Fused pyridines by a tandem aza-Wittig / heterocyclization strategy: Synthesis of 1,2,4-triazolo[1,5-a]pyridines and pyrido[1,2-b][1,2,4]triazines

Article abstract of DOI:10.1002/jhet.5570450322

(Chemical Equation Presented) The iminophosphorane 1-amino-6- (triphenylphosphoranylideneamino)-2-oxo-4-phenyl-1,2-dihydropyridine-3, 5-dicarbonitrile 2 prepared from 1,6-diaminopyridine 1 reacts with heterocumulenes such as carbon disulfide and phenylisocyanate, and with acid chlorides, acid anhydrides and haloketones to give directly the title compounds in an one-pot aza-Wittig / heterocyclic-ring closure process with good yields.

Full text of DOI:10.1002/jhet.5570450322

May-Jun 2008
773
Fused Pyridines by a Tandem Aza-Wittig / Heterocyclization Strategy:
Synthesis of 1,2,4-Triazolo[1,5-a]pyridines and Pyrido[1,2-b][1,2,4]triazines
Magda A. Barsy*, Eman A. El Rady and Fawi M. Abd El Latif
Department of Chemistry, Faculty of Science, South Valley University, Aswan 81528, Egypt.
Email: magdabarsy@hotmail.com
Received July 22, 2007
O
RCOCl
NC
Ph
N
NH
O
O
N
R
NC
Ph
NH2
NH2
NC
Ph
NH2
N
N
CN
N=PPh3
O
CN
CN
NC
Ph
N
N
RCOCH2X
N
1
2
R
CN
The iminophosphorane 1-amino-6-(triphenylphosphoranylideneamino)-2-oxo-4-phenyl-1,2-dihydro-
pyridine-3,5-dicarbonitrile 2 prepared from 1,6-diaminopyridine 1 reacts with heterocumulenes such as
carbon disulfide and phenylisocyanate, and with acid chlorides, acid anhydrides and haloketones to give
directly the title compounds in an one-pot aza-Wittig / heterocyclic-ring closure process with good yields.
J. Heterocyclic Chem., 45, 773 (2008).
have previously published the synthesis of fused
pyrimidines based on the tandem aza-Wittig annulation
strategy [32], and as a part of our ongoing studies we now
describe a novel one-pot synthesis of 1,2,4-triazolo[1,5-
a]pyridine and pyrido[1,2-b][1,2,4]triazines derivatives in
good yield.
INTRODUCTION
Triazoles and 1,2,4-triazines are important classes of
heterocyclic compounds. In particular, fused 1,2,4-
triazoles express antifungal [1], bactericidal [1,2],
anxiolytic [3,4], anticonvulsant [5] or herbicidal [6]
activities and can act as antidepressants [7]. Therefore,
versatile and widely applicable methods for their
synthesis are of considerable interest. Most methods for
the preparation of fused 1,2,4-triazoles are mainly based
on hydrazones as precursors. However, these methods
have some restrictions regarding their applicability and
the use of toxic reagents like lead tetracetate [8,9] and
bromine [9,10], also the products were formed in low
yield and isolated as salts [11,12]. Many 1,2,4-triazine
derivatives are well known to possess biological
activities, thus they have found use as herbicides [13,14].
In the last decade they have been screened in vitro
supporting their anti-HIV and anti-cancer activities [15-
18]. However the aza-Wittig reaction is a powerful tool
for the synthesis of five- to seven-membered nitrogen
heterocycles [19-26]. Annulation of ring systems with N-
heterocycles by means of an aza-Wittig reaction has
recently been widely utilized because of the availability of
RESULTS AND DISCUSSION
The key iminophosphorane 2 is easily prepared in 95 %
yield from the readily available 1,6-diamino-2-oxo-4-
phenyl-1,2-dihydropyridine-3,5-dicarbonitrile 1 by reaction
with triphenylphosphine/hexachloroethane and triethyl-
amine reagent system (the Appel method, i.e. the modified
Kirsanov reaction) [33] (Scheme 1). It is plausible that
the amino group in the 6-position is more reactive than that
attached to the ring nitrogen in the 1-position. However, the
X-ray crystallographic analysis of the product unequivo-
cally confirms its structure. All bond distances present the
expected values, bond angle analysis indicated that the
pyridine ring is planar, and the 4-phenyl is quite perpen-
dicular to it, while the phenyl rings of triphenylphosphine
group are almost coplanar with the pyridine ring and the
two others are perpendicular to it (Figure). Attempted
preparation of bis(iminophosphorane) 3 by reaction of 1
with two equivalents of the triphenylphosphine/
hexachloroethane/triethylamine reagent system was less
functionalized iminophosphoranes [27-31].
Many
important fused nitrogen heterocycles such as indole,
pyridine, pyrimidine and isoquinoline derivatives have
been synthesized via the intramolecular aza-Wittig
reaction [19-22], as well as by the intermolecular aza-
Wittig reaction followed by electrocyclization, intra-
molecular cycloaddition or heterocyclization [23-26]. We
efficient
and resulted in formation of the same
iminohosphorane 2. Preparation of 3 then was achieved by
treatment of 2 with an additional equivalent triphenyl
phosphine/hexachloroethane/triethylamine reagent system.

774
M. A. Barsy, E. A. El Rady and F. M. A. El Latif
Vol 45
Scheme 1
(a)
formation of triazolopyridine 7.
Presumably, the
conversion here involves an initial aza-Wittig reaction
between the iminophosphorane and the isocyanate to give
a carbodiimide 6 as highly reactive intermediate, which
readily undergoes heterocyclization to afford the final
triazolopyridine 7. The structure of 7 was determined
O
O
NC
Ph
NH2
NC
Ph
NH2
NH2
N
N
N=PPh3
CN
CN
1
based on microanalysis and spectral data. In its H-NMR
2
1
O
spectrum the characteristic chemical shifts of the aromatic
protons and NH groups are found at δ 7.1-7.8, 8.2 and
10.2, respectively.
(a)
(b)
NC
Ph
N=PPh3
N
N=PPh3
Heating iminophosphorane 2 with excess carbon
disulfide in presence of toluene in a sealed tube at 100 ºC
gave the 2-thiol derivative 9 through formation of the
presumed intermediate 8, which contains a cumulated
double bond at one end. An intramolecular cycloaddition
takes place to afford the 2-sulfanyl-triazolopyridine 9.
Structure of 9 was determined from its spectral data. The
mass spectrum showed the expected molecular ion peak at
m/z = 293 (35 %), the IR spectrum exhibited characteristic
bands at 1200, 1655, 2210 and at 3120 cm-1 due to the
thiol, carbonyl, nitrile and imino groups, respectively.
Compound 2 reacts with each of maleic anhydride and
phthalic anhydride in dry toluene to yield the corre-
sponding pyrrolo[1,2:2,3][1,2,4]triazolo[1,2-a]pyridine 11
and indolo[1,2:2,3][1,2,4]triazolo[1,2-a]pyridine 13,
respectively. Attack of the primary amino group of 2 on
one carbonyl group of the anhydride leading to malimido
and phthalimido intermediates 10 and 12 followed by
intramolecular aza-Wittig reaction can account for the
formation of the final products 11 and 13 (Scheme 3).
Also compound 2 reacts with phenacylbromide and
chloroacetyl chloride in refluxing toluene to yield
CN
3
(a) : 1 eq. PPh3, C2Cl6 / TEA, toluene / reflux 2h.
(b) : 2 eq. PPh3, C2Cl6 / TEA, toluene / reflux 2h.
Iminophosphorane 2 reacted with acetyl-, and benzoyl
chloride in refluxing toluene to afford the triazole-
pyridinone derivatives 5a,b, the structures of which were
confirmed on the basis of spectral and analytical data. The
IR spectra of 5a showed bands at 1651, 2220, and 3120
cm-1 assigned to C=O, CN and NH groups, respectively.
1
The H NMR spectrum of 5a showed two singlet signals
for the methyl and NH protons of triazole at δ 1.9 and
10.1, in addition to a multiplet for the aromatic protons at
δ 7.1-7.6 ppm. Formation of 5 is assumed to proceed via
aza-Wittig reaction between 2 and acid chloride yielding
an imidoyl chloride intermediate 4. The new generated
electrophilic center is then attacked by the 1-amino group
with release of hydrogen chloride and rearrangement to
the final product 5, (Scheme 2).
Also, the reaction of 2 with phenylisocyanate in dry
toluene at reflux temperature lead directly to the
Scheme 2
O
O
NC
Ph
NC
NH2
RCOCl
-HCl
N
NH
N
Cl
N=C
N
R
Ph
R
CN
CN
5a, R = CH3
b, R = Ph
4
O
O
O
NC
Ph
NH2
N
NC
Ph
NH2
NC
Ph
PhNCO
N
N
NH
NHPh
N=PPh3
N
N=C=N-Ph
CN
CN
CN
2
6
7
O
O
CS2
NC
Ph
NC
NH2
N
NH
SH
N
N
Ph
N=C=S
CN
CN
8
9

May-Jun 2008
Fused Pyridines by a Tandem Aza-Wittig / Heterocyclization Strategy
775
Figure. ORTEP Diagram of 1-amino-6-(triphenylphosphoranylideneamino)-2-oxo-4-phenyl-1,2-dihydro-
pyridine-3,5-dicarbonitrile (2).
Scheme 3
O
O
O
O
N
NC
Ph
NC
Ph
(a)
N
N
N
O
N
N=PPh3
CN
O
CN
NC
Ph
NH2
11
N
10
N=PPh3
O
CN
O
O
O
2
N
NC
(b)
NC
N
N
N
O
N=PPh3
Ph
Ph
N
CN
CN
12
13
(a) maleic anhydride, toluene / TEA, reflux 3h.
(b) phthalic anhydride, toluene / TEA, reflux 3h.
pyrido[1,2-b][1,2,4]triazines 15, and 17. The pathway to
the products was explained by the formation of inter-
mediates 14 and 16 resulting from aza-Wittig reaction
followed by release of hydrogen halide and air-oxidation.
The structure of the products was also established by their
spectral and analytical data. Likewise, sequential
treatment of iminophosphorane 2 with benzil under the
same reaction conditions afforded pyridotriazine 19
conditions (Scheme 4). In order to prepar new derivatives
of pyrido-triazepine, the bis(iminophosphorane) 3 was
allowed to react with each of acetyl acetone and/or
dibenzoylmethane under otherwise identical reaction
conditions, but the reaction was found unsuccessful.
EXPERIMENTAL
through
loss of water from the intermediate 18.
Melting points were determined on
a
Gallenkamp
Pyridotriazine 19 could also be obtained by reaction of
benzil and bis(iminophosphorane) 3 under the same
electrothermal melting point apparatus and are uncorrected. IR
spectra were recorded as potassium bromide pellets on a Pye-

776
M. A. Barsy, E. A. El Rady and F. M. A. El Latif
Vol 45
Scheme 4
O
O
NC
Ph
N
N
NC
Ph
NH2
N=C
PhCOCH2Br
-HBr, -H2
N
N
CH2Br
Ph
Ph
CN
O
CN
15
14
O
NC
Ph
NH2
O
N
ClCOCH2Cl
NC
Ph
N
N
NC
Ph
NH2
-HCl, -H2
N
N
N=PPh3
CH2Cl
CN
Cl
N=C
Cl
CN
CN
2
17
16
O
O
NC
Ph
N
N
Ph
Ph
NC
Ph
NH2
PhCO-COPh
-H2O
N
N
COPh
N=C
Ph
CN
CN
19
18
hexachloroethane (0.473 g, 2.0 mmol, 1.0 equiv.) and
triphenylphosphine (0.52 g, 2.0 mmol, 1.0 equiv.) in anhydrous
benzene (50.0 mL) triethylamine (0.4 mL, 4.0 mmol, 2.0
equiv.) was added dropwise. The resultant solution was heated at
reflux for 2 h. The mixture was filtered while still hot in order to
remove the precipitates and the filtrate was evaporated under
reduced pressure to give a solid product which was crystallized
from ethanol as colorless crystals; yield: 950 mg (95 %); mp 170
°C, ir: ν 1656 (CO), 2210 (CN), 3229, 3259 (NH2); IH nmr
(DMSO) δ: 7.1-7.8 (m, 20H, Ar-H), 8.9 (s, 2H, NH2); ms: m/z =
511 (M+, 85 %). Anal. Calcd. for C31H22N5OP (511.53): C,
72.79; H, 4.34; N,13.69; Found: C, 72.65; H, 4.25; N, 13.57.
Preparation of 1,6-bis(triphenylphosphoranylidene-
amino)-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbo-
nitrile (3). To a stirred mixture of 1-amino-6-(triphenylphos-
phoranylideneamino)-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-
dicarbonitrile 2, (0.771 g, 2.0 mmol), hexachloroethane (0.473 g,
2.0 mmol, 1.0 equiv.) and triphenylphosphine (0.52 g, 2.0 mmol,
1.0 equiv.) in anhydrous benzene (50.0 mL) triethylamine (0.4
mL, 4.0 mmol, 2.0 equiv.) was added dropwise. The resultant
solution was heated at reflux for 1.5 h. The mixture was filtered
while still hot in order to remove the precipitates and the filtrate
was evaporated under reduced pressure to give a solid product
Table 1
Crystal and Refinement Parameters for Compound 2
Molecular Formula
Molecular weight
Color
C31H22N5OP
511.525
White
Crystal system
Symmetry
a, Å
Prismatic
Orthorhombic
8.880 (3)
18.405 (5)
34.43 (2)
90.00
b Å
c, Å
α, deg
β, deg
γ, deg
v, Å
90.00
90.00
5500.0 (4)
8
1.236
Z
Density calculated, mg/mm-1
Reflections collected
Independent reflections
Data/restraints/parameters
Final R[I>2 σ(1)]
R (all data)
6178
3887 [R (int) = 0.030
3887/0/338
0.066
0.196
Unicam SP-1100 Spectrophotometer. 1H NMR spectra were
obtained in deuterated dimethyl sulfoxide on a Varian EM-390
spectrometer using tetramethylsilane (TMS) as an internal
reference. Mass spectra were recorded on a Hewlett Packard
MS-5988 spectrometer. The single crystal X-ray structural
analysis was performed using a maXus diffractometer with a
monochromator at (λ = 0.71073, T = 298 K). Elemental analysis
was carried out at the Microanalytical Center of Cairo
University, Egypt.
Preparation of 1-amino-6-(triphenylphosphoranylidene-
amino)-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile
(2). To a stirred mixture of 1,6-diamino-2-oxo-4-phenyl-1,2-
dihydropyridine-3,5-dicarbonitrile 1, (0.5 g, 2.0 mmol),
which was crystallized from ethanol as colorless crystals; yield:
I
750 mg (75 %); mp 315 °C, ir: ν 1656 (CO), 2210 (CN);
H
nmr (DMSO) δ: 6.9-7.9 (m, 35H, Ar-H); ms: m/z = 772 (M+, 90
%). Anal. Calcd. for C49H35N5OP2 (771.79): C, 76.26; H, 4.57;
N,9.07; Found: C, 76.35; H, 4.35; N, 9.12.
General procedure for the reaction of iminophosphorane
(2) with acid chlorides. To a solution of iminophosphorane 2
(0.51 g, 1.0 mmol) in 20 mL of dry toluene the appropriate acid
chloride (2.0 mmol) and triethylamine (0.2 mL, 2 mmol) were
added, and the reaction mixture was heated under reflux for 1.5
h. The solid that formed while the mixture was still hot was
separated by filtration, and the filtrate was then evaporated
under reduced pressure to give colorless crystals.

May-Jun 2008
Fused Pyridines by a Tandem Aza-Wittig / Heterocyclization Strategy
777
Table 2
Selected Bond Lengths, Bond Angles and Torsion Angles of 2
Bond Angles (º)a
Bond lengths (Å)
Torsion Angles (º)
O2-C7-N3
O2-C17-C5
N7-N3-C17
N7-N3-C8
N3-C8-N6
C4-C8-N6
N7-N3-C8-C4
N7-N3-C8-N6
N7-N3-C17-O2
N7-N3-C17-C5
C11-C4-C8-N3
C10-C4-C8-N3
O2-C17-C5-C11
O2-C17-C5-C12
-71.3(13)
8.4(9)
-4.5(9)
174.3(14)
-2.1(9)
177.0(113)
175.(2)
116.8(4)
24.3(5)
P1-N6
1.583(3)
1.787(4)
1.811(4)
1.797(4)
1.267(4)
1.368(4)
1.468(5)
1.389(4)
1.447(4)
1.416(5)
1.367(4)
1.372(5)
1.438(5)
1.404(5)
1.289(4)
1.148(4)
1.483(5)
1.156(5)
1.344(5)
1.381(5)
1.359(5)
P1-C15
P1-C20
P1-C22
O2-C17
N3-C8
N3-C17
N3-N7
C4-C8
C4-C10
C4-C11
C5-C11
C5-C12
C5-C17
N6-C8
N9-C10
C11-C13
C12-N16
C13-C18
C13-C19
C14-C15
117.1(4)
118.9(3)
125.2(4)
120.9(4)
178.2(4)
138.6(3)
119.5(2)
102.1(2)
114.1(2)
106.1(2)
104.5(2)
17.9(4)
C4-C10-N9
P1-N6-C8
1.4(10)
N6-P1-C20
N6-P1-C22
N6-P1-C15
C20-P1-C22
C15-P1-C22
C5-C11-C13
C11-C13-C19
C15-P-C20
C8-N3-C17
121.9(4)
109.0(2)0
123.8(4)
2-Methyl-5-oxo-7-phenyl-3, 5-dihydro[1,2,4]triazole[1,5-a]-
pyridine-6,8-dicarbonitrile (5a). Yield: 220 mg (81 %), mp
175 °C (dioxane), ir: ν 1650 (CO), 2220 (CN), 3120 (NH); H
nmr (DMSO) δ: 1.9 (s, 3H, CH3), 7.1-7.6 (m, 5H, Ar-H), 10.1
(s,1H, NH); ms: m/z = 275 (M+, 67 %). Anal. Calcd. for
C15H9N5O (275.27): C, 65.45; H, 3.30; N, 25.44; Found: C,
65.35; H, 3.15; N, 25.37.
General procedure for the reaction of iminophosphorane 2
with maleic and phthalic anhydride. A mixture of imino-
phosphorane 2 (0.5 g, 1.0 mmol) and the appropriate acid
anhydride (1.0 mmol) in dry toluene (20 mL), was heated at
reflux for 3 h. After cooling the solvent was evaporated, the
crude residue was suspended in methanol and the solid formed
was collected by filtration to give a colorless product.
1
2,7-Diphenyl-5-oxo-3,5-dihydro[1,2,4]triazolo[1,5-a]pyri-
dine-6,8-dicarbonitrile (5b). Yield : 300 mg (81 %) (dioxane);
Pyrrolo[1,2:2,3]triazolo[1,2-a]pyridine (11). Crystallized from
ethyl alcohol/acetic acid mixture (3:1) to yield: 220 mg (73 %);
mp 240 °C, ir: ν 1618, 1659 (CO), 2222 (CN); IH nmr (DMSO) δ:
5.1 (d, 1H, H-3), 5.7 (d, 1H, H-4), 7.1-7.8 (m, 5H, ArH); ms: m/ z
= 315 (M+2, 89 %). Anal. Calcd. for C17H7N5O2 (313.27): C,
65.18; H, 2.25; N, 22.36; Found: C, 65.37; H, 2.41; N, 22.47.
Indolo[1,2:2,3]triazolo[1,2-a]pyridine (13). Crystallized from
dioxane/H2O mixture (3:1) to yield: 240 mg (80 %); mp 305 °C,
1
mp 280 °C, ir: ν 1651 (CO), 2211 (CN), 3120 (NH); H nmr
(DMSO) δ: 6.9-7.5 (m, 10H, Ar-H), 10.2 (s, 1H, NH); ms: m/z =
339 (M+2, 90 %). Anal. Calcd. for C20H11N5O (337.34): C,
71.21; H, 3.29; N, 20.76; Found: C, 71.35; H, 3.15; N, 20.37.
Preparation of 5-oxo-7-phenyl-2-phenylamino-3,5-di-
hydro[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitrile (7). To
a solution of iminophosphorane 2 (0.51 g, 1.0 mmol) in 30 mL
of dry toluene phenylisocyanate (0.23 g, 2.0 mmol) was added.
The reaction mixture was heated under reflux for 1 h. The
yellow precipitate formed during reflux was collected by
filtration and crystallized from methanol, yield: 260 mg (76 %);
I
ir: ν 1630, 1650 (CO), 2220 (CN); H nmr (DMSO) δ: 7.0-7.6
(m, 9H, Ar-H); ms: m/z = 365 (M+2, 25 %). Anal. Calcd. for
C21H7N5O2 (363.34) C, 69.42; H, 2.50; N, 19.28; Found: C,
69.23; H, 2.38; N, 19.13.
Preparation of 2,8-diphenyl-6-oxo-pyrido[1,2-b][1,2,4]-
triazine-7,9-dicarbonitrile (15). To a solution of iminophos-
phorane 2 (0.51 g, 1.0 mmol) in 20 mL of dry toluene, phenacyl-
bromide (0.38 g, 2.0 mmol) and triethylamine (0.2 mL, 2 mmol)
were added, and the reaction mixture was heated under reflux
for 2 h. The solid that formed in the hot mixture was separated
by filtration, and the filtrate was evaporated under reduced
pressure to give yellow crystals, which were recrystallized from
ethanol. Yield: 240 mg (71 %); mp 250 °C, ir: ν 1650 (CO),
2211 (CN); IH nmr (DMSO) δ: 7.0-7.4 (m, 11H, Ar-H); ms: m/z
= 349 (M+, 82 %). Anal. Calcd. for C21H11N5O (349.35): C,
72.20; H, 3.17; N, 20.05; Found: C, 72.11; H, 3.25; N, 20.32.
Preparation of 2-chloro-6-oxo-8-phenyl-pyrido[1,2-b][1,2,4]-
triazine-7,9-dicarbonitrile (17). The preparation was carried
out by the same method used for the preparation of compound
15 using chloro acetyl chloride to give a colorless product and
crystallized from ethyl acetate / toluene (3:1) to yield: 220 mg
I
mp >300 °C, ir: ν 1650 (CO), 2222 (CN), 3130 (NH); H nmr
(DMSO) δ: 7.1-7.8 (m, 10 H, Ar-H), 8.2 (s, 1H, NH), 10.2 (s,
1H, NH); ms: m/z = 352 (M+, 40 %). Anal. Calcd. for C20H12N6O
(352.36): C, 68.17; H, 3.43; N, 23.85; Found: C, 68.31; H,
3.55; N, 23.57.
Preparation of 5-oxo-7-phenyl-2-thiol-3,5-dihydro[1,2,4]-
triazolo[1,5-a]pyridine-6,8-dicarbonitrile (9). To a solution of
iminophosphorane 2 (0.5 g, 1.0 mmol) in 15 mL of dry toluene
an excess of carbon disulfide (7 mL) was added. The reaction
mixture was heated in a sealed tube at 100 °C for 3 h. The
crystals that formed were collected and crystallized from a
mixture of DMF and H2O (1:1) as yellow crystals, yield: 240 mg
(83 %); mp 215 °C, ir: ν 1200 (SH), 1655 (CO), 2210 (CN),
1
3120 (NH); H nmr (DMSO) δ: 2.5 (s, 1H, SH), 6.9-7.3 (m,5H,
Ar-H), 10.3 (s, H, NH); ms: m/z = 293 (M+, 35 %). Anal. Calcd.
for C14H7N5OS (293.3): C, 57.33; H, 2.41; N, 23.88; Found: C,
57.11; H, 2.55; N, 23.57.
I
(71 %); mp 240 °C, ir: ν 1649 (CO), 2210 (CN); H nmr

778
M. A. Barsy, E. A. El Rady and F. M. A. El Latif
Vol 45
[13] Neunhoeffer, H. The Chemistry of Heterocyclic Compounds,
(Weissberger, A. & Taylor, E. C. (eds), 1978, 33, 189, New York,
Wiley.
[14] Neunhoeffer, H. Comprehensive Heterocycl. Chem.
(Katritzky, A. R. & Rees, C.W. (eds), Pargamon Press Oxford 1984,
Bolton, A. J. & Mckillop, A. (Vol. Eds.), 3, Part 2B, 285.
[15] Abdel-Rahman, R. M.; Morsy, J. M.; El-Edfawy, S.
Pharmazie 1999, 54, 667.
[16] Abdel-Rahman, R. M.; Seada, M.; Fawzy, M. Pharmazie
1994, 49, 811.
[17] Abdel-Rahman, R. M.; Morsy, J. M.; Hanafy, F. Pharmazie
1999, 54, 347.
[18] Abdel-Rahman, R. M. Pharmazie 2001, 56, 18.
[19] Takeuchi, H.; Yanagida, S.; Ozaki, T.; Hagiwara, S.; Eguchi,
S. J. Org. Chem.1989, 54, 431.
[20] Eguchi, S.; Goto, S. Heterocycl. Commun. 1994, 1, 51.
[21] Eguchi, S.; Yamashita, K.; Matsushita, Y. Synlett 1992, 295.
[22] Takeuchi, H.; Hagiwara, S.; Eguchi, S. Tetrahedron 1989,
45, 6375.
(DMSO) δ: 6.9-7.8 (m, 6H, Ar-H); ms: m/z = 309 (M+2, 65%).
Anal. Calcd. for C15H6N5OCl (307.70): C, 58.55; H, 1.96; N,
22.76; Found: C, 58.32; H, 1.89; N, 22.52.
Preparation of 6-oxo-2,3,8-triphenyl-pyrido[1,2-b][1,2,4]-
triazine-7,9-dicarbonitrile (19). A mixture of iminophos-
phorane 2 (0.51 g, 1.0 mmol), benzil (0.2 g, 1.0 mmol) and
triethylamine (0.2 mL, 2 mmol) in 30 mL of dry toluene was
heated at reflux for 3h. The solution was evaporated under
reduced pressure and the residue was collected and crystallized
from ethyl acetate as orange crystals, yield: 320 mg (76 %); mp
> 330 °C, ir: ν 1653 (CO), 2222 (CN); I H nmr (DMSO) δ: 7.3-
7.8(m, 15H, Ar-H); ms: m/z = 425 (M+, 35 %). Anal. Calcd. for
C27H15N5O (425.45): C, 76.22; H, 3.55; N, 16.46; Found: C,
76.11; H, 3.35; N, 16.72.
REFERENCES AND NOTES
[23] (a) Molina, P.; Fresneda, P. M. J. Chem. Soc. , Chem.
Commun. 1988, 1819. (b) Molina, P.; Alajarin, M.; Vidal, A.
Tetrahedron 1990, 46, 1063.
[1] El-Hawash, S. A.; Habib, N. S.; Fanaki, N. H. Pharmazie
1999, 45, 808-813.
[2] Brown, D. J.; Iwai, Y. Aust. J. Chem. 1979, 32, 2727-2733.
[3] Tarzia, G.; Ocelli, E.; Toja, E.; Barone, D.; Corsico, N.;
Gallico, L.; Luzzani, F. J. Med. Chem. 1988, 31, 1115-1123.
[4] Trust, R. I.; Albrigh, J. D. U. S. Patent 1980, 4 242 515.
[5] Tarzia, G.; Ocelli, E.; Barone, D. IL Farmaco 1989, 44, 3-16.
[6] (a) Peignier, R.; Cheme, A.; Cantregril, R.; Mortier, J. Eur.
Patent 441718; Chem. Abstr. 1991, 115 208000. (b) Cantegriil, R.;
Chem, A.; Mortier, J.; Peignier, R. Eur. Patent 483027; Chem. Abstr.
1992, 117 131214.
[24] Molina, P.; Vilaplana, M. J. Synthesis 1990, 474.
[25] (a) Wamhoff, H.; Schmidt, A. J. Org. Chem. 1993, 58, 6976
and references cited therein. (b) Sato, T.; Ohmori, H.; Ohkuho, T.;
Motoki, S. J. Chem. Soc. Chem. Commun. 1993, 1802.
[26] (a) Molina, P.; Alajarin, M.; Vidal, A. J. Chem. Soc. Chem.
Commun. 1990, 7. (b) Molina, P.; Alajarin, M.; Vidal, A. J. Org. Chem.
1990, 55, 6140.
[27] Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.; de los
Santos, J. M. Tetrahedron, 2007, 63, 523-575.
[28] Eguchi, S. Top. Heterocycl. Chem. 2006, 6, 113-156.
[29] Braese, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew.
Chem. Int. Ed. 2005, 44, 5188-5240.
[7] Sarges, S.; Howard, H. R.; Browne, R. G.; Lbel, L. A.;
Seymour, P. A.; Koe, B. K. J. Med. Chem. 1990, 33, 2240-2254.
[8] Bower, J. D.; Doyle, F. P. J. Chem. Soc. 1957, 727-732.
[9] Pollak, A.; Tisler, M. Tetrahedron 1966, 22, 2073-2079.
[10] Gibson, M. S. Tetrahedron 1963, 19, 1587-1589.
[11] Hadi, A.; Martin, N.; Seoane, C.; Soto, J. L. J. Heterocyclic
Chem. 1992, 29, 1229.
[30] Eguchi, S. Arkivoc 2005, ii, 98-119.
[31] Fresneda, P. M.; Molina, P. Synlett 2004, 1-17.
[32] Barsy, M. A.; El-Rady, A. E. J. Heterocyclic Chem. 2006,
43, 523.
[33] Appel, R.; Kleistuk, R.; Ziehn, K. D.; Knoll, F. Chem. Ber.
1970, 103, 3631.
[12] Al-Najjar, A. A.; Amer, S. A. R.; Riad, M.; Elghamry, I.;
Elnagdi, M. H. J. Chem. Res (S) 1996, 296-297.