Iron nitrate/TEMPO-catalyzed aerobic oxidative synthesis of quinazolinones from alcohols and 2-aminobenzamides with air as the oxidant

Article abstract of DOI:10.1039/c6ra12164k

A highly efficient, iron nitrate/TEMPO-catalyzed approach for the synthesis of quinazolinones has been achieved via a one-pot, tandem aerobic oxidative cyclization of primary alcohols with 2-aminobenzamides. This practical reaction tolerates a broad scope of substrates and could afford a variety of desirable products in good to excellent yields with air as the terminal green oxidant. Thus, the present synthetic protocol provides an efficient and concise strategy for the synthesis of quinazolinones.

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Iron nitrate/TEMPO-catalyzed aerobic oxidative synthesis of
quinazolinones from alcohols and 2-aminobenzamides with air as
the oxidant
Received 00th January 20xx,
Accepted 00th January 20xx
Yongke Hu, Lei Chen and Bindong Li *
DOI: 10.1039/x0xx00000x
A highly efficient, Iron nitrate/TEMPO-catalyzed approach for the synthesis of quinazolinones has been achieved via a one-
pot, tandem aerobic oxidative cyclization of primary alcohols with 2-aminobenzamides. This practical reaction tolerates a
broad scope of substrates and could afford a variety of desirable products in good to excellent yields with air as the
terminal green oxidant. Thus, the present synthetic protocol provides an efficient and concise strategy for the synthesis of
quinazolinones.
www.rsc.org/
best of our knowledge, several catalytic methods have been
reported for the synthesis of quinazolinones derivatives using
alcohols as the stating substrates. In 2011, Zhou described a
Introduction
Quinazolinone derivatives as an important class of N-containing
heterocyclic compounds exist widely in natural products and
synthetic drugs (Scheme 1).1 Specifically, they are assigned as
privileged scaffold in drug discovery and well-known for their broad
range of biological and pharmacological properties such as
anticancer,2 antibacterial, 3anticonvulsant4 and hypolipidemic5
activities.
[Cp*IrCl2]2-catalyzed one-pot oxidative cyclization of primary
alcohols with 2-aminobenzamides to quinazolinones under
20
hydrogen transfer conditions. Although this strategy was green,
atomo-efficient and the only by-products are environmentally
benign H2 and water, the turnover number of the catalytic system
was still low. In 2013, Wei and co-workers reported a one-pot two-
step catalytic system for synthesis of quinazolinones from primary
alcohols and 2-aminobenzamides.21 In their method, iodine was
used as catalyst, DMSO as the oxidant and various quinazolinones
were prepared in good yields, but this system produced
Because of their importance, the synthesis of substituted
quinazolinones has extensively attracted much attention and
numerous synthetic approaches have been developed. In general,
the main approaches usually utilize 2-halobenzamides,6 2-
aminobenzamides,7 2-nitrobenzamides, 8 2-aminobenzonitriles, 9
2-halobenzoic acids,10 and 2-aminobenzoic acids11 as suitable
substrates to form the quinazolinones (Scheme 2). Among the
plentiful methodologies, the most classical and common protocols
for the synthesis of quinazolinones are the condensation of 2-
aminobenzamides with aldehydes followed by oxidation of the
aminal intermediate in the present of stoichiometric or large excess
amounts of nonrenewable oxidants, such as KMnO4,12MnO2,
13DDQ,14 CuCl2 15and PhI(OAc)2 .16 However, the drawback of these
methods is that chemical unstable aldehydes are required. As is
well known, aldehydes can be easily prepared by the oxidation of
alcohols and numerous methods have been developed, eg., Swern
oxidation,17 Dess-Martin Oxidation18 and TEMPO-catalyzed
stoichiometric amount of poisonous dimethyl sulfide. Very recently,
22
Wu et al.
reported a new strategy for the synthesis of
quinazolinones based on ZnI2-catalyzed reaction of benzyl alcohols
23
with 2-aminobenzamides, and soon later Li et al.
developed a
similar FeCl3-catalyzed oxidative system, but both of the two
strategies required large excess amounts of tert-butyl
hydroperoxide (TBHP) as oxidant. Recently, molecular oxygen, as a
19
oxidation. Besides, alcohols are inexpensive, benign and readily
available chemical feedstock. It would be advantages to synthesize
quinazolinones directly from alcohols rather than aldehydes. To the
School of Chemical Engineering, Nanjing University of Science and Technology,
Nanjing 210094, P. R. China. E-mail: libindong@ njust.edu.cn;
Fax: +86(25)84315514;
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Scheme 1. Examples of synthetic and natural quinazolinones.
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Table 1
．
Optimization of reaction conditions.a
Fe catalyst
TEMPO
(mol %)
-
Base
(equiv)
Yield
(%)c
Entry
solvent
Toluene
(mol %)b
FeCl3 (5)
1
2
KOH(0.5)
48
FeBr3 (5)
-
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(1.0)
-
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
51
43
3
4
Fe2(SO4)3 (5)
Fe(acac)3 (5)
Fe (NO3)3 (5)
Fe (NO3)3 (5)
Fe (NO3)3 (5)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe(NO3)3(10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
Fe (NO3)3 (10)
-
-
38
5
-
60
6
5
75
7
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
81
8
95
Scheme 2. General synthetic methods for the preparation of
quinazolinones.
9
94
10
11
12
13
14
15
16
17
18
19
20
21d
22e
65
green oxidant, has received significant attention because O2 is
inexpensive, abundant and water is produced as the only benign by-
product. And aerobic oxidation of organic compounds catalyzed by
aminoxyl radicals such as 2, 2, 6, 6-tetramethylpiperidine-1-oxyl
(TEMPO) using O2 or air as the terminal oxidant has also been
extensively studied. To date, few catalytic systems have been
successfully developed for the synthesis of N-heterocyclic
compounds using molecular oxygen as the oxidant in the present of
K2CO3(0.5)
K3PO4(0.5)
75
61
t-BuOK(0.5) Toluene
85
CsOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
KOH(0.5)
Toluene
DMSO
DMF
93
87
24
TEMPO. It is well known that the Fe/TEMPO catalytic system has
59
been well studied for the aerobic oxidation of alcohols and amines,
Dioxane
CH3CN
DMC
43
25
and exhibits broad utilities in both academe and industry.
