Hydrolysis and hydrazinolysis of isatin-based ald-and ketazines

Article abstract of DOI:10.1155/2015/826489

The hydrolysis of isatin aldazine 4a-d afforded the unexpected 3,3'-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5) and 1,2-di(arylidene)hydrazines 6a-d through dual hydrolysis of 4a-d. A mechanism to explain the formation of 5 and 6a-d was proposed. In addition, the hydrazinolysis of 4a-d yielded 3-hydrazonoindolin-2-one (2) and 1,2-di(arylidene)hydrazines 6a-d instead of hydrazones 17a-d, while hydrazinolysis of isatin ketazine 5 gave the expected 3-hydrazonoindolin-2-one (2). These results indicated the ability of the title compounds for unusual hydrolysis and hydrazinolysis reactions.

Full text of DOI:10.1155/2015/826489

Hindawi Publishing Corporation
Journal of Chemistry
Volume 2015, Article ID 826489, 6 pages
http://dx.doi.org/10.1155/2015/826489
Research Article
Hydrolysis and Hydrazinolysis of Isatin-Based
Ald- and Ketazines
Hany S. Ibrahim,1 Soha R. Abdelhadi,1 and Hatem A. Abdel-Aziz2,3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt
2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
3Department of Applied Organic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt
Correspondence should be addressed to Hatem A. Abdel-Aziz; hatem 741@yahoo.com
Received 14 January 2015; Revised 10 April 2015; Accepted 17 April 2015
Academic Editor: Tanaji Talele
Copyright © 2015 Hany S. Ibrahim et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
e hydrolysis of isatin aldazine 4a–d afforded the unexpected 3,3ꢀ-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5) and 1,2-
di(arylidene)hydrazines 6a–d through dual hydrolysis of 4a–d. A mechanism to explain the formation of 5 and 6a–d was proposed.
In addition, the hydrazinolysis of 4a–d yielded 3-hydrazonoindolin-2-one (2) and 1,2-di(arylidene)hydrazines 6a–d instead of
hydrazones 17a–d, while hydrazinolysis of isatin ketazine 5 gave the expected 3-hydrazonoindolin-2-one (2). ese results indicated
the ability of the title compounds for unusual hydrolysis and hydrazinolysis reactions.
1. Introduction
On the other hand, azines undergo hydrolysis to regen-
erate the hydrazine and aldehydes or ketones. However,
ketazines are important intermediates in the production of
hydrazine hydrate when subjected to hydrolysis processes
[12]. In addition, the reaction of azines with hydrazine
(hydrazinolysis) regenerates the hydrazones [13]. In light
of the latter results and in continuation of our interest
in the chemistry of isatin-based azines 4 and 5, we hope
to report herein the unexpected results of hydrolysis and
hydrazinolysis of isatin aldazines 4a–d and isatin ketazines
5.
Isatin imines including Schiff bases 1b and isatin hydrazones
2, which are the product of condensation of amines or
hydrazines with isatins 1a, respectively, are considered as a
pharmacophore for diverse spectrum of biological activities
[1–5] (Figure 1). ey have been reported as anticancer
agents where they were found to be inhibitors of tyrosine
phosphatase Shp2 [6]. Furthermore, they have been identified
as kinase inhibitors and they also have been reported as cyto-
toxic agents towards U937 lymphoma cells [7]. In addition,
hydrazones 2 (R = –COAr) revealed a good cytotoxic activity
against K562, MDA-MB-468, and HT-29 cell lines [8].
2. Experimental
Isatin-based azines 4 are usually prepared by the con-
densation of isatin hydrazones 2 (R1 = H) with aldehydes or
ketones 3 to construct the connectivity >C=N–N=CR2R3 and
then the formation of isatin aldazines (4, R2 or R3 = H) or
2.1. General. Melting points were measured with a Stuart
melting point apparatus and were uncorrected. IR spectra
(KBr disks) were recorded with a Pye Unicam SP 1000 IR
spectrophotometer. e NMR spectra were recorded by Var-
ian Gemini-300BB 300 MHz FT-NMR spectrometers (Varian
isatin ketazines (4, R2 and R3 =
̸
H), respectively (Figure 1).
Isatin aldazines 4 showed a significant anticancer activity
against human breast cell line MCF-7 [9], whereas a series
of symmetrical and asymmetrical isatin ketazines 5 showed a
selective activity against multidrug-resistant cancer cells [10].
