Reaction of 1-acylthiosemicarbazides with ethenetetracarbonitrile

Article abstract of DOI:10.1002/jhet.5570440532

(Chemical Equation Presented) 1-Acylthiosemicarbazides 9a-d reacted with ethenetetracarbonitrile (TCNE, 2) in ethyl acetate with formation of N′-(4-amino-5,6-dicyano-2H-1,3-thiazin-2-ylidene) substituted hydrazide 10a-d, N′-(5-amino-3,4-dicyano-2H-pyrrol-

Full text of DOI:10.1002/jhet.5570440532

Sep-Oct 2007
1171
Reaction of 1-Acylthiosemicarbazides with Ethenetetracarbonitrile
Alaa A. Hassan*, Aboul-Fetouh E. Mourad and Ashraf H. Abou-Zied
Chemistry Department, Faculty of Science, El-Minia University, El-Minia, A. R. Egypt.
E-Mail: alaahassan2001@yahoo.com
Received October 20, 2006
S
C
O
H
CN
H
H
N
R
N
N
S
H
N
R
C
O
N
NH2
R
N
N
O
CN
N
N
N
+
+
+
NH2
N
NC
NH2
NC
CN
CN
R
O
NC
CN
CN
NC
1-Acylthiosemicarbazides 9a-d reacted with ethenetetracarbonitrile (TCNE, 2) in ethyl acetate with
formation of N'-(4-amino-5,6-dicyano-2H-1,3-thiazin-2-ylidene) substituted hydrazide 10a-d, N'-(5-amino-
3,4-dicyano-2H-pyrrol-2-ylidene)-2-substituted hydrazide 11a-d and 2-substituted imidazo[2,1-b][1,3,4]-
oxadiazole-5,6-dicarbonitrile 12a-d. Rationales for the conversions observed are presented.
J. Heterocyclic Chem., 44, 1171 (2007).
INTRODUCTION
tuted-5-phenyl-1,3,4-oxadiazoles 4 in addition to
compounds 5-8 (Chart 1) [17] are formed.
Cyclization of 1-acylthiosemicarbazides may be
achieved under various conditions [1-5]. For example,
1-acylthiosemicarbazides were cyclodehydrated with
concentrated sulphuric acid [1,2] or methanesulfonic acid
[3] to 2-amino-5-aryl-1,3,4-thiadiazols. 3-Mercapto-5-
aryl-s-triazoles have been obtained by cyclization of 1-
aroylthiosemicarbazides under alkaline conditions [4],
while their condensation with 2-chlorocyclohexanone
furnished 2-aroylhydrazino-4,5,6,7-tetrahydrobenzo-
thiazoles [5]. On the other hand, C-triazole-5-oyl-N-
phenylhydrazonoylbromide reacted with benzoylthio-
semicarbazide to give 5-phenylthiazole derivatives
[6,7]. Acetylthiosemicarbazide when condensed with
6,8-disubstituted-3-acetyl-coumarins in presence of
bromine or using lanthanum catalyst, yielded 2-
acetylhydrazino-4-coumarinylthiazole [8]. The reaction
of 1-chloro-1,4-diphenyl-2,3-diazabutadiene with
acetyl- and with 1-benzoylthiosemicarbazide yielded
initially the hydrochlorides of N2-acetyl- and N2-
benzoyl-ꢀ2-1,3,4-thiadiazoline-4-carboxamide hydra-
zones, which were converted by NaOH into the
corresponding free bases 4-substituted-ꢀ2-1,3,4-
thiadiazolines [9]. In the medicinal chemistry,
acylthiosemicarbazides have been studied for their
potential as therapeutic agents for the treatment of
hypertension and CNS depression [10] as well as
mitochondrial monoamine oxidase inhibitory (MAOI)
activity [11,12].
Chart 1
N
N
NC
CN
H
H
H
Ph
C
O
N
N
C
S
N
R
Ph
NHR
X
NC
CN
1
2
3
4
, X = S
, X = O
O
NC
O
S
CN
Ph
NC
N
N
H
Ph
N
N
R
S
N
N
CN
H
NC
CN
CN
H2N
6: a, R = C6H5CH2
b, R = H2C=CH-CH2
CN
5
Ph
O
O
N
Ph
N
N
NH
CN
CN
H2N
NC
CN
7
8
1,3,4: a: R = C6H5CO; b: R = C6H5; c: R = C6H5CH2; d: R = CH2=CHCH2; e: R = EtOOC
As will be outlined in detail below, in this paper we
report several heterocyclization of 1-acylthiosemicarba-
zide 9a-d using ethenetetracarbonitrile as a reaction
mediator and as a building block.
RESULTS AND DISCUSSION
Treatment of 9a-d with two molar equivalents of 2 in
ethyl acetate as solvent at room temperature resulted in a
brown colouration of the solution that quickly turned into
red, and formation of reddish brown precipitate of
thiazinylidenebenzoylhydrazide derivatives 10a-d (48-52
%) (Scheme 1). The filtrates were concentrated to dryness
and the residue subjected to vacuum sublimation to
remove any unreacted 2. Chromatographic separation of
the residue gave numerous zones, from which products 11
On the other hand, the interaction of thiosemicarbazide
derivatives with ethenetetracarbonitrile (TCNE, 2)
afforded various heterocyclic compounds via a single
electron transfer mechanism [13-18].
Recently, we have demonstrated that when 1,4-
disubstituted thiosemicarbazides 1 are reacted with 2, 2-
substituted-5-phenyl-1,3,4-thiadiazoles 3 and 2-substi-

1172
A. A. Hassan, A. E. Mourad and A. H. Abou-Zied
Vol 44
Scheme 1
Scheme 2
H
~H
2-H
9
9
+
2
9
+
2
+
R
N N
S
N
O
H H
+
2
+
R C N N C NH2
S
NH2
H
O
H
R
N
NH2
CN
R
N
C
NH
9a-d
NC
CN
10a-d
C
O
N
O
- HCN
CN
H
CN
S
NH
S
O
H
10a-d
NC
NC
(48-52%)
R
N N
CN
14
NC
CN
N
CHNH
i) - 2
ii) - H2S
+
CN
N N
O
NC
NH2
N
R
CN
11a-d
N
N
N NH
12a-d
+ 2
NH - 2 HCN
12a-d
(22-23%)
R
NH2
R
9-12: a: R = CH3; b: R = C6H5; c: R = 4-HO-C6H4;
d: R = 4-Br-C6H4-CH2
O
O
15
H
i) - S2
i) + 2
ii) - HCN
R
N N C NH2
2 x
9
11a-d
H
ii) + H2
(23-26%)
and 12 could be isolated (Scheme 1). In these cases, 2 is
"built in" completely or partially into the new structures.
The addition of the nucleophilic sites (N-H bonds or S-H)
of the starting materials 9a-d across the C=C double bond
of 2 may generate the four primary adducts (A, B, C, D)
producing from the sites N1, N2, SH and NH2 (Chart 2)
and tautomers that are capable of releasing HCN (which
effects a net tricyanovinylation) [19,20]. On the other
hand, [ꢀ4 + ꢀ2] cycloadditions of 2 with dehydrogenated
9a-d are not suggested to occur based on the nature of the
products formed. Thus, the structures of products 10-12
need to be derived from one suitable precursor out of the
previously suggested sites (Scheme 2). Structural
assignments of the products 10-12 are based on spectral
data and on combustion analyses.
O
16
amide CO groups in the range 1695-1685 cm-1. The H
nmr spectra show the presence of NH2 groups as broad
signals for 2H between ꢀ = 7.24-7.28 ppm, NH of amide
group as a broad signals for 1H between ꢀ = 10.81-10.88
ppm and for additionally 10a, the expected signals for the
acetyl group (ꢀ = 2.37 ppm). The 13C nmr spectra of 10a
showed signals around 118.71-118.93 (CN), 164.18 (C-
4), 155.32 (C-2), 121.22 and 121.74 (C-5 and C-6),
173.82 (C=O) and 26.42 (CH3).
1
Compounds 11a-d. N'-(5-Amino-3,4-dicyano-2H-
pyrrol-2-ylidene)-4-substituted benzohydrazide 11a-c
were obtained as characteristically orange crystals. Their
molecular structure are supported by the following
findings: for example 11b; the gross formula C13H8N6O
represents a products from one molecule of 9b and one of
2 with loss of sulphur and one molecule of HCN and
formation the pyrrole ring. The presence of an amide
group (ꢀC=O = 173.56 ppm) and the absence of both
thioamide function and or sulphur in 11b rules out any
oxa- or thiacyclic structures. Both a NH2 (ꢀH = 7.38 ppm)
and a low field NH group (ꢀH = 10.89 ppm) are present.
The mass spectrum shows the molecular ion at 264 and
fragments at m/z 105 (representing the benzoyl group
residue) and 131 (representing 5-amino-3,4-dicyano-
pyrrolylidenyl residue) from the cleavage of C2-N and
CO-NH bonds. The amide carbonyl stretch wavenumber
(1690 cm-1) points to some degree of electron withdrawal
from N2. The presence of two cyano groups in the
spectrum which show characteristic absorption at 2225
cm-1 and signals around 118.3 (CN), 155.69 (C-2) and
164.29 ppm (C-5) in the 13C nmr spectra lend further
support to the structure assigned 11b. Structure 11 was
accessible only from precursor (C) (Chart 2) after
elimination of sulphur but not from A, B and D.
Chart 2
O
C
S
O
C
S
C
H
H
N
R
R
N
N
C
NH2
R
N
NH2
CN
CN
NC
NC
NC
NC
H
H
CN
CN
A
B
O
C
H
N
N
C
S
NH2
O
C
H
H
R
N N C
NH
NC
CN
CN
S
H
CN
CN
NC
NC
NC
C
H
D
Compounds 10a-c. The molecular ions in their EI-
mass spectra confirm the molecular masses and gross
compositions. Further, the following common features of
the fragmentation patterns lead to support to the assigned
structures: loss of N2 giving intense (M+- 28) ions and
loss of R-C=O giving rise to the ion m/z = 191 common
in the spectra of all four compounds. The ir spectra show
characteristic absorptions for the NH2 and NH groups in
the range of 3420-3160, and 2220-2225 cm-1 for
conjugated CN groups, and bonds characteristic to an
While (C) would lead to 11 via 16, the isomeric
structure 11' would be accessible from D after elimination

Sep-Oct 2007
1-Acylthiosemicarbazides with Ethenetetracarbonitrile
1173
spectra [70 eV, electron impact mode] were obtained on an
AMD 604 instrument. Elemental analyses were carried out at
the Microanalytical Centre, Cairo University, Egypt. Preparative
layer chromatography was performed on air dried 1.0 mm thick
layers of slurry applied silica gel Merck PF254 on 48 cm wide
and 20 cm high glass plates. Zones were detected by their colour
or by quenching of indicator fluorescence upon exposure to 254
nm light.
of sulphur. The mass spectral fragmentation of the
product (see Fig. 1), however, is well in agreement with
structure 11 but not with structure 11'. Furthermore, the ir
spectrum of 11b in dilute CCl4 did not show the presence
of intermolecular H bridge as in structure 11' (Figure 1).
m/z 105
O
O
H
H
R
N
N
R
N N
Starting Materials.
N
N
H
Synthesis of 1-(4-bromophenylaceto)thiosemicarbazide
(9d). To a stirred solution of thiosemicarbazide (0.91 g, 10
mmol) in 50 ml dry acetone, p-bromophenylacetic acid (2.15 g,
10 mmol) was added and the mixture was refluxed for 3 h. A
white precipitate was formed, recrystallized from ethanol to give
colourless crystals (2.84 g, 85 %), m.p = 93-95 °C
NC
NH2
N
CN
H
m/z 66
CN
CN
11b, R = Ph
11`
Figure 1
1-Acetylthiosemicarbazide 9a; m.p = 165-167 °C (lit. [22-
24] 166 °C).
1-Benzoylthiosemicarbazide 9b; m.p = 195-197 °C (lit. [23-
28] 196-199 °C).
1-(4-Hydroxyphenyl)thiosemicarbazide 9c; m.p = 212-214
°C (lit. [29] 214-216 °C).
Compounds 12a-d. Compounds 12a-d do not contain
sulphur but contain five nitrogen atoms, thus for example
the molecular mass of 12d represents a gross composition
C13H6BrN5O reached from 9d and 2 after loss H2S and
two HCN. 2-(4-Bromobenzyl)imidazo[2,1-b][1,3,4]-
oxadiazole-5,6-dicarbonitrile was obtained.
Reaction of 1-acylthiosemicarbazides 9a-d with 2. A
solution of 9a-d (1 mmol) in 25 ml of dry ethyl acetate was
added dropwise with stirring at room temperature to 2 (2.0
mmol) in ethyl acetate (10 ml). The reaction mixture colour
changed gradually from brown to red, and the mixture was left
standing for 48 h. at room temperature, during which time a
crystalline reddish brown product separated. The resulting
solid material was filtered and the precipitate was washed with
ethanol, dried and recrystallized from sutiable solvent to give
N'-(4-amino-5,6-dicyano-2H-1,3-thiazin-2-ylidene) substituted
hydrazide 11a-d. The filtrate was concentrated to dryness and
the residue was sublimed at 80 °C under vacuum to remove
unreacted 2, then subjected to PLC (100 mg per plate) using
cyclohexane/ethyl acetate (1:1) as eluent to give numerous
coloured zones, the two intense of which were removed and
extracted. The fastest migrating zone (Rf = 0.56, orange)
contained N'-(5-amino-3,4-dicyano-2H-pyrrol-2-ylidene) sub-
stituted hydrazide 10a-d, while the slowest moving zone (Rf =
0.32, brown) contained 2-(substituted)imidazo[2,1-b][1,3,4]-
oxadiazole-5,6-dicarbonitrile 12a-d. Extraction of the zones
with acetone and concentration gave residues, which were
rechromatographed to improve purification.
The mass spectrum exhibited a molecular ion at m/z
327/329 (28 %). The ir spectrum showed strong band at
2210 cm-1 due to the cyano groups, 2980 (ali-CH) and
several peaks at 1640, 1600 cm-1 (C=N and aryl C=C).
The characteristic absorption of C-O-C fragment at 1090
cm-1 [21]. The 300 MHz 1H nmr (in DMSO-d6) displayed
broadened signal at 4.28 (Ph-CH2) in addition to aromatic
protons. The presence of CH2Ph is also evident from the
13C-DEPT-nmr spectrum exihibiting negative signals at ꢀ
= 52.90 ppm. The decoupled carbon spectrum of 12d
showed another signals at 164.33 and 122.78 ppm
assigned to (C-2 and C-5,6) respectively.
CONCLUSION
The reactions and the heterocyclic products here
provide insight into the spontaneous reactions between
the electron donating 1-acylthiosemicarbazides 9a-d and
a suitable electron acceptor 2. The reaction proceeds
through a fairly complex multistep process where two
kinds of ring forming reactions are observed. Thus,
ethenetetracarbonitrile (2) may act as a mediator and as a
building block in heterocyclization of thiosemicarbazides.
The results reported here supplement the rich chemistry
of ethenetetracarbonitrile (2).
N'-(4-Amino-5,6-dicyano-2H-1,3-thiazine-2-ylidene)aceto-
hydrazide (10a). This compound had mp 198-200°, red crystals
from acetonitrile, yield 115 mg (49 %); ir: 3390, 3220 (NH2,
1
NH), 2225 (CN), 1690 (CO) and 1635 (C=N) cm-1; H nmr
(DMSO-d6): ꢀ 2.37 (s, 3H, CH3), 7.28 (br, 2H, NH2), 10.81 (br,
1H, NH); 13C nmr (DMSO-d6): ꢀ 26.42 (CH3), 118.71, 118.93
(CN), 121.22, 121.74 (C-5 and C-6), 155.32 (C-2), 164.18 (C-4)
and 173.82 (CO); EI-MS m/z: % 234 (M+, 11), 206 (M-N2]+,
33), 191 ([M-CH3CO]+, 68), 137 (29), 121 (18), 93 (100). Anal.
Calcd. for C8H6N6OS (234.24): C, 41.02; H, 2.58; N, 35.88; S,
13.69. Found: C, 41.19; H, 2.46; N, 36.02; S, 13.57
EXPERIMENTAL
Melting points (uncorrected) were determined in open glass
capillaries on a Gallenkamp melting point apparatus. The ir
spectra were recorded from potassium bromide disks with a
N'-(4-Amino-5,6-dicyano-2H-1,3-thiazine-2-ylidene)benzo-
hydrazide (10b). This compound had mp 262-264°, reddish
brown crystals from methanol, yield 137 mg (51 %); ir: 3420,
3160 (NH2, NH), 2220 (CN), 1695 (CO) and 1640 (C=N) and
1
Shimadzu 408 instrument. The 300 MHz H and 75 MHz 13C
nmr spectra were recorded on Bruker WM 300 instrument,
Chemical shifts are expressed as ꢀ (ppm) with tetramethylsilane
as internal reference, s = singlet, m = multiplet; 13C assignments
have been made with the aid of DEPT 135/90 spectra. The mass
1
1600 (aryl) cm-1; H nmr (DMSO-d6): ꢀ 7.24 (br, 2H, NH2),
7.44-7.95 (m, 5H, phenyl-H), 10.88 (br, 1H, NH); 13C nmr
(DMSO-d6): ꢀ 118.52, 118.81 (CN), 121.14, 121.66 (C-5 and C-

1174
A. A. Hassan, A. E. Mourad and A. H. Abou-Zied
Vol 44
6), 127.84, 128.96, 132.82 (phenyl-CH), 142.56 (phenyl-C-1),
155.76 (C-2), 163.94 (C-4) and 173.96 (CO); EI-MS m/z: % 269
(M+, 26), 268 (M-N2]+, 24), 191 ([M-PhCO]+, 56), 175 (12), 149
(29), 105 (76), 77 (100). Anal. Calcd. for C13H8N6OS (296.31):
C, 52.70; H, 2.72; N, 28.36; S, 10.82. Found: C, 52.56; H, 2.83;
N, 28.41; S, 10.63.
6.93 (dd, 2H, aryl-H), 7.41 (br, 2H, NH2), 7.78-7.84 (m, 2H,
aryl-H), 9.19 (br, 1H, OH), 10.84 (br, 1H, NH); 13C nmr
(DMSO-d6): ꢀ 118.62, 118.93 (CN), 127.56 (C-4), 128.72
(C-3), 128.92, 130.12 (phenyl-CH), 136.84 (phenyl C-1),
152.34 (phenyl-C-4), 156.12 (C-2), 164.62 (C-5) and 173.67
(CO); EI-MS m/z %: 280 (M+, 17), 252 (11), 159 (36), 121
(33), 93 (100), 77 (76), 66 (23). Anal. Calcd. for C13H8N6O2
(280.24): C, 55.72; H, 2.88; N, 29.99. Found: C, 55.86; H,
2.69; N, 30.14.
N'-(4-Amino-5,6-dicyano-2H-1,3-thiazine-2-ylidene)-4-
hydroxybenzohydrazide (10c). This compound had mp 310-
312°, reddish brown crystals from methanol, yield 162 mg (52
%); ir: 3400-3190 (OH, NH2 and NH), 2225 (CN), 1685 (CO),
N'-(5-Amino-3,4-dicyano-2H-pyrrol-2-ylidene)-2-(4-bromo-
phenyl)acetohydrazide (11d). This compound had mp 133-35°,
orange crystals from ethanol, yield 82 mg (23 %); ir: 3386, 3260
(NH2 and NH), 2215 (CN), 1690 (CO), 1630, 1620 (C=N), 1600
1
1635 (C=N) and 1610 (aryl) cm-1; H nmr (DMSO-d6): ꢀ 6.90-
7.10 (dd, 2H, phenyl-H), 7.28 (br, 2H, NH2), 7.88-7.92 (m, 2H,
phenyl-H), 9.12 (br, 1H, OH), 10.84 (br, 1H, NH); 13C nmr
(DMSO-d6): ꢀ 118.41, 118.76 (CN), 121.42, 121.63 (C-5 and C-
6), 126.24, 128.93 (phenyl-CH), 136.82 (phenyl-C-1), 151.81
(phenyl-C-4), 164.12 (C-4), 172.88 (CO); EI-MS m/z: % 312
(M+, 22), 284 (M-N2]+, 26), 191 ([M-4-HO-C6H4CO]+, 56), 121
(74), 93 (100), 77 (46), 77 (100). Anal. Calcd. for C13H8N6O2S
(312.31): C, 50.00; H, 2.58; N, 26.91; S, 10.27. Found: C,
49.84; H, 2.42; N, 27.11; S, 10.09.
1
(aryl) cm-1; H nmr (DMSO-d6): ꢀ 4.23 (s, 2H, CH2), 6.95-7.11
(m, 2H, phenyl-H), 7.39 (br, 2H, NH2), 7.70-7.74 (m, 2H, aryl-
H), 10.86 (br, 1H, NH); 13C nmr (DMSO-d6): ꢀ 52.84 (CH2),
118.66, 118.93 (CN), 127.77, 128.18 (C-3, C-4), 131.92,
132.22 (phenyl-CH), 135.71 (phenyl-C-1), 136.12 (phenyl-C-4),
155.88 (C-2), 164.44 (C-5) and 173.61 (CO); EI-MS m/z: % 358
(M+, 32), 356 (29), 330 (11), 278 (26), 198 (44), 160 (27), 91
(74), 77 (100), 66 (36). Anal. Calcd. for C14H9BrN6O (357.16):
C, 47.08; H, 2.54; Br, 22.37; N, 23.53. Found: C, 46.88; H,
2.37; Br, 22.53; N, 23.69.
2-Methylimidazo[2,1-b][1,3,4]oxadiazole-5,6-dicarbonitrile
(12a). This compound had m.p = 225-227°, brown crystals from
acetonitrile, yield 40 mg (23 %); ir: 2985 (ali, CH), 2210 (CN),
1640 (C=N), 1085 (C-O-C) cm-1; 1H nmr (DMSO-d6): ꢀ 2.16 (s,
3H, CH3); 13C nmr (DMSO-d6): ꢀ 24.62 (CH3), 117.97 (CN),
127.77, 123.63 (C-5 and C-6), 156.12 (C-7'), 164.12 (C-2); EI-
MS m/z: % 173 (M+, 22), 158 (19), 97 (100), 69 (63). Anal.
Calcd. for C7H3N5O (173.13): C, 48.56; H, 1.75; N, 40.45.
Found: C, 48.71; H, 1.90; N, 40.26.
N'-(4-Amino-5,6-dicyano-2H-1,3-thiazine-2-ylidene)-2-(4-
bromophenyl)acetohydrazide (10d). This compound had mp
285-287°, deep red crystals from acetonitrile, yield 187 mg (48
%); ir: 3410-3215 (NH2 and NH), 2220 (CN), 1690 (CO), 1635
1
(C=N) and 1610 (aryl) cm-1; H nmr (DMSO-d6): ꢀ 4.26 (s, 2H,
CH2), 6.95-7.12 (m, 2H, phenyl-H), 7.26 (br, 2H, NH2), 7.68-
7.73 (m, 2H, phenyl-H), 10.82 (br, 1H, NH); 13C nmr (DMSO-
d6): ꢀ 52.88 (CH2), 118.36, 118.62 (CN), 121.32, 121.61 (C-5
and C-6), 131.94, 131.96, 132.12 (phenyl-CH), 134.76 (phenyl-
C-1), 135.12 (phenyl-C-4), 155.18 (C-2), 164.36 (C-4), 173.12
(CO); EI-MS m/z: % 391 (15), 389 (M+, 13), 360 (M-N2]+, 18),
191 ([M-(4-Br-C6H4CH2CO)]+, 61), 137 (12), 91 (100), 77 (56).
Anal. Calcd. For C14H9BrN6OS (389.23): C, 43.20; H, 2.33; Br,
20.53; N, 21.59; S, 8.24. Found: C, 43.36; H, 2.19; Br, 20.68; N,
21.41; S, 8.39.
N'-(5-Amino-3,4-dicyano-2H-pyrrol-2-ylidene)acetohydra-
zide (11a). This compound had mp 158-160°, orange crystals
from ethanol, yield 51 mg (25 %); ir: 3360, 3210 (NH2, NH),
2210 (CN), 1685 (CO) and 1625 (C=N) cm-1; 1H nmr (DMSO-
d6): ꢀ 2.34 (s, 3H, CH3), 7.41 (br, 2H, NH2), 10.76 (br, 1H, NH);
13C nmr (DMSO-d6): ꢀ 26.35 (CH3), 118.82, 119.31 (CN),
127.12 (C-4), 128.26 (C-3), 155.64 (C-2), 164.31 (C-5) and
173.44 (CO); EI-MS m/z: % 202 (M+, 11), 174 (24), 131 (19),
66 (28), 43 (100). Anal. Calcd. for C8H6N6O (202.17): C, 47.53;
H, 2.99; N, 41.57. Found: C, 47.68; H, 3.12; N, 41.41.
2-Phenylimidazo[2,1-b][1,3,4]oxadiazole-5,6-dicarbonitrile
(12b). This compound had mp 241-243°, brown crystals from
methanol, yield 54 mg (23 %); ir: 3090 (aryl-CH), 2215 (CN),
1
1635 (C=N), 1610 (aryl), 1090 (C-O-C) cm-1; H nmr (DMSO-
d6): ꢀ 7.34-7.68 (m, 5H, phenyl-CH); 13C nmr (DMSO-d6): ꢀ
118.12 (CN), 123.56 (C-5 and C-6), 128.96, 129.93, 131.14
(phenyl-CH), 136.12 (phenyl-C-1), 156.26 (C-7'), 164.34 (C-2);
EI-MS m/z: % 235 (M+, 32), 159 (28), 131 (12), 77 (100). Anal.
Calcd. for C12H5N5O (235.20): C, 61.28; H, 2.14; N, 29.78.
Found: C, 61.39; H, 1.93; N, 29.57.
2-(4-Hydroxyphenyl)imidazo[2,1-b][1,3,4]oxadiazole-5,6-
dicarbonitrile (12c). This compound had mp 222-223°, brown
crystals from acetonitrile, yield 55 mg (22 %); ir: 3490 (OH),
1
N'-(5-Amino-3,4-dicyano-2H-pyrrol-2-ylidene)benzohydra-
zide (11b). This compound had mp 212-214 °, yellowish brown
crystals from acetonitrile, yield 69 mg (26 %); ir: 3370, 3225
(NH2, NH), 2215 (CN), 1690 (CO) and 1630 (C=N), 1600 (aryl)
2215 (CN), 1640 (C=N), 1610 (aryl), 1085 (C-O-C) cm-1; H
nmr (DMSO-d6): ꢀ 6.88-7.48 (m, 4H, phenyl-CH), 9.18 (br, 1H,
OH); 13C nmr (DMSO-d6): ꢀ 118.64 (CN), 122.65 (C-5 and C-
6), 128.65, 130.64 (phenyl-CH), 135.42 (phenyl-C-1), 151.68
(phenyl-C-4), 156.22 (C-7'), 164.36 (C-2); EI-MS m/z: % 251
(M+, 36), 175 (18), 147 (12), 93 (100), 77 (66). Anal. Calcd. for
C12H5N5O2 (251.20): C, 57.38; H, 2.01; N, 27.88. Found: C,
57.56; H, 2.16; N, 27.67.
2-(4-Bromobenzoyl)imidazo[2,1-b][1,3,4]oxadiazole-5,6-
dicarbonitrile (12d). This compound had mp 266-268 °C, pale
brown crystals from methanol, yield 75 mg (23 %); ir: 2980 (ali-
CH), 2210 (CN), 1640 (C=N), 1600 (aryl), 1090 (C-O-C) cm-1;
1H nmr (DMSO-d6): ꢀ 4.28 (s, 2H, CH2), 6.95-7.47 (m, 4H,
phenyl-H); 13C nmr (DMSO-d6): ꢀ 52.90 (CH2), 118.66 (CN),
122.78 (C-5 and C-6), 131.32, 131.67 (phenyl-CH), 136.14
(phenyl-C-4), 139.15 (phenyl-C-1), 156.12 (C-7'), 164.33 (C-2);
EI-MS m/z: % 329 (M+, 28), 327 (25), 251 (36), 175 (23), 147
1
cm-1; H nmr (DMSO-d6): ꢀ 7.38 (br, 2H, NH2), 7.44-7.95 (m,
5H, phenyl-H), 10.89 (br, 1H, NH); 13C nmr (DMSO-d6): ꢀ
118.42, 118.86 (CN), 127.16 (C-4), 128.52 (C-3), 128.93,
129.26, 131.21 (phenyl-CH), 136.28 (phenyl C-1), 155.69 (C-2),
164.29 (C-5) and 173.56 (CO); EI-MS m/z: % 264 (M+, 32), 236
(M-N2]+, 13), 159 ([M-PHCO]+, 18), 105 (100), 66 (22), 42 (52).
Anal. Calcd. for C13H8N6O (264.24): C, 59.09; H, 3.05; N,
31.80. Found: C, 58.94; H, 3.21; N, 31.61.
N'-(5-Amino-3,4-dicyano-2H-pyrrol-2-ylidene)-4-hydroxy-
benzohydrazide (11c). This compound had mp 190-192°,
yellowish brown crystals from acetonitrile, yield 67 mg (24
%); ir: 3395-3230 (OH, NH2 and NH), 2220 (CN), 1685
1
(CO), 1630 (C=N), 1610 (aryl) cm-1; H nmr (DMSO-d6): ꢀ

Sep-Oct 2007
1-Acylthiosemicarbazides with Ethenetetracarbonitrile
1175
Pharmazie 1992, 47, 902.
(13), 91 (67), 77 (100). Anal. Calcd. for C13H6BrN5O (328.12):
C, 47.59; H, 1.84; Br, 24.35; N, 21.34. Found: C, 47.73; H,
1.65; Br, 24.14; N, 21.51.
[12] Pignatello, R.; Mazzone, S.; Castelli, F.; Mazzone, P.;
Raciti, G.; Mazzone, G. Pharmazie 1994, 49, 272.
[13] Hassan, A. A.; Ibrahim, Y. R.; El-Tamany, E. H.;
Semida, A. A.; Mourad, A. E. Phosphorus, Sulfur, Silicon 1995,
106, 167.
Acknowledgement. A. A. Hassan is indebted to the A. V.
Humboldt-Foundation for the donation of the Shimadzu 408 IR
spectrophotometer.
[14] Hassan, A. A., Mohamed, N. K.; Aly, A. A.; Mourad, A.
E. Monatsh. Chem. 1997, 128, 61.
[15] Hassan, A. A.; Mohamed, N. K.; Shawky, A. M.; Döpp,
D. Arkivoc. 2003, (i), 118. Availble at http:// www.arkat-
usa.org/akr/journal/2003/general/3708H/708H.pdf.
[16] Hassan, A. A.; Mourad, A. E.; El-Shaieb, K. M.; Abou-
Zied, A. H. Z. Naturforsch 2004, 59b, 910.
[17] Hassan, A. A.; El-Shaieb, K. M.; Shaker, R. M.; Döpp,
D. Heteroatom Chem. 2005, 16, 12.
[18] Gomaa, M. A.-M.; Hassan, A. A.; Shehatta, H. S.
Heteroatom Chem. 2006, 17, 261.
REFERENCES AND NOTES
[*] To whom correspondence should be addressed.
[1] Singh, S.; Yadav, L. D. S.; Singh, H. Indian J. Chem. 1981,
20B, 518.
[2] Yadav, L. D. S.; Shukla, K. N.; Singh, H. Indian J. Chem.
1989, 28B, 78.
[3] Kress, T. J.; Costantino, S. M. J. Heterocyclic Chem.
1980, 17, 607.
[19] Fataidi, A. J. Synthesis 1986 249.
[20] Fataidi, A. J. Synthesis 1987 749.
[4] Khazi, I. M.; Mahajanshetti, C. S. Monatsh. Chem. 1995,
126, 759.
[5] Balse, M. N.; Mahajanshetti, C. S. Indian J. Chem. 1980,
19B, 260.
[21] Charistos, D. A.; Vagenas, G. V.; Tzavellas, L. C.;
Tsoleridis, C. A.; Rodios, N. A. J. Heterocyclic. Chem. 1994, 31,
1593.
[22] Beyer, H.; Hohn, H.; Lassig, W. Chem. Ber 1952, 85,
1122.
[6] Abdel-Hamid, A. G.; Abdel-Riheem, N. A.; Emam, H. A.
J. Chem. Res. (S) 1999 532.
[23] Ohta, M.; Higashijima, T. Yakugaka Zasshi 1952, 72,
376; Chem. Abstr. 1953, 47, 22281e.
[7] Abdel-Hamid, A. G.; Metwally, N. H.; Bishai, N. S. J.
Chem. Res. (S) 2000 462.
[24] Ohta, M. Yakugaka Zasshi 1952, 72, 1636; Chem. Abstr.
1953, 47, 54879c.
[8] Vardhan, V. A.; Kumar, V. R.; Rao, V. R. Indian J.
Chem. 1999, 38B, 18.
[25] Shi, H.; Wang, Z. Y.; Shi, H.; Zhang, Z. Youji Huaxue
1996, 16, 242; Chem. Abstr. 1996, 125, 142224d.
[26] Beyer, H.; Kroeger, C. F.; Busse, G. Ann. 1960, 637, 135.
[27] Takogi, S.; Suhii, A. Yakugaku Zasshi 1958, 78, 280;
Chem. Abstr. 1958, 52, 65816f.
[9] Moss, S. F.; Taylor, D. R. J. Chem. Soc., Perkin Trans. I
1982 1987.
[10] Maxwell, R. A.; White, H. L. In (Iversen, L. L.; Iversen,
S. D.; Snyder, S. H. Eds.) Handbook of Psychopharmacology,
Plenum Press, New York, 1978 pp 83.
[28] Wang, Z.; Shi, A. Synthetic Commun. 2001, 31, 2841.
[29] Hoggarth, E. J. Chem. Soc. 1949 1163.
[11] Mazzone, G.; Pignatello, R.; Panico, A.; Mazzone, S.;
Puglisi, G.; Pennisi, G.; Raciti, G.; Mazzone, P.; Matera, M.