4(3H)-quinazolinone derivatives,a class of nitrogenous heterocyclic compounds,are of great interest to medicines and pesticides. Due to the excellent pharmacological and biological activities,these compounds have found widespread applications in anti-bacterial^[1],anti-fungal^[2],anti-viral^[3],insecticidal^[4],anti-microbial fields^[5],and so on. Kassab et al. have reported that 2-methyl-3-arylmethyleneamino-4(3H)-quinazolinones exhibited favorable anti-microbial activity for medical use^[6]. El-Barbary et al. and Narayan et al. have synthesized a series of 4(3H)-quinazolinones containing glycosyl and thiazolinyl groups^{[7, 8]}. Some of the above compounds have strong antibacterial and antifungal activities. Very recently,Wang and coworkers have evaluated the biological activity of some novel arylimine derivatives containing 4(3H)-quinazolinone moiety^[9]. The results indicated that some of the compounds showed strong antifungal activities against six fungi and three bacteria.

When it comes to the design of new pesticides and drugs,Schiff base moiety is one of the most important structure fragments. The reported resultant applications can be classified as fungicide,bactericide,antivirotic,herbicide,insecticide and antioxygen^{[10, 11, 12, 13, 14, 15]}. Furthermore,studies showed that the conjugates of Schiff base moiety and 4(3H)-quinazolinone moiety exhibited good bioactivities^{[16, 17, 18]}.

Motivated by the function of 4(3H)-quinazolinone moiety,we have firstly developed an efficient protocol for the synthesis of 3-aminoalkyl-2-arylaminoquinazolin-4(3H)-ones via aza-Wittig reaction^[19]. Very recently we have demonstrated that a series of 3-(2-hydroxyethyl)-2-(phenylamino) quinazolin-4(3H)-ones,in which the parent quinazolinone rings were decorated,can also be synthesized by this protocol^[20]. It was noteworthy that the antibacterial activity was significantly enhanced when the parent quinazolinone rings of the title compounds was substituted. Thus,it would be speculated that decoration of the parent quinazolinone ring could be considered as an effective way of improving their bioactivity. As the continuous study of the previous work,we herein aim at designing and synthesizing a series of novel 4(3H)-quinazolinone Schiff base derivatives that the parent quinazolinone ring was substituted by chlorine at 7-position ( Scheme 1 ). The antifungal activities of the compounds were also evaluated.

图 1

Scheme 1

a: NaNO2,HCl,0-5 ℃; b: NaN3,CH3COONa,0-5 ℃; c: CH3CH2OH,SOCl2,75 ℃,6 h; d: PPh3,CH2Cl2,r.t.,10 h; e: Ph-NCO,0-5 ℃,10 h; f: H2NCH2CH2NH2,CH2Cl2,r.t.,10 h; g: Ar-CHO,CH3CH2OH,78 ℃. Scheme 1 General procedure for the synthesis of target compounds 7a-7q

Melting points were determined with an YRT-3 melting-point apparatus and are uncorrected.¹H NMR spectra were recorded on a Bruker AV 400 NMR spectrometer with TMS as the internal reference. IR spectra were recorded in KBr pellets on an Affinity-1 FT/IR spectrometer. MS spectra were measured using a HP 5988A GC-MS spectrometer,and signals were given in m/z. Elementary analysis for carbon,hydrogen and nitrogen were performed on a Vario EL III elementary analyzer. All chemical reagents were commercially available and treated with standard methods before use. Solvents were dried in a routine way and redistilled.

The key intermediate 6 was prepared from starting material 2-amino-4-chlorobenzoic acid ( 1 ). The details can be found in our previous publication^[19].

3-(2-aminoethyl)-7-chloro-2-(phenylamino) quinazolin-4(3H)-one (6): white solid; m.p. 181-182 ℃; ¹H NMR (400 MHz,DMSO),δ : 7.97 (d,J=8.5 Hz,1H),7.64 (d,J=7.8 Hz,2H),7.38-7.36 (m,3H),7.22 (d,J=8.5 Hz,1H),7.07 (t,J=7.3 Hz,1H),6.06 (brs,3H),4.18 (s,2H),3.03 (s,2H); IR (KBr),ν: 3 344,3 283,3 185,3 079,2 840,2 353,1 678,1 575,1 320,1 245,768,695 cm^-1; MS(ESI): m/z=315.1 ([M+H]⁺),337.1 ([M+Na]⁺).

Compounds 6 (1.0 mmol) and absolute ethanol (20 mL) were added into a three-neck flask,and heated slowly until it dissolved completely. Aromatic aldehyde (1.5 mmol) was then added. The reaction was stirred at 78 ℃ until the finalization according to TLC analysis (V(EA) ∶V(PE) ∶V(TEA)=3 ∶1 ∶1). The solid was precipitated after the mixture cooled to room temperature. And,the crude was purified by recrystallization using ethanol.

The mycelial growth rate method was selected for screening fungicides at a concentration of 100 μ g/mL. All the tested compounds were dissolved in DMSO (1 mL) before mixing with potato dextrose agar (PDA; 90 mL). All fungi were cultivated in PDA at 27 ℃±1 ℃ for 4\|7 days to make new mycelium for the identification of antifungal activity. Then,mycelia dishes of approximately 6 mm diameter were cut from the culture medium. A mycelium was obtained by using a germ-free inoculation needle and inoculated in the middle of the PDA plate aseptically. The diameter of the fungal colonies (mm) was measured at the end of the incubation period (for 4-7 days at 27±1 ℃). DMSO in sterile distilled water served as the negative control,while the commercial fungicide chlorothalonil served as the positive control. Each treatment repeated three times. Antifungal activities of the test compounds in vitro were calculated via the following formula. I/%=[(d₀-d) / (d₀-0.6)]×100,in which I represents the inhibition rate, d₀ is the diameter of fungal growth in the blank control,and d is the diameter of fungi on treated PDA.

In this work,seventeen derivatives of 7-chloro-4(3H)-quinazolinone Schiff base ( 7 ) were designed and synthesized. By using the amine bridge,3-aminoethyl moiety of the key intermediate 6 ,various aromatic aldehydes were introduced. In the synthesis of compound 7 ,dichloromethane/ethanol solvent system and elevated temperature were used to achieve good solubility of compound 6 . Further optimization studies have been carried out by using 4-chrolobenzaldehyde and compound 6 as model compounds. The details are shown in Table 1.

Table 1">表 1(Table 1)

Table 1 Conditions optimization of synthesis of compound 7g Entry Solvent Temp./℃ Catalyst Time/h Yield/% 1 CH2Cl2 r.t.* / 12 50 2 CH2Cl2 r.t. NEt3 12 52 3 CH2Cl2 Reflux / 5 63 4 EtOH Reflux / 1.5 72 *r.t. Room temperature.

Table 1 Conditions optimization of synthesis of compound 7g

The reaction proceed smoothly in both DCM and ethanol. It might be concluded that the reaction at refluxed conditions is favorable in terms of yield and reaction rate. By contrast,at room temperature the reaction takes longer time with lower yields. The above difference may be rationalized that the condensation between 4-chrolobenzaldehyde and compound 6 is an endothermic reaction,and higher temperature is favorable for the synthesis. The refluxing absolute alcohol has just met the conditions. So,the reaction is faster and has higher yield. The reason could be that it can provide enough energy to overcome the energy barrier of the reaction,while the DCM could not. Moreover,the former solvent is beneficial to the following recrystallization. Notably,the reaction could even occur in the absence of triethylamine (TEA) that plays a role as a catalyst. However,TEA is very critical for monitoring the progress of the reaction by using TLC,because the target compounds are vulnerable to acids. That is to say,there would be a chemolysis if a base such as TEA was absent in the eluent.

The physio-chemical properties and elementary analysis data of the title compounds 7a-7q are shown in Table 2. The elementary analysis and spectroscopic data (¹H NMR,IR and MS,Table 3) of the obtained compound 7 are consistent with their assigned structures. For example,in the ¹H NMR spectra,a singlet appeared at δ 8.22-9.67 of compounds 7 is attributed to Qu—NH—Ar and —N CH—,respectively. A doublet appeared at approximately δ 8.10 belongs to Qu—C5—H. The singlet varying from δ 3.87-4.69 reveals the presence of Qu—CH₂— and N—CH₂—. In the IR spectra,compounds 7 shows characteristic absorption bands at 3 335-3 252 cm^-1,which are assigned to the N—H of Qu—NH—Ar. The absorption bands at 3 050 cm^-1 and 2 960 cm^-1 belong to the C—H of benzene and the saturated C—H (e.g. Qu—CH₂— and N—CH₂—),respectively. The strong absorption band appeared at a low frequency 1 672 cm^-1 is attributed to the C O group,due to its conjugation effect with C C and aromatic ring. The skeletal stretching frequency appeared at 1 600 cm^-1 somehow overlaps because of the frequencies of C N and C C vibration systems. Moreover,the absorption bands appeared at 895-650 cm^-1 belong to bending vibration outside of the C—H plane of benzene. In the MS spectra,the molecular ion peaks and fragmentation peaks agreed with the synthesized structures of compounds 7 . The molecular ion peaks generally exhibited as [M+H]⁺ and [M+Na]⁺.

Table 2">表 2(Table 2)

Table 2 Physical and chemical data of the title compounds 7a-7q exposure Compd. Ar Appearance Yield/ % m.p./ ℃ Elementary analysis (Calcd.,/%) C H N 7a Ph White solid 68 169-170 68.34 (68.57) 4.56 (4.75) 14.16 (13.91) 7b 4-F-Ph White solid 92 177-178 65.75 (65.64) 4.46 (4.31) 13.46 (13.31)/ 7c 2-Cl-Ph White solid 83 174-175 63.04 (63.17) 4.16 (4.15) 12.76 (12.81); 7d 4-Cl-Ph White solid 72 151-152 63.24 (63.17) 4.09 (4.15) 12.83 (12.81) 7e 2,4-di-Cl-Ph White solid 88 181-183 58.54 (58.56) 3.56 (3.63) 11.76 (11.88) 7f 2-Br-Ph White solid 68 163-164 57.14 (57.34) 3.66 (3.77) 11.76 (11.63) 7g 4-Br-Ph White solid 86 160-161 57.18 (57.34) 3.76 (3.77) 11.79 (11.63) 7h 2-OH-Ph Yellow solid 56 186-187 65.84 (65.95) 4.56 (4.57) 13.46 (13.38) 7i 4-OH-Ph White solid 45 159-160 65.88 (65.95) 4.59 (4.57) 13.32 (13.38) 7j 2-OCH3-Ph White solid 81 155-156 66.84 (66.59) 4.76 (4.89) 12.76 (12.94) 7k 4-OCH3-Ph White solid 90 151-152 66.89 (66.59) 4.86 (4.89) 13.06 (12.94) 7l 4-NO2-Ph Yellow solid 58 192-193 61.74 (61.68) 4.06 (4.05) 15.66 (15.64) 7m 3,4-methylenedioxybenzyl White solid 82 140-141 64.44 (64.50) 4.36 (4.29) 12.51 (12.54) 7n PhCHCH White solid 78 170-171 70.24 (70.01) 5.06 (4.94) 13.01 (13.06) 7o 2-ClPhCHCH White solid 76 168-169 64.84 (64.80) 4.36 (4.35) 12.06 (12.09) 7p 1-naphthyl White solid 75 196-198 71.76 (71.60) 4.76 (4.67) 12.26 (12.37) 7q 2-thienyl White solid 65 176-177 60.64 (60.52) 4.36 (4.32) 14.01 (14.12)

Table 2 Physical and chemical data of the title compounds 7a-7q

Table 3">表 3(Table 3)

