A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-aminobenzamides with aryl iodides leading to quinazolinones

Article abstract of DOI:10.1016/j.jorganchem.2018.09.003

The first heterogeneous carbonylative annulation of 2-aminobenzamides with aryl iodides was achieved in N,N-dimethylformamide (DMF) at 120 °C under 10 bar of carbon monoxide by using an MCM-41-immobilized bidentate phosphine palladium(II) complex [MCM-41-2P-Pd(OAc)₂] as catalyst and 1,8-diazabicycloundec-7-ene (DBU) as base, yielding a wide variety of quinazolinone derivatives in good to excellent yields. The new heterogeneous palladium catalyst can easily be prepared by a simple procedure from commercially readily available reagents, and recovered by filtration of the reaction solution, and recycled up to eight times without significant loss of activity.

Full text of DOI:10.1016/j.jorganchem.2018.09.003

Journal of Organometallic Chemistry 875 (2018) 35e45
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Journal of Organometallic Chemistry
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A highly efficient heterogeneous palladium-catalyzed carbonylative
annulation of 2-aminobenzamides with aryl iodides leading to
quinazolinones
,
, *
Shengyong You a b, Bin Huang a, Tao Yan a, Mingzhong Cai a
a Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal University,
Nanchang, 330022, PR China
b Institute of Applied Chemistry, Jiangxi Academy of Sciences, Nanchang, 330029, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first heterogeneous carbonylative annulation of 2-aminobenzamides with aryl iodides was achieved
in N,N-dimethylformamide (DMF) at 120 ꢀC under 10 bar of carbon monoxide by using an MCM-41-
immobilized bidentate phosphine palladium(II) complex [MCM-41-2P-Pd(OAc)2] as catalyst and 1,8-
diazabicycloundec-7-ene (DBU) as base, yielding a wide variety of quinazolinone derivatives in good to
excellent yields. The new heterogeneous palladium catalyst can easily be prepared by a simple procedure
from commercially readily available reagents, and recovered by filtration of the reaction solution, and
recycled up to eight times without significant loss of activity.
Received 25 May 2018
Received in revised form
14 August 2018
Accepted 1 September 2018
Available online 4 September 2018
Keywords:
Carbonylative annulation
Palladium
© 2018 Elsevier B.V. All rights reserved.
Quinazolinone
2-Aminobenzamide
Heterogeneous catalysis
1. Introduction
harsh reaction conditions. These problems have stimulated several
groups to apply transition metal-catalyzed reactions for the
Quinazolinones, existing in many natural alkaloids and phar-
maceuticals [1,2], are a significant class of annulated six-membered
nitrogen heterocycles. They are endowed with numerous phar-
macological and biological activities, including anticancer [3,4],
antibacterial [5], antifungal [6], antimalarial [7], antihypertensive
[8], antitubercular [9], inhibitors of derived growth factor receptor
phosphorylation [10], anticonvulsant [11], and other activities
[12e14]. Additionally, quinazolinones are also important building
blocks in the synthesis of natural products and bioactive com-
pounds [15,16]. As a result, a number of methods have been
developed for construction of quinazolinones [17]. Conventionally,
development of new protocols to substituted quinazolinones,
using Cu [22], Ir [23], Pt [24], and Pd [25e27] as catalysts.
Since the pioneering work of Heck and co-workers in 1974 [28],
palladium-catalyzed carbonylative transformation of organohalides
has become a powerful tool in modern organic synthesis [29e31].
The advantages of carbonylation reactions are (i) it is the most potent
methodology in the construction of carbonyl-containing com-
pounds, which increases the carbon number at the same time, and
(ii) carbon monoxide (CO) can be used as a cheap and readily
available C1 source, which is also in agreement with the green
chemistry principles. Recently, palladium-catalyzed carbonylative
annulation reactions have been successfully applied in the synthesis
of furanones, benzoxazinones, flavones, and other heterocycles
[32e35]. Wu and coworkers reported a palladium-catalyzed car-
bonylative synthesis of quinazolinones from 2-aminobenzamide and
aryl bromides with expensive BuPAd2 (di-1-adamantyl-n-butyl-
phosphine) as the ligand [36] [Eq. (1), in Scheme 1]. Although these
palladium-catalyzed carbonylative annulation reactions are highly
efficient for the construction of heterocycles, industrial applications
of these homogeneous palladium complexes remain a challenge
because they are quite expensive, cannot be recycled, and difficult to
such
a structure is synthesized by the condensation of 2-
halobenzoic acids, 2-halobenzamides, 2-aminobenzamides, 2-
aminobenzoic acids with amidines, benzyl alcohols, benzyl-
amines, acid amides or amino acids [18e21]. However, these
known methods generally suffer from certain disadvantages, such
as multistep synthesis, low yields, limited substrate scope, and/or
* Corresponding author.
E-mail addresses: caimzhong@163.com, mzcai@jxnu.edu.cn (M. Cai).
https://doi.org/10.1016/j.jorganchem.2018.09.003
0022-328X/© 2018 Elsevier B.V. All rights reserved.

36
S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
Scheme 1. Palladium-catalyzed carbonylative synthesis of quinazolinones.
separate from the product mixture, which is a particularly significant
drawback for their applications in the pharmaceutical industry.
Immobilization of the existing homogeneous palladium catalysts on
porous materials with high surface areas could be an attractive so-
lution to these problems since the immobilized catalysts can be
facilely separated from the reaction mixture by a simple filtration
process, and recycled for several times. There has been considerable
interest in the development of heterogeneous palladium catalytic
systems that can be efficiently recycled whilst maintaining the
inherent activity of the catalytic centre [37].
Mesoporous MCM-41 materials have recently been shown to be
powerful supports for immobilization of homogeneous catalysts
due to their outstanding advantages, such as extremely high sur-
face areas, large and defined pore sizes, big pore volumes and the
presence of a large number of silanol (SieOH) groups on the inner
surface in comparison with other solid supports [38e40]. So far,
some palladium [41e44], rhodium [45], molybdenum [46], gold
[47e49] and copper [50e52] complexes immobilized on MCM-41
have been successfully used as highly active and recyclable cata-
lysts in organic reactions. As a part of our continuing interest in the
development of efficient heterogeneous catalysts for organic syn-
thesis [43,49e52], herein we report the synthesis of an MCM-41-
immobilized bidentate phosphine palladium(II) complex [MCM-
41-2P-Pd(OAc)2] and its successful application to carbonylative
annulation of 2-aminobenzamides with aryl iodides under 10 bar of
CO leading to a wide variety of 2-aryl-substituted quinazolinones in
good to excellent yields [Eq. (2), in Scheme 1]. The new heteroge-
neous palladium catalyst exhibits high catalytic activity in the re-
action and can be facilely recovered via a simple filtration process
after the reactions, and its catalytic efficiency remains unchanged
even after recycling eight times.
mesoporous material MCM-41, N,N-bis((diphenylphosphino)
methyl)-3-(triethoxysilyl)propan-1-amine, and Pd(OAc)2 according
to the procedure summarized in Scheme 2. Firstly, the condensa-
tion of N,N-bis((diphenylphosphino)methyl)-3-(triethoxysilyl)
propan-1-amine with MCM-41 in toluene at 100 ꢀC for 24 h, fol-
lowed by the silylation with Me3SiCl in toluene at room tempera-
ture for 24 h gave a bidentate phosphino-functionalized MCM-41
material (MCM-41-2P). The latter was subsequently reacted with
Pd(OAc)2 in acetone under reflux for 72 h to generate the MCM-41-
immobilized bidentate phosphine palladium(II) complex [MCM-
41-2P-Pd(OAc)2] as a light yellow powder. The palladium content of
this complex was determined to be 0.36 mmol/g (3.83 wt%) by ICP-
AES. The energy dispersive X-ray spectroscopy (EDS) shows the
elements present in the material. EDS analysis of fresh MCM-41-2P-
Pd(OAc)2 complex (Fig.1) shows the presence of Si, O, C, N, P, and Pd
elements, confirming the successful anchoring of the palladium-
phosphine complex onto the MCM-41. The silanization of MCM-
41 was further confirmed by FTIR spectroscopy (Fig. 2). The FTIR
spectrum (Fig. 2a) of MCM-41 shows the SieO stretching absorp-
tion around 1095 cmꢁ1. In the FTIR spectrum (Fig. 2b) of MCM-41-
2P-Pd(OAc)2 absorptions at 1630, 1572 and 1413 cmꢁ1 (benzene
ring) were observed, indicating the presence of silylated palladiu-
m(II)- phosphine groups.
Fig. 3 shows the XRD patterns for the parent MCM-41 and the
MCM-41-2P-Pd(OAc)2 complex. Small angle X-ray diffraction pattern
of the parent MCM-41 showed three peaks corresponding to hex-
agonally ordered mesoporous phases. For the MCM-41-2P-Pd(OAc)2,
the (100) reflection of the parent MCM-41 was maintained after
introduction of the palladium complex, but the intensity decreased
apparently, while the (110) and (200) reflections became weak and
diffuse, which may be mainly due to contrast matching between the
silicate framework and organic moieties which are located inside the
channels of MCM-41. These results indicate that the structure of the
mesoporous MCM-41 remains intact through the functionalization
procedure, and the formation of the catalyst has taken place pref-
erentially inside the pore system of MCM-41.
2. Results and discussion
2.1. Synthesis and characterization of MCM-41-2P-Pd(OAc)2
complex
Morphological changes of MCM-41 and MCM-41-2P-Pd(OAc)2
were investigated by scanning electron microscopy (SEM). As
shown in Fig. 4, the morphology of MCM-41-2P-Pd(OAc)2 (Fig. 4b
The MCM-41-immobilized bidentate phosphine palladium(II)
complex [MCM-41-2P-Pd(OAc)2] was synthesized starting from

S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
37
Scheme 2. Preparation of MCM-41-2P-Pd(OAc)2 complex.
Fig. 1. Energy dispersive spectra (EDS) of MCM-41-2P-Pd(OAc)2.
Fig. 3. XRD patterns of the parent MCM-41 (1) and MCM-41-2P-Pd(OAc)2 (2).
indicating that the organic moieties were introduced into the inner
channels, but the pore still remained a narrow distribution. After
grafting the bidentate phosphine-palladium complex onto MCM-
41, the surface area and pore diameter decreased from 967.3 m2/g
and 2.7 nm to 658.4 m2/g and 2.3 nm, respectively, indicating that
the ordered mesostructure of the parent MCM-41 remained almost
unaltered. XPS analysis of the fresh MCM-41-2P-Pd(OAc)2 complex
was also performed to analyze the oxidation state of the Pd metal
(Fig. 7a). The observed binding energy values of 342.6 eV (Pd 3d3/
2) and 337.3 eV (Pd 3d5/2) on the XPS spectrum of the catalyst
indicated the existence of palladium as Pd(II) form.
Fig. 2. FTIR spectra of MCM-41 (a) and MCM-41-2P-Pd(OAc)2 (b).
2.2. Heterogeneous palladium-catalyzed carbonylative annulation
of 2-aminobenzamides with aryl iodides
and d) is similar to the particle form of MCM-41 (Fig. 4a and c),
suggesting a high possibility in the modification of palladium
complex on the inner channel of MCM-41 pores without any sig-
nificant change in the manner of MCM-41. The N2 adsorption-
desorption isotherms and pore size distributions for MCM-41 and
MCM-41-2P-Pd(OAc)2 are illustrated in Fig. 5 and Fig. 6, respec-
tively. As expected, the isotherms in Fig. 5 have remarkable changes
before and after grafting because the organic moieties entered the
channels, but both samples showed type IV isotherms, character-
istic of mesoporous materials according to the IUPAC classification.
As presented in Fig. 6, the pore volume and size of MCM-41-2P-
Pd(OAc)2 decreased apparently, compared with MCM-41, also
The MCM-41-immobilized bidentate phosphine palladium(II)
complex [MCM-41-2P-Pd(OAc)2] was then used as catalyst for
carbonylative annulation of 2-aminobenzamides with aryl
iodides. Initial experiments, with 2-aminobenzamide (1a) and
iodobenzene (2a) under 10 bar of carbon monoxide, were per-
formed to optimize the reaction conditions (base, solvent, reaction
temperature, catalyst quantity), and the results are summarized in
Table 1. At first, the base effect was examined in the presence of
2 mol% of MCM-41-2P-Pd(OAc)2 in DMF as solvent at 120 ꢀC, and a
significant base effect was observed. When DIPEA (diisopropyle-
thylamine), n-Bu3N, DMAP (4-dimethylaminopyridine), and

38
S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
Fig. 4. SEM images of MCM-41 (a and c) and MCM-41-2P-Pd(OAc)2 (b and d).
DABCO(1,4-diazabicyclo [2,2,2]octane) were used as bases, the re-
action produced 2-phenylquinazolin-4(3H)-one (3a) in low yields
(entries 1e4). To our delight, the yield of the desired 3a can be
improved to 90% by using DBU (1,8-diazabicyclo[5,4,0]undec-7-
ene) as base (entry 5), whereas inorganic bases such as K2CO3
and Cs2CO3 were ineffective (entries 6 and 7). Our next studies
focused on the effect of solvent on the model reaction by using DBU
as base (entries 8e11). When DMAc was used as solvent, the
desired 3a was also isolated in high yield, while other solvents such
as NMP, DMSO and DMI were substantially less effective. So, DMF
was the best choice (entry 5). Lowering reaction temperature
resulted in a decreased yield, and a considerable amount of non-
cyclized amide [N-(2-carbamoylphenyl)benzamide] was detected
as the by-product (entries 12 and 13). Raising reaction tempera-
ture to 130 ꢀC also resulted in a slightly decreased yield (entry 14).
When Pd(OAc)2 (2 mol%) and DPPP [1,3-bis(diphenylphosphino)
propane] (3 mol%) were used as catalyst system, the desired
product 3a was isolated in 91% yield (entry 15), indicating that the
catalytic activity of the MCM-41-2P-Pd(OAc)2 complex was com-
parable to that of homogeneous Pd(OAc)2/DPPP system. The use of
commercially available catalysts such as PdCl2(PPh3)2 or Pd/C
resulted in a low yield or no formation of the desired product
(entries 16 and 17), which revealing the key role of the ligand in this
transformation. Reducing the amount of the catalyst to 1 mol%
resulted in a lower yield, and a long reaction time was required
(entry 18). Increasing the amount of the catalyst to 4 mol% could
shorten the reaction time, but did not improve the yield signifi-
cantly (entry 19). In order to check the effect of Pd loading of the
catalyst on the reaction, the MCM-41-2P-Pd(OAc)2 complexes with
different Pd loadings were prepared by varying the MCM-41-2P/
Pd(OAc)2 feed ratio. The use of MCM-41-2P-Pd(OAc)2 with Pd
loading of 2.15 wt% resulted in a significant decrease in the yield,
and MCM-41-2P-Pd(OAc)2 with Pd loading of 4.94 wt% also affor-
ded a relatively lower yield (entries 20 and 21). So, the MCM-41-2P-
Pd(OAc)2 complex with Pd loading of 3.83 wt% was the most effi-
cient for this transformation. Thus, the optimized reaction condi-
tions for this carbonylative annulation are the use of MCM-41-2P-
Fig. 5. N2 adsorption/desorption isotherms of MCM-41 and MCM-41-2P-Pd(OAc)2.
Fig. 6. Pore size distributions of MCM-41 and MCM-41-2P-Pd(OAc)2.

S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
39
Fig. 7. XPS of the fresh MCM-41-2P-Pd(OAc)2 (a) and recycled MCM-41-2P-Pd(OAc)2 (b).
Table 1
to afford the corresponding 2-arylquinazolinones 3b-3i in 60e85%
yields. The reactivity of aryl iodides bearing electron-withdrawing
groups was lower than that of aryl iodides having electron-
donating groups. For example, the reactions of aryl iodides having
strong electron-withdrawing groups such as 4-(trifluoromethyl)
iodobenzene (2g), 4-iodobenzonitrile (2h), and 40-iodoacetophe-
none (2i) gave the corresponding products 3g-3i in only 60e65%
yields. The sterically hindered 2-iodoanisole (2j) and 2-
chloroiodobenzene (2k) also afforded the expected quinazoli-
nones 3j and 3k in good yields. Bulky 1-iodonaphthalene (2l) can
be applied as substrate as well and gave the desired 2-(naphthalen-
1-yl)quinazolin-4(3H)-one (3l) in 91% yield. Heteroatoms turned
out to be compatible with the employed reaction conditions. The
reactions of 2-iodofuran (2m), 2-iodothiophene (2n), 4-
iodopyridine (2o), and 3-iodopyridine (2p) with 1a could give the
corresponding 2-heterocycle substituted quinazolinones 3m-3p
in good yields.
The optimized reaction conditions were also applied to the
carbonylative annulation of substituted 2-aminobenzamides with a
variety of aryl and heteroaryl iodides, the results are also listed in
Table 2. 2-Aminobenzamides bearing various substituents 1b-1f,
regardless of their electronic properties and substitution positions,
could undergo the carbonylative annulation with various aryl or
heteroaryl iodides smoothly to give a variety of quinazolinone de-
rivatives 3q-3e' in 62e90% yields. The reactivity of electron-rich 2-
aminobenzamides was higher than that of electron-deficient ones.
In addition, three examples of biologically active analogues 3f'-3h'
(Acetildenafil and Sildenafil) were prepared by this methodology in
good yields through the reaction of 4-amino-1-methyl-3-n-propyl-
5-pyrazolecarboxamide (1g) with aryl iodides. A wide range of
functional groups, such as methyl, methoxy, chloro, fluoro, tri-
fluoromethyl, cyano, acetyl, and nitro were tolerated well. The
present method provides a novel, efficient and practical procedure
for the preparation of a variety of quinazolinone derivatives.
Remarkably, all of the products described here were purified by
simple filtration or recrystallization and no chromatography was
needed, which indicating the suitability of this protocol for large
scale application.
Carbonylative annulation of 2-aminobenzamide with iodobenzene in different
conditions.a
Entry
Base
Solvent
Temp. (ºC)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
DIPEA
n-Bu3N
DMAP
DABCO
DBU
K2CO3
Cs2CO3
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
NMP
DMSO
DMI
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
120
120
120
120
120
120
120
120
120
120
110
100
130
120
120
120
120
120
120
120
24
24
24
24
20
24
24
20
24
24
24
24
24
20
20
24
24
40
12
24
24
15
21
29
37
90
trace
trace
87
63
54
48
78
32
87
91
46
0
9
10
11
12
13
14
15c
16d
17e
18f
19g
20h
21i
69
91
67
84
DBU
a
Reaction conditions: 1a (1 mmol), 2a (1 mmol), base (2 mmol), MCM-41-2P-
Pd(OAc)2 (2 mol%) in solvent (2 mL) under 10 bar of CO.
b
Isolated yield.
Pd(OAc)2 (2 mol%) and DPPP (3 mol%) were used.
PdCl2(PPh3)2 (2 mol%) was used.
Pd/C (2 mol%) was used.
MCM-41-2P-Pd(OAc)2 (1 mol%) was used.
MCM-41-2P-Pd(OAc)2 (4 mol%) was used.
MCM-41-2P-Pd(OAc)2 with Pd loading of 2.15 wt% (2 mol%) was used.
MCM-41-2P-Pd(OAc)2 with Pd loading of 4.94 wt% (2 mol%) was used.
c
d
e
f
g
h
i
Pd(OAc)2 (2 mol%), DBU (2 equiv.) as base in DMF as solvent at
120 ꢀC under 10 bar of CO for 20 h (Table 1, entry 5).
With the optimized reaction conditions in hand, the generality
of this convenient and practical methodology was tested by using
various 2-aminobenzamides and a variety of aryl iodides as sub-
strates, and the results are listed in Table 2. First, the scope of aryl
iodides was examined by using 2-aminobenzamide (1a) as sub-
strate. As shown in Table 2, both electron-rich and electron-
deficient aryl iodides could undergo the carbonylative annulation
with 2-aminobenzamide (1a) effectively under identical conditions
2.3. Leaching test for MCM-41-2P-Pd(OAc)2
It would be a concern if the leaching of active Pd species into the
solution is substantial. A hot-filtration experiment [53] was per-
formed to examine the leaching of palladium species from MCM-
41-2P-Pd(OAc)2. For this, the carbonylative annulation reaction of
2-aminobenzamide (1a) with iodobenzene (2a) was carried out
until a conversion of approximately 30%. Then the catalyst was

40
S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
Table 2
B with 2-aminobenzamide (1) in the presence of DBU as base gives
intermediate C, which undergoes reductive elimination to afford
intermediate D and regenerate MCM-41-2P-Pd(0). Finally, inter-
mediate D undergoes intramolecular condensation to furnish the
desired quinazolinone (3). The intramolecular condensation of in-
termediate D to afford quinazolinones is responsible for the rela-
tively high reaction temperature required.
Heterogeneous palladium-catalyzed carbonylative synthesis of quinazolinones.a,b
3
2.5. Recycling of the catalyst
For the practical application of a heterogeneous precious metal
catalyst system, its stability and reusability are important factors.
The MCM-41-2P-Pd(OAc)2 catalyst can be facilely separated and
recovered by a simple filtration of the reaction mixture. We next
examined the recycling of MCM-41-2P-Pd(OAc)2 by using the car-
bonylative annulation reaction of 2-aminobenzamide (1a) with 1-
iodonaphthalene (2l). After completion of the reaction, the cata-
lyst was separated by simple filtration and washed with distilled
water, DMF and diethyl ether. After being dried at 80 ꢀC under
vacuum for 1 h, the recovered palladium catalyst was used in the
next run without further purification, and almost the same yield of
3l was observed for eight consecutive cycles (91%, 90%, 91%, 90%,
89%, 90%, 89%, and 88%, respectively) as shown in Fig. 8. Besides, to
examine palladium leaching of the heterogeneous catalyst, the
palladium content of the recovered catalyst after eight consecutive
runs was also determined by ICP-AES analysis and found to be
0.35 mmol/g, which is almost the same as that of the fresh one. The
recycled MCM-41-2P-Pd(OAc)2 was further characterized by X-ray
photoelectron spectroscopy (XPS) (Fig. 7b). The observed binding
energy values of 340.6 eV (Pd 3d3/2) and 335.4 eV (Pd 3d5/2) on the
XPS spectrum of the recycled catalyst indicated that the state of
palladium in the used catalyst was mainly Pd(0), which was in
agreement with the proposed mechanism. In our opinion, there are
two related factors that could explain the observed high catalytic
activity and stability of MCM-41-2P-Pd(OAc)2. First, the MCM-41
support has a regular pore diameter of ca. 5 nm and a specific
surface area >700 m2g-1 [38], which might give rise to efficient site
isolation and the optimum dispersion of the active sites on the
inner channel walls. The resulting nano-sized catalyst can serve as
an efficient bridge and fill the gap between homogeneous and
heterogeneous catalysts. In addition, the strong interaction be-
tween the bidentate phosphine ligand and the palladium centre
immobilized on the MCM-41 resulted in the formation of a stable
supported bidentate phosphine-palladium(II) complex, thereby
greatly improving the reusability of the heterogeneous palladium
catalyst.
a
Reaction conditions:
1 (1 mmol), 2 (1 mmol), DBU (2 mmol), MCM-41-2P-
Pd(OAc)2 (2 mol%) in DMF (2 mL) at 120 ꢀC under 10 bar of CO for 20 h.
b
Isolated yield.
removed by filtration from the solution at the reaction temperature
(120 ꢀC), and the filtrate was allowed to react further under iden-
tical reaction conditions. We found that, after this hot filtration, no
increase in conversion of 2-aminobenzamide (1a) was observed.
We also determined the palladium content in the filtrate by ICP-
AES analysis, and no palladium was detected in the clear solution.
These results exclude any contribution to the observed activity
from the leached palladium species, indicating that MCM-41-2P-
Pd(OAc)2 was stable during the carbonylative annulation, and the
observed catalysis was intrinsically heterogeneous.
3. Conclusions
In summary, we have developed a highly efficient heteroge-
neous palladium-catalyzed carbonylative annulation reaction of 2-
aminobenzamides with aryl iodides under 10 bar of carbon mon-
oxide leading to quinazolinones, which are commonly found in
many bioactive molecules. This heterogeneous carbonylative
annulation has many attractive features, such as: (1) the substrate
scope is broad, and a wide range of 2-aminobenzamides and aryl
iodides are allowed; (2) a variety of quinazolinone derivatives were
obtained in mostly good to excellent yields; (3) the reaction is
tolerant of a range of functional groups; (4) all of the products were
purified by simple filtration or recrystallization, and no chroma-
tography was needed; (5) this new palladium catalyst can easily be
prepared via a simple procedure from commercially readily avail-
able reagents, and recovered by filtration of the reaction solution,
and recycled up to eight times without significant loss of activity.
2.4. Possible mechanism of heterogeneous Pd-catalyzed
carbonylative annulation
A plausible reaction mechanism for this heterogeneous Pd-
catalyzed carbonylative annulation is shown in Scheme 3. Firstly,
MCM-41-2P-Pd(OAc)2 is reduced by CO to MCM-41-2P-Pd(0).
Oxidative addition of Ar-I (2) to MCM-41-2P-Pd(0) generates an
MCM-41-anchored arylpalladium(II) complex A, which is followed
by migratory insertion of carbon monoxide to produce an MCM-41-
anchored acylpalladium(II) complex B. The reaction of intermediate

S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
41
Scheme 3. Proposed catalytic cycle.
4. Experimental
were characterized by comparison of their spectra and physical
data with authentic samples. IR spectra were determined on a
PerkinElmer 683 instrument. 1H NMR spectra were recorded on a
Bruker Avance 400 MHz spectrometer with TMS as an internal
standard in DMSO‑d6 as solvent. 13C NMR spectra (100 MHz) were
recorded on a Bruker Avance 400 MHz spectrometer in DMSO‑d6 as
solvent. HRMS spectra were recorded on a Q-Tof spectrometer with
micromass MS software using electrospray ionization (ESI). Palla-
dium content was determined with inductively coupled plasma
atom emission Atomscan16 (ICP-AES, TJA Corporation). Micro-
analyses were measured by using a Yanaco MT-3 CHN micro-
elemental analyzer. X-ray diffraction (XRD) measurements were
carried out at room temperature using a Damx-rA (Rigaku) X-ray
powder diffractmeter. X-ray energy dispersive spectroscopy (EDS)
was performed using a microscope. Nitrogen adsorption/desorp-
tion isotherms were obtained using a Bel Japan Inc. Belsorp-HP at
77 K. Prior to gas adsorption measurements materials were
degassed for 6 h at 423 K. The SEM analysis of the catalyst was
recorded using a FESEM-TESCAN MIRA3. X-ray photoelectron
spectra (XPS) were recorded on XSAM 800 (Kratos).
4.1. General remarks
All reagents were obtained from commercial sources without
further purification, and commercially available organic bases and
solvents such as DIPEA (diisopropylethylamine), n-Bu3N, DMAP (4-
dimethylaminopyridine), DBU (1,8-diazabicyclo[5,4,0]undec-7-
ene), DABCO (1,4-diazabicyclo [2,2,2]octane), dimethyl sulfoxide
(DMSO), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone
(NMP), and 1,3-dimethyl-2-imidazolidone (DMI) were purified by
vacuum distillation. Mesoporous material MCM-41 [38] and N,N-
bis((diphenylphosphino)methyl)-3-(triethoxysilyl)propan-1-
amine [54] were prepared according to literature methods. The
products were purified by either washed with water, ethyl acetate
and finally hexane or recrystallization from MeOH. All the products
4.2. Preparation of MCM-41-2P-Pd(OAc)2 complex
N,N-Bis((diphenylphosphino)methyl)-3-(triethoxysilyl)propan-
1-amine (0.927 g, 1.5 mmol) was added to a suspension of 2.0 g of
the MCM-41 in 120 mL of dry toluene. The resulting mixture was
stirred at 100 ꢀC for 24 h under Ar. Then the solid was filtered,
washed with CHCl3 (20 mL), and dried in vacuum at 150 ꢀC for 5 h.
The dried white solid was then soaked in a solution of 2.5 g of
Me3SiCl in 100 mL of dry toluene at 25 ꢀC under stirring for 24 h.
The solid product was filtered, washed with acetone (3 ꢂ 20 mL),
and dried in vacuum at 120 ꢀC for 5 h to obtain 2.523 g of hybrid
material MCM-41-2P. The phosphorus content was found to be
0.81 mmol/g by elemental analysis.
In a small Schlenk tube, 1.00 g of the above-functionalized
MCM-41 (MCM-41-2P) was mixed with Pd(OAc)2 (86 mg,
Fig. 8. Recycle of the MCM-41-2P-Pd(OAc)2 complex.

42
S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
0.38 mmol) in 30 mL of dry acetone. The mixture was stirred at
60 ꢀC for 72 h under an argon atmosphere. The solid product was
filtered by suction, washed with acetone, distilled water and
acetone successively and dried under vacuum at 80 ꢀC for 5 h to
give 1.03 g of a light yellow palladium(II) complex [MCM-41-2P-
Pd(OAc)2]. The phosphorus and palladium content were found to be
0.75 mmol/g and 0.36 mmol/g (3.83 wt%), respectively.
1448, 1143, 946, 825, 708; 1H NMR (400 MHz, DMSO‑d6):
d 12.56
(br, 1H), 8.28e8.23 (m, 2H), 8.16 (dd, J ¼ 7.8, 1.0 Hz, 1H), 7.87e7.81
(m, 1H), 7.74 (d, J ¼ 7.6 Hz, 1H), 7.58e7.50 (m, 1H), 7.39 (t, J ¼ 9.0 Hz,
1
2H); 13C NMR (100 MHz, DMSO‑d6):
d
164.5 (d, JC-F ¼ 248.0 Hz),
3
162.7, 151.9, 135.1, 130.8 (d, JC-F ¼ 9.0 Hz), 129.7, 129.1, 127.9, 127.1,
2
126.3, 121.3, 116.1 (d, JC-F ¼ 21.8 Hz).
4.3.6. 2-(4-Chlorophenyl)quinazolin-4(3H)-one (3f) [55]
4.3. General procedure for the heterogeneous palladium-catalyzed
carbonylative synthesis of quinazolinones
White solid. IR (KBr): nmax/cmꢁ1 3330, 3072, 1665, 1603, 1476,
1450, 1146, 948, 823, 705; 1H NMR (400 MHz, DMSO‑d6):
d 12.45
(br, 1H), 8.16 (dd, J ¼ 8.0, 1.2 Hz, 1H), 8.10 (dd, J ¼ 7.8, 1.0 Hz, 1H),
A 12 mL vial was charged with MCM-41-2P-Pd(OAc)2 (2 mol%),
2-aminobenzamide (1 mmol), aryl iodide (1 mmol) (if solid) and a
stirring bar. Then, DMF (2 mL), aryl iodide (1 mmol) (if liquid) and
DBU (2 mmol) were injected by syringe under an argon
atmosphere. The vial was placed in an alloy plate, which was
transferred into a 300 mL Parr Instruments 4560 series autoclave
under an argon atmosphere. After flushing the autoclave three
times with CO, a pressure of 10 bar CO was fixed at ambient
temperature. The autoclave was heated for 20 h at 120 ꢀC. After
completion of the reaction, the autoclave was cooled to room
temperature and the pressure was released carefully. The reaction
mixture was diluted with ethyl acetate (10 mL) and filtered. The
palladium catalyst was washed with distilled water (2 ꢂ 5 mL)
and acetone (2 ꢂ 5 mL), and reused in the next run. The filtrate
was concentrated in vacuo and the pure product was isolated by
either washed with water, ethyl acetate and finally hexane or
recrystallization from MeOH.
7.80e7.69 (m, 2H), 7.51e7.37 (m, 2H), 6.96e6.88 (m, 2H); 13C NMR
(100 MHz, DMSO‑d6):
d 167.4, 151.8, 149.1, 135.1, 132.2, 132.0, 130.1,
129.2, 129.1, 127.2, 126.3, 121.5.
4.3.7. 2-(4-Trifluoromethylphenyl)quinazolin-4(3H)-one (3g) [35]
White solid. IR (KBr): nmax/cmꢁ1 3329, 3052, 1673, 1620, 1469,
1445,1140, 956, 803; 1H NMR (400 MHz, DMSO‑d6):
d 12.77 (br,1H),
8.35 (d, J ¼ 8.4 Hz, 2H), 8.18 (d, J ¼ 8.0 Hz, 1H), 8.05 (d, J ¼ 8.4 Hz,
2H), 7.88 (t, J ¼ 7.6 Hz, 1H), 7.78 (d, J ¼ 8.0 Hz, 1H), 7.57 (t, J ¼ 7.4 Hz,
1H); 13C NMR (100 MHz, DMSO‑d6):
d
162.6,151.7,148.9,137.1,135.2,
2
3
131.6 (q, JC-F ¼ 31.9 Hz), 129.2, 128.1, 127.6, 126.4, 126.0 (q, JC-
¼ 3.2 Hz), 124.4 (q, 1JC-F ¼ 270.5 Hz), 121.7.
F
4.3.8. 2-(4-Cyanophenyl)quinazolin-4(3H)-one (3h) [35]
White solid. IR (KBr): nmax/cmꢁ1 3335, 3068, 2240, 1671, 1622,
1466, 1440, 1142, 958, 805; 1H NMR (400 MHz, DMSO‑d6):
d 12.76
(br, 1H), 8.37 (d, J ¼ 5.6 Hz, 2H), 8.18 (d, J ¼ 6.4 Hz, 1H), 7.93 (d,
J ¼ 5.6 Hz, 2H), 7.92e7.78 (m, 2H), 7.58e7.56 (m, 1H); 13C NMR
4.3.1. 2-Phenylquinazolin-4(3H)-one (3a) [35]
(100 MHz, DMSO‑d6): d 162.8, 150.7, 149.5, 138.7, 134.4, 132.3, 129.1,
White solid. IR (KBr): nmax/cmꢁ1 3330, 3072, 1668, 1600, 1479,
127.8, 126.3, 125.8, 121.8, 116.8, 114.8.
1448, 1143, 946, 823, 763; 1H NMR (400 MHz, DMSO‑d6):
d
12.55 (s,
1H), 8.21e8.15 (m, 3H), 7.85e7.80 (m, 1H), 7.74 (d, J ¼ 8.0 Hz, 1H),
7.60e7.48 (m, 4H); 13C NMR (100 MHz, DMSO‑d6):
162.7, 152.8,
4.3.9. 2-(4-Acetylphenyl)quinazolin-4(3H)-one (3i) [35]
d
White solid. IR (KBr): nmax/cmꢁ1 3330, 3070, 1673, 1620, 1469,
149.2, 135.0, 133.2, 131.8, 129.0, 128.2, 128.0, 127.0, 126.3, 121.5.
1445, 1140, 956, 803; 1H NMR (400 MHz, DMSO‑d6):
d 12.73 (s, 1H),
8.32 (d, J ¼ 8.4 Hz, 2H), 8.18 (d, J ¼ 7.6 Hz,1H), 8.11 (d, J ¼ 8.4 Hz, 2H),
4.3.2. 2-(4-Methylphenyl)quinazolin-4(3H)-one (3b) [55]
7.88 (t, J ¼ 7.8 Hz, 1H), 7.79 (d, J ¼ 8.0 Hz, 1H), 7.57 (t, J ¼ 7.6 Hz, 1H),
White solid. IR (KBr): nmax/cmꢁ1 3332, 3070, 1666, 1601, 1477,
2.66 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d 198.2, 162.6, 152.0,
149.0, 139.1, 137.1, 135.2, 128.8, 128.6, 128.2, 127.5, 126.4, 121.6, 27.5.
1449, 1145, 948, 823, 705; 1H NMR (400 MHz, DMSO‑d6):
d
12.46 (s,
1H), 8.17 (d, J ¼ 7.2 Hz, 1H), 8.12 (d, J ¼ 8.0 Hz, 2H), 7.86e7.80 (m,
1H), 7.74 (d, J ¼ 8.0 Hz, 1H), 7.52 (t, J ¼ 7.6 Hz, 1H), 7.36 (d, J ¼ 8.0 Hz,
4.3.10. 2-(2-Methoxyphenyl)quinazolin-4(3H)-one (3j)
2H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d
162.7, 152.7,
White solid. IR (KBr): nmax/cmꢁ1 3328, 3059, 2960, 1697, 1625,
149.3, 141.9, 135.0, 130.4, 129.6, 128.1, 127.9, 126.8, 126.3, 121.4, 21.4.
1600, 1498, 1435, 1380, 1259, 1140, 956, 821; 1H NMR (400 MHz,
DMSO‑d6):
d
12.10 (s, 1H), 8.15 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.84e7.80 (m,
4.3.3. 2-(3-Methylphenyl)quinazolin-4(3H)-one (3c)
1H), 7.73e7.69 (m, 2H), 7.56e7.51 (m, 2H), 7.20 (d, J ¼ 8.4 Hz, 1H),
White solid. IR (KBr): nmax/cmꢁ1 3334, 3071, 1667, 1600, 1478,
7.12e7.07 (m, 1H), 3.87 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
1448, 1143, 946, 824, 765; 1H NMR (400 MHz, DMSO‑d6):
1H), 8.16 (dd, J ¼ 7.8, 1.0 Hz, 1H), 8.03 (s, 1H), 7.97 (d, J ¼ 7.6 Hz, 1H),
7.86e7.81 (m, 1H), 7.75 (d, J ¼ 7.6 Hz, 1H), 7.55e7.49 (m, 1H),
7.46e7.38 (m, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d
12.47 (s,
d 161.7, 157.7, 152.8, 149.5, 134.9, 132.7, 130.9, 127.9, 127.0, 126.2,
123.1, 121.5, 120.9, 112.4, 56.3. HRMS calcd for C15H12N2Oþ2 [Mþ]:
252.0899, found 252.0896.
d
162.7, 152.9, 149.2, 138.4, 135.1, 133.1, 132.5, 129.0, 128.7, 127.9,
4.3.11. 2-(2-Chlorophenyl)quinazolin-4(3H)-one (3k)
127.1, 126.3, 125.3, 121.4, 21.4. HRMS calcd for C15H12N2Oþ [Mþ]:
236.0950, found 236.0961.
Light yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3070, 1668, 1600,
1479, 1445, 1140, 946, 826, 725; 1H NMR (400 MHz, DMSO‑d6):
d
12.53 (s, 1H), 8.21e8.16 (m, 2H), 7.85e7.82 (m, 1H), 7.77e7.73 (m,
4.3.4. 2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3d) [56]
1H), 7.59e7.53 (m, 4H); 13C NMR (100 MHz, DMSO‑d6):
d
162.7,
White solid. IR (KBr): nmax/cmꢁ1 3332, 3067, 1668, 1604, 1479,
152.8, 149.2, 135.1, 133.2, 131.9, 129.1, 128.2, 128.0, 127.1, 126.3, 121.5.
HRMS calcd for C14H9ClN2Oþ [Mþ]: 256.0403, found 256.0412.
1446, 1145, 944, 823, 763; 1H NMR (400 MHz, DMSO‑d6):
d 12.41
(br, 1H), 8.21 (d, J ¼ 8.8 Hz, 2H), 8.14 (dd, J ¼ 8.0, 1.2 Hz, 1H),
7.84e7.79 (m, 1H), 7.71 (d, J ¼ 7.6 Hz, 1H), 7.51e7.47 (m, 1H), 7.10 (d,
4.3.12. 2-(Naphthalen-1-yl)quinazolin-4(3H)-one (3l) [35]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3061, 1668, 1601,
1560, 1505, 1499, 1468, 1155, 944, 816, 724, 705; 1H NMR (400 MHz,
J ¼ 9.2 Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d 167.5,
167.1, 157.1, 154.2, 139.7, 134.7, 132.5, 131.3, 131.0, 130.0, 125.9, 119.2,
60.7.
DMSO‑d6):
d
12.68 (s, 1H), 8.24 (dd, J ¼ 7.6, 1.2 Hz, 1H), 8.13 (d,
J ¼ 8.0 Hz, 1H), 8.08 (d, J ¼ 7.6 Hz, 1H), 8.04 (d, J ¼ 8.0 Hz, 1H),
7.87e7.79 (m, 1H), 7.75 (d, J ¼ 8.0 Hz, 1H), 7.66 (d, J ¼ 7.6 Hz, 1H),
7.64 (d, J ¼ 7.2 Hz, 1H), 7.62e7.56 (m, 3H); 13C NMR (100 MHz,
4.3.5. 2-(4-Fluorophenyl)quinazolin-4(3H)-one (3e) [35]
White solid. IR (KBr): nmax/cmꢁ1 3335, 3070, 1669, 1600, 1477,

S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
43
DMSO‑d6):
d
162.4, 154.2, 149.2, 135.0, 133.6, 132.2, 130.9, 130.8,
4.3.20. 6-Methoxy-2-(naphthalen-1-yl)quinazolin-4(3H)-one (3t)
128.8, 128.2, 127.9, 127.5, 127.3, 126.8, 126.3, 125.7, 125.5, 121.7.
Yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3061, 1668, 1601, 1560,
1499, 1468, 1155, 944, 816, 724, 705; 1H NMR (400 MHz, DMSO‑d6):
4.3.13. 2-(Furane-2-yl)quinazolin-4(3H)-one (3m) [56]
d
12.64 (s, 1H), 8.19e8.16 (m, 1H), 8.11 (d, J ¼ 8.4 Hz, 1H), 8.06e8.03
Light yellow solid. IR (KBr): nmax/cmꢁ1 3335, 3070, 1668, 1600,
(m, 1H), 7.79 (dd, J ¼ 7.2, 0.8 Hz, 1H), 7.70 (d, J ¼ 8.8 Hz, 1H),
1560, 1448, 1155, 944, 823, 763, 705; 1H NMR (400 MHz, DMSO‑d6):
7.67e7.56 (m, 4H), 7.48 (dd, J ¼ 8.8, 3.2 Hz, 1H), 3.93 (s, 3H); 13C
d
12.52 (s, 1H), 8.13 (dd, J ¼ 7.8, 1.0 Hz, 1H), 8.01 (d, J ¼ 0.8 Hz, 1H),
NMR (100 MHz, DMSO‑d6): d 162.2, 158.4, 151.8, 143.7, 133.6, 132.2,
7.79 (t, J ¼ 7.2 Hz, 1H), 7.69 (d, J ¼ 8.0 Hz, 1H), 7.64 (d, J ¼ 3.2 Hz, 1H),
130.8, 130.7, 129.7, 128.8, 128.1, 127.5, 126.8, 125.7, 125.5, 124.4,
122.5, 106.4, 56.2. HRMS calcd for C19H14N2Oþ2 [Mþ]: 302.1055,
found 302.1047.
7.52e7.49 (m, 1H), 6.75 (dd, J ¼ 3.4, 1.8 Hz, 1H); 13C NMR (100 MHz,
DMSO‑d6):
d 162.0, 149.2, 147.0, 146.6, 144.5, 135.1, 127.7, 126.9,
126.4, 121.6, 115.0, 113.0.
4.3.21. 6-Methoxy-2-(thiophen-2-yl)quinazolin-4(3H)-one (3u)
[22]
4.3.14. 2-(Thiophen-2-yl)quinazolin-4(3H)-one (3n) [35]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3071, 1667, 1601,
Pale yellow solid. IR (KBr): nmax/cmꢁ1 3332, 3070, 1668, 1600,
1479, 1448, 1157, 946, 821, 764, 708; 1H NMR (400 MHz, DMSO‑d6):
1479, 1448, 1155, 944, 823, 764, 712; 1H NMR (400 MHz, DMSO‑d6):
d
12.68 (s, 1H), 8.26 (dd, J ¼ 3.6, 0.8 Hz, 1H), 8.15 (dd, J ¼ 8.0, 1.2 Hz,
d
12.63 (br, 1H), 8.21e8.19 (m, 1H), 7.83 (d, J ¼ 4.8 Hz, 1H), 7.62 (d,
1H), 7.88 (dd, J ¼ 5.2, 0.8 Hz, 1H), 7.82e7.79 (m, 1H), 7.67 (d,
J ¼ 8.8 Hz, 1H), 7.54 (d, J ¼ 2.8 Hz, 1H), 7.41 (dd, J ¼ 9.0, 3.0 Hz, 1H),
J ¼ 8.0 Hz, 1H), 7.53e7.49 (m, 1H), 7.27e7.24 (m, 1H); 13C NMR
7.23 (dd, J ¼ 5.0, 3.8 Hz, 1H), 3.89 (s, 3H); 13C NMR (100 MHz,
(100 MHz, DMSO‑d6): d 162.3, 149.1, 148.3, 137.9, 135.1, 132.6, 129.9,
DMSO‑d6):
d 162.0, 158.1, 146.3, 143.5, 138.0, 131.9, 129.2, 128.8,
128.9, 127.4, 126.8, 126.5, 121.4.
124.5, 122.2, 106.7, 56.1.
4.3.15. 2-(Pyridin-4-yl)quinazolin-4(3H)-one (3o) [35]
4.3.22. 7-Methyl-2-phenylquinazolin-4(3H)-one (3v) [57]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3332, 3080, 2956, 1673,
White solid. IR (KBr): nmax/cmꢁ1 3330, 3071, 1665, 1603, 1475,
1620, 1469, 1434, 1275, 1120, 821, 758; 1H NMR (400 MHz,
1447, 1143, 946, 823, 765; 1H NMR (400 MHz, DMSO‑d6)
d 12.44 (br,
DMSO‑d6):
d
12.77 (s, 1H), 8.79 (dd, J ¼ 4.8, 1.6 Hz, 2H), 8.19 (dd,
1H), 8.18e8.16 (m, 2H), 8.03 (d, J ¼ 8.0 Hz, 1H), 7.60e7.51 (m, 4H),
7.32 (d, J ¼ 8.0 Hz, 1H), 2.45 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
J ¼ 8.0, 1.2 Hz, 1H), 8.12 (dd, J ¼ 4.8, 1.6 Hz, 2H), 7.91e7.86 (m, 1H),
7.80 (d, J ¼ 8.0 Hz, 1H), 7.61e7.56 (m, 1H); 13C NMR (100 MHz,
d
162.6, 152.8, 149.3, 145.5, 133.3, 131.8, 129.0, 128.4, 128.2, 127.6,
DMSO‑d6):
d 162.6, 151.1, 150.7, 148.7, 140.5, 135.2, 128.2, 127.8,
126.2, 119.0, 21.8.
126.4, 122.1, 122.0.
4.3.23. 7-Methyl-2-(4-methoxyphenyl)quinazolin-4(3H)-one (3w)
[22]
4.3.16. 2-(Pyridin-3-yl)quinazolin-4(3H)-one (3p) [35]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3070, 2958, 1671,
Light yellow solid. IR (KBr): nmax/cmꢁ1 3332, 3071, 1666, 1601,
1624, 1469, 1445, 1275, 1140, 956, 803; 1H NMR (400 MHz,
1479, 1449, 1145, 944, 823, 763; 1H NMR (400 MHz, DMSO‑d6):
DMSO‑d6):
d
12.73 (s, 1H), 9.30 (d, J ¼ 2.0 Hz, 1H), 8.76 (dd, J ¼ 4.6,
d
12.29 (s, 1H), 8.17 (d, J ¼ 8.8 Hz, 2H), 8.00 (d, J ¼ 8.0 Hz, 1H), 7.49 (s,
1H), 7.28 (d, J ¼ 8.4 Hz, 1H), 7.07 (d, J ¼ 8.8 Hz, 2H), 3.84 (s, 3H), 2.44
(s, 3H); 13C NMR (100 MHz, DMSO‑d6):
162.6, 162.3, 152.3, 149.5,
1.4 Hz, 1H), 8.52e8.49 (m, 1H), 8.18 (dd, J ¼ 7.8, 1.0 Hz, 1H),
7.87e7.84 (m, 1H), 7.78 (d, J ¼ 8.0 Hz, 1H), 7.61e7.54 (m, 2H); 13C
d
NMR (100 MHz, DMSO‑d6):
d 162.6, 152.3, 151.2, 149.2, 148.9, 135.9,
145.4, 129.8, 128.0, 127.4, 126.1, 125.4, 118.8, 114.4, 55.9, 21.8.
135.2, 129.2, 128.0, 127.4, 126.3, 124.0, 121.6.
4.3.24. 7-Methyl-2-(furane-2-yl)quinazolin-4(3H)-one (3x) [22]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3335, 3073, 1668, 1602,
1560, 1479, 1447, 1155, 944, 823, 763, 705.1H NMR (400 MHz,
4.3.17. 6-Methoxy-2-phenylquinazolin-4(3H)-one (3q) [57]
White solid. IR (KBr): nmax/cmꢁ1 3332, 3071, 1668, 1600, 1479,
1448, 1145, 944, 823, 763; 1H NMR (400 MHz, DMSO‑d6):
d 12.51 (s,
DMSO‑d6):
7.47 (s, 1H), 7.28 (d, J ¼ 8.0 Hz, 1H), 6.73 (dd, J ¼ 3.6 Hz, 1.6 Hz, 1H),
2.43 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
161.9, 149.2, 146.9,
d
12.39 (s, 1H), 8.00e7.97 (m, 2H), 7.60 (d, J ¼ 3.6 Hz,1H),
1H), 8.16 (dd, J ¼ 7.8, 1.4 Hz, 2H), 7.69 (d, J ¼ 8.8 Hz, 1H), 7.58e7.51
(m, 4H), 7.43 (dd, J ¼ 9.0, 3.0 Hz, 1H), 3.89 (s, 3H); 13C NMR
d
(100 MHz, DMSO‑d6): d 162.5, 158.2, 150.6, 143.7, 133.3, 131.5, 129.7,
146.6, 145.5, 144.5, 128.3, 127.4, 126.2, 119.2, 114.8, 112.9, 21.8.
129.0, 128.0, 124.6, 122.2, 106.3, 56.1.
4.3.25. 7-Methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (3y) [22]
Light yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3070, 1669, 1600,
1478, 1448, 1143, 946, 823, 706; 1H NMR (400 MHz, DMSO‑d6):
4.3.18. 6-Methoxy-2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3r)
White solid. IR (KBr): nmax/cmꢁ1 3334, 3073, 1667, 1601, 1478,
1449,1147, 942, 825, 765; 1H NMR (400 MHz, DMSO‑d6):
d 12.38 (br,
d
12.54 (s, 1H), 8.22 (d, J ¼ 3.2 Hz, 1H), 8.01 (d, J ¼ 8.0 Hz, 1H), 7.85
1H), 8.16 (d, J ¼ 8.8 Hz, 2H), 7.66 (d, J ¼ 8.8 Hz, 1H), 7.53 (d,
(d, J ¼ 4.8 Hz, 1H), 7.47 (s, 1H), 7.31 (d, J ¼ 8.0 Hz, 1H), 7.24 (dd,
J ¼ 3.2 Hz, 1H), 7.43 (dd, J ¼ 8.8, 3.2 Hz, 1H), 7.08 (d, J ¼ 8.8 Hz, 2H),
J ¼ 4.8, 4.0 Hz, 1H), 2.46 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
3.89 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d 162.6,
d
162.1, 149.2, 148.3, 145.7, 138.0, 132.5, 129.7, 128.9, 128.2, 127.1,
162.1, 157.9, 150.3, 143.7, 129.6, 129.3, 125.3, 124.5, 121.9, 114.4,
106.4, 56.1, 55.9. HRMS calcd for C16H14N2Oþ3 [Mþ]: 282.1004, found
282.1005.
126.3, 118.9, 21.8.
4.3.26. 7-Methyl-2-(pyridin-3-yl)quinazolin-4(3H)-one (3z)
Light yellow solid. IR (KBr): nmax/cmꢁ1 3331, 3070, 2958, 1675,
1625, 1600, 1469, 1445, 1380, 1140, 956, 803; 1H NMR (400 MHz,
4.3.19. 6-Methoxy-2-(4-chlorophenyl)quinazolin-4(3H)-one (3s)
White solid. IR (KBr): nmax/cmꢁ1 3331, 3070, 1666, 1600, 1479,
1445, 1143, 946, 820, 705; 1H NMR (400 MHz, DMSO‑d6):
d
12.57
DMSO‑d6):
d
12.59 (s, 1H), 9.28 (d, J ¼ 2.0 Hz, 1H), 8.74 (dd, J ¼ 4.8,
(br, 1H), 8.18 (d, J ¼ 8.4 Hz, 2H), 7.70 (d, J ¼ 8.8 Hz, 1H), 7.61 (d,
1.6 Hz,1H), 8.48e8.45 (m,1H), 8.02 (d, J ¼ 8.0 Hz,1H), 7.58e7.53 (m,
J ¼ 8.4 Hz, 2H), 7.54 (d, J ¼ 3.2 Hz, 1H), 7.45 (dd, J ¼ 8.8, 2.8 Hz, 1H),
2H), 7.33 (dd, J ¼ 8.0, 1.2 Hz, 1H), 2.45 (s, 3H); 13C NMR (100 MHz,
3.90 (s, 3H); 13C NMR (100 MHz, DMSO‑d6):
d
162.4, 158.4, 149.6,
DMSO‑d6): d 162.4, 152.2, 151.1, 149.2, 149.1, 145.6, 135.7, 129.2,
143.5, 136.4, 132.1, 129.8, 129.7, 129.1, 124.6, 122.3, 106.4, 56.1. HRMS
128.8, 127.6, 126.2, 123.9, 119.2, 21.8. HRMS calcd for C14H11N3Oþ
[Mþ]: 237.0902, found 237.0911.
calcd for C15H11ClN2Oþ2 [Mþ]: 286.0509, found 286.0504.

44
S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
4.3.27. 6-Chloro-2-phenylquinazolin-4(3H)-one (3a') [58]
4.3.34. 1-Methyl-5-(4-fluorophenyl)-3-propyl-1H-pyrazolo[4,3-d]
pyrimidin-7(6H)-one (3h')
White solid. IR (KBr): nmax/cmꢁ1 3331, 3073, 1666, 1601, 1479,
1449, 1143, 946, 823, 705; 1H NMR (400 MHz, DMSO‑d6):
d
12.69
White solid. IR (KBr): nmax/cmꢁ1 3264, 3064, 2933, 1675, 1575,
(br,1H), 8.16 (d, J ¼ 7.2 Hz, 2H), 8.08 (d, J ¼ 2.0 Hz,1H), 7.87e7.83 (m,
1421, 1311, 1145, 947, 836, 769; 1H NMR (400 MHz, DMSO‑d6):
1H), 7.76 (d, J ¼ 8.4 Hz, 1H), 7.63e7.53 (m, 3H); 13C NMR (100 MHz,
d
12.44 (br, 1H), 8.15e8.11 (m, 2H), 7.36 (t, J ¼ 8.8 Hz, 2H), 4.15 (s,
DMSO‑d6): d 161.8, 153.4, 147.9, 135.2, 132.9, 132.1, 131.3, 130.1, 129.1,
3H), 2.78 (t, J ¼ 7.4 Hz, 2H), 1.80e1.74 (m, 2H), 0.95 (t, J ¼ 7.4 Hz,
1
128.3, 125.3, 122.7.
3H); 13C NMR (100 MHz, DMSO‑d6):
d
164.0 (d, JC-F ¼ 254.5 Hz),
155.1, 149.7, 145.4, 138.3, 130.5 (d, 3JC-F ¼ 8.8 Hz), 129.9, 124.8, 116.0
2
(d, JC-F ¼ 21.8 Hz), 38.3, 27.6, 22.1, 14.3. HRMS calcd for
4.3.28. 6-Chloro-2-(thiophen-2-yl)quinazolin-4(3H)-one (3b') [58]
White solid. IR (KBr): nmax/cmꢁ1 3332, 3072, 1669, 1600, 1477,
C
15H15FN4Oþ [Mþ]: 286.1230, found 286.1227.
1448, 1145, 947, 823, 706; 1H NMR (400 MHz, DMSO‑d6):
d 12.76 (s,
Acknowledgements
1H), 8.21 (d, J ¼ 3.2 Hz, 1H), 8.01 (d, J ¼ 2.0 Hz, 1H), 7.87 (d,
J ¼ 4.8 Hz, 1H), 7.77 (dd, J ¼ 8.8, 2.4 Hz, 1H), 7.63 (d, J ¼ 8.4 Hz, 1H),
7.23 (t, J ¼ 4.4 Hz, 1H); 13C NMR (100 MHz, DMSO‑d6):
d 161.3, 148.7,
We thank the National Natural Science Foundation of China (No.
21462021) and Key Laboratory of Functional Small Organic Mole-
cule, Ministry of Education (No. KLFS-KF-201704) for financial
support.
147.9, 137.5, 135.1, 132.9, 130.9, 130.2, 129.6, 129.0, 125.5, 122.5.
4.3.29. 6-Fluoro-2-phenylquinazolin-4(3H)-one (3c')
White solid. IR (KBr): nmax/cmꢁ1 3331, 3070, 1667, 1602, 1478,
References
1449, 1143, 946, 825, 708; 1H NMR (400 MHz, DMSO‑d6):
d 12.63
(br, 1H), 8.16 (d, J ¼ 7.2 Hz, 2H), 7.83e7.77 (m, 2H), 7.74e7.68 (m,
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160.5 (d, JC-F ¼ 243.9 Hz), 152.4, 146.1, 133.0, 131.9, 130.7, 129.1,
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F
240.0697.
4.3.30. 7-Nitro-2-phenylquinazolin-4(3H)-one (3d') [22]
Yellow solid. IR (KBr): nmax/cmꢁ1 3330, 3070, 1668, 1600, 1518,
1448, 1352, 1143, 946, 823, 705; 1H NMR (400 MHz, DMSO‑d6):
d
12.91 (br, 1H), 8.45 (d, J ¼ 2.4 Hz, 1H), 8.37 (d, J ¼ 8.4 Hz, 1H),
8.25e8.20 (m, 3H), 7.65e7.56 (m, 3H); 13C NMR (100 MHz,
DMSO‑d6): 161.9, 155.1, 151.8, 149.6, 132.6, 132.5, 129.2, 128.6,
d
128.5, 125.8, 122.8, 120.5.
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4.3.31. 7-Nitro-2-(furane-2-yl)quinazolin-4(3H)-one (3e')
Yellow solid. IR (KBr): nmax/cmꢁ1 3335, 3070, 1668, 1601, 1520,
1479, 1448, 1342, 944, 823, 763, 705; 1H NMR (400 MHz, DMSO‑d6):
d
12.43 (s, 1H), 9.29 (d, J ¼ 1.6 Hz, 1H), 9.24 (d, J ¼ 2.4 Hz, 1H), 8.45
(d, J ¼ 8.8 Hz, 1H), 8.39e8.33 (m, 2H), 7.44 (d, J ¼ 8.8 Hz, 1H); 13C
NMR (100 MHz, DMSO‑d6):
d 160.1, 151.0, 142.8, 142.2, 134.6, 130.2,
126.0, 123.4, 120.9, 119.5, 117.7, 117.1. HRMS calcd for C12H7N3O4þ
[Mþ]: 257.0437, found 257.0429.
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4.3.32. 1-Methyl-5-phenyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-
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White solid. IR (KBr): nmax/cmꢁ1 3268, 3171, 2960, 2872, 1697,
1561, 1498, 1434, 1390, 1259, 1238, 823, 758; 1H NMR (400 MHz,
DMSO‑d6):
d 12.41 (s, 1H), 8.08e8.05 (m, 2H), 7.73e7.68 (m, 1H),
7.58e7.50 (m, 2H), 4.16 (s, 3H), 2.79 (t, J ¼ 7.4 Hz, 2H), 1.80e1.75 (m,
2H), 0.96 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6):
d 154.4,
151.5, 144.3, 135.9, 133.2, 128.3, 124.9, 119.5, 118.0, 38.4, 27.7, 22.1,
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d]pyrimidin-7(6H)-one (3g')
White solid. IR (KBr): nmax/cmꢁ1 3280, 3170, 2960, 1687, 1560,
1435, 1380, 1263, 1211, 928, 823; 1H NMR (400 MHz, DMSO‑d6):
d
12.32 (br, 1H), 8.13 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.40 (t, J ¼ 7.6 Hz, 1H),
6.99 (d, J ¼ 8.0 Hz, 1H), 6.95 (t, J ¼ 7.6 Hz, 1H), 4.16 (s, 3H), 3.82 (s,
3H), 2.80 (t, J ¼ 7.4 Hz, 2H), 1.78e1.72 (m, 2H), 0.95 (t, J ¼ 7.4 Hz,
3H); 13C NMR (100 MHz, DMSO‑d6):
d 167.1, 161.1, 155.1, 147.6, 134.2,
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HRMS calcd for C16H18N4O2þ [Mþ]: 298.1430, found 298.1435.

S. You et al. / Journal of Organometallic Chemistry 875 (2018) 35e45
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