Syntheses of 3,4,7-triazaacenaphthylene and pyrido[3,4,5-de]cinnoline derivatives

Article abstract of DOI:10.1002/hc.10168

The synthesis of 3,4,7-Triazaacenaphthylene and Pyrido[3,4,5-de]cinnoline derivatives was reported. The title compounds were prepared by four different routes. The reactivity of ylidene derivatives toward different type of organic reagents was described. The mass spectrum and IR spectrum of the products formed by the coupling of ylidene derivatives with diazonium salts were discussed.

Full text of DOI:10.1002/hc.10168

Heteroatom Chemistry
Volume 14, Number 5, 2003
Syntheses of 3,4,7-Triazaacenaphthylene and
Pyrido[3,4,5-de]cinnoline Derivatives
Abdel-Zaher A. Elassar and Yehya M. El-Kholy
Chemistry Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, Egypt
Received 14 February 2003
RESULTS AND DISCUSSION
ABSTRACT: The title compounds were prepared by
four different routes: (1) reaction of cycloalkanopyri-
dazines 3a–e with trichloroacetonitrile in basic
medium; (2) reaction of 3a–d with DMF DMA,
followed by nucleophilic treatment with a primary
amine; (3) reaction of 2-(dimethylamino)methylene-
cycloalkylidene-malononitrile with arene diazonium
salt, followed by amine treatment; (4) reaction of
cycloalkylidenemalononitrile with phenyl or benzoyl
isothiocyanate and heating the product with diazo-
Ylidene derivatives 1a,b readily coupled with diazo-
nium salts 2a–d to give products, which were estab-
lished as having structure 3a–e (see Scheme 1). The
mass spectrum of 3a showed molecular ion peak at
m/z 281 and its IR spectrum reveals the presence of
NH and cyano groups at 3320 and 2212 cm−1, re-
1
spectively. Moreover, the H NMR spectrum reveals
the presence of aromatic protons at δ 7.98–7.53 ppm.
In 13C NMR the low field signal at δ 165.16 ppm in-
dicates the imine carbon atom and the signal at δ
116.89 ppm indicates the presence of a cyano group.
The signals of other skeletal carbon atoms appeared
at expected positions. Similarly, the structures of
3b–e were established.
ꢀ
C
aminobenzene.
2003 Wiley Periodicals, Inc. Het-
eroatom Chem 14:427–433, 2003; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10168
Cycloalkanopyridazine 3a–d reacted readily un-
der basic condition with trichloroacetonitrile to
give 3,4,7-triazaacenaphthylene or cinnolineamine
derivatives 4a–d in good yield (see Scheme 2). The
product 4c could also be obtained in low yield by
treating 1b with trichloroacetonitrile to give 5, fol-
lowed by coupling with arene diazonium salt 2a. The
oxo derivative 4e was obtained in good yield by treat-
ing the pyridine derivative 5 with diazoaminoben-
zene in refluxing aqueous acetic acid/hydrochloric
acid mixture. The structures of 4a–e were estab-
lished on their elemental analysis and spectral data.
For example, mass spectra of 4a revealed molecular
ion peaks at m/z 424 (65%, M); 426 (60%, M + 2); 428
(25%, M + 4); 430 (3%, M + 6).
INTRODUCTION
Activated methylene nitriles are highly reactive
reagents that have found extensive application in or-
ganic synthesis [1–3]. Condensed azines comprise a
very interesting class of compounds because of their
biological and medicinal activities [4–6]. In the last
decade we reported several novel syntheses of azines,
utilizing activated nitriles as starting material [7–9].
Herein we report the reactivity of ylidene derivatives
1a,b toward different type of organic reagents with
the aim of preparing 3,4,7-triazaacenaphthylene and
cinnolineamine ring systems.
Furthermore, N,N-dimethylformamide dime-
thyl acetal (DMF DMA) reacts with 3a–d to give 6a–d
(Scheme 3). The structures of the isolated products
were confirmed on the basis of elemental analysis
Correspondence to: A. A. Elassar; e-mail: aelassar@yahoo.com.
2003 Wiley Periodicals, Inc.
c
ꢀ
427

428 Elassar and El-Kholy
SCHEME 1
1
and spectral data. For example, H NMR of com-
pound 6a revealed the presence of ethylenic proton
at δ 6.98 ppm in addition to the NMe2 protons at
δ 2.95 ppm. The reactivity of compounds 6a,b to-
ward some nitrogen nucleophiles was investigated.
Thus, enamine 6a,d reacted with hydrazine hydrate
7a or aromatic amines 7b,c to give pyridopyridazine
derivatives 9a–f. The intermediates 8 are believed
to form via addition of amino group to ethylenic
double bond followed by loss of dimethylamine. In-
tramolecular cyclization gives the final isolated prod-
ucts 9 (Scheme 3). Alternatively, compounds 1a,b
were treated with DMF DMA in DMF and piperi-
dine to give the condensation products 10a,b. The
latter coupled with arene diazonium salt 2b to give
the aldehydic derivatives 11a,b (Scheme 3). We as-
sume that the initially formed arylazo derivatives hy-
drolyze to aldehydic arylhydrazono derivatives fol-
lowed by cyclization. Transformation of an imino to
an aldehydic group has been reported under similar
reaction condition [10]. Compounds 11a,b reacted
with hydrazine hydrate in ethanolic DMF mixture to
give the final isolated products 9a,b. It is assumed
that the amino group adds to the electrophilic car-
bonyl carbon atom affording the nonisolated inter-
mediate 12, followed by intramolecular cyclization
and loss of water molecule. The structure of 9a,b was
SCHEME 3
established by elemental analysis and spectral data.
Thus, the IR spectrum of 9a revealed the disappear-
ance of the aldehydic carbonyl and cyano groups.
The 1H and 13C NMR spectra agree with the proposed
structure.
Moreover, the target ring system could be ob-
tained by treating 1a,b with phenylisothiocyanate
or benzoylisothiocyanate to give 14a–d through
the nonisolated intermediate 13, which was formed
upon addition of cyclic active methylene group to
isothiocyanate. The pyridazine ring could form by
coupling with either a benzenediazonium salt or a
diazoaminobenzene. With the latter high yields of
the product were obtained. Thus, compounds 14a-d
reacted with diazoaminobenzene 15a,b in aqueous
acetic acid/hydrochloric acid mixture to afford the
final isolated products 16a–h (Scheme 4). These
were established based on elemental analysis and
spectral data.
EXPERIMENTAL
All melting points are uncorrected. IR spectra were
recorded in KBr with a IR spectrophotometer Shi-
madzu 408. 1H NMR and 13C NMR spectra were
recorded on Varian EM-390 MHz spectrometer using
SCHEME 2

Syntheses of 3,4,7-Triazaacenaphthylene and Pyrido[3,4,5-de]cinnoline Derivatives 429
(m, 6H, 3CH2). Anal. for C14H11ClN4 (270.74): C,
62.10; H, 4.10; N, 20.69. Found: C, 62.32; H, 3.99; N,
20.65.
2-(4-Chlorophenyl)-3-imino-2,3,5,6,7,8-hexahy-
drocinnoline-4-carbonitrile (3c). Yellow crystals
(72%) from ethanol; mp 165◦C; IR: 3320 (NH), 3085
(CH-aromatic), 2998 (CH-aliphatic), 2212 (CN),
1
1650 cm−1 (C NH); H NMR: δ 7.78–7.21 (m, 4H,
Ar), 6.30 (br, 1H, NH), 2.82–1.17 (m, 8H, 4CH2).
Anal. for C15H13ClN4 (284.77): C, 63.26;H, 4.61; N,
19.67. Found: C, 63.36; H, 4.50; N, 19.85.
3-Imino-2-(3-nitrophenyl)-2,3,5,6,7,8-hexahydro-
cinnoline-4-carbonitrile (3d). Yellow crystals (76%)
from ethanol; mp 123◦C; IR: 3330 (NH), 3092 (CH-
SCHEME 4
aromatic), 2996 (CH-aliphatic), 2210 (CN), 1653
TMS as internal reference and chemical shifts δ are
expressed as ppm. Mass spectra were measured on
a Shimadzu GCMS-QP 1000 Ex mass spectrometer.
Microanalytical data were obtained from the Micro-
analytical Data Unit at Cairo University, Egypt. Com-
pounds 14a,c,d were prepared as described in the
previous publication [11,12].
1
cm−1 (C NH); H NMR: δ 7.97–7.43 (m, 4H, Ar),
6.20 (br, 1H, NH), 2.84–1.18 (m, 8H, 4CH2). Anal.
for C15H13N5O2 (295.33): C, 60.99; H, 4.44; N, 23.71.
Found: C, 61.00; H, 4.32; N, 23.73.
3-Imino-2-thiazol-2-yl-3,5,6,7-tetrahydro-2H-cy-
clopenta[c]pyridazine-4-carbonitrile
(3e). Pale
brown crystals (66%) from ethanol; mp 200◦C;
IR: 3239 (NH), 3089 (CH-aromatic), 2986 (CH-
aliphatic), 2211 (CN), 1654 cm−1 (C NH); 1H NMR:
δ 8.98 (br, 1H, NH), 7.99–7.46 (m, 2H, thiazolyl-
H), 1.85–1.07 (m, 6H, 3CH2). Anal. for C11H9N5S
(243.32): C, 54.29; H, 3.73; N, 28.78; S, 13.18. Found:
C, 54.32; H, 4.00; N, 28.58; S, 13.43.
General Method for the Preparation of 3a–e
A solution of the diazonium salts (prepared from
0.01 mol of aromatic or heteroaromatic amine with
the appropriate quantities of sodium nitrite and
hydrochloric acid) was added to cycloalkylidene-
malononitrile 1a or 1b (0.01 mol) in ethanol (50 ml)
and sodium hydroxide (0.50 g). The reaction mix-
ture was stirred at room temperature for 2 h. The
solid product, so formed, was collected by filtration
and recrystallized from ethanol.
General Method for the Preparation of 4a–e
Method A (4a–d): To a solution of 3a or 3b or 3c
or 3d (0.01 mol) in DMF, trichloroacetonitrile (0.01
mol) and few drops of piperidine were added. The
reaction mixture was heated under reflux for 1 h.
The reaction product was treated with ice-cold water
and the solid product, so formed, was filtered and
crystallized from proper solvent.
Method B (4e): A mixture of 5 (0.01 mol), di-
azoaminobenzene (0.01 mol), glacial acetic acid (15
ml), hydrochloric acid (15 ml, 36% wt/wt), and few
drops of water was heated under reflux for 3 h
and then allowed to cool. The reaction product was
neutralized using sodium bicarbonate solution. The
solid product so formed was collected by filtration,
washed with ice-cold water several times, dried, and
crystallized from a proper solvent.
3-Imino-2-(3-nitrophenyl)-3,5,6,7-tetrahydro-2H-
cyclopenta[c]pyridazine-4-carbonitrile (3a). Brown
crystals (78%) from ethanol; mp 147◦C; IR: 3320
(NH), 3088 (CH-aromatic), 2993 (CH-aliphatic),
2212 (CN), 1650 cm−1 (C NH); 1H NMR: δ 7.98–7.53
(m, 4H, Ar), 6.25 (br, 1H, NH), 1.82–1.45 (m, 6H,
3CH2); 13C NMR δ 165.16 (C-3), 157.12 (C-7a),
140.06, 139.12, 137.01, 135.11, 134.21, 129.61,
127.11, 124.10 (aromatic carbon atoms), 116.89
(CN), 28.66, 27.45, 25.98 (3CH2); MS: m/z 281 (M+).
Anal. for C14H11N5O2 (281.3): C, 59.77; H, 3.94; N,
24.90. Found: C, 60.01; H, 4.00; N, 25.01.
2-(4-Chlorophenyl)-3-imino-3,5,6,7-tetrahydro-
2H-cyclopenta[c]pyridazine-4-carbonitrile (3b).
Yellow crystals (70%) from ethanol; mp 140◦C;
IR: 3324 (NH), 3081 (CH-aromatic), 2995 (CH-
aliphatic), 2209 (CN); 1652 cm−1 (C NH); 1H NMR:
δ 7.89–7.33 (m, 4H, Ar), 6.05 (br, 1H, NH), 1.81–1.45
5-Imino-4-(3-nitrophenyl)-8-(trichloromethyl)-
1,2,4,5-tetrahydro-3,4,7-triazaacenaphthylen-6-amine
(4a). Brown crystals (65%) from ethanol; mp
>250◦C; IR: 3401, 3358, 3325 (NH2 & NH), 3100

430 Elassar and El-Kholy
(CH-aromatic), 2991 (CH-aliphatic), 1651 cm−1
(C NH); H NMR: δ 7.87–7.42 (m, 4H, Ar), 8.50,
piperidene was refluxed for 2 h. The reaction mixture
was evaporated under vacuum and the solid product
so formed was collected by filtration and crystallized
from ethanol.
1
6.25 (br, 3H, NH & NH2), 1.72–1.45 (m, 4H, 2CH2);
13C NMR: δ 158.93, 157.87, 155.59, 154.93, 153.32,
149.30, 148.33, 147.35, 145.72, 141.32, 139.39,
137.38, 134.36 (aromatic carbon atoms), 97.73
(CCl3), 27.76, 26.33 (2CH2); MS: m/z 424 (65%, M+),
426 (60%, M + 2), 428 (25%, M + 4), 430 (3%, M + 6).
Anal. for C16H11Cl3N6O2 (425.68): C, 45.14; H, 2.61;
N, 19.74. Found: C, 45.32; H, 2.60; N, 19.76.
Pale brown crystals (69%); mp 160◦C; IR: 3422,
3328 (NH2), 2989 (CH-aliphatic), 2213 cm−1 (CN); 1H
NMR: δ 8.05 (br, 2H, NH2), 1.85–105 (m, 8H, 4CH2).
Anal. for C11H10Cl3N3 (290.59): C, 45.46;H, 3.47; N,
14.46. Found: C, 45.66; H, 3.75; N, 14.36.
General Method for the Preparation of 6a–d
4-(4-Chlorophenyl)-5-imino-8-(trichloromethyl)-
1,2,4,5-tetrahydro-3,4,7-triazaacenaphthylen-6-amine
(4b). Yellow crystals (63%) from ethanol; mp
242◦C; IR: 3411, 3345, 3320 (NH2 & NH), 3100
(CH-aromatic), 2993 (CH-aliphatic), 1650 cm−1
A solution of pyridazines 3a or 3b or 3c or 3d (0.01
mol) in DMF (25 ml) was treated with DMF DMA
(0.01 mol) and few drops of piperidene. The reaction
mixture was heated under reflux for 2 h and then
treated with cold water. The reaction product was
collected by filtration and crystallized from proper
solvent.
1
(C NH); H NMR: δ 7.98–7.32 (m, 4H, Ar), 8.40,
6.25 (br, 3H, NH & NH2), 1.71–1.50 (m, 4H, 2CH2).
