Synthesis, Characterization and Study of
Chromatography Behavior of Novel (Azo–Anil)-Heterocyclic Compounds
Dr. Nagham Mahmood Aljamali1*,
Dr. Khdeeja Jabbar Ali1, Nuha Salman Salih2, Dr. Sajida
Hadi Ridha1
1Assist .Professor, Dept. of Chem., Educt. College, Kufa Univ., Iraq
2Lecturer, Dept of Chem., Science College, Kufa Univ., Iraq
*Corresponding Author E-mail: dr.Nagham_mj@yahoo.com
The present work
included synthesis of novel (azo-anil) compounds in high yield, which react
with (chloro acetyl chloride, sodium azide, alanine, o-thiol via condensation
reaction to produce various heterocycles (four, five, six, seven) membered
ring like (azetidine, imidazole, thiazine, oxazepine, diazepine, tetrazole) The
structure of the newly synthesized compounds were monitored by (TLC) and identified
by many techniques (FT.IR, 1H.NMR, C.H.N), melting points and study
of chromatography behavior .
KEYWORDS: Chromatography, azo–anil, heterocycle, thiazine, diazepine.
INTRODUCTION:
Literature survey
reveals that hetero cyclic compounds containing azo or imine group in there
structure posses various applications.
The chemistry of hetero cyclic compounds is studied extensively
because of its high synthesis and are used to design medicinal compounds. Many of
hetero cyclic compounds are synthesized, hundreds of them which have been
tested to find new prospective leads for different pharmacy, therapeutic areas(1-5)
.
The hetero cyclic compounds containing (imidazole(6) ,
thiazine, diazepine(6) ,azetidine(7), tetrazole,
oxazepine(8)) are the well class of compounds for its biological
applications(9-12) such as antitumor , anticancer, insecticidal,
antibacterial, antifungal, anti-inflammatory agents, anti tuberculosis,
antiepileptic, anti protozoal, anti HIV, antiviral, anticonvulsant. The hetero
cyclic compounds containing (azo or amine) groups have significant importance
in chemistry, they are used as intermediates for synthesis of pharmaceutical
compounds, as a legends(13) in coordination chemistry field for
preparation of metal complexes having a series of different structures .
The gas-liquid chromatography technique(14,15) is
method to separate and quantitatively determine of organic compounds, the mechanism
of separation in this technique depends on stationary phase, rate of carrier
gas, temperature, polarity of compounds, weight of compounds, functional groups
in separated compounds .
EXPERIMENTAL:
All measurement were carried out by: melting points in
electro thermal 9300, LTD, U.K., FT.IR, KBr–disc, Shimazdu 8300, 1H.NMR–spectra
in DMSO –solvent, and (C.H.N) analysis in Kashan University in Iran, chromatography
Technique in Iraq.
Synthesis of Compounds [TIA]:
2–(4–(2–thiophene)-1–(methyl-4–phenylimine)-6–methyl benzothiazol
azo:
4–methyl–aniline (0.01 mole) was reacted with (0.01 mole) of
ammonium thiocyanate in presence of (Br2 in glacial acetic acid )
with mechanical stirrer, then the precipitate was filtered and dried, which
(0.01 mole) dissolved in (2ml) of hydrochloric acid in (0-5)C0, then
solution of sodium nitrite (0.3 gm) added then ethanolic solution of 4 –methyl
benzaldehyde was added to mixture, after (36 hrs), the precipitate was filtered
and dried, which (0.01 mole) refluxed with (0.01 mole) of 2–amino thiophene in
presence of ethanol with drops of glacial acetic acid for (2hrs) to yield (89%)
of compound [TIA].
3
Synthesis of Compound [TCA]:
2–(4–(1–thiophene-3–chloro–azetidine-4–one)-1–(methylphenyl)-6–methyl
benzothiazole azo .
Equimolar (0.01 mole) of compound [TIA] and chloro acetyl chloride
were mixed in (30ml) of dioxane in presence of trimethyl at (5-10)Co,
the mixture was stirred for (5 hrs), then filtered and dried to give (84%) of
compound [TCA].
Synthesis of Compound [TTA] :
2-(4-(1-thiophene–tetrazole)-4-(methyl phenyl)-6-methyl
benzothiazole azo.
A mixture of (0.01mole) of compound [TIA] and sodium azide
(0.01mole) was heated in presence of (30ml) of tetrahydrofuran , the precipitate
was filtered and dried ,re crystallized from dioxane to give (81%) of compound
[TTA].
Synthesis of Compound [TMA]:
2-(4-(1-thiophene-4-methylimidazolone)-4-(methylphenyl)-6-methyl
benzothiazole azo .
A mixture of (0.01mole) of compound [TIA] and alanine (0.01mole)
was refluxed for (5hrs) in presence of (30ml) of dry benzene, the precipitate
was filtered and dried, then re crystallized to give (%84) of compound [TMA].
