Br?nsted acid-catalyzed selective C-C bond cleavage of 1,3-diketones: A facile synthesis of 4(3H)-quinazolinones in aqueous ethyl lactate

Article abstract of DOI:10.1039/c5ra17969f

A facile and green approach was developed for the synthesis of 4(3H)-quinazolinones by using camphorsulfonic acid as a catalyst in an aqueous solution of biodegradable ethyl lactate. Various 2-aryl-, 2-alkyl-, and 2-(4-oxoalkyl)quinazolinones were obtained by cyclization of 2-aminobenzamides with a wide range of acyclic or cyclic 1,3-diketones via C-C bond cleavage in satisfactory to excellent yields.

Full text of DOI:10.1039/c5ra17969f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: G. Shen, H. Zhou,
P. Du, S. Liu, K. Zou and Y. Uozumi, RSC Adv., 2015, DOI: 10.1039/C5RA17969F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 6
RSC Advances
View Article Online
DOI: 10.1039/C5RA17969F
Dynamic Article Links ►
RSC Advances
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/advances
Paper
Brønsted acid-catalyzed selective C-C bond cleavage of 1,3-diketones: a
facile synthesis of 4(3H)-quinazolinones in aqueous ethyl lactate
a
*a
a
a
a
Guanshuo Shen, Haifeng Zhou, Peng Du, Sensheng Liu, Kun Zou , and Yasuhiro Uozumi
*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
A facile and green approach was developed for the synthesis of 4(3H)-quinazolinones by using
camphorsulfonic acid as a catalyst in an aqueous solution of biodegradable ethyl lactate. Various 2-aryl-, 2-
alkyl-, and 2-(4-oxoalkyl)quinazolinones were obtained by cyclization of 2-aminobenzamides with a wide
range of acyclic or cyclic 1,3-diketones via C-C bond cleavage in satisfactory-to-excellent yields.
Introduction
The direct selective cleavage of unstrained C–C bond has attracted
much attention and emerged as a challenging transformation in
1
organic synthesis due to the high C–C bond strength. As
inexpensive and readily available starting materials, 1,3-diketones
have been widely used as important substrates in organic
2
synthesis. In 2010, Lei reported the first example of CuI-catalyzed
C–C bond cleavage of 1,3-diketones and arylation to give α-
3
a
3b
3c
3d,3e
amides,
arylketones.
The esters,
α-ketoesters,
α-
3
f
3g
ketoamides or α-amino acid esters could be obtained from the
reactions of 1,3-diketones with alcohols or amines via C–C bond
cleavage in the presence of Lewis acid, or under oxidation
conditions. Recently, CuI-catalyzed tandem cyclization of o-
3
h
3i
3j
halobenzoic acids, esters, or amides with 1,3-diketones leading
to isocoumarins was developed. Very recently, H -promoted
reactions of aliphatic primary amines with 1,3-diketones for the
Figure 1. Selected examples of alkaloids and marketed drugs incorporating
2
O
2
4
(3H)-quinazolinone cores.
3
k
synthesis of 1H-pyrrol-3(2H)-ones has also been realized.
Ethyl lactate is prepared by esterification of ethanol with lactic
4(3H)-quinazolinones are building blocks of many naturally
acid, both of which can be obtained by fermentation of biomass.
Ethyl lactate has recently attracted much attention and has been
used in organic synthesis as an environmentally benign and
4
occurring alkaloids and marketed drugs (Fig 1). Owing to their
importance and utility, a range of synthetic methods have been
5
-7
developed to construct quinazolinone derivatives. It should be
noted that most reported methods for the preparing of 4(3H)-
quinazolinones request expensive transition-metal catalysts in the
presence of oxidants and bases under harsh reaction conditions.
Therefore, more environmentally benign and efficient methods to
approach valuable quinazolinone derivatives are highly desirable.
8
biodegradable solvent. Continuing our research interest in green
9
catalysis, we have discovered a green approach for the synthesis
of 4(3H)-quinazolinones by cyclization of 2-aminobenzamides
with a wide range of acyclic or cyclic 1,3-diketones via C-C bond
cleavage in the presence of camphorsulfonic acid (CSA) as a
Brønsted catalyst in biodegradable ethyl lactate solution under
metal-, oxidant-, and radiation-free conditions (Scheme 1).
a
Hubei Key Laboratory of Natural Products Research and Development,
College of Biological and Pharmaceutical Sciences, China Three
Gorges University, Yichang 443002, People’s Republic of China.
Fax: +86-717-6395580
E-mail: haifeng-zhou@hotmail.com
Institute for Molecular Science, Myodaiji, Okazaki 444-8787, Japan
b
Fax: +81-564-595574
E-mail: uo@ims.ac.jp
Electronic Supplementary Information (ESI) available: Experimental
†
1
13
procedures, compound chracterizations, and copies of H NMR and
NMR spectra. See DOI: 10.1039/b000000x/
C
Scheme 1. A green approach to 4(3H)-quinazolinones.
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

RSC Advances
Page 2 of 6
View Article Online
DOI: 10.1039/C5RA17969F
Advances
paper
Results and Discussion
the attempted reaction of amide 1a and the more sterically
hindered 2,2,6,6-tetramethylheptane-3,5-dione (2D), even on
raising the temperature and prolonging the reaction time. 2-
Phenylquinazolin-4(3H)-one (3aE) was obtained by the reaction
of 1a with 1,3-diphenylpropane-1,3-dione (2E) in 79% yield.
Finally, the reactions of 1a with the unsymmetrical 1,3-
diketones 1-phenylbutane-1,3-dione (2F), 5,5-dimethylhexane-
2,4-dione (2G), and 1,1,1-trifluoropentane-2,4-dione (2H) were
examined, all gave the same product, 3aA, in 54–75% yield
through selective C–C bond cleavage. These results indicate that
the reactivity of the acetyl group is higher than that of the
benzoyl, pivaloyl, or trifluoroacetyl group.
For our initial studies, we chose the reaction of 2-
aminobenzamide (1a) with pentane-2,4-dione (2A) as a model
process for optimizing the reaction conditions (Table 1). No
reaction was observed when amide 1a was treated with dione
2
A in poly(ethylene glycol) (PEG-400) at 100 °C in the absence
of a catalyst (Table1, entry 1). However, the desired product
aA was obtained in various yields on adding 10 mol% of a
3
Brønsted acid catalyst to the reaction mixture (entries 2–6).
Among the tested Brønsted acid catalysts, p-toluenesulfonic
acid (TsOH·H
CCO H) gave yields of less than 10%. Moderate yields of
quinazolinone 3aA were obtained when
trifluoromethanesulfonic acid (F CSO H; entry 5) or natural
2
O), acetic acid (AcOH), and trifluoroacetic acid
(
F
3
2
a
3
3
Table 2. The scope of acyclic 1,3-diketones 2
camphorsulfonic acid (CSA; entry 6) was used as catalyst, with
CSA providing the higher yield (61%). When other green
solvents such as PEG-200, ethyl lactate, and water were
screened in this transformation, ethyl lactate gave the best
results (entries 6–9). To our delight, we obtained product 3aA in
up to 98% yield by using a mixture of ethyl lactate and water as
the solvent (entry 11). Decreasing the catalyst loading from 10
mol% to 5 mol% resulted in a relatively low yield (entry 12).
We therefore performed subsequent reactions of 2-
aminobenzamides with various 1,3-diketones in the presence of
O
O
N
O
O
CSA (10 mol%)
NH2
NH2
NH
R1
+
R1
R2
H O-ethyl lactate
2
100 oC, 16 h
1a
2A-H
3aA-3aH
b
Entry
2
3
Yield
1
R = R = Me
1
R = R = Et
1
R = R = i-Pr
1
R = R = t-Bu
2
R = R = Ph
1
R = Me, R = Ph
1
R = Me, R = t-Bu 2G
1
R = Me, R = CF
2
1
2
3
4
5
6
7
8
2A
2B
2C
2D
2E
3aA
3aB
3aC
3aD
3aE
3aA
3aA
3aA
98%
81%
59%
<1%
79%
75%
71%
54%
2
2
2
10 mol% camphorsulfonic acid as catalyst at 100 °C in a 1:9
1
(
v/v) mixture of ethyl lactate and water for 16–24 hours.
2
2F
a
2
Table 1. Optimization of the reaction conditions
2
3
2H
a
Reaction conditions: 2-aminobenzamide (1a; 0.2 mmol), pentane-2,4-
dione (2; 0.3 mmol), CSA (10 mol%), H O-ethyl lactate (9:1; 1.0 mL),
2
b
00 °C, 16 h. Isolated yield.
1
b
Entry
Catalyst
none
Solvent
Yield
c
1
2
3
4
5
6
7
8
9
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-200
ethyl lactate
NR
Next, we examined the scope of the reaction with respect to
the 2-aminobenzamides. Various N-substituted 2-
TsOH·H
AcOH
CCO
CSO
2
O
10%
<5%
<5%
48%
61%
42%
74%
43%
84%
98%
81%
aminobenzamides 1a-m were treated with pentane-2,4-dione
(2A) under the optimized conditions (Scheme 2). From the
reaction of 2-amino-N-methylbenzamide (1b), the desired
product 2,3-dimethylquinazolin-4(3H)-one (3bA) was isolated
in 76% yield. The N-aryl-2-aminobenzamides with electron-
donating groups (1d; 4-Me, 1e; 2-Me, and 1f; 4-MeO) or
F
3
2
H
F
3
3
H
d
CSA
CSA
CSA
CSA
CSA
CSA
H
2
O
2
electron-withdrawing groups (1g; 3-Cl, 1h; 4-Cl, and 1i; 3,4-Cl )
1
1
1
0
1
2
ethyl lactate–H
ethyl lactate–H
ethyl lactate–H
2
2
2
O (1:1)
O (1:9)
O (1:9)
on the benzene ring also underwent the transformation to give
the corresponding products 3cA–3iA in 56–93% yield. 3-
e
CSA
Benzyl-2-methylquinazolin-4(3H)-one (3jA) was prepared in 88%
yield by the reaction of 2-amino-N-benzylbenzamide with
pentane-2,4-dione (2A). The corresponding reactions of 2-
amino-6-fluorobenzamide and 2-amino-5-chlorobenzamide
gave quinazolinones 3kA and 3mA in 88% and 79% yield,
respectively.
a
Reaction conditions: 2-aminobenzamide (1a; 0.2 mmol), pentane-2,4-
dione (2A; 0.3 mmol), catalyst (10 mol%), solvent (1.0 mL), 100 °C, 16
e
h. Isolated yield. No reaction. CSA: camphorsulfonic acid. 5 mol% of
b
c
d
CSA was use.
Encouraged by these results, we extended the scope of diketone
reactant to include cyclic 1,3-diketones 4A-G (Table 3).
Treatment of 2-aminobenzamide (1a) with 1.5 equivalents of
cyclohexane-1,3-dione (4A) in the presence of 10 mol% natural
CSA in a 1:9 (v/v) mixture of ethyl lactate and water at 100 °C
for 24 h gave 2-(4-oxopentyl)quinazolin-4(3H)-one (5aA) in
With the optimized reaction conditions in hand, we examined
the reactions of 2-aminobenzamide (1a) with various acyclic
1
,3-diketones. As shown in Table 2, a lower yield of 3aB
comparing with that of 3aA was observed when the reaction of
a and heptane-3,5-dione (2B) was carried out under the
6
1% yield with full atom efficiency (Table 3, entry 1). When
reactions of 1a with other substituted cyclohexane-1,3-diones
B-E were carried out under the optimized conditions, the
1
optimized conditions (3aA: 98%; 3aB: 81%). The reaction of
amide 1a with sterically hindered 2,6-dimethylheptane-3,5-
dione (2C) provided the desired product 3aC in moderate yield
4
corresponding products 5aB-5aE were obtained in 35–84%
yield. Interestingly, 2-methylcyclohexane-1,3-dione (4E)
(
3aC: 59%). In contrast, the reactants remained unchanged in
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 2

Page 3 of 6
RSC Advances
View Article Online
DOI: 10.1039/C5RA17969F
Advances
paper
a
O
O
N
Table 3. Synthesis of 2-(4-oxoalkyl)quinazolinones 5
NHR4
O
O
CSA (10 mol%)
NR4
R3
R3
+
H2O-ethyl lactate
NH2
a-m
1
00 oC, 16 h
1
2A
3aA-3mA
a: R3 = R4 = H
b: R3 = H, R4 = Me
c: R3 = H, R4 = Ph
e: R3 = H, R4 = 2-CH C H
i: R3 = H, R4 = 3,4-Cl C H
3
6
4
2
6
4
f: R3 = H, R4 = 4-CH OC H
j: R3 = H, R4 = CH Ph
3
6
4
2
g: R3 = H, R4 = 3-ClC H
k: R3 = 6-F, R4 = H
m: R3 = 5-Cl, R4 = H
6
4
d: R3 = H, R4 = 4-CH3C6H4
h: R3 = H, R4 = 4-ClC H
6
4
O
N
N
O
N
O
N
N
N
3aA:98%
3bA: 76%
3cA: 67%
OMe
O
O
O
N
b
N
N
N
Entry
1
Substrate
Product
Yield
N
N
1/
4
1a/4A
5
O
5aA
61%
3
dA: 83%
3eA: 93%
3fA: 56%
NH
NH
O
O
Cl
Cl
Cl
O
N
N
O
O
N
O
Cl
N
N
N
2
3
4
1a/4B
1a/4C
1a/4D
5aB
5aC
35%
49%
38%
N
3
gA: 88%
3
hA: 69%
3iA: 82%
N
O
O
N
N
F
O
O
NH
NH
O
Cl
NH
N
NH
N
O
N
5
aD
3
jA: 88%
3kA: 88%
3mA: 79%
O
N
Scheme 2. The scope of 2-aminobenzamides 1. Reaction conditions: 2-
aminobenzamide (1; 0.2 mmol), pentane-2,4-dione (2A; 0.3 mmol),
O
5aE
5aF
5
6
1a/4E
1a/4F
84%
NH
NH
O
2
CSA (10 mol%), H O-ethyl lactate (9:1; 1.0 mL), 100 °C, 16 h, isolated
N
O
yield.
c
ND
exhibited a higher reactivity than 5-methylcyclohexane-1,3-
dione (4B) (entries 2 and 5). In contrast, cyclopentane-1,3-dione
N
O
O
(
4F) and 2-methyl-1,3-cyclopentane-1-3-dione (4G), which
contain a five-membered ring, did not give the desired products
aF and 5aG when treated with 1a (entries 6 and 7). We then
5aG
5bA
c
7
1a/4G
ND
NH
5
examined the scope of the reaction with respect to the 2-
aminobenzamides 1. In general, various 2-aminobenzamides 1
reacted with cyclohexane-1,3-dione (4A) under the optimized
conditions to give the corresponding products 5bA-5kA in 55–
N
O
O
8
9
1b/4A
1c/4A
78%
60%
N
N
O
98% yield (entries 8–17). With N-alkyl-substituted 2-
N
O
5
cA
aminobenzamides, products 5bA and 5jA were obtained in 78%
and 87% yield, respectively (entries 8 and 16). N-Aryl-
O
substituted
2-aminobenzamides
also
underwent
this
N
transformation. 2-aminobenzamides with an electron-rich
substituent on the aryl group gave products 5eA and 5fA in
relatively high yields (entries 10 and 12), whereas electron-
deficient aryl group-substituted 2-aminobenzamides gave
products 5gA and 5iA in relatively low yields (entries 13 and
5dA
5eA
5fA
O
1
1
0
1
1d/4A
1e/4A
1f/4A
96%
69%
84%
N
N
O
N
O
O
15). Finally, 2-amino-6-fluorobenzamide also reacted with
cyclohexane-1,3-dione (4A) to give the corresponding product
N
O
OMe
O
1
2
5kA in 98%.
N
1
0
Based on the results obtained above and the literature,
a
N
O
proposed reaction mechanism was shown in Scheme 3. The
Brønsted acid catalyzed condensation reaction of 2-
aminobenzamide 1 with 1, 3-diketone 4 would take place to
Cl
5gA
13
1g/4A
1h/4A
55%
80%
N
N
O
generate
a
ketimine intermediate A, followed by
N
tautomerization to give the enaminone intermediate B. Then, the
intramolecular nucleophilic addition of B would produce adduct
C. The C-C bond cleavage reaction would finally occur to
generate the desired product 5.
Cl
O
5
hA
14
O
N
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 |
3

RSC Advances
Page 4 of 6
View Article Online
DOI: 10.1039/C5RA17969F
Advances
paper
Cl
5
5
iA
jA
(39.60 ppm). NMR data were recorded on a Bruker 400 MHz
instrument. HRMS data were recorded with ESI ionization
sources on a Bruker Apex II instrument. Melting points were
determined on an X-4 apparatus.
1
5
1i/4A
1j/4A
62%
87%
Cl
O
O
N
N
16
O
2-Methylquinazolin-4(3H)-one (3aA); Typical Procedure
N
O
N
O
F
A flask was charged with 2-aminobenzamide (1a; 27.2 mg,
0.2 mmol), pentane-2,3-dione (2A; 30.0 mg, 0.3 mmol), CSA
5
kA
17
1k/4A
98%
NH
O
(
4.6 mg, 0.02 mmol), and 1:9 (v/v) ethyl lactate–H
The flask was sealed and the mixture was stirred at 100 °C for
6 h. When the reaction was complete (TLC), the mixture was
cooled to r.t., extracted with EtOAc (3 × 20 mL), and washed
with H O. The organic phase was dried (Na SO ), filtered, and
2
O (1.0 mL).
N
a
Reaction conditions: 2-aminobenzamide 1 (0.2 mmol), cyclic 1,3-
1
2
diketone 5 (0.3 mmol), CSA (10 mol%), 1:9 (v/v) ethyl lactate–H O (1.0
c
mL), 100 °C, 24 h. Isolated yield. Not detected.
b
2
2
4
concentrated under reduced pressure. The residue was purified
by column chromatography (silica gel) to give the
product 3aA (31.7 mg, 98%) as white solid; mp: 286–288 °C;
1
H NMR (400 MHz, CDCl ): δ = 2.61 (3 H, s), 7.45–7.49 (1H,
3
O
O
O
O
H+
NR4
m), 7.68 (1H, d, J = 7.6 Hz), 7.76 (1H, dt, J = 8.4 Hz, J = 1.6
1 2
13
NHR4
O
R3
+
R3
Hz), 8.28 (1H, dd, J
1
= 8.0 Hz, J
2
= 1.2 Hz), 12.19 (s, H);
C
NH2
R5
N
R5
NMR (100 MHz, CDCl ): δ = 22.1, 120.2, 126.2, 126.4, 127.0,
1
4
5
3
+
34.9, 149.4, 153.3, 164.4; HRMS (ESI): m/z [M+H] calcd. for
1
(
with 4A: R5 = H)
C H N O: 161.0709; found: 161.0714.
2
9
9
O
N
O
O
2
-(4-oxopentyl)quinazolin-4(3H)-one(5aA); Typical
NHR4
NHR4
NR4
R3
R3
Procedure
N
H
N
H
A
O
B
O
O
C
A flask was charged with 2-aminobenzamide (1a; 27.2 mg,
0
.2 mmol), cyclohexane-1,3-dione (4A; 33.6 mg, 0.3 mmol),
CSA (4.6 mg, 0.02 mmol), and 1:9 (v/v) ethyl lactate–H O (1.0
2
Scheme 3. A proposed reaction mechanism
mL). The flask was sealed and the mixture was stirred at 100 °C
for 24 h. When the reaction was complete (TLC), the mixture
was cooled to r.t., extracted with EtOAc (3 × 20 mL), and
washed with H O. The organic phase was dried (Na SO ),
Conclusions
2
2
4
filtered, and concentrated under reduced pressure. The residue
was purified by column chromatography (silica gel) to give the
In summary, we have developed an efficient, metal- and
oxidant-free green approach for the synthesis of 4(3H)-
quinazolinones. Various 2-aryl-, 2-alkyl-, and 2-(4-
oxoalkyl)quinazolinones were prepared by successive
condensation of 2-aminobenzamides with a wide range of
acyclic or cyclic 1,3-diketones, intramolecular nucleophile
addition, and selective C–C bond cleavage, catalyzed by natural
camphorsulfonic acid in an aqueous ethyl lactate solution.
Further applications of this methodology to synthesis of other
N-heterocycles are currently underway in our laboratory.
product 5aA (28.1 mg, 61%) as white solid; mp: 145–146 °C;
1
H NMR (CDCl , 400 MHz): δ = 2.13–2.20 (m, 2H), 2.18 (s,
3
3H), 2.64 (t, J = 7.2 Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 7.48 (dt,
J = 8.0 Hz, J = 1.2 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.77 (dt,
1
2
J
1
= 8.0 Hz, J
2
= 1.6 Hz, 1H), 8.29 (dd, J
1
= 8.0 Hz, J
2
= 1.2 Hz,
13
1
3
1
2
H), 11.52 (s, 1H); C NMR (CDCl , 100 MHz): δ = 21.1, 30.0,
4.7, 42.3, 120.6, 126.3, 126.5, 127.2, 134.8, 149.2, 155.8,
+
63.8, 208.2; HRMS (ESI): m/z [M+H] calcd. for C H N O :
3
1
3
14
2
2
31.1128; found: 231.1134.
Acknowledgements
Experimental Section
General remarks
We are grateful for financial support from the National Natural
Science Foundation of China (21202092) and for a Startup
Foundation from the China Three Gorges University
(KJ2012B080, KJ2014H008).
All reagents and solvents were purchased from commercial
suppliers and used without further purification unless otherwise
stated. Analytic thin-layer chromatography (TLC) was carried
out with silica gel GF 254-coated plates. All products were
isolated by column chromatography on silica gel (300–
4
00 mesh) using petroleum ether (PE; bp 60–90 °C) and ethyl
Notes and references
1
acetate. All compounds were characterized by H NMR
13
1
(
400 MHz), C NMR (100 MHz), and ESI-MS. All H NMR
shifts are reported in δ units (ppm) relative to the signals for
residual CHCl (δ = 7.26 ppm) or DMSO (δ = 2.50 ppm) in the
corresponding deuterated solvent. All C NMR spectra are
reported in ppm relative to CDCl (77.23 ppm) or DMSO-d
1
For selected recent reviews, see: (a) A. de Meijere, Chem. Rev., 2003,
03, 931–932; (b) M. E. Boom and D. Milstein, Chem. Rev., 2003,
1
3
1
3
103, 1759–1792; (c) C.-H. Jun, Chem. Soc. Rev., 2004, 33, 610–618;
(d) M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev., 2007, 107,
3
6
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 4

Page 5 of 6
RSC Advances
View Article Online
DOI: 10.1039/C5RA17969F
Advances
paper
3
2
2
2
117–3179; (e) Y. J. Park, J.-W. Park, C.-H. Jun, Acc. Chem. Res.,
(j) Q. Li, Y. Huang, T. Chen, Y. Zhou, Q. Xu, S.-F. Yin, L.-B.
Han, Org. Lett. 2014, 16, 3672–3675; (k) D. Zhao, T. Wang, J.-X.
Li, Chem. Commun., 2014, 50, 6471–6474; (l) D. Kumar, P. S.
Jadhavar, M. Nautiyal, H. Sharma, P. K. Meena, L. Adane, S.
Pancholia, A. K. Chakraborti, RSC.Adv., 2015, 5, 30819–30825;
(m) L. Lu, M.-M. Zhang, H. Jiang, X.-S. Wang, Tetrahedron Lett.,
2013, 54, 757–760; (n) X. Yang, G. Cheng, J. Shen, C. Kuai, X.
Cui, Org. Chem. Front., 2015, 2, 366–368.
008, 41, 222–234; (f) M. Tobisu and N. Chatani, Chem. Soc. Rev.,
008, 37, 300–307; (g) Y. Horino, Angew. Chem. Int. Ed., 2007, 46,
144–2146; (h) L. J. Gooßen, N. Rodríguez, K. Gooßen, Angew.
Chem. Int. Ed., 2008, 47, 3100–3120; (i) C. Najera and J. M.
Sansano, Angew. Chem. Int. Ed., 2009, 48, 2452–2456; (j) S. M.
Bonesi and M. Fagnoni, Chem. Eur. J., 2010, 16, 13572–13589; (k)
B. Rybtchinski and D. Milstein, Angew. Chem. Int. Ed., 1999, 38,
8
70–883; (l) R. H. Crabtree, Chem. Rev., 1985, 85, 245–269.
7
Carbonylative construction of quinazolinones, see: (a) X.-F. Wu, L.
He, H. Neumann and M. Beller, Chem. Eur. J. 2013, 19, 12635–
2
(a) J. Zhao, Y. Zhao, H. Fu, Org. Lett., 2012, 14, 2710–2713; (b) W.
P. Liu, J. Liu, D. Ogawa, Y. Nishihara, X. Guo, Z. Li, Org. Lett.,
1
2638; (b) H. Li, L. He, H. Neumann, M. Beller, X. F. Wu, Green
Chem. 2014, 16, 1336–1343; (c) L. He, M. Sharif, H. Neumann, M.
Beller, X. F. Wu, Green Chem. 2014, 16, 3763–3767; (d) C. Shen,
N. Y. T. Man, S. Stewart, X.-F. Wu, Org. Biomol. Chem. 2015, 13,
2
011, 13, 6272–6275; (c) A. Biswas, S. De Sarkar, R. Fro
Studer, Org. Lett., 2011, 13, 4966–4969; (d) Z.-Q. Rong, M.-Q. Jia,
S.-L. You, Org. Lett., 2011, 13, 4080 4083; (e) J. Xie, H. Jiang, Y.
Cheng, C. Zhu, Chem. Commun., 2012, 48, 979 981; (f) M. Gao,
Y. Yang, Y.-D. Wu, C. Deng, W.-M. Shu, D.-X. Zhang, L.-P. Cao,
N.-F. She, A.-X. Wu, Org. Lett., 2010, 12, 4026 4029; (g) Y. Liu
and J.-W. Sun, J. Org. Chem., 2012, 77, 1191; (h) L.-G. Meng, B.
Hu, Q.-P. Wu, M. Liang, S. Xue, Chem. Commun., 2009, 6089
091.
̈hlich, A.
4
422–4425; (e) J. Chen, K. Natte, A. Spannenberg, H. Neumann, P.
–
Langer, M. Beller, X.-F. Wu, Angew. Chem. Int. Ed. 2014, 53,
7579–7583; (f) L. He, H. Li, H. Neumann, M. Beller, X.-F. Wu,
Angew. Chem. Int. Ed. 2014, 53, 1420–1424; (g) H. Li, W. Li, A.
Spannenberg, W. Baumann, H. Neumann, M. Beller, X.-F. Wu,
Chem. Eur. J. 2014, 20, 8541–8544; (h) X.-F. Wu, S. Oschatz, A.
Block, A. Spannenberg, P. Langer, Org. Biomol. Chem., 2014, 12,
1865–1870; (i) J. Chen, H. Neumann, M. Beller, X.-F.Wu, Org.
Biomol. Chem., 2014, 12, 5835–5838; (j) X.-F. W, S. Oschatz, M.
Sharif, M. Beller, P. Langer, Tetrahedron, 2014, 70, 23–29; (k) M.
Mori, H. Kobayashi, M. Kimura and Y. Ban, Heterocycles, 1985,
23, 2803–2806.
–
–
–
6
3
For selected examples, see: (a) C. He, S. Guo, L. Huang, A. Lei, J.
Am. Chem. Soc., 2010, 132, 8273 8275; (b) A. Kawata, K. Takata,
Y. Kuninobu, K. Takai, Angew. Chem. Int. Ed., 2007, 46, 7793
–
8
(a) C. S. M. Pereira, V. M. T. M. Silva and A. E. Rodrigues, Green
Chem., 2011, 13, 2658–2071; (b) R. A. Sheldon, Green Chem.,
–
7
795; (c) C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc., 2013, 135,
5257 15262; (d) X. Sun, M. Wang, P. Li, X. Zhang, L. Wang,
3294; (e) S. Wang, Y. Yu, X. Chen,
H. Zhu, P. Du, G. Liu, L. Lou, H. Li, W. Wang, Tetrahedron. Lett.,
015, 56, 3093 3096; (f) X.B. Zhang, M. Wang, Y. Zhang, L.
Wang, RSC Adv., 2013, 3, 1311 1316; (g) J. Zhang, Y. Shao, Y.
Wang, H. Li, D. Xu, X. Wan, Org. Biomol. Chem., 2015, 13,
2
005, 7, 267–278; (c) J. S. Bennett, K. L. Charles, M. R. Miner, C.
1
–
F. Heuberger, E. J. Spina, M. F. Bartels and T. Foreman, Green
Chem., 2009, 11, 166–168; (d) A. Dandia, A. K. Jain and A. K.
Laxkar, Tetrahedron Lett., 2013, 54, 3929–3932; (e) P. P. Ghosh, S.
Paul and A. R. Das, Tetrahedron Lett., 2013, 54, 138–142.
Green Chem., 2013, 15, 3289
–
2
–
–
9
(a) H.-F. Zhou, Z. Li, Z. Wang, T. Wang, L. J. Xu, Y. He, Q.-H.
Fan, J. Pan, L. Gu and A. S. C. Chan, Angew. Chem. Int. Ed., 2008,
47, 8464–8467; (b) Z.-J. Wang, H.-F. Zhou, T.-L. Wang, Y.-M.
He, Q.-H. Fan, Green Chem., 2009, 11, 767–769; (c) Z.-Y. Ding,
T. Wang, Y.-M. He, F. Chen, H.-F. Zhou, Q.-H. Fan, Q. Guo and
A. S. C. Chan, Adv. Synth. Catal., 2013, 355, 3727–3735; (d) H.-F.
Zhou, Q.-H. Fan, W.-J. Tang, L.-J. Xu, Y.-M. He, G.-J. Deng, L.-
W. Zhao, L.-Q. Gu and A. S. C. Chan, Adv. Synth. Catal., 2006,
3
2
982
331
–
–
3987; (h) S. Cai, F. Wang, C. Xi, J. Org. Chem., 2012, 77,
2336; (i) X. Fan, Y. He, L. Cui, S. Guo, J. Wang, X. Zhang,
Eur. J. Org. Chem., 2012, 673
K. Barange, C. W. Kuo, P. M. Lei, C. F. Yao, J. Org. Chem., 2012,
–677; (j) V. Kavala, C. C. Wang, D.
7
7, 5022
–
5029; (k) X. Sun, X. Li, X. Zhang, L. Wang, Org. Lett.,
2129; (l) M. S. Mayo, X. Yu, X. Zhou, X. Feng,
767.
2
014, 16, 2126
–
Y. Yamamoto, M. Bao, Org. Lett., 2014, 16, 764
–
3
48, 2172–2182; (e) H.-F. Zhou, Q.-H. Fan, Y.-Y. Huang, L. Wu,
Y.-M. He, W.-J. Tang, L. Q. Gu and A. S. C. Chan, J. Mol. Catal.
A: Chem., 2007, 275, 47–53; (f) D. Pi, K. Jiang, H. Zhou, Y. Sui,
Y. Uozumi and K. Zou, RSC. Adv., 2014, 4, 57875–57844; (g) K.
Jiang, D. Pi, H. Zhou, S. Liu and K. Zou, Tetrahedron, 2014, 70,
4
(a) C. Wattanapiromsakul, P. I. Forster, P. G. Waterman,
Phytochemistry, 2003, 64, 609 615; (b) N. M. Abdel Gawad, H.
H. Georgey, R. M. Youssef, N. A. El-Sayed, Eur. J. Med. Chem.,
010, 45, 6058 6067.
–
2
–
3
056–3060; (h) S. Liu, K. Jiang, D. Pi, H. Zhou, Y. Uozumi and K.
Zou, Chin. J. Org. Chem., 2014, 34, 1369–1375.
5
6
For selected recent reviews, see: (a) A. Witt, J. Bergman, Curr. Org.
Chem., 2003, 7, 659 677; (b) D. J. Connolly, D. Cusack, T. P.
O’Sullivan, P. J. Guiry, Tetrahedron, 2005, 61, 10153 10202; (c)
L. He, H. Li, J. Chen, X.-F. Wu, RSC Adv., 2014, 4, 12065 12077.
–
10 S. Roy, M. P. Davydova, R. Pal, K. Gilmore, G. A. Tolstikov, S. F.
–
Vasilevsky, I. V. Alabugin, J. Org. Chem., 2011, 76, 7482–7490.
–
Received: ((will be filled in by the editorial staff))
Published online: ((will be filled in by the editorial staff))
For selected recent examples, see: (a) G. W. Wang, C. B. Miao, H.
Kang, Bull. Chem. Soc. Jpn., 2006, 79, 1426–1430; (b) N.
Mulakayala, B. Kandagatla, R. Ismail, K. Rapolu, P. Rao, C.
Mulakayala, C. S. Kumar, J. Iqbal, S. Orugani, Bioorg. Med. Chem.
Lett., 2012, 22, 5063–5066; (c) D. Zhan, T. Li, X. Zhang, C. Dai, H.
Wei, Y. Zhang, Q. Zeng, Synth. Commun., 2013, 43, 2493–2500;
(
d) M. Sharif, J. Opalach, P. Langer, M. Beller, X.-F. Wu, RSC
Adv., 2014, 4, 8–17; (e) J. Zhou, J. Fang, J. Org. Chem., 2011, 76,
730–7736; (f) A. J. A. Watson, A. C. Maxwell, J. M. Williams,
7
Org. Biomol. Chem., 2012, 10, 240–243; (g) H. Hikawa, Y. Ino, H.
Suzuki, Y. Yokoyama, J. Org. Chem., 2012, 77, 7046–7051; (h) W.
Ge, X. Zhu, Y. Wei, RSC Adv., 2013, 3, 10817–10822; (i) Y.-P.
Zhu, Z. Fei, M. Liu, F. Jia, A. Wu, Org. Lett., 2013, 15, 378–381;
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

RSC Advances
Page 6 of 6
Dynamic Article Links ►
RSC Advances
View Article Online
DOI: 10.1039/C5RA17969F
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/advances
Paper
Entry for the Table of Contents
Brønsted acid-catalyzed selective C-C bond cleavage of 1,3-diketones: a facile synthesis of 4(3H)-quinazolinones in aqueous ethyl
lactate
Guanshuo Shen, Haifeng Zhou, Peng Du, Sensheng Liu, Kun Zou and Yasuhiro Uozumi…….. Page No. – Page No.
5
0
5
O
O
O
O
naturally occurring
Brønsted acid catalyst
NHR'
NR' R"
R
+
R
in H O
2
NH2
N
biodegradable co-solvent
ethyl lactate)
R"
(
O
1
36 examples; 35-98% yields
no oxidant; no metal; no radiation
natural catalyst; green solvent
A facile and green approach was developed for the synthesis of 4(3H)-quinazolinones from 2-aminobenzamides and 1,3-diketones via C-
1
C bond cleavage catalyzed by camphorsulfonic acid in an aqueous solution of biodegradable ethyl lactate.
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 6