Efficient synthesis and fungicidal activities of 3,5,6,8-tetrahydro-4h- thiopyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-ones

Article abstract of DOI:10.1080/10426500802177216

The carbodiimides 4, obtained from reactions of iminophosphorane 3 with aromatic isocyanates, reacted with amines, phenols, or ROH to give 2-substituted 3,5,6,8-tetrahydro-4H-thiopyrano[4′,3′ :4,5]thieno [2,3-d]pyrimidin-4-ones 6 in the presence of a catalytic amount of sodium alkoxide or solid potassium carbonate in satisfactory yields. Compounds 6 exhibited fungicidal activity. For example, compounds 6e, 6m, and 6s showed 70% inhibition activities against Dothiorella gregaria in 100 mg/L.

Full text of DOI:10.1080/10426500802177216

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Phosphorus, Sulfur, and Silicon
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Efficient Synthesis and
Fungicidal Activities of
3,5,6,8-Tetrahydro-4H-
thiopyrano[4′,3′
:4,5]thieno[2,3-d]pyrimidin-4-
ones
Hai Xie a b , Nian-Yu Huang a & Ming-Wu Ding a
a Key Laboratory of Pesticide & Chemical Biology
of Ministry of Education , Central China Normal
University , Wuhan, P. R. China
b College of Chemistry & Chemical Engineering ,
Shanxi Datong University , Shanxi, P. R. China
Published online: 04 Feb 2009.
To cite this article: Hai Xie , Nian-Yu Huang & Ming-Wu Ding (2009) Efficient Synthesis
and Fungicidal Activities of 3,5,6,8-Tetrahydro-4H-thiopyrano[4′,3′ :4,5]thieno[2,3-
d]pyrimidin-4-ones, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:2,
480-491, DOI: 10.1080/10426500802177216
To link to this article: http://dx.doi.org/10.1080/10426500802177216
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Phosphorus, Sulfur, and Silicon, 184:480–491, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802177216
Efficient Synthesis and Fungicidal Activities of
3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-
d]pyrimidin-4-ones
Hai Xie,1,2 Nian-Yu Huang,1 and Ming-Wu Ding1
1Key Laboratory of Pesticide & Chemical Biology of Ministry of
Education, Central China Normal University, Wuhan, P. R. China
2College of Chemistry & Chemical Engineering, Shanxi Datong
University, Shanxi, P. R. China
The carbodiimides 4, obtained from reactions of iminophosphorane 3 with aro-
matic isocyanates, reacted with amines, phenols, or ROH to give 2-substituted
3,5,6,8-tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno [2,3-d]pyrimidin-4-ones 6 in the
presence of a catalytic amount of sodium alkoxide or solid potassium carbonate
in satisfactory yields. Compounds 6 exhibited fungicidal activity. For example,
compounds 6e, 6m, and 6s showed 70% inhibition activities against Dothiorella
gregaria in 100 mg/L.
Keywords Aza-Wittig reaction; carbodiimide; fungicidal activity; iminophosphorane;
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-one
INTRODUCTION
The derivatives of heterocycles containing the thienopyrimidinones
possess a broad spectrum of biological activities. They proved to show
significant antifungal, antibacterial, antimicrobial, anticonvulsant,
and angiotensin antagonistic activities.1−7 Some of these compounds
also show good antimalarial8 or potent multitargeted receptor tyrosine
kinase inhibitive activities.9 However, there are few reports about the
related thiopyranothienopyrimidinone systems,10−12 which are of con-
siderable interest as potential biological active heterocycles or phar-
maceuticals. Recently we have become interested in the preparation
Received 3 March 2008; accepted 15 April 2008.
We gratefully acknowledge financial support of this work by the National Natural
Science Foundation of China (Project No. 20772041) and Hubei Province (2006ABB016)
and the Key Project of Chinese Ministry of Education (No. 107082).
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
480

3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones
481
of N-heteroaryliminophosphoranes because these species are promis-
ing building blocks for the synthesis of nitrogen heterocycles.13−16
Herein we wish to report an efficient synthesis and fungicidal activ-
ity of various 2-substituted 3,5,6,8-tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]
thieno[2,3-d]pyrimidin-4-ones via iminophosphorane 3.
RESULTS AND DISCUSSION
The ethyl 2-amino-4,7-dihydro-5H-thieno[2,3-c]thiopyran-3-carboxy-
late 2, easily obtained by Gewald method from tetrahydrothiopyran-
4-one 1, ethyl cyanoacetate, and sulfur in the presence of morpholine,11
was converted to iminophosphorane 3 by treatment with triph-
enylphosphine, hexachloroethane, and triethylamine in dry acetonitrile
(Scheme 1).
O
COOEt
CNCH2COOEt
S
S, Morpholine
NH2
S
S
1
2
COOEt
PPh3, C2Cl6
NEt3
S
N=PPh3
S
3
SCHEME 1
Iminophosphorane 3 reacted with an equimolar quantity of the
aromatic isocyanates to give the carbodiimides 4, which were al-
lowed to react with aliphatic amines to provide guanidine inter-
mediates 5 (Y = NR1R2). By treatment with sodium ethoxide in
ethanol at room temperature, the intermediates 5 underwent in-
tramolecular heterocyclization to give the expected 2-amino 3,5,6,8-
tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones 6a–
6i in satisfactory yields. The results are listed in Table I. The re-
action of carbodiimide 4 with phenols produced 2-aryloxy-3,5,6,8-
tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d] pyrimidin-4-ones 6j–
6o (Y = OAr) in the presence of catalytic amount of potassium
carbonate in good yields (Table I). When carried out in the pres-
ence of catalytic amount of RO−Na+, the reaction of carbodiimide 4
with ROH took place smoothly and 2-alkoxy-3,5,6,8-tetrahydro-4H-

482
H. Xie et al.
TABLE I Preparation of Compounds 6
No.
Ar
Y
Conditions
Yield (%)a
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
6s
Ph
Ph
1-piperidinyl
1-pyrrolidinyl
4-morpholinyl
1-piperidinyl
1-pyrrolidinyl
NEt2
4-morpholinyl
1-piperidinyl
1-pyrrolidinyl
PhO
4-ClC6H4O
4-MeC6H4O
PhO
4-ClC6H4O
4-MeC6H4O
MeO
r.t./4 h
r.t./4 h
r.t./4 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./5 h
r.t./5 h
r.t./5 h
r.t./6 h
r.t./4 h
r.t./5 h
r.t./6 h
r.t./5 h
r.t./4 h
r.t./6 h
r.t./5 h
r.t./6 h
77
88
80
83
82
85
92
88
90
84
82
89
82
80
81
70
75
71
77
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-FC6H4
4-FC6H4
4-FC6H4
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
Ph
4-ClC6H4
4-FC6H4
EtO
MeO
EtO
a Isolated yields based on iminophosphorane3.
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d] pyrimidin-4-ones 6p–6s (Y = OR)
were obtained in satisfactory yields (Table I, Scheme 2).
The structure of the synthesized compound 6 was confirmed by its
spectral data and elemental analyses. For example, the IR spectra of
1
6a revealed a C O absorption band at 1678 cm−1. The H NMR spec-
tral data of 6a show the signals of –NCH2 at 3.07 ppm as triplets,
COOEt
N=PPh3
COOEt
N=C=NAr
ArNCO
HY
S
S
S
S
4
3
O
Ar
COOEt
NHAr
N
Base
S
S
Y
N
N
S
S
Y
5
6
SCHEME 2

3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones
483
TABLE II The Fungicidal Activities of Compounds 6
Inhibition rate (%, 100 mg/L)
Botrytis
cinereaper
Gibberella
zeae
Dothiorella
gregaria
Colletotrichum
gossypii
Compound
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
6s
13
26
39
26
48
35
35
22
30
39
26
57
22
30
22
22
35
43
30
17
22
35
22
26
13
22
22
30
22
22
35
27
48
30
22
22
30
35
60
60
60
40
70
30
30
50
60
50
0
50
70
50
50
40
50
50
70
9
18
18
23
18
9
18
18
23
18
13
22
14
32
23
22
13
23
27
and signals of piperidinyl ring’s CH2CH2CH2 at 1.22–1.41 ppm as mul-
tiplets. The thiopyran ring’s signals appeared at 3.78 ppm (8-CH) as
singlet and 2.91, 3.25 ppm (5,6-CH) as triplets. The phenyl signals ap-
peared at 7.31–7.49 ppm. The MS spectrum of 6a shows molecule ion
peak (M+) at m/z 383 with 100% abundance.
The biological activities of 6 were investigated, and the results
showed that they exhibited moderate to low fungicidal activities. As
indicated in Table II, most of the compounds showed moderate fungi-
cidal activity against Dothiorella gregaria at a dosage of 100 mg/L,
whereas all of them exhibited low fungicidal activities against Botrytis
cinereaper, Gibberella zeae, and Colletotrichum gossypii. Compounds
6e,6m, and6s showed the best inhibition activities (70%) against Doth-
iorella gregaria in 100 mg/L. (See Table II)
EXPERIMENTAL
Melting points were determined using a X-4 model apparatus and were
uncorrected. IR spectra were recorded on a PE-983 infrared spectrom-
eter as KBr pellets with absorption in cm−1. MS were measured on a

484
H. Xie et al.
1
Finnigan Trace MS spectrometer. H NMR spectra were recorded in
CDCl3 on a Varian Mercury Plus 600 (600 Hz) spectrometer and chem-
ical shifts (δ) were given in ppm using (CH3)4Si as an internal reference
(δ = 0). Elementary analyses were taken on a Vario EL III elementary
analysis instrument.
Preparation of Ethyl 2-Amino-4,7-dihydro-5H-thieno[2,3-c]
thiopyran-3-carboxylate (2)
To a stirred mixture of tetrahydrothiopyran-4-one (1; 5.8 g, 0.05 mol),
sulfur (1.6 g, 0.05 mole), and ethyl cyanoacetate (5.7 g, 0.05 mol) in
ethanol (20 mL), morpholine (6 mL) was added. The mixture was
stirred at 45◦C for 1 h. The product was crystallized after cooling. The
formed yellow solid was separated and recrystallized from methanol to
give 2 as light yellow crystals, 10.1 g (83%), m.p. 86–88◦C, Lit.11 m.p.
87–89◦C.
Preparation of Ethyl 2-[(Triphenylphosphanylidene)amino]-4,7-
dihydro-5H-thieno[2,3-c]thiopyran-3-carboxylate (3)
To a mixture of ethyl 2-amino-4,7-dihydro-5H-thieno[2,3-c]thiopyran-
3-carboxylate (2; 1.94 g, 8 mmol), triphenylphosphine (3.14 g, 12 mmol),
and hexachloroethane (2.84 g, 12 mmol) in dry CH3CN (30 mL), triethy-
lamine (2.42 g, 24 mmol) at room temperature was added dropwise. The
mixture was stirred for 2 h at room temperature. After the reaction mix-
ture was poured into cold water (100 mL), the precipitate obtained was
recrystallized from ethanol to give the desired iminophosphorane 3 in
89% yield with m.p. 200–202◦C. 1H NMR (CDCl3): δ 1.35 (t, 3H, J = 6.6
Hz, CH3), 2.82 (t, 2H, J = 6.0 Hz, CH2), 3.03 (t, 2H, J = 6.0 Hz, CH2),
3.44 (s, 2H, CH2), 4.29 (q, 2H, J = 6.6 Hz, OCH2), 7.47–7.81 (m, 15H,
Ar-H). MS: m/z (%) 503 (M+, 100%), 430 (59), 262 (88), 183 (67), 108
(50). Elemental Anal. Calcd. for C28H26NO2PS2: C, 66.88; H, 5.20; N,
2.78. Found: C, 66.62; H, 5.12; N, 2.97.
Preparation of 2-Dialkylamino-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones 6a–6i
To a solution of iminophosphorane 3 (1.01 g, 2 mmol) in anhydrous
CH2Cl2 (10 mL), aromatic isocyanate (2 mmol) was added under ni-
trogen atmosphere at room temperature. After the reaction mixture
was left unstirred for 6–12 h at 0–5◦C, the iminophosphorane 3 had
disappeared (TLC monitored). The solvent was removed under reduced

3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones
485
pressure and Et2O/petroleum ether (1:2, 20 mL) was added to precip-
itate triphenylphosphine oxide. Removal of the solvent gave carbodi-
imides 4, which were used directly without further purification. To the
solution of 4 in dichloromethane (10 mL) was added dialkylamine (2
mmol). After the reaction mixture was left unstirred for 4–6 h, the sol-
vent was removed and anhydrous EtOH (10 mL) with several drops
of EtONa in EtOH was added. The mixture was stirred for 6–12 h at
room temperature. The solution was condensed, and the residue was
recrystallized from EtOH to give the expected cyclic compounds 6a–6i
in good yields.
3-Phenyl-2-(1-piperidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6a)
1
Colorless crystals, m.p. 200–202◦C, H NMR (CDCl3, 600 MHz) δ
1.22–1.41 (m, 6H, CH2CH2CH2), 2.91 (t, 2H, J = 6.0 Hz, CH2), 3.07
(t, 4H, J = 4.8 Hz, 2NCH2), 3.25 (t, 2H, J = 6.0 Hz, CH2), 3.78 (s, 2H,
CH2), 7.31–7.49 (m, 5H, Ar-H); IR (cm−1), 1678, 1529, 1366, 1247; MS
m/z (%), 383 (100, M+), 368 (17), 350 (30), 77 (14). Elemental Anal.
Calcd. for C20H21N3OS2: C, 62.63; H, 5.52; N, 10.96. Found: C, 62.87;
H, 5.37; N, 10.88.
3-Phenyl-2-(1-pyrrolidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6b)
1
Colorless crystals, m.p. 226–228◦C, H NMR (CDCl3, 600 MHz) δ
1.68–1.74 (m, 4H, CH2CH2), 2.91 (t, 2H, J = 6.0 Hz, CH2), 3.03 (t, 4H,
J = 5.4 Hz, 2NCH2), 3.23 (t, 2H, J = 6.0 Hz, CH2), 3.76 (s, 2H, CH2),
7.30–7.48 (m, 5H, Ar-H); IR (cm−1), 1689, 1528, 1343, 1296; MS m/z
(%), 369 (100, M+), 336 (42), 131 (15), 77 (21). Elemental Anal. Calcd.
for C19H19N3OS2: C, 61.76; H, 5.18; N, 11.37. Found: C, 61.71; H, 5.02;
N, 11.53.
3-(4-Chlorophenyl)-2-(4-morpholinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6c)
1
Colorless crystals, m.p. 235–236◦C, H NMR (CDCl3, 600 MHz) δ
2.92 (t, 2H, J = 5.4 Hz, CH2), 3.10 (t, 4H, J = 4.2 Hz, 2NCH2), 3.24
(t, 2H, J = 5.4 Hz, CH2), 3.46 (t, 4H, J = 4.2 Hz, 2OCH2), 3.79 (s, 2H,
CH2), 7.29–7.49 (m, 4H, Ar-H); IR (cm−1), 1684, 1535, 1362, 1246; MS
m/z (%), 419 (100, M+), 386 (26), 197 (16), 111 (19). Elemental Anal.
Calcd. for C19H18ClN3O2S2: C, 54.34; H, 4.32; N, 10.01. Found: C, 54.13;
H, 4.38; N, 10.19.

486
H. Xie et al.
3-(4-Chlorophenyl)-2-(1-piperidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6d)
1
Colorless crystals, m.p. 218–220◦C, H NMR (CDCl3, 600 MHz) δ
1.27–1.44 (m, 6H, CH2CH2CH2), 2.91 (t, 2H, J = 6.0 Hz, CH2), 3.06
(t, 4H, J = 4.8 Hz, 2NCH2), 3.23 (t, 2H, J = 6.0 Hz, CH2), 3.78 (s, 2H,
CH2), 7.27–7.46 (m, 4H, Ar-H); IR (cm−1), 1689, 1528, 1368, 1247; MS
m/z (%), 417 (100, M+), 384 (31), 194 (18), 84 (16). Elemental Anal.
Calcd. for C20H20ClN3OS2: C, 57.47; H, 4.82; N, 10.05. Found: C, 57.42;
H, 4.64; N, 10.21.
3-(4-Chlorophenyl)-2-(1-pyrrolidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6e)
1
Colorless crystals, m.p. 231–232◦C, H NMR (CDCl3, 600 MHz) δ
1.70–1.78 (m, 4H, CH2CH2), 2.91 (t, 2H, J = 6.0 Hz, CH2), 3.05 (t, 4H,
J = 6.0 Hz, 2NCH2), 3.21 (t, 2H, J = 6.0 Hz, CH2), 3.75 (s, 2H, CH2),
7.25–7.45 (m, 4H, Ar-H); IR (cm−1), 1686, 1552, 1325, 1225; MS m/z
(%),403 (100, M+), 388 (17), 370 (37), 165 (12). Elemental Anal. Calcd.
for C19H18ClN3OS2: C, 56.49; H, 4.49; N, 10.40. Found: C, 56.58; H,
4.55; N, 10.49.
3-(4-Chlorophenyl)-2-diethylamino-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6f)
1
Colorless crystals, m.p. 248–250◦C, H NMR (CDCl3, 600 MHz) δ
0.86 (t, 6H, J = 7.2 Hz, 2CH3), 2.92 (t, 2H, J = 6.0 Hz, CH2), 3.06 (t,
4H, J = 7.8 Hz, 2NCH2), 3.23 (t, 2H, J = 6.0 Hz, CH2), 3.78 (s, 2H,
CH2), 7.22–7.46 (m, 4H, Ar-H); IR (cm−1), 1682, 1529, 1379, 1249; MS
m/z (%), 405 (100, M+), 376 (21), 266 (24), 197 (27). Elemental Anal.
Calcd. for C19H20ClN3OS2: C, 56.21; H, 4.97; N, 10.35. Found: C, 56.48;
H, 4.75; N, 10.22.
3-(4-Fluorophenyl)-2-(4-morpholinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6g)
Colorless crystals, m.p. 282–283◦C, 1H NMR (CDCl3, 600 MHz) δ 2.92
(t, 2H, J = 6.0 Hz, CH2), 3.09 (t, 4H, J = 4.2 Hz, 2NCH2), 3.24 (t, 2H,
J = 5.4 Hz, CH2), 3.45 (t, 4H, J = 4.2 Hz, 2OCH2), 3.79 (s, 2H, CH2),
7.18–7.34 (m, 4H, Ar-H); IR (cm−1), 1693, 1536, 1365, 1243; MS m/z
(%), 403 (100, M+), 370 (22), 197 (8), 95 (18). Elemental Anal. Calcd. for
C19H18FN3O2S2: C, 56.56; H, 4.50; N, 10.41. Found: C, 56.41; H, 4.36;
N, 10.47.

3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones
487
3-(4-Fluorophenyl)-2-(1-piperidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6h)
1
Colorless crystals, m.p. 263–265◦C, H NMR (CDCl3, 600 MHz) δ
1.27–1.44 (m, 6H, CH2CH2CH2), 2.92 (t, 2H, J = 6.0 Hz, CH2), 3.07
(t, 4H, J = 4.2 Hz, 2NCH2), 3.24 (t, 2H, J = 6.0 Hz, CH2), 3.79 (s, 2H,
CH2), 7.18–7.31 (m, 4H, Ar-H); IR (cm−1), 1685, 1528, 1370, 1247; MS
m/z (%), 401 (100, M+), 368 (36), 178 (15), 84 (19). Elemental Anal.
Calcd. for C20H20FN3OS2: C, 59.83; H, 5.02; N, 10.47. Found: C, 59.87;
H, 4.88; N, 10.71.
3-(4-Fluorophenyl)-2-(1-pyrrolidinyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6i)
1
Colorless crystals, m.p. 220–222◦C, H NMR (CDCl3, 600 MHz) δ
1.72–1.78 (m, 4H, CH2CH2), 2.91 (t, 2H, J = 6.0 Hz, CH2), 3.05 (t, 4H,
J = 6.0 Hz, 2NCH2), 3.21 (t, 2H, J = 6.0 Hz, CH2), 3.76 (s, 2H, CH2),
7.15–7.30 (m, 4H, Ar-H); IR (cm−1), 1685, 1529, 1344, 1217; MS m/z
(%), 387 (100, M+), 354 (39), 149 (24), 95 (24). Elemental Anal. Calcd.
for C19H18FN3OS2: C, 58.89; H, 4.68; N, 10.84. Found: C, 58.72; H, 4.41;
N, 10.91.
Preparation of 2-Aryloxy-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d] pyrimidin-4-ones 6j–6o
To the solution of 4 prepared above in dry acetonitrile (10 mL)
was added substituted phenol (2 mmol) and cat. solid K2CO3
(0.03 g, 0.2 mmol). The mixture was stirred for 4–6 h at room
temperature and filtered. The filtrate was condensed, and the
residue was recrystallized from dichloromethane-petroleum ether to
give 2-arlyoxy-3,5,6,8-tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5] thieno[2,3-
d]pyrimidin-4-ones 6j–6o.
2-Phenoxy-3-phenyl-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6j)
1
Colorless crystals, m.p. 268–269◦C, H NMR (CDCl3, 600 MHz) δ
2.95 (t, 2H, J = 6.0 Hz, CH2), 3.31 (t, 2H, J = 5.4 Hz, CH2), 3.79 (s,
2H, CH2), 7.12–7.56 (m, 10H, Ar-H); IR (cm−1), 1696, 1550, 1358, 1208;
MS m/z (%), 392 (100, M+), 359 (74), 253 (24), 77 (32). Elemental Anal.
Calcd. for C21H16N2O2S2: C, 64.26; H, 4.11; N, 7.14. Found: C, 64.13;
H, 4.35; N, 7.20.
2-(4-Chlorophenoxy)-3-phenyl-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6k)
1
Colorless crystals, m.p. 237–239◦C, H NMR (CDCl3, 600 MHz) δ
2.93 (t, 2H, J = 6.0 Hz, CH2), 3.28 (t, 2H, J = 5.4 Hz, CH2), 3.78 (s,

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2H, CH2), 7.05–7.56 (m, 9H, Ar-H); IR (cm−1), 1691, 1551, 1354, 1209;
MS m/z (%), 426 (100, M+), 393 (79), 253 (40), 77 (31). Elemental Anal.
Calcd. for C21H15ClN2O2S2: C, 59.08; H, 3.54; N, 6.56. Found: C, 59.31;
H, 3.51; N, 6.39.
2-(4-Methylphenoxy)-3-phenyl-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6l)
1
Colorless crystals, m.p. 254–255◦C, H NMR (CDCl3, 600 MHz) δ
2.35 (s, 3H, CH3), 2.93 (t, 2H, J = 6.0 Hz, CH2), 3.29 (t, 2H, J = 5.4
Hz, CH2), 3.77 (s, 2H, CH2), 6.98–7.54 (m, 9H, Ar-H); IR (cm−1), 1689,
1552, 1354, 1200; MS m/z (%), 406 (100, M+), 373 (68), 253 (36), 77 (28).
Elemental Anal. Calcd. for C22H18N2O2S2: C, 65.00; H, 4.46; N, 6.89.
Found: C, 64.93; H, 4.23; N, 6.95.
3-(4-Chlorophenyl)-2-phenoxy-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6m)
1
Colorless crystals, m.p. 279–281◦C, H NMR (CDCl3, 600 MHz) δ
2.93 (t, 2H, J = 6.0 Hz, CH2), 3.28 (t, 2H, J = 5.4 Hz, CH2), 3.77 (s,
2H, CH2), 7.10–7.52 (m, 9H, Ar-H); IR (cm−1), 1702, 1549, 1355, 1206;
MS m/z (%), 426 (100, M+), 393 (61), 287 (23), 77 (26). Elemental Anal.
Calcd. for C21H15ClN2O2S2: C, 59.08; H, 3.54; N, 6.56. Found: C, 59.18;
H, 3.31; N, 6.74.
2-(4-Chlorophenoxy)-3-(4-chlorophenyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6n)
1
Colorless crystals, m.p. 210–211◦C, H NMR (CDCl3, 600 MHz) δ
2.92 (t, 2H, J = 6.0 Hz, CH2), 3.26 (t, 2H, J = 6.0 Hz, CH2), 3.77 (s, 2H,
CH2), 7.05–7.51 (m, 8H, Ar-H); IR (cm−1), 1697, 1550, 1356, 1212; MS
m/z (%), 460 (100, M+), 427 (60), 287 (29), 111 (21). Elemental Anal.
Calcd. for C21H14Cl2N2O2S2: C, 54.67; H, 3.06; N, 6.07. Found: C, 54.51;
H, 3.13; N, 5.91.
3-(4-Chlorophenyl)-2-(4-methylphenoxy)-3,5,6,8-tetrahydro-
4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6o)
1
Colorless crystals, m.p. 253–255◦C, H NMR (CDCl3, 600 MHz) δ
2.36 (s, 3H, CH3), 2.93 (t, 2H, J = 6.0 Hz, CH2), 3.27 (t, 2H, J = 5.4
Hz, CH2), 3.77 (s, 2H, CH2), 6.97–7.51 (m, 8H, Ar-H); IR (cm−1), 1689,
1550, 1356, 1203; MS m/z (%), 440 (100, M+), 407 (61), 287 (34), 91 (25).
Elemental Anal. Calcd. for C22H17ClN2O2S2: C, 59.92; H, 3.89; N, 6.35.
Found: C, 59.74; H, 3.73; N, 6.39.

3,5,6,8-Tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones
489
Preparation of 2-Alkoxy-3,5,6,8-tetrahydro-4H-thiopyrano
[4ꢀ,3ꢀ:4,5] thieno[2,3-d] pyrimidin-4-ones 6p–6s
To the solution of 4 prepared above in ROH (10 mL) was added several
drops of RONa in ROH. The mixture was stirred for 4–6 h at room
temperature. The solution was condensed, and the residue was recrys-
tallized from dichloromethane-petroleum ether to give 2-alkoxy-3,5,6,8-
tetrahydro-4H-thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d] pyrimidin-4-ones 6p–
6s.
2-Methoxy-3-phenyl-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6p)
1
Colorless crystals, m.p. 147–149◦C, H NMR (CDCl3, 600 MHz) δ
2.93 (t, 2H, J = 6.0 Hz, CH2), 3.26 (t, 2H, J = 5.4 Hz, CH2), 3.80 (s, 2H,
CH2), 3.94 (s, 3H, OCH3), 7.14–7.48 (m, 5H, Ar-H); IR (cm−1), 1652,
1542, 1384, 1237; MS m/z (%), 330 (41, M+), 297 (37), 283 (100), 77
(52). Elemental Anal. Calcd. for C16H14N2O2S2: C, 58.16; H, 4.27; N,
8.48. Found: C, 58.37; H, 4.44; N, 8.41.
2-Ethoxy-3-phenyl-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6q)
1
Colorless crystals, m.p. 203–204◦C, H NMR (CDCl3, 600 MHz) δ
1.23 (t, 3H, J = 7.2 Hz, CH3), 2.93 (t, 2H, J = 6.0 Hz, CH2), 3.27 (t, 2H,
J = 5.4 Hz, CH2), 3.80 (s, 2H, CH2), 4.40 (q, 2H, J = 7.2 Hz, OCH2),
7.19–7.51 (m, 5H, Ar-H); IR (cm−1), 1689, 1549, 1355, 1206; MS m/z
(%), 344 (100, M+), 311 (50), 283 (39), 164 (29). Elemental Anal. Calcd.
for C17H16N2O2S2: C, 59.28; H, 4.68; N, 8.13. Found: C, 59.24; H, 4.85;
N, 8.21.
3-(4-Chlorophenyl)-2-methoxy-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6r)
1
Colorless crystals, m.p. 197–199◦C, H NMR (CDCl3, 600 MHz) δ
2.93 (t, 2H, J = 6.0 Hz, CH2), 3.24 (t, 2H, J = 5.4 Hz, CH2), 3.79 (s, 2H,
CH2), 3.93 (s, 3H, OCH3), 7.15–7.46 (m, 4H, Ar-H); IR (cm−1), 1700,
1555, 1350, 1092; MS m/z (%), 364 (100, M+), 349 (37), 331 (70), 153
(30). Elemental Anal. Calcd. for C16H13ClN2O2S2: C, 52.67; H, 3.59; N,
7.68. Found: C, 52.53; H, 3.78; N, 7.41.
2-Ethoxy-3-(4-fluorophenyl)-3,5,6,8-tetrahydro-4H-
thiopyrano[4ꢀ,3ꢀ:4,5]thieno[2,3-d]pyrimidin-4-ones (6s)
1
Colorless crystals, m.p. 128–130◦C, H NMR (CDCl3, 600 MHz) δ
1.24 (t, 3H, J = 7.2 Hz, CH3), 2.93 (t, 2H, J = 6.0 Hz, CH2), 3.26 (t, 2H,
J = 5.4 Hz, CH2), 3.79 (s, 2H, CH2), 4.40 (q, 2H, J = 7.2 Hz, OCH2),

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7.15–7.20 (m, 4H, Ar-H); IR (cm−1), 1676, 1518, 1344, 1090; MS m/z
(%), 362 (100, M+), 329 (35), 301 (34), 151 (23). Elemental Anal. Calcd.
for C17H15FN2O2S2: C, 56.34; H, 4.17; N, 7.73. Found: C, 56.48; H, 4.10;
N, 7.81.
Bioassays of Fungicidal Activities
The tested samples were dissolved in 10 mL of DMF at a concentration
of 500 mg/L. The solutions (2 mL) were mixed rapidly with thawed
potato glucose agar culture medium (8 mL) under 50◦C. The mixture
was poured into Petri dishes. After the dishes were cooled, the solidified
plates were incubated with 4 mm mycelium disk, inverted, and incu-
bated at 28◦C for 48 h. The mixed medium without sample was used as
the blank control. The mycelial elongation radius (mm) of fungi settle-
ments was measured after 48 h of culture. The growth inhibition rates
were calculated with the following equation: I = [(C– T)/C] × 100%.
Here, I is the growth inhibition rate (%), C is the control settlement
radius (mm), and T is the treatment group fungi settlement radius
(mm).
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