A convenient synthesis of novel symmetrical bis-Schiff bases of 2, 2′-thio-bis[4-methyl(2-aminophenoxy)phenyl ether] in solution and under solvent-free conditions

Article abstract of DOI:10.3184/030823409X12546490711047

A convenient and straightforward procedure for the synthesis of novel symmetrical bis-Schiff bases has been achieved through the condensation of the symmetrical primary bis-amine 2,2′-thio-bis[4-methyl(2-aminophenoxy) phenyl ether] with a series of aryl a

Full text of DOI:10.3184/030823409X12546490711047

656 RESEARCH PAPER
NOVEMBER, 656–658
JOURNAL OF CHEMICAL RESEARCH 2009
A convenient synthesis of novel symmetrical bis-Schiff bases of
2, 2'-thio-bis[4-methyl(2-aminophenoxy)phenyl ether] in solution
and under solvent-free conditions
Abbas Shockravia*, Mahdieh Sadeghpourb and Abolfazl Olyaeic
aFaculty of Chemistry, Tarbiat Moallem University, Mofatteh Ave., No 49, Postal Code 15614, Tehran, Iran
bDepartment of Chemistry, Islamic Azad University, Takestan Branch, Qazvin, Iran
cDepartment of Chemistry, Payame Noor University, Qazvin, Iran
A convenient and straightforward procedure for the synthesis of novel symmetrical bis-Schiff bases has been
achieved through the condensation of the symmetrical primary bis-amine 2,2'-thio-bis[4-methyl(2-aminophenoxy)
phenyl ether] with a series of aryl aldehydes in organic solvents at room temperature and in solvent-free media, in
moderate to high yields.
Keywords: bis-Schiff base, imine, bis-amine, solvent-free media, aldehyde
For many years particular attention has been paid to the
synthesis and study of diimino-Schiff bases. Schiff bases
are used as substrates in the preparation of a number of
industrial and biologically active compounds via ring closure,
cycloaddition and replacement reactions.1 Moreover, Schiff
bases are also known to show biological activities such as
antimicrobial2-5 antifungal6 and antitumor activity.7 On the
industrial scale, they have a wide range of applications such
as their use as dyes and pigments.8 Schiff bases have also been
employed as chelating agents capable of coordinating metal
ions to give complexes which serve as models for biological
systems.9,10
Conventionally, Schiff bases have been prepared by
refluxing mixtures of amines and carbonyl compounds
in an organic solvent, for example ethanol or methanol,11
but variations are known, such as treatment of the same
mixture at room temperature, refluxing the mixture in heptane
in the presence of acetic acid12 or azeotroping the mixture
with benzene in a Dean–Stark apparatus in the presence of
acid13 and by using a template procedure.14
In recent years, environmentally safer synthetic methods
have received considerable attention and some solvent-
free protocols have been developed. Catalysed synthesis
of imines under solvent-free conditions may be carried out
using microwave irradiation, ionic liquids, montmorillonite
clays,15 zeolites, silica, alumina or other matrices.16 Particular
attention has been paid to the synthesis and study of
bis-imine Schiff bases because of their applications in metal
ion complexation and their ability to act as inhibitors of
human a-thrombin and as antimicrobial agents.17-19
In continuation of our interest in the synthesis of bis-imine
Schiff bases, we now describe the synthesis of some novel
symmetrical bis-Schiff bases from 2,2'-thio-bis[4-methyl
(2-aminophenoxy)phenyl ether] (1) and aromatic aldehydes,
by condensation reactions in solution and in thermal solvent-
free conditions. Compound 1 has been synthesised already
and used as a novel complexing agent for Cd+2 and Co+2
with no significant interference from other ions such as Zn+2
being observed.20 Complexation studies of the Schiff base
derivatives of this ligand with heavy metal ions are currently
being studied in our laboratory.
showed that bis-amine 1 has not previously been used for the
synthesis of bis-Schiff base derivatives.
As the model reaction, we initially examined the reaction
of bis-amine 1 and 2-hydroxy benzaldehyde, in methanol
in the presence of formic acid catalyst at room temperature.
It was found that at least 20 h is needed for the reaction
to be completed. When this reaction was performed in
solvent-free conditions at 70–120°C in the absence of
acid catalyst, the corresponding Schiff base was obtained.
Our investigation demonstrated that the best result was
obtained when temperature was fixed at 100°C in which
case the reaction was completed in 2 minutes. Therefore,
we decided to examine the other reactions in solventless
conditions at 100°C in the absence of acid catalyst.