Synthesis of Compound [TBA]:
2-(4-(3-thiophene-benzothiazine-4-one)-4-(methyl phenyl)-6-methyl
benzothiazole azo.
Compound [TIA] (0.01mole) refluxed with (0.01mole) of O-thiol
benzoic acid in presence of dry benzene for (6hrs), the precipitate was
filtered and dried ,then re crystallized to produce (%83) of compound [TBA].
Synthesis of Compound [TOA]:
2-(4-(1-thiophene–oxazepine-4,7-dione)-4-(methyl phenyl)-6-methyl
benzothiazole azo.
A mixture (0.01mole) of compound [TIA] and (0.01mole) of maleic
anhydride refluxed for (6hrs) in presence of dry benzene, the precipitate was
filtered and dried, then re crystallized from benzene to produce (%86) of
compound [TOA].
Synthesis of Compound [THA]:
2-(4-(1-thiophene–3-hydroxydiazepine-4,7-dione)-4-(methyl
phenyl)-6-methyl benzothiazole azo.
Compound [TOA] (0.01mole) refluxed with (0.01mole) of hydroxyl
amine for (4hrs) in presence of dry benzene, the precipitate was filtered and
dried, then recrystallized to produce (%84) of compound [THA].
RESULTS AND DISCUSSION:
In this work ,we have synthesized seven
compounds, azo –Imine compound [TIA] was synthesized as a starting material ,
which is used in synthesis of various – membered ring (four, five, six, seven)
such as (azetidine, imidazole, tetrazole, thiazine, oxazepine ,diazepine) via
condensation reaction .
All formated compounds were characterized
by {FT.IR, 1H.NMR, (C.H.N)} spectra and other studies like chromate
graph behavior and solubility of compounds in various solvents and other
physical properties:
The FT.IR–spectra shown absorption band at (1640)cm-1 due
to (CH=N) imine group(16,17) in compound [TIA], which disappeared
and other bands appeared in formated compounds such as [(1695)cm-1
due to (-CO-N-) amide(6) ., (710)cm-1 to (C-Cl)] in
compound [TCA]., band at [(3151)cm-1 due to (-NH) of tetrazole ring]
in compound [TTA]., bands at [(1699)cm-1 to (-CO-N) amide and
(3175)cm-1 due(6) to (-NH) of imidazolone ring] in
compound [TMA]., bands at [(1695)cm-1 due to (-CO-N-) amide and
(1288)cm-1 due to (CH-S)] in compound [TBA]., bands at [(1686)cm-1
to lactam (-CO-N-), (1725)cm-1 to (lactone(19) (-CO-O)
and (3095)cm-1 due to (=CH) alkene] in compound [TOA]., bands at
[(1694)cm-1 to (-CO-N-) amide, (3290)cm-1 due to hydroxyl
group (OH) and (3095)cm-1 due to (=CH) alkene] in compound [THA] .,
and other data in table (1) and figures (1-4).
Table (1): FT.IR data (cm-1) of
compounds .
|
Comps
|
(-N=N-) azo
|
(-CO-N-) amide
|
Only Important Groups
|
|
[TIA]
|
1485
|
/
|
(CH=N)imine group:1640
|
|
[TCA]
|
1450
|
1695
|
(C-Cl):710
|
|
[TTA]
|
1492
|
/
|
(NH) end o cycle of tetrazole:3151
|
|
[TMA]
|
1464
|
1699
|
(NH) of imidazolone ring:3175
|
|
[TBA]
|
1498
|
1695
|
(CH-S):1288
|
|
[TOA]
|
1494
|
1686
|
(-CO-O-)lactone of oxazepine:1725 .,(=CH)
alkene :3098
|
|
[THA]
|
1498
|
1694
|
(OH) hydroxyl group:3290 ,(=CH)alkene
:3095
|
Fig (1): FT.IR spectra of Compound [ TIA ]
Fig ( 2 ): FT.IR spectra of Compound [ TCA
]
Fig ( 3 ): FT.IR spectra of Compound [ TTA
]
Fig ( 4 ): FT.IR spectra of Compound [ TMA
]
1H.NMR - spectra for some of synthesized compounds, shown signal
at 
(8.53) due to proton(13) of imine group (CH=N) in
compound [TIA] ., which disappeared and other signals appeared in formatted
compound such as : signals at [ 3.5 due to (N-CH-N) ., 5.5 due to (NH) of tetrazole] in compound
[TTA]., signals at [ 4.10 due to (O-CH-N) and (4.60, 4.45) due to (CH=CH) alkene ] in
compound [TOA]., signals at[ 4.08 due to (N-CH-N) ., (4.65 , 4.70) due to protons of alkene (CH=CH)
and 4.30 due to proton of hydroxyl group (OH)] in compound [THA].,
and other signals in table (2) and figures (5-7) .
Table (2):1H.NMR data (
PPM) of compounds .
|
Comps
|
Important peaks "only"
|
|
[TIA]
|
8.53(CH=N) imine group
|
|
[TTA]
|
3.5 (N-CH-N) endo cycle ., 5.5(NH) of
tetrazole ring.
|
|
[TOA]
|
4.10 (O-CH-N)endo cycle ., 4.60 ,
4.45(CH=CH) endo cycle
|
|
[THA]
|
4.08(N-CH-N) end o cycle ., 4.65, 4.70
(CH=CH) end o cycle ., 4.30(OH) hydroxyl group .
|
Fig ( 5 ): 1H.NMR spectra of Compound
[ TTA ]
Fig ( 6 ): 1H.NMR spectra of
Compound [ TOA ]
Fig ( 7 ): 1H.NMR spectra of
Compound [ THA ]
Physical properties:
(C.H.N)- analysis,from compared the
calculated with found data of these compounds ,the results were comparable ,
the data of analysis ,products % ,melting points are listed in table (3).
Table (3) Physical and Elemental Analysis of compounds.
|
Comps
|
M.P (Co)
|
Product
%
|
Calc./ Found
|
|
C%
|
H%
|
N%
|
S%
|
|
[TIA]
|
164
|
89
|
63.82
63.57
|
4.25
4.17
|
14.89
14.60
|
17.02
16.95
|
|
[TCA]
|
181
|
84
|
58.34
58.21
|
3.75
3.62
|
12.37
12.25
|
14.14
14.09
|
|
[TTA]
|
194
|
81
|
57.27
57.08
|
4.05
4.01
|
23.38
23.21
|
15.27
15.15
|
|
[TMA]
|
202
|
84
|
61.74
61.50
|
4.69
4.47
|
15.65
15.42
|
14.31
14.20
|
|
[TBA]
|
248
|
83
|
67.50
67.31
|
4.16
4.07
|
11.66
11.41
|
13.33
13.24
|
|
[TOA]
|
218
|
86
|
60.75
60.58
|
3.79
3.56
|
11.81
11.72
|
13.50
13.34
|
|
[THA]
|
230
|
84
|
58.89
58.63
|
3.88
3.64
|
14.31
14.19
|
13.08
13.01
|
Solubility of Compounds:
The solubility of formatted compounds was
studied in different solvents according polarity of solvents, the results are shown
in table (4).
Analysis of Synthesized Compounds by Gas
Chromatography:
Solutions of compounds were prepared in
concentration (1 ppm), and injected by using a syringe (Hamilton) in capacity
(10ml) through nitrogen (gas flow 25 ml/min), all data about column are shown
in table (5). The compounds separated according to polarity and molecular
weight, for this reason, compound [THA] separated in the first time due to its
polarity (presence of OH group in structure), then compounds [TMA] and [TTA],
then compound [TOA], after that compounds [TCA] and [TIA], while compound [TBA]
was separated in last time due to its high molecular weight more than other
compounds, Table (5) and figures (8-14).
Table (4): Solubility of Synthesized Compounds
|
Comps
|
Solvents
|
|
Ethanol
|
Methanol
|
DMSO
|
Benzene
|
Dioxane
|
THF
|
|
[TIA]
|
+
|
+
|
+
|
-
|
-
|
-
|
|
[TCA]
|
+
|
+
|
+
|
+
|
+
|
+
|
|
[TTA]
|
+
|
+
|
+
|
+
|
+
|
-
|
|
[TMA]
|
+
|
+
|
+
|
+
|
+
|
-
|
|
[TBA]
|
+
|
+
|
+
|
+
|
+
|
-
|
|
[TOA]
|
+
|
+
|
+
|
+
|
+
|
+
|
|
[THA]
|
+
|
+
|
+
|
+
|
+
|
+
|
Table ( 5): Specification Used Capillary Columns
|
Polarity
|
Max operatory Temp.(M.O.T)
|
Column dimension
|
Formula
|
Composition
|
Liquid phase
|
|
Low polar
|
300))
|
0.25mm I.D
0.12 Mm d.f
|
|
2,3-di-o-propionyl-6-t-butyl silyl
derivative of ᵞ-cyclodextrin phase
|
DP5-25
|
|
Moderately polar
|
-20C؛-280C؛-(300)C؛
|
0.25mm I.D 0.25Mm d. f
|
|
14%Cyanopropyl phenyl poly siloxane
|
FS-BP10
|
Fig ( 8): Chromotogram of Compound [ TIA ]
Fig ( 9): Chromotogram of Compound [ TCA ]
Fig ( 10): Chromotogram of Compound [ TBA
]
Fig ( 11): Chromotogram of Compound [ TMA
]
Fig ( 12): Chromotogram of Compound [ THA
]
Fig ( 13): Chromotogram of Compound [ TTA
]
Fig ( 14): Chromotogram of Compound [ TOA
]
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