New Efficient Synthesis of 2-Substituted 5,6,7,8-Tetrahydro-benzo-thieno[2, 3-d]pyrimidin-4(3H)-ones

Article abstract of DOI:10.1055/s-2003-44358

The carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates, reacted with secondary amines to give 2-dialkylamino-5,6,7,8-tetrahydro-benzothieno[2,3-d]pyrimidin-4(3H)-ones 6 in presence of catalytic EtO^-Na⁺. Reactions of 4 with phenols or ROH in presence of catalytic K₂CO₃ or RO ^-Na⁺ gave 2-aryl(alkyl)oxy-5,6,7,8-tetrahydro- benzothieno[2,3-d]pyrimidin-4(3H)-ones 6 in satisfactory yields. The effects of the nucleophiles on cyclization have been investigated.

Full text of DOI:10.1055/s-2003-44358

PAPER
75
New Efficient Synthesis of 2-Substituted 5,6,7,8-Tetrahydro-benzo-
thieno[2,3-d]pyrimidin-4(3H)-ones
S
ynthesis of 2-Substitu
i
ted 5, 6
n
,7, 8-Tetrahy
g
dro-benzothi
-
eno[2,3-
W
d]pyrimidin-4(3
H
)-onesu Ding,* Shang-Jun Yang, Jing Zhu
Institute of Organic Synthesis, Central China Normal University, Wuhan, 430079, P. R. China
Fax +86(27)87876070; E-mail: ding5229@yahoo.com.cn
Received 19 September 2003; revised 17 October 2003
and sulfur, was converted to iminophosphorane 3 via re-
action with triphenylphosphine, hexachloroethane and
Et3N (Scheme 1).16
Abstract: The carbodiimides 4, obtained from aza-Wittig reactions
of iminophosphorane 3 with aromatic isocyanates, reacted with sec-
ondary amines to give 2-dialkylamino-5,6,7,8-tetrahydro-ben-
zothieno[2,3-d]pyrimidin-4(3H)-ones 6 in presence of catalytic
EtO–Na+. Reactions of 4 with phenols or ROH in presence of cata-
lytic K2CO3 or RO–Na+ gave 2-aryl(alkyl)oxy-5,6,7,8-tetrahydro-
benzothieno[2,3-d]pyrimidin-4(3H)-ones 6 in satisfactory yields.
The effects of the nucleophiles on cyclization have been investi-
gated.
Iminophosphorane 3 reacted with aromatic isocyanates to
give carbodiimides 4, which were allowed to react with
secondary amines to provide guanidine intermediates 5.
Even in refluxing toluene, 5 did not cyclize, however, in
the presence of catalytic amount of NaOEt, 5 were con-
verted easily to 2-dialkylamino-5,6,7,8-tetrahydro-ben-
zothieno[2,3-d]pyrimidin-4(3H)-ones 6 in satisfactory
yields at room temperature (Scheme 2). It is noteworthy
that the isolated yields of 6 were good even when Y is the
bulky di-iso-propylamino group. The results are listed in
Table 1.
Key words: benzothieno[2,3-d]pyrimidin-4(3H)-ones, iminophos-
phorane, carbodiimide, aza-Wittig reaction, synthesis
The derivatives of heterocycles containing thienopyrimi-
dine system, which are well known bioisosteres of
quinazolines, are of great importances because of their re-
markable biological properties. For example, some 2-
alkoxy or 2-alkyl substituted thienopyrimidinones show
significant antifungal and antibacterial activities,1–4
whereas others exhibited good anticonvulsant and angio-
tensin or H1 receptor antagonistic activities.5–7 The chem-
istry of thienopyrimidinones have also received attention
because their starting materials, 2-amino-3-carbox-
ythiophenes, can be conveniently synthesized. Though
there are many known methods for the synthesis of
thienopyrimidinones,8–10 2-amino or 2-aryl(alkyl)oxy
substituted thienopyrimidinones are not easily accessible
by currently existing routes. Recently we became interest-
ed in the synthesis of imidazolinones and quinazolinones
via aza-Wittig reaction, with the aim of evaluating their
fungicidal activities.11–15 Here we wish to report a new ef-
ficient synthesis of 2-substituted 5,6,7,8-tetrahydro-ben-
The direct reaction of carbodiimide 4 with phenols did not
produce 2-aryloxy-5,6,7,8-tetrahydro-benzothieno[2,3-
d]pyrimidin-4(3H)-ones 6 either. However, when carried
out in presence of catalytic K2CO3, the reaction took place
to give 6 in good yields. The formation of 6 can be ratio-
nalized in terms of an initial nucleophilic addition of phe-
noxides to the carbodiimides 4 to give the intermediate 5
which cyclize to give 6. Irrespective of the fact whether
the substituents on the phenols were electron-withdraw-
ing or electron-releasing groups, the cyclization was com-
pleted smoothly at room temperature.
The direct reaction of carbodiimide 4 with ROH gave a
complex mixture, however, when the reaction was carried
out in presence of catalytic RO–Na+, the reaction took
place smoothly and 2-alkoxy-5,6,7,8-tetrahydro-ben-
zothieno[2,3-d]pyrimidin-4(3H)-ones 6 were obtained in
satisfactory yields.
zothieno[2,3-d]pyrimidin-4(3H)-ones
accessible iminophosphorane 3.
6
from easily
The structure of the synthesized compound 6 was con-
firmed by their spectral data. For example, the IR spectra
of 6a revealed C=O absorption bands at 1676 cm–1. The
The tetrahydrobenzo[b]thiophene 2, easily obtained by
Gewald method from cyclohexanone 1, ethyl cyanoactate
Scheme 1
SYNTHESIS 2004, No. 1, pp 0075–0079
x
x
.
x
x
.2
0
0
3
Advanced online publication: 03.12.2003
DOI: 10.1055/s-2003-44358; Art ID: F08403SS
© Georg Thieme Verlag Stuttgart · New York

76
M.-W. Ding et al.
PAPER
1H NMR spectral data of 6a show the signals of –NCH2 at
3.03 ppm as quartet and signals of cyclohexenyl CH2 at
2.92–2.71 and 1.84–1.78 ppm as mutiplets. The other sig-
nals appeared at 7.46–7.23 (m, 5 H, Ar-H) and 0.80 (t, 6
H, J = 7.0 Hz, 2 CH3). The MS spectrum of 6a shows an
obvious molecule ion peak at m/z 353 with 70% abun-
dance.
In conclusion, we have developed an efficient synthesis of
2-substituted 5,6,7,8-tetrahydro- benzothieno[2,3-d]pyri-
midin-4(3H)-ones via base-catalyzed reaction of func-
tionalized carbodiimides with various amine, phenols or
alcohols. Due to the easily accessible and versatile start-
ing material, this method has the potential in the synthesis
of many biologically and pharmaceutically active
thienopyrimidinones derivatives.
Scheme 2
Table 1 Preparation of 2-Substituted 5,6,7,8-Tetrahydro-benzo-
thieno[2,3-d]pyrimidin-4(3H)-ones
Melting points were uncorrected. MS were measured on a Finnigan
Trace MS spectrometer. IR spectra were recorded on a PE-983 in-
frared spectrometer as KBr pellets with absorption given in cm–1.
NMR spectra were recorded in CDCl3 on a Varian Mercury 300
spectrometer and resonances are given in ppm ( ) relative to TMS.
Elementary analyses were taken on a Perkin-Elmer CHN 2400 ele-
mentary analysis instrument.
Ar
6a Ph
6b Ph
Y
Conditions
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
Yield (%)a
NEt2
82
71
78
69
62
88
N(n-Pr)2
N(n-Bu)2
N(n-Pentyl)2
N(n-Hexyl)2
6c
Ph
6d Ph
Preparation of 2-Dialkylamino-5,6,7,8-tetrahydro-benzo-
thieno[2,3-d]pyrimidin-4(3H)-ones
6e
6f
Ph
Ph
To a solution of iminophosphorane 316 (2.42g, 5 mmol) in anhyd
CH2Cl2 (15 mL) was added aromatic isocyanate (5 mmol) under N2
at r.t. After the reaction mixture was left unstirred for 6–12 h at 0–
5 °C, the solvent was removed off under reduced pressure and Et2O/
petroleum ether (1:2, 20 mL) was added to precipitate triphe-
nylphosphine oxide. Removal of the solvent gave carbodiimides 4,
which were used directly without further purification.
6g Ph
6h Ph
r.t./6 h
85
N(i-Bu)2
N(i-Pr)2
r.t./12 h
r.t./12 h
r.t./6 h
r.t./6 h
80
75
85
84
To the solution of 4 prepared above in CH2Cl2 (15 mL) was added
dialkylamine (5 mmol). After the reaction mixture was left unstirred
for 5–6 h, the solvent was removed and anhyd EtOH (10 mL) with
several drops of EtONa in EtOH was added. The mixture was stirred
for 6–12 h at r. t. The solution was condensed and the residue was
recrystallized from EtOH to give 2-dialkylamino-5,6,7,8-tetrahy-
dro-benzothieno[2,3-d]pyrimidin-4(3H)-ones 6.
6i
6j
Ph
4-ClC6H5 NEt2
6k 4-ClC6H5
6l
4-ClC6H5
r.t./6 h
81
6a
White crystals; mp 144–145 °C.
IR (KBr): 1676 (C=O), 1532, 1383, 697 cm–1.
6m Ph
6n Ph
6o Ph
6p Ph
6q Ph
3-NO2C6H5O
4-ClC6H5O
4-BrC6H5O
PhO
r.t./10 h
r.t./8 h
r.t./8 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
r.t./6 h
62
76
66
81
80
73
67
77
83
71
82
1H NMR (300 MHz, CDCl3): = 7.46–7.23 (m, 5 H, Ar-H), 3.03 (q,
J = 6.9 Hz, 4 H, 2 × NCH2), 2.92–2.71 (m, 4 H, 2 × CH2), 1.84–1.78
(m, 4 H, 2 × CH2), 0.80 (t, J = 7.0 Hz, 6 H, 2 × CH3).
MS: m/z (%) = 353 (70) [M+], 324 (61), 281 (54), 248 (100), 179
(83), 152 (64).
4-MeSC6H5O
4-MeOC6H5O
Anal. Calcd for C20H23N3OS: C, 67.96; H, 6.56; N, 11.89. Found:
C, 67.88; H, 6.74; N, 11.97.
6r
6s
6t
Ph
6b
4-ClC6H5 4-BrC6H5O
4-MeC6H5 4-BrC6H5O
White crystals; mp 138–140 °C.
IR (KBr): 1675 (C=O), 1531, 1382, 705 cm–1.
1H NMR (300 MHz, CDCl3): = 7.48–7.24 (m, 5 H, Ar-H), 2.93 (t,
J = 7.5 Hz, 4 H, 2 × NCH2), 2.91–2.70 (m, 4 H, 2 × CH2), 1.85–1.78
(m, 4 H, 2 × CH2), 1.27–0.70 (m, 10 H, 2 × CH2CH3).
6u 4-MeC6H5 PhO
6v Ph
6w Ph
MeO
EtO
MS m/z (%) = 381 (100) [M+], 352 (37), 338 (52), 281 (59), 262
(52), 179 (76), 119 (33).
a Isolated yields based on iminophosphorane 3.
Synthesis 2004, No. 1, 75–79 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Substituted 5,6,7,8-Tetrahydro-benzothieno[2,3-d]pyrimidin-4(3H)-ones
77
Anal. Calcd for C22H27N3OS: C, 69.26; H, 7.13; N, 11.01. Found:
C, 69.52; H, 7.15; N, 10.91.
IR (KBr): 1683 (C=O), 1519, 1385, 700 cm–1.
1H NMR (300 MHz, CDCl3): = 7.47–7.24 (m, 5 H, Ar-H), 2.80 (d,
J = 6.9 Hz, 4 H, 2 × NCH2), 2.90–2.69 (m, 4 H, 2 × CH2), 1.84–1.71
(m, 6 H, 2 × CH2, 2 × CH), 0.77 (d, J = 6.6 Hz, 12 H, 4 × CH3).
MS: m/z (%) = 409 (98) [M+], 366 (99), 353 (82), 281 (100), 179
(62), 77 (84).
6c
White crystals; mp 120–122 °C.
IR (KBr): 1672 (C=O), 1534, 1383, 703 cm–1.
1H NMR (300 MHz, CDCl3): = 7.46–7.21 (m, 5 H, Ar-H), 2.95 (t,
J = 7.2 Hz, 4 H, 2 × NCH2), 2.90–2.69 (m, 4 H, 2 × CH2), 1.85–1.78
(m, 4 H, 2 × CH2), 1.23–0.79 (m, 14 H, 2 × CH2CH2CH3).
Anal. Calcd for C24H31N3OS: C, 70.38; H, 7.63; N, 10.26. Found:
C, 70.46; H, 7.75; N, 10.24.
MS: m/z (%) = 409 (100) [M+], 380 (10), 352 (39), 281 (46), 179
6i
(53), 91 (33).
White crystals; mp 172–174 °C.
Anal. Calcd for C24H31N3OS: C, 70.38; H, 7.63; N, 10.26. Found:
C, 70.42; H, 7.46; N, 10.17.
IR (KBr): 1670 (C=O), 1527, 1376, 694 cm–1.
1H NMR (300 MHz, CDCl3): = 7.45–7.20 (m, 5 H, Ar-H), 3.51–
3.41 (m, 2 H, 2 × NCH), 2.91–2.68 (m, 4 H, 2 × CH2), 1.84–1.76
(m, 4 H, 2 × CH2), 1.04 (d, J = 6.9 Hz, 12 H, 4 × CH3).
MS m/z (%) = 381 (82) [M+], 338 (100), 324 (34), 281 (78), 179
(38), 100 (76).
6d
White crystals; mp 50–51 °C.
IR (KBr): 1677 (C=O), 1531, 1379, 704 cm–1.
1H NMR (300 MHz, CDCl3): = 7.47–7.22 (m, 5 H, Ar-H), 2.94 (t,
J = 7.2 Hz, 4 H, 2 × NCH2), 2.90–2.70 (m, 4 H, 2 × CH2), 1.86–1.78
(m, 4 H, 2 × CH2), 1.24–0.81 [m, 18 H, 2 × (CH2)3CH3].
Anal. Calcd for C22H27N3OS: C, 69.26; H, 7.13; N, 11.01. Found:
C, 69.35; H, 7.37; N, 10.95.
MS: m/z (%) = 437 (100) [M+], 380 (45), 366 (88), 291 (82), 179
6j
(59), 91 (46).
White crystals; mp 185–187 °C.
Anal. Calcd for C26H35N3OS: C, 71.36; H, 8.06; N, 9.60. Found: C,
71.12; H, 8.01; N, 9.75.
IR (KBr): 1678 (C=O), 1531, 1381, 800 cm–1.
1H NMR (300 MHz, CDCl3) = 7.43–7.18 (m, 4 H, Ar-H), 3.04 (q,
J = 7.0 Hz, 4 H, 2 × NCH2), 2.90–2.69 (m, 4 H, 2 × CH2), 1.83–1.78
(m, 4 H, 2 × CH2), 0.83 (t, J = 7.0 Hz, 6 H, 2 × CH3).
MS: m/z (%) = 389 (25), 387 (76) [M+], 358 (50), 315 (51), 248 (65),
179 (100), 151 (70).
6e
White crystals; mp 54–55 °C.
IR (KBr): 1677 (C=O), 1531, 1383, 704 cm–1.
1H NMR (300 MHz, CDCl3): = 7.46–7.22 (m, 5 H, Ar-H), 2.94 (t,
J = 7.2 Hz, 4 H, 2 × NCH2), 2.90–2.70 (m, 4 H, 2 × CH2), 1.85–1.77
(m, 4 H, 2 × CH2), 1.25–0.83 [m, 22 H, 2 × (CH2)4CH3].
Anal. Calcd for C20H22ClN3OS: C, 61.92; H, 5.72; N, 10.83. Found:
C, 61.71; H, 5.65; N, 10.95.
MS: m/z (%) = 465 (100) [M+], 394 (57), 380 (69), 281 (79), 179
6k
(91), 91 (64).
White crystals; mp 193–195 °C.
Anal. Calcd for C28H39N3OS: C, 72.22; H, 8.44; N, 9.02. Found: C,
72.31; H, 8.48; N, 8.86.
IR (KBr): 1691 (C=O), 1526, 1452, 1247, 692 cm–1.
1H NMR (300 MHz, CDCl3): = 7.43–7.23 (m, 4 H, Ar-H), 3.03 (t,
J = 4.8 Hz, 4 H, 2 & times; NCH2), 2.88–2.70 (m, 4 H, 2 × CH2),
1.85–1.75 (m, 4 H, 2 × CH2), 1.42–1.25 [m, 6 H, (CH2)3].
