Synthesis and antifungal bioactivities of 3-alkylquinazolin- 4-one derivatives

Article abstract of DOI:10.3390/11060383

A simple, efficient, and general method has been developed for the synthesis of various 3-alkylquinazolin-4-one derivatives from quinazolin-4-one treated with alkyl bromides under phase transfer catalysis condition. The structures of the compounds were characterized by elemental analysis, IR, ¹H-NMR and ¹³C-NMR spectra. Title compound 6-bromo-3-propylquinazolin-4-one (3h) was found to possess good antifungal activity.

Full text of DOI:10.3390/11060383

Molecules 2006, 11, 383-392
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Synthesis and Antifungal Bioactivities of
3
-Alkylquinazolin- 4-one Derivatives
*
Guiping Ouyang, Peiquan Zhang, Gangfang Xu, Baoan Song , Song Yang, Linhong Jin, Wei
Xue, Deyu Hu, Ping Lu and Zhuo Chen
Center for Research and Development of Fine Chemicals, Guizhou University, Key Laboratory of
Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang, 550025, P. R.
China. E-mails: oygp710@163.com, pqzhang@126.com, xuguangf04@163.com, yangsdqj@126.com,
fcc.lhjin@gzu.edu.cn, shouldww@163.com, fcc.dyhu@gzu.edu.cn, luping217@sohu.com
*
8
Author to whom correspondence should be addressed; E-mail:songbaoan22@yahoo.com Tel.:(+86)
51 3620521, Fax: (+86) 851 3622211
Received: 26 April 2006 / Accepted: 12 June 2006 / Published: 12 June 2006
Abstract: A simple, efficient, and general method has been developed for the synthesis of
various 3-alkylquinazolin-4-one derivatives from quinazolin-4-one treated with alkyl
bromides under phase transfer catalysis condition. The structures of the compounds were
1
13
characterized by elemental analysis, IR, H-NMR and C-NMR spectra. Title compound
-bromo-3-propylquinazolin-4-one (3h) was found to possess good antifungal activity.
6
Keywords: Quinazolinone, Phase Transfer Catalyst, synthesis, antifungal activity
Introduction
A variety of the reports regarding synthetic studies of quinazolinone derivatives have been
presented due to the chemical and biological interests to the quinazoline [1, 2]. Quinazoline
compounds are widely used in agrochemicals as plant virucides [3], antifungal agents [4] and
herbicides [5]. According to recent data, quinazoline nucleus has attracted the attention of medicinal
chemists due to its well known anticancer activity, and many substituted quinazoline derivatives have
recently earned great interest in chemotherapy as antitumor drugs [6, 7]. In order to find potential new
plant fungicides and anticancer agents, we had designed and synthesized a series of

Molecules 2006, 11
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84
N-aryl-4-aminoquinazoline compounds, among which some compounds were found to possess
moderate bioactivity [8]. In this report we designed and synthesized series of
-alkylquinazolin-4-one derivatives and investigated their bioactivities. The synthetic route was shown
a
3
1
13
in Scheme 1. The structures of 3 were firmly established by well defined IR, H-NMR, C-NMR and
elemental analysis. Preliminary bioassay tests showed that some compounds displayed antifungal
activity against three fungi at 50 µg/mL in vitro, but with a degree of variation. It was found that title
compound 3h displayed strong in vitro antifungal activity on hyphal growth of F. oxysporum, Valsa
mali and Gibberella zeae.
Scheme 1 Synthetic route to the title compounds.
O
O
N
X
COOH
X
RX
X
HCONH2
NH
N R
PTC
NH2
N
1
3
2
X= H, F, Cl, Br. R= Et, n-Pr, Allyl
Results and Discussion
In order to optimize the reaction conditions, the synthesis of 3e was carried out under various
conditions. The effects of KOH concentration, reaction time, reaction temperature, presence or absence
of a phase transfer catalyst (PTC) on the reaction were investigated and the results are shown in Table
1
. When no tetrabutylammonium bromide was used as PTC, the reaction was relatively slow and the
product was obtained in 8.5 % refluxed at 88-90 °C for 1 h (Table 1, entry 5), while the use of the
PTC obviously accelerated the reaction (Table 1, entries 1-4). While the yield of 3e increased to 77.1
%
also in 1 h when the reaction was catalyzed by 0.08 equiv Bu
the amount of Bu NBr increased from 3 % to 5 %, 8 % and 10 %, 3e could be obtained in 38.8 % and
2.2 %, 77.1 % and 77.4 %, respectively (Table 1, entries 1-4). The effect of KOH concentration was
also studied. When KOH concentration increased from 10 %, to 20 %, 30 % and 35 % with Bu NBr as
4
NBr (Table 2, entries 3 and 5). When
4
6
4
catalyst, 3e could be obtained in 48.5 %, 69.1 %, 77.1 % and 83.0 %, respectively (entries 6-7, 3, 8).
Interestingly, lower yield of 3e was obtained when KOH concentration increased from 35 % to 40 %
(
entries 8-9), which indicated that 35 % was the best KOH concentration. Using 8 mol%
tetrabutylammonium bromide as catalyst, the yield of 3e increased from 55.9 % to 83.0 % when the
reaction time was prolonged from 0.5 to 1 h refluxed at 88-90 °C (entries 8, 14 and 15). When the
reaction time was prolonged further to 2 h, tiny improvement (83.8 %, entry 13) was obtained, as
compared to that of 1 h (83.0 %, entry 8). As for the reaction temperature, it could be seen that the
yield was relatively low when the reaction was carried out at 20-65°C (Table 1, entries 10-12) than that
at 88-90 °C (entry 8).

Molecules 2006, 11
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85
Table 1 Different reaction conditions for synthesis of 3e.
Reaction time KOH concentration
The amount of
Reaction
a
b
Entry
Yield / %
/
h
/ % (w/w)
Bu NBr / mol %
temperature / °C
88-90
4
1
2
3
4
5
6
7
8
9
1
30
30
30
30
3
38.8
62.2
77.1
77.4
8.5
1
1
1
1
1
1
1
1
1
1
1
2
5
88-90
8
88-90
10
88-90
30
10
20
35
40
35
35
35
35
35
35
0
8
8
8
8
8
8
8
8
8
8
88-90
88-90
48.5
69.1
83.0
74.0
4.3
88-90
88-90
88-90
1
0
20-25
1
1
2
3
4
5
40-45
13.3
65.0
83.8
74.5
55.9
1
1
1
1
60-65
88-90
0.75
0. 5
88-90
88-90
a
b
Reaction conditions: A mixture of quinazolin-4-one (1 equiv) (2e), 1-bromopropane (1 equiv),
Bu NBr (0.03-0.1 equiv), 10-40 % potassium hydroxide (10 mL) in toluene (10 mL) was stirred at
0-90°C for 0.5-2 h.
4
2
Yields of isolated products.
,
The effect of different organic phase was also investigated. When CHCl3, benzene ethyl atetate, and
toluene was used, the yields of 3e were 25.5 %, 45.2 %, 54.3 % and 83.0 %, respectively (Table 2). By
using toluene as the organic phase, the 3e synthesis was found to proceed smoothly in PTC condition
at 88-90°C.
Table 2 Effect of different organic solvents on the synthesis of 3e
a
b
Entry
Reaction time / h
organic phase
The amount of
Yield / %
solvent / mL
1
2
3
4
1
1
1
1
CHCl
3
10
10
10
10
25.5
45.2
54.3
83.0
6 6
C H
3
CH COOEt
Toluene
a
b
Reaction conditions: A mixture of quinazolin-4-one (1 mmol) (2e), 1-bromopropane (1.0 mmol),
Bu NBr (0.08 mmol), 35 % potassium hydroxide (84 mmol, 10mL) in toluene (10 mL) was stirred at
8-90°C for 1 h.
Yields of isolated products.
4
8

Molecules 2006, 11
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86
Using the optimized condition, the best result was obtained when intermediate 2 was treated with 1
equiv of alkyl halides and 84 equiv KOH (35%, 10 mL) under PTC conditions (Bu NBr, 0.08 equiv)
4
with toluene as solvent (10 mL) refluxed at 88-90 °C for 1 h. Under these reaction conditions, the
amination reaction proceeded smoothly, and the results are summarized in Table 3. Compounds 3e and
3
i were prepared previously in yields of 41% and 33%, respectively [8], by the reaction of metallic
derivatives of substituted or unsubstituted quinazolin-4-one with alkyl halides or dialkyl sulfate in
ethanol solvent for 6-24 hrs.
a
Table 3. Yields of the title compounds 3.
Compd
X-
3a
H
3b
F
3c
Cl
3d
Br
3e
H
3f
F
R-
Et
Et
Et
Et
n-Pr
83.0
3k
n-Pr
92.2
3l
b
Yields /%
79.5
3g
74.5
3h
74.5
3i
77.0
3j
Compd
X-
Cl
Br
H
F
Cl
Br
R-
n-Pr
83.1
n-Pr
87.0
allyl
70.0
allyl
72.7
allyl
82.5
allyl
70.9
b
Yields /%
a
All reactions were carried out in toluene (10 mL) at 88-90°C for 1 h
under PTC conditions with KOH (84 equiv) used as base.
Isolated yields.
b
The structures of title compounds 3 were established on the basis of their spectroscopic data.
-
1
They showed IR absorption bands at 3049-3099 (Ar-H), 1664-1678 (C=O), and 1451-1613 cm
1
(
skeleton vibration of aromatic ring). In the H NMR spectra of quinazolinone derivatives, the 2-H
signal appeared as a singlet in the 7.99-8.08 ppm range, while the 7-H peaks of 6-fluoro-
quinazolin-4-one derivatives were observed at about 7.72-7.73 ppm as a quartet. The 8-H of
6
-bromoquinazolin-4-one derivatives appear as a doublet at 7.57-7.60 ppm.
Antifungal activity bioassay
The antifungal bioassay results are given in Table 4. It could be seen that these newly synthesized
3
-alkylquinazolin-4-one derivatives exhibit weak to good antifungal activities. At 50 µg/mL,
compounds 3c, 3h and 3k inhibited growth of Gibberella zeae at 55.0 %, 50.3 % and 49.1 %
respectively. Compounds 3h, 3c, 3k, 3d and 3l exhibited good activities on Fusarium oxysporum at
4
7.2 %, 37.5 %, 36.4 %, 33.3 %, 32.4 %, respectively, which is slightly lower than that of hymexazol
(
55.4 %). Compounds 3l, 3k, 3c showed activities against Valsa mali at 30.4 %, 28.3 %, 24.4 %,
respectively, which is little higher than Hymexazol (22.5 %). Compounds 3h showed activities against
Valsa mali at 40.9 %, which is obviously higher than Hymexazol (22.5 %).

Molecules 2006, 11
Table 4. Inhibition effect of 3-alkylquinazolin-4-one derivatives on phytopathogenic fungi.
3
87
Compd (50 µg/mL)
Fusarium
oxysporum
17.9
Gibberella
zeae
17.6
11.8
55.0
35.4
17.3
17.0
5.5
Valsa mali
3
a
8.7
3
b
14.2
6.5
3
c
37.5
24.4
21.7
16.9
14.5
15.9
40.9
0.9
3d
33.3
3
e
21.2
3
f
4.9
3
g
20.4
3h
47.2
50.3
19.9
26.7
49.1
37.0
50.4
3
i
15.3
3
j
13.9
13.4
28.3
30.4
22.5
3
k
36.4
3
l
32.4
Hymexazol
Conclusions
55.4
In summary, the present new method of the formation of 3-alkylquinazolin-4-one derivatives under
phase transfer catalyst condition offers several advantages: fast reaction rates, less by-products, and
high yields. Where direct comparisons were possible our method was found to be superior to reported
methods It was also found that title compound 3h displayed good antifungal activity.
Acknowledgements
This work was financially supported by the National Nature Science Foundation of China (Grant
No. 20562003), the Foundation for New Century Talent in Guizhou Province of China and the
Foundation for Science and Technology Excellent Talent in Guizhou Province of China (2005[0515]).
Experimental
General
Unless otherwise indicated, all common reagents and solvents were used as obtained from
commercial suppliers without further purification. Melting points were determined on a XT-4
binocular microscope (Beijing Tech Instrument Co., China) and were not corrected. The IR spectra
1
13
were recorded on a Bruker VECTOR 22 spectrometer in KBr disks. H-NMR and C-NMR spectra
solvent CDCl ) were recorded on a JEOL ECX 500 MHz spectrometer at room temperature using
(
3
TMS as internal standard. Elemental analysis was performed by an Elementar Vario-III CHN analyzer.
The following compounds were prepared as described in the literature: quinazolin-4-one (2a): white
solid, yield 95.4%, m.p. 214~215°C (lit. [9], m.p. 215.5~216.5°C); 6-fluoroquinazolin-4-one (2b):

Molecules 2006, 11
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88
white solid, yield 70.8%, m.p. 258-260 °C (lit. [10], m.p. 255-257 °C); 6-chloroquinazolin-4-one (2c):
white solid, yield 78.5%, m.p. 257-260 °C (lit. [11], m.p. 259-259.5 °C) and 6-bromoquinazolin-4-one
(
2d): white solid, yield 69.5 %, m.p. 264-267°C (lit. [12], m.p. 267-269 °C).
Preparation of 3-Alkylquinazolin-4-one Derivatives 3a-3l
A mixture of quinazolin-4-one or 6-haloquinazolin-4-one (1.00 mmol), alkyl bromide (1.00 mmol)
and tetrabutylammonium bromide (26 mg, 0.08 mmol) was dissolved in toluene (10 mL) and 35%
aqueous potassium hydroxide (10 mL). The solution was stirred and refluxed for 1 h and then the
organic layer was separated and washed with water. After evaporation of solvent, the crude product
was purified by preparative TLC with petroleum ether/ethyl acetate (V/V=1:2) as developing solvent to
give title compounds 3.
3
-Ethylquinazolin-4-one (3a). White crystals, yield 79.5%; m.p. 76.5∼78.5 °C; (lit. [8], m.p. 99-101 °C,
-1 1
yield not reported). IR: 3049.2, 2960.5, 1674.2, 1612.5, 1562.3, 1471.7 cm ; H-NMR: δ 8.32 (d, 1H,
J=8.0Hz, quinazolinone H-5), 8.08 (s, 1H, quinazolinone H-2), 7.76-7.71 (m, 2H, quinazolinone
H-6,8), 7.51 (t, 1H, J=6.9Hz, quinazolinone H-7), 4.08 (q, 2H, J=7.5Hz, CH
2
), 1.43 (t, 3H, J=7.5Hz,
); C-NMR: δ 160.8 (quinazolinone C-4), 148.1 (quinazolinone C-2), 146.3 (quinazolinone C-9),
34.1 (quinazolinone C-7), 127.4 (quinazolinone C-5), 127.2 (quinazolinone C-6), 126.6
quinazolinone C-10), 122.2 (quinazolinone C-8), 42.1 (CH ), 14.9 (CH ); Anal. Calc. for C10
174.2): C, 68.95; H, 5.79; N, 16.08. Found: C, 68.80; H, 5.79; N, 16.18.
