International Journal of Application or Innovation in Engineering & Management (IJAIEM)
Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com
Volume 3, Issue 1, January 2014
ISSN 2319 - 4847
Synthesis, antimicrobial and antifungal
study of 2,4-substituted-1,5-substitutedbenzothiazepine
Swati.V. Gaikwad* ,DrA.B.Bhakea, DrS. E. Bhandarkarb
*research student,Department of Applied Chemistry, DBACER ,Nagpur–11
a
AssociateProfessor,Department of Applied Chemistry,YeshwantraoChavan C.O.E., Nagpur–33
b
Associate Professor, Department of Chemistry, G.V.I.S.H., Amravati
ABSTRACT
Synthesis of 2,4-substituted-1,5-substituted- benzothiazepine was first carried out by the acetylation of substituted α – napthol in
presence of glacial acetic acid and zinc chloride. The 1-(1-hydroxy-naphthalene-2-yl)ethanone obtained is then heated with
aromatic aldehyde using ethanol as a solvent and 40% KOH which on condensation gave 1-(substituted-1-hydroxynaphthalen -2yl)-3-aryl-prop-2-en-1-one.This compound on microwave irradiation in presence of substituted aminobenzothiol and zinc acetate
gave 2,4-substituted-1,5-substituted- benzothiazepine .The synthesized compounds are characterized by elemental analysis, 1H
NMR, IR Spectroscopy. Newly synthesized compound shows an excellent antimicrobial and antifungal activities.
Keywords: Synthesis, benzothiazepine,elementalanalysis,antimicrobial
INTRODUCTION
Benzothiazepines are seven membered heterocyclic compounds.Benzothiazepines have received a considerable attention
nowadays because of its versatile biological activities like anticonvulsant [1],CNS depressant
[2,3,4]
,anticancer[5],antifungal[6] and antimicrobial activities[7,8].As disease poses a major threat to human beings and
scientists are fighting to find solutions in the form of various medications, benzothiazepine finds its importance in
bioinorganic and medicinal chemistry in designing new therapeutic agents with improved pharmacological
properties.[9,10].Present work deals with the synthesis of 2,4-substituted-1,5-substituted- benzothiazepine and their
characterization by spectral analysis ( IR, 1H NMR ).
EXPERIMENTAL
All the melting points were taken in silicon oil bath with open capillary tubes and are uncorrected. IR spectra were
recorded on a Nicolet-Impact 400 FT-IR spectrometer 1 H NMR spectra were recorded on a Brucker AC300 FNMR
spectrometer(300 MHz), using TMS as an internal standard. Microanalysis of nitrogen was obtained by Kjeldahal’s
Method. Thin Layer Chromatography on silica gel-G, was used to check the purity of the compounds.
Procedure for the synthesis of 2-acetyl-substituted-1-naphthol:
In hot glacial acetic acid, fused ZnCl2 was added and refluxed till dissolved, then powdered substituted 1-naphthol was
added and the mixture was refluxed for about 8 hours then cooled & poured in acidulated water. The solid obtained was
filtered, washed, dried and recrystallized from rectified spirit to obtain compound (2a).
Synthesis of 1-(substituted-1-hydroxynaphthalen -2-yl)-3-aryl-prop-2-en-1-one (3a):
2-acetyl-substituted-1-naphthol and aromatic aldehydes were added in ethanol solvent. To this mixture KOH (10%)
solution was added dropwise with constant stirring. The reaction mixture was kept overnight. Then the mixture was
poured over crushed ice & little HCl. The product was filtered and recrystallized from ethanol to obtain the compounds
(3a).
Synthesis of 2,4-substituted-1,5-substituted- benzothiazepine (1-25):
1-(substituted-1-hydroxynaphthalen -2-yl)-3-aryl-prop-2-en-1-one and substituted 2-aminobenzenethiol was heated in
presence of catalyst zinc acetate to obtain a compound 2,4-substituted-1,5-substituted- benzothiazepine.The physical data
of newly synthesized compounds is given in Table.I
Table I - Physical and analytical characterization data of newly synthesized compounds
Volume 3, Issue 1, January 2014
Page 478
International Journal of Application or Innovation in Engineering & Management (IJAIEM)
Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com
Volume 3, Issue 1, January 2014
ISSN 2319 - 4847
R
R2
Melt
ing
Poin
0
t C
Compound
R1
% Nitrogen
%
Yield
Found
Calculated
R.F.