MS: m/z (%) = 401 (34), 399 (100) [M+], 370 (6), 315 (8), 221 (9),
179 (22).
6f
White crystals; mp 188–190 °C.
IR (KBr): 1680 (C=O), 1529, 1442, 1242, 701 cm–1.
1H NMR (300 MHz, CDCl3): = 7.47–7.23 (m, 5 H, Ar-H), 3.04 (t,
J = 5.4 Hz, 4 H, 2 × NCH2), 2.92–2.69 (m, 4 H, 2 × CH2), 1.84–1.77
(m, 4 H, 2 × CH2), 1.40–1.21 [m, 6 H, (CH2)3].
Anal. Calcd for C21H22ClN3OS: C, 63.07; H, 5.54; N, 10.51. Found:
C, 63.16; H, 5.61; N, 10.39.
MS: m/z (%) = 365 (100) [M+], 336 (15), 281 (24), 221 (27), 179
6l
(85), 77 (65).
White crystals; mp 191–193 °C.
Anal. Calcd for C21H23N3OS: C, 69.01; H, 6.34; N, 11.50. Found:
C, 69.17; H, 6.24; N, 11.38.
IR (KBr): 1693 (C=O), 1530, 1437, 1247, 833 cm–1.
1H NMR (300 MHz, CDCl3): = 7.45–7.23 (m, 4 H, Ar-H), 3.44 (t,
J = 4.2 Hz, 4 H, 2OCH2), 3.07 (t, J = 4.2 Hz, 4 H, 2 × NCH2), 2.90–
2.70 (m, 4 H, 2 × CH2), 1.86–1.78 (m, 4 H, 2 × CH2).
MS: m/z (%) = 403 (32), 401 (100) [M+], 356 (30), 315 (38), 246
(35), 179 (90), 111 (36).
6g
White crystals; mp 198–200 °C.
IR (KBr): 1677 (C=O), 1529, 1442, 1241, 706 cm–1.
1H NMR (300 MHz, CDCl3): = 7.48–7.29 (m, 5 H, Ar-H), 3.38 (t,
J = 4.2 Hz, 4 H, 2 × OCH2), 3.07 (t, J = 4.2 Hz, 4 H, 2 × NCH2),
2.90–2.71 (m, 4 H, 2 × CH2), 1.83–1.76 (m, 4 H, 2 × CH2).
Anal. Calcd for C20H20ClN3O2S: C, 59.77; H, 5.02; N, 10.45.
Found: C, 59.69; H, 5.25; N, 10.52.
MS: m/z (%) = 367 (100) [M+], 310 (27), 281 (25), 246 (18), 179
(81), 77 (75).
Preparation of 2-Aryloxy-5,6,7,8-tetrahydro-benzothieno[2,3-
d]pyrimidin-4(3H)-ones
To the solution of 4 prepared above in CH3CN (15 mL) was added
substituted phenol (5 mmol) and cat. solid K2CO3 (0.07 g, 0.5
mmol). The mixture was stirred for 6–10 h at r. t. and filtered, the
filtrate was condensed and the residual was recrystallized from
Anal. Calcd for C21H21N3O2S: C, 65.37; H, 5.76; N, 11.43. Found:
C, 65.35; H, 5.45; N, 11.58.
6h
White crystals; mp 187–189 °C.
Synthesis 2004, No. 1, 75–79 © Thieme Stuttgart · New York

78
M.-W. Ding et al.
PAPER
CH2Cl2–petroleum ether to give 2-aryloxy-5,6,7,8-tetrahydro-ben-
zothieno[2,3-d]pyrimidin-4(3H)-ones 6.
Anal. Calcd for C23H20N2O3S: C, 68.30; H, 4.98; N, 6.93. Found: C,
68.10; H, 4.76; N, 6.97.
6m
6s
White crystals; mp 189–191 °C.
White crystals; mp 236–238 °C.
IR (KBr): 1692 (C=O), 1529, 1350, 1219, 729 cm–1.
IR (KBr): 1692 (C=O), 1551, 1483, 1215, 957 cm–1
1H NMR (300 MHz, CDCl3): = 8.11–7.22 (m, 9 H, Ar-H), 2.96–
1H NMR (300 MHz, CDCl3) = 7.48–6.95 (m, 8 H, Ar-H), 2.91–
2.69 (m, 4 H, 2 × CH2), 1.87–1.79 (m, 4 H, 2 × CH2).
2.70 (m, 4 H, 2 × CH2), 1.87–1.78 (m, 4 H, 2 × CH2).
MS: m/z (%) = 419 (100) [M+], 391 (45), 281 (87), 253 (55), 122
MS: m/z (%) = 486 (70) [M+], 460 (16), 408 (17), 315 (91), 253
(33).
(100), 122 (81).
Anal. Calcd for C22H17N3O4S: C, 63.00; H, 4.09; N, 10.02. Found:
C, 62.88; H, 4.17; N, 9.84.
Anal. Calcd for C22H16BrClN2O2S: C, 54.17; H, 3.31; N, 5.74.
Found: C, 54.23; H, 3.25; N, 5.97.
6n
6t
White crystals; mp 179–180 °C.
White crystals; mp 137–138 °C.
IR (KBr): 1692 (C=O), 1552, 1485, 1215, 955 cm–1.
IR (KBr): 1693 (C=O), 1550, 1483, 1215, 956 cm–1.
1H NMR (300 MHz, CDCl3): =7.53–7.01 (m, 9 H, Ar-H), 2.95–
2.69 (m, 4 H, 2 × CH2), 1.88–1.78 (m, 4 H, 2 × CH2).
MS: m/z (%) = 410 (30), 408 (92) [M+], 281 (100), 254 (59), 77 (38).
1H NMR (300 MHz, CDCl3) = 7.35–7.06 (m, 8 H, Ar-H), 2.92–
2.70 (m, 4 H, 2 × CH2), 2.39 (s, 3 H, CH3), 1.87–1.78 (m, 4 H, 2 ×
CH2).
MS: m/z (%) = 468 (85), 466 (83) [M+], 440 (18), 349 (26), 295 (32),
253 (100), 122 (80).
Anal. Calcd for C22H17ClN2O2S: C, 64.62; H, 4.19; N, 6.85. Found:
C, 64.76; H, 4.12; N, 6.87.
Anal. Calcd for C23H19BrN2O2S: C, 59.11; H, 4.10; N, 5.99. Found:
C, 59.34; H, 4.27; N, 5.85.
6o
White crystals; mp 204–206 °C.
6u
IR (KBr): 1693 (C=O), 1549, 1484, 1215, 955 cm–1.
White crystals; mp 191–193 °C.
IR (KBr): 1692 (C=O), 1549, 1488, 1206, 737 cm–1.
1H NMR (300 MHz, CDCl3): = 7.37–7.06 (m, 9 H, Ar-H), 2.95–
2.67 (m, 4 H, 2 × CH2), 2.40 (s, 3 H, CH3), 1.86–1.78 (m, 4 H, 2 ×
CH2).
1H NMR (300 MHz, CDCl3): = 7.53–6.96 (m, 9 H, Ar-H), 2.93–
2.70 (m, 4 H, 2 × CH2), 1.87–1.78 (m, 4 H, 2 × CH2).
MS: m/z (%) = 454 (61), 452 (59) [M+], 373 (9), 281 (39), 145 (76),
77 (100).
Anal. Calcd for C22H17BrN2O2S: C, 58.29; H, 3.78; N, 6.18. Found:
C, 58.12; H, 3.05; N, 6.22.
MS: m/z (%) = 388 (87) [M+], 360 (8), 295 (100), 255 (27), 77 (39).
Anal. Calcd for C23H20N2O2S: C, 71.11; H, 5.19; N, 7.21. Found: C,
71.27; H, 5.12; N, 7.43.
6p
White crystals; mp 225–226 °C.
Preparation of 2-alkoxy-5,6,7,8-tetrahydro-benzothieno[2,3-
d]pyrimidin-4(3H)-ones
IR (KBr): 1692 (C=O), 1550, 1488, 1211, 956 cm–1.
1H NMR (300 MHz, CDCl3): = 7.53–7.07 (m, 10 H, Ar-H), 2.97–
2.69 (m, 4 H, 2 × CH2), 1.87–1.78 (m, 4 H, 2 × CH2).
MS: m/z (%) = 374 (81) [M+], 346 (8), 281 (31), 227 (8), 77 (100).
To the solution of 4 prepared above in ROH (15 mL) was added sev-
eral drops of RO–Na+ in ROH. The mixture was stirred for 6 h at r.t.
The solution was condensed and the residual was recrystallized
from CH2Cl2–petroleum ether to give 2-alkoxy-5,6,7,8-tetrahydro-
benzothieno[2,3-d]pyrimidin-4(3H)-ones 6.
Anal. Calcd for C22H18N2O2S: C, 70.57; H, 4.85; N, 7.48. Found: C,
70.59; H, 4.75; N, 7.32.
6v
6q
White crystals; mp 146–148 °C.
IR (KBr): 1683 (C=O), 1555, 1356, 1262 cm–1.
1H NMR (300 MHz, CDCl3): = 7.49–7.17 (m, 5 H, Ar-H), 3.90 (s,
3 H, OCH3), 2.93–2.70 (m, 4 H, 2 × CH2), 1.86–1.76 (m, 4 H, 2 ×
CH2).
White crystals; mp 203–205 °C.
IR (KBr): 1692 (C=O), 1552, 1486, 1210, 958 cm–1.
1H NMR (300 MHz, CDCl3): = 7.50–6.99 (m, 9 H, Ar-H), 2.93–
2.70 (m, 4 H, 2 × CH2), 2.47 (s, 3 H, SCH3), 1.88–1.78 (m, 4 H, 2 ×
CH2).
MS: m/z (%) = 312 (100) (M+), 298 (26), 284 (43), 226 (6), 119 (42).
MS: m/z (%) = 420 (84) [M+], 301 (56), 281 (54), 254 (100), 77 (49).
Anal. Calcd for C17H16N2O2S: C, 65.36; H, 5.16; N, 8.97. Found: C,
65.41; H, 5.04; N, 9.05.
Anal. Calcd for C23H20N2O2S2: C, 65.69; H, 4.79; N, 6.66. Found:
C, 65.76; H, 4.87; N, 6.62.
6w
6r
White crystals, mp 154–156 °C.
IR (KBr): 1684 (C=O), 1554, 1322, 1008 cm–1.
1H NMR (300 MHz, CDCl3): = 7.47–7.16 (m, 5 H, Ar-H), 4.38 (q,
J = 7.2 Hz, 2 H, OCH2), 2.93–2.70 (m, 4 H, 2 × CH2), 1.86–1.78 (m,
4 H, 2 × CH2), 1.22 (t, J = 7.2 Hz, 3 H, CH3).
White crystals; mp 204–206 °C.
IR (KBr): 1691 (C=O), 1550, 1485, 1202, 956 cm–1.
1H NMR (300 MHz, CDCl3): = 7.53–6.83 (m, 9 H, Ar-H), 3.78 (s,
3 H, OCH3), 2.95–2.68 (m, 4 H, 2 × CH2), 1.88–1.78 (m, 4 H, 2 ×
CH2).
MS: m/z (%) = 326 (88) [M+], 298 (26), 206 (30), 179 (100), 151
(47).
MS: m/z (%) = 404 (89) [M+], 281 (100), 257 (79), 122 (60), 77 (86).
Synthesis 2004, No. 1, 75–79 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Substituted 5,6,7,8-Tetrahydro-benzothieno[2,3-d]pyrimidin-4(3H)-ones
79
Anal. Calcd for C18H18N2O2S: C, 66.23; H, 5.56; N, 8.58. Found: C,
66.15; H, 5.57; N, 8.74.
(6) Taguchi, M.; Ota, T.; Hatayama, K. WO 9303040, 1993;
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(7) Shishoo, C. J.; Shirsath, V. S.; Rathod, I. S.; Yande, V. D.
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Acknowledgment
We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (Project
No.20102001).
(11) Ding, M. W.; Sun, Y.; Liu, Z. J. Synth. Commun. 2003, 33,
1267.
(12) Ding, M. W.; Sun, Y.; Yang, S. J.; Liu, X. P.; Liu, Z. J.
Synth. Commun. 2003, 33, 1651.
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Synthesis 2004, No. 1, 75–79 © Thieme Stuttgart · New York