Synthesis of some novel polyaza fused heterocyclic compounds

Article abstract of DOI:10.1002/jhet.329

(Chemical Equation Presented) 2-(1-Aryl-ethylidene)-malononitriles 1a-d undergo self dimerization in ethanol catalyzed by sodium ethoxide to afford 2-[4,6-diaryl-3-cyano-6-methyl-5,6-dihydropyridin-2(1H)-ylidene]-malononitrile derivatives 3a-d, respectively. The structure of the dimer was elucidated by X-ray crystallography and a plausible mechanism for its formation is depicted. Compound 3a couples with arene diazonium salts 4a-d to afford the hydrazo derivatives 5a-d; and reacts with hydrazine hydrate and phenylhydrazine 6a,b to afford the pyrazolo[3,4-h][1,6]naphthyridine derivatives7a,b; and with urea and thiourea 8a,b to afford the pyrimido[4,5-h][1,6]naphthyridine derivatives 9a,b, respectively.

Full text of DOI:10.1002/jhet.329

384
Synthesis of Some Novel Polyaza Fused Heterocyclic Compounds
Fathy M. Abdelrazek,a* Nadia H. Metwally,a Nazmi A. Kassab,a
Vol 47
Nehal A. Sobhy [1],a Peter Metz,b and Anna Jaegerb
aChemistry Department, Faculty of Science, Cairo University, Giza, Egypt
bInstitute of Organic Chemistry, Technical University of Dresden, 01069 Dresden, Germany
*E-mail: prof.fmrazek@gmail.com
Received September 15, 2009
DOI 10.1002/jhet.329
Published online 4 March 2010 in Wiley InterScience (www.interscience.wiley.com).
2-(1-Aryl-ethylidene)-malononitriles 1a-d undergo self dimerization in ethanol catalyzed by sodium
ethoxide to afford 2-[4,6-diaryl-3-cyano-6-methyl-5,6-dihydropyridin-2(1H)-ylidene]-malononitrile deriv-
atives 3a-d, respectively. The structure of the dimer was elucidated by X-ray crystallography and a
plausible mechanism for its formation is depicted. Compound 3a couples with arene diazonium salts
4a-d to afford the hydrazo derivatives 5a-d; and reacts with hydrazine hydrate and phenylhydrazine
6a,b to afford the pyrazolo[3,4-h][1,6]naphthyridine derivatives7a,b; and with urea and thiourea 8a,b to
afford the pyrimido[4,5-h][1,6]naphthyridine derivatives 9a,b, respectively.
J. Heterocyclic Chem., 47, 384 (2010).
INTRODUCTION
RESULTS AND DISCUSSION
Pyridines and pyrido-fused derivatives are important
heterocyclic compounds that find many pharmaceutical
and agrochemical applications [2–6]. In the last two
decades, we have been involved in a program aiming to
develop new simple routes for the synthesis of heterocy-
clic compounds of biological interest [7–18]. In the con-
text of this program, some newly substituted pyridines
and pyrido-fused heterocyclic derivatives were required
for biological evaluation. 2-(1-Arylethylidene)-malono-
nitrile derivatives 1a-d seemed good candidates to fulfill
this objective via their dimerization through the interme-
diate A to afford the pyridine-imine derivatives 2a-d
and then coupling of these expected pyridine derivatives
(Scheme 1) with arene diazonium salts followed by cy-
clization of the products to afford pyrido[3,2-c]pyrida-
zine derivatives.
Thus 2-(1-phenyl-ethylidene)-malononitrile derivative
1a (obtained from the condensation of acetophenone
with malononitrile according to the literature method)
[19] was refluxed in ethanol catalyzed by sodium ethox-
ide and we could isolate an analytically pure product
with mp 202ꢀC and in quantitative yield. The mass
spectrum of this obtained product showed a molecular
ion peak at m/z ¼ 336; which points out to a dimer of
1a. Theoretically different possible structures can be
assumed for this dimmer, however, based on the spectral
data it was thought that we have obtained the pyridine-
1
imine derivative 2a (Scheme 1). The H NMR spectrum
of this product revealed signals at d 1.74 (s, 3H,) assign-
able to one methyl group, 3.33 (d, 1H; J ¼ 18.6 Hz),
3.75 (d, 1H; J ¼ 18.6 Hz) assignable to two chemically
nonequivalent protons of
a methylene group and
C
V
2010 HeteroCorporation

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Synthesis of Some Novel Polyaza Fused Heterocyclic Compounds
385
Scheme 1. Preparation of compounds 3a-d.
aromatic multiplet (10H) at 7.29–7.56 beside an
exchangeable singlet (1H) at d 8.55 ppm assignable to
NH. These H NMR data seemed applicable to a struc-
tral and analytical data are now completely applicable to
this structure and also those of the hydrazo derivatives
5a-d (cf. Schemes 1 and 2 and the Experimental section).
It is assumed that the ethoxide anion abstracts one
proton from 1 to afford the anion B, which is electroni-
cally rearranged to the keteneimine C. This latter attacks
another molecule of 1 at the C¼¼C to afford D, which
undergoes rearrangement with migration of the malonyl
anion to the C¼¼N to afford E. Such rearrangement in
the keteneimine series are known in the literature [23].
The intermediate E undergoes cyclization and regains
its lost proton to afford the final isolable product 3a.
The cyclization of alkylidenemalononitriles under Mi-
chael reaction conditions is reported also to afford pyri-
dine derivatives [24].
1
ture like 2a. However the 13C NMR spectrum of this
reaction product revealed 18 signals at dC ¼ 28.3 (q);
44.02 (t); 49.45 (s), 56.94 (s); 101.03 (s); 113.68 (s);
114.86 (s); 115.42 (s); [124.81 (d), 127.51 (d), 128.15
(d), 128.64 (d), 128.85 (d), 132.04 (d), 135.41 (s),
142.73 (s) phenyl carbons], 157.73 (s), 168.85 (s). (cf.
Scheme 1 and Experimental section). These 13C NMR
values are not completely applicable to structure 2a.
Furthermore, when this product was allowed to couple
with the diazotized aromatic amines 4a-d (aniline,
p-chloroaniline, p-toluidine and p-anisidine) it afforded
highly colored hydrazo derivatives analyzed correctly as
derivatives of 2a; however, trials to cyclize these
hydrazo derivatives into the expected pyrido[3,2-c]pyrid-
azine derivatives failed under the different conditions
reported to effect such cyclizations[14,20]. This behav-
ior led us to the fact that the hydrazo group is not in the
vicinity of the cyano group and the structure is not 2a.
Thus it was mandatory to have an X-ray crystallo-
graphic picture of this compound. Fortunately, we could
obtain this X-ray [21,22] (Fig. 1). It shows clearly that
the cyano groups are located far away from the hydrazo
groups attached to the active methylene and that the
methyl and one phenyl group are attached to the same
carbon (C-2). The X-ray picture shows also that the
structure appears with one molecule of ethyl acetate; the
crystallization solvent. Thus structure 3a was unambigu-
ously established for this product (Scheme 1). All spec-
The
ethylidenemalononitrile
derivatives
1b-d
(obtained from the condensation of the corresponding
aryl methyl ketone with malononitrile according to liter-
ature method) [19] followed the same pathway under
the same reaction conditions, and we could obtain the
pyridine derivatives 3b-d, respectively (Scheme 1). All
analytical and spectral data are in complete agreement
with their proposed structures (cf. Experimental).
It is worth to mention that this dimerization of 1 to
give 3 could be catalyzed by aqueous NaOH in ethanol,
aqueous Na2CO3 in ethanol, or NaOEt in ethanol. All
these led to the same product in each case however the
maximum yields and the cleanest products were
achieved with NaOEt.
Although the obtained products are not the same
which we expected, however these products were found
Journal of Heterocyclic Chemistry
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386
F. M. Abdelrazek, N. H. Metwally, N. A. Kassab, N. A. Sobhy, P. Metz, and A. Jaeger
Vol 47
9a,b, respectively. It is apparent that the hydrazines and
ureas undergo cycloaddition to the two gem cyano
groups with the aid of the labile hydrogen of the pyri-
dine NH followed by further addition of the resulting
NH2 to the 5-cyano group.
The IR spectra of compounds 7a,b and 9a,b are all
void of any cyano absorption bands at the region of
tmax¼ 1980–2240 cmꢁ1. All spectral and analytical data
are in complete agreement with these structures (cf.
Experimental).
CONCLUSION
We could prepare some novel heterocyclic derivatives
of biological interest. All the reactions were carried out
using simple and clean eco-friendly synthetic methods.
No heavy metals or hazardous solvents are involved:
just ethanol, DMF, or water as solvents, sodium salts
are used as a catalyst.
Figure 1. X-ray crystallographic structure of compound 3a [21,22].
suitable also to fulfill our objective. Recently pyrazoles
were found to be potentially biologically active com-
pounds [25–27]. Also naphthyridine derivatives repre-
sent an important class of heterocyclic compounds due
to their marked wide range of biological activities, such
as anticonvulsant, antibacterial, anticancer, insecticidal,
and fungicidal effects [28–31]. Thus, in continuation
with our interest in naphthyridine synthesis [32], we
describe here the synthesis of some novel fused naph-
thyridine derivatives.
EXPERIMENTAL
Melting points were determined on an electrothermal (9100)
apparatus and are uncorrected. IR spectra were recorded as
KBr pellets on a Perkin Elmer 1430 spectrophotometer. The
1H NMR and 13C NMR spectra were taken on a Varian Gem-
ini 300 MHz spectrometer in DMSO-d6 using TMS as internal
standard and chemical shifts are expressed in d (ppm) values.
Mass spectra were taken on a Shimadzu GCMS-GB 1000 PX
(70 eV). Elemental analyses were carried out by the Microana-
lytical Center at Cairo University. The X-ray crystallography
was carried out in the Institute of Organic Chemistry, Techni-
cal University of Dresden, Germany.
Thus compound 3a reacts with hydrazine hydrate and
phenyl hydrazine 6a,b to afford the pyrazolo-naphthyri-
dine derivatives 7a,b, respectively.
Compound 3a reacts also with the urea derivatives
8a,b to afford the pyrimido-naphthyridine derivatives
Scheme 2. Preparation of compounds 5, 7, and 9.
Journal of Heterocyclic Chemistry
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Synthesis of Some Novel Polyaza Fused Heterocyclic Compounds
387
3.37 (s, 1H, J ¼ 18.6 Hz), 3.65 (s, 3H, CH3), 3.74 (s, 3H,
CH3), 7.24–7.44 (m, 8H, Ar. H), 9.66 (s, 1H D2O exchange-
able, NH).
Anal. Calcd. for C24H20N4O2 (396.44): C 72.71, H 5.08, N
14.13. Found: C 72.75, H 5.15, N 14.20.
The dimerization of 2-(1-aryl-ethylidene)-malononitrile
derivatives 1a-d: [Preparation of 3a-d]. To a solution of
each of 1a-d (10 mmol) in 15 mL of absolute ethanol was
added 2 mL of saturated sodium ethoxide solution (obtained
by dissolving 0.1 g of sodium metal in the least amount of
absolute ethanol). The reaction mixture was refluxed on a
water bath for 1 h, then left to cool to room temperature and
poured on ice cold water and acidified with drops of conc.
HCl till just neutral. The precipitated solids were collected by
filtration, washed with water, dried, and recrystallized to afford
3a-d, respectively.
2-(3-Cyano-6-methyl-4,6-diphenyl-5,6-dihydropyridin-2(1H)-
ylidene)-malononitrile 3a. Yellow crystals; yield (3.26 g;
96%), mp: 201–203ꢀC (EtOH/DMF). IR: tmax (cmꢁ1) 3445 &
3260 (NH), 2213, 2214, 2217 (3CN). MS, m/z ¼ 336 [Mþ];
dH: 1.74 (s, 3H, CH3), 3.33 (d, 1H; J ¼ 18.6 Hz), 3.75 (d, 1H;
J ¼ 18.6 Hz), 7.29–7.56 (m, 10H, 2Ph), 8.55 (s, 1H D2O
exchangeable, NH). dC ¼ 28.3 (q); 44.02 (t); 49.45 (s), 56.94
(s); 101.03 (s); 113.68 (s); 114.86 (s); 115.42 (s); [124.81 (d),
127.51 (d), 128.15 (d), 128.64 (d), 128.85 (d), 132.04 (d),
135.41 (s), 142.73 (s) phenyl carbons], 157.73 (s), 168.85 (s).
X-ray crystallographic data [21,22]: Yellow crystals,
C22H16N4*C4H8O2 (Mr ¼ 424.49 g molꢁ1), monoclinic, space
Azo coupling of 3a with arene diazonium chloride deriv-
atives 4a-d. Arene diazonium salts 4a-d (0.01 mol) were
freshly prepared by adding a solution of 0.01 mol of sodium
nitrite in 5 mL H2O to a cold solution of the hydrochloride
(0.01 mol) of the respective aryl amine: (aniline, p-chloroani-
line, p-toluidine, or p-anisidine, respectively, in 5 mL conc.
HCl) with stirring. The resulting solutions of the aryl diazo-
nium salts were added to a cold solution of 3a (0.01 mol), in
ethanol (35 mL) containing sodium acetate (2 g). The reaction
mixture was stirred at room temperature for 1 h in each case
and the solid products, so formed, were collected by filtration
and recrystallized from ethanol/DMF.
2-(3-Cyano-6-methyl-4,6-diphenyl-5-(2-phenylhydrazono)-5,6-
dihydropyridin-2(1H)-ylidene)-malononitrile 5a. Reddish brown
powder; yield (3.78 g; 85 %), mp: 195–197ꢀC (EtOH/DMF).
IR: tmax (cmꢁ1) 3372, 3307 and 3229 (NH), 2207–2215 (CN).
MS, m/z ¼ 441 [Mþþ1]; dH: 1.94 (s, 3H, CH3), 6.89–7.54 (m,
15H, Ar. H), 9.51 (s, 1H D2O exchangeable, NH), 10.02 (s,
1H, D2O exchangeable, hydrazone NH).
˚
˚
group P21/n (No. 14), a [A] ¼ 10.637(2), b [A] ¼ 19.286(4),
ꢀ
ꢀ
ꢀ
˚
Anal. Calcd. for C28H20N6 (440.50): C 76.35, H 4.58, N
19.08. Found: C 76.40, H 4.55, N 19.05.
c[A] ¼ 12.072(2), a[ ] ¼ 90.00, b[ ] ¼ 113.27(3), c[ ] ¼
90.00; V[A ] ¼ 2282.8(9), Z ¼ 4, Dcalc ¼ 1.235 g cmꢁ3
,
3
˚
F(000) ¼ 896 e, l(Mo Ka) ¼ 0.080 cmꢁ1; the final difference
2-(5-(2-(4-Chlorophenyl)-hydrazono)-3-cyano-6-methyl-4,6-
diphenyl-5,6-dihydropyridin-2(1H)-ylidene)-malononitrile 5b.
Dark red crystals; yield (4 g; 86%), mp: 234–235ꢀC (EtOH/
DMF). IR: tmax (cmꢁ1) 3338, 3290, and 3231 (NH), 2208–
2217 (CN). dH: 1.98 (s, 3H, CH3), 6.49–7.72 (m, 14H, Ar. H),
9.63 (s, 1H D2O exchangeable, NH), 10.07 (s, 1H, D2O
exchangeable, hydrazone NH).
Anal. Calcd. for C28H19ClN6 (474.94): C 70.81, H 4.03, Cl
7.46, N 17.69. Found: C 70.85, H 4.13, Cl 7.56, N 17.60.
2-[3-Cyano-6-methyl-4,6-diphenyl-5-(2-(4-tolyl-hydrazono))-
Fourier q ¼ 0.45 (ꢁ0.39) e Aꢁ3.crystal size ¼ 0.35 mmꢁꢂ1
˚
˚
0.13 mm ꢂ 0.07 mm. Max. resolution [sin y/kmax] ¼ 0.61 A
/
99.8%. Data were collected using a Bruker Nonius area detec-
tor at T[ꢀC]¼ꢁ75(2), with graphite monochromator with Mo
˚
Ka radiation (k ¼ 0.71073 A) using the CCD data collection
and SADABS absorption correction method; min. 85.1%; max
99.4%. Total No. of reflections are 57431, No. of independent
reflections 4201 were counted with observed reflections 2726.
No. of refined parameters 312/10 restrains. Rav¼ 0.099. The
2
5,6-dihydropyridin-2(1H)-ylidene]-malononitrile
5c. Brown
final R¼ 0.067 and RW ¼ 0.177 with error of fit 1.048.
crystals; yield (3.77 g; 83%), mp: 225–227ꢀC (EtOH/DMF).
IR: tmax (cmꢁ1) 3336, 3291, and 3233 (NH), 2205–2216 (CN).
dH: 1.93 (s, 3H, CH3), 2.34 (s, 3H, CH3), 6.86–7.73 (m, 14H,
Ar. H), 9.65 (s, 1H D2O exchangeable, NH), 10.05 (s, 1H,
D2O exchangeable, hydrazone NH).
Anal. Calcd. for C22H16N4 (336.39): C 78.55, H 4.79, N
16.66. Found: C 78.50, H 4.90, N 16.80.
2-[3-Cyano-4,6-bis-(4-chlorophenyl)-6-methyl-5,6-dihydro-
pyridin-2(1H)-ylidene]-malononitrile 3b. Deep green powder;
yield (3.93 g; 97%), mp: 158–160ꢀC (EtOH). IR: tmax (cmꢁ1
)
Anal. Calcd. for C29H22N6 (454.53): C 76.63, H 4.88, N
18.49. Found: C 76.65, H 4.90, N 18.55.
3442 & 3230 (NH), 2211–2117 (3CN). dH: 1.72 (s, 3H, CH3),
3.38 (d, 1H; J ¼ 18.5 Hz), 3.74 (d, 1H; J ¼ 18.5 Hz), 7.33–
7.63 (m, 8H, Ar. H), 9.71 (s, 1H D2O exchangeable, NH).
Anal. Calcd. for C22H14 Cl2N4 (405.28): C 65.20, H 3.48,
Cl 17.50, N 13.82. Found: C 65.35, H 3.55, Cl 17.80, N 13.90.
2-[3-Cyano-4,6-bis-(4-methylphenyl)-6-methyl-5,6-dihydro-
pyridin-2(1H)-ylidene]- malononitrile 3c. Brown powder; yield
(3.20 g; 88%), mp: 169–172ꢀC (EtOH). IR: tmax (cmꢁ1) 3442
& 3230 (NH), 2218–2224 (3CN). MS, m/z¼ 364 [Mþ]; dH:
1.74 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.26
(d, 1H, J ¼ 18.6 Hz), 3.36 (d, 1H; J ¼ 18 Hz), 7.05–7.42 (m,
8H, Ar. H), 9.65 (s, 1H D2O exchangeable, NH).
2-[3-Cyano-6-methyl-4,6-diphenyl-5-(2-(4-methoxyphenyl)-
hydrazono)-5,6-dihydropyridin-2(1H)-ylidene]-malononitrile
5d. Light brown crystals; yield (3.99 g; 85%), mp: 237–239ꢀC
(EtOH/DMF). IR: tmax (cmꢁ1) 3335, 3292, and 3232 (NH),
2208 & 2219 (CN). dH: 1.89 (s, 3H, CH3), 3.69 (s, 3H, CH3),
6.95–7.50 (m, 14H, Ar. H), 9.66 (s, 1H D2O exchangeable,
NH), 10.02 (s, 1H, D2O exchangeable, hydrazone NH).
Anal. Calcd. for C29H22N6O (470.52): C 74.03, H 4.71, N
17.86. Found: C 74.10, H 4.76, N 17.92.
The reaction of 3a with hydrazine hydrate and phenyl
hydrazine 6a,b. To a solution of 3a (0.01 mol) in ethanol (20
mL) was added 0.01 mol of either hydrazine hydrate 6a or
phenyl hydrazine 6b. The reaction mixture was refluxed for 2h
in each case, left overnight. The reaction mixture was then
poured on ice cold water and acidified with dil. HCl till just
neutral. The precipitated solids were filtered off and recrystal-
lized from ethanol.
Anal. Calcd. for C24H20N4 (364.44): C 79.10, H 5.53, N
15.37. Found C 79.25, H 5.55, N 15.60.
2-[3-Cyano-4,6-bis-(4-methoxyphenyl)-6-methyl-5,6-dihydro-
pyridin-2(1H)-ylidene]-malononitrile 3d. Coffee brown pow-
der; yield (3.72 g; 94%), mp: 181–183ꢀC (EtOH). IR: tmax
(cmꢁ1) 3443 & 3232 (NH), 2215–2226 (3CN). MS, m/z¼ 397
[Mþþ1]; dH: 1.70 (s, 3H, CH3), 3.29 (d, 1H, J ¼ 18.6 Hz),
Journal of Heterocyclic Chemistry
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F. M. Abdelrazek, N. H. Metwally, N. A. Kassab, N. A. Sobhy, P. Metz, and A. Jaeger
Vol 47
G., Eds.; Mc Graw-Hill Health Professions Divisions: New York,
1996; p 759.
2-Methyl-2,4-diphenyl-3,8-dihydro-2H-pyrazolo[3,4-h][1,6]
naphthyridine-5,9-diamine 7a. Yellow crystals; yield (2.9 g;
80%), mp: 120–122ꢀC (EtOH). IR: tmax (cmꢁ1) 3330, 3286–
3231 (NH & NH2). MS, m/z ¼ 368 [Mþ]; dH: 1.89 (s, 3H,
CH3), 3.32 (d, 1H; J ¼ 18.65 Hz), 3.45 (d, 1H; J ¼ 18.65
Hz), 6.60 (br. s, 4H, 2NH2), 7.15–7.56 (m, 10H, 2Ph), 11.65
(s, 1H D2O exchangeable, NH).
[5] Mizuta, E.; Nishikawa, K.; Omura, K.; Oka, Y. Chem
Pharm Bull 1976, 24, 2078.
[6] Kuczynski, L.; Leonard, M.; Aleksander, A.; Banaszkie-
wicz, W.; Responds, S. Pol J Pharmacol Pharm 1983, 34, 223.
[7] Abdelrazek, F. M.; Salah El-Din, A. M.; Mekky, A. E.
Tetrahedron 2001, 57, 1813.
Anal. Calcd. for C22H20N6 (368.43): C 71.72, H 5.47, N
22.81. Found: C 71.75, H 5.52, N 22.87.
[8] Abdelrazek, F. M.; Salah El-Din, A. M.; Mekky, A. E. Tet-
rahedron 2001, 57, 6787.
2-Methyl-2,4,8-triphenyl-3,8-dihydro-2H-pyrazolo[3,4-h][1,6]
naphthyridine-5,9-diamine 7b. Yellow crystals; yield (3.46 g;
78%), mp: 128–129ꢀC (EtOH). IR: tmax (cmꢁ1) 3333, 3285
(NH2). MS, m/z ¼ 444 [Mþ]; dH: 1.76 (s, 3H, CH3), 3.22 (d,
1H; J ¼ 18.65 Hz), 3.46 (d, 1H; J ¼ 18.65 Hz), 6.56 (br. s,
4H, 2NH2), 6.75–7.55 (m, 15H, 3Ph).
[9] Abdelrazek, F. M.; Metwally, N. H. Afinidad 2003, 60,
554.
[10] Abdelrazek, F. M.; Metz, P.; Farrag, E. K. Arch Pharm
Pharm Med Chem (weinheim) 2004, 337, 482.
[11] Abdelrazek, F. M. Synth Commun 2005, 35, 2251.
[12] Abdelrazek, F. M.; Michael, F. A. J Heterocycl Chem 2006,
43, 7.
Anal. Calcd. for C28H24N6 (444.53): C 75.65, H 5.44, N
18.91. Found: C 75.68, H 5.50, N 19.03.
[13] Abdelrazek, F. M.; Metwally, N. H.; Synth Commun 2006,
36, 83.
The reaction of 3a with urea and thiourea 8a,b. To a so-
lution of 3a (0.01 mol) in ethanol (20 mL) was added 0.01
mol of either urea 8a or thiourea 8b followed by few drops of
triethylamine. The reaction mixture was refluxed for 2 h in
each case and then left to cool overnight. The precipitated solids
were collected by filtration and recrystallized from ethanol/DMF.
5,10-Diamino-2-methyl-2,4-diphenyl-2,3-dihydropyrimido[4,5-
h][1,6]naphthyridin-8(1H)-one 9a. Yellow crystals; yield (3 g;
78%), mp: 147–149ꢀC (EtOH/DMF). IR: tmax (cmꢁ1) 3332,
3289, and 3230 (NH & NH2), 1667 (CO). MS, m/z ¼ 395
[Mþ-1]. dH: 1.74 (s, 3H, CH3), 3.32 (d, 1H; J ¼ 18.3 Hz),
3.75 (d, 1H; J ¼ 18.3 Hz), 7.29–7.57 (m, 14H, 2Phþ2NH2),
9.71 (s, 1H D2O exchangeable, NH).
[14] Abdelrazek, F. M.; Metz, P.; Metwally, N. H.; El-Mah-
rouky, S. F. Arch Pharm Chem life Sci (Weinheim) 2006, 339, 456.
[15] Abdelrazek, F. M.; Michael, F. A.; Mohamed, A. E. Arch
Pharm Chem life Sci (Weinheim) 2006, 339, 305.
[16] Abdelrazek, F. M.; Metz, P.; Kataeva, O.; Jaeger, A.; El-
Mahrouky, S. F. Arch Pharm Chem Life Sci (Weinheim) 2007, 340, 543.
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cycl Chem 2007, 44, 63.
[18] Abdelrazek, F. M.; Mohamed, A. M. Afinidad 2008, 65, 56.
[19] Wang, G.-W; Cheng, B. O. Arkivoc 2004, 9, 4.
[20] Abdelrazek, F. M.; Salah, A. M. Bull Chem Soc Jpn 1993,
66, 1722.
[21] Crystallographic data (excluding structure factors) for the
structure 2a reported in this article have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication no.
CCDC-744590. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax.:
(internat.) þ 441223/336–033; e-mail: deposit@ccdc.cam.ac.uk.
[22] Keller, E. SCHAKAL 99, A Computer Program for the
Graphic Representation of Molecular and Crystallographic Models;
Anal. Calcd. for C23H20N6O (396.44): C 69.68, H 5.08, N
21.20. Found: C 69.65, H 5.10, N 21.28.
5,10-Diamino-2-methyl-2,4-diphenyl-2,3-dihydropyrimido[4,5-
h][1,6]naphthyridine-8(1H)-thione 9b. Dark yellow crystals;
yield (3.2 g; 78%), mp: 160–162ꢀC (EtOH/DMF). IR: tmax
(cmꢁ1) 3335, 3291, and 3232 (NH & NH2). MS, m/z ¼ 412
[Mþ]. dH: 1.75 (s, 3H, CH3), 3.31 (d, 1H; J ¼ 18.32 Hz), 3.64
(d, 1H; J ¼ 18.32 Hz), 7.28–7.58 (m, 14H, 2Phþ2NH2), 9.66
(s, 1H D2O exchangeable, NH).
¨
Universitat Freiburg, Germany, 1999.
[23] Barker, M. W.; McHenry, W. E.; In The Chemistry of
Ketenes, Allenes and Related Compounds; Patai, S. Ed.; John Wiley:
New York, 1980; p 702.
Anal. Calcd. for C23H20N6S (412.51): C 66.97, H 4.89, N
20.37, S 7.77. Found: C 67.05, H 4.95, N 20.42, S 7.92.
[24] Igarashi, M.; Nakano, Y.; Takezawa, K.; Watanabe, T.;
Sato, S. Synth Commun 1987, 68.
Acknowledgments. F. M. Abdelrazek thanks the Alexander
von Humboldt Foundation (Germany) for granting a research
fellowship July–August 2009; during this time, the X-ray crys-
tallographic, elemental, and spectral data of compound 3a
were made.
[25] Wang, A. X.; Qinghua, X.; Lane, B.; Mollison, K. W.;
Hsieh, G. C.; Marsh, K.; Sheets, M. P.; Luly, J. R.; Coghlan, M. J.
Bioorg Med Chem Lett 1998, 8, 2787.
[26] Kim, H. H.; Park, T. G.; Moon, T. C.; Chang, H. W.;
Jahng, Y. Arch Pharm Res 1999, 2, 372.
[27] Park, H.-J.; Lee, K.; Park, S-J.; Ahn, B.; Lee, J.-C.; Yeong,
H.; Lee, C. K.-I. Bioorg Med Chem Lett 2005, 15, 3307.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet