A capable cobalt nano-catalyst for the N-formylation of various amines and its biological activity studies

Article abstract of DOI:10.1002/aoc.3874

The Fe₃O₄ magnetic nanoparticles (Fe₃O₄ MNPs) were modified with 1,10-phenanthroline-5,6-diol and the relevant Co complex (Fe₃O₄@Phendiol@Co) synthesized as a nano-magnetic heterogeneous catalyst to be used for the N-formylation of various amines at room temperature under solvent-free conditions. Also, in order to find the better concept of the catalyst role, the N-formylation reaction was carried out by the use of ultrasound irradiation in the absence of the Co nano-catalyst and the results were compared. The catalyst characterized by different methods such as the elemental analysis (CHN), ICP, FT-IR, XRD, EDX, SEM, TEM, TG-DTA, VSM and XPS. In addition, the antioxidant and the antibacterial activities of the Fe₃O₄@Phendiol@Co nano-catalyst and its Phendiol ligand were in vitro screened by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and disc diffusion methods. Results showed that they possess strong antioxidant activity (IC₅₀; 0.182?±?0.006?mg/ml) and good antibacterial potential in comparison to standards.

Full text of DOI:10.1002/aoc.3874

Received: 12 March 2017
DOI: 10.1002/aoc.3874
Revised: 8 April 2017
Accepted: 12 April 2017
F U L L PA P E R
A capable cobalt nano‐catalyst for the N‐formylation of various
amines and its biological activity studies
Davood Habibi
| Somayyeh Heydari | Mina Afsharfarnia
Department of Organic Chemistry, Faculty of
Chemistry, Bu‐Ali Sina University, Hamedan
The Fe O magnetic nanoparticles (Fe O4 MNPs) were modified with 1,10‐
3
4
3
6
517838683, Iran
phenanthroline‐5,6‐diol and the relevant Co complex (Fe O @Phendiol@Co) syn-
3
4
thesized as a nano‐magnetic heterogeneous catalyst to be used for the N‐formylation
of various amines at room temperature under solvent‐free conditions. Also, in order
to find the better concept of the catalyst role, the N‐formylation reaction was carried
out by the use of ultrasound irradiation in the absence of the Co nano‐catalyst and
the results were compared. The catalyst characterized by different methods such
as the elemental analysis (CHN), ICP, FT‐IR, XRD, EDX, SEM, TEM, TG‐DTA,
VSM and XPS. In addition, the antioxidant and the antibacterial activities of the
Fe O @Phendiol@Co nano‐catalyst and its Phendiol ligand were in vitro screened
Correspondence
Davood Habibi, Department of Organic
Chemistry, Faculty of Chemistry, Bu‐Ali
Sina University, Hamedan 6517838683, Iran.
Email: davood.habibi@gmail.com
3
4
by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and disc diffusion
methods. Results showed that they possess strong antioxidant activity (IC ;
50
0.182 ± 0.006 mg/ml) and good antibacterial potential in comparison to standards.
KEYWORDS
,10‐Phenanthroline‐5,6‐diol, biological activity studies, Co complex, Fe
heterogeneous catalyst, N‐formylation, synthesis
1
3 4
O magnetic nanoparticles,
[
6]
1
| INTRODUCTION
catalysts. K.V. Reddy and coworkers reported a facile
method for the N‐formylation of primary and secondary
amines by liquid phase oxidation of methanol in the presence
Introduction of a formyl group into the compounds has a very
long story and despite some published papers which have
mentioned that L.F. Fieser and J.E. Jones were two chemists
that reported the N‐formylation of amines in 1955, appar-
ently, F. Just was a first chemist who formylated
phenylhydrazine with formamide in 1886, and several
chemists proposed different procedures later. H.R. Hirst and
J.B. Cohen obtained N‐methylformamide by heating
methylaniline with formamide in glacial acetic acid solu-
[
7]
of hydrogen peroxide over basic copper hydroxyl salts. M.
A. Pasha and coworkers applied Amberlite IR‐120 as a reus-
able catalyst for N‐formylation of amines with formic acid in
microwave condition. The semiconductor catalyzed N‐
formylation of a variety of amines using formic acid as
formylating agent has been investigated by M. Swaminathan
and B. Krishnakumar and they were found that primary and
secondary amines to react efficiently with formic acid in the
[1]
[
8]
[2]
[
3]
tion.
G. Pettit and E. Thomas reported the facile
presence of TiO ‐P25 or sulfated Titania giving N‐formyl
2
formylation of aromatic amines with dimethylformamide in
derivatives in high yields at room temperature. Sulfated Tita-
[4]
the presence of sodium methoxide.
A.K. Bose and
nia is found to be more efficient and reusable than TiO ‐P25
2
[
9]
coworkers reported the microwave‐induced organic reaction
enhancement chemistry technique for the N‐formylation of
aliphatic and aromatic amines and amino heterocycles with
for N‐formylation of amines.
Also, several other formylating reagents have been devel-
[
10–24]
oped
for different purposes (protection of amino group,
[5]
aqueous formic acid. P.S. Rao and coworkers reported the
synthesis of pharmaceutical compounds, etc.), but due to
some difficulties such as formation of side products, thermal
N‐formylation of amines using ZnCl as novel Lewis acids
2
Appl Organometal Chem. 2017;e3874.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 14
https://doi.org/10.1002/aoc.3874

2
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HABIBI ET AL.
instability, long reaction times and the application of expen-
sive reagents, still there are high demands for new methods.
In continuation to our synthesis of the N‐containing com-
separated by filtration and washed with ethanol (20 ml).
The product was dried briefly in air and then in Vacuo.
[
25–32]
pounds,
nient procedure for the N‐formylation of anilines with formic
acid as formylating agent in the presence of
Fe O @Phendiol@Co nano‐catalyst as a heterogeneous cata-
we intend to report a mild, efficient and conve-
2
.1.3 | Surface modification of Fe O MNPs
3 4
[36]
with the Phendiol ligand (Fe O @Phendiol)
3
4
a
Fe O MNPs (0.5 g) were dispersed in water/ethanol solution
3 4
3
4
lyst under solvent‐free conditions at room temperature
Scheme 1).
(50 ml, 1:1) by sonication at room temperature for 20 min.
Then Phendiol ligand (0.25 g, 1.8 mmol) dissolved in ethanol
(
(5 ml) was added and placed under ultrasound irradiation for
3
hours. Then, Fe O @Phendiol was separated by an exter-
3
4
nal magnet, washed with ethanol (20 ml) and dried under
vacuum at 50 °C for 2 h.
2
| EXPERIMENTAL
2
.1 | Synthesis of Fe O @Phendiol@Co nano‐
3
4
catalyst
2
.1.4 | General procedure for preparation of
the Fe O @Phendiol@Co nano‐catalyst
2
.1.1 | General procedure for preparation of
3
4
[
33]
Fe O MNPs
3
4
Fe O @Phendiol (0.2 g) and Co(OAc) .4H O (0.747 g,
3
4
2
2
3
mmol) were mixed in ethanol (30 ml) and placed in an
The mixture of FeCl .6H O (11.44 g) and FeCl .4H O
3
2
2
2
ultrasonic bath for 3 h at room temperature. The resulting cat-
alyst was separated with an external magnet, washed with
ethanol (20 ml), dried in vacuum at 70 °C for 6 h, and kept
in a desiccator.
(
4.3 g) was dissolved in water (100 ml), and the solution
stirred for 0.5 h in 80 °C. The solution of 37% ammonia
was then added dropwise with vigorous stirring which a
black solid product obtained when a reaction media reached
to pH 10. The mixture was heated for 0.5 h at 70 °C and
the magnetite solid product filtered, washed with water
2
.2 | Typical procedure for the N‐formylation
(3 × 20 ml) and dried at 80 °C for 12 h.
of various amines by the Fe O @Phendiol@Co
3
4
A mixture of amine (1 mmol), formic acid (1.2 mmol), and
the Co nano‐catalyst (20 mg) was stirred at room temperature
until the TLC monitoring showed no further progress. After
washing the mixture with water, ethyl acetate (20 ml) was
added, the catalyst was separated by a strong magnet, the sol-
vent removed and the product recrystallized in ethanol.
2
.1.2 | Synthesis of a ligand
[
34]
Synthesis of 1,10‐phenanthroline‐5,6‐dione
An ice cold mixture of concentrated H SO (40 ml) and
HNO (20 ml) was added to 1,10‐phenanthroline (4.0 g,
2
4
3
22.2 mmol) and KBr (4.0 g, 33.6 mmol). The mixture was
heated at reflux for 4 h. The hot yellow solution was poured
over ice (500 ml) and neutralized carefully with NaOH until
2
.3 | Typical procedure for the N‐formylation
of various amines by the use of ultrasound
irradiation
neutral to slightly acidic pH. Extraction with CHCl followed
3
by drying with Na SO and removal of solvent gave 4.5 g
2
4
(
96%) of 1,10‐phenanthroline‐5,6‐dione.
A mixture of amine (1 mmol), formic acid (2.5 mmol), was
stirred by the use of ultrasound irradiation at room tempera-
ture until the TLC monitoring showed no further progress.
After addition of water (20 ml), the organic layer was sepa-
rated by ethyl acetate (20 ml); the solvent concentrated and
the solid recrystallized in ethanol.
[
35]
Synthesis of 1,10‐phenanthroline‐5,6‐diol (Phendiol)
mixture of 1,10‐phenanthroline‐5,6‐dione (0.70 g,
A
3
3
.33 mmol) and rubeanic acid (dithiooxamide, 0.480 g,
.99 mmol) was refluxed in ethanol (25 ml) for 16 h. Upon
cooling of the reaction mixture to room temperature, the
product in the form of a yellow‐brown precipitate was
2.4 | Apparatus and reagents
The IR spectra (KBr) were recorded on Perkin–Elmer GX
Fourier transform infrared spectrometer (FT‐IR). The NMR
spectra were recorded on a Bruker Ultra‐Shield 400 spectrom-
eter. The TEM images were recorded on a Zeiss‐EM10C‐80
KV transmission electron microscope, and the SEM images
were recorded on a Philips XL‐30 scanning electron
SCHEME 1 N‐formylation of amines by the Co nano‐catalyst

HABIBI ET AL.
3 of 14
microscope. The XRD measurements were done by a Bruker
D8 Advance powder diffractometer, using Cu Kα (λ = 1.54
A°) as the incident radiation. Size distributions were measured
by the Zetasizer Nano‐ZS‐90 (ZEN 3600, MALVERN) instru-
ment. In addition, the ICP measurements for the metal content
evaluation were performed using a Perkin‐Elmer ICP/6500.
Magnetic measurements were carried out at room temperature
using an Iranian Meghnatis Daghigh Kavir Co Vibrating
Sample Magnetometer (VSM). Chemicals and solvents were
purchased from the Merck and Aldrich chemical companies
and used without further purification.
3.2.1 | Characterization of the catalyst by the
elemental analysis (CHN) and ICP
The elemental analysis report for the C, and N elements was
about 16.43 and 0.16 respectively. The ICP analysis of the cat-
alyst showed that the Co content of the Fe O @Phendiol@Co
3
4
nano‐catalyst was about 0.255 mmol/g.
3.2.2 | Characterization of the catalyst by the
IR spectroscopy
The N‐formylation reaction of aniline with formic acid
was carried out in two different conditions: i) by the use of
the Co nano‐catalyst at room temperature under solvent‐free
conditions, and ii) by the use of ultrasound irradiation in
the absence of the Co nano‐catalyst.
Figure 1 shows the three FT‐IR spectra of: Fe O MNPs
3
4
(
blue), Fe O @Phendiol (green), and Fe O @Phendiol@Co
3 4 3 4
(
red). Fe O4 MNPs exhibits basic characteristic peak at
3
−
1
approximately 580 cm which was attributed to the presence
of the Fe–O stretching vibrations. The FT‐IR spectrum of
Fe O @Phendiol shows several original signals located at
the 3020–3066 cm (C‐H of pyridine ring), the peaks at
1
Both methods were comprehensively explained in the
Sections 2.2 and 2.3.
3
4
−
1
434–1437 cm− (C = C of pyridine ring) and 1670
1
3
| RESULTS AND DISCUSSION
.1 | Synthesis of Fe O @Phendiol@Co
(C = N of ligand). It could be concluded from the above
results that the Fe O4 MNPs was modified successfully.
3
3
Comparison of the two IR spectra (blue and green) confirms
anchoring of the Phendiol ligand on the surface of the mag-
netic nanoparticles. Furthermore, after complexing of Co with
3
4
nano‐catalyst
Synthesis of Fe O @Phendiol@Co catalyst was carried out
3
4
−
1
Fe O @Phendiol, the weak absorption peak at 413 cm was
3
4
via the four stages which comprehensively described in the
experimental section (Scheme 2).
appeared which is attributed to the Co‐N bands.
3
.2 | Characterization of
Fe O @Phendiol@Co nano‐catalyst
3
4
Formation of the Co nano‐catalyst was verified using the
CHN analysis, inductively coupled plasma.
(
ICP), FT‐IR, X‐ray diffraction (XRD), dispersive X‐ray
spectroscopy (EDX), scanning electron microscope.
SEM), transmission electron microscope (TEM),
(
thermogravimetry‐differential thermal analysis (TG‐DTA),
vibrating sample magnetometer (VSM) and XPS (X‐ray pho-
toelectron spectroscopy).
FIGURE 1 The IR spectra of Fe O MNPs (blue), Fe O @Phendiol
(green), and the Fe O @Phendiol@Co catalyst (red)
3 4
3
4
3 4
SCHEME 2 Schematic synthesis of the
Fe O @Phen@Co nano‐catalyst
3 4

4
of 14
HABIBI ET AL.
3
.2.3 | Characterization of the catalyst by the
XRD patterns
Figure 2 shows the XRD patterns of Fe O MNPs and the
3
4
Fe O @Phendiol@Co nano‐catalyst. The XRD pattern
3
4
exhibited peaks at 2θ of 10, 15–20, 30, 35, 43, 53, 57
and 63 correspond to the spinal structure of Fe O MNPs.
3
4
The XRD pattern of the Fe O @Phendiol@Co nano‐cata-
3
4
lyst exhibited broadened pattern due to its non‐crystalline
nature at 2θ = 30, 35, 43, 53, 57 and 63.
3
.2.4 | Characterization of the catalyst by the
EDX analysis
The chemical composition of the Fe O @Phendiol@Co cat-
3
4
alyst was determined by the EDX analysis (Figure 3). The
provided scans showed the presence of the anticipated ele-
ments in the structure of the catalyst, namely carbon, oxygen,
nitrogen, iron and cobalt.
3
.2.5 | Characterization of the catalyst by the
SEM and the TEM images
The morphology and the particle size distribution of the Co
nano‐catalyst were determined by the.
SEM and TEM images (Figures 4 and 5). According to
these figures, the nanoparticles appearance and their sizes
are similar, indicating that the Co nano‐catalyst purposely
coated to have good mechanical stability and have not been
destroyed during the whole modification. Also, the SEM
images of the Co nano‐catalyst showed that the sizes of the
catalysts are between 11.5 to about 14 nm.
FIGURE 3 The EDX analysis of Fe
Fe O @Phendiol@Co nano‐catalyst (right)
3 4
3
O
4
@Phendiol (left) and the
losses at 50 and 125 °C are probably due to the residual
water, the third step at 250 °C is attributed to the thermal
decomposition of the complex, and the fourth step is proba-
bly due to the thermal decomposition the Phendiol ligand
coating layers. On the basis of these results, the well grafting
of ligand groups on the support is verified and indicated that
the nano‐catalyst has approximately a good thermal stability
which is probably due to the strong interaction between the
Phendiol ligand and Fe O MNPs.
3
.2.6 | Characterization of the Co nano‐cata-
lyst by the TG‐DTA technique
The
thermogravimetric
analysis
curves
of
the
Fe O @Phendiol@Co nano‐catalyst show the mass loss of
3
4
3 4
the organic materials as they decompose upon heating
Figure 6). It can be observed that the nano‐catalyst shows
about four weight loss steps in the temperature range of 50,
25, 250 and 330 °C, respectively. The initial two weight
(
3
.2.7 | Characterization of the Co nano‐cata-
lyst by the VSM technique
1
The VSM analyses of Fe O MNPs (A), Fe O @Phendiol
3
4
3 4
(
B) and the Fe O @Phendiol@Co nano‐catalyst (C) were
3
4
performed in order to demonstrate their magnetic properties
(Figure 7). As can be seen, all three compounds have mag-
netic properties; however, magnetization of B (52 emu/g)
and C (about 16 emu/g) were decreased to some extent in
comparison with A (62 emu/g). This can be explained by
considering the reduction in the dipolar–dipolar interactions
between the magnetic nanoparticles after their modification
with the Phendiol ligand and complexation with the Co ions
which cause the more coating of Fe O MNPs.
FIGURE 2 The XRD patterns of Fe
Fe @Phendiol@Co catalyst
3
O
4
MNPs, and the
3 4
O
3
4

HABIBI ET AL.
5 of 14
FIGURE 5 The TEM images of the Fe
3
O
4
@Phendiol@Co nano‐
catalyst
3
3
.3 | Optimization of the reaction conditions
.3.1 | Optimization of N‐formylation
reactions by the Co nano‐catalyst
The next investigation of this study was to optimize the
N‐formylation reaction conditions (Table 1). Therefore,
the catalytic activity of the Fe O @Phendiol@Co nano‐
3
4
catalyst was investigated in the N‐formylation reaction of
aniline with formic acid as a model reaction in different
conditions (temperature, amount of the catalyst and
solvent). The best result was obtained with aniline/formic
acid with the molar ratio of 1:1.2 with 20 mg of the Co
nano‐catalyst at room temperature under solvent‐free con-
ditions (entry 2).
3 4
FIGURE 4 The SEM images of Fe O @Phendiol (left) and the
Fe
3
O
4
@Phendiol@Co nano‐catalyst (right)
3.3.2 | Optimization of N‐formylation
reactions by the use of ultrasound irradiation
3
.2.8 | Characterization of the catalyst by the
In order to find the better concept of the catalyst role, the
model reaction (the N‐formylation reaction of aniline with
formic acid) was carried out in different reaction condi-
tions (temperature, amount of the catalyst and solvent),
by the use of ultrasound irradiation in the absence of
the Co nano‐catalyst and the results were compared
(Table 2). The best result was obtained with aniline/
formic acid with the molar ratio of 1:2.5 with 20 mg of
XPS spectroscopy
The XPS spectrum relating to the core level presence of the
Co 2p is shown in Figure 8. The binding energy shows two
peaks at 794.0 and 811.2 which are attributed to the presence
of the Co 2p3/2 and Co 2p1/2, respectively. These data con-
firm the formation of the Fe O @Phendiol@Co nano‐cata-
3
4
[37]
lyst as well as the Co(II) oxidation state.

6
of 14
HABIBI ET AL.
FIGURE 6 TG‐DTA patterns of the Fe
3
O
4 2
@Phendiol@Co nano‐catalyst in N atmosphere
the Co nano‐catalyst at room temperature under solvent‐
free conditions (entry 9).
literature. The structures of the N‐formylated products were
in agreement with their IR and NMR spectra. In the IR spec-
tra, the NH2 peaks (two lines similar to the doublet in
HNMR), was disappeared and one strong absorption band
−1
3
3
.4 | N‐formylation of various amines
.4.1 | N‐formylation by the Co nano‐catalyst
appeared instead (N‐H stretching band, ̴3 300 cm ). Also,
−
1
one strong absorption band appeared at
̴1 700 cm which is
attributed to the carbonyl group.
According to the optimized reaction conditions, the syntheses
of various formamide derivatives were carried out from the
reaction of amines, formic acid, and the Fe O @Phendiol@
3
4
Co nano‐catalyst at room temperature (Table 3).
3
3
.6 | The plausible mechanism
The results showed that the Co nano‐catalyst was effec-
tive for application of various amines with electron releasing
or electron withdrawing groups (Entries 2–7 and 13–15).
Those compounds with the OH groups do not participate in
the reaction, probably due to the reactions with formic acid
.6.1 | Mechanism of N‐formylation reaction
by the Co nano‐catalyst
The plausible mechanism for the N‐formylation of amines by
formic acid in the presence of the Co nano‐catalyst is shown
in Scheme 3. The proposed mechanism is probably due to the
Lewis acidity of the Co nano‐catalyst by attaching to the car-
bonyl group to facilitate the nucleophilic attack of the amine
to form the intermediate with the subsequent formation of the
final product.
(Entries 16 and 17).
3
.4.2 | N‐formylation of amines by the use of
ultrasound irradiation
A mixture of amine and formic acid was stirred by the use of
ultrasound irradiation at room temperature until the TLC mon-
itoring showed no further progress. After addition of water,
the organic layer was separated by ethyl acetate; the solvent
concentrated and the solid recrystallized in ethanol (Table 4).
3
.6.2 | Mechanism of the N‐formylation
reaction by the use of ultrasound irradiation
Breaking of the C‐O bond in formic acid and the N‐H bond in
amine will accelerate formation of the product. Energy of the
bond dissociations will come from the formation of the
bubbles and their bursting by the help of the ultrasound
irradiation (Scheme 4).
3
.5 | Characterization of the N‐formylated
products:
All known compounds were characterized by comparing
their physical and spectral data with those reported in the

HABIBI ET AL.
7 of 14
FIGURE 8 The XPS spectrum of the Co(II) catalyst
in situ formation of harmful, toxic and corrosive mate-
rials, long reaction times, use of relatively high tempera-
ture, relatively low yields, difficulties in preparation of
the catalyst, formation of by‐product and impurities, hard
work‐up, use of homogeneous catalyst which cannot eas-
ily be recovered and reused, and the use of expensive cat-
[
38–56]
alyst.
None of the mentioned disadvantages are relatively
observed in our suggested procedure and the reactions were
taken place at room temperature under solvent‐free
conditions.
3
3
.8 | The biological activity studies
.8.1 | Antioxidant activity
Free radical scavenging activity of the compounds was mea-
[
57]
sured according to Mensor et al.
In order to obtain dilu-
tions, different concentrations of samples were prepared in
methanol (0.2 to 1.0 mg/ml) and 2.5 ml of each concentration
were added to 1.0 ml of alcohol solution of DPPH (0.3 mM).
The samples were first kept in darkness at room temperature
for 30 min and then bleaching of DPPH was read at 517 nm
against a blank (methanol). The inhibition in percent for each
concentration was calculated according to the following for-
mula: DPPH free radical scavenging (%) = [1–(A –A )/
s
b
A ] × 100, where, A is an absorbance of the reaction mixture
c
s
containing 2.5 ml of samples +1 ml of DPPH, A is an absor-
b
bance of the reaction mixture containing 2.5 ml of samples
+
1 ml of methanol and A is an absorbance of the control
c
3 4 3 4
FIGURE 7 The VSM analyses of Fe O (a), Fe O @Phendiol (B)
and the Fe O @Phendiol@Co nano‐catalyst (C)
3 4
sample containing 1 ml of DPPH +2.5 ml of methanol. Also
IC50 value, which represents the concentration of the sample
causing 50% inhibition, was determined. Tests were carried
out in triplicate and ascorbic acid was used as a positive
control.
3
.7 | Comparison of the catalytic performance
of the Co nano‐catalyst with the other catalysts
3.8.2 | Antibacterial activity
Several synthetic methods have been reported for the N‐
formylation reactions, but most of them are suffering from
some disadvantages such as the harsh reaction condition,
The potential antibacterial effects of the complexes were
evaluated against a panel of microorganisms including two

8
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HABIBI ET AL.
TABLE 1 Optimization of the N‐formylation reaction by the Co nano‐catalyst
Entry
Nano‐catalyst (mg)
Aniline (mmol)
HCOOH (mmol)
Time (min)
Yield (%)
1
2
3
4
5
20
20
20
40
40
1.0
1.0
1.0
1.0
1.0
1.0
1.2
1.5
1.2
1.5
20
15
15
15
15
90
95
94
94
95
TABLE 2 Optimization of the amine N‐formylation reaction by the use of ultrasound irradiation
Entry
Aniline (mmol)
HCOOH (mmol)
(°C)Temprature
Time (min)
Yield %
a
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
1
1
1
r.t.
r.t.
r.t.
60
60
r.t.
r.t.
r.t.
r.t.
r.t.
40
50
50
0
a
2
50
0
a
3
300
0
a
1
190
20
30
94
95
97
97
96
95
96
a
2
300
b
1
120
b
1.5
2
120
b
50
b
2.5
5
5
b
1
1
1
0
1
2
5
b
2.5
2.5
5
b
5
a
In the absence of ultrasound irradiation,
b
in the presence of ultrasound irradiation
TABLE 3 N‐formylation of amines by the Co nano‐catalyst
Entry
Starting material (1a–q)
Product (2a–o)
Time (min)
Yield (%)
1
15
90
2
15
95
3
4
20
8
91
91
5
15
93
(Continues)

HABIBI ET AL.
9 of 14
TABLE 3 (Continued)
Entry
Starting material (1a–q)
Product (2a–o)
Time (min)
Yield (%)
6
20
91
7
8
15
20
92
92
9
35
89
89
1
0
1
115
1
25
83
1
1
2
3
25
88
95
200
1
4
5
12
15
95
93
1
1
6
7
No reaction
No reaction
‐
‐
‐
‐
1
Gram‐positive [namely Bacillus cereus (PTCC 1247) and
Staphylococcus aureus (ATCC 25923)], and also two Gram‐
negative bacteria [namely Escherichia coli (ATCC 35218)
and Pseudomonas aeruginosa (ATCC 27853)]. Stock cul-
tures were maintained on nutrient agar media at 40 °C, then
subculture in nutrient Broth media at 37 °C, prior to each
antibacterial test. The complexes were dissolved in DMSO
to a final concentration of 1 mg/ml and then sterilized by filtra-
tion using 0.45 μm Millipore. Negative controls were prepared
by using DMSO and salts, and penicillin and gentamicin used
as positive reference standards. The diameters of the generated
inhibition zones by the complexes were measured as well.
[58]

1
0 of 14
HABIBI ET AL.
TABLE 4 N‐formylation of various amines by the use of ultrasound irradiation
Entry
Starting material
Product
Time (min)
Yield %
1
2
96
2
35
96
2
4
5
6
7
8
9
200
17
100
2
95
96
96
95
95
93
93
92
2
75
16
35
1
1
0
1
190
8
91
95
1
2
3
1
200
95
1
4
5
10
15
94
92
1
1
6
7
No reaction
‐
‐
‐
‐
1
No reaction

HABIBI ET AL.
11 of 14
SCHEME 3 Suggested mechanism for
the N‐formylation of amines by the Co nano‐
catalyst
SCHEME 4 N‐formylation of amines by
formic acid and the use of ultrasound
irradiations
[
59,60]
3
.8.3 | Statistical analysis
agents.
Results from antibacterial assessments of the
samples, positive and negative controls are presented in
Tables 6 and 7. The studied compounds were dissolved in
DMSO at concentrations of 0.01, 0.1 and 1.0 mg/ml. Since
DMSO was used as a solvent, it was also screened as
negative control against all bacteria in this study and no
activity was found. In this research, assessment of antibacte-
rial properties of the compounds showed the acceptable
concentration‐dependent inhibition effect in comparison
with some of positive controls. Old studies showed that
generally biological activity of compounds is attributed
mainly to its major components and also synergistic or
antagonistic effect of components in minor percentage of
All data are the average of triplicate analysis, and the variance
analysis was performed by the Excel procedures. Statistical
analysis was performed using student's t‐test and p value
<
0.05 was regarded as significant.
3
.8.4 | Antioxidant capacity
Our results showed that the synthesized compounds showed
excellent dose‐dependent (0.2–1 mg/ml) antiradical
properties (43.22 to 72.12%) (Table 5).
In all antioxidant assays, more activity is reflected in a
[
61]
lower IC value. Vitamin C (ascorbic acid) as a synthetic
50
reaction mixture
Among bacterial species taken in this
antioxidant represented the IC50 value lowers than of all the
compounds studied here (Figure 9). The effectiveness of the
compounds as DPPH radical scavengers ranged in the follow-
ing descending order: ascorbic acid (0.124 ± 0.004 mg/
ml) > C1 (0.182 ± 0.006 mg/ml) > C2 (0.570 ± 0.010 mg/ml).
study, E. coli (−) showed more resistance against all the
compounds. When comparing the antibacterial activity of
the studied samples, especially the Co complex to those of
the reference antibiotics, the inhibitory ability of some of
the compounds was found to be good. For example, while
all bacteria tested are resistant to penicillin, the antibacterial
effect of C1 was higher than those of penicillin on these
bacteria. The results indicate that the C1 and roughly the
C2 compounds can be used in the treatment of diseases
caused by the tested bacteria.
3
.8.5 | Antibacterial activity
As it is well known, Staphylococcus aureus (+), Escherichia
coli (−) and Bacillus species are agents of food poisoning
TABLE 5 Free radical scavenging activity (%) of the compounds (C1: The Co nano‐catalyst) and (C2: The Phendiol ligand) at different concen-
trations and standard. Experiment was performed in triplicate and expressed as mean ± SD. Values within column with different superscripts (a, b and
c) are significantly different (P < 0.05)
Concentration (mg/ml)
Compound
0.2
0.4
0.6
0.8
1
Average
64.55
a
a
a
a
a
a
b
b
a
c
b
a
c
c
a
C1
52.83 ± 0.9
55.21 ± 1.3
68.43 ± 2.8
74.16 ± 2.2
72.12 ± 1.6
C2
43.22 ± 0.5
80.74 ± 2.7
47.18 ± 2.9
82.16 ± 1.0
52.63 ± 2.1
81.85 ± 1.4
51.13 ± 0.9
80.31 ± 1.1
66.28 ± 2.3
79.14 ± 1.6
52.10
80.84
Ascorbic acid

1
2 of 14
HABIBI ET AL.
1
H NMR (90 MHz, acetone‐d ): δ = 8.93 (s, 1H), 8.36–6.95
6
H
(m, 5H).
N‐(4‐Nitrophenyl)formamide (entry 3): M.p. 196–
97 °C; FT‐IR (KBr, cm− ): 3265, 3091, 1688, 1620,
597, 1563, 1505, 1412, 1337, 1303, 1271, 1178, 1156,
1
1
1
1
1
112, 854, 773, 753, 689; H NMR (90 MHz, acetone‐
d6): δH = 9.77 (s, 1H), 8.49 (s, 1H), 8.25 (d,
J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H).
N‐(4‐Chlorophenyl)formamide (entry 4): M.p. 100–
−
1
1
7
1
02 °C; FT‐IR (KBr, cm ): 3259, 3060, 1686, 1669,
1
83, 611; H NMR (300 MHz, CDCl ): δ = 8.65 (s,
3
H
H), 8.34 (s, 1H), 7.67–7.02 (m, 4H).
N‐(4‐Bromophenyl)formamide (entry 5): M.p. 116–
−
1
FIGURE 9 Comparison of the DPPH radical scavenging ability
1
7
1
18 °C; FT‐IR (KBr, cm ): 3283, 3051, 1673, 1599,
(IC50 value) of the studied compounds (C1 and C2), and ascorbic acid
1
55, 571; H NMR (90 MHz, CDCl ): δH = 8.61 (s,
3
(as a positive control)
H), 7.46–6.52 (m, 4H), 6.31 (s, 1H).
N‐(4‐Acetylphenyl)formamide (entry 6): M.p. 104–
−
1
1
07 °C; FT‐IR (KBr, cm ): 3316, 3065, 1697, 1664,
1
3
.9 | Selected spectral data of the
[62]
1588, 1530; H NMR (90 MHz, acetone‐d
s, 1H), 8.32 (s, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.65 (d,
J = 8.8 Hz, 2H), 2.42 (s, 3H).
N‐(4‐Methylphenyl)formamide (entry 7): M.p. 52–54 °C;
): δ = 9.42
6 H
N‐formylated products (table 3):
(
N‐(Phenyl)formamide (entry 1): Mp 46–48 °C; FT‐IR
−1
1
(
KBr, cm ): 3450, 3065, 1740, 1450, 1150; H NMR
−
1
1
(
90 MHz, CDCl ): δ = 7.61–7.12 (m, 5H), 8.29 (s, 1H,
FT‐IR (KBr, cm ): 3200, 3031, 1663, 1607, 1587, 1507; H
NMR (300 MHz, CDCl ): δ = 8.89 (s, 1H), 8.62 (s, 1H),
3
H
cis), 8.66 (d, 1H, trans), 8.99 (brs, 1H, cis), 9.38 (brs,
H, trans).
N‐(2‐Chlorophenyl)formamide (entry 2): M.p. 76–80 °C;
3
H
1
8.32–6.98 (m, 4H), 2.29 (s, 3H).
N‐(1‐Naphthyl)formamide (entry 8): M.p. 141–143 °C;
−1
−1
FT‐IR (KBr, cm ): 3251, 3114, 2901, 1704, 1667, 739, 675;
FT‐IR (KBr, cm ): 3224, 3060, 1656, 1540, 1504, 1385;
TABLE 6 Antibacterial activities of compunds (C1 and C2). Experiment was performed in triplicate and expressed as mean ± SD. Values with
different superscripts within each column (a, b and c) for any bacteria in different concentrations are significantly different (P < 0.05), NA: Not Active
Inhibition zone (mm)
Compounds
C1
Concentration
P.aeruginosa (−)
E. coli (−)
B. cereus (+)
S.aureus (+)
a
a
a
a
1.0 (mg/ml)
11 ± 0.15
8 ± 0.36
9 ± 0.15
7 ± 0.36
11 ± 0.15
10 ± 0.36
7 ± 0.11
8 ± 0.33
b
b
b
a
0
.1 (mg/ml)
8 ± 0.21
c
0
0
.01 (mg/ml)
NA
NA
NA
C2
1.0 (mg/ml)
7 ± 0.14
NA
NA
NA
NA
NA
7 ± 0.26
NA
NA
8 ± 0.13
NA
0
.1 (mg/ml)
.01 (mg/ml)
NA
TABLE 7 Antibacterial activity of positive and negative controls, experiment was performed in triplicate and expressed as mean ± SD, NA: Not
Active
Inhibition zone (mm)
Positive controls
Gentamicin
Negative controls
Co(OAc)
Microorganism
Penicillin
Fe(OAc)
2
2
DMSO
S. aureus (+)
E. Coli (−)
32 ± 0.13
NA
NA
NA
NA
NA
NA
NA
NA
NA
7 ± 0.63
NA
NA
NA
NA
Na
B. Cereus (+)
P. aeruginosa (−)
25 ± 0.18
33 ± 0.34
NA
NA

HABIBI ET AL.
13 of 14
1
H NMR (300 MHz, CDCl ): δ = 8.83 (s, 1H), 8.65–7.27
irradiation in the absence of the Co nano‐catalyst and the
results were compared.
3
H
(m, 8H).
N,N‐Dibenzylformamide (entry 9): M.p. 51–52 °C; FT‐
IR (KBr, cm ): 2999, 1724, 1631, 1556, 1458, 1349; H
In addition, the antioxidant and the antibacterial activities
of the Co nano‐catalyst and its Phendiol ligand were screened
by DPPH.
−
1
1
NMR (90 MHz, acetone‐d ): δ = 8.13 (s, 1H), 7.23 (s,
6
H
10H), 4.40 (s, 2H), 4.25 (s, 2H).
N,N‐Diphenylformamide (entry 10): M.p. 69–71 °C;
ACKNOWLEDGEMENTS
−
1
1
FT‐IR (KBr, cm ): 3063, 2897, 1672, 1591, 1493;
H
NMR (500 MHz, CDCl ): δ = 8.69 (s, 1H), 7.45–7.20
We are thankful to the Bu‐Ali Sina University, Hamedan
6517838683 Iran, for the financial support of this work.
3
H
(m, 10H).
4
‐Phenylpiperazie‐1‐carbaldehyde (entry 11): M.p. 82–
−
1
8
1
1
4 °C; FT‐IR (KBr, cm ): 2916, 2814, 1654, 1632, 1599,
499, 1447, 1405, 1385, 1366, 1350, 1334, 1283, 1254,
239, 1197, 1149, 1092, 1057, 1033, 1007, 916, 766, 693;
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[
How to cite this article: Habibi D, Heydari S,
Afsharfarnia M. A capable cobalt nano‐catalyst for the
N‐formylation of various amines and its biological
activity studies. Appl Organometal Chem. 2017;
e3874. https://doi.org/10.1002/aoc.3874
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2
3