Value
2a
--
--
--
75
85
-
-
3a
--
C6H5
H
85
75
-
-
1
H
C6H5
H
76
68
4.66
4.78
0.65
2
H
OCH3
H
73
64
5.45
5.67
0.64
71
69
4.52
4.74
0.56
80
50
5.38
5.57
0.64
91
72
4.25
4.52
0.59
88
55
5.25
5.30
0.56
65
56
4.35
4.49
0.57
72
61
5.89
6.01
0.69
90
80
4.26
4.32
0.58
88
65
4.99
5.04
0.56
92
67
4.19
4.29
0.54
70
85
4.88
4.96
0.53
69
75
4.26
4.32
0.58
OCH3
88
80
4.85
5.04
0.62
R2
Melt
ing
Poin
0
t C
%
Yield
3
4
5
6
7
8
9
10
11
12
13
14
H
H
Br
Cl
H
H
OH
C6H5
H
OH
OCH3
H
OH
OH
Br
Cl
H
H
OCH3
C6H5
H
OCH3
OCH3
H
OCH3
Br
H
OCH3
Cl
H
H
C6H5
OCH3
H
OCH3
Compound
R1
R
% Nitrogen
Found
Calculated
R.F.
Value
15
H
Br
OCH3
95
55
4.20
4.29
0.63
16
H
Cl
OCH3
71
69
4.72
4.96
0.52
18
OH
C6H5
OCH3
80
50
4.08
4.12
0.65
19
OH
OCH3
OCH3
91
72
5.00
5.04
0.56
20
OH
Br
OCH3
88
55
4.02
4.09
0.54
21
OH
Cl
OCH3
65
56
4.65
4.69
0.53
22
OCH3
C6H5
OCH3
72
61
3.86
3.95
0.64
Volume 3, Issue 1, January 2014
Page 479
International Journal of Application or Innovation in Engineering & Management (IJAIEM)
Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com
Volume 3, Issue 1, January 2014
ISSN 2319 - 4847
23
OCH3
24
OCH3
25
OCH3
OCH3
Br
OCH3
OCH3
OCH3
Cl
90
80
70
85
69
75
4.75
4.79
0.56
3.90
3.93
0.58
4.45
4.48
0.55
SPECTRAL INTERPRETATION
IR (KBr) : 1650 (C=O), 3350 (-OH) , 3131(-NH)
NMR (CDCl3 + DMSO-d6) : δ 2.35 (s,3H,CH3), δ 6.88- 7.11 (m, 11H, Ar-H), δ 9.83 (s,1H,-OH) , δ 3.86(s,3H, OCH3)
SCHEME
OH
OH
O
+
HO
O
ZnCl2
CH3
CH3
(2a)
R1
R1
naphthalen-1-ol
acetic acid
O
10%KOH
R2
R1
R
R
SH
OH
S
HO
NH2
H
O
R
N
H
R2
R1
(3a)
(1-25)
R1 = H, OH, OCH3;
R = aryl, CH3, Br,Cl;
R2 = H, OCH3
ANTIMICROBIAL STUDIES
All abovebenzothiazepine derivatives have been studied for their antimicrobial activity against Escherichia coli,
Proteus mirabilis, Staphylococcus aureas, Pseudomonas aeruginosa,. The culture of each species was incubated at 370C
and the zone of inhibition was measured after 24 hr. Most of these compounds were found active.
Volume 3, Issue 1, January 2014
Page 480
International Journal of Application or Innovation in Engineering & Management (IJAIEM)
Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com
Volume 3, Issue 1, January 2014
ISSN 2319 - 4847
ACKNOWLEDGEMENT
The authors are thankful to Principal, YeshwantraoChavan C.O.E., Nagpur–33 for providing necessary laboratory
facilities.
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