Synthesis of 2,3-Disubstituted Quinazolinone Derivatives through Copper Catalyzed C-H Amidation Reactions

Article abstract of DOI:10.1002/ejoc.201501552

The synthesis of quinazolinone derivatives was achieved from 2-iodobenzamide derivatives and various benzylamines, allylamine, and cinnamylamine derivatives through a one-pot copper-catalyzed reaction. In this reaction, the amine component (benzylamine/allylamine/cinnamylamine) is N-arylated with 2-iodobenzamide derivatives through Ullman coupling, followed by an intramolecular C-H amidation in the presence of copper catalyst. Copper-catalyzed tandem-Ullman N-alkylation and intramolecular C-H amidation reaction protocol for the synthesis of 2-phenylquinazolinone and quinazolinone derivatives from N-substituted 2-iodo-benzamides and benzylamines, allyl, and cinnamylamine is achieved.

Full text of DOI:10.1002/ejoc.201501552

DOI: 10.1002/ejoc.201501552
Full Paper
C–H Amidation
Synthesis of 2,3-Disubstituted Quinazolinone Derivatives
through Copper Catalyzed C–H Amidation Reactions
Trimurtulu Kotipalli,[a] Veerababurao Kavala,[a] Donala Janreddy,[a] Vijayalakshmi Bandi,[a]
Chun-Wei Kuo,[a] and Ching-Fa Yao*[a]
Abstract: The synthesis of quinazolinone derivatives was component (benzylamine/allylamine/cinnamylamine) is N-aryl-
achieved from 2-iodobenzamide derivatives and various benzyl- ated with 2-iodobenzamide derivatives through Ullman cou-
amines, allylamine, and cinnamylamine derivatives through a pling, followed by an intramolecular C–H amidation in the pres-
one-pot copper-catalyzed reaction. In this reaction, the amine ence of copper catalyst.
Introduction
and 10-indolyldibenzo[b,f]azepine derivatives.[10] In continua-
tion of these studies, we wish to investigate the reaction of N-
substituted 2-iodo-benzamide derivatives with various benzyl-
amines in the presence of copper catalyst.
Quinazolinone derivatives are privileged structural motifs that
are found in many natural products and bioactive com-
pounds.[1] Quinazolinones exhibit a wide spectrum of biological
activities including antibacterial, anticonvulsants, antifungal,
antiviral, antimycobacterial, antimalarial, antidiabetic, and enzy-
matic inhibition activities.[2] In general, quinazolinone deriva-
tives are synthesized by oxidative condensation of anthranil-
amide derivatives with corresponding carbonyl compounds.[3]
2-Aminobenzoic acid derivatives, 2-amino-benzonitrile, and
2-halogen-substituted anilines are frequently used as starting
materials in the syntheses of substituted quinazolinones.[4]
However, some of these methods suffer from one or more prob-
lems that include low product yields, limited substrate scope,
and use of toxic chemicals. Methods that include benzylic
C–H amidation with benzyl alcohols,[5] copper-catalyzed
coupling reactions of 2-halogenobenzoic acid derivatives with
amidines,[6] radical approaches,[7] and many other methods[8]
address some of the shortcomings of classical methods to
access quinazolinone derivatives. However, an easy and efficient
method for the synthesis of quinazolinone derivatives from
easily accessible starting materials is highly desirable.
Results and Discussion
Fu and co-workers, Nagarajan et al., and Tang and co-workers
reported the synthesis of 3-substituted quinazolinone deriva-
tives by reaction of substituted 2-halobenzamides and
(aryl)methanamines in the presence of CuBr and air through
cascade Ullmann coupling and aerobic oxidative C–H amid-
ation.[11] However, they did not investigate the use of N-substi-
tuted 2-iodo-benzamides as substrates in their reaction.
To determine whether these substrates could be used in this
process, we examined the reaction of 2-iodo-N-methylbenz-
amide and benzylamine in the presence of CuI (20 mol-%) and
K2CO3 (3 equiv.) in dimethyl sulfoxide (DMSO) at 110 °C for 12 h.
Under these conditions, we obtained 2-(benzylamino)-N-meth-
ylbenzamide (3a) as a major product in 70 % isolated yield
(Table 1, Entry 1) along with traces of quinazolinone derivative.
Similar results were observed if the reaction was carried out in
the presence of other copper catalysts, such as CuBr and CuCl
(Table 1, Entries 2 and 3). Because the reaction did not produce
the desired product in the presence of air, we intended to use
external oxidants. To our delight, substantial improvement in
the yield of the desired product was observed if the reaction
was performed in the presence of manganese dioxide (Table 1,
Entry 4). Moreover, at 140 °C the yield of quinazolinone product
4a increased to 80 % (Table 1, Entry 5). Next, we screened differ-
ent oxidants, such as PhI(OAc)2, oxone, ceric ammonium nitrate
(CAN), and 1,4-benzoquinone (1,4-BQ), to optimize the oxidant
for this transformation (Table 1, Entries 4–9). MnO2 (Table 1,
Entry 5) was found to be the best choice of oxidant for this
reaction. To find out the appropriate solvent and base additive
for this reaction, we screened different bases and solvents.
Some bases, such as Na2CO3, Cs2CO3, and K3PO4, did not per-
form well in this transformation (Table 1, Entries 10–12). We
In recent years, copper catalyzed C–N bond-forming reac-
tions gained substantial focus in the synthesis of various N-
heterocycles.[9] For the past few years, our research has focused
on copper catalyzed C–C and C–N bond formation reactions
of 2-iodobenzamide derivatives in the construction of various
heterocycles, which includes 2-aminophenylbenzoxazoles, iso-
coumarin derivatives, indolo[1,2-a]-quinazolinone derivatives,
fused isoquinolinone derivatives, dibenzodiazepine derivatives,
[a] Department of Chemistry, National Taiwan Normal University,
88, Sec. 4, Tingchow Road, Taipei-116, Taiwan, R.O.C.
E-mail: cheyaocf@ntnu.edu.tw
cheyaocf@yahoo.com.tw
http://www.chem.ntnu.edu.tw/people/bio.php?PID=39
Supporting information and ORCID(s) from the author(s) for this article
are available on the WWW under http://dx.doi.org/10.1002/
ejoc.201501552.
Eur. J. Org. Chem. 2016, 1182–1193
1182
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
screened various solvents, such as N,N-dimethylacetamide used both of these conditions to investigate the scope and limi-
(DMA), dimethyl ether (DME), CH3CN, DMSO, and toluene tations of the reaction.
(Table 1, Entries 13–16). DMSO was found to be the best sol-
After having established the optimum reaction conditions,
vent. From the above experiments, we envisioned that the cop- we turned our attention to explore the reaction scope by using
per(II) species formed in situ may be the active catalyst for C– different substitution patterns on the benzene ring of N-substi-
H activation, which is generated from the copper(I) salt in the tuted 2-iodo-benzamides and various benzylamines for both
presence of oxidant. To examine the possibility of a CuII active the methods that used CuI/MnO2/O2 and CuII in the presence
species in this reaction, we screened different CuII salts for this of oxygen atmosphere (Table 2, Entries 4a–4q). The reaction of
reaction. To our delight, all the reactions with CuII salts fur- 2-iodo-N-methyl benzamide (1a) and benzylamine (2a) af-
nished corresponding quinazolinone derivative 4a in good forded corresponding quinazolinone derivative 4a with almost
yield. Among the CuII salts used in this reaction, Cu(OAc)2·2H2O identical yields for both methods. Ethyl, benzyl, and phenyl-
and CuSO4·5H2O were found to be efficient and provided de- substituted 2-iodo-benzamide derivatives (1b, 1c, 1d, and 1e)
sired product 4a in good yield (Table 1, Entries 17 and 18). provided better yields corresponding quinazolinone derivatives
From the optimization studies, CuI (20 mol-%), K2CO3 (3 equiv.), 4b, 4c, 4d, and 4e, respectively, with the CuII-catalyzed method
and MnO2 (4.5 equiv.) in DMSO under an oxygen atmosphere than with the CuI-catalyzed method.
at 140 °C (Table 1, Entry 5), and CuSO4·5H2O (30 mol-%) and
The reactions of benzylamine with N-phenyl-substituted 2-
K2CO3 (3 equiv.) in DMSO under an oxygen atmosphere at iodo-benzamides that contain electron-donating groups, such
140 °C (Table 1, Entry 19) were found to be the best conditions as methyl and methoxy, reacted smoothly under both reaction
to obtain desired quinazolinone derivative 4a; therefore, we conditions to give the desired N-phenyl-substituted 2-phenyl-
Table 1. Optimization of the reaction conditions for 4a.
[a] Al1 the reactions were performed with 1a (0.5 mmol), benzylamine (2.0 equiv.), K2CO3 (3.0 equiv.), and copper catalyst (20 mol-%) under an oxygen
atmosphere. [b] Yields refer to isolated and purified compounds. [c] MnO2 (4.5 equiv.) and other oxidants (2 equiv.) were used. [d] Catalyst (20 mol-%) was
used. [e] Catalyst (30 mol-%) was used.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1183
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 2. Scope of the reaction with benzylamines and various N-substituted 2-iodo-benzamides.[a,b]
[a] All reactions were performed on a 0.5 mmol scale. [b] Yields refer to isolated and purified compounds.
quinazolinone compounds in good yields (Table 2, Entries 4f– quinazolinone derivatives in moderate yields (Table 2, En-
4h). Subsequently, we tested the scope of 2-iodobenzamide tries 4m and 4n). Furthermore, 2-iodo-benzamide substrates
substrates that contain both electron-withdrawing and elec- that contain indolyl, furyl, and 2-bromo benzyl groups were
tron-donating groups on the benzene ring under both CuI- and treated with benzylamine under both conditions. Under CuI/
CuII-catalyzed conditions. Corresponding quinazolinone deriva- MnO2/O2 conditions, the reactions of these three derivatives
tives (Table 2, Entries 4i–4l) were obtained in good-to-moderate resulted in the formation of the desired products in low yields
yields. Under these reaction conditions, the substrate that pos- (Table 2, Entries 4o–4q). Next, we examined the reactions of
sesses dioxole substitution on the benzene ring and benzhydryl structurally diverse benzylamines with N-methyl-2-iodobenz-
on the amide resulted in the formation of the corresponding amide to obtain their corresponding quinazolinone derivatives
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1184
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(4r–4y). It is important to note that the reactions catalyzed by
To diversify this methodology further, we examined the reac-
CuI were faster than the CuII-catalyzed reactions. However, the tion of allylamine with N-substituted 2-iodo-benzamide sub-
chemical yields of the products are comparable for both meth- strates under both CuI/MnO2/O2 and CuII/O2 catalyzed reaction
ods (Table 3).
conditions (Table 4).
Table 3. Scope of the reaction with various benzylamine and N-substituted 2-iodo-benzamides.[a,b]
[a] All reactions were performed on a 0.5 mmol scale. [b] Yields refer to isolated and purified compounds.
Table 4. Optimization of the reaction conditions for 7b.
[a] All the reactions were performed under the following conditions, 1 (0.5 mmol), allylamine (2.0 equiv.), K2CO3 (3.0 equiv.), and MnO2 (4.5 equiv.) under an
oxygen atmosphere. [b] MnO2 (4.5 equiv.) and other oxidants (2 equiv.) were used. [c] Yields refer to isolated and purified compounds. [d] Catalyst (30 mol-
%) was used.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1185
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
The reaction of 2-iodo-N-methylbenzamide (1a) and allyl-
amine (5a) in the presence of copper iodide and MnO2 at
140 °C produced 3-methylquinazolin-4(3H)-one rather than 3-
methyl-2-vinylquinazolin-4(3H)-one (Table 4, Entry 1). Surprised
by this outcome, we then carried out optimization studies to
improve the yield of 3-methylquinazolin-4(3H)-one (7a). If MnO2
was replaced by other oxidants, such as oxone, hydrogen perox-
ide, and PhI(OAc)2, (Table 4, Entries 2–4), no marked improve-
ment in the yield of the product was observed. The reaction
afforded only Ullman product in solvents such as 1,4-dioxane
and ethanol (Table 4, Entries 5 and 6). The reaction in the pres-
ence of CuII sulfate under oxygen atmosphere resulted in for-
mation of Ullman coupled product only (Table 4, Entry 8). More-
over, we observed the formation of 3-methylquinazolin-4(3H)-
one (7a) in 30 % yield, when the reaction was conducted in the
presence of CuII sulfate and MnO2 (Table 4, Entry 8). The best
yield of desired product was only 40 % by using CuI/MnO2/O2
in DMSO at 140 °C (Table 4, Entry 1). Hence we applied these
conditions to examine the scope of the reaction with other sub-
stituted 2-iodobenzamides.
Scheme 1. Reactions of 2-bromo(N-benzyl)benzamide and 2-chloro(N-phen-
yl)benzamide with benzylamine.
As shown in Table 5, the reaction of N-methyl, N-benzyl, N-
phenyl, and N-phenyl-substituted 2-iodo-benzamides that con-
tain electron-donating groups, such as methyl and methoxy
substrates, and 2-iodo-4,5-dimethoxy-N-phenylbenzamide sub-
strates with allylamine resulted in corresponding quinazolinone
derivatives 7a–7f. However, yields of the corresponding pro-
ducts were poor.
Scheme 2. Reactions of 2-iodo(N-benzyl)benzamide and 2-chloro(N-phen-
yl)benzamide with benzylamine large scale experiment.
Finally, we investigated the reaction with an internal alkene-
containing allylamine such as 3-phenylprop-2-en-1-amine. Re-
action of 2-iodobenzamide derivative 1 and 3-phenylprop-2-en-
Furthermore, when the reactions were carried out with other 1-amine (8a) produced 3-styrylquinazolinone derivatives 9a–9k
halobenzamides, such as 2-bromo(N-benzyl)benzamide (1r) and under both CuI/MnO2/O2 and CuII/O2 conditions.
2-chloro(N-phenyl)benzamide (1s) derivatives, under the
present reaction conditions, the desired product was obtained
in good yield in the case of 2-bromo(N-benzyl)benzamide. How-
ever, moderate yield of the desired product was obtained with
2-chlorobenzamide derivative (Scheme 1).
As shown in Table 6, different N-substituted 2-iodo-benz-
amide derivatives reacted with 3-phenylprop-2-en-1-amine un-
der CuI/MnO2/O2 condition to give only poor yields of corre-
sponding 3-styrylquinazolinone derivatives 9a–9k. However,
the same reactions produced the same 3-styrylquinazolinone
Next, to determine the viability of this reaction on a large derivatives in moderate yields under CuII/O2 conditions. It is
scale, we carried out the reaction of 2-iodo (N-methylbenz- important to note that 3-styrylquinazolinone exhibits biological
amide) and benzylamine on a 5 mmol scale under the present activities that include anticonvulsant activity, central nervous
reaction conditions. The reaction produced desired quinazolin- system depressant activity, and so on.[13] Although several re-
one derivative 4a in 81 % isolated yield (Scheme 2).
search groups have synthesized these 3-strylquinazolinone de-
Table 5. Scope of the reaction with allylamine with N-substituted 2-iodo-benzamide[a,b]
[a] All reactions were performed on a 0.5 mmol scale. [b] Yields refer to isolated and purified compounds.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1186
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 6. Scope of the reaction with 3-phenylprop-2-en-1-amine with N-substituted 2-iodo-benzamide.[a,b]
[a] All reactions were performed on a 0.5 mmol scale. [b] Yields refer to isolated and purified compounds.
rivatives by different approaches,[14] the present approach is not product A in the presence of copper catalyst and potassium
reported in the literature.
carbonate. Subsequently, intermediate A was oxidized to form
imine intermediate B followed by cyclization to form com-
pound C. Compound C undergoes oxidation in the presence of
copper catalyst and oxidant to afford 3-methyl-2-phenylquin-
Plausible mechanistic pathways for the formation of 2-phen-
ylquinazolinone derivatives from the reaction of 2-iodobenz-
amide derivative and benzylamine in the presence of copper
catalyst are shown in Scheme 3. Initially, 2-iodo-N-methylbenz- azolin-4(3H)-one (1b). Another possibility is intermediate A un-
amide reacted with benzylamine to yield Ullmann N-arylated dergoes oxidation in the presence of oxidant to form 1,2-di-
Scheme 3. Plausible mechanistic pathway for the formation of 2-phenylquinazolinone.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1187
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
amido intermediate A′ followed by nucleophilic addition to observations support route b as the most reasonable mechanis-
form cyclized product B′. Cyclized intermediate B' undergoes tic pathway for the formation of product 1b.
dehydration in the presence of base to obtain the desired prod-
The mechanism for formation of quinazolinone derivatives
uct. To determine the best possible pathway for this reaction, 7a–7f from the reaction of N-substituted 2-iodo-benzamide
we carried out few control experiments. 2-Benzamido-N-meth- with allylamine in the presence of copper(I) and MnO2 may
ylbenzamide was subjected to the optimized reaction condi- be very similar with the formation of 2-phenylquinazolinone
tions. The desired product was not observed under these condi- (Scheme 4).
tions. Consequently, formation of the desired product through
In this reaction 2-allylquinazolinones might be formed,
route a could be disregarded. Dihydroquinoline derivative C which may undergo oxidative degradation of the terminal alk-
was reacted in the presence of copper(II) sulfate in DMSO under ene to form 3-formylquinazolinone derivatives. This formyl
oxygen atmosphere and afforded quinazolinone derivative 1b quinolone may then undergo oxidation to form 3-carboxylquin-
in good yield. Furthermore, a trace of intermediate dihydroquin- azolinone derivatives followed by decarboxylation[12] to gener-
oline derivative C was isolated in the reaction of 2-iodo-N-meth- ate quinazolinone derivatives (Scheme 4, Path 1). We were not
ylbenzamide and benzylamine in the presence of copper cata- able to isolate any intermediate proposed in the mechanism
lyst and oxygen at slightly lower temperature 120 °C. These except initially formed 2-(allylamino)-N-methylbenzamide (P)
Scheme 4. Plausible mechanistic pathways for the formation of N-substituted quinazolinone.
Scheme 5. Controlled experiments.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1188
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(0.5 mmol), benzylamines (2.0 equiv., 1 mmol) in DMSO as a solvent
under an oxygen atmosphere. The reaction mixture was then
heated to 140 °C and the progress of the reaction monitored by TLC.
The resulting reaction mixture was cooled to room temperature and
extracted with ethyl acetate. The combined ethyl acetate extracts
were washed with brine and dried with MgSO4. The resulting crude
compound was purified by flash column chromatography (petro-
leum ether/ethyl acetate, 10:3) on silica gel to afford the desired
product.
and 2-amino-N-methylbenzamide (U) compound. Based on our
observation, we speculate that initially formed 2-(allylamino)-
N-methylbenzamide may form a 2-amino-N-methylbenzamide
compound through thermal decomposition in which the allyl
group may be decomposed to formaldehyde. Both these com-
ponents might react together to form the quinazolinone deriva-
tive (Scheme 4, Path 2). We also carried out a few controlled
experiments, which are shown in Scheme 5.
The reaction of 2-(allylamino)-N-methylbenzamide under op-
timized reactions conditions provided desired quinzolinone de-
rivative 7b in 30 % yield. The reaction of 2-amino-N-benzyl-
benzamide and allylamine under the current reaction condi-
tions also produced desired quinazolinone derivative 7b. Both
these control experiments lend support to mechanistic pathway
2.
Spectral Data
3-Methyl-2-phenylquinazolin-4(3H)-one (4a):[3a] Yield 95 (80 %)
and 92 mg (78 %) for methods A and B, respectively. White solid,
m.p. 138–140 °C. 1H NMR (400 MHz, CDCl3): δH = 8.33 (d, J = 8.0 Hz,
1 H), 7.78–7.73 (m, 2 H), 7.57–7.48 (m, 6 H), 3.49 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δC = 162.9, 156.3, 147.5, 135.6, 134.4, 130.2,
129.0, 128.2, 127.7, 127.1, 126.8, 120.7, 34.4 ppm. MS (ESI+): m/z
(%) = 237.26 (100) [M + H]. HRMS (FAB+): calcd. for C15H13ON2 [M +
H]+ 237.1028; found 237.1022.
Conclusions
3-Ethyl-2-phenylquinazolin-4(3H)-one (4b): Yield 63 (50 %) and
88 mg (70 %) for methods A and B, respectively. White solid, m.p.
135–137 °C. 1H NMR (400 MHz, CDCl3): δH = 8.3 (d, J = 7.92 Hz, 1
H), 7.77–7.71 (m, 2 H), 7.54–7.47 (m, 6 H), 4.03 (q, J = 14.06, 7.02 Hz,
2 H), 1.21 (t, J = 7.02 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC =
162.1, 156.3, 147.4, 135.8, 134.4, 129.9, 129.0, 127.8, 127.6, 127.1,
126.9, 121.2, 41.3, 14.3 ppm. MS (ESI+): m/z (%) = 251.20 (100) [M +
H], 223.25 (28). HRMS (FAB+): calcd. for C16H15ON2 [M + H]+
251.1184; found 251.1189.
In conclusion, we have demonstrated a one-pot Ullman-type N-
alkylation reaction followed by intramolecular C–H amidation
reaction protocol for the synthesis of 2-phenylquinazolinone
and quinazolinone derivatives from N-substituted 2-iodo-
benzamides and benzylamines, allyl, and cinnamylamine. The
scope of this transformation is broad with good functional
group tolerance and uses easily available starting materials. Due
to the easy availability of the starting materials and cheap rea-
gents, such as CuSO4·5H2O, we believe this protocol provides a
simplified route to the synthesis of 2-phenylquinazolinone and
quinazolinone derivatives.
3-Benzyl-2-phenylquinazolin-4(3H)-one (4c):[3a] Yield 81 (52 %)
and 109 mg (70 %) for methods A and B, respectively. White solid,
m.p. 146–148 °C. 1H NMR (400 MHz, CDCl3): δH = 8.39–8.37 (m, 1
H), 7.79–7.75 (m, 2 H), 7.55–7.51 (m, 1 H), 7.48–7.45 (m, 1 H), 7.40
(t, J = 7.54 Hz, 2 H), 7.34 (d, J = 7.44 Hz, 2 H), 7.20 (t, J = 3.26 Hz, 3
H), 6.92 (dd, J = 6.28, 2.64 Hz, 2 H), 5.27 (s, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 162.6, 156.5, 147.4, 136.7, 135.4, 134.7, 130.0,
128.7, 128.6, 128.1, 127.7, 127.6, 127.3, 127.2, 127.1, 121.0, 48.9 ppm.
MS (ESI+): m/z (%) = 313.20 (100) [M + H], 353.19 (15). HRMS (FAB+):
Experimental Section
General Information: Reagents and solvents were purchased from
various commercial sources and were used as received without fur-
ther purification, unless otherwise stated. Column chromatography
was performed with 63–200 mesh silica gel. 1H and 13C NMR spectra
were recorded at 400 and 100 MHz, respectively. Chemical shifts
are reported relative to chloroform as internal standard. Melting
points were recorded with an electro thermal capillary melting-
point apparatus. HRMS spectra were recorded in TOF ESI or FAB+
mode.
+
calcd. for C21H17ON2 [M + H] 313.1341; found 313.1334.
3-(2-Methoxyethyl)-2-phenylquinazolin-4(3H)-one (4d):[4d] Yield
99.5 (71 %) and 92.5 mg (66 %) for methods A and B, respectively.
White solid, m.p. 80–82. 1H NMR (400 MHz, CDCl3): δH = 8.32 (d, J =
8.08 Hz, 1 H), 7.75–7.72 (m, 2 H), 7.56–7.53 (m, 2 H), 7.51–7.47 (m,
4 H), 4.23 (t, J = 5.76 Hz, 2 H), 3.57 (t, J = 5.76 Hz, 2 H), 3.15 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.5, 156.7, 147.4, 135.7,
134.6, 129.9, 128.8, 128.5, 127.6, 127.1, 126.8, 120.9, 69.4, 58.9,
45.4 ppm. MS (ESI+): m/z (%) = 281.17 (100) [M + H], 223.27 (33).
HRMS (FAB+): calcd. for C17H17O2N2 [M + H]+ 281.1290; found
281.1284.
General Procedure for the Synthesis of 2,3-Disubstituted Quin-
azolinone Derivatives
Method A: Copper iodide (20 mol-%) and potassium carbonate
(3.0 equiv.) were added to a stirred solution of N-substituted 2-iodo-
benzamide (0.5 mmol), benzylamines (2.0 equiv., 1 mmol) in DMSO
as a solvent under an oxygen atmosphere. The reaction mixture
was then heated to 140 °C. After 5 min, MnO2 (4.6 equiv., 200 mg)
was added to the reaction mixture at the same temperature.
Progress of the reaction was monitored by TLC. After completion of
the reaction, the resulting reaction mixture was cooled to room
temperature and extracted with ethyl acetate. The combined ethyl
acetate extracts were washed with brine and dried with MgSO4.
The resulting crude compound was then purified by flash column
chromatography (petroleum ether/ethyl acetate, 10:3) on silica gel
to afford the desired product.
2,3-Diphenylquinazolin-4(3H)-one (4e):[3a] Yield 109 (73 %) and
110 mg (74 %) for methods A and B, respectively. White solid, m.p.
1
168–170 °C. H NMR (400 MHz, CDCl3): δH = 8.33 (d, J = 7.92 Hz, 1
H), 7.80–7.78 (m, 2 H), 7.53–7.49 (m, 1 H), 7.31–7.27 (m, 3 H), 7.26–
7.15 (m, 5 H), 7.13–7.11 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 162.4, 155.4, 147.7, 137.8, 135.6, 134.9, 129.4, 129.3, 129.18,
129.16, 128.5, 128.1, 127.9, 127.47, 127.41, 121.1 ppm. MS (ESI+):
m/z (%) = 299.27 (100) [M + H]. HRMS (FAB+): calcd. for C20H15ON2
[M + H]+ 299.1184; found 299.1185.
2-Phenyl-3-(p-tolyl)quinazolin-4(3H)-one (4f):[8h] Yield 102 (65 %)
and 94 mg (60 %) for methods A and B, respectively. White solid,
m.p. 189–191 °C. 1H NMR (400 MHz, CDCl3): δH = 8.35 (d, J = 7.8 Hz,
1 H), 7.83–7.77 (m, 2 H), 7.54–7.50 (m, 1 H), 7.35–7.33 (m, 2 H), 7.27–
7.19 (m, 3 H), 7.10 (d, J = 8.16 Hz, 2 H), 7.02 (d, J = 8.24 Hz, 2 H),
Method B: Copper(II) sulfate pentahydrate (CuSO4·5H2O, 30 mol-%)
was added to a stirred solution of N-substituted 2-iodo-benzamide
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1189
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2.30 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.5, 155.5,
(100) [M + H]. HRMS (FAB+): calcd. for C15H12ON2Br [M + H]+
147.7, 138.5, 135.8, 135.2, 134.8, 129.8, 129.4, 129.1, 128.9, 128.1, 315.0133; found 315.0130.
127.9, 127.4, 127.3, 121.1, 21.3 ppm. MS (ESI+): m/z (%) = 313.29
7-Methyl-6-phenyl-[1,3]dioxolo[4,5-g]quinazolin-8(7H)-one
(100) [M + H]. HRMS (FAB+): calcd. for C21H17ON2 [M + H]+ 313.1341;
found 313.1347.
(4m): Yield 70 (50 %) and 68 mg (48.5 %) for methods A and B,
respectively. White solid, m.p. 180–182 °C. 1H NMR (400 MHz,
CDCl3): δH = 7.62 (s, 1 H), 7.54–7.49 (m, 5 H), 7.08 (s, 1 H), 6.10 (s, 2
H), 3.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.1, 155.0,
153.5, 147.8, 145.4, 135.6, 130.1, 129.0, 128.2, 115.8, 105.9, 103.7,
102.3, 96.2, 52.1, 34.3 ppm. MS (ESI+): m/z (%) = 281.24 (100) [M +
H]. HRMS (FAB+): calcd. for C16H13O3N2 [M + H]+ 281.0926; found
281.0932.
3-(2,4-Dimethylphenyl)-2-phenylquinazolin-4(3H)-one
Yield 129 (79 %) and 133.5 mg (82 %) for methods A and B, respec-
tively. White solid, m.p. 135–137 °C. 1H NMR (400 MHz, CDCl3): δH
(4g):
=
8.35 (d, J = 7.96 Hz, 1 H), 7.81–7.99 (m, 2 H), 7.54–7.50 (m, 1 H),
7.35–7.33 (m, 2 H), 7.26–7.19 (m, 3 H), 6.98–6.92 (m, 3 H), 2.26 (s, 3
H), 2.08 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.1, 155.7,
147.9, 139.0, 135.5, 135.3, 134.7, 134.4, 131.8, 129.5, 129.3, 128.8,
128.0, 127.9, 127.5, 127.4, 127.3, 121.1, 21.2, 18.0 ppm. MS (ESI+):
m/z (%) = 327.30 (100) [M + H]. HRMS (FAB+): calcd. for C22H19ON2
[M + H]+ 327.1497; found 327.1489.
