Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: Routes towards condensed thieno[2,3-b]pyridines

Article abstract of DOI:10.1016/j.tet.2003.09.031

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′ -e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.

Full text of DOI:10.1016/j.tet.2003.09.031

Tetrahedron 59 (2003) 8489–8498
Intramolecular 412 cycloaddition of thieno[2,3-e][1,2,4]triazines:
routes towards condensed thieno[2,3-b]pyridines
*
Yehia A. Ibrahim, Balkis Al-Saleh and Atta Allah A. Mahmoud
Department of Chemistry, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
Received 29 June 2003; revised 21 August 2003; accepted 11 September 2003
Abstract—Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines,
bisthieno[2,3-b:30,20-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have
been achieved by application of intramolecular 4þ2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered
with alkene or alkyne terminals.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
route towards [1]benzopyrano[4,3-b]thieno[2,3-e]pyridines
B (Scheme 1).1a
1,2,4-Triazines have been extensively used as electron
deficient dienes for the preparation of pyridine derivatives
through their reaction with electron rich dienophiles by the
application of Diels–Alder cycloaddition reactions with
inverse electron demand.1,2 Recently, interesting routes
towards pyridines and polypyridyl derivatives of potential
diverse applications have been reported.2,3 Some thieno-
pyridines have been prepared from 1,2,4-triazines via
intramolecular Diels–Alder cycloaddition reactions of
suitably tethered 1,2,4-triazines.1,2 Although not readily
found in nature, thienopyridines have found uses as
herbicides, components of antibiotics and as dyestuffs.1
Other interesting applications of thienopyridines are their
uses for the preparation of doped polymers, useful for
electrodes, displays and electromagnetic shields.4 In
addition, some derivatives showed interesting therapeutic
applications as antiglaucoma agents,5 anticonvulsants,6
calcium channel modulators,7 and others have been tested
for use in the therapy of arterial thrombotic disorders.8
Scheme 1.
In the present work, the behavior of the isomeric thieno[2,3-
e][1,2,4]triazines towards intramolecular Diels–Alder
reactions was studied. Scheme 1 illustrates the first attempts
to design suitable starting thieno[2,3-e][1,2,4]triazine
derivatives for use in the present objectives. The starting
3-methanesulfinyl-6-arylthieno[2,3-e][1,2,4]-triazines 5a,c
and 3-methanesulfonyl-6-arylthieno[2,3-e][1,2,4]triazines
6a-d were synthesized as outlined in Scheme 2. Thus,
condensation of the appropriate arylmethylketones 1a-e
with diethyl oxalate in methanolic sodium methoxide gave
the corresponding ethyl 4-aryl-2,4-dioxobutyrates 2a-e,
respectively. Condensation of the latter with S-methyl-
isothiosemicarbazide hydroiodide in pyridine gave the
corresponding 3-methylsulfanyl-6-(2-oxo-2-arylethyl)-
1,2,4-triazin-5(2H)-ones 3a-e, respectively (following
reported procedures).12,13 Compounds 3a-e were found to
exist in equilibrium with ca. 10% of the 6-methine tautomer
as shown by 1H NMR measured in DMSO-d6. Thiation and
cyclization of 3a-e took place simultaneously by the action
of phosphorus pentasulfide in pyridine to give the
Recently, the synthesis of the isomeric thieno[3,2-e]-
[1,2,4]triazines and thieno[2,3-e][1,2,4]triazines has been
described.9–11 We have also reported the first application of
thieno[3,2-e][1,2,4]triazines A as potential electron
deficient azadienes in inverse electron demand Diels–
Alder reactions. Results from this work gave an interesting
Keywords: 1,2,4-triazines; thieno[2,3-e][1,2,4]triazines; 2,3-dihydro-
furo[2,3-b]thieno[3,2-e]pyridines; bisthieno[2,3-b:30,20-e]pyridines; 5H-
chromeno[2,3-b]thieno[3,2-e]pyridines; 5H-benzo(f)chromeno[2,3-b]-
thieno[3,2-e]pyridines.
corresponding
3-methylsulfanyl-6-arylthieno[2,3-e]-
[1,2,4]triazines 4a-e, respectively (following reported11
procedure for 4a,b).
*
Corresponding author. Tel.: þ965-9464215; fax: þ965-4816482;
e-mail: yehiaai@kuc01.kuniv.edu.kw
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.031

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Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
Scheme 2.
Oxidation of 4a,c with m-chloroperoxybenzoic acid
(MCPBA, 1.1 equiv.) in dichloromethane gave the corre-
sponding sulfoxides 5a,c. On the other hand, the sulfones
6a-d were prepared by two different methods involving
either oxidation with m-chloroperoxybenzoic acid
(MCPBA, 2.1 equiv.) in dichloromethane at room
temperature or oxidation with hydrogen peroxide in acetic
acid.
Thus, hydrolysis of 3-methanesulfonyl-6-(4-methoxy-
phenyl)thieno[2,3-e][1,2,4] triazine 6b with NaOH (in
DCM/H2O) under phase transfer catalytic conditions using
benzyltriethylammonium chloride gave 6-(4-methoxy-
phenyl)thieno[2,3-e][1,2,4]triazin-3-ol 7b. The reaction of
6a,b with sodium methoxide in methanol gave the
corresponding 6-aryl-3-methoxythieno[2,3-e][1,2,4]tria-
zines 8a,b. On the other hand, the 3-phenoxy derivatives
9a,b were prepared by the reaction of 6a,b with sodium
phenoxide (prepared in situ from phenol and NaH in THF).
Similarly, the reaction of 6a,b with b-phenethyl alcohol in
THF and NaH gave the corresponding 6-aryl-3-b-phenethyl-
oxythieno[2,3-e][1,2,4]triazines 10a,b, respectively.
Compounds 6a-d were used as starting materials to prepare
new functionalized thieno[2,3-e][1,2,4]triazines via nucleo-
philic substitution reactions. Scheme 2 illustrates their
reactions with different nucleophiles in order to investigate
the synthesis of the target starting materials suitable for
intramolecular cycloaddition reactions.
Extension of these nucleophilic reactions to v-alkenyl and

Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
8491
Scheme 3.
v-alkynyl hydroxy compounds was investigated (Scheme2).
Thus, treatment of 6a-d with sodium 3-butyn-1-oxide
(prepared in situ from 3-butyn-1-ol and NaH in THF) gave
the corresponding 6-aryl-3-(3-butyn-1-yloxy)thieno[2,3-e]-
[1,2,4]triazines 11a-d in good to excellent yields. Similarly,
the 3-(2-allyphenoxy)-6-arylthieno[2,3-e][1,2,4]triazines
12a-d were obtained upon treatment of the sulfones 6a-d
with sodium 2-allylphenoxide (prepared in situ from 2-allyl-
phenol and NaH in THF). Also, 3-(1-allylnaphthalen-2-
yloxy)-6-(4-methoxyphenyl)thieno[2,3-e][1,2,4]triazine 13b
was readily synthesized by the reaction of 1-allyl-2-naphthol
and the sulfone 6b.
H2 (from D and E only) to form finally the corresponding
condensed pyridine systems 14a-d, 15a-d, 16b (Scheme 3).
Alternatively, the synthesis of the bisthieno[2,3-b:30,20-e]-
pyridines 20a-c were accomplished as shown in Scheme 4.
This starts by reacting the potassium salt of 6-b-arylvinyl-
2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones 17a-c with
4-bromo-1-butene in DMF to give the corresponding
6-arylvinyl-3-(3-buten-1-ylsulfanyl)-1,2,4-triazin-5(2H)-
ones 18a-c. Compounds 18a-c were readily converted into
their corresponding 6-aryl-3-(3-buten-1-ylsulfanyl)-
thieno[2,3-e][1,2,4]triazines 19a-e upon heating in pyridine
with phosphorus pentasulfide following our reported
procedures for the preparation of this ring system.10–12
Heating compounds 19a-e under different conditions were
investigated in order to find the optimum conditions to
achieve their intramolecular cycloaddition. Thus, the best
condition was achieved by heating each of compounds
19a-c in nitrobenzene under reflux for 1 h which led to the
formation of the corr0esponding expected 2-aryl-5,6-
dihydrobisthieno[2,3-b:3 ,20-e]pyridines 20a-c in 20–27%.
The latter were formed via the intermediate 4þ2 cyclo-
adducts D which subsequently lose N2 and H2 to give the
final products 20a-c.
Intramolecular cycloaddition reactions of 11a-d were
successful either by heating in an oil bath at 2008C for 1 h
or in refluxing nitrobenzene for 1 h to give the correspond-
ing expected 6-aryl-2,3-dihydrofuro[2,3-b]thieno[3,2-e]
pyridines 14a-d, respectively, in 48–55% yield. Similarly,
heating each of 12a-d in nitrobenzene at reflux for 1 h
afforded the corresponding 5H-chromeno[2,3-b]thieno[3,2-e]-
pyridines 15a-d in 42–59% yields. The benzochromeno
derivative 16b was similarly synthesized from 13b in 57%
yield. All these products 14–16 were formed by initial
[4þ2] intramolecular cycloaddition reactions through the
3,6-position of the triazine ring and the terminal ene or yne
moiety to give the corresponding cycloadducts C, D and E
intermediates followed by extrusion of nitrogen and loss of
The structures of all new compounds were established by
spectral and analytical data. Table 1 shows the proton NMR
Scheme 4.

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Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
Table 1. 1H NMR of the thienopyridine derivatives 14a-d, 15a-d, 16b, 20a-c
Product
1H NMRa d¼/J (Hz)
H3
H4
H5
H6
ArHs and other Hs
14a
14b
14c
7.36
7.24
7.28
7.84
7.77
7.78
3.36/8.4
3.35/8.4
3.36/8.4
4.74/8.4
4.75/8.4
4.74/8.4
7.33 (t, 1H, J¼7.6 Hz), 7.43 (t, 2H, J¼7.6 Hz), 7.68 (d, 2H, J¼7.6 Hz)
6.96 (d, 2H, J¼8.4 Hz), 7.61 (d, 2H, J¼8.4 Hz), 3.87 (s, 3H, OCH3)
6.50 (dd, 1H, J¼1.5, 3.6 Hz), 6.59 (d, 1H, J¼3.6 Hz), 7.47 (d, 1H,
J¼1.5 Hz)
14d
15a
7.21
7.39
7.75
7.89
3.35/8.4
4.26
4.74/8.4
7.07 (t, 1H, J¼4.2 Hz), 7.26 (d, 1H, J¼4 Hz), 7.29 (d, 1H, J¼4.4 Hz)
7.12 (t, 1H, J¼7.2 Hz), 7.21–7.28 (m, 3H), 7.38 (t, 1H, J¼7.2 Hz), 7.45 (t,
2H, J¼7.2 Hz), 7.71 (d, 2H, J¼7.2 Hz)
15b
15c
7.28
7.59
7.84
8.15
4.25
4.25
6.99 (d, 2H, J¼8.4 Hz), 7.11 (t, 1H, J¼7.2 Hz), 7.23 (m, 3H), 7.64 (d, 2H,
J¼8.4 Hz), 3.88 (s, 3H, OCH3)
6.67 (dd, 1H, J¼1.6, 3.2 Hz), 6.97 (d, 1H, J¼3.2 Hz), 7.16 (m, 2H), 7.31
(m, 2H), 7.83 (d, 1H, J¼1.6 Hz)
15d
16b
7.22
7.32
7.82
7.99
4.24
4.59
7.10 (t, 2H, J¼4.0 Hz), 7.27 (m, 5H)
6.99 (d, 2H, J¼8.4 Hz), 7.42 (d, 1H, J¼9.2 Hz), 7.50 (t, 1H, J¼7.6 Hz),
7.64 (m, 3H), 7.80 (d, 1H, J¼8.8 Hz), 7.90 (t, 2H, J¼8.8 Hz), 3.89 (s, 3H,
OCH3)
20a
20b
20c
7.36
7.22
7.20
7.68
7.68
7.67
3.41/7.6
3.40/7.6
3.40/7.6
3.50/7.6
3.50/7.6
3.50/7.6
7.37 (t, 1H, J¼7.5 Hz), 7.44 (t, 2H, J¼7.5 Hz), 7.69 (d, 2H, J¼7.5 Hz)
6.96 (d, 2H, J¼8.4 Hz), 7.69 (d, 2H, J¼7.5 Hz), 3.87 (s, 3H, OCH3)
7.07 (dd, 1H, J¼4, 4.8 Hz), 7.30 (d, 1H, J¼4 Hz), 7.31 (d, 1H, J¼4.8 Hz)
All NMR were measured in CDCl3 except 15c in DMSO-d6. Compounds 14a-d, 20a-c: H3 (s, 1H), H4 (s, 1H), H5 (t, 2H), H6 (t, 2H), for 15a-d, 16b: H3 (s,
a
1H), H4 (s, 1H), H5 (s, 2H).
contain heteroatoms suitably located for potential appli-
cations in complexation and supramolecular chemistry.
3. Experimental
All melting points are uncorrected. IR spectra were recorded
in KBr disks using a Perkin–Elmer System 2000 FT-IR
spectrophotometer. 1H and 13C NMR spectra were recorded
on a Bruker DPX 400, 400 MHz super-conducting NMR
spectrometer. Mass spectra were measured on a VG Auto-
spec-Q (high resolution, high performance, tri-sector
GC/MS/MS). Microanalyses were performed on a LECO
CHNS-932 Elemental Analyzer. S-Methylisothiosemi-
Figure 1. NMR signals assignment of 14b.
carbazide hydroiodide,14 compounds 2a,15 2b,16 2c,17
of the new thienopyridines 14a-d, 15a-d, 16b, 20a-d. The
2d,11 2e,17 3a,12 3b,13 4a,b,11 17a,18 17b19 were prepared
following reported procedures.
pyridine H4 proton of these new derivatives were found
downfield in the range of d¼7.66–7.89 in CDCl3. This was
confirmed for compound 15a by NOE-difference spectra
upon irradiation at d¼4.26 (H5) which enhanced H4 and H6.
On the other hand all new thienopyridines shows their
thiophene H3 more upfield at d¼7.21–7.39 in CDCl3. Full
proton and carbon signal assignments of 14b (Fig. 1) were
made using 1H NMR, H,H-COSY, HMQC and HMBC
NMR techniques. Compound 15c measured in DMSO-d6
showed downfield shifts of these H3, H4 protons.
3.1. 3-Methylsulfanyl-6-(2-oxo-2-arylethyl)-1,2,4-
triazin-5(2H)-ones 3c-e. General procedure
A solution of S-methylisothiosemicarbazide hydroiodide
(11.65 g, 50 mmol) and the appropriate ethyl 2,4-dioxo-4-
arylbutyrates 2c-e (50 mmol) in pyridine (50 ml) was heated
under reflux for 1 h. After cooling, water (300 ml) was
added and the solution was left at room temperature
overnight. The solid precipitated was collected, washed
with water and crystallized from ethanol.
2. Conclusions
3.1.1. 6-[2-(2-Furyl)-2-oxoethyl]-3-methylsulfanyl-1,2,4-
triazin-5(2H)-one (3c). From 2c. Yellow crystals, mp 223–
2248C, yield¼9.86 g (78%). MS: m/z¼251 (Mþ). IR: 3144,
1665, 1591, 1564, 1449, 1423, 1272, 1034. 1H NMR
(DMSO-d6) d¼2.46 (s, 3H, SMe), 4.09 (s, 2H), 6.76 (dd,
1H, J¼1.5, 4 Hz), 7.57 (d, 1H, J¼4.0 Hz), 8.03 (d, 1H,
J¼1.5 Hz), 13.95 (brs, 1H, NH). 1H NMR (DMSO-d6)
(methine tautomer) d¼2.45 (s, 3H, SMe), 6.25 (s, 1H), 6.67
(dd, 1H, J¼1.6, 3.5 Hz), 7.22 (d, 1H, J¼3.5 Hz), 7.89 (d,
1H, J¼1.5 Hz), 13.54 (brs, 1H, NH), 13.95 (brs, 1H, NH).
Anal. for C10H9N3O3S (251.3) calcd: C, 47.80; H, 3.61; N,
The present investigation offers an interesting synthetic
approaches towards new condensed thienopyridine ring
systems with other oxygen and sulfur heterocycles including
furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:30,20-e]-
pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-
benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines which have
been achieved by application of intramolecular [4þ2]
cycloaddition reactions of suitably designed thieno[2,3-e]-
[1,2,4]triazines tethered with terminal alkenes or alkynes.
These new aryl and heteroaryl condensed pyridine systems

Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
8493
16.72; S, 12.70. Found: C, 47.86; H, 3.75; N, 16.67; S,
12.64.
SMe), 7.52 (t, 1H, J¼6.0 Hz), 8.03 (t, 1H, J¼8.0 Hz), 8.40
(d, 1H, J¼8.0 Hz), 8.64 (s, 1H), 8.68, (d, 1H, J¼4.0 Hz).
Anal. for C11H8N4S2 (260.3) calcd: C, 50.75; H, 3.10; N,
21.52; S, 24.63. Found: C, 50.57; H, 3.24; N, 21.41; S,
24.93.
3.1.2. 3-Methylsulfanyl-6-[2-oxo-2-(2-thienyl)ethyl]-
1,2,4-triazin-5(2H)-one (3d). From 2d. Yellow crystals,
mp 216–2188C, yield¼10.36 g (78%). IR: 3188, 3054,
1
2929, 1691, 1602, 1417, 1341, 1022. H NMR (DMSO-d6)
3.3. 6-Aryl-3-methanesulfinylthieno[2,3-e][1,2,4]-
triazines 5a,c. General procedure
d¼2.45 (s, 3H, SMe), 4.25 (s, 2H), 7.29 (t, 1H, J¼4.0 Hz),
7.84 (d, 1H, J¼4.8 Hz), 8.09 (d, 1H, J¼3.6 Hz), 13.95 (brs,
1H, NH). 1H NMR (DMSO-d6) (methine tautomer) d¼2.45
(s, 3H, SMe), 6.29 (s, 1H), 7.18 (t, 1H, J¼4.0 Hz), 7.80 (d,
1H, J¼3.6 Hz), 8.06 (d, 1H, J¼4.8 Hz), 13.54 (brs, 1H,
NH), 13.95 (brs, 1H, NH). Anal. for C10H9N3O2S2 (267.3)
calcd: C, 44.93; H, 3.39; N, 15.72; S, 23.99. Found: C,
44.82; H, 3.60; N, 15.79; S, 23.82.
To a stirred solution of each of 4a,c (7.7 mmol) in
anhydrous dichloromethane (50 ml) at 08C, 3-chloroperoxy-
benzoic acid (77%, 1.9 g, 8.47 mmol, 1.1 equiv.) was added
portionwise. The solution was left stirring at room
temperature overnight. After removal of the solvent on
rotavap and trituration with ether, the product was
recrystallized from dichloromethane and ethanol.
3.1.3. 3-Methylsulfanyl-6-[2-oxo-2-(2-pyridyl)ethyl]-
1,2,4-triazin-5(2H)-one (3e). From 2e. Brown crystals,
mp 239–2418C, yield¼1.17 g (9%). MS: m/z¼262 (Mþ).
3.3.1. 3-Methanesulfinyl-6-phenylthieno[2,3-e][1,2,4]-
triazine (5a). From 4a. Yellow crystals, mp 179–1808C,
yield¼1.59 g (75%). IR: 2992, 2910, 1532, 1492, 1373,
1068, 756, 684. 1H NMR (CDCl3) d¼3.17 (s, 3H), 7.58 (m,
3H), 7.84 (dd, 2H, J¼2.4, 7.2 Hz), 8.03 (s, 1H). 13C NMR
(CDCl3) d¼41.5, 115.5, 127.6, 130.1, 131.9, 132.0, 154.3,
157.8, 163.1, 168.0. Anal. for C12H9N3OS2 (275.4) calcd: C,
52.35; H, 3.29; N, 15.26; S, 23.29. Found: C, 52.39; H, 3.32;
N, 15.11; S, 23.68.
1
IR: 3033, 1712, 1606, 1565, 1374, 1203, 750. H NMR
(DMSO-d6) d¼2.43 (s, 3H, SMe), 4.32 (s, 2H), 7.64
(m, 1H), 7.95 (m, 2H), 8.69 (d, 1H, J¼4.4 Hz), 13.87 (s, 1H,
1
NH). H NMR (DMSO-d6) (methine tautomer) d¼2.41 (s,
3H, SMe), 6.99 (s, 1H), 7.64 (m, 1H), 7.95 (m, 2H), 8.61 (d,
1H, J¼4.4 Hz), 12.60 (s, 1H, NH), 13.80 (s, 1H, NH). Anal.
for C11H10N4O2S (262.3) calcd: C, 50.37; H, 3.84; N, 21.36;
S, 12.22. Found: C, 50.60; H, 3.99; N, 21.22; S, 12.09.
3.3.2. 6-(2-Furyl)-3-methanesulfinylthieno[2,3-e][1,2,4]-
triazine (5c). From 4c. Yellow crystals, mp 188–1908C,
yield¼1.43 g (70%). IR: 3117, 3098, 3007, 2909, 1583,
1517, 1480, 1412, 1384, 1366, 1236, 1209, 1117, 1070,
3.2. 3-Methylsulfanyl-6-arylthieno[2,3-e][1,2,4]triazines
4c-e. General procedure
1
To a cold solution (58C) of each of 3c-e (23 mmol) in
pyridine (15 ml), phosphorus pentasulfide (10.21 g,
46 mmol) was added portionwise with stirring. The mixture
was then heated under reflux for 6 h. After cooling, the solid
precipitated was collected, washed with cold water and
ethanol and then recrystallized from DMF.
1033, 958, 881, 853, 841, 784. MS: m/z¼265 (Mþ). H
NMR (DMSO-d6) d¼3.06 (s, 3H, SOMe), 6.85 (dd, 1H,
J¼1.6, 3.6 Hz), 7.53 (d, 1H, J¼3.6 Hz), 8.07 (d, 1H,
J¼1.6 Hz), 8.24 (s, 1H). 13C NMR (CDCl3) d¼41.5,
113.3, 113.4, 113.6, 142.0, 146.3, 147.3, 157.5, 163.2,
167.7. Anal. for C10H7N3OS2 (265.4) calcd: C, 45.27; H,
2.66; N, 15.84; S, 24.17. Found: C, 45.45; H, 2.75; N, 16.03;
S, 23.95.
3.2.1. 6-(2-Furyl)-3-methylsulfanylthieno[2,3-e][1,2,4]-
triazine (4c). From 3c. Reddish brown crystals, mp 182–
1838C, yield¼4.58 g (79%). MS: m/z¼249 (Mþ). IR: 3436,
3.4. 3-Methanesulfonyl-6-arylthieno[2,3-e][1,2,4]-
triazines 6a-d. General procedures
1
3095, 1594, 1514, 1362, 1199, 1018. H NMR (CDCl3)
d¼2.75 (s, 3H, SMe), 6.60 (dd, 1H, J¼1.6, 3.6 Hz), 6.90 (d,
1H, J¼3.6 Hz), 7.62 (d, 1H, J¼1.6 Hz), 7.70 (s, 1H). Anal.
for C10H7N3OS2 (249.3) calcd: C, 48.18; H, 2.83; N, 16.85;
S, 25.72. Found: C, 47.98; H, 2.92; N, 16.76; S, 25.67.
(a) To a stirred ice cooled solution of each of the appropriate
derivative 4 (7.7 mmol) in dichloromethane (50 ml) and
acetic acid (50 ml) was added hydrogen peroxide (30%,
8.7 ml) and the mixture was left stirring over night at room
temperature. Dichloromethane was distilled off under
reduced pressure at 508C. After cooling and dilution with
water the precipitate was collected and recrystallized from
dichloromethane and ethanol.
3.2.2. 3-Methylsulfanyl-6-(2-thienyl)thieno[2,3-e]-
[1,2,4]triazine (4d). From 3d. Yellow crystals, mp 160–
1628C, yield¼4.82 g (79%). MS: m/z¼265 (Mþ). IR: 3435,
1
1623, 1550, 1496, 1373, 1240, 1067. H NMR (CDCl3)
d¼2.76 (s, 3H, SMe), 7.16 (dd, 1H, J¼3.6, 4.8 Hz), 7.47
(dd, 1H, J¼1.2, 3.6 Hz), 7.51 (dd, 1H, J¼1.2, 4.8 Hz), 7.64
(s, 1H). 13C NMR (CDCl3) d¼14.6, 115.2, 128.0, 128.9,
129.1, 135.9, 141.4, 154.1, 162.1, 168.1. Anal. for
C10H7N3S3 (265.4) calcd: C, 45.26; H, 2.66; N, 15.83.
Found: C, 45.33; H, 2.82; N, 15.85.
(b) To a stirred solution of each of the appropriate derivative
4 (7.7 mmol) in anhydrous dichloromethane (50 ml) at 08C,
3-chloroperoxybenzoic acid (77%, 3.44 g, 15.4 mmol,
2 equiv.) was added portionwise. The solution was left
stirring at room temperature overnight. After triturating with
ether, the product was collected and recrystallized from
DCM/EtOH.
3.2.3. 3-Methylsulfanyl-6-(2-pyridyl)thieno[2,3-e]-
[1,2,4]triazine (4e). From 3e. Green crystals, mp 230–
2328C, yield¼2.99 g (50%). MS: m/z¼260 (Mþ). IR:
1583, 1511, 1457, 1433, 1371, 1244, 1116, 1070, 991,
3.4.1. 3-Methanesulfonyl-6-phenylthieno[2,3-e][1,2,4]-
triazine (6a). From 4a using procedures a and b.
Yellow crystals, mp 263–2648C, yield¼1.7 g (76%).
1
887, 88, 772, 709. H NMR (DMSO-d6) d¼2.69 (s, 3H,

8494
Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
IR: 3082, 3051, 2920, 1652, 1534, 1491, 1476, 1118, 1069,
841, 754, 684. 1H NMR (DMSO-d6) d¼3.59 (s,
3H, SO2Me), 7.59 (m, 3H), 8.05 (m, 2H), 8.63 (s, 1H).
Anal. for C12H9N3O2S2 (291.4) calcd: C, 49.47; H, 3.11; N,
14.42; S, 22.01. Found: C, 49.08; H, 3.28; N, 14.42; S,
21.86.
dilution with water the precipitate was collected, dried
and crystallized from ethanol.
3.5.1. 3-Methoxy-6-phenylthieno[2,3-e][1,2,4]triazine
(8a). From 6a. Yellow crystals, mp 169–1708C, yield¼0.25
g (60%). MS: m/z¼243 (Mþ). IR: 1625, 1529, 1475, 1384,
1
1305, 1128, 1095, 1055. H NMR (CDCl3) d¼4.28 (s, 3H,
3.4.2. 3-Methanesulfonyl-6-(4-methoxyphenyl)thieno-
[2,3-e][1,2,4]triazine (6b). From 4b using procedures a
and b. Orange crystals, mp 256–2578C, yield 1.63 g (73%).
MS: m/z¼321 (Mþ). IR: 3086, 2927, 1603, 1502, 1379,
1247, 1183, 1128, 1083, 1026, 838, 577, 535, 495. 1H NMR
(DMSO-d6) d¼3.57 (s, 3H, SO2Me), 3.87 (s, 3H, OCH3),
7.14 (m, 2H), 8.02 (m, 2H), 8.48 (s, 1H). 13C NMR (DMSO-
d6) d¼41.3, 56.5, 115.0, 116.0, 124.6, 130.0, 155.3, 159.3,
160.3, 162.3, 163.0. Anal. for C13H11N3O3S2 (321.4) calcd:
C, 48.59; H, 3.45; N, 13.07; S, 19.95. Found: C, 48.40; H,
3.51; N, 13.02; S, 20.17.
OMe), 7.52 (m, 3H), 7.76 (m, 2H), 7.83 (s, 1H). 13C NMR
(CDCl3) d¼56.7, 115.8, 127.3, 130.0, 130.9, 133.0, 148.0,
154.3, 162.6, 164.3. Anal. for C12H9N3OS (243.3) calcd: C,
59.24; H, 3.73; N, 17.27; S, 13.18. Found: C, 59.24; H, 3.79;
N, 17.27; S, 13.37.
3.5.2. 3-Methoxy-6-(4-methoxyphenyl)thieno[2,3-
e][1,2,4]triazine (8b). From 27. Yellow crystals, mp
210–2128C, yield¼0.31 g (67%). MS: m/z¼273 (Mþ). IR:
1604, 1536, 1507, 1473, 1387, 1312, 1256, 1180, 1051, 837.
1H NMR (DMSO-d6) d¼3.83 (s, 3H, ArOMe), 4.11 (s, 3H,
OMe), 7.05 (d, 2H, J¼7.5 Hz), 7.80 (d, 2H, J¼7.5 Hz), 8.07
(s, 1H). 13C NMR (CDCl3) d¼56.1, 56.7, 114.0, 115.3,
125.5, 128.7, 148.0, 154.6, 161.9, 162.4, 164.4. Anal. for
C13H11N3O2S (273.3) calcd: C, 57.13; H, 4.06; N, 15.37; S,
11.73. Found: C, 57.32; H, 4.03; N, 15.48; S, 11.78.
3.4.3. 6-(2-Furyl)-3-methanesulfonylthieno[2,3-e][1,2,4]-
triazine (6c). From 4c using procedure a. Yield 1.67 g
(74%) mp 253–2558C. IR: 3148, 3110, 3041, 3017, 2936,
1589, 1510, 1445, 1389, 1365, 1310, 1140, 1117, 1072,
1
1026, 973, 955, 883, 823, 787. MS: m/z¼281 (Mþ). H
NMR (DMSO-d6) d¼3.57 (s, 3H, SO2Me), 6.87 (dd, J¼2.4,
3.6 Hz, 1H), 7.59 (d, 1H, J¼3.6 Hz), 8.10 (d, 1H,
J¼1.6 Hz), 8.32 (s, 1H). Anal. for C10H7N3O3S2 (281.3)
calcd: C, 42.70; H, 2.51; N, 14.94; S, 22.80. Found: C,
43.01; H, 2.65; N, 15.08; S, 22.82.
3.6. Preparation of 9–13. General procedure
A mixture of NaH (0.1 g NaH 60% in mineral oil washed
with hexane) in dry THF (5 ml) and each of phenol,
2-phenylethanol, 3-butyn-1-ol, 2-allylphenol or 1-allyl-2-
naphthol (2 mmol) was warmed till hydrogen gas cease to
evolve. To this mixture was added each of 6a,b (1.7 mmol)
with stirring. After stirring overnight at room temperature
under nitrogen, water was added to the mixture and
precipitate was collected, dried and crystallized from
ethanol.
3.4.4. 3-Methanesulfonyl-6-(2-thienyl)-thieno[2,3-e]-
[1,2,4]triazine (6d). From 4d using procedure a. Yield
1.76 g (80%), mp 262–2648C. MS: m/z¼297 (Mþ). 1H
NMR (DMSO-d6) d¼3.57 (s, 3H, SO2Me), 7.32 (t, 1H,
J¼3.6 Hz), 7.98 (m, 2H), 8.35 (s, 1H). Anal. for
C10H7N3O2S3 (297.4) calcd: C, 40.39; H, 2.37; N, 14.13;
S, 32.35. Found: C, 40.64; H, 2.49; N, 14.31; S, 32.37.
3.6.1. 3-Phenoxy-6-phenylthieno[2,3-e][1,2,4]triazine
(9a). From phenol and 6a. Yellow crystals, mp 165–
1678C, yield¼0.46 g (88%). MS: m/z¼305 (Mþ). IR: 1631,
3.4.5. 6-(4-Methoxyphenyl)thieno[2,3-e][1,2,4]triazin-3-
ol (7b). To a stirred solution of 6b (0.1 g, 0.31 mmol) in
DCM (10 ml) and benzyltriethylammonium chloride (0.1 g)
was added a solution of NaOH (1.35 g in 2 ml of water). The
mixture was kept stirring overnight at room temperature and
DCM was removed by heating on water bath at 508C. The
mixture was then acidified with dilute HCl and the
precipitate was collected, washed with water and crystal-
lized from ethanol into yellow crystals of 7b, mp 3038C,
yield¼0.05 g (62%). MS: m/z¼259 (Mþ). IR: 3433, 1638,
1601, 1502, 1256, 1179, 1079. 1H NMR (DMSO-d6)
d¼3.84 (s, 3H, OMe), 7.09 (d, 2H, J¼8.8 Hz), 7.64 (s,
1H), 7.79 (d, 2H, J¼8.8 Hz), 13.60 (s, 1H). 13C NMR
(CDCl3) d¼56.3, 113.1, 115.6, 125.0, 128.9, 144.9, 147.0,
152.5, 162.0, 173.7. Anal. for C12H9N3O2S (259.3) calcd: C,
55.59; H, 3.50; N, 16.21; S, 12.37. Found: C, 55.32; H, 3.70;
N, 15.90; S, 12.63.
1
1600, 1564, 1498, 1456, 1433, 1361, 1349, 1275, 752. H
NMR (CDCl3) d¼7.33 (m, 3H), 7.52 (m, 5H), 7.74 (m, 2H),
7.86 (s, 1H). Anal. for C17H11N3OS (305.4) calcd: C, 66.87;
H, 3.63; N, 13.76; S, 10.50. Found: C, 66.67; H, 3.72; N,
13.79; S, 10.56.
3.6.2. 6-(4-Methoxyphenyl)-3-phenoxythieno[2,3-
e][1,2,4]triazine (9b). From phenol and 6b. Yellow
crystals, mp 216–2188C, yield¼0.4 g (70%). IR: 3093,
3056, 2971, 1603, 1532, 1507, 1489, 1422, 1397, 1357,
1306, 1259, 1195, 1182, 1132, 1094, 1026, 845, 808, 783,
765, 689. 1H NMR (DMSO-d6) d¼3.84 (s, 3H, OMe), 7.10
(d, 2H, J¼8.3 Hz), 7.33 (m, 3H), 7.50 (t, 2H, J¼7.5 Hz),
7.87 (d, 2H, J¼8.4 Hz), 8.20 (s, 1H). Anal. for
C18H13N3O2S (335.4) calcd: C, 64.46; H, 3.91; N, 12.53;
S, 9.56. Found: C, 64.37; H, 3.86; N, 12.58; S, 9.48.
3.5. 3-Methoxy-6-arylthieno[2,3-e][1,2,4]triazines 8a,b.
General procedure
3.6.3. 6-Phenyl-3-(2-phenylethoxy)thieno[2,3-e][1,2,4]-
triazine (10a). From 2-phenylethanol and 6a. Yellow
crystals, mp 131–1328C, yield¼0.42 g (74%). MS:
m/z¼333 (Mþ). IR: 1531, 1483, 1467, 1448, 1428, 1374,
To a solution of sodium methoxide (prepared from 0.19 g
Na in 10 ml of distilled methanol) was added each of 6a,b
(1.7 mmol) with stirring. Stirring was then continued
overnight at room temperature under nitrogen. After
1
1300, 1088, 1055, 754. H NMR (CDCl3) d¼3.26 (t, 2H,
J¼7.2 Hz), 4.85 (t, 2H, J¼7.2 Hz), 7.27 (t, 1H, J¼6.0 Hz),
7.36 (m, 4H), 7.51 (m, 3H), 7.75 (d, 2H, J¼7.5 Hz), 7.82 (s,

Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
8495
1H). Anal. for C19H15N3OS (333.4) calcd: C, 68.45; H,
4.53; N, 12.60; S, 9.62. Found: C, 68.17; H, 4.55; N, 12.61;
S, 9.44.
3.6.9. 3-(2-Allylphenoxy)-6-phenylthieno[2,3-e][1,2,4]-
triazine (12a). From 2-allylphenol and 6a. Yellow crystals,
mp 124–1268C, yield¼0.41 g (69%). MS: m/z¼345 (Mþ).
IR: 3056, 2976, 2907, 2841, 1639, 1520, 1487, 1403, 1297,
1
3.6.4. 6-(4-Methoxyphenyl)-3-(2-phenylethoxy)-
thieno[2,3-e][1,2,4]triazine (10b). From 2-phenylethanol
and 6b. Yellow crystals, mp 157–1588C, yield¼0.45 g
(73%). MS: m/z¼363 (Mþ). IR: 3419, 1604, 1503, 1428,
1077. H NMR (CDCl3) d¼3.42 (d, 2H, J¼6.4 Hz), 5.00
(m, 2H), 5.92 (m, 1H), 7.23 (dd, 1H, J¼1.6, 7.6 Hz), 7.34
(m, 3H), 7.52 (m, 3H), 7.76 (dd, 2H, J¼1.6, 7.6 Hz), 7.87 (s,
1H). 13C NMR (CDCl3) d¼34.9, 115.6, 116.8, 122.4, 126.7,
127.2, 128.2, 129.8, 130.9, 131.2, 132.7, 132.8, 136.2,
148.8, 151.3, 154.8, 162.4, 163.9. Anal. for C20H15N3OS
(345.4) calcd: C, 69.54; H, 4.38; N, 12.16; S, 9.28. Found:
C, 69.72; H, 4.47; N, 12.44; S, 9.14.
1
1347, 1310, 1259, 1177. H NMR (Acetone-d6) d¼3.23 (t,
2H, J¼6.8 Hz), 3.90 (s, 3H, OMe), 4.80 (t, 2H, J¼6.8 Hz),
7.11 (d, 2H, J¼7.1 Hz), 7.25 (t, 1H, J¼7.3 Hz), 7.34 (t, 2H,
J¼6.9 Hz), 7.41 (d, 2H, J¼7.3 Hz), 7.86 (d, 2H, J¼7.1 Hz),
7.91 (s, 1H). Anal. for C20H17N3O2S (363.41) calcd: C,
66.16; H, 4.71; N, 11.56; S, 8.82. Found: C, 65.77; H, 4.78;
N, 11.67; S, 8.68.
3.6.10. 3-(2-Allylphenoxy)-6-(4-methoxyphenyl)-
thieno[2,3-e][1,2,4]triazine (12b). From 2-allylphenol
and 6b. Yellow crystals from chloroform and ethanol, mp
143–1448C, yield¼0.33 g (57%). MS: m/z¼375 (Mþ). IR:
3064, 3000, 2930, 2840, 1603, 1485, 1400, 1292, 1263,
3.6.5. 3-(But-3-ynyloxy)-6-phenylthieno[2,3-e][1,2,4]-
triazine (11a). From 3-butyn-1-ol and 6a. Yellow crystals,
mp 177–1788C, yield¼0.35 g (73%). MS: m/z¼281 (Mþ).
IR: 1521, 1486, 1449, 1371, 1303, 1281, 1094, 1015,
1
1219, 1082, 1016, 920. H NMR (DMSO-d6) d¼3.34 (br,
2H), 3.85 (s, 3H, OMe), 4.96 (2d, 2H, J¼9.3, 18.4 Hz), 5.86
(m, 1H), 7.10 (d, 2H, J¼8.8 Hz), 7.30 (t, 2H, J¼6.8 Hz),
7.37 (t, 2H, J¼9.2 Hz), 7.87 (d, 2H, J¼8.8 Hz), 8.23 (s, 1H).
Anal. for C21H17N3O2S (375.45) calcd: C, 67.18; H, 4.56;
N, 11.19; S, 8.54. Found: C, 67.24; H, 4.53; N, 11.20; S,
8.25.
1
756, 786. H NMR (CDCl3) d¼2.08 (t, 1H, J¼2.4 Hz),
2.87 (dt, 2H, J¼2.4, 7.1 Hz), 4.76 (t, 2H, J¼7.1 Hz),
7.53 (m, 3H), 7.76 (dd, 2H, J¼1.6, 7.6 Hz), 7.84 (s, 1H).
13C NMR (CDCl3) d¼19.6, 66.9, 70.8, 80.2, 115.5,
127.1, 129.8, 130.8, 132.7, 148.2, 154.4, 161.6, 164.1.
Anal. for C15H11N3OS (281.3) calcd: C, 64.04; H, 3.94; N,
14.94; S, 11.40. Found: C, 63.91; H, 4.02; N, 15.05; S,
11.81.
3.6.11. 3-(2-Allylphenoxy)-6-(2-furyl)thieno[2,3-e]-
[1,2,4]triazine (12c). From 2-allylphenol and 6c. Orange
crystals, mp 130–1328C, yield¼0.41 g (68%). MS:
m/z¼335 (Mþ). IR: 3132, 3102, 3077, 3054, 3004, 2977,
2906, 1586, 1526, 1488, 1400, 1302, 1216, 1171, 1075, 816.
1H NMR (CDCl3) d¼3.42 (d, 2H, J¼6.4 Hz), 5.00 (m, 2H),
5.90 (m, 1H), 6.60 (dd, 1H, J¼1.6, 3.6 Hz), 6.88 (d, 1H,
J¼3.6 Hz), 7.22 (dd, 1H, J¼1.2, 7.6 Hz), 7.31 (m, 3H), 7.62
(d, 1H, J¼1.6 Hz), 7.74 (s, 1H). Anal. for C18H13N3O2S
(335.4) calcd: C, 64.46; H, 3.91; N, 12.53; S, 9.56. Found:
C, 64.57; H, 3.98; N, 12.52; S, 9.50.
3.6.6. 3-(But-3-ynyloxy)-6-(4-methoxyphenyl)thieno[2,3-
e][1,2,4]triazine (11b). From 3-butyn-1-ol and 6b.Yellow
crystals, mp 170–1718C, yield¼0.38 g (72%). IR: 1605,
1
1535, 1505, 1492, 1428, 1314, 1256, 1184, 1047, 824. H
NMR (CDCl3) d¼2.08 (t, 1H, J¼2.4 Hz), 2.86 (dt, 2H,
J¼2.4, 7.2 Hz), 3.91 (s, 3H), 4.75 (t, 2H, J¼7.2 Hz), 7.03
(dd, 2H, J¼2, 6.8 Hz), 7.69 (dd, 2H, J¼2, 6.8 Hz), 7.70 (s,
1H). 13C NMR (CDCl3) d¼19.6, 56.0, 66.8, 70.7, 80.2,
113.8, 115.2, 125.3, 128.6, 148.1, 154.6, 161.5, 161.8,
164.2. Anal. for C16H13N3O2S (311.4) calcd: C, 61.72; H,
4.21; N, 13.50; S, 10.30. Found: C, 61.66; H, 4.26; N, 13.51;
S, 10.08.
3.6.12. 3-(2-Allylphenoxy)-6-(2-thienyl)thieno[2,3-e]-
[1,2,4]triazine (12d). From 2-allylphenol and 6d.
Yellow crystals, mp 105–1068C, yield¼0.38 g (64%).
MS: m/z¼350 (Mþ). IR: 3060, 2976, 2922, 2906, 1640,
1485, 1402, 1303, 1218, 1091, 706. 1H NMR (CDCl3)
d¼3.41 (d, 2H, J¼6.5 Hz), 5.00 (2d, 2H, J¼9.2, 15.2 Hz),
5.93 (m, 1H), 7.15 (t, 1H, J¼4.4 Hz), 7.22 (d, 1H,
J¼7.6 Hz), 7.33 (m, 3H), 7.45 (d, 1H, J¼3.6 Hz), 7.50 (d,
1H, J¼5.2 Hz), 7.68 (s, 1H). 13C NMR (CDCl3) d¼34.9,
114.9, 116.8, 122.4, 126.7, 127.9, 128.2, 128.9, 129.0,
131.2, 132.7, 135.9, 136.1, 141.8, 151.3, 154.6, 162.4,
164.0. Anal. for C18H13N3OS2 (351.5) calcd: C, 61.52; H,
3.73; N, 11.96; S, 18.25. Found: C, 61.80; H, 3.89; N, 11.92,
S, 18.43.
3.6.7. 3-(But-3-ynyloxy)-6-(2-furyl)thieno[2,3-e][1,2,4]-
triazine (11c). From 3-butyn-1-ol and 6c. Orange crystals,
mp 174–1758C, yield¼0.40 g (87%). MS: m/z¼271 (Mþ).
IR: 1599, 1520, 1427, 1359, 1304, 1091, 1024, 972, 824. 1H
NMR (CDCl3) d¼2.08 (t, 1H, J¼2.4 Hz), 2.85 (dt, 2H,
J¼2.4, 6.8 Hz), 4.74 (t, 2H, J¼6.8 Hz), 6.59 (dd, 1H, J¼1.5,
3.5 Hz), 6.87 (d, 1H, J¼3.5 Hz), 7.61 (d, 1H, J¼1.5 Hz),
7.70 (s, 1H). Anal. for C13H9N3O2S (271.3) calcd: C, 57.55;
H, 3.34; N, 15.49; S, 11.82. Found: C, 57.73; H, 3.51; N,
15.56; S, 12.12.
3.6.8. 3-(But-3-ynyloxy)-6-(2-thienyl)thieno[2,3-e]-
[1,2,4]triazine (11d). From 3-butyn-1-ol and 6d. Green
crystals, mp 153–1548C, yield¼0.42 g (87%). MS:
m/z¼287 (Mþ). IR: 3266, 3087, 3059, 1543, 1523, 1485,
3.6.13. 3-(1-Allyl-2-naphthalenyloxy)-6-(4-methoxy-
phenyl)thieno[2,3-e][1,2,4]triazine (13b). From 6b and
1-allyl-2-naphthol. Yield 69%, green crystals, mp 176–
1788C. IR: 3085, 3000, 2959, 1635, 1604, 1576, 1504, 1489,
1421, 1398, 1304, 1256, 1214, 1180, 1092, 1026, 984, 918,
841, 818. 1H NMR (CDCl3) d¼3.91 (s, 3H, OMe), 3.92 (d,
2H, J¼8.8 Hz) 4.96 (2d, 2H, J¼8.4, 16.8 Hz), 5.98 (m, 1H),
7.03 (d, 2H, J¼8.3 Hz), 7.37 (d, 1H, J¼8.8 Hz), 7.55 (m,
2H), 7.69 (d, 2H, J¼8.4 Hz), 7.76 (s, 1H), 7.86 (d, 1H,
J¼8.8 Hz), 7.92 (d, 1H, J¼8 Hz), 8.09 (d, 1H, J¼8.4 Hz).
