(Substituted Ylidene)Amino-2-Oxo-Indolylidene Thioureas and Bis(2-Oxo-Indolylidene)Urea from (Ylidene)Thiocarbonohydrazides and Isatylidene Malononitrile

Article abstract of DOI:10.1002/jhet.2660

A simple and efficient synthesis of (substituted ylidene)(2-oxoindolylidene)thiocarbohydrazones and bis(2-oxoindolylidene)urea was achieved by the reaction of (substituted ylidene)thiocarbonohydrazides with isatylidene malononitrile. Rational for this conversation involving the nucleophilic additions on the dicyanomethylene carbon atom is presented. The structures of the products have been confirmed by using spectral and single-crystal X-ray analyses.

Full text of DOI:10.1002/jhet.2660

Month 2016
(Substituted Ylidene)Amino-2-Oxo-Indolylidene Thioureas and Bis(2-
Oxo-Indolylidene)Urea from (Ylidene)Thiocarbonohydrazides and
Isatylidene Malononitrile
Alaa A. Hassan, Shaaban K. Mohamed, Fathy F. Abdel-Latif,a Sara M. Mostafa,a Mohamed Abdel-Aziz,c
a
a,b
*
Joel T. Mague,d Mehmet Akkurt,e Stefan Bräse,f and Martin Niegerg
aChemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
bChemistry and Environmental Division, Manchester Metropolitan University, Manchester, M1 5GD, England
cDepartment of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 El-Minia, Egypt
dDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
eDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey
fInstitute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
gLaboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O Box 55 (A. I. Virtasen aukio 1)
00014 Helsinki, Finland
*
E-mail: alaahassan2001@mu.edu.eg
Additional Supporting Information may be found in the online version of this article.
Received January 7, 2016
DOI 10.1002/jhet.2660
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A simple and efficient synthesis of (substituted ylidene)(2-oxoindolylidene)thiocarbohydrazones and bis
(2-oxoindolylidene)urea was achieved by the reaction of (substituted ylidene)thiocarbonohydrazides with
isatylidene malononitrile. Rational for this conversation involving the nucleophilic additions on the
dicyanomethylene carbon atom is presented. The structures of the products have been confirmed by using
spectral and single-crystal X-ray analyses.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
malononitrile of isatin reacted with substituted
carbohydrazides [17], α-azidoketones [18], and amidrazones
[19] to give spiro-heterocyclic compounds. 4-Substituted
thiosemicarbazides reacted with isatylidene malononitrile
to give the derivatives of spiro(indoline)thiadiazolones [20].
Amino-1,3,4-thiadiazolyl-1H-pyrazole derivatives and
furo-imidazo[3.3.3]propellanes have been synthesized via
the reactions of thiocarbonohydrazides with TCNE
[21] and (1,3-dioxo-2,3-dihydro-1H-indene-2-ylidene)pro-
panedinitrile [22].
Isatin nucleus is probably one of the most widely distrib-
uted heterocyclic ring systems found in many alkaloids [1]
and drugs [2,3] as well as dyes [4]. Many synthetic
methodologies have been developed for constructing
spiro-cycles containing 2-oxoindole, most of which based
on cycloaddition or condensation reactions [5–11].
Earlier, Joshi et al. [12] followed by Badawy et al. [13]
have been reported that condensation of isatins with
thiocarbohydrazide gave 2-oxo-1′,2′,4′,5′-tetrazine-6′-thiones
as spiro system rather than the expected thiocarbohydrazones
[12,13]. Latter, this work was repeated by Manda
and Giangarapu [14,15] and subsequently claimed that
the previous work was in error and a series new β-isatin
Recently, substituted aminothiazolylhydrazonoindolin-
2-ones 3a–d were prepared via condensation of
thiocarbohydrazides 1a–d with isatylidene malononitrile
2 in EtOH/piperidine at room temperature (Scheme 1) [23].
aldehyde-N,N″-thiocarbohydrazone
was
synthesized
by condensation 5-substituted isatins with aldehyde
thiocarbohydrazones.
RESULTS AND DISCUSSION
On the other hand, 3-(dicyanomethylene)-2-indolone
Inspired by these observations, we envisioned that treat-
(isatylidene malononitrile) [16] that is
a
ylidene
ment of (ylidene)thiocarbohydrazides 4a–j with isatylidene
© 2016 Wiley Periodicals, Inc.