However, its application in the catalytic oxidative synthesis of N-
heterocycles is rare.
75
trace
trace
87
Herein, we report a new approach to quinazolinones from 2-
aminobenzamides and primary alcohols using cheap and nontoxic
Fe(NO3)3 as the catalyst, TEMPO as the co-catalyst and air as the
terminal oxidant. This catalytic system provides an efficient and
convenient method for the synthesis of diverse quinazolinones
from easily accessible starting materials.
H2O
Toluene
Toluene
Toluene
90
23f
trace
a
Reaction condition: 1a (1 mmol), 2a (1 mmol), Fe catalyst,
TEMPO, base and solvent (2 mL) in a 10 mL Schlenk tube stirred
for 12 h at 100 °C under air balloon and then monitored by TLC.
Results and discussion
c
b Fe(NO3)3·9H2O = Fe(NO3)3 unless otherwise noted. Isolated
Initially, 2-aminobenzamide (1a) and benzyl alcohol (2a) were
employed as model substrates to optimize the reaction conditions.
The optimized results including catalyst, solvent, base and reaction
temperature were summarized in Table 1. As listed in Table 1, iron
salts such as FeCl3, FeBr3, Fe2(SO4)3, Fe(acac)3 and Fe(NO3)3 were
screened in the present of KOH at 100 oC under air balloon (Table 1,
entries 1-5). To our delight, Fe (NO3)3 showed higher catalytic
activity than other iron salts and the desired product 3a was
isolated in 60% yield (Table 1, entry 5). When TEMPO (5 mol %) was
added in the reaction, it could greatly enhance the product yield to
75% (Table 1, entry 6). Further, we found that 10 mol% of Fe(NO3)3
and 10 mol% of TEMPO were sufficient for this transformation
(Table 1, entries 6-8). Next, we screened different bases, the results
revealed that KOH and CsOH were the most effective for the
reaction and gave good yield of 3a (Table 1, entries, 8, 11-14). The
e
f
yield. d Reaction at 90 °C. Reaction at 120 °C. Reaction carried
out under nitrogen.
amount of base was also tested (Table 1, entries 8-10).
Subsequently, the effect of solvents was investigated to further
optimize the reaction. It was also found that toluene showed the
best efficiency compared with other solvents such as DMSO, DMF,
dioxane, CH3CN, DMC and H2O (Table 1, entries 15-20). In addition,
the reaction activities were found inhibited with higher or lower the
reaction temperature than100 oC (Table 1, entries 21 and 22).
When the reaction was carried out under nitrogen, the desired
product was not observed, which indicated that the importance of
molecular oxygen as the terminal oxidant (Table 1, entry 23).
Therefore, we chose 10 mol% Fe(NO3)3, 10 mol% TEMPO, 0.5 equiv
2 | J. Name., 2012, 00, 1-3
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KOH in toluene at 100 oC under air as standard reaction
conditions(Table 1, entry 8).
With the optimized reaction conditions in hand, the scope and
generality of this Fe/TEMPO-catalyzed tandem reaction for
synthesis of 2-substituted quinazolinones were explored and the
results were summarized in Table 2. Firstly, we investigated the
reaction between 2-aminobenzamide (1a) and various primary
alcohols (2) under standard condition. To our delights, electron-
donating and electron-withdrawing groups were well tolerated in
the reactions. Generally, as is shown in Table 2, primary benzylic
alcohols bearing electron-donating groups such as methyl, methoxyl,
tert-butyl gave the target products in excellent isolated yields of 87-
96% (Table 2, 3ab-3ag). However, the electron-withdrawing groups
such as -F, -Br, -Cl, -NO2 and -CF3 substituted benzylic alcohols gave
comparably low yields of products (Table 2, 3ah-3an). The methyl 4-
(hydroxymethyl)benzoate could also be converted to the desired
products in the absence of KOH (Table 2, 3ao). The reaction of 1-
naphthylmethanol and 2-naphthylmethanol with 1a produced the
corresponding products 3ap and 3aq in 88% and 81% yields,
respectively. Notably, both piperonyl alcohol and cinnamyl alcohol
were well-tolerated in the present catalytic system (Table 2, 3ar and
3as). In addition, heterocyclic alcohols such as 2-pyridinemethanol,
2-furanemethanol and 2-thiophenemethanol were tested
successively and the desired products were obtained in 70-88%
yields as well (Table 2, 3at-3av). In the case of aliphatic alcohols
Table 2． Aerobic oxidative synthesis of quinazolinones from 2a
and various primary alcohols. a
Table 3．Aerobic oxidative synthesis of quinazolinones from
primary alcohols and a series 2-aminobenzamides. a
O
O
O
N
O
Cl
NH
NH
NH
N
N
3ba, 93%
3da, 86%
3ca, 90%
O
O
O
Br
O2N
NH
NH
N
NH
NH
NH
N
Cl
N
N
3ea, 83%
3ga, 83%
3fa, 76%
O
O
O
Cl
NH
Cl
N
N
N
O
O
O
3gu, 80%
3cu, 87%
3du, 82%
O
O
O
N
N
N
N
N
3ha, 82%
3he, 79%
3hi, 88%
Br
O
O
O
Ph
Ph
N
N
N
N
a
3id, 43%
3ia, 51%
Reaction condition: 1a (1 mmol), 2 (1 mmol), Fe(NO3)3·9H2O (10
a
mol %), TEMPO (10 mol %), KOH (0.5 equiv) , toluene (2 mL), in a 10
mL Schlenk tube stirred for 12 h at 100 °C under air balloon and
then monitored by TLC. Isolated yield. b The reaction was performed
without KOH. c Reaction for 24h.
Reaction condition: 1 (1 mmol), 2 (1 mmol), Fe(NO3)3·9H2O (10
mol %), TEMPO (10 mol %), KOH (0.5 equiv) , toluene (2 mL), in a 10
mL Schlenk tube stirred for 12 h at 100 °C under air balloon and
then monitored by TLC. Isolated yield.
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such as phenethyl alcohol, n-butyl alcohol and n-pentyl alcohol
could also be transformed to the desired products in 46- 65% yields
(Table 2, 3aw-3ay).
To further expand the substrate scope, we investigated the
reactions of substituted 2-aminobenzamides with primary alcohols
and the results were summarized in Table 3. It was observed that 2-
aminobenzamides bearing electron-withdrawing or electron-
donating functional groups could be smoothly converted to the
desired products in good yields of 76-93% (Table 3,3ba-3ga). And
the reaction of 2-furanemethanol with different substituted 2-
aminobenzamides proceeded smoothly to generate the
corresponding products 3cu, 3du and 3gu in the yield of 87%, 82%
and 80%, respectively. Furthermore, the reaction of sterically
Scheme 4. A plausible reaction mechanism.
demanding
2-amino-N-methylbenzamide
and
2-amino-N-
phenylbenzamide were found to be effective and the corresponding
products were produced in good yields (Table 3, 3ha, 3he , 3hi, 3ia
and 3id).
Conclusions
In summary, we have disclosed
a
one-pot efficient
Fe(NO3)3/TEMPO-catalyzed protocol for aerobic oxidative synthesis
of quinazolinones from easily accessible primary alcohols and 2-
aminobenzamides with molecular oxygen as the terminal oxidant.
This synthetically valuable procedure exhibits good functional group
tolerance and a variety of quinazolinones are obtained in moderate
to excellent yields. In addition, a plausible reaction mechanism has
been proposed and further more synthetic applications of this
catalytic system are under way in our laboratory.
Experimental Section
Experimental details
All reagents were purchased from commercial suppliers without
further purification. Column chromatography was carried out over
200-300 mesh silica gel. The 1H and 13C NMR spectra were recorded
on a Bruker Avance III 500 MHz spectrometer with deuterated
dimethyl sulfoxide (DMSO-d6) or CDCl3 as the solvent and
tetramethylsilane (TMS) as an internal standard at room
temperature. Chemical shifts are given in δ relative to TMS, and the
coupling constants J are given in hertz. High-resolution mass spectra
(HRMS) were obtained on an Agilent mass spectrometer using ESI-
TOF (electrospray ionization-time of flight). IR spectra were
recorded on a NicoletiS10 FT-IR spectrometer as KBr pellets.
Melting points were determined using an electrothermal capillary
melting point apparatus.
Scheme 3. Control experiments
To elucidate the reaction mechanism, the following control
experiments were carried out. As shown in Scheme 3, firstly,
benzaldehyde (4) was generated in suit from benzyl alcohol (2a)
under standard condition. Next, we conducted the reaction of 2-
aminobenzamide (1a) and benzaldehyde (4) in the absence of
Fe(NO3)3, TEMPO and KOH under nitrogen atmosphere in toluene,
which resulted in 96% yield of 2-phenyl-2,3-dihydroquinazolin-4(1
H)-one (5). Then, the aminal intermediate (5) was oxidized to the
desired product in 98% yield under standard condition.
Based on the results above, a plausible mechanism of the
oxidative condensation of 2-aminobenzamides with primary
alcohols is presented in Scheme 4. The initial step involves the
aerobic oxidation of alcohols to the corresponding aldehydes (I)
catalyzed by Fe/TEMPO which has been already reported by Ma et
al..25b Next, the aldehydes react with 2-aminobenzamides to form
the imine intermediates (II), which after cyclization generates 2, 3-
dihydroquinazolinones (III). At last, the aminal intermediates (III)
undergo an aerobic oxidative dehydrogenation to give the
corresponding quinazolinone products.
Typical procedure for the synthesis of quinazolinones.
To a mixture of 2-aminobenzamide 1a (1 mmol), benzyl alcohol 2a
(1 mmol), Fe(NO3)3·9H2O (10 mol %), TEMPO (10 mol %) , KOH (0.5
equiv) and toluene (2 mL) were added in a 10 mL Schlenk tube.
Then the mixture was stirred at 100 oC for 12 h under air balloon.
The progress of the reaction was monitored by TLC. After
completion of the reaction, the solution was diluted with ethyl
acetate, washed with water, and then the organic layer was
separated and dried over anhydrous MgSO4. The solvent was
concentrated under reduced pressure and the crude product was
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purified by column chromatography on silica gel using PE/EtOAc as 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.40 (d, J = 2.2 Hz, 2H), 6.71 (s, 1H), 3.86
eluent to afford the pure product 3a.
(s, 6H); 13C NMR (125 MHz, DMSO-d6): δ=162.4, 160.7, 152.0, 148.8,
134.8, 127.8, 126.8, 126.0, 121.2, 105.7, 104.0, 55.7.
2-Phenylquinazolin-4(3H)-one (3aa):6c White solid; 95% yield (211
mg); mp 236-237 °C; IR (KBr): 3193, 3061, 1660, 1605,1481,769 cm-1;
1H NMR (500 MHz, DMSO-d6): δ=12.57 (br s, 1H), 8.21–8.17 (m,
3H), 7.85 (t, J = 7.6 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.62–7.52 (m,
4H); 13C NMR (125 MHz, DMSO-d6): δ 162.4, 152.4, 148.9, 134.7,
132.9, 131.5, 128.7, 127.9, 127.6, 126.7, 126.0, 121.1.
2-(4-Fluorophenyl)quinazolin-4(3H)-one (3ah):6c Yellow solid; 85%
yield (204 mg); mp 284–286 °C; IR (KBr): 3171, 3047, 1659, 1601,
1482, 1095 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.58 (br s, 1H),
8.32–8.21 (m, 2H), 8.16 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 7.4 Hz, 1H),
7.74 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 7.3 Hz, 1H), 7.40 (t, J = 8.5 Hz,
2H); 13C NMR (125 MHz, DMSO-d6): δ=164.2 (d, J = 249.4 Hz), 162.4,
151.6, 148.8, 134.8, 130.5 (d, J = 7.7 Hz), 129.4, 127.6, 126.8, 126.0,
121.0, 115.8(d, J = 21.9 Hz) .
2-(o-Tolyl)quinazolin-4(3H)-one (3ab):7g White solid; 87% yield (205
mg); mp 216–218 °C; IR (KBr): 3159, 3057,1674, 1609, 1485 cm-1; 1H
NMR (500 MHz, DMSO-d6): δ=12.46 (br s, 1H), 8.18 (d, J = 7.9 Hz,
1H), 7.86–7.83 (m, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.58–7.48 (m, 2H),
7.47–7.40 (m, 1H), 7.38 – 7.30 (m, 2H), 2.40 (s, 3H); 13C NMR (125
MHz, DMSO-d6): δ=161.9, 154.5, 148.9, 136.3, 134.6, 134.4, 130.70,
130.1, 129.3, 127.5, 126.8, 126.0, 125.9, 121.2, 19.7.
2-(4-Bromophenyl)quinazolin-4(3H)-one (3ai):7e White solid; 89%
yield (266 mg); mp 293-295 °C; IR (KBr): 3123, 3027, 1668, 1599,
1480 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.63 (br s, 1H), 8.15
(m, 3H), 7.85 (t, J = 7.5 Hz, 1H), 7.76 (t, J = 9.2 Hz, 3H), 7.54 (t, J = 7.3
Hz, 1H); 13C NMR (125 MHz, DMSO - d6): δ=162.3, 151.6, 148.7,
134.9, 132.1, 131.8, 130.0, 127.7, 127.0, 126.1, 125.4, 121.2.
2-(m-Tolyl)quinazolin-4(3H)-one (3ac):6c White solid; 90% yield
(212 mg); mp 221-223 °C; IR (KBr): 3119, 2963, 1672, 1608, 1488
2-(4-Chlorophenyl)quinazolin-4(3H)-one (3aj):20White solid; 90%
yield (230 mg); mp 298-300 °C; IR (KBr): 3163, 3056, 1668, 1600,
1477 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.62 (br s, 1H), 8.28 –
1
cm-1; H NMR (500 MHz, DMSO-d6): δ=12.49 (br s, 1H), 8.17 (d, J =
7.8 Hz, 1H), 8.04 (s, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.87–7.82 (m, 1H),
7.76 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.46–7.38 (m, 2H),
2.42 (s, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.4, 152.5, 149.0, 8.10 (m, 3H), 7.85 (d, J = 6.9 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.63 (d,
J = 7.7 Hz, 2H), 7.54 (t, J = 6.7 Hz, 1H); 13C NMR (125 MHz, DMSO-
138.1, 134.7, 132.8, 132.2, 128.7, 128.5, 127.7, 126.7, 126.0, 125.1,
121.2, 21.1.
d6): δ=162.3, 151.5, 148.8, 136.5, 134.8, 131.7, 129.8, 128.9, 127.7,
127.0, 126.0, 121.2.
2-(p-Tolyl)quinazolin-4(3H)-one (3ad):6c White solid; 95% yield (224
mg); mp 241-243 °C; IR (KBr): 3173, 3062, 1655, 1601, 1487 cm-1; 1H
NMR (500 MHz, DMSO-d6): δ=12.48 (br s, 1H), 8.16 (d, J = 7.8 Hz,
1H), 8.11 (d, J = 8.2 Hz, 2H), 7.87–7.80 (m, 1H), 7.74 (d, J = 8.0 Hz,
2-(3-Chlorophenyl)quinazolin-4(3H)-one (3ak):20 White solid; 81%
yield (207 mg); mp 295-296 °C; IR (KBr): 3172, 3062, 1672, 1608,
1471 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.63 (br s, 1H), 8.25 (s,
1H), 8.21 – 8.12 (m, 2H), 7.86 (t, J = 7.5 Hz, 1H), 7.77 (d, J = 8.1 Hz,
1H), 7.67 (d, J = 8.1 Hz, 1H), 7.54 – 7.61ppm (m, 2H); 13C NMR (125
MHz, DMSO-d6): δ=162.3, 151.2, 148.7, 134.9, 133.6, 131.3, 130.7,
128.8, 127.8, 127.7, 127.1, 126.6, 126.1, 121.3 .
1H), 7.52 (t, J = 7.4 Hz, 1H), 7.36 (d, J = 8.1 Hz, 2H), 2.40 (s, 3H); 13
C
NMR (125 MHz, DMSO-d6): δ=162.4, 152.4, 149.0, 141.6, 134.7,
130.1, 129.4, 127.9, 127.6, 126.6, 126.0, 121.1, 21.2.
2-(4-Methoxyphenyl) quinazolin-4(3H)-one (3ae):6c White solid;
96% yield (242 mg); mp 248–251 °C; IR (KBr): 3174, 3062, 1667,
1598,1484, 1061 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.42 (br s,
1H), 8.21 (d, J = 8.9 Hz, 2H), 8.14 (d, J = 6.9 Hz, 1H), 7.82 (t, J = 7.6
Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.10 (d, J =
8.9 Hz, 2H), 3.86 (s, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.5,
162.0, 152.0, 149.1, 134.7, 129.6, 127.5, 126.3126.0, 125.0, 120.9,
114.2, 55.6.
2-(4-Nitrophenyl)quinazolin-4(3H)-one (3al):20 Brown solid;72%
yield (192 mg); mp >300 °C; IR (KBr): 3082, 2945, 1673, 1608, 1519,
1
1486, 1345 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.84 (br s, 1H),
8.41 (dd, J = 17.8, 8.5 Hz, 4H), 8.19 (d, J = 7.7 Hz, 1H), 7.89 (t, J = 7.4
Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H); 13C NMR (125
MHz, DMSO-d6): δ=162.3, 150.9, 149.2, 148.5, 138.7, 135.0, 129.5,
127.9, 127.5, 126.1, 123.8, 121.4.
2-(4-(tert-Butyl)phenyl)quinazolin-4(3H)-one (3af):22 White solid;
2-(3-Nitrophenyl)quinazolin-4(3H)-one (3am):20 Brown solid;67%
94% yield (261 mg); mp 239–242 °C; IR (KBr): 3176, 3063, 1667,
1
1595, 1483 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.50 (br s, 1H),
yield (179 mg); mp >300 °C; IR (KBr): 3078,2966, 1672, 1604,1525,
1
1447, 1320 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.88 (br s, 1H),
8.15 (t, J = 8.0 Hz, 3H), 7.84 (t, J = 7.6 Hz, 1H), 7.74 (d, J = 8.1 Hz,
1H), 7.57 (d, J = 8.4 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 1.33 (s, 9H); 13
C
9.03 (s, 1H), 8.62 (d, J = 7.5 Hz, 1H), 8.44 (d, J = 7.7 Hz, 1H), 8.19 (d, J
= 7.6 Hz, 1H), 7.92 – 7.78 (m, 3H), 7.58 (t, J = 7.2 Hz, 1H); 13C NMR
(125 MHz, DMSO-d6): δ=162.3, 150.7, 148.5, 148.2, 135.0, 134.5,
134.2, 130.5, 127.9, 127.4, 126.1, 126.0, 122.9, 121.4.
NMR (125 MHz, DMSO-d6): δ=162.4, 154.5, 152.3, 149.0, 134.7,
130.1, 127.7, 127.6, 126.6, 126.0, 125.6, 121.1, 34.8, 31.1.
2-(3, 5-Dimethylphenyl)quinazolin-4(3H)-one (3ag):7bWhite solid;
92% yield (259 mg); mp 248–250 °C; IR (KBr): 3178, 3068, 1667,
1608, 1460, 1073 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.49 (br
s, 1H), 8.17 (d, J = 7.9 Hz, 1H), 7.87–7.82 (m, 1H), 7.76 (d, J = 7.9 Hz,
2-(4-(Trifluoromethyl)phenyl)quinazolin-4(3H)-one (3an):26 White
solid; 83% yield (241 mg); mp 284–286 °C; IR (KBr): 3180, 3045,
1663, 1602, 1489, 1336 cm-1; 1H NMR (500 MHz, DMSO-d6):
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Journal Name
δ=12.75 (br s, 1H), 8.38 (d, J = 7.1 Hz, 2H), 8.19 (d, J = 7.0 Hz, 1H), 4.5 Hz, 1H), 8.47 (d, J = 7.9 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H), 8.09 (td,
7.90 (m, 3H), 7.79 (d, J = 7.3 Hz, 1H), 7.57 (s, 1H); 13C NMR (125 J = 7.8, 1.5 Hz, 1H), 7.91–7.86 (m, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.70 –
MHz, DMSO-d6): δ=162.5, 151.6, 148.9, 137.1, 135.1, 131.7(q, JC- 7.64 (m, 1H), 7.59 (t, J = 7.4 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
F=31.7), 129.2, 128.1, 127.6, 126.3, 125.9 (q, JC-F = 3.2 Hz), 124.4(q, δ=160.9, 150.1, 149.2, 148.9, 148.6, 138.2, 134.9, 127.9, 127.4,
JC-F = 271.5 Hz), 121.7.
126.8, 126.3, 122.3, 122.2.
2-(4-Methoxycarbonylphenyl)quinazolin-4(3H)-one (3ao):7c Light 2-(Furan-2-yl)-Quinazolinone-4(3H)-one (3au):22 White solid; 88%
yellow solid; 48% yield (134 mg); mp 254-256°C; IR (KBr): 3172, yield (187 mg); mp 218-220 °C; IR (KBr): 3176, 3019, 1620, 1601,
1
3060, 2956, 1929, 1663, 1439, 1279, 1112 cm-1; H NMR (500 MHz, 1479, 770 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.53 (br s, 1H),
DMSO-d6) δ=12.70 (s, 1H), 8.31 (d, J = 8.3 Hz, 2H), 8.18 (d, J = 7.8 Hz, 8.14 (dd, J = 7.9, 1.2 Hz, 1H), 8.02 (d, J = 1.0 Hz, 1H), 7.85–7.80 (m,
1H), 8.10 (d, J = 8.2 Hz, 2H), 7.87 (t, J = 7.3 Hz, 1H), 7.78 (d, J = 8.0 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.65 (d, J = 3.4 Hz, 1H), 7.53–7.48 (m,
Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 3.91 (s, 3H). 13C NMR (125 MHz, 1H), 6.77 (dd, J = 3.5, 1.7 Hz, 1H); 13C NMR (125 MHz, DMSO-d6):
DMSO-d6) δ=165.8, 162.3, 151.6, 148.7, 137.0, 134.9, 131.9, 129.4, δ=161.7, 148.8, 146.8, 146.3, 144.2, 134.8, 127.4, 126.6, 126.1,
128.4, 127.8, 127.2, 126.1, 121.3, 52.6.
121.3, 114.7, 112.7.
2-(Naphthalen-1-yl)quinazolin-4(3H)-one (3ap):7d White solid; 88%
yield (239 mg); mp 278-281 °C; IR (KBr): 3156, 2998, 1671, 1651,
1467, 764 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.67 (br s, 1H),
8.23 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 7.7 Hz, 1H), 8.13 (d, J = 8.2 Hz,
1H), 8.05 (d, J = 8.4 Hz, 1H), 7.87 (t, J = 7.6 Hz, 1H), 7.80 (d, J = 7.0
Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.57 - 7.62
(m, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.1, 153.9, 148.9,
134.7, 133.3, 131.9, 130.6, 130.4, 128.5, 127.9, 127.7, 127.3, 127.0,
126.5, 126.0, 125.4, 125.2, 121.4.
2-(Thiophen-2-yl)quinazolin-4(3H)-one (3av):22 White solid; 81%
(184 mg); mp 275-276 °C; IR (KBr): 3171, 3051, 1660, 1610, 1491
1
cm-1; H NMR (500 MHz, DMSO-d6): δ=12.66 (br s, 1H), 8.25 (d, J =
4.6 Hz, 1H), 8.14 (d, J = 7.9 Hz, 1H), 7.88 (d, J = 5.0 Hz, 1H), 7.81 (t, J
= 7.7 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.27–
7.23 (m, 1H); 13C NMR (125 MHz, DMSO-d6): δ=162.0, 148.8, 148.0,
137.5, 134.9, 132.3, 129.6, 128.7, 127.1, 126.5, 126.2, 121.1.
2-Benzylquinazolin-4(3H)-one (3aw):20 White solid; 65% (153 mg);
mp 245-247°C; IR (KBr): 3170, 3058, 1660, 1600, 1482 cm-1; 1H NMR
(500 MHz, DMSO-d6): δ=12.41 (br s, 1H), 8.08 (d, J = 7.8 Hz, 1H),
7.78 (t, J = 7.7 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.47 (t, J = 7.5 Hz,
1H), 7.38 (d, J = 7.4 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.24 (t, J = 7.3
Hz, 1H), 3.94 (s, 2H); 13C NMR (125 MHz, DMSO-d6): δ=162.0, 156.1,
149.1, 136.7, 134.6, 129.0, 128.7, 127.1, 127.0, 126.4, 125.9, 120.9,
41.0.
2-(Naphthalen-2-yl)quinazolin-4(3H)-one(3aq):22 White solid; 81%
yield (220 mg); mp 214-216 °C; IR (KBr): 3192, 3056, 1666, 1612,
1471, 769 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.68 (br s, 1H),
8.83 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 7.6 Hz, 1H), 8.13 –
7.97 (m, 3H), 7.87 (t, J = 7.2 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.65 (s,
2H), 7.55 (t, J = 7.1 Hz, 1H). 13C NMR (125 MHz, DMSO-d6): δ=162.5,
152.5, 148.9, 134.8, 134.3, 132.5, 130.2, 129.1, 128.33, 128.28,
128.1, 127.8, 127.7, 127.1, 126.8, 126.1, 124.7, 121.2.
2-Propylquinazolin-4(3H)-one (3ax):7d White solid; 46% yield (86
mg); mp 203-205 °C; IR (KBr): 3167, 3030, 2964, 1672, 1607, 1470
1
cm-1; H NMR (500 MHz, DMSO-d6): δ=12.16 (br s, 1H), 8.08 (d, J =
2-(3,4-Methylenedioxyphenyl) quinazolin-4(3H)-one (3ar):27 White
solid; 90% yield (239 mg); mp 276-278 °C; IR (KBr): 3130, 3061,
1652, 1606, 1474, 1104 cm-1; 1H NMR (500 MHz, DMSO-d6):
δ=12.38 (br s, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 7.7 Hz, 2H),
7.75 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.08 (d, J
= 8.1 Hz, 1H), 6.15 (s, 2H); 13C NMR (125 MHz, DMSO-d6): δ=162.4,
151.8, 150.2, 148.9, 147.9, 134.7, 127.5, 126.7, 126.4, 126.0, 123.0,
120.9, 108.4, 107.7, 102.1.
7.8 Hz, 1H), 7.80 – 7.74 (m, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.46 (t, J =
7.5 Hz, 1H), 2.58 (t, J = 7.5 Hz, 2H), 1.79 – 1.71 (m, 2H), 0.94 (t, J =
7.4 Hz, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.0, 157.5, 149.1,
134.4, 127.0, 126.1, 125.8, 121.0, 36.5, 20.4, 13.7 ppm.
2-Butylquinazolin-4(3H)-one (3ay):20 White solid; 51% yield (103
mg); mp 108-110°C; IR (KBr): 3167, 3031, 2967, 1671, 1616, 1471
1
cm-1; H NMR (500 MHz, DMSO-d6): δ=12.17 (br s, 1H), 8.08 (d, J =
7.1 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.46 (t, J
= 7.5 Hz, 1H), 2.6 (t, J = 8 Hz, 2H), 1.75 – 1.67 (m, 2H), 1.34 (m, 2H),
0.91 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.0,
157.7, 149.1, 134.4, 127.0, 126.0, 125.8, 121.0, 34.4, 29.1, 21.9,
13.8.
2-Styrylquinazolin-4(3H)-one (3as):7d Light yellow solid; 79% yield
(196 mg); mp 226-228 °C; IR (KBr): 3186, 3042, 1662, 1607, 1446
1
cm-1; H NMR (500 MHz, DMSO-d6): δ=12.34 (br s, 1H), 8.12 (d, J =
7.7 Hz, 1H), 7.96 (d, J = 16.2 Hz, 1H), 7.82 (t, J = 7.4 Hz, 1H), 7.68 (t, J
= 7.7 Hz, 3H), 7.50 -7.42 (m, 4H), 7.02 (d, J = 16.2 Hz, 1H); 13C NMR
(125 MHz, DMSO-d6): δ=161.9, 151.6, 149.2, 138.4, 135.2, 134.7,
130.0, 129.3, 127.8, 127.3, 126.4, 126.0, 121.3.
6-Methoxy-2-phenylquinazolin-4(3H)-one (3ba):6c Light yellow
solid; 93% yield (234 mg); mp 244–246 °C; IR (KBr): 3156, 3018,
1666, 1620, 1448, 1028 cm-1; 1H NMR (500 MHz, DMSO-d6);
δ=12.52 (br s, 1H), 8.17 (d, J = 7.0 Hz, 2H), 7.71 (d, J = 8.9 Hz, 1H),
7.59–7.52 (m, 4H), 7.45 (dd, J = 8.9, 2.8 Hz, 1H), 3.90 (s, 3H); 13C
NMR (125 MHz, DMSO-d6): δ=162.2, 157.9, 150.3, 143.4, 133.0,
131.2, 129.4, 128.8, 127.7, 124.3, 122.0, 106.1, 55.8.
2-(Pyridin-2-yl)quinazolin-4(3H)-one (3at):28 White solid;70% yield
(156 mg); mp 170-173 °C; IR (KBr): 3176, 3080, 1672, 1606, 1005
cm-1; 1H NMR (500 MHz, DMSO-d6): δ=11.86 (br s, 1H), 8.77 (d, J =
6 | J. Name., 2012, 00, 1-3
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7-Chloro-2-(2-furanyl)-quinazolin-4(3H)-one (3gu):30 White solid;
7-Methyl-2-phenylquinazolin-4(3H)-one (3ca):29 White solid; 90% 80% yield (197 mg); mp 275-277 °C; IR (KBr): 3126, 3016, 1663,
1
yield (212 mg); mp 229−231 °C; IR (KBr): 3139, 3051, 1652, 1616, 1597, 1443 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.65 (br s, 1H),
1488 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.46 (br s, 1H), 8.18 (d, 8.11 (d, J = 7.7 Hz, 1H), 8.03 (s, 1H), 7.70 (d, J = 41.1 Hz, 2H), 7.52 (d,
J = 7.1 Hz, 2H), 8.05 (d, J = 8.0 Hz, 1H), 7.62 – 7.52 (m, 4H), 7.35 (d, J J = 7.4 Hz, 1H), 6.77 (s, 1H); 13C NMR (125 MHz, DMSO-d6): δ=161.2,
= 8.0 Hz, 1H), 2.48 (s, 3H); 13C NMR (125 MHz, DMSO-d6): δ=162.3, 150.0, 147.2, 145.9, 145.4, 139.4, 128.2, 126.8, 126.5, 120.2, 115.4,
152.5, 149.0, 145.2, 133.0, 131.5, 128.8, 128.2, 127.9, 127.3, 125.9, 112.8.
118.8, 21.5.
3-Methyl-2-phenylquinazolin-4(3H)-one (3ha):6c White solid; 82%
6-Chloro-2-phenylquinazolin-4(3H)-one (3da):26 White solid; 86% yield (194 mg); mp 125-127 °C; IR (KBr): 3058, 1676, 1609, 1473,
yield (220 mg); mp 276–278 °C; IR (KBr): 3161, 3026, 1671, 1603, 762 cm-1; H NMR (500 MHz, CDCl3): δ=8.34 (d, J = 8.0 Hz, 1H), 7.77
1
1481 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.71 (br s, 1H), 8.18 (d, (d, J = 3.7 Hz, 2H), 7.59–7.50 (m, 6H), 3.51 (s, 3H); 13C NMR (125
J = 6.4 Hz, 2H), 8.09 (s, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.77 (d, J = 8.2 MHz, CDCl3): δ=162.5, 155.9, 147.0, 135.1, 134.1, 129.8, 128.7,
Hz, 1H), 7.64-7.52 (m, 3H); 13C NMR (125 MHz, DMSO-d6): δ=161.5, 127.8, 127.2, 126.7, 126.4, 120.3, 34.0.
153.0, 147.7, 134.9, 132.6, 131.8, 130.9, 129.9, 128.8, 128.0, 125.1,
122.4.
3-Methyl-2-(4-methoxyphenyl)quinazolin-4(3H)-one (3he):7d White
solid; 79% yield (210 mg); mp 141-143 °C; IR (KBr): 3058, 1672,
1
6-Bromo-2-phenylquinazolin-4(3H)-one (3ea):29 White solid;83% 1603,1472, 1021 cm-1; H NMR (500 MHz, CDCl3): δ=8.32 (d, J = 7.7
yield (249 mg); mp 284−286 °C; IR (KBr): 3166, 3057, 1663, 1598, Hz, 1H), 7.78–7.70 (m, 2H), 7.56–7.51 (m, 2H), 7.48 (m, 1H), 7.03 (d,
1462 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.74 (br s, 1H), 8.23 (s, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.53 (s, 3H); 13C NMR (125 MHz, CDCl3):
1H), 8.18 (d, J = 7.4 Hz, 2H), 7.98 (d, J = 10.0 Hz, 1H), 7.70 (d, J = 8.6 δ=157.9, 155.9, 151.0, 142.4, 129.2, 124.7, 122.7, 122.4, 121.7,
Hz, 1H), 7.64–7.50 (m, 3H); 13C NMR (125 MHz, DMSO-d6): δ=161.4, 121.6, 115.3, 109.2, 50.4, 29.4.
153.1, 147.9, 137.6, 132.6, 131.8, 130.0, 128.8, 128.2, 128.0, 122.8,
119.1.
3-Methyl-2-(4-bromophenyl)quinazolin-4(3H)-one (3hi):7e White
solid; 88% yield (276 mg); mp >300 °C; IR (KBr): 3059, 1674, 1609,
6-Nitro-2-phenylquinazolin-4(3H)-one (3fa):20 Yellow solid; 76% 1473 cm-1; 1H NMR (500 MHz, CDCl3): δ=8.33 (d, J = 8.1 Hz, 1H), 7.77
yield (203 mg); mp 296−298 °C; IR (KBr): 3160, 3081, 1672, 1606, (m, 2H), 7.69 (d, J = 8.3 Hz, 2H), 7.57 – 7.50 (m, 1H), 7.48 (d, J = 8.3
1530, 1451, 1351 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=13.01 (br s, Hz, 2H), 3.51 (s, 3H).13C NMR (125 MHz, CDCl3): δ=162.3, 154.8,
1H), 8.85 (d, J = 2.5 Hz, 1H), 8.57 (dd, J = 9.0, 2.6 Hz, 1H), 8.23 (d, J = 146.9, 134.0, 131.9, 129.5, 127.2, 127.0, 126.5, 124.4, 120.3, 34.0.
7.6 Hz, 2H), 7.93 (d, J = 9.0 Hz, 1H), 7.66 (t, J = 7.2 Hz, 1H), 7.59 (t, J
2,3-Diphenylquinazolin-4(3H)-one (3ia):6c White solid; 51% yield
(152 mg); mp 151-153 °C; IR (KBr): 3123, 3080, 1682, 1604, 1471,
1271; 1H NMR (500 MHz, DMSO) δ=8.21 (d, J = 8.2 Hz, 1H), 7.91 (t, J
= 7.0 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.39–
7.20 (m, 10H). 13C NMR (125 MHz, DMSO) δ=161.6, 155.4, 147.4,
138.0, 135.8, 135.0, 129.7, 129.1,128.8, 128.3, 127.7, 127.6,
127.3,126.6, 120.9.
= 7.5 Hz, 2H); 13C NMR (125 MHz, DMSO-d6): δ= 161.8, 155.9, 153.1,
144.9, 132.5, 132.3, 129.3, 128.9, 128.7, 128.4, 122.2, 121.2.
7-Chloro-2-phenylquinazolin-4(3H)-one (3ga):6c White solid; 83%
yield (212 mg); mp 284-286 °C; IR (KBr): 3171, 3080, 1664, 1600,
1
1487 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.68 (br s, 1H), 8.20 –
8.14 (m, 3H), 7.80 (s, 1H), 7.64–7.52 (m, 4H); 13C NMR (125 MHz,
DMSO-d6): δ= 161.9, 154.0, 150.0, 139.3, 132.6, 131.9, 128.8, 128.1,
127.0, 126.7, 120.0.
3-Phenyl-2-(p-tolyl)quinazolin-4(3H)-one (3id): 6c White solid; 43%
yield (134 mg); mp 170-172 °C; IR (KBr): 3127, 3060, 2956, 1729,
1663, 1429, 1279; 1H NMR (500 MHz, DMSO) δ=8.19 (d, J = 7.9 Hz,
1H), 7.89 (t, J = 7.7 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.59 (t, J = 7.5
7-Methyl-2-furanylquinazolin-4(3H)-one (3cu):6b White solid; 87%
yield (197 mg); mp 240-242 °C; IR (KBr):3118, 3029, 1656, 1607,
1477 cm-1; 1H NMR (500 MHz, DMSO-d6): δ=12.42 (br s, 1H), 8.01 (d,
J = 7.9 Hz, 2H), 7.62 (d, J = 3.2 Hz, 1H), 7.51 (s, 1H), 7.32 (d, J = 7.9
Hz, 1H), 6.75 (s, 1H), 2.46 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
δ=161.6, 149.0, 146.8, 146.3, 145.3, 144.2, 128.1, 127.1, 126.0,
118.9, 114.5, 112.7, 21.5.
Hz, 1H), 7.35 – 7.24 (m, 7H), 7.03 (d, J = 8.0 Hz, 2H), 2.22 (s, 3H). 13
C
NMR (125 MHz, DMSO) δ=161.6, 155.3, 147.5, 138.7, 138.1, 134.9,
133.0, 129.7, 129.1, 128.8, 128.3,128.2, 127.6, 127.2, 126.6, 120.8,
21.0.
Procedure for the preparation of compound 5
6-Chloro-2-(2-furanyl)-quinazolin-4(3H)-one (3du): White solid;
A mixture of 1a (1 mmol) and benzaldehyde (1 mmol) in toluene (2
mL) was stirred at 100 oC for 6 h under a N2 atmosphere. After
completion of the reaction, the solution was diluted with ethyl
acetate, washed with water, and then the organic layer was
separated and dried over anhydrous MgSO4. The solvent was
evaporated under reduced pressure and the crude product was
purified by chromatography on silica gel, eluting with PE/EtOAc, to
afford 5 as white solid in 90% isolated yield.
82% yield (202 mg); mp293-295 °C; IR (KBr): 3179, 3028, 1657,
1
1617, 1456 cm-1; H NMR (500 MHz, DMSO-d6): δ=12.69 (br s, 1H),
8.06 (d, J = 2.3 Hz, 1H), 8.02 (s, 1H), 7.84 (dd, J = 8.7, 2.5 Hz, 1H),
7.71 (d, J = 8.7 Hz, 1H), 7.65 (d, J = 3.4 Hz, 1H), 6.77 ppm (dd, J = 3.3,
1.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): δ=160.8, 147.6, 147.0,
146.0, 144.6, 134.9, 130.8, 129.6, 125.1, 122.6, 115.1, 112.8. HRMS
(ESI) m/z calcd for C12H7ClN2O2 [M + H]+ 247.0274, found 247.0288.
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ARTICLE
Journal Name
16 R. Cheng, T. Guo, D. Zhang-Negrerie, Y. Du and K. Zhao, Synthesis,
2013, 45, 2998-3006.
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2-Phenyl-2,3-dihydroquinazolin-4(1H)-one:31 White solid; 96% yield
(215mg);
mp
216-218°C;
IR
(KBr):
3302,
3169,
3059,2961,1668,1609, 1474 cm-1; 1H NMR (500 MHz, DMSO-d6) δ
8.28 (s, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.3 Hz, 2H), 7.37 (m,
3H), 7.24 (t, J = 7.5 Hz, 1H), 7.10 (s, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.67
(t, J = 7.4 Hz, 1H), 5.75 (s, 1H); 13C NMR (125 MHz, DMSO-d6):
δ=163.8, 148.0, 141.8, 133.5, 128.6, 128.5, 127.5, 127.0, 117.3,
115.1, 114.6, 66.7.
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Graphical Abstract
A highly efficient, one-pot Fe(NO3)3/TEMPO-catalyzed protocol for aerobic oxidative synthesis of quinazolinones
from easily accessible primary alcohols and 2-aminobenzamides with molecular oxygen as the terminal oxidant.