3-(2,2-Diphenylethyl)-2-phenylquinazolin-4(3H)-one (4n): Yield
130.5 (65 %) and 120.5 mg (60 %) for methods A and B, respectively.
1
White solid, m.p. 121–123 °C. H NMR (400 MHz, CDCl3): δH = 8.34
(d, J = 7.76 Hz, 1 H), 7.74 (t, J = 7.28 Hz, 1 H), 7.66 (d, J = 7.92 Hz,
1 H), 7.52–7.45 (m, 2 H), 7.40 (t, J = 7.32 Hz, 2 H), 7.15–7.08 (m, 8
H), 6.93 (m, 4 H), 4.80 (d, J = 4.24 Hz, 2 H), 4.49 (t, J = 7.48 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.8, 156.2, 147.2, 140.9,
135.4, 134.5, 134.1, 129.9, 128.7, 128.5, 128.4, 127.6, 127.1, 127.0,
126.9, 120.9, 50.7, 48.5 ppm. MS (ESI+): m/z (%) = 403.16 (100) [M +
H]. HRMS (FAB+): calcd. for C28H23ON2 [M + H]+ 403.1810; found
403.1816.
3-(4-Methoxyphenyl)-2-phenylquinazolin-4(3H)-one
Yield 110 (67 %) and 113 mg (69 %) for methods A and B, respec-
tively. White solid, m.p. 199–200 °C. 1H NMR (400 MHz, CDCl3): δH
(4h):[8h]
=
8.34 (d, J = 7.88 Hz, 1 H), 7.82–7.79 (m, 2 H), 7.54–7.50 (m, 1 H),
7.35–7.32 (m, 2 H), 7.26–7.20 (m, 3 H), 7.06–7.02 (m, 2 H), 6.81 (dd,
J = 9.52, 2.64 Hz, 2 H), 3.76 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 162.7, 159.3, 155.7, 147.7, 135.8, 134.8, 130.4, 130.2, 129.4,
129.1, 128.2, 127.9, 127.4, 127.3, 121.1, 114.4, 55.5 ppm. MS (ESI+):
m/z (%) = 329.25 (100) [M + H]. HRMS (FAB+): calcd. for C21H17O2N2
[M + H]+ 329.1290; found 329.1284.
3-(Furan-2-ylmethyl)-2-phenylquinazolin-4(3H)-one (4o):[4d]
Yield 68 (45 %) and 90.5 mg (60 %) for methods A and B, respec-
tively. Yellow solid, m.p. 115–117 °C. 1H NMR (400 MHz, CDCl3): δH
=
8.35–8.33 (m, 1 H), 7.76–7.72 (m, 2 H), 7.52–7.48 (m, 6 H), 7.26 (d,
J = 1.4 Hz, 1 H), 6.25–6.24 (m, 1 H), 6.08 (d, J = 3.28 Hz, 1 H), 5.20
(s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.2, 156.1, 149.4,
147.3, 142.2, 135.3, 134.7, 130.1, 128.8, 128.3, 127.7, 127.3, 127.1,
121.0, 110.6, 109.0, 42.6 ppm. MS (ESI+): m/z (%) = 303.09 (100) [M
+ H]. HRMS (FAB+): calcd. for C19H15O2N2 [M + H]+ 303.1134; found
303.1134.
6-Methoxy-2,3-diphenylquinazolin-4(3H)-one (4i):[8h] Yield 107
(65 %) and 107 mg (65 %) for methods A and B, respectively. White
1
solid, m.p. 202–204 °C. H NMR (400 MHz, CDCl3): δH = 7.75 (d, J =
8.88 Hz, 1 H), 7.70 (d, J = 2.96 Hz, 1 H), 7.40 (dd, J = 8.88, 3.0 Hz, 1
H), 7.32–7.29 (m, 4 H), 7.28–7.24 (m, 1 H), 7.22–7.17 (m, 3 H), 7.15–
7.13 (m, 2 H), 3.93 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC
=
162.3, 159.0, 153.2, 142.3, 138.0, 135.7, 129.5, 129.3, 129.3, 129.2,
129.1, 128.5, 128.1, 125.0, 121.9, 106.8, 56.0 ppm. MS (ESI+): m/z
(%) = 329.31 (100) [M + H]. HRMS (FAB+): calcd for C21H17O2N2 [M
+ H]+ 329.1290; found 329.1292.
3-(2-Bromobenzyl)-2-phenylquinazolin-4(3H)-one (4p). Yield 80
(41 %) and 78 mg (40 %) for methods A and B, respectively. White
1
solid, m.p. 147–149 °C. H NMR (400 MHz, CDCl3): δH = 8.37 (d, J =
7.8 Hz, 1 H), 7.83–7.82 (m, 2 H), 7.57–7.53 (m, 1 H), 7.49–7.43 (m, 2
H), 7.35 (t, J = 7.6 Hz, 2 H), 7.31–7.29 (m, 2 H), 7.23–7.19 (m, 1 H),
7.13–7.09 (m, 1 H), 6.93 (d, J = 7.0 Hz, 1 H), 5.25 (s, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δC = 162.5, 156.6, 147.5, 135.7, 135.0, 134.9,
133.0, 130.2, 128.9, 128.9, 128.0, 127.9, 127.8, 127.7, 127.5, 127.3,
127.2, 122.4, 120.8, 49.8 ppm. MS (ESI+): m/z (%) = 391.12 (100) [M
+ H]. HRMS (FAB+): calcd. for C21H16ON2Br [M + H]+ 391.0446; found
391.0453.
6,7-Dimethoxy-2,3-diphenylquinazolin-4(3H)-one (4j): Yield 106
(59 %) and 117 mg (65 %) for methods A and B, respectively. White
solid, m.p. 245–247 °C. 1H NMR (400 MHz, CDCl3): δH = 7.66 (s, 1 H),
7.32–7.28 (m, 4 H), 7.28–7.21 (m, 4 H), 7.19 (d, J = 1.44 Hz, 1 H),
7.16–7.13 (m, 2 H), 4.01 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 161.8, 155.4, 154.3, 149.6, 143.9, 138.0, 135.8, 129.3, 129.3,
129.1, 129.1, 128.5, 128.1, 114.4, 108.4, 106.2, 56.5 ppm. MS (ESI+):
m/z (%) = 359.32 (100) [M + H]. HRMS (FAB+): calcd. for C22H19O3N2
[M + H]+ 359.1396; found 359.1398.
3-[2-(1H-Indol-3-yl)ethyl]-2-phenylquinazolin-4(3H)-one (4q):
Yield 80.5 (44 %) and 64 mg (35 %) for methods A and B, respec-
tively. Yellow solid, m.p. 282–284 °C. 1H NMR (400 MHz, CDCl3): δH
=
7-Chloro-2,3-diphenylquinazolin-4(3H)-one (4k): Yield 100
(60 %) and 108 mg (65 %) for methods A and B, respectively. White
8.40 (d, J = 7.72 Hz, 1 H), 7.97 (br. s, 1 H), 7.80–7.73 (m, 2 H), 7.56–
7.49 (m, 2 H), 7.47–7.43 (m, 2 H), 7.39 (dd, J = 13.66, 5.78 Hz, 2 H),
7.29 (d, J = 8.2 Hz, 1 H), 7.14–7.11 (m, 1 H), 6.93 (d, J = 5.44 Hz, 1
H), 6.82 (s, 1 H), 4.30 (t, J = 7.86 Hz, 1 H), 3.07 (t, J = 7.84 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.4, 156.5, 147.4, 136.3,
135.6, 134.6, 129.8, 129.0, 128.0, 127.7, 127.3, 127.2, 126.9, 122.4,
122.2, 121.2, 119.6, 118.7, 112.1, 111.2, 46.9, 24.7 ppm. MS (ESI–):
m/z (%) = 364.0 (100) [M – 1]. HRMS (FAB+): calcd. for C24H20ON3
[M + H]+ 366.1606; found 366.1602.
1
solid, m.p. 188–189 °C. H NMR (400 MHz, CDCl3): δH = 8.28 (d, J =
8.52 Hz, 1 H), 7.82 (d, J = 1.84 Hz, 1 H), 7.48 (dd, J = 8.54, 1.94 Hz,
1 H), 7.34–7.30 (m, 5 H), 7.28–7.19 (m, 3 H), 7.14 (dd, J = 5.3, 2.82 Hz,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 161.9, 156.6, 148.6, 141.1,
137.6, 135.3, 129.7, 129.2, 129.2, 129.1, 128.9, 128.7, 128.2, 128.0,
127.5, 119.6 ppm. MS (ESI+): m/z (%) = 333.25 (100) [M + H]. HRMS:
calcd. for C20H14ON2Cl [M + H]+ 333.0795; found 333.0793.
6-Bromo-3-methyl-2-phenylquinazolin-4(3H)-one (4l): Yield 75.5
(48 %) and 78.5 mg (50 %) for methods A and B, respectively. White
2-(2-Chlorophenyl)-3-Methylquinazolin-4(3H)-one (4r):[3a] Yield
1
solid, m.p. 138–140 °C. H NMR (400 MHz, CDCl3): δH = 8.46 (d, J =
84 (62 %) and 67.5 mg (50 %) for methods A and B, respectively.
1
2.32 Hz, 1 H), 7.83 (dd, J = 8.66, 2.23 Hz, 1 H), 7.61 (d, J = 8.72 Hz,
White solid, m.p. 129–131 °C. H NMR (400 MHz, CDCl3): δH = 8.33
1 H), 7.57–7.52 (m, 5 H), 3.50 (s, 3 H) ppm. 13C NMR (100 MHz, (d, J = 8.0 Hz, 1 H), 7.77–7.71 (m, 2 H), 7.53–7.40 (m, 5 H), 3.38 (s, 3
CDCl3): δC = 161.8, 156.7, 146.3, 137.7, 135.3, 130.4, 129.5, 129.4, H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.2, 153.8, 147.3, 134.8,
129.1, 128.1, 122.1, 120.6, 34.6 ppm. MS (ESI+): m/z (%) = 315.21
134.4, 132.4, 131.3, 130.0, 129.6, 127.7, 127.6, 127.4, 126.8, 121.0,
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1190
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
32.4 ppm. MS (ESI+): m/z (%) = 271.24 (100) [M + H]. HRMS (FAB+): 147.5, 146.5, 144.9, 134.4, 127.6, 127.2, 126.9, 120.6, 115.7, 112.0,
calcd. for C15H12ON2Cl [M + H]+ 271.0638; found 271.0640.
2-(4-Chlorophenyl)-3-methylquinazolin-4(3H)-one (4s):[3a] Yield
33.1 ppm. MS (ESI+): m/z (%) = 227.24 (100) [M + H]. HRMS (FAB+):
calcd. for C13H11O2N2 [M + H]+ 227.0821; found 227.0817.
3-Methylquinazolin-4(3H)-one (7a):[12] Yield 32 mg (40 %). White
88 (65 %) and 84 mg (62 %) for methods A and B, respectively.
1
1
White solid, m.p. 168–170 °C. H NMR (400 MHz, CDCl3): δH = 8.33
solid, m.p. 71–73 °C. H NMR (400 MHz, CDCl3): δH = 8.24–8.22 (m,
(d, J = 8.6 Hz, 1 H), 7.79–7.71 (m, 2 H), 7.55–7.50 (m, 5 H), 3.50 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.8, 155.2, 147.4, 136.6,
134.6, 134.0, 129.7, 129.4, 127.7, 127.4, 126.9, 120.7, 34.4 ppm. MS
(ESI+): m/z (%) = 271.25 [M + H 100]. HRMS (FAB+): calcd. for
C15H12ON2Cl [M + H]+ 271.0638; found 271.0644.
1 H), 7.98 (s, 1 H), 7.70–7.61 (m, 2 H), 7.45–7.41 (m, 1 H), 3.53 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 161.7, 148.4, 146.9, 134.3,
127.6, 127.5, 126.7, 122.1, 34.2 ppm. MS (ESI+): m/z (%) = 161.22 [M
+ H 100]. HRMS (FAB+): calcd. for C9H9ON2 [M + H]+ 161.0715; found
161.0717.
3-Benzylquinazolin-4(3H)-one (7b):[3d] Yield 20 mg (17 %). White
solid, m.p. 121–123 °C. 1H NMR (400 MHz, CDCl3): δH = 8.33 (dd, J =
7.94, 1.1 Hz, 1 H), 8.10 (s, 1 H), 7.77–7.69 (m, 2 H), 7.52–7.48 (m, 1
H), 7.36–7.29 (m, 5 H), 5.20 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 161.2, 148.2, 146.5, 135.9, 134.5, 129.2, 128.5, 128.2, 127.7,
127.5, 127.1, 122.4, 49.8 ppm. MS (ESI+): m/z (%) = 237.13 (100) [M
+ H]. HRMS (FAB+): calcd. for C15H13ON2 [M + H]+ 237.1028; found
237.1026.
2-(4-Bromophenyl)-3-methylquinazolin-4(3H)-one (4t): Yield
94.5 (60 %) and 112 mg (71 %) for methods A and B, respectively.
White solid, m.p. 168–170 °C. 1H NMR (400 MHz, CDCl3): δH = 8.32–
8.29 (m, 1 H), 7.77–7.65 (m, 4 H), 7.52–7.45 (m, 3 H), 3.48 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.7, 155.2, 147.3, 134.6,
134.4, 132.3, 129.9, 127.7, 127.4, 126.9, 124.7, 120.7, 34.4 ppm. MS
(ESI+): m/z (%) = 315.20 (100) [M + H]. HRMS (FAB+): calcd. for
C15H12ON2Br [M + H]+ 315.0133; found 315.0136.
2-(2-Methoxyphenyl)-3-methylquinazolin-4(3H)-one (4u):[15]
3-Phenylquinazolin-4(3H)-one (7c):[3d] Yield 35.5 mg (32 %). White
solid, m.p. 150–152 °C. 1H NMR (400 MHz, CDCl3): δH = 8.38–8.36
(m, 1 H), 8.13 (s, 1 H), 7.83–7.76 (m, 2 H), 7.57–7.53 (m, 3 H), 7.51–
7.47 (m, 1 H), 7.44–7.41 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δC = 160.9, 148.0, 146.2, 137.6, 134.7, 129.8, 129.3, 127.8, 127.7,
127.4, 127.2, 122.6 ppm. MS (ESI+): m/z (%) = 223.17 (100) [M +
H]. HRMS (FAB+): calcd. for C14H11ON2 [M + H]+ 223.0871; found
223.0869.
Yield 66.5 (50 %) and 64 mg (48 %) for methods A and B, respec-
tively. White solid, m.p. 189–191 °C. 1H NMR (400 MHz, CDCl3): δH
=
8.34 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 3.64 Hz, 2 H), 7.51–7.46 (m, 2
H), 7.42 (dd, J = 7.46, 1.54 Hz, 1 H), 7.11 (t, J = 7.5 Hz, 1 H), 7.00 (d,
J = 8.4 Hz, 1 H), 3.82 (s, 3 H), 3.40 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δC = 163.6, 156.5, 154.9, 147.8, 134.2, 131.7, 129.7, 127.7,
127.0, 126.8, 125.0, 121.5, 121.0, 111.2, 55.7, 32.5 ppm. MS (ESI+):
m/z (%) = 267.26 (100) [M + H]. HRMS (FAB+): calcd. for C16H15O2N2
[M + H]+ 267.1134; found 267.1136.
6,7-Dimethoxy-3-phenylquinazolin-4(3H)-one (7d):[8k] Yield
28.2 mg (20 %). White solid, m.p. 193–195 °C. 1H NMR (400 MHz,
CDCl3): δH = 8.03 (s, 1 H), 7.66 (s, 1 H), 7.55–7.52 (m, 2 H), 7.49–7.47
(m, 1 H), 7.43 (dd, J = 7.08, 1.44 Hz, 2 H), 7.15 (s, 1 H), 4.02 (s, 3 H),
3.99 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 160.3, 155.2,
149.8, 145.1, 144.3, 137.9, 129.7, 129.1, 127.2, 115.8, 108.2, 106.2,
56.5 ppm. MS (ESI+): m/z (%) = 283.25 (100) [M + H]. HRMS (FAB+):
calcd. for C16H15O3N2[M + H]+ 283.1083; found 283.1075.
2-(4-Methoxyphenyl)-3-methylquinazolin-4(3H)-one (4v):[3a]
Yield 80 (60 %) and 86.5 mg (65 %) for methods A and B, respec-
tively. White solid, m.p. 150–152 °C. 1H NMR (400 MHz, CDCl3): δH
=
8.31 (d, J = 8.0 Hz, 1 H), 7.74–7.70 (m, 2 H), 7.52 (dd, J = 10.0, 2.3 Hz,
2 H), 7.49–7.45 (m, 1 H), 7.02 (d, J = 8.6 Hz, 2 H), 3.87 (s, 3 H), 3.52
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 163.1, 161.1, 156.2,
147.6, 134.4, 129.9, 127.9, 127.6, 126.9, 126.8, 120.6, 114.4, 55.6,
34.6 ppm. MS (ESI+): m/z (%) = 267.26 (100) [M + H]. HRMS (FAB+):
calcd. for C16H15O2N2 [M + H]+ 267.1134; found 267.1131.
3-(o-Tolyl)quinazolin-4(3H)-one (7e):[3d] Yield 35 mg (30 %). White
solid, m.p. 102–104 °C. 1H NMR (400 MHz, CDCl3): δH = 8.38–8.36
(m, 1 H), 8.02 (s, 1 H), 7.81–7.79 (m, 2 H), 7.57–7.53 (m, 1 H), 7.42–
7.35 (m, 3 H), 7.25 (d, J = 7.88 Hz, 1 H), 2.20 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 160.5, 148.1, 146.6, 136.7, 135.9, 134.7, 131.5,
129.9, 128.0, 127.7, 127.7, 127.5, 127.3, 122.5, 17.9 ppm. MS (ESI+):
m/z (%) = 237.32 (100) [M + H]. HRMS (TOF–ES+): calcd. for
C15H13ON2 [M + H]+ 237.1028; found 237.1030.
2-[4-(tert-Butyl)phenyl]-3-methylquinazolin-4(3H)-one (4w):
Yield 65.7 (45 %) and 58.5 mg (40 %) for methods A and B, respec-
tively. White solid, m.p. 192–194 °C. 1H NMR (400 MHz, CDCl3): δH
=
8.32 (d, J = 7.76 Hz, 1 H), 7.75–7.73 (m, 2 H), 7.55–7.52 (m, 2 H),
7.51–7.47 (m, 3 H), 3.53 (s, 3 H), 1.36 (s, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 163.0, 156.5, 153.5, 147.6, 134.4, 132.7, 127.9,
127.7, 127.0, 126.8, 126.0, 120.7, 35.1, 34.5, 31.4 ppm. MS (ESI+): m/z
(%) = 293.28 [M + H 100]. HRMS (FAB+): calcd. for C19H21ON2 [M +
H]+ 293.1654; found 293.1648.
3-(2-Methoxyphenyl)quinazolin-4(3H)-one (7f):[3d] Yield 32 mg
(25 %). White solid, m.p. 158–160 °C. 1H NMR (400 MHz, CDCl3): δH =
8.37–8.34 (m, 1 H), 7.96 (s, 1 H), 7.80–7.74 (m, 2 H), 7.54–7.50 (m, 1
H), 7.48–7.44 (m, 1 H), 7.33 (dd, J = 7.68, 1.72 Hz, 1 H), 7.11–7.07
(m, 2 H), 3.80 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 160.8,
154.8, 148.2, 147.3, 134.5, 131.1, 129.3, 127.6, 127.4, 127.3, 126.1,
122.8, 121.1, 112.4, 56.0 ppm. MS (EI+): m/z (%) = 252.0 (78), 221.1
(100). HRMS (TOF–ES+): calcd. for C15H13O2N2 [M + H]+ 253.0977;
found 253.0977.
2-(2,5-Dimethylphenyl)-3-methylquinazolin-4(3H)-one (4x):
Yield 99 (75 %) and 92.5 mg (70 %) for methods A and B, respec-
tively. White solid, m.p. 95–97 °C. 1H NMR (400 MHz, CDCl3): δH
=
8.34 (d, J = 7.9 Hz, 1 H), 7.78–7.72 (m, 2 H), 7.52–7.48 (m, 1 H), 7.20
(s, 2 H), 7.14 (s, 1 H), 3.35 (s, 3 H), 2.36 (s, 3 H), 2.18 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δC = 162.6, 156.4, 147.6, 136.4, 135.1,
134.4, 132.2, 130.8, 130.7, 128.0, 127.7, 127.1, 126.8, 120.8, 32.8, 21.0,
18.7 ppm. MS (ESI+): m/z (%) = 265.30 [M + H 100]. HRMS (FAB+):
calcd. for C17H17ON2 [M + H]+ 265.1341; found 265.1334.
2-(Furan-2-Yl)-3-methylquinazolin-4(3H)-one (4y):[3a] Yield 68
(60 %) and 69 mg (61 %) for methods A and B, respectively. Yellow
solid, m.p. 106–108 °C. 1H NMR (400 MHz, CDCl3): δH = 8.30–8.28
(m, 1 H), 7.76–7.72 (m, 2 H), 7.65 (dd, J = 1.66, 0.7 Hz, 1 H), 7.49–
7.45 (m, 1 H), 7.15 (d, J = 3.52 Hz, 1 H), 6.60 (dd, J = 3.48, 1.8 Hz, 1
H), 3.77 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.7, 147.7,
3-Methyl-2-styrylquinazolin-4(3H)-one (9a):[14d] Yield 52.5 (40 %)
and 78.5 mg (60 %) for methods A and B, respectively. White solid,
m.p. 170–172 °C. 1H NMR (400 MHz, CDCl3): δH = 8.28 (d, J = 8.08 Hz,
1 H), 8.00–7.96 (m, 1 H), 7.73–7.70 (m, 2 H), 7.62 (d, J = 6.64 Hz, 2
H), 7.46–7.38 (m, 4 H), 7.14–7.10 (m, 1 H), 3.76 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δC = 162.5, 152.5, 147.7, 141.3, 135.5, 134.4,
130.0, 129.1, 128.0, 127.4, 127.0, 126.6, 120.6, 119.2, 30.9 ppm. MS
(ESI+): m/z (%) = 263.27 (100) [M + H]. HRMS (FAB+): calcd. for
C17H15ON2 [M + H]+ 263.1184; found 263.1179.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1191
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
3-Benzyl-2-styrylquinazolin-4(3H)-one (9b):[14e] Yield 59 (35 %) (dd, J = 7.64, 1.8 Hz, 2 H), 7.38–7.32 (m, 6 H), 7.29 (d, J = 7.36 Hz, 3
and 89.5 mg (53 %) for methods A and B, respectively. White solid,
m.p. 138–140 °C. 1H NMR (400 MHz, CDCl3): δH = 8.34 (d, J = 8.0 Hz,
1 H), 7.95–7.91 (m, 1 H), 7.77–7.76 (m, 2 H), 7.49–7.44 (m, 3 H), 7.38–
7.35 (m, 5 H), 7.31–7.27 (m, 3 H), 7.04–7.00 (m,1 H), 5.52 (s, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δC = 162.6, 152.7, 147.8, 141.2, 136.5,
H), 7.02–6.98 (m, 1 H), 5.52 (s, 2 H), 3.92 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 162.4, 158.5, 150.5, 142.5, 140.3, 136.6, 135.6,
129.7, 129.2, 129.1, 129.0, 127.9, 127.8, 126.7, 125.1, 121.4, 119.6,
106.5, 56.0, 47.1 ppm. MS (ESI+): m/z (%) = 369.20 (M + H, 100).
HRMS (TOF–ES+): calcd. for C24H21O2N2 [M + H]+ 369.1603; found
135.5, 134.6, 129.9, 129.2, 129.0, 127.9, 127.5, 127.3, 126.7, 120.7, 369.1602.
119.6, 47.1 ppm. MS (ESI+): m/z (%) = 339.27 (100) [M + H]. HRMS
6,7-Dimethoxy-3-phenyl-2-styrylquinazolin-4(3H)-one (9i):
(FAB+): calcd. for C23H19ON2 [M + H]+ 339.1497: found 339.1499.
Method B. Yield 87 mg (45 %). Yellow solid, m.p. 283–285 °C. 1H
NMR (400 MHz, CDCl3): δH = 7.90–7.86 (m, 1 H), 7.61–7.54 (m, 4 H),
7.33–7.28 (m, 7 H), 7.20 (s, 1 H), 6.38–6.34 (m, 1 H), 4.05 (s, 3 H),
3.99 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 161.8, 155.4,
7-Fluoro-3-phenyl-2-styrylquinazolin-4(3H)-one (9c): Yield 42.5
(25 %) and 39.5 mg (23 %) for methods A and B, respectively. White
1
solid, m.p. 203–205 °C. H NMR (400 MHz, CDCl3): δH = 8.30 (q, J =
8.78, 6.22 Hz, 1 H), 8.00–7.96 (m, 1 H), 7.62–7.56 (m, 3 H), 7.43 (dd, 150.8, 149.3, 144.2, 139.0, 137.4, 135.6, 130.0, 129.6, 129.4, 128.9,
J = 9.78, 2.34 Hz, 1 H), 7.32–7.31 (m, 7 H), 7.20–7.15 (m, 1 H), 6.38–
127.8, 120.3, 114.4, 107.9, 106.2, 56.5, 56.5 ppm. MS (ESI+): m/z (%) =
385.31 (M + H, 100). HRMS (TOF–ES+): calcd. for C24H21O3N2 [M +
H]+ 385.1552; found 385.1553.
6.34 (m,1 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 168.2 (d, JC-F
=
25 Hz), 161.8, 153.1, 150.2 (d, JC-F = 13 Hz), 140.9, 136.9, 135.3, 130.2,
130.1, 130.0 (d, JC-F = 10 Hz), 129.7, 129.0, 128.8, 128.0, 119.7, 117.8,
115.6 (d, JC-F = 23 Hz), 112.8 (d, JC-F = 21 Hz) ppm. MS (ESI+): m/z
(%) = 343.31(100) [M + H]. HRMS (FAB+): calcd. for C22H16ON2F [M
+ H]+ 343.1247; found 343.1245.
7-Chloro-3-phenyl-2-styrylquinazolin-4(3H)-one (9j): Method B.
Yield 90 mg (50 %). White solid, m.p. 187–189 °C. 1H NMR (400 MHz,
CDCl3): δH = 8.21 (d, J = 8.56 Hz, 1 H), 8.00–7.96 (m, 1 H), 7.79 (d,
J = 1.88 Hz, 1 H), 7.62–7.55 (m, 3 H), 7.40 (dd, J = 8.5, 1.9 Hz, 1 H),
7.32–7.30 (m, 7 H), 6.38–6.34 (m, 1 H) ppm. 13C NMR (100 MHz,
7-Phenyl-6-styryl-[1,3]dioxolo[4,5-g]quinazolin-8(7H)-one (9d):
Yield 46 (25 %) and 73.5 mg (40 %) for methods A and B, respec- CDCl3): δC = 161.9, 153.0, 149.0, 140.9, 140.9, 136.9, 135.3, 130.2,
tively. Yellow solid, m.p. 254–256 °C. 1H NMR (400 MHz, CDCl3): δH
=
130.1, 129.7, 129.0, 128.8, 128.0, 127.3, 127.0, 119.7, 119.5 ppm. MS
7.91–7.87 (m, 1 H), 7.60 (s, 1 H), 7.58–7.52 (m, 3 H), 7.31–7.25 (m,7
(ESI+): m/z (%) = 359.38 (M + H, 100). HRMS (TOF–ES+): calcd. for
H), 7.15 (s, 1 H), 6.37–6.33 (m, 1 H), 6.13 (s, 2 H) ppm. 13C NMR C22H16ON2Cl [M + H]+ 359.0951; found 359.0954.
(100 MHz, CDCl3): δC = 161.8, 153.9, 150.7, 147.7, 145.9, 139.4, 137.2,
2-(4-Methoxystyryl)-3-phenylquinazolin-4(3H)-one (9k):[14d]
135.6, 130.0, 129.7, 129.5, 128.9, 128.9, 127.9, 120.0, 116.1, 105.8,
104.2, 102.3 ppm. MS (ESI+): m/z (%) = 369.32 (100) [M + H]. HRMS
(FAB+): calcd. for C23H17O3N2 [M + H]+ 369.1239; found 369.1230.
Method B. Yield 89 mg (50 %). Yellow solid, m.p. 182–184 °C. 1H
NMR (400 MHz, CDCl3): δH = 8.27 (d, J = 7.84 Hz, 1 H), 7.95–7.91 (m,
1 H), 7.77–7.75 (m, 2 H), 7.59–7.52 (m, 3 H), 7.45–7.41 (m, 1 H), 7.31–
7.29 (m, 2 H), 7.24–7.23 (m, 1 H), 6.82–6.79 (m, 2 H), 6.23–6.20 (m,
1 H), 3.77 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.5, 161.1,
152.3, 147.8, 140.0, 137.2, 134.8, 130.0, 129.6, 129.4, 128.8, 128.2,
127.3, 127.2, 126.5, 120.9, 117.4, 114.4, 55.5 ppm. MS (ESI+): m/z
(%) = 355.34 (M + H, 100). HRMS (TOF–ES+): calcd. for C23H19O2N2
3-Phenyl-2-styrylquinazolin-4(3H)-one (9e):[14d] Method B. Yield
81 mg (50 %). White solid, m.p. 188–200 °C. 1H NMR (400 MHz,
CDCl3): δH = 8.31 (d, J = 7.88 Hz, 1 H), 7.99–7.95 (m, 1 H), 7.80–7.79
(m, 2 H), 7.62–7.53 (m, 3 H), 7.49–7.45 (m, 1 H), 7.34–7.28 (m, 7 H),
6.41–6.37 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.5,
151.9, 148.0, 140.1, 137.2, 135.5, 134.8, 130.1, 129.8, 129.5, 128.9, [M + H]+ 355.1447; found 355.1447.
128.9, 127.9, 127.5, 127.3, 126.8, 121.1, 120.1 ppm. MS (EI+): m/z
3-Methyl-2-phenyl-2,3-dihydroquinazolin-4(1H)-one (C):
(%) = 324 [M+, 78], 323.1 (M – 1 100). HRMS (TOF–ES+): calcd. for
Method A. Yield Trace. White solid, m.p. 176–178 °C. 1H NMR
(400 MHz, CDCl3): δH = 7.93 (dd, J = 7.8, 1.28 Hz, 1 H), 7.40–7.34 (m,
5 H), 7.25–7.21 (m, 1 H), 6.81 (t, J = 7.5 Hz, 1 H), 6.54 (d, J = 7.96 Hz,
1 H), 5.69 (s, 1 H), 4.70 (br. s, 1 H), 2.85 (s 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 163.7, 145.5, 139.6, 133.5, 129.5, 129.2, 128.6,
126.9, 119.2, 115.7, 114.2, 74.4, 32.1 ppm. MS (ESI+): m/z (%) =
239.14 (M + H, 100). HRMS (TOF–ES+): calcd. for C15H15ON2 [M +
H]+ 239.1184; found 239.1187.
C
22H17ON2 [M + H]+ 325.1341; found 325.1342.
2-Styryl-3-(p-tolyl)quinazolin-4(3H)-one (9f):[14d] Method B. Yield
89.5 mg (53 %). White solid, m.p. 206–208 °C. 1H NMR (400 MHz,
CDCl3): δH = 8.30 (d, J = 7.88 Hz, 1 H), 7.99–7.95 (m, 1 H), 7.79 (d,
J = 3.92 Hz, 2 H), 7.49–7.44 (m, 1 H), 7.37 (d, J = 8.08 Hz, 2 H), 7.34–
7.30 (m, 5 H), 7.19 (d, J = 8.12 Hz, 2 H), 6.46–6.42 (m, 1 H), 2.48 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δC = 162.6, 152.1, 148.0, 140.1,
139.5, 135.6, 134.7, 134.4, 130.8, 129.8, 128.9, 128.5, 128.0, 127.5,
127.4, 126.7, 121.1, 120.1, 21.5 ppm. LRMS (EI+): m/z (%) = 338.14
(78), 337.1 (M – 1 100). HRMS (TOF–ES+): calcd. for C23H19ON2 [M +
H]+ 339.1497; found 339.1497.
2-(Allylamino)-N-benzylbenzamide (P): Method A. Yield 600 mg
1
(45 %). White solid, m.p. 63–65 °C. H NMR (400 MHz, CDCl3): δH
=
7.79 (br. s, 1 H), 7.38–7.26 (m, 7 H), 6.68 (d, J = 8.36 Hz, 1 H), 6.58–
6.54 (m, 1 H), 6.39 (br. s, 1 H), 6.00–5.90 (m, 1 H), 5.33–5.28 (m, 1
2-Styryl-3-(o-tolyl)quinazolin-4(3H)-one (9g): Method B. Yield H), 5.19–5.15 (m, 1 H), 4.59 (d, J = 5.64 Hz, 2 H), 3.83 (s, 2 H) ppm.
100 mg (59 %). White solid, m.p. 162–164 °C. 1H NMR (400 MHz,
CDCl3): δH = 8.32 (d, J = 7.76 Hz, 1 H), 8.05–8.01 (m, 1 H), 7.81 (d,
J = 6.2 Hz, 2 H), 7.50–7.42 (m, 4 H), 7.31–7.29 (m, 5 H), 7.23 (d, J =
7.48 Hz, 2 H), 6.37–6.33 (m, 1 H), 2.14 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δC = 161.9, 151.9, 148.1, 140.5, 136.2, 136.2 135.4,
134.8, 131.6, 129.9, 129.8, 128.9, 128.7, 127.9, 127.8, 127.5, 127.4
126.7, 121.1, 119.3, 17.8 ppm. MS (ESI+): m/z (%) = 339.44 (M + H,
100). HRMS (TOF–ES+): calcd. for C23H19ON2 [M + H]+ 339.1497;
found 339.1498.
13C NMR (100 MHz, CDCl3): δC = 169.8, 149.8, 138.5, 135.1, 135.0,
132.9, 128.9, 127.9, 127.6, 127.4, 116.1, 116.1, 115.1, 114.9, 112.2,
45.6, 43.8 ppm.
2-Amino-N-benzylbenzamide (U): Method A. Yield 290 mg (25 %).
White solid, m.p. 134–136 °C. 1H NMR (400 MHz, CDCl3): δH = 7.37–
7.34 (m, 4 H), 7.33–7.28 (m, 2 H), 7.22–7.18 (m, 1 H), 6.68 (d, J =
8.16 Hz, 1 H), 6.62 (t, J = 7.54 Hz, 1 H), 6.39 (br. s, 1 H), 5.55 (s, 2 H),
4.59 (d, J = 5.68 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δC
=
169.3, 148.9, 138.4, 132.5, 128.9, 128.9, 128.8, 128.8, 128.8, 127.8,
3-Benzyl-6-methoxy-2-styrylquinazolin-4(3H)-one (9h): Method
127.6, 127.3, 117.4, 116.6, 115.9, 43.7 ppm. MS (ESI+): m/z (%) =
B. Yield 100 mg (54 %). Yellow solid, m.p. 162–164 °C. 1H NMR 227.12 (M + H, 100). HRMS (TOF–ES+): calcd. for C14H15ON2 [M +
(400 MHz, CDCl3): δH = 7.88–7.84 (m, 1 H), 7.71–7.67 (m, 2 H), 7.43 H]+ 227.1184; found 227.1185.
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1192
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
H. Neumann, M. Beller, X.-F. Wu, Angew. Chem. Int. Ed. 2014, 53, 1420;
Angew. Chem. 2014, 126, 1444; d) T. Songsichan, J. Promsuk, V. Rukachai-
sirikul, J. Kaeobamrung, Org. Biomol. Chem. 2014, 12, 4571; e) Q. Li, Y.
Huang, T. Chen, Y. Zhou, Q. Xu, S.-F. Yin, L.-B. Han, Org. Lett. 2014, 16,
3672; f) D. Zhao, T. Wang, J.-X. Li, Chem. Commun. 2014, 50, 6471; g) L.
Xu, Y. Jiang, D. Ma, Org. Lett. 2012, 14, 1150; h) H. Wang, X. Cao, F. Xiao,
S. Liu, G.-J. Deng, Org. Lett. 2013, 15, 4900; i) T. Songsichan, J. Promsuk,
V. Rukachaisirikul, J. Kaeobamrung, Org. Biomol. Chem. 2014, 12, 4571; j)
Y. Feng, Y. Li, G. Cheng, L. Wang, X. Cui, J. Org. Chem. 2015, 80, 7099; k)
K. Sreeramamurthy, E. Ashok, V. Mahendar, G. Santoshkumar, P. Das, Syn-
lett 2010, 721.
Acknowledgments
Financial support by the Ministry of Science and Technology
of the Republic of China (MOST 103-2113-M-003-008-MY3), the
National Taiwan Normal University (103-07-C), and the Instru-
mentation Center at National Taiwan Normal University is grate-
fully acknowledged. The authors are grateful to Mr. Ting-Shen
Kuo, Hsiu-Ni Huan, Mei-Ling Chen, and Chiu-Hui He for provid-
ing single-crystal X-ray data, and mass, HRMS, and NMR spec-
troscopic data.
[9] a) F. Y. Kwong, S. L. Buchwald, Org. Lett. 2003, 5, 793; b) S. V. Ley, A. W.
Thoma, Angew. Chem. Int. Ed. 2003, 42, 5400; Angew. Chem. 2003, 115,
5558; c) R. Martín, C. H. Larsen, A. Cuenca, S. L. Buchwald, Org. Lett. 2007,
9, 3379; d) M. Periasamy, P. Vairaprakash, M. Dalai, Organometallics 2008,
27, 1963; e) Z. Zhang, Y. Yu, L. S. Liebeskind, Org. Lett. 2008, 10, 3005; f)
P.-Y. Yao, Y. Zhang, R. P. Hsung, K. Zhao, Org. Lett. 2008, 10, 4275; g) J. Y.
Dong, Y. Wang, Q. J. Xiang, X. R. Lv, W. Weng, Q. L. Zeng, Adv. Synth.
Catal. 2013, 355, 692; h) S. Fantasia, J. Windisch, M. Scalone, Adv. Synth.
Catal. 2013, 355, 627; i) D. Kundu, S. Bhadra, N. Mukherjee, B. Sreedhar,
B. C. Ranu, Chem. Eur. J. 2013, 19, 15759; j) D. Toummini, A. Tlili, J. Bergès,
F. Ouazzani, M. Taillefer, Chem. Eur. J. 2014, 20, 14619; k) B. Y.-H. Tan, Y.-
C. Teo, A.-H. Seow, Eur. J. Org. Chem. 2014, 1541; l) C. Zhu, M. Yi, D. Wei,
X. Chen, Y. Wu, X. Cui, Org. Lett. 2014, 16, 1840; m) N. He, Y. Huo, J. Liu,
Y. Huang, S. Zhang, Q. Cai, Org. Lett. 2015, 17, 374.
[10] a) V. Kavala, C.-C. Wang, D. K. Barange, C.-W. Kuo, P.-M. Lei, C.-F. Yao, J.
Org. Chem. 2012, 77, 5022; b) V. Kavala, D. Janreddy, M. J. Raihan, C.-W.
Kuo, C. Ramesh, C.-F. Yao, Adv. Synth. Catal. 2012, 354, 2229; c) T. Kotipalli,
V. Kavala, D. Janreddy, C.-W. Kuo, T.-S. Kuo, H.-N. Huang, C.-H. He, C.-F.
Yao, RSC Adv. 2014, 4, 2274; d) V. Kavala, C.-C. Wang, Y.-H. Wang, C.-W.
Kuo, D. Janreddy, W.-C. Huang, T.-S. Kuo, C.-H. He, M.-L. Chen, C.-F. Yao,
Adv. Synth. Catal. 2014, 356, 2609.
[11] a) W. Xu, Y. Jin, H. Liu, Y. Jiang, H. Fu, Org. Lett. 2011, 13, 1274; b) K.
Sreenivas, N. Ramkumar, R. Nagarajan, Org. Biomol. Chem. 2012, 10, 3417;
c) L.-X. Wang, J.-F. Xiang, Y.-L. Tang, Eur. J. Org. Chem. 2014, 2682.
[12] K. R. Rao, A. Raghunadh, R. Mekala, S. B. Meruva, T. V. Pratap, T. Krishna,
D. Kalita, E. Laxminarayana, B. Prasad, M. Pal, Tetrahedron Lett. 2014, 55,
6004.
[13] a) R. Bouley, M. Kumarasiri, Z. Peng, L. H. Otero, W. Song, M. A. Suckow,
V. A. Schroeder, W. R. Wolter, E. Lastochkin, N. T. Antunes, H. Pi, S. Vaku-
lenko, J. A. Hermoso, M. Chang, S. Mobashery, J. Am. Chem. Soc. 2015,
137, 1738; b) M. Gross, R. Burli, P. Jones, M. Garcia, B. Batiste, J. Kaizerman,
H. Moser, V. Jiang, U. Hoch, J. X. Duan, R. Tanaka, K. W. Johnson, Anti-
microb. Agents Chemother. 2003, 47, 3448; c) H. J. Hess, T. H. Cronin, A.
Scriabine, J. Med. Chem. 1968, 11, 130.
Keywords: Synthetic methods · Homogeneous catalysis ·
Nitrogen heterocycles · Amides · Copper
[1] a) J. F. Wolf, T. L. Rathman, M. C. Sleevi, J. A. Campbell, T. D. Greenwood,
J. Med. Chem. 1990, 33, 161; b) A. Witt, J. Bergman, Curr. Org. Chem.
2003, 7, 659; c) R. P. Maskey, M. Shaaban, I. Grun-Wollny, H. Laatsch, J.
Nat. Prod. 2004, 67, 1131; d) S. B. Mhaske, P. Argade, Tetrahedron 2005,
62, 9787; e) A. Hamid, A. Elomri, A. Daich, Tetrahedron Lett. 2006, 47,
1777.
[2] a) M. S. Malamas, J. Millen, J. Med. Chem. 1991, 34, 1492; b) S. E. De Las-
zlo, C. S. Quagliato, W. J. Greenlee, A. A. Patchett, R. S. L. Chang, V. J.
Lotti, T.-B. Chen, S. A. Scheck, K. A. Faust, S. S. Kivlighn, T. S. Schorn, G. J.
Zingaro, P. K. S. Siegl, J. Med. Chem. 1993, 36, 3207; c) N. J. Liverton, D. J.
Armstrong, D. A. Claremon, D. C. Remy, J. J. Baldwin, R. J. Lynch, G. Zhang,
R. J. Gould, Bioorg. Med. Chem. Lett. 1998, 8, 483; d) L. Rahbaek, J. Brein-
holt, J. Nat. Prod. 1999, 62, 904; e) L. Rahbaek, J. Breinholt, J. C. Frisvad,
C. Christophersen, J. Org. Chem. 1999, 64, 1689; f) J.-R. Dai, B. K. Carte,
P. J. Sidebottom, A. L. S. Yew, S.-B. Ng, Y. Huang, M. S. Butler, J. Nat. Prod.
2001, 64, 125; g) D. Zhang, X. Yang, J. S. Kang, H. D. Choi, B. W. Son, J.
Antibiot. 2008, 61, 40; h) A. H. Amin, D. R. Mehta, S. S. Samarth, Prog.
Drug Res. 1970, 14, 218; i) S. Johne, Prog. Drug Res. 1982, 26, 259; j) S.
Sinha, M. Srivastava, Prog. Drug Res. 1994, 43, 143.
[3] a) N. Y. Kim, C.-H. Cheon, Tetrahedron Lett. 2014, 55, 2340; b) B. V. S.
Reddy, G. Narasimhulu, N. Umadevi, J. S. Yadav, Synlett 2012, 23, 1364;
c) D. Zhan, T. Li, H. Wei, W. Weng, K. Ghandi, Q. Zeng, RSC Adv. 2013, 3,
9325; d) Y. Bao, Y. Yan, K. Xu, J. Su, Z. Zha, Z. Wang, J. Org. Chem. 2015,
80, 4736.
[4] a) H. Li, L. He, H. Neumann, M. Beller, X.-F. Wu, Green Chem. 2014, 16,
1336; b) X.-F. Wu, S. Oschatz, M. Sharif, M. Beller, P. Langer, Tetrahedron
2014, 70, 23; c) Y. Shen, C. Han, S. Cai, P. Lu, Y. Wang, Tetrahedron Lett.
2012, 42, 5671; d) J.-F. Liu, J. Lee, A. M. Dalton, G. Bi, L. Yu, C. M. Baldino,
E. M. Elory, M. Brown, Tetrahedron Lett. 2005, 46, 1241.
[14] a) A. Kamala, E. V. Bharathi, M. J. Ramaiah, D. Dastagiri, J. S. Reddy, A.
Viswanath, F. Sultana, S. N. C. V. L. Pushpavalli, M. Pal-Bhadra, H. K. Srivas-
tava, G. N. Sastry, A. Juvekar, S. Sen, S. Zingde, Bioorg. Med. Chem. 2010,
18, 526; b) D. Raffa, G. Daidone, B. Maggio, S. Cascioferro, F. Plescia, D.
Schillaci, Farmaco 2004, 59, 215; c) V. Jatav, P. Mishra, S. Kashaw, J. P.
Stables, Eur. J. Med. Chem. 2008, 43, 135; d) D. Kumar, P. S. Jadhavar, M.
Nautiyal, H. Sharma, P. K. Meena, L. Adane, S. Pancholia, A. K. Chakraborti,
RSC Adv. 2015, 30819; e) S. Guo, Y. Li, L. Tao, W. Zhang, X. Fan, RSC Adv.
2014, 59289.
[5] a) M. Sharif, J. Opalach, P. Langer, M. Beller, X.-F. Wu, RSC Adv. 2014, 4, 8;
b) J. Safari, S. Gandomi-Ravandi, RSC Adv. 2014, 4, 11654; c) J. Fang, J.
Zhou, Org. Biomol. Chem. 2012, 10, 2389; d) H. Hikawa, Y. Ino, H. Suzuki,
Y. Yokoyama, J. Org. Chem. 2012, 77, 7046.
[6] a) H. Chai, J. Li, L. Yang, H. Lu, Z. Qi, D. Shi, RSC Adv. 2014, 4, 44811; b)
D. Yang, H. Fu, L. Hu, Y. Jiang, Y. Zhao, J. Comb. Chem. 2009, 11, 653; c)
B. Li, L. Samp, J. Sagal, C. M. Hayward, C. Yang, Z. Zhang, J. Org. Chem.
2013, 78, 1273; d) X. Liu, H. Fu, Y. Jiang, Y. Zhao, Angew. Chem. Int. Ed.
2009, 48, 348; Angew. Chem. 2009, 121, 354.
[15] CCDC 1407555 (for 4u) and 1426722 (for C) contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[7] a) S. Laclef, M. Harari, J. Godeau, I. Schmitz-Afonso, L. Bischoff, C. Hoarau,
V. Levacher, C. Fruit, T. Besson, Org. Lett. 2015, 17, 1700.
[8] a) L. He, H. Li, J. Chen, X.-F. Wu, RSC Adv. 2014, 4, 12065; b) I. Khan, A.
Ibrar, N. Abbas, A. Saeed, Eur. J. Med. Chem. 2014, 76, 193; c) L. He, H. Li,
Received: December 10, 2015
Published Online: January 22, 2016
Eur. J. Org. Chem. 2016, 1182–1193
www.eurjoc.org
1193
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim