Dicyanomethylene compounds and heterocyclization of acylthiosemicarbazides

Article abstract of DOI:10.1002/jhet.5570450205

(Chemical Equation Presented) (1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene) propanedinitrile (1, in ethyl acetate solution), 3-(dicyanomethylene)-2-indolone (2, in ethanol/piperidine solution) and 7,7′,8,8′- tetracyanoquinodimethane (3, in pyridine solution)

Full text of DOI:10.1002/jhet.5570450205

Mar-Apr 2008
323
Dicyanomethylene Compounds and Heterocyclization of
Acylthiosemicarbazides
Alaa A. Hassan*, Aboul-Fetouh E. Mourad and Ashraf H. Abou-Zeid
Chemistry Department, Faculty of Science, Minia University, El-Minia, A. R. Egypt.
E-Mail: alaahassan2001@yahoo.com
Received January 26, 2007
NH2
O
N
HN
H
N
O
C
R
C
N
H
N
R
N
CN
O
C
S
Dicyanomethylene
acceptors
NC
H
N
H
N
O
R
C
NH2
O
C
H
N N
N
R
NC
CN
S
N
(1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile (1, in ethyl acetate solution), 3-(dicyano-
methylene)-2-indolone (2, in ethanol/piperidine solution) and 7,7',8,8'-tetracyanoquinodimethane (3, in
pyridine solution) act on substituted acylthiosemicarbazides 4a-d, forming the derivatives of oxoindeno-
pyrrolylidenehydrazide (5a-d and 7a-d), thiazoloindolylidenehydrazide (12a-d), pyrroloindolylidene-
hydrazide (13a-d) and spiro[pyrrolylidene-4,1'(cyclohexa-2',5'-dienylidene)]propanedinitrile (18a-d).
Rationales for these conversiones involving the nucleophilic addition on dicyanomethylene carbon atom
are presented.
J. Heterocyclic Chem., 45, 323 (2008).
Chart 1
INTRODUCTION
NC
O
O
Selective combination of two or more different electron
accepting functional groups into one molecule leads to a
series of new electron acceptors with unique properties.
Such a composite acceptor is (1,3-dioxo-2,3-dihydro-1H-
inden-2-ylidene)propanedinitrile (1), also referred to as
2-(dicyanomethylene)-1,3-indanedione [1], may be
considered as a strong organic π-acid [2]. It readily adds
nuclephiles such as aromatic and aliphatic amines at the
dicyanomethylene carbon atom with release of hydrogen
cyanide [3-7]. Acceptor (1) is also able to generate
iminum ions from the tertiary cyclic amines and
formation the α-cyanated amines [8]. Additionally, the
reaction of 1 with arylazoaminopyrazoles [9,10], 2-mer-
captobenzazoles [11], thiocarbohydrazide and thiocarba-
zones [12] as well as N-arylisoindolines [13] have been
reported.
CN
CN
CN
NC
NC
CN
CN
N
H
O
(TCNQ, 3)
2
1
RESULTS AND DISCUSSION
Treatment of 4a-d with two molar equivalents of (1,3-
dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile
(1) in ethyl acetate as solvent at room temperature
resulted in a yellow colouration of the solution which later
became brown. Concentration of the reaction mixture
yielded a brown precipitate 5 (56-63 %). The remaining
soluble materials were subjected to preparative layer
chromatography. From the one significant yellow zone
and by crystallization, the N'-(3-cyano-4-oxoindeno[1,2-
b]pyrrol-2(4H)-ylidene) substituted hydrazides 7 were
obtained in 29-33 % yield.
The IR spectrum of 5b shows absorption bands
characteristic of NH groups at 3395, 3210, strong cyano
groups at 2210, two carbonyl absorption at 1735 and 1675
cm-1. 1H-NMR spectrum of 5b clearly supports the
presence of two different broad signals centered at δ 11.12
and 11.28 ppm due to the amide-NH and pyrrole-NH,
respectively. In the 13C-NMR spectrum the carbonyl
groups of benzohydrazide and oxoindeno C-4 resonate at
δ = 174.12 and 182.12 ppm, respectively. Further peaks at
116.11 ppm (CN), at 155.63 (pyrrole-C2) and 60.12 ppm
(pyrrole-C3), besides the aromatic carbons support the
Closely analogous 3-(dicyanomethylene)-2-indolone
(2) [14] which is a ylidenemalononitrile like 1 reacted
with ketene S,S- and N,S-acetals [15], active methylene
compounds [16-20] and cyclohexanedione [21] to give
spiro heterocyclic compounds. The reaction of N,N'-
diarylacetamidines with 1 afforded indenoazepine-6-ones
[22]. In contrast, spiro[2,3-dihydroindol-3,4'-pyridino]-5'-
carbonitriles were obtained from the reaction of N,N'-
diarylacetamidines with 2 [22].
Encouraged by these results, in the present work we
describe the chemical behaviour of acylthiosemi-
carbazides 4a-d towards acceptor systems 1-3.

324
A. A. Hassan, A.-F. E. Mourad and A. H. Abou-Zeid
Vol 45
Scheme 2
assigned structure. Elemental analysis of 5b suggested a
gross formula C20H11N5O2. This was also confirmed by
the mass spectrum which exhibited the molecular ion at
m/z 353 (12 %). It is worthy to note that the mass spectra
of compounds 5a-d show the loss of C(CN)2 as well as the
acyl group from the molecular ions. The alternative
structure 6 could be ruled out on the basis of IR, 1H-NMR
and 13C-NMR spectroscopy.
O
H
N C R
O
H
N N C R
CN
N
N
+
4a-d
+
2
S
NH
N
N
9 (52-57%)
8 (35-39%)
4,8,9: a, R = CH3-; b, R = C6H5-; c, R = 4-HO-C6H4-; d, R = 4-Br-C6H4-CH2-
The IR spectra of 8a-d in KBr disc shows absorption
Scheme 1
characteristic of NH groups at 3350-3375, and carbonyl
O
1
group at 1690-1700 cm-1. The H-NMR spectrum of 8a
H
H
R
C N N
N
clearly shows the presence of aryl protons and amide-NH.