1
1434, 1373, 1304, 1283, 1098, 1022, 847, 784. H NMR
(CDCl3) d¼2.08 (t, 1H, J¼2 Hz), 2.85 (dt, 2H, J¼2, 7 Hz),
4.74 (t, 2H, J¼7 Hz), 7.15 (dd, 1H, J¼4.0, 8.4 Hz), 7.48 (m,
2H), 7.64 (s, 1H). Anal. for C13H9N3OS2 (287.4) calcd: C,
54.34; H, 3.16; N, 14.62; S, 22.32. Found: C, 53.99; H, 3.30;
N, 14.61; S, 22.62.

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Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
Anal. for C25H19N3O2S (425.5) calcd: C, 70.57; H, 4.50; N,
9.88; S, 7.54. Found: C, 70.31; H, 4.54; N, 9.98; S, 7.21.
3.7.3. 3-(3-Buten-1-ylsulfanyl)-6-[2-(2-thienyl)vinyl]-
1,2,4-triazin-5(2H)-one (18c). From 17c. Yellow crystals,
mp 200–2028C, yield 2.0 g (89%). IR: 3195, 3075, 3004,
2964, 2900, 1700 (m), 1593 (br), 1504, 1448, 1373, 1357,
1282, 1201, 1042, 1008, 963, 916, 853, 790, 701. 1H NMR
(CDCl3) d¼2.52 (q, 2H, J¼7.2 Hz), 3.35 (t, 2H, J¼7.2 Hz),
5.12 (2d, 2H, J¼8.6, 16.5 Hz), 5.80 (m, 1H), 6.99 (d, 1H,
J¼16.0 Hz), 7.07 (m, 1H), 7.25 (d, 1H, J¼3.6 Hz), 7.28 (s,
1H), 7.34 (d, 1H, J¼5 Hz) 8.28 (d, 1H, J¼16.0 Hz), 10.50
(brs, 1H, NH). Anal. for C13H13N3OS2 (291.4) calcd: C,
53.59; H, 4.50; N, 14.42; S, 22.01. Found: C, 53.90; H, 4.56;
N, 14.42; S, 22.22.
3.6.14. 3-Mercapto-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-
5(2H)-one 17c. A mixture of 4-(2-thinyl)-2-oxo-3-butenoic
acid (20 mmol) and thiosemicarbazide (20 mmol) in water
(50 ml) was heated under reflux for 15 min. The mixture
was left overnight at room temperature. The precipitate
formed was collected, washed with cold water, dried to give
2-oxo-4-(2-thienyl)but-3-enoic acid thiosemicarbazone
(4.72 g, 93%) which was dissolved in aqueous potassium
hydroxide solution (1 M, 25 ml). The mixture was then
heated under reflux for 20 min. After cooling, the solution
was acidified with hydrochloric acid and the precipitate was
collected, washed with water and recrystallized from DMF
to give yellow crystals of 17c, mp 288–2908C, yield 4.88 g
(91%). IR: 3196, 3093, 2899, 2200–3200 (br), 1699, 1611,
1548, 1518, 1500, 1437, 1326, 1274, 1214, 1198, 1139,
1100, 1009, 960, 814, 775, 701, 676. 1H NMR (DMSO-d6)
d¼6.74 (d, 1H, J¼16.4 Hz), 7.11 (t, 1H, J¼4.0 Hz), 7.40 (d,
1H, J¼3.2 Hz), 7.61 (d, 1H, J¼5.2 Hz), 7.96 (d, 1H,
J¼16.4 Hz), 13.20 (br, 1H), 13.58 (br, 1H). 13C NMR
(DMSO-d6) d¼119.1, 129.0, 129.6, 129.8, 130.9, 142.2,
145.1, 154.0, 173.4. Anal. for C9H7N3OS2.H2O (225.3)
calcd: C, 42.34; H, 3.55; N, 16.46; S, 25.12. Found: C,
42.30; H, 3.53; N, 16.28; S, 25.00.
3.8. 3-(3-Buten-1-ylsulfanyl)-6-arylthieno[2,3-e][1,2,4]-
triazines 19a-c. General procedure
Phosphorus pentasulfide (0.7 g, 3.2 mmol, 2 equiv.) was
added portionwise with shaking to a solution of each of
18a-c (1.6 mmol) in pyridine (5 ml). The reaction mixture
was heated under reflux for 6 h. After cooling, the mixture
was added to ice cold potassium hydroxide solution, left
overnight and the precipitate formed was collected, washed
with water and crystallized from ethanol.
3.8.1. 3-(3-Buten-1-ylsulfanyl)-6–phenylthieno[2,3-e]-
[1,2,4]triazine (19a). From 18a. Pale yellow crystals, mp
190–1918C, yield 0.17 g (35%). IR: 3091, 3053, 2975,
2901, 1636, 1538, 1512, 1490, 1442, 1369, 1237, 1173,
1116, 1064, 997, 914, 887, 839, 756, 690. 1H NMR (CDCl3)
d¼2.61 (q, 2H. J¼6.8 Hz), 3.42 (t, 2H. J¼7.2 Hz), 5.15 (2d,
2H, J¼10.4, 16.8 Hz), 5.94 (m, 1H), 7.52 (m, 3H), 7.77 (d,
2H, J¼6.4 Hz), 7.82 (s, 1H). 13C NMR (CDCl3) d¼30.7,
33.6, 115.9, 117.1, 127.2, 129.8, 130.9, 132.7, 136.5, 148.5,
154.4, 162.0, 167.8. Anal. for C15H13N3S2 (299.4) calcd: C,
60.17; H, 4.38; N, 14.03; S, 21.42. Found: C, 60.18; H, 4.37;
N, 14.36; S, 21.67.
3.7. 3-(3-Buten-1-ylsulfanyl)-6-(2-Arylvinyl)-1,2,4-
triazin-5(2H)-ones 18a-c. General procedure
Each of 17a-c (7.66 mmol) was dissolved in methanolic
potassium hydroxide solution (0.47 g, 1.1 equiv. in 20 ml of
distilled methanol). After evaporating the methanol,
4-bromo-1-butene (1.14 g, 1.1 equiv.) was added followed
by DMF (10 ml). The mixture was then heated on a
boiling water bath for 1 h then cooled and poured over
100 ml of cold water. The precipitate formed was
collected, washed with water, dried and recrystallized
from ethanol.
3.8.2. 3-(3-Buten-1-ylsulfanyl)-6-(4-methoxyphenyl)-
thieno[2,3-e][1,2,4]triazine (19b). From 18b. Brown
crystals, mp 126–1278C, yield 0.15 g (28%). 1H NMR
(CDCl3) d¼2.61 (q, 2H, J¼7.2 Hz), 3.42 (t, 2H, J¼7.2 Hz),
3.91 (s, 3H), 5.16 (2d, 2H, J¼10.4, 16.8 Hz), 5.93 (m, 1H),
7.04 (d, 2H, J¼8.8 Hz), 7.70 (s, 1H), 7.71 (d, 2H, J¼8.8 Hz).
Anal. for C16H15N3OS2 (329.5) calcd: C, 58.33; H, 4.59; N,
12.75; S, 19.47. Found: C, 58.22; H, 4.35; N, 12.85; S, 19.25.
3.7.1. 3-(3-Buten-1-ylsulfanyl)-6-styryl-1,2,4-triazin-
5(2H)-one (18a). From 17a. Pale yellow crystals, mp
198–2008C, yield 1.5 g (69%). IR: 3180, 3060, 3025, 2978,
1603 (br), 1555, 1510, 1442, 1381, 1325, 1304, 1281, 1222,
1206, 1002, 973, 917, 745, 690. 1H NMR (DMSO-d6)
d¼2.45 (m, 2H), 3.24 (t, 2H, J¼7.2 Hz), 5.11 (m, 2H), 5.83
(m, 1H), 7.14 (d, 2H, J¼16.4 Hz), 7.39 (m, 3H), 7.65 (d, 2H,
J¼7.2 Hz), 7.96 (d, 1H, J¼16.4 Hz), 14.0 (br, 1H). Anal. for
C15H15N3OS (285.4) calcd: C, 63.13; H, 5.30; N, 14.72; S,
11.24. Found: C, 63.12; H, 5.31; N, 14.71; S, 11.16.
3.8.3. 3-(3-Buten-1-ylsulfanyl)-6-(2-thienyl)thieno[2,3-e]-
[1,2,4]triazine (19c). From 18c. Yellow crystals, mp 104–
1058C, yield¼0.18 g (36%). 1H NMR(CDCl3) d¼2.60(q, 2H,
J¼7.2 Hz), 3.42 (t, 2H, J¼7.2 Hz), 5.15 (2d, 2H, J¼10.4,
16.8 Hz), 5.95 (m, 1H), 7.16 (t, 1H, J¼4.4 Hz), 7.47 (d, 1H,
J¼3.6 Hz), 7.51 (d, 1H, J¼4.8 Hz), 7.64 (s, 1H). Anal. for
C13H11N3S3 (305.4) calcd: C, 51.12; H, 3.63; N, 13.76; S,
31.49. Found: C, 51.26; H, 3.69; N, 13.80; S, 31.08.
3.7.2. 3-(3-Buten-1-ylsulfanyl)-6-(2-p-methoxyphenyl-
vinyl)-1,2,4-triazin-5(2H)-one (18b). From 17b. Yellow
crystals, mp 212–2138C, yield 19.6 g (81%). IR: 3179,
3070, 2978, 2905, 1685 (w), 1604 (br), 1571, 1511, 1450,
1421, 1381, 1329, 1290, 1252, 1222, 1175, 1031, 1001, 977,
915, 825, 792. 1H NMR (CDCl3) d¼2.52 (t, 2H, J¼7.2 Hz),
3.37 (q, 2H, J¼7.6 Hz), 3.83 (s, 3H, OMe), 5.15 (2d, 2H,
J¼9.2, 16 Hz), 5.82 (m, 1H), 6.92 (d, 2H, J¼8.4 Hz), 7.10
(d, 1H, J¼16.4 Hz), 7.56 (d, 2H, J¼8.4 Hz), 8.00 (d, 1H,
J¼16.4 Hz), 10.26 (br, 1H, NH). Anal. for C16H17N3O2S
(305.4) calcd: C, 60.93; H, 5.43; N, 13.32; S, 10.17. Found:
C, 60.78; H, 5.39; N, 13.59; S, 10.05.
