Mo (CO)6-assisted Pd-supported magnetic graphene oxide-catalyzed carbonylation-cyclization as an efficient way for the synthesis of 4(3H)-quinazolinones

Article abstract of DOI:10.1002/aoc.4769

In this paper, a novel catalyst is introduced based on the immobilization of palladium on modified magnetic graphene oxide nanoparticles. The catalyst is characterized by several methods, including transmission electron microscopy, scanning electron microscopy, X-ray fluorescence, vibrating-sample magnetometer, Fourier transform-infrared and dynamic light scattering (DLS) analysis. The activity of the catalyst was investigated in the synthesis of 4(3H)-quinazolinones via Pd-catalyzed carbonylation-cyclization of N-(2-bromoaryl) benzimidamides by Mo (CO)₆. The Mo (CO)₆ is used as a carbon monoxide source for performing the reaction under mild conditions. The catalyst showed good reusability, and no change in activity was observed after 10?cycles of recovery.

Full text of DOI:10.1002/aoc.4769

Received: 17 August 2018
DOI: 10.1002/aoc.4769
Revised: 9 November 2018
Accepted: 23 November 2018
F U L L P A P E R
Mo (CO)6‐assisted Pd‐supported magnetic graphene oxide‐
catalyzed carbonylation‐cyclization as an efficient way for
the synthesis of 4(3H)‐quinazolinones
Saeed Bahadorikhalili1 | Samira Ansari2 | Haleh Hamedifar2 | Leila Ma'mani3 |
Mohsen Babaei1 | Rahim Eqra1 | Mohammad Mahdavi4
1 Institute of Mechanics, Iranian Space
In this paper, a novel catalyst is introduced based on the immobilization of
palladium on modified magnetic graphene oxide nanoparticles. The catalyst is
characterized by several methods, including transmission electron microscopy,
scanning electron microscopy, X‐ray fluorescence, vibrating‐sample
magnetometer, Fourier transform‐infrared and dynamic light scattering (DLS)
analysis. The activity of the catalyst was investigated in the synthesis of 4(3H)‐
quinazolinones via Pd‐catalyzed carbonylation‐cyclization of N‐(2‐bromoaryl)
benzimidamides by Mo (CO)6. The Mo (CO)6 is used as a carbon monoxide source
for performing the reaction under mild conditions. The catalyst showed good
reusability, and no change in activity was observed after 10 cycles of recovery.
Research Center, Shiraz, Iran
2 CinnaGen Medical Biotechnology
Research Center, Alborz University of
Medical Sciences, Karaj, Iran
3 Department of Nanotechnology,
Agricultural Biotechnology Research
Institute of Iran (ABRII), Agricultural
Research, Education and Extension
Organization (AREEO), Karaj, Iran
4 Endocrinology and Metabolism Research
Centre, Endocrinology and Metabolism
Clinical Sciences Institute, Tehran
University of Medical Science, Tehran,
Iran
KEYWORDS
carbonyl insertion, magnetic graphene oxide, molybdenum hexacarbonyl, palladium catalyst,
quinazolinones
Correspondence
Mohammad Mahdavi, Endocrinology and
Metabolism Research Centre,
Endocrinology and Metabolism Clinical
Sciences Institute, Tehran University of
Medical Science, Tehran, Iran.
Email: momahdavi@sina.tums.ac.ir
Samira Ansari, CinnaGen Medical
Biotechnology Research Center, Alborz
University of Medical Sciences, Karaj, Iran.
Email: ansaris@cinnagen.com
1 | INTRODUCTION
products, are examples of clinically important
quinazolinone‐type medications with antimalarial activ-
4(3H)‐Quinazolinone and its derivatives are important
nitrogen‐containing heterocycles that possess a wide range
of pharmacological activities, such as anti‐ulcer,[1] anti-
convulsant,[2] hypolipidemic,[3] anticancer,[4] and anti‐
inflammatory.[5] Some 4(3H)‐quinazolinone derivatives
have been reported as anti‐mycobacterial active agents
against the strains of mycobacterium kansasii, mycobacte-
rium tuberculosis, mycobacterium fortuitum, mycobacte-
rium avium and mycobacterium intracellulare.[6]
Febrifugine and isofebrifugine, as bioactive natural
ity.[7–9] Therefore, several synthetic approaches have been
reported for the preparation of 4(3H)‐quinazolinones.
Palladium‐catalyzed oxidative insertion reaction of
isocyanide with anthranilamide,[10] carboxylic acids and
amines,[11] the carboxylation of ortho C–H bonds in
anilides leading to N‐acyl anthranilic acids and then treat-
ment with anilines in the presence of PCl3,[12] and the
reaction of nitriles with lithiated anthranilamides[13] are
reported for the preparation of this class or compounds.
In addition, other methods including microwave‐assisted
Appl Organometal Chem. 2019;e4769.
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https://doi.org/10.1002/aoc.4769

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BAHAORIKHALILI ET AL.
condensation of anthranilic acids, oxidative reaction
between benzyl halides, isatoic anhydride and primary
amines,[14] and the condensation of imidates with
anthranilic acids,[15–17] are reported for this purpose.
cyclization of 2‐bromoanilines, trimethyl orthoformate
and amines,[20] and the condensation of aldehydes and
anthranilamide or its derivatives in the presence of
[21]
CuCl2
are other reported methods, which are applied
Amine‐induced
thermal
rearrangement
for the preparation of these compounds. Regarding the
great advantages of palladium in catalytic transformations,
several efforts have been focused on immobilization of this
metal on nanoparticles, which results in higher activity
and easier recovery of the catalyst.[22,23] Among several
nanoparticles that are used as support, magnetic graphene
oxide (MGO) is an appropriate choice because of various
benefits, including high surface area, functionalization
ability, high stability, and magnetic properties.[24–26]
Carbon monoxide is an important C1 building block in
organic synthesis, which in combination with transition
metal catalysts leads to install a carbonyl group into an
organic compound.[27–32] The notable disadvantage of this
route is high toxicity and the need for an excess amount of
CO gas. Therefore, chemists have developed alternative
methods that avoid direct use of CO gas.[33–38] Although
some protocols involve the generation of CO from an
organic precursor such as silacarboxylic acid, acid
chlorides, or carbon dioxide have recently been devel-
oped,[33–36,39] they need the complex and multistep
synthesis and generate high‐weight byproducts. Over the
past years, the use of Mo (CO)6 as a CO precursor in the
of iminobenzoxazines,[18] phosphine‐catalyzed intramo-
lecular aza‐Wittig reaction,[10] copper iodide‐catalyzed
reaction between anthranilamide, and terminal alkynes
and azides[19] have also been used for the synthesis of
4(3H)‐quinazolinone. Palladium‐catalyzed carbonylative
(a)
(b)
(c)
(d)
SCHEME
1
Palladium‐catalyzed
synthesis
of
4(3H)‐
quinazolinones in the presence of Mo (CO)6, reagents and
conditions. (a) NaSH, triethylene glycol, 110°C; (b) benzothioamide,
chloroform, benzyl bromide, reflux; (c) bromoaniline, acetonitrile,
room temperature (r.t.); (d) Mo (CO)6, DBU, Pd@MGO, reflux
SCHEME 2 The synthesis of Pd@MGO nanocatalyst

BAHAORIKHALILI ET AL.
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Pd‐catalyzed gas‐free carbonylative reactions has been
reported. The reported reactions include amino‐, amido‐
and alkoxycarbonylations, carbonylative cyclizations and
carbonylative cross‐couplings, using Mo (CO)6 as a solid
source of CO.[38]
We have had several efforts on the synthesis of novel
quinazolinone derivatives and extending novel methodol-
ogies for the synthesis of these compounds,[24,40–44]
as well as several projects on the transition metal‐
catalyzed reactions.[45–52] Due to the pharmacological
significance of 4(3H)‐quinazolinones and the chemical
importance of CO generation and carbonylation reaction
on one hand, and the efficiency of palladium catalyst on
the other hand, we wish to report a new method
for the efficient synthesis of 4(3H)‐quinazolinones
via the palladium‐catalyzed carbonylation‐cyclization
of N‐(2‐bromoaryl) benzimidamides by molybdenum
2 | RESULTS AND DISCUSSION
The designed palladium catalyst is fabricated by immobi-
lization of Pd on modified MGO. For this purpose, ini-
tially, superparamagnetic graphene oxide nanosheets
were synthesized and confirmed according to previously
reported methods.[51] Afterwards, the MGO was function-
alized by triazine‐coupled amine moieties. MGO was first
functionalized by 3‐aminopropyltriethoxysilane. Triazine‐
coupled amine moieties were attached to the MGO via
the
reaction
between
cyanuric
chloride
and
trichlorotriazine with 3‐aminopropylsilane. The triazine
functionalities were used as an appropriate ligand for
immobilizing palladium nanoparticles on the surface of
MGO nanosheets. Therefore, synthesized MGO was reacted
with Pd (OAc)2 to provide Pd@MGO as the designed cata-
lyst (Scheme 2). The structure of the nanocatalyst was char-
acterized by diverse techniques, including transmission
electron microscopy (TEM), scanning electron microscopy
(SEM), vibrating‐sample magnetometer (VSM), Fourier
transform‐infrared (FT‐IR) spectroscopy, and inductively
coupled plasma‐atomic emission spectrometry (ICP‐AES)
analysis. ICP was applied for determining the leaching of
the palladium after the reaction completion.
hexacarbonyl.
In
this
method,
molybdenum
hexacarbonyl is used as CO source for the synthesis of
the desired products. A novel catalyst is synthesized
based on the immobilization of palladium on
dendrimer‐like triazine structures. The reaction scheme
is presented in Scheme 1.