The bis-Schiff bases 3a–h were synthesised by condensation
of 2,2'-thio-bis[4-methyl (2-aminophenoxy)phenyl ether] (1)
and aromatic aldehydes 2a–h (2-hydroxy benzaldehyde,
5-bromo-2-hydroxy
benzaldehyde,
2-hydroxy-5-nitro
benzaldehyde, 4-choloro-3-nitro benzaldehyde, 3-indol
carbaldehyde, 4-nitro benzaldehyde, 3-nitro benzaldehyde
and 2-nitro benzaldehyde respectively) in methanol in the
presence of formic acid catalyst at room temperature and
solvent-free conditions at 100°C for the appropriate time
(Scheme 1).
Compounds 3a–h were identified on the basis of
spectroscopic data. The IR spectra of 3a–h showed the
characteristic C=N absorption bands at 1622, 1621, 1632,
1632, 1625, 1639, 1629 and 1619 cm-1, respectively. The
absorption band of NH in 3e was observed at 3384 cm-1.
The hydroxyl absorption bands for 3a–c absorbed weakly in
their IR spectra because the hydroxyl groups were located
at the ortho-position with respect to the imino-groups,
which probably were involved in enol-keto tautomerisation
processes. In the aliphatic region, the 1H NMR spectra
of 3a–h show a singlet peak arising from CH3 at about
d 2.20 ppm, hydroxyl protons of 3a–c were presented as broad
signals at about d 13.50 ppm due to enol-keto tautomerisation
and the remaining protons of the corresponding aromatic
molecules and imine protons were presented in the aromatic
regions. All of the products 3a–h were pale-coloured powders
and were analytically pure as isolated. Yields, melting points
and reaction times are summarised in Table 1.
As part of a continuous effort to develop new N,O,S-
ligand derivatives relevant to bis-Schiff bases, we report
two methods for the synthesis of novel bis-Schiff bases with
bis-amine 1, one in methanol in the presence of formic acid
catalyst at room temperature and a second in solvent-free
conditions, in almost quantitative yields. Our literature survey
In summary, we have successfully developed a quick,
convenient and efficient method for the synthesis of novel
bis-Schiff base derivatives. Compared to other previously
reported procedures in the literature, the solventless method
has advantages such as omitting organic solvent, no need for a
catalyst, generality and simplicity of procedure, easy product
separation, lower reaction time, and high yields; merits to be
* Correspondent. E-mail: Abbas_shockravi@yahoo.co.uk
PAPER: JC090337

JOURNAL OF CHEMICAL RESEARCH 2009 657
Ar
Ar
NH2
O
H2N
O
N
O
N
O
S
S
Solvent-free / 100oC
or MeOH / r.t.
+ ArCHO
CH3
CH3
CH3
CH3
3
1
2
NO2
Br
H
N
a:
c:
d:
e:
Ar =
b:
Cl
NO2
HO
HO
HO
f:
g:
NO2
h:
NO2
O2N
Scheme 1
Table 1 Reaction times, yields and melting points of the products 3 in CH3OH and solventless condition
Products
Ar
CH3OH (r.t.)
Solventless
Mp (°C)
75–76
Time/h
20
Yield/%
75
Time/min
2
Yield/%
90
3a
HO
Br
3b
15
80
2
92
188–190
HO
NO2
3c
7
80
72
2
5
87
89
184–185
169–171
HO
Cl
NO2
3d
25
H
N
3e
25
65
3
85
98–99
NO2
3f
15
18
78
75
3
3
90
89
178–180
164–165
3g
NO2
5h
16
80
4
92
139–140
O2N
O-Rapid Heraeus elemental analyser (Wellesley, MA). Progress of
the reactions was monitored by TLC using precoated sheets of silica
gel Merck 60 F254 on aluminium.
recommended. The compounds 3a–h are potential chelating
agents for metal ions and this aspect is currently under study
in our research laboratory.
General procedure for the synthesis of compounds 3a–h in
methanol: A solution of [2,2-thio-bis[4-methyl(2-aminophenoxy)
phenyl ether] (1) (1.0 mmol), an aromatic aldehyde (2.0 mmol) and
formic acid (0.005 g of 98% aqueous solution, 0.1 mmol), in methanol
(40 mL) was stirred for the time given in Table 1 at room temperature.
At the end of the reaction, water was added to the coloured solutions
until solid products precipitated. The products were then filtered,
washed with cold methanol, dried and purified by recrystallisation
from EtOH–H2O to give bis-Schiff bases 3 as crystals.
Experimental
All commercially available chemicals and reagents were used without
further purification. Melting points (uncorrected) were determined by
an Electrothermal engineering LTD 9100 apparatus. IR spectra were
recorded on a Perkin-Elmer model 543, the 1H- and 13C NMR spectra
were obtained using Bruker Avance DRX 300 apparatus at 298 K.
Chemical shifts (d) are reported in ppm and are referenced to the
NMR solvent peak. Elemental analyses were carried out by a CHN–
PAPER: JC090337

658 JOURNAL OF CHEMICAL RESEARCH 2009
General procedure for the synthesis of compounds 3a–h in
solvent-free conditions: A mixture of compound 1 (1.0 mmol) and
an aromatic aldehyde (2.0 mmol) was magnetically stirred on a
preheated oil bath at 100°C for the appropriate time as indicated in
Table 1. The progress of the reaction was monitored by TLC. After
completion, the reaction mixture was cooled to room temperature
and ethanol–water (1:1) 10 mL was added until solid products
precipitated. The precipitate was filtered, washed with cold ethanol,
dried and purified by recrystallisation from EtOH–H2O to give bis-
Schiff base 3 as crystals.
2,2'-Thio-bis[N-(3-nitrobenzylidene)-2-(4-tolyloxy)benzamine] (3g):
Yellow crystals. IR (KBr): 1629 (C=Nimine) cm-1. 1H NMR (300 MHz,
CDCl3): d 2.16 (s, 6H, CH3), 6.78–8.49 (m, 22H, ArH), 8.57 (s, 2H,
imine-H). 13C NMR (75 MHz, CDCl3): d 21.01, 118.96, 119.78,
123.33, 123.78, 124.39, 125.34, 127.27, 129.60, 129.85, 133.23,
134.19, 134.57, 134.62, 138.39, 142.35, 148.78, 148.87, 153.62,
160.44. Anal. Calcd for C40H30N4O6S: C, 69.16; H, 4.32; N, 8.07.
Found: C, 69.11; H, 4.38; N, 8.15%.
2,2'-Thio-bis[N-(2-nitrobenzylidene)-2-(4-tolyloxy)benzamine]
(3h): Yellow crystals. IR (KBr): 1619 (C=Nimine) cm-1. 1H NMR
(300 MHz, CDCl3): d 2.19 (s, 6H, CH3), 6.77–8.04 (m, 22H, ArH),
8.90 (s, 2H, imine-H). 13C NMR (75 MHz, CDCl3): d 21.01, 118.94,
119.90, 121.87, 124.51, 124.63, 124.93, 125.46, 127.62, 129.49,
130.06, 130.66, 131.30, 131.83, 133.41, 133.73, 142.86, 149.33,
154.21, 158.06. Anal. Calcd for C40H30N4O6S: C, 69.16; H, 4.32; N,
8.07. Found: C, 69.10; H, 4.40; N, 7.95%.
2,2'-Thio-bis[2-(2-(4-tolyloxy)phenylimino)methyl)phenol]
1
(3a): Yellowish crystals. IR (KBr): 1622 (C=Nimine) cm-1. H NMR
(300 MHz, acetone-d6): d 2.19 (s, 6H, CH3), 6.72–7.45 (m, 24H,
ArH), 8.89 (s, 2H, imine-H), 13.14 (s, 2H, OH). 13C NMR (75 MHz,
acetone-d6): d 20.61, 117.62, 119.54, 119.58, 119.61, 120.21, 121.57,
124.92, 126.08, 128.59, 130.32, 133.58, 133.90, 134.00, 134.91,
140.09, 150.91, 154.05, 162.12, 165.21. Anal. Calcd for C40H32N2O4S:
C, 75.47; H, 5.03; N, 4.40. Found: C, 75.55; H, 5.10; N, 4.45%.
2,2'-Thio-bis[2-{2-(4-tolyloxy)(phenylimino)methyl}-5-bromo-
phenol] (3b): Yellow crystals. IR (KBr): 1621 (C=Nimine) cm-1.
1H NMR (300 MHz, CDCl3): d 2.20 (s, 6H, CH3), 6.76–7.37 (m, 20H,
ArH), 8.63 (s, 2H, imine-H), 13.32 (broad, 2H, OH). 13C NMR (75 MHz,
CDCl3): d 20.69, 110.14, 118.40, 119.16, 119.30, 120.58, 122.16,
123.65, 125.49, 127.83, 129.56, 133.23, 134.27, 134.53, 135.58, 137.95,
149.80, 152.52, 160.35, 163.14. Anal. Calcd for C40H30N2Br2O4S: C,
60.30; H, 3.77; N, 3.52. Found: C, 60.25; H, 3.65; N, 3.60%.
We thank the Research Council of the Tarbiat Moallem
University for financial support.
Received 12 December 2009; accepted 24 September 2009
Paper 08/0337 doi: 10.3184/030823409X12546490711047
Published online: 16 November 2009
2,2'-Thio-bis[2-(2-(4-tolyloxy)phenylimino)methyl)-5-nitrophenol]
(3c): Orange crystal. IR (KBr): 1632 (C=Nimine) cm-1. 1H NMR
(300 MHz, acetone-d6): d 2.22 (s, 6H, CH3), 6.80–8.48 (m, 20H,
ArH), 9.15 (s, 2H, imine-H), 14.73 (s, 2H, OH). 13C NMR (75 MHz,
acetone-d6): d 20.66, 118.85, 119.06, 119.24, 120.58, 121.23, 124.68,
126.48, 128.92, 129.58, 129.68, 130.53, 134.09, 135.58, 137.68,
140.43, 151.52, 153.53, 163.21, 168.22. Anal. Calcd for C40H30N4O8S:
C, 66.11; H, 4.13; N, 7.71. Found: C, 65.95; H, 4.04; N, 7.75%.
2,2'-Thio-bis[N-(4-chloro-3-nitrobenzylidene)-2-(4-tolyloxy)
benzamine] (3d): Yellowish crystals. IR (KBr): 1632 (C=Nimine) cm-1.
1H NMR (300 MHz, acetone-d6): d 2.14 (s, 6H, CH3), 6.73–8.18 (m,
20H, ArH), 8.63 (s, 2H, imine-H). 13C NMR (75 MHz, acetone-d6):
d 20.54, 115.63, 118.60, 119.30, 122.58, 125.05, 125.48, 128.11,
128.70, 130.09, 130.27, 132.41, 133.45, 133.58, 134.44, 137.55,
142.81, 149.85, 154.48, 159.38. Anal. Calcd for C40H28N4Cl2O6S: C,
62.90; H, 3.66; N, 7.34. Found: C, 62.95; H, 3.72; N, 7.41%.
2,2'-Thio-bis[N-((1H-indol-3-yl)methylene)-2-(4-tolyloxy)
benzamine] (3e): Pink crystals. IR (KBr): 3423 (NH) and 1619
(C=Nimine) cm-1. 1H NMR (acetone-d6): d 2.24 (s, 6H, CH3), 4.39
(broad, 2H, NH), 6.55–7.14 (m, 26H, ArH and imine-H). 13C NMR
(75 MHz, acetone-d6): d 20.50, 112.24, 116.73, 117.17, 117.32,
117.49, 117.87, 120.47, 120.56, 121.74, 123.75, 124.95, 125.62,
125.69, 129.90, 130.13, 133.02, 133.55, 133.77, 140.69, 143.49,
154.80. Anal. Calcd for C44H34N4O2S: C, 77.42; H, 4.98; N, 8.21.
Found: C, 77.38; H, 5.04; N, 8.30%.
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2,2'-Thio-bis[N-(4-nitrobenzylidene)-2-(4-tolyloxy)benzamine] (3f):
Yellow crystals. IR (KBr): 1632 (C=Nimine) cm-1. 1H NMR (300 MHz,
CDCl3): d 2.18 (s, 6H, CH3), 6.78–7.30 (m, 14H, ArH), 7.83 (d, 4H,
J = 8.71 Hz, ArH), 8.15(d, 4H, J = 8.71 Hz, ArH) 8.60 (s, 2H, imine-H).
13C NMR (75 MHz, CDCl3): d 21.04, 118.63, 120.06, 123.27, 124.07,
124.63, 125.12, 127.63, 129.62, 129.77, 133.19, 134.12, 142.05,
142.40, 148.78, 149.52, 153.75, 160.48. Anal. Calcd for C40H30N4O6S:
C, 69.16; H, 4.32; N, 8.07. Found: C, 69.08; H, 4.22; N, 8.17%.
PAPER: JC090337