Moreover, bis-Schiff bases of isatins 4 represent significant
antiglycation activity [11].
1
Inc., Palo Alto, CA). H and 13C spectra were run at 300
and 75 MHz, respectively, in deuterated dimethyl sulfoxide
(DMSO-ꢀ6). Chemical shifs (ꢁ ) are reported relative to
TMS as internal standard. All couHpling constant (ꢂꢃ values are
given in Hertz. Chemical shifs (ꢁ ) are reported relative to
C

2
Journal of Chemistry
R2
R3
X
O
N
NH
N
R2
R3
O
N
O
N
N
O
H
HN
N
O
H
1a, X = O
1b, X = =N-R
2, X = =N-NH-R
3
4
5
Figure 1: General structure of 1–5.
DMSO-ꢀ6 as internal standards. e abbreviations used are as
follows: s: singlet; d: doublet; and m: multiplet. Mass spectra
were recorded on Helwett Packard 5988 spectrometer at
70 eV. Reaction courses and product mixtures were routinely
monitored by thin layer chromatography (TLC) on silica
(DMSO-d6) ꢁ 6.90 (d, 1H, J = 7.5 Hz, H4 of isatin), 7.02 (t, 1H,
J = 7.8 Hz, H5 of isatin), 7.41 (t, 1H, J = 7.8 Hz, H6 of isatin),
7. 63 (d, 2H, J = 8.4 Hz, Ar–H), 7.85 (d, 1H, J = 7.5 Hz, H7
of isatin), 7.98 (d, 2H, J = 8.4, Ar–H), 8.61 (s, 1H, N=CH),
10.86 (s, D O exchangeable, 1H, NH); 13C NMR (DMSO-d6)
2
gel precoated F Merck plates. Unless otherwise noted, all
ꢁ 110.73, 110.98, 116.26, 128.82, 129.23, 130.37, 130.45, 132.24,
133.92, 136.65, 141.72, 145.07, 150.29, 158.75, 164.35 (C=O); MS
m/z (%) 285 (M+ + 2, 6.78), 283 (M+, 20.10), 255 (89.86), 145
(16.96), 138 (54.66), 111 (95.01).
254
solvents and reagents were commercially available and were
used without further purification.
2.2. Synthesis of Isatin Aldazines 4a–d. A mixture of 3-
hydrazonoindolin-2-one (2) (0.161 g, 1 mmol) and aldehyde
from 3a–c (1 mmol) in acetic acid (25 mL) was stirred at room
temperature for 12 h. e resulted precipitate was filtered,
dried, and finally crystallized from EtOH/DMF to afford
hydrazones 4a–c, respectively. Aldazines 4a–d were also
prepared by the reaction of 2 with 3a–d in refluxing ethanol,
in the presence of catalytic amount of glacial acetic acid for
6 h [10].
2.2.4.
3-((4-Methoxybenzylidene)hydrazono)indolin-2-one
(4d). Yield (69%), mp = 182-183∘C (lit. mp = 182∘C [14]); IR
(KBr) v 3194 (NH), 1732 (C=O), 1606 (C=N) cm−1; 1H NMR
(DMSO-d6) ꢁ 3.87 (s, 6H, 2OCH ), 6.89 (d, 1H, J = 7.5 Hz,
3
H4 of isatin), 7.04 (t, 1H, J = 7.8 Hz, H5 of isatin), 7.12 (d, 2H,
J = 8.4, Ar–H), 7.39 (t, 1H, J = 7.5 Hz, H6 of isatin), 7.94 (d,
2H, J = 8.4 Hz, Ar–H), 8.02 (d, 1H, J = 7.8 Hz, H7 of isatin),
8.61 (s, 1H, N=CH), 10.76 (s, D O exchangeable, 1H, NH);
2
13C NMR (DMSO-d6) ꢁ 55.55 (OCH ), 110.58, 110.81, 114.62,
3
2.2.1. 3-((Benzylidene)hydrazono)indolin-2-one (4a). Yield
(62%), mp > 300∘C (lit. mp 300∘C [14]); IR (KBr) v 3280
114.87, 116.59, 122.13, 122.36, 126.32, 128.79, 128.86, 130.91,
131.03, 133.29, 133.52, 144.80, 145.15, 150.65, 161.81, 161.93,
162.58, 163.36, 164.69 (C=O); MS m/z (%) 279 (M+, 30.31),
251 (100), 134 (17.79).
1
(NH), 1722 (C=O), 1614 (C=N) cm−1; H NMR (DMSO-
d6) ꢁ 6.90 (d, 1H, J = 7.8 Hz, H4 of isatin), 7.04 (t, 1H, J =
7.5 Hz, H5 of isatin), 7.42 (t, 1H, J = 7.5 Hz, H6 of isatin), 7.51
(d, 1H, J = 7.8 Hz, H7 of isatin), 7.57–7.99 (m, 5H, Ar–H),
2.3. Hydrolysis of Isatin Aldazines 4a–d
8.61 (s, 1H, N=CH), 10.97 (s, D O exchangeable, 1H, NH);
2
13C NMR (DMSO-d6) ꢁ 110.95, 111.19, 115.73, 122.39, 122.63,
128.03, 128.25, 134.26, 134.47, 144.70, 145.16, 163.36 (C=O); MS
m/z (%) 249 (M+, 30.02), 221 (17.03), 145 (35.41).
Method A. A solution of isatin aldazines 4a–d (1 mmol) in
H O/AcOH (1 : 3, v : v, 25 mL) was refluxed for 4 h. e given
2
3,3ꢀ-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5) was fil-
tered while hot and crystallized from EtOH/DMF. e filtrate
of the latter reaction was concentrated. e solid formed
was washed with 50% ethanol, dried, and crystallized from
EtOH to give 1,2-di(arylidene)hydrazines 6a–d. e physical
constants of 5 and 6a–d were identical with that reported.
2.2.2. 3-((4-Nitrobenzylidene)hydrazono)indolin-2-one (4b)
[11]. Yield (66%), mp 254–256∘C; IR (KBr) v 3161 (NH), 1734
(C=O), 1616 (C=N) cm−1; 1H NMR (DMSO-d6) ꢁ 6.90 (d, 1H,
J = 7.8 Hz, H4 of isatin), 7.01 (t, 1H, J = 7.5 Hz, H5 of isatin),
7. 41 (t, 1H, J = 7.5 Hz, H6 of isatin), 7.73 (d, 1H, J = 7.8 Hz,
H7 of isatin), 8.20 (d, 2H, J = 8.7 Hz, Ar–H), 8.37 (d, 2H, J =
Method B. A mixture of 3-hydrazonoindolin-2-one (2)
(0.161 g, 1 mmol) and the appropriate aldehyde from 3a–c
8.7, Ar–H), 8.66 (s, 1H, N=CH), 10.86 (s, D O exchangeable,
2
1H, NH); 13C NMR (DMSO-d6) ꢁ 110.85, 111.08, 116.01, 122.29,
122.53, 124.23, 128.59, 128.78, 129.64, 133.98, 134.19, 139.06,
145.27, 148.97, 149.67, 156.21, 156.35, 164.10 (C=O); MS m/z (%)
294 (M+, 10.49), 266 (100).
(1 mmol) in H O/AcOH (1 : 3, v : v, 25 mL) was refluxed for
2
4 h. Ketazine 5 was filtered while hot and crystallized from
EtOH/DMF while aldazines 6a–d were isolated from the
filtrate afer evaporation of the solvent.
2.2.3. 3-((4-Chlorobenzylidene)hydrazono)indolin-2-one (4c).
2.3.1. 3,3ꢀ-(Hydrazine-1,2-diylidene)diindolin-2-one (5) [8].
Yield (78%), mp = 270–272∘C (lit. mp = 200∘C [14]); IR
Yield (46%), mp > 300∘C; IR (KBr) v 3276 (2NH), 1722
(2C=O), 1615 (2C=N) cm−1; 1H NMR (DMSO-d6) ꢁ 6.82 (d,
(KBr) v 3248 (NH), 1734 (C=O), 1604 (C=N) cm−1; 1H NMR

Journal of Chemistry
3
O
NH2
O
N
O
Ar–CHO
NH
3a–d
N
H2N–NH2
N
Ar
Ar
N
N
+
O
H2O/AcOH
reflux
HN
N
N
N
O
H
H
6a–d
5
1a
2
Ar
Ar–CHO AcOH, rt
3a–d
N
H2O/AcOH
reflux
2 + 3a–d
O
N
H
4a–d
Ar
3, 4, 6
a Ph
4-Cl-C H
b
c 4-MeO6-C64H4
d 4-NO2-C6H4
Scheme 1: e reaction of 3-hydrazonoindolin-2-one (2) with aldehydes 3a–d.
2H, ꢂ = 7.8 Hz, H5 of isatin), 6.96 (t, 2H, ꢂ = 7.5 Hz, H6
e formed precipitate was filtered, washed with ethanol,
of isatin), 7.14 (t, 2H, ꢂ = 7.5 Hz, H7 of isatin), 7.34 (d, 2H,
dried, and finally crystallized from EtOH/DMF to give 3-
ꢂ = 7.8 Hz, H4 of isatin), 10.55 (s, D O exchangeable, 2H,
hydrazonoindolin-2-one (2) with mp = 217–219∘C (Lit. mp
2
= 219–220∘C [16]); IR (KBr) V 3361–3215 (NH, NH ), 1687
2NH); 13C NMR (DMSO-d6) ꢁ 111.59, 116.26, 123.03, 128.66,
2
(C=O), 1608 (C=N) cm−1; 1H NMR (DMSO-d6) ꢁ 6.87 (d, 1H,
J = 7.5; Hz, H5 of isatin), 6.97 (t, 1H, J = 7.8 Hz, H6 of isatin),
7. 15 (t, 1H, J = 7.8 Hz, H7 of isatin), 7.37 (d, 1H, J = 7.5 Hz,
134.89, 145.22, 145.68, 163.89 (2C=O).
2.3.2. 1,2-Di(benzylidene)hydrazine (6a). Yield (70%), mp =
95–97∘C (Lit. mp = 92–93∘C [15]). IR 1615–1620 (2C=N) cm−1;
1H NMR (DMSO-d6) ꢁ 7.57–7.99 (m, 10H, Ar–H), 8.61 (s, 2H,
N=CH); MS m/z (%) 209 (M+ + 1, 11.68), 208 (M+, 79.43), 207
(100), 138 (100).
H4 isatin), 9.55 (d, 1H, J = 14.0 Hz, D O exch., amino H),
2
10.56 (d, 1H, J = 14.0 Hz, D O exch., amino H), 10.72 (s, D O
2
2
exch., 1H, NH isatin); MS m/z (%) 161.1 (M+). e filtrate was
evaporated under vacuum. e obtained residue was filtered,
washed with 50% ethanol, dried, and crystallized from EtOH
to yield 1,2-di(arylidene)hydrazines 6a–d.
2.3.3. 1,2-Bis(-4-chlorobenzylidene)hydrazine (6b). Yield
(82%), mp = 211–213∘C (Lit. mp = 207-208∘C [15]) IR 1617–
1
1625 (2C=N) cm−1; H NMR (DMSO-d6) ꢁ 7. 56 (d, 4H,
2.5. Hydrazinolysis of 5. To a solution of 5 (0.29 g, 1 mmol)
in ethanol (25 mL), hydrazine hydrate (0.06 g 0.12 mmol) was
added. e reaction was refluxed for 5 h. e formed pre-
cipitate was filtered, washed with ethanol, dried, and finally
crystallized from EtOH/DMF to give hydrazonoindolin-2-
one (2).
J = 8.4 Hz, Ar–H), 7.88 (d, 4H, J = 8.4 Hz, Ar–H), 8.61 (s,
2H, N=CH); 13C NMR (DMSO-d6) ꢁ 128.93, 129.89, 132.56,
135.791, 160.44 (2C=N); MS m/z (%) 279 (M+ + 2, 9.68), 277
(M+, 31.14), 165 (100), 138 (23.01), 111 (34.85).
2.3.4. 1,2-Bis(4-methoxybenzylidene)hydrazine (6c). Yield
(77%), mp = 170–172∘C (Lit. mp = 175∘C [15]) IR 1615–1622
3. Results and Discussion
(2C=N) cm−1; 1H NMR (DMSO-d6) ꢁ 3.83 (s, 6H, OCH ),
3
7. 0 4 (d, 4H, J = 8.4 Hz, Ar–H), 7.79 (d, 4H, J = 8.4 Hz, Ar–H),
In the reaction of 3-hydrazonoindolin-2-one (2) (R = H)
with aldehydes 3a–d in glacial acetic acid for 12 h, at ambient
temperature, isatin aldazines 4a–d were isolated extensively.
e targeted aldazines 4a–d were also prepared by the
reaction of 3-hydrazonoindolin-2-one (2) with aldehydes 3a–
d in refluxing ethanol, in the presence of catalytic amount of
glacial acetic acid for 6 h (Scheme 1) [9].
8.61 (s, 2H, N=CH); 13C NMR (DMSO-d6) ꢁ 55.27 (2OCH ),
3
114.23, 126.53, 129.83, 160.35, 161.62 (2C=N); MS m/z (%) 268
(M+, 18.37), 161 (31.72), 134 (26.80), 107 (16.07).
2.3.5. 1,2-Bis(4-nitrobenzylidene)hydrazine (6d). Yield (74%),
mp = 223–225∘C (Lit. mp = 223.3-223.4∘C [16]) IR 1610–1617
(2C=N) cm−1; 1H NMR (DMSO-d6) ꢁ 7. 55 (d, 4H, ꢂ = 8.4 Hz,
Ar–H), 7.88 (d, 4H, ꢂ = +8.4 Hz, Ar–H), 8.60 (s, 2H, N=CH);
MS m/z 272 (%) 298 (M , 10.03), 252 (100), 176 (50.55).
Hydrolysis of hydrazones 4a–d by their refluxing in
H O/AcOH afforded reddish precipitates during reflux in
2
each case. ese precipitates showed identical physical and
chemical properties and they are not matched with the
expected hydrazone 2 (R = H) (Scheme 1).
2.4. Hydrazinolysis of 4a–d. To a solution of hydrazones 4a–
d (1 mmol) in ethanol (25 mL), hydrazine hydrate (0.06 g
0.12 mmol) was added. e reaction was refluxed for 5 h.
1
e H NMR spectrum of the isolated precipitate did
not show the characteristic signal of NH of 2 and its mass
2

4
Journal of Chemistry
OH2
+
O
H
H
+
∙∙
+
N
∙∙
N
+
∙∙ N
N
Ar
Ar
+
H2O
HOH2
N
N
H
Ar
H
HN
HN
O
O
HN
O
7a–d
4a–d
8a–d
+
HOH2
H
H
O
N
+
N
N
Ar
Ar
H3O+
N
H
HN
12a–d
HN
O
O
∙∙
9a–d
H2O
H2O
H
H +H
O
H
N
O
+
N
Ar + H2O
N
H
N
Ar
H
HN
N
HN
13a–d
O
O
10a–d
H2O
H
NH2
+
H
N
O
H3O+
Ar
+
NH2NH2 + 1a
OH Ar
N
11a–d
O
N
H
2
HN
O
14a–d
1a
Ar + H3O+
O
H2O
3a–d
+
O
O
OH
2
H
O
+
H2O
5
H
H
N+
HN
16
+
N
O
N
Ar
H
17a–d
+
H2O
1a
HN
O
3a–d
15a–d
H3O+
N
6a–d
+
Ar
H2O
+
NH2
17a–d
3a, d + NH2NH2
Figure 2: e proposed mechanism for the hydrolysis of isatin aldazines 4a–d in refluxing H O/AcOH.
2
spectrum exhibited molecular ion peak at m/z = 290. e lat-
ter data proposed the assigned structure 3,3ꢀ-(hydrazine-1,2-
diylidene)bis(indolin-2-one) (5) for the isolated compound.
An authentic sample of compound 5 is prepared [10] and it
was identical in all respects with the isolated compound in
our hands.
2 with aldehydes 3a–d in H O/AcOH, 3,3ꢀ-(hydrazine-1,2-
2
diylidene)bis(indolin-2-one) (5) and aldazines 6a–d were
also isolated.
Keeping in mind the reported data about the mech-
anism of hydrolysis of –C=N– imines [21], we are inter-
ested in proposing a mechanism to explain the formation
of 3,3ꢀ-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5) and
1,2-di(arylidene)hydrazines 6a–d. In this mechanism, dual
acidic hydrolysis of aldazines 4a–d took place in their two
nucleophilic centers which are accessible to attack by two
protons from the acidic medium (Figure 2). e first pathway,
in which acidic proton attack took place by the nitrogen
of –N=C–Ar followed by hydrolysis to give intermediates
7(a–d)–10(a–d), respectively, yielded aldehydes 3a–d and
3-hydrazonoindolin-2-ones (2) which would not undergo
further hydrolysis. e second pathway, in which the other
Afer evaporation of the filtrates of the latter reactions,
they gave in each case a compound with melting points
97∘C (Ar = Ph), 213∘C (Ar = 4-Cl-C H ), 172∘C (Ar =
6
4
4-MeO-C H ), and 225∘C (Ar = 4-NO -C H ), respec-
6
4
2
6
4
tively. ese values do not match this reported for 2, 217–
219∘C. Our attempts to explore these unknown compounds
guided us to assign structure 1,2-di(arylidene)hydrazines 6a–
d for the isolated compounds. We found that the analytical
data of authentic samples of isolated compounds is iden-
tical with those of 6a–d [17–20]. Interestingly, refluxing

Journal of Chemistry
5
Ar
N
NH2
O
N
N
NH2–NH2
N
+ Ar
O
Ar
H
N
N
N
6a–d
H
H
2
4a–d
NH2
Ar
H
O
H
Ar
N
∙∙
N
N
N
NH2–NH2
NH
N
H
N
N
4a–d
Ar
N
N
N
H
HN
HN
HN
N
O
O
Ar
19a–d
H
O
4a–d
18a–d
∙∙
NH2–NH2
NH2
NH2
N
H
HN
N
2
+ H2N
N
Ar
N
Ar
Ar
+
N
Ar
N
6a–d
O
HN
20a–d
N
17a–d
O
H
2
Scheme 2: Hydrazinolysis of aldazines 4a–d.
O
NH2
N
O
NH2
NH
NH
∙∙
HN
H
N
NH2–NH2
N
O
N
N
N
HN
H
HN
O
O
2
5
21
Scheme 3: Hydrazinolysis of 3,3ꢀ-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5).
nitrogen of hydrazone function attacked the acidic proton
followed by hydrolysis to give intermediates 12(a–d)–15(a–
d), respectively, yielded indoline-2,3-dione (1) and the cor-
responding hydrazones 17a–d without further hydrolysis.
Finally, the reaction of 1a with 2 (R = Hꢃ and 3a–d with 17a–
d led to the formation of final products 3,3ꢀ-(hydrazine-1,2-
diylidene)bis(indolin-2-one) (5) and aldazines 6a–d, respec-
tively. e expected last step is hydrolysis of 2 (R = Hꢃ and/or
17a–d.
hydrazinolysis product (Scheme 3). e previous reaction
proceeded through the attack of nucleophilic nitrogen of
hydrazine on ketazine 5 to form the nonisolable intermediate
21 and then the formation of 3-hydrazonoindolin-2-one (2).
4. Conclusion
In conclusion, we reported herein the hydrolysis of isatin
aldazines 4a–d which gave unusual product 3,3ꢀ-(hydrazine-
1,2-diylidene)bis(indolin-2-one) (5) and aldazines 6a–d were
formed through dual acidic hydrolysis. e hydrazinolysis
of isatin aldazines 4a–d yielded 3-hydrazonoindolin-2-one
(2) and 6a–d instead of 17a–d. ese results established the
ability of the title compounds for unusual hydrolysis and
hydrazinolysis reactions.
According to the previous results and in light of behavior
of hydrazine hydrate towards certain –N=N– containing
compounds [12], we stimulated to explore the reactivity of
hydrazine hydrate towards –N=C– function in aldazines 4a–
d. us, the reaction of 4a–d with hydrazine hydrate in
refluxing ethanol afforded 3-hydrazonoindolin-2-one (2) and
1,2-di(arylidene)hydrazines 6a–d, respectively, instead of 2
and 17a–d (Scheme 2).
Conflict of Interests
Hydrazine, as a nucleophile, attacked the carbon of
–N=C– function of two molecules of hydrazones 4a–d
to form the nonisolable intermediates 18a–d and 19a–d,
respectively (Scheme 3). Finally, the nonisolable intermedi-
ate 19a–d afforded 3-hydrazonoindolin-2-one (2) and 1,2-
di(arylidene)hydrazines 6a–d as final isolated compounds.
Consequently, the reaction of hydrazine hydrate with
C-3 of 3,3ꢀ-(hydrazine-1,2-diylidene)bis(indolin-2-one) (5)
yielded the corresponding 3-hydrazonoindolin-2-one (2) as
e authors have declared that there is no conflict of interests.
Acknowledgments
e authors would like to extend their sincere appreciation to
the Deanship of Scientific Research at King Saud University
for its funding of this research through the Research Group
Project no. RGP-VPP-321. Department of Pharmaceutical

6
Journal of Chemistry
Chemistry, Faculty of Pharmacy, Egyptian Russian Univer-
sity, Cairo, Egypt, is highly appreciated for supporting this
research.
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