The structures of the obtained nanosheets were char-
acterized by TEM and SEM (Figure 1). The introduction
of iron oxides onto the graphene oxide nanosheets was
evident from TEM and SEM results. Iron oxide nanopar-
ticles can be seen as dark spots within the graphene oxide
nanosheets. As can be seen in Figure 1, the formation of
magnetic iron oxide nanoparticles on the graphene oxide
nanosheets can be clearly seen.
The magnetic behavior of the nanocatalyst was evalu-
ated using the VSM technique. The magnetic hysteresis
assessed by VSM in an applied magnetic field at room
temperature (r.t.) with the field sweeping from −8000 to
+8000 Oe can be observed in Figure 2. The
FIGURE
1
Scanning electron microscopy (SEM; a) and
FIGURE 2 Vibrating‐sample magnetometer (VSM) curves of
transmission electron microscopy (TEM) images (b) of Pd@MGO
MGO and Pd@MGO

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BAHAORIKHALILI ET AL.
superparamagnetic nature of MGO and Pd@MGO has
been shown by its S‐type magnetization hysteresis loop.
It can be clearly observed that the magnetic behavior of
MGO is slightly decreased by functionalization, but the
catalyst still has superparamagnetic behavior. We note
that the catalyst is magnetically recoverable. After
reaction completion, the catalyst was separated from the
reaction mixture by an external magnet and reused in
the next run without any additional process.
Fe3O4 is confirmed by the appearance of the vibration
band of Fe–O at about 572 cm−1, in the FT‐IR spectrum
of MGO. The appearance of such bands in the FT‐IR
spectrum of Pd@MGO is in agreement with the attach-
ment of triazine‐coupled amine moieties to the MGO.
The bands at 3430 cm−1 are due to the N–H groups of
triazine‐coupled amine moieties attached to the surface.
In addition, absorption bands at 1583 and 1607 cm−1
TABLE 1 Optimization of the carbonylation‐cyclization of N‐(2‐
bromophenyl) benzimidamide by Mo (CO)6
Fourier transform‐infrared spectroscopy was applied
to prove the covalent attachment of triazine‐coupled
amine moieties to the MGO. In the IR spectrum of GO,
the strong bands at 3430 and 1246 cm−1 are attributed
to the stretching and bending of the O–H bond, respec-
tively. The aromatic C=C bond in unoxidized graphitic
domains bands appeared at 1630 cm−1. The existence of
a
Entry
Solvent
Base
Yield (%)b
1
dioxane
dioxane
dioxane
DMF
TEA
60
75
44
38
49
18
21
34
56
28
11
27
19
14
2
DBU
3
DMAP
TEA
4
5
DMF
DBU
6
DMF
DMAP
K2CO3
TEA
7
DMF
8
CH3CN
CH3CN
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
DBU
10
11
12
13
14
DMAP
TEA
No base
DMAP
K2CO3
aReaction conditions: use of N‐(2‐bromophenyl) benzimidamide (1 mmol),
Mo (CO)6 (1.5 mmol), base (1.5 mmol), in the presence of 5 mol% of
Pd@MGO in a solvent (5 mL); under reflux conditions.
FIGURE 3 Fourier transform‐infrared (FT‐IR) spectra for (a)
graphene oxide, (b) magnetic graphene oxide (MGO), and (c)
Pd@MGO
bIsolated yield.
Bold signifies best reaction condition.
FIGURE 4 XRF results of Pd@MGO

BAHAORIKHALILI ET AL.
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TABLE 3 The synthesis of 4(3H)‐quinazolinones 2 via the
can be correlated to C=N bonds of triazine. The attach-
ment of dendrimer‐like functionalities to MGO was
established by Si‐O bonding, which can be proved by
observing vibration bands at 1097 cm−1. The FT‐IR spec-
tra of GO, MGO and Pd@MGO can be seen in Figure 3.
It is believed that functionalization of MGO by
triazine‐coupled amine moieties is an appropriate ligand
for palladium. To prove the successful immobilization of
palladium on the modified graphene oxide, the X‐ray
fluorescence (XRF) technique was applied. The XRF
results for Pd@MGO catalyst are presented in Figure 4.
The presence of palladium in the structure of the catalyst
can clearly be observed in the XRF results. In agreement
with the XRF results, the Pd content of the obtained solid
catalyst was 0.11 mmol per gram of Pd@MGO catalyst
using ICP‐AES. For investigating the stability of the cata-
lyst, Pd@MGO was poured into dioxane and stirred for
72 hr. Then the solid particles were separated by an exter-
nal magnet and the liquid was analyzed by ICP. The ICP
carbonylation‐cyclization of N‐(2‐bromoaryl) benzimidamides by
a
Mo (CO)6
Product
5a
Product
Yield (%)b
77
5b
73
5c
5d
5e
5f
73
73
75
66
TABLE 2 The effect of different palladium salts, ligands and
different source of carbon monoxide donors on the carbonylation‐
a
cyclization of N‐(2‐bromophenyl) benzimidamide by Mo (CO)6
Palladium
Entry salt
Ligand
CO source Yield (%)b
1
Pd (OAc)2
PPh3
Mo (CO)6
61
2
Pd (OAc)2
Pd (OAc)2
Pd (OAc)2
Pd (OAc)2
Pd (OAc)2
PdCl2
2,2′‐bipyridine Mo (CO)6
42
3
BINAPc
Mo (CO)6
Mo (CO)6
Mo (CO)6
Mo (CO)6
Mo (CO)6
57
d
4
P(o‐tolyl)3
69
e
5
PCy3
47
6
–
Trace
64
5g
5h
5i
70
68
70
72
7
PPh3
10
11
12
13
14
15
16
17
18
19
PdCl2
2,2′‐bipyridine Mo (CO)6
27
PdCl2
BINAP
Mo (CO)6
Mo (CO)6
Mo (CO)6
Mo (CO)6
Mo (CO)6
Mo (CO)6
Cr (CO)6
W (CO)6
Fe (CO)5
39
PdCl2
P(o‐tolyl)3
55
PdCl2
PCy3
34
PdCl2
–
Trace
0
–
BINAP
Pd@MGO
Pd@MGO
Pd@MGO
Pd@MGO
–
–
–
–
75
42
37
55
5j
aReaction conditions: use of N‐(2‐bromophenyl) benzimidamide (1 mmol),
CO source (1.5 mmol), in the presence of 5 mol% of palladium catalyst; 5
hr; under reflux conditions.
bIsolated yield.
c2,2′‐Bis (diphenylphosphino)‐1,1′‐binaphthyl.
dTri(o‐tolyl)phosphine.
aReaction conditions: use of benzimidamides (1 mmol), Mo (CO)6 (1.5
mmol), in the presence of 5 mol% of Pd@MGO in dioxane (5 mL); 5 hr;
under reflux conditions.
bIsolated yields.
eTricyclohexylphosphine.
Bold signifies best reaction condition.
Bold signifies best reaction condition.

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BAHAORIKHALILI ET AL.
results proved that no leaching occurred in the reaction
conditions.
for the reaction performance. The source of carbon mon-
oxide donors is also an important factor, which can sig-
nificantly affect the reaction performance. Therefore,
the reaction was tested in the presence of different carbon
monoxide donor sources. It can be observed in Table 2
(entries 17–19) that Cr (CO)6, W (CO)6 and Fe (CO)5 have
not been efficient like Mo (CO)6.
To show the generality and scope of these new proto-
cols, we examined the carbonylation‐cyclization of N‐(2‐
bromoaryl) benzimidamides by Mo (CO)6 in the presence
of 5 mol% of Pd@MGO and 1.5 equiv. of DBU in dioxane
under reflux conditions to generate 4(3H)‐quinazolinones
(Table 3).
To synthesize the 4(3H)‐quinazolinones, the
carbonylation‐cyclization
of
N‐(2‐bromophenyl)
benzimidamide by 1.5 equiv. of Mo (CO)6 was investi-
gated in the presence of 5 mol% Pd@MGO and 1.5 equiv.
of various bases in different solvents under reflux condi-
tions. In order to find optimal reaction conditions, the
reaction was performed in the presence of various bases
in different solvents. The results of the optimization of
the bases and the solvents are presented in Table 1. As
shown in Table 1, the best yield of 4(3H)‐quinazolinone
was obtained using DBU as a base in dioxane under
reflux conditions (Table 1, entry 2, 75%). We note that
the reaction led to the desired product in the other
conditions, but the other bases (TEA, DMAP, K2CO3)
and solvents [CH3CN and dimethylformamide (DMF)]
did not give the better yield of product (Table 1, entries
1 and 3–10).
For finding the activity and applicability of Pd@MGO,
the reaction was performed in the presence of the sup-
ported catalyst and also in the presence of various
palladium salts with different ligands. Two significant
variables, which highly affect the reaction performance
and the yields of the products, are the kind of palladium
and the ligands. The reaction was performed with N‐(2‐
bromophenyl) benzimidamide in the presence of molyb-
denum hexacarbonyl and DBU base by using different
palladium salts and ligands. The results are presented in
Table 2. The results show that Pd@MGO catalyzes the
reaction best. Other palladium salts also give the desired
products, but in much lower isolated yields. A blank
run containing all the reaction components except palla-
dium salt did not lead to any amount of the desired prod-
uct. This observation proves that palladium is necessary
All the reactions reached completion within 5 hr for
1
4(3H)‐quinazolinones. H‐NMR analysis of the reaction
mixtures clearly indicated the formation of the 4(3H)‐
quinazolinones in excellent yields. The structures of the
1
4(3H)‐quinazolinones were deduced from H‐ and 13C‐
NMR spectral data. It can be observed in Table 3 that
all the substrates gave the desired products in the reaction
conditions. Various substrates with electron‐donating and
electron‐withdrawing functionalities were used in the
reaction and produced the products in good isolated
yields. These results show that this method is an efficient
way for the synthesis of 4(3H)‐quinazolinone derivatives.
Table 3 shows the products that were synthesized in
the optimized reaction conditions. As can be seen, vari-
ous N‐(2‐bromophenyl) benzimidamide derivatives were
used as starting material for the reaction. Substrates bear-
ing electron‐donating or electron‐withdrawing function-
alities were used in the reaction, and this resulted in the
desired products in good isolated yields. Moreover, the
starting material with heteroaryl functionality was suc-
cessfully used in the reaction to give the product
(Table 3, product 7j).
FIGURE 5 Recyclability of Pd@MGO
after 10 cycles

BAHAORIKHALILI ET AL.
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FIGURE 6 XRF results of Pd@MGO catalyst after the fifth cycle
An advantage of Pd@MGO catalyst is its reusability.
The catalyst was isolated from the reaction mixture after
the reaction was completed and washed with ethanol
and reused in the reaction under the same reaction condi-
tions. The reusability results are presented in Figure 5. It
can be observed that after 10 sequential recoveries, the
activity of the catalyst was not changed and no change
in the reaction performance and the isolated yield of the
products was observed. In addition, the catalyst was sep-
arated from the reaction mixture and the solution was
analyzed by ICP for any possible leaching of palladium
from the catalyst. The ICP results did not show any palla-
dium in the solution. This observation proves the stability
and reusability of the catalyst.
the carbon monoxide in the presence of Pd@MGO and
DBU in dioxane under reflux conditions. The generated
CO was efficiently incorporated into a palladium‐
catalyzed carbonylation‐cyclization reaction without the
need for complex systems. The use of simple materials
and good yield of the products are the other advantages
of our protocol. In addition, the catalyst shows very good
recovery results, and no appreciable loss in the activity of
Pd@MGO catalyst was observed after 10 sequential runs.
4 | EXPERIMENTAL
4.1 | Preparation of Pd@MGO catalyst
In order to prove the exact role of molybdenum in the
reaction, the catalyst was isolated after the fifth run and
analyzed by XRF. In the XRF results, it was observed that
molybdenum is also present in the catalyst. It was neces-
sary to determine if the molybdenum also acts as a cata-
lyst in the reaction. Therefore, a reaction was performed
in the presence of all the reaction components, but using
triazine‐functionalized MGO instead of Pd@MGO. In this
case, no product was formed in the absence of palladium
in the structure of the catalyst. This proves that palladium
is the catalyst of the reaction, and the presence of this cat-
alyst is essential for reaction performance (Figure 6).
For the preparation of the catalyst, graphene oxide was
first synthesized by the oxidation of graphite. MGO nano-
particles were then prepared by the co‐precipitation of
Fe2+ and Fe3+ onto the graphene oxide nanosheets. We
have previously reported this procedure.[51] For
functionalizing MGO by (3‐aminopropyl) triethoxysilane,
a solution of (3‐aminopropyl) triethoxysilane in ethanol
was prepared (10 mmol in 50 mL) and added drop‐wise
to a suspension containing MGO (1 g) in 50:50 v/v mix-
ture of water and ethanol (50 mL). The pH of the reaction
mixture was established as pH 4 by the addition of HCl.
The reacting mixture was stirred for 24 hr. Then the solid
product was separated by an external magnet and washed
by 50:50 v/v mixture of water and ethanol (3 ×, 50 mL).
The product was dried at 60°C under reduced pressure.
3 | CONCLUSIONS
In summary, we have developed a MGO‐supported
palladium‐catalyzed carbonylation‐cyclization of N‐(2‐
bromoaryl) benzimidamide by Mo (CO)6 as a CO source
for the synthesis of 4(3H)‐quinazolinones. The catalyst
is active and catalyzes the reaction to give the desired
products in good isolated yields. The Mo (CO)6 generates
In
a
round‐bottomed flask, 3‐aminopropyl‐
functionalized MGO (1 g) and tetrahydrofuran (20 mL)
were poured and sonicated for 15 min. Cyanuric chloride
(10 mmol) was added, and the reaction mixture was
stirred at r.t. (about 23°C) for 24 hr. The product was
magnetically separated and washed with tetrahydrofuran

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BAHAORIKHALILI ET AL.
and dried at 60°C in vacuum. The product was dispersed
in DMF (20 mL) and sonicated for 15 min. A solution of
bis(3‐aminopropyl) amine (10 mmol) and N,N‐
diisopropylethylamine (10 mmol) in DMF (20 mL) was
added to the mixture and stirred at 80°C for 24 hr. The
product was separated by a magnet, and washed with eth-
anol and dried at 60°C in vacuum. The last two steps
were repeated once more for the modification of MGO
by dendrimer‐like triazine structures.
The product was dispersed in dry dichloromethane,
and palladium acetate (3 mmol) was added. The mixture
was stirred under argon atmosphere at r.t. for 24 hr. The
final product was separated and washed with dichloro-
methane (2 × 20 mL) and diethyl ether (2 × 20 mL).
Pd@MGO catalyst was obtained as a dark solid after
drying the product in vacuum for 12 hr.
at r.t., and then the solvent was evaporated by a rotary
evaporator. The product was washed with dichlorometh-
ane and dried in a vacuum oven for 12 hr.
4.5 | General procedure for the
preparation of 4(3H)‐quinazolinones
A
mixture of N‐(2‐bromobenzyl) benzimidamide
(1 mmol), Mo (CO)6 (1.5 mmol) and DBU (1.5 mmol), in
the presence of 5 mol% Pd@MGO in dioxane (5 mL)
was stirred for 5 hr under reflux conditions. After comple-
tion of the reaction, the mixture was cooled to r.t. and the
catalyst was separated using an external magnet. The
white precipitate was filtered, washed with diethyl ether
and EtOAc (1:1, 4 × 3 mL), and then recrystallized from
EtOH to give the product as white crystals.
4.2 | General procedure for the
preparation of benzothioamide
4.6 | Characterization data for 2‐
substituted quinazolin‐4(3H)‐ones (7a–j)
To a round‐bottomed flask, benzonitrile (10 mmol),
triethylene glycol (20 mL) and NaSH (20 mmol) were
added. The reaction mixture was stirred at r.t., and then
concentrated sulfuric acid (1 mL) was added. The temper-
ature was raised to 110°C and the mixture stirred for 72
hr. After the reaction completion, 400 mL of saturated
ammonium chloride solution was added and the product
was extracted with ethyl acetate. The organic layer was
washed with water (3 × 50 mL), dried over sodium
sulfate, and the solvent was evaporated to give
benzothioamide product.
The image of 1H NMR and 13C NMR are presented in the
supporting information.
4.6.1 | 2‐(4‐(Dimethylamino)phenyl)
quinazolin‐4(3H)‐one (5a)
Yellow solid; yield: 0.204 g, 77%; m.p.: 236–238°C; lit. m.
p.: 236–238°C.[35] IR (KBr) (νmax/cm−1): 3321 (NH),
1653 (C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 3.04
(6H, s), 6.79 (2H, d, J = 8.5 Hz), 7.42 (1H, t, J = 8.0 Hz),
7.65 (1H, d, J = 8.0 Hz), 7.73 (1H, t, J = 8.0 Hz), 8.11
(1H, d, J = 8.0 Hz), 8.12 (2H, d, J = 8.5 Hz), 12.22 (1H,
s, NH). 13C‐NMR (125.8 MHz, DMSO‐d6): δ 39.5, 111.3,
118.4, 120.2, 125.3, 125.7, 126.4, 128.8, 131.4, 134.3,
148.7, 152.3, 162.2. Anal. calcd for C16H15N3O: C, 72.43;
H, 5.70; N, 15.84. Found: C, 72.38; H, 5.63; N, 15.90.
4.3 | General procedure for the
preparation of benzyl benzimidothioate
A solution of benzothioamide (10 mmol) in chloroform
(20 mL) was poured into a round‐bottomed flask, and
then benzyl bromide (9 mmol) was added. The reaction
mixture was stirred under reflux conditions for 6 hr, and
then cooled by placing the reaction flask in an ice bath.
The benzyl benzimidothioate was formed as a white
precipitate, separated by filtration and dried in a
vacuum oven.
4.6.2 | 2‐(4‐Methoxyphenyl)quinazolin‐
4(3H)‐one (5b)
White solid; yield: 0.184 g, 73%; m.p.: 246–248°C; lit. m.p.:
247–248°C.[30] IR (KBr) (νmax/cm−1): 3312 (NH), 1668
1
(C=O); H‐NMR (500.1 MHz, DMSO‐d6): δ 3.85 (3H, s,
CH3), 7.08 (2H, d, J = 8.5 Hz), 7.48 (1H, t, J = 7.5 Hz),
7.70 (1H, d, J = 7.5 Hz), 7.80 (1H, t, J = 7.5 Hz), 8.14
(1H, d, J = 7.5 Hz), 8.20 (2H, d, J = 8.5 Hz), 12.33 (1H, s,
NH). 13C‐NMR (125.8 MHz, DMSO‐d6): δ 55.3, 113.9,
120.6, 124.7, 125.7, 125.9, 127.1, 129.3, 134.3, 148.8,
151.8, 161.8, 162.2. Anal. calcd for C15H12N2O2: C, 71.42;
H, 4.79; N, 11.10. Found: C, 71.49; H, 4.85; N, 11.04.
4.4 | General procedure for the
preparation of N‐(2‐bromophenyl)
benzimidamide
A solution of bromoaniline (10 mmol) in acetonitrile
(20 mL) was prepared, and then benzyl benzimidothioate
(10 mmol) was added. The mixture was stirred for 12 hr

BAHAORIKHALILI ET AL.
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3
22.6 Hz), 120.8, 125.7, 126.4, 127.2, 129.1, 130.2 (d, JC‐F
4.6.3 | 2‐(3‐Methoxyphenyl)quinazolin‐
4(3H)‐one (5c)
1
= 8.8 Hz), 134.4, 148.5, 151.3, 162.5 (d, JC‐F = 104.3 Hz),
164.9. Anal. calcd for C14H9FN2O: C, 69.99; H, 3.78; N,
11.66. Found: C, 70.04; H, 3.84; N, 11.71.
White solid; yield: 0.184 g, 73%; m.p.: 206–208°C; lit. m.p.:
209–210°C.[37] IR (KBr) (νmax/cm−1): 3323 (NH), 1668
1
(C=O); H‐NMR (500.1 MHz, DMSO‐d6): δ 3.87 (3H, s,
4.6.7 | 2‐(2‐Chlorophenyl)quinazolin‐
4(3H)‐one (5g)
OCH3), 7.14 (1H, d, J = 7.0 Hz), 7.45 (1H, t, J = 7.5 Hz),
7.52 (1H, t, J = 7.5 Hz), 7.73–7.85 (4H, m), 8.16 (1H, t, J
= 8.0 Hz), 12.45 (1H, s, NH). 13C‐NMR (125.8 MHz,
DMSO‐d6): δ 55.3, 112.5, 117.4, 120.0, 120.9, 125.7,
126.4, 127.4, 129.6, 133.9, 134.4, 148.6, 151.9, 159.3,
162.1. Anal. calcd for C15H12N2O2: C, 71.42; H, 4.79; N,
11.10. Found: C, 71.38; H, 4.73; N, 11.14.
White solid; yield: 0.179 g, 70%; m.p.: 196–197°C; lit. m.p.:
196–197°C.[37] IR (KBr) (νmax/cm−1): 3316 (NH), 1657
(C=O); H‐NMR (500.1 MHz, DMSO‐d6): δ 7.50 (1H, t,
J = 8.0 Hz), 7.75–7.62 (3H, m), 7.67 (1H, d, J = 7.5 Hz),
7.71 (1H, d, J = 8.0 Hz), 7.85 (1H, t, J = 8.0 Hz), 8.19
(1H, d, J = 8.0 Hz), 12.58 (1H, s, NH). 13C‐NMR (125.8
MHz, DMSO‐d6): δ 121.2, 125.7 (2C), 126.9, 127.1, 127.4,
129.5, 130.7, 131.4, 133.7, 134.4, 148.5, 152.1, 161.3. Anal.
calcd for C14H9ClN2O: C, 65.51; H, 3.53; N, 10.91. Found:
C, 65.60; H, 3.48; N, 10.97.
1
4.6.4 | 2‐(2‐Methoxyphenyl)quinazolin‐
4(3H)‐one (5d)
White solid; yield: 0.181 g, 72%; m.p.: 208–210°C; lit. m.p.:
209–212°C.[39] IR (KBr) (νmax/cm−1): 3323 (NH), 1662
1
(C=O); H‐NMR (500.1 MHz, DMSO‐d6): δ 3.88 (3H, s,
4.6.8 | 2‐(2‐Nitrophenyl)quinazolin‐4(3H)‐
OCH3), 7.08 (1H, t, J = 7.0 Hz), 7.19 (1H, d, J = 8.5 Hz),
7.50–7.55 (2H, m), 7.70 (1H, d, J = 8.0 Hz), 7.49 (1H, d,
J = 7.5 Hz), 7.82 (1H, t, J = 7.5 Hz), 8.16 (1H, d, J = 7.5
Hz), 12.00 (1H, s, NH). 13C‐NMR (125.8 MHz,
DMSO‐d6): δ 55.7, 111.8, 120.3, 120.9, 122.5, 125.7,
126.4, 127.3, 130.3, 132.1, 134.2, 148.9, 152.2, 157.1,
161.1. Anal. calcd for C15H12N2O2: C, 71.42; H, 4.79; N,
11.10. Found: C, 71.39; H, 4.84; N, 11.03.
one (5h)
Yellow solid; yield: 0.182 g, 68%; m.p.: 208–210°C; lit. m.
p.: 208–210°C.[35] IR (KBr) (νmax/cm−1): 3318 (NH),
1654 (C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 7.57
(1H, t, J = 7.5 Hz), 7.66 (1H, d, J = 7.5 Hz), 7.81–7.93
(4H, m), 8.18–8.22 (2H, m), 12.79 (1H, s, NH). 13C‐NMR
(125.8 MHz, DMSO‐d6): δ 121.1, 124.4, 125.8, 127.0,
127.2, 129.1, 131.3, 131.4, 133.8, 134.5, 147.4, 148.4,
151.5, 161.4. Anal. calcd for C14H9N3O3: C, 62.92; H,
3.39; N, 15.72. Found: C, 63.01; H, 3.44; N, 15.76.
4.6.5 | 2‐Phenylquinazolin‐4(3H)‐one (5e)
White solid; yield: 0.166 g, 75%; m.p.: 233–235°C; lit. m.p.:
234–235°C.[30] IR (KBr) (νmax/cm−1): 3314 (NH), 1662
(C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 7.51–7.61
(4H, m), 7.75 (1H, d, J = 8.0 Hz), 7.84 (1H, t, J = 8.0 Hz),
8.16 (1H, d, J = 8.0 Hz), 8.20 (2H, d, J = 7.0 Hz), 12.50
(1H, s, NH). 13C‐NMR (125.8 MHz, DMSO‐d6): δ 120.9,
125.7, 126.4, 127.4, 127.6, 128.5, 131.2, 132.6, 134.4,
148.7, 152.2, 162.1. Anal. calcd for C14H10N2O: C, 75.66;
H, 4.54; N, 12.60. Found: C, 75.71; H, 4.49; N, 12.65.
4.6.9 | 2‐(3‐Nitrophenyl)quinazolin‐4(3H)‐
one (5i)
Yellow solid; yield: 0.187 g, 70%; m.p.: 349–352°C; lit. m.
p.: 352–354°C.[37] IR (KBr) (νmax/cm−1): 3318 (NH),
1659 (C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 7.57
(1H, t, J = 7.5 Hz), 7.79–7.86 (3H, m), 8.17 (1H, d, J =
7.0 Hz), 8.41 (1H, d, J = 7.0 Hz), 8.61 (1H, d, J = 7.0
Hz), 9.02 (1H, s), 12.82 (1H, s, NH). 13C‐NMR (125.8
MHz, DMSO‐d6): δ 122.6, 125.6, 125.8, 127.0, 127.5,
130.2, 133.9 (2C), 134.3, 134.6, 147.9, 149.2, 154.9, 162.0.
Anal. calcd for C14H9N3O3: C, 62.92; H, 3.39; N, 15.72.
Found: C, 62.85; H, 3.31; N, 15.67.
4.6.6 | 2‐(4‐Fluoropheny)quinazolin‐
4(3H)‐one (5f)
Yellow solid; yield: 0.158 g, 66%; m.p.: 290–292°C; lit. m.
p.: 293–295°C.[38] IR (KBr) (νmax/cm−1): 3315 (NH),
1664 (C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 7.38
(2H, t, J = 9.0 Hz), 7.52 (1H, t, J = 7.5 Hz), 7.73 (1H, d,
J = 7.5 Hz), 7.83 (1H, t, J = 7.5 Hz), 8.15 (1H, d, J = 7.5
4.6.10 | 2‐(Thiophen‐2‐yl)quinazolin‐
4(3H)‐one (5j)
Hz), 8.26 (2H, dd, J = 9.0, 5.5 Hz), 12.53 (1H, s, NH).
Yellow solid; yield: 0.164 g, 72%; m.p.: 273–275°C; lit. m.
p.: 275–276°C.[30] IR (KBr) (νmax/cm−1): 3316 (NH),
2
13C‐NMR (125.8 MHz, DMSO‐d6): δ 115.4 (d, JC‐F
=

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BAHAORIKHALILI ET AL.
1664 (C=O); 1H‐NMR (500.1 MHz, DMSO‐d6): δ 7.24 (1H,
t, J = 6.0 Hz), 7.49 (1H, t, J = 8.0 Hz), 7.66 (1H, d, J = 8.0
Hz), 7.80 (1H, t, J = 8.0 Hz), 7.86 (1H, d, J = 6.0 Hz), 8.13
(1H, d, J = 8.0 Hz), 8.23 (1H, d, J = 6.0 Hz), 12.62 (1H, s,
NH). 13C‐NMR (125.8 MHz, DMSO‐d6): δ 120.8, 125.9,
126.2, 126.8, 128.3, 129.3, 132.0, 134.5, 137.3, 147.7,
148.6, 161.6. Anal. calcd for C12H8N2OS: C, 63.14; H,
3.53; N, 12.27. Found: C, 63.19; H, 3.60; N, 12.22.
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How to cite this article: Bahadorikhalili S,
Ansari S, Hamedifar H, et al. Mo (CO)6‐assisted Pd‐
supported magnetic graphene oxide‐catalyzed
carbonylation‐cyclization as an efficient way for the
synthesis of 4(3H)‐quinazolinones. Appl
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