Metal- and Oxidant-Free Synthesis of Quinazolinones from β-Ketoesters with o-Aminobenzamides via Phosphorous Acid-Catalyzed Cyclocondensation and Selective C-C Bond Cleavage

Article abstract of DOI:10.1021/acs.joc.5b00937

A general and efficient phosphorous acid-catalyzed cyclocondensation of β-ketoesters with o-aminobenzamides via selective C-C bond cleavage leading to quinazolinones is developed. This reaction proceeds smoothly under metal- and oxidant-free conditions, giving both 2-alkyl- and 2-aryl-substituted quinazolinones in excellent yields. This strategy can also be applied to the synthesis of other N-heterocycles, such as benzimidazoles and benzothiazoles.

Full text of DOI:10.1021/acs.joc.5b00937

Article
pubs.acs.org/joc
Metal- and Oxidant-Free Synthesis of Quinazolinones from
β‑Ketoesters with o‑Aminobenzamides via Phosphorous Acid-
Catalyzed Cyclocondensation and Selective C−C Bond Cleavage
Zhongwen Li, Jianyu Dong, Xiuling Chen, Qiang Li, Yongbo Zhou,* and Shuang-Feng Yin
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha, 410082, People’s Republic of China
S
* Supporting Information
ABSTRACT: A general and efficient phosphorous acid-catalyzed
cyclocondensation of β-ketoesters with o-aminobenzamides via
selective C−C bond cleavage leading to quinazolinones is developed.
This reaction proceeds smoothly under metal- and oxidant-free
conditions, giving both 2-alkyl- and 2-aryl-substituted quinazolinones
in excellent yields. This strategy can also be applied to the synthesis of
other N-heterocycles, such as benzimidazoles and benzothiazoles.
of 2-amino-thiophenols/anilines with β-diketones for the
synthesis of benzothiazoles and benzimidazoles has been
explored. However, the protocol is not well suited for 2-aryl-
substituted N-heterocycles. Therefore, highly general and
metal- and oxidant-free syntheses of quinazolinones or other
N-heterocycles, especially with broad substrate scope, still
remain highly desirable.
INTRODUCTION
■
N-Heterocyclic compounds are the most abundant and integral
scaffolds that occur ubiquitously in a large number of bioactive
natural products, synthetic drugs, pharmaceuticals, and agro-
chemicals.1 Among the various N-heterocycles, quinazolinones
are a privileged class of compounds with a diverse spectrum of
biological activities and therapeutic potential.2,3 Quinazolinones
are commonly prepared by the condensation of o-amino-
benzamides with aldehydes4 using oxidants or carboxylic acid
derivatives5 under harsh conditions. Recently, oxidative
condensations of the alcohol,6 methylarene,7 or amines8 with
o-aminobenzamides have also been developed. However,
despite these notable advances,9 they generally suffer from
one or more drawbacks, such as requirement of stoichiometric
or excess amounts of strong oxidants, high temperatures, and
transition metal catalysts. Thus, undesired side reactions
inevitably take place, which decrease the selectivity to
quinazolinones. For example, most of the procedures are not
well suited for 2-alkyl-substituted quinazolinones,4−8 because
aliphatic aldehydes or the in situ-generated aliphatic aldehydes
are chemically unstable under harsh conditions. In addition,
transition metal catalyzed syntheses of quinazolinones starting
from other substrates have also been extensively studied.9,10
Transition metals are toxic and must be carefully removed from
the products, especially for the drug and pharmaceutical
industry. In this respect, a metal- and oxidant-free strategy
would be a promising choice, but it has not been frequently
used for the synthesis of quinazolinones.11 Although oxidants
and/or metals are also generally required for the synthesis of
other N-heterocycles, metal- and oxidant-free methods have
been developed, especially for benzothiazoles and benzimida-
zoles.12 A notable case is reported by Yu, Bao, and co-
workers,12a in which a convenient TsOH-catalyzed cyclization
The C−C bond is the most fundamental bond and is
widespread in organic compounds. C−C bond cleavage is a
topic of significant importance in organic synthesis, which
allows the construction of a new C−C bond directly from inert
starting materials. Hence, many strategies, such as strained
molecules (three- or four-membered ring compounds) and
chelation assistance, have been employed for this purpose.13
Although significant advances have been made in the past
decades, the development of selective C−C bond cleavage by a
catalytic reaction is a challenging problem in organic chemistry,
especially for the cleavage of unstrained C−C bonds. To meet
this challenge, transition metals are frequently employed.14
However, it is particularly of interest to achieve C−C bond
cleavage by metal-free strategies, which are still scarce.12a,15
Herein, in continuation of our ongoing research on the
synthesis of N-heterocycles,7b,16 we report a general and
efficient method for the preparation of quinazolinones from the
readily available β-ketoesters via phosphorous acid-catalyzed
cyclocondensation and selective C−C bond cleavage eq 1. This
reaction takes place under mild conditions to produce both 2-
alkyl-substituted and 2-aryl-substituted quinazolinones in
excellent yields with a high tolerance to a variety of functional
groups.
Received: April 26, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00937
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able. Thus, phosphorous acid is preferable to organic acid as
catalyst. However, to the best of our knowledge, phosphorous
acid catalyzed systems are rarely reported.17 Solvents also
played an important role in this reaction. When aprotic solvents
such as toluene, hexane, CH3CN, CHCl3, dioxane, and DMF
were used, low yields of 3a were observed (Table 1, entries 14−
19). In sharp contrast, the protic solvents such as ethanol and
methanol provided 3a in excellent yields (Table 1, entries 2 and
20). Notably, the reaction could take place smoothly in water at
100 °C, producing 3a in 93% yield (Table 1, entry 22).
Accounting for miscibility with the catalyst and organic
substrates, lower temperature, higher yield, and environmental
acceptance, ethanol was chosen as the best solvent for the next
reactions.
RESULTS AND DISCUSSION
■
In a typical experiment, 2-aminobenzamide 1a (0.2 mmol) was
treated with ethyl acetoacetate 2a (0.26 mmol) in the presence
of H3PO3 (50 wt % aqueous solution, 0.02 mmol) in ethanol
(0.5 mL) at 25 °C. After 60 h, 2-methylquinazolin-4(3H)-one
3a was produced in 80% yield with 20% 1a recovered (GC
yield; Table 1, entry 1). The higher reaction temperature could
a
As shown in Table 2, this phosphorous acid-catalyzed
cyclocondensation could be applied to a variety of β-ketoesters
to produce the corresponding quinazolinones 1 in excellent
yields via R(CO)−C(α) bond cleavage, regardless of the steric
hindrance and electronic effect of the substituents. Aliphatic β-
ketoesters 2a−2d reacted smoothly with 2-aminobenzamide 1a
to produce the corresponding alkyl-substituted quinazolinones
3a−3d in excellent yields (89−95%; Table 2, entries 1−4).
Remarkably, when ethyl 3-cyclopropyl-3-oxopropanoate 2e was
employed as the substrate, 2-cyclopropyl-substituted quinazo-
linone 3e was elaborated in 95% yield, with the strained
cyclopropyl group untouched (Table 2, entry 5). Functional
groups such as chloro and ether were also tolerable in this acid
catalytic system, generating the corresponding quinazolinones
3f and 3g in 89% and 92% yields, respectively (Table 2, entries
6 and 7). When aryl-substituted β-ketoesters 2h−2k were
employed as the substrates, 2-aryl functionalized quinazoli-
nones 3h−3k were readily elaborated in excellent yields (88−
93%; Table 2, entries 8−11). We were excited to find that
heteroaryl β-ketoester 2l was applicable to the present
transformation, and the corresponding 2-heteroaryl-substituted
quinazolinone 3l was obtained in 86% yield (Table 2, entry 12).
As for 2-aminobenzamides 1, in addition to the simplest 1a, the
methyl-substituted 1b, chloro-substituted 1c, and fluoro-
substituted 1d also served as good substrates to produce the
cyclocondensation products efficiently (86−95% yields Table 2,
entries 13−18). Furthermore, the cyclocondensation of the
substituted N-methylbenzamide 1e with β-ketoesters 2g and 2h
also proceeded smoothly in the presence of 10 mol % H3PO3,
affording the corresponding quinazolinones 3s and 3t in 95%
and 94% yields, respectively (Table 2, entries 19 and 20). It was
noted that all of the consumed 2-aminobenzamides were
completely transformed into corresponding quinazolinones in
this phosphorous acid-catalyzed reaction system.
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
solvent (mL) temp (°C) time (h) yield (%)
1
2
3
4
5
6
7
8
9
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
TsOH·H2O
50%HCI
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
Toluene
Hexane
CH3CN
CHCl3
Dioxane
DMF
25
50
60
15
10
8
80
>99
>99
>99
>99
82
80
100
120
50
5
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
50
57
Ph2P(O)OH
50%H3PO4
50%H3PO3
50%H3PO3
none
50
88
50
91
c
10
50
87
d
11
50
74
12
13
14
15
16
17
18
19
20
21
22
50
trace
trace
8
none
100
50
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50%H3PO3
50
34
50
30
50
27
50
63
50
68
MeOH
H2O
50
>99
39
50
H2O
100
93
a
Reaction conditions: 2-aminobenzamide 1a (0.2 mmol), ethyl
acetoacetate 2a (0.26 mmol), acid catalyst (0.02 mmol, 10 mol %),
solvent (0.5 mL) in 5 mL Schlenk tube. GC yield. H3PO3 (0.01
b
c
d
mmol, 5 mol %). H3PO3 (0.002 mmol, 1 mol %).
Compared with β-ketoesters, β-diketones were subjected to
this reaction system. Aliphatic β-diketones 4a−4c worked well
with 2-aminobenzamide 1a to produce the corresponding
quinazolinones 3a, 3b, and 3u in 91% to 96% yields (Table 3,
entries 1−3). The reaction of bulky substituted β-diketone 4d
should be carried out at a higher temperature (Table 3, entry
4). Substituted 2-aminobenzamides 1b−1e were also applicable
to the transformation, giving the corresponding products 3v−
3z3 in excellent yields (90−96%; Table 3, entries 5−12),
whereas when 1-methyl-3-phenyl-1,3-dione 4e, an unsymmetric
β-diketone, was examined, only CH3C(O)-C bond cleavage
took place to afford the 2-alkyl-substituted quinazolinone 3a
(Table 3, entry 13). The PhC(O)-C bond was stable in this
catalytic system, which was further confirmed by the treatment
of 1,3-diphenylpropane-1,3-dione (4f) at high temperature
shorten the reaction time (Table 1, entries 2−5). For example,
when the reaction was carried out at 50 °C for 15 h, the desired
product 3a was produced in nearly quantitative yield. Various
Brønsted acids could catalyze the reaction without the aid of
any ligand, additive, or metal, and H3PO3 showed the highest
efficiency (Table 1, entries 6−9). When the catalyst loading was
decreased to 5 mol %, 3a was obtained in 87% yield (Table 1,
entry 10). A further decrease of H3PO3 (1 mol %) resulted in
relatively low yield of 3a (74%; Table 1, entry 11). H3PO3 is
crucial for the current catalytic system, and only a trace of 3a
was detected in the absence of acid catalyst, even at high
temperature (Table 1, entries 12 and 13). Phosphorous acid is a
relatively weak inorganic acid. It is water-miscible, easily
separable from organic product, and environmentally accept-
B
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a
Table 2. H3PO3-Catalyzed Cyclocondensation Reactions of 2-Aminobenzamides with β-Ketoesters
a
Reaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-ketoester 2 (0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol), EtOH (0.5 mL) in 5 mL
b
c
d
Schlenk tube, 50 °C, 15 h. Isolated yield. 80 °C, 24 h. 100 °C, 24 h.
(130 °C; Table 3, entry 14). The above results showed that
reactions using β-diketones as the substrates were sensitive to
the steric hindrance of the substrates and the aryl-substituted β-
diketones were inactive in this cyclocondensation reaction (vide
infra).
In addition to quinazolinones, this strategy was also
applicable to the formation of other N-heterocycles such as
benzimidazoles 7 and benzothiazoles 8. As shown in Table 4, o-
phenylenediamine 5 and o-aminothiophenol 6 readily reacted
with various β-ketoesters via cyclocondensation and selective
C−C bond cleavage to produce both 2-alkyl- and 2-aryl-
substituted benzothiazoles 7 and benzothiazoles 8 in excellent
yields, respectively. As described above, Bao has reported a
similar method for the synthesis of benzothiazoles and
benzimidazoles using β-diketones as the substrates.12a Although
the strong Brønsted acid was used, low efficiency was observed
for the substrates with bulky substituents. Release of half of the
substituents, especially for bulky substituents, was another
drawback of the protocol. In contrast to the reported method,
this phosphorous acid-catalyzed reaction system employs β-
C
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a
Table 3. H3PO3-Catalyzed Cyclocondensation of 2-
Aminobenzamides with β-Diketones
Table 4. Synthesis of Benzimidazoles and Benzothiazoles
a
a
a
Reaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-diketone 4
Reaction conditions: o-substituted aniline 5 or 6 (0.2 mmol), β-
(0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol), EtOH (0.5 mL) in
5 mL Schlenk tube, 50 °C, 15 h. Isolated yield. 80 °C, 24 h. 100 °C,
24 h. 130 °C, 24 h.
ketoester 2 (0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol), EtOH
(0.5 mL) in 5 mL Schlenk tube, 50 °C, 15 h. Isolated yield. 80 °C,
24 h.
b
c
d
b
c
e
intermediate I, followed by protonation to give ketiminium II.
The intramolecular nucleophilic addition of II produces the
adduct III. Finally, the desired product 3 was obtained by the
C−C bond cleavage under acidic conditions. At this stage, the
reason for the highest performance of phosphorous acid
remains unclear, which is an ongoing research in our laboratory.
In conclusion, by the use of easily available phosphorous acid
and ketoesters, we have developed a general and efficient
method for the preparation of quinazolinones under metal- and
oxidant-free conditions, which features a broad range of
substrate scope. The available substrates, ease of operation,
excellent yield, and selectivity make it very practical for the
synthesis of N-heterocycles.
ketoesters as the substrates, and the C−C cleavage is selectively
occurred to incorporate the bulky substituents into N-
heterocycles highly efficiently, with only the small groups
released. Furthermore, this protocol is not sensitive to the steric
hindrance of the substituents, and is applicable to 2-aryl-
substituted N-heterocycles. Therefore, the present finding
shows many advantages over the previously reported method,
especially in terms of green reagent, high compatibility with
aryl-substitutes, and high atom-economy.
In order to clarify the reaction pathway, the reaction of 2-
aminobenzamide 1a (0.2 mmol) with ethyl acetoacetate 2a
(0.26 mmol) was traced by GC and GC-Mass under the
optimum conditions (Scheme 1). After 6 h, quinazolinone 3a
and imine Ia were observed in 36% and 57% yields,
respectively. By prolonging the reaction time to 15 h, the
imine Ia was completely converted to 3a. Therefore, imine Ia
probably served as the reaction intermediate.
EXPERIMENTAL SECTION
■
General Information. Except where otherwise noted, all
reactions were carried out in Schlenk tubes under N2
atmosphere. Reagents were used as received unless otherwise
noted. 1H and 13C NMR spectra were recorded on a 400 MHz
As shown in Scheme 2, this reaction probably proceeds via a
typical Brønsted acid-catalyzed mechanism,18 which is similar
to that of Bao’s work.12a Initially, in the presence of H3PO3, the
condensation reaction of 1 with 2 takes place to generate imine
1
spectrometer (400 MHz for H and 100 MHz for 13C NMR
spectroscopy). CDCl3 or DMSO-d6 was used as the solvent.
D
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Scheme 1. Control Reaction
(s, br, 1H), 8.29 (d, J = 7.3 Hz, 1H), 7.77 (t, J = 7.6 Hz 1H),
7.71 (d, J = 7.9 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H), 2.85 (q, J =
7.6 Hz, 2H), 1.46 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.4, 157.6, 149.5, 134.8, 127.2, 126.3, 126.2, 120.5,
29.1, 11.5.
Scheme 2. Proposed Mechanism
2-Propylquinazolin-4(3H)-one (3c).10i Following the gen-
eral procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 34.6 mg,
1
92%; mp: 202−204 °C. H NMR (400 MHz, CDCl3) δ 11.81
(s, br, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H),
7.71 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H), 2.79 (t, J =
7.2 Hz, 2H,); 1.90−1.96 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 164.2, 156.8, 149.3, 134.8, 127.1,
126.4, 126.2, 120.5, 37.7, 21.0, 13.7.
2-tert-Butylquinazolin-4(3H)-one (3d).1c Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 36.0 mg,
1
Chemical shifts for H NMR are referred to internal Me4Si (0
ppm) and reported as follows: chemical shift (δ ppm),
multiplicity, integration, and coupling constant (Hz). Data for
13C NMR are reported in ppm relative to the center line of a
triplet at 77.0 ppm for chloroform-d. The electron ionization
(EI) method was used as the ionization method for the HRMS
measurement, and the mass analyzer type is TOF for EI.
General Experimental Procedure for the Synthesis of
N-Heterocycle Derivatives. A 5 mL Schlenk tube equipped
with a magnetic stir bar was charged with o-aminophenyl
derivative (1, 5, or 6 0.2 mmol), β-diketone/ketoester (2 or 4
0.26 mmol), H3PO3 (0.02 mmol, 10 mol %), and ethanol (0.5
mL). The reaction mixture was stirred at 50 °C for 15 h. The
reaction was monitored by GC or GC-MS. After completion of
the reaction, the resulting solution was cooled to room
temperature, and neutralized with saturated solution of
NaHCO3. The product was extracted with EtOAc, dried over
anhydrous Na2SO4, and concentrated in vacuo. The crude
product was purified by flash column chromatography(eluent:
ethyl acetate/petroleum ether = 1/2−1/5) on silica gel to
afford the desired product.
1
89%; mp: 207−208 °C. H NMR (400 MHz, CDCl3) δ 11.18
(s, br, 1H), 8.29 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 8.2 Hz 1H),
7.72 (d, J = 8.4 Hz, 1H), 7.46 (t, J = 7.2 Hz, 1H), 1.50 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 163.8, 162.1, 149.2, 134.5,
127.7, 126.3, 126.1, 120.6, 37.5, 28.3.
2-Cyclopropylquinazolin-4(3H)-one (3e).1c Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 35.3 mg,
1
95%; mp: 231−234 °C. H NMR (400 MHz, CDCl3) δ 12.23
(s, br, 1H), 8.26 (d, J = 7.9 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H),
7.60 (d, J = 8.2 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 2.06−2.00
(m, 1H), 1.42−1.29 (m, 2H), 1.21−1.06 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 164.3, 158.3, 149.8, 134.7, 126.9, 126.2,
125.6, 120.3, 14.6, 9.8.
2-Chloromethylquinazolin-4(3H)-one (3f).19 Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/1) to afford a yellow solid. Yield: 34.5 mg,
1H and 13C Spectral Data of the Products. 2-
Methylquinazolin-4(3H)-one (3a).16a Following the general
procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 30.4 mg,
1
89%; mp: 249−252 °C. H NMR (400 MHz, DMSO-d6) δ
12.64 (s, br, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.90 (t, J = 7.6 Hz,
1H), 7.74 (d, J = 8.1 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 4.61 (s,
2H); 13C NMR (100 MHz, DMSO-d6) δ 162.0, 152.8, 148.7,
135.2, 127.8, 127.4, 126.4, 121.7, 43.7.
1
95%; mp: 236−238 °C. H NMR (400 MHz, CDCl3) δ 12.17
(s, br, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H),
7.68 (d, J = 8.1 Hz, 1H), 7.47 (t, J = 7.3 Hz, 1H), 2.61 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 164.4, 153.3, 149.4, 134.9,
127.0, 126.4, 126.2, 120.2, 22.1.
2-Methoxymethylquinazolin-4(3H)-one (3g).20 Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
35.0 mg, 92%; mp: 188−190 °C. 1H NMR (400 MHz, CDCl3)
δ 10.15 (s, 1H), 8.30 (d, J = 7.9 Hz, 1H), 7.77 (t, J = 7.6 Hz,
1H), 7.67 (d, J = 8.1 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 4.51 (s,
2-Ethylquinazolin-4(3H)-one (3b).10i Following the general
procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 32.4 mg,
1
93%; mp: 228−230 °C. H NMR (400 MHz, CDCl3) δ 11.95
E
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2H), 3.56 (s, 3H); 13C NMR (100 MHz, CHCl3) δ 161.8,
152.7, 148.6, 134.7, 127.0, 126.8, 126.5, 121.5, 71.1, 59.3.
2-Phenylquinazolin-4(3H)-one (3h).6b Following the gen-
eral procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 40.4 mg,
21.2, 14,6, 9.5. HRMS (EI) m/z: [M]+ calcd. for C12H12N2O
200.0950; found 200.0936.
2-(4-Fluorophenyl)-6-methylquinazolin-4(3H)-one (3n).
Following the general procedure, the crude product was
purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/4) to afford a white
1
1
solid. Yield: 46.2 mg, 91%; mp: 280−283 °C. H NMR (400
91%; mp: 235−236 °C. H NMR (400 MHz, CDCl3) δ 12.09
MHz, DMSO-d6) δ 12.51 (s, br, 1H), 8.28−8.21 (m, 2H), 7.96
(s, 1H), 7.70−7.62 (m, 2H), 7.44−7.35 (m, 2H), 2.47 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 164.5 (d, JC−F = 247.8 Hz),
162.7, 151.2, 147.2, 136.9, 136.5, 130.7 (d, JC−F = 8.8 Hz),
(s, br, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.30 (dd, J = 6.5, 3.0 Hz,
2H), 7.85 (d, J = 7.9 Hz, 1H), 7.83−7.77 (m, 1H), 7.62−7.55
(m, 3H), 7.51 (t, J = 7.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 164.0, 151.8, 149.5, 134.9, 132.8, 131.6, 129.0, 128.0,
127.5, 126.7, 126.3, 120.8.
129.8 (d, JC−F = 2.8 Hz), 127.9, 125.8, 121.1, 116.2 (d, JC−F
=
21.9 Hz), 21.4. HRMS (EI) m/z: [M]+ calcd. for C15H11FN2O
254.0847; found 254.0854.
2-(4-Fluorophenyl)quinazolin-4(3H)-one (3i).6b Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/3) to afford a white solid. Yield:
42.7 mg, 89%; mp: 291−294 °C. 1H NMR (400 MHz, DMSO-
d6) δ 8.28−8.23 (m, 2H), 8.16 (d, J = 7.9 Hz, 1H), 7.84 (t, J =
7.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H),
7.40 (t, J = 8.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ
164.5 (d, JC−F = 247.7 Hz), 162.7, 151.9, 149.1, 135.1, 130.9 (d,
2-Cyclopropyl-6-chloroquinazolin-4(3H)-one (3o).10a Fol-
lowing the general procedure, the crude product was purified
by column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
40.9 mg, 93%; mp: 292−295 °C. 1H NMR (400 MHz, DMSO-
d6) δ 12.49 (s, br, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.71 (d, J = 8.7
Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 2.00−1.94 (m, 1H), 1.10−
1.06 (m, 2H), 1.04−1.01 (m, 2H); 13C NMR (100 MHz,
DMSO-d6) δ 161.8, 160.9, 149.4, 134.6, 129.6, 129.0, 125.2,
122.3, 14.2, 10.1.
JC−F = 8.9 Hz), 129.7, 127.9, 127.1, 126.3, 121.4, 116.1 (d, JC−F
= 21.7 Hz).
2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3j).6b Follow-
ing the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
46.9 mg, 93%; mp: 276−280 °C. 1H NMR (400 MHz, DMSO-
d6) δ 12.41 (s, br, 1H), 8.19 (d, J = 8.9 Hz, 2H), 8.13 (dd, J =
7.9, 1.0 Hz, 1H), 7.84−7.77 (m, 1H), 7.70 (d, J = 8.0 Hz, 1H),
7.48 (t, J = 7.5 Hz, 1H), 7.08 (d, J = 8.9 Hz, 2H), 3.84 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 162.8, 162.3, 152.3, 149.4,
135.0, 129.9, 127.8, 126.6, 126.3, 125.3, 121.2, 114.5, 55.9.
2-(4-Nitrophenyl)quinazolin-4(3H)-one (3k).6b Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/1) to afford a yellow solid. Yield:
47.0 mg, 88%; mp: >300 °C. 1H NMR (400 MHz, DMSO-d6)
δ 12.79 (s, br, 1H), 8.43−8.37 (m, 4H), 8.19 (d, J = 7.7 Hz,
1H), 7.89 (t, J = 7.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.59 (t, J
= 7.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 162.5,
151.2, 149.5, 148.8, 139.0, 135.3, 129.8, 128.2, 127.8, 126.4,
124.1, 121.7.
6-Chloro-2-(4-methoxyphenyl)quinazolin-4(3H)-one
(3p).10c Following the general procedure, the crude product
was purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/3) to afford a white
1
solid. Yield: 50.9 mg, 89%; mp: 290−292 °C. H NMR (400
MHz, DMSO-d6) δ 12.56 (s, br, 1H), 8.18 (d, J = 8.7 Hz, 2H),
8.05 (d, J = 2.1 Hz, 1H), 7.82 (d, J = 8.7 Hz, 1H), 7.71 (d, J =
8.7 Hz, 1H), 7.09 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 162.5, 161.9, 152.8, 148.2, 135.1,
130.7, 130.1, 125.3, 125.0, 122.4, 114.5, 56.0.
5-Fluoro-2-propylquinazolin-4(3H)-one (3q). Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/5) to afford a white solid. Yield: 37.9 mg,
1
92%; mp: 216−220 °C. H NMR (400 MHz, CDCl3) δ 11.81
(s, 1H), 7.68 (dd, J = 13.6, 8.0 Hz, 1H), 7.49 (d, J = 8.2 Hz,
1H), 7.15−7.05 (m, 1H), 2.75 (t, J = 7.6 Hz, 2H), 1.96−1.86
(m, 2H), 1.07 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.8, 161.3 (d, JC−F = 263.8 Hz), 158.0, 151.5, 135.1
(d, JC−F = 10.4 Hz), 123.1, 112.8 (d, JC−F= 20.3 Hz),110.4, 37.5,
20.8, 13.6. HRMS (EI) m/z: [M]+ calcd. for C11H11FN2O:
206.0856, found 206.0849.
2-(4-Pyridinyl)quinazolin-4(3H)-one (3l).1c Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/2) to afford a pale yellow solid. Yield: 38.4
mg, 86%; mp: 281−284 °C. 1H NMR (400 MHz, DMSO-d6) δ
12.65 (s, br, 1H), 8.79 (d, J = 5.5 Hz, 2H), 8.19 (d, J = 7.5 Hz,
1H), 8.12 (d, J = 5.9 Hz, 2H), 7.88 (t, J = 7.1 Hz, 1H), 7.79 (d,
J = 8.0 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 162.5, 151.0, 150.7, 148.7, 140.3, 135.2, 128.2,
127.8, 126.4, 122.0, 121.9.
2-Cyclopropyl-6-methylquinazolin-4(3H)-one (3m). Fol-
lowing the general procedure, the crude product was purified
by column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
38.0 mg, 95%; mp: 252−256 °C. 1H NMR (400 MHz, CDCl3)
δ 11.81 (s, br, 1H),8.04 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.50
(d, J = 8.3 Hz, 1H), 2.47 (s, 3H), 2.02−1.95 (m, 1H), 1.32−
1.28 (m, 2H), 1.15−1.09 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 164.1, 157.1, 147.8, 136.2, 135.7, 126.8, 125.6, 120.1,
5-Fluoro-2-(4-methoxyphenyl)quinazolin-4(3H)-one
(3r).5e Following the general procedure, the crude product was
purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/2) to afford a white
1
solid. Yield: 46.4 mg, 86%; mp: 289−292 °C. H NMR (400
MHz, DMSO-d6) δ 12.42 (s, br, 1H), 8.19 (d, J = 8.8 Hz, 2H),
7.78 (dd, J = 13.9, 8.2 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.22
(dd, J = 10.7, 8.4 Hz, 1H), 7.10 (d, J = 8.9 Hz, 2H), 3.85 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ 162.6, 161.0 (d, JC−F
= 261.1 Hz), 160.1, 153.3, 151.6, 135.5 (d, JC−F = 10.6 Hz),
130.1, 124.7, 123.8 (d, JC−F = 4.0 Hz), 114.5, 112.9 (d, JC−F
=
20.4 Hz), 110.6, 56.0.
2-(Methoxymethyl)-3-methyl-quinazolin-4(3H)-one (3s).
Following the general procedure, the crude product was
purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/4) to afford a pale yellow
1
liquid. Yield: 38.8 mg, 95%. H NMR (400 MHz, CDCl3) δ
F
DOI: 10.1021/acs.joc.5b00937
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
8.28−8.23 (m, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.67 (d, J = 7.3
Hz, 1H), 7.46 (t, J = 6.8 Hz, 1H), 4.55 (s, 2H), 3.67 (s, 3H),
3.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.3, 152.5,
146.7, 134.1, 127.3, 127.2, 126.7, 120.8, 73.8, 58.5, 30.3. HRMS
(EI) m/z: [M]+ calcd. for C11H12N2O2 204.0886; found
204.0876.
33.1 mg, 93%; mp: 243−245 °C. 1H NMR (400 MHz, DMSO-
d6) δ 12.22 (s, br, 1H), 7.73 (dd, J = 13.9, 7.8 Hz, 1H), 7.38 (d,
J = 8.2 Hz, 1H), 7.24−7.13 (m, 1H), 2.33 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 161.0 (d, JC−F = 260.8 Hz), 159.5,
155.9, 151.7, 135.3 (d, JC−F = 10.5 Hz), 123.1, 112.6 (d, JC−F
=
20.3 Hz), 110.6, 21.7.
3-Methyl-2-phenylquinazolin-4(3H)-one (3t).16a Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
44.4 mg, 94%; mp: 134−138 °C. 1H NMR (400 MHz, CDCl3)
δ 8.33 (d, J = 7.8 Hz, 1H), 7.78−7.73 (m, 2H), 7.57−7.52 (m,
2H), 7.51−7.48 (m, 4H), 3.50 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.7, 156.1, 147.3, 135.3, 134.3, 130.1, 128.9, 127.9,
127.5, 127.0, 126.7, 120.5, 34.2.
5-Fluoro-2-(1-methylethyl)quinazolin-4(3H)-one (3z1).
Following the general procedure, the crude product was
purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/5) to afford a white
1
solid. Yield: 37.1 mg, 90%; mp: 212−214 °C; H NMR (400
MHz, CDCl3) δ 11.16 (s, br, 1H), 7.70−7.64 (m, 1H), 7.50 (d,
J = 8.2 Hz, 1H), 7.11−7.05 (m, 1H), 3.05−2.94 (m, 1H), 1.42
(d, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 161.8,
161.4 (d, JC−F = 263.7 Hz), 161.4 (d, JC−F = 3.0 Hz), 151.5,
134.9 (d, JC−F = 10.3 Hz), 123.3 (d, JC−F = 4.2 Hz), 112.8 (d,
2-(1-Methylethyl)quinazolin-4(3H)-one (3u).10i Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
34.2 mg, 91%; mp: 224−226 °C. 1H NMR (400 MHz, CDCl3)
δ 11.57 (s, br, 1H), 8.30 (d, J = 7.1 Hz, 1H), 7.77 (t, J = 7.5 Hz,
1H), 7.72 (d, J = 7.4 Hz, 1H), 7.46 (t, J = 7.4 Hz, 1H), 3.05 (m,
1H), 1.45 (d, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ
164.1, 160.8, 149.5, 134.7, 127.4, 126.3, 126.2, 120.7, 34.9, 20.4.
2,6-Dimethylquinazolin-4(3H)-one (3v).1c Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 33.1 mg,
J
C−F= 20.4 Hz), 110.5, 34.8, 20.3. HRMS (EI) m/z: [M]+ calcd.
for C11H11FN2O 206.0848; found 206.0851.
2,3-Dimethylquinazolin-4(3H)-one (3z2).16a Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/4) to afford a white solid. Yield: 33.4 mg,
1
96%; mp: 112−114 °C. H NMR (400 MHz, CDCl3) δ 8.23
(d, J = 8.0 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.59 (d, J = 8.1 Hz,
1H), 7.42 (t, J = 7.5 Hz, 1H), 3.60 (s, 3H), 2.60 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 162.2, 154.4, 147.2, 134.1, 126.7,
126.5, 126.3, 120.2, 31.0, 23.6.
3-Methyl-2-(1-methylethyl)quinazolin-4(3H)-one (3z3).
Following the general procedure, the crude product was
purified by column chromatography on silica gel and eluted
with ethyl acetate/petroleum ether (1/4) to afford a white
1
95%; mp: 248−250 °C. H NMR (400 MHz, CDCl3) δ 12.16
(s, br, 1H), 8.06 (s, 1H), 7.57 (s, br, 2H), 2.58 (s, 3H), 2.48 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 164.4, 152.5, 147.4,
136.5, 136.3, 126.8, 125.5, 120.0, 21.9, 21.2.
1
solid. Yield: 37.6 mg, 93%; mp: 79−82 °C. H NMR (400
2-Ethyl-6-methylquinazolin-4(3H)-one (3w).16a Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/4) to afford a white solid. Yield:
35.3 mg, 94%; mp: 224−226 °C. 1H NMR (400 MHz, CDCl3)
δ 11.86 (s, br, 1H), 8.07 (s, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.59
(d, J = 1.8 Hz, 1H), 2.82 (q, J = 7.6 Hz, 2H), 2.49 (s, 3H), 1.45
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.3,
156.7, 147.5, 136.5, 136.2, 127.0, 125.6, 120.2, 29.0, 21.2, 11.6.
6-Chloro-2-ethylquinazolin-4(3H)-one (3x).16a Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/3) to afford a white solid. Yield:
38.9 mg, 94%; mp: 253−256 °C. 1H NMR (400 MHz, DMSO-
d6) δ 12.12 (s, br, 1H), 8.01 (s, 1H), 7.78 (s, 1H), 7.62 (s, 1H),
2.63 (s, 2H), 1.25 (s, 2H), 13C NMR (100 MHz, DMSO-d6) δ
161.7, 159.9, 148.2, 134.7, 130.4, 129.4, 125.1, 122.5, 11.7.
2-(tert-Butyl)-6-chloroquinazolin-4(3H)-one (3y). Follow-
ing the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/3) to afford a white solid. Yield:
42.9 mg, 91%; mp: 228−232 °C. 1H NMR (400 MHz, CDCl3)
δ 10.84 (s, br, 1H), 8.22 (d, J = 1.5 Hz, 1H), 7.69 (dd, J = 8.9,
2.3 Hz, 1H), 7.67 (d, J = 4.9 Hz, 1H), 1.48 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 162.6, 162.3, 147.7, 134.9, 132.1, 129.4,
125.5, 121.6, 37.5, 28.2. HRMS (EI) m/z: [M]+ calcd. for
C12H13ClN2O 236.0711; found 236.0704.
MHz, CDCl3) δ 8.24 (d, J = 8.8 Hz, 1H), 7.69 (t, J = 7.6 Hz,
1H), 7.63 (d, J = 7.5 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 3.66 (s,
3H), 3.24−3.14 (m, 1H), 1.37 (d, J = 6.7 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ 162.8, 161.1, 147.3, 133.9, 127.1, 126.6,
126.1, 120.2, 32.1, 30.0, 20.8. HRMS (EI) m/z: [M]+ calcd. for
C12H14N2O 202.1148; found 202.1156.
2-Methyl-1H-benzo[d]imidazole (7a).12a Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a white solid. Yield: 25.1 mg,
95%; mp: 179−181 °C. 1H NMR (400 MHz, CDCl3) δ 9.69 (s,
br, 1H), 7.56 (dd, J = 6.0, 3.2 Hz, 2H), 7.22 (dd, J = 6.0, 3.2 Hz,
2H), 2.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 151.4,
138.7, 122.1, 114.4, 14.9.
2-Propyl-1H-benzo[d]imidazole (7b).16a Following the
general procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a white solid. Yield: 29.8 mg,
1
93%; mp: 158−160 °C. H NMR (400 MHz, CDCl3) δ 11.05
(s, 1H), 7.56 (dd, J = 5.8, 3.1 Hz, 2H), 7.21 (dd, J = 5.9, 3.1 Hz,
2H), 2.96 (t, J = 7.5 Hz, 2H), 1.96−1.84 (m, 2H), 0.98 (t, J =
7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 155.6, 138.5,
122.1, 114.5, 31.1, 21.7, 13.8.
2-(Methoxymethyl)-1H-benzo[d]imidazole (7c).10b Follow-
ing the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/50) to afford a white solid. Yield:
29.5 mg, 91%; mp: 142−144 °C. 1H NMR (400 MHz, CDCl3)
δ 7.60 (dd, J = 5.8, 3.1 Hz, 2H), 7.25 (dd, J = 6.0, 3.1 Hz, 2H),
4.78 (s, 2H), 3.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
151.5, 122.5, 115.1, 68.3, 59.0.
5-Fluoro-2-methylquinazolin-4(3H)-one (3z).1c Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/5) to afford a white solid. Yield:
G
DOI: 10.1021/acs.joc.5b00937
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2-(4-Methoxyphenyl)-1H-benzo[d]imidazole (7d).16b Fol-
lowing the general procedure, the crude product was purified
by column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/100) to afford a white solid. Yield:
42.6 mg, 95%; mp: 233−236 °C. 1H NMR (400 MHz, DMSO-
d6) δ 8.16 (d, J = 8.7 Hz, 2H), 7.62 (dd, J = 5.9, 3.2 Hz, 2H),
7.25 (dd, J = 6.0, 3.1 Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H), 3.85 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ 161.7, 151.3, 138.2,
129.0, 123.1, 121.5, 115.0, 55.9.
AUTHOR INFORMATION
Corresponding Author
*E-mail: zhouyb@hun.edu.cn. Fax: (+) 86-731-88821171.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial supports by National Natural Science Foundation of
China (Grant Nos. 21172062, 21273066, 21273067), and
Doctoral Fund of Ministry of Education of China
(20110161120008) are gratefully appreciated.
2-Isopropylbenzo[d]thiazole (8a).12a Following the general
procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a yellow liquid. Yield: 32.9
1
REFERENCES
mg, 93%. H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz,
■
1H), 7.82 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 7.32 (t, J
= 7.6 Hz, 1H), 3.47−3.36 (m, 1H), 1.47 (d, J = 6.9 Hz, 6H);
13C NMR (100 MHz, CDCl3) δ 178.5, 153.1, 134.6, 125.7,
124.5, 122.5, 121.4, 34.0, 22.8.
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2-Propylbenzo[d]thiazole (8b).10b Following the general
procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a yellow liquid. Yield: 33.3
1
mg, 94%. H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz,
1H), 7.83 (d, J = 7.9 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 7.34 (t, J
= 7.1 Hz, 1H), 3.09 (t, J = 15.2 Hz, 2H), 1.96−1.86 (m, 2H),
1.06 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.2,
153.2, 135.1, 125.8, 124.6, 122.5, 121.4, 36.2, 23.1, 13.7.
2-Cyclopropylbenzo[d]thiazole (8c).5c Following the gen-
eral procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a yellow liquid. Yield: 32.2
1
mg, 92%. H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.1 Hz,
1H), 7.75 (d, J = 7.9 Hz, 1H), 7.39 (t, J = 7.7 Hz, 1H), 7.27 (t, J
= 7.6 Hz, 1H), 2.40−2.32 (m, 1H), 1.20−1.77(m, 4H); 13C
NMR (100 MHz, CDCl3) δ 174.3, 153.2, 134.0, 125.7, 124.1,
121.9, 121.2, 15.1, 11.6.
2-Phenylbenzo[d]thiazole (8d).12a Following the general
procedure, the crude product was purified by column
chromatography on silica gel and eluted with ethyl acetate/
petroleum ether (1/50) to afford a pale white solid. Yield: 39.7
1
mg, 94%; mp: 112−114 °C. H NMR (400 MHz, CDCl3) δ
8.12−8.05 (m, 3H), 7.88 (d, J = 8.0 Hz, 1H), 7.49−7.46 (m,
4H), 7.36 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
168.0, 154.1, 135.0, 133.6, 130.9, 129.0, 127.5, 126.3, 125.1,
123.2, 121.6.
2-(4-Methoxyphenyl)benzo[d]thiazole (8e).16b Following
the general procedure, the crude product was purified by
column chromatography on silica gel and eluted with ethyl
acetate/petroleum ether (1/50) to afford a pale yellow solid.
1
Yield: 44.8 mg, 93%; mp: 141−144 °C. H NMR (400 MHz,
CDCl3) δ 8.04 (dd, J = 8.8, 2.5 Hz, 3H), 7.86 (d, J = 7.9 Hz,
1H), 7.47 (t, J = 7.7 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 6.99 (d, J
= 8.8 Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
167.8, 161.8, 154.2, 134.8, 129.0, 126.4, 126.1, 124.7, 122.7,
121.4, 114.3, 55.4.
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ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b00937.
Control reaction and copies of 1H and 13C NMR spectra
for products (PDF)
H
DOI: 10.1021/acs.joc.5b00937
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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DOI: 10.1021/acs.joc.5b00937
J. Org. Chem. XXXX, XXX, XXX−XXX