Green and Facile Synthesis of New 3-(Phenylallylideneamino)indeno[1,2-d]imidazoles

Article abstract of DOI:10.1134/S107042801903028X

A green and facile strategy has been proposed for the synthesis of previously unknown 3a,8a-dihydroxy-3-[(3-phenylprop-2-en-1-ylidene)amino]-2-sulfanylidene-2,3,3a,8a-tetrahydro-1H-indeno[1,2-{und}]imidazol-8-one and 3a,8a-dihydroxy-3-[(3-phenylprop-2-en-

Full text of DOI:10.1134/S107042801903028X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 3, pp. 412–414. © Pleiades Publishing, Ltd., 2019.
SHORT
COMMUNICATIONS
Green and Facile Synthesis
of New 3-(Phenylallylideneamino)indeno[1,2-d]imidazoles
a
R. M. Ghalib
a
Department of Chemistry, Faculty of Sciences and Arts-Khulais, University of Jeddah,
Jeddah, P.O. Box 355, 21921 Kingdom of Saudi Arabia
e-mail: raza2005communications@gmail.com
Received November 26, 2018; revised November 29, 2018 accepted December 17, 2018
Abstract—A green and facile strategy has been proposed for the synthesis of previously unknown 3a,8a-di-
hydroxy-3-[(3-phenylprop-2-en-1-ylidene)amino]-2-sulfanylidene-2,3,3a,8a-tetrahydro-1H-indeno[1,2-d]imid-
azol-8-one and 3a,8a-dihydroxy-3-[(3-phenylprop-2-en-1-ylidene)amino]-1,3,3a,8a-tetrahydroindeno[1,2-d]-
imidazole-2,8-dione in excellent yields by condensation of cinnamaldehyde thiosemicarbazone and semi-
carbazone, respectively, with ninhydrin in boiling dioxane. The reaction is clean, simple, and free of work-up
and column chromatography.
Keywords: green synthesis, semicarbazones, thiosemicarbazones, 3-phenylallylideneamine, ninhydrin,
cinnamaldehyde, indeno[1,2-d]imidazol-8-ones.
DOI: 10.1134/S107042801903028X
Ninhydrin undergoes electrophilic substitution at
the C atom. It has been utilized as a building block
esterase [10]. Novel anticancer benzazocine deriva-
tives were synthesized by a green and facile strategy
starting from ninhydrin, and their structures were
determined by spectral analysis and single crystal
X-ray analysis [11]. A literature survey revealed no
published data on 3-(phenylallylideneamino)indeno-
[1,2-d]imidazoles 3 and 4.
2
in the synthesis of many heterocyclic compounds such
as indenoimidazoles, quinoxalines, and benzazocines.
Hydrazones exhibit biological activity and play a key
role in the synthesis of heterocyclic compounds [1, 2].
Indenoimidazoles are heterocyclic molecules of exten-
sive biological significance [3, 4]. The synthesis and
supramolecular and crystal structures of several in-
denoimidazoles with antimicrobial and cholinesterase
inhibitory activities were reported in [5–8]. These
compounds were prepared by reaction of ninhydrin
with urea, phenylurea, and phenylthiourea at a molar
ratio of 1:1 in acetic acid [5, 6]. 3a,8a-Dihydroxy-2-
sulfanylidene-1,3,3a,8a-tetrahydroindeno[1,2-d]imid-
azol-8(2H)-one showed antimicrobial activity against
gram positive and gram negative bacterial strains, as
well as the fungal strain Candida albicans [8].
Ninhydrin reacted with o-phenylenediamine at a molar
ratio of 1:1 to give 11H-indeno[1,2-b]quinoxalin-11-
one [9]. Biindenoquinoxaline was synthesized from
ninhydrin; its structure was established by spectral
methods and single crystal X-ray analysis. It showed
good anticancer and antibacterial activities, selective
inhibitory activity against acetylcholinesterase, and
moderate inhibitory activity against butyrylcholin-
The target products were synthesized in two steps.
In the first step, (thio)semicarbazones 1 and 2 were
prepared in 100% yield by condensation of cinnamal-
dehyde with thiosemicarbazide and semicarbazide,
respectively. The spectral parameters of compounds 1
and 2 were fully consistent with the previously pub-
lished data [12–16]. The second step was the reaction
of 1 and 2 with ninhydrin in boiling dioxane. Indeno-
imidazoles 3 and 4 were obtained in 90–92% yield in
a short time (2 h). The reaction is likely to involve
nucleophilic addition of the terminal nitrogen of (thio)-
2
semicarbazone 1 or 2 to C of ninhydrin, followed by
1
attack from the same side of the internal nitrogen on C
of ninhydrin [2]. The structure of compounds 3 and 4
1
was assigned on the basis of their FT-IR, H NMR,
1
3
13
C NMR, DEPT-135, C–H HSQC, and mass spectra
and elemental analyses.
General procedure for the synthesis of com-
pounds 3 and 4. A mixture of cinnamaldehyde
4
12

GREEN AND FACILE SYNTHESIS OF NEW 3-(PHENYLALLYLIDENEAMINO)-...
413
X
H
CHO
N
NH2
+
H N
2
Ph
N
Ph
N
NH2
H
X
1
, 2
O
O
OH
OH
O
O
Ph
Ph
H
H
N
N
N
OH
N
dioxane, reflux
N
–
H O
2
X
OH
O
N
X
HO
H
3, 4
1
, 3, X = S; 2, 4, X = O.
(
1 mmol) and thiosemicarbazide (1 mmol) or semicar-
6.94–6.90 m (2H), 7.92–6.99 m (11H), 8.84–8.83 d
13
bazide hydrochloride (1 mmol) in double-distilled
water (50 mL) containing a catalytic amount of acetic
acid (1 mL) was refluxed for 30 min with stirring to
obtain thiosemicarbazone 1 or semicarbazone 2,
respectively, in quantitative yield. A mixture of nin-
hydrin (1 mmol) and (thio)semicarbazone 1 or 2
(1H, J = 8.7 Hz), 8.90 br.s (1H). C NMR spectrum
(DMSO-d ), δ , ppm: 83.45 (COH), 88.76 (COH),
6
C
123.19 (CH), 124.45 (CH), 125.98 (CH), 126.36 (2C,
CH), 127.99 (CH), 128.21 (2C, CH), 129.99 (CH),
131.13, 135.51, 136.59 (CH), 137.30 (CH), 147.21
(
CH), 150.64, 151.43 (C=O), 194.43 (C=O). Mass
+
spectrum: m/z 350.1145 [M + H] . Found, %: C 65.48;
(
1 mmol) in dioxane (50 mL) was refluxed with
H 4.41; N 12.21; O 18.40. C H N O . Calculated, %:
stirring for 2 h, the progress of the reaction being
monitored by TLC.
19 15
3
4
C 65.32; H 4.33; N 12.03; O 18.32.
Ninhydrin (Sigma-Aldrich) and solvents (Merck)
were purchased commercially and used without further
purification. Thin-layer chromatography was done on
silica gel 60 F254 plates (Merck). The IR spectra were
recorded on a Perkin Elmer Spectrum II FT IR spec-
3
a,8a-Dihydroxy-3-[(3-phenylprop-2-en-1-
ylidene)amino]-2-sulfanylidene-2,3,3a,8a-tetra-
hydro-1H-indeno[1,2-d]imidazol-8-one (3). Yield
.3 g (90%), yellowish solid, mp 138.6°C. IR spec-
trum, ν, cm : 3519 (NH), 3325 (OH), 3082 (C–Harom),
949 (=C–H), 2108, 1718 (C=O), 1607 (C=Carom),
497, 1410, 1267, 1110, 970. H NMR spectrum
3
–
1
1
13
trometer in potassium bromide discs. The H and
C
2
1
1
NMR spectra were recorded on a Bruker Avance 600
1
13
spectrometer (600 MHz for H; 150 MHz for C)
with tetramethylsilane as an internal standard. The
mass spectra were obtained on an Agilent 6520
Q-TOF mass spectrometer. Elemental analysis was
performed with a Perkin Elmer 240 analyzer. The
melting points were taken on a Stuart SMP30 Digital
Melting Point Apparatus by open capillary method and
are uncorrected.
(
7
8
(
1
DMSO-d ), δ, ppm: 6.99–6.96 t (1H, J = 9 Hz), 7.12–
6
.10 d (1H, J = 15.66 Hz), 7.96–7.34 m (12H), 9.01–
1
3
.99 d (1H, J = 6.6 Hz). C NMR spectrum
DMSO-d ), δ , ppm: 86.83 (COH), 91.43 (COH),
6 C
23.41 (CH), 124.80 (CH), 125.38 (CH), 126.60 (2C,
CH), 128.24 (2C, CH), 128.30 (CH), 130.38 (CH),
1
1
spectrum: m/z 366.0920 [M + H] . Found, %: C 62.49;
H 4.09; N 11.71; O 13.3; S 8.61. C H N O S. Calcu-
31.26, 135.30, 136.98 (CH), 139.06 (CH), 149.57,
49.93 (CH), 175.57 (C=S), 193.37 (C=O). Mass
+
ACKNOWLEDGMENTS
1
9
15
3
3
lated, %: C 62.45; H 4.14; N 11.50; O 13.14; S 8.78.
a,8a-Dihydroxy-3-[(3-phenylprop-2-en-1-
ylidene)amino]-1,3,3a,8a-tetrahydro-1H-indeno-
1,2-d]imidazole-2,8-dione (4). Yield 3.22 g (92%),
The author thanks Faculty of Sciences & Arts,
University of Jeddah, Khulais, Kingdom of Saudi
Arabia, for providing research facilities.
3
[
–
1
yellowish solid, mp 179.8°C. IR spectrum ν, cm :
CONFLICT OF INTERESTS
3
2
1
533 (NH), 3330 (OH), 3083 (C–Harom), 2950 (=C–H),
108, 1718 (C=O), 1596 (C=Carom), 1404, 1351, 1186,
The author declares the absence of conflict of
interests.
1
126, 966. H NMR spectrum (DMSO-d ), δ, ppm:
6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 3 2019

4
14
GHALIB
9. Ghalib, R.M., Hashim, R., Sulaiman, O., Hemama-
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