Synthesis of some new tetrahydrobenzo[b] thiophene derivatives and tetrahydrobenzo-thienopyrimidine derivatives under microwave irradiation

Article abstract of DOI:10.1080/00397911.2010.501479

2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one (4) was reacted with either aliphatic or aromatic primary amines such as benzylamine, cyclohexylamine, p-toluidine, and=or p-anisidine to give carboxamide derivatives 5a-d, respectively. A

Full text of DOI:10.1080/00397911.2010.501479

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Synthesis of Some New
Tetrahydrobenzo[b]thiophene
Derivatives and
Tetrahydrobenzothienopyrimidine
Derivatives Under Microwave Irradiation
A. A. Abdalha a , M. K. Abou El-Regal a , M. A. El-Kassaby a & A. T. Ali
a
a Faculty of Science, Chemistry Department, Ain Shams University,
Abbassia, Cairo, Egypt
Version of record first published: 29 Jun 2011.
To cite this article: A. A. Abdalha, M. K. Abou El-Regal, M. A. El-Kassaby & A. T. Ali (2011): Synthesis
of Some New Tetrahydrobenzo[b]thiophene Derivatives and Tetrahydrobenzothienopyrimidine
Derivatives Under Microwave Irradiation, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 41:19, 2811-2821
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Synthetic Communications1, 41: 2811–2821, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.501479
SYNTHESIS OF SOME NEW TETRAHYDROBENZO[b]
THIOPHENE DERIVATIVES AND TETRAHYDROBENZO-
THIENOPYRIMIDINE DERIVATIVES UNDER
MICROWAVE IRRADIATION
A. A. Abdalha, M. K. Abou El-Regal, M. A. El-Kassaby, and
A. T. Ali
Faculty of Science, Chemistry Department, Ain Shams University,
Abbassia, Cairo, Egypt
GRAPHICAL ABSTRACT
Abstract 2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one (4) was
reacted with either aliphatic or aromatic primary amines such as benzylamine, cyclohexyla-
mine, p-toluidine, and=or p-anisidine to give carboxamide derivatives 5a–d, respectively. A
bifunctional nucleophile such as ethanolamine was also reacted with 4, giving the carboxamide
derivative 5e. Aminolysis of 4 with secondary amines such as piperidine and=or morpholine
afforded the benzamide derivatives 6a and=or 6b, respectively. Fusion of 4 with hydrazine
hydrate yielded the pyrimidine derivative 7 and carbohydrazide derivative 8. Thiation of 4
with phosphorous pentasulfide gave thienothiazine derivative 9, which reacted with benzyla-
mine to give the pyrimidine derivative 10. Carbon nucleophiles such as ethyl cyanoacetate
and=or malononitrile were subjected to react with 4 to give oxopropanoate 11 and=or oxopro-
panoic acid 12 derivatives, respectively. Microwave irradiation of 4 and formamide yielded
the pyrimidinone derivative 13, which were subjected to react with phosphorous pentasulfide,
a mixture of phosphorous oxychloride and phosphorous pentachloride and=or methyl iodide,
to give 14, 15, and=or 16, respectively.
Keywords Microwave; tetrahydrobenzothiophene; tetrahydrothienopyrimidine
INTRODUCTION
The utility of microwaves in heterocyclic synthesis is now receiving consider-
able attention.[1–4] As a part of a recent project aiming to explore potential utility
of microwaves as an energy source for heterocyclic synthesis, we report here on
Received May 3, 2010.
Address correspondence to A. T. Ali, Faculty of Science, Chemistry Department, Ain Shams
University, Abbassia 11566, Cairo, Egypt. E-mail: amirataher82@yahoo.com
2811

2812
A. A. ABDALHA ET AL.
synthesis of new thienopyrimidines and tetrahydrobenzothiophene derivatives of
expected biological activities, where large number of thienopyrimidines
a
were reported in literature as virucides, bactericides, fungicides, acaricides, and insec-
ticides[5,6] as well as having anticancer, antiviral, antitumor, anti-inflammatory,
antihistaminic, activities, and analgesic.[7–15] Also, a large number of tetrahydroben-
zothieno derivatives were reported as anticancer, antibacterial, antimicrobial, and
antifungal agents.[16,17] Tetrahydrobenzothiophene derivatives were reported
also as inhibitors of hepatitis C virus NS5B polymerase.[18] The therapeutic impor-
tance of thienopyrimidines as well as tetrahydrobenzothiophene derivatives
prompted us to construct several analogs by exotic combinations of groups and
active moieties.
