Iraqi National Journal of Chemistry,2012,volume47, 378-390 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
Synthesis and Characterization some of Pyridine Derivatives
Abdullah jawad kadhim
Chemistry Department, College of Education, University of Al-Qadissiyah
Iraq 2012
Email:abdullah_m1975@yahoo.com
(NJC)
(Recevied on 72/5 /2012 )
(Accepted for publication
72/9/2012)
Abstract
Starting compound (2,6-dimethyl-4-phenyl-3,5-diethoxy carbonyl -1,4dihydropyridine)(1) has been prepared by treating (2mole) from ethylacetoacetate
with benzaldehyde, which reacted with (2mole) hydrazine hydrate and ethanol to give
hydrazide derivative(2), then converted hydrazide group to oxadiazole and triazole
rings by reacted with (2mole) from carbon disulphide and potassium hydroxide to
give compound(3) and with (2mole) from carbon disulphide and potassium hydroxide
then (2mole) from hydrazine hydrate to give compound (4). hydrazide derivative (2)
also reacted with P-nitrobenzaldehyde and P-chlorobenzaldehyde to give (5) and (6)
respectively.
Keywords: Pyridine, 1,4-dihydropyridine, benzaldehyde, synthesis compounds
‫الخالصة‬
‫ثنائي هيدرو‬-4، 0- ‫ثنائي ايثوكسي كربونيل‬-5, 3-‫فنيل‬-4-‫ ثنائي مثيل‬-6, 2( ‫المركب االساسي‬
‫ والذي تفاعل مع‬،‫مول) من المركب اثيل اسيتو اسيتيت مع البنز الديهايد‬2( ‫) حضر بمعاملة‬0( )‫بيريدين‬
‫ ثم حولت مجموعة الهيد ارزيد الى‬،)2( ‫مول) من الهيد ارزين المائي بوجود االيثانول ليعطي مشتق الهيد ارزيد‬2(
‫مول) من المركب ثنائي كبريتيد الكربون وهيدروكسيد‬2( ‫حلقات االوكسادايازول والترايازول بمفاعلة المشتق مع‬
‫مول) من‬2( ‫مول) من ثنائي كبريتيد الكربون وهيدروكسيد البوتاسيوم ثم‬2( ‫) ومع‬3( ‫البوتاسيوم ليعطي المركب‬
)5( ‫) تفاعل ايضا مع االلديهايدات ليعطي المركبات‬2( ‫ مشتق الهيد ارزين‬.)4( ‫الهيد ارزين المائي ليعطي المركب‬
.)6( ‫و‬
378
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
hypertension
Introduction
classes of heterocyclic compounds due
1-Melting points were determined by
using Melting Point SMP3 apparatus
2- F.T.I.R. spectra were recorded by using
to their pharmacological activity as
calcium antagonists or agonists(1). The
Fourier Transform Infrared
1, 4-DHPs cause vasorelaxation by
Spectrophotometer (F.T.I.R) 8400 S
blocking voltage operated calcium
Shimadzu apparatus.
channel in smooth muscle cells and
3- U.V. spectra were recorded by using
also by increasing NO release from the
U.V-Visible Spectrophotometer 1650 PC
intact endothelium. Recently, some
Shimadzu
other pharmacological activities have
apparatus
been reported such as: antitumor,(2)
antiviral
Synthesis Methods
antidiabetic,(4)
and antianginal
(6)
Note : All the methods are general
methods.
also many
Synthesis of starting
material(3,5-diethylcarboxylate
-2,6-dimethyl-4-phenyl-1,4dihydropyridine(1)
natural products and bioactive agents
such as nifedipine,(7) nitrendipine(8) and
felodipine(9) are 1,4-dihydropyridine
A
derivatives (1,4-DHPs).The 1,4-DHPs
(0.1mole),
have also been extensively utilized as
various
processes(10).1,4-dihydro
of
with 60% aqueous ethanol (10ml) to
yield yellow prisms(12). The purity of
compounds prepared was examined by
biological
using the thin layer chromotogravea. Rf
properties(11). For example, the 1,4-
values of these compounds were
DHP derived drugs such as nefidine,
measured using eluent (acetic acid:
and nimodipine are frequently used as
cardiovascular
blockers)
for
agents
the
ethanol: water)2:4:4 respectively by
2+
(Ca channel
treatment
(28ml)
filter off separated product and wash
products and synthetic compounds
range
ethylacetoacetate
resulting mixture then allow cooling.
pyridine
in a growing number of both natural
wide
benzaldehyde
(60ml) under reflux for 3hr. to
redox
(DHP) structural subunit is contained
with
of
hydroxide (8ml) (0.2mole) in ethanol
study the mechanism and synthetic
of
mixture
(0.2mole) and concentrated ammonium
analogs of NAD(P)H coenzymes to
potential
pectoris
Experimental Part
Instruments
DHPs) are one of the most important
(5)
angina
diseases.
1, 4-Dihydropyridines (1, 4-
bronchodilating,(3)
and
of
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Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
using silica gel on glass plates . Rf for
(10ml)
this compound is 0.84
hydrate (0.02mole) and refluxed for
2,6-Dimethyl-3,5dicarbohydrazide-4-phenyl-1,4
dihydro pyridine (2)
4hr.,cold and softened with water and
and
hydrazine
filtered
and filtered then recrystallized from
(13)
. Rf for this compound is
recrystallized
from
A mixture of compound (2)
0.687 .
(0.01mole)
5,5'-(2,6-dimethyl-4-phenyl1,4-dihydropyridine-3,5diyl)bis (1,3, 4-oxadiazole-2thiol)(3)
3hr.,the mixture was cold and filtered
then recrystllized from ethanol. Rf for
this compound is 0.853 .
(0.01mol) was added to ethanol which
contain
(0.02mol)
potassium
and
(2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5diyl)bis(N'-(4-chlorobenzylidene)formic
hydrazide(6)
hydroxide
carbondisuphide
(0.02mole) the mixture was refluxed
even out hydrogen sulphide. Cooled
A mixture of compound (2)
and filtered then recrystallized from
(0.01mole)
ethanol. Rf for this compound is 0.743 .
chlorobenzaldehyde)
5,5'-(2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5-diyl)bis(4amino-4H-1,2,4-triazole-3thiol)(4)
(0.02mol)
and
(4-
(0.02mole)
in
mixture was cold and filtered then
recrystllized from ethanol. Rf for this
compound is 0.778 .
(0.01mol) was added to ethanol which
potassium
and
ethanol was refluxed for 3hr.,the
Solution of carbohydrazide (2)
contain
and(2-nitrobenzaldehyde)
(0.02mole) in ethanol was refluxed for
Solution of carbohydrazide (2)
is
and
(2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5diyl)bis(N'-(2-nitrobenzylidene)formic
hydrazide(5)
refluxed the mixture for 3hr. cooled
is
hydrazine
ethanol. Rf for this compound is 0.881 .
hydrate
(0.06mole) in ethanol (30ml) then
ethanol
add
acidified by hydrochloric acid, then
A mixture of starting material
(0.03mol)
water,then
Note: All chromatographic methods
hydroxide
were used (0.001 mol) of compounds
carbondisulphide
prepared with volumetric ratios 2:4:4
(0.02mole) the mixture was refluxed
of eluent (solvents) as a general way to
on water bath for 1hr., then remove the
bring models to measure the Rf values.
solvent and melt remaining with
Rf % values shown in the table (3-1).
380
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
EtOOC
+
CH2
COOEt
CHO
+HC
O
O
H3 C
EtOOC
NH4/EtOH
2
COOEt
H 3C
CH3
CH3
N
H
(1)
EtOH NH2NH2
N
N
N
1)KOH/CS2
N
HS
SH
N
H2N
N
H
CH3
CONHNH2
KOH/CS2
N
N
H3C
N
H
O
H3C
CH3
(2)
(4)
N
H
Cl
CH
N
NH
O
C
C
CHO
CH3
H3C
N
H
NH
N
CH
CH3
(3)
NO2
NO2
O
N
SH
O
NH2
Cl
N
HS
2)NH2NH2
N
H3C
H2NHNOC
Cl
CH
CH3
O2N
N
NH
O
O
C
C
H3C
(6)
N
H
NH
N
CH
CH3
(5)
the bond (C = O) of the ester group.