The 13C-NMR of 8a shows signals at 154.92, 164.22 and
163.28 due to thiazole-C-2, C-8a and C-3a, respectively
and at 173.44 for (CO) in addition to the aryl carbons. The
molecular formulae of compounds 8a-d are supported by
elemental analysis and mass spectra which gave the
expected molecular ion peaks.
NC
NC
O
5 (56-63 %)
R
N
O
N
O
C
H
N
H
N
Compounds 9a-d show a characteristic yellow colour.
The gross formula of 9b was confirmed by the mass
spectrum, which exhibited the molecular ion at m/z 313
(26 %). The IR spectrum showed absorption at 3395 and
N
R
C
S
NH2 +
1
NC
O
CN
4a-d
6
O
C
N
H
N
1
3210 (NH), 2215 (CN), and 1695 cm-1 (CO). The H-
R
N
NMR spectrum of 9b displayed two broad signals at
11.12 ppm for amide-NH and 11.33 ppm for pyrrole-NH
in addition to the aromatic protons. In it’s 13C-NMR
spectrum C-2, C-3, C-8a and C-3a resonate at δ = 156.73,
112.36, 164.22 and 148.69 ppm, respectively; further
peaks are at δ = 173.94 (CO) and 118.14 (CN).
NC
O
7 (29-33 %)
4,5,7: a, R = CH3-; b, R = C6H5-; c, R = 4-HO-C6H4-; d, R = 4-Br-C6H4-CH2-
7,7,8,8-Tetracyanoquinodimethane (TCNQ, 3) is very
well-known electron-acceptor molecule [23], which has
been successfully used for the preparation of electrically
conducting salts and CT-complexes [24]. The interest of
TCNQ has been focused on it’s potential applications on
molecular rectifiers [25], nonlinear optical materials [26],
organic ferromagents [27] and organic chromophores with
electron accepting properties [28]. Recently, it has been
found that the addition of 1,8-diaminonaphthalene to
For the formation of oxoindenopyrrolylidene
derivatives 7a-d, the mass spectrum as well as elemental
analysis of 7b established the molecular formula
C19H10N4O2. The IR spectrum showed the carbonyl groups
at 1735 and 1670 cm-1. These carbonyl groups appeared at
δ = 172.63 for the amide carbonyl group and δ = 183.12
1
for oxoindeno-C4, in the 13C-NMR spectrum. The H-
NMR spectrum of 7b showed one broad signal at δ =
11.10 ppm (NH) in addition to the aromatic protons. In
the 13C-NMR spectrum the pyrrole-C-2, C-3, C-4 and C-
8b absorb at δ = 156.12, 124.17, 183.12 and 164.35,
respectively. Also, the 13C-NMR of 7b clearly indicates
the presence of one cyano group at 118.47 ppm beside the
aromatic carbons.
The weaker acceptor 2, being easily accessible from
isatine [14], was expected to react similarly to 1 with
the acylthiosemicarbazides 4a-d. Reflux of one mole of
4a-d with two equivalents of 2 in ethanol/piperidene
resulted in pink colouration of the solution, which later
became pale brown. The residue remaining after
concentration was subjected to preparative layer
chromatography to give substituted thiazoloindolylidene
8a-d (35-39 %) and substituted pyrroloindolylidene 9a-
d (52-57 %) (Scheme 2).
Scheme 3
NH2
HN
O
H
N
R
C
N
CN
N
N
+
4a-d
3
+
+
NH2
R
O
10 (9-12%)
NC
CN
11a-d (67-73 %)
CNCN
NC
NC
CN
CN
CNCN
12 (7-11 %)
4,10,11: a, R = CH3-; b, R = C6H5-; c, R = 4-HO-C6H4-; d, R = 4-Br-C6H4-CH2-

Mar-Apr 2008
Dicyanomethylene Compounds and Heterocyclization of Acylthiosemicarbazides
325
Scheme 4
TCNQ (3) afforded 2-[4-(1H,3H-pyrimidin-2-ylidene)-
cyclohexa-2,5-dienylidene]malononitrile [29].
TCNQ-H
+
4a-d +
2 X 4
4
(TCNQ, 3)
+ TCNQ-H
4
Pyridine solution of TCNQ (3) and 4a-d in a molar
ratio of 2:1 were kept at 100 °C for 2 hours with
admission of air. Chromatographic separation of the
residue after concentration gave numerous coloured
zones, from which products 11a-d could be isolated. In
addition, the known compounds 10a-c [30-34], 12 [35]
were found in small quantities in all cases.
NH2
O
C
H
N
NC
NC
- S2
N
R
11a-d
CN
+ TCNQ-H
H
NC
16
NC
NC
CN
H
+ H
TCNQ-H
Structural assignment of products 11a-d is based on
spectral data and on combustion analysis. The elemental
analysis of 11b supporting the gross formula C20H13N7O,
and the mass spectrum which gave a correct molecular ion
at m/z 367 (17%). The IR spectrum of 11b showed NH2
and NH absorption bands at ν = 3425 and 3330-3240,
cyano groups at 2215, 2220, and carbonyl group at 1690
4
CN
17
12
3
4
17
+
+ 3
10
- H2S
CONCLUSION
The reactions and products presented here provide
1
cm-1. The H-NMR spectrum revealed three broad signals
insight into the spontaneous reactions between the
electron donors 1-acylthiosemicarbazides 4a-d and
electron acceptors (1,3-dioxo-2,3-dihydro-1H-inden-2-
ylidene)propanedinitrile (1), 3-(di-cyanomethylene)-2-
indolone (2) and 7,7,8,8-tetracyanoquinodimethane
(TCNQ, 3). In a fairly complex and multistep process,
fused heterocyclic and spiro[pyrrolylidene-4,1'-(cyclo-
hexa-2',5'-dienylidene)]propanedinitrile products are
formed from 4a-d and 1, 2 or 3. The predominant
products 5, 7, 8 and 9 have an intenesting fused hetero-
cyclic systems. Further, compounds 11a-d resemble
analogues of the family of heterocyclic tetracyanoquino-
dimethanes [29,36,37]. The results reported here
supplement the rich chemistry of 1-acylthio-
semicarbazides 4a-d.
with the ratio 2:1:1 at δ = 8.16, 11.10 and 11.31 related to
NH2, amide-NH and pyrrole-NH, respectively. The 13C-
NMR spectrum of 11b confirmed its 1H-NMR spectral data
by the appearance of signals at 48.63 (q-C-4), 64.12
(pyrrole-C-3), 74.18 (C-7'), 156.21 (C-5), 164.93 (C-2) and
174.39 (CO). The analytical data of compound 11 could
also match for other isomers of products 13-15 (Figure 1).
Ph
H2N
H2N
NH2
66
O
N
N
N
O
161
H
N
HN
H2N
NC
105
Ph C N N
O
NC
NC
CN
Ph
NH2
CN
14
NC
CN
NC
CN
1) 3-CN
2) 2-NH2
3) no C=O
4) q-C
13
11b
1) 3-CN
2) 2-NH, 1-NH2
3) C=O
1) 3-CN
2) no C=O
3) q-C
EXPERIMENTAL
Mp’s were determined with a Gallenkamp melting point apparatus
and are uncorrected. The IR specra were recorded with a Shimadzue
408 or a Bruker Vector 22 FT-IR spectrometers using potassium
4) q-C
4) 2-NH2
H
HN
N N C Ph
H2N
N N C Ph
1
bromide pellets. H 300 MHz and 13C NMR 75 MHz spectra were
NC
O
NC
NC
O
1
N
recorded on a Bruker WM 300 instrument, 500 MHz H and 125
N
NC
MHz 13C NMR spectra on a Bruker DRX 500 spectrometer.
Chemical shifts are expressed as δ [ppm] with reference to
tetramethylsilane as an internal standard, s = singlet, d = doublet, m =
multiplet. 13C assignments (qC = quaternary carbon atoms) were
made with the aid of DEPT 135/90 spectra for compound 5a,d, 7a,d,
8a,d, 9a,d and 11a,d. The mass spectra (70 eV, electron impact
mode) were recorded on an AMD 604 instrument. Elemental
analyses were carried out at the microanalytical center, Cairo
University, Egypt. For preparative layer chromatography (plc) 1.0
mm thick air-dried layers of slurry applied silica gel Merck Pf254 on
48 cm wide and 20 cm high glass plates were used, zones were
detected by their colour and indicator fluorescence quenching upon
exposure to 254 nm light and extracted with acetone.
NH2
15
NH2
1) 2-CN
2) 2-NH2
3) C=O
4) no q-C
Figure 1
The alternative structures 13-15 could also be ruled out
on the basis of 1H-NMR, 13C-NMR and the fragment ions
in the mass spectrum of 11b at m/z 303, 237, 206, 105
and 66. As shown in Figure 1, structure 11b fits best to all
the spectroscopic data (see experimental section).
Formation of the spiro compounds 11a-d derived from
TCNQ may be rationalizes as out lined in Scheme 4.
Starting Materials. 1-Acylthiosemicarbazides 4a-c were
prepared according to the procedures published in literature. The
1H-NMR spectral data of 4a-c were in full accord with the
published data.

326
A. A. Hassan, A.-F. E. Mourad and A. H. Abou-Zeid
Vol 45
1-Acetylthiosemicarbazide (4a); m.p = 165-167 °C (lit. [38]
compound was obtained as brown crystals (acetonitrile), mp
185-187°; ir: NH 3390, 3220, CN 2220, CO 1730, 1670, aryl
166 °C). 1-Benzoylthiosemicarbazide (4b); m.p = 195-197 °C
(lit. [39] 196-199 °C. 1-(4-Hydroxyphenzoyl)thiosemicarbazide
(4c); m.p = 212-214 °C (lit. [40] 214-216 °C).
1
1610 cm-1; H nmr: δ 4.31 (s, 2H, CH2), 6.95-8.10 (m, 8H, aryl
H), 11.06 (br, 1H, amide-NH); 11.26 (br, 1H, pyrrole-NH); 13C
nmr: δ 52.76 (CH2), 116.71 (CN), 124.95 (C-3a), 126.92,
126.91, 127.44, 128.28, 132.11, 132.34 (aryl-CH), 132.18,
134.19, 135.16 (aryl-C), 155.64 (C-2), 156.67 (C-8b), 174.12
(amide-CO), 182.13 (C-4); ms: m/z 447/445 (M+, 21), 365 (76),
260 (28), 198 (43), 105 (61), 90 (100), 77 (74), 65 (44). Anal.
Calcd. for C21H12BrN5O2: C, 56.52; H, 2.70; Br, 17.91; N, 15.69.
Found: C, 56.71; H, 2.57; Br, 18.11; N, 15.53.
1-(4-Bromo-phenylacetyl)thiosemicarbazide (4d). To
a
srirred 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 hours. A white
precipitate was formed, recrystallized from ethanol to give
colourless crystals (2.84 g, 85 %), m.p = 93-95 °C.
2-(1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedi-
nitrile(dicyanomethyleneindane-1,3-diane (1) was prepared
according to Chatterjee [1]. 3-(Dicyanomethylene)-2-indolone
(2) was prepared according to Fatiadi [14]. 7,7,8,8-
Tetracyanoquinodimethane (TCNQ, 3) was bought from Merck.
Reaction of 1-acylthiosemicarbazides 4a-d with (1). To a
solution of 1.0 mmol of 4a-d in 20 ml ethyl acetate 416 mg (2.0
mmol) of (1) were added within two minutes, the initially yellow
solution first turned red and then brown and was stirred for 3 h
at 20 °C. The mixture was left standing for 48 h at room
temperature, after which time a brown precipitate of 5a-d was
collected and crystallized. The mother liquor was separated by
plc using cyclohexane/ethyl acetate (1:1) to give a reddish
orange colour zone contaning compounds 7a-d.
