Efficient synthesis and fungicidal activities of 2-alkylthiobenzofuro[3,2- d]pyrimidinones

Article abstract of DOI:10.1080/10426500903008922

2-Alkylthiobenzofuro[3,2-d]pyrimidinones 5 and 6 were synthesized by S-alkylation of 2,3-dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-ones 4, which were obtained via aza-Wittig reaction of iminophosphorane 2 with CS2 and further reaction of the product

Full text of DOI:10.1080/10426500903008922

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Phosphorus, Sulfur, and Silicon and the
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Efficient Synthesis and Fungicidal
Activities of 2-Alkylthiobenzofuro[3,2-
d]Pyrimidinones
a b
a
a
Yang-Gen Hu
, Wen-Qing Wang & Ming-Wu Ding
a
Key Laboratory of Pesticide & Chemical Biology of Ministry of
Education , Central China Normal University , Wuhan, P. R. China
b
Department of Medicinal Chemistry , Yunyang Medical College ,
Shiyan, P. R. China
Published online: 23 Mar 2010.
To cite this article: Yang-Gen Hu , Wen-Qing Wang & Ming-Wu Ding (2010) Efficient Synthesis and
Fungicidal Activities of 2-Alkylthiobenzofuro[3,2-d]Pyrimidinones, Phosphorus, Sulfur, and Silicon and
the Related Elements, 185:4, 857-864, DOI: 10.1080/10426500903008922
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Phosphorus, Sulfur, and Silicon, 185:857–864, 2010
Copyright ꢀ
Taylor & Francis Group, LLC
C
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903008922
EFFICIENT SYNTHESIS AND FUNGICIDAL ACTIVITIES
OF 2-ALKYLTHIOBENZOFURO[3,2-d]PYRIMIDINONES
1
,2
1
1
Yang-Gen Hu, Wen-Qing Wang, and Ming-Wu Ding
1
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education,
Central China Normal University, Wuhan, P. R. China
Department of Medicinal Chemistry, Yunyang Medical College, Shiyan,
2
P. R. China
2-Alkylthiobenzofuro[3,2-d]pyrimidinones 5 and 6 were synthesized by S-alkylation of 2,3-
dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-ones 4, which were obtained via aza-
Wittig reaction of iminophosphorane 2 with CS2 and further reaction of the product with
various amines. Compounds 5 and 6 exhibited fungicidal activity. For example, compound
6a, which has a small N-substituted methyl group, showed the best inhibitive activity (91%)
against Dothiorella gregaria at 50 mg/L.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Aza-Wittig reaction; benzofuro[3,2-d]pyrimidinone; carbon disulfide; fungicidal
activity; iminophosphorane
INTRODUCTION
The derivatives of heterocycles containing the benzofuropyrimidinone system are
of great importance because of their remarkable biological properties. For example, some
derivatives of benzofuropyrimidinones have shown good analgesic, anti-inflammatory, and
1,2
antimicrobial activities, whereas others exhibited good anticoccidial and blood sugar-
lowering activities.3 The literature-reported methods for the preparation of some repre-
sentative derivatives of benzofuro[3,2-d]pyrimidin-4(3H)-one involve the reaction of 3-
amino-2-(ethoxycarbonyl) benzofuran with orthoformate and an amine, the rearrangement
of benzofuro[3,2-d]oxazines by treatment with an amine, or the cyclization of 3-amino-
,4
5
–8
2-(aminocarbonyl)benzofuran with acyl chlorides.
However, 2-thioxobenzofuro[3,2-
d]pyrimidin-4(3H)-ones are not easily accessible by currently existing routes. Recently
aza-Wittig reactions were applied to produce carbodiimides able to undergo a plethora of
Received 19 March 2009; accepted 30 April 2009.
We gratefully acknowledge financial support of this work by the Science Leader Plan of Wuhan City
(
No. 200750730312), National Natural Science Foundation of China (Project No. 20772041), and Key Project of
Hubei Provincial Department of Education (No. D200724001).
Address correspondence to Ming-Wu Ding, Key Laboratory of Pesticide & Chemical Biology of Ministry
of Education, Central China Normal University, Wuhan 430079, P. R. China. E-mail: ding5229@yahoo.com.cn
8
57

8
58
Y.-G. HU ET AL.
heterocyclization reactions.9–12 We have been interested in the synthesis of quinazolinones,
thienopyrimidinones, and imidazolinones via the reaction of α- or β-ethoxycarbonyl car-
1
3–18
bodiimides with various nucleophiles under mild conditions.
The method was also
utilized in the synthesis of some 2-amino or 2-aryl(alkyl)oxy substituted benzofuro[3,2-
d]pyrimidin-4(3H)-ones.16 In this article we wish to report further an efficient synthesis
and fungicidal activities of 2-alkylthio substituted benzofuro[3,2-d]pyrimidin-4(3H)-ones
by the aza-Wittig reaction of β-ethoxycarbonyl iminophosphorane 2 with CS2, followed
by reaction with amines and halides under basic conditions.
RESULTS AND DISCUSSION
As shown in Scheme 1, iminophosphorane 2, obtained from amine 1 with triph-
enylphosphine, hexachloroethane, and triethylamine, reacted with excess carbon disulfide
to give isothiocyanate 3. While the reaction of 3 with aliphatic primary amines took place
smoothly at room temperature to give directly 2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-
one 4 in 72–88% yields, aromatic primary amines required reaction in acetonitrile in the
presence of sodium ethoxide. The results are listed in Table I. S-Alkylation of 4 with
alkyl halides or methyl 3-(2-(bromomethyl)phenyl)-3-methoxyacrylate in the presence of
potassium carbonate provided 2-alkylthio-benzofuro[3,2-d]pyrimidin-4(3H)-ones 6 and 7
◦
1
2
in 74–89% yields at 50 C. There are no obvious effects of the R or R groups on the
reaction, and the products 6 and 7 were obtained in good yields. It is noteworthy that
isothiocyante 3 can generally be prepared from the reaction of the corresponding ethyl 3-
aminobenzofuran-2-carboxylate with the highly toxic thiophosgene. The method described
here provides an efficient synthesis of isothiocyante 3 without using the highly toxic
thiophosgene. The methyl 3-(2-(bromomethyl)phenyl)-3-methoxyacrylate was selected as
the main halide because the products 6 obtained can be regarded as the analogues of
NH2
COOEt
N=PPh
3
NCS
COOEt
PPh3
C Cl
NEt3
CS2
2
6
COOEt
O
O
O
1
2
3
SR2
N
N
R1
2
R X/K CO (s)
2
3
O
O
H
S
5
N
1
R NH
2
N
R1
O
O
COOMe
K CO (s)
2
3
4
MeO
S
N
MeO
N R1
COOMe
O
CH Br
O
2
6
Scheme 1

2-ALKYLTHIOBENZOFURO[3,2-d]PYRIMIDINONES
859
Table I Preparation of compounds 4, 5, and 6
R1
R X
2
Condition
Yield (%)
Compd.
4
4
4
4
4
4
4
4
5
5
5
5
6
6
6
6
6
6
6
6
a
b
c
d
e
Me
Et
n-Pr
n-Bu
n-C5H11
PhCH2
H
4-ClC6H4
n-Pr
n-Pr
n-Pr
n-Pr
Me
Et
n-Pr
n-Bu
n-C5H11
PhCH2
H
r.t. / 05 h
r.t. / 0.5 h
r.t. / 1 h
r.t. / 1 h
r.t. / 1 h
r.t. / 1 h
r.t. / 0.5 h
84
86
82
81
72
86
88
80
86
82
85
86
87
88
87
79
74
86
89
84
f
g
h
a
b
c
d
a
b
c
d
e
f
g
h
a
r.t. / 3 h
◦
n-PrBr
PhCH2Cl
n-BuBr
BrCH2COOEt
50 C / 3 h
◦
50 C / 4 h
◦
50 C / 4 h
◦
50 C / 2 h
◦
50 C / 4 h
◦
50 C / 4 h
◦
50 C / 6 h
◦
50 C / 5 h
◦
50 C / 5 h
◦
50 C / 4 h
◦
50 C / 4 h
◦
4-ClC6H4
50 C / 6 h
aThen treated with sodium ethoxide in ethanol at r.t. for 2 h.
Strobilurin fungicides. Strobilurin fungicides are an important class of agricultural fungi-
cides and exhibit strong fungicidal activity against various fungi by binding to electron
transfer at the ubiquinol-oxidation center (Qo-site) of the bc1-enzyme complex (complex
19–21
III).
By using the above synthetic method, the new Strobilurin derivatives 6 containing
benzofuro[3,2-d]pyrimidinone were obtained in good yields.
The structure of compounds 5 and 6 was confirmed by their spectral data. For example,
the H NMR spectrum of 6b shows two singlets at 3.72 and 3.86 ppm and a singlet due to
1
the two OCH3, respectively. The signals of NCH2CH3 appear at 1.36 ppm as triplets and
4.24 ppm as quarterlets, respectively. The signals attributable to the Ar–Hs are found at
7
.18–8.05 ppm as multiplet respectively. The IR spectra of 6b revealed C O absorption
−1
bands at 1700 cm . The MS spectrum of 6b shows a molecular ion peak at m/z 450 with
1% abundance.
The biological activities of 5 and 6 were investigated (see the Supplemental Materials
1
available online, Table S1).
In conclusion, we described an efficient synthesis of 2-alkylthio substituted
benzofuro[3,2-d]pyrimidin-4(3H)-ones by the aza-Wittig reaction. This protocol presented
many advantages, such as good to excellent yields, mild reaction conditions, readily avail-
able starting materials, and simple purification procedure. The preliminary investigation
on the biological activities shows that one of the compounds exhibited good fungicidal
activities.
EXPERIMENTAL
Unless otherwise noted, all materials were commercially available and were used
1
directly without further purification. All solvents were redistilled before use. H NMR

8
60
Y.-G. HU ET AL.
spectra were recorded on a Mercury-Plus 400 or 600 spectrometer in CDCl3 or DMSO-d6
with TMS as the internal reference. MS spectra were determined using a Trace MS 2000
organic mass spectrometer. Elemental analyses were performed on a Vario EL III elemental
analysis instrument. Melting points were taken on an X-4 binocular microscope melting
point apparatus (Beijing Tech Instruments Co., Beijing, China) and are uncorrected. The
12
iminophosphorane 2 was prepared according to the reported method.
General Preparation of 2,3-Dihydro-2-thioxobenzofuro
3,2-d]pyrimidin-4(1H)-one 4a-4h
[
To a solution of iminophosphorane 2 (9.30 g, 20 mmol) in anhydrous methylene
dichloride and acetonitrile (20 mL, v/v = 1:1), excess carbon disulfide (15 mL) was
added. After the reaction mixture was refluxed for 24–28 h, the solvent was condensed
under reduced pressure and ether (10 mL) was added to precipitate triphenylphosphine
sulfide. The precipitate was removed by filtration, and the filtrate was evaporated to give
ethyl 3-isothiocyanato-benzofuran-2-carboxylate 3, which was used directly without further
purification. To a solution of the crude 3 in CH3CN (20 mL), amine (20 mmol) was added
and the mixture was stirred for 0.5–1 h at room temperature. While an aromatic amine
was used, the solvent was removed, and anhydrous EtOH (10 mL) with several drops of
EtONa in EtOH was added. The mixture was stirred for 2 h at room temperature. The
precipitated solid was collected and washed with ethanol and crystallized from methylene
dichloride/petroleum ether to give 2,3-dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-
ones 4.
3
-Methyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4a).
◦
1
White solid, mp > 300 C. H NMR (600 MHz, DMSO-d6): 3.70 (s, 3H, NCH3), 7.36–7.95
m, 4H, Ar H). MS (70 eV) m/z (%): 232 (M , 100), 202 (7), 159 (30), 130 (10), 103
33), 76 (5). Anal. Calcd for C11H8N2O2S (232.3): C, 56.88; H, 3.47; N, 12.06. Found: C,
+
(
(
56.71, H, 3.69; N, 12.24.
3
-Ethyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4b).
◦
1
White solid, mp > 300 C. H NMR (600 MHz, DMSO-d6): 1.17 (t, J = 7.2 Hz, 3H,
CH3), 4.59 (q, J = 7.2 Hz, 2H, NCH2), 7.38–7.96 (m, 4H, Ar H). MS (70 eV) m/z (%):
+
2
46 (M , 100), 218 (56), 202 (34), 159 (55), 130 (26), 103 (58), 77 (40). Anal. Calcd for
C12H10N2O2S (246.3): C, 58.52; H, 4.09; N, 11.37. Found: C, 58.27, H, 4.04; N, 11.48.
-Propyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4c).
3
◦
1
White solid, mp > 300 C. H NMR (400 MHz, DMSO-d6): 0.89 (t, J = 7.2 Hz, 3H, CH3),
1
(
.52–1.58 (m, 2H, CH2), 4.45 (t, J = 7.2 Hz, 2H, NCH2), 7.35–7.93 (m, 4H, Ar H). MS
+
70 eV) m/z (%): 260 (M , 66), 217 (98), 158 (100), 129 (31), 102 (82), 76 (16). Anal.
Calcd for C13H12N2O2S (260.3): C, 59.98; H, 4.65; N, 10.76. Found: C, 59.84, H, 4.46; N,
0.84.
1
3
-Butyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4d).
◦
1
White solid, mp 295–296 C. H NMR (400 MHz, DMSO-d6): 0.93 (t, J = 7.2 Hz, 3H,
CH3), 1.40–1.78 (m, 4H, 2×CH2), 4.17 (t, J = 7.2 Hz, 2H, NCH2), 7.36–7.98 (m, 4H,
+
Ar H). MS (70 eV) m/z (%): 274 (M , 59), 241 (100), 218 (35), 202 (36), 160 (33), 130
(
11), 103 (30), 76 (7). Anal. Calcd for C14H14N2O2S (274.3): C, 61.29; H, 5.14; N, 10.21.
Found: C, 61.48, H, 5.12; N, 10.07.
-Pentyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4e).
3
◦
1
White solid, mp 290–292 C. H NMR (600 MHz, DMSO-d6): 0.82 (t, J = 7.2 Hz, 3H,
CH3), 1.24–2.87 (m, 6H, 3×CH2), 4.50 (t, J = 7.2 Hz, 2H, CH2), 7.36–7.94 (m, 4H,

2-ALKYLTHIOBENZOFURO[3,2-d]PYRIMIDINONES
861
+
Ar H). MS (70 eV) m/z (%): 288 (M , 16), 255 (100), 217 (39), 201 (31), 158 (35), 129
(
11), 102 (43), 87 (20). Anal. Calcd for C15H16N2O2S (288.4): C, 62.48; H, 5.59; N, 9.71.
Found: C, 62.54, H, 5.32; N, 9.53.
-Benzyl-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one (4f).
3
◦
1
White solid, mp > 300 C. H NMR (600 MHz, DMSO-d6): 5.86 (s, 2H, CH2), 7.17–7.94
(
(
m, 9H, Ar H), 8.07 (s, 1H, NH). MS (70 eV) m/z (%): 308 (100), 275 (43), 202 (6), 148
4), 91 (8). Anal. Calcd for C17H12N2O2S (308.4): C, 66.22; H, 3.92; N, 9.08. Found: C,
66.14, H, 3.75; N, 9.26.
2
-Thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-4(1H)-one
(4g). White
◦
1
solid, mp > 300 C. H NMR (600 MHz, DMSO-d6): 7.36–7.65 (m, 3H, Ar H), 7.92–7.93
m, 1H, Ar H). MS (70 eV) m/z (%): 218 (M , 77), 160 (41), 103 (100), 76 (28). Anal.
+
(
Calcd for C10H6N2O2S (218.2): C, 55.04; H, 2.77; N, 12.84. Found: C, 55.19, H, 2.64; N,
2.95.
1
3
-(4-Chlorophenyl)-2-thioxo-2,3-dihydrobenzofuro[3,2-d]pyrimidin-
◦
1
4
7
(1H)-one (4h). White solid, mp > 300 C; H NMR (600 MHz, DMSO-d6): δ =
+
.35–8.26 (m, 8H, Ar H). MS (70 eV) m/z (%): 328 (M , 100), 295 (18), 202 (25), 159
(56), 130 (29), 103 (59), 76 (18). Anal. Calcd for C16H9ClN2O2S (328.8): C, 58.45; H,
2.76; N, 8.52. Found: C, 58.22, H, 2.81; N, 8.78.
General Preparation of 2-Alkylthiobenzofuro[3,2-d]pyrimidin-4(3H)-one
5a–5d and 6a–6h
To a solution of 2,3-dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-one 4 (1
mmol) in dry DMF (5 mL), alkyl halide (1 mmol) and solid potassium carbonate (0.28 g, 2
◦
mmol) were added. The mixture was stirred for 3–6 h at 50 C. The solution was cooled and
diluted with water (20 mL). The solid product obtained was filtered and recrystallized from
methylene dichloride/petroleum ether (v/v) to give 2-alkylthiobenzofuro[3,2-d]pyrimidin-
4(3H)-ones 5 and 6.
3
-Propyl-2-propylthiobenzofuro[3,2-d]pyrimidin-4(3H)-one (5a). White
◦
1
crystals, mp 122–124 C. H NMR (400 MHz, CDCl3): 1.02 (t, J = 7.2 Hz, 3H, CH3),
1
4
1
1
1
9
.10 (t, J = 7.2 Hz, 3H, CH3), 1.82–1.89 (m, 4H, 2CH2), 3.34 (t, J = 7.2 Hz, 2H, SCH2),
13
.18 (t, J = 7.2 Hz, 2H, NCH2), 7.39–8.01 (m, 4H, Ar H). C NMR (100 MHz, CDCl3):
57.9, 156.8, 153.5, 142.3, 136.1, 129.2, 123.5, 122.3, 121.1, 112.6, 46.1, 34.3, 21.9, 21.1,
+
3.4, 11.1. MS (70 eV) m/z (%): 302 (M , 100), 259 (86), 232 (21), 217 (62), 202 (32),
60 (32), 130 (22), 102 (30). Anal. Calcd for C16H18N2O2S (302.4): C, 63.55; H, 6.00; N,
.26. Found: C, 63.78; H, 5.84; N, 9.49.
2
-Benzylthio-3-propylbenzofuro[3,2-d]pyrimidin-4(3H)-one (5b). White
◦
1
crystals, mp 118–119 C. H NMR (400 MHz, CDCl3): 0.99 (t, J = 7.2 Hz, 3H, CH3),
.79–1.85 (m, 2H, CH2), 4.18 (t, J = 7.2 Hz, 2H, NCH2), 4.60 (s, 2H, SCH2), 7.29–8.06
m, 9H, Ar H). 13C NMR (100 MHz, CDCl3): 157.0, 156.6, 153.2, 142.0, 136.0, 135.6,
1
(
1
29.1, 129.0, 128.2, 127.3, 123.4, 122.0, 120.9, 112.5, 45.9, 36.6, 20.9, 10.8. MS (70 eV)
+
m/z (%): 350 (M , 100), 317 (25), 308 (31), 275 (80), 260 (89), 232 (21), 202 (46), 159
(
20), 130 (24), 102 (20), 91 (93). Anal. Calcd for C20H18N2O2S (350.4): C, 68.55; H, 5.18;
N, 7.99. Found: C, 68.39; H, 5.26; N, 7.88.
-Butylthio-3-propylbenzofuro[3,2-d]pyrimidin-4(3H)-one
2
(5c). White
crystals, mp 130–131 C. H NMR (400 MHz, CDCl3): 1.00 (t, J = 7.2 Hz, 3H, CH3),
.04 (t, J = 7.2 Hz, 3H, CH3), 1.52–1.87 (m, 6H, 3CH2), 3.36 (t, J = 7.2 Hz, 2H, SCH2),
◦
1
1

8
62
Y.-G. HU ET AL.
4
1
2
.18 (t, J = 7.2 Hz, 2H, NCH2), 7.40–8.00 (m, 4H, Ar H). 13C NMR (100 MHz, CDCl3):
58.0, 156.9, 153.6, 142.4, 136.2, 129.3, 123.6, 122.4, 121.2, 112.7, 46.1, 32.1, 30.6, 22.0,
+
1.1, 13.6, 11.2. MS (70 eV) m/z (%): 316 (M , 36), 258 (81), 231 (51), 217 (100), 201
(
6
60), 184 (38), 158 (72), 128 (65), 101 (66). Anal. Calcd for C17H20N2O2S (316.4): C,
4.53; H, 6.37; N, 8.85. Found: C, 64.47; H, 6.31; N, 8.76.
Ethyl 2-(3-propylbenzofuro[3,2-d]pyrimidin-4(3H)-on-2-ylthio)acetate
◦
1
(
5d). White crystals, mp 142–143 C. H NMR (400 MHz, CDCl3): 1.04 (t, J = 7.2 Hz,
3
4
3
H, CH3), 1.29 (t, J = 7.2 Hz, 3H, CH3), 1.86–1.91 (m, 2H, CH2), 4.08 (s, 2H, SCH2),
.17–4.29 (q, J = 7.2 Hz, 4H, 2CH2), 7.39–7.95 (m, 4H, Ar H). MS (70 eV) m/z (%):
+
46 (M , 100), 300 (13), 260 (67), 230 (23), 202 (10), 172 (15), 130 (13). Anal. Calcd for
C17H18N2O4S (346.4): C, 58.94; H, 5.24; N, 8.09. Found: C, 58.77; H, 5.36; N, 8.01.
Methyl (2E)-3-methoxy-2-(2-{[(3-methyl-4-oxo-3,4-dihydrobenzofuro[3,
2
-d]pyrimidin-2-yl) thio]methyl}phenyl)acrylate (6a). White solid, mp 160–162
◦
1
C. H NMR (600 MHz, CDCl3): 3.62 (s, 3H, NCH3), 3.69 (s, 3H, OCH3), 3.87 (s, 3H,
OCH3), 4.58 (s, 2H, SCH2), 7.17–8.06 (m, 9H, Ar H and CH ). IR (KBr): 1700 (C O),
−1
+
1
625, 1516, 1350, 1258 cm . MS (70 eV) m/z (%): 436 (M , 9), 404 (25), 357 (8), 301
(100), 232 (20), 202 (19), 145 (99), 130 (30), 115 (34), 103 (40), 91 (8). Anal. Calcd for
C23H20N2O5S (436.5): C, 63.29; H, 4.62; N, 6.42. Found: C, 63.17, H, 4.71; N, 6.19.
Methyl (2E)-3-methoxy-2-(2-{[(3-ethyl-4-oxo-3,4-dihydrobenzofuro[3,2-
◦
d]pyrimidin-2-yl)thio] methyl}phenyl)acrylate (6b). White solid, mp 152–154 C.
1
H NMR (600 MHz, CDCl3): 1.36 (t, J = 7.2 Hz, 3H, CH3), 3.72 (s, 3H, OCH3), 3.86
(
s, 3H, OCH3), 4.24 (q, J = 7.2 Hz, 2H, NCH2), 4.56 (s, 2H, SCH2), 7.18–8.05 (m, 9H,
13
Ar H and CH ). C NMR (100 MHz, CDCl3): 167.8, 160.2, 157.8, 157.0, 153.4, 142.4,
1
36.3, 135.0, 132.9, 131.4, 130.3, 129.5, 128.2, 127.7, 123.8, 122.4, 121.3, 112.9, 110.2,
−1
62.0, 51.7, 39.9, 35.0, 13.0. IR (KBr): 1700 (C O), 1518, 1253, 1119 cm . MS (70 eV)
+
m/z (%): 450 (M , 11), 418 (17), 315 (100), 245 (10), 204 (6), 145 (44), 129 (6), 115 (10),
1
6
02 (9). Anal. Calcd for C24H22N2O5S (450.5): C, 63.98; H, 4.92; N, 6.22; Found: C,
3.79, H, 5.11; N, 6.03.
Methyl (2E)-3-methoxy-2-(2-{[(3-propyl-4-oxo-3,4-dihydrobenzofuro[3,2-
◦
d]pyrimidin-2-yl)thio] methyl}phenyl)acrylate (6c). White solid, mp 148–150 C.
1
H NMR (600 MHz, CDCl3): δ = 0.99 (t, J = 7.2 Hz, 3H, CH3), 1.77–1.81 (m, 2H, CH2),
3
.72 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.12 (t, J = 7.2 Hz, 2H, NCH2), 4.56 (s, 2H,
SCH2), 7.17–8.04 (m, 9H, Ar H and CH ). IR (KBr): 1688 (C O), 1632, 1518, 1253
−1
+
cm . MS (70 eV) m/z (%): 464 (M , 12), 432 (17), 329 (100), 287 (9), 259 (27), 204 (38),
1
6
45 (90), 129 (41), 115 (35), 103 (40), 91 (10). Anal. Calcd for C25H24N2O5S (464.5): C,
4.64; H, 5.21; N, 6.03. Found: C, 64.55; H, 5.32; N, 5.91.
Methyl (2E)-3-methoxy-2-(2-{[(3-butyl-4-oxo-3,4-dihydrobenzofuro[3,2-
◦
d]pyrimidin-2-yl)thio] methyl}phenyl)acrylate (6d). White solid, mp 103–105 C.
1
H NMR (600 MHz, CDCl3): δ = 0.96 (t, J = 7.2 Hz, 3H, CH3), 1.40–1.75 (m, 4H,
CH2CH2), 3.72 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 4.15 (t, J = 7.2 Hz, 2H, NCH2), 4.57
+
(
s, 2H, SCH2), 7.18–8.04 (m, 9H, Ar H and CH ). MS (70 eV) m/z (%): 478 (M , 6),
4
45 (7), 343 (100), 287 (8), 273 (10), 218 (11), 202 (15), 186 (8), 145 (32), 115 (7). Anal.
Calcd for C26H26N2O5S (478.6): C, 65.25; H, 5.48; N, 5.85. Found: C, 65.06; H, 5.36; N,
.77.
5
Methyl (2E)-3-methoxy-2-(2-{[(3-pentyl-4-oxo-3,4-dihydrobenzofuro[3,2-
◦
d]pyrimidin-2-yl)thio] methyl}phenyl)acrylate (6e). White solid, mp 92–93 C.
1
H NMR (400 MHz, CDCl3): δ = 0.91 (t, J = 7.2 Hz, 3H, CH3), 1.36–1.76 (m, 6H,
CH2CH2CH2), 3.70 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 4.14 (t, J = 7.2 Hz, 2H, NCH2),

2-ALKYLTHIOBENZOFURO[3,2-d]PYRIMIDINONES
863
4
.57 (s, 2H, SCH2), 7.17–8.04 (m, 9H, Ar H and CH ). IR (KBr): 1700 (C O), 1625,
−1
+
1516, 1126 cm . MS (70 eV) m/z (%): 492 (M , 8), 460 (13), 357 (100), 287 (14), 204
(7), 145 (31), 115 (4). Anal. Calcd for C27H28N2O5S (492.6): C, 65.83; H, 5.73; N, 5.69;
Found: C, 65.89; H, 5.64; N, 5.57.
Methyl (2E)-3-methoxy-2-(2-{[(3-benzyl-4-oxo-3,4-dihydrobenzofuro[3,
2
-d]pyrimidin-2-yl)thio] methyl}phenyl)acrylate (6f). White solid, mp 206–207
◦
1
C. H NMR (600 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 4.53 (s,
13
2
H, SCH2), 5.43 (s, 2H, NCH2), 7.14–8.05 (m, 14H, Ar H and CH ). C NMR (100
MHz, CDCl3): 167.8, 160.3, 158.5, 156.9, 153.7, 142.4, 135.8, 135.1, 132.8, 132.2, 132.1,
1
31.5, 131.3, 130.2, 129.5, 128.5, 128.3, 128.2, 127.7, 123.8, 122.3, 121.3, 112.8, 110.1,
−1
61.9, 51.6, 35.0, 30.2. IR (KBr): 1702 (C O), 1633, 1512, 1254, 1130 cm . MS (70
+
eV) m/z (%): 512 (M , 9), 480 (12), 389 (15), 377 (100), 307 (54), 275 (37), 248 (15),
202 (42), 145 (80), 130 (26), 115 (17), 103 (12), 91 (38). Anal. Calcd for C29H24N2O5S
(512.6): C, 67.95; H, 4.72; N, 5.47. Found: C, 68.12; H, 4.68; N, 5.31.
Methyl (2E)-3-methoxy-2-(2-{[(4-oxo-3,4-dihydrobenzofuro[3,2-d]pyrimi
◦
1
din-2-yl)thio]methyl} phenyl)acrylate (6g). White solid, mp 238–240 C. H NMR
(
7
1
400 MHz, CDCl3): δ = 3.74 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 4.53 (s, 2H, SCH2),
+
.15–8.08 (m, 9H, Ar H and CH ), 11.57 (s, 1H, NH). MS (70 eV) m/z (%): 422 (M ,
00), 390 (84), 357 (11), 330 (10), 287 (7), 189 (76), 145 (39), 130 (28), 102 (99), 75 (43).
Anal. Calcd for C22H18N2O5S (422.4): C, 62.55; H, 4.29; N, 6.63. Found: C, 62.37; H,
.08; N, 6.45.
Methyl (2E)-3-methoxy-2-(2-[{[3-(4-chlorophenyl)-4-oxo-3,4-dihydroben
zofuro[3,2-d] pyrimidin-2-yl]thio}methyl]phenyl)acrylate (6h). White solid, mp
4
◦
1
2
(
10–212 C. H NMR (400 MHz, CDCl3): 3.60 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 4.43
13
s, 2H, SCH2), 7.10–8.11 (m, 13H, Ar H and CH ). C NMR (100 MHz, CDCl3): 167.7,
1
1
60.2, 159.3, 157.2, 153.7, 143.2, 136.3, 134.8, 133.7, 132.9, 131.3, 130.5, 130.3, 130.0,
29.8, 128.2, 127.7, 124.0, 122.3, 121.4, 113.0, 110.1, 61.8, 51.5, 35.8. IR (KBr): 1705
−1
+
(
C O), 1506, 1227, 1129 cm . MS (70 eV) m/z (%): 532 (M , 18), 499 (16), 397 (100),
28 (16), 255 (23), 205 (17), 145 (80), 130 (20), 102 (29). Anal. Calcd for C28H21ClN2O5S
3
(533.0): C, 63.10; H, 3.97; N, 5.26. Found: C, 63.01; H, 4.10; N, 5.11.
Bioassays of Fungicidal Activity
The fungicidal activities against six kinds of fungi, Fusarium oxysporium, Rhizocto-
nia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, Bipolaris mayclis,
21
and Colletotrichum gossypii, were tested according to the reported method. (See the
Supplemental Materials.)
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