Fused polyaza-heterocycles and 1,3,4-thiadiazoles via a tricyano synthon

Article abstract of DOI:10.1002/jhet.5570450113

(Chemical Equation Presented) Treatment of 2-cyano-3-phenyl-2- pentenedinitrile with some heterocyclic diazonium salts afforded the corresponding heterocyclic hydrazones. Some of the latter hydrazones were converted into fused polyazaheterocycles upon boi

Full text of DOI:10.1002/jhet.5570450113

Jan-Feb 2008
137
Fused Polyaza-heterocycles and 1,3,4-Thiadiazoles via
A Tricyano Synthon
Kamal M. Dawood*,a and Mohamed A. Raslanb
aDepartment of Chemistry, Faculty of Chemistry, University of Cairo, Giza, Egypt
bChemistry Department, Faculty of Science, Aswan, South Valley University
E-mail: dr_dawood@yahoo.com
Received March 25, 2007
NH2
NC
CN
CN
NC
Ph
NC
Ph
CN
CN
N
Ph
Ph
N
X
N
R
N
S
N
N
N
R
Treatment of 2-cyano-3-phenyl-2-pentenedinitrile with some heterocyclic diazonium salts afforded the
corresponding heterocyclic hydrazones. Some of the latter hydrazones were converted into fused polyaza-
heterocycles upon boiling in pyridine. Reaction of 2-cyano-3-phenyl-2-pentenedinitrile with
phenylisothiocyanate gave a tricyano-thiole derivative which on treatment with hydrazonoyl chlorides and
1-(benzothiazol-2-yl)-2-bromoethanone furnished 1,3,4-thiadiazole and thiazole derivatives, respectively.
J. Heterocyclic Chem., 45, 137 (2008).
Firstly, the reactions of 2-cyano-3-phenyl-2-pentene-
dinitrile (2) towards several heterocyclic diazonium
salts were undertaken to synthesize heterocyclic
hydrazones and consequently bridgehead-nitrogen
heterocycles. Thus, the reactivity of 2-cyano-3-phenyl-
INTRODUCTION
ꢀ,ꢁ-Unsaturated nitriles are important synthetic
intermediates in organic synthesis and key precursors in
the synthesis of different carbocycles and heterocycles [1-
4]. Heterocyclic hydrazones have remarkable wide scope
of applications in the synthesis of fused heterocycles [5].
In addition, benzimidazole has been an important
pharmacophore and privileged structure in medicinal
chemistry [6] encompassing a diverse range of biological
activities including antiarrhythmic, antiulcer,
antihistamine, antifungal, antiviral and cytotoxicity [7].
Pyrazole derivatives are also attracting important
applications in the field of medicinal chemistry [8,9].
Furthermore, 1,3,4-thiadiazoles were reported as highly
anti-inflammatory [10], antimicrobial [11] and
anticonvulsant [12] agents. 2-cyano-3-phenyl-2-
pentenedinitrile (2) is known two decades ago and has
been used in the synthesis of pyridazines [13,14], pyrroles
[15], thiophenes [16] and some photosensitive materials
[17,18], however, its use in the synthesis of polyfused
heterocycles and 1,3,4-thiadiazole derivatives has not
been reported so far. In continuation to our work on the
synthesis of fused polyaza-heterocycles [19-24], we
studied the reactivity of compound 2 with different
nitrogen electrophiles as a convenient route to the entitled
compounds.
2-pentenedinitrile
2
with the 5-methylpyrazole
diazonium salt 3a at room temperature afforded the
corresponding pyrazolylhydrazone 4a (Scheme 1). The
hydrazone 4a was isolated in excellent yield and its
structure was substantiated from its elemental analyses
1
and spectral data (IR, MS, H- and 13C NMR). Its IR
spectrum showed absorption peaks at 3367, 3218 and
1
2234 cm-1 due to NH and CꢂN functions. The H NMR
spectrum also revealed two singlet signals at ꢃ 2.35,
6.37 due to CH3 and pyrazole-4-CH protons and two
broad signals (D2O-exchangeable) at ꢃ 9.44 and 13.09
corresponding to pyrazole-NH and hydrazone-NH
protons, respectively in addition to an aromatic
multiplet in the region ꢃ 7.64-7.74. When the latter
hydrazone 4a was refluxed in pyridine it underwent an
intramolecular cyclization and afforded a dark brown
solid product that was identified as 8-amino-2-methyl-
6-phenylpyrazolo-[5,1-c]pyrido[2,3-e][1,2,4]triazine-7-
1
carbonitrile (6a) based on its spectral data. The H-
NMR spectrum of the isolated product 6a was free of
the two broad signals at ꢃ 9.44 and 13.09 corres-
ponding to pyrazole-NH and hydrazone-NH protons,
and exhibited instead only one signal (D2O-
exchangeable) integrated for two protons at ꢃ 8.73 in
addition to signals at ꢃ 2.21 and 5.51 due to CH3 and
pyrazole-4-CH besides an aromatic multiplet at ꢃ 7.41-
7.53.
RESULTS AND DISCUSSION
2-cyano-3-phenyl-2-pentenedinitrile (2) was prepared
via treatment of benzoylacetonitrile (1) with
malononitrile according to reported procedure [15].

138
K. M. Dawood and M. A. Raslan
Vol 45
Scheme 1
[5,1-c][1,2,4]triazine intermediate 5c as depicted in
Scheme 1. The polyaza fused heterocyclic system 6c was
1
O
confirmed from its H and 13C-NMR spectra. In contrast,
CN
1
the hydrazones 4b, 4d and 7 could not be converted into
the corresponding fused systems 6b, 6d and 9 even after
30 hours of prolonged heating in pyridine and they were
completely recovered without any change in their physical
properties (color, mp, IR and 1H NMR spectra).
Ph
CH2(CN)2
NC
Ph
CN
CN
Next, we turned out our attention to the reaction of
2-cyano-3-phenyl-2-pentenedinitrile (2) with phenyl
isothiocyanate, in dimethylformamide, in the presence of
potassium hydroxide, to afford the corresponding
potassium salt 10 which was converted into 4-mercapto-
2-phenyl-4-(phenylamino)buta-1,3-diene-1,1,3-tricarbo-
nitrile (11) upon treatment with dilute hydrochloric acid
2
H
N
H
N
N
N2 NO3
N2 HSO4
X
N
R
3a-d
3e
NC
CN
N
NC
Ph
CN
N
1
(Scheme 2). H NMR spectrum of the reaction product
CN
Ph
H
N
CN
was free of any aliphatic protons which means that
compound 11 is solely present in 11A form instead of its
tautomer 11B. Compound 11 is a versatile multifunctional
reagent and its reactivity towards hydrazonoyl chlorides
12a-c is studied. Thus, reaction of compound 11 with C-
phenyl-N-phenylhydrazonoyl chloride (12a) in refluxing
ethanol and in the presence of triethylamine afforded the
corresponding 1,3,4-thiadiazole derivative 14a. Formation
of the latter structure is assumed to proceed via
elimination of aniline molecule from the intermediate 13a
as outlined in Scheme 2. The 1,3,4-thiadiazole structure
14a was confirmed from the elemental analyses and
spectral data of the isolated product. The IR spectrum
revealed broad absorption band at 2212 cm-1 due to two
nitrile functions. Its mass spectrum revealed a peak at m/z
429 corresponding to the molecular ion (M+).
In a similar manner compound 11 reacted with
equimolar amounts of C-(4-chlorophenyl)-N-phenyl-
hydrazonoyl chloride (12b) and C-(2-benzothiazolylcar-
bonyl)-N-phenylhydrazonoyl chloride (12c) and furnished
in each case, only one isolable product (as tested by TLC
analysis) which have the 1,3,4-thiadiazole structures
14b,c based on their elemental and spectral analyses (see
experimental part).
H
N
N
N
H
N
H
X
R
N
4a-d
7
NC
CN
N
NC
CN
NH2
NH2
Ph
N
N
X
Ph
N
R
N
N
N
N
8
5a,c
NH2
NH2
NC
Ph
NC
Ph
N
N
N
X
N
N
R
N
N
N
N
3-6
R
X
N
9
6a,c
a
b
c
d
CH3
C6H5
4-CH3C6H4 CH
CH
CH
H
N
Next, the reactions of 2-cyano-3-phenyl-2-pentene-
dinitrile (2) toward further heterocyclic diazonium salts
were also investigated. It was found that compound 2
couples smoothly with the diazonium salts of 5-amino-3-
phenylpyrazole (3b), 5-amino-3-(p-toyl)pyrazole (3c), 5-
amino-1,2,4-triazole (3d), and 2-aminobenzimidazole (3e)
to afford the corresponding hydrazones 4b, 4c, 4d and 7,
respectively (Scheme 1). The IR spectra of the isolated
products showed, in each case, two absorption bands in
the region 3400–3100 cm-1 corresponding to two NH
groups in addition to nitrile function around 2230 cm-1,
respectively. Compounds 4c underwent an intramolecular
cyclization upon boiling in pyridine to afford the
corresponding fused heterocyclic system; 8-amino-6-
phenyl-2-(p-tolyl)-pyrazolo[5,1-c]pyrido[2,3-e][1,2,4]-
triazine-7-carbonitrile (6c) via the non-isolable pyrazolo-
Similar treatment of compound 11 with 1-(benzo-
thiazol-2-yl)-2-bromoethanone (15) in refluxing benzene
in the presence of triethylamine resulted in the formation
of a single product for which the thiazole 17 or thiophene
18 structures can be assumed. However, the elemental and
spectral data of the reaction product were in complete
accordance with the thiazole derivative 17. 1H NMR
spectrum of 17 displayed a multiplet in the region 7.41-
8.23 due to aromatic protons. Moreover, the mass
spectrum of 17 exhibited a peak at 485 corresponding to
the molecular ion (M+). These results indicate that the
reaction of compound 11 with 15 proceeds via loss of
water molecule from the non-isolable intermediate 16 but
not via the addition of active methylene to the cyano
group, as shown in Scheme 2.

Jan-Feb 2008
Fused Polyaza-heterocycles and 1,3,4-Thiadiazoles via A Tricyano Synthon
139
Scheme 2
NC
CN
CN
S K
NC
CN
CN
SH
NC
CN
CN
NC
Ph
CN
CN
PhNCS
HCl
Ph
Ph
Ph
DMF/KOH
PhHN
PhHN
2
PhHN
S
10
11A
11B
Cl
NHPh
R
N
N
12a-c
S
Br
NC
CN
NC
CN
O
15
CN
CN
S
Ph
Ph
Ph
- PhNH2
NC
CN
CN
PhHN
N
S
R
H
N
N
Ph
N
R
Ph
N
14a-c
PhHN
S
13a-c
S
O
16
R
12-14
NC
Ph
CN
CN
-H2O
C6H5
4-ClC6H4
a
b
NC
Ph
CN
NH2
O
N
Ph
S
N
N
S
c
PhHN
S
S
S
O
18
N
17
EXPERIMENTAL
Melting points were measured with a Gallenkamp apparatus
and are uncorrected. IR spectra were recorded on Shimadzu FT-
In a similar manner compound 11 reacted with
equimolar amounts of C-(4-chlorophenyl)-N-phenyl-
hydrazonoyl chloride (12b) and C-(2-benzothiazolylcar-
bonyl)-N-phenylhydrazonoyl chloride (12c) and furnished
in each case, only one isolable product (as tested by TLC
analysis) which have the 1,3,4-thiadiazole structures
14b,c based on their elemental and spectral analyses (see
experimental part).
1
IR 8101 PC infrared spectrophotometer. The H NMR spectra
were determined in CDCl3 or DMSO-d6 at 300 MHz on a Varian
Mercury VX 300 NMR spectrometer using TMS as an internal
standard. Mass spectra were measured on a GCMS-QP1000 EX
spectrometer at 70 eV. Elemental analyses were carried out at
the Microanalytical center of Cairo University. 2-cyano-3-
phenyl-2-pentenedinitrile (2) [15], heterocyclic diazonium salts
3a-e [25-28], hydrazonyl halides 12a-c [29,30] and 1-(benzo-
thiazol-2-yl)-2-bromoethanone 15 [31] were prepared following
the reported literature procedures.