3.9. Thienopyridines 14–16, 20. General procedures
(a) A solution of each of 11–13, 19 (0.2 mmol) in
nitrobenzene (2 ml) was heated under reflux for 1 h. After
cooling the precipitated crystals were collected, washed
with petroleum ether (40–60) and recrystallized from
choroform/ethanol to give the corresponding thieno-
pyridines 14–16 and 20.

Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
8497
(b) Compound 11a (0.17 mmol) was heated neat at 2008C
on an oil bath for 1 h. After cooling, the solid was
recrysallized from chloroform and ethanol.
156.5. Anal. for C20H13NOS (315.4) calcd: C, 76.17; H,
4.15; N, 4.44; S, 10.17. Found: C, 75.81; H, 4.25; N, 4.72; S,
9.97.
3.9.1. 6-Phenyl-2,3-dihydrofuro[2,3-b]thieno[3,2-e]pyri-
dine (14a). From 11a using procedures a (yield 48%) and b
(yield 54%). Pale brown crystals, mp 257–2588C. IR: 3064,
2972, 2917, 1558, 1570, 1518, 1487, 1473, 1437, 1403,
1358, 1249, 1224, 1195, 1048, 995, 954, 938, 911, 757, 742,
703, 687. MS: m/z¼253 (Mþ). 1H NMR (CDCl3) d¼3.36 (t,
2H, J¼8.4 Hz), 4.74 (t, 2H, J¼8.4 Hz), 7.33 (t, 1H,
J¼7.6 Hz), 7.36 (s, 1H), 7.43 (t, 2H, J¼7.6 Hz), 7.68 (d,
2H, J¼7.6 Hz), 7.84 (s, 1H). Anal. for C15H11NOS (253.3)
calcd: C, 71.12; H, 4.38; N, 5.53; S, 12.66. Found: C, 70.79;
H, 4.39; N, 5.86; S, 12.57.
3.9.6. 2-(4-Methoxyphenyl)-5H-chromeno[2,3-b]-
thieno[3,2-e]pyridine (15b). From 12b. White crystals,
mp 280–2818C, yield¼29 mg (50%). IR: 3033, 2952, 2910,
2835, 1607, 1589, 1555, 1525, 1499, 1458, 1389, 1307,
1291, 1253, 1231, 1182, 1031, 896, 831, 817, 810, 749, 730.
MS: m/z¼345 (Mþ). 1H NMR (CDCl3) d¼3.88 (s, 3H), 4.25
(s, 2H), 6.99 (d, 2H, J¼8.4 Hz), 7.11 (t, 1H, J¼7.2 Hz), 7.23
(m, 3H), 7.28 (s, 1H), 7.64 (d, 2H, J¼8.4 Hz), 7.84 (s, 1H).
Anal. for C21H15NO2S (345.4) calcd: C, 73.02; H, 4.38; N,
4.05; S, 9.28. Found: C, 73.09; H, 4.37; N, 4.29; S, 9.12.
3.9.7. 2-(2-Furyl)-5H-chromeno[2,3-b]thieno[3,2-e]pyri-
dine (15c). From 12c. Brown crystals, mp 223–2248C,
yield¼26 mg (50%). IR: 3109, 3060, 1589, 1549, 1490,
1459, 1429, 1389, 1305, 1271, 1231, 1058, 1015, 970, 913,
3.9.2. 6-(4-Methoxyphenyl)-2,3-dihydrofuro[2,3-b]-
thieno[3,2-e]pyridine (14b). From 11b. Orange crystals,
mp 260–2618C, yield¼25 mg (52%). IR: 2909, 2836, 1607,
1567, 1524, 1494, 1450, 1405, 1248, 1181, 1046, 1028, 995,
1
896, 754, 728. MS: m/z¼305 (Mþ). H NMR (DMSO-d6)
1
907, 832, 807, 745, 698. MS: m/z¼283 (Mþ). H NMR
d¼4.25 (s, 2H), 6.67 (dd, 1H, J¼1.6, 3.2 Hz), 6.97 (d, 1H,
J¼3.2 Hz), 7.16 (m, 2H), 7.31 (m, 2H), 7.59 (s, 1H), 7.83 (d,
1H, J¼1.6 Hz), 8.15 (s, 1H). Anal. for C18H11NO2S (305.4)
calcd: C, 70.80; H, 3.63; N, 4.59; S, 10.50. Found: C, 70.76;
H, 3.66; N, 4.80; S, 10.26.
(CDCl3) d¼3.35 (t, 2H, J¼8.4 Hz), 3.87 (s, 3H), 4.75 (t, 2H,
J¼8.4 Hz), 6.96 (d, 2H, J¼8.4 Hz), 7.24 (s, 1H), 7.61 (d,
2H, J¼8.4 Hz), 7.77 (s, 1H). 13C NMR (CDCl3) d¼28.3,
55.8, 70.2, 114.8, 115.7, 119.2, 127.5, 127.7, 128.3, 129.4,
140.6, 158.7, 160.0, 167.0. Anal. for C16H13NO2S (283.4)
calcd: C, 67.82; H, 4.62; N, 4.94; S, 11.32. Found: C, 67.52;
H, 4.60; N, 5.18; S, 10.98.
3.9.8. 2-(2-Thienyl)-5H-chromeno[2,3-b]thieno[3,2-e]-
pyridine (15d). From 12d. Green crystals, mp 253–
2548C, yield¼32 mg (59%). IR: 3063, 3035, 1589, 1555,
1532, 1489, 1458, 1421, 1386, 1305, 1269, 1229, 1188,
1058, 962, 895, 836, 812, 758, 693. MS: m/z¼320 (Mþ). 1H
NMR (CDCl3) d¼4.24 (s, 2H), 7.10 (m, 2H), 7.22 (s, 1H),
7.27 (m, 5H), 7.82 (s, 1H). 13C NMR (CDCl3) d¼28.9,
113.7, 116.6, 117.7, 120.1, 124.4, 125.9, 126.3, 128.6,
128.7, 129.1, 131.9, 132.7, 136.5, 137.7, 152.2, 156.7,
158.3. Anal. for C18H11NOS2 (321.4) calcd: C, 67.26; H,
3.45; N, 4.36; S, 19.95. Found: C, 67.35; H, 3.51; N, 4.59; S,
20.12.
3.9.3. 6-(2-Furyl)-2,3-dihydrofuro[2,3-b]thieno[3,2-e]-
pyridine (14c). From 11c. Green crystals, mp 254–2558C,
yield¼20 mg (49%). IR: 3075, 2973, 2920, 1561, 1513,
1475, 1437, 1402, 1357, 1250, 1211, 1185, 1152, 1043,
1017, 994, 970, 954, 922, 850, 793, 743, 727, 670. 1H NMR
(CDCl3) d¼3.36 (t, 2H, J¼8.4 Hz), 4.74 (t, 2H, J¼8.4 Hz),
6.50 (dd, 1H, J¼1.5, 3.6 Hz), 6.59 (d, 1H, J¼3.6 Hz), 7.28
(s, 1H), 7.47 (d, 1H, J¼1.5 Hz), 7.78 (s, 1H). Anal. for
C13H9NO2S (243.3) calcd: C, 64.24; H, 3.57; N, 5.76; S,
13.18. Found: C, 63.92; H, 3.67; N, 5.83; S, 13.36.
3.9.9. 2-(4-Methoxyphenyl)-5H-benzo(f)chromeno[2,3-b]-
thieno[3,2-e]pyridine (16b). From 13b. Buff crystals,
mp¼270–2728C, yield¼38 mg (57%). IR: 3060, 2936,
2835, 1626, 1607, 1526, 1498, 1443, 1388, 1292, 1253,
3.9.4. 6-(2-Thienyl)-2,3-dihydrofuro[2,3-b]thieno[3,2-e]-
pyridine (14d). From 11d. Orange crystals, mp 237–2388C,
yield¼24 mg (55%). IR: 3116, 3064, 2969, 2925, 1606,
1567, 1534, 1492, 1470, 1420, 1399, 1358, 1247, 1180,
1042, 993, 953, 917, 836, 814, 742, 692. 1H NMR (CDCl3)
d¼3.35 (t, 2H, J¼8.4 Hz), 4.74 (t, 2H, J¼8.4 Hz), 7.07 (t,
1H, J¼4.2 Hz), 7.21 (s, 1H), 7.26 (d, 1H, J¼4 Hz), 7.29 (d,
1H, J¼4.4 Hz), 7.75 (s, 1H). 13C NMR (CDCl3) d¼28.2,
70.4, 117.2, 118.4, 125.0, 125.5, 128.36, 128.38, 128.9,
133.9, 137.9, 158.8, 167.3. Anal. for C13H9NOS2 (259.4)
calcd: C, 60.21; H, 3.50; N, 5.40; S, 24.73. Found: C, 60.10;
H, 3.56; N, 5.84; S, 24.84.
1
1175, 1079, 1033, 813, 743. MS: m/z¼394 (Mþ). H NMR
(CDCl3) d¼3.89 (s, 3H), 4.59 (s, 2H), 6.99 (d, 2H, J¼8.4 Hz),
7.32 (s, 1H), 7.42 (d, 1H, J¼9.2 Hz), 7.50 (t, 1H, J¼7.6 Hz),
7.64 (m, 3H), 7.80 (d, 1H, J¼8.8 Hz), 7.90 (t, 2H, J¼8.8 Hz),
7.99(s, 1H). Anal. for C25H17NO2S (395.5) calcd:C, 75.93;H,
4.33; N, 3.54; S, 8.11. Found: C, 75.63; H, 4.33; N, 3.79; S,
7.88.
3.9.10. 2-Phenyl-5,6-dihydrobisthieno[2,3-b:30,20-e]pyri-
dine (20a). From 19a. Pale brown crystals, mp 220–2218C,
yield¼10 mg (25%). IR: 3045, 2969, 2920, 2845, 1585,
1505, 1477, 1423, 1355, 1260, 1203, 1123, 1071, 1019, 933,
896, 825, 758, 742, 722, 686. MS: m/z¼269 (Mþ). 1H NMR
(CDCl3) d¼3.41 (t, 2H, J¼7.6 Hz), 3.51 (t, 2H, J¼7.6 Hz),
7.36 (s, 1H), 7.37 (t, 1H, J¼7.5 Hz), 7.44 (t, 2H, J¼7.5 Hz),
7.68 (s, 1H), 7.69 (d, 2H, J¼7.5 Hz). 13C NMR (CDCl3)
d¼32.2, 33.7, 116.8, 125.9, 126.6, 128.8, 129.4, 131.0,
131.5, 134.5, 142.5, 160.8, 166.7. Anal. for C15H11NS2
(269.4) calcd: C, 66.88; H, 4.12; N, 5.20; S, 23.80. Found:
C, 66.51; H, 4.22; N, 5.41; S, 23.70.
3.9.5. 2-Phenyl-5H-chromeno[2,3-b]thieno[3,2-e]pyri-
dine (15a). From 12a. Buff crystals, mp 287–2888C,
yield¼23 mg (42%). IR: 3055, 3027, 1589, 1555, 1518,
1488, 1388, 1302, 1284, 1265, 1228, 1188, 1062, 895, 910,
1
750, 687. MS: m/z¼314 (Mþ). H NMR (CDCl3) d¼4.26
(s, 2H), 7.12 (t, 1H, J¼7.2 Hz), 7.21–7.28 (m, 3H), 7.38 (t,
1H, J¼7.2 Hz), 7.39 (s, 1H), 7.45 (t, 2H, J¼7.2 Hz), 7.71 (d,
2H, J¼7.2 Hz), 7.89 (s, 1H). 13C NMR (CDCl3) d¼28.9,
113.4, 116.3, 117.6, 118.7, 120.0, 124.2, 126.7, 128.5,
128.9, 129.0, 129.5, 132.0, 132.8, 134.4, 143.2, 152.1,

8498
Y. A. Ibrahim et al. / Tetrahedron 59 (2003) 8489–8498
Kozhevnikov, V. N.; Nikitina, T. V.; Rusinov, V. L.;
Chupakhin, O. N.; Eremenko, I. L.; Aleksandrov, G. G.
Tetrahedron Lett. 2002, 43, 4923–4925. (f) Rykowski, A.;
Branowska, D.; Kielak, J. Tetrahedron lett. 2000, 41,
3657–3659.
3.9.11. 2-(4-Methoxyphenyl)-5,6-dihydrobisthieno[2,3-b:
30,20-e]pyridine (20b). From 19b. Pale brown crystals, mp
235–2368C, yield¼9 mg (20%). IR: 3005, 2935, 2834,
1604, 1576, 1514, 1483, 1439, 1356, 1297, 1250, 1179,
1110, 1030, 898, 819. MS: m/z¼299 (Mþ). 1H NMR
(CDCl3) d¼3.40 (t, 2H, J¼7.6 Hz), 3.50 (t, 2H, J¼7.6 Hz),
3.87 (s, 3H), 6.96 (d, 2H, J¼8.4 Hz), 7.22 (s, 1H), 7.68 (s,
1H), 7.69 (d, 2H, J¼7.5 Hz). Anal. for C16H13NOS2 (299.4)
calcd: C, 64.18; H, 4.38; N, 4.68; S, 21.42. Found: C, 64.24;
H, 4.50; N, 4.99; S, 21.49.
3. (a) Pabst, G. R.; Pfu¨ller, O. C.; Sauer, J. Tetrahedron 1999, 55,
5047–5066. (b) Pabst, G. R.; Sauer, J. Tetrahedron 1999, 55,
5067–5088. (c) Pabst, G. R.; Sauer, J. Tetrahedron Lett. 1998,
39, 6687–6690. (d) Pabst, G. R.; Schmid, K.; Sauer, J.
Tetrahedron Lett. 1998, 39, 6691–6694. (e) Pabst, G. R.;
Sauer, J. Tetrahedron Lett. 1998, 39, 8817–8820. (f) Pfu¨ller,
O. C.; Sauer, J. Tetrahedron Lett. 1998, 39, 8821–8824.
(g) Pfu¨ller, O. C.; Sauer, J. Tetrahedron Lett. 1998, 39,
8825–8828.
3.9.12. 2-(2-Thienyl)-5,6-dihydrobisthieno[2,3-b:30,20-e]-
pyridine (20c). From 19c. Green crystals, mp 198–1998C,
yield¼11 mg (27%). IR: 3100, 3057, 2934, 1584, 1520,
1478, 1411, 1357, 1338, 1263, 1185, 1122, 1016, 897, 836,
815, 743, 697. MS: m/z¼275 (Mþ). 1H NMR (CDCl3)
d¼3.40 (t, 2H, J¼7.6 Hz), 3.50 (t, 2H, J¼7.6 Hz), 7.07 (dd,
1H, J¼4, 4.8 Hz), 7.20 (s, 1H), 7.30 (d, 1H, J¼4 Hz), 7.31
(d, 1H, J¼4.8 Hz), 7.67 (s, 1H). Anal. for C13H9NS3 (275.4)
calcd: C, 56.69; H, 3.29; N, 5.09; S, 34.93. Found: C, 56.87;
H, 3.49; N, 5.37; S, 34.66.
4. Kubota, F. (Toyobo Co.). Jpn. Pat. 90170823, 1990; Chem.
Abstr. 1991, 114, 15982.
5. (a) Hoffman, J. M., Jr. (Merck and Co.). US Pat. 4808595,
1989; Chem. Abstr. 1989, 111, 115159. (b) Hoffman, J. M., Jr.;
Shepard, K. L. (Merck and Co.). EU Pat. 271273, 1988; Chem.
Abstr. 1988, 109, 230989.
6. Fischer, U.; Schneider, F.; Widmer, U. (Hofman La Roche and
Co.). Eur. Pat. 183998, 1986; Chem. Abstr. 1987, 107, 134200.
7. Holland, D. R.; Wikel, J. H. (Eli Lilly and Co.). US Pat.
4902694, 1990; Chem. Abstr., 1990, 113, 34706.
Acknowledgements
8. Jakobowski, J. A.; Smith, G.; Sall, D. Annual Report in
Medicinal Chemistry; Bristol, J. A., Ed.; Academic: New
York, 1992; Vol. 27, p 99.
The support of the University of Kuwait received through
research grant no. SC02/99 and the facilities of ANALAB
and SAF (grants no. GS01/01, GS02/01, GS03/01) are
gratefully acknowledged. Also, the support of the Graduate
School at the University of Kuwait to Atta Allah
A. Mahmoud is highly appreciated.
9. Saleh, R. M. Indian J. Chem. 1991, 30B, 313–319.
10. Ibrahim, Y. A. Chem. Ind. (London) 1979, 585–586.
11. (a) Ibrahim, Y. A.; Abdel-Hady, S. A. L.; Badawy, M. A.;
Gazala, M. A. H. J. Heterocycl. Chem. 1982, 19, 913–915.
(b) Abdel-Hady, S. A. L.; Badawy, M. A.; Kadry, A. M.;
Ibrahim, Y. A. Sulfur Lett. 1988, 8, 153–162. (c) Ibrahim,
Y. A.; Mansour, A. K.; Ibrahim, M. R. Sulfur Lett. 1999, 22,
41–49.
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