Functionalized 2-hydrazinobenzothiazole with isatin and some carbohydrates under conventional and ultrasound methods and their biological activities

Article abstract of DOI:10.1002/jhet.1986

Several chemical reactions were carried out on 3-(benzothiazol-2-yl-hydrazono)-1,3-dihydro-indol-2-one (2). 3-(Benzothiazol-2-yl-hydrazono)-1-alkyl-1,3-dihydro-indol-2-one 3a-c have been achieved. Reaction of compound 2 with ethyl bromoacetate in the presence of K₂CO₃ resulted the uncyclized product 4. Reaction of compound 2 with benzoyl chloride afforded dibenzoyl derivative 5. Compound 2 was smoothly acetylated by acetic anhydride in pyridine to give diacetyl derivative 6b. Moreover, when compound 4 reacted with methyl hydrazine, it yielded dihydrazide derivative 7, whereas the hydrazinolysis of this compound with hydrazine hydrate gave the monohydrazide derivative 8. {N-(Benzothiazol-2-yl-N'-(3-oxo-3,4-dihydro-2H- 1,2,4-triaza-fluoren-9-ylidene)hydrazino]-acetic acid ethyl ester (9) was prepared by ring closure of compound 8 by the action of glacial acetic acid. In addition, the reaction of 2-hydrazinobenzothiazole (1) with D-glucose and D-arabinose in the presence of acetic acid yielded the hydrazones 10a,b, respectively. Acetylation of compound 10b gave compound 11b. On the other hand, compound 13 was obtained by the reaction of compound 1 with gama-D-galactolactone (12). Acetylation of compound 13 with acetic anhydride in pyridin gave the corresponding N¹-acetyl-N²-(benzothiazolyl)-2-yl)-2,3,4,5,6-penta-O-acetyl-D-galactohydrazide (14). Better yields and shorter reaction times were achieved using ultrasound irradiation. The structural investigation of the new compounds is based on chemical and spectroscopic evidence. Some selected derivatives were studied for their antimicrobial and antiviral activities.

Full text of DOI:10.1002/jhet.1986

Month 2014
Functionalized 2-Hydrazinobenzothiazole with Isatin and Some
Carbohydrates under Conventional and Ultrasound Methods and Their
Biological Activities
Khadija O. Badahdah,* Hamida M. Abdel Hamid, and Sawsan A. Noureddin
Chemistry Department, Faculty of Science, King Abdul Aziz University, Jeddah, Saudi Arabia
*
E-mail: kbadahdah@yahoo.com
Received May 22, 2012
DOI 10.1002/jhet.1986
Published online in Wiley Online Library (wileyonlinelibrary.com).
Several chemical reactions were carried out on 3-(benzothiazol-2-yl-hydrazono)-1,3-dihydro-indol-2-one
(2). 3-(Benzothiazol-2-yl-hydrazono)-1-alkyl-1,3-dihydro-indol-2-one 3a–c have been achieved. Reaction of
2 3
compound 2 with ethyl bromoacetate in the presence of K CO resulted the uncyclized product 4. Reaction
of compound 2 with benzoyl chloride afforded dibenzoyl derivative 5. Compound 2 was smoothly acetylated
by acetic anhydride in pyridine to give diacetyl derivative 6b. Moreover, when compound 4 reacted with
methyl hydrazine, it yielded dihydrazide derivative 7, whereas the hydrazinolysis of this compound with
0
hydrazine hydrate gave the monohydrazide derivative 8. {N-(Benzothiazol-2-yl-N -(3-oxo-3,4-dihydro-2H-
1
,2,4-triaza-fluoren-9-ylidene)hydrazino]-acetic acid ethyl ester (9) was prepared by ring closure of com-
pound 8 by the action of glacial acetic acid. In addition, the reaction of 2-hydrazinobenzothiazole (1) with
D-glucose and D-arabinose in the presence of acetic acid yielded the hydrazones 10a,b, respectively. Acety-
lation of compound 10b gave compound 11b. On the other hand, compound 13 was obtained by the reaction
of compound 1 with gama-D-galactolactone (12). Acetylation of compound 13 with acetic anhydride
1
2
in pyridin gave the corresponding N -acetyl-N -(benzothiazolyl)-2-yl)-2,3,4,5,6-penta-O-acetyl-D-galacto-
hydrazide (14). Better yields and shorter reaction times were achieved using ultrasound irradiation. The
structural investigation of the new compounds is based on chemical and spectroscopic evidence. Some
selected derivatives were studied for their antimicrobial and antiviral activities.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
with isatin in the presence of AcOH under ultrasound
irradiation for 10 min resulted the corresponding 3-
Considerable attention has been paid in the chemistry
of benzothiazole derivatives, which have been studied
extensively and were found to have diverse chemical
reactivity and broad spectrum of biological activity [1–8].
On the other hand, isatin derivatives were reported to show
a variety of biological activities [9–14], such as antibacterial,
antifungal, anti-HIV, and anticonvulsant activities. Carbohy-
drates are important classes of compounds found in many
natural and synthetic products with a wide range of pharma-
ceutical properties [15]. Consequently, the objective of the
present study was devoted to the synthesis of functionalized
(
benzothiazol-2-yl-hydrazono)-1,3-dihydro-indol-2-one (2).
A regioselective N-alkylation of compound 2 with
excess amount of methyl iodide, ethyl iodide, and benzyl
chloride has been achieved by using NaH as a base to give
the N-alkyl derivatives 3a–c. On the other hand,
carbethoxymethylation of 2 with ethyl bromoacetate in the
presence of anhydrous K CO3 as catalyst resulted the
2
uncyclized product 4 in 62 % yield within 4.5 h. Improve-
ment of the isolated yield to 74% and significant reduction
in the reaction time have been achieved (30 min) under
ultrasound irradiation. Spectral analysis proved that
carboethoxymethylathion took place at both the nitrogen
atoms of isatin ring and hydrazone moiety. N-Benzoylation
of compound 2 with benzoyl chloride in presence of
2
-hydrazinobenzothiazole (1) with isatin and some carbohy-
drates to explore their potential antibacterial, antifungal, and
antiviral activities. To improve the yields of the isolated
products and reduce the reaction times, we decided to use
ultrasound irradiation [16] as a nonconventional energy in
the synthesis of some selected derivatives.
0
pyridine gave benzoic acid N-benzothiazol-2-yl-N -
(1-benzoyl-2-oxo-1,2-dihydro-indol-3-ylidene)hydrazide (5).
Its IR spectrum showed no absorption band in the range
3
hydrazone moiety in addition to bands at 1780.74 and
1721.0 cm for two benzoyl groups. C NMR spectrum
ꢀ
1
140 cm , indicating the absence of NH group of
RESULTS AND DISCUSSION
ꢀ
1
13
2-Hydrazinobenzothiazole (1) can be obtained by
irradiation of 2-mercaptobenzothiazole in absolute EtOH and
showed two signals at d 167.39 and 168.96 ppm because
C
hydrazine hydrate for 30 min. The reaction of compound 1
of two benzoyl groups. Spectral analysis proved that
©
2014 HeteroCorporation

K. O. Badahdah, H. M. Abdel Hamid, and S. A. Noureddin
Vol 000
ꢀ
1
benzoylation took place at both the nitrogen atoms of
isatin ring and hydrazone moiety. Although acetylation
3307.93 cm
for NH group. The functionalized in
compound 8 made a valuable key precursor for the for-
mation of fused heterocyclic compound. Thus, treatment
of compound 8 with glacial AcOH afforded {N-
of compound 2 with Ac O in pyridine did not afford the
2
expected product 6a, the isolated product was compound
0
6
b, and its structure was assigned on the basis of the
(benzothiazol-2-yl-N -(3-oxo-3,4-dihydro-2H-1,2,4-triaza-
spectral characteristics. The IR spectrum of the product
showed no absorption for an amide group and showed
fluoren-9-ylidene)hydrazino]-acetic acid ethyl ester (9) in
94% yield (Scheme 2).
The reaction of 2-hydrazinobenzothiazole (1) with equimo-
lar amounts of a number of monosaccharides in an aqueous
ethanolic solution and in the presence of a catalytic amount
of glacial AcOH were performed either under conventional
ꢀ
1
absorption bands at 1735.40 and 1705.06 cm because
1
of OAc and NAc groups, respectively. H NMR spectrum
showed two singlets for six protons because of two acetyl
groups, at d 2.67 and 4.57 ppm. Attempted deacetylation
H
of 6b with aqueous solution of NaOH and subsequent
acidification with acetic acid gave a product identical with
compound 2 (Scheme 1).
Scheme 2
Reaction of compound 4 with methyl hydrazine gave
0
the corresponding dihydrazide, {N-(benzothiazol-2-yl-N -
0
[
1-(N -methylhydrazinocarbonylmethyl)-2-oxo-1,2-dihydro-
indol-3-ylidene]-hydrazino}-acetic acid N -methylhydrazide
0
(
1
7). Its IR spectrum showed no absorption bands in the range
ꢀ
1
700cm , indicating the absence of ester carbonyl groups.
1
The H NMR spectrum showed two singlet signals at dH
2
.98 and 3.08 ppm because of two CH groups. On the other
3
hand, nucleophilic attack of hydrazine on the carbonyl-ester of
4
has been proceeded by ultrasound irradiation for 15 min to
afford the corresponding monohydrazide, {N-(benzothiazol-2-
0
0
yl-N -[1-(N -methylhydrazinocarbonylmethyl)-2-oxo-1,2-
dihydro-indol-3-ylidene]hydrazino}-acetic acid ethyl ester
(8) instead of dihydrazide in 91% yield; conventional heating
required 5 h to give 78% yield. Its IR spectrum showed a
ꢀ
1
band of carbonyl-ester at 1719.37cm and a band at
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Functionalized 2-Hydrazinobenzothiazole with Isatin and Some Carbohydrates under
Conventional and Ultrasound Methods and Their Biological Activities
heating or under ultrasound irradiation. The hydrazones 10a,b
could be prepared from the monosaccharides D-glucose and
D-arabinose, respectively. The arylidene derivatives 10a,b
were characterized by the absence of an NH band in their IR
spectra and by the presence of the arylidene proton NCH sig-
(Pseudomonas aeruginosa, ATCC10145, and Sarcina
lutea, ATCC-9341) and antifungal activities against two
fungi (Penicillium crysogenum and Candida albicans
IMRU3669) by disc diffusion method at 5 mg/mL disc
concentration [17,18]. DMF is used as solvent control.
The bacteria and fungi were maintained on nutrient agar
and Czapek’s Dox agar medium, respectively. The results
are measured in millimeter (mm). Ampicillin trihydrate
was used as a standard drug against Gram positive and
Gram negative bacteria. Against fungi, Ketoconazole was
used as a standard drug.
For antibacterial activity, most of the tested compounds
were found to possess various antibacterial activities
(Table 2 and Fig. 1). The tested compounds are more active
against Gram positive than the Gram negative bacteria.
Compound 2 was the most active derivative giving the best
antibacterial activity against M. luteus and S. lutea
compared with ampicillin trihydrate. Furthermore, the
antibacterial activities of compounds 3a and 3c against
M. luteus were higher than ampicillin trihydrate.
1
nal in the H NMR spectra. When the reactions were carried
out under ultrasound irradiation, 10 min was required to give
higher yield with higher purity. Treatment of compound 10b
ꢁ
with Ac O in pyridine at 0 C gave colorless crystalline
2
product 11b, whose combustion analysis indicated that
preacetylation had taken place on both the polyol residue
and on NH groups. Alternatively, compound 13 could be
obtained in 86% yield by ultrasound irradiation of a mixture
of compound 1 in EtOH with gama-D-galactolactone (12) in
the presence of glacial AcOH for 5 min; conventional heating
required 7 h to give 71% yield. Acetylation of compound 13
1
2
with Ac O in pyridin gave the corresponding N -acetyl-N -
2
(benzothiazolyl)-2-yl)-2,3,4,5,6-penta-O-acetyl-D-galacto-hy-
drazide (14); the acetylation took place on the N-atom of the
hydrazide group in addition to the polyol residue (Scheme 3).
Table 1 shows that when using ultrasound irradiation in
the synthesis of some selected derivatives (1, 2, 4, 8, 10a,b,
and 13), the reactions need shorter time (5–30 min) to be
completed and give higher product yields (72–99%) with
higher purity compared with conventional methods.
Table 1
Synthesis of some derivatives under both ultrasound irradiation and con-
ventional methods.
Ultrasound
Conventional
Biological activity.
Biological activity tests were
performed at the Biotechnology lab of Egyptian Petroleum
Research Institute, Cairo, Egypt.
Compounds
Time (min) % Yield
Time (h) % Yield
1
2
4
8
30
10
30
15
10
10
5
99
94
74
91
84
72
86
5
92
78
62
78
70
55
71
Antimicrobial activity. Compounds 2–5, 6b, 8, 10a,b,
3
1
3, and 14 were screened for their in vitro antibacterial
4.5
5
and antifungal activity. The antibacterial activity of these
compounds were tested against two Gram positive
bacteria (Bacillus pumilus, NCTC8214, and Micrococcus
luteus, ATCC-25922) and two Gram negative bacteria
1
1
1
0a
0b
3
3
8
7
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. O. Badahdah, H. M. Abdel Hamid, and S. A. Noureddin
Vol 000
Table 2
Antimicrobial screen of the tested compound.