Table 3 1H NMR,IR spectra and MS of the title compounds 7a-7q Compd. 1H NMR (400 MHz,CDCl3),δ IR (KBr),ν/cm-1 MS (ESI),m/z 7a 4.17 (s,2H),4.69 (s,2H),7.10 (t,J=7.2 Hz,1H),7.19 (d,J=8.2 Hz,1H),7.33 (t,J=7.5 Hz,2H),7.39-7.64 (m,6H),7.74 (brs,2H),8.10 (d, J=8.4 Hz,1H),8.41(s,1H),9.05 (brs,1H) 3 237,3 036,2 965,1 650,1 591,1 451,1 375,1 279,1 233,778,683 403.2 ([M+H]+), 425.2 ([M+Na]+) 7b 4.13 (s,2H),4.65 (s,2H),7.10-7.14 (m,3H),7.20 (d,J =8.4 Hz,1H),7.33 (t,J =7.7 Hz,2H),7.46-7.52 (m,3H),7.76 (brs,2H),8.11 (d, J=8.5 Hz,1H),8.38 (s,1H),8.94 (brs,1H) 3 294,3 051,2 902,1 672,1 605,1 589,1 500,1 456,1 334,1 236,779,698 421.2 ([M+H]+), 443.2 ([M+Na]+) 7c 4.19 (s,2H),4.66 (s,2H),7.09 (t,J=7.3 Hz,1H),7.21 (d,J=8.4 Hz,1H),7.27-7.29 (m,2H),7.31-7.34 (m,2H),7.40-7.50 (m,3H),7.98-8.01 (m,2H),8.12 (d,J=8.5 Hz,1H),8.86 (s,1H),9.06 (brs,1H) 3 252,3 057,2 965,1 672,1 607,1 584,1 539,1 441,1 335,1 271,746,689 438.2 ([M+H]+), 460.2 ([M+Na]+) 7d 4.09 (s,2H),4.60 (s,2H),7.10 (t,J=8.4 Hz,1H),7.17 (d,J=7.8 Hz,1H),7.32 (t,J=7.5 Hz,2H),7.37 (d,J=7.8 Hz,2H),7.43 (s,1H),7.47 (d,J=7.7 Hz,2H),7.64 (d,J=7.7 Hz,2H),8.08 (d,J=8.4 Hz,1H),8.34 (s,1H),8.84 (s,1H) 3 271,3 046,2 905,1 669,1 580,1 463,1 334,1 245,763,689 438.2 ([M+H]+), 460.2 ([M+Na]+) 7e 4.18 (s,2H),4.66 (s,2H),7.10-7.14 (m,1H),7.20-7.26 (m,2H),7.30-7.36 (m,3H),7.47 (s,4H),7.91-7.93 (m,1H),8.11 (d,J=8.4 Hz,1H),8.87 (brs,1H) 3 265,3 053,2 920,1 672,1 595,1 576,1 457,1 330,1 247,767,680 472.2 ([M+H]+), 494.2 ([M+Na]+) 7f 4.21 (s,2H),4.69 (s,2H),7.09 (t,J=7.5 Hz,1H),7.21 (d,J=8.1 Hz,1H),7.29-7.32 (m,3H),7.34-7.42 (m,2H),7.47 (s,3H),7.64-7.70 (m,1H),8.09 (brs,1H),8.11 (d,J=8.5 Hz,1H),8.80 (s,1H) 3 224,3 109,2 963,1 674,1 597,1 572,1 551,1 452,1 340,1 244,745,683 482.3 ([M+H]+), 504.3 ([M+Na]+) 7g 4.12 (s,2H),4.63 (s,2H),7.13 (t,J=8.0 Hz,1H),7.20 (d,J=8.0 Hz,1H),7.35 (t,J=7.6 Hz,2H),7.46 (s,1H),7.50 (d,J=8.0 Hz,2H),7.55-7.65 (m,4H),8.11 (d,J=8.4 Hz,1H),8.36 (s,1H),8.87 (s,1H) 3 262,3 040,2 862,1 680,1 643,1 591,1 547,1 433,1 342,1 325,1 236,746,689 482.3 ([M+H]+), 504.3 ([M+Na]+) 7h 4.16 (s,2H),4.60 (s,2H),6.92 (t,J=7.4 Hz,1H),6.98-7.14 (m,2H),7.19-7.26 (m,3H),7.29-7.45 (m,7H),8.10 (d,J=8.5 Hz,1H),8.41 (s,1H) 3 379,3 059,2 938,1 672,1 614,1 598,1 556,1 460,1 338,1 265,767,696 419.3 ([M+H]+), 441.3 ([M+Na]+) 7i 4.04 (s,2H),4.59 (s,2H),6.79 (d,J=7.9 Hz,2H),7.06 (t,J=7.3 Hz,1H),7.16-7.18 (m,1H),7.24-7.36 (m,3H),7.43 (s,3H),7.56 (d,J=7.8 Hz,2H),8.08 (d,J=8.4 Hz,1H),8.26 (s,1H),9.14 (s,1H) 3 391,3 245,3 053,2 971,1 664,1 563,1 469,1 308,1 250,759,686 419.3 ([M+H]+), 441.3 ([M+Na]+) 7j 3.87 (s,3H),4.11 (s,2H),4.63 (s,2H),6.94-6.99 (m,2H),7.07 (t,J=7.3 Hz,1H),7.19 (d,J=8.5 Hz,1H),7.27-7.31 (m,2H),7.45-7.55 (m,4H),7.90 (d,J=7.7 Hz,1H),8.11 (d,J=8.5 Hz,1H),8.82 (s,1H),9.32 (s,1H) 3 292,3 040,2 961,1 680,1 607,1 583,1 562,1 499,1 458,1 335,1 246,773,748 433.3 ([M+H]+), 455.3 ([M+Na]+) 7k 3.88 (s,3H),4.11 (s,2H),4.65 (s,2H),6.94 (d, J=8.1 Hz,2H),7.10 (t, J=7.3 Hz,1H),7.19 (d, J=8.4 Hz,1H),7.33 (t,J=8.0 Hz,2H),7.44 (s,1H),7.55 (s,2H),7.73 (s,2H),8.10 (d,J =8.5 Hz,1H),8.30 (s,1H),9.16 (s,1H) 3 335,3 040,2 924,2 835,1 656,1 607,1 585,1 540,1 449,1 308,1 243,770,695 433.3 ([M+H]+), 455.3 ([M+Na]+) 7l 4.20 (s,2H),4.68 (s,2H),7.13 (t, J=7.9 Hz,1H),7.19-7.23 (m,1H),7.36 (t,J=7.7 Hz,2H),7.44 (s,1H),7.53 (d,J=7.7Hz,2H),7.90 (d,J=8.5 Hz,2H),8.11 (d,J=8.5Hz,1H),8.27 (d,J=8.6 Hz,2H),8.51 (s,1H),8.57 (s,1H) 3 306,3 047,2 893,1 667,1 588,1 553,1 455,1 334,1 247,759,691 448.2 ([M+H]+), 470.2 ([M+Na]+) 7m 4.12 (s,2H),4.66 (s,2H),6.07 (s,2H),6.87 (d, J=7.4 Hz,1H),7.10 (t,J=7.6 Hz,1H),7.19 (d,J=9.0 Hz,1H),7.36 (t,J=7.8 Hz,2H),7.44 (s,1H),7.55-7.91 (m,4H),8.09 (d,J =8.5 Hz,1H),8.22 (s,1H),9.00 (s,1H) 3 272,3 036,2 901,1 671,1 590,1 553,1 491,1 453,1 325,1 254,765,697 447.3 ([M+H]+), 469.3 ([M+Na]+) 7n 4.12 (s,2H),4.58 (s,2H),6.82-6.88 (m,1H),7.08-7.14 (m,1H),7.15-7.20 (m,1H),7.26-7.34 (m,3H),7.36-7.50 (m,5H),7.52-7.59 (m,1H),7.67 (d,J=8.4 Hz,2H),8.11-8.14 (m,1H),8.16 (d,J=8.9 Hz,1H),9.60 (s,1H) 3 280,3 039,2 964,2 885,1 678,1 606,1 583,1 545,1 483,1 458,1 329,1247,750,690 429.3 ([M+H]+), 451.2 ([M+Na]+) 7o 4.12 (s,2H),4.56 (s,2H),6.81-6.89 (m,1 H),7.05 (d,J=16.5 Hz,1H),7.14-7.16 (m,1H),7.32-7.43 (m,5H),7.44-7.48 (m,3H),7.64-7.66 (m,2H),8.05-8.09 (m,2H),9.67 (s,1H) 3 258,3 034,1 678,1 606,1 583,1 545,1 456,1 315,1 251,754,688 464.1 ([M+H]+), 486.1 ([M+Na]+) 7p 4.17 (s,2H),4.65 (s,2H),7.04-7.08 (m,1H),7.16-7.18 (m,1H),7.27-7.30 (m,2H),7.43 (d,J=2.0 Hz,1H),7.51-7.59 (m,4H),7.79-7.95 (m,4H),8.10 (d,J=8.5 Hz,2H),8.55 (s,1H),9.13 (s,1H) 3 254,3 057,2 841,1 668,1 606,1 577,1 462,1 340,1 249,743,687 453.3 ([M+H]+), 475.3 ([M+Na]+) 7q 4.21 (s,2H),4.56 (s,2H),7.03-7.11 (m,2H),7.14-7.18 (m,1H),7.30-7.38 (m,3H),7.40-7.46 (m,2H),7.66 (s,2H),8.05-8.10 (m,1H),8.42 (s,1H),8.65 (s,1H) 3 260,3 042,2 985,2 911,1 671,1 570,1 451,1 330,1 241,768,697 397.3 ([M+H]+), 419.2 ([M+Na]+)

Table 3 1H NMR,IR spectra and MS of the title compounds 7a-7q

The antifungal activities of the obtained compounds against fungal species were screened and evaluated. Five fungal species including Corynespora cassiicola Wei,Colletotrichum musae Arx,Phomopsis mangiferae Ahmad,Colletotrichum gloeosporioides Penz and Fusarium oxysporum f.sp.niveum were used by the poison plate technique. Chlorothalonil was used as the reference. As shown in Table 4,some of the title compounds were active at 100 μ g/mL. Most of them were sensitive to P.mangiferae,which exhibited inhibition rates ranging from 43.39%±0.43% to 98.18%±1.07%.The compound 7e showed excellent fungicidal activity against C.cassiicola (inhibition rate 26.21%±1.11%) and P.mangiferae (inhibition rate 98.18%±1.07%),which are even equal to that of the commercial fungicide chlorothalonil (25.64%±1.31% and 100%).

The preliminary SAR based on activity against those aforementioned fungi showed that the difference of Ar group influenced the antifungal activity. From Table 4,we may conclude that these Ar containing electron-withdrawing groups (e.g. 7c,7d,7e,7l ) showed better activities than those of electron-donating groups (e.g. 7h,7i,7j,7k ). Therefore,it could be inferred that electron-withdrawing groups were favorable in the design of the title compounds for improving antifungal activities.

Table 4">表 4(Table 4)

Table 4Fungicidal activity of the target compounds at a concentration of 100 μg/mL Compd. Inhibition rate*/% Corynespora cassiicola Colletotrichum musae Phomopsis mangiferae Colletotrichum gloeosporioides Fusarium oxysporum 7a 3.11±1.18 14.91±0.90 61.74±3.55 20.44±1.91 6.29±0.28 7b 6.72±0.72 19.25±0.35 75.83±2.11 25.57±0.81 17.78±1.94 7c 6.13±0.96 23.00±1.21 77.92±1.14 38.51±0.68 22.31±4.36 7d 5.52±0.44 18.67±1.32 76.44±0.79 28.45±0.57 20.26±0.72 7e 26.21±1.11 53.32±2.26 98.18±1.07 44.25±0.52 31.44±0.98 7f 6.16±1.43 34.50±0.75 67.76±3.55 23.79±1.12 17.58±0.91 7g 3.13±0.32 39.12±5.95 66.22±1.38 27.59±1.56 12.47±0.88 7h — 25.33±0.47 50.37±0.71 24.25±1.41 11.63±0.45 7i — 23.58±0.93 58.12±1.29 21.03±3.12 11.08±1.46 7j — 26.71±1.22 45.35±0.45 23.33±0.89 14.85±1.16 7k — 20.65±2.51 43.39±0.43 27.18±0.79 10.72±2.17 7l 18.12±1.09 50.86±0.81 80.94±0.64 38.51±0.41 16.65±0.69 7m 12.58±2.04 33.26±0.76 53.17±0.24 29.08±0.16 12.66±0.93 7n 4.42±0.25 21.27±1.46 66.13±2.21 22.95±0.67 6.43±1.29 7o 5.13±0.13 22.72±0.76 69.43±1.26 23.28±0.47 7.72±2.15 7p — 24.69±1.17 19.94±0.92 25.86±1.04 6.85±0.31 7q 9.22±0.73 36.63±0.85 58.11±0.28 29.02±0.39 16.34±3.17 chlorothalonil 25.64±1.31 88.08±0.53 100 77.59±1.44 60.67±0.65 *Average of three replicates.

Table 4 Fungicidal activity of the target compounds at a concentration of 100 μg/mL

In summary,a new series of 7-chloro-4(3H)-quinazolinone Schiff bases were designed and synthesized smoothly by controlling the reaction conditions. The antifungal activities of the compounds were also evaluated and most of them displayed fungicidal activities albeit with different levels. The preliminary bioassay data demonstrated that electron-withdrawing substitution was preferable to improve the fungicidal activities of the target compounds. Further investigations on structural optimization and fungicidal activities are underway.