Anal. for C16H11Cl4N5 (415.12): C, 46.29; H, 2.67; N,
16.87. Found: C, 46.53; H, 2.59; N, 16.59.
(5E)-5-[(Dimethylamino)methylene]-3-imino-2-
(3-nitrophenyl)-3,5,6,7-tetrahydro-2H-cyclopenta[c]-
pyridazine-4-carbonitrile (6a). Brown crystals
(75%) from EtOH; mp 197◦C; IR: 3323 (NH), 3100
(CH-aromatic), 2981 (CH-aliphatic), 2210 (CN),
2-(4-Chlorophenyl)-3-imino-6-(trichloromethyl)-
2,7,8,9-tetrahydro-3H-pyrido[3,4,5-de]cinnolin-4-
amine (4c). Yellow crystals (63%) from ethanol;
mp 284◦C; IR: 3434, 3373, 3331 (NH2 & NH), 3101
(CH-aromatic), 2997 (CH-aliphatic), 1651 cm−1
1
1651 cm−1 (C NH); H NMR: δ 7.93–7.15 (m, 4H,
1
Ar), 6.98 (s, 1H, CH), 5.89 (br, 1H, NH), 2.95 (s, 6H,
2Me), 1.71–1.51 (m, 4H, 2CH2). Anal. for C17H16N6O2
(336.39): C, 60.69; H, 4.80; N, 24.98. Found: C, 60.71;
H,4.94; N, 24.76.
(C NH); H NMR: δ 7.76–7.01 (m, 4H, Ar), 8.40,
6.24 (br, 3H, NH & NH2), 1.85–1.06 (m, 6H, 3CH2).
Anal. for C17H13Cl4N5 (429.15): C, 47.57; H, 3.05; N,
16.32. Found: C, 47.58; H, 3.00; N, 16.36.
3-Imino-2-(3-nitrophenyl)-6-(trichloromethyl)-
2,7,8,9-tetrahydro-3H-pyrido[3,4,5-de]cinnolin-4-
amine (4d). Brown crystals (73%) from DMF; mp
124◦C; IR: 3422, 3331, 3321 (NH2 & NH), 3100
(CH-aromatic), 2996 (CH-aliphatic), 1653 cm−1
(5E)-2-(4-Chlorophenyl)-5-[(dimethylamino)me-
thylene]-3-imino-3,5,6,7-tetrahydro-2H-cyclopenta-
[c]pyridazine-4-carbonitrile (6b). Pale brown crys-
tals (78%) from EtOH; mp 213◦C; IR: 3329 (NH),
3099 (CH-aromatic), 2983 (CH-aliphatic), 2211
(CN), 1650 cm−1 (C NH); 1H NMR: δ 7.67–7.15
(m, 4H, Ar), 6.98 (s, 1H, CH), 5.87 (br, 1H, NH),
2.45 (s, 6H, 2Me), 1.70–1.51 (m, 4H, 2CH2). Anal.
for C17H16ClN5 (325.83): C, 62.66; H, 4.95; N, 21.49.
Found: C, 62.41; H, 4.83; N, 21.43.
1
(C NH); H NMR: δ 7.88–7.24 (m, 4H, Ar), 8.42,
6.31 (br, 3H, NH & NH2), 1.82–1.06 (m, 6H, 3CH2).
Anal. for C17H13Cl3N6O2 (439.71): C, 46.43; H, 2.98;
N, 19.11. Found: C, 46.34; H, 3.01; N, 19.00.
4-Amino-2-phenyl-6-(trichloromethyl)-2,7,8,9-
tetrahydro-3H-pyrido[3,4,5-de]cinnolin-3-one (4e).
Brown crystals (70%) from DMF; mp 108◦C; IR:
3418, 3321 (NH2), 3095 (CH-aromatic), 2992 (CH-
aliphatic), 1659 cm−1 (CO); 1H NMR: δ 7.57–7.10
(m, 5H, Ar), 8.40 (br, 2H, NH2), 1.80–1.07 (m, 6H,
3CH2). Anal. for C17H13Cl3N4O (395.69): C, 51.59; H,
3.31; N, 14.16. Found: C, 51.22; H, 3.53; N, 14.00.
(5E)-2-(4-Chlorophenyl)-5-[(dimethylamino)me-
thylene]-3-imino-2,3,5,6,7,8-hexahydrocinnoline-4-
carbonitrile (6c). Yellow crystals (64%) from EtOH;
mp 201◦C; IR: 3331 (NH), 3100 (CH-aromatic), 2983
1
(CH-aliphatic), 2212 (CN), 1653 cm−1 (C NH); H
NMR: δ 7.87–7.15 (m, 4H, Ar), 6.98 (s, 1H, CH), 5.89
(br, 1H, NH), 2.45 (s, 6H, 2Me), 1.83–1.08 (m, 6H,
3CH2). Anal. for C18H18ClN5 (339.86): C, 63.60; H,
5.34; N, 20.61. Found: C, 63.93; H, 5.41; N, 20.41.
3-Amino-1-(trichloromethyl)-5,6,7,8-tetrahydro-
iosquinoline-4-carbonitrile (5)
(5E)-5-[(Dimethylamino)methylene]-3-imino-2-
(3-nitrophenyl)-2,3,5,6,7,8-hexahydro-cinnoline-4-
carbonitrile (6d). Yellow crystals (66%) from EtOH;
A solution of ylidene 1b (0.01 mol) in DMF (20 ml),
trichloroacetonitrile (0.01 mol), and few drops of

Syntheses of 3,4,7-Triazaacenaphthylene and Pyrido[3,4,5-de]cinnoline Derivatives 431
mp 189◦C; IR: 3331(NH), 3100 (CH-aromatic), 2985
8.69 (s, 1H, Pyridine-H), 7.89–7.01 (m, 9H, Ar), 6.85,
5.59 (br, 2H, 2NH), 1.85–1.07 (m, 4H, 2CH2). Anal.
for C21H16N6O2 (384.43): C, 65.60; H, 4.20; N, 21.86.
Found: C, 65.71; H, 4.20; N, 21.83.
1
(CH-aliphatic), 2212 (CN), 1651 cm−1 (C NH); H
NMR: δ 7.98–7.13 (m, 4H, Ar), 6.97 (s, 1H, CH), 5.79
(br, 1H, NH), 2.46 (s, 6H, 2Me), 1.85–1.07 (m, 6H,
3CH2). Anal. for C18H18N6O2 (350.42): C, 61.69; H,
5.18; N, 23.98. Found: C, 61.39; H, 5.01; N, 23.74.
2-(3-Nitrophenyl)-5-phenyl-5,7,8,9-tetrahydro-3H-
pyrido[3,4,5-de]cinnoline-3,4-(2H)-diimine (9d).
Brown crystals (76%) from DMF/EtOH; mp 165◦C;
IR: 3331, 3219 (2NH), 3101 (CH-aromatic), 2996
(CH-aliphatic), 1652, 1657 cm−1 (2C NH); 1H NMR:
δ 8.57 (s, 1H, Pyridine-H), 7.91–7.11 (m, 9H, Ar),
6.85, 5.77 (br, 2H, 2NH), 2.79–1.23 (m, 6H, 3CH2).
Anal. for C22H18N6O2 (398.46): C, 66.31; H, 4.56; N,
21.09. Found: C, 66.31; H, 4.81; N, 21.38.
General Method for the Preparation of 9a–f
Method A: To a solution of 6a or 6b or 6c or 6d
(0.01 mol) in DMF (25 ml), hydrazine hydrate (0.01
mol) or aniline (0.01 mol) or 2-aminopyridine (0.01
mol) was added. The reaction mixture was heated
under reflux for 2 h. Ice-cold water was added and the
solid product so formed was collected by filtration
and crystallized from proper solvent.
4-(3-Nitrophenyl)-7-pyridin-2-yl-1,2,4,7-tetrahy-
dro-3,4,7-triazaacenaphthylene-5,6-diimine (9e).
Brown crystals (76%) from DMF/EtOH; mp 134◦C;
IR: 3345, 3219 (2NH), 3103 (CH-aromatic), 2993
(CH-aliphatic), 1653, 1657 cm−1 (2C NH); 1H NMR:
δ 8.78 (s, 1H, Pyridine-H), 7.84–7.21 (m, 8H, pyridine
& Ar), 6.75, 5.59 (br, 2H, 2NH), 1.85–1.17 (m, 4H,
2CH2). Anal. for C20H15N7O2 (385.42): C, 62.32; H,
3.93; N, 25.44. Found: C, 62.31; H, 4.01; N, 25.53.
Method B: To
a solution of 11a or11b
(0.01 mol), in ethanol/DMF mixture (1:1, 30 ml), hy-
drazine hydrate (0.01 mol) was added. The reaction
mixture was heated under reflux for 2 h. Ice-cold
water added and the solid product so formed was
collected by filtration and crystallized from proper
solvent.
5,6-Diimino-4-(3-nitrophenyl)-1,2,4,6-tetrahydro-
3,4,7-triazaacenaphthylen-7(5H)-amine (9a). Yel-
low crystals (79%) from DMF/EtOH; mp 157◦C;
IR: 3412, 3334, 3226, 3215 (NH2, 2NH), 3100
(CH-aromatic), 2993 (CH-aliphatic), 1651, 1656
cm−1 (2C NH); 1H NMR: δ 10.32 (br, 2H, NH2),
8.03 (s, 1H, Pyridine-H), 7.89–7.10 (m, 4H, Ar),
6.95, 5.79 (br, 2H, 2NH), 1.85–1.07 (m, 4H, 2CH2);
13C NMR: δ 159.13, 158.78, 158.33, 157.02, 153.21,
149.12, 148.25, 147.68, 143.21, 138.21, 137.25,
135.01, 132.35 (aromatic carbon atoms), 26.35,
27.60 (2CH2); MS: m/z323 (73.03%, M+). Anal. for
C15H13N7O2 (323.35): C, 55.71; H, 4.06; N, 30.32.
Found: C, 55.69; H, 4.31; N, 30.63.
2-(3-Nitrophenyl)-5-pyridin-2-yl-5,7,8,9-tetrahy-
dro-3H-pyrido[3,4,5-de]cinnoline-3,4(2H)-diimine
(9f). Brown crystals (73%) from DMF/EtOH; mp
176◦C; IR: 3365, 3223 (2NH), 3100 (CH-aromatic),
1
2998 (CH-aliphatic), 1651, 1653 cm−1 (2C NH); H
NMR: δ 8.35 (s, 1H, Pyridine-H), 7.91–7.12 (m, 8H,
pyridine & Ar), 6.65, 6.09 (br, 2H, 2NH), 2.80–1.11
(m, 6H, 3CH2). Anal. for C21H17N7O2 (399.45): C,
63.13; H, 4.29; N, 24.55. Found: C, 63.31; H, 4.39; N,
24.63.
General Method for the Preparation of 10a,b
3,4-Diimino-2-(3-nitrophenyl)-2,7,8,9-tetrahydro-
3H-pyrido[3,4,5-de]cinnolin-5(4H)-amine (9b). Yel-
low crystals (72%) from DMF/EtOH; mp 168◦C;
IR: 3411, 3333, 3229, 3220 (NH2, 2NH), 3099 (CH-
aromatic), 2995 (CH-aliphatic), 1652, 1656 cm−1
A solution of ylidene derivatives 1a or 1b (0.01
mol) in DMF (25 ml) was treated with DMF DMA
(0.01 mol) and few drops of piperidine. The reaction
mixture was heated under reflux for 2 h and then
treated with ice-cold water. The reaction product was
collected by filtration and crystallized from proper
solvent.
1
(2C NH). H NMR: δ 10.02 (br, 2H, NH2), 8.13 (s,
1H, Pyridine-H), 7.79–7.10 (m, 4H, Ar), 6.85, 5.77
(br, 2H, 2NH), 2.78–1.11 (m, 6H, 3CH2). Anal. for
C16H15N7O2 (337.38): C, 56.95; H, 4.49; N, 29.06.
Found: C, 57.01; H, 4.53; N, 29.01.
{(2E)-2-[(Dimethylamino)methylene]cyclopenty-
lidene}malononitrile (10a). Yellow crystals (76%)
from DMF/EtOH; mp 145◦C; IR: 2998 (CH-aliphatic),
2220, 2221 (2CN), 1400 (C N); 1H NMR: δ 6.69
(s, 1H, CH), 2.46 (s, 6H, 2CH3), 1.83–1.44 (m, 6H,
3CH2). Anal. for C11H13N3 (187.27): C, 70.54; H, 7.01;
N, 22.44. Found: C, 70.31; H, 7.30; N, 22.62.
4-(3-Nitrophenyl)-7-phenyl-1,2,4,7-tetrahydro-
3,4,7-triazaacenaphthylene-5,6-diimine (9c). Brown
crystals (74%) from DMF/EtOH; mp >250◦C; IR:
3331, 3219 (2NH), 3100 (CH-aromatic), 2998 (CH-
1
aliphatic), 1650, 1655 cm−1 (2C NH); H NMR: δ

432 Elassar and El-Kholy
{(2E)-2-[(Dimethylamino)methylene]cyclohexay-
lidene}malononitrile (10b). Yellow crystals (74%)
from DMF/EtOH; mp 153◦C; IR: 2989 (CH-aliphatic),
(m, 5H, Ar), 6.52 (br, 2H, NH2), 1.85–1.17 (m, 6H,
3CH2). Anal. for C16H13N3OS (295.39): C, 65.05; H,
4.44; N, 14.22; S, 10.85. Found: C, 65.00; H, 4.34; N,
14.01; S, 11.00.
1
2220, 2221 (2CN), 1401 (C N); H NMR: δ 6.94 (s,
1H, CH), 2.45 (s, 6H, 2Me), 2.81–1.17 (m, 8H, 4CH2).
Anal. for C12H15N3 (201.30): C, 71.59; H, 7.52; N,
20.87. Found: C, 71.35; H, 7.31; N, 20.71.
General Method for the Preparation of 16a–h
A mixture of 14a or 14b or 14c or 14d (0.01 mol),
diazoaminobenzene (0.01 mol), glacial acetic acid
(15 ml), hydrochloric acid (15 ml, 36% wt/wt), and
few drops of water was heated under reflux for 3 h
and then allowed to cool. The reaction product was
neutralized using sodium bicarbonate solution. The
solid product so formed was collected by filtration,
washed with ice-cold water several times, dried, and
crystallized from a proper solvent.
General Method for the Preparation of 11a,b
A solution of the diazonium salts, (prepared as de-
scribed in the preparation of 3a–d) was added drop-
wise with strong stirring for 2 h, to a solution of 10a
or 10b (0.01 mol) in DMF and a solution of NaOH
(0.1 g dissolved in 10 ml of water). The solid product
so formed was collected by filtration and crystallized
from proper solvent.
6-Amino-4-(3-nitrophenyl)-7-phenyl-8-thioxo-1,8-
ethano-2,4,7,8-tetrahydro-3,4,7-triazaacenaphthylene-
5(1H)-one (16a). Deep yellow crystals (70%) from
DMF; mp 188◦C; IR: 3343, 3332 (NH2), 3100 (CH-
5-Formyl-3-imino-2-(3-nitrophenyl)-3,5,6,7-tetra-
hydro-2,3,5,6,7-2H-cyclopenta[c]pyridazine-4-carbon-
itrile (11a). Red crystals (69%) from acetone; mp
144◦C; IR: 3323 (NH), 3100 (CH-aromatic), 2991
(CH-aliphatic), 2212 (CN), 1728 (CO), 1652 cm−1
1
aromatic), 2992 (CH-aliphatic), 1658 cm−1 (CO); H
1
NMR: δ 7.82–7.23 (m, 9H, Ar), 6.51 (br, 2H, NH2),
1.85–1.06 (m, 4H, 2CH2); MS: m/z417 (M+). Anal. for
C21H15N5O3S (417.48): C, 60.41; H, 3.62; N, 16.77; S,
7.68. Found: C, 65.51; H, 3.45; N, 16.98; S, 7.83.
(C NH); H NMR: δ 10.45 (s, 1H, CHO), 7.98–7.23
(m, 4H, Ar), 6.23 (br, 1H, NH), 2.84–1.53 (m, 5H,
1CH & 2CH2); 13C NMR: δ 204.70 (CHO), 165.01,
157.36, 151.71, 143.31, 139.01, 137.37, 135.30,
134.31, 125.20, 124.93 (aromatic carbon atoms),
116.31 (CN), 37.31, 29.36, 27.29 (3CH2); MS: m/z
309 (65.30%, M+). Anal. for C15H11N5O3 (309.31): C,
58.24; H, 3.59; N, 22.64. Found: C, 58.24; H, 3.52; N,
22.46.
6-Amino-4,7-diphenyl-8-thioxo-1,8-ethano-2,4,7,
8-tetrahydro-3,4,7-triazaacenaphthylene-5(1H)-one
(16b). Brown crystals (71%) from DMF; mp 218◦C;
IR: 3342, 3329 (NH2), 3104 (CH-aromatic), 2994
1
(CH-aliphatic), 1559 cm−1 (CO); H NMR: δ 7.72–
5-Formyl-3-imino-2-(3-nitrophenyl)-2,3,5,6,7,8-
hexahydrocinnoline-4-carbonitrile (11b). Red crys-
tals (72%) from acetone; mp 158◦C; IR: 3333 (NH),
3100 (CH-aromatic), 2992 (CH-aliphatic), 2210
7.23 (m, 10H, Ar), 6.53 (br, 2H, NH2), 1.85–1.07 (m,
4H, 2CH2). Anal. for C21H16N4OS (372.48): C, 67.71;
H, 4.33; N, 15.04; S, 8.60. Found: C, 67.60; H, 4.05;
N, 14.91; S, 8.31.
1
(CN), 1727 (CO), 1653 cm−1 (C NH); H NMR: δ
10.50 (s, 1H, CHO), 7.97–7.20 (m, 4H, Ar), 6.05 (br,
1H, NH), 2.86–1.43 (m, 7H, 1CH & 3CH2). Anal. for
C16H13N5O3 (323.34): C, 59.42; H, 4.06; N, 21.66.
Found: C, 59.38; H, 3.84; N, 21.77.
6-Amino-7-benzoyl-4-(3-nitrophenyl)-8-thioxo-1,
8-ethano-2,4,7,8-tetrahydro-3,4,7-triazaacenaphthy-
lene-5(1H)-one (16c). Yellow crystals (74%) from
DMF; mp 243◦C; IR: 3343, 3329 (NH2), 3103 (CH-
aromatic), 2997 (CH-aliphatic), 1651, 1659 cm−1
(2CO); 1H NMR: δ 7.91–7.21 (m, 9H, Ar), 6.54
(br, 2H, NH2), 1.85–1.07 (m, 4H, 2CH2). Anal. for
C22H15N5O4S (445.49): C, 59.30; H, 3.40; N, 15.72; S,
7.19. Found: C, 59.37; H, 3.13; N, 16.01; S, 7.28.
3-Amino-2-benzoyl-1-thioxo-2,5,6,7-tetrahydro-
1H-cyclopenta[c]pyridine-4-carbonitrile (14b)
To a solution of 1a (0.01 mol) in ethanol (25 ml),
benzoyl isothiocyanate (0.01 mol) and few drops of
piperidine were added. The reaction mixture was
heated under reflux for 3 h. The solid product so
formed, upon treating the reaction mixture with ice-
cold water, was collected by filtration and crystallized
from ethanol.
6-Amino-7-benzoyl-4-phenyl-8-thioxo-1,8-ethano-
2,4,7,8-tetrahydro-3,4,7-triazaacenaphthylene-5(1H)-
one (16d). Brown crystals (73%) from DMF; mp
>250◦C; IR: 3343, 3328 (NH2), 3100 (CH-aromatic),
2998 (CH-aliphatic), 1655, 1661 cm−1 (2CO); 1H
NMR: δ 7.85–7.31 (m, 10H, Ar), 6.53 (br, 2H, NH2),
1.85–1.10 (m, 4H, 2CH2). Anal. for C22H16N4O2S
Brown crystals (64%); mp 173◦C; IR: 3342, 3328
(NH2), 3101 (CH-aromatic), 2993 (CH-aliphatic),
1
2210 (CN), 1661 cm−1 (CO); H NMR: δ 7.54–7.01

Syntheses of 3,4,7-Triazaacenaphthylene and Pyrido[3,4,5-de]cinnoline Derivatives 433
(400.49): C, 65.97; H, 4.03; N, 13.99; S, 8.00. Found:
C, 66.01; H, 3.98; N, 14.02; S, 8.34.
4-Amino-5-benzoyl-2-phenyl-6-thioxo-2,5,6,7,8,9-
hexahydro-3H-pyrido[3,4,5-de]cinnoline-3-one (16h).
Brown crystals (70%) from DMF; mp 212◦C; IR:
3331, 3328 (NH2), 3101 (CH-aromatic), 2989
(CH-aliphatic), 1660, 1658 cm−1 (2CO); 1H NMR:
7.73–7.22 (m, 10H, Ar), 6.51 (br, 2H, NH2), 2.85–1.37
(m, 6H, 3CH2). Anal. for C23H18N4O2S (414.52): C,
66.63; H, 4.38; N, 13.51; S, 7.73. Found: C, 66.89; H,
4.00; N, 13.80; S, 7.82.
4-Amino-2-(3-nitrophenyl)-5-phenyl-6-thioxo-2,5,
6,7,8,9-hexahydro-3H-pyrido[3,4,5-de]cinnoline-3-one
(16e). Deep yellow crystals (74%) from DMF; mp
206◦C; IR: 3348, 3335 (NH2), 3100 (CH-aromatic),
1
2992 (CH-aliphatic), 1663 cm−1 (CO); H NMR: δ
7.93–7.22 (m, 9H, Ar), 6.52 (br, 2H, NH2), 2.85–1.37
(m, 6H, 3CH2). Anal. for C22H17N5O3S (431.51): C,
61.23; H, 3.97; N, 16.23; S, 7.43. Found: C, 61.60; H,
3.61; N, 16.43; S, 7.34.
REFERENCES
[1] Elassar, A. A.; Elkholy, Y. M.; Elnagdi, M. H. J Prakt
Chem 1998, 340, 491.
4-Amino-2,5-diphenyl-6-thioxo-2,5,6,7,8,9-hexa-
hydro-3H-pyrido[3,4,5-de]cinnoline-3-one (16f).
Brown crystals (73%) from DMF; mp 233◦C; IR:
3342, 3329 (NH2), 3099 (CH-aromatic), 2989 (CH-
aliphatic), 1659 cm−1 (CO); 1H NMR: δ 7.83–7.32
(m, 10H, Ar), 6.52 (br, 2H, NH2), 2.85–1.36 (m, 6H,
3CH2). Anal. for C22H18N4OS (386.51): C, 68.36; H,
4.70; N, 14.49; S, 8.29. Found: C, 68.21; H, 4.57; N,
14.23; S, 8.29.
[2] Ram, V. J.; Srivastava, P.; Nath, M.; Saxena, A. S.
Synthesis 1999, 11, 1884.
[3] Gola, A.; Samartzi, E.; Bardakos, V.; Petroliagi, M.;
Igglessi-Markopoulou, O.; Markopoulos, J.; Barkley,
J. V. J Heterocycl Chem 2000, 37, 681.
[4] Elassar, A. A.; Elkholy, Y. M.; Elnagdi, M. H. Phar-
mazie 1996, 51, 714.
[5] Findlay, J. W. A.; Coker, G. G. US Patent 4 639 459 (Cl.
514-343; A61K 31/44), 1987.
[6] Arora, V. K.; Edward, E. E. J Heterocycl Chem 1999,
36, 201.
[7] Elassar, A. A. Pharmazie 1998, 53, 223.
[8] Elassar, A. A. J Chem Res (S) 1999, 96.
[9] (a) Al-Omran, F.; Al-Awadhi, N.; Elassar, A. A.;
El-Khair, A. A. J Chem Res (S) 2000, 20; (b) Al-Omran,
F.; Al-Awadhi, N.; Elassar, A. A.; El-Khair, A. A. J Chem
Res (M) 2000, 237.
[10] Al-Omran, F.; Abdel Khalik, M. M.; Elkhair, A. A;
Elnagdi, M. H. Synthesis 1997, 91.
[11] Gewald, K.; Liebscher, J.; Keydel, M. J Prakt Chem
1970, 312, 533.
4-Amino-5-benzoyl-2-(3-nitrophenyl)-6-thioxo-2,
5,6,7,8,9-hexahydro-3H-pyrido[3,4,5-de]cinnoline-3-
one (16g). Yellow crystals (72%) from DMF; mp
195◦C; IR: 3342, 3328 (NH2), 3100 (CH-aromatic),
2997 (CH-aliphatic), 1663, 1659 cm−1 (2CO); 1H
NMR: 7.93–7.22 (m, 9H, Ar), 6.50 (br, 2H, NH2),
2.85–1.35 (m, 6H, 3CH2). Anal. for C23H17N5O4S
(459.52): C, 60.11; H, 3.73; N, 15.24; S, 6.97. Found:
C, 60.45; H, 3.51; N, 15.50; S, 6.90.
[12] El-Sayed, A. M.; Abdel-Ghany, H. J Heterocycl Chem
2000, 37, 1233.