Studies with condensed aminothiophenes: Further investigation on the reactivity of condensed aminothiophenes toward electron poor and acetylenes under microwave heating

Article abstract of DOI:10.1002/jhet.5570430306

The reaction of aminothienopyridazines 8a,b, aminothienocoumarin 13 and aminothienonaphthopyran 14 with enaminones 9, 17 and 20a,b under microwave irradiation affords either a mixture of both condensations C-1 alkylation products 15 and 16 or amino moiety

Full text of DOI:10.1002/jhet.5570430306

May-Jun 2006
559
Studies with Condensed Aminothiophenes: Further Investigation on the
Reactivity of Condensed Aminothiophenes Toward Electron Poor and
Acetylenes under Microwave Heating
Balkis Al-Saleh* and Morsy A. El-Apasery
Department of Chemistry, Faculty of Science, University of Kuwait, P. O. Box 5969, 13060 Safat, Kuwait
Received June 22, 2005
R
R
O
O
S
S
O
O
H
O
O
N
N
NH2
N
R1O
R1O
Me2N
O
N
N
+
N
O
N
O
O
9
Ar
O
8a,b
R2
R
R2
AcOH / HCl
S
O
R2
R2
11a,b
Me
N
R1O
S
O
H
O
O
O
N
O
N
O
HO
NMe2
N
N
O
Ar
12, Ar = 4-H3C-C6H4
21a-d
The reaction of aminothienopyridazines 8a,b, aminothienocoumarin 13 and aminothienonaphthopyran
14 with enaminones 9, 17 and 20a,b under microwave irradiation affords either a mixture of both
condensations C-1 alkylation products 15 and 16 or amino moiety alkylation and diethylamine elimination
or only one of these products depending on nature of substituents on the thiophene ring. On the other hand
reaction of these condensed aminothiophenes with 3-dimethylaminoacrylaldehyde afforded 24 and 25.
J. Heterocyclic Chem., 43, 559 (2006).
the behaviour of 2 towards acetylenes and could show
that the products initially claimed to be thiepins are
really C-1 alkylation products (Scheme I).
Introduction.
The exact pattern of reactivity of condensed amino-
thiophenes toward electron poor olefins and acetylenes
is not completely defined. Initially Elnagdi et. al., [1,2]
reported that despite the fact that thiophenes are highly
inactive as electron rich dienes, condensed amino-
thienopyridazines 1 are highly reactive and do add
electron poor olefins to yield products of 4+2 cyclo-
addition that readily lose hydrogen sulphide to yield
phthalazienes 2 in a novel rout to this ring system.
Subsequently Döpp et.al., [3] reported that the thieno-
coumarin 3 has also added electron poor olefins in a
similar fashion yielding dibenzopyranones 4. The
reaction with dimethylacetylenedicarboxylate with that
thienocoumarin afforded thiepines 5 [5], via a rear-
rangement of the initially formed cycloadducts. Al-
Omran et.al., [5,6] have also claimed thiepine formation
in reactions of several condensed aminothiophenes with
electron poor acetylenes. On the other hand Elnagdi
et.al., [7] have noted that enaminones, ꢀ-nitrostyrene
and phenyl vinyl ketone reacts with 1 and 2 to yield
products of C-1 alkylation 6, 7 [7] that are believed to
be formed via a dipolar cycloaddition mechanism. In
light of this finding Elnagdi et.al.,[8] has reinvestigated
Results and Discussion.
In conjugation of this work we report here results of our
further work in this area. It has been found that 8a,b [9]
reacts with the enaminone 9 recently prepared by Al-
Mousawi et.al., [10] to yield products of condensation via
dimethylamine elimination for which structures 10 or
11a,b seemed possible. Structure 11a,b was established
for this product based on the 1H NMR and IR spectral data
that revealed involvement of aminofunction in the
reaction. Further confirmation of this structure assignment
was obtained via successful conversion of 11b into the
thiophene 12 through hydrolysis of the alkylated amino
moiety (Scheme II).
Typical for primary enaminone compound 11 existed
solely in Z form as this form is fixed by hydrogen bond
and this preferred over sterically and stereoelectronically
fixed E form. The Z structure was readily concluded
based on considering J values for olefinic protons.
1
Assignment of H and 13C NMR signal was made based
on HMQC - 2D spectroscopy.

560
B. Al-Saleh and M. A. El-Apasery
Vol 43
Moreover these were also found very similar to
assignment of a simulated spectroscopy using ACD
LABS. It is of value to report here that enaminone 9 could
be prepared in our laboratory via reacting of
dimethylformamide dimethylacetal (DMFDMA) with
phthalimidoacetone in a microwave oven at 840W for 60
seconds. Yield of this synthesis is 74 % much higher than
that obtained by literature procedure [10].
The reaction of the thienocoumarin 13 and the
benzothienocoumarin 14 with enaminone 9 has afforded
only C-1 alkylation products 15 and 16 respectively
1
(Scheme III), as indicated from H NMR that revealed
amino signal at ꢀ 8.68 ppm and trans olefinic protons at ~
ꢀ 6.3 and 8.3 (J = 15 Hz). This find parallel to reported C-
1 alkylation of thienocoumarins and thienonaphtho-
benzopyran on reaction with enaminones [7]. Further
confirmation of structure was obtained via HMQC - 2D
spectroscopy that enabled assignment of 13C NMR
spectra.
The reaction of enaminone 17 [11], prepared here via
microwave heating of a mixture of benzylideneacetone
with DMFDMA, with 8a,b and 14 has afforded 18a,b and
19 (Scheme IV). The cis-trans diene structures 18a,b and
In contrast to this compound 13 reacted with 3-
dimethylaminoacrylaldehyde to afford products of cyclo-
addition and dimethylamine elimination. This was
assigned structure 24 and was also formed from reaction
of 13 with acrolein. Similarly, compound 14 reacted with
3-dimethylaminoacrylaldehyde or acrolein to yield 25.
Possible formation of C-1 alkylation products could be
readily eliminated based on 1H NMR that revealed
absence of the two olefinic proton doublet (Scheme VI).
It can thus be concluded that outcome of reaction of
aminothienocoumarins with electron poor olefins and
acetylenes is dependent on nature of reagents used.
1
19 were assigned based on H NMR that revealed cis
olefinic proton doublet of doublet as well as a trans
olefinic doublet. Assignment of 13C NMR was made after
inspection of HMQC – 2D spectra of the reaction product.
Compounds 8a,b, 13 and 14 reacted with the
enaminones 20a,b [12] to yield the N-alkylated products
1
21a-d, 22a,b and 23a,b as indicated from H NMR that
showed low field NH signal at ꢀ ca.13 ppm (Scheme V).

May-Jun 2006
Further Investigation on the Reactivity of Condensed Aminothiophenes
561
Aminofunction, C-1 as well as the diene system are all
possible sites of attack. However, in no case thiepins has
resulted from such additions as has been claimed earlier
[13].
Scheme VI
O
HS
H
NH2
O
O
O
H
O
H
Me2N
24
13,14
13,14
NH2
O
O
O
H
SH
25
a microwave oven DAEWOO, edition II (KOR-8667).
Compounds 13 and 14 were prepared following published
procedure [5].
General Procedure for the Preparation of Compounds 11a,b,
(15) and (16).
A mixture of each of 8a,b, 13 and 14 (10 mmole) and
compound 9 (2.58 g, 10 mmoles) in the presence of few drops of
acetic acid was irradiated in a microwave oven at 690W for 120
sec. The solid products obtained were crystallized from
ethanol/dioxane (1:3).
Ethyl 5-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-oxobut-1-enyl-
amino]-4-oxo-3-phenyl-3,4-dihydrothieno[3,4-d]pyridazine-1-
carboxylate (11a).
Compound 11a was obtained as buff crystals 1.76 g (33%),
mp. 269-271º, ir (KBr): 3420 (NH), 1778, 1720, 1661 (CO)
cm-1; ms: m/z = 528 (M+, 100), 486 (78), 326 (38), 277 (15), 160
1
(41), 104 (39), 77 (41); H nmr (deuteriochloroform): ꢀ 1.41 (t,
3H, J = 8 Hz, CH3), 4.43 (q, 2H, J = 8 Hz, CH2), 4.58 (s, 2H,
CH2), 5.58 (d, 1H, J = 8 Hz, olefinic-H), 7.02 (d,d, 1H, J = 8 Hz,
olefinic-H), 7.28 (t, 1H, J = 7.2 Hz, phenyl-H), 7.39 (t, 2H, J =
7.6 Hz, phenyl-H), 7.55 (d, 2H, J = 8 Hz, phenyl-H), 7.70 (s, 1H,
thiophene-H), 7.72-7.75 (m, 2H, arom-H), 7.85-7.87 (m, 2H,
arom-H), 12.88 (d, 1H, J = 12 Hz, NH), 13C nmr (deuterio-
chloroform): ꢀ 192.2, 168.3, 163.4, 158.4 (CO), 153.6 (C-5),
142.1 (C-1), 140.8 (C-9), 134.7 (C-14), 133.4 (C-21), 132.8 (C-
19a), 129.4 (C-7), 128.8 (C-7a), 128.4 (C-11), 126.7 (C-12),
126.2 (C-10), 124.1 (C-20), 110.5 (C-4a), 98.3 (C-15), 62.7
(ester CH2), 46.4 (C-17), 14.8 (ester CH3).
Anal. Calcd. For C27H20N4O6S (528.54): C, 61.36; H, 3.81; N,
10.60; S, 6.07. Found C, 61.25; H, 3.92; N, 10.81; S, 5.88.
EXPERIMENTAL
Methyl 5-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-oxobut-1-
enylamino]-7-methyl-4-oxo-3-p-tolyl-3,4-dihydrothieno[3,4-d]-
pyridazine-1-carboxylate (11b).
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, 400MHz super-conducting NMR spectrometer
in deuteriochloroform or dimethylsulfoxide-d6 as solvent and
TMS as internal standard; chemical shifts are reported in ꢀ units
(ppm). Mass spectra were measured on a VG Autospec-Q (high
resolution, high performance, tri-sector GC/MS/MS).
Compound 11b was obtained as buff crystals 2.67 g (49%),
mp. 248-250º, ir (KBr): 3460 (NH), 1767, 1716, 1656 (CO)
cm-1; ms: m/z = 542 (M+, 100), 500 (40), 371 (25), 340 (28), 291
(14), 160 (28), 104 (22), 91 (18), 77 (10); 1H nmr
(deuteriochloroform ): ꢀ 2.36 (s, 3H, CH3), 2.60 (s, 3H, CH3),
3.98 (s, 3H, OCH3), 4.58 (s, 2H, CH2), 5.52 (d, 1H, J = 8 Hz,
olefinic-H), 6.93 (d,d, 1H, J = 8 Hz, olefinic-H), 7.17 (d, 2H, J =
8.3 Hz, p-tolyl-H), 7.37 (d, 2H, J = 8.3 Hz, p-tolyl-H), 7.72-7.74
Microanalyses were performed on
a LECO CHNS-932
Elemental Analyzer. Microwave experiments were conducted in

562
B. Al-Saleh and M. A. El-Apasery
Vol 43
(m, 2H, arom-H), 7.85-7.87 (m, 2H, arom-H), 12.88 (d, 1H, J =
12 Hz, NH), 13C nmr (deuteriochloroform ): 200.5, 197.2, 164.5,
158.0 (CO), 148.0, 146.5, 138.5, 137.9, 135.9, 130.5, 130.2,
129.9, 126.3, 126.2, 125.5, 124.1, 116.4, 111.0, 53.8 (OCH3),
51.2 (CH2), 29.9, 15.8 (2CH3).
General Procedure for the Preparation of Compounds 18a,b and
19.
A mixture of each of 8a,b and 14 (10 mmol) and compound
17 (2.01 g, 10 mmol) in acetic acid / dioxane (6 ml, 2:1 by
volume) was irradiated in a microwave oven at 560W for 90 sec.
The solid products so formed were crystallized from dioxane /
ethanol.
Anal. Calcd. For C28H22N4O6S (542.56): C, 61.98; H, 4.09; N,
10.33; S, 5.91. Found C, 61.81; H, 4.30; N, 10.31; S, 5.79.
2-[4-(3-Amino-4-oxo-4H-5-oxa-2-thiacyclopenta[a]naphthalen-
1-yl)-2-oxo-3-butenyl] isoindole-1,3-dione (15).
Ethyl 4-oxo-5-(3-oxo-5-phenylpenta-1,4-dienylamino)-3-
phenyl-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate (18a).
Compound 15 was obtained as orange crystals (2.79 g, 65%),
mp.> 300°, ir (KBr): 3438 and 3328 (NH2), 1770, 1713, 1637
(CO) cm-1; ms: m/z = 430 (M+,22), 270 (100), 241 (18), 160
(10), 115 (12), 77 (15); 1H nmr (dimethylsulfoxide-d6): ꢀ 4.88 (s,
2H, CH2), 6.39 (d, 1H, J = 15 Hz, trans olefinic-H), 7.33-7.38
(m, 2H, coumarinyl-H), 7.51 (t, 1H, J = 7.6 coumarinyl-H),
7.89-7.96 (m, 4H, arom-H), 8.10 (d, 1H, J = 8.0 Hz, coumarinyl-
H), 8.33 (d, 1H, J = 15 Hz, trans olefinic-H), 8.68 (br s, 2H,
NH2, D2O exchangeable), 13C nmr (dimethylsulfoxide-d6): ꢀ
191.6, 168.6, 159.2 (CO), 167.6 (C-3), 153.0 (C-5a), 136.3 (C-
1), 136.1 (C-10), 135.8 (C-17), 132.5 (C-9b), 131.9 (C-15a),
127.3 (C-9), 126.0 (C-8), 124.3 (C-16), 119.4 (C-7), 118.7 (C-
6), 118.6 (C-9a), 113.0 (C-11), 101.9 (C-3a), 46.6 (CH2).
Compound 18a was obtained as buff crystals 2.80 g (59%),
mp. 222-224º, ir (KBr): 3450 (NH), 1719, 1663 (CO) cm-1; ms:
m/z = 471 (M+,22), 397 (100), 315 (32), 172 (22), 131 (50), 103
(40), 77 (30); 1H nmr (deuteriochloroform): ꢀ 1.43 (t, 3H, J = 7.2
Hz, CH3), 4.45 (q, 2H, J = 7.2 Hz, CH2), 5.74 (d, 1H, J = 8 Hz,
cis olefinic-H), 6.80 (d, 1H, J = 16 Hz, trans olefinic-H), 7.11
(d,d, 1H, J = 8 Hz, cis olefinic-H), 7.38-7.40 (m, 5H, arom-H),
7.45-7.57 (m, 3H, arom-H), 7.68 (d, 2H, J = 8 Hz, arom-H), 7.70
(s, 1H, thiophene-H), 7.73 (d, 1H, J = 16 Hz, trans olefinic-H),
13.73 (d, 1H, J = 12 Hz, NH), 13C nmr (deuteriochloroform ): ꢀ
= 190.0, 164.5, 158.5, (CO), 154.0 (C-5), 142.5 (C-18), 141.8
(C-1), 136.6 (C-9), 133.4 (C-14), 130.8 (C-19), 129.5 (C-7),
129.3 (C-22), 128.9 (C-20), 128.7 (C-21), 128.6 (C-7a), 128.3
(C-11), 127.1 (C-12), 126.7 (C-17), 126.5 (C-10), 110.0 (C-15),
102.9 (C-4a), 62.6 (ester CH2), 14.8 (ester CH3).
Anal. Calcd. For C23H14N2O5S (430.43): C, 64.18; H, 3.28; N,
6.51; S, 7.45. Found C, 63.94; H, 3.41; N, 6.85; S, 7.22.
2-[4-(17-Amino-12-oxo-12H-11-oxa-16-thiacyclopenta[a]phen-
anthren-15-yl)-2-oxo-3-butenyl]isoindole-1,3-dione (16).
Anal. Calcd. For C26H21N3O4S (471.53): C, 66.23; H, 4.49; N,
8.91; S, 6.80. Found C, 66.25; H, 4.57; N, 9.07; S, 6.61.
Compound 16 was obtained as orange crystals (2.78 g, 58%),
mp. > 300°, ir (KBr): 3427 and 3320 (NH2), 1772, 1716, 1637
(CO) cm-1; ms: m/z = 480 (M+, 25), 417 (26), 320 (100), 292
(18), 267 (21), 160 (20), 83 (22); 1H nmr (dimethylsulfoxide-d6):
ꢀ 4.89 (s, 2H, CH2), 6.40 (d, 1H, J = 15 Hz, trans olefinic-H),
7.68-7.70 (m, 2H, arom-H), 7.84–7.99 (m, 6H, arom-H), 8.10 (d,
1H, J = 8.8 Hz, arom-H), 8.31 (d, 1H, J = 9 Hz, arom-H), 8.39
(d, 1H, J = 15 Hz, trans olefinic-H), 7.75 (br s, 2H, NH2, D2O
exchangeable),. 13C nmr (dimethylsulfoxide-d6): ꢀ = 191.5,
168.6, 158.9 (CO), 148.9, 140.0, 136.3, 135.8, 134.6, 132.6,
129.4, 128.8, 128.5, 125.6, 124.3, 124.1, 123.2, 123.0, 119.0,
114.1, 112.8, 111.6, 46.7 (CH2).
Methyl 7-methyl-4-oxo-5-(3-oxo-5-phenylpenta-1,4-dienyl-
amino)-3-p-tolyl-3,4-dihydrothieno[3,4-d]pyridazine-1-carbox-
ylate (18b).
Compound 18b was obtained as buff crystals 2.58 g (53%),
mp.214-216 ir (KBr): 3440 (NH), 1736, 1656 (CO) cm-1; ms:
m/z = 485 (M+,42), 426 (78), 329 (100), 270 (42), 131 (80), 91
1
(72); H nmr (deuteriochloroform): ꢀ 2.40 (s, 3H, CH3), 2.58 (s,
3H, CH3), 3.99 (s, 3H, OCH3), 5.68 (d, 1H, J = 8 Hz, cis
olefinic-H), 6.77 (d, 1H, J = 16 Hz, trans olefinic-H), 7.01 (d,d,
1H, J = 8 Hz, cis olefinic-H), 7.23 (d, 2H, J = 8.2 Hz, p-tolyl-H),
7.37-7.39 (m, 3H, arom-H), 7.48 (d, 2H, J = 8.2 Hz, p-tolyl-H),
7.55-7.62 (m, 2H, arom-H), 7.70 (d, 1H, J = 16 Hz, trans
olefinic-H), 13.69 (d, 1H, J = 12 Hz, NH), 13C nmr (deuterio-
chloroform): ꢀ 189.7, 164.8, 158.4 (CO), 150.1 (C-5), 142.6 (C-
18), 142.2 (C-7), 138.3 (C-1), 135.7 (C-9), 132.8 (C-12), 130.5
(C-14), 129.8 (C-19), 129.5 (C-11), 128.9 (C-22), 128.7 (C-20),
127.2 (C-21), 126.5 (C-17), 126.1 (C-10), 123.8 (C-7a), 112.3
(C-15), 102.5 (C-4a), 53.6 (ester CH3), 21.7 (p-tolyl CH3), 15.3
(thieno CH3).
Anal. Calcd. For C27H16N2O5S (480.49): C, 67.49; H, 3.36; N,
5.83; S, 6.67. Found C, 67.16; H, 3.63; N, 5.98; S, 6.37.
7-Methyl-4,5-dioxo-3-p-tolyl-3,4,5,7-tetrahydrothieno[3,4-d]-
pyridazine-1-carboxylic acid (12).
A solution of compound 11b (5.42g, 10 mmol) in acetic acid /
hydrochloric acid (10 mL, 3:1 by volume) was refluxed for 3
hrs, then allowed to cool to room temperature. The solid product
so formed was collected by filtration and crystallized from
ethanol. Compound 12 was obtained as yellow crystals 2.82 g
(89%), mp. 232º, ir (KBr): 3445 (OH), 1749, 1701, 1642 (CO)
cm-1; ms: m/z = 316 (M+, 100), 372 (30), 243 (10), 165 (10), 107
Anal. Calcd. For C27H23N3O4S (485.55): C, 66.79; H, 4.77; N,
8.65; S, 6.60. Found C, 66.47; H, 4.80; N, 8.84; S, 6.42.
17-(3-Oxo-5-phenylpenta-1,4-dienylamino)-11-oxa-16-thiacycl-
openta[a]phenanthren-12-one (19).
1
(88), 91 (31), 77 (15); H nmr (dimethylsulfoxide-d6): ꢀ = 1.72
(s, 3H, CH3), 2.39 (s, 3H, CH3), 3.45 (br, 1H, OH, D2O
exchangeable), 5.46 (q, 1H, J = 6.8 Hz, thiophenone-H), 7.34 (d,
2H, J = 8.3 Hz, p-tolyl-H), 7.43 (d, 2H, J = 8.3 Hz, p-tolyl-H),
13C nmr (dimethylsulfoxide-d6): ꢀ = 192.3, 164.4, 161.5 (CO),
155.8, 139.7, 139.1, 134.6, 130.3, 129.9, 126.8, 44.7 (thio-
phenone-C), 22.4, 21.7 (2CH3).
Compound 19 was obtained as buff crystals 3.36 g (79%),
mp. 290-292°,. ir (KBr): 3298 (NH), 1715, 1655 (CO) cm-1; ms:
m/z = 423 (M+,84), 345 (58), 267 (64), 170 (38), 130 (76), 77
1
(42); H nmr (deuteriochloroform): ꢀ 5.81 (d, 1H, J = 8 Hz, cis
olefinic-H), 6.85 (d, 1H, J = 16 Hz, trans olefinic-H), 6.96 (s,
1H, thiophene-H), 7.12 (d,d, 1H, J = 8 Hz, cis olefinic-H), 7.41-
7.43 (m, 3H, arom-H), 7.54-7.65 (m, 4H, arom-H), 7.70-7.82
(m, 3H, arom -H), 7.82 (d, 1H, J = 16 Hz, trans olefinic-H), 8.56
Anal. Calcd. For C15H12N2O4S (316.33): C, 56.95; H, 3.82; N,
8.86; S, 10.14. Found C, 56.68; H, 3.99; N, 8.93; S, 10.07.

May-Jun 2006
Further Investigation on the Reactivity of Condensed Aminothiophenes
563
(d, 1H, J = 8.1 Hz, arom-H), 13.59 (d, 1H, J = 12 Hz, NH), 13
C
2H, CH2), 2.40 (s, 3H, CH3), 2.56 (t, 4H, J = 6.4 Hz, 2CH2), 2.63
(s, 3H, CH3), 3.99 (s, 3H, OCH3), 7.24 (d, 2H, J = 8.3 Hz, p-
tolyl-H), 7.47 (d, 2H, J = 8.3 Hz, p-tolyl-H), 8.22 (d, 1H, J =
13.2 Hz, ethylenic-H), 14.39 (d, 1H, J = 13.2 Hz, NH), 13C nmr
(deuteriochloroform): ꢀ 200.7, 197.6, 164.5, 158.0 (CO), 148.7,
146.4, 138.5, 135.9, 130.2, 129.6, 126.3, 125.5, 124.2, 116.5,
112.3, 53.8 (OCH3), 39.4, 38.4 (cyclohexane 2CH2), 21.7 (CH3),
19.8 (cyclohexane CH2), 15.7 (CH3).
nmr (deuteriochloroform ): ꢀ 190.2, 157.4 (CO), 142.7, 141.7,
135.6, 134.7, 134.5, 130.7, 130.3, 129.5, 129.4, 128.9, 128.7,
128.2, 127.9, 127.6, 127.2, 125.0, 124.5, 123.1, 120.5, 112.7,
10.3.2, 102.0.
Anal. Calcd. For C26H17NO3S (423.48): C, 73.74; H, 4.05; N,
3.31; S, 7.57. Found C, 73.35; H, 4.17; N, 3.56; S, 7.36.
General Procedure for the Preparation of Compounds 21- 23.
Anal. Calcd. For C23H21N3O5S (451.49): C, 61.18; H, 4.69; N,
9.31; S, 7.10. Found C, 61.23; H, 4.97; N, 9.47; S, 7.00.
A mixture of each of 8a,b, 13 and 14 (10 mmoles) and
compound 20a,b (10 mmoles) in acetic acid / dimethylform-
amide (4 ml, 3:1 by volume) was irradiated in a microwave oven
at 840W for 60 sec then left to cool to room temperature. The
solid products obtained were crystallized from dimethyl-
formamide.
Methyl 5-[(4,4-dimethyl-2,6-dioxocyclohexylidenemethyl)-amino]-
7-methyl-4-oxo-3-p-tolyl-3,4-dihydrothieno[3,4-d]pyrid-azine-
1-carboxylate (21d).
Compound 21d was obtained as yellow crystals 2.16 g (45%),
mp. 242º, ir (KBr): 3431 (NH), 1726, 1666 (CO) cm-1; ms: m/z
= 479 (M+,100), 420 (24), 329 (30), 254 (38), 105 (52), 91 (25);
1H nmr (deuteriochloroform): ꢀ 1.08 (s, 6H, 2CH3), 2.40 (s, 3H,
CH3), 2.45 (s, 2H, CH2), 2.49 (s, 2H, CH2), 2.66 (s, 3H, CH3),
3.99 (s, 3H, OCH3), 7.24 (d, 2H, J = 8.3 Hz, p-tolyl-H), 7.47 (d,
2H, J = 8.3 Hz, p-tolyl-H), 8.18 (d, 1H, J = 13.3 Hz, ethylenic-
H), 14.36 (d, 1H, J = 13.1 Hz, NH), 13C nmr (deuteriochloro-
form): ꢀ 200.5, 197.2, 164.5, 159.1 (CO), 148.0, 146.5, 138.6,
137.9, 135.9, 130.5, 129.9, 126.2, 124.1, 116.4, 111.2, 53.8
(OCH3), 52.2 (cyclohexane carbon),. 32.5, 31.6 (cyclohexane
2CH2), 29.8, 21.7, 15.8 (3CH3).
Ethyl 5-[(2,6-dioxocyclohexylidenemethyl)amino]-4-oxo-3-
phenyl-3,4-dihydrothieno[3,4-d]pyridazine -1-carboxylate (21a).
Compound 21a was obtained as buff crystals 2.01 g (46%),
mp. 252-254 ir (KBr): 3405 (NH), 1715, 1668 (CO) cm-1; ms:
m/z = 437 (M+,78), 364 (35), 315 (100), 226 (38), 91 (62), 77
1
(58); H nmr (deuteriochloroform): ꢀ 1.36 (t, 3H, J = 7.2 Hz,
CH3), 2.01-2.08 (m, 2H, CH2), 2.60 (t, 4H, J = 6.3 Hz, 2CH2),
4.50 (q, 2H, J = 7.1 Hz, CH2), 7.37 (t, 1H, J = 7.4 phenyl-H),
7.47 (t, 2H, J = 7.9 phenyl-H), 7.64 (d, 2H, J = 8.2 phenyl-H),
8.02 (s, 1H, thiophene-H), 8.31 (d, 1H, J = 13.2 Hz, ethylenic-
H), 14.39 (d, 1H, J = 13.2 Hz, NH), 13C nmr (deuterio-
chloroform): ꢀ 201.0, 197.5, 163.2, 158.0 (CO), 150.6 (C-5),
148.7 (C-14), 140.6 (C-1), 133.4 (C-9), 129.3 (C-7), 128.8 (C-
11), 128.6 (C-12), 126.6 (C-7a), 115.5 (C-10), 115.2 (C-4a),
112.5 (C-15), 62.9 (ester CH2), 38.6 (C-19), 38.4 (C-17), 19.7
(C-18), 14.8 (ester CH3).
Anal. Calcd. For C25H25N3O5S (479.55): C, 62.61; H, 5.25; N,
8.76; S, 6.69. Found C, 62.55; H, 5.61; N, 8.93; S, 6.64.
2-[(4-Oxo-4H-5-oxa-2-thiacyclopenta[a]naphthalen-3-ylamino)-
methylene]cyclohexane-1,3-dione (22a).
Compound 22a was obtained as buff crystals 1.64 g (48%),
mp. 242°, ir (KBr): 3435 (NH), 1707, 1668 (CO) cm-1; ms: m/z
= 339 (M+,84), 254 (26), 217 (100), 202 (28), 89 (22), 63 (28);
1H nmr (dimethylsulfoxide-d6): ꢀ 1.94-1.98 (m, 2H, CH2), 2.74
(t, 4H, J = 6.8 Hz, 2CH2), 7.30-7.37 (m, 2H, coumarinyl-H),
7.43-7.48 (m, 1H, coumarinyl-H), 7.89 (s, 1H, thiophene-H),
8.05 (d, 1H, J = 7.7 Hz, coumarinyl-H), 8.12 (d, 1H, J = 13 Hz,
ethylenic-H), 13.70 (d, 1H, J = 13.1 Hz, NH), 13C nmr
(dimethylsulfoxide-d6): ꢀ 201.3, 197.0, 163.3 (CO), 158.6,
154.4, 151.2, 148.8, 133.4, 130.1, 126.0, 125.1, 119.2, 117.7,
109.9, 98.7, 39.8, 38.4, 19.6 (cyclohexane 3CH2).
Anal. Calcd. For C22H19N3O5S (437.47): C, 60.40; H, 4.38; N,
9.61; S, 7.33. Found C, 60.42; H, 4.56; N, 9.72; S, 7.08.
Ethyl 5-[(4,4-dimethyl-2,6-dioxocyclohexylidenemethyl)amino]-
4-oxo-3-phenyl-3,4-dihydrothieno[3,4-d]pyridazine-1-carbox-
ylate (21b).
Compound 21b was obtained as buff crystals 2.96 g (63%),
mp. 260-262º, ir (KBr): 3390 (NH), 1713, 1669 (CO) cm-1; ms:
m/z = 465 (M+,60), 392 (56), 315 (100), 299 (42), 226 (58), 91
(78), 77 (60); 1H nmr (deuteriochloroform): ꢀ 1.09 (s, 6H,
2CH3), 1.47 (t, 3H, J = 7.2 Hz, CH3), 2.52 (s, 2H, CH2), 2.91 (s,
2H, CH2), 4.46 (q, 2H, J = 7.2 Hz, CH2), 7.37-(t, 1H, J = 7.4
phenyl-H), 7.46 (t, 2H, J = 7.8 phenyl-H), 7.61 (d, 2H, J = 8.2
phenyl-H), 8.00 (s, 1H, thiophene-H), 8.29 (d, 1H, J = 13.2 Hz,
ethylenic-H), 14.38 (d, 1H, J = 13.2 Hz, NH), 13C nmr
(deuteriochloroform): ꢀ = 200.6, 197.1, 163.2, 158.1 (CO),
150.7, 148.0, 140.6, 133.5, 129.6, 129.3, 128.6, 126.2, 115.4,
115.1, 111.2, 62.9 (ester CH2), 52.2 (cyclohexane carbon), 32.5,
32.0 (cyclohexane 2CH2), 29.2 (CH3), 14.7 (ester CH3).
Anal. Calcd. For C18H13NO4S (339.37): C, 63.71; H, 3.86; N,
4.13; S, 9.45. Found C, 63.29; H, 3.90; N, 4.31; S, 9.43.
5,5-Dimethyl-2-[(4-oxo-4H-5-oxa-2-thiacyclopenta[a]naphthal-
en-3-ylamino)methylene]cyclohexane-1,3-dione (22b).
Compound 22b was obtained as buff crystals 2.64 g (72%),
mp. 274°, ir (KBr): 3480 (NH), 1709, 1678 (CO) cm-1; ms: m/z
367 (M+,100), 352 (38), 241 (22), 217 (80), 174 (26), 145 (22),
1
83 (20); H nmr (deuteriochloroform ): ꢀ 1.10 (s, 6H, 2CH3),
Anal. Calcd. For C24H23N3O5S (465.52): C, 61.92; H, 4.98; N,
9.03; S, 6.89. Found C, 61.71; H, 5.22; N, 8.79; S, 6.62.
2.50 (s, 2H, CH2), 2.56 (s, 2H, CH2), 7.20 (s, 1H, thiophene-H),
7.29-7.36 (m, 2H, coumarinyl-H), 7.44 (t, 1H, J = 8.4 Hz,
coumarinyl-H), 7.77 (d, 1H, J = 8.8 Hz, coumarinyl-H), 8.29 (d,
1H, J = 12.8 Hz, ethylenic-H), 14.12 (d, 1H, J = 12 Hz, NH),
13C nmr (deuteriochloroform ): ꢀ 200.4, 196.9, 158.4 (CO),
154.0, 151.2, 147.8, 147.6, 134.2, 130.5, 125.2, 123.7, 118.2,
117.0, 111.3, 105.2, 52.2 (cyclohexane carbon), 32.3, 31.4
(cyclohexane 2CH2), 29.7 (CH3).
Methyl 5-[(2,6-dioxocyclohexylidenemethyl)amino]-7-methyl-
4-oxo-3-p-tolyl-3,4-dihydrothieno[3,4-d]pyridazine-1-carbox-
ylate (21c).
Compound 21c was obtained as yellow crystals 2.40 g (53%),
mp. 254º, ir (KBr): 3430 (NH), 1729, 1663 (CO) cm-1; ms: m/z
= 451 (M+,95), 392 (25), 329 (78), 270 (38), 254 (42), 105 (65),
Anal. Calcd. For C20H17NO4S (367.42): C, 65.38; H, 4.66; N,
3.81; S, 8.73. Found C, 65.17; H, 4.64; N, 3.94; S, 8.52.
1
91 (42), 60 (22); H nmr (deuteriochloroform): ꢀ 2.02-2.07 (m,

564
B. Al-Saleh and M. A. El-Apasery
Vol 43
2-[(12-Oxo-12H-11-oxa-16-thiacyclopenta[a]phenanthren-17-
ylamino)methylene]cyclohexane-1,3-dione (23a).
(CO), 159.8, 150.9, 150.6, 130.8, 130.5, 126.3, 125.8, 125.0,
118.0, 109.7, 109.4, 106.5.
Anal. Calcd. For C14H9NO3S (271.29): C, 61.98; H, 3.34; N,
5.16; S, 11.82. Found C, 61.69; H, 3.50; N, 5.32; S, 11.73.
Compound 23a was obtained as buff crystals 2.42 g (62%),
mp. 298°, ir (KBr): 3390 (NH), 1703, 1668 (CO) cm-1; ms: m/z
389 (M+,60), 267 (100), 252 (20), 195 (22), 139 (22), 58 (32);1H
nmr (deuteriochloroform): ꢀ 2.09-2.15 (m, 2H, CH2), 2.62 (t,
4H, J = 6.4 Hz, 2CH2), 7.23 (s, 1H, thiophene-H), 7.59-7.65 (m,
2H, arom-H), 7.74 (d, 1H, J = 6.8 Hz, arom-H), 7.86 (d, 1H, J =
6.4 Hz, arom-H), 8.11 (d, 1H, J = 6.8 Hz, arom-H), 8.33 (d, 1H,
J = 12.8 Hz, ethylenic-H), 8.53 (d, 1H, J = 8 Hz, arom-H), 14.20
(d, 1H, J = 12 Hz, NH), 13C nmr (deuteriochloroform): ꢀ 201.2,
195.6, 168.7 (CO), 148.7, 146.0, 144.8, 141.4, 139.0, 134.4,
128.3, 128.2, 127.8, 125.5, 123.0, 120.3, 114.2, 112.9, 110.0,
106.8, 38.9, 38.5, 19.7 (cyclohexane 3CH2).
7-Amino-10-mercapto-6-oxo-6H-dibenzo[c,h]chromene-8-carb-
aldehyde (25).
Compound 25 was obtained as brown crystals (2.10 g, 65%),
mp. > 300°, ir (KBr): 3443 and 3307 (NH2), 1702 (br) (CO)
cm-1; ms: m/z 321 (M+,28), 267 (100), 223 (28), 105 (58), 91
1
(32), 60 (28); H nmr (dimethylsulfoxide-d6): ꢀ 7.61-7.84 (m,
3H, arom-H), 7.95 (s, 1H, SH, D2O exchangeable), 7.98 (d, 1H,
J = 8.6 Hz, arom-H), 8.12 (d, 1H, J = 7.7 Hz, arom-H), 8.23 (br ,
2H, NH2, D2O exchangeable), 8.30 (d, 1H, J = 7.7 Hz, arom-H),
8.46 (d, 1H, J = 8 Hz, arom-H), 10.98 (s, 1H, CHO).
Anal. Calcd. For C18H11NO3S (321.35): C, 67.28; H, 3.45; N,
4.36; S, 9.98 Found C, 67.00; H, 3.54; N, 4.51; S, 9.65.
Anal. Calcd. For C22H15NO4S (389.42): C, 67.85; H, 3.88; N,
3.60; S, 8.23. Found C, 67.62; H, 4.00; N, 3.82; S, 8.15.
5,5-Dimethyl-2-[(12-oxo-12H-11-oxa-16-thiacyclopenta[a]-
phenanthren-17-ylamino) methylene]cyclohexane-1,3-dione (23b).
Acknowledgement.
The authors are grateful to University of Kuwait, Research
Administration for financial support through project SC 02/02.
Analytical facilities provided by SAF are greatly appreciated.
Compound 23b was obtained as buff crystals 2.56 g (61%),
mp.> 300°, ir (KBr): 3385 (NH), 1711, 1673 (CO) cm-1; ms: m/z
417 (M+,44), 389 (100), 267 (60), 195 (28), 139 (24), 73 (40); 1H
nmr (deuteriochloroform ): ꢀ 1.05 (s, 6H, 2CH3), 2.43 (s, 2H,
CH2), 2.54 (s, 2H, CH2), 7.18 (s, 1H, thiophene-H), 7.54-7.64
(m, 2H, arom-H), 7.69 (d, 1H, J = 8 Hz, arom-H), 7.82 (d, 1H, J
= 8 Hz, arom-H), 8.03 (d, 1H, J = 8 Hz, arom-H), 8.24 (d, 1H, J
= 12.8 Hz, ethylenic-H), 8.49 (d, 1H, J = 8 Hz, arom-H), 14.10
(d, 1H, J = 12 Hz, NH), 13C nmr (deuteriochloroform ): ꢀ
200.6, 197.2, 165.2 (CO), 158.9, 155.2, 148.0, 135.0, 134.7,
128.3, 128.2, 127.8, 125.5, 124.4, 123.0, 120.3, 112.3, 111.2,
110.3, 106.3, 52.4 (cyclohexane carbon), 31.6, 30.2 (cyclo-
hexane 2CH2), 29.1 (CH3).
REFERENCES
[1] B. Al-Saleh, M. M. Abdelkhalik, M. A. El-Apasery and M.
H. Elnagdi, J. Chem. Res., 23 (2005).
[2] A. Al-Naggar, M. M. Abdelkhalik and M. H. Elnagdi,
J. Chem. Res. (S), 648 Ibid. (M). 2801 (1999).
[3] E. Nyiondi-Bonguen, E. Sopbue Fondjo, T. Fomum
and D. Döpp, J. Chem. Soc. Perkin Trans. 1, 2191 (1994).
[4] M. M. Abdelkhalik, A. M. Negm, A. I. Elkhouly and M. H.
Elnagdi, Heteroatom Chemistry, 15, 502 (2004).
Anal. Calcd. For C24H19NO4S (417.48): C, 69.05; H, 4.59; N,
3.36; S, 7.68. Found C, 68.85; H, 4.74; N, 3.52; S, 7.64.
[5] F. Al-Omran, M. M. Abdelkhalik, H. Al-Awadi and M.
H. Elnagdi, Tetrahedron, 52, 11915 (1996).
[6] H. Al-Awadi, F. Al-Omran, M. H. Elnagdi, L.
Infantes, C. Foces-Foces, N. Iagerovic, J. Elguero, Tetrahedron,
51, 12745 (1995).
[7] A. Al-Etaibi, N. Al-Awadi, F. Al-Omran, M. M.
Abdelkhalik and M. H. Elnagdi, J. Chem. Res. (S), 4 Ibid. (M).
151 (1999).
[8] F. A. Abu-Shanab, B. Wakefield, F. Al-Omran, M. M.
Abdelkhalik and M. H. Elnagdi, J. Chem. Res. (S), 488 Ibid. (M).
2924 (1995).
General Procedure for the Preparation of Compounds 24 and 25.
A solution of each of 13 and 14 (10 mmoles) and 3-
dimethylaminoacrylaldehyde or acrylaldehyde (10 mmoles) in
dimethylformamide (10 ml) was refluxed for 4 hrs. The solvent
was removed and the residue cooled to deposit a solid, which
was crystallized from dioxane.
7-Amino-10-mercapto-6-oxo-6H-benzo[c]chromene-8-carbalde-
hyde (24).
[9] M. H. Elnagdi, A.M. Negm, A.W. Erian, Liebigs Ann. Chem.,
1255 (1989).
[10] S. Al-Mousawi, E. John, N. Al-Kandery, J. Heterocyclic
Chem., 41, 381 (2004).
[11] S. Al-Mousawi, M. M. Abdelkhalik, S. El-Sherbiny, E.
John, and M. H. Elnagdi, J. Heterocyclic Chem., 38, 949 (2001).
[12] S. Al-Mousawi, M. M. Abdelkhalik, E. John, and M. H.
Elnagdi, J. Heterocyclic Chem., 40, 689 (2003).
Compound 24 was obtained as brown crystals 2.08 g (77%),
mp. 280-282°, ir (KBr): 3426 and 3296 (NH2), (br) 1697 (CO)
cm-1; ms: m/z 271 (M+,54), 217 (100), 149 (42), 107 (88), 91
1
(26), 77 (28); H nmr (dimethylsulfoxide-d6): ꢀ 7.05-7.48 (m,
4H, arom-H), 7.73 (s, 1H, SH, D2O exchangeable), 7.79 (br, 2H,
NH2, D2O exchangeable), 8.05 (d, 1H, J = 8 Hz, arom-H), 10.93
(s, 1H, CHO), 13C nmr (dimethylsulfoxide-d6): ꢀ 169.6, 161.4
[13] F. Al-Omran, N. Al-Awadi, A. Elassar, A. El-Khair, J. Chem.
Res. (S), 20 Ibid. (M). 237 (2000).