N'-(3,3-Dicyano-4-oxoindeno[1,2-b]pyrrol-2(1H,3H,4H)-
ylidene)acetohydrazide (5a). This compound was obtained as
brown crystals (acetonitrile), mp 215-217°; ir: NH 3385, 3200,
CN 2215, CO 1730, 1670, aryl 1590 cm-1; 1H nmr: δ 2.36 (s, 3H,
CH3), 7.53-8.10 (m, 4H, aryl H), 11.08 (br, 1H, amide-NH);
11.25 (br, 1H, pyrrole-NH); 13C nmr: δ 20.79 (CH3), 59.78 (C-
3), 116.14 (CN), 124.81 (C-3a), 127.81, 128.44, 132.24, 132.71
(aryl-CH), 134.75, 137.33 (aryl-C), 156.18 (C-8b), 155.76 (C-2),
170.38 (amide-CO), 181.89 (C-4); ms: m/z 291 (M+, 16), 227
(31), 199 (18), 178 (22), 135 (36), 105 (61), 43 (100), 15 (97).
Anal. Calcd. for C15H9N5O2: C, 61.85; H, 3.11; N, 24.04. Found:
C, 62.03; H, 2.96; N, 24.19.
N'-(3-Cyano-4-oxoindeno[1,2-b]pyrrol-2(4H)-ylidene)-
acetohydrazide (7a). This compound was obtained as brown
crystals (ethanol), mp 196-198°; ir: NH 3360, CN 2220, CO
1
1730, 1660, C=N 1610, aryl 1585 cm-1; H nmr: δ 2.38 (s, 3H,
CH3), 7.61-7.82 (m, 4H, aryl-H), 11.05 (br, 1H, amide-NH) ; 13
C
nmr: δ 20.67 (CH3), 118.12 (CN), 124.13 (C-3), 129.76, 130.24,
131.62, 132.42 (aryl-CH), 134.79, 139.32 (aryl-C), 149.75 (C-
3a), 155.78 (C-2), 164.16 (C-8b), 173.88 (amide-CO), 182.72
(C-4); ms: m/z 264 (M+, 23), 221 (32), 195 (24), 167 (12), 139
(22), 105 (73), 43 (100). Anal. Calcd. for C14H8N4O2: C, 63.64;
H, 3.05; N, 21.20. Found: C, 63.48; H, 2.87; N, 21.39.
N'-(3-Cyano-4-oxoindeno[1,2-b]pyrrol-2(4H)-ylidene)benz-
ohydrazide (7b). This compound was obtained as yellow crystals
(acetonitrile), mp 240-242°; ir: NH 3385, CN 2220, CO 1735,
1
1670, C=N 1620, aryl 1600 cm-1; H nmr: δ 7.24-7.88 (m, 4H,
aryl-H), 11.10 (br, 1H, amide-NH); 13C nmr: δ 118.47 (CN),
124.17 (C-3), 128.56, 129.96, 130.12, 130.74, 131.66, 132.24,
132.46 (aryl-CH), 134.76, 134.93, 139.68 (aryl-C), 149.66 (C-
3a), 156.12 (C-2), 164.35 (C-8b), 172.63 (amide-CO), 183.12 (C-
4); ms: m/z 326 (M+, 19), 300 (16), 272 (21), 244 (8), 221 (26),
105 (100), 77 (63), 65 (54). Anal. Calcd. for C19H10N4O2: C, 69.93;
H, 3.09; N, 17.17. Found: C, 70.12; H, 2.86; N, 16.95.
N'-(3-Cyano-4-oxoindeno[1,2-b]pyrrol-2(4H)-ylidene)4-
hydroxybenzohydrazide (7c). This compound was obtained as
brown crystals (methanol), mp 265-267°; ir: OH, NH 3430-
1
N'-(3,3-Dicyano-4-oxoindeno[1,2-b]pyrrol-2(1H,3H,4H)-
ylidene)benzohydrazide (5b). This compound was obtained as
brown crystals (acetonitrile), mp 263-265°; ir: NH 3395, 3210,
3370, CN 2215, CO 1735, 1660, C=N 1620, aryl 1595 cm-1; H
nmr: δ 6.96-7.82 (m, 8H, aryl-H), 9.36 (br, 1H, OH), 11.10 (br,
1H, amide-NH); 13C nmr: δ 118.22 (CN), 124.12 (C-3), 126.18,
127.93, 128.96, 129.76, 130.26, 131.66, 132.48 (aryl-CH),
134.78, 139.96, 139.94, 161.94 (aryl-C), 149.70 (C-3a), 156.12
(C-2), 156.12 (C-2), 164.63 (C-8b); ms: m/z 342 (M+, 22), 316
(14), 288 (7), 221 (19), 121 (100), 105 (79), 92 (83), 77 (62), 65
(46). Anal. Calcd. for C19H10N4O3: C, 66.67; H, 2.94; N, 16.36.
Found: C, 66.49; H, 3.06; N, 16.53.
2-(4-Bromophenyl)-N'-(3-cyano-4-oxoindeno[1,2-b]pyrrol-
2(4H)-ylidene)benzohydrazide (7d). This compound was
obtained as red crystals (methanol), mp 160-162°; ir: NH 3375,
CN 2210, CO 1730, 1660, C=N 1615, aryl 1585 cm-1; 1H nmr: δ
4.28 (s, 2H, CH2), 6.94-7.86 (m, 8H, aryl-H), 11.05 (br, 1H,
amide-NH) ; 13C nmr: δ 52.46 (CH2), 117.93 (CN), 123.86 (C-
3), 126.10, 127.66, 129.92, 130.28, 131.67, 132.12, 132.64
(aryl-CH), 134.76, 137.92, 139.84 (aryl-C), 149.56 (C-3a),
155.88 (C-2), 164.69 (C-8b), 174.44 (amide-CO), 183.12 (C-4);
ms: m/z 420/ 418 (M+, 34), 392 (12), 364 (9), 284 (24), 233 (21),
198 (73), 105 (100), 91 (81), 77 (63), 65 (54). Anal. Calcd. for
C20H11BrN4O2: C, 57.30; H, 2.64; Br, 19.06; N, 13.36. Found: C,
57.18; H, 2.76; Br, 18.82, N, 13.54.
1
CN 2210, CO 1735, 1675, aryl 1600 cm-1; H nmr: δ 7.11-8.18
(all m, 9H, aryl H), 11.12 (br, 1H, amide-NH); 11.28 (br, 1H,
pyrrole-NH); 13C nmr: δ 60.12 (C-3), 116.11 (CN), 124.48 (C-
3a), 127.51, 127.83, 128.46, 128.90, 132.22, 132.62 (aryl-CH),
134.28, 134.79, 137.39 (aryl-C), 156.28 (C-8b), 155.63 (C-2),
174.12 (amide-CO), 182.12 (C-4); ms: m/z 353 (M+, 12), 289
(33), 261 (18), 156 (44), 105 (100), 77 (67), 65 (53). Anal.
Calcd. for C20H11N5O2: C, 67.99; H, 3.14; N, 19.82. Found: C,
67.81; H, 3.26; N, 20.03.
N'-(3,3-Dicyano-4-oxoindeno[1,2-b]pyrrol-2(1H,3H,4H)-
ylidene)-4-hydroxybenzohydrazide (5c). This compound was
obtained as red crystals (acetonitrile), mp 275-277°; ir: OH, NH
3460-3220, CN 2220, CO 1730, 1675, aryl 1610 cm-1; 1H nmr: δ
6.98-8.11 (all m, 8H, aryl H), 9.12 (br, 1H, OH), 11.08 (br, 1H,
amide-NH); 11.27 (pyrrole-NH); 13C nmr: δ 59.12 (C-3), 116.22
(CN), 124.66 (C-3a), 126.11, 126.33, 127.55, 128.46, 132.18,
132.44 (aryl-CH), 134.33, 134.72, 157.62 (aryl-C), 156.83 (C-
8b), 155.43 (C-2), 173.58 (amide-CO), 181.89 (C-4); ms: m/z
369 (M+, 21), 352 (18), 305 (26), 277 (11), 172 (22), 121 (100),
105 (86), 93 (76), 77 (56). Anal. Calcd. for C20H11N5O3: C,
65.04; H, 3.00; N, 18.96. Found: C, 64.64; H, 2.88; N, 19.18.
2-(4-Bromophenyl)-N'-(3,3-dicyano-4-oxoindeno-[1,2-b]-
pyrrol-2(1H,3H,4H)-ylidene)acetohydrazide (5d). This
Reaction of acylthiosemicarbazides 4a-d with 2. 1-Acyl-
thiosemicarbazides 4a-d (1 mmol) were dissolved in 20 ml
absolute ethanol with two drops of piperidine and added to the
indolone 2 (2 mmol) in 25 ml ethanol, the mixture was heated

Mar-Apr 2008
Dicyanomethylene Compounds and Heterocyclization of Acylthiosemicarbazides
327
under reflux for 15 h, cooled to room temperature, concentrated
and subjected to plc using cyclohexane/ethyl acetate (1:1) to
give numerous coloured zones, the two intense of which were
removed and extracted. The fastest migrating one contained the
thiazoloindolylidenehydrazide derivatives 8a-d. The slowest
migrating zone (which is always characterized by yellow colour)
contained pyrroloindolylidene hydrazide derivatives 9a-d.
Extraction of the zones with acetone and crystallized.
N'-(2H-Thiazolo[5,4-b]indol-2-ylidene]acetohydrazide (8a).
This compound was obtained as brown crystals (acetonitrile), mp
214-216°; ir: NH 3360, CO 1690, C=N 1620, aryl 1580 cm-1; 1H
nmr: δ 2.36 (s, 2H, CH3), 7.37-7.68 (m, 4H, aryl-H), 11.08 (br,
1H, amide-NH); 13C nmr: δ 21.31 (CH3), 127.93, 128.14, 129.22,
130.51 (aryl-CH), 134.77, 149.56 (aryl-C), 154.92 (C-2), 163.28
(C-8b), 164.22 (C-3a), 173.44 (amide-CO); ms: m/z 244 (M+, 26),
201 (22), 109 (53), 91 (38), 77 (54), 43 (100), 28 (29). Anal.
Calcd. for C11H8N4O5: C, 54.09; H, 3.30; N, 22.94; S, 13.13.
Found: C, 53.89; H, 3.49; N, 23.17; S, 13.32.
9H, aryl-H), 11.12 (br, 1H, amide-NH), 11.33 (br, 1H, pyrrole-
NH), 13C nmr: δ 118.14 (CN), 112.36 (C-3), 127.35, 127.76,
127.83, 128.94, 129.36, 130.24 (aryl-CH), 132.36, 146.76 (aryl-
C), 148.69 (C-3a), 156.73 (C-2), 164.22 (C-8a), 173.94 (CO);
ms: m/z 313 (M+, 26), 287 (14), 259 (6), 208 (26), 105 (100),
103 (87), 91 (81), 77 (63), 65 (41). Anal. Calcd. for C18H11N5O:
C, 69.00; H, 3.54; N, 22.35. Found: C, 68.76; H, 3.71; N, 22.11.
N'-(3-Cyanopyrrolo[2,3-b]indol-2(1H)-ylidene)-4-hydroxy-
benzohydrazide (9c). This compound was obtained as yellow
crystals (acetonitrile), mp 241-243°; ir: OH 3435, NH 3210, CN
1
2220, C=O 1690, C=N 1625, aryl 1610 cm-1; H nmr: δ 6.92-
7.83 (m, 8H, aryl-H), 9.42 (br, 1H, OH), 11.08 (br, 1H, amide-
NH), 11.32 (br, 1H, pyrrole-NH), 13C nmr: δ 111.94 (C-3),
118.14 (CN), 126.13, 127.23, 127.76, 128.94, 129.33 (aryl-CH),
132.16, 133.82, 146.76, 161.93 (aryl-C), 149.76 (C-3a), 156.22
(C-2), 164.37 (C-8a), 173.88 (CO); ms: m/z 329 (M+, 17), 312
(7), 286 (12), 258 (14), 208 (31), 121 (92), 103 (76), 93 (100),
77 (62), 65 (49). Anal. Calcd. for C18H11N5O2: C, 65.65; H, 3.37;
N, 21.27. Found: C, 65.89; H, 3.51; N, 21.02.
2-(4-Bromophenyl)-N'-(3-cyanopyrrolo[2,3-b]indol-2(1H)-
ylidene)-4-acetohydrazide (9d). This compound was obtained
as orange crystals (methanol), mp 223-225°; ir = NH 3375,
3215, CN 2220, C=O 1695, C=N 1610, aryl 1585 cm-1; 1H nmr:
δ 4.22 (s, 2H, CH2), 6.92-7.44 (m, 8H, aryl-H), 11.03 (br, 1H,
amide-NH), 11.26 (br, 1H, pyrrole-NH), 13C nmr: δ 52.76 (CH2),
111.88 (C-3), 118.26 (CN), 126.12, 127.23, 127.76, 129.36,
131.94, 132.26 (aryl-CH), 130.12, 131.14, 146.76 (aryl-C),
151.36 (C-3a), 156.18 (C-2), 164.44 (C-8a), 173.28 (CO); ms:
m/z 406/404 (M+, 21), 378 (14), 298 (11), 207 (31), 179 (42),
151 (88), 91 (100), 77 (67). Anal. Calcd. for C19H12BrN5O: C,
56.19; H, 2.97; Br, 19.67; N, 17.25. Found: C, 56.38; H, 2.67;
Br, 19.86; N, 17.10.
N'-(2H-Thiazolo[5,4-b]indol-2-ylidene]benzohydrazide (8b).
This compound was obtained as brown crystals (methanol), mp
233-235°; ir: NH 3375, CO 1695, C=N 1610, aryl 1600 cm-1; 1H
nmr: δ 7.24-7.72 (m, 9H, aryl-H), 11.10 (br, 1H, amide-NH); 13
C
nmr: δ 127.66, 127.93, 129.13, 130.63, 132.12 (aryl-CH),
134.54, 134.61, 149.76 (aryl-C), 155.13 (C-2), 163.76 (C-8b),
164.62 (C-3a), 172.14 (amide-CO); ms: m/z 306 (M+, 16), 278
(9), 171 (24), 135 (53), 105 (100), 77 (67), 65 (48). Anal. Calcd.
for C16H10N4O5: C, 62.73; H, 3.29; N, 18.29; S, 10.47. Found: C,
62.51; H, 3.16; N, 18.11; S, 10.66.
4-Hydroxy-N'-(2H-thiazolo[5,4-b]indol-2-ylidene]benzo-
hydrazide (8c). This compound was obtained as brown crystals
(acetonitrile), mp 274-276°; ir: OH, NH 3420-3350, C=O 1700,
1
C=N 1625, aryl 1600 cm-1; H nmr: δ 6.92-7.78 (aryl-H), 9.23
(br, 1H, OH), 11.05 (br, 1H, amide-NH), 13C nmr: δ 126.22,
127.46, 128.93, 130.54, 130.96, 131.14 (aryl-CH), 134.61,
149.58, 161.92 (aryl-C), 155.13 (C-2), 163.26 (C-8a), 164.53
(C-3a), 173.12 (amide-CO); ms: m/z 322 (M+, 16), 305 (5), 294
(16), 201 (34), 135 (26), 121 (73), 93 (100), 77 (71), 65 (62).
Anal. Calcd. for C16H10N4O2S: C, 59.62; H, 3.13; N, 17.38; S,
9.95. Found: C, 59.46; H, 2.98; N, 17.56; S, 10.14.
2-(4-Bromophenyl-N'-(2H)-thiazolo[5,4-b]indol-2-ylidene]-
acetohydrazide (8d). This compound was obtained as brown
crystals (ethanol), mp 181-183°; ir: NH 3355, C=O 1690, C=N 1620,
aryl 1590 cm-1; 1H nmr: δ 4.28 (s, 2H, CH2), 6.91-7.77 (m, 8H, aryl),
11.05 (br, 1H, amide-NH); ms: m/z 400/ 398 (M+, 22), 318 (19), 198
(42), 135 (24), 118 (37), 91 (74), 77 (100), 65 (52). Anal. Calcd. for
C17H11BrN4OS: C, 51.14; H, 2.78; Br, 20.01; N, 14.03; S, 8.03.
Found: C, 51.31; H, 2.91; Br, 19.86; N, 13.84; S, 8.21.
Reaction of 4a-d with (TCNQ, 3). To a solution of 3 (408
mg, 2.0 mmol) in dry pyridine (15 ml) a solution of 4a-d (1.0
mmol) in 10 ml of pyridine was added dropwise over 5 min at
room temperature. The mixture was warmed gently without
increasing the temperature above 100 °C and kept at this
temperature with stirring and admission of air for 3 hours. The
solvent was removed and concentrated to dryness at 50 °C. The
residue was taken up several times with cold ethanol (10 ml) and
the slurry was concentrated again to remove any residual
pyridine. The residue was dissolved in acetone and separated by
preparative layer chromatography using chloroform/methanol
(20:1) as eluent into numerous zones, three of which were
extracted. The fastest migrating zone, which quenched all
indicator fluorescence upon exposure to 254 nm uv-light
contained oxadiazole derivatives (10a-d). The material confined
to the start was re-chromatographed using chloroform/methanol
(10:1) to give another two zones, the faster migrating one
contained (12), whereas the second zone (deep blue) contained
11a-d. Extraction of the zones with acetone gave a residue,
which was rechromatographed with some eluent to enhance
separation. Recrystallization from suitable solvents afforded
compounds 10, 11 and 12.
N'-(3-Cyanopyrrolo[2,3-b]indol-2(1H)-ylidene)acetohydra-
zide (9a). This compound was obtained as yellow crystals
(ethanol), mp 186-188°; ir: NH 3380, 3190, CN 2220, C=O
1
1685, C=N 1620, aryl 1600 cm-1; H nmr: δ 2.40 (s, 3H, CH3),
7.42-7.81 (m, 4H, aryl-H), 11.08 (br, 1H, amide-NH), 11.31 (br,
1H, pyrrole-NH), 13C nmr: δ 21.76 (CH3), 112.62 (C-3), 117.32
(CN), 127.92, 128.22, 129.36 (aryl-CH), 132.12, 146.76 (aryl-
C), 148.56 (C-3a), 156.24 (C-2), 164.18 (C-8a), 173.71 (CO);
ms: m/z 251 (M+, 31), 225 (13), 148 (27), 103 (41), 43 (100), 28
(53). Anal. Calcd. for C13H9N5O: C, 62.15; H, 3.61; N, 27.87.
Found: C, 62.37; H, 3.42; N, 28.11.
N'-(2-Amino-3-cyano)spiro[pyrrol-5-ylideneacetohydrazide-
4,1'-(cyclohexa-2',5'-dienylidene)]propanedinitrile (11a). This
compound was obtained as blue crystals (acetonitrile), mp 296-
298°; ir: NH2 3430, NH 3320-3250, CN 2225, 2210, CO 1695,
C=N 1620, aryl 1600 cm-1; 1H nmr: δ 2.39 (s, 3H, CH3), 6.38, 6.66
(d, d, 4H, C-1,2,4,5), 8.12 (br, 2H, NH2), 11.06 (br, 1H, amide-
NH), 11.28 (br, 1H, pyrrole-NH), 13C nmr: δ 22.11 (CH3), 48.56
(q-C-4), 63.64 (pyrrole-C-3), 74.22 (C-7'), 117.93, 119.12 (CN),
N'-(3-Cyanopyrrolo[2,3-b]indol-2(1H)-ylidene)benzohy-
drazide (9b). This compound was obtained as yellow crystals
(acetonitrile), mp 204-206°C; ir: NH 3395, 3210, CN 2215,
1
C=O 1695, C=N 1620, aryl 1595 cm-1; H nmr: δ 7.12-7.94 (m,

328
A. A. Hassan, A.-F. E. Mourad and A. H. Abou-Zeid
Vol 45
[2] Rappoport, Z.; Ta-Shma, K. J. Chem. Soc. 1971, (B), 1461.
[3] Fischer-Colbrie, H.; Aigner, H.; Junek, H. Monatsh. Chem.,
1975, 106, 743.
[4] Rapport, Z.; Ladkani, D. J. Chem. Soc., Perkin Trans. 2
1973, 1045.
[5] Fatiadi, A. J. Synthesis, 1986, 249, and references cited
therein.
[6] Junek, H.; Klade, M.; Biza, P.; Geringer, M.; Sterk, H.
Liebigs Ann. Chem., 1990, 741.
[7] Junek, H.; Fischer-Colbric, H.; Hermetter, A. Z. Naturforsch,
1977, 32b, 898.
124.34, 128.89 (quino-CH), 155.93 (C=N, C-5), 164.89 (C-2),
174.18 (CO), 177.73 (C-4'); ms: m/z 305 (M+, 26), 262 (27), 198
(22), 163 (19), 109 (26), 66 (16), 43 (100), 28 (74). Anal. Calcd. for
C15H11N7O: C, 59.01; H, 3.63; N, 32.12. Found: C, 58.78; H, 3.79;
N, 32.36.
N'-(2-Amino-3-cyano)spiro[pyrrol-5-ylidenebenzohydrazide-
4,1'-(cyclohexa-2',5'-dienylidene)]propanedinitrile (11b). This
compound was obtained as deep blue crystals (acetonitrile), mp
311-313°; ir: NH2 3425, NH 3330-3240, CN 2220, 2215, CO 1690,
1
C=N 1620, aryl 1595 cm-1; H nmr: δ 6.28, 6.62 (d, d, 4H, C-
[8] Döpp, D.; J schke, S.; Henkel, G. Z. Naturforsch, 2002, 57b,
460.
[9] Hassan, A. A.; Ibrahim, Y. R.; Mohamed, N. K.; Mourad, A.
E. Liebigs Ann. Chem., 1991, 71.
[10] Hassan, A. A.; Mohamed, N. K.; Ibrahim, Y. R.; Mourad, A.
E. Liebigs Ann. Chem., 1993, 659.
[11] Hassan, A. A.; Mohamed, N. K.; El-Tamany, E. H.; Ali, B.
A.; Mourad, A. E. Monatsh. Chem., 1995, 126, 653.
[12] Hassan, A. A.; Mohamed, N. K.; Aly, A. A.; Mourad, A. E.
Monatsh. Chem., 1997, 128, 61.
[13] Döpp, D.; Hassan, A. A.; Nour El-Din, A. M.; Mourad, A. E.;
Lehmann, C. W.; Rust, J. Tetrahedron, 2006, 62, 11618.
[14] Fatiadi, A. J. Synthesis, 1978, 165.
[15] El-Saghier, A. M. M. Phosphours, Sulfur, Silicon, Related
Elements, 2004, 179, 1237.
[16] Ali, A. S. E.; Afeefy, H.; Metwally, M. A. J. Chem. Res.
1994, (s), 14.
[17] Abdel-Latif, F. F.; Shaker, R. M. Bull. Chem. Soc. Fr., 1991,
87.
1,2,4,5), 7.18-7.83 (m, 5H, aryl-H), 8.16 (br, 2H, NH2), 11.10 (br,
1H, amide-NH), 11.31 (br, 1H, pyrrole-NH), 13C nmr: δ 48.63 (q-
C-4), 64.12 (pyrrole-C-3), 74.18 (C-7'), 118.11, 119.22 (CN),
124.44, 128.18 (quino-CH), 126.61, 129.74, 132.11 (aryl-CH),
134.56 (aryl-C), 156.21 (C=N, C-5), 164.93 (C-2), 174.39 (CO),
177.61 (C-4'); ms: m/z 367 (M+, 17), 303 (21), 237 (16), 206 (6),
105 (86), 77 (100), 66 (61). Anal. Calcd. for C20H13N7O: C, 65.39;
H, 3.57; N, 26.09. Found: C, 65.57; H, 3.41; N, 25.82.
4-Hydroxy-N'-(2-amino-3-cyano)spiro[pyrrol-5-ylidene-
benzohydrazide-4,1'-(cyclohexa-2',5'-dienylidene)]propane-
dinitrile (11c). This compound was obtained as deep blue
crystals (methanol), mp 332-334°; ir: OH 3470, NH2 3910, NH
3325-3260, CN 2215, 2210, CO 1695, C=N 1615, aryl 1600
1
cm-1; H nmr: δ 6.31, 6.64 (d, d, 4H, C-1,2,4,5), 6.96-7.78 (m,
4H, aryl-H), 8.16 (br, 2H, NH2), 9.36 (br, 1H, OH), 11.08 (br,
1H, amide-NH), 11.32 (br, 1H, pyrrole-NH), 13C nmr: δ 48.59
(q-C-4), 63.95 (pyrrole-C-3), 74.22 (C-7'), 117.98, 119.16 (CN),
124.16, 127.72 (quino-CH), 128.11, 129.56 (aryl-CH), 134.41,
159.21 (aryl-C), 155.96 (C=N, C-5), 165.06 (C-2), 174.31 (CO),
177.42 (C-4'); ms: m/z 383 (M+, 14), 319 (17), 262 (24), 238
(16), 225 (9), 206 (6), 121 (82), 93 (100), 77 (76), 66 (51). Anal.
Calcd. for C20H13N7O2: C, 62.66; H, 3.42; N, 25.58. Found: C,
62.89; H, 3.28; N, 25.35.
[18] Dworczak, R. Monatsh. Chem., 1991, 122, 731.
[19] Hafez, E. A.; Abdel-Galil, F. M.; Sherif, S. M.; El-Nagdi, M.
H. J. Heterocyclic Chem., 1986, 23, 1375.
[20] Abdel-Latif, F. F.; Gohar, A. M. N.; Fahmy, A. M.; Badr, M.
Z. A. Bull. Chem. Soc. Jpn., 1986, 59, 1235.
[21] Al-Omran, F.; El-Ghamry, I.; El-Nagdi, M. H. Org. Prep.
and Proceedures international, 1998, 30, 363.
2-(4-Bromophenyl)-N'-(2-amino-3-cyano)spiro[pyrrol-5-yl-
idenebenzohydrazide-4,1'-(cyclohexa-2',5'-dienylidene)]pro-
panedinitrile (11d). This compound was obtained as blue crystals
(acetonitrile), mp 264-266°; ir: NH2 3425, NH 3330, 3255, CN
2220, 2215, CO 1690, C=N 1620, aryl 1600 cm-1; 1H nmr: δ 4.26
(S, 2H, CH2), 6.28, 6.62 (d, d, 4H, C-1,2,4,5), 7.03-7.42 (m, 4H,
aryl-H), 8.16 (br, 2H, NH2), 11.05 (br, 1H, amide-NH), 11.31 (br,
1H, pyrrole-NH); 13C nmr: δ 48.62 (q-C-4), 52.16 (CH2), 64.11
(pyrrole-C-3), 73.92 (C-7'), 118.11, 119.22 (CN), 124.10, 127.53
(quino-CH), 131.96, 132.26 (aryl-CH), 128.11, 134.76 (aryl-C),
156.06 (C=N, C-5), 164.86 (C-2), 174.26 (CO), 177.42 (C-4'); ms:
m/z 459/461 (M+, 21), 395 (14), 381 (26), 331 (11), 303 (15), 261
(24), 198 (76), 118 (66), 91 (71), 77 (100), 66 (86). Anal. Calcd.
for C21H14BrN7O : C, 54.80; H, 3.07; Br, 17.36; N, 21.30. Found:
C, 55.05; H, 2.86; Br, 17.54; N, 21.52.
[22] Döpp, D.; Gomaa, M. A.; Henkel, H.; Nour El-Din, A. M. J.
Chem. Soc. Perkin Trans. 1996, II, 573.
[23] Wheland, R. C.; Martin, E. L. J. Org. Chem., 1975, 40, 3101.
[24] Martin, N.; Seoane, C. "Organic Conductive Molecules and
Polymers", Nalwa (ed.). N. S.; Wiley, 1996.
[25] Metzger, R. M.; Shumaker, R. R.; Cara, M. P.; Laidlow, R.
K.; Panetta, L. A.; Torres, E. Langmuir, 1988, 4, 298.
[26] Ashwell, G. J.; Downay, E. Je.; Kuczynski, A. P.;
Szablewski, M.; Sandy, I. M.; Bryce, M. R.; Grainger, A. M.; Hasan, M.
J. Chem. Soc. Faraday Trans., 1990, 86, 1117.
[27] Miller, J. S.; Calabrese, J. C.; Harlow, R. L.; R. L. Dixan, R.
L.; Zhang, J. H.; Rieff, W. M.; Chittipeddi, S.; Selover, M. A.; Epstein,
A. J. J. Am. Chem. Soc., 1990, 112, 5496.
[28] Zaidi, N. A.; Bryce, M. R.; Cross, G. H. Tetrahedron Lett.,
2000, 41, 4645.
[29] Aly, A. A.; El-Shaieb, K. M. Tetrahedron, 2004, 60, 3797.
[30] De, S. C. J. Indian Chem. Soc., 1930, 7, 651.
[31] Henkleiss, P.; Westphal, G., Kraft, R. Tetrahedron, 1973, 29,
2937.
[32] Bansal, R. K. J. Indian Chem. Soc., 1989, 59, 277.
[33] Rivera, N. R.; Balesells, J.; Hansen, K. B. Tetrahedron Lett.,
2006, 47, 4889.
[34] Ghlen, H.; Moeckel, K. Ann., 1962, 651, 133.
[35] El-Kacemi, K.; Lamache, M. Electrochimica Acta, 1986, 31,
845.
2-Amino-5-(4-bromobenzyl)oxadiazole (10d). This compound
was obtained as colourless crystals (ethanol), mp 185-187°; ir:
1
NH2 3410, C=N 1630, aryl 1595 cm-1; H nmr: δ 4.21 (s, 2H,
CH2), 6.88 (br, 2H, NH2), 7.14-7.69 (m, 4H, aryl-H); ms: m/z
255/253 (M+, 33), 211 (21), 131(36), 90 (87), 77 (100). Anal.
Calcd. for C9H8N3BrO: C, 42.54; H, 3.17; N, 16.54. Found: C,
42.78; H, 2.98; N, 16.29.
Acknowledgement. A. A. Hassan is indebted to the A. V.
Humboldt-Foundation for the donation of the Shimadzu 408 IR
spectrophotometer.
[36] El-Shaieb, K. M.; Mourad, A. E.; Hassan, A. A. Heteroatom
Chem., 2004, 15, 63.
[37] Bryce, M. R.; Chinarro, E.; Green, A.; Martin, N.; Moore, A.
J.; Sanchez, L.; Seoane, C. Synthetic Metals, 1997, 86, 1857.
[38] Beyer, H.; Hohn, H.; Lassig, W. Chem. Ber., 1952, 85, 1122.
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