A. A. Hassan, S. K. Mohamed, F. F. Abdel-Latif, S.M. Mostafa,
M. Abdel-Aziz, J. T. Mague, M. Akkurt, S. Bräse, and M. Nieger
Vol 000
Scheme 1. Reaction of 1a–d with isatylidene malononitrile (2).
and the gross compositions. Furthermore, the common
features of the fragmentation patterns supported the
assigned structures.
The EI mass spectra of 5a–j are characterized by molecular
ions of low intensity and loss of 28amu (may be dinitrogen
or carbonyl group), loss of 118amu (probably PhN¼C¼O),
and loss 103 amu (Ph-C≡N) from the molecular ion. The IR
spectrum of 5i in KBr showed broad bands at 3437–3351
(NH’s), strong bands at 1698 related to oxoindolylidene
carbonyl group, and another band at 1619 because of
C¼N. Bands are characteristic of vibrational coupling of
C¼S and C–N groups at 1357 and 995 cmꢀ1. The 1H
NMR spectrum of 5i clearly showed the presence of three
different broad signals with the ratio 1:1:1 centered at
14.82, 12.62, and 11.30 ppm attributed to two NH’s of
thiocarbohydrazone and indolone-NH, respectively. The
1H NMR clearly indicated the azomethine CH¼N group,
which appeared as singlet centered at 8.10ppm, in addition
to the aromatic protons. The 13C NMR spectrum of 5i
supported the presence of thione group at 174.91ppm;
indolone-CO (162.65), CH¼N (144.23), and aromatic
carbon signals appeared in the regular region (refer to the
Experimental section).
malononitrile 2 in the presence of EtOH/piperidine at room
temperature would form oxoindole moiety bearing fused
spiro-thiadiazoles via nucleophilic attack of thione sulfur
atom on the double bond of C¼N in compound 5 or would
lead to spiro(indoline) [1,2,4] triazolethione via intramo-
lecular nucleophilic attack of NH4 on C¼N.
Quite surprisingly, when we carried out the reaction of
4a–j with 2, we observed (substituted ylidene)amino-2-
oxo-indolylidene thioureas and bis[2-oxo-indolylidene)-
urea 5a–j and 6, respectively (Scheme 2) instead of the
anticipated spiro(indoline)thiadiazole and spiro(indoline)-
triazolethione derivatives.
4
1
The downfield shift of NH in H NMR and upfield of
In the present investigation, (substituted ylidene)-
C¼O in 13C NMR of 5a–j may be because of intramolec-
thiocarbonohydrazides 4a–j bearing
a selective of
4
ular hydrogen bonding between NH and indolone –CO.
aliphatic, aromatic, and heterocyclic substituents were
suggested for investigation with 2.
The analytical data of 5a–j would also match for other
isomers of products 7, 8, and 9 (Fig. 1).
Alternative structures 7 and 8 could be ruled out on the
basis of 13C NMR spectra and the presence of C¼S group
in the isolated products (175.54–174.60 ppm).
We will concentrate on the interplay between the forma-
tion of the product 5a–j and 9. The alternative structures
5 and 9 have very similar spectroscopic data, and it is very
difficult to differentiate between them by the normal 1H or
13C NMR spectral data. Gratifyingly, the structures of 5a–j
Structural assignment of compounds 5a–j and 6 are
based on spectral data, on combustion, and single-crystal
X-ray analyses. The molecular structure of the products
5a–j was elucidated from their mass spectrometric analy-
1
ses, IR, H NMR, and 13C NMR spectra. The molecular
ions in their EI mass spectra confirm the molecular masses
Scheme 2. Reaction of 4a–j with isatylidene malononitrile (2).
Figure 1. Alternative structures 5a–j and 7–9.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
(Ylidene)Amino-2-Oxo-Indolylidene Thioureas and Bis(2-Oxo-Indolylidene)Urea
from (Ylidene)Thiocarbonohydrazides and Isatylidene Malononitrile
Figure 2. Molecular structure of 5e with intramolecular hydrogen bonding
shown as dotted lines. [Color figure can be viewed in the online issue, which
is available at wileyonlinelibrary.com.]
Figure 3. Molecular structure of 6 in the crystal (one crystallographic
independent molecule is shown; displacement parameters are drawn at
50% probability level).
A perspective view of the molecule with the crystallo-
graphic atom numbering is given in Figure 3. The C(1)-S
(1) bond length of 1.662 (4) Å, N(3)-C(4) 1.281 (5) Å
and N(14)-C(15) 1.288 (5) Å have double bond character
for C¼S and C¼N double bonds, respectively. Whereas,
bond length N(2)-N(3) 1.352 (4) Å, N(13)-N14) 1.349
(4) Å, C(1)-N(13) 1.360 (4) Å, and C(1)-N(2) 1.358 (5)
Å suggest that these bonds have single bond character as
they are comparable with N–N and C–N σ-bond.
have been unambiguously confirmed by a single-crystal
X-ray structure analysis for 5e (Fig. 2 and Tables S1–S10
in the Supporting Information).
The molecule 5e is nearly planar with a dihedral angle be-
tween the two six-membered rings being only 0.9(1)° while
the dihydroindole portion is slightly folded by 2.7(2)° about
the C3…C8 axis. The conformation is partially aided by the
intramolecular N3–H3a…O1 hydrogen bond. The packing
consists of offset stacks formed by complementary, slipped
π–π stacking interactions between the 3-nitrophenyl and
the five-membered ring portion of the indole moiety in two
centrosymmetrically related molecules (C2–Cgi=3.33(1)Å
(Cg=centroid of the C11–C16 ring with i=1ꢀx, 1ꢀ y,
1ꢀ z). These units, in turn, associate through antiparallel
π–π interactions of the C1¼¼O1 moieties, with a distance
of 3.02(1)Å between their centroids to complete the stacking
motifs (Fig. S4 in the Supporting Information). These stacks
further associate through weak N4–H4a…S1 interactions
(Fig. S5 in the Supporting Information) [24–26].
1,3-Bis({(3Z)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]-amino}-
urea 6 was formed as one of the products in the course of
the reaction of 4a–j with 2. The structure of 6 is further
supported by characteristic IR, NMR, mass spectrometry
data, and comparison with authentic sample [14,15].
Moreover, the structure of 6 was confirmed ambiguously
by single X-ray structure analysis (Fig. 3, and Tables
S11–S17 in the Supporting Information; note that the
crystalographic numbering does not correspond to systematic
IUPAC numbering rules).
The formation of 2-oxo-indolylidenethiourea and bis
(2-oxo-indolylidene)urea derivatives 5a–j and 6 can be
rationalized as depicted in Scheme 3. An initial nucleo-
philic attack by NH2 of 4a–j on the electrophilic C¼C of
isatylidene malononitrile 2, where the three electron-
withdrawing groups (two nitrile and one carbonyl groups)
facilitate this reaction to form the intermediate 10, elimina-
tion of a molecule of malononitrile afforded the formation
of 5a–j. As a result, this synthesis allows much wider
substrate scope and provides a general and practical access
to 5aꢀj and 6. The formation of compounds 5aꢀj is
required for the formation of bis(2-oxo-indolylidene)urea
6 via hydrolysis of 5a–j and elimination of a molecule of
substituted aldehyde (Scheme 3). The methine carbon of
5a–j had to act as an electrophile with sense of an
“umpolung” [27]. This behavior is not unexpected,
because aldehydehydrazones are known to react as
azaenamines [27–29]. On the other hand, compound 5a–j
is required to form the spiro-cyclic alternative structures
7–9. It may be concluded that the azomethine group
abstracted a molecule of H2O to give compound 6 faster
The molecule of 6 is nearly planar (mean deviation from
the LS plane of all nonhydrogen atoms 0.145Å; the
oxoindole moieties are planar: unit A (C4 to O12) 0.027Å,
unit B (C15 to C23) 0.014Å). The angle between the two
oxoindole moieties is 14.0°, and the angle between
oxoindole moieties and thiourea group are 9.4° (between
thiourea group and oxoindole A) and 4.6° (between thio-
urea group and oxoindole B). For intramolecular and inter-
molecular hydrogen bonds (also involving the two water
solvent molecules), refer to supporting information.
2
than the intramolecular nucleophilic attack of C¼S or N
on indolone C¼N.
CONCLUSION
An efficient and fast reaction of isatylidene malononitrile
with (substituted ylidene)thiocarbonohydrazides for the
synthesis of 3-{[(3Z)-2-oxo-2,3-dihydro-1H-indol-3-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. Hassan, S. K. Mohamed, F. F. Abdel-Latif, S.M. Mostafa,
M. Abdel-Aziz, J. T. Mague, M. Akkurt, S. Bräse, and M. Nieger
Vol 000
Scheme 3. The mechanism of formation 5a–j and 6.
ylidene]amino}-1-[(E)-(substituted ylidene)amino]thiourea
and N′,2-bis(2-oxoindolin-3-ylidene)-hydrazine-1-
carbothiohydrazine. These new protocols have the advan-
tages of simple and fast operation and low cost and are an
environmentally benign procedure.
13C NMR (75 MHz, DMSO-d6) δC =175.42 (C¼S),
140.20 (CH¼N), 148.12 (Ar–C), 148.00 (Ar–C–NO2),
131.40, 130.34, 127.45, 122.40 (Ar–CH). MS m/z (%)
239 (M+, 100), 193 (20), 164 (60), 149 (65), (23), 90
(70), 75 (50). Anal. Calcd. for C8H9N5O2S (239.25); C,
40.16; H, 3.79; N, 29.27; S, 13.40. Found C, 40.03; H,
3.83; N, 29.38; S, 13.26.
EXPERIMENTAL
Reaction of 4a–j with 3-(dicyanomethylene)-2-indolone
(2).
Substituted (hydrazinecarbonothioyl)hydrazine-
Gallenkamp melting point apparatus were used for
determination the melting points. The IR spectra (KBr
discs) were recorded on a Bruker FT-IR and Shimadzu
carbothioamides 4a–j (1.0 mmol) were dissolved in 20mL
absolute ethanol with two drops of piperidine and added
to the indolone 2 (1.0 mmol) in 20mL absolute ethanol.
The mixture was stirred at room temperature for 30min.
A reddish orange precipitate were formed and subjected to
(preparative layer chromatography) using toluene-ethyl
acetate (10:2) as a developing solvent to afford two zones:
the fastest migrating zone contained compound 5a–j and
the slowest one contained compound 6.
1
408 instruments. H NMR and 13C NMR spectra were
determined using
a
Mercury 300BB spectrometer
1
(300 MHz for H NMR and 75 MHz for 13C NMR) with
tetramethylsilane as the internal standard; the chemical
shifts are expressed in δ and coupling constants in Hz.
The 13C NMR assignments (q = quaternary carbon atoms)
were made with the aid of DEPT 135/90 spectra. Mass
spectra (70 eV, electron impact mode) were measured
using VG Autospec QMS 30 and MSg (AEI) spectrometer
instrument. Elemental analyses were carried out at the
Microanalytical Center, Cairo University, Egypt. Preparative
layer chromatography used air-dried 1.0-mm-thick layer of
slurry applied silica gel Merck (wide and 20-cm-high glass
plates Pf254) on 48 cm using the listed solvents.
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(4-methoxybenzylidene)amino]thiourea
(5a).
Yellow
crystals (acetonitrile) (0.198g, 56%), mp: 232–234°C (lit.
228–231°C) [37]. 13C NMR (75 MHz, DMSO-d6)
δC = 174.62 (C¼S), 162.35 (CO), 150.97 (Ar–C–O),
144.14 (CH¼N), 142.20 (C¼N), 141.81, 137.23, 131.01
(Ar–C), 128.98, 125.85, 124.20, 122.30, 120.53, 119.86
(Ar–CH), 55.22 (OCH3).
Starting materials.
3-(Dicyanomethylene)-2-indolone
or isatylidene malononitrile 2 was prepared according to
Fatiadi [16]. Substituted (hydrazinecarbonothioyl)
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(3,4-dimethoxybenzylidene)amino]thiourea (5b).
Yellow
crystals (acetonitrile) (0.203 g, 53%), mp: 225–227°C (lit.,
222–225°C) [14]. 13C NMR (75 MHz, DMSO-d6)
δC =174.60 (C¼S), 162.29 (CO), 150.96, 149.05
(Ar–C–O), 144.00 (CH¼N), 142.24 (C¼N), 141.82,
137.26, 131.00 (Ar–C), 126.99, 126.06, 122.83, 122.28,
122.01, 120.51, 119.89 (Ar–CH), 55.55, 55.46 (OCH3).
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
hydrazinecarbothioamides 4a–d,f–j were prepared
according to the literature: 4a [30,31], 4b [32], 4c [33], 4d
[30,32], 4f [30,32], 4g [33], 4h [34,35], 4i [36], and 4j [37].
3-Nitro(hydrazinecarbonothioyl)hydrazinecarbothioamides
(4e). Colourless crystals (ethanol), (0.200 g, 84%), mp:
198–200°C. IR (KBr) υ = 3330–3112 (NH’s), 1586
(Ar–C¼C), 1350, 999 (C¼S and C–N str.). 1H NMR
(3,4,5-trimethoxybenzylidene)amino]thiourea (5c).
Yellow
4
(300 MHz, DMSO-d6) δH = 11.44 (br, 1H, NH), 9.83 (br,
crystals (acetonitrile) (0.190 g, 46%), mp: 248–250°C. IR
(KBr) υ =3443–3358 (NH’s), 1697 (CO), 1620 (C¼N),
1H, 2NH), 8.30 (s, 1H, CH¼N), 8.15–7.90 (m, 2H,
Ar–CH), 7.70–7.40 (m, 2H, Ar–CH), 4.85 (br, 2H, NH2).
1588 (Ar–C¼C), 1348, 995 (C¼S, C–N str.) cmꢀ1
.
1H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
(Ylidene)Amino-2-Oxo-Indolylidene Thioureas and Bis(2-Oxo-Indolylidene)Urea
from (Ylidene)Thiocarbonohydrazides and Isatylidene Malononitrile
NMR (300MHz, DMSO-d6) δH = 14.64 (br, 1H, 4NH), 12.59
(br, 1H, NH), 11.23 (br, 1H, indolone-NH), 8.09 (s, 1H,
Calcd. for C16H13N5O2S (339.37); C, 55.63; H, 3.86; N,
20.64; S, 9.45. Found C, 55.81; H, 3.76; N, 20.78; S, 9.56.
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(3-naphthalene-2-ylmethylene)amino]thiourea (5g). Yellow
crystals (acetonitrile) (0.180g, 48%), mp: 220–222°C. IR
(KBr) υ=3425–3355 (NH’s), 1707 (CO), 1618 (C¼N),
2
CH¼N), 7.60–7.57 (m, 1H, Ar–H), 7.39–7.34 (m, 1H, Ar–
H), 7.25 (m, 1H, Ar–H), 7.12–7.11 (m, 1H, Ar–H), 7.09–
7.07 (m, 1H, Ar–H), 6.96–6.94 (m, 1H, Ar–H), 3.89 (s, 3H,
OCH3), 3.83 (s, 3H, OCH3), 3.74 (s, 3H, OCH3). 13C NMR
(75MHz, DMSO-d6) δC = 174.60 (C¼S), 162.29 (CO),
152.96, 149.35 (Ar–C–O), 143.59 (CH¼N), 142.30 (C¼N),
141.85, 137.48, 131.08 (Ar–C), 128.79, 124.21, 122.31,
120.57, 119.82 (Ar–CH), 60.00, 56.00 (OCH3). MS m/z (%)
413 (M+, 9), 385 (62), 253 (50), 209 (23), 194 (33), 160
(100), 118 (22), 103 (30), 77 (59). Anal. Calcd. for
C19H19N5O4S (413.45); C, 55.19; H, 4.63; N, 16.94; S, 7.76.
Found C, 55.32; H, 4.72; N, 17.11; S, 7.64.
1
1586 (Ar–C¼C), 1358, 991 (C¼S, C–N str.) cmꢀ1. H
NMR (300 MHz, DMSO-d6) δH =14.60 (br, 1H, 4NH),
12.65 (br, 1H, 2NH), 11.32 (br, 1H, indolone-NH), 8.25 (s,
1H, CH¼N), 8.05–8.00 (m, 3H, Ar–H), 7.68–7.57 (m, 8H,
Ar–H). 13C NMR (75 MHz, DMSO-d6) δC =174.91
(C¼S), 162.68 (CO), 144.00 (CH¼N), 142.03 (C¼N),
141.00, 137.40, 133.47, 131.10, 130.50 (Ar–C), 129.42,
128.76, 128.29, 127.60, 127.26, 126.20, 125.49, 122.70,
120.81 (Ar–CH). MS m/z (%) 373 (M+, 9), 345 (14), 282
(20), 228 (44), 213 (14), 169 (55), 160 (90), 155 (100),
118 (45), 103 (61), 77 (25). Anal. Calcd. for C20H15N5OS
(373.43); C, 64.33; H, 4.05; N, 18.75; S, 8.59. Found C,
64.49; H, 3.97; N, 18.87; S, 8.44.
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(4-chlorobenzylidene)amino]thiourea (5d). Yellow crystals
(acetonitrile) (0.164g, 46%), mp: 142–144°C (lit.,
138–140°C) [14,37]. 13C NMR (75 MHz, DMSO-d6)
δC = 175.02 (C¼S), 162.35 (CO), 143.90 (CH¼N),
142.71 (C¼N), 141.90, 137.59, 134.31, 132. 31 (Ar–C),
131.05, 128.77, 128.67, 122.26, 120.55, 119.81 (Ar–CH).
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(3-nitrobenzylidene)amino]thiourea (5e). Yellow crystals
(acetonitrile) (0.165 g, 45%), mp: 240–242°C. IR (KBr)
υ= 3439–3309 (NH’s), 1690 (CO), 1610 (C¼N), 1583
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(furan-3-ylmethylene)amino]thiourea
(5h).
Yellow
crystals (acetonitrile) (0.160 g, 51%), mp: 224–226°C. IR
(KBr) υ =3437–3351 (NH’s), 1698 (CO), 1619 (C¼N),
1
1586 (Ar–C¼C), 1346, 996 (C¼S, C–N str.) cmꢀ1. H
NMR (300MHz, DMSO-d6) δH = 14.89 (br, 1H, 4NH),
1
2
(Ar–C¼C), 1350, 991 (C¼S, C–N str.) cmꢀ1. H NMR
12.90 (br, 1H, NH), 11.31 (br, 1H, indolone-NH), 8.35
(300 MHz, DMSO-d6) δH = 14.64 (br, 1H, 4NH), 12.75
(s, 1H, CH¼N), 7.61–7.59 (m, 1H, Ar–H), 7.45–7.40 (m,
2H, Ar–H), 7.17–7.15 (m, 2H, Ar–H), 7.00–6.97 (m, 2H,
Ar–H). 13C NMR (75 MHz, DMSO-d6) δC =174.80
(C¼S), 162.71 (CO), 146.90 (furyl-CH), 144.40 (CH¼N),
142.41 (C¼N), 141.60, 137.12 (Ar–C), 129.61, 125.80,
121.16, 119.30 (Ar–CH), 121.08 (furyl-C), 112.60 (furyl-
CH). MS m/z (%) 313 (M+, 10), 285 (5), 153 (20), 160
(47), 118 (50), 109 (90), 103 (70), 95 (54), 77 (100).
Anal. Calcd. for C14H11N5O2S (313.33); C, 53.66; H,
3.54; N, 22.35; S, 10.21. Found C, 53.49; H, 3.44; N,
22.47; S, 10.34.
2
(br, 1H, NH), 11.33 (br, 1H, indolone-NH), 8.45 (s, 1H,
CH¼N), 8.33–8.24 (m, 3H, Ar–H), 7.59–7.56 (m, 2H,
Ar–H), 7.10 (m, 1H, Ar–H), 6.96–6.93 (m, 2H, Ar–
H).13C NMR (75 MHz, DMSO-d6) δC = 175.54 (C¼S),
162.66 (CO), 148.32 (Ar–C–NO2), 144.37 (CH¼N),
142.28 (C¼N), 142.08, 138.00, 133.06 (Ar–C), 131.44,
130.34, 127.50, 124.60, 122.53, 121.92, 120.82, 120.67
(Ar–CH). MS m/z (%) 368 (M+, 30), 322 (22), 219 (50),
204 (23), 160 (100), 149 (15), 118 (85), 77 (59). Anal.
Calcd. for C16H12N6O3S (368.37); C, 52.17; H, 3.28; N,
22.81; S, 8.70. Found C, 52.28; H, 3.36; N, 22.69; S, 8.82.
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(pyridin-2-ylmethylene)amino]thiourea
(5i).
Yellow
(2-hydroxybenzylidene)amino]thiourea
(5f).
Yellow
crystals (acetonitrile) (0.168 g, 52%), mp: 234–236°C. IR
(KBr) υ =3430–3362 (NH’s), 1698 (CO), 1619 (C¼N),
crystals (acetonitrile) (0.170 g, 50%), mp: 232–234°C. IR
(KBr) υ =3457 (OH), 3440–3310 (NH’s), 1698 (CO),
1619 (C¼N), 1585 (Ar–C¼C), 1353, 990 (C¼S, C–N
1
1598 (Ar–C¼C), 1350, 994 (C¼S, C–N str.) cmꢀ1. H
NMR (300MHz, DMSO-d6) δH = 14.82 (br, 1H, 4NH),
2
str.) cmꢀ1
.
1H NMR (300 MHz, DMSO-d6) δH =14.47
12.62 (br, 1H, NH), 11.30 (br, 1H, indolone-NH), 8.10
(br, 1H, 4NH), 12.72 (br, 1H, 2NH), 11.30 (br, 1H,
indolone-NH), 10.02 (br, 1H, OH), 8.55 (s, 1H, CH¼N),
7.61–7.59 (m, 2H, Ar–H), 7.44–7.29 (m, 2H, Ar–H),
7.14–7.11 (m, 2H, Ar–H), 7.00–6.88 (m, 2H, Ar–H). 13C
NMR (75 MHz, DMSO-d6) δC = 174.76 (C¼S), 162.70
(CO), 156.42 (Ar–C–O), 143.60 (CH¼N), 142.32 (C¼N),
141.85, 137.32, 134.12 (Ar–C), 129.60, 129.00, 128.30,
125.87, 122.50, 121.16, 120.80, 119.45 (Ar–CH). MS m/z
(%) 339 (M+, 30), 311 (35), 248 (60), 219 (37), 178 (53),
160 (50), 118 (65), 106 (100), 103 (75), 77 (20). Anal.
(s, 1H, CH¼N), 8.04–7.78 (m, 3H, Ar–H), 7.75–7.72 (m,
3H, Ar–H), 7.70–7.61 (m, 2H, Ar–H). 13C NMR
(75 MHz, DMSO-d6) δC = 174.91 (C¼S), 162.65 (CO),
144.23 (CH¼N), 142.04 (C¼N), 141.56, 139.47, 137.14
(Ar–C), 131.60, 129.52, 128.02, 127.30, 125.74, 122.46,
121.14, 119.33 (Ar–CH). MS m/z (%) 324 (M+, 20), 296
(34), 233 (10), 219 (8), 203 (12), 160 (43), 118 (100), 103
(40), 77 (17). Anal. Calcd. for C15H12N6OS (324.36); C,
55.54; H, 3.73; N, 25.91; S, 9.89. Found C, 55.33; H,
3.82; N, 26.03; S, 9.74.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. Hassan, S. K. Mohamed, F. F. Abdel-Latif, S.M. Mostafa,
M. Abdel-Aziz, J. T. Mague, M. Akkurt, S. Bräse, and M. Nieger
Vol 000
[10] Feldman, K. S.; Karatjas, A. G. Org Lett 2006, 8, 4137.
3-{[(3Z)-2-Oxo-2,3-dihydro-1H-indol-3-ylidene]amino}-1-[(E)-
(hexan-2-ylmethylene)amino]thiourea (5j). Yellow crystals
(acetonitrile) (0.136 g, 43%), mp: 202–204°C. IR (KBr)
υ= 3427–3224 (NH’s), 1697 (CO), 1617 (C¼N), 1595
[11] Alizadeh, A.; Mokhtari, J. Tetrahedron 2011, 67, 3519.
[12] Joshi, K. C.; Jain, R.; Dandia, A.; Sharma, V. J Heterocyclic
Chem 1986, 23, 97.
[13] Badawy, M. A.; Abdel-Hady, S. A. Arch Pharm (Weinheim)
1991, 324, 349.
[14] Manda, K. S.; Thota, S.; Yerra, R.; Karki, S. S.; Balzarini, J.;
De Clereq, E.; Tokuda, H. Lett Drug Des Discovery 2012, 9, 934.
[15] Gangarapu, K.; Manda, S.; Jallapally, A.; Thota, S.; Karki,
S. S.; Balzarini, J.; De Clereq, E.; Tokuda, H. Med Chem Res 2014, 23,
1046.
[16] Fatiadi, A. J. Synthesis 1978, 1978, 165.
[17] Hassan, A. A.; Ibrahim, Y. R.; Shawky, A. M. J Heterocyclic
Chem 2009, 46, 616.
[18] Kanialraja, J.; Babu, T. H.; Muralidharau, D.; Perumal, P. T.
Synlett 2012, 23, 1950.
[19] Mohamed, A. M.; Alsharari, M. A.; Aly, A. A. J Chem Res
2010, 34, 200.
[20] Hassan, A. A.; Abdel-Latif, F. F.; Nour El-Din, A. M.;
Abdel-Aziz, M.; Mostafa, S. M.; Bräse, S. J Heterocyclic Chem
2011, 48, 1050.
[21] Hassan, A. A.; Mohamed, S. K.; Abdel-Latif, F. F.; Mostafa,
S. M.; Mague, J. M.; Akkurt, M.; Abdel-Aziz, M. Tetrahedron Lett
2016, 57, 345.
[22] Hassan, A. A.; Mohamed, S. K.; Abdel-Latif, F. F.; Mostafa,
S. M.; Abdel-Aziz, M.; Mague, J. M.; Akkurt, M. Synlett 2016, 27, 412.
[23] Hassan, A. A.; Abdel-Latif, F. F.; Abdel-Aziz, M.; Mostafa,
S. M.; Bräse, S.; Nieger, M. J Heterocyclic Chem 2015, 53, 633.
[24] Brandenburg, K.; Putz, H., (2012). DIAMOND, Crystal
Impact GbR, Bonn, Germany.
1
(Ar–C¼C), 1343, 995 (C¼S, C–N str.) cmꢀ1. H NMR
(300 MHz, DMSO-d6) δH = 14.62 (br, 1H, 4NH), 12.60
2
(br, 1H, NH), 11.32 (br, 1H, indolone-NH), 8.00–7.70
(m, 2H, Ar–H), 7.65–7.62 (m, 2H, Ar–H), 6.90 (s, 1H,
CH¼N), 2.24–2.20 (m, 2H, CH2), 1.45 (m, 2H, CH2),
1.30 (m, 4H, 2CH2), 0.85 (t, 3H, J =6.7, CH3). 13C NMR
(75 MHz, DMSO-d6) δC = 174.70 (C¼S), 162.61 (CO),
144.22 (CH¼N), 142.43 (C¼N), 141.55, 137.10 (Ar–C),
129.50, 125.76, 121.03, 119.28 (Ar–CH), 30.50, 25.12,
24.73, 21.43 (CH2), 13.54 (CH3). MS m/z (%) 317 (M+,
40), 289 (33), 219 (75), 204 (26), 160 (50), 157 (90), 113
(70), 98 (20), 91 (100). Anal. Calcd. for C15H19N5OS
(317.41); C, 56.76; H, 6.03; N, 22.06; S, 10.10. Found C,
56.59; H, 5.92; N, 22.23; S, 10.18.
N,2-Bis(2-oxoindolin-3-ylidene)hydrazine-1-carbothiohydrazine
(6). Orange crystals (acetonitrile) (20–31%), mp: 262–264°C
(lit., 260–262°C) [14,15].
[25] Bruker APEX2, SAINT, SADABS, SHELXT and SHELXTL;
Bruker AXS, Inc.: Madison, WI, 2014.
[26] Sheldrick, G. M. SHELXL–2014; University of Göttingen:
Göttingen, Germany, 2014.
Acknowledgements. Alaa A. Hassan is indebted to AvH
foundation for the donation of a Shimadzu 408 IR instrument.
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[28] Endes, D.; Syrig, G.; Raabe, G.; Fernández, R.; Gasch, C.;
Lassaletta, J. M. Synthesis 1996, 1996, 48.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet