Copper-Catalyzed Self-Condensation of Benzamide: Domino Reactions towards Quinazolinones

Article abstract of DOI:10.1002/ejoc.201800660

We herein report a simple and highly efficient microwave-assisted, copper-catalyzed and ligand-free synthetic method for 2-substituted 4(3H)-quinazolinones as domino reaction. This reaction proceeds via self-condensation of substrate (2-bromo/iodo benzamide) in the presence of a strong base and copper catalyst. The substituted quinazolinones were obtained in one-pot reaction by intramolecular cyclization (condensation) via Ullmann–type intermediate. Both the intermediates and quinazolinones were obtained in good yield and can be further used as building blocks for developing the potential novel drug-like compounds.

Full text of DOI:10.1002/ejoc.201800660

DOI: 10.1002/ejoc.201800660
Full Paper
Ullman Reactions
Copper-Catalyzed Self-Condensation of Benzamide: Domino
Reactions towards Quinazolinones
Nisar Sayyad,[a] Zamani Cele,[a] Rajeshwar Reddy Aleti,[a] Milan Bera,[b]
Srinivasulu Cherukupalli,[a] Balakumar Chandrasekaran,[a] Narva Deshwar Kushwaha,[a] and
Rajshekhar Karpoormath*[a]
Abstract: We herein report a simple and highly efficient micro- tained in one-pot reaction by intramolecular cyclization (con-
wave-assisted, copper-catalyzed and ligand-free synthetic densation) via Ullmann–type intermediate. Both the intermedi-
method for 2-substituted 4(3H)-quinazolinones as domino reac- ates and quinazolinones were obtained in good yield and can
tion. This reaction proceeds via self-condensation of substrate be further used as building blocks for developing the potential
(2-bromo/iodo benzamide) in the presence of a strong base novel drug-like compounds.
and copper catalyst. The substituted quinazolinones were ob-
Introduction
reaction temperatures.[10,12,13] Despite these advances, it has
been a challenge to synthesize highly functionalized quinazol-
inones from easily accessible starting materials and by employ-
ing green chemistry techniques.
In 2011, Zhou et al.[14] for the first time demonstrated one-
pot base-free domino reaction between primary alcohols and
o-aminobenzamides via Iridium (Ir) catalyzed dehydrogenation,
affording quinazolinones in good yields (Scheme 1a). Similarly,
Quinazolinones are valuable heterocyclic scaffolds that form the
backbone of many biologically active molecules and are wide-
spread in both natural products and pharmaceuticals.[1] They
have been assigned as privileged structures in drug develop-
ment.[2] The quinazolinone derivatives exhibit a wide range of
pharmacological activities such as anticancer, anti-microbial,
anti-inflammatory, antitubercular, antiviral,[1,3–7] and are core
structures in several marketed drugs such as Methaqualone,
Etaqualone, Afloqualone, Chloroqualone, Quinethazone,
Fluproquazone, Tiacrilast, Raltitrexed etc.[5,6] Additionally, quin-
azolinones have been used as ligands in the central nervous
system (CNS) as a CNS stimulant, analgesic, tranquilizer, and
antianxietic etc.[8,9]
The stability of the quinazolinone nucleus towards the oxid-
ation, reduction and hydrolysis reactions has motivated re-
searchers to introduce many bioactive moieties to this nucleus
and create new potential medicinal agents. Due to its broad
synthetic and medicinal applications of these molecules, there
has been much effort directed towards their synthesis.[10]
Over the years several new methodologies have been re-
ported for the synthesis of quinazolinone by using different
synthetic approach. However, the catalytic approach offers
numerous synthetic benefits over classical approach[11] which
includes; shorter reaction times, extended scope and reduced
[a] Department of Pharmaceutical Chemistry, College of Health Sciences,
University of KwaZulu-Natal (Westville Campus),
Private Bag X54001, Durban 4000, South Africa.
E-mail: karpoormath@ukzn.ac.za
https://www.ukzn.ac.za/
[b] Department of Chemistry, Indian Institute of Technology Bombay Powai,
Mumbai 400 076, India
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201800660.
Scheme 1. Metal catalyzed approach leading to quinazolinone.
1 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Full Paper
Xu et al.[15] reported copper-catalyzed domino synthesis of 1.25 equiv. of base and 0.1–0.25 equiv. of the copper catalyst
quinazolinone via Ullmann-type coupling by aerobic oxidative (entry 19, 24). Further, the effect of dilution was investigated
C–H amidation (Scheme 1b). In 2016, Upadhyaya et al.[12] re- (Table S5), and it revealed that with the decrease in dilution
ported a one-pot synthesis of 2-substituted quinazolinones by drastically improved the yield of the desired product B (entry
employing ligand and base-free multi-pathway domino strat- 28–32).
egy with copper(I) iodide (CuI) as catalyst. This methodology
provides a novel synthetic approach, utilizing inexpensive and
readily available multiform substrates. Further, this one-pot re-
action proceeds via multi-pathway coupled self-sequenced
domino reaction involving oxidative addition, reductive amin-
ation, an intermolecular oxidative nitrogenation of benzylic
C(sp3)–H bond, intramolecular cyclization and oxidative de-
hydrogenation (Scheme 1c). However, this methodology utilizes
tert-butyl hydroperoxide (TBHP) as an oxidant and trimethylsilyl
azide (TMSN3) as a nitrogen source, which are crucial for the
reaction, making this methodology expensive and non-eco-
friendly as well as inconvenient.
In recent years, Microwave assisted organic synthesis (MAOS)
is preferred over conventional methods and has emerged as
a new “lead” with wide applications in chemical synthesis. In
comparison to conventional synthetic methods MAOS are sim-
ple, clean, fast, efficient, and economic mainly due to its highly
accelerated rate of reaction leading to reduction in reaction
time with increased yield and purity.[15] Similarly, MAOS tech-
nique offers an environmental friendly approach with the wide
applications in the field of green chemistry. Further, this tech-
nique found to be compatible with almost all kinds of reactions
such as heterocyclic synthesis,[16,17] organometallic cross-cou-
pling reactions,[18–22] rearrangement,[23–26] cycloaddition[27,28]
etc.
By taking the above preliminary optimization results in to an
account, we have reported standard preliminary reaction condi-
tions “a” (Table S2) and performed further screening of base
(Table S6), catalyst (Table S7), solvent (Table S8) and leaving
group (Table S9). Screening of eight different bases revealed
that organic (entry 38–39) and weak inorganic bases (entry 36–
37) resulted in no product, while the product formation was
only observed with strong inorganic bases such as NaOH, KOH,
and Cs2CO3 (entry 33–35). The optimal base performance was
observed with Cs2CO3 (entry 35). In addition, screening of the
catalyst indicated that both Copper I and II are equally the best
catalysts for this transformation (entry 41–46), with CuII giving
slightly better yields.
Our initial investigation showed that solvent played a crucial
role and it also acted as a substrate. Performing the reaction in
aprotic non-polar solvents (entry 61–68) resulted in no product
formation while the desired product in good yield was obtained
in polar solvents like alcohols (entry 53–58). Further, combina-
tion of the non-polar aprotic solvent such as 1,2-dichloroethane
(DCE) and ethanol decreased the rate of product formation (en-
try 69–70). In addition, replacement of copper catalysts (entry
48–52) with other oxidants resulted in no product formation.
This confirmed that the reaction proceeds via Ullmann-type.
Study of different leaving groups (halogens) on substrate A (en-
try 71–76) revealed that iodine gave the best results, followed
by bromine, while no product was obtained with chlorine as a
substituent. Similarly, the reactions with fluoro and nitro deriva-
tives of substrate A resulted in intermediate C only (entry 72,
74, 75), with incomplete consumption of the starting material
A.
After optimizing the reaction condition “b” (Table S2), we
also explored the scope of the reaction by using different alco-
hols as substrates, summarized in Table 1. Furthermore, the re-
activity of different substituted 2-bromobenzamide (Substrate
A) were investigated, revealing that the neutral groups, such as
methyl substituents on the ortho and para positions gave high
product yield 92 and 87 % respectively (entry 9 and 10) as pre-
sented in Table 2. It is notable that the substrates with electron
withdrawing groups (bromo and chloro) afforded good yield
(entry 11–13), while moderate yields were presented for sub-
strates with electron donating substituents (entry 14–15).
In our current approach, we present a straightforward, mild,
economic and environmental friendly microwave assisted cop-
per-catalyzed strategy for the synthesis of 2-substituted 4(3H)-
quinazolinone derivatives. This reaction proceeds via self-con-
densation of 2-bromo/iodo benzamides (Scheme 1d). Thus the
proposed methodology is very attractive in comparison with
the earlier reported methods due to: a) absence of ligand and
oxidant, b) use of common substrate (2-bromobenzamide) and
c) alcohols acts as solvent as well as the substrate.
Results and Discussion
In the present work, we report a simple and efficient microwave
assisted copper-catalyzed novel methodology to synthesize
quinazolinone derivatives from 2-bromo/iodo benzamide. This
reaction was performed in the presence of a base and different
alcohols acting as both solvent and substrate. The preliminary
reactions were performed with 0.25 equiv. Cu(OAc)2 and
1.25 equiv. Cs2CO3 by varying reaction time and temperature.
All the reactions were monitored by TLC. The best results were
obtained at 120 °C in 10 min. By maintaining the optimized
conditions (time: 10 min and temperature: 120 °C), the optimal
stoichiometric ratio of base and catalyst loading with respect
to substrate A (2-bromobenzamide) was determined. It was ob-
The structure of the desired compound 6B (CCDC 1834560)
was confirmed by X-ray single crystal diffraction analysis (Fig-
ure 1).
Slightly, better yields were obtained when reactions were
performed by conventional method (seal tube) as compared to
the microwave synthesis (entry 77–83). However, the duration
of the reaction time was quite long (4 h) at 120–150 °C (Table
S10).
Unlike the conventional heating, the microwave synthesis
served that the base (Cs2CO3) and catalyst [Cu(OAc)2] played a was rapid (10 min), safer and with minimal solvent require-
crucial role (entry 16 and 23), and best yields were obtained at ment.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
2
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 1. Derivatization using different solvents with optimized reaction condi-
tion (b).
Figure 1. X-ray structure of compound 6B.
Mechanistic Study/Controlled Reactions
To investigate the plausible reaction mechanism, controlled ex-
periments were carried out with optimized reaction condition
“b”, as shown in Scheme 2. From the reaction of 2-bromobenz-
amide (substrate A) with benzamide resulted in complete con-
sumption of substrate A, while the benzamide remained unre-
acted as shown in reaction Scheme 2-(1). This finding is in sup-
port of our assumption i.e. the reaction occurs by self-conden-
sation of 2-bromobenzamide only. In addition, reaction with
N-phenyl benzamide [Scheme 2-(2)] resulted in intermediate
formation only. This further confirms our proposed reaction
mechanism is Ullmann-type, where the intermediate C acts as
a nucleophile resulting in the formation of intermediate C1. In
addition, the relative rates of formation of intermediates C and
C1 were investigated. The reaction with substrate A [Scheme 2-
(3)] was done under reaction condition “b”, followed by step-
wise excess addition of A at regular intervals for the consump-
tion of the intermediate C. However, there was no significant
increase in the yield ratio of B and C. Similarly, as mentioned
earlier that decreasing the dilution increases the formation of
product B (Table S5). From these investigations, it is confirmed
that the rate of formation of intermediate C was faster than C1.
[a] Detection (by 1H NMR) of C (10–20 %) in each reaction. [b] Determined
by 1H NMR of crude reaction mixture. [c] Isolated yield. [d] Reaction time
20 min (10 + 10). [e] Water work up, extracted with Dichloromethane. n.d.
Not Detected.
Table 2. Derivatization using different substituted 2-bromobenzamides (A)
with optimized reaction condition (b).
Scheme 2. Controlled reactions using optimized reaction condition (b) [A
(0.499 mmol), Cs2CO3 (0.623 mmol), CuI (0.049 mmol), Ethanol (1 mL)]: 1) 2-
bromobenzamide and benzamide as starting material. 2) 5-chloro, 2-bromo,
N-phenyl benzamide. 3) Stepwise addition of 2-bromobenzamide.
[a] Detection (by 1H NMR) of C (10–20 %) in each reaction. [b] Determined
by 1H NMR of crude reaction mixture. [c] Isolated yield.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
3
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 3. Proposed reaction mechanism.
by column chromatography on neutral alumina (pH = 7), in di-
chloromethane as mobile phase.
Proposed Reaction Mechanism
Based on our observations and results obtained, we propose a
possible reaction mechanism for the quinazolinone synthesis
(Scheme 3). This is a copper-catalyzed self-condensation of 2-
bromo/iodo benzamide via Ullmann-type domino reaction. The
reaction proceeds by formation of two intermediates C and C1.
In case of C, solvent acts as a nucleophile while in case of C1
the intermediate C acts as a nucleophile. The intermediate C1
further undergoes intramolecular cyclization (condensation) to
yield the desired product B.
2-(2-Methoxyphenyl)quinazolin-4(3H)-one (1B):[31,32] White solid,
1H NMR (400 MHz, CDCl3, 25 °C): δ = 10.94 (br. s, 1 H), 8.57 (dd, J =
8.0, 1.5 Hz, 1 H), 8.30 (dd, J = 8.0, 1.3 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1
H), 7.77 (t, J = 7.6 Hz, 1 H), 7.53 (t, J = 8.0 Hz, 1 H), 7.47 (t, J =
7.6 Hz, 1 H), 7.18 (t, J = 7.6 Hz, 1 H), 7.08 (d, J = 8.3 Hz, 1 H), 4.06
(s, 3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.4, 158.0,
151.4, 148.0, 134.9, 134.1, 132.3, 127.3, 127.0, 126.8, 122.3, 118.9,
112.1, 56.5 ppm. Mass: HRMS (ESI+) m/z for C15H12N2O2 + Na+: calcd,
275.0796; found 275.0795.
2-(2-Ethoxyphenyl)quinazolin-4(3H)-one (2B):[32] White solid, 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 11.09 (br. s, 1 H), 8.54 (dd, J =
8.0, 1.7 Hz, 1 H), 8.30 (dd, J = 8.0, 1.1 Hz, 1 H), 7.79 (m, 1 H), 7.76
(m, 1 H), 7.49 (m, 1 H), 7.46 (m, 1 H), 7.16 (t, J = 7.7 Hz, 1 H), 7.05
(d, J = 8.2 Hz, 1 H), 4.30 (q, J = 7.0 Hz, 2 H), 1.60 (t, J = 7.0 Hz, 3 H)
ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.6, 157.1, 151.0,
149.3, 134.4, 133.2, 131.5, 127.9, 126.5, 126.4, 121.9, 121.4, 112.9,
65.4, 14.6 ppm. Mass: HRMS (ESI+) m/z for C16H14N2O2 + Na+: calcd,
289.0953; found 289.0962.
Conclusions
In summary, we have developed a novel synthetic methodology
for the synthesis of substituted quinazolinones from cheap and
commonly available reagents. To the best of our knowledge,
our research group is the first to report one-pot Ullmann-type
synthesis of pharmacologically important quinazolinone scaf-
fold from a single substrate (2-bromobenzamide). The scope of
this new methodology was further explored to obtain deriva-
tives of quinazolinone by using different solvents. Both the scaf-
folds quinazolinone (B) and intermediate C can be used as a
building block in developing pharmaceutically important bio-
active molecules.[29,30,5] The most attractive feature of this
methodology is that it is one-pot synthesis using inexpensive
catalysts and single substrate. It is a simple and quick reaction
with wide scope for derivatization employing green chemistry
methods. This work will certainly attract the attention of re-
searchers as well as industries.
2-(2-Propoxyphenyl)quinazolin-4(3H)-one (3B): Pale yellow solid,
1H NMR (400 MHz, CDCl3, 25 °C): δ = 11.06 (br. s, 1 H), 8.48 (dd, J =
8.0, 1.7 Hz, 1 H), 8.22 (dd, J = 8.0, 1.4 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1
H), 7.69 (dt, J = 7.6, 1.5 Hz, 1 H), 7.42 (dt, J = 8.0, 1.7 Hz, 1 H), 7.39
(dt, J = 7.5, 1.4 Hz, 1 H), 7.08 (t, J = 7.7 Hz, 1 H), 6.98 (d, J = 8.4 Hz,
1 H), 4.11 (t, J = 6.5 Hz, 2 H), 1.93 (q, J = 7.0 Hz, 2 H), 1.09 (t, J =
7.4 Hz, 3 H), ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.8,
157.5, 151.1, 149.3, 134.5, 133.3, 131.5, 127.8, 126.5, 126.5, 121.8,
121.2, 119.8, 112.9, 71.2, 22.5, 10.7 ppm. Mass: HRMS (ESI+) m/z for
C17H16N2O2 + H+: calcd, 281.1290; found 281.1288.
2-(2-Isopropoxyphenyl)quinazolin-4(3H)-one (4B): Pale yellow
solid, 1H NMR (400 MHz, CDCl3, 25 °C): δ = 11.23 (br. s, 1 H), 8.61
(d, J = 7.5 Hz, 1 H), 8.30 (d, J = 7.8 Hz, 1 H), 7.92 (d, J = 7.6 Hz, 1
H), 7.77 (t, J = 7.4 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.47 (t, J =
7.5 Hz, 1 H), 7.17 (t, J = 7.4 Hz, 1 H), 7.07 (d, J = 8.2 Hz, 1 H), 4.81
(m, 1 H), 1.51 (d, J = 6.0 Hz, 6 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 161.3, 156.5, 151.4, 148.4, 134.8, 133.6, 131.9, 127.5,
126.8, 126.6, 122.1, 121.1, 119.8, 114.9, 73.3, 22.4 ppm. Mass: HRMS
(ESI+) m/z for C17H16N2O2 + Na+: calcd, 303.1109; found 303.1113.
2-(2-Butoxyphenyl)quinazolin-4(3H)-one (5B): Yellow solid, 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 11.23 (br. s, 1 H), 8.76 (d, J =
8.0 Hz, 1 H), 8.30 (d, J = 8.0 Hz, 1 H), 8.24 (d, J = 6.0 Hz, 1 H), 7.83
(t, J = 7.5 Hz, 1 H), 7.57 (t, J = 8.0 Hz, 1 H), 7.53 (m, 1 H), 7.24 (t, J =
7.6 Hz, 1 H), 7.09 (d, J = 8.4 Hz, 1 H), 4.25 (t, J = 6.5 Hz, 2 H), 1.97
(m, 2 H), 1.59 (m, 2 H), 1.04 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR
Experimental Section
General Synthetic Procedure: By microwave: All the reagents and
solvent were added in microwave reaction tube as per reaction con-
dition “a” or “b” (Table S2), then reaction was continued in micro-
wave reactor as per set parameters as shown in Table S3. Reaction
progress was monitored with TLC in 50 % Ethyl acetate/Hexane or
in DCM. By conventional method: All the reagents were added in
reaction tube (seal tube), resulting reaction mixture heated to
120 °C for 4 h. Reaction progress was monitored with TLC in 50 %
Ethyl acetate/hexane or in DCM. Column Purification: Solvent evap-
orated from reaction mixture on rotary evaporator, residue purified
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
4
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(400 MHz, CDCl3, 25 °C): δ = 160.5, 157.8, 146.0, 135.2, 134.8, 132.3,
127.3, 126.5, 126.0, 122.2, 120.4, 116.8, 113.0, 69.8, 31.0, 19.2,
14.0 ppm. Mass: HRMS (ESI+) m/z for C18H18N2O2 + H+: calcd,
295.1447; found 295.1445.
6-Chloro-2-(5-chloro-2-ethoxyphenyl)quinazolin-4(3H)-one
(13B): White Solid, H NMR (400 MHz, CDCl3, 25 °C): δ = 11.09 (br.
1
s, 1 H), 8.43 (d, J = 2.4 Hz, 1 H), 8.16 (s, 1 H), 7.65 (d, J = 8.7 Hz, 1
H), 7.62 (dd, J = 8.8, 2.5 Hz, 1 H), 7.36 (dd, J = 8.8, 2.5 Hz, 1 H), 6.92
(d, J = 8.9 Hz, 1 H), 4.22 (q, J = 7.0 Hz, 2 H), 1.53 (t, J = 7.0 Hz, 3 H)
ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 160.7, 155.9, 149.9,
147.7, 135.1, 133.0, 132.6, 131.0, 129.6, 127.3, 125.9, 122.4, 121.0,
114.5, 65.9, 14.7 ppm. Mass: HRMS (ESI+) m/z for C16H12N2O2 Cl2 +
Na+: calcd, 357.0174; found 357.0178.
2-[2-(Allyloxy)phenyl]quinazolin-4(3H)-one (6B): White solid
(crystal), 1H NMR (400 MHz, CDCl3, 25 °C): δ = 11.04 (br. s, 1 H), 8.43
(dd, J = 8.0, 1.6 Hz, 1 H), 8.25 (d, J = 8.0 Hz, 1 H), 7.73 (m, 2 H), 7.41
(m, 2 H), 7.09 (t, J = 7.6 Hz, 1 H), 6.98 (d, J = 8.3 Hz, 1 H), 6.08 (m,
1 H), 5.45 (d, J = 17.2 Hz, 1 H), 5.36 (d, J = 10.5 Hz, 1 H), 4.71 (d, J =
5.2 Hz, 2 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.7, 156.7,
150.8, 149.3, 134.4, 133.0, 131.6, 131.5, 127.7, 126.4, 126.3, 121.9,
121.1, 120.2, 119.2, 113.2, 70.0 ppm. Mass: HRMS (ESI+) m/z for
C17H14N2O2 + Na+: calcd, 301.0953; found 301.0959.
2-(2-Ethoxy-5-methoxyphenyl)-6-methoxyquinazolin-4(3H)-one
1
(14B): Yellow solid, H NMR (400 MHz, CDCl3, 25 °C): δ = 11.18 (br.
s, 1 H), 8.00 (d, J = 2.5 Hz, 1 H), 7.96 (dd, J = 9.0, 2.7 Hz, 1 H), 7.71
(d, J = 8.5 Hz, 1 H), 7.59 (d, J = 2.7 Hz, 1 H), 7.30 (dd, J = 8.8, 2.9 Hz,
1 H), 6.91 (d, J = 9.0 Hz, 1 H), 4.16 (q, J = 6.9 Hz, 2 H), 3.86 (s, 3 H),
3.82 (s, 3 H), 1.50 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 161.5, 158.4, 154.3, 151.4, 148.8, 143.7, 129.3, 124.9,
120.6, 119.6, 115.0, 114.5, 105.9, 66.1, 56.0, 55.9, 14.9 ppm. Mass:
HRMS (ESI+) m/z for C18H18N2O4 + Na+: calcd, 349.1164; found
349.1167.
2-[2-(Pentyloxy)phenyl]quinazolin-4(3H)-one (7B): Semisolid, 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 11.03 (br. s, 1 H), 8.49 (dd, J =
8.0, 1.9 Hz, 1 H), 8.23 (d, J = 8.0 Hz, 1 H), 7.71 (m, 1 H), 7.69 (m, 1
H), 7.42 (m, 1 H), 7.38 (m, 1 H), 7.09 (t, J = 7.6 Hz, 1 H), 6.99 (d, J =
8.4 Hz, 1 H), 4.16 (t, J = 6.7 Hz, 2 H), 1.92 (m, 2 H), 1.48 (m, 2 H),
1.38 (m, 2 H), 0.98 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (400 MHz,
CDCl3, 25 °C): δ = 161.5, 157.4, 151.3, 149.0, 134.2, 132.9, 131.5,
127.8, 126.4, 126.2, 121.6, 121.4, 120.2, 112.7, 69.6, 28.6, 22.2, 22.3,
13.8 ppm. Mass: HRMS (ESI+) m/z for C17H14N2O2 + H+: calcd,
309.1603; found 309.1605.
2-(2-Ethoxy-4,5-dimethoxyphenyl)-6,7-dimethoxyquinazolin-
4(3H)-one (15B): Yellow solid, 1H NMR (400 MHz, CDCl3, 25 °C): δ =
11.01 (br. s, 1 H), 7.95 (s, 1 H), 7.51 (s, 1 H), 7.15 (s, 1 H), 6.48 (s, 1
H), 4.18 (q, J = 7.0 Hz, 2 H), 3.95 (s, 3 H), 3.92 (s, 3 H), 3.91 (s, 3 H),
3.87 (s, 3 H), 1.51 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 161.1, 155.1, 152.8, 152.4, 149.7, 148.7, 145.5, 144.0,
114.2, 112.4, 111.4, 107.9, 105.4, 98.3, 66.5, 56.5, 56.3, 56.3, 56.2,
14.9 ppm. Mass: HRMS (ESI+) m/z for C20H22N2O6 + Na+: calcd,
409.1376; found 409.1378.
2-Methoxybenzamide (1C):[34,35] White solid, 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 8.12 (dd, J = 8.0, 1.5 Hz, 1 H), 7.66 (br. s, 1 H),
7.39 (t, J = 8.0 Hz, 1 H), 6.99 (t, J = 7.6 Hz, 1 H), 6.90 (d, J = 8.2 Hz,
1 H), 6.43 (br. s, 1 H), 3.87 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 167.3, 157.9, 133.4, 132.5, 121.2, 111.4, 77.4, 77.1, 76.8,
55.9 ppm. Mass: HRMS (ESI+) m/z for C8H9NO2 + Na+: calcd,
174.0531; found 174.0532.
2-Ethoxybenzamide (2C):[36] White solid, 1H NMR (400 MHz, CDCl3,
25 °C): δ = 8.15 (dd, J = 8.0, 1.9 Hz, 1 H), 7.80 (br. s, 1 H), 7.38 (dt,
J = 8.0, 1.9 Hz, 1 H), 6.99 (t, J = 7.6 Hz, 1 H), 6.89 (d, J = 8.5 Hz, 1
H), 6.08 (br. s, 1 H), 4.13 (q, J = 7.0 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H)
ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 167.3, 157.4, 133.4,
132.6, 121.2, 112.4, 77.3, 64.8, 14.9 ppm. Mass: HRMS (ESI+) m/z for
C9H11NO2 + Na+: calcd, 188.0687; found 188.0688.
2-Propoxybenzamide (3C):[33] Pale yellow solid, 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 8.13 (dd, J = 8.0, 2.0 Hz, 1 H), 7.78 (br. s, 1 H),
7.37 (dt, J = 7.8, 1.9 Hz, 1 H), 6.98 (dt, J = 7.6, 1.0 Hz, 1 H), 6.89 (d,
J = 8.2 Hz, 1 H), 6.35 (br. s, 1 H), 4.01 (t, J = 6.5 Hz, 2 H), 1.82 (m, 2
H), 1.00 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C):
δ = 167.4, 157.5, 133.4, 132.6, 121.1, 120.9, 112.4, 70.7, 22.6,
10.7 ppm. Mass: HRMS (ESI+) m/z for C10H13NO2 + Na+: calcd,
202.0844; found 202.0839.
2-(2-Ethoxy-3-methylphenyl)-8-methylquinazolin-4(3H)-one
1
(9B): White solid, H NMR (400 MHz, CDCl3, 25 °C): δ = 10.88 (br. s,
1 H), 8.19 (dd, J = 7.0, 1.6 Hz, 1 H), 8.09 (dd, J = 8.0, 1.3 Hz, 1 H),
7.54 (d, J = 7.4 Hz, 1 H), 7.28 (t, J = 7.6 Hz, 1 H), 7.28 (d, J = 7.5 Hz,
1 H), 7.13 (t, J = 7.7 Hz, 1 H), 3.85 (q, J = 7.1 Hz, 2 H), 2.63 (s, 3 H),
2.29 (s, 3 H), 1.40 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 162.2, 155.9, 149.6, 147.8, 136.4, 135.1, 134.8, 132.4,
129.1, 126.2, 125.2, 125.0, 124.1, 121.4, 70.8, 17.7, 16.1, 15.5 ppm.
Mass: HRMS (ESI+) m/z for C18H18N2O2 + Na+: calcd, 317.1266; found
317.1265.
2-(2-Ethoxy-4-methylphenyl)-7-methylquinazolin-4(3H)-one
(10B): Pale yellow solid, 1H NMR (400 MHz, CDCl3, 25 °C): δ = 11.01
(br. s, 1 H), 8.34 (d, J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.52 (s,
1 H), 7.18 (d, J = 8.0 Hz, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H),
4.19 (q, J = 7.0 Hz, 2 H), 2.43 (s, 3 H), 2.33 (s, 3 H), 1.52 (t, J = 7.0 Hz,
3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.8, 157.2, 151.2,
149.4, 145.4, 144.2, 131.3, 127.9, 127.3, 126.2, 122.7, 118.7, 117.1,
113.6, 65.2, 22.0, 21.9, 14.8 ppm. Mass: HRMS (ESI+) m/z for
C18H18N2O2 + Na+: calcd, 317.1266; found 317.1271.
6-Bromo-2-(5-bromo-2-ethoxyphenyl)quinazolin-4(3H)-one
1
(11B): White solid, H NMR (400 MHz, CDCl3, 25 °C): δ = 11.04 (br.
s, 1 H), 8.60 (d, J = 2.5 Hz, 1 H), 8.34 (d, J = 2.3 Hz, 1 H), 7.78 (dd,
J = 8.6, 1.3 Hz, 1 H), 7.60 (d, J = 8.6 Hz, 1 H), 7.52 (dd, J = 9.0, 2.5 Hz,
1 H), 6.87 (d, J = 9.0 Hz, 1 H), 4.23 (q, J = 7.0 Hz, 2 H), 1.55 (t, J =
7.0 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 160.5, 156.4,
149.9, 148.0, 137.9, 136.0, 134.0, 129.8, 129.1, 122.7, 121.3, 120.5,
114.9, 114.5, 65.9, 14.7 ppm. Mass: HRMS (ESI+) m/z for C16H12N2O2
+ Na+: calcd, 444.9163; found 444.9169.
2-Isopropoxybenzamide (4C):[36] White solid, 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 8.13 (dd, J = 7.5, 2.0 Hz, 1 H), 7.86 (br. s, 1 H),
7.35 (dt, J = 7.9, 1.9 Hz, 1 H), 6.96 (t, J = 7.6 Hz, 1 H), 6.89 (d, J =
8.4 Hz, 1 H), 6.35 (br. s, 1 H), 4.67 (m, 1 H), 1.34 (d, J = 6.0 Hz, 6 H)
ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 167.6, 156.3, 133.3,
132.7, 121.2, 113.8, 71.9, 22.2 ppm. Mass: HRMS (ESI+) m/z for
C10H13NO2 + Na+: calcd, 202.0844; found 202.0840 [M + Na]+. Note:
reaction was incomplete.
7-Chloro-2-(4-chloro-2-ethoxyphenyl)quinazolin-4(3H)-one
1
(12B): White solid, H NMR (400 MHz, CDCl3, 25 °C): δ = 10.96 (br.
s, 1 H), 8.42 (d, J = 8.0 Hz, 1 H), 8.13 (d, J = 8.6 Hz, 1 H), 7.72 (s, 1
H), 7.34 (d, J = 8.4 Hz, 1 H), 7.07 (d, J = 8.0 Hz, 1 H), 6.98 (s, 1 H),
4.2 (q, J = 6.6 Hz, 2 H), 1.56 (t, J = 6.6 Hz, 3 H) ppm. 13C NMR
(400 MHz, CDCl3, 25 °C): δ = 161.0, 157.7, 151.3, 149.9, 140.9, 139.5,
132.8, 128.0, 127.3, 127.2, 122.3, 119.7, 117.9, 113.6, 66.0, 14.7 ppm. 2-Butoxybenzamide (5C):[33] Pale yellow solid, H NMR (400 MHz,
1
Mass: HRMS (ESI+) m/z for C16H12N2O2 Cl2 + Na+: calcd, 357.0174;
CDCl3, 25 °C): δ = 8.13 (dd, J = 8.0, 2.0 Hz, 1 H), 7.77 (br. s, 1 H),
found 357.0179.
7.36 (dt, J = 8.0, 2.0 Hz, 1 H), 6.97 (t, J = 7.5 Hz, 1 H), 6.89 (d, J =
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
5
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
8.2 Hz, 1 H), 6.47 (br. s, 1 H), 4.04 (t, J = 6.6 Hz, 2 H), 1.77 (m, 2 H),
(t, J = 7.0 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 167.1,
1.43 (m, 2 H), 0.92 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (400 MHz, 152.7, 143.2, 113.8, 112.5, 97.6, 65.7, 56.0, 15.0 ppm.
CDCl3, 25 °C): δ = 167.6, 157.5, 133.3, 132.5, 121.0, 120.9, 112.3, 68.8,
5-Chloro-2-ethoxy-N-phenylbenzamide (16): White solid, 1H NMR
31.2, 19.4, 13.8 ppm. Mass: HRMS (ESI+) m/z for C11H15NO2 + Na+:
(400 MHz, CDCl3, 25 °C): δ = 9.95 (s, 1 H), 8.19 (d, J = 2.9 Hz, 1 H),
calcd, 216.1000; found 216.0997.
7.58 (d, J = 8.1 Hz, 2 H), 7.33–7.27 (m, 3 H), 7.06 (t, J = 7.5 Hz, 1 H),
2-(Allyloxy)benzamide (6C): Yellow solid, 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 8.13 (d, J = 7.5 Hz, 1 H), 7.72 (br. s, 1 H), 7.36 (t,
J = 8.0 Hz, 1 H), 6.99 (t, J = 7.5 Hz, 1 H), 6.89 (d, J = 8.4 Hz, 1 H),
6.38 (br. s, 1 H), 6.01 (m, 1 H), 5.32 (m, 2 H), 4.60 (d, J = 5.5 Hz, 2 H)
ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 167.4, 157.0, 133.3,
132.5, 132.1, 121.4, 119.3, 112.7, 77.4, 77.1, 76.8, 69.9 ppm. Mass:
HRMS (ESI+) m/z for C10H11NO2 + Na+: calcd, 200.0687; found
200.0683.
6.86 (d, J = 8.7 Hz, 1 H), 4.18 (q, J = 7.0 Hz, 2 H), 1.56 (t, J = 7.0 Hz,
3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 161.8, 155.1, 138.2,
132.7, 132.1, 129.1, 126.9, 124.3, 123.0, 120.0, 113.9, 65.5, 14.8, ppm.
Mass: HRMS (ESI+) m/z for C15H14NO2Cl + Na+: calcd, 298.0611;
found 298.0612.
CCDC 1834560 (for 6B) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
2-(Pentyloxy)benzamide (7C): White solid, 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 8.14 (dd, J = 8.0, 2.0 Hz, 1 H), 7.77 (br. s, 1 H),
7.37 (dt, J = 8.0, 2.0 Hz, 1 H), 6.99 (t, J = 7.6 Hz, 1 H), 6.89 (d, J =
8.2 Hz, 1 H), 6.10 (br. s, 1 H), 4.05 (t, J = 6.6 Hz, 2 H), 1.80 (m, 2 H),
1.37 (m, 4 H), 0.87 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (400 MHz,
CDCl3, 25 °C): δ = 167.3, 157.5, 133.3, 132.6, 121.1, 120.9, 112.4, 69.2,
28.9, 28.3, 22.4, 14.0 ppm. Mass: HRMS (ESI+) m/z for C12H17NO2 +
Na+: calcd, 230.1157; found 230.1158.
Acknowledgments
The authors wish to thank College of Health Science (CHS),
UKZN (Westville campus) and National Research Foundation
(NRF), South Africa (Grant No. 99546, 103728 and 112079) for
financial support. Authors would like to acknowledge Mr Sizwe
Zamisa for X-RAY crystal structure analysis and Ms Caryl K. A.
Janse van Rensburg and Mr Craig Grimmer from School of
Chemistry, University of KwaZulu-Natal (PMB campus), Pieter-
maritzburg, South Africa for HRMS and NMR analysis.
2-Ethoxy-3-methylbenzamide (9C):[37] 1H NMR (400 MHz, CDCl3,
25 °C): δ = 7.82 (d, J = 8.0 Hz, 1 H), 7.66 (br. s, 1 H), 7.25 (d, J =
7.3 Hz, 1 H), 7.04 (t, J = 7.6 Hz, 1 H), 5.97 (br. s, 1 H), 3.86 (q, J =
7.0 Hz, 2 H), 2.24 (s, 3 H), 1.35 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR
(400 MHz, CDCl3, 25 °C): δ = 168.1, 155.8, 134.8, 132.0, 129.4, 126.1,
124.3, 70.3, 16.0, 15.6 ppm.
Keywords: Nitrogen heterocycles · Domino reactions ·
Synthetic methods · Homogeneous catalysis · Copper
1
2-Ethoxy-4-methylbenzamide (10C): H NMR (400 MHz, CDCl3,
25 °C): δ = 8.02 (d, J = 8.0 Hz, 1 H), 7.77 (br. s, 1 H), 6.81 (d, J =
8.0 Hz, 1 H), 6.69 (s, 1 H), 5.95 (br. s, 1 H), 4.11 (q, J = 7.0 Hz, 2 H),
2.31 (s, 3 H), 1.43 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3,
25 °C): δ = 167.4, 157.3, 144.2, 132.6, 122.2, 118.1, 113.3, 64.6, 22.0,
15.1 ppm.
[1] S. B. Mhaske, N. P. Argade, Tetrahedron 2006, 62, 9787–9826.
[2] X. F. Wu, L. He, H. Neumann, M. Beller, Chem. Eur. J. 2013, 19, 12635–
12638.
[3] R. K. Parmar SS, J. Med. Chem. 1968, 11, 635–636.
[4] A. M. Alafeefy, A. E. Ashour, J. Enzyme Inhib. Med. Chem. 2012, 27, 541–
545.
[5] A. Rashmi, K. Ashish, N. Gill, A. Rana, Int. Res. J. Pharm. 2011, 2, 22–28.
[6] B. K. Tiwary, K. Pradhan, A. K. Nanda, R. Chakraborty, J. Chem. Biol. Ther.
2015, 1, 1–7.
5-Bromo-2-ethoxybenzamide (11C):[38] 1H NMR (400 MHz, CDCl3,
25 °C): δ = 8.23 (d, J = 2.0 Hz, 1 H), 7.71 (br. s, 1 H), 7.45 (dd, J =
8.6, 2.5 Hz, 1 H), 6.77 (d, J = 8.8 Hz, 1 H), 6.16 (br. s, 1 H), 4.11 (q,
J = 7.0 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR (400 MHz,
CDCl3, 25 °C): δ = 165.8, 156.2, 135.8, 135.1, 122.5, 114.2, 113.4, 65.2,
14.8 ppm.
[7] M. Asif, Int. J. Med. Chem. 2014, 2014, 1–27.
[8] Y. Mitobe, S. Ito, T. Mizutani, T. Nagase, N. Sato, S. Tokita, Bioorg. Med.
Chem. Lett. 2009, 19, 4075–4078.
4-Chloro-2-ethoxybenzamide (12C): 1H NMR (400 MHz, CDCl3,
25 °C): δ = 8.06 (d, J = 7.0 Hz, 1 H), 7.64 (br. s, 1 H), 6.96 (s, 1 H),
6.89 (s, 1 H), 6.08 (br. s, 1 H), 4.12 (q, J = 7.0 Hz, 2 H), 1.45 (t, J =
7.0 Hz, 3 H) ppm. 13C NMR (400 MHz, CDCl3, 25 °C): δ = 166.2, 157.7,
139.2, 133.7, 121.4, 119.1, 112.9, 65.4, 14.6 ppm.
[9] N. Malecki, P. Carato, B. Rigo, J. F. Goossens, R. Houssin, C. Bailly, J. P.
Hénichart, Bioorg. Med. Chem. 2004, 12, 641–647.
[10] T. M. M. Maiden, J. P. A. Harrity, Org. Biomol. Chem. 2016, 14, 8014–8025.
[11] Y. Kabri, A. Gellis, P. Vanelle, Green Chem. 2009, 11, 201–208.
[12] K. Upadhyaya, R. K. Thakur, S. K. Shukla, R. P. Tripathi, J. Org. Chem. 2016,
81, 5046–5055.
[13] S. Laclef, M. Harari, J. Godeau, I. Schmitz-Afonso, L. Bischoff, C. Hoarau,
V. Levacher, C. Fruit, T. Besson, Org. Lett. 2015, 17, 1700–1703.
[14] J. Zhou, J. Fang, J. Org. Chem. 2011, 76, 7730–7736.
[15] W. Xu, Y. Jin, H. Liu, Y. Jiang, A. H. Fu, Org. Lett. 2011, 13, 1274–1277.
[16] K. Bougrin, A. Loupy, M. Soufiaoui, J. Photochem. Photobiol. C 2005, 6,
139–167.
5-Chloro-2-ethoxybenzamide (13C): White Solid, 1H NMR
(400 MHz, CDCl3, 25 °C): δ = 8.10 (d, J = 2.4 Hz, 1 H), 7.73 (br. s, 1
H), 7.31 (dd, J = 8.8, 2.5 Hz, 1 H), 6.83 (d, J = 8.9 Hz, 1 H), 6.00 (br.
s, 1 H), 4.11 (q, J = 7.0 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H) ppm. 13C
NMR (400 MHz, CDCl3, 25 °C): δ = 165.8, 155.8, 133.0, 132.3, 126.6,
122.4, 114.5, 65.4, 14.8 ppm.
[17] A. Majumder, R. Gupta, A. Jain, Green Chemistry Letters and Reviews 2013,
6, 151–182.
[18] M. Larhed, G. Lindeberg, A. Hallberg, Tetrahedron Lett. 1996, 37, 8219–
8222.
[19] M. Larhed, A. Hallberg, J. Org. Chem. 1996, 61, 9582–9584.
[20] C. G. Blettner, W. A. König, W. Stenzel, T. Schotten, J. Org. Chem. 1999,
64, 3885–3890.
[21] A. K. Sharma, K. Gowdahalli, J. Krzeminski, S. Amin, J. Org. Chem. 2007,
72, 8987–8989.
2-Ethoxy-5-methoxybenzamide (14C): 1H NMR (400 MHz, CDCl3,
25 °C): δ = 7.93 (br. s, 1 H), 7.84 (d, J = 9.0 Hz, 1 H), 7.68 (d, J =
3.2 Hz, 1 H), 7.66 (d, J = 8.9 Hz, 1 H), 6.10 (br. s, 1 H), 4.08 (q, J =
7.0 Hz, 2 H), 3.75 (s, 3 H), 1.41 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR
(400 MHz, CDCl3, 25 °C): δ = 167.0, 153.7, 151.4, 129.4, 121.2, 115.4,
114.0, 65.4, 55.9, 15.0 ppm.
2-Ethoxy-4,5-dimethoxybenzamide (15C): 1H NMR (400 MHz,
CDCl3, 25 °C): δ = 7.79 (br. s, 1 H), 7.64 (s, 1 H), 6.44 (s, 1 H), 6.16
(br. s, 1 H), 4.10 (q, J = 7.0 Hz, 2 H), 3.84 (s, 3 H), 3.82 (s, 3 H), 1.42
[22] V. P. Mehta, E. V. Van der Eycken, Chem. Soc. Rev. 2011, 40, 4925.
[23] I. R. Trehan, J. S. Brar, A. K. Arora, G. L. Kad, J. Chem. Educ. 1997, 74, 324.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
6
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[24] S. Horikoshi, T. Watanabe, M. Kamata, Y. Suzuki, N. Serpone, RSC Adv.
2015, 5, 90272–90280.
[25] R. Raj, C. Biot, S. Carrère-Kremer, L. Kremer, Y. Guérardel, J. Gut, P. J.
Rosenthal, D. Forge, V. Kumar, Chem. Biol. Drug Des. 2014, 83, 622–629.
[26] A. G. Nerkar, D. Pawale, M. R. Ghante, S. D. Sawant, Int. J. Pharm. Pharm.
Sci. 2013, 5, 564–566.
[33]
[34]
[35]
[36]
P. Villuendas, E. Serrano, E. P. Urriolabeitia, New J. Chem. 2015, 39, 3077–
3083.
W. Zhan, L. Ji, Z. m. Ge, X. Wang, R. t. Li, Tetrahedron 2018, 74, 1527–
1532.
Z. Yan, A. Liu, M. Huang, M. Liu, H. Pei, L. Huang, H. Yi, W. Liu, A. Hu, Eur.
J. Med. Chem. 2018, 149, 170–181.
[27] P. Appukkuttan, V. P. Mehta, E. V. Van. der Eycken, Chem. Sco. Rev. 2010,
39, 1467–1477.
J. Su, Q. Chen, L. Lu, Y. Ma, G. H. L. Auyoung, R. Hua, Tetrahedron 2018,
74, 303–307.
[28] K. M. Brummond, D. Chen, Org. Lett. 2005, 7, 3473–3475.
[29] J. H. He, H. Y. Liu, Z. Li, J. H. Tan, T. M. Ou, S. L. Huang, L. K. An, D. Li,
L. Q. Gu, Z. S. Huang, Eur. J. Med. Chem. 2013, 63, 1–13.
[30] Y. Wu, P. Sun, K. Zhang, T. Yang, H. Yao, A. Lin, J. Org. Chem. 2016, 81,
2166–2173.
[37] I. T. M. Ing. A. v. Kreisler, Ing. K. Schonwald, Pharmacologically Active New
Substituted Benzamides, 1963, DE1152403.
[38] S. Shimokawa, Y. Kawagoe, K. Moriyama, H. Togo, Org. Lett. 2016, 18,
784–787.
[31] M. K. Krapf, J. Gallus, M. Wiese, Eur. J. Med. Chem. 2017, 139, 587–611.
[32] Q. Qiu, B. Liu, J. Cui, Z. Li, X. Deng, H. Qiang, J. Li, C. Liao, B. Zhang, W.
Shi, et al., J. Med. Chem. 2017, 60, 3289–3302.
Received: April 28, 2018
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
7
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Ullman Reactions
N. Sayyad, Z. Cele, R. R. Aleti,
M. Bera, S. Cherukupalli,
B. Chandrasekaran, N. D. Kushwaha,
R. Karpoormath* ................................ 1–8
Copper-Catalyzed
tion of Benzamide: Domino Reac-
tions towards Quinazolinones
Self-Condensa-
New synthetic method is developed to nique. It is oxidant and ligand-free,
prepare 2-substituted 4(3H)-Quinazol- copper-catalysed self-condensation of
inone using green chemistry tech- 2-halobenzamide.
DOI: 10.1002/ejoc.201800660
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
8
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim