Palladium(II) N^O Chelating Complexes Catalyzed One-Pot Approach for Synthesis of Quinazolin-4(3 H)-ones via Acceptorless Dehydrogenative Coupling of Benzyl Alcohols and 2-Aminobenzamide

Article abstract of DOI:10.1021/acs.organomet.0c00814

A convenient protocol for the one-pot synthesis of quinazolin-4(3H)-ones using palladium(II) complexes via dehydrogenative coupling of readily available benzyl alcohols and 2-aminobenzamide has been described. New structurally related Pd(II) N^O chelating complexes of general configuration [Pd(L)Cl(PPh3)] (where L = dimethylamino benzoylhydrazone ligands) have been designed and synthesized. The formation of the complexes has been recognized by analytical and spectral methods (FT-IR, NMR, HR-MS). The presence of a square-planar geometry around the palladium(II) ion was confirmed by single crystal X-ray diffraction study. A wide range of substituted quinazolinones have been successfully achieved from a diverse range of benzyl alcohols in good to excellent yields using 1.0 mol % of catalyst loading under aerobic conditions. Furthermore, control experiments reveal that the dehydrogenative coupling reaction involves initially the formation of an aldehyde intermediate and subsequent formation of a cyclic aminal intermediate.

Full text of DOI:10.1021/acs.organomet.0c00814

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Article
Palladium(II) N^O Chelating Complexes Catalyzed One-Pot
Approach for Synthesis of Quinazolin-4(3H)‑ones via Acceptorless
Dehydrogenative Coupling of Benzyl Alcohols and
2‑Aminobenzamide
Sundarraman Balaji, Gunasekaran Balamurugan, Rengan Ramesh,* and David Semeril
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ABSTRACT: A convenient protocol for the one-pot synthesis of
quinazolin-4(3H)-ones using palladium(II) complexes via dehydro-
genative coupling of readily available benzyl alcohols and 2-
aminobenzamide has been described. New structurally related Pd(II)
N^O chelating complexes of general configuration [Pd(L)Cl(PPh3)]
(where L = dimethylamino benzoylhydrazone ligands) have been
designed and synthesized. The formation of the complexes has been
recognized by analytical and spectral methods (FT-IR, NMR, HR-
MS). The presence of a square-planar geometry around the
palladium(II) ion was confirmed by single crystal X-ray diffraction
study. A wide range of substituted quinazolinones have been
successfully achieved from a diverse range of benzyl alcohols in
good to excellent yields using 1.0 mol % of catalyst loading under
aerobic conditions. Furthermore, control experiments reveal that the
dehydrogenative coupling reaction involves initially the formation of an aldehyde intermediate and subsequent formation of a cyclic
aminal intermediate.
ologies suffer in providing the desired products of
quinazolinone due to low yield, long reaction time, multistep
reaction sequences, need of oxidants like DDQ,11a CuCl2,11b
MnO2,11c KMnO4,11d I2,11e and t-BuOOH.11f−h Further,
limitation associated with the above synthetic routes is the
use of unstable aldehydes through oxidation of alcohols using
toxic oxidants.
To accomplish the greener strategy, the transition-metal-
catalyzed acceptorless alcohol dehydrogenation (AAD)
methodology12 is one of the attractive and convenient
methodologies for the synthesis of quinazolinone and other
N-heterocycles.13 Zhou and co-workers disclosed the synthesis
of quinazolinones using 2.5 mol % of Ir catalyst from the
coupling of benzyl alcohols and 2-aminobenzamides under
inert condition.14 Watson and co-workers achieved the access
of quinazolinones using 5 mol % of a ruthenium catalyst under
a N2 atmosphere.15 Wu and co-workers developed a ZnI2/
INTRODUCTION
■
Nitrogen heterocycles exhibit momentous interest over the
years due to their presence in an extensive range of synthetic
and natural organic compounds.1 Among them, quinazolinones
and their derivatives are an important class of compounds
found in a large number of natural products.2 Significantly, a
diverse range of molecules with quinazolin-4(3H)-ones display
a broad spectrum of bioactivities.3−9 (Figure 1) Therefore, a
vast number of synthetic approaches have been established10
due to the immense biological needs of quinazolinone and its
derivatives in various fields.9,10d However, all these method-
Received: December 30, 2020
Published: March 4, 2021
Figure 1. Examples of bioactive quinazolinones.
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TBHP catalyst for the synthesis of quinazolinones from the
reaction of 2-aminobenzamide and benzyl alcohols.16 Iron-
catalyzed oxidative synthesis of quinazolinones from primary
alcohols has been reported in the presence of expensive TBHP
oxidant.17 Hu and co-workers have described a report on the
synthesis of quinazolinones from alcohols and 2-amino-
benzamides with iron nitrate/TEMPO.18 Zhang et al. has
reported ruthenium-catalyzed dehydrogenative coupling of 2-
aminobenzamides and allylic alcohols.20 Recently, direct access
of quinazolinones from aromatic primary alcohols were
documented by Paul and co-workers using nickel(II) (5 mol
%) and copper(II) (5 mol %) catalysts.19,21
Remarkably, the Pd-catalyzed cross-coupling reactions have
given a great contribution in the construction of heterocyclic
compounds,22 especially for the synthesis of quinazolinones.23
Yokoyama et al. investigated quinazolinone synthesis from the
reaction of 2-aminobenzamide and an excess of alcohol at the
expense of 5 mol % of a Pd(OAc)2/TPPMS catalyst in H2O
medium.24a Beller et al. synthesized quinazolinone from the
coupling reaction of 2-aminobenzamide and aryl halide under
catalytic condition of Pd(OAc)2/BuPAd2 and a carbon
monoxide (10 bar) atmosphere in DMF.24b Zhu et al. reported
the synthesis of quinazolinone from multi-component reaction
of anthranilamide, aryl halide, and tert-butyl isocyanide with
optimal catalytic condition of PdCl2 (5 mol %)/DPPP and
CaCl2 as an additive in toluene at 145 °C under a N2
atmosphere.24c Liu et al. described quinazolinones synthesis
using Pd(TFA)2 (10 mol %) and bpy (20 mol %) under an
oxygen atmosphere.24d Zhu et al. examined the synthesis of
quinazolinone from multi-component reaction of substituted
anthranilamide with arylboronic acids, tertbutylisocyanide, and
Cu(OAc)2 with the reaction condition of Pd(PPh3)2Cl2 under
a N2 atmosphere in DMF.24e The same research group has
reported the synthesis of quinazolinone from 2-amino-
benzamide, bromobenzene, and Mo(CO)6 under the condition
of PdCl2/BuPAd2 and DBU in DMF under air24f (Scheme 1).
Further, hydrazone based metal complexes are involved as
effective catalysts in coupling reactions. Hydrazones act as
spectator ligands which keep the metal ion reactive in solution
and stabilize specific metal oxidation states. They can be used
to tune the reactivity of a metal by defining the steric and
electronic properties of the complex as a whole.25 Especially,
the presence of a dimethylamino group on the ligand enhances
the reaction rate in the palladium-catalyzed aerobic dehydro-
genation reaction.26
The synthesis of quinazolinones from the dehydrogenative
coupling of alcohols with 2-aminobenzamide under aerobic
condition using palladium(II) hydrazone complexes has not
been well explored in the literature. Therefore, in continuation
of our previous reports,27,28 we wish to describe the easy access
of a wide range of quinazolinones via dehydrogenation of
benzyl alcohols under mild reaction conditions by newly
synthesized palladium(II) benzoylhydrazone complexes. Grat-
ifyingly, the present methodology is considered an atom-
economical and environmentally benign protocol which
releases water as the only byproduct.
RESULTS AND DISCUSSION
■
The dimethylamino benzoylhydrazone ligands were easily
prepared from the condensation of dimethylaminobenzalde-
hyde and 4-substituted benzhydrazide in ethanol.29 Complex-
ation was accomplished by reacting these ligands with the
palladium(II) precursor [PdCl2(PPh3)2] in a 1:1 molar ratio in
the presence of an equivalent of Et3N as a base. The resulting
reddish orange complexes of common formula, [Pd(L)Cl-
(PPh3)] (Scheme 2), were obtained in good yields. The
Scheme 2. Synthesis of Pd(II) Benzoylhydrazone
Complexes
Scheme 1. Synthetic Strategies for Quinazolinone
Formation
addition of Et3N in the reaction mixture assists the amido-
imidol tautomerization for effortless coordination of imidolate
oxygen. All the palladium complexes are stable in air and
readily dissolved in most organic solvents. The newly formed
palladium benzoylhydrazone complexes were authenticated
with the help of analytical and different spectral techniques.
A medium to strong band is observed in the region 3034−
3095 cm−1 due to νN‑H of the hydrazone moiety of the ligands.
In addition, the νCN and νCO absorption frequencies of the
ligands appear around 1539−1568 cm−1 and 1610−1642 cm−1,
respectively. The νCN stretching frequencies were decreased
to 1579−1582 cm−1 upon complexation, which confirm that
imine nitrogen is coordinated to a palladium ion. Furthermore,
the disappearance of νCO bands and appearance of new bands
in the region of 1341−1345 cm−1 indicated the coordination of
imidolate oxygen via tautomerization. It is inferred from the IR
spectra that the imine nitrogen and imidolate oxygen of the
benzoylhydrazone ligand coordinate to the palladium(II) ion.
The NMR spectral studies support the bidentate coordinat-
ing character of the ligand to metal in the synthesized
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1
palladium(II) benzoylhydrazone complexes. In the H NMR
spectra of complexes 1−3, aromatic protons of the phenyl
group of triphenylphosphine and benzoylhydrazone ligands
were observed as multiplets at δ 6.70−8.32 ppm. Azomethine
proton (NC-H) was observed as a doublet at δ 7.90−7.94
ppm in all three complexes. The single azomethine proton
showed a doublet instead of a singlet due to its coupling with
the phosphorus nuclei of the triphenyphosphine ligand.30 After
the complex formation, the absence of a signal around 10.29−
11.55 ppm indicates the disappearance of the −NH proton of
ligands due to coordination of imidolate oxygen to the
palladium ion through enolization. In addition, complex 3
displayed a methoxy signal of the benzoylhydrazone ring as
singlet at δ 3.80 ppm (SI, Figures S1−S3). Further, carbon
NMR of the complexes 1−3 showed a downfield shift of the
carbonyl group to 175.00, 173.94, and 174.98 ppm,
respectively, which results from the reduced bond order
(−NC−O) upon complexation (−NH−CO) with Pd. In
contrast, the upfield shift of imine carbon (CN) to 152.26,
152.54, and 151.92 was observed during the nitrogen
coordination of the benzoylhydrazone ligand with the
palladium precursor. Moreover, the complex 3 showed that
an additional signal at δ 55.30 ppm was due to the presence of
methoxy carbon (SI, Figures S4−S6). The 31P NMR spectrum
of a representative complex 1 showed a sharp singlet at 24.25
ppm, which indicates the presence of PPh3 (SI, Figure S7).
Furthermore, the composition of the complexes has been
established by high resolution mass spectrometry (HRMS)
analysis (SI, Figures S8−S10). Mass spectrometric measure-
ment was carried out under positive ion ESI mode using
acetonitrile. The mass spectra of all the complexes show a well-
defined molecular ion peak at m/z = 675.1507 ([M + 2H]+),
709.1116 ([M + 2H]+), and 705.1604 ([M + 2H]+) peak
fragments. Hence, the mass spectral data are in good
agreement with the structural composition of the complexes.
Single crystals of complexes 2 and 3 were isolated from a
CH2Cl2/methanol mixture at room temperature. The solid-
state molecular structures of palladium(II) benzoylhydrazone
complexes 2 and 3 were resolved by X-ray crystallography. The
summary of the crystallographic data and refinement
parameters are given in Table S1, and the selected bond
lengths along with bond angles are gathered in Table S2. The
Figure 2. ORTEP diagram of the complex 2 with 30% probability. All
the hydrogen atoms were omitted for clarity. The bond angles (deg)
around the Pd(1) ion: O(1)−Pd(1)−N(2) = 78.77(8), N(2)−
Pd(1)−P(1) = 175.92(6), O(1)−Pd(1)−Cl(2) = 174.95(5). Bond
lengths (Å): N(2)−Pd(1) = 2.059(2), O(1)−Pd(1) = 2.0106(18),
P(1)−Pd(1) = 2.2650(7), Cl(2)−Pd(1) = 2.2806(7).
Figure 3. ORTEP diagram of the complex 3 with 30% probability. All
the hydrogen atoms were omitted for clarity. The bond angles (deg)
around the Pd(1) ion: O(1)−Pd(1)−N(1) = 78.90(8), N(1)−
Pd(1)−P(1) = 174.25(6), O(1)−Pd(1)−Cl(1) = 175.22(5). Bond
lengths (Å): N(1)−Pd(1) = 2.055(2), O(1)−Pd(1) = 2.0100(18),
P(1)−Pd(1) = 2.2561(7), Cl(1)−Pd(1) = 2.2790(7).
the reaction of 2-aminobenzamide (1a) and benzyl alcohol
(2a) as a benchmark substrate using 1 mol % of complex 1
(Table 1). The satisfactory yield (Table 1, entry 1) of
synthesized quinazolinone helped us to investigate various
catalytic parameters such as bases, solvents, and reaction
temperatures (Table 1). Further, the screening of solvents
dictated that nonpolar m-xylene outperformed the other
solvents (toluene, 1,4-dioxane, THF, acetonitrile, methanol,
ethanol, DMF, DMSO, and H2O) that were examined in this
catalytic reaction (Table 1, entries 1−10). Also, the
optimization of different bases revealed that KOH was found
to be more effective than other bases including NaOH, tBuOK,
Cs2CO3, K2CO3, Na2CO3, NaHCO3, Et3N) (Table 1, entries 1
and 11−17) employed in the reaction. Therefore, we are
pleased to compromise that the complex 1 is found to exhibit
relatively high yield (entry 18, 88%) of desired quinazolinone
under the catalytic conditions of m-xylene/KOH at 110 °C.
The coupling reaction was unsuccessful in the absence of
either catalyst or base (Table 1, entries 21 and 22).
̅
complex 2 crystallized in triclinic form with the P1 space
group, whereas complex 3 crystallized in the monoclinic P21/n
space group. The ORTEP views of the complexes are shown in
Figures 2 and 3, which clearly indicate that the ligand binds to
palladium metal in a bidentate (N^O) manner through the
imine nitrogen and imidolate oxygen with a formation of a five-
membered chelate ring.
The bite angles of N(2)−Pd(1)−O1(1) and N(12)−
Pd(1)−O1(1) in complexes 2 and 3 are 78.77(8)° and
78.90(8)°, respectively. The other positions were occupied by
chloride and phosphine ligands. Eventually, the palladium(II)
ion is present in a ONPCl square-planar environment as
reflected in all the bond parameters.31,25d,e
The remarkable applications of palladium catalysts to an
extensive variety of coupling reactions motivated us to tune the
present Pd(II) hydrazone complexes as catalysts in the direct
synthesis of bioactive quinazolinones via dehydrogenative
coupling substituted benzyl alcohols and 2-aminobenzamide
under aerobic condition.
Once the various catalytic parameters were optimized, the
effect of substituents of all the complexes on the catalytic
reaction has been investigated. At most, all the complexes (1−
3) showed good catalytic activity in the formation of
quinazolinone product with appreciable yields. However, on
the basis of experimental results, the complex 3 relatively
provided a better yield than complex 1 and complex 2 due to
the presence of an electron-donating methoxy group (Table 2,
To initiate the optimization of reaction conditions, we have
selected the formation of 2-phenylquinazolin-4(3H)-one from
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a
a
Table 1. Optimization of Reaction Conditions
Table 3. Effect of Catalyst Loading
b
b
entry
complex 3 (mol %)
yield (%)
entry
solvent
base
T (°C)
time (h)
yield (%)
1
2
3
4
5
1
91
66
41
25
14
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
m-xylene
toluene
dioxane
THF
acetonitrile
methanol
ethanol
DMF
DMSO
H2O
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
m-xylene
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
Na2CO3
K2CO3
NaHCO3
KOH
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
110
110
80
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
82
61
40
26
65
15
12
75
63
30
50
55
45
90
69
77
15
88
90
50
<10
NR
10
15
22
0.5
0.2
0.1
0.05
a
Reaction conditions: 2-aminobenzamide 1a (1 mmol), benzyl
alcohol 2a (1.10 mmol), catalyst (0.05−1 mol %), KOH (1.5
mmol) in m-xylene at 110 °C for 24 h under open air. Isolated yield.
b
alcohols (Table 4). It is noted that the benzyl alcohol and their
derivatives were found to be effective coupling partners with o-
Table 4. Dehydrogenative Coupling of 2-Aminobenzamide
1a and Various Benzyl Alcohols 2a Catalyzed by Complex
a b
,
3
Cs2CO3
tBuOK
Et3N
KOH
KOH
c
KOH
d
110
110
110
110
110
e
KOH
KOH
KOH
KOH
f
23
24
25
g
h
a
General reaction conditions: 2-aminobenzamide 1a (1 mmol),
benzyl alcohol 2a (1.10 mmol), complex 1 (1 mol %), KOH (1.5
b
mmol) in m-xylene at 70−130 °C for 24 h under open air. Isolated
c
d
e
f
g
yield. N2 atm. No base. No catalyst. PdCl2. Pd(OAc)2.
h
[PdCl2(PPh3)2].
a
Table 2. Effect of the Substituent of Catalyst
b
entry
Pd complex
yield (%)
1
2
3
[Pd(L1)Cl(PPh3)] (1)
[Pd(L2)Cl(PPh3)] (2)
[Pd(L3)Cl(PPh3)] (3)
82
86
91
a
Reaction conditions: 2-aminobenzamide 1a (1 mmol), alcohol 2a
(1.10 mmol), base (1.5 mmol), m-xylene at 110 °C for 24 h under
a
General reaction conditions: 2-aminobenzamide 1a (1 mmol),
benzyl alcohol 2a (1.10 mmol), catalyst (1 mol %), KOH (1.5 mmol)
in m-xylene at 110 °C for 24 h under open air. Isolated yields.
b
open air. Isolated yield.
b
aminobenzamide to provide a respective quinazolinone with
good yield. The reaction of benzyl alcohol with o-amino-
benzamide resulted in the formation 2-phenylquinazolin-
4(3H)-one 3a in 91% yield. Further, the benzyl alcohols
bearing electron-donating substituents at ortho, meta, and para
positions effectively reacted with 2-aminobenzamide to give
the corresponding quinazolinones 3b−3h in 71−89% yields.
Gratifyingly, the catalytic efficiency was proved for the reaction
of sterically hindered 3,4,5-trimethoxybenzyl alcohol with 2-
aminobenzamide to give the desired 3i in 77% yield. In the
case of benzyl alcohol with electron-withdrawing substituents
such as 3-fluorobenzyl alcohol, 4-chlorobenzyl alcohol, and 2-
entries 1−3). Hence, the complex 3 was kept as a
representative catalyst to explore the broad substrate scope
using a diverse range of alcohols. Furthermore, the effect of
catalyst loading was verified under optimal reaction conditions.
From the results, the catalytic reaction proceeds well with 1
mol % and a drop in the yields upon decreasing the catalyst
loading to 0.5, 0.2, 0.1, or 0.05 mol % (Table 3, entries 1−5).
Having optimized conditions in our hand, the scope of the
palladium-catalyzed acceptorless dehydrogenate reaction was
interestingly probed for the coupling of 2-aminobenzamide
with various aromatic, polycyclic, and heterocyclic aromatic
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bromobenzyl alcohol, the yields of the respective quinazoli-
nones 3l−3j were 58−69%. More interestingly, we use the
current catalytic protocol for introducing a heterocyclic ring in
the quinazolin-4(3H)-one. Hence, the heterocyclic aromatic
alcohols such as 2-pyridine methanol, 2-thiophene methanol,
and furfuryl alcohol smoothly coupled with 2-aminobenzamide
to give the corresponding products 3m−3o in 65−67% yields.
In addition, the coupling reaction of piperonyl alcohol with 2-
aminobenzamide afforded the respective quinazolinone 3p in
55%yield. Noticeably, reactions of polycyclic alcohols, namely,
2-naphthalenemethanol and 9-anthracenemethanol, underwent
dehydrogenative coupling with 2-aminobenzamide to give a
moderate yield of quinazolinones 3q and 3r as 59% and 56%,
respectively. In addition, application of biphenyl-4-methanol in
the catalysis course resulted the preferred product 3s with 58%
yield. The reaction of indole-3-carbinal with 2-aminobenza-
mide resulted in product 3t in 54% yield (SI, Figures S15−
S54). Attempts were made for coupling reaction of aliphatic
alcohols such as 1-propene-3-ol, n-hexanol, and n-butyl alcohol
with 2-aminobenzamide, and they were found to be ineffective
toward quinazolinone formation.
Control experiments were carried out in order to investigate
the mechanism behind the catalytic acceptorless dehydrogen-
ation coupling reaction. In the absence of 2-aminobenzamide
2a, benzyl alcohol 1a gives rise to the corresponding aldehyde
intermediate 1a′ in 6 h under optimized reaction conditions
(Figures S11 and S12). Further, 1a′ and amide 2a yielded the
cyclic aminal intermediate 2a′ in 6−12 h (Figures S13, S14,
and S55). Furthermore, the completion of quinazolin-4(3H)-
ones product 3a was reached when the reaction time was
extended up to 24 h (Scheme 3a). The reaction of 1a′ and 2a
aminal intermediate and proceeds through the dehydrogen-
ative pathway19 with the help of the palladium(II) catalyst.
To get more understanding about the impact of electron-
donating and electron-withdrawing substituents of substrates
on catalytic reactivity, an intermolecular competitive experi-
ment has been carried out under optimized reaction conditions
using benzyl alcohol bearing electron-donating (4-methoxy) 2e
and electron-withdrawing (4-chloro) 2k with 2-aminobenza-
mide. The outcome of the control reaction proves that the
electron-rich substrate 3e shows more reactivity than the
electron-deficient substrate 3k (Scheme 4).
Scheme 4. Competitive Control Experiment between EDG
and EWG
On the basis of the control experiments and previous
reports, a possible reaction mechanism has been depicted in
Scheme 5 for the dehydrogenative coupling of 2-amino-
Scheme 5. Plausible Mechanism for the Synthesis of
Quinazolinone
Scheme 3. Control Experiments for Mechanistic Studies
benzamide with primary alcohol using the palladium catalyst.
The coupling reaction is supposed to begin with the formation
of palladium−alkoxy species (B). Then, the (B) undergoes β-
H elimination to provide benzaldehyde (B′) along with the
formation of a palladium−hydride species (C). Further, the in
situ formed benzaldehyde (B′) condensed with 2-amino-
benzamide to form cyclic aminal intermediate (C′). The
palladium−hydride species (C) formed in this mechanism and
cyclic aminal C′ are oxidized by molecular oxygen33,26 with the
release of water, followed by coordination of more basic
nitrogen14 on C′ to the palladium ion produced amino
palladium species (D). Thereafter, the formed amino
palladium species (D) undergoes dehydrogenation to form
quinazolin-4(3H)-one (E) with the release of water.
was conducted in the absence of complex 3 at 12 h, and 41% of
isolated yield of 2a′ was obtained (Scheme 3b). Further,
reaction of t-butanol or phenol32 with 2-aminobenzamide
under the optimized experimental conditions was carried out
in order to establish dehydrogenation via AAD. It has been
observed that no quinazolinone product was formed which
clearly indicates methylene hydrogen of benzyl alcohol
influences the AAD strategy (Scheme 3c). Hence, we strongly
believe that the synthesis of the quinazolinones occurs via
alcohol dehydrogenation along with the formation of a cyclic
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H2, H3, H5, H6), 3.06 (s, 6H, N(CH3)2). 13C NMR (100 MHz,
CDCl3, δ, ppm):174.98 (NC−O), 161.27(C14), 151.92 (CN),
135.31 (C4), 134.88 (C11), 134.77 (C18, C24, C30), 131.08 (C19,
C23, C25, C29), 131.06 (C20, C22, C26, C28, C32, C34), 130.64
(C21, C27, C33), 129.21 (C12, C16), 128.55 (C13), 128.37 (C15,
C5), 124.56 (C3), 119.25 (C2) 113.08 (C6), 111.08 (C1), 55.30
(OCH3), 40.03 (N(CH3)2). ESI-MS: displays a peak at m/z 705.1604
([M + 2H]+), (calcd: 0.703.1037). The CCDC number for complex 3
is 1565995.
General Protocol for Synthesis of Quinazolinones. Under an
open air atmosphere, a mixture of [Pd(L)Cl(PPh3)] (0.005 mmol),
KOH (1.5 mmol), alcohol (1.10 mmol), and 2-aminobenzamide (1.0
mmol) was dissolved in 10 mL of m-xylene, and the mixture was
placed in an oil bath and heated at 110 °C for 24 h. After the
completion of the reaction by TLC, the resulting mixture was
concentrated and the formed quinazolinone was isolated by column
chromatography using silica gel with hexane:ethyl acetate (85:15) as
an eluent.
CONCLUSIONS
■
In summary, we report palladium(II) benzoylhydrazone
complexes as efficient catalysts for the direct synthesis of
quinazolin-4(3H)-ones from acceptorless dehydrogenative
coupling of substituted benzyl alcohols and 2-aminobenza-
mide. This approach unveiled a broad substrate scope to
synthesize a wide variety of quinazolinone derivatives with the
maximum yield of 91% at 1 mol % catalyst loading. This
straightforward protocol operates at aerobic conditions, and
water is the only byproduct. Control experiments and the
mechanistic investigation indicate the coupling reaction
proceeds via dehydrogenation of alcohols. The present results
undoubtedly explore a chance for the creation of distinct and
valuable biologically important heterocycles using palladium
catalysts.
Competitive Control Experiment between EDG and EWG. 4-
Methoxybenzyl alcohol 2e (1.10 mmol), 4-chlorobenzyl alcohol 2k
(1.10 mmol), 2-aminobenzamide (1 mmol), KOH (1.5 mmol), and
catalyst 3 (1 mol %), were stirred in m-xylene at 110 °C (oil bath) for
18 h under open air. The completion of the reaction was monitored
by TLC, and the formed 3e and 3k were isolated by column
chromatography using hexane:ethyl acetate (85:15) as an eluent with
41% and 18% isolated yields, respectively.
Spectral Data for 2-Phenyl-2,3-dihydroquinazolin-4(1H)-
one (2a′).14 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 8.35 (s,
1H), 7.66−7.64 (m, 1H), 7.52 (d, J = 6.9 Hz, 2H), 7.43−7.34 (m,
3H), 7.28−7.24 (m, 1H), 7.16 (s, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.70
(t, J = 7.4 Hz, 1H), 5.78 (s, 1H). 13C{1H} NMR (100 MHz, DMSO-
d6):δ (ppm) = 163.63, 147.85, 147.57, 133.33, 128.45, 128.32, 127.35,
126.85, 117.12, 114.90, 114.39, 66.53. Calcd m/z for C14H12N2O:
224.1050). Found: 225.1021 ([M + H]+).
EXPERIMENTAL SECTION
■
Materials, methods, and crystal data collection are given in the
Supporting Information (SI).
Synthesis of New Pd(II) Benzoylhydrazone Complexes.
Upon dissolution of the dimethylamino benzoylhydrazone ligands
(1 mmol) in benzene (15−20 mL), [PdCl2(PPh3)2] (1 mmol) was
added, and the resultant mixture was refluxed for 3 h under open air
(Scheme 2). The completion of the complexation was monitored by
TLC; reaction color changes from yellow to orange. The resulting
orange solution was dried in vacuo and treated for column
chromatography to get the complexes with good yields (85−90%).
All the complexes were highly soluble in CH3OH, CH2Cl2, CHCl3,
and acetone.
Characterization of Complexes (1−3). Complex 1. Reddish-
orange solid. Yield: 43 mg, 85%, m.p.: 233 °C (with decomposition);
Anal. calcd: C34H31N3OClPdP: C, 60.90, H, 4.66, N, 6.26%; found: C,
60.75, H, 4.51, N, 6.15%. FT-IR (KBr, cm−1): 1579 ν(CN), 1342
ν(C‑O), 1521 ν(CNNC). 1H NMR (CDCl3, δ ppm): 8.31 (d, J = 9.0
Hz, 2H, H12, H16), 7.94 (d, 4JH‑P = 5.7 Hz, 1H, CHN), 7.81−7.72
(m, 8H, PPh3), 7.54−7.43 (m, 10H, H13, H14, H15, PPh3), 7.26 (dd,
J = 9.1, 5.9 Hz, 2H, H3, H5), 6.72 (d, J = 9.0 Hz, 2H, H2, H6), 3.06
(s, 6H, N(CH3)2). 13C NMR (100 MHz, CDCl3, δ, ppm): 175.00
(NC−O), 154.26 (CN), 135.48 (C9) 135.09 (C17, C23, C29),
134.88 (C18, C22, C24, C28, C30, C34), 134.77 (C19, C21, C25,
C27, C31, C33), 132.06 (C20, C26, C32), 131.11 (C1), 131.08 (C4),
130.11 (C3, C5), 129.01 (C2, C6), 128.50 (C14), 128.39 (C10),
127.76 (C13), 119.19 (C11), 111.10 (C12), 40.04 (N(CH3)2). ESI-
MS: displays a peak at m/z 675.1507 ([M + 2H]+) (calcd: 673.0907).
Complex 2. Reddish-orange solid. Yield: 41 mg, 88%, m.p: 248 °C
(with decomposition); Anal. calcd: C34H30N3OCl2PdP: C, 57.93, H,
4.28, N, 5.96%; found: C, 57.77, H, 4.11, N, 5.90%. FT-IR (KBr,
Characterization of the Catalytic Isolated Product of
Quinazolinones. 2-Phenylquinazolin-4(3H)-one (3a).24f White
1
solid (91%, 148 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) =
12.57 (s, 1H), 8.22−8.17 (m, 3H, H5, H9, H13), 7.86−7.83 (m, 1H,
H8), 7.76 (d, J = 7.9 Hz, 1H, H7), 7.60−7.52 (m, 4H, H6, H10, H11,
H12). 13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm) = 162.26 (C
O), 152.29 (CN), 148.67 (C-N), 134.53 (C-7), 132.68 (C-14),
131.34 (C-11), 128.55 (C12, C19), 127.73 (C9, C13), 127.45 (C6),
126.52 (C8), 125.82 (C5, C8), 120.93 (C4a).
2-(o-Aminophenyl)quinazolin-4(3H)-one (3b).34 Yellow solid
1
(76%, 132 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.16
(s, 1H), 8.14 (d, J = 7.9 Hz, 1H), 7.81−7.70 (m, 3H), 7.47 (t, J = 7.4
Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.10 (s, 2H), 6.86 (d, J = 8.2 Hz,
1H), 6.61 (t, J = 7.5 Hz, 1H). 13C{1H} NMR (100 MHz, DMSO-d6)
δ (ppm) = 162.13, 153.61, 149.40, 147.95, 134.44, 131.80, 128.85,
126.74, 126.14, 125.71, 120.40, 116.61, 115.02, 112.34.
cm−1): 1582 ν(CN), 1341 ν(C‑O), 1518 ν(CNNC)
.
1H NMR
2-(3-(Dimethylamino)phenyl)quinazolin-4(3H)-one (3c).35 White
(CDCl3, δ ppm): 8.27 (d, J = 8.9 Hz, 2H, H12, H16), 7.93 (d, 4JH‑P
=
1
solid (74%, 144 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) =
5.7 Hz, 1H, CHN), 7.78 (dd, J = 11.9, 7.3 Hz, 6H, PPh3), 7.63 (d, J
= 8.5 Hz, 2H, H13, H15), 7.55−7.44 (m, 9H, PPh3), 7.26−7.21 (m,
2H, H3, H5), 6.72 (d, J = 9.0 Hz, 2H, H2, H6), 3.07 (s, 6H,
N(CH3)2). 13C NMR (100 MHz, CDCl3, δ, ppm): 173.94 (NC−
O), 152.54 (CN), 136.07 (C1), 135.47 (C9), 134.87 (C17, C23,
C29), 134.76 (C18, C22, C24, C28, C30, 34), 131.15 (C19, C21,
C25, C27, C31, C33), 131.12 (C20, C26, C32), 130.63 (C4), 130.29
(C3, C5), 129.06 (C2, C6), 128.50 (C14), 128.39 (C10), 127.96
(C13), 119.00 (C11), 111.10 (C12), 40.03 (N(CH3)2). ESI-MS:
displays a peak at m/z 709.1116 ([M + 2H]+) (calcd: 707.0542). The
CCDC number for complex 2 is 1833169.
12.48(s, 1H), 8.15 (d, J = 7.8 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.73
(d, J = 8.0 Hz, 1H), 7.52−7.47 (m, 3H), 7.32 (t, J = 7.9 Hz, 1H),
6.90−6.88 (m, 1H), 2.97 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-
d6) δ (ppm) = 162.35, 152.92, 150.38, 148.73, 134.49, 133.22, 129.12,
127.39, 126.35, 125.58, 120.87, 115.53, 115.04, 111.09.
2-(2-Methoxyphenyl)quinazolin-4(3H)-one (3d).36 White solid
1
(75%, 138 mg). H NMR (400 MHz, DMSO-d6) (ppm): 12.12 (s,
1H), 8.15 (dd, J = 7.9, 1.4 Hz, 1H), 7.85−7.81 (m, 1H), 7.71 (dd, J =
7.6, 1.7 Hz, 2H), 7.56−7.53 (m, 2H), 7.20 (d, J = 8.4 Hz, 1H), 7.10
(t, J = 7.5 Hz, 1H), 3.86 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-
d6) (δ ppm): 161.26, 157.09, 152.33, 134.39, 132.20, 130.41, 126.53,
125.75, 122.57, 120.93, 120.40, 111.82, 55.73.
Complex 3. Reddish-orange solid. Yield: 42 mg, 90%, m.p: 240 °C
(with decomposition); Anal. calcd: C35H33N3O2ClPdP: C, 60.0,
H,4.74, N, 6.02%; found: C, 59.80, H, 4.65, N, 6.5%. FT-IR (KBr,
2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3e).24f White solid
(89%, 165 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.43 (s,
1H), 8.20 (d, J = 8.9 Hz, 2H), 8.13 (dd, J = 7.9, 1.0 Hz, 1H), 7.83−
7.79 (m, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.1 Hz, 1H), 7.09
(d, J = 8.9 Hz, 2H), 3.85 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-
cm−1): 1579 ν(CN), 1345 ν(C‑O), 1495 ν(CNNC)
.
1H NMR
(CDCl3, δ ppm): 8.30 (d, J = 8.9 Hz, 2H, H12, H16), 7.90 (d, 4JH‑P
=
5.8 Hz, 1H, CHN), 7.81−7.76 (m, 6H, PPh3), 7.68 (d, J = 8.8 Hz,
2H, H13, H15), 7.54−7.43 (m, 9H), 6.74 (dd, J = 22.6, 8.9 Hz, 4H,
730
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Article
d6) δ (ppm) = 162.54, 152.08, 148.86, 134.45, 129.42, 127.12, 126.03,
125.80, 124.92, 120.63, 113.94, 55.42.
NMR (100 MHz, DMSO-d6) δ (ppm) = 166.30, 152.84, 149.89,
141.79, 132.96, 130.12, 128.05, 126.11, 125.89, 124.50, 121.16.
2-(Benzo[d][1,3]dioxol-5-yl)quinazolin-4(3H)-one (3p).35 White
2-(m-Tolyl)quinazolin-4(3H)-one (3f).19 White solid (73%, 126
mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.46 (s, 1H), 8.15
(d, J = 7.9 Hz, 1H), 7.99 (s, 1H), 7.94 (d, J = 7.2 Hz, 1H), 7.83 (t, J =
7.6 Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.44−
7.38 (m, 2H), 2.39 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ
(ppm) = 162.33, 152.47, 148.60, 137.94, 134.61, 132.57, 132.00,
128.51, 128.21, 127.31, 126.54, 125.81, 124.83, 120.82, 20.91.
2-(p-Tolyl)quinazolin-4(3H)-one (3g).24d White solid (85%, 147
mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.53 (s, 1H), 8.20
(d, J = 7.0 Hz, 1H), 8.14 (d, J = 8.1 Hz, 2H), 7.87 (dd, J = 11.1, 4.1
Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.56 (t, J = 7.0 Hz, 1H), 7.40 (d, J
= 7.9 Hz, 2H), 2.44 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ
(ppm) = 162.32, 152.25, 148.70, 141.44, 134.55, 129.83, 129.16,
127.63, 127.28, 126.37, 125.80, 120.80, 20.94.
1
solid (55%, 107 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) =
8.12 (d, J = 7.7 Hz, 1H), 7.80 (dd, J = 11.1, 4.3 Hz, 2H), 7.74 (d, J =
1.4 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H), 7.07
(d, J = 8.2 Hz, 1H), 6.13 (s, 2H). 13C{1H} NMR (100 MHz, DMSO-
d6) δ (ppm) = 162.77, 152.10, 149.91, 14876, 147.60, 134.38, 127.11,
125.79, 122.77, 120.68, 108.21, 107.53, 101.79.
2-(Naphthalen-2-yl)quinazolin-4(3H)-one (3q).38 White solid
1
(59%, 118 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.67
(s, 1H), 8.24−8.16 (m, 2H), 8.12 (d, J = 8.2 Hz, 1H), 8.05 (dd, J =
6.4, 2.8 Hz, 1H), 7.89−7.85 (m, 1H), 7.80 (d, J = 7.0 Hz, 1H), 7.74
(d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.67−7.57 (m, 3H).
13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm) = 162.08, 153.82,
148.63, 134.49, 133.10, 131.74, 130.34, 130.22, 128.31, 127.63,
127.31, 127.04, 126.75, 126.34, 125.15, 125.05, 121.15.
2-(4-Isopropylphenyl)quinazolin-4(3H)-one (3h).24f White solid
1
(71%, 138 mg). H NMR NMR (400 MHz, CDCl3), δ (ppm) =
2-(Anthracen-9-yl)quinazolin-4(3H)-one (3r).19 White solid (56%,
132 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.89 (s, 1H),
8.87 (s, 1H), 8.35 (d, J = 7.5 Hz, 1H), 8.25 (d, J = 8.1 Hz, 2H), 7.95
(t, J = 7.2 Hz, 1H), 7.79−7.85 (dd, J = 17.4, 8.2 Hz, 3H), 7.69 (t, J =
7.5 Hz, 1H), 7.57−7.64 (m, 4H). 13C{1H} NMR (100 MHz, DMSO-
d6) δ (ppm) = 161.75, 153.04, 148.86, 134.56, 130.56, 128.98, 128.70,
128.52, 127.50, 127.04, 126.00, 125.65, 125.02, 121.62.
12.24 (s, 1H), 8.22 (d, J = 7.7 Hz, 1H), 8.15 (d, J = 8.3 Hz, 2H),
7.72−7.64 (m, 2H), 7.39−7.35 (m, 1H), 7.31 (d, J = 8.3 Hz, 2H),
2.90 (dt, J = 13.8, 6.9 Hz, 1H), 1.21 (d, J = 6.9 Hz, 6H). 13C{1H}
NMR (100 MHz, CDCl3) δ (ppm) = 164.43, 152.87, 152.06, 149.76,
134.79, 130.39, 127.93, 127.72, 127.08, 126.47, 126.35, 120.77, 34.19,
23.83.
2-(3,4,5-Trimethoxyphenyl)quinazolin-4(3H)-one (3i).37 White
2-([1,1′-Biphenyl]-4-yl)quinazolin-4(3H)-one (3s).24f White solid
(58%, 127 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.61(s,
1H), 8.31 (s, 1H), 8.18 (d, J = 7.5 Hz, 1H), 7.77−7.88 (m, 7H),
7.43−7.56 (m, 4H). 13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm)
= 162.20, 151.88, 148.75, 142.80, 138.93, 134.60, 131.51, 129.04,
128.35, 127.49, 126.82, 126.72, 125.84, 120.97.
1
solid (77%, 177 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) =
12.58 (s, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.88 (t, J = 7.5 Hz, 1H), 7.79
(d, J = 8.1 Hz, 1H), 7.61 (s, 2H), 7.56 (t, J = 7.4 Hz, 1H), 3.95 (s,
6H), 3.80 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm) =
162.35, 152.82, 151.70, 148.57, 140.14, 134.58, 127.62, 127.38,
126.44, 125.81, 120.75, 105.10, 103.35, 60.11, 56.06.
2-(1H-Indol-3-yl)quinazolin-4(3H)-one (3t).39 Yellow solid (54%,
103 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.28 (s, 2H),
8.12 (d, J = 7.6 Hz, 1H), 7.51−7.80 (m, 6H). 13C{1H} NMR (100
MHz, DMSO-d6) δ (ppm) = 160.73, 148.69, 145.37, 134.29, 127.17,
126.71, 125.80, 122.56.
2-(3-Fluorophenyl)quinazolin-4(3H)-one (3j).36 White solid (69%,
122 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.59 (s, 1H),
8.15−7.99 (m, 3H), 7.78 (d, J = 33.8 Hz, 2H), 7.58−7.42 (m, 3H).
13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm) = 162.22, 151.10,
148.34, 134.64, 130.75, 127.47, 126.87, 125.83, 123.88, 121.03,
118.10, 114.60, 114.36.
2-(4-Chlorophenyl)quinazolin-4(3H)-one (3k).37 White solid
ASSOCIATED CONTENT
1
■
(68%, 128 mg). H NMR (400 MHz, DMSO-d6) (ppm): 8.28 (d, J
sı
= 8.6 Hz, 2H), 8.09−8.07 (m, 1H), 7.71−7.67 (m, 1H), 7.63 (d, J =
7.8 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.39−7.35 (m, 1H). 13C{1H}
NMR (100 MHz, DMSO-d6) δ (ppm) = 166.50, 155.55, 149.91,
135.14, 135.01, 132.89, 129.57, 128.19, 126.70, 125.82, 124.87,
121.26.
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00814.
Complete details of materials, methods, and crystal data
collection. Tables for crystallographic data, refinement
parameters, selected bond lengths, and bond angles.
Figures illustrating the NMR spectra of complexes,
intermediates, and quinazolinone catalytic products.
HRMS spectra of complexes and cyclic aminal
intermediate (PDF)
2-(2-Bromophenyl)quinazolin-4(3H)-one (3l).21 White solid
1
(58%, 128 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.59
(s, 1H), 8.21 (t, J = 8.8 Hz, 3H), 7.87 (t, J = 7.6 Hz, 1H), 7.78 (d, J =
8.1 Hz, 1H), 7.63−7.54 (m, 3H). 13C{1H} NMR (100 MHz, DMSO-
d6) δ (ppm) = 162.22, 152.27, 148.69, 137.88, 134.56, 132.67, 131.36,
128.57, 128.46, 128.25, 127.73, 127.47, 126.55, 125.82, 124.85,
120.93.
2-(Pyridin-3-yl)quinazolin-4(3H)-one (3m).38 Yellow solid (67%,
1
110 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) = 8.70 (s, 1H),
Accession Codes
8.51−8.44 (m, 2H), 8.14 (d, J = 6.9 Hz, 1H), 7.95 (s, 1H), 7.73 (d, J
= 18.4 Hz, 2H), 7.45 (d, J = 41.1 Hz, 1H), 6.96 (s, 1H), 6.56−6.38
(m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6) δ (ppm) = 13C NMR
(101 MHz, DMSO) δ 172.38, 166.98, 153.00, 149.98, 148.88, 137.23,
136.24, 132.87, 131.72, 129.74, 126.87, 125.92, 125.10, 123.69,
122.61, 121.75, 120.63, 115.23, 113.87.
CCDC 1565995 and 1833169 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
2-(Furan-3-yl)quinazolin-4(3H)-one (3n).38 Yellow solid, (65%,
101 mg). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 12.58 (s, 1H),
8.18 (d, J = 7.9 Hz, 1H), 8.06 (s, 1H), 7.90−7.85 (m, 1H), 7.75 (d, J
= 8.1 Hz, 1H), 7.69 (d, J = 3.4 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H), 6.81
(dd, J = 3.5, 1.7 Hz, 1H). 13C{1H} NMR (100 MHz, DMSO-d6) δ
(ppm) = 161.87, 151.34, 146.74, 144.00, 143.73, 134.83, 134.47,
127.12, 126.46, 125.90, 121.07, 114.48, 112.51.
AUTHOR INFORMATION
■
Corresponding Author
Rengan Ramesh − Centre for Organometallic Chemistry,
School of Chemistry, Bharathidasan University,
Tiruchirappalli 620 024, India; orcid.org/0000-0002-
0257-8792; Phone: 0431-2407053; Email: ramesh_bdu@
yahoo.com, rramesh@bdu.ac.in; Fax: 0091-431-2407045
2-(Thiophen-3-yl)quinazolin-4(3H)-one (3o).38 Yellow solid
1
(66%, 111 mg). H NMR (400 MHz, DMSO-d6) δ (ppm) = 8.06
(dd, J = 8.0, 1.8 Hz, 2H), 7.69−7.63 (m, 2H), 7.56 (d, J = 8.1 Hz,
1H), 7.35−7.31 (m, 1H), 7.16 (dd, J = 5.0, 3.8 Hz, 1H). 13C{1H}
731
https://dx.doi.org/10.1021/acs.organomet.0c00814
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pubs.acs.org/Organometallics
Article
Larijani, B.; Mahdavi, M. Novel quinazolin-4(3H)-one linked to 1,2,3-
triazoles: Synthesis and anticancer activity. Chem. Biol. Drug Des.
2018, 92, 1373−1381.
Authors
Sundarraman Balaji − Centre for Organometallic Chemistry,
School of Chemistry, Bharathidasan University,
Tiruchirappalli 620 024, India
Gunasekaran Balamurugan − Centre for Organometallic
Chemistry, School of Chemistry, Bharathidasan University,
Tiruchirappalli 620 024, India
David Semeril − Laboratoire de Chimie Inorganique et
Catalyse, Institut de Chimie, Universite de Strasbourg, UMR
7177, CNRS, Strasbourg 67070, France
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Quinazolinone derivatives as marker for various biological activities.
Int. Res. J. Pharm. 2013, 4 (3), 49−58.
https://pubs.acs.org/10.1021/acs.organomet.0c00814
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors sincerely thank the Indo-French Centre for the
Promotion of Advanced Research (IFCPAR/CEFIPRA) for
financial support (Scheme No: Project No: 5005-1) and
DST−FIST, New Delhi, for HR-MS and NMR facilities at the
School of Chemistry, Bharathidasan University, Tiruchirappal-
li-24.
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