A Convenient Synthesis of New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates

Article abstract of DOI:10.1515/znb-2003-1212

Reaction of N-{3-cyano-6-[4(5-oxo-2-phenylhydrazono-4,5-dihydroimidazol-1- yl)phenyl]-4-phenylpyridin-2-yl}formimidic ethyl ester (3) and 3-[4-(3-amino-4-imino-5-phenyl-3,4-dihydropyrido[2,3-d]pyrimidin-7-yl)phenyl] -2-phenyl-5-phenylhydrazono-3,5-dihydroimidazol-4-one (4) with different reagents has been investigated and discussed. Some of the obtained compounds were tested for their antimicrobial activity.

Full text of DOI:10.1515/znb-2003-1212

A Convenient Synthesis of New Pentaazacyclopentanaphthalene
and Pentaazaphenanthrene Derivates
Yvette A. Issac and Aly A. Aly
Chemistry Department, Faculty of Science, Benha University, Benha, Egypt
Reprint requests to Dr. Y. A. Issac. E-mail: Issacyvetteb@hotmail.com
Z. Naturforsch. 58b, 1227 – 1233 (2003); received March 10, 2003
Reaction of N-{3-cyano-6-[4(5-oxo-2-phenylhydrazono-4,5-dihydroimidazol-1-yl)phenyl]-4-phe-
nylpyridin-2-yl}formimidic ethyl ester (3) and 3-[4-(3-amino-4-imino-5-phenyl-3,4-dihydropyri-
do[2,3-d]pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-dihydroimidazol-4-one (4) with
different reagents has been investigated and discussed. Some of the obtained compounds were tested
for their antimicrobial activity.
Key words: Pyridopyrimidine, Malononitrile, Pentaazacyclopentanaphthalene,
Pentaazaphenanthrene
Introduction
with phenylhydrazine furnished the expected pyrido-
pyrimidines 4, 5a,b, 6 and 7 as products (Scheme 1).
The structure of the above compounds was confirmed
Pyridopyrimidines deserve interest due to their bi-
ological and pharmacological activities [1 – 3]. Some
of them showed potential antibacterial properties [4],
while other derivatives have been used as dihydrofo-
late reductase inhibitors and as antitumor agents [5, 6].
Also some of these derivatives showed antimicro-
bial activities [7], diuretic properties [8] and activity
against platelet aggregation [9]. In continuation of our
previous articles [10– 14] directed towards facile syn-
thesis of heterocycles of biological interest, we thought
to explore the utility of compounds 3 and 4 as key pre-
cursors for synthesis of several hitherto unreported an-
nulated pyridopyrimidines.
1
by IR, H and 13C NMR, mass spectra and elemental
analysis.
Compound 4 proved to be highly reactive towards
various reagents and underwent numerous chemical
transformations, resulting in construction of a wide
range of annulated and substituted pyridopyrimidine
systems. Thus, when equimolar amounts of 4 and
diethyl oxalate were refluxed in ethanol, pentaaza-
cyclopenta[a]naphthalene derivative 8 was obtained
(Scheme 2). Assignment of structure 8 was based
on spectral data, where the IR spectrum of the iso-
lated product displayed the CO absorption band near
1735 cm−1 corresponding to CO (ester). Also, hydrol-
ysis of the product with sodium hydroxide yielded the
corresponding carboxylic acid 9.
Results and Discussion
Treatment of acetophenone derivatives [15] with
benzaldehyde afforded the required starting chalcones
Furthermore, treatment of 4 with ethyl cyanoac-
1. Condensation of equimolar amounts of 1 and mal- etate in absolute ethanol under refluxing condi-
ononitrile in the presence of ammonium acetate fur- tion furnished compound 10. When compound 4
nished 2-amino-4-phenylnicotinonitriles 2. The reac- was allowed to react with carbon disulfide, 2-
tion apparantly involves an intramolecular heterocy- thioxopentaazacyclopenta[a]naphthalene 11 was iso-
clization via an anticipated Michael-type addition [16, lated in fairly good yield.
17] to give the final isolable product 2 (Scheme 1).
Treatment of 2 with equimolar amounts of triethyl or-
thoformate and acetic anhydride afforded the target key
reagents 3 [18].
An even more convenient access to 2-phenylamino-
1,3,3a,5,6-pentaazacyclo-penta[a]naphthalenes 13 was
achieved by treatment of pyridopyrimidine 4 with
phenyl isocyanate to afford the corresponding phenyl-
Cyclization of 3 with hydrazine hydrate, methyl or urea derivative 12 which in turn yielded compound 13
benzyl amine, sodium hydrogen sulfide and finally via loss of water molecule. Alternatively, compound 13
c
0932–0776 / 03 / 1200–1227 $ 06.00 ꢀ 2003 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

1228
Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
Scheme 1.
Scheme 2.
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
1229
Scheme 3.
Table 1. Antimicrobial activity.
Antimicrobial Activity
Bacillus
subtilis
Bacillus
cereus
Aspergillus
niger
Penicillium
spp.
Compd.
No.
The antimicrobial activity of some synthesized
derivatives towards different strains of various organ-
isms was tested using the hole plate and filter paper
method [19]. The tested compounds were dissolved in
10% acetone (v/v), at concentrations of 125, 250 and
500 µg/ml. The results are summarized in Table 1. It
should be noted that other pharmacological studies are
still in progress.
A
+
+
MIC
125
500
A
+
+
MIC
250
250
A
–
MIC
–
A
–
+
++
+
+
MIC
–
4
5
6
7
10
11
15
17a
17b
+
125
250
500
125
125
250
250
250
500
250
250
250
250
–
++ 125
++ 500 +++
+
–
500
–
+
250
+
+
++ 250
++ 125 +++ 250 ++
++
–
+
+
250
125
+
–
+
125
–
125
+
+
+
–
–
++ 125
–
–
Experimental Section
A = antimicrobial activity of tested compounds; MIC = minimum in-
hibitory concentration; + > 5 mm slightly active; ++ > 7 mm mod-
erately active; +++ > 9 mm highly active.
Melting points are uncorrected. IR spectra were recorded
on Perkin Elmer 298 Spectrophotometer. 1H and 13C NMR
spectra were obtained on an Varian Gemini 200 MHz and
50 MHz instrument. Mass spectra were recorded on Shi-
madzu GCMS-QP 1000EX (EI 70 ev) instrument. All reac-
tions were monitored by thin layer chromatography, carried
out on 0.2 mm silica gel 60 F254 (Merck) plates.
was prepared through an independent route involv-
ing reaction of 4 with an equimolar amount of phenyl
isothiocyanate affording a single product, which was
found to be identical in all aspects (m.p., mixed m.p.,
TLC and IR data) with 13.
On refluxing compound 4 with formic acid or acetic
acid 14a and 14b were formed respectively. Compound
14a could be also obtained via an alternative route in-
volving refluxing of compound 4 with triethyl ortho-
formate in dimethyl formamide.
13C NMR values of phenyl groups for compounds 3 – 17
are the same as in compound 2 with δ 0.1 – 0.3 ppm.
2-phenyl-3-[4-(3-phenylacryloyl)phenyl]-5-phenylhydraz-
one-3,5-dihydroimidazol-4-one (1)
A mixture of 3-[4-acetylphenyl]-2-phenyl-5-phenylhydr-
azono-3,5-dihydroimidazol-4-one [15] (0.01 mol) and ben-
zaldehyde (0.01 mol) was dissolved in ethanol (100 ml). To
the cold stirred mixture, KOH (6.2 g) in water (65 ml) was
added dropwise over a period of 30 min and stirring was con-
tinued for 3 h. The mixture was left overnight at room tem-
perature then poured onto ice/water. The separated product
was filtered off◦and crystallized from ethanol. Yield (77%),
As an extension of the synthetic route, the behaviour
of 4 in construction of polyfunctionally substituted
pentaazaphenanthrenes was investigated. Thus, treat-
ing of 4 with oxalyl chloride in benzene under reflux-
ing condition gave pentaazaphenanthrene-2,3-diones
15 (Scheme 3). Similarly compound 4 was subjected to
the reaction with an equimolar amount of chloroacetyl
chloride in dry dioxane to furnish the corresponding
phenanthrene 16. The latter was allowed to react with
the appropriate aromatic aldehydes in the presence of
sodium acetate to afford 17a,b in good yields.
˜
m.p. 180 – 182 C. – IR: ν = 3220 (NH), 1690 – 1680 (CO),
1620 cm−1 (C=N). – 1H NMR (DMSO): δ = 6.92, 8.22 (2d,
J = 14 Hz, 2H, 2CH olefinic), 7.35 – 7.98 (m, 19H, Ar-H),
11.35 (s, 1H, NH, exchangeable). – MS: m/z(%) = 470 (62)
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

1230
Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
[M+.]. – C30H22N4O2: calcd. C 76.58, H 4.71, N 11.91; able). – 13C NMR: δ = 121.3 (C–6), 123.0 (C–4a), 139.8
found C 76.70, H 4.90, N 11.90.
(C–4), 150.2 (C–5), 153.2 (C–2), 155.8 (C–8a), 158.2 (C–
7). – MS: m/z(%) = 575 (41) [M+.]. – C34H25N9O: calcd.
C 70.94, H 4.38, N 21.90; found C 71.10, H 4.40, N 21.80.
2-Amino-6-{4-[5-oxo-2-phenyl-4-phenylhydrazono-4,5-di-
hydroimidazol-1-yl]phenyl}-4-phenylnicotinonitrile (2)
3-[4-(4-Imino-5-phenyl-3-substituted-3,4-dihydropyrido-
[2,3-d]pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydraz-
ono-3,5-dihydroimidazol-4-one (5a,b)
A mixture of an equimolar amount from 1 and mal-
ononitrile (0.01 mol) was refluxed in ethanol (20 ml) con-
taining ammonium acetate (0.01 mol) for 10 h. The solid
General procedure: A mixture of 3 (0.001 mol) and the
appropriate amine (0.001 mol) in ethanol (20 ml) was re-
fluxed for 12 h. The reaction mixture was poured onto ice wa-
ter and neutralized with dilute hydrochloric acid. The solid
product was filtered off, dried and crystallized from the ap-
propriate solvent.
product was triturated and crystallized from benzene. Yield
◦
˜
(62%), m.p. 301 – 303 C. – IR: ν = 3360, 3340 (NH2),
3200 (NH), 2230 (CN), 1690 (CO), 1610 cm−1 (C=N). –
1H NMR (DMSO): δ = 3.25 (s, 2H, NH2, exchangeable),
7.35 – 7.98 (m, 20H, Ar-H), 11.33 (s, 1H, NH, exchange-
able). – 13C NMR: δ = 110.5 (C–3), 114.4 (CN), 122.3 (C–
5), 148.8 (C–4), 155.1 (C=N.NH ), 157.3 (C–6), 160.0 (CO),
162.4 (C–2), 165.1 (C–2 imidaz.), 117.3, 119.4, 121.3, 127.2,
127.6, 128.4, 129.8, 129.8, 129.9, 130.0, 130.1, 133.8, 134.2,
137.6, 138.8, 145.6 (C–aromatic ). – MS: m/z(%) = 533 (56)
[M+.]. – C33H23N7O: calcd. C 74.28, H 4.34, N 18.38; found
C 74.00, H 4.50, N 18.20.
3-[4-(4-Imino-3-methyl-5-phenyl-3,4-dihydropyrido[2,3-d]-
pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-
dihydroimidazol-4-one (5a)
◦
˜
Yield (43%), m.p. 140 – 142 C (ethanol). – IR: ν =
3220 – 3190 (NH), 1670 cm−1 (CO). – 1H NMR (CDCl3):
δ = 3.51 (s, 3H, CH3), 5.80 (s, 1H, NH, exchangeable),
7.37 – 7.99 (m, 20H, Ar-H), 8.22 (s, 1H, pyrimi. H), 10.92 (s,
1H, NH, exchangeable). – MS: m/z(%) = 574 (28) [M+.]. –
C35H26N8O: calcd. C 73.16, H 4.56, N 19.50; found C 73.20,
H 4.70, N 19.50.
N-{3-Cyano-6-[4-(5-oxo-2-phenyl-4-phenylhydrazono-
4,5-dihydroimidazol-1-yl)phenyl]-4-phenylpyridin-2-yl}
formimidic ethyl ester (3)
To a solution of 2 (0.005 mol) in acetic anhydride (20 ml)
triethyl orthoformate (0.005 mol) was added. The reaction
mixture was refluxed for 5 h then poured onto cold water. The
solid product was collected by filtration, washed with water,
3-[4-(3-Benzyl-4-imino-5-phenyl-3,4-dihydropyrido[2,3-d]-
pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-
dihydroimidazol-4-one (5b)
dried and crystallized from benzene/petroleum ether (1:1).
◦
◦
˜
Yield (86%), m.p. 150 – 152 C. – IR: ν = 3160 (NH), 2220
˜
Yield (62%), m.p.190 – 192 C (ethanol). – IR: ν = 3220 –
1
(CN), 1685 (CO), 1615 cm−1 (C=N). – H NMR (CDCl3):
3180 (NH), 1670 cm−1 (CO). – 1H NMR (DMSO): δ = 5.58
(s, 1H, NH, exchangeable), 6.22 (s, 2H, CH2), 7.38 – 7.98
(m, 25H, Ar-H), 8.22 (s, 1H, pyrimi. H), 11.38 (s, 1H, NH,
exchangeable). – 13C NMR: δ = 53.3 (CH2), 121.5 (C–6),
123.1 (C–4a), 139.0 (C–4), 150.3 (C–5), 153.3 (C–2), 155.9
(C–8a), 158.3 (C–7). – MS: m/z(%) = 650 (22) [M+.]. –
C41H30N8O: calcd. C 75.67, H 4.65, N 17.22; found C 75.70,
H 4.50, N 17.00.
δ = 1.39 (t, J = 8.1 Hz, 3H, CH3), 4.7 (q, J = 8.1 Hz,
2H, CH2), 7.48 – 7.99 (m, 20H, Ar-H), 8.23 (s, 1H, olefinic
CH), 11.35 (s, 1H, NH, exchangeable). – 13C NMR: δ =
14.8 (CH3), 59.7(OCH2), 118.5 (CN), 122.0 (C–5), 130.3
(N=CH), 141.0 (C–3), 148.6 (C–4), 157.5 (C–6), 163.0 (C–
2). – MS: m/z(%) = 589 (53) [M+.]. – C36H27N7O2: calcd.
C 73.33, H 4.62, N 16.63; found C 73.10, H 4.70, N 16.60.
3-[4-(3-Amino-4-imino-5-phenyl-3,4-dihydropyrido[2,3-d]-
pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-
dihydroimidazol-4-one (4)
2-Phenyl-5-phenylhydrazono-3-[4-(5-phenyl-4-thioxo-
3,4-dihydropyrido[2,3-d]pyrimidin-7-yl)phenyl]-3,5-
dihydroimidazol-4-one (6)
To a solution of 3 (0.005 mol) in benzene (30 ml) hy-
To a solution of 3 (0.001 mol) in absolute ethanol (20 ml)
drazine hydrate (2 ml in 2 ml H2O) was added. The reac- sodium hydrogen sulfide (0.0011 mol) was added. The reac-
tion mixture was stirred for 45 min, then allowed to stand tion mixture was refluxed for 7 h then poured onto ice. The
overnight whereby the solid product was collected by fil- formed solid product was collected by filtration, dried and
◦
tration, dried and crystallized from benzene. Yield (71%), crystallized from AcOH. Yield (45%), m.p. 191 – 192 C.
◦
˜
˜
m.p. 221 – 223 C. – IR: ν = 3390 – 3320 (NH2), 3210 – 3180 – IR: ν = 3210 – 3190 (NH), 1680 (CO), 1610 (C=N),
(NH), 1690 (CO), 1620 cm−1 (C=N). – 1H NMR (DMSO): 1310 cm−1 (CS). – 1H NMR (DMSO): δ = 5.91 (s, 1H,
δ = 5.61 (s, 1H, NH, exchangeable), 7.35 – 7.99 (m, 20H, NH, exchangeable), 7.29 – 7.82 (m, 20H, Ar-H), 8.60 (s, 1H,
Ar-H), 8.23 (s, 1H, pyrimi. H), 11.22 (s, 1H, NH, exchange- pyrimi.), 10.91 (s, 1H, NH, exchangeable). – 13C NMR: δ =
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
1231
121.2 (C–6), 123.1 (C–4a), 150.4 (C–5), 154.0 (C–2), 156.1 7-[4-(5-Oxo-2-phenyl-4-phenylhydrazono-4,5-dihydro-
(C–8a), 158.3 (C–7), 173.2 (C–4). – MS: m/z(%) = 577 (44) imidazol-1-yl)phenyl]-9-phenyl-1,3,3a,5,6-pentaaza-
[M+.]. – C34H23N7OS: calcd. C 70.69, H 4.01, N 16.97; cyclopenta[a]napthalen-2-acetonitrile (10)
found C 70.90, H 4.00, N 17.00.
A mixture of 4 (0.005 mol) and ethyl cyanoacetate
(0.01 mol) in absolute ethanol (30 ml) was refluxed for 7 h.
The formed solid product was filtered off, dried and crys-
tallized from ethanol. Yield (56%), m.p. 205 – 206 ◦C. – I−R1:
(C=N). – 1H NMR (DMSO): δ = 4.20 (s, 2H, CH2), 7.35 –
7.99 (m, 20H, Ar-H), 9.26 (s, 1H, pyrimi. H), 11.32 (s, 1H,
NH, exchangeable). – 13C NMR: δ = 22.4 (CH2), 115.2
(CN), 120.6 (C–8), 122.1 (C–9a), 148.3 (C–9b), 150.2 (C–9),
157.0 (C–5a), 158.2 (C–7), 158.4 (C–4), 160.8 (C–2). – MS:
m/z(%) = 624 (33) [M+.]. – C37H24N10O: calcd. C 71.14,
H 3.87, N 22.42; found C 71.00, H 3.90, N 22.60.
3-[4-(4-Imino-3-phenylamino-5-phenyl-3,4-dihydro-
pyrido[2,3-d]pyrimidin-7-yl)phenyl]-2-phenyl-5-phenyl-
hydrazono-3,5-dihydroimidazol-4-one (7)
˜
ν = 3160 (NH), 2240 (CN), 1695 (CO amide), 1620 cm
To a solution of 3 (0.001 mol) in ethanol (20 ml) phenyl-
hydrazine (0.001 mol) was added. The reaction mixture was
refluxed for 3 h then poured onto ice water, filtered off,
dried and crystallized from benzene. Yield (58%), m.p. 203 –
◦
−1
˜
205 C. – IR: ν = 3210 – 3170 (NH), 1680 (CO), 1610 cm
(C=N). – 1H NMR (DMSO): δ = 5.56 (s, 1H, NH, exchange-
able), 7.39 – 7.98 (m, 25H, Ar-H), 8.21 (s, 1H, pyrimi.H),
9.93, 10.25 (2s, 2H, 2NH, exchangeable). – MS: m/z(%) =
651 (18) [M+.]. – C40H29N9O: calcd. C 73.72, H 4.49,
N 19.34; found C 73.90, H 4.30, N 19.40.
2-Phenyl-5-phenylhydrazono-3-[4-(9-phenyl-2-thioxo-2,3-
dihydro-1,3,3a,5,6-pentaazacyclopenta[a]naphthalene-
7-yl)phenyl]-3,5-dihydroimidazol-4-one (11)
To a solution of 4 (0.001 mol) in absolute ethanol (50 ml)
excess of carbon disulfide (5 ml) was added. The reaction
mixture was heated on water bath for 4 h. The formed
solid product was collected by filtration, dried and crystal-
lized◦from benzene/ethanol (3:1). Yield (65%), m.p. 190 –
(C=N), 1250 cm−1 (CS). – 1H NMR (DMSO): δ = 7.39 –
7.96 (m, 20H, Ar-H), 8.70 (s, 1H, NH, exchange-able), 9.27
(s, 1H, pyrimi.H), 11.32 (s, 1H, NH exchangeable). – MS:
m/z(%) = 617 (22) [M+.]. – C35H23N9OS: calcd. C 68.06,
H 3.75, N 20.41; found C 68.20, H 3.60, N 20.50.
7-{4-[5-Oxo-2-phenyl-4-phenylhydrazono-4,5-dihydro-
imidazol-1-yl]phenyl}-9-phenyl-1,3,3a,5,6-pentaaza-
cyclopenta[a]naphthalene-2-carboxylic acid ester (8)
A mixture of 4 (0.001 mol) and diethyl oxalate
(0.001 mol) in absolute ethanol (30 ml) was refluxed for
5 h. After cooling the formed solid product was filtered
off, dried and crystallized from ethanol. Yield (77%), m.p.
˜
192 C. – IR: ν = 3260 – 3200 (NH), 1692 (CO), 1610
◦
˜
251 – 253 C. – IR: ν = 3180 (NH), 1735 (CO ester), 1690
1
(CO amide), 1625 cm−1 (C=N). – H NMR (DMSO): δ =
1.37 (t, J = 8.2 Hz, 3H, CH3,), 4.36 (q, J = 8.2 Hz, 2H,
CH2), 7.47 – 7.99 (m, 20H, Ar-H), 9.22 (s, 1H, pyrimi. H),
10.98 (s, 1H, NH, exchangeable). – 13C NMR: δ = 14.4
(CH3), 62.4 (CH2), 121.2 (C–8), 123.0 (C–9a), 148.6 (C–
9b), 150.4 (C–9), 156.2 (C–5a), 156.8 (C–2), 158.2 (C–7),
158.8 (C–4), 167.3 (CO). – MS: m/z(%) = 657 (44) [M+.].
– C38H27N9O3: calcd. C 69.40, H 4.14, N 19.17; found
C 69.30, H 4.20, N 19.20.
N-{4-Imino-7-[4-(5-oxo-2-phenyl-4-phenylhydrazono-4,5-
dihydroimidazol-1-yl)-phenyl]-5-phenyl-4H-pyrido[2,3-d]-
pyrimidin-3-yl}-3-phenylurea (12)
To a solution of 4 (0.001 mol) in absolute ethanol (30 ml)
phenyl isocyanate (0.001 mol) was added, then the reaction
mixture was refluxed for 12 h. After cooling the formed
precipitate was filtered off, dried and crystallized from ben-
◦
˜
zene. Yield (58%), m.p. 268 – 269 C. – IR: ν = 3490 – 3200
(OH, NH), 1690 – 1680 cm−1 (CO). – 1H NMR (DMSO):
δ = 5.56, 6.35, 7.32 (3s, 3H, 3NH, exchangeable), 7.36 –
8.1 (m, 25H, Ar-H), 9.23 (s, 1H, pyrimi. H), 11.12 (s, 1H,
NH, exchangeable). – 13C NMR: δ = 121.6 (C–6), 123.3
(C–4a), 141.0 (C–4), 150.5 (C–5), 153.4 (C–2), 155.8 (C–
8a), 158.9 (C–7), 162.8 (CO). – MS: m/z(%) = 694 (20)
[M+.]. – C41H30N10O2: calcd. C 70.88, H 4.35, N 20.16;
found C 70.80, H 4.40, N 20.30.
Preparation of 9 from 8
A mixture of 8 (0.001 mol) and sodium hydroxide 10%
(20 ml) was refluxed for 5 h. After cooling the reaction mix-
ture was poured onto ice water and neutralized with dilute
hydrochloric acid. The formed solid product was filtered off,
dried and crystallized from benzene. Yield (54%), m.p. 180 –
◦
−1
˜
181 C. – IR: ν = 3470 (OH), 1705 (CO acid), 1685 cm
(CO amide). – 1H NMR (DMSO): δ = 7.38 – 7.87 (m, 20H,
Ar-H), 9.22 (s, 1H, pyrimi. H), 10.81, 12.9 (2s, 2H, NH, OH,
exchangeable). – 13C NMR: δ = 122.2 (C–8), 123.1 (C–9a),
148.9 (C–9b), 150.4 (C–9), 156.4 (C–5a), 158.1 (C–7), 158.3
(C–2), 158.6 (C–4), 174.5 (CO). – MS: m/z(%) = 629 (42)
[M+.]. – C36H23N9O3: calcd. C 68.67, H 3.68, N 20.02;
found C 68.70, H 3.50, N 20.00.
2-Phenyl-5-phenylhydrazono-3-[4-(9-phenyl-2-phenyl-
amino-1,3,3a,5,6-penta-azacyclopenta[a]naphthalene-
7-yl)phenyl]-3,5-dihydroimidazol-4-one (13)
Method A: To a solution of 4 (0.001 mol) in abso-
lute ethanol (30 ml) phenyl isothiocyanate (0.001 mol) was
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

1232
Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
added. The reaction mixture was refluxed for 20 h then left Method B
aside at room temperature whereby the solid product was col-
Equimolar amounts from 4 and triethyl orthoformate
lected by filtration, dried and crystallized from ethanol. Yield
(0.005 mol) were refluxed in DMF for 8 h. The solvent was
evaporated in vacuo and the resulting solid product was crys-
tallized to give 14a.
◦
˜
(53%), m.p. 240 – 243 C. – IR: ν = 3250 – 3200 (NH), 1690
(CO), 1620 cm−1 (C=N). – 1H NMR (DMSO): δ = 7.35
(s, 1H, NH, exchangeable), 7.41 – 7.98 (m, 25H, Ar-H), 9.25
(s, 1H, pyrimi. H), 11.11 (s, 1H, NH, exchangeable). – MS:
m/z(%) = 676 (38) [M+.]. – C41H28N10O: calcd. C 72.77,
H 4.17, N 20.70; found C 72.80, H 4.20, N 20.60.
7-[4-(5-Oxo-2-phenyl-4-phenylhydrazono-4,5-dihydro-
imidazol-1-yl)phenyl]-5-phenyl-1,4,8,9,10a-pentaaza-
phenanthrene-2,3-dione (15)
Method B: To a solution of 12 (0.001 mol) in ethanol
(30 ml) concentrated hydrochloric acid (3 ml) was added,
then the reaction mixture was refluxed for 4 h. After cooling
the formed precipitate was collected by filtration, washed,
dried and crystallized.
To a solution of 4 (0.003 mol) in dry benzene (30 ml) ox-
alyl chloride (3 ml) was added and the reaction mixture was
refluxed for 9 h. After cooling the solid product was collected
by filtration, dried and crystallized from acetic acid. Yield
◦
˜
(62%), m.p. 236 – 238 C. – IR: ν = 3400 – 3250 (OH, NH),
1690 – 1680 (CO), 1622 cm−1 (C=N). – 1H NMR (DMSO):
δ = 7.39 (s, 1H, NH, exchangeable), 7.55 – 7.76 ( m, 20H,
Ar-H), 8.21 ( s, 1H, pyrimi. H), 11.29 (s, 1H, NH, exchange-
able). – 13C NMR: δ = 122.3 (C–6), 123.0 (C–4b), 150.1
(C–5), 150.7 (C–4a), 154.0 (CO), 156.2 (C–8a), 157.8 (C–
7), 158.3 (CO), 158.9 (C–10). – MS: m/z(%) = 629 (61)
[M+.]. – C36H23N9O3: calcd. C 68.67, H 3.68, N 20.02;
found C 68.80, H 3.70, N 20.00.
3-[4-(2-Alkyl-9-phenyl-1,3,3a,5,6-pentaazacylopenta[a]-
naphthalene-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-
3,5-dihydroimidazol-4-one (14a,b)
General procedure
Method A
A mixture of 4 (0.001 mol) and excess of the appropriate
carboxylic acid (15 ml) was refluxed for 10 h. After cooling
and dilution with water the precipitate was filtered off, dried
and crystallized from the appropriate solvent to give 14a,b.
7-[4-(5-Oxo-2-phenyl-4-phenylhydrazono-4,5-dihydro-
imidazol-1-yl)phenyl]-5-phenyl-3H-1,4,8,9,10a-pentaaza-
phenanthren-2-one (16)
A mixture of 4 (0.004 mol) and chloroacetyl chloride
(0.004 mol) in dry dioxane (40 ml) was allowed to stand at
room temperature overnight. The formed precipitate was fil-
tered off, dried◦and crystallized from dioxane. Yield (66%),
1685 (CO), 1615 cm−1 (C=N). – 1H NMR (DMSO): δ =
5.21 (s, 2H, CH2), 7.41 (s, 1H, NH, exchangeable), 7.56 –
7.99 (m, 20H, Ar-H), 8.22 (s, 1H, pyrimi.H), 11.26 (s, 1H,
NH, exchangeable). – 13C NMR: δ = 55.8 (CH2), 121.8 (C–
6), 123.1 (C–4b), 150.2 (C–5), 150.3 (C–4a), 154.4 (CO),
156.8 (C–8a), 157.6 (C–7), 158.8 (C–10). – MS: m/z(%) =
615 (51) [M+.]. – C36H23N9O2: calcd. C 70.23, H 4.09,
N 20.48; found C 70.40, H 4.10, N 20.50.
2-Phenyl-5-phenyhydrazono-3-[4-(9-phenyl-1,3,3a,5,6-
pentaazacyclopenta[a]naphthalene-7-yl)phenyl]-3,5-
dihydroimidazol-4-one (14a)
◦
˜
m.p. 281 – 283 C. – IR: ν = 3370 – 3220 (OH, NH), 1690 –
˜
Yield (67%), m.p. 270 – 272 C (benzene). – IR: ν = 3200
(NH), 1685 (CO), 1620 – 1615 cm−1 (C=N). – 1H NMR
(DMSO): δ = 7.38 – 8.20 (m, 21H, Ar-H + triazine H), 9.31
(s,1H, pyrimi. H), 11.02 (s, 1H, NH, exchangeable). – 13C
NMR: δ = 121.0 (C–8), 122.0 (C–9a), 139.3 (C–2), 148.0
(C–9b), 150.2 (C–9), 156.6 (C–5a), 157.9 (C–7), 158.7 (C–
4). – MS: m/z(%) = 585 (23) [M+.]. – C35H23N9O: calcd.
C 71.78, H 3.96, N 21.53; found C 71.80, H 4.10, N 21.50.
3-[4-(2-Methyl-9-phenyl-1,3,3a,5,6-pentaazacyclopenta[a]-
naphthalene-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-
dihydroimidazol-4-one (14b)
3-Arylidene-7-[4-(5-oxo-2-phenyl-4-phenylhydrazono-4,5-
dihydroimidazol-1-yl)phenyl]-5-phenyl-3H-1,4,8,9,10a-
pentaazaphenanthren-2-one (17a,b)
◦
Yield (63%), m. p. 236 – 238 C (benzene). – 1H NMR
General procedure
(DMSO): δ = 2.6 (s, 3H, CH3), 7.38 – 8.0 (m, 20H, Ar-H),
9.22 (s, 1H, pyrimi.H), 11.22 (s, 1H, NH, exchangeable).
A mixture of 4 (0.002 mol) and the appropriate aromatic
–
13C NMR: δ = 22.1 (CH3), 121.1 (C–8), 122.2 (C–9a), aldehyde (0.002 mol) was refluxed for 6 h in acetic acid
136.9 (C–2), 148.1 (C–9b), 149.8 (C–9), 156.6 (C–5a), 157.7 (20 ml) containing anhydrous sodium acetate (1 g). The re-
(C–7), 158.2 (C–4). – MS: m/z(%) = 599 (31) [M+.]. – action mixture left aside whereby the solid product was col-
C36H25N9O: calcd. C 72.11, H 4.20, N 21.02; found C 72.30, lected by filtration, washed thoroughly with water, dried and
H 4.30, N 21.00.
crystallized from the appropriate solvent.
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM

Y. A. Issac – A. A. Aly · New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates
1233
3-Benzylidene-7-[4-(5-oxo-2-phenyl-4-phenylhydrazono-
4,5-dihydro-imidazol-1-yl)phenyl]-5-phenyl-3H-
1,4,8,9,10a-pentaazaphenanthren-2-one (17a)
3-(3-Nitrobenzylidene)-7-[4-(5-oxo-2-phenyl-4-phenyl-
hydrazono-4,5-dihydroimidazol-1-yl)phenyl]-5-phenyl-
3H-1,4,8,9,10a-pentaazaphenanthren-2-one (17b)
◦
◦
˜
Yield (76%), m.p. 292 – 294 C (ethanol). – IR: ν =
3390 – 3210 (OH, NH), 1690 (CO), 1620 cm−1 (C=N). –
1H NMR (DMSO): δ = 7.53 – 7.99 (m, 24H, Ar-H), 7.82
(s, 1H, NH, exchangeable), 8.16 (s, 1H, olefinic H), 8.22
(s, 1H, pyrimi.H), 10.38 (s, 1H, NH, exchangeable). – MS:
m/z(%) = 748 (21) [M+.]. – C43H28N10O4: calcd. C 68.98,
H 3.77, N 18.71; found C 68.80, H 3.90, N 18.60.
˜
Yield (56%), m.p. 265 – 267 C (ethanol). – IR: ν =
3390 – 3200 (OH, NH), 1685 (CO), 1620 cm−1 (C=N). –
1H NMR (DMSO): δ = 7.53 – 7.98 (m, 25H, Ar-H), 7.81
(s, 1H, NH, exchangeable), 8.15 (s, 1H, olefinic H), 8.22
(s, 1H, pyrimi.H), 10.39 (s, 1H, NH, exchangeable). – 13C
NMR: δ = 121.9 (C–6), 123.2 (C–4b), 128.0 (CHAr‘),
134.3 (C=CHAr‘), 150.3 (C–5), 150.5 (C–4a), 154.3 (CO),
156.9 (C–8a), 158.0 (C–7), 159.2 (C–10), 127.7, 129.8,
130.3, 133.9 (C–Ar‘). – MS: m/z(%) = 703 (51) [M+.].
– C43H29N9O2: calcd. C 73.39, H 4.15, N 17.91; found
C 73.50, H 4.30, N 17.90.
Acknowledgement
All strains were kindly supplied from Botany Department,
Faculty of Science, Benha University, Benha, Egypt.
[10] Y. A. Issac, Bull. Chem.. Soc. Jpn. 72, 503 (1999).
[11] Y. A.Issac, Sulfur Lett. 23, 287 (2000).
[12] Y. A. Issac, E. G. El-Karim, G. D. Shafie, S. B. Mo-
hamed, Sulfur Lett. 25, 183 (2002).
[13] Y. A. Issac, Z. Naturforsch. 54b, 1048 (1999).
[14] M. H. Arsanious, Y. A. Issac, L. S. Boulous, Het-
eroatom Chem. 12(7), 594 (2001).
[1] J. W. Bae, S. H. Lee, Y. Cho, Y. J. Jung, H. J. Hwang,
C. M. Yoon, Teterahedron Lett. 41, 5899 (2000).
[2] J. Quiroga, A. Hormaza, B. Insuasty, M. Nogueras,
A. Sanchez, N. Hanold, H. Meier, J. Heterocyclic
Chem. 34, 521 (1997).
[3] S. Youssef, S. El-Bahaie, E. Nabih, J. Chem. Research
(s) 521 (1999).
[15] A. H. Harhash, M. H. El Nagdi, A. A. El Banani, Tetra-
hedron 31, 25 (1975).
[16] J. J. Figueras, J. Org. Chem. 31, 803 (1966).
[17] H. Yamanka, S. Ohba, S. Konnos, Heterocycles, 26,
2856 (1987).
[4] N. Suzki, Chem. Pharm. Bull. 28, 761 (1980).
[5] A. Gangjee, A. Vasudevan, F. Queener, R. Kisliuk, J.
Med. Chem. 38, 1778 (1995).
[6] A. Gangjee, U.S. Patent 5, 508, 281 (1996), Chem. Ab-
str. 125, 33667a (1996).
[18] S. S. Sangapoure, Y. S. Agasimundin, Indian J. Chem.
19B, 115 (1980).
[7] S. A. K. Sharma, L. Prakash, Heterocyclic Commun. 1,
89 (1994).
[19] C. Leifert, S. Chidbouree, S. Hampson, S. Workman,
D. Sigee, H. A. S. Epton, A. Harbour, J. Appl. Bact.
78, 97 (1995).
[8] A. Monge, V. Martinez, C. Sanmartin, M. A. Simon,
Spanish Patent E S 2, 056, 742 (1994), Chem. Abstr.
122, 105912q (1995).
[9] G. Hou, D. Gravier, F. Casadebaig, J. Dupin,
H. Bernard, M. Boiseau, Pharmazie 50, 719 (1995).
Brought to you by | University of California
Authenticated
Download Date | 1/15/16 2:36 AM