General Procedure for the Reaction of 2-cyano-3-phenyl-
2-pentenedinitrile (2) with Heterocyclic Diazonium Salts. To
a cold solution of 2-cyano-3-phenyl-2-pentenedinitrile (2)
(0.58 g, 3 mmol), in pyridine (20 ml), was added the
appropriate heterocyclic diazonium salt of 5-amino-3-
methylpyrazole (3a), 5-amino-3-phenylpyrazole (3b),
5-amino-3-(p-tolyl)pyrazole (3c), 3-amino-1,2,4-triazole
(3d) or 2-aminobenzimidazole (3e) (3 mmol of each) that
were prepared according to literature procedures. The addition
was carried out portion-wise with stirring at 0–5°C over a
period of 30 min. After complete addition, the reaction
mixture was stirred for further 4h, then kept in an ice-chest for
12h, and finally diluted with water. The precipitated solid was
collected, washed with water, dried and recrystallized from
Similar treatment of compound 11 with 1-(benzo-
thiazol-2-yl)-2-bromoethanone (15) in refluxing benzene
in the presence of triethylamine resulted in the formation
of a single product for which the thiazole 17 or thiophene
18 structures can be assumed. However, the elemental and
spectral data of the reaction product were in complete
accordance with the thiazole derivative 17. 1H NMR
spectrum of 17 displayed a multiplet in the region 7.41-
8.23 due to aromatic protons. Moreover, the mass
spectrum of 17 exhibited a peak at 485 corresponding to
the molecular ion (M+). These results indicate that the
reaction of compound 11 with 15 proceeds via loss of
water molecule from the non-isolable intermediate 16 but
not via the addition of active methylene to the cyano
group, as shown in Scheme 2.

140
K. M. Dawood and M. A. Raslan
Vol 45
obtained as pale brown powder (DMF/EtOH), Yield (0.24 g,
79%); mp. 266-268 °C; ir (KBr) ꢀmax/cm-1: 3130 (NH), 2225
(CꢀN), 1589 (C=N); H nmr (DMSO-d6) ꢁ 2.21 (s, 3H, CH3),
5.51 (s, 1H, pyrazole-4-CH), 7.41-7.53 (m, 5H, ArH), 8.73 (br.s,
2H, D2O-exchangeable); For C16H11N7 Calcd: C, 63.78; H, 3.68;
N, 32.54%. Found: C, 63.59; H, 3.55; N, 32.22%.
ethanol/DMF to afford the corresponding heterocyclic
hydrazones 4a-d and 7 respectively.
1
3-(2-(3-Methyl-1H-pyrazol-5-yl)hydrazono)-2-phenylprop-
1-ene-1,1,3-tricarbonitrile (4a). This compound was obtained
as greenish-yellow crystals (DMF/EtOH), Yield (0.84 g, 93%);
mp. 238-240 °C; ir (KBr) ꢀmax/cm-1: 3367, 3218 (NH), 2234
1
8-Amino-6-phenyl-2-(p-tolyl)-pyrazolo[5,1-c]pyrido-[2,3-e]-
[1,2,4]triazine-7-carbonitrile (6c). This compound was
obtained as green amorphous (DMF/EtOH), Yield (0.31 g,
82%); mp. 257-258 °C; ir (KBr) ꢀmax/cm-1: 3125 (NH), 2230
(CꢀN), 1604 (C=N); H nmr (DMSO-d6) ꢁ 2.35 (s, 3H, CH3),
6.37 (s, 1H, pyrazole-4-CH), 7.64-7.74 (m, 5H, ArH), 9.44 (s,
1H, D2O-exchangeable), 13.09 (s, 1H, D2O-exchangeable); 13C
nmr ꢁ 11.5, 98.3, 114.4, 114.8, 122.3, 129.6, 129.7, 129.9,
130.1, 131.5, 132.2, 141.8, 146.1, 146.3, 152.1; MS (m/z) 301
(M+), 275, 260, 198, 180, 153, 127, 100, 77. For C16H11N7
Calcd: C, 63.78; H, 3.68; N, 32.54%. Found: C, 63.61; H, 3.72;
N, 32.18%.
1
(CꢀN), 1580 (C=N); H nmr (DMSO-d6) ꢁ 2.40 (s, 3H, CH3),
3.40 (br. s, 2H, D2O-exchangeable), 7.07 (s, 1H, pyrazole-4-
CH), 7.33-7.38 (m, 2H, ArH), 7.58-7.75 (m, 4H, ArH), 7.98-
8.09 (m, 3H, ArH); 13C nmr ꢁ 21.9, 98.5, 114.8, 124.6, 126.2,
127.6, 127.8, 128.7, 129.7, 130.1, 130.9, 131.5, 132.9, 133.7,
134.9, 140.8, 141.9, 152.1, 159.8, 166.1; MS (m/z) 377 (M+),
352, 336, 288, 233, 180, 165, 118, 91, 77, 65. For C22H15N7
Calcd: C, 70.01; H, 4.01; N, 25.98%. Found: C, 69.65; H, 3.73;
N, 25.66%.
3-(2-(3-Phenyl-1H-pyrazol-5-yl)hydrazono)-2-phenyl prop-
1-ene-1,1,3-tricarbonitrile (4b). This compound was obtained
as brownish-yellow crystals (DMF/EtOH), Yield (0.93 g,
86%); mp. 271-273 °C; ir (KBr) ꢀmax/cm-1: 3381, 3229 (NH),
1
2241 (CꢀN), 1629 (C=N); H nmr (DMSO-d6) ꢁ 7.06 (s, 1H,
pyrazole-4-CH), 7.42-7.95 (m, 10H, ArH), 9.70 (s, 1H, D2O-
exchangeable), 13.85 (s, 1H, D2O-exchangeable); MS (m/z) 363
(M+), 337, 260, 180, 116, 77. For C21H13N7 Calcd: C, 69.41; H,
3.61; N, 26.98%. Found: C, 69.22; H, 3.41; N, 26.59%.
4-Mercapto-2-phenyl-4-(phenylamino)buta-1,3-diene-1,1,
3-tricarbonitrile (11). To a stirred solution of potassium
hydroxide (0.56 g, 10 mmol) in dimethylformamide (20 ml), 2-
cyano-3-phenyl-2-pentenedinitrile (2) (1.93 g, 10 mmol) was
added. After stirring for 30 min, phenyl isothiocyanate (1.35 g,
10 mmol) was added to the resulting mixture. Stirring was
continued for 6 h then poured onto crushed ice containing
hydrochloric acid. The solid product so-formed was collected by
filtration, washed with water, dried and finally recrystallized
from EtOH/DMF to afford of 4-mercapto-2-phenyl-4-(phenyl-
amino)buta-1,3-diene-1,1,3-tricarbonitrile (11) as brown powder
in 2.43 g, 74% yield, mp. 240-242°C; ir (KBr) ꢀmax/cm-1: 3386
(NH), 2206 (CꢀN), 1589 (C=C); 1H nmr (DMSO-d6) ꢁ 7.33-7.69
(m, 10H, ArH), 9.85 (s, 1H, NH, D2O-exchangeable), 14.34 (s,
1H, SH, D2O-exchangeable); MS (m/z) 328 (M+), 261, 213, 160,
119, 107, 92, 66. For C19H12N4S Calcd: C, 69.49; H, 3.68; N,
17.06%. Found: C, 69.71; H, 3.55; N, 16.77%.
General Procedure for the Reaction of 4-Mercapto-2-
phenyl-4-(phenylamino)buta-1,3-diene-1,1,3-tricarbonitrile
(11) with Hydrazonoyl Chlorides 12a-c. To a solution of 11
(0.328 g, 1 mmol) in ethanol (20 ml) and the appropriate
hydrazonoyl chlorides 12a-c (1 mmol of each), triethylamine
(0.5 ml) was added. The mixture was refluxed for 3h then
allowed to cool. The formed solid was collected by filtration,
washed with ethanol and recrystallized from dimethyl-
formamide (DMF) to afford the corresponding 1,3,4-thiadiazole
derivatives 14a-c.
3-(2-(3-p-Tolyl-1H-pyrazol-5-yl)hydrazono)-2-phenyl prop-
1-ene-1,1,3-tricarbonitrile (4c). This compound was obtained
as brown powder (DMF/EtOH), Yield (1.05 g, 93%); mp. 265-
267 °C; ir (KBr) ꢀmax/cm-1: 3386, 3175 (NH), 2221 (CꢀN), 1590
1
(C=N); H nmr (DMSO-d6) ꢁ 2.37 (s, 3H, CH3), 7.02 (s, 1H,
pyrazole-4-CH), 7.33-7.38 (m, 3H, ArH), 7.65-7.81 (m, 6H,
ArH), 9.51 (s, 1H, D2O-exchangeable), 13.77 (s, 1H, D2O-
exchangeable); 13C nmr ꢁ 21.9, 96.2, 114.4, 114.8, 122.5, 126.4,
129.2, 129.6, 129.9, 130.6, 131.5, 132.2, 139.7, 144.7, 146,
146.1, 152.8, 159.8; MS (m/z) 377 (M+), 328, 311, 285, 198,
156, 118, 91, 77. For C22H15N7 Calcd: C, 70.01; H, 4.01; N,
25.98%. Found: C, 69.65; H, 3.73; N, 25.66%.
3-(2-(2H-1,2,4-Triazol-3-yl)hydrazono)-2-phenylprop-1-
ene-1,1,3-tricarbonitrile (4d). This compound was obtained as
greenish-yellow crystals (DMF/EtOH), Yield (0.75 g, 87%);
mp. 286-288 °C; ir (KBr) ꢀmax/cm-1 3326, 3140 (NH), 2215
1
(CꢀN), 1605 (C=N); H nmr (DMSO-d6) ꢁ 6.72 (s, 1H, triazole
H-5), 7.42-7.80 (m, 5H), 9.51 (br.s, 1H), 13.68 (br. s, 1H); MS
(m/z) 288 (M+), 262, 198, 179, 144, 127, 100, 84, 67. For
C14H8N8 Calcd: C, 58.33; H, 2.80; N, 38.87%. Found: C, 58.02;
H, 2.63; N, 38.49%.
3-(2-(1H-Benzimidazol-2-yl)hydrazono)-2-phenylprop-1-
ene-1,1,3-tricarbonitrile (7). This compound was obtained as
red crystals (DMF/EtOH), Yield (0.82 g, 81%); mp. 278-279
°C; ir (KBr) ꢀmax/cm-1: 3332, 3155 (NH), 2206 (CꢀN), 1639
2-Phenyl-3-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)-
prop-1-ene-1,1,3-tricarbonitrile (14a). This compound was
obtained as orange-red powder (DMF/EtOH), Yield (0.28 g,
65%); mp. 280-282 °C; ir (KBr) ꢀmax/cm-1: 2212 (CꢀN), 1583
1
(C=N); H nmr (DMSO-d6) ꢁ 7.35-7.80 (m, 9H, ArH), 10.95 (s,
1H, D2O-exchangeable), 13.15 (s, 1H, D2O-exchangeable); MS
(m/z) 337 (M+), 312, 272, 182, 118, 90, 77. For C19H11N7 Calcd:
C, 67.65; H, 3.29; N, 29.06%. Found: C, 67.89; H, 3.41; N,
28.77%.
General Procedure for the Cyclization of the Heterocyclic
Hydrazones 4a,c. A solution of the appropriate hydrazone 4a
or 4c (1 mmol) in pyridine (10 ml) was refluxed for 12h, then
left to cool. The solid that formed was collected by filtration,
washed with ethanol, dried and finally recrystallized from
DMF/ethanol to afford the corresponding fused heterocycles
6a and 6c, respectively
1
(C=C); H NMR (DMSO-d6) ꢁ 7.31-7.69 (m, ArH); MS (m/z)
429 (M+), 381, 364, 276, 194, 173, 121, 105, 91, 77. For
C26H15N5S Calcd: C, 72.71; H, 3.52; N, 16.31; S, 7.47%. Found:
C, 72.39; H, 3.61; N, 16.02; S, 7.44%.
3-(5-(4-Chlorophenyl)-3-phenyl-1,3,4-thiadiazol-2(3H)-yli-
dene)-2-phenylprop-1-ene-1,1,3-tricarbonitrile (14b). This
compound was obtained as brownish-red crystals
(DMF/EtOH), Yield (0.366 g, 79%); mp. 287-289 °C; ir (KBr)
ꢀ
max/cm-1: 2220 (CꢀN); 1H nmr (DMSO-d6) ꢁ 7.39-7.82 (m,
ArH); MS (m/z) 463 (M+), 327, 295, 228, 165, 91. For
C26H14ClN5S Calcd: C, 67.31; H, 3.04; N, 15.10; S, 6.91%.
Found: C, 66.94; H, 3.12; N, 14.88; S, 7.02%.
8-Amino-2-methyl-6-phenylpyrazolo[5,1-c]pyrido-[2,3-e]-
[1,2,4]triazine-7-carbonitrile (6a). This compound was

Jan-Feb 2008
Fused Polyaza-heterocycles and 1,3,4-Thiadiazoles via A Tricyano Synthon
141
[8] Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Nishiguchi, G.;
Carlson, K.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J.
Med. Chem. 2000, 43, 4934.
3-(5-(Benzothiazol-2-yl)carbonyl-3-phenyl-1,3,4-thiadia-
zol-2(3H)-ylidene)-2-phenylprop-1-ene-1,1,3-tricarbonitrile
(14c): This compound was obtained as orange-red powder
(DMF), Yield (0.35 g, 67%); mp. > 300°C; ir (KBr) ꢀmax/cm-1:
2220 (CꢀN), 1647 (C=O); 1H nmr (DMSO-d6) ꢁ 7.51-8.20 (m,
ArH); MS (m/z) 514 (M+), 483, 395, 249, 162, 134, 105, 77. For
C28H14N6OS2 Calcd: C, 65.35; H, 2.74; N, 16.33; S, 12.46%.
Found: C, 65.24; H, 3.06; N, 16.10; S, 12.17%.
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Gulen, D. Bioorg. Med. Chem. 2002, 10, 2893.
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Campeanu, G.; Cimpeanu, V.; Supuran, C. T. Bioorg. Med. Chem. 2004,
12, 2717. (b) Archana; Srivastava, V. K.; Kumar, A. Eur. J. Med. Chem.
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Heteroatom Chem. 1995, 6, 281.
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[17] Andreu, R.; Cerdan, M. A.; Garin, J.; Orduna, J. Arkivoc
2004, 32.
Reaction of Compound 11 with 1-(Benzothiazol-2-yl)-2-
bromoethanone (15). To a solution of 11 (0.328 g, 1 mmol) in
ethanol (20 ml) and 1-(benzothiazol-2-yl)-2-bromoethanone (15)
(0.254 g, 1 mmol), triethylamine (0.5 ml) was added. The
mixture was refluxed for 2h then allowed to cool. The formed
solid was collected by filtration, washed with ethanol and
recrystallized from DMF to afford 3-(4-(benzothiazol-2-yl)-3-
phenylthiazol-2(3H)-ylidene)-2-phenylprop-1-ene-1,1,3-tricar-
bonitrile (17) as dark-brown crystals. Yield (0.306 g, 63%); mp.
1
250-252°C; ir (KBr) ꢀmax/cm-1: 2214 (CꢀN), 1596 (C=N); H
nmr (DMSO-d6) ꢁ 7.41-8.23 (m, ArH); MS (m/z) 485 (M+), 437,
345, 303, 231, 172, 134, 77. For C28H15N5S2 Calcd: C, 69.26; H,
3.11; N, 14.42; S, 13.21%. Found: C, 69.39; H, 3.32; N, 14.23;
S, 13.24%.
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