1
3
CH
3
1
(
(
2
3
10 2
H N O
3
2
1
7
-Ethyl-6-fluoroquinazolin-4-one (3b). White crystals, yield 74.5%; m.p. 94.5∼96.5 °C; IR: 3058.6,
974.2, 1674.2, 1626.0, 1606.7, 1487.1 cm ; H-NMR: δ 8.05 (s, 1H, quinazolinone H-2), 7.94 (dd,
H, J=8.6Hz, 2.9Hz, quinazolinone H-5), 7.73 (q, 1H, JH-F=4.5Hz, JH-H=4.0Hz, quinazolinone H-7),
-1 1
2 3
.50-7.48 (m, 1H, quinazolinone H-8), 4.08 (q, 2H, J=7.5Hz, CH ), 1.44 (t, 3H, J=7.5Hz, CH );
1
3
C-NMR: δ 162.1 (quinazolinone C-4), 160.1 (quinazolinone C-6), 145.6 (quinazolinone C-2), 144.7
(
quinazolinone C-9), 129.8 (quinazolinone C-10), 123.4 (quinazolinone C-8), 122.8 (quinazolinone
2 3 9 2
C-7), 111.7 (quinazolinone C-5), 42.3 (CH ), 14.8 (CH ); Anal. Calc. for C10H FN O (192.2): C, 62.49;
H, 4.72; N, 14.58. Found: C, 62.34; H, 4.62; N, 14.45.
6
2
8
1
-Chloro-3-ethylquinazolin-4-one (3c). White crystals, yield 74.5%; m.p. 104∼106°C; IR: 3099.2,
-1 1
980.0, 1666.5, 1626.5, 1604.8, 1469.8 cm ; H-NMR: δ 8.28 (d, 1H, J=2.5Hz, quinazolinone H-5),
.06 (s, 1H, quinazolinone H-2), 7.70-7.65 (m, 2H, quinazolinone H-7,8), 4.07 (q, 2H, J=7.5Hz, CH ),
); C-NMR: δ 159.9 (quinazolinone C-4), 146.6 (quinazolinone C-2), 146.4
2
13
.43 (t, 3H, J=7.5Hz, CH
3
(
quinazolinone C-9), 134.6 (quinazolinone C-7), 133.1 (quinazolinone C-6), 129.0 (quinazolinone C-5),
26.0 (quinazolinone C-10), 123.2 (quinazolinone C-8), 42.3 (CH ), 14.8 (CH ); Anal. Calc. for
C H ClN O (208.6): C, 57.57; H, 4.35; N, 13.43. Found: C, 57.67; H, 4.25; N, 13.43.
1
2
3
1
0
9
2
6
-Bromo-3-ethylquinazolin-4-one (3d). White crystals, yield 77.0%; m.p. 76.5∼78.5°C; (lit. [13],
-1
neither yield nor any properties given). IR: 3085.3, 2978.1, 1664.6, 1600.9, 1587.9, 1465.9 cm ;
1
H-NMR: δ 8.44 (d, 1H, J=2.0Hz, quinazolinone H-5), 8.07 (s, 1H, quinazolinone H-2), 7.81 (dd, 1H,
J=9.2Hz, 1.7Hz, quinazolinone H-7), 7.57 (d, 1H, J=8.6Hz, quinazolinone H-8), 4.07 (q, 2H, J=7.5Hz,

Molecules 2006, 11
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89
1
3
CH
46.6 (quinazolinone C-9), 137.3 (quinazolinone C-7), 133.5 (quinazolinone C-5), 129.2
quinazolinone C-10), 123.5 (quinazolinone C-8), 120.8 (quinazolinone C-6), 42.3 (CH ), 14.8 (CH );
2 3
), 1.43 (t, 3H, J=7.5Hz, CH ); C-NMR: δ 159.7 (quinazolinone C-4), 146.9 (quinazolinone C-2),
1
(
2
3
9 2
Anal. Calc. for C10H BrN O (253.1): C, 47.46; H, 3.58; N, 11.07. Found: C, 47.33; H, 3.48; N, 11.18.
3
-Propylquinazolin-4-one (3e). White crystals, yield 83.0%; m.p. 82∼83°C; (lit. [8], m.p. 95-96 °C).
-1
1
IR: 3075.3, 2964.6, 1674.2, 1610.6, 1562.3, 1471.7 cm ; H-NMR: δ 8.33 (d, 1H, J=8.0Hz,
quinazolinone H-5), 8.05 (s, 1H, quinazolinone H-2), 7.78-7.71 (m, 2H, quinazolinone H-6,8), 7.51 (t,
1
H, J=8.0Hz, quinazolinone H-7), 3.98 (t, 2H, J=7.5Hz, NCH ), 1.87-1.82 (m, 2H, CH ), 1.01 (t, 3H,
2 2
1
3
J=7.5Hz, CH ); C-NMR: δ 161.1 (quinazolinone C-4), 148.0 (quinazolinone C-2), 146.6
3
(
quinazolinone C-9), 134.1 (quinazolinone C-7), 127.4 (quinazolinone C-5), 127.2 (quinazolinone C-6),
1
26.7 (quinazolinone C-10), 122.1 (quinazolinone C-8), 48.6 (NCH ), 22.7 (CH ), 11.1 (CH ); Anal.
2 2 3
12 2
Calc. for C11H N O (188.2): C, 70.19; H, 6.43; N, 14.88. Found: C, 70.14; H, 6.28; N, 15.03.
6
2
1
7
3
-Fluoro-3-propylquinazolin-4-one (3f). White crystals, yield 92.2%; m.p. 96∼98°C; IR: 3082.6,
960.7, 1676.1, 1610.6, 1608.1, 1481.3 cm ; H-NMR: δ 8.01 (s, 1H, quinazolinone H-2), 7.95 (dd,
H, J=8.6Hz, 2.9Hz, quinazolinone H-5), 7.73 (q, 1H, JH-F=4.5Hz, JH-H=4.0Hz, quinazolinone H-7),
-1 1
.50-7.46 (m, 1H, quinazolinone H-8), 3.98 (t, 2H, J=7.5Hz, NCH
2
), 1.86-1.81 (m, 2H, CH
2
), 1.01 (t,
1
3
H, J=7.5Hz, CH
3
); C-NMR: δ 162.2 (quinazolinone C-4), 160.4 (quinazolinone C-6), 146.0
(
quinazolinone C-2), 144.8 (quinazolinone C-9), 129.9 (quinazolinone C-10), 123.6 (quinazolinone
C-8), 122.7 (quinazolinone C-7), 111.8 (quinazolinone C-5), 48.8 (NCH ), 22.7 (CH ), 11.2 (CH );
Anal. Calc. for C11 O (206.2): C, 64.07; H, 5.38; N, 13.58. Found: C, 64.18; H, 5.40; N, 13.44.
2
2
3
H11FN
2
6
-Chloro-3-propylquinazolin-4-one (3g) [CAS number 501917-08-4, but no references given]. White
-1
crystals, yield 83.1%; m.p. 130.0∼131.5°C; IR: 3085.2, 2956.9, 1674.2, 1612.5, 1556.6, 1469.7 cm ;
1
H-NMR: δ 8.26 (d, 1H, J=2.3Hz, quinazolinone H-5), 8.03 (s, 1H, quinazolinone H-2), 7.68-7.65 (m,
2
H, quinazolinone H-7,8), 3.97 (t, 2H, J=7.5Hz, NCH
2
), 1.86-1.82 (m, 2H, CH
2
), 1.01 (t, 3H, J=7.5Hz,
1
3
CH
3
); C-NMR: δ 160.1 (quinazolinone C-4), 146.9 (quinazolinone C-2), 146.7 (quinazolinone C-9),
1
34.6 (quinazolinone C-7), 133.1 (quinazolinone C-6), 129.1 (quinazolinone C-5), 126.1
(
quinazolinone C-10), 123.3 (quinazolinone C-8), 48.8 (NCH ), 22.7 (CH ), 11.2 (CH ); Anal. Calc.
2
2
3
2
for C11H11ClN O (222.7): C, 59.33; H, 4.98; N, 12.58. Found: C, 59.43; H, 4.94; N, 12.57.
6
2
8
-Bromo-3-propylquinazolin-4-one (3h). White crystals, yield 87.0%; m.p. 132.5∼134.5°C; IR: 3075.2,
955.0, 1666.5, 1610.6, 1597.1, 1465.9 cm ; H-NMR: δ 8.44 (d, 1H, J=2.0Hz, quinazolinone H-5),
.04 (s, 1H, quinazolinone H-2), 7.82 (dd, 1H, J=9.2Hz, 1.7Hz, quinazolinone H-7), 7.57 (d, 1H,
-1 1
J=8.6Hz, quinazolinone H-8), 3.97 (t, 2H, J=7.5Hz, NCH
2
), 1.86-1.81 (m, 2H, CH
); C-NMR: δ 159.9 (quinazolinone C-4), 146.9 (quinazolinone C-2), 146.7
quinazolinone C-9), 137.3 (quinazolinone C-7), 129.3 (quinazolinone C-5), 129.2 (quinazolinone
C-10), 123.5 (quinazolinone C-8), 120.8 (quinazolinone C-6), 48.7 (NCH ), 22.6 (CH ), 11.1 (CH );
2
), 1.01 (t, 3H,
1
3
J=7.5Hz, CH
3
(
2
2
3
Anal. Calc. for C11
H11BrN
2
O (267.1): C, 49.46; H, 4.15; N, 10.49. Found: C, 49.73; H, 4.24; N, 10.45.
3
-Allylquinazolin-4-one (3i). White crystals, yield 70.0%; m.p. 63∼65°C; (lit. [8] m.p. 65-68 °C). IR:
061.0, 1676.1, 1610.6, 1562.3, 1473.6 cm ; H-NMR: δ 8.33 (d, 1H, J=8.0Hz, quinazolinone H-5),
-1 1
3

Molecules 2006, 11
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90
8
.04 (s, 1H, quinazolinone H-2), 7.78-7.71 (m, 2H, quinazolinone H-6,8), 7.52 (t, 1H, J=8.0Hz,
2
quinazolinone H-7), 6.03-5.98 (m, 1H, CH=C), 5.32-5.26 (m, 2H, C=CH ), 4.66 (d, 2H, J=6.0Hz,
1
3
CH ); C-NMR: δ 160.9 (quinazolinone C-4), 148.1 (quinazolinone C-2), 146.3 (quinazolinone C-9),
2
1
1
34.4 (CH=C), 131.9 (quinazolinone C-7), 127.6 (quinazolinone C-5), 127.4 (quinazolinone C-6),
26.9 (quinazolinone C-10), 122.2 (quinazolinone C-8), 119.0 (C=CH ), 48.4 (CH ); Anal. Calc. for
2
2
C H N O (186.2): C, 70.95; H, 5.41; N, 15.04. Found: C, 70.99; H, 5.15; N, 15.02.
1
1
10
2
3
-Allyl-6-fluoroquinazolin-4-one (3j). White crystals, yield 72.7%; m.p. 79.0∼80.5°C; IR: 3090.5,
666.5, 1610.6, 1574.0, 1458.2 cm ; H-NMR: δ 7.99 (s, 1H, quinazolinone H-2), 7.94 (dd, 1H,
-
1
1
1
J=8.6Hz, 2.9Hz, quinazolinone H-5), 7.73 (q, 1H, JH-F=4.5Hz, JH-H=4.0Hz, quinazolinone H-7),
7
.51-7.46 (m, 1H, quinazolinone H-8), 6.03-5.95 (m, 1H, CH=C), 5.34-5.26 (m, 2H, C=CH
2
), 4.66 (d,
1
3
2H, J=5.6Hz, CH2); C-NMR: δ 162.4 (quinazolinone C-4), 159.9 (quinazolinone C-6), 145.4
(
quinazolinone C-2), 144.8 (quinazolinone C-9), 131.6(CH=C), 129.9 (quinazolinone C-10), 123.3
quinazolinone C-8), 122.7 (quinazolinone C-7), 119.1 (C=CH ), 111.6 (quinazolinone C-5), 48.4
(
2
(
CH ); Anal. Calc. for C H FN O (204.2): C, 64.70; H, 4.44; N, 13.72. Found: C, 64.51; H, 4.32; N,
2
11
9
2
1
3.64.
3
1
1
-Allyl-6-chloroquinazolin-4-one (3k). White crystals, yield 82.5%; m.p. 113∼115°C; IR: 3088.7,
678.1, 1610.6, 1574.8, 1470.0 cm ; H-NMR: δ 8.28 (d, 1H, J=2.5Hz, quinazolinone H-5), 8.03 (s,
-
1 1
H, quinazolinone H-2), 7.71-7.66 (m, 2H, quinazolinone H-7,8), 6.02-5.96 (m, 1H, CH=C), 5.34-5.26
1
3
(
(
(
2 2
m, 2H, C=CH ), 4.65 (d, 2H, J=5.5Hz, CH ); C-NMR: δ 159.8 (quinazolinone C-4), 146.4
quinazolinone C-2), 146.3 (quinazolinone C-9), 134.8 (CH=C), 133.2 (quinazolinone C-7), 131.5
quinazolinone C-6), 129.1 (quinazolinone C-5), 126.2 (quinazolinone C-10), 123.1 (quinazolinone
2 2 9 2
C-8), 119.2 (C=CH ), 48.5 (CH ); Anal. Calc. for C11H ClN O (220.7): C, 59.88; H, 4.11; N, 12.70.
Found: C, 59.80; H, 4.07; N, 12.64.
3
-Allyl-6-bromoquinazolin-4-one (3l). [CAS number 459416-38-7, but no references given]. White
-1 1
crystals, yield 70.9%; m.p. 118∼120°C; IR: 3068.8, 1670.4, 1610.6, 1577.9, 1464.0 cm ; H-NMR: δ
8
1
5
.45 (d, 1H, J=2.5Hz, quinazolinone H-5), 8.05 (s, 1H, quinazolinone H-2), 7.85 (dd, 1H, J=9.2Hz,
.7Hz, quinazolinone H-7), 7.60 (d, 1H, J=8.6Hz, quinazolinone H-8), 6.02-5.96 (m, 1H, CH=C),
1
3
2 2
.34-5.27 (m, 2H, C=CH ), 4.65 (d, 2H, J=5.5Hz, CH ); C-NMR: δ 159.6 (quinazolinone C-4), 146.7
(
(
quinazolinone C-2), 146.5 (quinazolinone C-9), 137.5 (quinazolinone C-7), 131.5(CH=C), 129.4
quinazolinone C-5), 129.2 (quinazolinone C-10), 123.4 (quinazolinone C-8), 121.1 (quinazolinone
C-6), 119.3 (C=CH ), 48.5 (CH ); Anal. Calc. for C H BrN O (265.1): C, 49.84; H, 3.42; N, 10.57.
2
2
11
9
2
Found: C, 49.84; H, 3.38; N, 10.65.
Bioassays
The antifungal activity of all synthesized compounds 3a-l was tested against three pathogenic fungi,
namely Fusarium oxysporum, Gibberella zeae, and Valsa mali, by the poison plate technique [14].
Compounds 3a-l were dissolved in acetone (10 mL) before mixing with Potato Dextrose Agar (PDA,
9
0 mL). The final concentration of compounds 3a-l in the medium were fixed at 50 µg/mL. Three
kinds of fungi were incubated in PDA at 25±1 °C for 5 days to get new mycelium for antifungal assay,

Molecules 2006, 11
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then a mycelia disk of approximately 0.45 cm diameter cut from the culture medium was picked up
with a sterilized inoculation needle and inoculated in the center of PDA plate. The inoculated plates
were incubated at 25±1°C for 5 days. Acetone in sterilized distilled water served as control, while
hymexazole was used as positive control For each treatment, three replicates were carried out. The
radial growth of the fungal colonies was measured on the sixth day and the data were statistically
analyzed. The in vitro inhibiting effects of the test compounds on the fungi were calculated by the
A − B
formula CV =
, where A represents the diameter of fungi growth on untreated PDA, B
A
represents the diameter of fungi on treated PDA, and CV represents the rate of inhibition.
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Sample Availability: Samples of the compounds are available from authors.
2006 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
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