RESULTS AND DISCUSSION
The key starting material, 2-phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]
[1,3]oxazine-4-one[19] (4), has been obtained in fair yield via the cyclization of
4,5,6,7-tetrahydrobenzothiophene-2-benzoylamino-3-carboxylic acid (3) with freshly
distilled acetic anhydride (Scheme 1). Benzothiophene derivative (3) was obtained
by benzoylation of 4,5,6,7-tetrahydrobenzothiophen-2-amino-3-carboxylic acid
(2).[20] It was found that 2 was obtained upon alkaline hydrolysis of 4,5,6,
7-tetrahydrobenzo-thiophen-2-amino-3-ethyl carboxylate (1),[21] which was prepared
via Gewald reaction of cyclohexanone and ethyl cyanoacetate in the presence of
sulfur[22] (Scheme 1).
The structure of compound 4 was established by elemental analysis as well as
1
spectral data [infrared (IR), mass (MS), H NMR] and chemically via aminolysis
under microwave irradiation with either aliphatic or aromatic primary amines such
as benzylamine, cyclohexylamine, p-toluidine, and=or p-anisidine to give the corre-
sponding carboxamide derivatives 5a–d, respectively (Scheme 2). Bifunctional
nucleophiles such as ethanolamine also reacted with 4 under microwave irradiation
to give 2-benzamido-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxamide (5e). Secondary amines such as piperidine and=or morpholine also
reacted with 4 under microwave irradiation, giving N-[3-(piperidine-1-carbonyl)-4,5,
Scheme 1. Synthesis of 2-phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazine-4-one (4).

TETRAHYDROBENZO[b]THIOPHENE DERIVATIVES
2813
6,7-tetrahydrobenzo[b]-thiophene-2-yl]benzamide (6a) and=or N-[3-(morpholine-4-
carbonyl)-4,5,6,7-tetrahydro-benzo[b]-thiophene-2-yl]benzamide (6b). Unfortunately,
hydrazinolysis of 4 with hydrazine hydrate under microwave irradiation gave
unreacted product, whereas when 4 was fused with hydrazine hydrate in an electro-
mental instrument, 2-phenyl-3-amino-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]
pyrimidin-4-one (7) and 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbo-
hydrazide (8) were obtained.
Alternatively, treatment of oxazinone derivative (4) with phosphorous
pentasulfide under microwave irradiation yielded 2-phenyl-5,6,7,8-tetrahydro-4H-
benzothieno[2,3-d][1,3]-thiazine-4-one (9), which upon aminolysis by benzylamine
under microwave irradiation afforded the pyrimidine derivative (10) according to
the following mechanism:
Microwave irradiation of oxazinone derivative (4) with carbon nucleophiles
such as ethyl cyanoacetate in ethoxide as a catalytic base afforded ethyl-3-(2-
benzamido-4,5,6,7-tetraydrobenzo[b]thiophene-3-yl)-2-cyano-3-oxopropanoate (11)
in fairly good yield. On the other hand, no product was formed upon reaction of
4 with malononitrile under microwave irradiation. Instead, reflux of 4 with an
ethanolic solution of malononitrile in the presence of sodium ethoxide as a catalytic
base gave 3-(2-benzamido-4,5,6,7-tetra-hydrobenzo[b]thiophen-3-yl)-2-cyano-3-
oxopropanoic acid (12).
Treatment of oxazinone derivative (4) with formamide under microwave
irradiation yielded 2-phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]pyrimidine-4-
(3H)-one (13), whose structure was confirmed by elemental analysis as well as
spectral data. Furthermore, chemical proofs were achieved via the following:
(i) Microwave irradiation of 13 with phosphorous pentasulfide, which gave 2-
phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]pyrimidine-4-(3H)-thione (14)
in quantitative good yield.
(ii) Chlorination of 13 with a mixture of phosphorous oxychloride and phosphor-
ous pentachloride under heat in water bath for a long time, which afforded
2-phenyl-4-chloro-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine (15).

2814
A. A. ABDALHA ET AL.
Scheme 2. Reactions of benzothieno[2,3-d][1,3]oxazine-4-one 4 with nitrogen and carbon nucleophiles.
