Synthesis and antioxidant evaluation of Schiff bases derived from 2,6-pyridinedicarboxylic acid

Article abstract of DOI:10.2174/157017812801322480

A series of novel Schiff bases derived from dipicolinic acid was synthesized and evaluated for antioxidant and iron chelating activity. In most cases Schiff bases derived from di-hydrazide showed higher antioxidant activity than the ones derived from mono-hydrazide and some of them are very promising considering the fact of being better antioxidants than the standards used in the investigation. For iron chelating activity substituents had a greater impact on the activity than mono or di-hydrazide skeleton.

Full text of DOI:10.2174/157017812801322480

Letters in Organic Chemistry, 2012, 9, 401-410
401
Synthesis and Antioxidant Evaluation of Schiff Bases Derived from 2,6-
Pyridinedicarboxylic Acid
Maja Molnar*, Milan ꢀa iꢁ and Sanja Zec Zrinuꢂiꢁ
Department of Applied Chemistry and Ecology, Faculty of Food Technology, J. J. Strossmayer University, Franje
Kuhaꢀa 20, 31 000 Osijek, Croatia
Received November 15, 2011: Revised February 25, 2012: Accepted May 03, 2012
Abstract: A series of novel Schiff bases derived from dipicolinic acid was synthesized and evaluated for antioxidant and
iron chelating activity. In most cases Schiff bases derived from di-hydrazide showed higher antioxidant activity than the
ones derived from mono-hydrazide and some of them are very promising considering the fact of being better antioxidants
than the standards used in the investigation. For iron chelating activity substituents had a greater impact on the activity
than mono or di-hydrazide skeleton.
Keywords: Antioxidant, dipicolinic acid, metal chelating, Schiff base.
1. INTRODUCTION
and antitumor activities and various 2,6-bis-substituted pyri-
dine derivatives also show antibacterial activities [10].
Dipicolinic acid (2,6-pyridinedicarboxylic acid) was first
discovered in a biological system in 1936 and is now known
to be a major component of bacterial spores [1], where it
occurs in substational amounts (5-14% dry weight), includ-
ing the species of Bacillus and Clostridium [2]. It appears to
contribute to the resistance of the spores to UV radiation [1]
and to be important for their stability and germination. Dipi-
colinic acid is present in nature as an oxidative degradation
product of vitamins, coenzymes and alkaloid and is a com-
ponent of fulvic acid [3] and it has frequently been cited in
the literature as a plant sterilizing and water germicidal agent
[3].
Compounds with the structure of –C=N– (azomethine
group) are known as Schiff bases, which are usually synthe-
sized from the condensation of primary amines and active
carbonyl groups and they have been of great interest for
many years. They represent an important class of compounds
in medicinal and pharmaceutical field, showing biological
applications including antibacterial [11-14], antifungal [12-
15] and antitumor activity [11]. These compounds play an
important role in the development of coordination chemistry
related to catalysis and enzymatic reactions, magnetism and
molecular architectures [16]. A. González, et al. [17] have
synthesized tin(IV) complexes derived from pyridine Schiff
bases and some of them have shown an excellent antioxidant
activity in rat brain homogenate on inhibition of thiobarbi-
turic acid reactive substances.
It shows various biological functions including activa-
tion/inactivation of some metalloenzymes, inhibition of elec-
tron transport system [4], inhibition of lipid peroxidation and
protection of glutathione reductase from the copper-
dependent inactivation [4] and is known to be an antioxidant
for ascorbic acid in foods as well [3].
Our work was based on the fact that reactive oxygen spe-
cies (ROS), which are generated in living organisms as by-
products of many metabolic reactions, can cause oxidative
damage which is associated with many diseases. Also, transi-
tion metals can stimulate lipid peroxidation, thus the chelat-
ing of such species would have a significant role in lipid
peroxidation prevention. So, except for the synthesis of dipi-
colinic acid derivatives, our investigation comprised of anti-
oxidant and metal chelating investigation of these com-
pounds.
Dipicolinic acid, synthesized in large amount in the spore
of genus Bacillus, is a potent metal-chelator, so the com-
plexation of metal ions by 2,6-pyridinedicarboxylic acid has
been extensively investigated and due to its low toxicity and
amphophilic nature, it is a desirable metal ion ligand [5].
Dipicolinic acid is known to form stable chelates with metal
ions and oxometal cations and can display widely varying
coordination demeanor functioning as a bidentate, tridentate,
meridian or bridging ligand [6].
Other interesting properties are its biological activity [7],
like its ability to stabilize unusual oxidation states [8]. The
iron complexes have also been used as well as specific mo-
lecular tools in DNA cleavage [9]. In general, substituted
pyridine derivatives show antimicrobial, anti-inflammatory
2. CHEMISTRY
The synthesis of the target compounds was carried out as
outlined in Fig. (1). The starting compound (dimethyl pyri-
dine-2,6-dicarboxylate) (2) was prepared by esterification of
pyridine-2,6-dicarboxylic acid (1). Compound 2 in reaction
with 86% hydrazine hydrate in methanol at room tempera-
ture gave a compound, which was a mixture of the major
product, 6-methyloxycarbonyl-2-pyridinecarboxylic acid
hydrazide (so-called mono-hydrazide), and a minor product,
*Address correspondence to this author at the Department of Applied
Chemistry and Ecology, Faculty of Food Technology, J. J. Strossmayer
University, Franje Kuha a 20, 31 000 Osijek, Croatia; Tel: 00385 98 918
2391; Fax: 00385 31 207 115; E-mail: maja.molnar@ptfos.hr
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

402 Letters in Organic Chemistry, 2012, Vol. 9, No. 6
Molnar et al.
O
O
H
N
H
O
O
1
CH3OH
O
O
N
O
O
2
2H2NNH2
H2NNH2
H
H
N
H
O
N
N
N
NH2
H2N
N
NH2
O
O
O
O
3
4
2Ar-CHO
Ar-CHO
H
H
N
H
N
N
O
Ar
N
N
N
Ar
N
N
Ar
O
O
O
O
6a-s
5a-s
Entry
a
Ar
Entry
h
Ar
Cl
Entry
o
Ar
HO
OH
Cl
b
c
i
j
p
q
r
HO
Br
HO
HO
HO
H3CO
HO
H3CO
H3CO
H3CO
d
HO
k
Br
OCH3
e
l
s
F
H3CO
O
f
m
n
g
N
H3CO
Fig. (1). Synthesis of Schiff bases derived from dipicolinic acid.

Synthesis and Antioxidant Evaluation of Schiff Bases
Letters in Organic Chemistry, 2012, Vol. 9, No. 6
403
2,6-pyridinedicarboxylic acid di-hydrazide (so-called di-
hydrazide). Mono-hydrazide was separated from di-
hydrazide by recrystallization from ethanol. Both, mono (3)
and di-hydrazide (4), in reaction with aromatic aldehydes
gave Schiff bases 5a-s and 6a-s.
sorbance of the complex formed between Fe2+ and ferrozine
was measured at 562 nm. Metal chelating efficiency of sam-
ples was compared to the chelating activtiy of EDTA diso-
dium salt. The chelating activity of the compound for Fe2+
was calculated as:
chelating activity = [(A0 –A1)/ A0]ꢀ100%
3. PHARMACOLOGY
A0 - absorbance of the control (blank, without samples) at
562 nm
3.1. Scavenging of DPPH (1,1-diphenyl-2-picrylhydrazyl
radical)
A1 - absorbance in the presence of the methanol/DMSO sam-
ple solution at 562 nm
Determination of antioxidant activity was performed ac-
cording to the procedure described in the literature [18, 19]
with some modifications. DMSO (dimethyl sulfoxide) was
used as a solvent [20], due to the low solubility of synthe-
sized compounds in ethanol and methanol.
4. RESULTS AND DISCUSSION
4.1. Antioxidant Activity
In the DPPH and phosphomolybdenum assay methods
hydrogen and electron transfer from antioxidants to DPPH.
and Mo(VI) complex occurs. These transfers depened on the
structure of antioxidants. The reason we used ascorbic acid
as standard in both antioxidant investigations is that ascorbic
acid has the ability to donate hydrogen and electrons and can
be detected by both assay models.
DMSO solution of the corresponding synthesized com-
pound (0.75 mL; 0.2 mM) was added to a DMSO solution of
DPPH radical (0.2 mM), so that the final concentration of
DPPH radical and the synthesized compound in a solution
was 0.1 mM. The mixture was shaken and allowed to stand
at room temperature. After 30 min the absorbance at 517 nm
was determined and the scavenging activity was calculated
according to the formula below. Ascorbic acid (AA) was
used as a reference compound.
4.1.1. Scavenging of 1,1-diphenyl-2-picrylhydrazyl Radical
DPPH free radical, which possesses an odd electron,
gives a strong absorption maximum at 517 nm and is purple
in colour. The colour turns from purple to yellow when the
odd electron of DPPH radical becomes paired with hydrogen
from a free radical scavenging antioxidant to form the re-
duced DPPH-H. The method used in this work applies to the
overall antioxidant capacity of the sample after 30 minutes
of incubation. DPPH scavenging activity was determined
against ascorbic acid as a standard compound.
scavenging actvitiy (%) = ((Ab + As – Am)/Ab)*100
Ab – absorbance of 0.1 mM DMSO solution of DPPH radical
at 517 nm
As – absorbance of 0.1 mM DMSO solution of test com-
pound at 517 nm
Am – absorbance of DMSO mixture of test compound and
DPPH radical at 517 nm
Data in Table 1 show that most of the Schiff bases de-
rived from dipocolinic acid do not show significant scaveng-
ing activity on DPPH radical. The only exceptions are com-
pounds 6q and 5q with scavenging activity around 50% and
6r and 5r with a scavenging activity 42% and 27%. In both
cases, if we compare Schiff bases with the same -Ar, the
ones derived from di-hydrazide showed higher scavenging
activity than the ones derived from mono-hydrazide. The
best scavenging activity is accomplished with the compound
6q, Schiff base with 3,4-dihydroxyphenyl substituent, fol-
lowed by the compound 5q, with the same substituent, but
derived from mono-hydrazide. It is obvious that in case of
dipicolinic acid Schiff bases, m-, p-substitution on phenyl
ring, with electron donating groups, is important for DPPH
scavenging activity, since, only the compounds with this
kind of substitution show moderate scavenging activity in
comparison with all the rest, whose activity is not signifi-
cant.
3.2. Evaluation of Antioxidant Activity by Phosphomo-
lybdenum Method
The antioxidant activity of tested dipicolinic acid deriva-
tives was evaluated by the phosphomolybdenum method
according to the procedure of Prieto et al. (1999) [21]. This
method is based on the reduction of Mo(VI) to Mo(V) by the
tested compounds followed by formation of green phos-
phate/Mo(V) complex at acid pH. An aliquot of 100 μL of
sample solution (2 mM in DMSO) is mixed with 1 mL of the
reagent solution (0.6 M sulphuric acid, 28 mM sodium phos-
phate and 4 mM ammonium molybdate). The samples are
incubated in a water bath at 95 °C for 90 minutes. Samples
are cooled to room temperature and the absorbance was
measured at 695 nm. The antioxidant activity was expressed
relative to the antioxidant activity of the same concentration
of ascorbic acid, on molar basis.
4.1.2. Evaluation of Antioxidant Activity by Phosphomo-
lybdenum Method
3.3. Iron Chelating Activity
The chelating activity of dipicolinic acid derivatives for
ferrous ions Fe2+ was measured according to the literature
method [22] with some modifications. Solution of FeCl2
(0.025 mL; 2 mM) was added to 1 mL 2 mM metha-
nol/DMSO solution (4:1) of the compound investigated. Af-
ter 30 s, 0.05 mL of ferrozine (5 mM) was added. Samples
were incubated at room temperature for 10 min and the ab-
Data in Fig. (2) show that substituents on phenyl ring
have a great influence on antioxidant activity. The effects of
various substituents on phenyl ring of Schiff bases derived
from mono-hydrazide in descending order were found to be:
2-OCH3 (5e) > H (5a) > 3-OH (5c) > 3-OCH3 (5f) > 3-Cl
(5i) > 4-OCH3 (5g) > styryl (5o) > 2-OH (5b) > 4-F (5l) >

404 Letters in Organic Chemistry, 2012, Vol. 9, No. 6
Molnar et al.
1.3
1.2
1.1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
compound
Fig. (2). Antioxidant activities of Schiff bases derived from dipicolinic acid relative to ascorbic acid (Am – activity relative to ascorbic acid
(AA) on a molar basis).
Table 1. DPPH Radical Scavenging Activity of Dipicolinic Acid Derivatives 5a-s and 6a-s a
Compound
Scavenging Activity on DPPH (%)
Compound
Scavenging Activity on DPPH (%)
AAb
5a
6a
5b
6b
5c
6c
5d
6d
5e
6e
5f
90.01
-
AAb
6j
90.01
-
0.49
7.84
6.06
3.82
5.02
7.00
6.83
6.11
4.69
4.79
5.60
5.07
5.86
-
5k
6k
5l
0.32
-
-
6l
-
5m
6m
5n
6n
5o
6o
5p
6p
5q
6q
5r
-
0.14
9.02
7.49
-
0.38
7.17
7.49
49.24
53.99
26.89
41.74
5.45
-
6f
5g
6g
5h
6h
5i
-
4.53
4.05
-
6r
6i
6s
5j
5s
aData are means of three replicates.
bAscorbic acid is used as standard.
- Indicated compounds are inactive.
3,4-(OH)2 (5q)> 4-OH (5d) > 3-Br (5j) > 4-OH-3-OCH3 (5r)
> 2-Cl (5h) > 3-phenoxy (5m)> 2,4-(OH)2 (5p) > 4-Br (5k) >
4-N,N-(CH3)2 (5n) > 3,4,5-(OCH3)3 (5s).
OCH3 (6f) > H(6a) > 4-OH (6d) > 4-Br (6k)> 3-Br (6j) >
3,4,5-(OCH3)3 (6s) > styryl (6o) > 4-OH-3-OCH3 (6r) > 4-F
(6l)> 3-phenoxy (6m) > 3,4-(OH)2 (6q) > 2-OCH3 (6e) > 2-
Cl(6h).
The effects of various substituents on phenyl ring of
Schiff bases derived from di-hydrazide in descending order
were found to be: 2-OH (6b) > 2,4-(OH)2 (6p) > 4-N,N-
(CH3)2 (6n) > 4-OCH3 (6g) > 3-Cl (6i) > 3-OH (6c) > 3-
In general, Schiff bases derived from di-hydrazide show
better antioxidant activity, than the ones derived from mono-
hydrazide, with the exception of 6l, 6m, 6q, 6e and 6h.

Synthesis and Antioxidant Evaluation of Schiff Bases
Letters in Organic Chemistry, 2012, Vol. 9, No. 6
405
Schiff bases 6b, 6p, 6n and 6g showed excellent antioxidant
activity, compounds 6b, 6p, 6n better than ascorbic acid,
1.18, 1.5 and 1.13 times better, respectively, and 6g the same
as ascorbic acid. None of Schiff bases derived from mono-
hydrazide showed better antioxidant activity than ascorbic
acid. All of the compounds having greater antioxidant activ-
ity in comparison to ascorbic acid, posses one or two elec-
tron donating groups in ortho (6b) or para (6n) position or in
ortho and para position (6p). Considering all data above, it
is obvious that substituents on phenyl ring have a different
influence on antioxidant activity in Shiff bases derived from
mono-hydrazydes and ones derived from di-hydrazides.
The formation of red coloured complex was inhibited by
compounds 5p, 5b, 6p, 5j, 6g. These compounds showed
moderate chelating activity, but not comparable with EDTA.
All of these compounds possess one or two electron donating
groups in o- and p- position, with the exception of 5j, which
possesses electron withdrawing –Br group in m- position.
Addition of electron donating groups has been proven to
enhance iron chelating activity [25]. Compounds showing
the best activity, 5p, 5b and 6p, bear hydroxyl group in posi-
tion 2 of aryl ring, which could be significant because lots of
synthetic iron chelators posses the same moiety in the same
position [25]. Other compounds showed low or no chelating
activity under these conditions.
When comparing the results gained by two different anti-
oxidant assays performed in this work, DPPH and phospho-
molybdenum assay respectively, they appeared to be differ-
ent. It is expected because completely different and complex
mechanisms and conditions are involved and thus the results
are different, which is also in agreement with other authors
[23, 24].
5. CONCLUSION
The present work comprises the synthesis of dipicolinic
acid derivatives known as Schiff bases. The investigation
includes antioxidant and chelating activity determination of
the compounds above. For DPPH scavenging activity as well
as antioxidant activity determined by phosphomolybdenum
method compounds derived from di-hydrazide showed
higher scavenging activity than the ones derived from mono-
hydrazide. It is obvious that the position and electron donat-
ing groups had a significant influence on all the activities
investigated.
4.2. Iron Chelating Activity
This investigation is based upon complex formation be-
tween ferrozine and Fe2+, which is red in colour. In the pres-
ence of chelating agents, the complex formation is disrupted
with the result that the red colour of the complex is de-
creased. Therefore, the chelating activity of the coexisting
chelator is estimated by measurement of colour reduction at
562 nm.
6. EXPERIMENTAL
Table 2. Ferrous ion Chelating Activity of Dipicolinic Acid
Derivatives 5a-s and 6a-s a,c
6.1. Materials and Methods
Melting points were determined on Electrothermal Capil-
lary melting point apparatus and are uncorrected. Thin-layer
chromatography was performed with fluorescent silica gel
plates HF254 Merck, which were checked under UV 254 and
365 nm light, using benzene:acetone:acetic acid (8:1:1) as a
solvent. The elemental analysis for C, H and N was done on
a Perkin-Elmer Analyzer 2440. Infrared spectra (ꢀmax-cm-1)
were recorded on a Beckmann FT-IR 3303, using KBr disks.
1H NMR spectra were recorded on JEOL EX-270 MHz
NMR Spectrometer at 293 K in DMSO-d6. The MS spectra
were recorded on LC/MS/MS (API 2000). The absorbance
was measured on UV visible spectrophotometer Helios ꢀ,
(Thermo Spectronic, Cambridge UK).
Compound
Chelating Activity (%)
EDTAb
5a
5b
5c
6c
5d
5e
6e
5f
97.43
8.57
25.14
10.24
4.15
5.68
0.56
7.19
4.80
5g
6g
6i
3.12
6.2.
Preparation
of
Dimethyl
pyridine-2,6-
dicarboxylate(2)
11.14
7.66
To a solution of dipicolinic acid (10 mmol) in 40 mL of
methanol, 1.5-1.8 mL of sulphuric acid is added. Mixture is
refluxed for 2-3 hours and left at room temperature, until
crystals are formed. Crystals are filtered and recrystallized
from ethanol.
5j
11.27
1.90
6j
5k
5l
6.25
4.89
Yield (94%), M.p. 121 °C, Rf = 0.57. FT-IR (KBr) ꢀmax
(cm-1): 3450, 3063, 2968, 1742, 1572, 1450, 1290, 1244,
5o
5p
6p
0.38
1
1165, 995, 758 and 696; H NMR ꢁ (ppm): 3.68 (s, 6H,
63.74
20.48
2OCH3), 8.03 (t, 1H, py-H); 8.26 (d, 2H, py-H), MS m/z:
196.0 [M + H+], (M =195.18); Anal. Calcd. for C9H9NO4
(195.05): C, 55.39; H, 4.65; N, 7.18%; Found: C, 55.30; H,
4.61; N, 7.21.
aData are means of three replicates.
bEDTA disodium salt is used as standard.
cCompounds not listed in the Table did not show chelating activity.

406 Letters in Organic Chemistry, 2012, Vol. 9, No. 6
Molnar et al.
6.3.
Preparation
of
6-methyloxycarbonyl-2-
7.02-7.66 (m, 4H, arom.), 7.92 (t, 1H, py-H), 8.25 (d, 2H,
py-H), 8.78 (s, H, N=CH), 11.56 (s, H, OH), 11.88 (s, H,
NH); MS m/z: 298.0 [M - H+], (M = 299.28); Anal. Calcd.
for C21H17N5O4 (299.28): C, 62.53; H, 4.25; N, 17.36%;
Found: C, 62.50; H, 4.27; N, 17.31%.
pyridinecarboxylic acid hydrazide(3) and pyridine-2,6-
dicarbohydrazide (4) [26]
Anhydrous hydrazine (98 %, 3.27 g, 0.200 mol in 150
mL methanol) was added dropwise to a stirred warm solu-
tion of dimethylpyridine-2,6-dicarboxylate (19.8 g; 0.102
mol in 500 mL methanol) over a period of 18 h. A white
crystalline solid formed during the reaction, was filtered off,
washed with methanol and dried under vacuum. The result-
ing compound is a mixture of 6-methyloxycarbonyl-2-
pyridinecarboxylic acid hydrazide (mono-hydrazide) and
pyridine-2,6-dicarbohydrazide (di-hydrazide), approximately
9:1 and they are separated by recrystallization from ethanol.
6.4.3. 6-[(3-hydroxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5c)
Yield (99%), M.p. 249 °C, Rf = 0.22. FT-IR (KBr) ꢀmax
(cm-1): 3433, 3281, 1710, 1697, 1579, 1529, 1492, 1435,
1
1313, 1286, 1249, 1145, 790 and 690; H NMR ꢁ (ppm):
3.68 (s, 3H, OCH3), 7.02-7.60(m, 4H, arom.), 7.92 (t, 1H,
py-H), 8.25 (d, 2H, py-H), 8.46 (s, H, N=CH), 9.83 (s, H,
OH), 11.80 (s, H, NH); MS m/z: 298.0 [M - H+], (M =
299.28); Anal. Calcd. for C21H17N5O4 (299.28): C, 62.53; H,
4.25; N, 17.36%; Found: C, 62.50; H, 4.28; N, 17.31%.
6.3.1. 6-Methyloxycarbonyl-2-pyridinecarboxylic acid hy-
drazide(3)
Yield (85%), M.p. 183-184 °C, Rf = 0.14. FT-IR (KBr)
ꢀmax (cm-1): 3433, 3371, 3043, 1740, 1686, 1510, 1428, 1274,
1250, 1158, 987, 739 and 664; H NMR ꢁ (ppm): 3.69 (s,
6.4.4. 6-[(4-hydroxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5d)
1
3H, OCH3), 4.52 (d, 2H, NH2), 8.12 (t, 1H, py-H), 8.16 (d,
2H, py-H), 9.86 (s, 1H, NH); MS m/z: 196.0 [M + H+], (M
=195.18); Anal. Calcd. for C7H9N5O2 (195.08): C, 43.08; H,
4.65; N, 35.88%; Found: C, 43.01; H, 4.63; N, 35.91%.
Yield (92%), M.p. 170 °C, Rf = 0.22. FT-IR (KBr) ꢀmax
(cm-1): 3584, 3394, 3219, 1718, 1662, 1603, 1541, 1516,
1
1440, 1365, 1298, 1281, 1246, 1165, 844 and 679; H NMR
ꢁ (ppm): 3.69 (s, 3H, OCH3), 6.82-7.70 (m, 4H, arom.), 7.92
(t, 1H, py-H), 8.25 (d, 2H, py-H), 8.64 (s, H, N=CH), 9.54
(s, H, OH), 11.85 (s, H, NH); MS m/z: 298.0 [M - H+], (M =
299.28); Anal. Calcd. for C21H17N5O4 (299.28): C, 62.53; H,
4.25; N, 17.36%; Found: C, 62.50; H, 4.28; N, 17.31%.
6.3.2. Pyridine-2,6-dicarbohydrazide(4)
Yield (10%), M.p. 284 °C, Rf = 0.03. FT-IR (KBr) ꢀmax
(cm-1): 3333, 3271, 3063, 1747, 1676, 1514, 1438, 1294,
1
1255, 1157, 989, 729 and 665; H NMR ꢁ (ppm): 4.53 (d,
6.4.5. 6-[(2-methoxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5e)
4H, 2NH2), 8.01 (t, 1H, py-H); 8.26 (d, 2H, py-H), 9.96 (s,
2H, 2NH); MS m/z: 196.1 [M + H+], (M =195.18); Anal.
Calcd. for C7H9N5O2 (195.08): C, 43.08; H, 4.65; N,
35.88%; Found: C, 43.01; H, 4.63; N, 35.91%.
Yield (92 %), M.p. 117 °C, Rf = 0.39. FT-IR (KBr) ꢀmax
(cm-1): 3452, 3182, 3047, 2960, 1741, 1680, 1601, 1560,
1
1437, 1290, 1247, 1163, 997 and 756; H NMR ꢁ (ppm):
3.88 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 7.02-7.78 (m, 4H,
arom.), 7.95 (t, 1H, py-H), 8.27 (d, 2H, py-H), 8.84 (s, H,
N=CH), 11.91 (s, H, NH); MS m/z: 314.0 [M + H+], (M =
313.31); Anal. Calcd. for C23H21N5O6 (313.11): C, 64.03; H,
4.91; N, 16.23%; Found: C, 64.00; H, 5.09; N, 16.16%.
6.4. Preparation of Schiff Bases from Mono-hydrazide
(5a – s)
Equimolar amount of 6-methyloxycarbonyl-2-pyridinec-
arboxylic acid hydrazide (3) and appropriate aromatic alde-
hyde (a – s) in ethanol, with a few drops of acetic acid, is
refluxed for 3 hours. After cooling, the solution is poured
onto crushed ice and filtered. Crude product is recrystallized
from ethanol.
6.4.6. 6-[(3-methoxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5f)
Yield (98%), M.p. 111-117 °C, Rf = 0.42. FT-IR (KBr)
ꢀmax (cm-1): 3529, 3470, 3255, 2978, 1726, 1693, 1583, 1535,
6.4.1. 6-Benzylidenehydrazinocarbonyl-2-
methoxycarbonyl-pyridine(5a)
1
1433, 1307, 1236, 1157, 1078, 989 and 749; H NMR ꢁ
(ppm): 3.80 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 7.02-7.56
(m, 4H, arom.), 7.95 (t, 1H, py-H), 8.26 (d, 2H, py-H), 8.74
(s, H, N=CH), 11.78 (s, H, NH); MS m/z: 314.0 [M + H+],
(M = 313.31); Anal. Calcd. for C23H21N5O6 (313.11): C,
64.03; H, 4.91; N, 16.23%; Found: C, 63.96; H, 4.88; N,
16.24%.
Yield (83%), M.p. 105 °C, Rf = 0.63. FT-IR (KBr) ꢀmax
(cm-1): 3518, 3468, 3201, 3049, 1728, 1670, 1537, 1437,
1
1367, 1300, 1240, 1165, 1108 and 685; H NMR ꢁ (ppm):
3.69 (s, 3H,
OCH3), 7.22-7.80 (m, 5H, arom.), 8.12 (t, 1H, py-H),
8.26 (d, 2H, py-H), 8.56 (s, H, N=CH), 11.81 (s, H, NH);
MS m/z: 284.0 [M + H+], (M = 283.28); Anal. Calcd. for
C21H17N5O2 (283.14): C, 67.91; H, 4.61; N, 18.86%; Found:
C, 67.89; H, 4.62; N, 18.80%.
6.4.7. 6-[(4-methoxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5g)
Yield (95%), M.p. 109-111 °C, Rf = 0.40. FT-IR (KBr)
ꢀmax (cm-1): 3520, 3450, 3230, 2920, 1728, 1688, 1530, 1440,
1
1300, 1240, 1180 and 1015; H NMR ꢁ (ppm): 3.73 (s, 3H,
6.4.2. 6-[(2-hydroxybenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine(5b)
OCH3), 3.86 (s, 3H, OCH3), 7.02-7.84 (m, 4H, arom.), 7.98
(t, 1H, py-H), 8.26 (d, 2H, py-H), 8.84 (s, H, N=CH), 11.85
(s, H, NH); MS m/z: 314.0 [M + H+], (M = 313.31); Anal.
Calcd. for C 23H21N5O6 (313.11): C, 64.03; H, 4.91; N,
16.23%; Found: 64.00; H, 4.98; N, 16.19%.
Yield (88%), M.p. 164 °C, Rf = 0.46. FT-IR (KBr) ꢀmax
(cm-1): 3516, 3437, 2997, 1724, 1668, 1620, 1535, 1240,
1
1157, 750 and 684; H NMR ꢁ (ppm): 3.70 (s, 3H, OCH3),

Synthesis and Antioxidant Evaluation of Schiff Bases
Letters in Organic Chemistry, 2012, Vol. 9, No. 6
407
6.4.8. 6-[(2-chlorobenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5h)
(s, 3H, OCH3), 7.11-7.85 (m, 9H, arom.), 7.96 (t, 1H, py-H),
8.25 (d, 2H, py-H),8.74 (s, H, N=CH), 11.89 (s, H, NH); MS
m/z: 374.0 [M - H+], (M = 375.12); Anal. Calcd. for
C33H25N5O4 (375.12): C, 71.34; H, 4.54; N, 12.61%; Found:
C, 71.32; H, 4.50; N, 12.59%.
Yield (89%), M.p. 145-151 °C, Rf = 0.52. FT-IR (KBr)
ꢀ
max (cm-1): 3547, 3476, 3207, 2953, 1732, 1676, 1637, 1585,
1
1537, 1442, 1365, 1300, 1244, 1159, 767 and 682; H NMR
ꢁ (ppm): 3.69 (s, 3H, OCH3), 7.40-7.87 (m, 4H, arom.), 7.98
(t, 1H, py-H), 8.26 (d, 2H, py-H), 8.99 (s, H, N=CH), 11.81
(s, H, NH); MS m/z: 315.9 [M - H+], (M = 317.73); Anal.
Calcd. for C21H15Cl2N5O2 (317.06): C, 57.29; H, 3.43; N,
15.91%; Found: C, 57.31; H, 3.42; N, 16.01%.
6.4.14. 6-[(4-dimethylaminobenzylidene)hydrazine-
carbonyl]-2-methoxycarbonylpyridine (5n)
Yield (98%), M.p. 150 °C, Rf = 0.25. FT-IR (KBr) ꢀmax
(cm-1): 3537, 3473, 3209, 1724, 1666, 1597, 1523, 1431,
1
1363, 1296, 1240, 1176, 815, 732 and 682; H NMR ꢁ
6.4.9. 6-[(3-chlorobenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5i)
(ppm): 3.02 (s, 6H, N(CH3)2), 3.69 (s, 3H, OCH3), 6.81-7.50
(m, 4H, arom.),7.96 (t, 1H, py-H), 8.25 (d, 2H, py-H), 8.94
(s, H, N=CH), 11.80 (s, H, NH); MS m/z: 327.1 [M + H+],
(M = 326.35); Anal. Calcd. for C25H27N7O2 (326.35): C,
65.63; H, 5.95; N, 21.43%; Found: C, 65.60; H, 5.91; N,
21.39%.
Yield (92%), M.p. = 135 °C, Rf = 0.54. FT-IR (KBr) ꢀmax
(cm-1): 3517, 3460, 3292, 3203, 1732, 1681, 1627, 1535,
1
1307, 1242, 1159, 787 and 684; H NMR ꢁ (ppm): 3.69 (s,
3H, OCH3), 7.26-7.91 (m, 4H, arom.), 7.96 (t, 1H, py-H),
8.28 (d, 2H, py-H), 8.84 (s, H, N=CH), 11.76 (s, H, NH);
MS m/z: 318.0 [M + H+], (M = 317.73); Anal. Calcd. for
C21H15Cl2N5O2 (316.06): C, 57.29; H, 3.43; N, 15.91%;
Found: C, 57.28; H, 3.40; N, 15.96%.
6.4.15. 6-[(3-phenylallylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5o)
Yield (87%), M.p. 200 °C, Rf = 0.37. FT-IR (KBr) ꢀmax
(cm-1): 3448, 3238, 3043, 1722, 1664, 1624, 1537, 1440,
6.4.10. 6-[(3-bromobenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5j)
1
1317, 1363, 1244, 1130, 987, 748 and 688; H NMR ꢁ
(ppm): 3.89 (s, 3H, OCH3), 6.82 (m, H, HC=CH), 7.12 (m,
H, HC=CH), 7.34-7.72 (m, 5H, arom.),7.95 (t, 1H, py-H),
8.27 (d, 2H, py-H), 8.50 (s, H, N=CH), 10.88 (s, H, NH);
MS m/z: 307.9 [M - H+], (M = 309.32). Anal. Calcd. for
C25H21N5O2(309.32): C, 70.91; H, 5.00; N, 16.54%; Found:
C, 70.89; H, 5.04; N, 16.51%.
Yield (91%), M.p. 163 °C, Rf = 0.59. FT-IR (KBr) ꢀmax
(cm-1): 3547, 3466, 3292, 3203, 1732, 1681, 1627, 1535,
1
1307, 1242, 1159, 787 and 684; H NMR ꢁ (ppm): 3.72 (s,
3H, OCH3), 7.34-7.86 (m, 4H, arom.), .), 7.96 (t, 1H, py-H),
8.25 (d, 2H, py-H), 8.84 (s, H, N=CH), 11.91 (s, H, NH);
MS m/z: 359.9 [M - H+], (M = 362.18); Anal. Calcd. for
C15H12BrN3O3 (361.18): C, 49.74; H, 3.34; Br, 22.06; N,
11.60%; Found: C, 49.78; H, 3.31; Br, 22.04; N, 11.68%.
6.4.16. 6-[(2,4-dihydroxybenzylidene)hydrazinocarbonyl]-
2-methoxycarbonylpyridine (5p)
6.4.11. 6-[(4-bromobenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5k)
Yield (45%), M.p. 283 °C, Rf = 0.14. FT-IR (KBr) ꢀmax
(cm-1): 3531, 3431, 3196, 1728, 1658, 1631, 1581, 1506,
1437, 1327, 1244, 976, 736 and 682; 1H NMR ꢁ (ppm): 3.69
(s, 3H, OCH3), 6.41-7.65 (m, 3H, arom.), 7.95 (t, 1H, py-H),
8.27 (d, 2H, py-H), 8.74 (s, H, N=CH), 9.89 (s, H, OH),
11.80 (s, H, NH), 11.88 (s, H, OH); MS m/z: 314.0 [M - H+],
(M = 315.28); Anal. Calcd. for C21H17N5O6(315.28): C,
57.93; H, 3.94; N, 16.09%; Found: C, 57.91; H, 3.92; N,
16.00%.
Yield (90%), M.p. 162 °C, Rf = 0.59. FT-IR (KBr) ꢀmax
(cm-1): 3433, 3173, 3026, 1728, 1674, 1585, 1537, 1440,
1
1361, 1298, 1246, 1151, 997, 736 i 686; H NMR ꢁ (ppm):
3.71 (s, 3H, OCH3), 7.38-7.82 (m, 4H, arom.), 7.96 (t, 1H,
py-H), 8.25 (d, 2H, py-H), 8.94 (s, H, N=CH), 11.84 (s, H,
NH); MS m/z: 361.7 [M - H+], (M = 362.18); Anal. Calcd.
for C15H12BrN3O3 (361.18): C, 49.74; H, 3.34; Br, 22.06; N,
11.60; O, 13.25%; Found: C, 49.82; H, 3.33; Br, 22.10; N,
11.62; O, 13.23%.
6.4.17. 6-[(3,4-dihydroxybenzylidene)hydrazinocarbonyl]-
2-methoxycarbonylpyridine (5q)
6.4.12. 6-[(4-fluorobenzylidene)hydrazinocarbonyl]-2-
methoxycarbonylpyridine (5l)
Yield (52%), M.p. 270 °C, Rf = 0.1. FT-IR (KBr) ꢀmax
(cm-1): 3294, 3255, 2953, 1720, 1672, 1583, 1525, 1441,
1
1367, 1305, 1242, 1149, 993, 839, 736 and 672; H NMR ꢁ
Yield (65%), M.p. 170-175 °C, Rf = 0.53. FT-IR (KBr)
ꢀmax (cm-1): 3547, 3466, 3292, 3203, 1732, 1681, 1627, 1535,
(ppm): 3.70 (s, 3H, OCH3), 6.80-7.44 (m, 3H, arom.), 7.95
(t, 1H, py-H), 8.27 (d, 2H, py-H), 8.74 (s, H, N=CH), 9.48
(s, 2H, 2OH), 11.91 (s, H, NH); MS m/z: 314.0 [M - H+], (M
= 315.28); Anal. Calcd. for C21H17N5O6 (315.28): C, 57.93;
H, 3.94; N, 16.09%; Found: C, 57.90; H, 3.94; N, 16.09%.
1
1307, 1242, 1159, 787 and 684; H NMR ꢁ (ppm): 3.68 (s,
3H, OCH3), 7.06-7.80 (m, 4H, arom.), 7.96 (t, 1H, py-H),
8.25 (d, 2H, py-H), 8.94 (s, H, N=CH), 11.88 (s, H, NH);
MS m/z: 300.0 [M - H+], (M = 301.27); Anal. Calcd. for
C15H12FN3O3 (301.07): C, 59.80; H, 4.01; F, 6.31; N, 13.95;
O, 15.93%; Found: C, 59.81; H, 4.03; F, 6.29; N, 13.92; O,
15.96%.
6.4.18. 6-[(3-hydroxy-4-methoxybenzylidene)hydrazine-
carbonyl]-2-methoxycarbonylpyridine (5r)
Yield (93%), M.p. 187 °C, Rf = 0.27. FT-IR (KBr): ꢀmax
(cm-1): 3581, 3462, 3196, 1728, 1674, 1599, 1543, 1512,
6.4.13.
6-[(3-phenoxybenzylidene)hydrazinocarbonyl]-2-
1
methoxycarbonylpyridine (5m)
1429, 1244, 736 and 682; H NMR ꢁ (ppm): 3.73 (s, 3H,
OCH3), 3.88 (s, 3H, OCH3), 6.90-7.48 (m, 3H, arom.), 7.95
(t, 1H, py-H), 8.27 (d, 2H, py-H), 8.94 (s, H, N=CH), 9.68
(s, H, OH), 11.90 (s, H, NH); MS m/z: 330.0 [M + H+], (M =
Yield (80%), M.p. 89-93°C, Rf = 0.60. FT-IR (KBr) ꢀmax
(cm-1): 3485, 3036, 1726, 1672, 1575, 1541, 1483, 1437,
1300, 1247, 1163, 954, 720 and 688; 1H NMR ꢁ (ppm): 3.89

408 Letters in Organic Chemistry, 2012, Vol. 9, No. 6
Molnar et al.
329.31). Anal. Calcd. for C23H21N5O6 (463.15): C, 59.61; H,
4.57; N, 15.11%; Found: C, 59.66; H, 4.53; N, 15.09%.
ꢁ (ppm): 6.85-7.88 (m, 8H, arom.), 7.95 (t, 1H, py-H), 8.28
(d, 2H, py-H), 8.66 (s, 2H, 2N=CH), 9.83 (s, 2H, 2OH),
11.82 (s, 2H, 2NH); MS m/z: 402.0 [M - H+], (M = 403.39);
Anal. Calcd. for C21H17N5O4 (403.13): C, 62.53; H, 4.25; N,
17.36%; Found: , 62.50; H, 4.28; N, 17.31%.
6.5.5. (N2'E,N6'E)-N2',N6'-bis(2-methoxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6e)
6.4.19. 6-[(3,4,5-trimethoxybenzylidene)hydrazine-
carbonyl]-2-methoxycarbonylpyridine (5s)
Yield (96%), M.p. 182-185 °C, Rf = 0.36. FT-IR (KBr):
ꢀ
max (cm-1): 3493, 2999, 2962, 2839, 1740, 1676, 1612, 1577,
1
1506, 1329, 1248, 1128, 999 and 738; H NMR ꢁ (ppm):
3.68 (s, 9H, 3OCH3), 3.89 (s, 3H, OCH3), 7.04 (m, 2H,
arom.), 7.95 (t, 1H, py-H), 8.27 (d, 2H, py-H), 8.74 (s, H,
N=CH), 11.91 (s, H, NH); MS m/z: 374.0 [M + H+], (M =
373.36); Anal. Calcd. for C27H29N5O8 (373.36): C, 58.80; H,
5.30; N, 12.70%; Found: C, 58.78; H, 5.31; N, 12.67%.
Yield (93%), M.p. 228°C, Rf = 0.59. FT-IR (KBr) ꢀmax
(cm-1): 3452, 3182, 3047, 2960, 1741, 1680, 1601, 1560,
1
1437, 1290, 1247, 1163, 997 and 756; H NMR ꢁ (ppm):
3.80 (s, 6H, OCH3), 7.18-7.72 (m, 8H, arom.), 7.95 (t, 1H,
py-H), 8.26 (d, 2H, py-H), 8.78 (s, 2H, 2N=CH), 11.92 (s,
2H, 2NH),; MS m/z: 432.1 [M + H+], (M = 431.44); Anal.
Calcd. for C23H21N5O6 (431.16): C, 64.03; H, 4.91; N,
16.23%; Found: C, 64.00; H, 5.09; N, 16.16%.
6.5. Preparation of Schiff bases from di-hydrazide
(6a – s)
Ethanolic solution of 0.01 mole of pyridine-2,6-
dicarbohydrazide (4) and 0.02. mole of aromatic aldehyde (a
– s), with a few drops of acetic acid, is refluxed for 3 hours.
After cooling, the solution is poured onto crushed ice, fil-
tered and dried. Crude product is recrystallized from ethanol.
6.5.1. (N2'E,N6'E)-N2',N6'-dibenzylidenepyridine-2,6-
dicarbohydrazide (6a)
6.5.6. (N2'E,N6'E)-N2',N6'-bis(3-methoxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6f)
Yield (86%), M.p. 285 °C, Rf = 0.42. FT-IR (KBr) ꢀmax
(cm-1): 3529, 3470, 3255, 2978, 1726, 1693, 1583, 1535,
1
1433, 1307, 1236, 1157, 1078, 989 and 749; H NMR ꢁ
(ppm): 3.81 (s, 6H, OCH3), 7.16-7.75 (m, 8H, arom.), 7.95
(t, 1H, py-H), 8.26 (d, 2H, py-H), 8.57 (s, 2H, 2N=CH),
11.93 (s, 2H, 2NH)); MS m/z: 432.0 [M + H+], (M =
431.44); Anal. Calcd. for C23H21N5O6 (431.16): C, 64.03; H,
4.91; N, 16.23%; Found: C, 63.96; H, 4.88; N, 16.24%.
6.5.7. (N2'E,N6'E)-N2',N6'-bis(4-methoxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6g)
Yield (79 %), M.p. >300 °C; Rf = 0.42. FT-IR (KBr) ꢀmax
(cm-1): 3518, 3468, 3201, 3049, 1728, 1670, 1537, 1437,
1
1367, 1300, 1240, 1165, 1108 and 685; H NMR ꢁ (ppm):
7.22-7.86 (m, 10H, arom.), 7.96 (t, 1H, py-H), 8.27 (d, 2H,
py-H), 8.84 (s, 2H, 2N=CH), 11.86 (s, 2H, 2NH), MS m/z:
372.2 [M + H+], (M = 371.39); Anal. Calcd. for C21H17N5O2
(371.14): C, 67.91; H, 4.61; N, 18.86%; Found: C, 67.89; H,
4.62; N, 18.80%.
6.5.2. (N2'E,N6'E)-N2',N6'-bis(2-hydroxybenzylidene)pyr-
idine-2,6-dicarbohydrazide (6b)
Yield (93%), M.p. 280 °C, Rf = 0.31. FT-IR (KBr) ꢀmax
(cm-1): 3520, 3450, 3230, 2920, 1728, 1688, 1530, 1440,
1
1300, 1240, 1180 and 1015; H NMR ꢁ (ppm): 3.78 (s, 6H,
OCH3), 7.14-7.86 (m, 8H, arom.), 7.95 (t, 1H, py-H), 8.25
(d, 2H, py-H), 8.62 (s, 2H, 2N=CH),11.80 (s, 2H, 2NH));
MS m/z: 432.1 [M + H+], (M = 431.44); Anal. Calcd. for C
23H21N5O6 (431.16): C, 64.03; H, 4.91; N, 16.23%; Found:
64.00; H, 4.98; N, 16.19%.
6.5.8. (N2'E,N6'E)-N2',N6'-bis(2-chlorobenzylidene)pyridine-
2,6-dicarbohydrazide (6h)
Yield (80%), M.p. >300 °C, Rf = 0.90. FT-IR (KBr) ꢀmax
(cm-1):3516, 3437, 2997, 1724, 1668, 1620, 1535, 1240,
1
1157, 750 and 684. H NMR ꢁ (ppm): 7.02-7.66 (m, 8H,
arom.), 7.96 (t, 1H, py-H), 8.27 (d, 2H, py-H), 8.74 (s, 2H,
2N=CH), 11.26 (s, 2H, 2OH); 11.86 (s, 2H, 2NH), MS m/z:
402.1 [M - H+], (M = 403.39); Anal. Calcd. for C21H17N5O4
(403.13): C, 62.53; H, 4.25; N, 17.36%; Found: C , 62.50; H,
4.27; N, 17.31%.
6.5.3. (N2'E,N6'E)-N2',N6'-bis(3-hydroxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6c)
Yield (89%), M.p. >300 °C, Rf = 0.89. FT-IR (KBr) ꢀmax
(cm-1): 3547, 3476, 3207, 2953, 1732, 1676, 1637, 1585,
1
1537, 1442, 1365, 1300, 1244, 1159, 767 and 682; H NMR
ꢁ (ppm): 7.36-7.75 (m, 8H, arom.), 7.95 (t, 1H, py-H), 8.24
(d, 2H, py-H), 8.76 (s, 2H, 2N=CH), 11.93 (s, 2H, 2NH);
MS m/z: 439.9 [M - H+], (M = 440.28); Anal. Calcd. for
C21H15Cl2N5O2 (439.06): C, 57.29; H, 3.43; N, 15.91%;
Found: C, 57.31; H, 3.42; N, 16.01%.
Yield (92%), M.p. >300 °C, Rf = 0.10. FT-IR (KBr) ꢀmax
(cm-1): 3433, 3281, 1710, 1697, 1579, 1529, 1492, 1435,
1
1313, 1286, 1249, 1145, 790 and 690. H NMR ꢁ (ppm):
7.12-7.48 (m, 8H, arom.), 7.96 (t, 1H, py-H), 8.27 (d, 2H,
py-H), 8.64 (s, 2H, 2N=CH), 9.83 (s, 2H, 2OH), 11.96 (s,
2H, 2NH),; MS m/z: 402.0 [M - H+], (M = 403.39); Anal.
Calcd. for C21H17N5O4 (403.13): C, 62.53; H, 4.25; N,
17.36%; Found: , 62.50; H, 4.28; N, 17.31%.
6.5.4. (N2'E,N6'E)-N2',N6'-bis(4-hydroxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6d)
6.5.9. (N2'E,N6'E)-N2',N6'-bis(3-chlorobenzylidene)pyridine-
2,6-dicarbohydrazide (6i)
Yield (78%), M.p. 292 °C, Rf = 0.42. FT-IR (KBr) ꢀmax
(cm-1): 3547, 3466, 3292, 3203, 1732, 1681, 1627, 1535,
1307, 1242, 1159, 787 and 684; 1H NMR ꢁ (ppm): 7.46-7.91
(m, 8H, arom.), 7.94 (t, 1H, py-H), 8.26 (d, 2H, py-H), 8.74
(s, 2H, 2N=CH), 11.88 (s, 2H, 2NH); MS m/z: 439.9 [M –
H+], (M = 440.28); Anal. Calcd. for C21H15Cl2N5O2 (439.06):
C, 57.29; H, 3.43; N, 15.91%; Found: C, 57.28; H, 3.40; N,
15.96%.
Yield (98 %), M.p. >300 °C, Rf = 0.14. FT-IR (KBr) ꢀmax
(cm-1): 3584, 3394, 3219, 1718, 1662, 1603, 1541, 1516,
1
1440, 1365, 1298, 1281, 1246, 1165, 844 and 679; H NMR

Synthesis and Antioxidant Evaluation of Schiff Bases
Letters in Organic Chemistry, 2012, Vol. 9, No. 6
409
6.5.10. (N2'E,N6'E)-N2',N6'-bis(3-bromobenzylidene)pyri-
dine-2,6-dicarbohydrazide (6j)
7.62 (m, 10H, arom.), 7.95 (t, 1H, py-H), 8.27 (d, 2H, py-H),
7.81 (s, 2H, 2 HC=N), 10.96 (s, 2H, HN-N); MS m/z: 422.0
[M - H+], (M = 423.47); Anal. Calcd. for C25H21N5O2
(423.17): C, 70.91; H, 5-00; N, 16.54%; Found: C, 70.89; H,
5.04; N, 16.51%.
6.5.16. (N2'E,N6'E)-N2',N6'-bis(2,4-dihydroxybenzylidene)
pyridine-2,6-dicarbohydrazide (6p)
Yield (94%), M.p. 283-285 °C, Rf = 0.53. FT-IR (KBr)
ꢀ
max (cm-1): 3527, 3446, 3281, 3213, 1730, 1684, 1630, 1535,
1303, 1240, 1158, 789 and 680; 1H NMR ꢁ(ppm): 7.41-7.82
(m, 8H, arom.), 7.94 (t, 1H, py-H), 8.25 (d, 2H, py-H), 8.72
(s, 2H, 2N=CH), 11.85 (s, 2H, 2NH); MS m/z: 527.9 [M -
H+], (M = 529.18); Anal. Calcd. for C21H15Br2N5O2 (529.18):
C, 47.66; H, 2.86; Br, 30.20; N, 13.23; O, 6.05%; Found: C,
47.56; H, 2.89; Br, 31.05; N, 13.30; O, 6.15%.
Yield (45%), M.p. >300 °C, Rf = 0.56. FT-IR (KBr) ꢀmax
(cm-1): 3531, 3431, 3196, 1728, 1658, 1631, 1581, 1506,
1437, 1327, 1244, 976, 736 and 682; 1H NMR ꢁ (ppm): 6.38-
7.63 (m, 6H, arom.), 7.95 (t, 1H, py-H), 8.27 (d, 2H, py-H),
8.74 (s, 2H, 2N=CH), 9.89 (s, 2H, OH), 11.85 (s, 2H, 2NH),
11.88 (s, 2H, OH); MS m/z: 434.0 [M - H+], (M = 435.39);
Anal. Calcd. for C21H17N5O6 (435.12): C, 57.93; H, 3.94; N,
16.09%; Found: C, 57.91; H, 3.92; N, 16.00%.
6.5.11. (N2'E,N6'E)-N2',N6'-bis(4-bromobenzylidene)pyri-
dine-2,6-dicarbohydrazide (6k)
Yield (90%), M.p. 277 °C, Rf = 0.42. FT-IR (KBr) ꢀmax
(cm-1): 3538, 3456, 3279, 3208, 1734, 1680, 1636, 1538,
1304, 1242, 1159, 786 and 688; 1H NMR ꢁ (ppm): 7.48-7.76
(m, 8H, arom.), 7.94 (t, 1H, py-H), 8.25 (d, 2H, py-H), 8.64
(s, 2H, 2N=CH), 11.86 (s, 2H, 2NH); MS m/z: 527.8 [M -
H+], (M = 529.18); Anal. Calcd. for C21H15Br2N5O2 (529.18):
C, 47.66; H, 2.86; Br, 30.20; N, 13.23; O, 6.05%; Found: C,
47.58; H, 2.84; Br, 31.08; N, 13.32; O, 6.18%.
6.5.17. (N2'E,N6'E)-N2',N6'-bis(3,4-dihydroxybenzylidene)
pyridine-2,6-dicarbohydrazide (6q)
Y = (63%), M.p. >300 °C, Rf = 0.38. FT-IR (KBr) ꢀmax
(cm-1): 3294, 3255, 2953, 1720, 1672, 1583, 1525, 1441,
1
1367, 1305, 1242, 1149, 993, 839, 736 and 672; H NMR ꢁ
6.5.12. (N2'E,N6'E)-N2',N6'-bis(4-fluorobenzylidene)pyri-
dine-2,6-dicarbohydrazide (6l)
(ppm): 6.82-7.38 (m, 6H, arom.), 7.95 (t, 1H, py-H), 8.26 (d,
2H, py-H), 8.64 (s, 2H, 2N=CH), 9.68 (s, 4H, OH), 11.80 (s,
2H, 2NH); MS m/z: 434.0 [M - H+], (M = 435.39); Anal.
Calcd. for C21H17N5O6 (435.12): C, 57.93; H, 3.94; N,
16.09%; Found: C, 57.90; H, 3.94; N, 16.09%.
6.5.18.(N2'E,N6'E)-N2',N6'-bis(3-hydroxy-4-
methoxybenzylidene)pyridine-2,6-dicarbohydrazide (6r)
Yield (73%), M.p. 277 °C, Rf = 0.35. FT-IR (KBr) ꢀmax
(cm-1): 3548, 3449, 3270, 3214, 1733, 1685, 1630, 1532,
1306, 1242, 1158, 786 and 684; 1H NMR ꢁ (ppm): 7.34-7.85
(m, 8H, arom.), 7.94 (t, 1H, py-H), 8.25 (d, 2H, py-H), 8.76
(s, 2H, 2N=CH), 11.88 (s, 2H, 2NH)); MS m/z: 406.0 [M -
H+], (M = 407.37); Anal. Calcd. for C21H15F2N5O2 (407.37):
C, 61.91; H, 3.71; F, 9.33; N, 17.19; O, 7.85%; Found: C,
62.05; H, 3.65; F, 9.40; N, 17.24; O, 7.80%.
Yield (88%), M.p. 276-280 °C, Rf = 0.22. FT-IR (KBr)
ꢀ
max (cm-1): 3581, 3462, 3196, 1728, 1674, 1599, 1543, 1512,
1
1429, 1244, 736 and 682; H NMR ꢁ (ppm): 3.81 (s, 6H,
OCH3), 6.92-7.62 (m, 6H, arom.), 7.94 (t, 1H, py-H), 8.26
(d, 2H, py-H), 8.65 (s, 2H, 2N=CH), 9.88 (s, 2H, OH), 11.86
(s, 2H, 2NH),); MS m/z: 462.6 [M - H+], (M = 463.44); Anal.
Calcd. for C23H21N5O6 (463.15): C, 59.61; H, 4.57; N,
15.11%; Found: C, 59.66; H, 4.53; N, 15.09%.
6.5.13. (N2'E,N6'E)-N2',N6'-bis(3-phenoxybenzylidene)pyri-
dine-2,6-dicarbohydrazide (6m)
Yield (88%), M.p. 140 °C, Rf = 0.56. FT-IR (KBr) ꢀmax
(cm-1): 3485, 3036, 1726, 1672, 1575, 1541, 1483, 1437,
1300, 1247, 1163, 954, 720 and 688; 1H NMR ꢁ (ppm): 7.12-
7.52 (m, 18H, arom.), 7.94 (t, 1H, py-H), 8.25 (d, 2H, py-H),
8.68 (s, 2H, 2N=CH), 11.86 (s, 2H, 2 NH),; MS m/z: 554.0
[M - H+], (M = 555.58); Anal. Calcd. for C33H25N5O4
(555.19): C, 71.34; H, 4.54; N, 12.61%; Found: C, 71.32; H,
4.50; N, 12.59%.
6.5.19.(N2'E,N6'E)-N2',N6'-bis(3,4,5-trimethoxybenzylidene)
pyridine-2,6-dicarbohydrazide (6s)
Yield (92%), M.p. >300 °C, Rf = 0.32. FT-IR (KBr) ꢀmax
(cm-1): 3493, 2999, 2962, 2839, 1740, 1676, 1612, 1577,
1
1506, 1329, 1248, 1128, 999 and 738; H NMR ꢁ (ppm):
6.5.14.(N2'E,N6'E)-N2',N6'-bis(4-dimethylamino-
benzylidene)pyridine-2,6-dicarbohydrazide (6n)
3.84 (s, 18H, OCH3), 7.04-7.42 (s, 4H, arom.), 7.94 (t, 1H,
py-H), 8.25 (d, 2H, py-H), 8.56 (s, 2H, 2N=CH), 11.84 (s,
2H, 2NH); MS m/z: 552.0 [M + H+], (M = 551.55). Anal.
Calcd. for C27H29N5O8 (551.20): C, 58.80; H, 5.30; N,
12.70%; Found: C, 58.78; H, 5.31; N, 12.67%.
Yield (94%), M.p. >300 °C, Rf = 0.46. FT-IR (KBr): ꢀmax
(cm-1): 3547, 3473, 3209, 1724, 1666, 1597, 1523, 1431,
1
1363, 1296, 1240, 1176, 815, 732 and 682; H NMR ꢁ
(ppm): 3.04 (s, 12H, N(CH3)2), 6.80-7.58 (m, 8H, arom.),
7.94 (t, 1H, py-H), 8.25 (d, 2H, py-H), 8.77 (s, 2H, 2N=CH),
11.89 (s, 2H, 2NH); MS m/z: 458.1 [M + H+], (M = 457.53);
Anal. Calcd. for C25H27N7O2 (457.22): C, 65.63; H, 5.95; N,
21.43%; Found: C, 65.60; H, 5.91; N, 21.39%.
ACKNOWLEDGEMENT
Declared none.
6.5.15. (N2'E,N6'E)-N2',N6'-bis((E)-3-phenylallylidene)pyri-
dine-2,6-dicarbohydrazide (6o)
CONFLICT OF INTEREST
Declared none.
Yield (77%), M.p. 282 °C, Rf = 0.47. FT-IR (KBr) ꢀmax
(cm-1): 3448, 3238, 3043, 1722, 1664, 1624, 1537, 1440,
1317, 1363, 1244, 1130, 987, 748 and 688. H NMR ꢁ
(ppm): 6.80 (m, 2H, HC=CH), 7.21 (m, 2H, HC=CH), 7.31-
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