The synthesis of some new hydrazone derivatives containing the benzothiazole moiety

Article abstract of DOI:10.2298/JSC110321171O

Hydrazones are an important class of compounds found in many synthetic products. Due to their importance in synthetic chemistry, the present article reports the synthesis of a new series of ten compounds based on the coupling of 2-oxo-3(2H)-benzothiazoleacetic acid, hydrazide and 2-thioxo-3(2H)- -benzothiazoleacetic acid, hydrazide with different aldehydes. The structures of the synthesized compounds were confirmed by elemental analyses, IR, ¹H- -NMR, ¹³C-NMR and FAB⁺-MS spectral data. Copyright 2012 (CC) SCS.

Full text of DOI:10.2298/JSC110321171O

J. Serb. Chem. Soc. 77 (2) 141–146 (2012)
UDC 547–304.6+547.53+547.78+542.913
JSCS–4256
Original scientific paper
The synthesis of some new hydrazone derivatives
containing the benzothiazole moiety
1
1
1
*
AHMET ÖZDEMİR , GÜLHAN TURAN-ZITOUNI , ZAFER ASIM KAPLANCIKLI
and MEHLİKA DİLEK ALTINTOP1
1Anadolu University, Faculty of Pharmacy, Department of
Pharmaceutical Chemistry, 26470, Eskişehir, Turkey
(Received 21 March, revised 2 June 2011)
Abstract: Hydrazones are an important class of compounds found in many syn-
thetic products. Due to their importance in synthetic chemistry, the present ar-
ticle reports the synthesis of a new series of ten compounds based on the coup-
ling of 2-oxo-3(2H)-benzothiazoleacetic acid, hydrazide and 2-thioxo-3(2H)-
-benzothiazoleacetic acid, hydrazide with different aldehydes. The structures of
the synthesized compounds were confirmed by elemental analyses, IR, 1H-
-NMR, 13C-NMR and FAB+–MS spectral data.
Keywords: hydrazone; 2-benzothiazolinone; 2-mercaptobenzothiazole; aroma-
tic aldehydes.
INTRODUCTION
Hydrazone derivatives have attracted a great deal of interest in synthetic
chemistry and considerable research on them in relation to their synthetic utility
has been accomplished. Hydrazones are extensively studied as reactants or re-
1
action intermediates since they can readily undergo various ring closure reactions.
Among the benzothiazole derivatives, benzothiazol-2-ones and 2-mercapto-
benzothiazoles have received considerable attention in organic chemistry asso-
2
ciated with their importance in nucleophilic substitution reactions. The present
study also confirmed that the ease of nucleophilic substitution depends on the
nucleophilicity.
All these observations gave encouragement to commence a research program
for the synthesis of new hydrazone derivatives containing a heterocyclic moiety.
After careful screening of various heteronuclei, benzothiazole was chosen as the
focus of attention. In this respect, it should be noted that this heterocyclic scaf-
fold still attracts the attention of material chemists, because of its use as a che-
mically and thermally stable electron-withdrawing moiety in push-pull systems
*Corresponding author. E-mail: ahmeto@anadolu.edu.tr
doi: 10.2298/JSC110321171O
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ÖZDEMİR et al.
3–6
with potential application in nonlinear optics. Furthermore, various derivatives
bearing the benzothiazole moiety display antimicrobial and anticancer activi-
7–9
ties.
It was therefore expected that the newly synthesized hydrazone deriva-
tives bearing a benzothiazole moiety might be of potential interest or could serve
as potential intermediates in medicinal chemistry. Herein, the synthesis of new
hydrazone derivatives bearing a benzothiazole moiety is described.
RESULTS AND DISCUSSION
Chemistry
Among several synthetic routes to derivatives 1a–j, it was decided to inves-
tigate the synthesis of acylhydrazine derivatives as key intermediates. This com-
pound could be transformed to 1a–j using classical functional group intercon-
version, i.e. CONHNH → CONHN=CH–CH –O–Ar. Finally, the new target
2
2
compounds 1a–j were obtained, in good yields (70–88 %), by condensing hydra-
zides (n,o) with the corresponding appropriate aldehydes in absolute ethanol, as
illustrated in Table I and Scheme 1.
TABLE I. Some characteristics of the synthesized compounds
R3
R2
O
R
N
N
H
O
R1
Compd. Ar R1
R2
R3 Yield, % Molecular formula M.W., g mol-1 M.p., °C
1a
1b
1c
1d
1e
1f
1g
1h
1i
n
n
n
n
n
o
o
o
o
o
H
H
H
CH3
CH3
H
H
H
CH3
CH3
CH3
C(CH3)3
OCH3
CH3
H
CH3
C(CH3)3
OCH3
CH3
H
H
H
H
CH3
H
H
H
H
CH3
71
88
70
77
79
80
78
81
79
75
C18H17N3O3S
C21H23N3O3S
C18H17N3O4S
C19H19N3O3S
C19H19N3O3S
C18H17N3O2S2
C21H23N3O2S2
C18H17N3O3S2
C19H19N3O2S2
C19H19N3O3S2
355.42
397.50
299.5
369.45
369.45
371.48
413.56
387.48
385.51
385.51
213–214
209–211
203–204
218–220
226–227
138–140
142–144
145–147
136–137
86–88
1j
H
The nucleophilic substitution of 2(3H)-benzothiazolone shows an important
difference when compared with that of 2-mercaptobenzothiazole. The enolizable
character of the amide moiety allows several useful substitutions at the level of
10
the N position of the 2(3H)-benzothiazolone under base-catalyzed conditions .
On the other hand, the nucleophilic reactivity of 2-mercaptobenzothiazole asso-
ciated with the presence of nitrogen and sulfur atoms holding a pair of electrons
on either side of the >C=S group increases the electron donating capacity of “S”
11
to form a bond with a halogenated carbon atom. The fact that the S-substituted
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HYDRAZONE DERIVATIVES CONTAINING BENZOTHIAZOLE MOIETY
143
derivatives were the dominant species indicates that sulfur-containing anions are
more stable and stronger nucleophiles due to d-orbital delocalization of sulfur
2
compared to the nucleophilic properties of the nitrogen-containing anions.
R3
R2
R3
R2
K2CO3
DMF
O
O
Br
+
O
O
HO
O
R1
R1
2N H2SO4
R3
O
R2
H
O
R1
m
O
NH2
H
N
N
H
O
O
N
S
1.
2.
Cl
O
S
O
n
H2N-NH2
O
+
H
N
NH2
N
N
H
S
S
S
S
o
R3
R2
H
R3
R2
O
N
NH2
Ar
Ar
N
+
H
N
O
O
O
H
O
R1
n, o
R1
m
1a-j
R :
R1, R3 :
H, CH3, OCH3, C(CH3)3
H, CH3
2
Scheme 1. The general synthetic reactions (see Table I for details of R, R1 and R2 of 1a–j).
The purity of the synthesized compounds was checked by elemental analy-
ses. The structures of the various synthesized compounds were determined based
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144
ÖZDEMİR et al.
1
13
+
on spectral data analysis, i.e., IR, H-NMR, C-NMR and FAB -MS spectral
data. These data are given in the Supplementary material to this paper.
The IR data provided functional group evidence for the formation of the ex-
pected structures. In the IR spectra, some significant stretching bands due to N–H,
–1
–1
C=O, C=C and C=N were observed at 3339–3175 cm , 1687–1680 cm and
–1
1610–1485 cm , respectively. The IR spectra of the acid hydrazides 1a–e showed
a peak at 1680–1683 cm due to the exocyclic carbonyl function derived from
hydrazide structure, beside the endocyclic carbonyl peak (1770–1768 cm ) at
–1
–1
position 2 of the 2(3H)-benzothiazolone ring.
According to the literature, hydrazones may exist as E/Z geometric isomers
about the C=N double bonds and cis/trans amide conformers. In addition, hydra-
zones derived from aldehydes and substituted hydrazides are present in solution
in the E form. It was reported that when hydrazones are dissolved in d -dimethyl
6
sulfoxide solution, the E geometrical isomers of these compounds undergo a ra-
12,13
pid cis/trans amide equilibrium, in which the cis conformer predominates.
1
In the 400 MHz H-NMR spectra of the compounds, the –O–CH –CO pro-
2
tons were observed as singlets at 4.55 and 4.87–4.90 ppm. The –O–CH –CH=
2
protons appeared as multiplets at 4.63–4.72 ppm. The –N=CH– proton was ob-
served as a triplet at 7.47–7.94 ppm. The –NH–N= proton was observed as two
broad singlets at 11.41–11.47 ppm. All the other aliphatic and aromatic protons
were observed within the expected regions.
1
The H-NMR data were also consistent with the assigned structures. In the
H-NMR spectra of the compounds, paired peaks for each of the protons
1
–O–CH –CH=, –N=CH– and –NH–N=, corresponding to the (E)- and (Z)-forms
2
of the compounds, were observed. For each compound, the intensities of these
paired peaks differed from others, due to the variable amounts of the (E)- and
(Z)-isomers, which are usually unequal.
Additional support for the structures of the synthesized compounds was pro-
13
vided by their C-NMR spectra, in which chemical shift values of the carbon
atoms at around 164.56–164.64 ppm (hydrazide C=O), and 142.61–142.99 ppm
1
(imine N=CH) corroborated the hydrazide character deduced from the H-NMR
data. The mass spectra of compounds showed [M+1] peaks in agreement with
their molecular formula.
EXPERIMENTAL
All chemicals were obtained from Aldrich (Steinheim, Germany). All melting points
(m.p.) were determined in open capillaries on a Gallenkamp apparatus (Weiss-Gallenkamp,
Loughborough, UK) and are uncorrected. The purity of the compounds was routinely checked
by thin layer chromatography (TLC) using silica gel 60G (Merck, Darmstadt, Germany). Ele-
mental analyses were performed on a Perkin Elmer EAL 240 elemental analyzer. Spectro-
1
scopic data were recorded using the following instruments: H-NMR, a Bruker 400 MHz
spectrometer; 13C-NMR, a Bruker 100 MHz spectrometer (Bruker, Billerica, Massachusetts,
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HYDRAZONE DERIVATIVES CONTAINING BENZOTHIAZOLE MOIETY
145
USA) and MS-FAB, a VG Quattro Mass spectrometer (Agilent, Minnesota, USA). The NMR
spectra were recorded in DMSO-d6 using TMS as an internal standard.
General procedure for the synthesis of the compounds
Synthesis of substituted phenoxyacetaldehyde (m). These compounds used in the syn-
theses were prepared according to methods reported in the literature.14,15
Synthesis of 2-oxo-3(2H)-benzothiazoleacetic acid, hydrazide (n). This compound was
prepared according to the literature, by reacting 2-oxo-3(2H)-benzothiazoleacetic acid, ethyl
ester with hydrazine hydrate.16,17
Synthesis of 2-thioxo-3(2H)-benzothiazoleacetic acid, hydrazide (o). This compound was
prepared in accordance with a previously described method, by reacting 2-thioxo-3(2H)-ben-
zothiazoleacetic acid, ethyl ester with hydrazine hydrate.16,17
Synthesis of the 2-phenoxyethylidene hydrazide derivatives (1a–j). Equimolar quantities
of acetylhydrazines (30 mmol) and an appropriate aldehyde in 25 ml of absolute ethanol were
refluxed for 10–12 h. The reaction mixture was then cooled and the solid precipitated was
recrystallized from an appropriate solvent. Some characteristics of the synthesized compounds
are given in Table I.
CONCLUSIONS
In the present work, appropriate aldehyde derivatives were synthesized via
the treatment of the compounds bearing an acetal group with sulfuric acid, which
catalyzes the hydrolysis of acetals affording aldehydes proning to nucleophilic
addition reactions. Hydrazone derivatives were obtained by reaction of the alde-
hyde derivatives with appropriate hydrazides.
SUPPLEMENTARY MATERIAL
Characteristics and spectral data of synthesized compounds are available electronically
from http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
И З В О Д
СИНТЕЗА НОВИХ ХИДРАЗОНСКИХ ДЕРИВАТА КОЈИ САДРЖЕ
БЕНЗОТИАЗОЛСКУ СТРУКТУРУ
AHMET ÖZDEMIR1, GÜLHAN TURAN-ZITOUNI1, ZAFER ASIM KAPLANCIKLI1 и MEHLIKA DILEK ALTINTOP1
1Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskişehir, Turkey
Хидразони су важна класа једињења која се садржи у многим синтетичким произво-
дима. Због њихове важности у синтетској хемији, у овом раду је приказана синтеза нове
серије од десет једињења. Синтеза се заснива на купловању хидразида 2-оксо-3(2H)-
бензотиазолсирћетне киселине и хидразида 2-тиоксо-3(2H)-бензотиазолсирћетне киселине са
различитим алдехидима. Структуре синтетисаних једињења одређене су на основу елемен-
талне анализе, IC, 1H-NMR, 13C-NMR и FAB+-MS спектроскопских података.
(Примљено 21. марта, ревидирано 2. јуна 2011)
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