(iii) Alkylation of 13 by reflux with methyl iodide in potassium carbonate as a catalytic
base, which afforded the expected methoxypyrimidine derivative (16) (Scheme 2).
EXPERIMENTAL
Melting points were measured on an electrothermal melting-point apparatus,
and elemental analysis was carried out at the Microanalytical Unit, Cairo Univer-
sity, Giza, Egypt. IR spectra were measured on a Unicam SP-1200 spectrometer
using the KBr Wafer technique. 1H NMR spectra were measured in dimethylsulfox-
ide (DMSO-d6) or CDCl3 on a Varian Plus instrument (300 MHz). MS were deter-
mined on a HP model MS-S988 at electron energy 70 eV.
4,5,6,7-Tetrahydrobenzothiophene-2-benzoylamino-3-carboxylic
Acid (3)
A mixture of 4,5,6,7-tetrahydrobenzo[b]thiophene-2-amino-3-carboxylic acid
(2) (0.01 mol) in dry pyridine (30 ml) and benzoyl chloride (0.02 mol) was stirred
for 1 h in an ice bath. After cooling, the reaction mixture was acidified with ice-cold
hydrochloric acid. The solid formed after complete acidification was collected and
recrystallized to give 3.

TETRAHYDROBENZO[b]THIOPHENE DERIVATIVES
2815
2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazine-
4-one (4)
A mixture of 3 (0.01 mol) and acetic anhydride (10 ml) was heated on a water
bath for 5 h. The solid formed after removal of excess acetic anhydride was triturated
with petroleum ether 40–60 ꢀC and recrystallized from petroleum ether 80–100 ꢀC to
give 4 as yellow crystals; mp 138–140 ꢀC, yield: 40%. IR (cmꢁ1): 1750 cmꢁ1 (nCO). 1H
NMR (d in ppm): 8.28–8.25 (2d, 2H), 7.59–7.49 (m, 3H), 2.99–2.95 (t, 2H), 2.82–2.79
(t, 2H), 1.93–1.87 (m, 4H). MS (m=z), %: 283 (Mþ, 11.3), 255 (3.7), 105 (78.8), 77
(100). Anal. calcd. for C16H13NO2S (283.35): C, 67.82; H, 4.62; N, 4.94. Found:
C, 67.84; H, 4.61; N, 4.93.
2-Benzamido-N-benzyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxamide (5a)
A mixture of 4 (0.01 mol) and benzylamine (0.01 mol) was exposed to micro-
waves at 600 W for 3 min, and after cooling the reaction mixture was treated with
ice-cold hydrochloric acid. The solid mass was filtered and recrystallized from tolu-
ene to give 5a as colorless crystals; mp 190–192 ꢀC, yield: 80%. IR (cmꢁ1): 3342, 3242
1
(nNH), 1631.5 cmꢁ1 (nCO). H NMR (d in ppm): 13.23 (s, 1H), 8.07–8.04 (d, 2H),
7.57–7.32 (m, 8H), 6.29 (s, 1H), 4.69–4.68 (d, 2H), 2.73–2.71 (m, 4H), 1.86–1.84
(m, 4H). MS (m=z), %: 390 (Mþ, 6.3), 285 (1.7), 105 (100), 77 (74.4). Anal. calcd.
for C23H22N2O2S (390.50): C, 70.74; H, 5.68; N, 7.17. Found: C, 70.76; H, 5.67;
N, 7.16.
2-Benzamido-N-cyclohexyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxamide (5b)
A mixture of 4 (0.01 mol) and cyclohexylamine (0.01 mol) was exposed to
microwaves at 900 W for 5 min. After cooling, the reaction mixture was poured on
ice-cold hydrochloric acid, and then the solid was filtered and recrystallized from
toluene to give 5b as colorless crystals; mp 244–46 ꢀC, yield: 75%. IR (cmꢁ1): 3345
1
(nNH), 1670 cmꢁ1 (nCO). H NMR (d in ppm): 13.19 (s, 1H), 8.06–8.03 (2d, 2H),
7.56–7.48 (m, 3H), 5.94–5.91 (br, 1H), 4.06–4.03 (m, 1H), 2.75–2.72 (m, 4H),
2.06–1.35 (m, 14H). MS (m=z), %: 382 (Mþ, 18), 284 (8.3), 179 (6.6), 105 (100), 77
(71.2). Anal. calcd. for C22H26N2O2S (382.52): C, 69.08; H, 6.85; N, 7.32. Found:
C, 69.06; H, 6.84; N, 7.31.
2-Benzamido-N-p-tolyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxamide (5c)
A mixture of 4 (0.01 mol) and p-toluidine (0.02 mol) was exposed to microwaves
at 900 W. for 5 min. After cooling, the reaction mixture was poured on ice-cold
hydrochloric acid, and then the solid was filtered and recrystallized from petroleum
ether 60–80 ꢀC to give 5c as colorless crystals; mp 198–200 ꢀC, yield: 70%. IR (cmꢁ1):
1
3258, 3113.5 (nNH), 1640cmꢁ1 (nCO). H NMR (d in ppm): 13.03 (s, 1H), 8.06–8.03
(2d, 2H), 7.64–7.20 (m, 8H), 2.91–2.78 (2t, 4H), 2.37 (s, 3H), 1.93–1.92 (m, 4H). MS

2816
A. A. ABDALHA ET AL.
(m=z), %: 390 (Mþ, 8.1), 285 (2.7), 284 (10.7), 107 (100), 105 (80.4). Anal. calcd. for
C23H22N2O2S (390.50): C, 70.74; H, 5.68; N, 7.17. Found: C, 70.76; H, 5.68; N, 7.16.
2-Benzamido-N-(4-methoxylphenyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-3-carboxamide (5d)
A mixture of 4 (0.01 mol) and p-anisidine (0.02 mol) was exposed to microwaves
at 900 W for 10 min. After cooling, the reaction mixture was poured on ice-cold
hydrochloric acid, and then the solid mass was filtered and recrystallized from toluene
to give 5d as colorless crystals; mp 214–216 ꢀC, yield: 80%. IR (cmꢁ1): 3372.5, 3267
1
(nNH), 1671 cmꢁ1 (nCO). H NMR (d in ppm): 13.04 (s, 1H), 8.06–8.03 (d, 2H),
7.60–7.46 (m, 6H), 6.96–6.93 (d, 2H), 3.84 (s, 3H), 2.89–2.88 (t, 2H), 2.79–2.75
(t, 2H), 1.92–1.88 (m, 4H). MS (m=z), %: 406 (Mþ, 6.6), 284 (10.9), 123 (100), 105
(57). Anal. calcd. for C23H22N2O3S (406.50): C, 67.96; H, 5.46; N, 6.89. Found: C,
67.97; H, 5.46; N, 6.88.
2-Benzamido-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-3-carboxamide (5e)
A mixture of 4 (0.01 mol) and ethanolamine (0.02 mol) was exposed to micro-
waves at 600 W for 3 min. After cooling, the reaction mixture was poured on ice-cold
hydrochloric acid, and then the solid was filtered and recrystallized from toluene to
give 5e as yellow crystals; mp 192–194 ꢀC, yield: 75%. IR (cmꢁ1): 3484.7, 3448 (nNH),
1
1637 cmꢁ1 (nCO). H NMR (d in ppm): 13.74 (s, 1H), 7.91–7.88 (2d, 2H), 7.68–7.60
(m, 3H), 7.30 (br, 1H), 4.79–4.76 (t, 2H), 3.58–3.56 (t, 2H), 3.54 (s, 1H), 2.75–2.67
(2 t, 4H), 1.77 (m, 4H). MS (m=z), %: 344 (Mþ, 11.6), 284 (3.9), 105 (100), 77
(94.4). Anal. calcd. for C18H20N2O3S (344.43): C, 62.77; H, 5.85; N, 8.13. Found:
C, 62.78; H, 5.86; N, 8.14.
N-[3-(Piperidine-1-carbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-
2-yl]benzamide (6a)
A mixture of 4 (0.01 mol) and piperidine (0.02 mol) was exposed to microwaves
at 900 W for 5 min. After cooling, the reaction mixture was poured on ice-cold hydro-
chloric acid, and then the solid was filtered and recrystallized from petroleum ether
80–100 ꢀC to give 6a as colorless crystals; mp 180–182 ꢀC, yield: 50%. IR (cmꢁ1):
1
3188.7 (nNH), 1660 cmꢁ1 (nCO). H NMR (d in ppm): 10.12 (s, 1H), 7.94–7.91 (2d,
2H), 7.56–7.49 (m, 3H), 3.8–2.64 (2 t, 4H), 2.74–2.72 (t, 2H), 2.50–2.48 (t, 2H),
1.87–1.62 (m, 10H). MS (m=z), %: 368 (Mþ, 11.4), 284 (10.8), 105 (100), 84 (44.4).
Anal. calcd. for C21H24N2O2S (368.49): C, 68.45; H, 6.56; N, 7.60. Found: C,
68.47; H, 6.55; N, 7.60.
N-[3-(Morpholine-4-carbonyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-2-yl]-benzamide (6b)
A mixture of 4 (0.01 mol) and morpholine (0.02 mol) was exposed to micro-
waves at 600 W for 5 min. After cooling, the reaction mixture was poured on ice-cold

TETRAHYDROBENZO[b]THIOPHENE DERIVATIVES
2817
hydrochloric acid, and then the solid was filtered and recrystallized from toluene to
give 6b as colorless crystals; mp 254–256 ꢀC, yield: 90%. IR (cmꢁ1): 3221.5, 3195.5
1
(nNH), 1662 cmꢁ1 (nCO). H NMR (d in ppm): 10.75 (s, 1H), 7.93–7.92 (2d, 2H),
7.88–7.51 (m, 3H), 3.62–3.50 (m, 8H), 2.67–2.40 (2 t, 4H), 1.79–1.71 (m, 4H). MS
(m=z), %: 284 (Mþ – 86, 3.9), 105 (16.9), 86 (14.3), 77 (100). Anal. calcd. for
C20H22N2O3S (370.47): C, 64.84; H, 5.99; N, 7.56. Found: C, 64.85; H, 5.98; N, 7.58.
2-Phenyl-3-amino-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]pyrimidin-
4-one (7) and 2-Benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carbohydrazide (8)
A mixture of 4 (0.01 mol) and hydrazine hydrate (0.01 mol) was heated in an
electrothermal instrument at 100–110 ꢀC. After cooling, the reaction mixture was
poured on ice-cold hydrochloric acid, and then the product mass was filtered and
recrystallized to give 7 and 8.
Compound 7. Recrystallized from petroleum ether 60–80 ꢀC as colorless
crystals; mp 114–116 ꢀC, yield: 30%. IR (cmꢁ1): 3287, 3212 (nNH), 1657.5 cmꢁ1
1
(nCO). H NMR (d in ppm): 7.94–7.92 (2d, 2H), 7.87–7.50 (m, 3H), 4.08–4.05 (m,
2H), 2.72–2.67 (2t, 4H), 1.77–1.75 (m, 4H). MS (m=z), %: 297 (Mþ, 50.4), 281
(33.1), 269 (3.6), 150 (5.2), 103 (10.3), 77 (100). Anal. calcd. for C16H15N3OS
(297.37): C, 64.62; H, 5.08; N, 14.13. Found: C, 64.61; H, 5.08; N, 14.11.
Compound 8. Recrystallized from ethanol as yellow crystals; mp 203–205 ꢀC,
yield: 60%. IR (cmꢁ1): 3356.5, 3238 (nNH), 1655.6, 1626.6 cmꢁ1 (nCO). 1H NMR (d in
ppm): 12.32 (s, 1H), 8.87 (s, 1H), 7.92–7.89 (2d, 2H), 7.68–7.58 (m, 3H), 4.70 (br,
2H), 2.71–2.66 (2t, 4H), 1.75–1.73 (m, 4H). MS (m=z), %: 284 (Mþ ꢁ 31, 3.5), 180
(8.9), 105 (100), 77 (66.5). Anal. calcd. for C16H17N3O2S (315.39): C, 60.93; H,
5.43; N, 13.32. Found: C, 60.94; H, 5.44; N, 13.30.
2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]thiazin-4-
one (9)
A mixture of 4 (0.01 mol) and phosphorus pentasulphide (0.01 mol) was
exposed to microwaves at 900 W for 2.5 min. The reaction mixture was triturated
with boiling water, collected, and recrystallized from petroleum ether 60–80 ꢀC to
1
give 9 as red crystals; mp 117–119 ꢀC, yield: 70%. IR (cmꢁ1): 1749 cmꢁ1 (nCO). H
NMR (d in ppm): 8.25–8.23 (2d, 2H), 7.55–7.44 (m, 3H), 2.98–2.94 (t, 2H),
2.80–2.77 (t, 2H), 1.90–1.84 (m, 4H). MS (m=z), %: 299 (Mþ, 4.9), 283 (30.3), 255
(9.8), 105 (78.4), 77 (100). Anal. calcd. for C16H13NOS2 (299.41): C, 64.18; H, 4.38;
N, 4.68. Found: C, 64.20; H, 4.39; N, 4.67.
2-Phenyl-4-benzyloxy-5,6,7,8-tetrahydrobenzothieno[2,3-d]
pyrimidine (10)
A mixture of 9 (0.01 mol) and benzylamine (0.01 mol) was exposed to micro-
waves at 900 W for 6 min. After cooling, the reaction mixture was poured on ice-cold
hydrochloric acid, and then the solid was filtered and recrystallized from petroleum

2818
A. A. ABDALHA ET AL.
ether 40–60 ꢀC to give 10 as orange crystals; mp 140–142 ꢀC, yield: 10%. IR (cmꢁ1): no
1
bands for NH or CO. H NMR (d in ppm): 8.03–8.01 (2d, 2H), 7.54–7.32 (m, 8H),
4.86 (s, 2H), 3.29 (t, 2H), 2.86 (t, 2H), 1.91–1.55 (m, 4H). MS (m=z), %: 372 (Mþ,
6.8), 265 (9.8), 107 (53), 91 (100), 77 (50.8). Anal. calcd. for C23H20N2OS (372.48):
C, 74.16; H, 5.41; N, 7.52. Found: C, 74.18; H, 5.40; N, 7.50.
Ethyl-3-(2-benzamido-4,5,6,7-tetraydrobenzo[b]thiophene-3-yl)-2-
cyano-3-oxo-propanoate (11)
A mixture of 4 (0.01 mol) and ethyl cyanoacetate (0.01 mol) in the presence of
sodium ethoxide was exposed to microwaves at 900 W for 3 min. After cooling, the
reaction mixture was poured on ice-cold hydrochloric acid, and then the solid was
filtered and recrystallized from petroleum ether 80–100 ꢀC to give 11 as yellow crys-
1
tals; mp 176–178 ꢀC, yield: 20%. IR (cmꢁ1): 3294 (nNH), 1677, 1647 cmꢁ1 (nCO). H
NMR (d in ppm): 14.43 (s, 1H), 9.28 (s, 1H), 7.92–7.88 (2d, 2H), 7.60–7.53 (m, 3H),
4.48–4.43 (q, 2H), 2.77–2.73 (2t, 4H), 1.92–1.89 (t, 2H), 1.81–1.79 (t, 2H), 1.44–1.42
(t, 3H). MS (m=z), %: 396 (Mþ, 13.6), 350 (22), 291 (5.4), 105 (100), 77 (53.4). Anal.
calcd. for C21H20N2O4S (396.46): C, 63.62; H, 5.08; N, 7.07. Found: C, 63.60; H,
5.06; N, 7.08.
3-(2-Benzamido-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)-2-cyano-3-
oxopropanoic Acid (12)
A mixture of 4 (0.01 mol) and malononitrile (0.02 mol) in ethanol (50 ml) was
refluxed in the presence of sodium ethoxide (0.01 mol) for 8 h. After cooling, the
reaction mixture was poured on ice-cold hydrochloric acid, and then the solid was
filtered and recrystallized from toluene to give 12 as brown crystals; mp
1
184–186 ꢀC, yield: 30%. IR (cmꢁ1): 3243.7 (nNH), 1668, 1636 cmꢁ1 (nCO). H NMR
(d in ppm): 12.02 (s, 1H), 8.02–7.98 (2d, 2H), 7.63–7.50 (m, 3H), 2.88–2.71 (2t,
4H), 1.89–1.84 (m, 4H). MS (m=z), %: 368 (Mþ, 0.9), 179 (32.03), 105 (100), 77
(10.8). Anal. calcd. for C19H16N2O4S (368.41): C, 61.94; H, 4.38; N, 7.60. Found:
C, 61.96; H, 4.36; N, 7.60.
2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]pyrimidine-4-
(3H)-one (13)
A mixture of 4 (0.01 mol) and formamide (0.04 mol) was exposed to micro-
waves at 900 W for 5 min. After cooling, the reaction mixture was poured on ice-cold
hydrochloric acid, and then the solid mass was filtered and recrystallized from tolu-
ene to give 13 as colorless crystals; mp 200–202 ꢀC, yield: 90%. IR (cmꢁ1): 3395
1
(nNH), 1651 cmꢁ1 (nCO). H NMR (d in ppm): 10.75 (s, 1H), 7.92–7.89 (2d, 2H),
7.64–7.51 (m, 3H), 2.66–2.64 (t, 2H), 2.48–2.40 (t, 2H), 1.79–1.71 (m, 4H). MS
(m=z), %: 282 (Mþ, 13.1), 179 (14.8), 105 (42.6), 104 (13.1), 77 (100). Anal. calcd.
for C16H14N2OS (282.36): C, 68.06; H, 5.00; N, 9.92. Found: C, 68.05; H, 4.99; N,
9.91.

TETRAHYDROBENZO[b]THIOPHENE DERIVATIVES
2819
2-Phenyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d]pyrimidine-4-(3H)-
thione (14)
A mixture of 13 (0.01 mol) and phosphorus pentasulphide (0.02 mol) was
exposed to microwaves at 900 W for 10 min. After cooling, the reaction mixture
was triturated with boiling water, collected, and recrystallized from toluene to give
14 as orange crystals; mp 286–288 ꢀC, yield: 30%. IR (cmꢁ1): 3100 (nNH). 1H
NMR (d in ppm): 12.48 (s, 1H), 8.14–8.10 (2d, 2H), 7.59–7.49 (m, 5H), 2.93–2.91
(t, 2H), 2.76–2.74 (t, 2H), 1.81–1.79 (m, 4H). MS (m=z), %: 298 (Mþ, 13.4), 296
(100), 265 (9.8), 77 (86.6). Anal. calcd. for C16H14N2S2(298.43): C, 64.39; H, 4.73;
N, 9.39. Found: C, 64.40; H, 4.72; N, 9.37.
2-Phenyl-4-chloro-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine (15)
A mixture of 13 (0.01 mol) and phosphorus oxychloride (10 ml) in the presence
of phosphorus pentachloride (1 g) was heated on a water bath for 18 h. After cooling,
the reaction mixture was poured on crushed ice. The solid was filtered and recrystal-
lized from petroleum ether 80–100 ꢀC to give 15 as yellow crystals; mp 154–156 ꢀC,
yield: 20%. IR (cmꢁ1): no bands for NH or CO. 1H NMR (d in ppm): 8.51–8.47 (2d,
2H), 7.52–7.47 (m, 3H), 3.14–3.12 (t, 2H), 2.89–2.87 (t, 2H), 1.96–1.92 (m, 4H). MS
(m=z), %: 302 (M þ 2, 19.68), 300 (Mþ, 52.7), 265 (7.7), 103 (66.2), 77 (100). Anal.
calcd. for C16H13ClN2S (300.81): C, 63.89; H, 4.36; N, 9.31. Found: C, 63.90; H,
4.35; N, 9.30.
2-Phenyl-4-methoxy-5,6,7,8-tetrahydrobenzothieno Pyrimidine (16)
A mixture of 13 (0.01 mol) and methyl iodide (0.02 mol) in the presence of
anhydrous K2CO3 (2 g) in dry acetone (20 ml) was refluxed on a water bath for
20 h. The reaction mixture was filtered to separate K2CO3, and the solvent was
evaporated. The solid was recrystallized from ethanol to give 16 as colorless crystals;
1
mp 158–160 ꢀC, yield: 30%. IR (cmꢁ1): no bands for NH or CO. H NMR (d in
ppm): 8.44–8.38 (2d, 2H), 7.55–7.48 (m, 3H), 4.07 (s, 3H), 2.78–2.49 (2t, 4H),
1.77–1.73 (m, 4H). MS (m=z), %: 296 (Mþ, 100), 295 (21.7), 281 (15.7), 103 (28.6),
77 (73.1). Anal. calcd. for C17H16N2OS (296.39): C, 68.89; H, 5.44; N, 9.45. Found:
C, 68.88; H, 5.43; N, 9.45.
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