Discussion
3,5-diethylcarboxylate -2,6dimethyl-4-phenyl-1,4 dihydro
pyridine(1)
This
frequency is
frequency
in
the
less than the
carbonyl
bond
aldehydes and ketones, due to the
This compound was diagnosed
spectroscopy
phenomenon of resonance between the
(F.T.I.R), which showed a sharp
two atoms of oxygen in the ester
absorption at the pack (3348-3448 cm-
group, as well as the emergence of
1
) back to the bond (N-H), as well as
absorption when the pack (732 cm-1)
the emergence of a package when the
back to the benzene ring unilateral
sharp absorption (1635 cm-1) back to
compensation and pack at (3016 cm-1)
by
using
infrared
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Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
back to (C-H) aromatic. Table (3-2)
either bond (C-O-C) has emerged
shows the other packets absorption of
strong at (1210 cm-1).Table (3-2)
compound.
shows the other packets absorption of
3,5-dicarbohydrazide-2,6dimethyl-4-phenyl-1,4-dihydro
pyridine(2)
compound.
5,5'-(2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5-diyl)bis (4amino-4H-1,2,4-triazole-3thiol)(4)
Spectroscopy showed infrared
absorption package at (3178-3278 cmto a group (NH2) primary
The infrared measurements of the
amine , while the group emerged (N-
compound observed the disappearance
H) secondary amide at (3399 cm-1),
of bond absorption (C = O) and the
either bond (C = O) has remained at
emergence
(1630 cm-1) because it is in the case of
absorption at (1658-1689 cm-1) back to
resonance with a group (N-H) , as well
the bond (C = N), and survival a bond
as the package absorption appeared at
(NH2) due to the formation triazole
(1420 cm-1) due to (C-N) bond. Table
ring. As well as the emergence of weak
(3-2)
absorption package at (2414 cm-1) back
1
) bake
shows
the
other
packets
of
a
new
package
to the bond (S-H) either the bond (C-S)
absorption of compound.
has emerged at the frequency (717 cm-
5,5'-(2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5diyl)bis(1,3,4-oxadi
azole-2thiol)(3)
1
). Table (3-2) shows the other packets
absorption of compound.
3, 5-di (2-nitrobenzilidine) form
amide-2, 6-dimethyl-4-phenyl 1, 4-dihydropyridine(5)
Showed spectral measurements
of the infrared absorption of the
disappearance of a package bond
Spectroscopy
showed
the
(C=O) and a new absorption appeared
compound similar to compound (2) in
pack at (1655-1685 cm-1) back to
the frequencies of bonds (N-H) and
(C=N), as well as the measurements
(C=O), but appeared the package at
showed the disappearance of a package
(1500m-1) bake to a group (NO2) and
bond NH2 absorption due to the
the package of absorption at 700cm-1
formation oxadiazole ring, in addition
back to the benzene ring bilateral
to that ,the appearance of weak
compensation. Table (3-2) shows the
absorption package at (2265 cm-1) back
other packets absorption of compound.
to bond (S-H), and the package of
2,6-dimethyl-4-phenyl-1,4dihydropyridine-3,5-diyl)bis(N'-
absorption at (702 cm-1) back to (C-S),
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Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
emergence of absorption when the
(4-chloro-benzylidene)formic
hydrazide(6)
packet (780 cm-1) back to the bond (C-
The spectral measurements of
Cl), as noted the survival of other
the infrared of this compound similar
packages as they are in the above
to compound (5), but was noted the
compound
Compound
Molecular
formula
Starting material
(1)
C19H23NO4
2
Solvent
Yield %
Rf %
m.p. Cº
Color
Ethanol
71
84
150-151
Yellow
C15H19N5O2
Ethanol
94
68.7
129-130
Yellow
3
C17H15N5O2
Ethanol
44
74.3
160-161
Yellow light
4
C17H19N9
Ethanol
52
88.1
173-174
Dark gray
5
C29H25N7O6
Ethanol
78
85.3
144-145
Yellow
6
C29H25N5O2 Cl2
Ethanol
93
77.8
192-193
Dark brown
Table (3-2) (F.T.I.R) spectra of compounds
Comp.
C-H aromat cm-1
Starting
material (1)
-------
2
3101
C-H aliphatic cm-1
------
2908
(C=C) cm-1
(C=N) cm-1
Other cm-1
1473-1515
(COOEt)
(1238-1338)
(C=O) 1650
1420-1473
(C=O) 1630 cm1
(C-N)1420 cm-1
3
3093
2970
1500-1655
4
3089
2981
1658-1689
5
3100
2980
1580-1650
C-N(1300)
No2 (1500)
6
3100
2980
1500-1650
C-N(1300)
C-Cl (780)
383
(N-H)
3340-3440
--------
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
2800
2400
2383.85
2306.71
2000
1800
1600
1635.52
1515.94
1473.51
1400
Fig. (1) (F.T.I.R) spectrum of starting material(1)
2700.16
2646.15
1396.37
1338.51
1200
1238.21
1145.64
1083.92
1000
1022.20
972.06
800
779.19
732.90
600
628.75
597.89
551.60
400
1/cm
439.74
405.02
384
82.5
3016.46
%T
3244.05
75
3348.19
67.5
60
52.5
45
37.5
30
22.5
15
3200
3600
4000
FTIR Measurement
3448.49
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
2000
1800
1600
1620.09
1473.51
1400
1411.80
1200
1195.78
1087.78
1000
800
600
632.61
400
1/cm
462.88
385
90
2684.73
2400
Fig.(2) (F.T.I.R) spectrum of compound (2)
2800
2908.45
2831.31
%T
3101.32
82.5
3278.76
3178.47
75
67.5
60
52.5
45
37.5
30
22.5
4000
3600
3200
FTIR Measurement
3379.05
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
2715.59
2400
2298.99
2090.69
2075.26
2000
1967.26
1890.11
1866.97
1843.82
1820.68
1800
1600
Fig.(3) (F.T.I.R) spectrum of compound (3)
2800
3093.61
3058.89
3028.03
2970.17
2935.46
2904.60
1685.67
1650.95
1623.95
1577.66
1488.94
1400
1454.23
1392.51
1373.22
1299.93
1200
1249.79
1211.21
1168.78
1122.49
1091.63
1000
1049.20
1022.20
964.34
910.34
883.34
800
767.62
736.76
702.04
600
640.32
601.75
574.75
400
1/cm
524.60
501.46
432.03
386
45
3340.48
3305.76
%T
3440.77
3421.48
40
35
30
25
20
15
10
5
0
-5
-10
3200
3600
4000
FTIR Measurement
3992.37
3903.65
3838.08
3799.51
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
2869.88
2781.16
2738.73
2400
2000
1800
1600
1689.53
1658.67
1643.24
1623.95
1581.52
1400
1496.66
1454.23
1200
1000
1373.22
1323.08
1299.93
1249.79
1211.21
1168.78
1141.78
1126.35
1087.78
1049.20
1022.20
972.06
914.20
800
829.33
779.19
767.62
736.76
702.04
678.90
600
640.32
601.75
578.60
400
1/cm
501.46
432.03
387
70
2800
Fig.(4) (F.T.I.R) spectrum of compound (4)
2939.31
2900.74
%T
3200
3039.60
2981.74
60
3600
3236.33
3089.75
3058.89
50
40
30
20
10
0
-10
-20
4000
3340.48
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
Fig.(5) (F.T.I.R) spectrum of compound (5)
388
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
Fig.(6) (F.T.I.R) spectrum of compound (6)
389
Iraqi National Journal of Chemistry,2012,volume47 ‫ العدد السابع واالربعون‬2102-‫المجلة العراقية الوطنية لعلوم الكيمياء‬
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