Mean values of inhibition zones (mm)
Tested
compounds
Bacillus pumilus
Micrococcus luteus
Pseudomonas aeruginosa
Sarcina lutea
Peneicillium
Candida
2
14.0
15.0
16.0
14.0
15.0
13.0
14.0
—
15.0
15.0
16.0
16.0
34.0
—
32.0
26.0
18.0
27.0
12.0
12.0
14.0
—
12.0
13.0
13.0
13.0
25.0
—
12.0
13.0
—
14.0
—
—
—
13.0
—
—
35.0
28.0
17.0
28.0
—
—
19.0
—
12.0
—
—
—
30.0
—
18.0
14.0
14.0
15.0
14.0
—
—
13.0
—
13.0
—
3
3
3
4
5
6
8
1
1
1
1
a
b
c
—
—
b
14.0
—
13.0
12.0
13.0
14.0
—
0a
0b
3
15.0
16.0
14.0
18.0
—
—
—
29.0
—
4
a
Amp.
Ket.
—
24.0
b
21.0
a
Amp. = ampicillin trihydrate.
Ket. = ketoconazole.
b
However, the activities of the tested compounds are less
than those of Ketoconazole.
Antiviral activity. The antiviral activity of compounds
2
–5, 4b, 8, 10a,b, 13, and 14 was tested against Coxsackie
B4 (Cox B4), Herpes simplex (HSV-1), and Hepatitis A
HAV) viruses using plaque assay [19]. All tested samples
(
showed less than 10% effect which is not considered as a
good result (not antiviral candidates).
EXPERIMENTAL
Figure 1. Antibacterial screen of the tested compounds. [Color figure can
be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Commercially available solvents and reagents were purified
according to the standard procedures. All melting points were
measured on a Mel-Temp apparatus (Dubuque, IA) and are
uncorrected. Thin layer chromatography (TLC) was performed
on aluminum silica gel 60 F254 (E-Merk). The spots were
detected by iodine and UV light absorption. IR spectra were
recorded for the compounds in a FTIR, Perkin Elmer SP
Also, most of the tested compounds were found to pos-
sess various antifungal activities toward fungi (Table 2 and
Fig. 2). Compounds 2, 10b, and 14 were found to possess
higher antifungal activity compared with other derivatives.
1
13
1
00 Spectrometer. H NMR and C NMR spectra were
recorded on Bruker WM 400 and 600 MHz spectrometers
using TMS or the signal of the deuterated solvent was used
as internal standard. Chemical shifts (d) are given in ppm relative
to the signal for TMS as standard and coupling constants in Hz.
The reactions that were carried out by ultrasound irradiation were
performed using Daihan (Wiseclean, D-400H) ultrasonic bath.
Microanalysis was performed by Perkin Elmer elemental analyzer
at the Faculty of Science, King Abdul Aziz University.
2
-Hydrazinobenzothiazole (1)
Method A. A solution of 2-mercaptobenzothiazole (3.0 g,
7.9 mmol) in absolute EtOH (60 mL) was treated with
1
hydrazine hydrate (10 mL). The reaction mixture was refluxed
on water bath for 5 h. The mixture was cooled and the solvent
was evaporated in vacuo. The separated product was filtered
and crystallized from EtOH to give pale yellow crystals (2.70 g,
Figure 2. Antifungal screen of the tested compounds. [Color figure can be
viewed in the online issue, which is available at wileyonlinelibrary.com.]
ꢁ ꢁ
92% yield); m.p. 194 C [lit. [20], m.p. 189–194 C].
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Functionalized 2-Hydrazinobenzothiazole with Isatin and Some Carbohydrates under
Conventional and Ultrasound Methods and Their Biological Activities
Method B.
A solution of 2-mercaptobenzothiazole (3.0 g,
(0.41 mL, 5.05 mmol) was added, and the mixture was allowed
1
7.9 mmol) in absolute EtOH (60 mL) was treated with
under reflux for 5.5 h. The obtained product was filtered off,
hydrazine hydrate (10 mL). The reaction mixture was sonicated
at a frequency of 40 kHz for 30 min at 45 C. The mixture was
dried, and crystallized from EtOH to give orange crystals (0.55 g,
ꢁ
ꢁ
85% yield); m.p. 278 C, R : 0.38 (EtAc–n-hexane, 1:3). FTIR:
f
ꢀ
1
1
cooled, and the solvent was evaporated in vacuo. The separated
product was filtered and crystallized from EtOH to give an
identical product with the product that was obtained from
3183.0 (NH), 1693.23 (OCN), and 1620.6 cm (CN). H NMR
(600 MHz, DMSO-d ): d = 1.38 (t, 3H, J = 7.2, CH ); 4.39 (q,
6
H
3
2H, CH ); 6.79 (d, 1H, J = 7.8 Hz, indol, C ─H); 6.86 (d, 1H,
2
7
ꢁ
method A (2.92 g, 99% yield); m.p. 194–196 C.
J = 7.8Hz, indol, C ─H); 7.03, 7.35 (2t, each 1H, J = 7.8 Hz,
4
3
-(Benzothiazol-2-yl-hydrazono)-1,3-dihydro-indol-2-one (2)
indol, C5,6─H); 7.29, 7.44 (2t, each 1H, J = 7.2 Hz, benzothiazole,
Method A.
1.0 g, 6.05 mmol) in a mixture of EtOH–DMF (1:1) (50 mL)
was treated with isatin (0.89g, 6.05 mmol) in absolute EtOH
30 mL) and AcOH (5 drops). The reaction mixture was heated
A solution of 2-hydrazinobenzothiazole (1)
C5,6─H); 7.81 (d, 1H, J = 7.2 Hz, benzothiazole, C ─H); 8.23 (d,
4
(
1
H, J = 7.2 Hz, benzothiazole, C ─H); 13.4 (bs, 1H, D O
7 2
13
exchangeable, NH). C NMR (150MHz, DMSO-d ): d = 12.11
6
C
(
(
CH ); 40.20 (CH ); 110.03, 117.78, 121.55, 121.88, 123.18,
3 2
under reflux for 3 h. The product that separated out was filtered
1
1
23.25, 124.24, 126.97, 127.08, 131.27, 139.39, 142.96 (Ar─C);
39.39 (CN, indol); 143.06 (CO); 165.35 (CN, thiazol). Anal.
off, dried, and crystallized from EtOH to give deep orange crystals
ꢁ ꢁ
1.39 g, 78% yield); m.p. 312 C [lit. [21], m.p. 276–278 C].
(
Calcd for C H N OS (322.38): C, 63.33; H, 4.38; N, 17.38%.
17 14 4
ꢀ
1
FTIR: 1626.51 (CN), 1692.58 (OCN), and 3141.90 cm (NH).
Found: C, 62.87; H, 3.95; N, 16.93%.
1
H NMR (600 MHz, DMSO-d ): d = 6.98 (d, 1H, J =7.2 Hz,
3-(Benzothiazol-2-yl-hydrazono)-1-benzyl-1,3-dihydro-indol-
2-one (3c). A solution of 2 (0.59 g, 2.0 mmol) and NaH (0.10 g,
4.17 mmol) in a mixture of EtOH–DMF (10:1) (100mL) was
heated under reflux for 4h. Benzyl chloride (0.5mL, 4.33mmol)
was added, and the mixture was reflux for additional 16h. The
product that separated out was filtered off, dried, and crystallized
6
H
isatin, C ─H); 7.12, 7.28 (2t, each 1H, J = 7.5 Hz, isatin, C5,6─H);
7
7.37, 7.42 (2t, each 1H, J = 7.7 Hz, benzothiazole, C5,6─H); 7.56
(
d, 1H, J =7.8 Hz, isatin, C ─H); 7.65 (d, 1H, J =7.2 Hz,
4
benzothiazole, C ─H); 7.96 (d, 1H, J= 7.8 Hz, benzothiazole,
4
1
3
C
7
─H); 11.30, 13.40 (2s, 2H, D
NMR (150 MHz, DMSO-d ):
20.44, 121.91, 122.40, 123.26, 126.34, 130.70, 133.39, 141.42
Ar─C); 141.59 (CN, indol); 151.26 (CO); 165.44 (CN, thiazole).
Anal. Calcd for C15 OS (294.33): C, 61.21; H, 3.42; N,
9.04%. Found: C, 61.68; H, 3.05; N, 18.58%.
Method B. A solution of 2-hydrazinobenzothiazole (1)
2.0 g, 12.10 mmol) in a mixture of EtOH–DMF (1:1) (90 mL)
2
O exchangeable, 2 NH).
C
from EtOH to give deep yellow crystals (0.58 g, 74% yield); m.p.
6
d = 111.05, 119.46, 119.98,
C
ꢁ
3
1
00 C, R
f
: 0.67 (EtAc–n-hexane, 1:3). FTIR: str. 3140.87 (NH),
1
(
ꢀ
1
1
693.27 (OCN), and 1627 cm
(CN). H NMR (600 MHz,
DMSO-d ): d = 2.09 (s, 2H, N─CH ); 6.97 (d, 1H, J = 7.8 Hz,
H N
10 4
6
H
2
indol, C
.34, 7.39 (2t, each 1H, J = 7.2 Hz, benzothiazole, C5,6─H); 7.54
d, 1H, J= 7.2 Hz, indol, C ─H); 7.54 (d, 1H, J = 7.2 Hz,
7
─H); 7.10, 7.25 (2t, each 1H, J= 8.4 Hz, indol, C5,6─H);
1
7
(
(
4
benzothiazole, C ─H); 7.65 (d, 1H, J =7.8Hz, benzothiazole,
was treated with isatin (1.78 g, 12.10 mmol) in EtOH (60 mL)
and AcOH (0.5 mL). The reaction mixture was sonicated at a
4
C ─H); 6.85–8.28 (m, 5H, Ar─H); 13.89 (bs, 1H, D O
7 2
13
ꢁ
6 C
exchangeable, NH). C NMR (150 MHz, DMSO-d ): d = 31.26
frequency of 40 kHz for 10 min at 40 C and processed as before
ꢁ
(CH ); 111.78, 117.45, 120.79, 122.62, 123.01, 123.35, 124.23,
to give compound 2 (3.34 g, 94% yield); m.p. 312–314 C. IR
and H NMR spectra were superimposable with the spectra
2
1
127.23, 128.50, 131.02, 131.71 (Ar─C); 138.93 (CN, indole);
from method A.
141.96 (CN, thiol); 208.74 (CO). Anal. Calcd for C22 OS
16 4
H N
3
-(Benzothiazol-2-yl-hydrazono)-1-methyl-1,3-dihydro-
(384.45): C, 68.73; H, 4.19; N, 14.57%. Found: C, 68.91; H, 4.28;
N, 14.25%.
indol-2-one (3a). A solution of compound 2 (0.59 g, 2.0 mmol)
and NaH (0.10 g, 4.17 mmol) in a mixture of EtOH–DMF (10:1)
0
[N-Benzothiazol-2-yl-N -(1-ethoxycarbonylmethyl-2-oxo-1,2-
(
(
100mL) was heated under reflux for 4 h. Then, methyl iodide
0.27 mL, 4.34 mmol) was added, and the mixture was reflux for
dihydro-indol-3-ylidene)-hydrazino]acetic acid ethyl ester (4)
Method A. To a solution of compound 2 (1.0g, 3.40mmol) in
additional 14 h. The product that separated out was filtered off,
dried, and crystallized from EtOH–DMF to give deep orange
a mixture of EtOH–DMF (1:1) (100 mL), anhydrous K CO (0.7g,
2 3
5.06mmol) was added. The mixture was heated under reflux for
2.5 h, cooled, and then treated with ethyl bromoacetate (1.13 mL,
10.19 mmol). The reaction mixture was heated under reflux for
4.5 h. It was poured onto crushed ice. and the product that
separated out was filtered off, washed with water, and dried. It
ꢁ
crystals (0.54 g, 87% yield); m.p. 296 C, R : 0.49 (EtAc–n-
f
hexane, 1:3). FTIR: 3181.77 (NH), 1695.38 (OCN), and
ꢀ
1
1
1
626.0cm (CN). H NMR (600MHz, DMSO-d
6 H
): d = 3.83 (s,
3
H, CH ); 6.87 (d, 1H, J = 7.8 Hz, indol, C ─H); 6.82 (d, 1H,
3
4
J = 7.8 Hz, indol, C ─H); 7.05, 7.12 (2t, each 1H, J = 7.8 Hz,
was crystallized from EtOH to give yellow crystals (0.98g, 62%
7
ꢁ
indol, C5,6─H); 7.31, 7.46 (2t, each 1H, J = 7.8 Hz, benzothiazole,
yield); m.p. = 276 C, R
f
: 0.16 (EtAc–n-hexane, 1:3). FTIR:
ꢀ
1
1
C
1
5,6─H); 7.81 (d, 1H, J = 7.8 Hz, benzothiazole, C
H, J = 7.2 Hz, benzothiazole, C ─H); 13.42 (bs, 1H, D
exchangeable, NH). C NMR (150 MHz, DMSO-d ): d = 31.91
4
─H); 8.30 (d,
1620.08 (OCN); 1725.02 and 1743.33 cm (COOEt). H NMR
(600 MHz, CDCl ): d = 1.61, 1.64 (2t, 6H, 2 CH ); 4.28, 4.29
(2q, 4H, 2 CH CH ); 5.01 (s, 2H, N─CH ); 5.10 (s, 2H, N─CH
indol); 6.87 (d, 1H, J = 7.8 Hz, isatin, C ─H); 7.08,7.24 (2t, each
7
2
O
3
H
3
1
3
2
3
2
2
,
6
C
(
CH ); 109.92, 117.72, 120.15, 120.59, 121.49, 121.85, 123.98,
7
3
1
26.50, 127.31, 131.22, 141.75, 142.92 (Ar─C); 140.43 (CN,
1H, J = 7.2 Hz, isatin, C5,6─H); 7.27, 7.37 (2t, each 1H,
J = 7.2Hz, benzothiazole, C5,6─H); 7.58 (d, 1H, J = 7.2 Hz, isatin,
indol); 143.02 (CO); 165.39 (CN, thiazol). Anal. Calcd for
OS (308.36): C, 62.32; H, 3.92; N, 18.17%. Found: C,
2.75; H, 4.35; N, 17.98%.
-(Benzothiazol-2-yl-hydrazono)-1-ethyl-1,3-dihydro-indol-
-one (3b). A solution of compound 2 (0.59 g, 2.0 mmol) and
C
6
H N
16 12 4
C
4
─H); 7.70 (d, 1H, J = 7.2 Hz, benzothiazole, C
4
─H); 8.20
─H). C NMR (150 MHz,
); 45.91, 46.04 (2 CH COO);
3
); 109.68, 116.43, 118.42, 121.25,
13
(d, 1H, J = 7.2 Hz, benzothiazole C
CDCl ): d = 14.11, 14.22 (2 CH
62.10, 62.20 (2 CH CH
7
3
3
C
3
2
2
2
NaH (0.10 g, 4.17 mmol) in a mixture of EtOH–DMF (10:1)
122.46, 123.01, 126.69, 127.79, 130.50, 131.15, 141.56, 143.74
(Ar─C); 139.39 (CN, indol); 159.43 (CO, indol); 166.69
ꢁ
(
100mL) was heated to 100 C for 4 h. Then, ethyl iodide
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. O. Badahdah, H. M. Abdel Hamid, and S. A. Noureddin
Vol 000
ꢀ
1
(
CN, thiazol); 166.12, 166.28 (2 COO). Anal. Calcd for
(EtAc–n-hexane, 1:3). FTIR: 3422.02 (NH) and 1620.08 cm
1
C H N O S (466.51): C, 59.22; H, 4.75; N, 12.01%. Found: C,
5
23
22
4
5
6 H
(OCN). H NMR (600 MHz, DMSO-d ): d = 2.98, 3.08 (2s, 6H,
9.23; H, 4.26; N, 12.27%.
Method B. A solution of compound 2 (0.65 g, 2.21 mmol) in
2
CH ); 4.35 (s, 2H, NCH ); 4.49 (s, 2H, NCH , indol); 6.80–7.84
3
2
2
13
(
m, 8H, Ar─H); 8.30 (bs, 4H, D
NMR (150 MHz, DMSO-d ): d
thiazol); 61.34 (CH N–indol); 127.13, 127.35, 127.49, 128.08,
2
O exchangeable, 4NH).
C
a mixture of EtOH–DMF (1:1) (60 mL) was treated with ethyl
bromoacetate (0.75 mL, 6.76 mmol) and anhydrous K CO3
(
frequency of 40 kHz for 30 min at 40 C and processed as before
to give compound 4 (0.76 g, 74% yield); m.p. 273–274 C. IR
and H NMR spectra were superimposable with the spectra
from method A.
6
C 3 2
= 30.87 (2CH ); 42.58 (CH N–
2
2
0.5 g, 3.62 mmol). The reaction mixture was sonicated at a
1
28.48, 129.14, 130.30, 130.63, 130.75 (Ar─C); 143.53 (CO,
indol); 169.92 (CN); 184.09, 184.49 (2CONH). Anal. Calcd for
C H N O S (466.52): C, 54.07; H, 4.75; N, 24.02%. Found: C,
ꢁ
ꢁ
21 22 8 3
1
5
4.47; H, 4.92; N, 23.43%.
0 0
{N-(Benzothiazol-2-yl-N -[1-(N -methylhydrazinocarbonyl-
methyl)-2-oxo-1,2-dihydro-indol-3-ylidene]hydrazino}-acetic acid
ethyl ester (8)
0
Benzoic acid N-benzothiazol-2-yl-N -(1-benzoyl-2-oxo-1,2-
dihydro-indol-3-ylidene)hydrazide (5).
A solution of 2
(
0.8 g, 2.72 mmol) in dry pyridine (12 mL) was cooled in an
Method A.
Hydrazine hydrate (1.0 mL) was added to a
ice bath, then treated with benzoyl chlorid (12 mL) with
stirring. The mixture was kept at rt overnight; it was poured
onto crushed ice. The product that separated out was filtered off,
solution of compound 4 (0.37 g, 0.79 mmol) in absolute EtOH
(40 mL). The mixture was heated under reflux for 5 h. The solid
mass, which separated out upon cooling, was filtered, dried, and
recrystallized from EtOH–DMF in deep orange crystals (0.28 g,
washed repeatedly with water, dried, and crystallized from EtOH
ꢁ
ꢁ
to give orange crystals (1.29 g, 94% yield); m.p. 261–263 C, R
f
:
78% yield); m.p. 296 C, R : 0.71 (EtAc–n-hexane, 1:1). FTIR:
f
ꢀ
1
0
.65 (EtAc–n-hexane, 1:3). FTIR: 1780.74, 1721.17 (CO─Ph),
3307.93 (N─H); 1719.37 (COOEt); 1678.23 and 1650.8 cm
(OCN). H NMR (400 MHz, DMSO-d ): d = 1.23 (t, 3H,
6 H
ꢀ
1
1
1
1
692.59 (OCN), and 1597.14 cm (CN). H NMR (600 MHz,
1
3
DMSO-d
6
):
d
H
= 7.32–8.57 (m, 18H, Ar─H).
C
NMR
3 2 2 3
J = 9.54, CH CH ); 4.20 (q, 2H, CH CH ); 5.15 (s, 2H,
(
150MHz, DMSO-d ): d = 114.47, 115.21, 119.69, 119.75,
6 C
CH
─H); 7.02 (t, 1H, J = 7.3 Hz, isatin, C
benzothiazole, C ─H + isatin, C ─H); 7.44 (t, 1H, J = 7.2 Hz,
2 2
–indol); 5.21 (s, 2H, NCH ); 6.86 (d, 1H, J = 7.3 Hz, isatin,
1
1
23.06, 123.19, 126.70, 127.11, 128.09, 128.21, 128.55, 128.65,
29.33, 129.49, 129.76, 130.74, 132.58, 132.97 (Ar─C); 132.97
C
7
5
─H); 7.29 (m, 2H,
6
6
(
CN, indol); 134.62 (CO, indol); 163.02 (CN, thiazol); 167.39,
benzothiazole, C ─H); 7.64 (d, 1H, J = 8.2 Hz, benzothiazole,
5
1
68.96 (2COPh). Anal. Calcd for C H N O S (502.54): C,
29 18 4 3
C ─H); 7.83 (d, 1H, J = 7.8 Hz, isatin, C ─H); 8.11 (d, 1H,
4
4
6
9.31; H, 3.61; N, 11.15%. Found: C, 68.28; H, 3.68; N, 11.10%.
Acetic acid 3-(N-acetyl-N’-benzothiazol-2-yl-hydrazono)-
J = 6.72 Hz, benzothiazole,
exchangeable, NHNH2).
C
7
2
─H); 10.62 (bs, 3H, D O
13
C NMR (150MHz, DMSO-d6):
3
H-indol-2-yl ester (6b). A solution of compound 2 (0.8 g,
d = 39.80 (CH ); 39.91 (CH CONH); 40.03 (CH COO); 45.92
(CH CH ); 109.93, 111.79, 117.62, 120.11, 121.50, 121.97,
2 3
C
3
2
2
2
.72 mmol) in dry pyridine (12 mL) was cooled in an ice
bath, then treated with Ac O (12 mL) with stirring for 2 h.
The mixture was kept at rt overnight, then poured onto crushed
122.95, 123.76, 126.83, 127.60 (Ar─C); 131.36 (CN, indol);
2
162.05 (CN, thiazol); 165.33 (CO, indol); 165.35 (CONH NH );
2
2
ice. The product that separated out was filtered off, washed
173.04 (COO). Anal. Calcd for C H N O S (452.49): C, 55.74;
21 20 6 4
repeatedly with water, dried, and crystallized from EtOH to give
H, 4.46; N, 18.57%. Found: C, 55.47; H, 3.97; N, 18.26%.
Method B. Hydrazine hydrate (1.0 mL) was added to a
ꢁ
orange crystals (1.0 g, 97% yield); m.p. 208–210 C, R
f
: 0.71
(
1
EtAc–n-hexane, 1:3). FTIR: 1735.40 (OAc), 1705.06 (NAc), and
solution of compound 4 (0.35 g, 0.75 mmol) in absolute EtOH
ꢀ
1
1
604.83 cm (CN). H NMR (400 MHz, DMSO-d ): d = 2.67
(40 mL). The reaction mixture was sonicated at a frequency of
6
H
13
ꢁ
(
s, 3H, OAc), 4.57 (s, 3H, NAc), 7.19–8.17 (m, 8H, Ar─H).
NMR (150 MHz, DMSO-d ): d = 26.46, 26.60 (2 CH ); 113.05,
15.81, 116.50, 119.31, 119.41, 123.13, 123.29, 123.90, 124.82,
C
40 kHz for 15 min at 40 C and processed as before to give
ꢁ
6
C
3
compound 8 (0.31 g, 91% yield); m.p. 293–295 C.
0
1
{N-(Benzothiazol-2-yl-N -(3-oxo-3,4-dihydro-2H-1,2,4-triaza-
1
26.14, 126.89, 127.21 (Ar─C); 130.59, 139.65 (CN, indole);
fluoren-9-ylidene)hydrazino]-acetic acid ethyl ester (9).
A
1
63.96 (CN, thiazole); 170.61 (CH COO); 176.07 (CH CON).
solution of compound 8 (0.1g, 0.22mmol) in glacial AcOH
(6 mL) was heated under reflux for 5h. The mixture was poured
onto crushed ice. The product was crystallized from EtOH–DMF
3
3
14 4 3
Anal. Calcd for C19H N O S (378.40): C, 60.31; H, 3.73; N,
1
4.81%. Found: C, 60.27; H, 3.60; N, 14.60%.
ꢁ
Effect of alkali on compound 6b. A solution of 6b (0.1 g,
to give yellow crystals (0.09 g, 94% yield); m.p. 316 C, R : 0.67
f
0
.26 mmol) and NaOH (0.11 g, 2.75 mmol) in H O–EtOH (1:1)
(EtAc–n-hexane, 1:3). FTIR: 1708.98 (COO), 1670.04 (OCN),
2
ꢀ
1
1
(
10 mL) was boiled under reflux for 4 h. The mixture was
1611.08 (CN), and 3184.87 cm
(NH). H NMR (600 MHz,
cooled and acidified with AcOH. The product that separated
out was filtered off and crystallized from EtOH to give deep
orange crystals (0.08 g, 88% yield); m.p. 308–310 C. IR
DMSO-d ): d = 1.83 (t, 3H, CH CH ); 4.45 (q, 2H, CH CH );
6
H
3
2
2
3
5.01 (s, 2H, CH –indol); 5.13 (s, 2H, N─CH ); 6.82 (d, 1H,
2
2
ꢁ
J =7.8 Hz, isatin C ─H); 7.01, 7.23 (2t, 2H, J =7.2Hz, isatin
7
spectra were superimposable with the spectra of compound 2.
C5,6─H); 7.28, 7.38 (2t, 2H, J =7.2Hz, benzothiazole C5,6─H);
0
0
{
N-(Benzothiazol-2-yl-N -[1-(N -methylhydrazinocarbonyl-
7.47 (d, 1H, J= 8.4 Hz, benzothiazole C ─H); 7.77 (d, 1H, J= 7.8
4
methyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-acetic
Hz, isatin C ─H); 8.22 (d, 1H, J = 7.8 Hz, benzothiazole C ─H);
4
7
0
13
acid N -methylhydrazide (7). A solution of compound 4 (0.4 g,
10.60 (bs, 1H, D O exchangeable, NH). C NMR (150 MHz,
2
0
.85 mmol) in EtOH (40 mL) was treated with methyl hydrazine
DMSO-d6): dC =39.79 (CH3); 39.91 (CH CONH); 40.03
2
(
1.0mL, 19.1mmol). The reaction mixture was heated under
(CH COO); 45.68 (CH CH ); 109.85, 110.10, 111.79, 117.62,
2
2
3
reflux for 14h. The solvent was evaporated in vacuo, and the
residue was treated with warm acetone. The separated product
121.50, 122.14, 122.98, 123.67, 126.86, 127.94 (Ar─C); 131.38
(CN, indol); 143.75 (CN, triazin), 164.46 (CN, thiazol); 165.35
(CONH); 173.01 (COO). Anal. Calcd for C H N O S (434.47):
was filtered, dried, and crystallized from EtOH to give deep
21 18 6 3
ꢁ
orange crystals (0.25 g, 63% yield); m.p. 105–108 C, R : 0.16
C, 58.05; H, 4.18; N, 19.34%. Found: C, 58.24; H, 4.35; N, 19.84%.
f
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Functionalized 2-Hydrazinobenzothiazole with Isatin and Some Carbohydrates under
Conventional and Ultrasound Methods and Their Biological Activities
0
2
OAc); 2.56 (s, 3H, NAc); 4.32 (dd, 2H, CH ); 4.59 (dd, 1H, H-2 );
5.22 (m, 1H, H-3 ); 5.61 (m, 1H, H-4 ); 7.32, 7.43 (2t, each 1H,
Sugar (benzothiazol-2-yl)hydrazones
0
0
Method A.
A solution of 2-hydrazinobenzothiazole (1)
(
0.46 g, 2.78 mmol) in a mixture of EtOH–DMF (1:1) (45 mL)
J= 7.2 Hz, benzothiazole, C6,5─H); 7.73 (d, 1H, J=8.4Hz,
was added to a solution of the appropriate monosaccharide
2.78 mmol) in small amount of H O and AcOH (3 drops). The
benzothiazole, C
─H); 7.81 (d, 1H, J= 7.2 Hz, benzothiazole,
4
13
(
7
C ─H); 8.61 (d, 1H, HCN). C NMR (150 MHz, CDCl ):
3
2
d = 20.52, 20.80, 22.09, 23.48 (4 OCOCH ); 35.40 (NCOCH );
reaction mixture was heated on a boiling water bath from 3 to 8 h.
The solvent was evaporated in vacuo, and the solid mass which
separated out was filtered off, washed with water, and crystallized
from EtOH to give colorless crystals.
C
3
3
5
1
1
2
3.78 (C-4); 61.95 (CH ); 63.73 (C-3); 71.02 (C-2); 120.43,
21.22, 123.70, 124.06, 126.34 (Ar─C); 132.71 (CH); 149.69,
51.39, 170.36, 185.24 (4 CO); 159.80 (NCO); 167.0 (CN,
25 3 9
thiazol). Anal. Calcd for C22H N O S (507.51): C, 52.06; H, 4.97;
N, 8.28%. Found: C, 51.56; H, 5.34; N, 8.40%.
Method B.
0.46 g, 2.78 mmol) in a mixture of EtOH–DMF (1:1) (45 mL)
was added to a solution of the appropriate monosaccharide
2.78 mmol) in small amount of H O and AcOH (3 drops). The
reaction mixture was sonicated at a frequency of 40 kHz for
0 min at rt. Then, the solvent was evaporated in vacuo. The
A solution of 2-hydrazinobenzothiazole (1)
(
N-(Benzothiazolyl-2-yl)-D-galactono-hydrazide (13)
Method A.
A solution of compound 1 (1.68 g, 10.16 mmol)
(
2
in absolute EtOH–DMF (3:1) (30 mL) was added to a solution of
gama-D-galactolactone (12) (1.81 g, 10.16 mmol) in EtOH (20 mL)
and AcOH (2 mL). The reaction mixture was heated on a boiling
water bath for 7 h. The precipitate that separated out after cooling
was filtered, dried, and crystallized from EtOH–DMF to give
1
product that separated out was filtered, washed with water, and
crystallized from EtOH to give colorless crystals.
ꢁ
colorless crystals (2.48 g, 71% yield); m.p. 188 C. FTIR: 3411.58
D-Glucose (benzothiazol-2-yl)hydrazone (10a).
From
ꢀ
1
1
(
OH), 3209.24 (N─H), and 1680.73 cm
(OCN). H NMR
=3.41–3.45 (m, 3H, H-5 , 6 ,6 ); 3.49
(t, 1H, J=9.6Hz, H-4 ); 3.74 (m, 1H, H-3 ); 3.84 (t, 1H, J=8.4Hz,
H-2 ); 4.16, 4.25, 4.34, 4.35, 5.32 (5d, 5H, D
method A: (0.64 g, 70% yield); from method B: (0.76 g, 84%
0
0
00
ꢁ
(600 MHz, DMSO-d
6
): d
H
yield); m.p. 167–168 C, R : 0.71 (EtAc–MeOH, 1:1). FTIR:
f
0
0
ꢀ
1
1
3
400 (OH) and 1561.91 cm
= 2.97, 3.04, 3.13, 3.19 (4m, 4H, H-6 , 6 , 5
and H-4 ); 3.67 (t, 1H, J = 9.6 Hz, H-3 ); 3.86 (t, 1H, J = 9 Hz,
(CN). H NMR (600 MHz,
0
00
0
0
2
O exchangeable,
DMSO-d
): d
6 H
0
0
5 OH); 7.07, 7.26 (2t, each 1H, J = 7.2 Hz, benzothiazole,
5,6─H); 7.41 (d, 1H, J = 7.8 Hz, benzothiazole, C ─H); 7.71
d, 1H, J = 7.2 Hz, benzothiazole, C ─H); 9.78, 10.12 (2s, 2H,
O exchangeable, 2NH). C NMR (150 MHz, DMSO-d ):
= 56.07 (CH ); 68.84 (C-2); 71.13 (C-3); 78.80 (C-4); 79.24
(C-5); 118.72, 121.27, 121.51, 125.71, 130.45, 152.35
Ar─C); 170.57 (CN); 173.86 (OCN). Anal. Calcd for
S (343.36): C, 45.47; H, 4.99; N, 12.24%. Found:
0
C
4
H-2 ); 4.55, 4.89, 4.97, 5.02, 6.17 (5d, 5H, D O exchangeable,
2
(
D
7
5
C
(
OH); 7.01, 7.22 (2t, each 1H, J = 6.6 Hz, benzothiazole,
5,6─H); 7.34 (d, 1H, J = 7.8 Hz, benzothiazole, C ─H); 7.71
d, 1H, J = 7.2 Hz, benzothiazole, C ─H); 9.29 (s, 1H, HCN);
1
3
2
6
4
d
C
2
7
1
3
1
0.25 (s, 1H, D O exchangeable, NH). C NMR (150 MHz,
2
(
DMSO-d ): d = 62.05 (CH ); 71.02 (C-5); 72.23 (C-4); 74.68
6
C
2
13 17 3 6
C H N O
(
1
C-3); 77.60 (C-2); 117.99, 120.50, 120.90, 125.20, 130.53,
53.10 (Ar─C + CH); 172.84 (CN, thiazol). Anal. Calcd for
S (327.36): C, 47.70; H, 5.23; N, 12.84%. Found:
C, 45.56; H, 5.13; N, 12.29%.
Method B. A solution of compound 1 (1.68 g, 10.16 mmol)
in absolute EtOH–DMF (3:1) (30 mL) was added to a solution of
gama-D-galactolactone (12) (1.81 g, 10.16 mmol) in EtOH
13 17 3 5
C H N O
C, 47.10; H, 4.94; N, 12.32%.
D-Arabinose (benzothiazol-2-yl)hydrazone (10b).
From
(
20 mL) and AcOH (2 mL). The reaction mixture was sonicated
method A: (0.45 g, 55% yield); from method B: (0.59 g, 72%
ꢁ
ꢁ
at a frequency of 40 kHz for 5 min at 30 C and processed as
before to give compound 13 (3.0 g, 86% yield); m.p. 178–180 C.
IR and H NMR spectra were superimposable with the spectra
yield); m.p. 201–202 C, R : 0.83 (EtAc–MeOH, 1:1). FTIR:
f
ꢁ
3
1
d
440 (OH), 3112.53 (str1., NH), 1606.37 (CN), and
1
ꢀ
1
574.91 cm
(bend., NH). H NMR (400 MHz, DMSO-d
6
):
0
from method A.
H
= 4.38 (m, 1H, H-4 ); 4.45, 4.53, 4.54, 4.84 (4d, 4H, D
2
O
1
2
0
00
N -Acetyl-N -(benzothiazolyl)-2-yl)-2,3,4,5,6-penta-O-acetyl-
D-galacto-hydrazide (14). A cold solution of compound 13
0.54 g, 1.57 mmol) in dry pyridine (12 mL) was cooled in an ice
exchangeable, 4OH); 4.61, 4.64 (2dd, 2H, H-5 , H-5 ); 4.72 (t,
0
0
1
H, H-2 ); 4.87 (dd, 1H, H-3 ); 7.09, 7.38 (2t, each 1H,
J = 7.2 Hz, benzothiazole, C6,5─H); 7.49 (d, 1H, J = 6.8 Hz,
benzothiazole, C ─H); 7.75 (d, 1H, J = 6.8 Hz, benzothiazole,
─H); 7.70 (d, 1H, HCN); 11.89 (bs, 1H, D O exchangeable,
NH). C NMR (150 MHz, DMSO-d ): d = 63.41 (CH ); 70.14
(
bath, then treated with Ac O (20 mL) with stirring. The mixture
2
4
was kept overnight at rt, then poured onto crushed ice. The product
that separated out was filtered off, washed repeatedly with water,
dried, and crystallized from EtOH to give colorless crystals (0.59 g,
C
7
2
13
6
C
2
(
1
C-4); 70.92 (C-3); 73.51 (C-2); 120.71, 121.01, 121.41,
21.48, 125.52, 125.89 (Ar─C + CH); 167.05 (CN, thiazol).
Anal. Calcd for C12 S (297.33): C, 48.47; H, 5.08; N,
4.13%. Found: C, 48.28; H, 4.92; N, 13.66%.
ꢁ
6
1
4% yield); m.p. 138–140 C, R : 0.23 (EtAc–n-hexane, 1:3). FTIR:
f
ꢀ
1
1
740.28 (OAc) and 1712.33 cm (NAc). H NMR (600 MHz,
): d = 1.69 (s, 3H, NAc), 2.05, 2.11, 2.15, 2.19, 2.33 (5s,
5H, 5 OAc); 3.72 (q, 1H, H-5 ); 3.97, 4.28 (2dd, 2H, H-6 ,6 );
.28 (t, 1H, H-3 ); 5.57 (d, 1H, H-2 ); 5.68 (dd, 1H, H-4 ); 7.44,
.98 (2t, each 1H, J= 7.2 Hz, benzothiazole, C5,6─H); 7.87 (d, 1H,
15 3 4
H N O
CDCl
3
H
1
2
2
0
0
00
1
5
7
2
,3,4,5-Tetra-O-acetyl-D-arabino-N -acetyl-N -(benzothiazol-
-yl) hydrazone (11b). A solution of compound 10b (0.5 g,
.68 mmol) in dry pyridine (10 mL) was cooled in ice bath, then
O (10 mL) with stirring. The mixture was kept at
8–20 C overnight, then poured onto crushed ice. The product was
extracted with CH Cl (2 ꢂ 20 mL), and the solvent was evaporated
0
0
0
2
1
treated with Ac
2
J= 7.8 Hz, benzothiazole,
benzothiazole, C ─H); 8.96 (bs, 1H, D
NMR (150 MHz, DMSO-d ): d = 20.36 (NCOCH
20.68, 21.0 (5 OCOCH ); 61.95 (CH ); 68.29 (C-3); 67.58 (C-5);
68.60 (C-4); 67.33 (C-2); 121.01,121.29, 122.55, 124.70, 126.26,
133.79 (Ar─C); 169.82 (CN); 170.29 (NCOCH ); 170.45, 170.51,
170.54, (5 CO). Anal. Calcd for C25 12S (595.58): C, 50.42;
H, 4.91; N, 7.06%. Found: C, 50.91; H, 5.09; N, 7.52%.
C ─H); 7.95 (d, 1H, J=8.4Hz,
7
13
ꢁ
1
4
2
O exchangeable, NH).
C
); 20.61, 20.65,
3
2
2
6
C
under reduced pressure. The product that separated out was filtered,
3
2
dried, and crystallized from CHCl
3
as colorless needles (0.52 g,
ꢁ
f
61% yield); m.p. 126–128 C, R : 0.39 (EtAc–n-hexane, 1:3). FTIR:
3
ꢀ
1
1
1741.56 (OAc), 1688.14 (NAc), and 1600.07 cm (CN). H NMR
H N O
29 3
(
600 MHz, CDCl ): d = 1.92, 1.94, 2.08, 2.30 (4s, each 3H, 4
3 H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. O. Badahdah, H. M. Abdel Hamid, and S. A. Noureddin
Vol 000
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2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet