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Tikrit Journal of Pure Science 23 (4) 2018
ISSN: 1813 – 1662 (Print)
E-ISSN: 2415 – 1726 (On Line)
32
Tikrit Journal of Pure Science
Journal Homepage: http://main.tu-jo.com/ojs/index.php/TJPS/index
Synthesis, diagnosis and biological activity study of some heterocyclic
compounds derived from 2-aminobenzothiazole
Shaimaa hatem Abdullah
Education Collage for pure Science , Tikrit University , Tikrit , Iraq
A r t i c l e i n f o.
Article history:
-Received: 5 / 11 / 2017
-Accepted: 23 / 1 / 2018
-Available online: / / 2018
Keywords: 2-aminobenzothiazole,
amidazolidine, Preslott method,
Muller Hinton.
Corresponding Author:
Name: Shaimaa hatem Abdullah
E-mail: abadfars@gmail.com
Tel:
Abstract
This study includes synthesis of some benzothiazole derivatives from
treatment 2 -aminothiazole with choroacyle chloride to form 1-hydrogen-
benzothiazole-2yl-2-chloroastiamide(1).the last one was reacted with
urea, thiurea, thiosymigarizaide, 2- amibenzothiazole and para-
aminoaniline, respectively to form the compounds (2,6). Some shiff
bases for 2-aminobenzothiazole (7,8) were prepared from the reacting
with aromatic aldehydes and it was cycled by reaction with glycine to
form two derivatives of amidazolidine (9,10). The prepared compounds
were diagnosed by IR spectra and H1NMR for proton, then, the bacterial
susceptibility towards some prepared compounds(1,2,5,6,7)were
estimated against E.coli and Proteus mirabilis .
1- Introduction
Thiazole derivatives occupy an im portant position
among heterocycle that are containing N and S atoms
[1,2], several of thiazole derivatives are
charachterized by their biological and
pharmacological activity[3,4], therefore, it was
studied at a wide range including several fields.
thiazole cycle plays an important role in medicine [5]
due to using it as antibiotic drugs against microbes
[6], tuberculosis[7], viruses[8], malaria [9] and
HIV[10] also in development of allergy [11] and in
synthesis of sulfonylamide[12]. Benzothiazoles are
used as anticancer [13] with mixture of amino acids
complexes that introduced into the transference and
replacement mechanisms of trace elements ions in
human body [14]. The nucleus of benzothiazole are
linkaged with various activities of antihistamine[15],
some of chloride-cobalt complexes which contain
benzothiazole were also showed high activity in
increasing of agriculture production[16]. the
functional benzothiazole was reported to show the
reverse applications as light stabilizer and complexity
factors with metal [17] .
2- Experment & Methods
2-1 Methods
General procedure for Synthesis of benzothiazole-
2yl-2chloroastiamide[18] (1)
(0.01 mol) (1.5 gm) 2-aminobenzothiazole, that
dissolved in 15 ml of dry benzene, and was mixed
with (0.01 mol) (1ml) chloroacytle chloride, that
dissolved in (5ml) from the same solvent. drops from
triethyleamine were added to mixture then, refluxed
in water bath for 3 hr., left the mixture to cool then
filtered and using distill water to wash the precipitant,
finally, it was recrystallized from ethanol.
General procedure for Synthesis of benzothiazole-
2yl- oxazole/thiazole-2,5-diamine[19] (2- 3)
(0.01mol)(2.19gm) from compound (1) was dissolved
in (60ml) ethanol, then (0.01mol) (1.6gm) urea and
(0.76gm ) thiurea were added gradually . the mixture
was refluxed in water bath for24 hr. and left to cool,
after that, drops of 10%NaOH were added to it, then,
the precipitant was filtered and recrystallized from
ethanol .
General procedure for Synthesis of benzothiazole-
2yl( 3-thiosymicarbizide) acetamide [19] (4)
(0.01mol) (2.9fm) from compound (1) was dissolved
in (30ml) ethanol, then (0.01mol) (0.91gm)
thiosinicarbazide was added gradually, and after
addition some drops of pyridine, the mixture was
refluxed for 24 hr., then the precipitant was cooled,
filtered and recrystallized from ethanol.
General procedure for Synthesis of 2-
(benzothiazole-2-yl) amino(benzothiazole-2-yl)
acetamide [20] (5)
(0.01mol)(2.19gm) from compound (1) was dissolved
in (20ml) ethanol, then, (0.01mol) (1.5gm) from 2-
Tikrit Journal of Pure Science 23 (4) 2018
ISSN: 1813 – 1662 (Print)
E-ISSN: 2415 – 1726 (On Line)
33
aminobenzothiazole was added gradually . the
mixture was refluxed for 6hr. and cooled. And it was
neutralized with 10% sodium bicarbonate, then, the
precipitant was filtered and washed by distill water,
finally, it was recrystallized from ethanol.
General procedure for Synthesis of 2-(4-
anilineo)(benzothiazole-2yl) acetamide [20] (6)
(0.01mol) (2.19gm) from compound (1) was
dissolved in (20ml) ethanol, then (0.01mol) (1.08gm)
p-phenylene diamine was added gradually. The
mixture was refluxed for 6hr. then, it was
concentrated to one-third the volume, and calibrated
by 10% sodium bicarbonate. The precipitant was
filtered and washed with distill water, and
recrystallized from ethanol .
General procedure for Synthesis of (4-chloro/4-
hydroxy) benzlydine-2-aminobenzothiazole [21] (7-
8)
(0.01mol) (2.19gm) from 2-aminobenzothiazole was
mixed with (0.01mol) aromatic aldehyde in (30ml)
ethanol. The mixture was refluxed for 6 hr., then, the
solution was cooled for 24 hr. at 0°C. The precipitant
was filtered and recrystallized from ethanol.
General procedure for Synthesis of [3-
(benzothiazole-2-yl)-2-(4-chloro/4-
hydroxy)phenyl] amidazolldine-on [21] (9-10)
(0.01mol) from compound (7,8), that dissolved in
THF, was mixed with (0.01mol) glycine ,which
dissolved in (15ml) THF,. The mixture was refluxed
for 24hr.. the precipitant was cooled, filtered and
recrystallized from ethanol.
2-2 Bacterial susceptibility test for some prepared
compounds (1- 2- 5- 6-7)
Two species of pathogenic bacteria, that resistance to
antibiotics, were used , which were E.coli and
Proteus Mirabilis. the bacterial isolates were taken
ready and diagnosed from laboratory of biology
department in education collage of pure science /
Tikrit university.
2-2-1 culture media
a- Nutrient broth: it was prepared and used
according to the company's instructions, it sterilized
by autoclave at 121°C for 15 min. under 15bar/inch2 .
then, poured in petri dishes or special tubes and left to
cool [22]
b- Muller Hinton agar: this medium is used to
measure the biological activity for antibiotics and
pharmacological, also is used to measure the diameter
of inhibition zone [23].
2-2-2 Chemical solutions
The chemical solutions for some prepared compounds
were prepared at concentration (0.01-0.1 gm/5ml) and
sterilized by autoclave at 121°C for 15 min under 15
bar/inch2, then left to cool before used .
2-2-3 Estimation of biological activity by diffusion
methods
The biological activity was estimated by followed a
Kirby Bauer method ; it has been spread (0.1ml) from
bacterial suspension on the petri dishes that
containing muller hinton agar and left for 5 min. to
diffuse into medium. after that, 4 pores in each dishes
were done using sterilize cort porer (5mm diameter).
(0.1 ml) from prepared solutions were added to each
pores while the fourth pore filled by DMSO as
control sample. All dishes were incubated for 24 hr.
at 37°C [24-25]. The inhibition diameter was
measured around each pore in Mm according to
Preslott method [26]
Results and discussion:
The amino group in 2-aminobenzothiazole reacted
with chloroacetyl chloride to form the compound (1)
as shown in table (1) and figure(5). The IR spectra for
this compound showed absorption band at 3506cm-1
for stretch of (NH ) bond and the absorption band at
1693 cm-1 for stretch of(C=O)bond, and also at 715
cm-1 for (C=C) bond. The H-NMR spectra of this
compound was showed a dual signal at frequency
(4.46-4.51 δ ppm) attributed to (2H,CH2 ) protons,
and a signal at (8 δ ppm) to ( H, NH)proton, as well
as, a signal showed at range (7.24-7.98 δppm)
attributed to (4H, phenyl group) as shown in figure
(1).
The compound (1) was reacted with urea and thiurea
to formed oxazole and thiazole (2-3) respectively .
IR spectra for these compounds showed absorption
band at (3465 cm-1 ) attributed to stretch (NH2) bond ,
and at ( 1155cm-1 ) to stretch of( C-O ) band . as
shown in table (1).
The compound (1) was reacted with
thiocymicambarzide and 2- aminobenzothiazole and
para aminoaniline to form compounds (4-5-6). IR
spectra for these compounds showed absorption band
at range (3506-3382 cm-1) attributed to stretch of (N-
H) bond , also at (1666-1616cm-1) to stretch of (C=O)
bond, and at (1242 cm-1) to (C=S) bond, as shown in
table (2). H-NMR spectra was showed a dual signal
for compound (5) at range (3.59-3.66δppm) attributed
to (2H-CH2) proton, and a single signal at (4.15
δppm) to (H, CH2 –NH) proton, and at (7.96 δ ppm) to
(H, NH-CO) proton, also H-NMR showed a signal at
(6.99-7.68 δppm) attributed to (8H,phenyl group), as
shown in figure (2).
The compound 2-aminobenzothiazole was also
reacted with aromatic aldehydes to form shiff bases
of compounds (7-8), IR spectra showed absorption
band for these compounds at range (1631-1643 cm-1)
attributed to stretch (C=O) bond, also at (744 cm-1) to
stretch (C-Cl) bond and (3392 cm-1) to stretch (C-
OH) bond as shown in table (3)and figure (6). H-
NMR spectra for compound (7) showed a signal at
(10 δ ppm) attributed to (H-CH ) proton, as well as, a
signal at range (6.97-7.95δppm) to (8H-phenyl
group), as shown in figure (3), while compound (8)
was showed a signal at ( 3.39 δ ppm) attributed to
(H,OH) proton and a signal at range (7.64 δppm) to
(H-CH) proton, as well as, a signal showed at range
(6.62-6.97 δ ppm) attributed to (8H, phenyl group)
proton , as shown in figure (4).
The compound (7-8) were cycled using glycine and
THF as solvent to formation amideazoldine-4-on
Tikrit Journal of Pure Science 23 (4) 2018
ISSN: 1813 – 1662 (Print)
E-ISSN: 2415 – 1726 (On Line)
34
compounds that represent by compounds (9-10). IR
spectra for these compounds was showed absorption
band at range (1633-1683 cm-1 ) attributed to stretch
of (C=O) bond , also at (3332-3402 cm-1) to stretch of
(N=H) bond as shown in table (4) .
Biological activity for some compounds (1- 2-5-6-
7)
The biological activity of some compounds (1-2-5-6-
7) was measured ,where compounds (1-2) showed a
high efficiency towards Proteus mirabilis
(susceptibility), also compound (6) showed an
efficiency towards E.coli, while the rest compounds
were ineffective towards these species of bacteria but
compound (5) was had a low efficiency towards
E.coli. as shown in table (5).
(2)
Table (1) The results of IR spectra for (1-2-3) compounds
C – O
NH2
C-Cl
C - S
C = O
N – H
Ar – H
No. Comp
ـــــ
ـــــ
755
ــــــ
1693
3506
3047
( 1 )
1155
3465
ـــــــ
ــــــ
ــــــ
ــــــ
3050
( 2 )
ــــــ
3450
ــــــ
1080
ــــــ
ــــــ
3065
( 3 )
(3)
(4)
(5)
(6)
(1)
Tikrit Journal of Pure Science 23 (4) 2018
ISSN: 1813 – 1662 (Print)
E-ISSN: 2415 – 1726 (On Line)
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Table (2) The results of IR spectra for (4-5-6)compounds
C = S
C = O
CH2 Aleph
N – H
Ar – H Orma
No. Comp
1242
1641
2929
3360
3070
( 4 )
ــــــ
1622
2925
3382
3035
( 5 )
ــــــ
1616
2889
3313
3052
( 6 )
Table (3) The results of IR spectra for (7-8) compounds
C-OH
C – Cl
N=C – H Aleph
𝛎C = N
𝛎A – H arom
No. of comp
ـــــــ
744
2935
1637
3077
( 7 )
3392
ــــــ
2927
1643
3053
( 8 )
Table (4)Tthe results of IR spectra for (9-10) compounds
C=O
𝐂 − 𝐍
𝛎 N – H
𝛎Ar – h arom
No. of comp
1683
1591
3332
3063
( 9 )
1633
1541
3402
3037
( 10 )
Table (5) The results of biological activity for (1-2-5-6-7 ) compounds
Proteus
E.coil
No.comp
S
M
(1)
D
M
(2)
M
R
(5)
M
S
(6)
M
M
(7)
Comparative with ciprofloxacin
Sensitive intermediate Resistant
≽ 21 MM 15 – 20 ≼ 14
Table (6) The physical properties for (1-10) compounds
Solvent
Mp
Yiled%
Colour
Format
No . of comp
Benzene
187 – 190
90 %
Off -yellow
C9H7N2SOCl
( 1 )
Ethanol
228 – 230
93 %
White
C10H8N4SO
( 2 )
Ethanol
238 – 340
34 - %
White
C10H8N4S2
( 3 )
Ethanol
250 – 252
62 %
White
C10H11N5S2O
( 4 )
Ethanol
243 - 245
72 %
White
C16H12N4S2O
( 5 )
Ethanol
110-112
19 %
Grey
C15H4N4SO
( 6 )
Ethanol
115 – 118
59 %
Off- green
C14H9N2SCl
( 7 )
Ethanol
105 – 107
35 %
Orange
C14H10N2SO
( 8 )
THF
185 – 188
%40
Yellow
C16H12N3SCl
( 9 )
THF
Oily
____
Yellow
C16H13N3SO2
( 10 )
Figure (1) H1 NMR for compound (1)
Tikrit Journal of Pure Science 23 (4) 2018
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Figure (2) H1 NMR for compound (5)
Figure (3) H1 NMR for compound (7)
Figure (4) H1 NMR for compound(8)
Figure (5) FTIR for compound(1)
Tikrit Journal of Pure Science 23 (4) 2018
ISSN: 1813 – 1662 (Print)
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Figure (6) FTIR for compound (8)
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2
2 1
22[1]2
[6-2]2[8,7]
glycine[10,9]
[7,6,5,2,1]
(Escherichia Coli)(Proteus Mirabilis)
