CO2↑
Rꢃ
R
R
Rꢃ
EntryA
Amine
Acid
Product
Time [h]
Cu
Yield [%]B
Cu
Ni
6
Ni
85
H
N
COOH
NH2
1
2
5
80
75
H
N
NH2
COOH
COOH
COOH
9
15
3
8.5
65
55
75
44
Cl
Cl
H
N
NH2
3
4
5
14
65
78
53
Brl
Br
H
N
NH2
2
5
O2N
O2N
COOH
COOH
COOH
NH2
N
H
5
H
N
NH2
6
7
10
8.5
5
75
90
88
90
Cl
Cl
Cl
H
N
NH2
5.5
Cl
Cl
Cl
Cl
COOH
NH2
8
4.5
4.5
7.5
38
45
N
H
Cl
Me
NH2
N
H
9
9
45
53
43
57
COOH
Me
H
N
Me
NH2
10
20
18
COOH
Me
AReaction conditions: benzoic acids (1.3 mmol), amine (3 mmol), CuNP-PNF (200 mL), KOH (7 mmol), and DMSO (3 mL).
BIsolated pure product.
One of the important aspects of this methodology is the
successful reaction of sterically hindered benzoic acids and
amines; for example 2-methyl benzoic acid gives the desired
products in good yield. Meanwhile, ortho-substituted benzoic
acids require longer reaction times and give relatively lower
product yields than para-substituted. The obtained results from
Table 2 showed that the N-arylation reaction in the presence of
CuNP-PNF in comparison with NiNP-PNF proceeds more
rapidly and efficiently. A suggested mechanism for the decar-
boxylative C–N cross-coupling reaction is outlined in Scheme 2.
In order to further investigate the catalytic activities of these
two new catalysts, the synthesis of 5-substituted 1H-tetrazole was
studied as well. Initially, the reaction of 2-hydroxy-benzonitrile
with sodium azide in the presence of Ni NPs supported on the

F
A. Ghorbani-Choghamarani and Z. Taherinia
Table 3. Optimisation of the reaction conditions for the synthesis of
1,5-tetrazole
Comparison of Catalysts
To evaluate the catalytic activity of PNFs decorated with Ni
and Cu NPs, we compared the results for the synthesis of
5-(4-bromophenyl)-1H-tetrazole and diphenylamine in the pres-
ence of these catalysts with previously reported procedures
(Tables 5 and 6). This catalyst leads to a good reaction time and
higher yield than other reported catalysts. More importantly,
compared with other catalysts, NiNP- and CuNP-PNF are easily
prepared and can be reused four times without any significant loss
of their activity.
N
CN
N
NiNP-PNF (cat.)
NaN3
ꢂ
R
N
solvent, temp. (ꢄC)
N
H
R
EntryA Solvent Temp. [8C] Catalyst [mL] Time [h] Yield [%]
1
2
3
4
5
6
7
DMSO
DMF
H2O
120
120
120
120
100
80
200
200
200
200
200
200
100
30 min
50 min
1
80
65
Conclusions
N.R.
90
PEG
PEG
PEG
PEG
20 min
1
In summary, we demonstrate an effective route for the C–N
cross coupling reaction via decarboxylative N-arylation of
substituted carboxylic acids without use of halocarbon pre-
cursors. The synthesis of substituted tetrazoles has also been
studied. Copper and nickel as cost effective and non-toxic
metals immobilised on woven peptide nanofibres are success-
fully applied to catalyse the described reactions.
90
2
66
120
20 min
40
AReaction conditions: sodium azide (1.2 mmol), 2-hydroxy-benzonitrile
(1 mmol), NiNP-PNF (200 mL), solvent (2 mL). N.R. ¼ no reaction.
