Synthesis and fungicidal activity of 2-substituted-3-(4-fluorophenyl)- benzofuro [3,2-d] pyrimidin-4(3H)-ones

Article abstract of DOI:10.1002/jhet.277

(Chemical Equation Presented) Carbodiimide, obtained from aza-Wittig reaction of iminophosphorane with 4-fluorophenyl isocyanate, reacted with various nucleophiles under mild conditions to give a series of 2-substituted-3-(4-fluorophenyl)-benzofuro [3,2-d] pyrimidin-4(3H)-ones in satisfactory yield. Their structures were confirmed using NMR, EI-Ms, IR, and elementary analysis, and compound 7b was further analyzed by single-crystal. The preliminary bioassays indicated that these compounds showed moderate fungicidal activities against six kinds of fungi at a concentration of 50 mg/L.

Full text of DOI:10.1002/jhet.277

January 2010
Synthesis and Fungicidal Activity of 2-Substituted-3-(4-
Fluorophenyl)-benzofuro [3,2-d] Pyrimidin-4(3H)-ones
219
Yang-Gen Hu,* Jing Xu, Hai-Tao Gao, and Zuan Ma
Department of Pharmacy, Taihe Hospital of Yunyang Medical College and Institute of Medicinal
Chemistry, Yunyang Medical College, Shiyan 442000, China
*E-mail: huyangg111@yahoo.com.cn
Received July 7, 2009
DOI 10.1002/jhet.277
Published online 5 January 2010 in Wiley InterScience (www.interscience.wiley.com).
Carbodiimide, obtained from aza-Wittig reaction of iminophosphorane with 4-fluorophenyl isocya-
nate, reacted with various nucleophiles under mild conditions to give a series of 2-substituted-3-(4-fluo-
rophenyl)-benzofuro [3,2-d] pyrimidin-4(3H)-ones in satisfactory yield. Their structures were confirmed
using NMR, EI-Ms, IR, and elementary analysis, and compound 7b was further analyzed by single-crys-
tal. The preliminary bioassays indicated that these compounds showed moderate fungicidal activities
against six kinds of fungi at a concentration of 50 mg/L.
J. Heterocyclic Chem., 47, 219 (2010).
INTRODUCTION
RESULT AND DISCUSSION
Benzofuropyrimidinones are important heterocycles
bearing remarkable biological activities. Some of them
have shown good analgesic, anti-inflammatory, and anti-
microbial activities [1–3], whereas others exhibited good
anticoccidial and blood sugar-lowering activities [4,5].
On the other hand, many examples have been demon-
strated that incorporation of fluorine atom in molecular
structure of heterocyclic compounds often resulted in
the improvement of pharmacological properties of the
compounds as compared to their non-fluorine analogs
[6,7]. The introduction of a fluorine atom to the benzo-
furopyrimidinone system is expected to influence the
biological activities significantly. However, there is
no report of a generally useful synthesis of 2-substi-
tuted-3-(4-fluorophenyl)-benzofuro [3,2-d] pyrimidin-
4(3H)-ones.
Synthesis. The iminophosphorane 2 reacted with p-
fluorophenyl isocyanate to give carbodiimide 3, which
were allowed to react with secondary amines to provide
guanidine intermediates 4 (Y¼R2N). In the presence of
catalytic amount of sodium ethoxide, 4 were converted
easily to 2-dialkylamino-3-p-fluorophenyl-benzofuro
[3,2-d] pyrimidin-4(3H)-ones 5 in satisfactory yields at
room temperature (Scheme 1).
The reaction of carbodiimide 3 with phenols produced
2-aryloxy-3-p-fluorophenyl-benzofuro [3,2-d] pyrimidin-
4(3H)-ones 5 (Y ¼ ArO) in the presence of catalytic
amount of potassium carbonate in good yields. The
direct reaction of carbodiimide 3 with primary alcohol
(ROH) gave 2-alkoxy-3-p-fluorophenyl-benzofuro [3,2-
d] pyrimidin-4(3H)-ones 5 (Y ¼ RO) in excellent yields
in the presence of catalytic amount of ROꢀNaþ. The
results are listed in Table 1.
The aza-Wittig reactions of functionalized iminophos-
phoranes with isocyanates have been applied to produce
carbodiimides, functional groups consisting of the for-
mula N¼¼C¼¼N, able to undergo a plethora of heterocyc-
lization reactions [8,9]. Here, in continuation of our ear-
lier work [10,11], we wish to report a new method of
the previously unreported incorporation of fluorine atom
in molecular structure of benzofuropyrimidinones via
the aza-Wittig reactions of functionalized iminophos-
phorane with 4-fluorophenyl isocyanate under mild con-
dition, which synthesized 2-substituted-(4-fluorophenyl)-
benzofuro [3,2-d] pyrimidin-4(3H)-ones.
The reaction of carbodiimide 3 with primary amine
RNH2 in the presence of EtOꢀNaþ produced only 2-
alkylamino-3-p-fluorophenyl-benzofuro [3,2-d] pyrimi-
din-4(3H)-ones 7, and the other isomer 8 was not found
(Scheme 2). The same selectivity was also observed in
similar cases [11]. The results are also listed in Table 1.
The structures of all products were confirmed using
NMR, IR, elemental analysis, and MS. The structure of
1
7 was deduced from its H NMR data. Among the pos-
sible regioisomers, we obtained only 7 from the reaction
mixture after recrystallization; the other isomer 8 was
C
V
2010 HeteroCorporation

220
Y.-G. Hu, J. Xu, H.-T. Gao, and Z. Ma
Vol 47
Scheme 1
1
not found by H NMR analysis of the reaction mixture.
Furthermore, a single crystal of 7b was obtained from a
CH2Cl2 solution of 7b. X-ray structure analysis verified
again the proposed structure [12] (Fig. 1), which showed
that all ring atoms in the benzofuro [3,2-d] pyrimidinone
system are essentially coplanar; the C15-C20 phenyl
ring is twisted with respect to it, with a dihedral angle
of 87.35(3)ꢁ. Intermolecular C---H. . .O and N---H. . .O
hydrogen bonds link the molecules, helping to stabilize
the crystal structure. Further stability the crystal struc-
ture is provided by offset p–p stacking interactions
involving the fused benzofuro [3,2-d] pyrimidin system
moieties.
are also listed in Table 2. It was found that the com-
pounds showed moderate fungicidal activities when fluo-
rine atom was introduced. As a result, fluorine contain-
ing compounds 5i (79%) displayed better fungicidal
activities than non-substituted phenyl compounds 5j
(42%) to B. cinerea.
In conclusion, we have developed an efficient synthe-
sis of 2-substituted-3-(4-fluorophenyl)-benzofuro [3,2-d]
pyrimidin-4(3H)-ones via the aza-Wittig reactions of
functionalized iminophosphorane with 4-fluorophenyl
isocyanate. Because of the mild reaction condition, good
yields, easily accessible starting material, and straight-
forward product isolation, we think that the versatile
synthetic approach discussed here in many cases com-
pares favorably with other existing methods. The pre-
liminary bioassay indicated that all compounds showed
moderate fungicidal activities against six kinds of fungi,
F. oxysporum, R. solani, B. cinerea, G. zeae, D. grega-
ria, and C. gossypii at a concentration of 50 mg/L.
Fungicidal activity. The fungicidal activities of com-
pounds 5 and 7 were screened against six kinds of fungi,
Fusarium oxysporum, Rhizoctonia solani, Botrytis cin-
erea, Gibberella zeae, Dothiorella gregaria, and Colle-
totrichum gossypii at a concentration of 50 mg/L
according to the reported method [13] and the results
Table 1
EXPERIMENTAL
Yields of compounds 5 and 7.
The NMR spectrums (CDCl3) were recorded on Varian XL-
400 spectrometer with TMS as an internal standard, and IR
spectrum was taken on a Shimadzu IR-408 Infrared spectrome-
ter in KBr Pellets (m in cmꢀ1). The mass spectra were meas-
Compounds
Ar
Y(R)
Yield (%)a
84
5a
p-F-Ph
5b
p-F-Ph
85
Scheme 2
5c
5d
5e
5f
5g
5h
5i
p-F-Ph
p-F-Ph
p-F-Ph
AN(C2H5)2
AN(i-C3H7)2
3,4-dimethylphenoxy
87
80
87
81
88
87
89
82
83
79
88
83
p-F-Ph 4-Chloro-2-methyl-phenoxy
p-F-Ph
p-F-Ph
p-F-Ph
Ph
4-Methyl-phenoxy
Methoxy
Ethoxy
5jb
7a
7b
7c
7db
Ethoxy
n-Propyl
n-Butyl
Cyclohexyl
n-Propyl
p-F-Ph
p-F-Ph
p-F-Ph
Ph
a Yields of isolated products based on iminophosphorane 2.
b Ref. 11.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Synthesis and Fungicidal Activity of 2-Substituted-3-(4-Fluorophenyl)-benzofuro
[3,2-d] Pyrimidin-4(3H)-ones
221
The mixture was stirred for 1–4 h at room temperature. The
solution was concentrated under reduced pressure and the re-
sidual was recrystallized from ethanol and dichloromethane (v/
v ¼ 1:1) at room temperature to give 2-substituted-benzofuro
[3,2-d] pyrimidin-4(3H)-ones 5a–5d.
2-(4-Morpholinyl)-3-(4-fluro-phenyl)-benzofuro [3,2-d] pyr-
imidin-4(3H)-one (5a). White crystals (yield: 0.61 g, 84%),
1
Mp: 233–234ꢁC. H NMR (CDCl3, 400 MHZ) d ¼ 3.15 (t, J
¼ 4.8, 4H, 2 ꢂ OCH2), 3.47 (t, J ¼ 4.8, 4H, 2 ꢂ NCH2),
7.21–8.03 (m, 8H, Ar-H); IR (KBr): 1701 (C¼¼O), 1538, 1253,
1109 cmꢀ1; MS (70 eV) m/z (%): 365 (Mþ, 60), 320 (69), 308
(93), 214 (40), 130 (56), 102 (47), 86 (48); Anal. Calcd for
C20H16FN3O3 (365.4): C, 65.75; H, 4.41; N, 11.50; Found: C,
65.83; H, 4.50; N, 11.43.
2-(1-Piperidinyl)-3-(4-fluro-phenyl)-benzofuro [3,2-d] pyri-
midin-4(3H)-one (5b). White crystals (yield: 0.62 g, 85%),
Mp: 253–255ꢁC. 1H NMR (CDCl3, 400 MHZ) d ¼1.27–1.47
(m, 6H, 3 ꢂ CH2), 3.11–3.14 (m, 4H, 2 ꢂ NCH2), 7.19–8.03
(m, 8H, Ar-H); IR (KBr): 1703 (C¼¼O), 1540, 1248, 1098
cmꢀ1; MS (70 eV) m/z (%): 363 (Mþ, 100), 320 (27), 254
(32), 223 (24), 178 (89), 130 (21), 102 (69), 84 (51); Anal.
Calcd for C21H18FN3O2 (363.4): C, 69.41; H, 4.99; N, 11.56;
Found: C, 69.50; H, 5.12; N, 11.44.
Figure 1. X-ray crystal structure of 7b.
ured on a Finnigan Trace MS spectrometer. Elemental analyses
were taken on a Vario EL III elementary analysis instrument.
The melting points were determined on X4 microscopic melt-
ing apparatus (uncorrected). All the solvents and materials
were reagent grade and purified as required.
2-Diethylamino-3-(4-fluro-phenyl)-benzofuro [3,2-d] pyri-
midin-4(3H)-one (5c). White crystals (yield: 0.61 g, 87%),
General procedure for the preparation of 2-dialkyla-
mino-3-(4-fluorophenyl)-benzofuro [3,2-d] pyrimidin-4(3H)-
ones 5a–5d. To a solution of iminophosphorane 2 (0.93 g, 2
mmol) in dry methylene chloride (15 mL) was added p-Fluoro-
phenyl isocyanate (2 mmol) under nitrogen at room tempera-
ture. After the reaction mixture was stood for 8–12 h at 0–
5ꢁC, the solvent was removed off under reduced pressure and
ether/petroleum ether (1:2, 20 mL) was added to precipitate
triphenylphosphine oxide. After filtration, the solvent was
removed to give carbodiimide 3, which was used directly with-
out further purification. To the solution of 3 prepared above in
methylene chloride (15 mL) was added dialkylamine (2
mmol). After the reaction mixture was allowed to stand for
0.5–4 h, the solution was condensed and anhydrous ethanol
(10 mL) with several drops of EtOꢀNaþ in EtOH was added.
1
Mp: 177–179ꢁC. H NMR (CDCl3, 400 MHZ) d ¼ 0.88 (t, J
¼ 7.2 Hz, 6H, 2 ꢂ CH3), 3.11 (q, J ¼ 7.2 Hz, 4H, 2 ꢂ
NCH2), 7.18–8.03 (m, 8H, Ar-H); IR (KBr): 1704 (C¼¼O),
1537, 1245, 1112 cmꢀ1; MS (70 eV) m/z (%): 351 (Mþ, 90),
322 (100), 254 (46), 228 (77), 184 (48), 130 (66), 102 (75), 94
(52); Anal. Calcd for C20H18FN3O2 (351.4): C, 68.36; H, 5.16;
N, 11.96; Found: C, 68.43; H, 5.25; N, 11.85.
2-Diisopropylamino-3-(4-fluro-phenyl)-benzofuro
pyrimidin-4(3H)-one (5d). White crystals (yield: 0.61 g, 80%),
[3,2-d]
1
Mp: 171–172ꢁC; H NMR (CDCl3, 400 MHZ) d ¼ 1.13 (d, J
¼ 6.4 Hz, 12H, 4 ꢂ CH3), 3.52 (m, 2H, 2 ꢂ NCH), 7.17–8.00
(m, 8H, Ar-H); IR (KBr): 1702 (C¼¼O), 1539, 1245, 1098
cmꢀ1; MS (70 eV) m/z (%): 379 (Mþ, 14), 336 (100), 322
(22), 130 (9.5), 102 (4), 99 (17); Anal. Calcd for
Table 2
The fungicidal activities of 5 and 7 (50 mg/L).
Relative inhibition %
Fusarium
oxysporium
Rhizoctonia
solani
Botrytis
cinerea
Gibberella
zeae
Dothiorella
gregaria
Colletotrichum
gossypii
Compounds
5a
5b
5c
5d
5e
5f
5g
5h
5i
21.1
47.5
48.5
42.2
54.3
55.6
31.1
38.5
60.7
39.8
45.9
35.9
32.2
28.5
30.2
68.5
62.2
17.1
62.4
66.4
12.0
18.1
62.4
53.6
17.1
17.1
42.2
45.1
45.0
78.0
75.0
25.0
50.0
58.8
30.0
75.0
79.0
42.0
57.0
35.0
55.0
35.0
41.4
62.9
28.6
38.6
31.4
56.1
42.9
15.7
60.0
31.2
18.6
18.6
21.4
28.6
50.5
32.8
22.9
37.7
24.7
39.5
34.7
25.9
53.5
26.5
40.6
10.0
15.9
27.9
31.1
43.3
48.5
28.5
48.5
65.2
64.4
32.2
60.7
47.8
21.1
38.5
38.5
48.5
5j
7a
7b
7c
7d
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

222
Y.-G. Hu, J. Xu, H.-T. Gao, and Z. Ma
Vol 47
C22H22FN3O2 (379.4): C, 69.64; H, 5.84; N, 11.07; Found: C,
69.71; H, 5.92; N, 11.00.
CH3), 4.50 (d, J ¼ 7.2, 2H, CH2), 7.19–8.02 (m, 8H, Ar-H);
IR (KBr): 1699 (C¼¼O), 1540, 1339, 1112 cmꢀ1; MS (70 eV)
m/z (%): 324 (Mþ, 96), 295 (46), 185 (68), 158 (100), 130
(20), 102 (70), 95 (10); Anal. Calcd for C18H13FN2O3 (324.3):
C, 66.66; H, 4.04; N, 8.64. Found: C, 66.71; H, 4.10; N, 8.60.
General procedure for the preparation of 2-alkylamino-
benzofuro [3,2-d] pyrimidin-4(3H)-ones 7a–7c. To the solu-
tion of carbodiimide 3 (ca. 2 mmol) prepared above in methyl-
ene chloride (15 mL) was added alkylamine (2 mmol). After
the reaction mixture was allowed to stand for 0.5–2 h, the so-
lution was condensed and anhydrous ethanol (10 mL) with
several drops of EtOꢀNaþ in EtOH was added. The mixture
was stirred for 1–4 h at room temperature. The solution was
concentrated under reduced pressure and the residual was
recrystallized from ethanol and dichloromethane (v/v ¼ 1:2) at
room temperature to give 2-alkylamino-benzofuro [3,2-d] pyri-
midin-4(3H)-ones 7a–7c.
General procedure for the preparation of 2-aroxy-3-(4-
fluorophenyl)-benzofuro [3,2-d] pyrimidin-4(3H)-ones 5e–
5g. To the solution of carbodiimide 3 (ca. 2 mmol) prepared
above in CH3CN (15 mL) was added K2CO3 (0.2 mmol) and
ArOH (2 mmol) in anhydrous CH3CN (10 mL). The mixture
was stirred for 6–8 h at 50–60ꢁC. The solution was concen-
trated under reduced pressure and the residue was recrystal-
lized from dichloromethane and ethanol (v/v ¼ 2:1) at room
temperature to give 5e–5g.
2-(3,4-Dimethylphenoxy)-3-(4-fluro-phenyl)-benzofuro [3,2-
d] pyrimidin-4(3H)-one (5e). White crystals (87% yields),
Mp: 172–173ꢁC. 1H NMR (400 MHz, CDCl3) d ¼ 2.25 (s,
6H, 2 ꢂ CH3), 6.91–7.84 (m, 11H, Ar-H); 13C NMR (CDCl3,
100 MHz) d ¼ 19.1, 19.8, 112.7, 116.4, 116.6, 118.2, 121.7
(1), 122.3, 123.5, 129.5, 129.8 (2), 130.2, 130.5, 134.3, 135.5,
138.0, 142.0, 149.7, 153.6, 157.2, 161.4, 163.8; IR (KBr):
1698 (C¼¼O), 1536, 1332, 1112 cmꢀ1; MS (70 eV) m/z (%):
400 (47), 262 (100),130 (30),102 (16), 95 (6); Anal. Calcd for
C19H16FN3O2 (400.4): C, 71.99; H, 4.28; N, 7.00. Found: C,
72.05; H, 4.34; N, 6.96.
2-(4-Chloro-2-methyl-phenoxy)-3-(4-fluro-phenyl)-benzofuro
[3,2-d] pyrimidin-4(3H)-one (5f). White crystals (81% yield),
Mp: 241–242ꢁC. 1H NMR (400 MHz, CDCl3) d ¼ 2.18 (s,
3H, Ar-CH3), 7.16–7.82 (m, 13H, Ar-H); 13C NMR (CDCl3,
100 MHz) d ¼ 16.5, 112.8, 116.8, 121.8, 122.2, 123.7, 127.5,
127.7, 129.4, 129.8, 130.2, 131.6, 134.1, 135.7, 142.0, 145.1,
151.5, 153.4, 157.3, 161.6, 164.1. IR (KBr): 1701 (C¼¼O),
1543, 1328, 1098 cmꢀ1; MS (70 eV) m/z (%): 420 (Mþ, 22),
282 (100), 130 (21), 95 (4); Anal. Calcd for C23H14ClFN2O3
(420.1): C, 65.64; H, 3.35; N, 6.66. Found: C, 65.61; H, 3.37;
N, 6.59.
3-(4-Fluorophenyl)-2-(n-propylamino)-benzofuro
[3,2-d]
pyrimidin-4(3H)-one (7a). White crystals (yield: 0.56 g, 83%),
Mp: 199–200ꢁC; 1H NMR (400 MHz, CDCl3) d ¼ 0.87 (t, J
¼ 7.2 Hz, 3H, CH3), 1.54–1.60 (m, 2H, CH2), 3.42–3.47 (m,
2H, NCH2), 4.11 (s, 1H, NH), 7.30–8.02 (m, 8H, Ar-H); IR
(KBr): 3341 (NAH), 1699 (C¼¼O), 1540, 1342, 1111 cmꢀ1
;
MS (70 eV) m/z (%): 337 (Mþ, 32), 294 (100), 185 (35), 160
(64), 130 (71), 102 (82), 95 (53); Anal. Calcd for
C19H16FN3O2 (337.4): C, 67.65; H, 4.78; N, 12.46. Found: C,
67.71; H, 4.84; N, 12.37.
3-(4-Fluorophenyl)-2-(n-butylamino)-benzofuro [3,2-d] pyr-
imidin-4(3H)-one (7b). White crystals (yield: 0.56 g, 79%),
Mp: 191–192ꢁC. 1H NMR (400 MHz, CDCl3) d ¼ 0.89 (t, J
¼ 7.2 Hz, 3H, CH3), 1.25–1.54 (m, 4H, 2 ꢂ CH2), 3.43–3.47
(m, 2H, NCH2), 4.14 (s, 1H, NH), 7.29–8.01 (m, 8H, Ar-H);
13C NMR (CDCl3, 100 MHz) d ¼ 13.6, 19.8, 31.0, 41.8,
112.6, 117.6 (2), 121.5, 122.9, 123.0, 129.2, 130.8 (1), 132.9,
144.6, 151.8, 153.6, 157.2, 161.7,164.2. IR (KBr): 3336
(NAH), 1704 (C¼¼O), 1533, 1340, 1115 cmꢀ1; MS (70 eV) m/
z (%): 351 (Mþ, 78), 334 (41),308 (35), 294 (100), 185 (48),
130 (70),102 (82), 95 (52); Anal. Calcd for C20H18FN3O2
(351.4): C, 68.36; H, 5.16; N, 11.96. Found: C, 68.33; H,
5.20; N, 11.89.
2-(4-Methyl-phenoxy)-3-(4-fluro-phenyl)-benzofuro [3,2-d]
pyrimidin-4(3H)-one (5g). White crystals (88% yield), Mp:
1
170–172ꢁC. H NMR (400 MHz, CDCl3) d ¼ 2.37 (s, 3H, Ar-
CH3), 7.04–7.86 (m, 13H, Ar-H); 13C NMR (CDCl3, 100
MHz) d ¼ 20.8, 112.8, 116.4, 116.7, 120.9, 121.3, 122.9,
123.2, 129.6, 129.8 (2), 130.5, 135.5, 135.7, 142.0, 149.6,
153.5, 157.3, 161.4, 163.9. IR (KBr): 1705 (C¼¼O), 1539,
1346, 1108 cmꢀ1; MS (70 eV) m/z (%): 386 (Mþ, 44), 249
(100), 130 (27), 95 (6); Anal. Calcd for C23H15FN2O3 (386.4):
C, 71.50; H, 3.91; N, 7.25. Found: C, 71.42; H, 3.88; N, 7.19.
General procedure for the preparation of 2-alkoxy-3-(4-
fluorophenyl)-benzofuro [3,2-d] pyrimidin-4(3H)-ones 5h–
5i. To the solution of carbodiimide 3 (ca. 2 mmol) prepared
above in anhydrous ROH (8 mL) was added ROꢀNaþ (0.2
mmol, 10% equiv) in ROH. The mixture was stirred for 4–6 h
at room temperature. The solution was condensed and the resi-
due was recrystallized from ROH to give 5h–5i.
2-(Cyclohexylamino)-3-(4-fluorophenyl)-benzofuro [3,2-d]
pyrimidin-4(3H)-one (7c) White crystals (yield: 0.66 g, 88%),
1
Mp: 188–190ꢁC. H NMR (400 MHz, CDCl3) d ¼ 1.05–1.42
(m, 6H, 3 ꢂ CH2), 1.60–1.62 (m, 4H, 2 ꢂ CH2), 1.96–1.99
(m, 1H, CH), 4.02–4.05 (m, 1H, NH), 7.19–8.04 (m, 9H, Ar-
H); IR (KBr): 1704 (C¼¼O), 1533, 1340, 1115 cmꢀ1; MS (70
eV) m/z (%): 377 (Mþ, 22), 294 (100), 185 (20), 130 (29),102
(30), 98 (27), 55 (26); Anal. Calcd for C22H20FN3O2 (377.4):
C, 70.01; H, 5.34; N, 11.13. Found: C, 69.97; H, 5.37; N,
11.08.
2-Methoxy-3-(4-florophenyl)-benzofuro [3,2-d] pyrimidin-
4(3H)-one (5h). White crystals (yield: 0.54 g, 87%), Mp: 236–
237ꢁC. 1H NMR (400 MHz, CDCl3) d ¼ 4.04 (s, 3H, CH3),
7.19–8.03 (m, 8H, Ar-H); IR (KBr): 1701 (C¼¼O), 1541, 1340,
1108 cmꢀ1; MS (70 eV) m/z (%): 310 (100), 136 (33), 130
(47), 108 (98), 102 (68), 95 (28), 75 (16); Anal. Calcd for
C19H16FN3O2 (310.3): C, 65.81; H, 3.57; N, 9.03. Found: C,
65.87; H, 3.62; N, 8.98.
Fungicidal testing. F. oxysporium, R. solani, B. cinereap-
ers, G. zeae, D. gregaria, and C. gossypii were provided
through the courtesy of the Center for bioassay, Central China
Normal University. The tested samples were dissolved in 0.5
mL of DMF, added to a drop of emulsifying agent (Tween 80)
and sterile water at a concentration of 500 mg/L. The solutions
(1 mL) were mixed rapidly with thawed potato glucose agar
culture medium (9 mL) under 50ꢁC. The mixtures were poured
into Petri dishes. After the dishes were cooled, the solidified
plates were incubated with 4 mm mycelium disk, inverted, and
incubated at 28ꢁC for 48 h. The mixed medium without
2-Ethoxy-3-(4-florophenyl)-benzofuro [3,2-d] pyrimidin-
4(3H)-one (5i). White crystals (yield: 0.56 g, 89%), Mp: 202–
1
204ꢁC. H NMR (400 MHz, CDCl3) d ¼ 1.28 (t, J ¼ 7.2, 3H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Synthesis and Fungicidal Activity of 2-Substituted-3-(4-Fluorophenyl)-benzofuro
[3,2-d] Pyrimidin-4(3H)-ones
223
[2] Wendt, J. A.; Deeter, S. D.; Bove, S. E.; Knauer, C. S.;
Brooker, R. M.; Augelli-Szafran, C. E.; Schwarz, R. D.; Kinsora, J. J.;
Kilgore, K. S. Bioorg Med Chem Lett 2007, 17, 5396.
[3] Bodke, Y.; Sangapure, S. S. J Indian Chem Soc 2003, 80,
187.
sample was used as the blank control. Three replicates of each
test were carried out. The mycelial elongation radius (mm) of
fungi settlements was measured after 48 h of culture. The
growth inhibition rates were calculated with the following
equation: I ¼ [(CꢀT)/C] ꢂ 100%. Here, I is the growth inhibi-
tion rate (%), C is the control settlement radius (mm), and T is
the treatment group fungi settlement radius (mm).
[4] Glazer, E. A.; McFarland, J. W. US Patent 4,725,599, 2008;
Chem Abstr 1989, 110, 231654x.
[5] Ishida, A.; Inage, M.; Akatsuka, H.; Inamasu, M.; Mitsui,
T. JP 6,220,059, 1994; Chem Abstr 1995, 122, 81390q.
[6] Elliott, A. J.; Hudlicky, M. In Chemistry of Organic Fluo-
rine Compounds. II. A Critical Review; Avlath, A. E., Ed.; American
chemical society: Washington, DC, 1995; pp 1119–1125.
[7] Smart, B. E. J Fluor Chem 2001, 121, 3.
Crystal structure determination. Single crystal X-ray dif-
fraction data for 7b at 292 K on a Bruker Smart Apex Area CCD
equipped with Mo Ka radiation (k ¼ 0.71073 Aꢁ). Crystallo-
graphic data (excluding structure factors) for the structures in
this article have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication No. CCDC
671114. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ.
[8] Ulrich, H. Chemistry and Technology of Carbodiimides;
John Wiley & Sons, Ltd.: Chichester, 2007.
[9] Li, Q.; Wei, Y.; Hao, J.; Zhu, Y.; Wang, L. J Am Chem
Soc 2007, 129, 5810.
Acknowledgments. The authors acknowledge the financial sup-
port of this work by the Key Science Research Project of Hubei
Provincial Department of Education (No. D200724001), the
Science Research Project of Yunyang Medical College (No.
2006QDJ16), and the Science Innovation Team Research Project
of Yunyang Medical College (No. 2008 CXG01).
[10] Ding, M. W.; Xu, S. Z.; Zhao, J. F. J Org Chem 2004, 69,
8366.
[11] Hu, Y. G.; Liu, M. G.; Ding, M. W. Helv Chim Acta 2008,
91, 862.
[12] Crystal data of 7b. C20H18FN3O2, Mr ¼ 351.37; Crystal
system: tetragonal; space group: P-42(1)c; unit cell dimensions: a ¼
˚
˚
11.0922(6), b ¼ 11.0922(6), c ¼ 28.6271(15)A, V ¼ 3522.2(3) A3, Z
¼ 8, Dc ¼ 1.325, F (000) ¼ 1472, l ¼ 0.095 mmꢀ1, MoKa radiation
(k ¼ 0.71073), R ¼ 0.0498, wR ¼ 0.1238 for 2336 observed reflec-
tions with I > 2r(I).
REFERENCES AND NOTES
[1] Naya, S.; Ohtoshi, H.; Nitta, M. J Org Chem 2006, 71,
176.
[13] Ren, Q.; Cui, Z.; He, H.; Gu, Y. J Fluor Chem 2007, 128,
1369.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet