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Article

Synthesis and Antifungal Bioactivities of 3-Alkylquinazolin- 4-one Derivatives

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
*
Author to whom correspondence should be addressed.
Molecules 2006, 11(6), 383-392; https://doi.org/10.3390/11060383
Submission 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 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.

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 N-aryl-4-aminoquinazoline compounds, among which some compounds were found to possess moderate bioactivity [8]. In this report we designed and synthesized a series of 3-alkylquinazolin-4-one derivatives and investigated their bioactivities. The synthetic route was shown in Scheme 1. The structures of 3 were firmly established by well defined IR, 1H-NMR, 13C-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.
Scheme 1. Synthetic route to the title compounds.
Molecules 11 00383 g001

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 Bu4NBr (Table 2, entries 3 and 5). When the amount of Bu4NBr increased from 3 % to 5 %, 8 % and 10 %, 3e could be obtained in 38.8 % and 62.2 %, 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 Bu4NBr as 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).
Table 1. Different reaction conditions for synthesis of 3e.
Table 1. Different reaction conditions for synthesis of 3e.
Entry aReaction time / hKOH concentration / % (w/w)The amount of Bu4NBr / mol %Reaction temperature / °CYield b / %
1130388-9038.8
2130588-9062.2
3130888-9077.1
41301088-9077.4
5130088-908.5
6110888-9048.5
7120888-9069.1
8135888-9083.0
9140888-9074.0
10135820-254.3
11135840-4513.3
12135860-6565.0
13235888-9083.8
140.7535888-9074.5
150. 535888-9055.9
a Reaction conditions: A mixture of quinazolin-4-one (1 equiv) (2e), 1-bromopropane (1 equiv), Bu4NBr (0.03-0.1 equiv), 10-40 % potassium hydroxide (10 mL) in toluene (10 mL) was stirred at 20-90°C for 0.5-2 h. b 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
Table 2. Effect of different organic solvents on the synthesis of 3e
Entry aReaction time / horganic phaseThe amount of solvent / mLYield b / %
11CHCl31025.5
21C6H61045.2
31CH3COOEt1054.3
41Toluene1083.0
a Reaction conditions: A mixture of quinazolin-4-one (1 mmol) (2e), 1-bromopropane (1.0 mmol), Bu4NBr (0.08 mmol), 35 % potassium hydroxide (84 mmol, 10mL) in toluene (10 mL) was stirred at 88-90°C for 1 h. b Yields of isolated products.
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 (Bu4NBr, 0.08 equiv) 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 3i 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.
Table 3. Yields of the title compounds 3.a
Table 3. Yields of the title compounds 3.a
Compd3a3b3c3d3e3f
X-HFClBrHF
R-EtEtEtEtn-Prn-Pr
bYields /%79.574.574.577.083.092.2
Compd3g3h3i3j3k3l
X-ClBrHFClBr
R-n-Prn-Prallylallylallylallyl
bYields /%83.187.070.072.782.570.9
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. b Isolated yields.
The structures of title compounds 3 were established on the basis of their spectroscopic data. 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 1H 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 47.2 %, 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 %).
Table 4. Inhibition effect of 3-alkylquinazolin-4-one derivatives on phytopathogenic fungi.
Table 4. Inhibition effect of 3-alkylquinazolin-4-one derivatives on phytopathogenic fungi.
Compd (50 μg/mL)Fusarium oxysporumGibberella zeaeValsa mali
3a17.917.68.7
3b14.211.86.5
3c37.555.024.4
3d33.335.421.7
3e21.217.316.9
3f4.917.014.5
3g20.45.515.9
3h47.250.340.9
3i15.319.90.9
3j13.926.713.4
3k36.449.128.3
3l32.437.030.4
Hymexazol55.450.422.5

Conclusions

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.

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 were recorded on a Bruker VECTOR 22 spectrometer in KBr disks. 1H-NMR and 13C-NMR spectra (solvent CDCl3) were recorded on a JEOL ECX 500 MHz spectrometer at room temperature using 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): 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, yield not reported). IR: 3049.2, 2960.5, 1674.2, 1612.5, 1562.3, 1471.7 cm-1; 1H-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, CH2), 1.43 (t, 3H, J=7.5Hz, CH3); 13C-NMR: δ 160.8 (quinazolinone C-4), 148.1 (quinazolinone C-2), 146.3 (quinazolinone C-9), 134.1 (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 (CH2), 14.9 (CH3); Anal. Calc. for C10H10N2O (174.2): C, 68.95; H, 5.79; N, 16.08. Found: C, 68.80; H, 5.79; N, 16.18.
3-Ethyl-6-fluoroquinazolin-4-one (3b). White crystals, yield 74.5%; m.p. 94.5~96.5 °C; IR: 3058.6, 2974.2, 1674.2, 1626.0, 1606.7, 1487.1 cm-1; 1H-NMR: δ 8.05 (s, 1H, quinazolinone H-2), 7.94 (dd, 1H, J=8.6Hz, 2.9Hz, quinazolinone H-5), 7.73 (q, 1H, JH-F=4.5Hz, JH-H=4.0Hz, quinazolinone H-7), 7.50-7.48 (m, 1H, quinazolinone H-8), 4.08 (q, 2H, J=7.5Hz, CH2), 1.44 (t, 3H, J=7.5Hz, CH3); 13C-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 C-7), 111.7 (quinazolinone C-5), 42.3 (CH2), 14.8 (CH3); Anal. Calc. for C10H9FN2O (192.2): C, 62.49; H, 4.72; N, 14.58. Found: C, 62.34; H, 4.62; N, 14.45.
6-Chloro-3-ethylquinazolin-4-one (3c). White crystals, yield 74.5%; m.p. 104~106°C; IR: 3099.2, 2980.0, 1666.5, 1626.5, 1604.8, 1469.8 cm-1; 1H-NMR: δ 8.28 (d, 1H, J=2.5Hz, quinazolinone H-5), 8.06 (s, 1H, quinazolinone H-2), 7.70-7.65 (m, 2H, quinazolinone H-7,8), 4.07 (q, 2H, J=7.5Hz, CH2), 1.43 (t, 3H, J=7.5Hz, CH3); 13C-NMR: δ 159.9 (quinazolinone C-4), 146.6 (quinazolinone C-2), 146.4 (quinazolinone C-9), 134.6 (quinazolinone C-7), 133.1 (quinazolinone C-6), 129.0 (quinazolinone C-5), 126.0 (quinazolinone C-10), 123.2 (quinazolinone C-8), 42.3 (CH2), 14.8 (CH3); Anal. Calc. for C10H9ClN2O (208.6): C, 57.57; H, 4.35; N, 13.43. Found: C, 57.67; H, 4.25; N, 13.43.
6-Bromo-3-ethylquinazolin-4-one (3d). White crystals, yield 77.0%; m.p. 76.5~78.5°C; (lit. [13], neither yield nor any properties given). IR: 3085.3, 2978.1, 1664.6, 1600.9, 1587.9, 1465.9 cm-1; 1H-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, CH2), 1.43 (t, 3H, J=7.5Hz, CH3); 13C-NMR: δ 159.7 (quinazolinone C-4), 146.9 (quinazolinone C-2), 146.6 (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 (CH2), 14.8 (CH3); Anal. Calc. for C10H9BrN2O (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). IR: 3075.3, 2964.6, 1674.2, 1610.6, 1562.3, 1471.7 cm-1; 1H-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, 1H, J=8.0Hz, quinazolinone H-7), 3.98 (t, 2H, J=7.5Hz, NCH2), 1.87-1.82 (m, 2H, CH2), 1.01 (t, 3H, J=7.5Hz, CH3); 13C-NMR: δ 161.1 (quinazolinone C-4), 148.0 (quinazolinone C-2), 146.6 (quinazolinone C-9), 134.1 (quinazolinone C-7), 127.4 (quinazolinone C-5), 127.2 (quinazolinone C-6), 126.7 (quinazolinone C-10), 122.1 (quinazolinone C-8), 48.6 (NCH2), 22.7 (CH2), 11.1 (CH3); Anal. Calc. for C11H12N2O (188.2): C, 70.19; H, 6.43; N, 14.88. Found: C, 70.14; H, 6.28; N, 15.03.
6-Fluoro-3-propylquinazolin-4-one (3f). White crystals, yield 92.2%; m.p. 96~98°C; IR: 3082.6, 2960.7, 1676.1, 1610.6, 1608.1, 1481.3 cm-1; 1H-NMR: δ 8.01 (s, 1H, quinazolinone H-2), 7.95 (dd, 1H, J=8.6Hz, 2.9Hz, quinazolinone H-5), 7.73 (q, 1H, JH-F=4.5Hz, JH-H=4.0Hz, quinazolinone H-7), 7.50-7.46 (m, 1H, quinazolinone H-8), 3.98 (t, 2H, J=7.5Hz, NCH2), 1.86-1.81 (m, 2H, CH2), 1.01 (t, 3H, J=7.5Hz, CH3); 13C-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 (NCH2), 22.7 (CH2), 11.2 (CH3); Anal. Calc. for C11H11FN2O (206.2): C, 64.07; H, 5.38; N, 13.58. Found: C, 64.18; H, 5.40; N, 13.44.
6-Chloro-3-propylquinazolin-4-one (3g) [CAS number 501917-08-4, but no references given]. White 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; 1H-NMR: δ 8.26 (d, 1H, J=2.3Hz, quinazolinone H-5), 8.03 (s, 1H, quinazolinone H-2), 7.68-7.65 (m, 2H, quinazolinone H-7,8), 3.97 (t, 2H, J=7.5Hz, NCH2), 1.86-1.82 (m, 2H, CH2), 1.01 (t, 3H, J=7.5Hz, CH3); 13C-NMR: δ 160.1 (quinazolinone C-4), 146.9 (quinazolinone C-2), 146.7 (quinazolinone C-9), 134.6 (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 (NCH2), 22.7 (CH2), 11.2 (CH3); Anal. Calc. for C11H11ClN2O (222.7): C, 59.33; H, 4.98; N, 12.58. Found: C, 59.43; H, 4.94; N, 12.57.
6-Bromo-3-propylquinazolin-4-one (3h). White crystals, yield 87.0%; m.p. 132.5~134.5°C; IR: 3075.2, 2955.0, 1666.5, 1610.6, 1597.1, 1465.9 cm-1; 1H-NMR: δ 8.44 (d, 1H, J=2.0Hz, quinazolinone H-5), 8.04 (s, 1H, quinazolinone H-2), 7.82 (dd, 1H, J=9.2Hz, 1.7Hz, quinazolinone H-7), 7.57 (d, 1H, J=8.6Hz, quinazolinone H-8), 3.97 (t, 2H, J=7.5Hz, NCH2), 1.86-1.81 (m, 2H, CH2), 1.01 (t, 3H, J=7.5Hz, CH3); 13C-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 (NCH2), 22.6 (CH2), 11.1 (CH3); Anal. Calc. for C11H11BrN2O (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: 3061.0, 1676.1, 1610.6, 1562.3, 1473.6 cm-1; 1H-NMR: δ 8.33 (d, 1H, J=8.0Hz, quinazolinone H-5), 8.04 (s, 1H, quinazolinone H-2), 7.78-7.71 (m, 2H, quinazolinone H-6,8), 7.52 (t, 1H, J=8.0Hz, quinazolinone H-7), 6.03-5.98 (m, 1H, CH=C), 5.32-5.26 (m, 2H, C=CH2), 4.66 (d, 2H, J=6.0Hz, CH2); 13C-NMR: δ 160.9 (quinazolinone C-4), 148.1 (quinazolinone C-2), 146.3 (quinazolinone C-9), 134.4 (CH=C), 131.9 (quinazolinone C-7), 127.6 (quinazolinone C-5), 127.4 (quinazolinone C-6), 126.9 (quinazolinone C-10), 122.2 (quinazolinone C-8), 119.0 (C=CH2), 48.4 (CH2); Anal. Calc. for C11H10N2O (186.2): C, 70.95; H, 5.41; N, 15.04. Found: C, 70.99; H, 5.15; N, 15.02.
3-Allyl-6-fluoroquinazolin-4-one (3j). White crystals, yield 72.7%; m.p. 79.0~80.5°C; IR: 3090.5, 1666.5, 1610.6, 1574.0, 1458.2 cm-1; 1H-NMR: δ 7.99 (s, 1H, quinazolinone H-2), 7.94 (dd, 1H, 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=CH2), 4.66 (d, 2H, J=5.6Hz, CH2); 13C-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=CH2), 111.6 (quinazolinone C-5), 48.4 (CH2); Anal. Calc. for C11H9FN2O (204.2): C, 64.70; H, 4.44; N, 13.72. Found: C, 64.51; H, 4.32; N, 13.64.
3-Allyl-6-chloroquinazolin-4-one (3k). White crystals, yield 82.5%; m.p. 113~115°C; IR: 3088.7, 1678.1, 1610.6, 1574.8, 1470.0 cm-1; 1H-NMR: δ 8.28 (d, 1H, J=2.5Hz, quinazolinone H-5), 8.03 (s, 1H, 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 (m, 2H, C=CH2), 4.65 (d, 2H, J=5.5Hz, CH2); 13C-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 C-8), 119.2 (C=CH2), 48.5 (CH2); Anal. Calc. for C11H9ClN2O (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 crystals, yield 70.9%; m.p. 118~120°C; IR: 3068.8, 1670.4, 1610.6, 1577.9, 1464.0 cm-1; 1H-NMR: δ 8.45 (d, 1H, J=2.5Hz, quinazolinone H-5), 8.05 (s, 1H, quinazolinone H-2), 7.85 (dd, 1H, J=9.2Hz, 1.7Hz, quinazolinone H-7), 7.60 (d, 1H, J=8.6Hz, quinazolinone H-8), 6.02-5.96 (m, 1H, CH=C), 5.34-5.27 (m, 2H, C=CH2), 4.65 (d, 2H, J=5.5Hz, CH2); 13C-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=CH2), 48.5 (CH2); Anal. Calc. for C11H9BrN2O (265.1): C, 49.84; H, 3.42; N, 10.57. 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, 90 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, 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 formula CV = Molecules 11 00383 i001, where A represents the diameter of fungi growth on untreated PDA, B represents the diameter of fungi on treated PDA, and CV represents the rate of inhibition.

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]).

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  • Sample Availability: Samples of the compounds are available from authors.

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MDPI and ACS Style

Ouyang, G.; Zhang, P.; Xu, G.; Song, B.; Yang, S.; Jin, L.; Xue, W.; Hu, D.; Lu, P.; Chen, Z. Synthesis and Antifungal Bioactivities of 3-Alkylquinazolin- 4-one Derivatives. Molecules 2006, 11, 383-392. https://doi.org/10.3390/11060383

AMA Style

Ouyang G, Zhang P, Xu G, Song B, Yang S, Jin L, Xue W, Hu D, Lu P, Chen Z. Synthesis and Antifungal Bioactivities of 3-Alkylquinazolin- 4-one Derivatives. Molecules. 2006; 11(6):383-392. https://doi.org/10.3390/11060383

Chicago/Turabian Style

Ouyang, Guiping, Peiquan Zhang, Gangfang Xu, Baoan Song, Song Yang, Linhong Jin, Wei Xue, Deyu Hu, Ping Lu, and Zhuo Chen. 2006. "Synthesis and Antifungal Bioactivities of 3-Alkylquinazolin- 4-one Derivatives" Molecules 11, no. 6: 383-392. https://doi.org/10.3390/11060383

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