Experimental
PNF as a catalyst was selected as a model reaction and different
parameters including the solvent type and temperature were
considered to develop the scope of this reaction further and the
results are summarised in Table 3. After optimising the reaction
conditions, it is worth noting that, among the examined organic
solvents (H2O, DMSO, DMF, polyethylene glycol (PEG)) we
found that PEG gave the desired product in a good yield under
heating at 1208C for 20 min (Table 3, entry 4). Also, the reaction
rate was increased by increasing the reaction temperature. To
understand the scope and effectiveness of the catalyst (PNFs
decorated with Ni or Cu NPs) different substituted benzonitriles
(Table 4) were selected and used under the determined condi-
tions. Results show that benzonitriles containing electron-donat-
ing groups, such as 2-hydroxy-benzonitrile, gave very good
yields in a shorter reaction time than electron-withdrawing
containing ones (Table 4, entry 10), probably because of the
chelating effect of the hydroxy group to the copper or nickel
catalyst, which facilitated the catalysis to the desired product. On
the other hand, the reaction yields were sensitive to steric effects
on the benzonitriles. The sterically hindered ortho-substituted
benzonitriles were proved to be problematic for this catalytic
system and produced the corresponding products with much
longer times (Table 4, entries 1, 2, 3).
The obtained optimised conditions for the Ni catalyst were
applied for the synthesis of a variety of 5-substituted 1H-
tetrazoles synthesised using sodium azide (1.2 mmol) and a
nitrile compound (1 mmol) in the presence of CuNP-PNF at
1208C (Table 4). As it can be seen from Table 4, CuNP-PNF is
more effective in comparision with NiNP-PNF.
The details of the reaction mechanism are not clear at this
time, but one simple hypothesis is presented in Scheme 3. The
first step involves coordination of the nitrile nitrogen atoms to
Ni or Cu to form complex A, which accelerates the cyclisation
step. It seems that the [3 þ 2] cycloaddition between the two
metal-coordinated CꢂN bonds of the nitrile compound and
azide ion takes place readily to form the intermediate B. Finally,
acidic work-up affords desired products C and D (Scheme 2).
The recoverability and reusability of the Ni NP supported on
the PNF in an N-arylation reaction over four successive runs, was
investigated (see Experimental). It was found that NiNP-PNF
could be reused multiple times without a significant decrease in
its catalytic activity (Fig. 7).
Instrumentation
NMR spectra were acquired on a Bruker Avance III 400 MHz.
Melting points were measured with an Electrothermal 9100
apparatus. The particles size and morphology were investigated by
a JEOL JEM-2010 scanning electron microscope on an acceler-
ating voltage of 200 kV. Vertex 70 Fourier-transform infrared
(FT-IR), Varian Cary 300 Bio UV-Vis, and Varian Cary spec-
trofluorimeter spectrometers were used for analysis of PNFs,
CuCl, Ni(NO3)2ꢀ6H2O, CuNP-PNF, and NiNP-PNF which were
studied at room temperature in aqueous solution.
Preparation of PNFs
The PNFs were prepared by a published procedure.[27]
Synthesis of NiNP-PNFs
PNF (30.14 mg, 0.04 mmol) was dissolved in 0.2 mL of doubly
distilled water and 0.8 mL of phosphate buffer solution (pH 8)
was added. The solution was then sonicated for a few minutes.
This mixture was stirred overnight at 808C. In the next step Ni
(NO3)2ꢀ3H2O (6.5 mg, 0.02 mmol) was added to the reaction
mixture and stirred for 12 h at 808C to obtain NiNP-PNF
quantitatively.
Synthesis of CuNP-PNFs
PNF (30.14 mg, 0.04 mmol) was dissolved in 0.2 mL of doubly
distilled water and 0.8 mL phosphate buffer solution (pH 8). The
solution was then sonicated for a few minutes. The reaction was
allowed to continue at 808C overnight. In the next step CuCl
(2.2 mg, 0.02 mmol) was added to the reaction mixture and
heated to 808C for 12 h to obtain CuNP-PNF quantitatively.
General Procedure for the Synthesis of 1,5-Substituted
Tetrazoles
To a stirred mixture of sodium azide (1.2 mmol) in PEG-400
(2 mL), a nitrile compound (1 mmol) and NiNP-PNF (200 mL)
were added and heated at 1208C under atmospheric conditions.
The reaction progress was monitored by TLC. Upon reaction
completion, the mixture was allowed to cool to ambient tem-
perature and then filtered and extracted with ethyl acetate. The

Cu and NiNP-PNF for the Synthesis of Tetrazoles and Anilines
G
Table 4. Synthesis of tetrazoles catalysed by NiNP- or CuNP-PNF in PEG
CuNP-PNF (cat.)
or
NiNP-PNF (cat.)
CN
N
N
ꢂ
R
NaN3
N
PEG, 120ꢄC
N
H
R
EntryA
Nitrile compound
Product
Time [h]
Yield [%]B
Cu
7
Ni
Cu
71
Ni
N
N
CN
Cl
N
1
3.5
75
N
H
Cl
CN
N
N
N
2
3
4
6
3
8
3
2
5
85
90
75
90
95
93
N
H
Cl
Cl
N
N
CN
N
Cl
N
H
Cl
N
CN
N
N
N
H
NO2
O2N
N
N
CN
N
HO
5
6
7
6.5
2
82
90
80
95
85
73
N
HO
H
N
N
CN
Br
N
3
4.5
8
N
H
Br
N
N
CN
N
O2N
8.5
N
O2N
H
CN
N
N
O
N
8
10
8
78
90
85
73
95
87
N
H
O
N
N
N
CN
N
9
4
2.5
N
H
N
CN
OH
N
10
20 min
15 min
N
H
OH
AReaction conditions: sodium azide (1.2 mmol), nitrile compound (1 mmol), CuNP- or NiNP-PNF (200 mL), and PEG (2 mL).
BPure isolated yield.
organic layer was washed with 1 N HCl, dried with anhydrous
Na2SO4, and filtered to afford pure 5-substituted tetrazoles.
NiNP-PNF. The progress of the reaction was monitored by TLC.
After reaction completion, the mixture was cooled to room tem-
perature and was extracted with ethyl acetate (2 ꢃ 20mL). The
organic extract was washed twice with water and dried with
anhydrous Na2SO4, and then filtered and the solvent was evapo-
rated to give the corresponding aryl amine. The crude product was
purified by preparative TLC.
General Procedure for the Synthesis of Secondary Amines
The reaction was conducted at 1308C in DMSO (3mL) with
substituted amine (3 mmol), substituted benzoic acid (1.3 mmol),
KOH (7 mmol), and 200 mL of the solution containing CuNP- or

H
A. Ghorbani-Choghamarani and Z. Taherinia
H
N
R
RNH
M
nanofibres decorated
with M ꢁ Cu and Ni
M
M
M
PNF
c
O
reductive-
elimination
OH
KOH
KOH
RNH2
M
O
ꢀ ꢂ
OK
oxidative-
M
addition
b
O
O
RNH2
M
ꢀCO2
a
Scheme 2. Proposed mechanism for the synthesis of secondary amines through cross-coupling reaction of benzoic
acids with amines catalysed by peptide nanofibres decorated with Cu or Ni nanoparticles.
M
M
PNF
nanofibres decorated with M
RCN
N
N
N
N
NH
N
NaN3
R
M
R
ꢂ
N
H
N
H
D
C
ꢂ
M
R C
N
ꢀ
N
Na
N
R
ꢂ
N
ꢀ
ꢂ
ꢀ
N
N
N
N
Na
B
A
M ꢁ Cu or Ni
M
Scheme 3. Proposed mechanism for the synthesis of 5-substituted tetrazole catalysed by peptide nanofibres
decorated with Ni or Cu nanoparticles.
4-Chloro-N-phenylaniline (Table 2, entry 3)
N-Benzylaniline (Table 2, entry 5)
The title compound was obtained as a colourless solid. Mp
The title compound was obtained as a colourless oil,[46] dH
(400 MHz, CDCl3) 7.66–7.68 (m, 4H), 7.33–7.38 (m, 6H), 3.72
(s, 2H), 3.44 (br s, 1H, NH).
69.08C (lit. 62–638C[44]), dH (300 MHz, CDCl3) 7.82–7.68 (m,
1H), 7.55–7.50 (m, 1H), 7.39–7.30 (m,4H), 7.1–6.90 (m,1H), 6.71
(s, 1H).
4-Bromo-N-phenylaniline (Table 2, entry 3)
2-Methyl-N-phenylaniline (Table 2, entry 9)
The title compound was obtained as a pale yellow solid, mp
87–898C (lit. 888C[45]), dH (400 MHz, CDCl3) 7.91–7.93 (d, J 8,
2H), 7.53–7.55 (t, J 8.2, 2H), 4.41–7.43 (d, J 8, 2H), 7.10–7.12
(t, J 5.2, 1H), 7.70–7.72 (t, J 8, 2H), 5.33 (br s, 1H, NH).
The title compound was obtained as a yellow oil,[47] dH
(400 MHz, CDCl3) 7.49–7.58 (m, 6H), 7.28–7.30 (m, 3H), 6.89
(br s, 1H, NH), 1.61 (s, 3H). dC (100 MHz, CDCl3) 151.7, 150.2,
131, 129.1, 128.7, 127.4, 122.9, 120.5. vmax (KBr)/cmꢁ1 3450,

Cu and NiNP-PNF for the Synthesis of Tetrazoles and Anilines
I
3199, 3078, 2925, 2857, 1583, 1427, 1369, 1222, 1147, 1084,
1004.
vmax (KBr)/cmꢁ1 3508, 3101, 2919, 2854, 2690, 2617, 2547,
1608, 1521, 1439, 1346, 1156, 1101, 1024, 991, 951, 854, 721.
Diphenylamine (Table 2, entry 1)
Bis(4-chlorophenyl)amine (Table 2, entry 7)
The title compound was obtained as a pale yellow solid, mp
548C (lit. 52–538C[48]), dH (400 MHz, CDCl3) 7.95–7.97 (d, J
7.3, 2H), 7.49–7.56 (m, 2H), 7.29 (br s, 1H, NH). dC (100 MHz,
CDCl3) 150.2, 139.7, 139.5, 129.7126.2, 124.7, 121.9, 113.7.
nmax (KBr)/cmꢁ1 3695, 3059, 2925, 2857, 1581, 1453, 1294,
1216, 1150, 1069, 1015, 921, 771, 687, 525.
The title compound was obtained as a yellow solid, mp
77–788C. (lit. 778C[49]), dH (400 MHz, DMSO) 7.39 (d, J 7.6,
2H, ArH), 7.17 (d, J 7.6, 2H, ArH), 4.29 (s, 1H). vmax (KBr)/
cmꢁ1 3437, 2925, 2857, 1600, 1500, 1391, 1330, 1133, 1084,
831, 713, 540.
N-Benzyl-2-methylbenzenamine (Table 2, entry 7)
4-Nitro-N-phenylaniline (Table 2, entry 4)
The title compound was obtained as a yellow solid, mp
57–608C (lit. 59–608C[50]). dH (300 MHz, CDCl3) 7.94–7.88
(m, 4H), 7.74–7.68 (m, 1H), 7.61–7.40 (m, 1H), 4.20 (s, 2H), 2.3
(s, 3H).
The title compound was obtained as a yellow solid, mp
135–1368C (lit. 132–1358C[49]), dH (400 MHz, CDCl3) 8.14–
8.16 (d, J 8.7, 2H),7.42–7.44 (t, J 7.2, 2H), 7.23–7.25 (m, 3H),
6.96–6.98 (d, J 9.2, 2H), 6.36 (br s, 1H). dC (100 MHz, CDCl3)
150.2, 139.8, 139.5, 129.8, 126.3, 124.7, 121.9, 113.7.
5-(3-Chlorophenyl)-1H-tetrazole (Table 4, entry 2)
The title compound was obtained as a white solid, mp
132–1348C (lit. 1378C[51]), dH (400 MHz, DMSO) 8.07
(m, 1H), 8.01–8.04 (m, 1H), 7.63–7.60 (m, 2H), 6.13 (s, 1H).
90
85
80
75
70
65
60
5-(3-Nitrophenyl)-1H-tetrazole (Table 4, entry 4)
The title compound was obtained as a white solid, mp
149–1518C (lit. 154–1568C[51]), dH (400 MHz, DMSO) 8.82
(s, 1H), 8.44–8.4 (m, 1H), 7.10 (d, J 7.2, 1H), 7.89 (t, J 8, 1H).
vmax (KBr)/cmꢁ1 3852, 3308, 3085, 2975, 2894, 2752, 1621,
1524, 1348, 1243, 1156, 1076, 1011, 912, 865, 819, 727.
5-(4-Bromophenyl)-1H-tetrazole (Table 4, entry 6)
5
4
3
2
1
The title compound was obtained as a white solid, mp 2658C
(lit. 2648C[52]), dH (400 MHz, DMSO) 7.97–8.00 (m, 2H),
7.82–7.86 (m, 2H). vmax (KBr)/cmꢁ1 3443, 2956, 2923, 2861,
2766, 1601, 1423, 1317, 1152, 1055, 998, 734.
Run
Fig. 7. Reusability of the Ni (II) immobilized on peptide nanofibre for the
synthesis of bis (p-chlorophenyl) amine.
Table 5. Comparison of CuNP- and NiNP-PNF for the synthesis of 5-(4-Bromophenyl)-1H-tetrazole with previously reported procedures
Entry
Catalyst
Solvent
Yield [%]A
Time [h]
Ref.
[35]
[18]
[36]
[37]
[38]
1
2
3
4
5
6
7
MCMBSA
DMF
PEG
DMF
DMF
DMF
PEG
PEG
78
95
90
91
96
95
90
12
3
CuII immobilized on Fe3O4@SiO2@L-arginine
copper(I) chloride
nano-TiCl4.SiO2
12
2
AlCl3 on g-Al2O3
CuNP-PNF
1.5
2
This work
This work
NiNP-PNF
3
AIsolated yields.
Table 6. Comparison of CuNP- and NiNP-PNF for the synthesis diphenylamine with previously reported procedures
Entry
Catalyst
Phenylating reagent
Solvent
Base
Yield [%]A
Temp. [8C]
Time [h]
Ref.
[39]
[40]
[41]
[42]
[43]
1
2
3
4
5
6
7
CuI
PhI
DMF
K2CO3
NaOAc
K3PO4
NaOt-Bu
KOtBu,
KOH
79
83
94
94
94
80
85
110
100
80
20
10
17
16
1.5
6
Pd(OAc)2
CuI (Ligand)
Ni (cod)2
CuIITMHD
CuNP-PNF
NiNP-PNF
PhGeMe3
toluene
DMSO
DMF
PhI
Aryl imidazolylsulfonates
PhI
105
120
120
120
toluene
DMSO
DMSO
benzoic acid
benzoic acid
This work
This work
KOH
5
AIsolated yields.

J
A. Ghorbani-Choghamarani and Z. Taherinia
5-(4-Nitrophenyl)-1H-tetrazole (Table 2, entry 3)
[11] D. Habibi, M. Nasrollahzadeh, L. Mehrabi, S. Mostafaee, Monatsh.
Chem. 2013, 144, 725. doi:10.1007/S00706-012-0871-9
[12] A. R. Kazemizadeh, N. Hajaliakbarib, R. Hajianb, N. Shajaria,
A. Ramaza, Helv. Chim. Acta 2012, 95, 594. doi:10.1002/HLCA.
201100327
[13] P. Mani, A. K. Singh, S. K. Awasthi, Tetrahedron Lett. 2014, 55, 1879.
doi:10.1016/J.TETLET.2014.01.117
[14] M. Parveen, F. Ahmad, A. M. Malla, S. Azaz, New J. Chem. 2015, 39,
The title compound was obtained as a yellow solid, mp 214–
2178C (lit. 2188C[52]), dH (500 MHz, DMSO) 8.55 (d, J 8.8, 1H),
8.29 (d, J 8.65, 1H). vmax (KBr)/cmꢁ1 3508, 3101, 2967, 2919,
2854, 2547, 1646, 1608, 1521, 1349, 1156, 1101, 1024, 991,
721, 696.
2028. doi:10.1039/C4NJ02079K
[15] A. Kumar, R. Narayanan, H. Shechter, J. Org. Chem. 1996, 61, 4462.
doi:10.1021/JO952269K
[16] S. Hajra, D. Sinha, M. Bhowmick, J. Org. Chem. 2007, 72, 1852.
doi:10.1021/JO062432J
5-Phenyl-1H-tetrazole (Table 2, entry 8)
The title compound was obtained as a white solid, mp 225–
2278C (lit. 214–2168C[52]), dH (500 MHz, DMSO) 8.04–8.02
(m, 2H), 7.61–7.57 (m, 3H).
[17] M. Nikoorazm, A. Ghorbani-Choghamarani, M. Khanmoradi, Appl.
Organomet. Chem. 2016, 30, 705. doi:10.1002/AOC.3494
[18] A. Ghorbani-Choghamarani, L. Shiri, G. Azadi, RSC Adv. 2016, 6,
32660.
[19] D. Habibi, M. Nasrollahzadeh, Y. Bayat, Synth. Commun. 2011, 41,
2135. doi:10.1080/00397911.2010.497728
[20] G. Venkateshwarlu, A. Premalatha, K. C. Rajanna, P. K. Saiprakash,
Synth. Commun. 2009, 39, 4479. doi:10.1080/00397910902917682
[21] A. N. Chermahini, A. Teimouri, F. Momenbeik, A. Zarei, Z.
Dalirnasab, A. Ghaedi, M. Roosta, J. Heterocycl. Chem. 2010, 47,
913. doi:10.1002/JHET.382
2-(1H-Tetrazol-5-yl) phenol (Table 4, entry 10)
The title compound was obtained as a white solid, mp 2248C
(lit. 224–2258C[51]), dH (400 MHz, DMSO) 8.00–8.02 (m, 1H),
7.40–7.44 (m, 1H), 7.08–7.11 (m, 1H), 6.99–7.03 (m, 1H), 11.10
(br, 1H), 15.73 (br, 1H).
Recoverability and Reusability of NiNP-PNF
The reaction was performed in DMSO at 1308C, using 4-
chlorobenzoic acid (1.3 mmol), 4-chloroaniline (3 mmol), and
KOH (7 mmol) in the presence of NiNP-PNF (200 mL). Upon
completion of the reaction, the mixture was cooled to room
temperature. The organic layer was extracted with ethyl acetate
(2 ꢃ 20 mL), which led to the precipitation of NiNP-PNF. The
resulting precipitate was washed with ethyl acetate (2 ꢃ 20 mL)
and dried before being used in the next run.
[22] M. Zaarour, M. El Roz, B. Dong, R. Retoux, R. Aad, J. Cardin,
C. Dufour, F. Gourbilleau, J.-P. Gilson, S. Mintova, Langmuir 2014,
30, 6250. doi:10.1021/LA5006743
[23] R. Kou, Y. Shao, D. Mei, Z. Nie, D. Wang, C. Wang, J. Liu, J. Am.
Chem. Soc. 2011, 133, 2541. doi:10.1021/JA107719U
[24] C. M. Crudden, M. Sateesh, R. Lewis, J. Am. Chem. Soc. 2005, 127,
10045. doi:10.1021/JA0430954
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2002, 107, 56. doi:10.1016/S0378-7753(01)00980-6
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2378. doi:10.1039/B100618P
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[28] S. Zhang, Biotechnology 2004, 22, 151.
[29] H. Zhao, Y. Wei, J. Xu, J. Kan, W. Su, M. Hong, J. Org. Chem. 2011,
Conflicts of Interest
The authors declare no conflicts of interest.
76, 882. doi:10.1021/JO102175F
[30] Z. Duan, S. Ranjit, P. Zhang, X. Liu, Chem. – Eur. J. 2009, 15, 3666.
doi:10.1002/CHEM.200900133
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doi:10.1002/ANIE.201208755
Acknowledgement
The authors thank the research facilities of Ilam University, Ilam, Iran, for
financial support of this research project.
[32] Y. Zhang, S. Patel, N. Mainolfi, Chem. Sci. 2012, 3, 3196. doi:10.1039/
C2SC20606D
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